"Gap hunting" to characterize clustered probe signals in Illumina methylation array data.

PubMed

Andrews, Shan V; Ladd-Acosta, Christine; Feinberg, Andrew P; Hansen, Kasper D; Fallin, M Daniele

2016-01-01

The Illumina 450k array has been widely used in epigenetic association studies. Current quality-control (QC) pipelines typically remove certain sets of probes, such as those containing a SNP or with multiple mapping locations. An additional set of potentially problematic probes are those with DNA methylation distributions characterized by two or more distinct clusters separated by gaps. Data-driven identification of such probes may offer additional insights for downstream analyses. We developed a procedure, termed "gap hunting," to identify probes showing clustered distributions. Among 590 peripheral blood samples from the Study to Explore Early Development, we identified 11,007 "gap probes." The vast majority (9199) are likely attributed to an underlying SNP(s) or other variant in the probe, although SNP-affected probes exist that do not produce a gap signals. Specific factors predict which SNPs lead to gap signals, including type of nucleotide change, probe type, DNA strand, and overall methylation state. These expected effects are demonstrated in paired genotype and 450k data on the same samples. Gap probes can also serve as a surrogate for the local genetic sequence on a haplotype scale and can be used to adjust for population stratification. The characteristics of gap probes reflect potentially informative biology. QC pipelines may benefit from an efficient data-driven approach that "flags" gap probes, rather than filtering such probes, followed by careful interpretation of downstream association analyses. Our results should translate directly to the recently released Illumina EPIC array given the similar chemistry and content design.

Exon-Specific QTLs Skew the Inferred Distribution of Expression QTLs Detected Using Gene Expression Array Data

PubMed Central

Veyrieras, Jean-Baptiste; Gaffney, Daniel J.; Pickrell, Joseph K.; Gilad, Yoav; Stephens, Matthew; Pritchard, Jonathan K.

2012-01-01

Mapping of expression quantitative trait loci (eQTLs) is an important technique for studying how genetic variation affects gene regulation in natural populations. In a previous study using Illumina expression data from human lymphoblastoid cell lines, we reported that cis-eQTLs are especially enriched around transcription start sites (TSSs) and immediately upstream of transcription end sites (TESs). In this paper, we revisit the distribution of eQTLs using additional data from Affymetrix exon arrays and from RNA sequencing. We confirm that most eQTLs lie close to the target genes; that transcribed regions are generally enriched for eQTLs; that eQTLs are more abundant in exons than introns; and that the peak density of eQTLs occurs at the TSS. However, we find that the intriguing TES peak is greatly reduced or absent in the Affymetrix and RNA-seq data. Instead our data suggest that the TES peak observed in the Illumina data is mainly due to exon-specific QTLs that affect 3′ untranslated regions, where most of the Illumina probes are positioned. Nonetheless, we do observe an overall enrichment of eQTLs in exons versus introns in all three data sets, consistent with an important role for exonic sequences in gene regulation. PMID:22359548

Total RNA Sequencing Analysis of DCIS Progressing to Invasive Breast Cancer

DTIC Science & Technology

2015-09-01

EPICOPY to obtain reliable copy number variation ( CNV ) data from the methylome array data, thereby decreasing the DNA requirements in half...in the R statistical environment. Samples were assessed for good performance on the array using detection p-values, a metric implemented by...Illumina to identify probes detected with confidence. Samples less than 90% of probes detected were removed from the analysis and probes undetected in any

Epigenome-Wide DNA Methylation in Hearing Ability: New Mechanisms for an Old Problem

PubMed Central

Wolber, Lisa E.; Steves, Claire J.; Tsai, Pei-Chien; Deloukas, Panos; Spector, Tim D.

2014-01-01

Epigenetic regulation of gene expression has been shown to change over time and may be associated with environmental exposures in common complex traits. Age-related hearing impairment is a complex disorder, known to be heritable, with heritability estimates of 57–70%. Epigenetic regulation might explain the observed difference in age of onset and magnitude of hearing impairment with age. Epigenetic epidemiology studies using unrelated samples can be limited in their ability to detect small effects, and recent epigenetic findings in twins underscore the power of this well matched study design. We investigated the association between venous blood DNA methylation epigenome-wide and hearing ability. Pure-tone audiometry (PTA) and Illumina HumanMethylation array data were obtained from female twin volunteers enrolled in the TwinsUK register. Two study groups were explored: first, an epigenome-wide association scan (EWAS) was performed in a discovery sample (n = 115 subjects, age range: 47–83 years, Illumina 27 k array), then replication of the top ten associated probes from the discovery EWAS was attempted in a second unrelated sample (n = 203, age range: 41–86 years, Illumina 450 k array). Finally, a set of monozygotic (MZ) twin pairs (n = 21 pairs) within the discovery sample (Illumina 27 k array) was investigated in more detail in an MZ discordance analysis. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25 (cg01161216, p = 6.6×10−6), FGFR1 (cg15791248, p = 5.7×10−5) and POLE (cg18877514, p = 6.3×10−5). Replication of these results in a second sample confirmed the presence of differential methylation at TCF25 (p(replication) = 6×10−5) and POLE (p(replication) = 0.016). In the MZ discordance analysis, twins' intrapair difference in hearing ability correlated with DNA methylation differences at ACP6 (cg01377755, r = −0.75, p = 1.2×10−4) and MEF2D (cg08156349, r = −0.75, p = 1.4×10−4). Examination of gene expression in skin, suggests an influence of differential methylation on expression, which may account for the variation in hearing ability with age. PMID:25184702

Ready to clone: CNV detection and breakpoint fine-mapping in breast and ovarian cancer susceptibility genes by high-resolution array CGH.

PubMed

Hackmann, Karl; Kuhlee, Franziska; Betcheva-Krajcir, Elitza; Kahlert, Anne-Karin; Mackenroth, Luisa; Klink, Barbara; Di Donato, Nataliya; Tzschach, Andreas; Kast, Karin; Wimberger, Pauline; Schrock, Evelin; Rump, Andreas

2016-10-01

Detection of predisposing copy number variants (CNV) in 330 families affected with hereditary breast and ovarian cancer (HBOC). In order to complement mutation detection with Illumina's TruSight Cancer panel, we designed a customized high-resolution 8 × 60k array for CGH (aCGH) that covers all 94 genes from the panel. Copy number variants with immediate clinical relevance were detected in 12 families (3.6%). Besides 3 known CNVs in CHEK2, RAD51C, and BRCA1, we identified 3 novel pathogenic CNVs in BRCA1 (deletion of exons 4-13, deletion of exons 12-18) and ATM (deletion exons 57-63) plus an intragenic duplication of BRCA2 (exons 3-11) and an intronic BRCA1 variant with unknown pathogenicity. The precision of high-resolution aCGH enabled straight forward breakpoint amplification of a BRCA1 deletion which subsequently allowed for fast and economic CNV verification in family members of the index patient. Furthermore, we used our aCGH data to validate an algorithm that was able to detect all identified copy number changes from next-generation sequencing (NGS) data. Copy number detection is a mandatory analysis in HBOC families at least if no predisposing mutations were found by sequencing. Currently, high-resolution array CGH is our first choice of method of analysis due to unmatched detection precision. Although it seems possible to detect CNV from sequencing data, there currently is no satisfying tool to do so in a routine diagnostic setting.

Development and Evaluation of a 9K SNP Array for Peach by Internationally Coordinated SNP Detection and Validation in Breeding Germplasm

PubMed Central

Scalabrin, Simone; Gilmore, Barbara; Lawley, Cynthia T.; Gasic, Ksenija; Micheletti, Diego; Rosyara, Umesh R.; Cattonaro, Federica; Vendramin, Elisa; Main, Dorrie; Aramini, Valeria; Blas, Andrea L.; Mockler, Todd C.; Bryant, Douglas W.; Wilhelm, Larry; Troggio, Michela; Sosinski, Bryon; Aranzana, Maria José; Arús, Pere; Iezzoni, Amy; Morgante, Michele; Peace, Cameron

2012-01-01

Although a large number of single nucleotide polymorphism (SNP) markers covering the entire genome are needed to enable molecular breeding efforts such as genome wide association studies, fine mapping, genomic selection and marker-assisted selection in peach [Prunus persica (L.) Batsch] and related Prunus species, only a limited number of genetic markers, including simple sequence repeats (SSRs), have been available to date. To address this need, an international consortium (The International Peach SNP Consortium; IPSC) has pursued a coordinated effort to perform genome-scale SNP discovery in peach using next generation sequencing platforms to develop and characterize a high-throughput Illumina Infinium® SNP genotyping array platform. We performed whole genome re-sequencing of 56 peach breeding accessions using the Illumina and Roche/454 sequencing technologies. Polymorphism detection algorithms identified a total of 1,022,354 SNPs. Validation with the Illumina GoldenGate® assay was performed on a subset of the predicted SNPs, verifying ∼75% of genic (exonic and intronic) SNPs, whereas only about a third of intergenic SNPs were verified. Conservative filtering was applied to arrive at a set of 8,144 SNPs that were included on the IPSC peach SNP array v1, distributed over all eight peach chromosomes with an average spacing of 26.7 kb between SNPs. Use of this platform to screen a total of 709 accessions of peach in two separate evaluation panels identified a total of 6,869 (84.3%) polymorphic SNPs. The almost 7,000 SNPs verified as polymorphic through extensive empirical evaluation represent an excellent source of markers for future studies in genetic relatedness, genetic mapping, and dissecting the genetic architecture of complex agricultural traits. The IPSC peach SNP array v1 is commercially available and we expect that it will be used worldwide for genetic studies in peach and related stone fruit and nut species. PMID:22536421

BeadArray Expression Analysis Using Bioconductor

PubMed Central

Ritchie, Matthew E.; Dunning, Mark J.; Smith, Mike L.; Shi, Wei; Lynch, Andy G.

2011-01-01

Illumina whole-genome expression BeadArrays are a popular choice in gene profiling studies. Aside from the vendor-provided software tools for analyzing BeadArray expression data (GenomeStudio/BeadStudio), there exists a comprehensive set of open-source analysis tools in the Bioconductor project, many of which have been tailored to exploit the unique properties of this platform. In this article, we explore a number of these software packages and demonstrate how to perform a complete analysis of BeadArray data in various formats. The key steps of importing data, performing quality assessments, preprocessing, and annotation in the common setting of assessing differential expression in designed experiments will be covered. PMID:22144879

Imputation across genotyping arrays for genome-wide association studies: assessment of bias and a correction strategy.

PubMed

Johnson, Eric O; Hancock, Dana B; Levy, Joshua L; Gaddis, Nathan C; Saccone, Nancy L; Bierut, Laura J; Page, Grier P

2013-05-01

A great promise of publicly sharing genome-wide association data is the potential to create composite sets of controls. However, studies often use different genotyping arrays, and imputation to a common set of SNPs has shown substantial bias: a problem which has no broadly applicable solution. Based on the idea that using differing genotyped SNP sets as inputs creates differential imputation errors and thus bias in the composite set of controls, we examined the degree to which each of the following occurs: (1) imputation based on the union of genotyped SNPs (i.e., SNPs available on one or more arrays) results in bias, as evidenced by spurious associations (type 1 error) between imputed genotypes and arbitrarily assigned case/control status; (2) imputation based on the intersection of genotyped SNPs (i.e., SNPs available on all arrays) does not evidence such bias; and (3) imputation quality varies by the size of the intersection of genotyped SNP sets. Imputations were conducted in European Americans and African Americans with reference to HapMap phase II and III data. Imputation based on the union of genotyped SNPs across the Illumina 1M and 550v3 arrays showed spurious associations for 0.2 % of SNPs: ~2,000 false positives per million SNPs imputed. Biases remained problematic for very similar arrays (550v1 vs. 550v3) and were substantial for dissimilar arrays (Illumina 1M vs. Affymetrix 6.0). In all instances, imputing based on the intersection of genotyped SNPs (as few as 30 % of the total SNPs genotyped) eliminated such bias while still achieving good imputation quality.

Customization and design of directed self-assembly using hybrid prepatterns

NASA Astrophysics Data System (ADS)

Cheng, Joy; Doerk, Gregory S.; Rettner, Charles T.; Singh, Gurpreet; Tjio, Melia; Truong, Hoa; Arellano, Noel; Balakrishnan, Srinivasan; Brink, Markus; Tsai, Hsinyu; Liu, Chi-Chun; Guillorn, Michael; Sanders, Daniel P.

2015-03-01

Diminishing error tolerance renders the customization of patterns created through directed self-assembly (DSA) extremely challenging at tighter pitch. A self-aligned customization scheme can be achieved using a hybrid prepattern comprising both organic and inorganic regions that serves as a guiding prepattern to direct the self-assembly of the block copolymers as well as a cut mask pattern for the DSA arrays aligned to it. In this paper, chemoepitaxy-based self-aligned customization is demonstrated using two types of organic-inorganic prepatterns. CHEETAH prepattern for "CHemoepitaxy Etch Trim using a self-Aligned Hardmask" of preferential hydrogen silsesquioxane (HSQ, inorganic resist), non-preferential organic underlayer is fabricated using electron beam lithography. Customized trench or hole arrays can be achieved through co-transfer of DSA-formed arrays and CHEETAH prepattern. Herein, we also introduce a tone-reversed version called reverse-CHEETAH (or rCHEETAH) in which customized line segments can be achieved through co-transfer of DSA-formed arrays formed on a prepattern wherein the inorganic HSQ regions are nonpreferential and the organic regions are PMMA preferential. Examples of two-dimensional self-aligned customization including 25nm pitch fin structures and an 8-bar "IBM" illustrate the versatility of this customization scheme using rCHEETAH.

CIDR

Science.gov Websites

NGS Pretesting and QC Using Illumina Infinium Arrays CIDR IGES Posters - 2017 A Comparison of Methods fragmentation methods for input into library construction protocol Development of a Low Input FFPE workflow for Evaluation of Copy Number Variation (CNV) detection methods in whole exome sequencing (WES) data CIDR AGBT

Comparison of Comparative Genomic Hybridization Technologies across Microarray Platforms

EPA Science Inventory

In the 2007 Association of Biomolecular Resource Facilities (ABRF) Microarray Research Group (MARG) project, we analyzed HL-60 DNA with five platforms: Agilent, Affymetrix 500K, Affymetrix U133 Plus 2.0, Illumina, and RPCI 19K BAC arrays. Copy number variation (CNV) was analyzed ...

37 CFR 211.4 - Registration of claims of protection in mask works.

Code of Federal Regulations, 2010 CFR

2010-07-01

... adding metal-connection layers to unpersonalized gate arrays may separately register the entire unpersonalized gate array and the custom metallization layers. Applicants seeking to register separately entire unpersonalized gate arrays or custom metallization layers should make the nature of their claim clear at Space 8...

Microbial genome sequencing using optical mapping and Illumina sequencing

USDA-ARS?s Scientific Manuscript database

Introduction Optical mapping is a technique in which strands of genomic DNA are digested with one or more restriction enzymes, and a physical map of the genome constructed from the resulting image. In outline, genomic DNA is extracted from a pure culture, linearly arrayed on a specialized glass sli...

Implementation of Quality Management in Core Service Laboratories

PubMed Central

Creavalle, T.; Haque, K.; Raley, C.; Subleski, M.; Smith, M.W.; Hicks, B.

2010-01-01

CF-28 The Genetics and Genomics group of the Advanced Technology Program of SAIC-Frederick exists to bring innovative genomic expertise, tools and analysis to NCI and the scientific community. The Sequencing Facility (SF) provides next generation short read (Illumina) sequencing capacity to investigators using a streamlined production approach. The Laboratory of Molecular Technology (LMT) offers a wide range of genomics core services including microarray expression analysis, miRNA analysis, array comparative genome hybridization, long read (Roche) next generation sequencing, quantitative real time PCR, transgenic genotyping, Sanger sequencing, and clinical mutation detection services to investigators from across the NIH. As the technology supporting this genomic research becomes more complex, the need for basic quality processes within all aspects of the core service groups becomes critical. The Quality Management group works alongside members of these labs to establish or improve processes supporting operations control (equipment, reagent and materials management), process improvement (reengineering/optimization, automation, acceptance criteria for new technologies and tech transfer), and quality assurance and customer support (controlled documentation/SOPs, training, service deficiencies and continual improvement efforts). Implementation and expansion of quality programs within unregulated environments demonstrates SAIC-Frederick's dedication to providing the highest quality products and services to the NIH community.

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

PubMed

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; Orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather S; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van't; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Dos Santos Silva, Isabel; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Berg, David Van Den; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; McLean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; van den Ouweland, Ans M W; van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-Gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-04-01

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

Candidate genes for Alzheimer's disease are associated with individual differences in plasma levels of beta amyloid peptides in adults with Down syndrome.

PubMed

Schupf, Nicole; Lee, Annie; Park, Naeun; Dang, Lam-Ha; Pang, Deborah; Yale, Alexander; Oh, David Kyung-Taek; Krinsky-McHale, Sharon J; Jenkins, Edmund C; Luchsinger, José A; Zigman, Warren B; Silverman, Wayne; Tycko, Benjamin; Kisselev, Sergey; Clark, Lorraine; Lee, Joseph H

2015-10-01

We examined the contribution of candidates genes for Alzheimer's disease (AD) to individual differences in levels of beta amyloid peptides in adults with Down syndrom, a population at high risk for AD. Participants were 254 non-demented adults with Down syndrome, 30-78 years of age. Genomic deoxyribonucleic acid was genotyped using an Illumina GoldenGate custom array. We used linear regression to examine differences in levels of Aβ peptides associated with the number of risk alleles, adjusting for age, sex, level of intellectual disability, race and/or ethnicity, and the presence of the APOE ε4 allele. For Aβ42 levels, the strongest gene-wise association was found for a single nucleotide polymorphism (SNP) on CAHLM1; for Aβ40 levels, the strongest gene-wise associations were found for SNPs in IDE and SOD1, while the strongest gene-wise associations with levels of the Aβ42/Aβ40 ratio were found for SNPs in SORCS1. Broadly classified, variants in these genes may influence amyloid precursor protein processing (CALHM1, IDE), vesicular trafficking (SORCS1), and response to oxidative stress (SOD1). Copyright © 2015 Elsevier Inc. All rights reserved.

Genome-Wide SNP Detection, Validation, and Development of an 8K SNP Array for Apple

PubMed Central

Chagné, David; Crowhurst, Ross N.; Troggio, Michela; Davey, Mark W.; Gilmore, Barbara; Lawley, Cindy; Vanderzande, Stijn; Hellens, Roger P.; Kumar, Satish; Cestaro, Alessandro; Velasco, Riccardo; Main, Dorrie; Rees, Jasper D.; Iezzoni, Amy; Mockler, Todd; Wilhelm, Larry; Van de Weg, Eric; Gardiner, Susan E.; Bassil, Nahla; Peace, Cameron

2012-01-01

As high-throughput genetic marker screening systems are essential for a range of genetics studies and plant breeding applications, the International RosBREED SNP Consortium (IRSC) has utilized the Illumina Infinium® II system to develop a medium- to high-throughput SNP screening tool for genome-wide evaluation of allelic variation in apple (Malus×domestica) breeding germplasm. For genome-wide SNP discovery, 27 apple cultivars were chosen to represent worldwide breeding germplasm and re-sequenced at low coverage with the Illumina Genome Analyzer II. Following alignment of these sequences to the whole genome sequence of ‘Golden Delicious’, SNPs were identified using SoapSNP. A total of 2,113,120 SNPs were detected, corresponding to one SNP to every 288 bp of the genome. The Illumina GoldenGate® assay was then used to validate a subset of 144 SNPs with a range of characteristics, using a set of 160 apple accessions. This validation assay enabled fine-tuning of the final subset of SNPs for the Illumina Infinium® II system. The set of stringent filtering criteria developed allowed choice of a set of SNPs that not only exhibited an even distribution across the apple genome and a range of minor allele frequencies to ensure utility across germplasm, but also were located in putative exonic regions to maximize genotyping success rate. A total of 7867 apple SNPs was established for the IRSC apple 8K SNP array v1, of which 5554 were polymorphic after evaluation in segregating families and a germplasm collection. This publicly available genomics resource will provide an unprecedented resolution of SNP haplotypes, which will enable marker-locus-trait association discovery, description of the genetic architecture of quantitative traits, investigation of genetic variation (neutral and functional), and genomic selection in apple. PMID:22363718

A SNP resource for Douglas-fir: de novo transcriptome assembly and SNP detection and validation.

PubMed

Howe, Glenn T; Yu, Jianbin; Knaus, Brian; Cronn, Richard; Kolpak, Scott; Dolan, Peter; Lorenz, W Walter; Dean, Jeffrey F D

2013-02-28

Douglas-fir (Pseudotsuga menziesii), one of the most economically and ecologically important tree species in the world, also has one of the largest tree breeding programs. Although the coastal and interior varieties of Douglas-fir (vars. menziesii and glauca) are native to North America, the coastal variety is also widely planted for timber production in Europe, New Zealand, Australia, and Chile. Our main goal was to develop a SNP resource large enough to facilitate genomic selection in Douglas-fir breeding programs. To accomplish this, we developed a 454-based reference transcriptome for coastal Douglas-fir, annotated and evaluated the quality of the reference, identified putative SNPs, and then validated a sample of those SNPs using the Illumina Infinium genotyping platform. We assembled a reference transcriptome consisting of 25,002 isogroups (unique gene models) and 102,623 singletons from 2.76 million 454 and Sanger cDNA sequences from coastal Douglas-fir. We identified 278,979 unique SNPs by mapping the 454 and Sanger sequences to the reference, and by mapping four datasets of Illumina cDNA sequences from multiple seed sources, genotypes, and tissues. The Illumina datasets represented coastal Douglas-fir (64.00 and 13.41 million reads), interior Douglas-fir (80.45 million reads), and a Yakima population similar to interior Douglas-fir (8.99 million reads). We assayed 8067 SNPs on 260 trees using an Illumina Infinium SNP genotyping array. Of these SNPs, 5847 (72.5%) were called successfully and were polymorphic. Based on our validation efficiency, our SNP database may contain as many as ~200,000 true SNPs, and as many as ~69,000 SNPs that could be genotyped at ~20,000 gene loci using an Infinium II array-more SNPs than are needed to use genomic selection in tree breeding programs. Ultimately, these genomic resources will enhance Douglas-fir breeding and allow us to better understand landscape-scale patterns of genetic variation and potential responses to climate change.

Design of a bovine low-density SNP array optimized for imputation

USDA-ARS?s Scientific Manuscript database

The Illumina BovineLD BeadChip was designed to support imputation to higher density genotypes in dairy and beef breeds by including single-nucleotide polymorphisms (SNPs) that had a high minor allele frequency as well as uniform spacing across the genome except at the ends of the chromosome where de...

Performance comparison of SNP detection tools with illumina exome sequencing data—an assessment using both family pedigree information and sample-matched SNP array data

PubMed Central

Yi, Ming; Zhao, Yongmei; Jia, Li; He, Mei; Kebebew, Electron; Stephens, Robert M.

2014-01-01

To apply exome-seq-derived variants in the clinical setting, there is an urgent need to identify the best variant caller(s) from a large collection of available options. We have used an Illumina exome-seq dataset as a benchmark, with two validation scenarios—family pedigree information and SNP array data for the same samples, permitting global high-throughput cross-validation, to evaluate the quality of SNP calls derived from several popular variant discovery tools from both the open-source and commercial communities using a set of designated quality metrics. To the best of our knowledge, this is the first large-scale performance comparison of exome-seq variant discovery tools using high-throughput validation with both Mendelian inheritance checking and SNP array data, which allows us to gain insights into the accuracy of SNP calling through such high-throughput validation in an unprecedented way, whereas the previously reported comparison studies have only assessed concordance of these tools without directly assessing the quality of the derived SNPs. More importantly, the main purpose of our study was to establish a reusable procedure that applies high-throughput validation to compare the quality of SNP discovery tools with a focus on exome-seq, which can be used to compare any forthcoming tool(s) of interest. PMID:24831545

Quantitative trait loci markers derived from whole genome sequence data increases the reliability of genomic prediction.

PubMed

Brøndum, R F; Su, G; Janss, L; Sahana, G; Guldbrandtsen, B; Boichard, D; Lund, M S

2015-06-01

This study investigated the effect on the reliability of genomic prediction when a small number of significant variants from single marker analysis based on whole genome sequence data were added to the regular 54k single nucleotide polymorphism (SNP) array data. The extra markers were selected with the aim of augmenting the custom low-density Illumina BovineLD SNP chip (San Diego, CA) used in the Nordic countries. The single-marker analysis was done breed-wise on all 16 index traits included in the breeding goals for Nordic Holstein, Danish Jersey, and Nordic Red cattle plus the total merit index itself. Depending on the trait's economic weight, 15, 10, or 5 quantitative trait loci (QTL) were selected per trait per breed and 3 to 5 markers were selected to tag each QTL. After removing duplicate markers (same marker selected for more than one trait or breed) and filtering for high pairwise linkage disequilibrium and assaying performance on the array, a total of 1,623 QTL markers were selected for inclusion on the custom chip. Genomic prediction analyses were performed for Nordic and French Holstein and Nordic Red animals using either a genomic BLUP or a Bayesian variable selection model. When using the genomic BLUP model including the QTL markers in the analysis, reliability was increased by up to 4 percentage points for production traits in Nordic Holstein animals, up to 3 percentage points for Nordic Reds, and up to 5 percentage points for French Holstein. Smaller gains of up to 1 percentage point was observed for mastitis, but only a 0.5 percentage point increase was seen for fertility. When using a Bayesian model accuracies were generally higher with only 54k data compared with the genomic BLUP approach, but increases in reliability were relatively smaller when QTL markers were included. Results from this study indicate that the reliability of genomic prediction can be increased by including markers significant in genome-wide association studies on whole genome sequence data alongside the 54k SNP set. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

ChAMP: updated methylation analysis pipeline for Illumina BeadChips.

PubMed

Tian, Yuan; Morris, Tiffany J; Webster, Amy P; Yang, Zhen; Beck, Stephan; Feber, Andrew; Teschendorff, Andrew E

2017-12-15

The Illumina Infinium HumanMethylationEPIC BeadChip is the new platform for high-throughput DNA methylation analysis, effectively doubling the coverage compared to the older 450 K array. Here we present a significantly updated and improved version of the Bioconductor package ChAMP, which can be used to analyze EPIC and 450k data. Many enhanced functionalities have been added, including correction for cell-type heterogeneity, network analysis and a series of interactive graphical user interfaces. ChAMP is a BioC package available from https://bioconductor.org/packages/release/bioc/html/ChAMP.html. a.teschendorff@ucl.ac.uk or s.beck@ucl.ac.uk or a.feber@ucl.ac.uk. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Coverage and efficiency in current SNP chips

PubMed Central

Ha, Ngoc-Thuy; Freytag, Saskia; Bickeboeller, Heike

2014-01-01

To answer the question as to which commercial high-density SNP chip covers most of the human genome given a fixed budget, we compared the performance of 12 chips of different sizes released by Affymetrix and Illumina for the European, Asian, and African populations. These include Affymetrix' relatively new population-optimized arrays, whose SNP sets are each tailored toward a specific ethnicity. Our evaluation of the chips included the use of two measures, efficiency and cost–benefit ratio, which we developed as supplements to genetic coverage. Unlike coverage, these measures factor in the price of a chip or its substitute size (number of SNPs on chip), allowing comparisons to be drawn between differently priced chips. In this fashion, we identified the Affymetrix population-optimized arrays as offering the most cost-effective coverage for the Asian and African population. For the European population, we established the Illumina Human Omni 2.5-8 as the preferred choice. Interestingly, the Affymetrix chip tailored toward an Eastern Asian subpopulation performed well for all three populations investigated. However, our coverage estimates calculated for all chips proved much lower than those advertised by the producers. All our analyses were based on the 1000 Genome Project as reference population. PMID:24448550

Custom ceramic microchannel-cooled array for high-power fiber-coupled application

NASA Astrophysics Data System (ADS)

Junghans, Jeremy; Feeler, Ryan; Stephens, Ed

2018-03-01

A low-SWaP (Size, Weight and Power) diode array has been developed for a high-power fiber-coupled application. High efficiency ( 65%) diodes enable high optical powers while minimizing thermal losses. A large amount of waste heat is still generated and must be extracted. Custom ceramic microchannel-coolers (MCCs) are used to dissipate the waste heat. The custom ceramic MCC was designed to accommodate long cavity length diodes and micro-lenses. The coolers provide similar thermal performance as copper MCCs however they are not susceptible to erosion and can be cooled with standard filtered water. The custom ceramic micro-channel cooled array was designed to be a form/fit replacement for an existing copperbased solution. Each array consisted of three-vertically stacked MCCs with 4 mm CL, 976 nm diodes and beamshaping micro-optics. The erosion and corrosion resistance of ceramic array is intended to mitigate the risk of copperbased MCC corrosion failures. Elimination of the water delivery requirements (pH, resistivity and dissolved oxygen control) further reduces the system SWaP while maintaining reliability. The arrays were fabricated and fully characterized. This work discusses the advantages of the ceramic MCC technology and describes the design parameters that were tailored for the fiber-coupled application. Additional configuration options (form/fit, micro-lensing, alternate coolants, etc.) and on-going design improvements are also discussed.

Identification of a single nucleotide polymorphism indicative of high risk in acute myocardial infarction

PubMed Central

Shalia, Kavita; Saranath, Dhananjaya; Rayar, Jaipreet; Shah, Vinod K.; Mashru, Manoj R.; Soneji, Surendra L.

2017-01-01

Background & objectives: Acute myocardial infarction (AMI) is a major health concern in India. The aim of the study was to identify single nucleotide polymorphisms (SNPs) associated with AMI in patients using dedicated chip and validating the identified SNPs on custom-designed chips using high-throughput microarray analysis. Methods: In pilot phase, 48 AMI patients and 48 healthy controls were screened for SNPs using human CVD55K BeadChip with 48,472 SNP probes on Illumina high-throughput microarray platform. The identified SNPs were validated by genotyping additional 160 patients and 179 controls using custom-made Illumina VeraCode GoldenGate Genotyping Assay. Analysis was carried out using PLINK software. Results: From the pilot phase, 98 SNPs present on 94 genes were identified with increased risk of AMI (odds ratio of 1.84-8.85, P=0.04861-0.003337). Five of these SNPs demonstrated association with AMI in the validation phase (P<0.05). Among these, one SNP rs9978223 on interferon gamma receptor 2 [IFNGR2, interferon (IFN)-gamma transducer 1] gene showed a significant association (P=0.00021) with AMI below Bonferroni corrected P value (P=0.00061). IFNGR2 is the second subunit of the receptor for IFN-gamma, an important cytokine in inflammatory reactions. Interpretation & conclusions: The study identified an SNP rs9978223 on IFNGR2 gene, associated with increased risk in AMI patient from India. PMID:29434065

Genome-wide association study using a high-density SNP-array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of eNOS

PubMed Central

Salvi, Erika; Kutalik, Zoltán; Glorioso, Nicola; Benaglio, Paola; Frau, Francesca; Kuznetsova, Tatiana; Arima, Hisatomi; Hoggart, Clive; Tichet, Jean; Nikitin, Yury P.; Conti, Costanza; Seidlerova, Jitka; Tikhonoff, Valérie; Stolarz-Skrzypek, Katarzyna; Johnson, Toby; Devos, Nabila; Zagato, Laura; Guarrera, Simonetta; Zaninello, Roberta; Calabria, Andrea; Stancanelli, Benedetta; Troffa, Chiara; Thijs, Lutgarde; Rizzi, Federica; Simonova, Galina; Lupoli, Sara; Argiolas, Giuseppe; Braga, Daniele; D’Alessio, Maria C.; Ortu, Maria F.; Ricceri, Fulvio; Mercurio, Maurizio; Descombes, Patrick; Marconi, Maurizio; Chalmers, John; Harrap, Stephen; Filipovsky, Jan; Bochud, Murielle; Iacoviello, Licia; Ellis, Justine; Stanton, Alice V.; Laan, Maris; Padmanabhan, Sandosh; Dominiczak, Anna F.; Samani, Nilesh J.; Melander, Olle; Jeunemaitre, Xavier; Manunta, Paolo; Shabo, Amnon; Vineis, Paolo; Cappuccio, Francesco P.; Caulfield, Mark J.; Matullo, Giuseppe; Rivolta, Carlo; Munroe, Patricia B.; Barlassina, Cristina; Staessen, Jan A; Beckmann, Jacques S.; Cusi, Daniele

2012-01-01

Essential hypertension is a multi-factorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a two-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1,865 cases and 1,750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1,385 cases and 1,246 controls that were genotyped with a custom array of 14,055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial nitric oxide synthase (eNOS) gene (odds ratio 1.54; 95% CI 1.37-1.73; combined p=2.58·10−13). A meta-analysis, using other in-silico/de novo genotyping data for a total of 21714 subjects, resulted in an overall odds ratio of 1.34 (95% CI 1.25-1.44, p=1.032·10−14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI 0.16-3.66) for systolic and 1.40 (95% CI 0.25-2.55) for diastolic blood pressure. We identified in-silico a potential binding site for ETS transcription-factors directly next to rs3918226, suggesting a potential modulation of eNOS expression. Biological evidence links eNOS with hypertension, as it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus. PMID:22184326

Genome-wide association studies identify four ER negative–specific breast cancer risk loci

PubMed Central

Garcia-Closas, Montserrat; Couch, Fergus J; Lindstrom, Sara; Michailidou, Kyriaki; Schmidt, Marjanka K; Brook, Mark N; orr, Nick; Rhie, Suhn Kyong; Riboli, Elio; Feigelson, Heather s; Le Marchand, Loic; Buring, Julie E; Eccles, Diana; Miron, Penelope; Fasching, Peter A; Brauch, Hiltrud; Chang-Claude, Jenny; Carpenter, Jane; Godwin, Andrew K; Nevanlinna, Heli; Giles, Graham G; Cox, Angela; Hopper, John L; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Dicks, Ed; Howat, Will J; Schoof, Nils; Bojesen, Stig E; Lambrechts, Diether; Broeks, Annegien; Andrulis, Irene L; Guénel, Pascal; Burwinkel, Barbara; Sawyer, Elinor J; Hollestelle, Antoinette; Fletcher, Olivia; Winqvist, Robert; Brenner, Hermann; Mannermaa, Arto; Hamann, Ute; Meindl, Alfons; Lindblom, Annika; Zheng, Wei; Devillee, Peter; Goldberg, Mark S; Lubinski, Jan; Kristensen, Vessela; Swerdlow, Anthony; Anton-Culver, Hoda; Dörk, Thilo; Muir, Kenneth; Matsuo, Keitaro; Wu, Anna H; Radice, Paolo; Teo, Soo Hwang; Shu, Xiao-Ou; Blot, William; Kang, Daehee; Hartman, Mikael; Sangrajrang, Suleeporn; Shen, Chen-Yang; Southey, Melissa C; Park, Daniel J; Hammet, Fleur; Stone, Jennifer; Veer, Laura J Van’t; Rutgers, Emiel J; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Peto, Julian; Schrauder, Michael G; Ekici, Arif B; Beckmann, Matthias W; Silva, Isabel dos Santos; Johnson, Nichola; Warren, Helen; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Marme, Federick; Schneeweiss, Andreas; Sohn, Christof; Truong, Therese; Laurent-Puig, Pierre; Kerbrat, Pierre; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Milne, Roger L; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Müller, Heiko; Arndt, Volker; Stegmaier, Christa; Lichtner, Peter; Lochmann, Magdalena; Justenhoven, Christina; Ko, Yon-Dschun; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Greco, Dario; Heikkinen, Tuomas; Ito, Hidemi; Iwata, Hiroji; Yatabe, Yasushi; Antonenkova, Natalia N; Margolin, Sara; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Balleine, Rosemary; Tseng, Chiu-Chen; Van Den Berg, David; Stram, Daniel O; Neven, Patrick; Dieudonné, Anne-Sophie; Leunen, Karin; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Peterlongo, Paolo; Peissel, Bernard; Bernard, Loris; Olson, Janet E; Wang, Xianshu; Stevens, Kristen; Severi, Gianluca; Baglietto, Laura; Mclean, Catriona; Coetzee, Gerhard A; Feng, Ye; Henderson, Brian E; Schumacher, Fredrick; Bogdanova, Natalia V; Labrèche, France; Dumont, Martine; Yip, Cheng Har; Taib, Nur Aishah Mohd; Cheng, Ching-Yu; Shrubsole, Martha; Long, Jirong; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Tollenaar, Robertus A E M; Seynaeve, Caroline M; Kriege, Mieke; Hooning, Maartje J; Van den Ouweland, Ans M W; Van Deurzen, Carolien H M; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Balasubramanian, Sabapathy P; Cross, Simon S; Reed, Malcolm W R; Signorello, Lisa; Cai, Qiuyin; Shah, Mitul; Miao, Hui; Chan, Ching Wan; Chia, Kee Seng; Jakubowska, Anna; Jaworska, Katarzyna; Durda, Katarzyna; Hsiung, Chia-Ni; Wu, Pei-Ei; Yu, Jyh-Cherng; Ashworth, Alan; Jones, Michael; Tessier, Daniel C; González-Neira, Anna; Pita, Guillermo; Alonso, M Rosario; Vincent, Daniel; Bacot, Francois; Ambrosone, Christine B; Bandera, Elisa V; John, Esther M; Chen, Gary K; Hu, Jennifer J; Rodriguez-gil, Jorge L; Bernstein, Leslie; Press, Michael F; Ziegler, Regina G; Millikan, Robert M; Deming-Halverson, Sandra L; Nyante, Sarah; Ingles, Sue A; Waisfisz, Quinten; Tsimiklis, Helen; Makalic, Enes; Schmidt, Daniel; Bui, Minh; Gibson, Lorna; Müller-Myhsok, Bertram; Schmutzler, Rita K; Hein, Rebecca; Dahmen, Norbert; Beckmann, Lars; Aaltonen, Kirsimari; Czene, Kamila; Irwanto, Astrid; Liu, Jianjun; Turnbull, Clare; Rahman, Nazneen; Meijers-Heijboer, Hanne; Uitterlinden, Andre G; Rivadeneira, Fernando; Olswold, Curtis; Slager, Susan; Pilarski, Robert; Ademuyiwa, Foluso; Konstantopoulou, Irene; Martin, Nicholas G; Montgomery, Grant W; Slamon, Dennis J; Rauh, Claudia; Lux, Michael P; Jud, Sebastian M; Bruning, Thomas; Weaver, Joellen; Sharma, Priyanka; Pathak, Harsh; Tapper, Will; Gerty, Sue; Durcan, Lorraine; Trichopoulos, Dimitrios; Tumino, Rosario; Peeters, Petra H; Kaaks, Rudolf; Campa, Daniele; Canzian, Federico; Weiderpass, Elisabete; Johansson, Mattias; Khaw, Kay-Tee; Travis, Ruth; Clavel-Chapelon, Françoise; Kolonel, Laurence N; Chen, Constance; Beck, Andy; Hankinson, Susan E; Berg, Christine D; Hoover, Robert N; Lissowska, Jolanta; Figueroa, Jonine D; Chasman, Daniel I; Gaudet, Mia M; Diver, W Ryan; Willett, Walter C; Hunter, David J; Simard, Jacques; Benitez, Javier; Dunning, Alison M; Sherman, Mark E; Chenevix-Trench, Georgia; Chanock, Stephen J; Hall, Per; Pharoah, Paul D P; Vachon, Celine; Easton, Douglas F; Haiman, Christopher A; Kraft, Peter

2013-01-01

Estrogen receptor (ER)-negative tumors represent 20–30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry1. The etiology2 and clinical behavior3 of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition4. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10−12 and LGR6, P = 1.4 × 10−8), 2p24.1 (P = 4.6 × 10−8) and 16q12.2 (FTO, P = 4.0 × 10−8), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers. PMID:23535733

Using stereotactic brain atlases for small rodents and nonhuman primates for optrode array customization

NASA Astrophysics Data System (ADS)

Boutte, Ronald W.; Merlin, Sam; Griffiths, Brandon; Parry, Trent; Blair, Steve

2017-02-01

As the optogenetic field expands its need to target with high specificity only grows more crucial. This work will show a method for customizing soda-lime glass optrode arrays so that fine structures within the brains of small rodents and nonhuman primates can be optically interrogated below the outer cortical layer. An 8 × 6 array is customized for optrode length (400 μm ), optrode width (75 μm ), optrode pitch (400 μm ), backplane thickness (500 μm ), and overall form factor (3.45 mm × 2.65 mm ). The 400 μm long optrode is capable of illuminating the cortical Layer IV of rhesus macaque ( Macaca Fascicularis ) and the motor cortex of small mice ( Mus Musculus ).

Paternal sperm DNA methylation associated with early signs of autism risk in an autism-enriched cohort.

PubMed

Feinberg, Jason I; Bakulski, Kelly M; Jaffe, Andrew E; Tryggvadottir, Rakel; Brown, Shannon C; Goldman, Lynn R; Croen, Lisa A; Hertz-Picciotto, Irva; Newschaffer, Craig J; Fallin, M Daniele; Feinberg, Andrew P

2015-08-01

Epigenetic mechanisms such as altered DNA methylation have been suggested to play a role in autism, beginning with the classical association of Prader-Willi syndrome, an imprinting disorder, with autistic features. Here we tested for the relationship of paternal sperm DNA methylation with autism risk in offspring, examining an enriched-risk cohort of fathers of autistic children. We examined genome-wide DNA methylation (DNAm) in paternal semen biosamples obtained from an autism spectrum disorder (ASD) enriched-risk pregnancy cohort, the Early Autism Risk Longitudinal Investigation (EARLI) cohort, to estimate associations between sperm DNAm and prospective ASD development, using a 12-month ASD symptoms assessment, the Autism Observation Scale for Infants (AOSI). We analysed methylation data from 44 sperm samples run on the CHARM 3.0 array, which contains over 4 million probes (over 7 million CpG sites), including 30 samples also run on the Illumina Infinium HumanMethylation450 (450K) BeadChip platform (∼485 000 CpG sites). We also examined associated regions in an independent sample of post-mortem human brain ASD and control samples for which Illumina 450K DNA methylation data were available. Using region-based statistical approaches, we identified 193 differentially methylated regions (DMRs) in paternal sperm with a family-wise empirical P-value [family-wise error rate (FWER)] <0.05 associated with performance on the Autism Observational Scale for Infants (AOSI) at 12 months of age in offspring. The DMRs clustered near genes involved in developmental processes, including many genes in the SNORD family, within the Prader-Willi syndrome gene cluster. These results were consistent among the 75 probes on the Illumina 450K array that cover AOSI-associated DMRs from CHARM. Further, 18 of 75 (24%) 450K array probes showed consistent differences in the cerebellums of autistic individuals compared with controls. These data suggest that epigenetic differences in paternal sperm may contribute to autism risk in offspring, and provide evidence that directionally consistent, potentially related epigenetic mechanisms may be operating in the cerebellum of individuals with autism. © The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

missMethyl: an R package for analyzing data from Illumina's HumanMethylation450 platform.

PubMed

Phipson, Belinda; Maksimovic, Jovana; Oshlack, Alicia

2016-01-15

DNA methylation is one of the most commonly studied epigenetic modifications due to its role in both disease and development. The Illumina HumanMethylation450 BeadChip is a cost-effective way to profile >450 000 CpGs across the human genome, making it a popular platform for profiling DNA methylation. Here we introduce missMethyl, an R package with a suite of tools for performing normalization, removal of unwanted variation in differential methylation analysis, differential variability testing and gene set analysis for the 450K array. missMethyl is an R package available from the Bioconductor project at www.bioconductor.org. alicia.oshlack@mcri.edu.au Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Jllumina - A comprehensive Java-based API for statistical Illumina Infinium HumanMethylation450 and Infinium MethylationEPIC BeadChip data processing.

PubMed

Almeida, Diogo; Skov, Ida; Lund, Jesper; Mohammadnejad, Afsaneh; Silva, Artur; Vandin, Fabio; Tan, Qihua; Baumbach, Jan; Röttger, Richard

2016-10-01

Measuring differential methylation of the DNA is the nowadays most common approach to linking epigenetic modifications to diseases (called epigenome-wide association studies, EWAS). For its low cost, its efficiency and easy handling, the Illumina HumanMethylation450 BeadChip and its successor, the Infinium MethylationEPIC BeadChip, is the by far most popular techniques for conduction EWAS in large patient cohorts. Despite the popularity of this chip technology, raw data processing and statistical analysis of the array data remains far from trivial and still lacks dedicated software libraries enabling high quality and statistically sound downstream analyses. As of yet, only R-based solutions are freely available for low-level processing of the Illumina chip data. However, the lack of alternative libraries poses a hurdle for the development of new bioinformatic tools, in particular when it comes to web services or applications where run time and memory consumption matter, or EWAS data analysis is an integrative part of a bigger framework or data analysis pipeline. We have therefore developed and implemented Jllumina, an open-source Java library for raw data manipulation of Illumina Infinium HumanMethylation450 and Infinium MethylationEPIC BeadChip data, supporting the developer with Java functions covering reading and preprocessing the raw data, down to statistical assessment, permutation tests, and identification of differentially methylated loci. Jllumina is fully parallelizable and publicly available at http://dimmer.compbio.sdu.dk/download.html.

Jllumina - A comprehensive Java-based API for statistical Illumina Infinium HumanMethylation450 and MethylationEPIC data processing.

PubMed

Almeida, Diogo; Skov, Ida; Lund, Jesper; Mohammadnejad, Afsaneh; Silva, Artur; Vandin, Fabio; Tan, Qihua; Baumbach, Jan; Röttger, Richard

2016-12-18

Measuring differential methylation of the DNA is the nowadays most common approach to linking epigenetic modifications to diseases (called epigenome-wide association studies, EWAS). For its low cost, its efficiency and easy handling, the Illumina HumanMethylation450 BeadChip and its successor, the Infinium MethylationEPIC BeadChip, is the by far most popular techniques for conduction EWAS in large patient cohorts. Despite the popularity of this chip technology, raw data processing and statistical analysis of the array data remains far from trivial and still lacks dedicated software libraries enabling high quality and statistically sound downstream analyses. As of yet, only R-based solutions are freely available for low-level processing of the Illumina chip data. However, the lack of alternative libraries poses a hurdle for the development of new bioinformatic tools, in particular when it comes to web services or applications where run time and memory consumption matter, or EWAS data analysis is an integrative part of a bigger framework or data analysis pipeline. We have therefore developed and implemented Jllumina, an open-source Java library for raw data manipulation of Illumina Infinium HumanMethylation450 and Infinium MethylationEPIC BeadChip data, supporting the developer with Java functions covering reading and preprocessing the raw data, down to statistical assessment, permutation tests, and identification of differentially methylated loci. Jllumina is fully parallelizable and publicly available at http://dimmer.compbio.sdu.dk/download.html.

Development and Evaluation of a Genome-Wide 6K SNP Array for Diploid Sweet Cherry and Tetraploid Sour Cherry

PubMed Central

Peace, Cameron; Bassil, Nahla; Main, Dorrie; Ficklin, Stephen; Rosyara, Umesh R.; Stegmeir, Travis; Sebolt, Audrey; Gilmore, Barbara; Lawley, Cindy; Mockler, Todd C.; Bryant, Douglas W.; Wilhelm, Larry; Iezzoni, Amy

2012-01-01

High-throughput genome scans are important tools for genetic studies and breeding applications. Here, a 6K SNP array for use with the Illumina Infinium® system was developed for diploid sweet cherry (Prunus avium) and allotetraploid sour cherry (P. cerasus). This effort was led by RosBREED, a community initiative to enable marker-assisted breeding for rosaceous crops. Next-generation sequencing in diverse breeding germplasm provided 25 billion basepairs (Gb) of cherry DNA sequence from which were identified genome-wide SNPs for sweet cherry and for the two sour cherry subgenomes derived from sweet cherry (avium subgenome) and P. fruticosa (fruticosa subgenome). Anchoring to the peach genome sequence, recently released by the International Peach Genome Initiative, predicted relative physical locations of the 1.9 million putative SNPs detected, preliminarily filtered to 368,943 SNPs. Further filtering was guided by results of a 144-SNP subset examined with the Illumina GoldenGate® assay on 160 accessions. A 6K Infinium® II array was designed with SNPs evenly spaced genetically across the sweet and sour cherry genomes. SNPs were developed for each sour cherry subgenome by using minor allele frequency in the sour cherry detection panel to enrich for subgenome-specific SNPs followed by targeting to either subgenome according to alleles observed in sweet cherry. The array was evaluated using panels of sweet (n = 269) and sour (n = 330) cherry breeding germplasm. Approximately one third of array SNPs were informative for each crop. A total of 1825 polymorphic SNPs were verified in sweet cherry, 13% of these originally developed for sour cherry. Allele dosage was resolved for 2058 polymorphic SNPs in sour cherry, one third of these being originally developed for sweet cherry. This publicly available genomics resource represents a significant advance in cherry genome-scanning capability that will accelerate marker-locus-trait association discovery, genome structure investigation, and genetic diversity assessment in this diploid-tetraploid crop group. PMID:23284615

Semicustom integrated circuits and the standard transistor array radix (STAR)

NASA Technical Reports Server (NTRS)

Edge, T. M.

1977-01-01

The development, application, pros and cons of the semicustom and custom approach to the integration of circuits are described. Improvements in terms of cost, reliability, secrecy, power, and size reduction are examined. Also presented is the standard transistor array radix, a semicustom approach to digital integrated circuits that offers the advantages of both custom and semicustom approaches to integration.

European Ancestry as a Risk Factor for Atrial Fibrillation in African Americans

PubMed Central

Marcus, Gregory M.; Alonso, Alvaro; Peralta, Carmen A.; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A.; Fox, Ervin R.; Levitzky, Yamini S.; Mehra, Reena; Kerr, Kathleen F.; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T.; Paltoo, Dina N.; Soliman, Elsayed Z.; Benjamin, Emelia J.; Heckbert, Susan R.

2010-01-01

Background Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown if the higher riskis due to genetic or environmental factors. As African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. Methods and Results We studied whites (n=4,543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10,902) and Africa Americans (n=3,517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3,517). Percent European ancestry in African Americans was estimated using 1,747 ancestry informative markers (AIMs) from the Illumina custom ITMAT-Broad-CARe (IBC) array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3,517 ARIC participants developed incident AF. A meta-analysis from the two studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (HR 1.13, 95% CI 1.03–1.23, p=0.007). After adjusting for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% CI 1.07–1.29, p=0.001). A second analysis using 3,192 AIMs from a genome wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. Conclusion European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative. PMID:21098467

European ancestry as a risk factor for atrial fibrillation in African Americans.

PubMed

Marcus, Gregory M; Alonso, Alvaro; Peralta, Carmen A; Lettre, Guillaume; Vittinghoff, Eric; Lubitz, Steven A; Fox, Ervin R; Levitzky, Yamini S; Mehra, Reena; Kerr, Kathleen F; Deo, Rajat; Sotoodehnia, Nona; Akylbekova, Meggie; Ellinor, Patrick T; Paltoo, Dina N; Soliman, Elsayed Z; Benjamin, Emelia J; Heckbert, Susan R

2010-11-16

Despite a higher burden of standard atrial fibrillation (AF) risk factors, African Americans have a lower risk of AF than whites. It is unknown whether the higher risk is due to genetic or environmental factors. Because African Americans have varying degrees of European ancestry, we sought to test the hypothesis that European ancestry is an independent risk factor for AF. We studied whites (n=4543) and African Americans (n=822) in the Cardiovascular Health Study (CHS) and whites (n=10 902) and African Americans (n=3517) in the Atherosclerosis Risk in Communities (ARIC) Study (n=3517). Percent European ancestry in African Americans was estimated with 1747 ancestry informative markers from the Illumina custom ITMAT-Broad-CARe array. Among African Americans without baseline AF, 120 of 804 CHS participants and 181 of 3517 ARIC participants developed incident AF. A meta-analysis from the 2 studies revealed that every 10% increase in European ancestry increased the risk of AF by 13% (hazard ratio, 1.13; 95% confidence interval, 1.03 to 1.23; P=0.007). After adjustment for potential confounders, European ancestry remained a predictor of incident AF in each cohort alone, with a combined estimated hazard ratio for each 10% increase in European ancestry of 1.17 (95% confidence interval, 1.07 to 1.29; P=0.001). A second analysis using 3192 ancestry informative markers from a genome-wide Affymetrix 6.0 array in ARIC African Americans yielded similar results. European ancestry predicted risk of incident AF. Our study suggests that investigating genetic variants contributing to differential AF risk in individuals of African versus European ancestry will be informative.

Investigation of rare and low-frequency variants using high-throughput sequencing with pooled DNA samples

PubMed Central

Wang, Jingwen; Skoog, Tiina; Einarsdottir, Elisabet; Kaartokallio, Tea; Laivuori, Hannele; Grauers, Anna; Gerdhem, Paul; Hytönen, Marjo; Lohi, Hannes; Kere, Juha; Jiao, Hong

2016-01-01

High-throughput sequencing using pooled DNA samples can facilitate genome-wide studies on rare and low-frequency variants in a large population. Some major questions concerning the pooling sequencing strategy are whether rare and low-frequency variants can be detected reliably, and whether estimated minor allele frequencies (MAFs) can represent the actual values obtained from individually genotyped samples. In this study, we evaluated MAF estimates using three variant detection tools with two sets of pooled whole exome sequencing (WES) and one set of pooled whole genome sequencing (WGS) data. Both GATK and Freebayes displayed high sensitivity, specificity and accuracy when detecting rare or low-frequency variants. For the WGS study, 56% of the low-frequency variants in Illumina array have identical MAFs and 26% have one allele difference between sequencing and individual genotyping data. The MAF estimates from WGS correlated well (r = 0.94) with those from Illumina arrays. The MAFs from the pooled WES data also showed high concordance (r = 0.88) with those from the individual genotyping data. In conclusion, the MAFs estimated from pooled DNA sequencing data reflect the MAFs in individually genotyped samples well. The pooling strategy can thus be a rapid and cost-effective approach for the initial screening in large-scale association studies. PMID:27633116

Artificial Muscle (AM) Cilia Array for Underwater Systems

DTIC Science & Technology

2016-12-15

structures, including cilia-like structures. Specifically, a custom 3D printer was created that utilizes custom-made Nafion filament for 30 printing of custom... printing ) of IPMC material to create custom-shaped AM structures, including cilia-like structures. Various custom-shaped AM structures were fabricated via...integrating square cross-section IPMC actuators with a printed circuit board power delivery system. IV. Concise Accomplishments Performance

PipeCraft: Flexible open-source toolkit for bioinformatics analysis of custom high-throughput amplicon sequencing data.

PubMed

Anslan, Sten; Bahram, Mohammad; Hiiesalu, Indrek; Tedersoo, Leho

2017-11-01

High-throughput sequencing methods have become a routine analysis tool in environmental sciences as well as in public and private sector. These methods provide vast amount of data, which need to be analysed in several steps. Although the bioinformatics may be applied using several public tools, many analytical pipelines allow too few options for the optimal analysis for more complicated or customized designs. Here, we introduce PipeCraft, a flexible and handy bioinformatics pipeline with a user-friendly graphical interface that links several public tools for analysing amplicon sequencing data. Users are able to customize the pipeline by selecting the most suitable tools and options to process raw sequences from Illumina, Pacific Biosciences, Ion Torrent and Roche 454 sequencing platforms. We described the design and options of PipeCraft and evaluated its performance by analysing the data sets from three different sequencing platforms. We demonstrated that PipeCraft is able to process large data sets within 24 hr. The graphical user interface and the automated links between various bioinformatics tools enable easy customization of the workflow. All analytical steps and options are recorded in log files and are easily traceable. © 2017 John Wiley & Sons Ltd.

Forward-Looking Intracardiac Ultrasound Imaging Using a 1-D CMUT Array Integrated With Custom Front-End Electronics

PubMed Central

Nikoozadeh, Amin; Wygant, Ira O.; Lin, Der-Song; Oralkan, Ömer; Ergun, A. Sanlı; Stephens, Douglas N.; Thomenius, Kai E.; Dentinger, Aaron M.; Wildes, Douglas; Akopyan, Gina; Shivkumar, Kalyanam; Mahajan, Aman; Sahn, David J.; Khuri-Yakub, Butrus T.

2009-01-01

Minimally invasive catheter-based electrophysiological (EP) interventions are becoming a standard procedure in diagnosis and treatment of cardiac arrhythmias. As a result of technological advances that enable small feature sizes and a high level of integration, nonfluoroscopic intracardiac echocardiography (ICE) imaging catheters are attracting increasing attention. ICE catheters improve EP procedural guidance while reducing the undesirable use of fluoroscopy, which is currently the common catheter guidance method. Phased-array ICE catheters have been in use for several years now, although only for side-looking imaging. We are developing a forward-looking ICE catheter for improved visualization. In this effort, we fabricate a 24-element, fine-pitch 1-D array of capacitive micromachined ultrasonic transducers (CMUT), with a total footprint of 1.73 mm × 1.27 mm. We also design a custom integrated circuit (IC) composed of 24 identical blocks of transmit/receive circuitry, measuring 2.1 mm × 2.1 mm. The transmit circuitry is capable of delivering 25-V unipolar pulses, and the receive circuitry includes a transimpedance preamplifier followed by an output buffer. The CMUT array and the custom IC are designed to be mounted at the tip of a 10-Fr catheter for high-frame-rate forward-looking intracardiac imaging. Through-wafer vias incorporated in the CMUT array provide access to individual array elements from the back side of the array. We successfully flip-chip bond a CMUT array to the custom IC with 100% yield. We coat the device with a layer of polydimethylsiloxane (PDMS) to electrically isolate the device for imaging in water and tissue. The pulse-echo in water from a total plane reflector has a center frequency of 9.2 MHz with a 96% fractional bandwidth. Finally, we demonstrate the imaging capability of the integrated device on commercial phantoms and on a beating ex vivo rabbit heart (Langendorff model) using a commercial ultrasound imaging system. PMID:19126489

ECL gate array with integrated PLL-based clock recovery and synthesis for high-speed data and telecom applications

NASA Astrophysics Data System (ADS)

Rosky, David S.; Coy, Bruce H.; Friedmann, Marc D.

1992-03-01

A 2500 gate mixed signal gate array has been developed that integrates custom PLL-based clock recovery and clock synthesis functions with 2500 gates of configurable logic cells to provide a single chip solution for 200 - 1244 MHz fiber based digital interface applications. By customizing the digital logic cells, any of the popular telecom and datacom standards may be implemented.

Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.

EPA Science Inventory

To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norwa...

Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications.

PubMed

Cresswell, George D; Apps, John R; Chagtai, Tasnim; Mifsud, Borbala; Bentley, Christopher C; Maschietto, Mariana; Popov, Sergey D; Weeks, Mark E; Olsen, Øystein E; Sebire, Neil J; Pritchard-Jones, Kathy; Luscombe, Nicholas M; Williams, Richard D; Mifsud, William

2016-07-01

The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH) in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA) are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT); current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Next generation diagnostics of cystic fibrosis and CFTR-related disorders by targeted multiplex high-coverage resequencing of CFTR.

PubMed

Trujillano, D; Ramos, M D; González, J; Tornador, C; Sotillo, F; Escaramis, G; Ossowski, S; Armengol, L; Casals, T; Estivill, X

2013-07-01

Here we have developed a novel and much more efficient strategy for the complete molecular characterisation of the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, based on multiplexed targeted resequencing. We have tested this approach in a cohort of 92 samples with previously characterised CFTR mutations and polymorphisms. After enrichment of the pooled barcoded DNA libraries with a custom NimbleGen SeqCap EZ Choice array (Roche) and sequencing with a HiSeq2000 (Illumina) sequencer, we applied several bioinformatics tools to call mutations and polymorphisms in CFTR. The combination of several bioinformatics tools allowed us to detect all known pathogenic variants (point mutations, short insertions/deletions, and large genomic rearrangements) and polymorphisms (including the poly-T and poly-thymidine-guanine polymorphic tracts) in the 92 samples. In addition, we report the precise characterisation of the breakpoints of seven genomic rearrangements in CFTR, including those of a novel deletion of exon 22 and a complex 85 kb inversion which includes two large deletions affecting exons 4-8 and 12-21, respectively. This work is a proof-of-principle that targeted resequencing is an accurate and cost-effective approach for the genetic testing of CF and CFTR-related disorders (ie, male infertility) amenable to the routine clinical practice, and ready to substitute classical molecular methods in medical genetics.

75 FR 55303 - Proposed Information Collection; Comment Request; Commercial Service Annual Customer Satisfaction...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

... Request; Commercial Service Annual Customer Satisfaction Survey AGENCY: International Trade Administration... assistance services. The CS uses an Annual Customer Satisfaction Survey to measure client's overall satisfaction with the full array of services and experiences they have had with the CS on an annual basis. The...

The impact of methylation quantitative trait loci (mQTLs) on active smoking-related DNA methylation changes.

PubMed

Gao, Xu; Thomsen, Hauke; Zhang, Yan; Breitling, Lutz Philipp; Brenner, Hermann

2017-01-01

Methylation quantitative trait loci (mQTLs) are the genetic variants that may affect the DNA methylation patterns of CpG sites. However, their roles in influencing the disturbances of smoking-related epigenetic changes have not been well established. This study was conducted to address whether mQTLs exist in the vicinity of smoking-related CpG sites (± 50 kb) and to examine their associations with smoking exposure and all-cause mortality in older adults. We obtained DNA methylation profiles in whole blood samples by Illumina Infinium Human Methylation 450 BeadChip array of two independent subsamples of the ESTHER study (discovery set, n  = 581; validation set, n  = 368) and their corresponding genotyping data using the Illumina Infinium OncoArray BeadChip. After correction for multiple testing (FDR), we successfully identified that 70 out of 151 previously reported smoking-related CpG sites were significantly associated with 192 SNPs within the 50 kb search window of each locus. The 192 mQTLs significantly influenced the active smoking-related DNA methylation changes, with percentage changes ranging from 0.01 to 18.96%, especially for the weakly/moderately smoking-related CpG sites. However, these identified mQTLs were not directly associated with active smoking exposure or all-cause mortality. Our findings clearly demonstrated that if not dealt with properly, the mQTLs might impair the power of epigenetic-based models of smoking exposure to a certain extent. In addition, such genetic variants could be the key factor to distinguish between the heritable and smoking-induced impact on epigenome disparities. These mQTLs are of special importance when DNA methylation markers measured by Illumina Infinium assay are used for any comparative population studies related to smoking-related cancers and chronic diseases.

Methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern.

PubMed

Philibert, Robert A; Terry, Nicolas; Erwin, Cheryl; Philibert, Winter J; Beach, Steven Rh; Brody, Gene H

2014-01-01

Genome-wide methylation arrays are increasingly used tools in studies of complex medical disorders. Because of their expense and potential utility to the scientific community, current federal policy dictates that data from these arrays, like those from genome-wide genotyping arrays, be deposited in publicly available databases. Unlike the genotyping information, access to the expression data is not restricted. An underlying supposition in the current nonrestricted access to methylation data is the belief that protected health and personal identifying information cannot be simultaneously extracted from these arrays. In this communication, we analyze methylation data from the Illumina HumanMethylation450 array and show that genotype at 1,069 highly informative loci, and both alcohol and smoking consumption information, can be derived from the array data. We conclude that both potentially personally identifying information and substance-use histories can be simultaneously derived from methylation array data. Because access to genetic information about a database subject or one of their relatives is critical to the de-identification process, this risk of de-identification is limited at the current time. We propose that access to genome-wide methylation data be restricted to institutionally approved investigators who accede to data use agreements prohibiting re-identification.

Computationally expanding infinium HumanMethylation450 BeadChip array data to reveal distinct DNA methylation patterns of rheumatoid arthritis

PubMed Central

Li, Chengzhe; Ai, Rizi; Wang, Mengchi; Firestein, Gary S.; Wang, Wei

2016-01-01

Motivation: DNA methylation signatures in rheumatoid arthritis (RA) have been identified in fibroblast-like synoviocytes (FLS) with Illumina HumanMethylation450 array. Since <2% of CpG sites are covered by the Illumina 450K array and whole genome bisulfite sequencing is still too expensive for many samples, computationally predicting DNA methylation levels based on 450K data would be valuable to discover more RA-related genes. Results: We developed a computational model that is trained on 14 tissues with both whole genome bisulfite sequencing and 450K array data. This model integrates information derived from the similarity of local methylation pattern between tissues, the methylation information of flanking CpG sites and the methylation tendency of flanking DNA sequences. The predicted and measured methylation values were highly correlated with a Pearson correlation coefficient of 0.9 in leave-one-tissue-out cross-validations. Importantly, the majority (76%) of the top 10% differentially methylated loci among the 14 tissues was correctly detected using the predicted methylation values. Applying this model to 450K data of RA, osteoarthritis and normal FLS, we successfully expanded the coverage of CpG sites 18.5-fold and accounts for about 30% of all the CpGs in the human genome. By integrative omics study, we identified genes and pathways tightly related to RA pathogenesis, among which 12 genes were supported by triple evidences, including 6 genes already known to perform specific roles in RA and 6 genes as new potential therapeutic targets. Availability and implementation: The source code, required data for prediction, and demo data for test are freely available at: http://wanglab.ucsd.edu/star/LR450K/. Contact: wei-wang@ucsd.edu or gfirestein@ucsd.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26883487

Tomato breeding in the genomics era: insights from a SNP array.

PubMed

Víquez-Zamora, Marcela; Vosman, Ben; van de Geest, Henri; Bovy, Arnaud; Visser, Richard G F; Finkers, Richard; van Heusden, Adriaan W

2013-05-27

The major bottle neck in genetic and linkage studies in tomato has been the lack of a sufficient number of molecular markers. This has radically changed with the application of next generation sequencing and high throughput genotyping. A set of 6000 SNPs was identified and 5528 of them were used to evaluate tomato germplasm at the level of species, varieties and segregating populations. From the 5528 SNPs, 1980 originated from 454-sequencing, 3495 from Illumina Solexa sequencing and 53 were additional known markers. Genotyping different tomato samples allowed the evaluation of the level of heterozygosity and introgressions among commercial varieties. Cherry tomatoes were especially different from round/beefs in chromosomes 4, 5 and 12. We were able to identify a set of 750 unique markers distinguishing S. lycopersicum 'Moneymaker' from all its distantly related wild relatives. Clustering and neighbour joining analysis among varieties and species showed expected grouping patterns, with S. pimpinellifolium as the most closely related to commercial tomatoes earlier results. Our results show that a SNP search in only a few breeding lines already provides generally applicable markers in tomato and its wild relatives. It also shows that the Illumina bead array generated data are highly reproducible. Our SNPs can roughly be divided in two categories: SNPs of which both forms are present in the wild relatives and in domesticated tomatoes (originating from common ancestors) and SNPs unique for the domesticated tomato (originating from after the domestication event). The SNPs can be used for genotyping, identification of varieties, comparison of genetic and physical linkage maps and to confirm (phylogenetic) relations. In the SNPs used for the array there is hardly any overlap with the SolCAP array and it is strongly recommended to combine both SNP sets and to select a core collection of robust SNPs completely covering the entire tomato genome.

RCP: a novel probe design bias correction method for Illumina Methylation BeadChip.

PubMed

Niu, Liang; Xu, Zongli; Taylor, Jack A

2016-09-01

The Illumina HumanMethylation450 BeadChip has been extensively utilized in epigenome-wide association studies. This array and its successor, the MethylationEPIC array, use two types of probes-Infinium I (type I) and Infinium II (type II)-in order to increase genome coverage but differences in probe chemistries result in different type I and II distributions of methylation values. Ignoring the difference in distributions between the two probe types may bias downstream analysis. Here, we developed a novel method, called Regression on Correlated Probes (RCP), which uses the existing correlation between pairs of nearby type I and II probes to adjust the beta values of all type II probes. We evaluate the effect of this adjustment on reducing probe design type bias, reducing technical variation in duplicate samples, improving accuracy of measurements against known standards, and retention of biological signal. We find that RCP is statistically significantly better than unadjusted data or adjustment with alternative methods including SWAN and BMIQ. We incorporated the method into the R package ENmix, which is freely available from the Bioconductor website (https://www.bioconductor.org/packages/release/bioc/html/ENmix.html). niulg@ucmail.uc.edu Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

78 FR 69018 - Improving the Resiliency of Mobile Wireless Communications Networks; Reliability and Continuity...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... offer their customers an increasing array of ``smartphones'' and data-centric devices, such as tablets... basis to provide service to their customers? 38. Additionally, the proposal would allow providers to... customers with comparable levels of service within that county? 40. Second, will consumers find this metric...

Motion camera based on a custom vision sensor and an FPGA architecture

NASA Astrophysics Data System (ADS)

Arias-Estrada, Miguel

1998-09-01

A digital camera for custom focal plane arrays was developed. The camera allows the test and development of analog or mixed-mode arrays for focal plane processing. The camera is used with a custom sensor for motion detection to implement a motion computation system. The custom focal plane sensor detects moving edges at the pixel level using analog VLSI techniques. The sensor communicates motion events using the event-address protocol associated to a temporal reference. In a second stage, a coprocessing architecture based on a field programmable gate array (FPGA) computes the time-of-travel between adjacent pixels. The FPGA allows rapid prototyping and flexible architecture development. Furthermore, the FPGA interfaces the sensor to a compact PC computer which is used for high level control and data communication to the local network. The camera could be used in applications such as self-guided vehicles, mobile robotics and smart surveillance systems. The programmability of the FPGA allows the exploration of further signal processing like spatial edge detection or image segmentation tasks. The article details the motion algorithm, the sensor architecture, the use of the event- address protocol for velocity vector computation and the FPGA architecture used in the motion camera system.

The optics inside an automated single molecule array analyzer

NASA Astrophysics Data System (ADS)

McGuigan, William; Fournier, David R.; Watson, Gary W.; Walling, Les; Gigante, Bill; Duffy, David C.; Rissin, David M.; Kan, Cheuk W.; Meyer, Raymond E.; Piech, Tomasz; Fishburn, Matthew W.

2014-02-01

Quanterix and Stratec Biomedical have developed an instrument that enables the automated measurement of multiple proteins at concentration ~1000 times lower than existing immunoassays. The instrument is based on Quanterix's proprietary Single Molecule Array technology (Simoa™ ) that facilitates the detection and quantification of biomarkers previously difficult to measure, thus opening up new applications in life science research and in-vitro diagnostics. Simoa is based on trapping individual beads in arrays of femtoliter-sized wells that, when imaged with sufficient resolution, allows for counting of single molecules associated with each bead. When used to capture and detect proteins, this approach is known as digital ELISA (Enzyme-linked immunosorbent assay). The platform developed is a merger of many science and engineering disciplines. This paper concentrates on the optical technologies that have enabled the development of a fully-automated single molecule analyzer. At the core of the system is a custom, wide field-of-view, fluorescence microscope that images arrays of microwells containing single molecules bound to magnetic beads. A consumable disc containing 24 microstructure arrays was developed previously in collaboration with Sony DADC. The system cadence requirements, array dimensions, and requirement to detect single molecules presented significant optical challenges. Specifically, the wide field-of-view needed to image the entire array resulted in the need for a custom objective lens. Additionally, cost considerations for the system required a custom solution that leveraged the image processing capabilities. This paper will discuss the design considerations and resultant optical architecture that has enabled the development of an automated digital ELISA platform.

Design automation techniques for custom LSI arrays

NASA Technical Reports Server (NTRS)

Feller, A.

1975-01-01

The standard cell design automation technique is described as an approach for generating random logic PMOS, CMOS or CMOS/SOS custom large scale integration arrays with low initial nonrecurring costs and quick turnaround time or design cycle. The system is composed of predesigned circuit functions or cells and computer programs capable of automatic placement and interconnection of the cells in accordance with an input data net list. The program generates a set of instructions to drive an automatic precision artwork generator. A series of support design automation and simulation programs are described, including programs for verifying correctness of the logic on the arrays, performing dc and dynamic analysis of MOS devices, and generating test sequences.

A Single Multiplex crRNA Array for FnCpf1-Mediated Human Genome Editing.

PubMed

Sun, Huihui; Li, Fanfan; Liu, Jie; Yang, Fayu; Zeng, Zhenhai; Lv, Xiujuan; Tu, Mengjun; Liu, Yeqing; Ge, Xianglian; Liu, Changbao; Zhao, Junzhao; Zhang, Zongduan; Qu, Jia; Song, Zongming; Gu, Feng

2018-06-15

Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy. However, there are no reports at present that show FnCpf1-mediated multiplex genome editing via a single customized CRISPR RNA (crRNA) array. In the present study, we utilize a single customized crRNA array to simultaneously target multiple genes in human cells. In addition, we also demonstrate that a single customized crRNA array to target multiple sites in one gene could be achieved. Collectively, FnCpf1, a powerful genome-editing tool for multiple genomic targets, can be harnessed for effective manipulation of the human genome. Copyright © 2018 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Genome-Wide Mapping of Copy Number Variation in Humans: Comparative Analysis of High Resolution Array Platforms

PubMed Central

Haraksingh, Rajini R.; Abyzov, Alexej; Gerstein, Mark; Urban, Alexander E.; Snyder, Michael

2011-01-01

Accurate and efficient genome-wide detection of copy number variants (CNVs) is essential for understanding human genomic variation, genome-wide CNV association type studies, cytogenetics research and diagnostics, and independent validation of CNVs identified from sequencing based technologies. Numerous, array-based platforms for CNV detection exist utilizing array Comparative Genome Hybridization (aCGH), Single Nucleotide Polymorphism (SNP) genotyping or both. We have quantitatively assessed the abilities of twelve leading genome-wide CNV detection platforms to accurately detect Gold Standard sets of CNVs in the genome of HapMap CEU sample NA12878, and found significant differences in performance. The technologies analyzed were the NimbleGen 4.2 M, 2.1 M and 3×720 K Whole Genome and CNV focused arrays, the Agilent 1×1 M CGH and High Resolution and 2×400 K CNV and SNP+CGH arrays, the Illumina Human Omni1Quad array and the Affymetrix SNP 6.0 array. The Gold Standards used were a 1000 Genomes Project sequencing-based set of 3997 validated CNVs and an ultra high-resolution aCGH-based set of 756 validated CNVs. We found that sensitivity, total number, size range and breakpoint resolution of CNV calls were highest for CNV focused arrays. Our results are important for cost effective CNV detection and validation for both basic and clinical applications. PMID:22140474

A 4×8-Gbps VCSEL array driver ASIC and integration with a custom array transmitter module for the LHC front-end transmission

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

Guo, Di; Liu, Chonghan; Chen, Jinghong

This paper describes the design, fabrication and experiment results of a 4×8-Gbps Vertical-Cavity Surface-Emitting Laser (VCSEL) array driver ASIC with the adjustable active-shunt peaking technique and the novel balanced output structure under the Silicon-on-Sapphire (SOS) process, and a custom array optical transmitter module, featuring a compact size of 10 mm×15 mm×5.3 mm. Both the array driver ASIC and the module have been fully tested after integration as a complete parallel transmitter. Optical eye diagram of each channel passes the eye mask at 8 Gbps/ch with adjacent channel working simultaneously with a power consumption of 150 mW/ch. As a result, themore » optical transmission of Bit-Error Rate (BER) less than 10E-12 is achieved at an aggregated data rate of 4×8-Gbps.« less

A 4×8-Gbps VCSEL array driver ASIC and integration with a custom array transmitter module for the LHC front-end transmission

DOE PAGES

Guo, Di; Liu, Chonghan; Chen, Jinghong; ...

2016-03-21

This paper describes the design, fabrication and experiment results of a 4×8-Gbps Vertical-Cavity Surface-Emitting Laser (VCSEL) array driver ASIC with the adjustable active-shunt peaking technique and the novel balanced output structure under the Silicon-on-Sapphire (SOS) process, and a custom array optical transmitter module, featuring a compact size of 10 mm×15 mm×5.3 mm. Both the array driver ASIC and the module have been fully tested after integration as a complete parallel transmitter. Optical eye diagram of each channel passes the eye mask at 8 Gbps/ch with adjacent channel working simultaneously with a power consumption of 150 mW/ch. As a result, themore » optical transmission of Bit-Error Rate (BER) less than 10E-12 is achieved at an aggregated data rate of 4×8-Gbps.« less

CMOS array design automation techniques. [metal oxide semiconductors

NASA Technical Reports Server (NTRS)

Ramondetta, P.; Feller, A.; Noto, R.; Lombardi, T.

1975-01-01

A low cost, quick turnaround technique for generating custom metal oxide semiconductor arrays using the standard cell approach was developed, implemented, tested and validated. Basic cell design topology and guidelines are defined based on an extensive analysis that includes circuit, layout, process, array topology and required performance considerations particularly high circuit speed.

Agreement in DNA methylation levels from the Illumina 450K array across batches, tissues, and time

PubMed Central

Forest, Marie; O'Donnell, Kieran J.; Voisin, Greg; Gaudreau, Helene; MacIsaac, Julia L.; McEwen, Lisa M.; Silveira, Patricia P.; Steiner, Meir; Kobor, Michael S.; Meaney, Michael J.; Greenwood, Celia M.T.

2018-01-01

ABSTRACT Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array. Redundancy analysis enabled visual assessment of agreement of replicate samples overall and showed good agreement after removing effects of tissue type, age, and sex. At the probe level, analysis of variance contrasts separating technical and biological replicates clearly showed better agreement between technical replicates versus longitudinal samples, and suggested increased stability for buccal cells versus blood or blood spots. Intraclass correlations (ICCs) demonstrated that inter-individual variability is of similar magnitude to within-sample variability at many probes; however, as inter-individual variability increased, so did ICC. Furthermore, we were able to demonstrate decreasing agreement in methylation levels with time, despite a maximal sampling interval of only 576 days. Finally, at 6 popular candidate genes, there was a large range of stability across probes. Our findings highlight important sources of technical and biological variation in DNA methylation across different tissues over time. These data will help to inform longitudinal sampling strategies of future EWAS. PMID:29381404

A 2-Stage Genome-Wide Association Study to Identify Single Nucleotide Polymorphisms Associated With Development of Erectile Dysfunction Following Radiation Therapy for Prostate Cancer

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

Kerns, Sarah L.; Departments of Pathology and Genetics, Albert Einstein College of Medicine, Bronx, New York; Stock, Richard

2013-01-01

Purpose: To identify single nucleotide polymorphisms (SNPs) associated with development of erectile dysfunction (ED) among prostate cancer patients treated with radiation therapy. Methods and Materials: A 2-stage genome-wide association study was performed. Patients were split randomly into a stage I discovery cohort (132 cases, 103 controls) and a stage II replication cohort (128 cases, 102 controls). The discovery cohort was genotyped using Affymetrix 6.0 genome-wide arrays. The 940 top ranking SNPs selected from the discovery cohort were genotyped in the replication cohort using Illumina iSelect custom SNP arrays. Results: Twelve SNPs identified in the discovery cohort and validated in themore » replication cohort were associated with development of ED following radiation therapy (Fisher combined P values 2.1 Multiplication-Sign 10{sup -5} to 6.2 Multiplication-Sign 10{sup -4}). Notably, these 12 SNPs lie in or near genes involved in erectile function or other normal cellular functions (adhesion and signaling) rather than DNA damage repair. In a multivariable model including nongenetic risk factors, the odds ratios for these SNPs ranged from 1.6 to 5.6 in the pooled cohort. There was a striking relationship between the cumulative number of SNP risk alleles an individual possessed and ED status (Sommers' D P value = 1.7 Multiplication-Sign 10{sup -29}). A 1-allele increase in cumulative SNP score increased the odds for developing ED by a factor of 2.2 (P value = 2.1 Multiplication-Sign 10{sup -19}). The cumulative SNP score model had a sensitivity of 84% and specificity of 75% for prediction of developing ED at the radiation therapy planning stage. Conclusions: This genome-wide association study identified a set of SNPs that are associated with development of ED following radiation therapy. These candidate genetic predictors warrant more definitive validation in an independent cohort.« less

Differences in candidate gene association between European ancestry and African American asthmatic children.

PubMed

Baye, Tesfaye M; Butsch Kovacic, Melinda; Biagini Myers, Jocelyn M; Martin, Lisa J; Lindsey, Mark; Patterson, Tia L; He, Hua; Ericksen, Mark B; Gupta, Jayanta; Tsoras, Anna M; Lindsley, Andrew; Rothenberg, Marc E; Wills-Karp, Marsha; Eissa, N Tony; Borish, Larry; Khurana Hershey, Gurjit K

2011-02-28

Candidate gene case-control studies have identified several single nucleotide polymorphisms (SNPs) that are associated with asthma susceptibility. Most of these studies have been restricted to evaluations of specific SNPs within a single gene and within populations from European ancestry. Recently, there is increasing interest in understanding racial differences in genetic risk associated with childhood asthma. Our aim was to compare association patterns of asthma candidate genes between children of European and African ancestry. Using a custom-designed Illumina SNP array, we genotyped 1,485 children within the Greater Cincinnati Pediatric Clinic Repository and Cincinnati Genomic Control Cohort for 259 SNPs in 28 genes and evaluated their associations with asthma. We identified 14 SNPs located in 6 genes that were significantly associated (p-values <0.05) with childhood asthma in African Americans. Among Caucasians, 13 SNPs in 5 genes were associated with childhood asthma. Two SNPs in IL4 were associated with asthma in both races (p-values <0.05). Gene-gene interaction studies identified race specific sets of genes that best discriminate between asthmatic children and non-allergic controls. We identified IL4 as having a role in asthma susceptibility in both African American and Caucasian children. However, while IL4 SNPs were associated with asthma in asthmatic children with European and African ancestry, the relative contributions of the most replicated asthma-associated SNPs varied by ancestry. These data provides valuable insights into the pathways that may predispose to asthma in individuals with European vs. African ancestry.

Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer.

PubMed

Bojesen, Stig E; Pooley, Karen A; Johnatty, Sharon E; Beesley, Jonathan; Michailidou, Kyriaki; Tyrer, Jonathan P; Edwards, Stacey L; Pickett, Hilda A; Shen, Howard C; Smart, Chanel E; Hillman, Kristine M; Mai, Phuong L; Lawrenson, Kate; Stutz, Michael D; Lu, Yi; Karevan, Rod; Woods, Nicholas; Johnston, Rebecca L; French, Juliet D; Chen, Xiaoqing; Weischer, Maren; Nielsen, Sune F; Maranian, Melanie J; Ghoussaini, Maya; Ahmed, Shahana; Baynes, Caroline; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; McGuffog, Lesley; Barrowdale, Daniel; Lee, Andrew; Healey, Sue; Lush, Michael; Tessier, Daniel C; Vincent, Daniel; Bacot, Françis; Vergote, Ignace; Lambrechts, Sandrina; Despierre, Evelyn; Risch, Harvey A; González-Neira, Anna; Rossing, Mary Anne; Pita, Guillermo; Doherty, Jennifer A; Alvarez, Nuria; Larson, Melissa C; Fridley, Brooke L; Schoof, Nils; Chang-Claude, Jenny; Cicek, Mine S; Peto, Julian; Kalli, Kimberly R; Broeks, Annegien; Armasu, Sebastian M; Schmidt, Marjanka K; Braaf, Linde M; Winterhoff, Boris; Nevanlinna, Heli; Konecny, Gottfried E; Lambrechts, Diether; Rogmann, Lisa; Guénel, Pascal; Teoman, Attila; Milne, Roger L; Garcia, Joaquin J; Cox, Angela; Shridhar, Vijayalakshmi; Burwinkel, Barbara; Marme, Frederik; Hein, Rebecca; Sawyer, Elinor J; Haiman, Christopher A; Wang-Gohrke, Shan; Andrulis, Irene L; Moysich, Kirsten B; Hopper, John L; Odunsi, Kunle; Lindblom, Annika; Giles, Graham G; Brenner, Hermann; Simard, Jacques; Lurie, Galina; Fasching, Peter A; Carney, Michael E; Radice, Paolo; Wilkens, Lynne R; Swerdlow, Anthony; Goodman, Marc T; Brauch, Hiltrud; Garcia-Closas, Montserrat; Hillemanns, Peter; Winqvist, Robert; Dürst, Matthias; Devilee, Peter; Runnebaum, Ingo; Jakubowska, Anna; Lubinski, Jan; Mannermaa, Arto; Butzow, Ralf; Bogdanova, Natalia V; Dörk, Thilo; Pelttari, Liisa M; Zheng, Wei; Leminen, Arto; Anton-Culver, Hoda; Bunker, Clareann H; Kristensen, Vessela; Ness, Roberta B; Muir, Kenneth; Edwards, Robert; Meindl, Alfons; Heitz, Florian; Matsuo, Keitaro; du Bois, Andreas; Wu, Anna H; Harter, Philipp; Teo, Soo-Hwang; Schwaab, Ira; Shu, Xiao-Ou; Blot, William; Hosono, Satoyo; Kang, Daehee; Nakanishi, Toru; Hartman, Mikael; Yatabe, Yasushi; Hamann, Ute; Karlan, Beth Y; Sangrajrang, Suleeporn; Kjaer, Susanne Krüger; Gaborieau, Valerie; Jensen, Allan; Eccles, Diana; Høgdall, Estrid; Shen, Chen-Yang; Brown, Judith; Woo, Yin Ling; Shah, Mitul; Azmi, Mat Adenan Noor; Luben, Robert; Omar, Siti Zawiah; Czene, Kamila; Vierkant, Robert A; Nordestgaard, Børge G; Flyger, Henrik; Vachon, Celine; Olson, Janet E; Wang, Xianshu; Levine, Douglas A; Rudolph, Anja; Weber, Rachel Palmieri; Flesch-Janys, Dieter; Iversen, Edwin; Nickels, Stefan; Schildkraut, Joellen M; Silva, Isabel Dos Santos; Cramer, Daniel W; Gibson, Lorna; Terry, Kathryn L; Fletcher, Olivia; Vitonis, Allison F; van der Schoot, C Ellen; Poole, Elizabeth M; Hogervorst, Frans B L; Tworoger, Shelley S; Liu, Jianjun; Bandera, Elisa V; Li, Jingmei; Olson, Sara H; Humphreys, Keith; Orlow, Irene; Blomqvist, Carl; Rodriguez-Rodriguez, Lorna; Aittomäki, Kristiina; Salvesen, Helga B; Muranen, Taru A; Wik, Elisabeth; Brouwers, Barbara; Krakstad, Camilla; Wauters, Els; Halle, Mari K; Wildiers, Hans; Kiemeney, Lambertus A; Mulot, Claire; Aben, Katja K; Laurent-Puig, Pierre; Altena, Anne Mvan; Truong, Thérèse; Massuger, Leon F A G; Benitez, Javier; Pejovic, Tanja; Perez, Jose Ignacio Arias; Hoatlin, Maureen; Zamora, M Pilar; Cook, Linda S; Balasubramanian, Sabapathy P; Kelemen, Linda E; Schneeweiss, Andreas; Le, Nhu D; Sohn, Christof; Brooks-Wilson, Angela; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Cybulski, Cezary; Henderson, Brian E; Menkiszak, Janusz; Schumacher, Fredrick; Wentzensen, Nicolas; Le Marchand, Loic; Yang, Hannah P; Mulligan, Anna Marie; Glendon, Gord; Engelholm, Svend Aage; Knight, Julia A; Høgdall, Claus K; Apicella, Carmel; Gore, Martin; Tsimiklis, Helen; Song, Honglin; Southey, Melissa C; Jager, Agnes; den Ouweland, Ans M Wvan; Brown, Robert; Martens, John W M; Flanagan, James M; Kriege, Mieke; Paul, James; Margolin, Sara; Siddiqui, Nadeem; Severi, Gianluca; Whittemore, Alice S; Baglietto, Laura; McGuire, Valerie; Stegmaier, Christa; Sieh, Weiva; Müller, Heiko; Arndt, Volker; Labrèche, France; Gao, Yu-Tang; Goldberg, Mark S; Yang, Gong; Dumont, Martine; McLaughlin, John R; Hartmann, Arndt; Ekici, Arif B; Beckmann, Matthias W; Phelan, Catherine M; Lux, Michael P; Permuth-Wey, Jenny; Peissel, Bernard; Sellers, Thomas A; Ficarazzi, Filomena; Barile, Monica; Ziogas, Argyrios; Ashworth, Alan; Gentry-Maharaj, Aleksandra; Jones, Michael; Ramus, Susan J; Orr, Nick; Menon, Usha; Pearce, Celeste L; Brüning, Thomas; Pike, Malcolm C; Ko, Yon-Dschun; Lissowska, Jolanta; Figueroa, Jonine; Kupryjanczyk, Jolanta; Chanock, Stephen J; Dansonka-Mieszkowska, Agnieszka; Jukkola-Vuorinen, Arja; Rzepecka, Iwona K; Pylkäs, Katri; Bidzinski, Mariusz; Kauppila, Saila; Hollestelle, Antoinette; Seynaeve, Caroline; Tollenaar, Rob A E M; Durda, Katarzyna; Jaworska, Katarzyna; Hartikainen, Jaana M; Kosma, Veli-Matti; Kataja, Vesa; Antonenkova, Natalia N; Long, Jirong; Shrubsole, Martha; Deming-Halverson, Sandra; Lophatananon, Artitaya; Siriwanarangsan, Pornthep; Stewart-Brown, Sarah; Ditsch, Nina; Lichtner, Peter; Schmutzler, Rita K; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Tseng, Chiu-Chen; Stram, Daniel O; van den Berg, David; Yip, Cheng Har; Ikram, M Kamran; Teh, Yew-Ching; Cai, Hui; Lu, Wei; Signorello, Lisa B; Cai, Qiuyin; Noh, Dong-Young; Yoo, Keun-Young; Miao, Hui; Iau, Philip Tsau-Choong; Teo, Yik Ying; McKay, James; Shapiro, Charles; Ademuyiwa, Foluso; Fountzilas, George; Hsiung, Chia-Ni; Yu, Jyh-Cherng; Hou, Ming-Feng; Healey, Catherine S; Luccarini, Craig; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Rebbeck, Timothy R; Piedmonte, Marion; Singer, Christian F; Friedman, Eitan; Thomassen, Mads; Offit, Kenneth; Hansen, Thomas V O; Neuhausen, Susan L; Szabo, Csilla I; Blanco, Ignacio; Garber, Judy; Narod, Steven A; Weitzel, Jeffrey N; Montagna, Marco; Olah, Edith; Godwin, Andrew K; Yannoukakos, Drakoulis; Goldgar, David E; Caldes, Trinidad; Imyanitov, Evgeny N; Tihomirova, Laima; Arun, Banu K; Campbell, Ian; Mensenkamp, Arjen R; van Asperen, Christi J; van Roozendaal, Kees E P; Meijers-Heijboer, Hanne; Collée, J Margriet; Oosterwijk, Jan C; Hooning, Maartje J; Rookus, Matti A; van der Luijt, Rob B; Os, Theo A Mvan; Evans, D Gareth; Frost, Debra; Fineberg, Elena; Barwell, Julian; Walker, Lisa; Kennedy, M John; Platte, Radka; Davidson, Rosemarie; Ellis, Steve D; Cole, Trevor; Bressac-de Paillerets, Brigitte; Buecher, Bruno; Damiola, Francesca; Faivre, Laurence; Frenay, Marc; Sinilnikova, Olga M; Caron, Olivier; Giraud, Sophie; Mazoyer, Sylvie; Bonadona, Valérie; Caux-Moncoutier, Virginie; Toloczko-Grabarek, Aleksandra; Gronwald, Jacek; Byrski, Tomasz; Spurdle, Amanda B; Bonanni, Bernardo; Zaffaroni, Daniela; Giannini, Giuseppe; Bernard, Loris; Dolcetti, Riccardo; Manoukian, Siranoush; Arnold, Norbert; Engel, Christoph; Deissler, Helmut; Rhiem, Kerstin; Niederacher, Dieter; Plendl, Hansjoerg; Sutter, Christian; Wappenschmidt, Barbara; Borg, Ake; Melin, Beatrice; Rantala, Johanna; Soller, Maria; Nathanson, Katherine L; Domchek, Susan M; Rodriguez, Gustavo C; Salani, Ritu; Kaulich, Daphne Gschwantler; Tea, Muy-Kheng; Paluch, Shani Shimon; Laitman, Yael; Skytte, Anne-Bine; Kruse, Torben A; Jensen, Uffe Birk; Robson, Mark; Gerdes, Anne-Marie; Ejlertsen, Bent; Foretova, Lenka; Savage, Sharon A; Lester, Jenny; Soucy, Penny; Kuchenbaecker, Karoline B; Olswold, Curtis; Cunningham, Julie M; Slager, Susan; Pankratz, Vernon S; Dicks, Ed; Lakhani, Sunil R; Couch, Fergus J; Hall, Per; Monteiro, Alvaro N A; Gayther, Simon A; Pharoah, Paul D P; Reddel, Roger R; Goode, Ellen L; Greene, Mark H; Easton, Douglas F; Berchuck, Andrew; Antoniou, Antonis C; Chenevix-Trench, Georgia; Dunning, Alison M

2013-04-01

TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.

Developing a gate-array capability at a research and development laboratory

NASA Astrophysics Data System (ADS)

Balch, J. W.; Current, K. W.; Magnuson, W. G., Jr.; Pocha, M. D.

1983-03-01

Experiences in developing a gate array capability for low volume applications in a research and development (R and D) laboratory are described. By purchasing unfinished wafers and doing the customization steps in-house. Turnaround time was shortened to as little as one week and the direct costs reduced to as low as $5K per design. Designs generally require fast turnaround (a few weeks to a few months) and very low volumes (1 to 25). Design costs must be kept at a minimum. After reviewing available commercial gate array design and fabrication services, it was determined that objectives would best be met by using existing internal integrated circuit fabrication facilities, the COMPUTERVISION interactive graphics layout system, and extensive computational capabilities. The reasons and the approach taken for; selection for a particular gate array wafer, adapting a particular logic simulation program, and how layout aids were enhanced are discussed. Testing of the customized chips is described. The content, schedule, and results of the internal gate array course recently completed are discussed. Finally, problem areas and near term plans are presented.

A SNP resource for Douglas-fir: de novo transcriptome assembly and SNP detection and validation

PubMed Central

2013-01-01

Background Douglas-fir (Pseudotsuga menziesii), one of the most economically and ecologically important tree species in the world, also has one of the largest tree breeding programs. Although the coastal and interior varieties of Douglas-fir (vars. menziesii and glauca) are native to North America, the coastal variety is also widely planted for timber production in Europe, New Zealand, Australia, and Chile. Our main goal was to develop a SNP resource large enough to facilitate genomic selection in Douglas-fir breeding programs. To accomplish this, we developed a 454-based reference transcriptome for coastal Douglas-fir, annotated and evaluated the quality of the reference, identified putative SNPs, and then validated a sample of those SNPs using the Illumina Infinium genotyping platform. Results We assembled a reference transcriptome consisting of 25,002 isogroups (unique gene models) and 102,623 singletons from 2.76 million 454 and Sanger cDNA sequences from coastal Douglas-fir. We identified 278,979 unique SNPs by mapping the 454 and Sanger sequences to the reference, and by mapping four datasets of Illumina cDNA sequences from multiple seed sources, genotypes, and tissues. The Illumina datasets represented coastal Douglas-fir (64.00 and 13.41 million reads), interior Douglas-fir (80.45 million reads), and a Yakima population similar to interior Douglas-fir (8.99 million reads). We assayed 8067 SNPs on 260 trees using an Illumina Infinium SNP genotyping array. Of these SNPs, 5847 (72.5%) were called successfully and were polymorphic. Conclusions Based on our validation efficiency, our SNP database may contain as many as ~200,000 true SNPs, and as many as ~69,000 SNPs that could be genotyped at ~20,000 gene loci using an Infinium II array—more SNPs than are needed to use genomic selection in tree breeding programs. Ultimately, these genomic resources will enhance Douglas-fir breeding and allow us to better understand landscape-scale patterns of genetic variation and potential responses to climate change. PMID:23445355

GLINT: a user-friendly toolset for the analysis of high-throughput DNA-methylation array data.

PubMed

Rahmani, Elior; Yedidim, Reut; Shenhav, Liat; Schweiger, Regev; Weissbrod, Omer; Zaitlen, Noah; Halperin, Eran

2017-06-15

GLINT is a user-friendly command-line toolset for fast analysis of genome-wide DNA methylation data generated using the Illumina human methylation arrays. GLINT, which does not require any programming proficiency, allows an easy execution of Epigenome-Wide Association Study analysis pipeline under different models while accounting for known confounders in methylation data. GLINT is a command-line software, freely available at https://github.com/cozygene/glint/releases . It requires Python 2.7 and several freely available Python packages. Further information and documentation as well as a quick start tutorial are available at http://glint-epigenetics.readthedocs.io . elior.rahmani@gmail.com or ehalperin@cs.ucla.edu. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

A Larger Chocolate Chip-Development of a 15K Theobroma cacao L. SNP Array to Create High-Density Linkage Maps.

PubMed

Livingstone, Donald; Stack, Conrad; Mustiga, Guiliana M; Rodezno, Dayana C; Suarez, Carmen; Amores, Freddy; Feltus, Frank A; Mockaitis, Keithanne; Cornejo, Omar E; Motamayor, Juan C

2017-01-01

Cacao ( Theobroma cacao L.) is an important cash crop in tropical regions around the world and has a rich agronomic history in South America. As a key component in the cosmetic and confectionary industries, millions of people worldwide use products made from cacao, ranging from shampoo to chocolate. An Illumina Infinity II array was created using 13,530 SNPs identified within a small diversity panel of cacao. Of these SNPs, 12,643 derive from variation within annotated cacao genes. The genotypes of 3,072 trees were obtained, including two mapping populations from Ecuador. High-density linkage maps for these two populations were generated and compared to the cacao genome assembly. Phenotypic data from these populations were combined with the linkage maps to identify the QTLs for yield and disease resistance.

A group arrival retrial G - queue with multi optional stages of service, orbital search and server breakdown

NASA Astrophysics Data System (ADS)

Radha, J.; Indhira, K.; Chandrasekaran, V. M.

2017-11-01

A group arrival feedback retrial queue with k optional stages of service and orbital search policy is studied. Any arriving group of customer finds the server free, one from the group enters into the first stage of service and the rest of the group join into the orbit. After completion of the i th stage of service, the customer under service may have the option to choose (i+1)th stage of service with θi probability, with pI probability may join into orbit as feedback customer or may leave the system with {q}i=≤ft\\{\\begin{array}{l}1-{p}i-{θ }i,i=1,2,\\cdots k-1\\ 1-{p}i,i=k\\end{array}\\right\\} probability. Busy server may get to breakdown due to the arrival of negative customers and the service channel will fail for a short interval of time. At the completion of service or repair, the server searches for the customer in the orbit (if any) with probability α or remains idle with probability 1-α. By using the supplementary variable method, steady state probability generating function for system size, some system performance measures are discussed.

Low SWaP multispectral sensors using dichroic filter arrays

NASA Astrophysics Data System (ADS)

Dougherty, John; Varghese, Ron

2015-06-01

The benefits of multispectral imaging are well established in a variety of applications including remote sensing, authentication, satellite and aerial surveillance, machine vision, biomedical, and other scientific and industrial uses. However, many of the potential solutions require more compact, robust, and cost-effective cameras to realize these benefits. The next generation of multispectral sensors and cameras needs to deliver improvements in size, weight, power, portability, and spectral band customization to support widespread deployment for a variety of purpose-built aerial, unmanned, and scientific applications. A novel implementation uses micro-patterning of dichroic filters1 into Bayer and custom mosaics, enabling true real-time multispectral imaging with simultaneous multi-band image acquisition. Consistent with color image processing, individual spectral channels are de-mosaiced with each channel providing an image of the field of view. This approach can be implemented across a variety of wavelength ranges and on a variety of detector types including linear, area, silicon, and InGaAs. This dichroic filter array approach can also reduce payloads and increase range for unmanned systems, with the capability to support both handheld and autonomous systems. Recent examples and results of 4 band RGB + NIR dichroic filter arrays in multispectral cameras are discussed. Benefits and tradeoffs of multispectral sensors using dichroic filter arrays are compared with alternative approaches - including their passivity, spectral range, customization options, and scalable production.

Flexible Integration of Both High Imaging Resolution and High Power Arrays for Ultrasound-Induced Thermal Strain Imaging (US-TSI)

PubMed Central

Stephens, Douglas N.; Mahmoud, Ahmed M.; Ding, Xuan; Lucero, Steven; Dutta, Debaditya; Yu, Francois T.H.; Chen, Xucai

2013-01-01

Ultrasound-induced thermal strain imaging (US-TSI) for carotid artery plaque detection requires both high imaging resolution (<100 μm) and sufficient US induced heating to elevate the tissue temperature (~1-3°C within 1-3 cardiac cycles) in order to produce a noticeable change in sound speed in the targeted tissues. Since the optimization of both imaging and heating in a monolithic array design is particularly expensive and inflexible, a new integrated approach is presented that utilizes independent ultrasound arrays to meet the requirements for this particular application. This work demonstrates a new approach in dual-array construction. A 3D printed manifold was built to support both a high resolution 20 MHz commercial imaging array and 6 custom heating elements operating in the 3.5-4 MHz range. For the application of US-TSI on carotid plaque characterization, the tissue target site is 20 to 30 mm deep, with a typical target volume of 2 mm (elevation) × 8 mm (azimuthal) × 5 mm (depth). The custom heating array performance was fully characterized for two design variants (flat and spherical apertures), and can easily deliver 30 W of total acoustic power to produce intensities greater than 15 W/cm2 in tissue target region. PMID:24297029

Design of a 9K illumina BeadChip for polar bears (Ursus maritimus) from RAD and transcriptome sequencing.

PubMed

Malenfant, René M; Coltman, David W; Davis, Corey S

2015-05-01

Single-nucleotide polymorphisms (SNPs) offer numerous advantages over anonymous markers such as microsatellites, including improved estimation of population parameters, finer-scale resolution of population structure and more precise genomic dissection of quantitative traits. However, many SNPs are needed to equal the resolution of a single microsatellite, and reliable large-scale genotyping of SNPs remains a challenge in nonmodel species. Here, we document the creation of a 9K Illumina Infinium BeadChip for polar bears (Ursus maritimus), which will be used to investigate: (i) the fine-scale population structure among Canadian polar bears and (ii) the genomic architecture of phenotypic traits in the Western Hudson Bay subpopulation. To this end, we used restriction-site associated DNA (RAD) sequencing from 38 bears across their circumpolar range, as well as blood/fat transcriptome sequencing of 10 individuals from Western Hudson Bay. Six-thousand RAD SNPs and 3000 transcriptomic SNPs were selected for the chip, based primarily on genomic spacing and gene function respectively. Of the 9000 SNPs ordered from Illumina, 8042 were successfully printed, and - after genotyping 1450 polar bears - 5441 of these SNPs were found to be well clustered and polymorphic. Using this array, we show rapid linkage disequilibrium decay among polar bears, we demonstrate that in a subsample of 78 individuals, our SNPs detect known genetic structure more clearly than 24 microsatellites genotyped for the same individuals and that these results are not driven by the SNP ascertainment scheme. Here, we present one of the first large-scale genotyping resources designed for a threatened species. © 2014 John Wiley & Sons Ltd.

A Larger Chocolate Chip—Development of a 15K Theobroma cacao L. SNP Array to Create High-Density Linkage Maps

PubMed Central

Livingstone, Donald; Stack, Conrad; Mustiga, Guiliana M.; Rodezno, Dayana C.; Suarez, Carmen; Amores, Freddy; Feltus, Frank A.; Mockaitis, Keithanne; Cornejo, Omar E.; Motamayor, Juan C.

2017-01-01

Cacao (Theobroma cacao L.) is an important cash crop in tropical regions around the world and has a rich agronomic history in South America. As a key component in the cosmetic and confectionary industries, millions of people worldwide use products made from cacao, ranging from shampoo to chocolate. An Illumina Infinity II array was created using 13,530 SNPs identified within a small diversity panel of cacao. Of these SNPs, 12,643 derive from variation within annotated cacao genes. The genotypes of 3,072 trees were obtained, including two mapping populations from Ecuador. High-density linkage maps for these two populations were generated and compared to the cacao genome assembly. Phenotypic data from these populations were combined with the linkage maps to identify the QTLs for yield and disease resistance. PMID:29259608

Base resolution methylome profiling: considerations in platform selection, data preprocessing and analysis

PubMed Central

Sun, Zhifu; Cunningham, Julie; Slager, Susan; Kocher, Jean-Pierre

2015-01-01

Bisulfite treatment-based methylation microarray (mainly Illumina 450K Infinium array) and next-generation sequencing (reduced representation bisulfite sequencing, Agilent SureSelect Human Methyl-Seq, NimbleGen SeqCap Epi CpGiant or whole-genome bisulfite sequencing) are commonly used for base resolution DNA methylome research. Although multiple tools and methods have been developed and used for the data preprocessing and analysis, confusions remains for these platforms including how and whether the 450k array should be normalized; which platform should be used to better fit researchers’ needs; and which statistical models would be more appropriate for differential methylation analysis. This review presents the commonly used platforms and compares the pros and cons of each in methylome profiling. We then discuss approaches to study design, data normalization, bias correction and model selection for differentially methylated individual CpGs and regions. PMID:26366945

ArrayNinja: An Open Source Platform for Unified Planning and Analysis of Microarray Experiments.

PubMed

Dickson, B M; Cornett, E M; Ramjan, Z; Rothbart, S B

2016-01-01

Microarray-based proteomic platforms have emerged as valuable tools for studying various aspects of protein function, particularly in the field of chromatin biochemistry. Microarray technology itself is largely unrestricted in regard to printable material and platform design, and efficient multidimensional optimization of assay parameters requires fluidity in the design and analysis of custom print layouts. This motivates the need for streamlined software infrastructure that facilitates the combined planning and analysis of custom microarray experiments. To this end, we have developed ArrayNinja as a portable, open source, and interactive application that unifies the planning and visualization of microarray experiments and provides maximum flexibility to end users. Array experiments can be planned, stored to a private database, and merged with the imaged results for a level of data interaction and centralization that is not currently attainable with available microarray informatics tools. © 2016 Elsevier Inc. All rights reserved.

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)

PubMed Central

Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Alonso, M. Rosario; Andrulis, Irene L.; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W.; Benitez, Javier; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M.; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F.; Fasching, Peter A.; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G.; Goldberg, Mark S.; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A.; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L.; Muir, Kenneth; Neuhausen, Susan L.; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schmutzler, Rita K.; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C.; Stram, Daniel O.; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H.; Tessier, Daniel C.; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M.; Vincent, Daniel; Winqvist, Robert; Wu, Anna H.; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D. P.; Hall, Per; Edwards, Stacey L.; Simard, Jacques; French, Juliet D.; Chenevix-Trench, Georgia; Dunning, Alison M.

2016-01-01

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90–0.94; P = 8.96 × 10−15)) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10−09, r2 = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10−11, r2 = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus. PMID:27600471

Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs).

PubMed

Darabi, Hatef; Beesley, Jonathan; Droit, Arnaud; Kar, Siddhartha; Nord, Silje; Moradi Marjaneh, Mahdi; Soucy, Penny; Michailidou, Kyriaki; Ghoussaini, Maya; Fues Wahl, Hanna; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Alonso, M Rosario; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier; Bogdanova, Natalia V; Bojesen, Stig E; Brauch, Hiltrud; Brenner, Hermann; Broeks, Annegien; Brüning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Choi, Ji-Yeob; Conroy, Don M; Couch, Fergus J; Cox, Angela; Cross, Simon S; Czene, Kamila; Devilee, Peter; Dörk, Thilo; Easton, Douglas F; Fasching, Peter A; Figueroa, Jonine; Fletcher, Olivia; Flyger, Henrik; Galle, Eva; García-Closas, Montserrat; Giles, Graham G; Goldberg, Mark S; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A; Hallberg, Emily; Hamann, Ute; Hartman, Mikael; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jakubowska, Anna; Johnson, Nichola; Kang, Daehee; Khan, Sofia; Kosma, Veli-Matti; Kriege, Mieke; Kristensen, Vessela; Lambrechts, Diether; Le Marchand, Loic; Lee, Soo Chin; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Mannermaa, Arto; Manoukian, Siranoush; Margolin, Sara; Matsuo, Keitaro; Mayes, Rebecca; McKay, James; Meindl, Alfons; Milne, Roger L; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Olswold, Curtis; Orr, Nick; Peterlongo, Paolo; Pita, Guillermo; Pylkäs, Katri; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schmutzler, Rita K; Seynaeve, Caroline; Shah, Mitul; Shen, Chen-Yang; Shu, Xiao-Ou; Southey, Melissa C; Stram, Daniel O; Surowy, Harald; Swerdlow, Anthony; Teo, Soo H; Tessier, Daniel C; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Vachon, Celine M; Vincent, Daniel; Winqvist, Robert; Wu, Anna H; Wu, Pei-Ei; Yip, Cheng Har; Zheng, Wei; Pharoah, Paul D P; Hall, Per; Edwards, Stacey L; Simard, Jacques; French, Juliet D; Chenevix-Trench, Georgia; Dunning, Alison M

2016-09-07

Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.

Large-Scale Interaction Profiling of Protein Domains Through Proteomic Peptide-Phage Display Using Custom Peptidomes.

PubMed

Seo, Moon-Hyeong; Nim, Satra; Jeon, Jouhyun; Kim, Philip M

2017-01-01

Protein-protein interactions are essential to cellular functions and signaling pathways. We recently combined bioinformatics and custom oligonucleotide arrays to construct custom-made peptide-phage libraries for screening peptide-protein interactions, an approach we call proteomic peptide-phage display (ProP-PD). In this chapter, we describe protocols for phage display for the identification of natural peptide binders for a given protein. We finally describe deep sequencing for the analysis of the proteomic peptide-phage display.

Defense Industrial Base Assessment: U.S. Integrated Circuit Design and Fabrication Capability

DTIC Science & Technology

2009-05-01

in the U.S for the period 2003-2006, with projections to 2011.6 The resulting draft OTE survey was field tested for accuracy and usability with a...custom application specific integrated circuits (ASICs) to field programmable gate arrays (FPGAs). Companies of all sizes can manufacture these IC...able to design one-time Electronically Programmable Gate Arrays (EPGAs) while nine are able to design Field Programmable Gate Arrays (FPGAs). Eight

Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes

PubMed Central

Vasson, Aurélie; Leroux, Céline; Orhant, Lucie; Boimard, Mathieu; Toussaint, Aurélie; Leroy, Chrystel; Commere, Virginie; Ghiotti, Tiffany; Deburgrave, Nathalie; Saillour, Yoann; Atlan, Isabelle; Fouveaut, Corinne; Beldjord, Cherif; Valleix, Sophie; Leturcq, France; Dodé, Catherine; Bienvenu, Thierry; Chelly, Jamel; Cossée, Mireille

2013-01-01

The frequency of disease-related large rearrangements (referred to as copy-number mutations, CNMs) varies among genes, and search for these mutations has an important place in diagnostic strategies. In recent years, CGH method using custom-designed high-density oligonucleotide-based arrays allowed the development of a powerful tool for detection of alterations at the level of exons and made it possible to provide flexibility through the possibility of modeling chips. The aim of our study was to test custom-designed oligonucleotide CGH array in a diagnostic laboratory setting that analyses several genes involved in various genetic diseases, and to compare it with conventional strategies. To this end, we designed a 12-plex CGH array (135k; 135 000 probes/subarray) (Roche Nimblegen) with exonic and intronic oligonucleotide probes covering 26 genes routinely analyzed in the laboratory. We tested control samples with known CNMs and patients for whom genetic causes underlying their disorders were unknown. The contribution of this technique is undeniable. Indeed, it appeared reproducible, reliable and sensitive enough to detect heterozygous single-exon deletions or duplications, complex rearrangements and somatic mosaicism. In addition, it improves reliability of CNM detection and allows determination of boundaries precisely enough to direct targeted sequencing of breakpoints. All of these points, associated with the possibility of a simultaneous analysis of several genes and scalability ‘homemade' make it a valuable tool as a new diagnostic approach of CNMs. PMID:23340513

Friction Stir Weld Inspection Through Conductivity Imaging Using Shaped Field MWM(Registered Trademark) - Arrays

NASA Technical Reports Server (NTRS)

Goldfine, Neil; Grundy, David; Zilberstein, Vladimir; Kinchen, David G.; McCool, Alex (Technical Monitor)

2002-01-01

Friction Stir Welds (FSW) of Al 2195-T8 and Al 2219-T8, provided by Lockheed Martin Michoud Operations, were inspected for lack-of-penetration (LOP) defects using a custom designed MWM-Array, a multi-element eddy-current sensor. MWM (registered trademark) electrical conductivity mapping demonstrated high sensitivity to LOP as small as 0.75 mm (0.03 in.), as confirmed by metallographic data that characterized the extent of LOP defects. High sensitivity and high spatial resolution was achieved via a 37-element custom designed MWM-Array allowing LOP detection using the normalized longitudinal component of the MWM measured conductivity. This permitted both LOP detection and correlation of MWM conductivity features with the LOP defect size, as changes in conductivity were apparently associated with metallurgical features within the near-surface layer of the LOP defect zone. MWM conductivity mapping reveals information similar to macro-etching as the MWM-Array is sensitive to small changes in conductivity due to changes in microstructure associated with material thermal processing, in this case welding. The electrical conductivity measured on the root side of FSWs varies across the weld due to microstructural differences introduced by the FSW process, as well as those caused by planar flaws. Weld metal, i.e., dynamically recrystallized zone (DXZ), thermomechanically affected zone (TMZ), heat-affected zone (HAZ), and parent metal (PM) are all evident in the conductivity maps. While prior efforts had met with limited success for NDE (Nondestructive Evaluation) of dissimilar alloy, Al2219 to Al2195 FSW, the new custom designed multi-element MWM-Array achieved detection of all LOP defects even in dissimilar metal welds.

Application specific serial arithmetic arrays

NASA Technical Reports Server (NTRS)

Winters, K.; Mathews, D.; Thompson, T.

1990-01-01

High performance systolic arrays of serial-parallel multiplier elements may be rapidly constructed for specific applications by applying hardware description language techniques to a library of full-custom CMOS building blocks. Single clock pre-charged circuits have been implemented for these arrays at clock rates in excess of 100 Mhz using economical 2-micron (minimum feature size) CMOS processes, which may be quickly configured for a variety of applications. A number of application-specific arrays are presented, including a 2-D convolver for image processing, an integer polynomial solver, and a finite-field polynomial solver.

Deep insight into the Ganoderma lucidum by comprehensive analysis of its transcriptome.

PubMed

Yu, Guo-Jun; Wang, Man; Huang, Jie; Yin, Ya-Lin; Chen, Yi-Jie; Jiang, Shuai; Jin, Yan-Xia; Lan, Xian-Qing; Wong, Barry Hon Cheung; Liang, Yi; Sun, Hui

2012-01-01

Ganoderma lucidum is a basidiomycete white rot fungus and is of medicinal importance in China, Japan and other countries in the Asiatic region. To date, much research has been performed in identifying the medicinal ingredients in Ganoderma lucidum. Despite its important therapeutic effects in disease, little is known about Ganoderma lucidum at the genomic level. In order to gain a molecular understanding of this fungus, we utilized Illumina high-throughput technology to sequence and analyze the transcriptome of Ganoderma lucidum. We obtained 6,439,690 and 6,416,670 high-quality reads from the mycelium and fruiting body of Ganoderma lucidum, and these were assembled to form 18,892 and 27,408 unigenes, respectively. A similarity search was performed against the NCBI non-redundant nucleotide database and a customized database composed of five fungal genomes. 11,098 and 8, 775 unigenes were matched to the NCBI non-redundant nucleotide database and our customized database, respectively. All unigenes were subjected to annotation by Gene Ontology, Eukaryotic Orthologous Group terms and Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes from the Ganoderma lucidum mycelium and fruiting body stage were analyzed, resulting in the identification of 13 unigenes which are involved in the terpenoid backbone biosynthesis pathway. Quantitative real-time PCR was used to confirm the expression levels of these unigenes. Ganoderma lucidum was also studied for wood degrading activity and a total of 22 putative FOLymes (fungal oxidative lignin enzymes) and 120 CAZymes (carbohydrate-active enzymes) were predicted from our Ganoderma lucidum transcriptome. Our study provides comprehensive gene expression information on Ganoderma lucidum at the transcriptional level, which will form the foundation for functional genomics studies in this fungus. The use of Illumina sequencing technology has made de novo transcriptome assembly and gene expression analysis possible in species that lack full genome information.

Deep Insight into the Ganoderma lucidum by Comprehensive Analysis of Its Transcriptome

PubMed Central

Yu, Guo-Jun; Wang, Man; Huang, Jie; Yin, Ya-Lin; Chen, Yi-Jie; Jiang, Shuai; Jin, Yan-Xia; Lan, Xian-Qing; Wong, Barry Hon Cheung; Liang, Yi; Sun, Hui

2012-01-01

Background Ganoderma lucidum is a basidiomycete white rot fungus and is of medicinal importance in China, Japan and other countries in the Asiatic region. To date, much research has been performed in identifying the medicinal ingredients in Ganoderma lucidum. Despite its important therapeutic effects in disease, little is known about Ganoderma lucidum at the genomic level. In order to gain a molecular understanding of this fungus, we utilized Illumina high-throughput technology to sequence and analyze the transcriptome of Ganoderma lucidum. Methodology/Principal Findings We obtained 6,439,690 and 6,416,670 high-quality reads from the mycelium and fruiting body of Ganoderma lucidum, and these were assembled to form 18,892 and 27,408 unigenes, respectively. A similarity search was performed against the NCBI non-redundant nucleotide database and a customized database composed of five fungal genomes. 11,098 and 8, 775 unigenes were matched to the NCBI non-redundant nucleotide database and our customized database, respectively. All unigenes were subjected to annotation by Gene Ontology, Eukaryotic Orthologous Group terms and Kyoto Encyclopedia of Genes and Genomes. Differentially expressed genes from the Ganoderma lucidum mycelium and fruiting body stage were analyzed, resulting in the identification of 13 unigenes which are involved in the terpenoid backbone biosynthesis pathway. Quantitative real-time PCR was used to confirm the expression levels of these unigenes. Ganoderma lucidum was also studied for wood degrading activity and a total of 22 putative FOLymes (fungal oxidative lignin enzymes) and 120 CAZymes (carbohydrate-active enzymes) were predicted from our Ganoderma lucidum transcriptome. Conclusions Our study provides comprehensive gene expression information on Ganoderma lucidum at the transcriptional level, which will form the foundation for functional genomics studies in this fungus. The use of Illumina sequencing technology has made de novo transcriptome assembly and gene expression analysis possible in species that lack full genome information. PMID:22952861

Elucidation of the ‘Honeycrisp’ pedigree through haplotype analysis with a multi-family integrated SNP linkage map and a large apple (Malus×domestica) pedigree-connected SNP data set

PubMed Central

Howard, Nicholas P; van de Weg, Eric; Bedford, David S; Peace, Cameron P; Vanderzande, Stijn; Clark, Matthew D; Teh, Soon Li; Cai, Lichun; Luby, James J

2017-01-01

The apple (Malus×domestica) cultivar Honeycrisp has become important economically and as a breeding parent. An earlier study with SSR markers indicated the original recorded pedigree of ‘Honeycrisp’ was incorrect and ‘Keepsake’ was identified as one putative parent, the other being unknown. The objective of this study was to verify ‘Keepsake’ as a parent and identify and genetically describe the unknown parent and its grandparents. A multi-family based dense and high-quality integrated SNP map was created using the apple 8 K Illumina Infinium SNP array. This map was used alongside a large pedigree-connected data set from the RosBREED project to build extended SNP haplotypes and to identify pedigree relationships. ‘Keepsake’ was verified as one parent of ‘Honeycrisp’ and ‘Duchess of Oldenburg’ and ‘Golden Delicious’ were identified as grandparents through the unknown parent. Following this finding, siblings of ‘Honeycrisp’ were identified using the SNP data. Breeding records from several of these siblings suggested that the previously unreported parent is a University of Minnesota selection, MN1627. This selection is no longer available, but now is genetically described through imputed SNP haplotypes. We also present the mosaic grandparental composition of ‘Honeycrisp’ for each of its 17 chromosome pairs. This new pedigree and genetic information will be useful in future pedigree-based genetic studies to connect ‘Honeycrisp’ with other cultivars used widely in apple breeding programs. The created SNP linkage map will benefit future research using the data from the Illumina apple 8 and 20 K and Affymetrix 480 K SNP arrays. PMID:28243452

Expression Comparison of Oil Biosynthesis Genes in Oil Palm Mesocarp Tissue Using Custom Array

PubMed Central

Wong, Yick Ching; Kwong, Qi Bin; Lee, Heng Leng; Ong, Chuang Kee; Mayes, Sean; Chew, Fook Tim; Appleton, David R.; Kulaveerasingam, Harikrishna

2014-01-01

Gene expression changes that occur during mesocarp development are a major research focus in oil palm research due to the economic importance of this tissue and the relatively rapid increase in lipid content to very high levels at fruit ripeness. Here, we report the development of a transcriptome-based 105,000-probe oil palm mesocarp microarray. The expression of genes involved in fatty acid (FA) and triacylglycerol (TAG) assembly, along with the tricarboxylic acid cycle (TCA) and glycolysis pathway at 16 Weeks After Anthesis (WAA) exhibited significantly higher signals compared to those obtained from a cross-species hybridization to the Arabidopsis (p-value < 0.01), and rice (p-value < 0.01) arrays. The oil palm microarray data also showed comparable correlation of expression (r2 = 0.569, p < 0.01) throughout mesocarp development to transcriptome (RNA sequencing) data, and improved correlation over quantitative real-time PCR (qPCR) (r2 = 0.721, p < 0.01) of the same RNA samples. The results confirm the advantage of the custom microarray over commercially available arrays derived from model species. We demonstrate the utility of this custom microarray to gain a better understanding of gene expression patterns in the oil palm mesocarp that may lead to increasing future oil yield. PMID:27600348

Expression Comparison of Oil Biosynthesis Genes in Oil Palm Mesocarp Tissue Using Custom Array.

PubMed

Wong, Yick Ching; Kwong, Qi Bin; Lee, Heng Leng; Ong, Chuang Kee; Mayes, Sean; Chew, Fook Tim; Appleton, David R; Kulaveerasingam, Harikrishna

2014-11-13

Gene expression changes that occur during mesocarp development are a major research focus in oil palm research due to the economic importance of this tissue and the relatively rapid increase in lipid content to very high levels at fruit ripeness. Here, we report the development of a transcriptome-based 105,000-probe oil palm mesocarp microarray. The expression of genes involved in fatty acid (FA) and triacylglycerol (TAG) assembly, along with the tricarboxylic acid cycle (TCA) and glycolysis pathway at 16 Weeks After Anthesis (WAA) exhibited significantly higher signals compared to those obtained from a cross-species hybridization to the Arabidopsis (p-value < 0.01), and rice (p-value < 0.01) arrays. The oil palm microarray data also showed comparable correlation of expression (r² = 0.569, p < 0.01) throughout mesocarp development to transcriptome (RNA sequencing) data, and improved correlation over quantitative real-time PCR (qPCR) (r² = 0.721, p < 0.01) of the same RNA samples. The results confirm the advantage of the custom microarray over commercially available arrays derived from model species. We demonstrate the utility of this custom microarray to gain a better understanding of gene expression patterns in the oil palm mesocarp that may lead to increasing future oil yield.

Developing custom fire behavior fuel models from ecologically complex fuel structures for upper Atlantic Coastal Plain forests

Treesearch

Bernard R. Parresol; Joe H. Scott; Anne Andreu; Susan Prichard; Laurie Kurth

2012-01-01

Currently geospatial fire behavior analyses are performed with an array of fire behavior modeling systems such as FARSITE, FlamMap, and the Large Fire Simulation System. These systems currently require standard or customized surface fire behavior fuel models as inputs that are often assigned through remote sensing information. The ability to handle hundreds or...

Serial multiplier arrays for parallel computation

NASA Technical Reports Server (NTRS)

Winters, Kel

1990-01-01

Arrays of systolic serial-parallel multiplier elements are proposed as an alternative to conventional SIMD mesh serial adder arrays for applications that are multiplication intensive and require few stored operands. The design and operation of a number of multiplier and array configurations featuring locality of connection, modularity, and regularity of structure are discussed. A design methodology combining top-down and bottom-up techniques is described to facilitate development of custom high-performance CMOS multiplier element arrays as well as rapid synthesis of simulation models and semicustom prototype CMOS components. Finally, a differential version of NORA dynamic circuits requiring a single-phase uncomplemented clock signal introduced for this application.

FPGA Vision Data Architecture

NASA Technical Reports Server (NTRS)

Morfopoulos, Arin C.; Pham, Thang D.

2013-01-01

JPL has produced a series of FPGA (field programmable gate array) vision algorithms that were written with custom interfaces to get data in and out of each vision module. Each module has unique requirements on the data interface, and further vision modules are continually being developed, each with their own custom interfaces. Each memory module had also been designed for direct access to memory or to another memory module.

A sub-millimeter resolution PET detector module using a multi-pixel photon counter array

NASA Astrophysics Data System (ADS)

Song, Tae Yong; Wu, Heyu; Komarov, Sergey; Siegel, Stefan B.; Tai, Yuan-Chuan

2010-05-01

A PET block detector module using an array of sub-millimeter lutetium oxyorthosilicate (LSO) crystals read out by an array of surface-mount, semiconductor photosensors has been developed. The detector consists of a LSO array, a custom acrylic light guide, a 3 × 3 multi-pixel photon counter (MPPC) array (S10362-11-050P, Hamamatsu Photonics, Japan) and a readout board with a charge division resistor network. The LSO array consists of 100 crystals, each measuring 0.8 × 0.8 × 3 mm3 and arranged in 0.86 mm pitches. A Monte Carlo simulation was used to aid the design and fabrication of a custom light guide to control distribution of scintillation light over the surface of the MPPC array. The output signals of the nine MPPC are multiplexed by a charge division resistor network to generate four position-encoded analog outputs. Flood image, energy resolution and timing resolution measurements were performed using standard NIM electronics. The linearity of the detector response was investigated using gamma-ray sources of different energies. The 10 × 10 array of 0.8 mm LSO crystals was clearly resolved in the flood image. The average energy resolution and standard deviation were 20.0% full-width at half-maximum (FWHM) and ±5.0%, respectively, at 511 keV. The timing resolution of a single MPPC coupled to a LSO crystal was found to be 857 ps FWHM, and the value for the central region of detector module was 1182 ps FWHM when ±10% energy window was applied. The nonlinear response of a single MPPC when used to read out a single LSO was observed among the corner crystals of the proposed detector module. However, the central region of the detector module exhibits significantly less nonlinearity (6.5% for 511 keV). These results demonstrate that (1) a charge-sharing resistor network can effectively multiplex MPPC signals and reduce the number of output signals without significantly degrading the performance of a PET detector and (2) a custom light guide to permit light sharing among multiple MPPC and to diffuse and direct scintillation light can reduce the nonlinearity of the detector response within the limited dynamic range of a typical MPPC. As a result, the proposed PET detector module has the potential to be refined for use in high-resolution PET insert applications.

A sub-millimeter resolution PET detector module using a multi-pixel photon counter array.

PubMed

Song, Tae Yong; Wu, Heyu; Komarov, Sergey; Siegel, Stefan B; Tai, Yuan-Chuan

2010-05-07

A PET block detector module using an array of sub-millimeter lutetium oxyorthosilicate (LSO) crystals read out by an array of surface-mount, semiconductor photosensors has been developed. The detector consists of a LSO array, a custom acrylic light guide, a 3 x 3 multi-pixel photon counter (MPPC) array (S10362-11-050P, Hamamatsu Photonics, Japan) and a readout board with a charge division resistor network. The LSO array consists of 100 crystals, each measuring 0.8 x 0.8 x 3 mm(3) and arranged in 0.86 mm pitches. A Monte Carlo simulation was used to aid the design and fabrication of a custom light guide to control distribution of scintillation light over the surface of the MPPC array. The output signals of the nine MPPC are multiplexed by a charge division resistor network to generate four position-encoded analog outputs. Flood image, energy resolution and timing resolution measurements were performed using standard NIM electronics. The linearity of the detector response was investigated using gamma-ray sources of different energies. The 10 x 10 array of 0.8 mm LSO crystals was clearly resolved in the flood image. The average energy resolution and standard deviation were 20.0% full-width at half-maximum (FWHM) and +/-5.0%, respectively, at 511 keV. The timing resolution of a single MPPC coupled to a LSO crystal was found to be 857 ps FWHM, and the value for the central region of detector module was 1182 ps FWHM when +/-10% energy window was applied. The nonlinear response of a single MPPC when used to read out a single LSO was observed among the corner crystals of the proposed detector module. However, the central region of the detector module exhibits significantly less nonlinearity (6.5% for 511 keV). These results demonstrate that (1) a charge-sharing resistor network can effectively multiplex MPPC signals and reduce the number of output signals without significantly degrading the performance of a PET detector and (2) a custom light guide to permit light sharing among multiple MPPC and to diffuse and direct scintillation light can reduce the nonlinearity of the detector response within the limited dynamic range of a typical MPPC. As a result, the proposed PET detector module has the potential to be refined for use in high-resolution PET insert applications.

A sub-millimeter resolution PET detector module using a multi-pixel photon counter array

PubMed Central

Song, Tae Yong; Wu, Heyu; Komarov, Sergey; Siegel, Stefan B; Tai, Yuan-Chuan

2010-01-01

A PET block detector module using an array of sub-millimeter lutetium oxyorthosilicate (LSO) crystals read out by an array of surface-mount, semiconductor photosensors has been developed. The detector consists of a LSO array, a custom acrylic light guide, a 3 × 3 multi-pixel photon counter (MPPC) array (S10362-11-050P, Hamamatsu Photonics, Japan) and a readout board with a charge division resistor network. The LSO array consists of 100 crystals, each measuring 0.8 × 0.8 × 3 mm3 and arranged in 0.86 mm pitches. A Monte Carlo simulation was used to aid the design and fabrication of a custom light guide to control distribution of scintillation light over the surface of the MPPC array. The output signals of the nine MPPC are multiplexed by a charge division resistor network to generate four position-encoded analog outputs. Flood image, energy resolution and timing resolution measurements were performed using standard NIM electronics. The linearity of the detector response was investigated using gamma-ray sources of different energies. The 10 × 10 array of 0.8 mm LSO crystals was clearly resolved in the flood image. The average energy resolution and standard deviation were 20.0% full-width at half-maximum (FWHM) and ±5.0%, respectively, at 511 keV. The timing resolution of a single MPPC coupled to a LSO crystal was found to be 857 ps FWHM, and the value for the central region of detector module was 1182 ps FWHM when ±10% energy window was applied. The nonlinear response of a single MPPC when used to read out a single LSO was observed among the corner crystals of the proposed detector module. However, the central region of the detector module exhibits significantly less nonlinearity (6.5% for 511 keV). These results demonstrate that (1) a charge-sharing resistor network can effectively multiplex MPPC signals and reduce the number of output signals without significantly degrading the performance of a PET detector and (2) a custom light guide to permit light sharing among multiple MPPC and to diffuse and direct scintillation light can reduce the nonlinearity of the detector response within the limited dynamic range of a typical MPPC. As a result, the proposed PET detector module has the potential to be refined for use in high-resolution PET insert applications. PMID:20393236

A 1-MHz 2-D CMUT array for HIFU thermal ablation

NASA Astrophysics Data System (ADS)

Yoon, Hyo-Seon; Vaithilingam, Srikant; Park, Kwan Kyu; Nikoozadeh, Amin; Firouzi, Kamyar; Choe, Jung Woo; Watkins, Ronald D.; Oguz, Huseyin Kagan; Kupnik, Mario; Pauly, Kim Butts; Khuri-Yakub, Pierre

2017-03-01

We developed a fully-populated 2-D capacitive micromachined ultrasonic transducer (CMUT) array for high intensity focused ultrasound (HIFU) treatment. The 2-D CMUT array, which consists of 20 × 20 square CMUT elements with an element-to-element pitch of 1 mm, was designed and fabricated using the thick-buried-oxide (BOX) fabrication process. It was then assembled on a custom interface board that can provide various array configurations depending on the desired applications. In this study, the interface board groups the CMUT array elements into eight channels, based on the phase delay from the element to the targeted focal point at a 20-mm distance from the array surface, which corresponds to an F-number of 1. An 8-channel phase generating system supplies continuous waves with eight different phases to the eight channels of the CMUT array through bias-tees and amplifiers. This array aperture, grouped into eight channels, gives a focusing gain of 6.09 according to field simulation using Field II. Assuming a peak-to-peak pressure of 1 MPa at the surface of the array, our custom temperature simulator predicts successful tissue ablation at the focus. During the measurements, each channel was tuned with a series inductor for an operational frequency of 1 MHz. With a CMUT DC bias of 100 V and a 1-MHz AC input voltage of 55 V, we achieved peak-to-peak output pressures of 173.9 kPa and 568.7 kPa at the array surface and at the focus, respectively. The focusing gain calculated from this measurement is 3.27, which is lower than the simulated gain of 6.09 because of the mutual radiation impedance among the CMUT cells. Further optimization of the operating condition of this array and design improvements for reducing the effect of mutual radiation impedance are currently on-going.

C-MOS bulk metal design handbook. [LSI standard cell (circuits)

NASA Technical Reports Server (NTRS)

Edge, T. M.

1977-01-01

The LSI standard cell array technique was used in the fabrication of more than 20 CMOS custom arrays. This technique consists of a series of computer programs and design automation techniques referred to as the Computer Aided Design And Test (CADAT) system that automatically translate a partitioned logic diagram into a set of instructions for driving an automatic plotter which generates precision mask artwork for complex LSI arrays of CMOS standard cells. The standard cell concept for producing LSI arrays begins with the design, layout, and validation of a group of custom circuits called standard cells. Once validated, these cells are given identification or pattern numbers and are permanently stored. To use one of these cells in a logic design, the user calls for the desired cell by pattern number. The Place, Route in Two Dimension (PR2D) computer program is then used to automatically generate the metalization and/or tunnels to interconnect the standard cells into the required function. Data sheets that describe the function, artwork, and performance of each of the standard cells, the general procedure for implementation of logic in CMOS standard cells, and additional detailed design information are presented.

The OncoArray Consortium: A Network for Understanding the Genetic Architecture of Common Cancers.

PubMed

Amos, Christopher I; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R; Gayther, Simon A; Casey, Graham; Hunter, David J; Sellers, Thomas A; Gruber, Stephen B; Dunning, Alison M; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A; Hazelett, Dennis J; Bojesen, Stig E; Caga-Anan, Charlisse; Haiman, Christopher A; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E; Couch, Fergus J; Forman, Judith L; Giles, Graham G; Conti, David V; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske-Hohlfeld, Irene; Hicks, Belynda D; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline; Soucy, Penny; Manz, Judith; Cunningham, Julie M; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel; Lindström, Sara; Adams, Marcia; McKay, James D; Phelan, Catherine M; Benlloch, Sara; Kelemen, Linda E; Brennan, Paul; Riggan, Marjorie; O'Mara, Tracy A; Shen, Hongbing; Shi, Yongyong; Thompson, Deborah J; Goodman, Marc T; Nielsen, Sune F; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L; Shelford, Tameka; Edlund, Christopher K; Taylor, Jack A; Field, John K; Park, Sue K; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J; Marchini, Jonathan; Amin Al Olama, Ali; Peters, Ulrike; Eeles, Rosalind A; Seldin, Michael F; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C; Pharoah, Paul D P; Chenevix-Trench, Georgia; Chanock, Stephen J; Simard, Jacques; Easton, Douglas F

2017-01-01

Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126-35. ©2016 AACR. ©2016 American Association for Cancer Research.

The OncoArray Consortium: a Network for Understanding the Genetic Architecture of Common Cancers

PubMed Central

Amos, Christopher I.; Dennis, Joe; Wang, Zhaoming; Byun, Jinyoung; Schumacher, Fredrick R.; Gayther, Simon A.; Casey, Graham; Hunter, David J.; Sellers, Thomas A.; Gruber, Stephen B.; Dunning, Alison M.; Michailidou, Kyriaki; Fachal, Laura; Doheny, Kimberly; Spurdle, Amanda B.; Li, Yafang; Xiao, Xiangjun; Romm, Jane; Pugh, Elizabeth; Coetzee, Gerhard A.; Hazelett, Dennis J.; Bojesen, Stig E.; Caga-Anan, Charlisse; Haiman, Christopher A.; Kamal, Ahsan; Luccarini, Craig; Tessier, Daniel; Vincent, Daniel; Bacot, François; Van Den Berg, David J.; Nelson, Stefanie; Demetriades, Stephen; Goldgar, David E.; Couch, Fergus J.; Forman, Judith L.; Giles, Graham G.; Conti, David V.; Bickeböller, Heike; Risch, Angela; Waldenberger, Melanie; Brüske, Irene; Hicks, Belynda D.; Ling, Hua; McGuffog, Lesley; Lee, Andrew; Kuchenbaecker, Karoline B.; Soucy, Penny; Manz, Judith; Cunningham, Julie M.; Butterbach, Katja; Kote-Jarai, Zsofia; Kraft, Peter; FitzGerald, Liesel M.; Lindström, Sara; Adams, Marcia; McKay, James D.; Phelan, Catherine M.; Benlloch, Sara; Kelemen, Linda E.; Brennan, Paul; Riggan, Marjorie; O’Mara, Tracy A.; Shen, Hongbin; Shi, Yongyong; Thompson, Deborah J.; Goodman, Marc T.; Nielsen, Sune F.; Berchuck, Andrew; Laboissiere, Sylvie; Schmit, Stephanie L.; Shelford, Tameka; Edlund, Christopher K.; Taylor, Jack A.; Field, John K.; Park, Sue K.; Offit, Kenneth; Thomassen, Mads; Schmutzler, Rita; Ottini, Laura; Hung, Rayjean J.; Marchini, Jonathan; Al Olama, Ali Amin; Peters, Ulrike; Eeles, Rosalind A.; Seldin, Michael F.; Gillanders, Elizabeth; Seminara, Daniela; Antoniou, Antonis C.; Pharoah, Paul D.; Chenevix-Trench, Georgia; Chanock, Stephen J.; Simard, Jacques; Easton, Douglas F.

2016-01-01

Background Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers and cancer related traits. Methods The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions Results from these analyses will enable researchers to identify new susceptibility loci, perform fine mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental and lifestyle related exposures. Impact Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. PMID:27697780

Power enhancement via multivariate outlier testing with gene expression arrays.

PubMed

Asare, Adam L; Gao, Zhong; Carey, Vincent J; Wang, Richard; Seyfert-Margolis, Vicki

2009-01-01

As the use of microarrays in human studies continues to increase, stringent quality assurance is necessary to ensure accurate experimental interpretation. We present a formal approach for microarray quality assessment that is based on dimension reduction of established measures of signal and noise components of expression followed by parametric multivariate outlier testing. We applied our approach to several data resources. First, as a negative control, we found that the Affymetrix and Illumina contributions to MAQC data were free from outliers at a nominal outlier flagging rate of alpha=0.01. Second, we created a tunable framework for artificially corrupting intensity data from the Affymetrix Latin Square spike-in experiment to allow investigation of sensitivity and specificity of quality assurance (QA) criteria. Third, we applied the procedure to 507 Affymetrix microarray GeneChips processed with RNA from human peripheral blood samples. We show that exclusion of arrays by this approach substantially increases inferential power, or the ability to detect differential expression, in large clinical studies. http://bioconductor.org/packages/2.3/bioc/html/arrayMvout.html and http://bioconductor.org/packages/2.3/bioc/html/affyContam.html affyContam (credentials: readonly/readonly)

Comprehensive performance comparison of high-resolution array platforms for genome-wide Copy Number Variation (CNV) analysis in humans.

PubMed

Haraksingh, Rajini R; Abyzov, Alexej; Urban, Alexander Eckehart

2017-04-24

High-resolution microarray technology is routinely used in basic research and clinical practice to efficiently detect copy number variants (CNVs) across the entire human genome. A new generation of arrays combining high probe densities with optimized designs will comprise essential tools for genome analysis in the coming years. We systematically compared the genome-wide CNV detection power of all 17 available array designs from the Affymetrix, Agilent, and Illumina platforms by hybridizing the well-characterized genome of 1000 Genomes Project subject NA12878 to all arrays, and performing data analysis using both manufacturer-recommended and platform-independent software. We benchmarked the resulting CNV call sets from each array using a gold standard set of CNVs for this genome derived from 1000 Genomes Project whole genome sequencing data. The arrays tested comprise both SNP and aCGH platforms with varying designs and contain between ~0.5 to ~4.6 million probes. Across the arrays CNV detection varied widely in number of CNV calls (4-489), CNV size range (~40 bp to ~8 Mbp), and percentage of non-validated CNVs (0-86%). We discovered strikingly strong effects of specific array design principles on performance. For example, some SNP array designs with the largest numbers of probes and extensive exonic coverage produced a considerable number of CNV calls that could not be validated, compared to designs with probe numbers that are sometimes an order of magnitude smaller. This effect was only partially ameliorated using different analysis software and optimizing data analysis parameters. High-resolution microarrays will continue to be used as reliable, cost- and time-efficient tools for CNV analysis. However, different applications tolerate different limitations in CNV detection. Our study quantified how these arrays differ in total number and size range of detected CNVs as well as sensitivity, and determined how each array balances these attributes. This analysis will inform appropriate array selection for future CNV studies, and allow better assessment of the CNV-analytical power of both published and ongoing array-based genomics studies. Furthermore, our findings emphasize the importance of concurrent use of multiple analysis algorithms and independent experimental validation in array-based CNV detection studies.

Comparison of illumina and 454 deep sequencing in participants failing raltegravir-based antiretroviral therapy.

PubMed

Li, Jonathan Z; Chapman, Brad; Charlebois, Patrick; Hofmann, Oliver; Weiner, Brian; Porter, Alyssa J; Samuel, Reshmi; Vardhanabhuti, Saran; Zheng, Lu; Eron, Joseph; Taiwo, Babafemi; Zody, Michael C; Henn, Matthew R; Kuritzkes, Daniel R; Hide, Winston; Wilson, Cara C; Berzins, Baiba I; Acosta, Edward P; Bastow, Barbara; Kim, Peter S; Read, Sarah W; Janik, Jennifer; Meres, Debra S; Lederman, Michael M; Mong-Kryspin, Lori; Shaw, Karl E; Zimmerman, Louis G; Leavitt, Randi; De La Rosa, Guy; Jennings, Amy

2014-01-01

The impact of raltegravir-resistant HIV-1 minority variants (MVs) on raltegravir treatment failure is unknown. Illumina sequencing offers greater throughput than 454, but sequence analysis tools for viral sequencing are needed. We evaluated Illumina and 454 for the detection of HIV-1 raltegravir-resistant MVs. A5262 was a single-arm study of raltegravir and darunavir/ritonavir in treatment-naïve patients. Pre-treatment plasma was obtained from 5 participants with raltegravir resistance at the time of virologic failure. A control library was created by pooling integrase clones at predefined proportions. Multiplexed sequencing was performed with Illumina and 454 platforms at comparable costs. Illumina sequence analysis was performed with the novel snp-assess tool and 454 sequencing was analyzed with V-Phaser. Illumina sequencing resulted in significantly higher sequence coverage and a 0.095% limit of detection. Illumina accurately detected all MVs in the control library at ≥0.5% and 7/10 MVs expected at 0.1%. 454 sequencing failed to detect any MVs at 0.1% with 5 false positive calls. For MVs detected in the patient samples by both 454 and Illumina, the correlation in the detected variant frequencies was high (R2 = 0.92, P<0.001). Illumina sequencing detected 2.4-fold greater nucleotide MVs and 2.9-fold greater amino acid MVs compared to 454. The only raltegravir-resistant MV detected was an E138K mutation in one participant by Illumina sequencing, but not by 454. In participants of A5262 with raltegravir resistance at virologic failure, baseline raltegravir-resistant MVs were rarely detected. At comparable costs to 454 sequencing, Illumina demonstrated greater depth of coverage, increased sensitivity for detecting HIV MVs, and fewer false positive variant calls.

A customized metal oxide semiconductor-based gas sensor array for onion quality evaluation: system development and characterization.

PubMed

Konduru, Tharun; Rains, Glen C; Li, Changying

2015-01-12

A gas sensor array, consisting of seven Metal Oxide Semiconductor (MOS) sensors that are sensitive to a wide range of organic volatile compounds was developed to detect rotten onions during storage. These MOS sensors were enclosed in a specially designed Teflon chamber equipped with a gas delivery system to pump volatiles from the onion samples into the chamber. The electronic circuit mainly comprised a microcontroller, non-volatile memory chip, and trickle-charge real time clock chip, serial communication chip, and parallel LCD panel. User preferences are communicated with the on-board microcontroller through a graphical user interface developed using LabVIEW. The developed gas sensor array was characterized and the discrimination potential was tested by exposing it to three different concentrations of acetone (ketone), acetonitrile (nitrile), ethyl acetate (ester), and ethanol (alcohol). The gas sensor array could differentiate the four chemicals of same concentrations and different concentrations within the chemical with significant difference. Experiment results also showed that the system was able to discriminate two concentrations (196 and 1964 ppm) of methlypropyl sulfide and two concentrations (145 and 1452 ppm) of 2-nonanone, two key volatile compounds emitted by rotten onions. As a proof of concept, the gas sensor array was able to achieve 89% correct classification of sour skin infected onions. The customized low-cost gas sensor array could be a useful tool to detect onion postharvest diseases in storage.

A Customized Metal Oxide Semiconductor-Based Gas Sensor Array for Onion Quality Evaluation: System Development and Characterization

PubMed Central

Konduru, Tharun; Rains, Glen C.; Li, Changying

2015-01-01

A gas sensor array, consisting of seven Metal Oxide Semiconductor (MOS) sensors that are sensitive to a wide range of organic volatile compounds was developed to detect rotten onions during storage. These MOS sensors were enclosed in a specially designed Teflon chamber equipped with a gas delivery system to pump volatiles from the onion samples into the chamber. The electronic circuit mainly comprised a microcontroller, non-volatile memory chip, and trickle-charge real time clock chip, serial communication chip, and parallel LCD panel. User preferences are communicated with the on-board microcontroller through a graphical user interface developed using LabVIEW. The developed gas sensor array was characterized and the discrimination potential was tested by exposing it to three different concentrations of acetone (ketone), acetonitrile (nitrile), ethyl acetate (ester), and ethanol (alcohol). The gas sensor array could differentiate the four chemicals of same concentrations and different concentrations within the chemical with significant difference. Experiment results also showed that the system was able to discriminate two concentrations (196 and 1964 ppm) of methlypropyl sulfide and two concentrations (145 and 1452 ppm) of 2-nonanone, two key volatile compounds emitted by rotten onions. As a proof of concept, the gas sensor array was able to achieve 89% correct classification of sour skin infected onions. The customized low-cost gas sensor array could be a useful tool to detect onion postharvest diseases in storage. PMID:25587975

Evaluation of SNP Data from the Malus Infinium Array Identifies Challenges for Genetic Analysis of Complex Genomes of Polyploid Origin.

PubMed

Troggio, Michela; Surbanovski, Nada; Bianco, Luca; Moretto, Marco; Giongo, Lara; Banchi, Elisa; Viola, Roberto; Fernández, Felicdad Fernández; Costa, Fabrizio; Velasco, Riccardo; Cestaro, Alessandro; Sargent, Daniel James

2013-01-01

High throughput arrays for the simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) have made the rapid genetic characterisation of plant genomes and the development of saturated linkage maps a realistic prospect for many plant species of agronomic importance. However, the correct calling of SNP genotypes in divergent polyploid genomes using array technology can be problematic due to paralogy, and to divergence in probe sequences causing changes in probe binding efficiencies. An Illumina Infinium II whole-genome genotyping array was recently developed for the cultivated apple and used to develop a molecular linkage map for an apple rootstock progeny (M432), but a large proportion of segregating SNPs were not mapped in the progeny, due to unexpected genotype clustering patterns. To investigate the causes of this unexpected clustering we performed BLAST analysis of all probe sequences against the 'Golden Delicious' genome sequence and discovered evidence for paralogous annealing sites and probe sequence divergence for a high proportion of probes contained on the array. Following visual re-evaluation of the genotyping data generated for 8,788 SNPs for the M432 progeny using the array, we manually re-scored genotypes at 818 loci and mapped a further 797 markers to the M432 linkage map. The newly mapped markers included the majority of those that could not be mapped previously, as well as loci that were previously scored as monomorphic, but which segregated due to divergence leading to heterozygosity in probe annealing sites. An evaluation of the 8,788 probes in a diverse collection of Malus germplasm showed that more than half the probes returned genotype clustering patterns that were difficult or impossible to interpret reliably, highlighting implications for the use of the array in genome-wide association studies.

Association of vitamin D levels and risk of ovarian cancer: a Mendelian randomization study.

PubMed

Ong, Jue-Sheng; Cuellar-Partida, Gabriel; Lu, Yi; Fasching, Peter A; Hein, Alexander; Burghaus, Stefanie; Beckmann, Matthias W; Lambrechts, Diether; Van Nieuwenhuysen, Els; Vergote, Ignace; Vanderstichele, Adriaan; Anne Doherty, Jennifer; Anne Rossing, Mary; Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan; Goodman, Marc T; Bogdanova, Natalia; Dörk, Thilo; Dürst, Matthias; Hillemanns, Peter; Runnebaum, Ingo B; Antonenkova, Natalia; Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M; Edwards, Robert P; Kelley, Joseph L; Modugno, Francesmary; Moysich, Kirsten B; Ness, Roberta B; Cannioto, Rikki; Høgdall, Estrid; Høgdall, Claus K; Jensen, Allan; Giles, Graham G; Bruinsma, Fiona; Kjaer, Susanne K; Hildebrandt, Michelle At; Liang, Dong; Lu, Karen H; Wu, Xifeng; Bisogna, Maria; Dao, Fanny; Levine, Douglas A; Cramer, Daniel W; Terry, Kathryn L; Tworoger, Shelley S; Stampfer, Meir; Missmer, Stacey; Bjorge, Line; Salvesen, Helga B; Kopperud, Reidun K; Bischof, Katharina; Aben, Katja Kh; Kiemeney, Lambertus A; Massuger, Leon Fag; Brooks-Wilson, Angela; Olson, Sara H; McGuire, Valerie; Rothstein, Joseph H; Sieh, Weiva; Whittemore, Alice S; Cook, Linda S; Le, Nhu D; Gilks, C Blake; Gronwald, Jacek; Jakubowska, Anna; Lubiński, Jan; Kluz, Tomasz; Song, Honglin; Tyrer, Jonathan P; Wentzensen, Nicolas; Brinton, Louise; Trabert, Britton; Lissowska, Jolanta; McLaughlin, John R; Narod, Steven A; Phelan, Catherine; Anton-Culver, Hoda; Ziogas, Argyrios; Eccles, Diana; Campbell, Ian; Gayther, Simon A; Gentry-Maharaj, Aleksandra; Menon, Usha; Ramus, Susan J; Wu, Anna H; Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Timorek, Agnieszka; Szafron, Lukasz; Cunningham, Julie M; Fridley, Brooke L; Winham, Stacey J; Bandera, Elisa V; Poole, Elizabeth M; Morgan, Terry K; Risch, Harvey A; Goode, Ellen L; Schildkraut, Joellen M; Pearce, Celeste L; Berchuck, Andrew; Pharoah, Paul Dp; Chenevix-Trench, Georgia; Gharahkhani, Puya; Neale, Rachel E; Webb, Penelope M; MacGregor, Stuart

2016-10-01

In vitro and observational epidemiological studies suggest that vitamin D may play a role in cancer prevention. However, the relationship between vitamin D and ovarian cancer is uncertain, with observational studies generating conflicting findings. A potential limitation of observational studies is inadequate control of confounding. To overcome this problem, we used Mendelian randomization (MR) to evaluate the association between single nucleotide polymorphisms (SNPs) associated with circulating 25-hydroxyvitamin D [25(OH)D] concentration and risk of ovarian cancer. We employed SNPs with well-established associations with 25(OH)D concentration as instrumental variables for MR: rs7944926 (DHCR7), rs12794714 (CYP2R1) and rs2282679 (GC). We included 31 719 women of European ancestry (10 065 cases, 21 654 controls) from the Ovarian Cancer Association Consortium, who were genotyped using customized Illumina Infinium iSelect (iCOGS) arrays. A two-sample (summary data) MR approach was used and analyses were performed separately for all ovarian cancer (10 065 cases) and for high-grade serous ovarian cancer (4121 cases). The odds ratio for epithelial ovarian cancer risk (10 065 cases) estimated by combining the individual SNP associations using inverse variance weighting was 1.27 (95% confidence interval: 1.06 to 1.51) per 20 nmol/L decrease in 25(OH)D concentration. The estimated odds ratio for high-grade serous epithelial ovarian cancer (4121 cases) was 1.54 (1.19, 2.01). Genetically lowered 25-hydroxyvitamin D concentrations were associated with higher ovarian cancer susceptibility in Europeans. These findings suggest that increasing plasma vitamin D levels may reduce risk of ovarian cancer. © The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Identification of two novel mammographic density loci at 6Q25.1.

PubMed

Brand, Judith S; Li, Jingmei; Humphreys, Keith; Karlsson, Robert; Eriksson, Mikael; Ivansson, Emma; Hall, Per; Czene, Kamila

2015-06-03

Mammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci. Participants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account. Genome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10(-8) for percent MD and P = 8.7 × 10(-9) for absolute MD) and AREG (rs10034692, P = 6.7 × 10(-9) for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10(-9) for percent MD and P = 2.5 × 10(-8) for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10(-8) for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response. We identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.

Polymorphism in the IL18 gene and epithelial ovarian cancer in non-Hispanic white women

PubMed Central

Palmieri, Rachel T.; Wilson, Melanie A.; Iversen, Edwin S.; Clyde, Merlise A.; Calingaert, Brian; Moorman, Patricia G.; Poole, Charles; Anderson, A. Rebecca; Anderson, Stephanie; Anton-Culver, Hoda; Beesley, Jonathan; Hogdall, Estrid; Brewster, Wendy; Carney, Michael E.; Chen, Xiaoqing; Chenevix-Trench, Georgia; Chang-Claude, Jenny; Cunningham, Julie M.; DiCioccio, Richard A.; Doherty, Jennifer A.; Easton, Douglas F.; Edlund, Christopher K.; Gayther, Simon A.; Gentry-Maharaj, Aleksandra; Goode, Ellen L.; Goodman, Marc T.; Kjaer, Susanne Kruger; Hogdall, Claus K; Hopkins, Michael P.; Jenison, Eric L.; Blaakaer, Jan; Lurie, Galina; McGuire, Valerie; Menon, Usha; Moysich, Kirsten B.; Ness, Roberta B.; Pearce, Celeste Leigh; Pharoah, Paul D.P.; Pike, Malcolm C.; Ramus, Susan J.; Rossing, Mary Anne; Song, Honglin; Terada, Keith Y.; Van Den Berg, David; Vierkant, Robert A.; Wang-Gohrke, Shan; Webb, Penelope M.; Whittemore, Alice S.; Wu, Anna H.; Ziogas, Argyrios; Berchuck, Andrew; Schildkraut, Joellen M.

2009-01-01

Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine whether low penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNPs) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (p=0.002) with a <25% chance of being a false positive finding (q-value=0.240). Using a multivariate model search algorithm over eleven IL18 tagging SNPs, we found the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (OR=1.24, 95% CI: 1.06, 1.45). In a replication stage, twelve independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (OR=0.99, 95% CI: 0.94, 1.05) when data from the twelve OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial NCO data. This analysis demonstrates the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. PMID:19064572

Genome-wide association study for milking speed in French Holstein cows.

PubMed

Marete, Andrew; Sahana, Goutam; Fritz, Sébastien; Lefebvre, Rachel; Barbat, Anne; Lund, Mogens Sandø; Guldbrandtsen, Bernt; Boichard, Didier

2018-04-25

Using a combination of data from the BovineSNP50 BeadChip SNP array (Illumina, San Diego, CA) and a EuroGenomics (Amsterdam, the Netherlands) custom single nucleotide polymorphism (SNP) chip with SNP pre-selected from whole genome sequence data, we carried out an association study of milking speed in 32,491 French Holstein dairy cows. Milking speed was measured by a score given by the farmer. Phenotypes were yield deviations as obtained from the French evaluation system. They were analyzed with a linear mixed model for association studies. We identified SNP on 22 chromosomes significantly associated with milking speed. As clinical mastitis and somatic cell score have an unfavorable genetic correlation with milking speed, we tested whether the most significant SNP on these 22 chromosomes associated with milking speed were also associated with clinical mastitis or somatic cell score. Nine hundred seventy-one genome-wide significant SNP were associated with milking speed. Of these, 86 were associated with clinical mastitis and 198 with somatic cell score. The most significant association signals for milking speed were observed on chromosomes 7, 8, 10, 14, and 18. The most significant signal was located on chromosome 14 (ZFAT gene). Eleven novel milking speed quantitative trait loci (QTL) were observed on chromosomes 7, 10, 11, 14, 18, 25, and 26. Twelve candidate SNP for milking speed mapped directly within genes. Of these 10 were QTL lead SNP, which mapped within the genes HMHA1, POLR2E, GNB5, KLHL29, ZFAT, KCNB2, CEACAM18, CCL24, and LHPP. Limited pleiotropy was observed between milking speed QTL and clinical mastitis. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

CNV-WebStore: online CNV analysis, storage and interpretation.

PubMed

Vandeweyer, Geert; Reyniers, Edwin; Wuyts, Wim; Rooms, Liesbeth; Kooy, R Frank

2011-01-05

Microarray technology allows the analysis of genomic aberrations at an ever increasing resolution, making functional interpretation of these vast amounts of data the main bottleneck in routine implementation of high resolution array platforms, and emphasising the need for a centralised and easy to use CNV data management and interpretation system. We present CNV-WebStore, an online platform to streamline the processing and downstream interpretation of microarray data in a clinical context, tailored towards but not limited to the Illumina BeadArray platform. Provided analysis tools include CNV analsyis, parent of origin and uniparental disomy detection. Interpretation tools include data visualisation, gene prioritisation, automated PubMed searching, linking data to several genome browsers and annotation of CNVs based on several public databases. Finally a module is provided for uniform reporting of results. CNV-WebStore is able to present copy number data in an intuitive way to both lab technicians and clinicians, making it a useful tool in daily clinical practice.

Customized Oligonucleotide Array-Based Comparative Genomic Hybridization as a Clinical Assay for Genomic Profiling of Chronic Lymphocytic Leukemia

PubMed Central

Sargent, Rachel; Jones, Dan; Abruzzo, Lynne V.; Yao, Hui; Bonderover, Jaime; Cisneros, Marissa; Wierda, William G.; Keating, Michael J.; Luthra, Rajyalakshmi

2009-01-01

Chromosome gains and losses used for risk stratification in chronic lymphocytic leukemia (CLL) are commonly assessed by multiprobe fluorescence in situ hybridization (FISH) studies. We designed and validated a customized array-comparative genomic hybridization (aCGH) platform as a clinical assay for CLL genomic profiling. A 60-mer, 44,000-probe oligonucleotide array with a 50-kb average spatial resolution was augmented with high-density probe tiling at loci that are frequently aberrant in CLL. Aberrations identified by aCGH were compared with those identified by a FISH panel, including locus-specific probes to ATM (11q22.3), the centromeric region of chromosome 12 (12p11.1–q11), D13S319 (13q14.3), LAMP1 (13q34), and TP53 (17p13.1). In 100 CLL samples, aCGH/FISH concordance was seen for 89% of FISH-called aberrations at the ATM (n = 18), D13S319 (n = 42), LAMP (n = 12), and TP53 (n = 22) loci and for chromosome 12 (n = 14). Eighty-four percentage of FISH/aCGH discordant calls were in samples either at or below the limit of aCGH sensitivity (10% to 25% FISH aberration-containing cells). Therefore, aCGH profiling is a feasible routine clinical test with comparable results to multiprobe FISH studies; however, it may be less sensitive than FISH in cases with low-level aberrations. Further, a customized array design can provide comprehensive genomic profiling with additional accuracy in both identifying and defining the extent of small aberrations at target loci. PMID:19074592

Using RNA-Seq to assemble a rose transcriptome with more than 13,000 full-length expressed genes and to develop the WagRhSNP 68k Axiom SNP array for rose (Rosa L.).

PubMed

Koning-Boucoiran, Carole F S; Esselink, G Danny; Vukosavljev, Mirjana; van 't Westende, Wendy P C; Gitonga, Virginia W; Krens, Frans A; Voorrips, Roeland E; van de Weg, W Eric; Schulz, Dietmar; Debener, Thomas; Maliepaard, Chris; Arens, Paul; Smulders, Marinus J M

2015-01-01

In order to develop a versatile and large SNP array for rose, we set out to mine ESTs from diverse sets of rose germplasm. For this RNA-Seq libraries containing about 700 million reads were generated from tetraploid cut and garden roses using Illumina paired-end sequencing, and from diploid Rosa multiflora using 454 sequencing. Separate de novo assemblies were performed in order to identify single nucleotide polymorphisms (SNPs) within and between rose varieties. SNPs among tetraploid roses were selected for constructing a genotyping array that can be employed for genetic mapping and marker-trait association discovery in breeding programs based on tetraploid germplasm, both from cut roses and from garden roses. In total 68,893 SNPs were included on the WagRhSNP Axiom array. Next, an orthology-guided assembly was performed for the construction of a non-redundant rose transcriptome database. A total of 21,740 transcripts had significant hits with orthologous genes in the strawberry (Fragaria vesca L.) genome. Of these 13,390 appeared to contain the full-length coding regions. This newly established transcriptome resource adds considerably to the currently available sequence resources for the Rosaceae family in general and the genus Rosa in particular.

Space Environment Testing of Photovoltaic Array Systems at NASA's Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Phillips, Brandon S.; Schneider, Todd A.; Vaughn, Jason A.; Wright, Kenneth H., Jr.

2015-01-01

To successfully operate a photovoltaic (PV) array system in space requires planning and testing to account for the effects of the space environment. It is critical to understand space environment interactions not only on the PV components, but also the array substrate materials, wiring harnesses, connectors, and protection circuitry (e.g. blocking diodes). Key elements of the space environment which must be accounted for in a PV system design include: Solar Photon Radiation, Charged Particle Radiation, Plasma, and Thermal Cycling. While solar photon radiation is central to generating power in PV systems, the complete spectrum includes short wavelength ultraviolet components, which photo-ionize materials, as well as long wavelength infrared which heat materials. High energy electron radiation has been demonstrated to significantly reduce the output power of III-V type PV cells; and proton radiation damages material surfaces - often impacting coverglasses and antireflective coatings. Plasma environments influence electrostatic charging of PV array materials, and must be understood to ensure that long duration arcs do not form and potentially destroy PV cells. Thermal cycling impacts all components on a PV array by inducing stresses due to thermal expansion and contraction. Given such demanding environments, and the complexity of structures and materials that form a PV array system, mission success can only be ensured through realistic testing in the laboratory. NASA's Marshall Space Flight Center has developed a broad space environment test capability to allow PV array designers and manufacturers to verify their system's integrity and avoid costly on-orbit failures. The Marshall Space Flight Center test capabilities are available to government, commercial, and university customers. Test solutions are tailored to meet the customer's needs, and can include performance assessments, such as flash testing in the case of PV cells.

Leak Detection in Spacecraft Using a 64-Element Multiplexed Passive Array to Monitor Structure-Borne Noise

NASA Astrophysics Data System (ADS)

Holland, Stephen D.; Song, Jun-Ho; Chimenti, D. E.; Roberts, Ron

2006-03-01

We demonstrate an array sensor method intended to locate leaks in manned spacecraft using leak-generated, structure-borne ultrasonic noise. We have developed and tested a method for sensing and processing leak noise to reveal the leak location involving the use of a 64-element phased-array. Cross-correlations of ultrasonic noise waveforms from a leak into vacuum have been used with a phased-array analysis to find the direction from the sensor to the leak. This method measures the propagation of guided ultrasonic Lamb waves passing under the PZT array sensor in the spacecraft skin structure. This paper will describe the custom-designed array with integrated electronics, as well as the performance of the array in prototype applications. We show that this method can be used to successfully locate leaks to within a few millimeters on a 0.6-m square aluminum plate.

A novel scalable manufacturing process for the production of hydrogel-forming microneedle arrays.

PubMed

Lutton, Rebecca E M; Larrañeta, Eneko; Kearney, Mary-Carmel; Boyd, Peter; Woolfson, A David; Donnelly, Ryan F

2015-10-15

A novel manufacturing process for fabricating microneedle arrays (MN) has been designed and evaluated. The prototype is able to successfully produce 14×14 MN arrays and is easily capable of scale-up, enabling the transition from laboratory to industry and subsequent commercialisation. The method requires the custom design of metal MN master templates to produce silicone MN moulds using an injection moulding process. The MN arrays produced using this novel method was compared with centrifugation, the traditional method of producing aqueous hydrogel-forming MN arrays. The results proved that there was negligible difference between either methods, with each producing MN arrays with comparable quality. Both types of MN arrays can be successfully inserted in a skin simulant. In both cases the insertion depth was approximately 60% of the needle length and the height reduction after insertion was in both cases approximately 3%. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel scalable manufacturing process for the production of hydrogel-forming microneedle arrays

PubMed Central

Lutton, Rebecca E.M.; Larrañeta, Eneko; Kearney, Mary-Carmel; Boyd, Peter; Woolfson, A.David; Donnelly, Ryan F.

2015-01-01

A novel manufacturing process for fabricating microneedle arrays (MN) has been designed and evaluated. The prototype is able to successfully produce 14 × 14 MN arrays and is easily capable of scale-up, enabling the transition from laboratory to industry and subsequent commercialisation. The method requires the custom design of metal MN master templates to produce silicone MN moulds using an injection moulding process. The MN arrays produced using this novel method was compared with centrifugation, the traditional method of producing aqueous hydrogel-forming MN arrays. The results proved that there was negligible difference between either methods, with each producing MN arrays with comparable quality. Both types of MN arrays can be successfully inserted in a skin simulant. In both cases the insertion depth was approximately 60% of the needle length and the height reduction after insertion was in both cases approximately 3%. PMID:26302858

High-Reliability Pump Module for Non-Planar Ring Oscillator Laser

NASA Technical Reports Server (NTRS)

Liu, Duncan T.; Qiu, Yueming; Wilson, Daniel W.; Dubovitsky, Serge; Forouhar, Siamak

2007-01-01

We propose and have demonstrated a prototype high-reliability pump module for pumping a Non-Planar Ring Oscillator (NPRO) laser suitable for space missions. The pump module consists of multiple fiber-coupled single-mode laser diodes and a fiber array micro-lens array based fiber combiner. The reported Single-Mode laser diode combiner laser pump module (LPM) provides a higher normalized brightness at the combined beam than multimode laser diode based LPMs. A higher brightness from the pump source is essential for efficient NPRO laser pumping and leads to higher reliability because higher efficiency requires a lower operating power for the laser diodes, which in turn increases the reliability and lifetime of the laser diodes. Single-mode laser diodes with Fiber Bragg Grating (FBG) stabilized wavelength permit the pump module to be operated without a thermal electric cooler (TEC) and this further improves the overall reliability of the pump module. The single-mode laser diode LPM is scalable in terms of the number of pump diodes and is capable of combining hundreds of fiber-coupled laser diodes. In the proof-of-concept demonstration, an e-beam written diffractive micro lens array, a custom fiber array, commercial 808nm single mode laser diodes, and a custom NPRO laser head are used. The reliability of the proposed LPM is discussed.

Development of a 63K SNP Array for Cotton and High-Density Mapping of Intraspecific and Interspecific Populations of Gossypium spp.

PubMed Central

Hulse-Kemp, Amanda M.; Lemm, Jana; Plieske, Joerg; Ashrafi, Hamid; Buyyarapu, Ramesh; Fang, David D.; Frelichowski, James; Giband, Marc; Hague, Steve; Hinze, Lori L.; Kochan, Kelli J.; Riggs, Penny K.; Scheffler, Jodi A.; Udall, Joshua A.; Ulloa, Mauricio; Wang, Shirley S.; Zhu, Qian-Hao; Bag, Sumit K.; Bhardwaj, Archana; Burke, John J.; Byers, Robert L.; Claverie, Michel; Gore, Michael A.; Harker, David B.; Islam, Md S.; Jenkins, Johnie N.; Jones, Don C.; Lacape, Jean-Marc; Llewellyn, Danny J.; Percy, Richard G.; Pepper, Alan E.; Poland, Jesse A.; Mohan Rai, Krishan; Sawant, Samir V.; Singh, Sunil Kumar; Spriggs, Andrew; Taylor, Jen M.; Wang, Fei; Yourstone, Scott M.; Zheng, Xiuting; Lawley, Cindy T.; Ganal, Martin W.; Van Deynze, Allen; Wilson, Iain W.; Stelly, David M.

2015-01-01

High-throughput genotyping arrays provide a standardized resource for plant breeding communities that are useful for a breadth of applications including high-density genetic mapping, genome-wide association studies (GWAS), genomic selection (GS), complex trait dissection, and studying patterns of genomic diversity among cultivars and wild accessions. We have developed the CottonSNP63K, an Illumina Infinium array containing assays for 45,104 putative intraspecific single nucleotide polymorphism (SNP) markers for use within the cultivated cotton species Gossypium hirsutum L. and 17,954 putative interspecific SNP markers for use with crosses of other cotton species with G. hirsutum. The SNPs on the array were developed from 13 different discovery sets that represent a diverse range of G. hirsutum germplasm and five other species: G. barbadense L., G. tomentosum Nuttal × Seemann, G. mustelinum Miers × Watt, G. armourianum Kearny, and G. longicalyx J.B. Hutchinson and Lee. The array was validated with 1,156 samples to generate cluster positions to facilitate automated analysis of 38,822 polymorphic markers. Two high-density genetic maps containing a total of 22,829 SNPs were generated for two F2 mapping populations, one intraspecific and one interspecific, and 3,533 SNP markers were co-occurring in both maps. The produced intraspecific genetic map is the first saturated map that associates into 26 linkage groups corresponding to the number of cotton chromosomes for a cross between two G. hirsutum lines. The linkage maps were shown to have high levels of collinearity to the JGI G. raimondii Ulbrich reference genome sequence. The CottonSNP63K array, cluster file and associated marker sequences constitute a major new resource for the global cotton research community. PMID:25908569

MethLAB: a graphical user interface package for the analysis of array-based DNA methylation data.

PubMed

Kilaru, Varun; Barfield, Richard T; Schroeder, James W; Smith, Alicia K; Conneely, Karen N

2012-03-01

Recent evidence suggests that DNA methylation changes may underlie numerous complex traits and diseases. The advent of commercial, array-based methods to interrogate DNA methylation has led to a profusion of epigenetic studies in the literature. Array-based methods, such as the popular Illumina GoldenGate and Infinium platforms, estimate the proportion of DNA methylated at single-base resolution for thousands of CpG sites across the genome. These arrays generate enormous amounts of data, but few software resources exist for efficient and flexible analysis of these data. We developed a software package called MethLAB (http://genetics.emory.edu/conneely/MethLAB) using R, an open source statistical language that can be edited to suit the needs of the user. MethLAB features a graphical user interface (GUI) with a menu-driven format designed to efficiently read in and manipulate array-based methylation data in a user-friendly manner. MethLAB tests for association between methylation and relevant phenotypes by fitting a separate linear model for each CpG site. These models can incorporate both continuous and categorical phenotypes and covariates, as well as fixed or random batch or chip effects. MethLAB accounts for multiple testing by controlling the false discovery rate (FDR) at a user-specified level. Standard output includes a spreadsheet-ready text file and an array of publication-quality figures. Considering the growing interest in and availability of DNA methylation data, there is a great need for user-friendly open source analytical tools. With MethLAB, we present a timely resource that will allow users with no programming experience to implement flexible and powerful analyses of DNA methylation data.

Genetics Home Reference: cri-du-chat syndrome

MedlinePlus

... Pinkel D. High-resolution mapping of genotype-phenotype relationships in cri du chat syndrome using array comparative ... for Links Data Files & API Site Map Subscribe Customer Support USA.gov Copyright Privacy Accessibility FOIA Viewers & ...

Utah optrode array customization using stereotactic brain atlases and 3-D CAD modeling for optogenetic neocortical interrogation in small rodents and nonhuman primates.

PubMed

Boutte, Ronald W; Merlin, Sam; Yona, Guy; Griffiths, Brandon; Angelucci, Alessandra; Kahn, Itamar; Shoham, Shy; Blair, Steve

2017-10-01

As the optogenetic field expands, the need for precise targeting of neocortical circuits only grows more crucial. This work demonstrates a technique for using Solidworks ® computer-aided design (CAD) and readily available stereotactic brain atlases to create a three-dimensional (3-D) model of the dorsal region of area visual cortex 4 (V4D) of the macaque monkey ( Macaca fascicularis ) visual cortex. The 3-D CAD model of the brain was used to customize an [Formula: see text] Utah optrode array (UOA) after it was determined that a high-density ([Formula: see text]) UOA caused extensive damage to marmoset ( Callithrix jacchus ) primary visual cortex as assessed by electrophysiological recording of spiking activity through a 1.5-mm-diameter through glass via. The [Formula: see text] UOA was customized for optrode length ([Formula: see text]), optrode width ([Formula: see text]), optrode pitch ([Formula: see text]), backplane thickness ([Formula: see text]), and overall form factor ([Formula: see text]). Two [Formula: see text] UOAs were inserted into layer VI of macaque V4D cortices with minimal damage as assessed in fixed tissue cytochrome oxidase staining in nonrecoverable surgeries. Additionally, two [Formula: see text] arrays were implanted in mice ( Mus musculus ) motor cortices, providing early evidence for long-term tolerability (over 6 months), and for the ability to integrate the UOA with a Holobundle light delivery system toward patterned optogenetic stimulation of cortical networks.

Adaptive Injection-locking Oscillator Array for RF Spectrum Analysis

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

Leung, Daniel

2011-04-19

A highly parallel radio frequency receiver using an array of injection-locking oscillators for on-chip, rapid estimation of signal amplitudes and frequencies is considered. The oscillators are tuned to different natural frequencies, and variable gain amplifiers are used to provide negative feedback to adapt the locking band-width with the input signal to yield a combined measure of input signal amplitude and frequency detuning. To further this effort, an array of 16 two-stage differential ring oscillators and 16 Gilbert-cell mixers is designed for 40-400 MHz operation. The injection-locking oscillator array is assembled on a custom printed-circuit board. Control and calibration is achievedmore » by on-board microcontroller.« less

MethLAB

PubMed Central

Kilaru, Varun; Barfield, Richard T; Schroeder, James W; Smith, Alicia K

2012-01-01

Recent evidence suggests that DNA methylation changes may underlie numerous complex traits and diseases. The advent of commercial, array-based methods to interrogate DNA methylation has led to a profusion of epigenetic studies in the literature. Array-based methods, such as the popular Illumina GoldenGate and Infinium platforms, estimate the proportion of DNA methylated at single-base resolution for thousands of CpG sites across the genome. These arrays generate enormous amounts of data, but few software resources exist for efficient and flexible analysis of these data. We developed a software package called MethLAB (http://genetics.emory.edu/conneely/MethLAB) using R, an open source statistical language that can be edited to suit the needs of the user. MethLAB features a graphical user interface (GUI) with a menu-driven format designed to efficiently read in and manipulate array-based methylation data in a user-friendly manner. MethLAB tests for association between methylation and relevant phenotypes by fitting a separate linear model for each CpG site. These models can incorporate both continuous and categorical phenotypes and covariates, as well as fixed or random batch or chip effects. MethLAB accounts for multiple testing by controlling the false discovery rate (FDR) at a user-specified level. Standard output includes a spreadsheet-ready text file and an array of publication-quality figures. Considering the growing interest in and availability of DNA methylation data, there is a great need for user-friendly open source analytical tools. With MethLAB, we present a timely resource that will allow users with no programming experience to implement flexible and powerful analyses of DNA methylation data. PMID:22430798

Focal-plane detector system for the KATRIN experiment

NASA Astrophysics Data System (ADS)

Amsbaugh, J. F.; Barrett, J.; Beglarian, A.; Bergmann, T.; Bichsel, H.; Bodine, L. I.; Bonn, J.; Boyd, N. M.; Burritt, T. H.; Chaoui, Z.; Chilingaryan, S.; Corona, T. J.; Doe, P. J.; Dunmore, J. A.; Enomoto, S.; Formaggio, J. A.; Fränkle, F. M.; Furse, D.; Gemmeke, H.; Glück, F.; Harms, F.; Harper, G. C.; Hartmann, J.; Howe, M. A.; Kaboth, A.; Kelsey, J.; Knauer, M.; Kopmann, A.; Leber, M. L.; Martin, E. L.; Middleman, K. J.; Myers, A. W.; Oblath, N. S.; Parno, D. S.; Peterson, D. A.; Petzold, L.; Phillips, D. G.; Renschler, P.; Robertson, R. G. H.; Schwarz, J.; Steidl, M.; Tcherniakhovski, D.; Thümmler, T.; Van Wechel, T. D.; VanDevender, B. A.; Vöcking, S.; Wall, B. L.; Wierman, K. L.; Wilkerson, J. F.; Wüstling, S.

2015-04-01

The focal-plane detector system for the KArlsruhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high-vacuum system, a high-vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system. It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.

A High-Resolution SNP Array-Based Linkage Map Anchors a New Domestic Cat Draft Genome Assembly and Provides Detailed Patterns of Recombination.

PubMed

Li, Gang; Hillier, LaDeana W; Grahn, Robert A; Zimin, Aleksey V; David, Victor A; Menotti-Raymond, Marilyn; Middleton, Rondo; Hannah, Steven; Hendrickson, Sher; Makunin, Alex; O'Brien, Stephen J; Minx, Pat; Wilson, Richard K; Lyons, Leslie A; Warren, Wesley C; Murphy, William J

2016-06-01

High-resolution genetic and physical maps are invaluable tools for building accurate genome assemblies, and interpreting results of genome-wide association studies (GWAS). Previous genetic and physical maps anchored good quality draft assemblies of the domestic cat genome, enabling the discovery of numerous genes underlying hereditary disease and phenotypes of interest to the biomedical science and breeding communities. However, these maps lacked sufficient marker density to order thousands of shorter scaffolds in earlier assemblies, which instead relied heavily on comparative mapping with related species. A high-resolution map would aid in validating and ordering chromosome scaffolds from existing and new genome assemblies. Here, we describe a high-resolution genetic linkage map of the domestic cat genome based on genotyping 453 domestic cats from several multi-generational pedigrees on the Illumina 63K SNP array. The final maps include 58,055 SNP markers placed relative to 6637 markers with unique positions, distributed across all autosomes and the X chromosome. Our final sex-averaged maps span a total autosomal length of 4464 cM, the longest described linkage map for any mammal, confirming length estimates from a previous microsatellite-based map. The linkage map was used to order and orient the scaffolds from a substantially more contiguous domestic cat genome assembly (Felis catus v8.0), which incorporated ∼20 × coverage of Illumina fragment reads. The new genome assembly shows substantial improvements in contiguity, with a nearly fourfold increase in N50 scaffold size to 18 Mb. We use this map to report probable structural errors in previous maps and assemblies, and to describe features of the recombination landscape, including a massive (∼50 Mb) recombination desert (of virtually zero recombination) on the X chromosome that parallels a similar desert on the porcine X chromosome in both size and physical location. Copyright © 2016 Li et al.

Design and calibration of a six-axis MEMS sensor array for use in scoliosis correction surgery

NASA Astrophysics Data System (ADS)

Benfield, David; Yue, Shichao; Lou, Edmond; Moussa, Walied A.

2014-08-01

A six-axis sensor array has been developed to quantify the 3D force and moment loads applied in scoliosis correction surgery. Initially this device was developed to be applied during scoliosis correction surgery and augmented onto existing surgical instrumentation, however, use as a general load sensor is also feasible. The development has included the design, microfabrication, deployment and calibration of a sensor array. The sensor array consists of four membrane devices, each containing piezoresistive sensing elements, generating a total of 16 differential voltage outputs. The calibration procedure has made use of a custom built load application frame, which allows quantified forces and moments to be applied and compared to the outputs from the sensor array. Linear or non-linear calibration equations are generated to convert the voltage outputs from the sensor array back into 3D force and moment information for display or analysis.

Operation's Concept for Array-Based Deep Space Network

NASA Technical Reports Server (NTRS)

Bagri, Durgadas S.; Statman, Joseph I.; Gatti, Mark S.

2005-01-01

The Array-based Deep Space Network (DSNArray) will be a part of more than 10(exp 3) times increase in the downlink/telemetry capability of the Deep space Network (DSN). The key function of the DSN-Array is to provide cost-effective, robust Telemetry, Tracking and Command (TT&C) services to the space missions of NASA and its international partners. It provides an expanded approach to the use of an array-based system. Instead of using the array as an element in the existing DSN, relying to a large extent on the DSN infrastructure, we explore a broader departure from the current DSN, using fewer elements of the existing DSN, and establishing a more modern Concept of Operations. This paper gives architecture of DSN-Array and its operation's philosophy. It also describes customer's view of operations, operations management and logistics - including maintenance philosophy, anomaly analysis and reporting.

Genome-wide profiling of chromosomal alterations in renal cell carcinoma using high-density single nucleotide polymorphism arrays

PubMed Central

Chen, Meng; Ye, Yuanqing; Yang, Hushan; Tamboli, Pheroze; Matin, Surena; Tannir, Nizar M.; Wood, Christopher G.; Gu, Jian; Wu, Xifeng

2009-01-01

Purpose The identification of genetic aberrations may help understand the mechanisms of tumorigenesis and has important implications in diagnosis, prognosis, and treatment. Methods We applied Illumina's 317K high-density SNP-arrays to profile chromosomal aberrations in clear cell renal cell carcinoma (ccRCC) from 80 patients and analyzed the association of LOH/amplification events with clinicopathological characteristics and telomere length. Results The most common loss of heterozygosity (LOH) were 3p (69 cases) including 38 whole 3p arm losses, 30 large fragment LOH (spanning 3p21-36), and 1 interstitial LOH (spanning 3p12-14, 3p21-22, 3p24.1-24.2, and 3p24.3), followed by chromosome losses at 8p12-pter, 6q23.3-27, 14q24.1-qter, 9q32-qter, 10q22.3-qter, 9p13.3-pter, 4q28.3-qter, and 13q12.1-21.1. We also found several smallest overlapping regions of LOH that contained tumor suppressor genes. One smallest LOH in 8p12 had a size of 0.29 Mb and only contained one gene (NRG1). The most frequent chromosome gains were at 5q (32 cases), including 10 whole 5q amplification, 21 large amplifications encompassing 5q32-ter, and 1 focal amplification in 5q35.3 (0.42 Mb). The other common chromosome gains were 1q25.1-qter, 7q21.13-qter, 8q24.12-qter, and whole 7p arm. Significant associations of LOH at 9p, 9q, 14q, and 18q were observed with higher nuclear grade. Significant associations with tumor stage were observed for LOH at 14q, 18p, and 21q. Finally, we found that tumors with LOH at 2q, 6p, 6q, 9p, 9q, and 17p had significantly shorter telomere length than those without LOH. Conclusion This is the first study to use Illumina's SNP-CGH array that provides a close estimate of the size and frequency of chromosome LOH and amplifications of ccRCC. The identified regions and genes may become diagnostic and prognostic biomarkers as well as potential targets of therapy. PMID:19521957

Commentary on "identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array." Eeles RA, Olama AA, Benlloch S, Saunders EJ, Leongamornlert DA, Tymrakiewicz M, Ghoussaini M, Luccarini C, Dennis J, Jugurnauth-Little S, Dadaev T, Neal DE, Hamdy FC, Donovan JL, Muir K, Giles GG, Severi G, Wiklund F, Gronberg H, Haiman CA, Schumacher F, Henderson BE, Le Marchand L, Lindstrom S, Kraft P, Hunter DJ, Gapstur S, Chanock SJ, Berndt SI, Albanes D, Andriole G, Schleutker J, Weischer M, Canzian F, Riboli E, Key TJ, Travis RC, Campa D, Ingles SA, John EM, Hayes RB, Pharoah PD, Pashayan N, Khaw KT, Stanford JL, Ostrander EA, Signorello LB, Thibodeau SN, Schaid D, Maier C, Vogel W, Kibel AS, Cybulski C, Lubinski J, Cannon-Albright L, Brenner H, Park JY, Kaneva R, Batra J, Spurdle AB, Clements JA, Teixeira MR, Dicks E, Lee A, Dunning AM, Baynes C, Conroy D, Maranian MJ, Ahmed S, Govindasami K, Guy M, Wilkinson RA, Sawyer EJ, Morgan A, Dearnaley DP, Horwich A, Huddart RA, Khoo VS, Parker CC, Van As NJ, Woodhouse CJ, Thompson A, Dudderidge T, Ogden C, Cooper CS, Lophatananon A, Cox A, Southey MC, Hopper JL, English DR, Aly M, Adolfsson J, Xu J, Zheng SL, Yeager M, Kaaks R, Diver WR, Gaudet MM, Stern MC, Corral R, Joshi AD, Shahabi A, Wahlfors T, Tammela TL, Auvinen A, Virtamo J, Klarskov P, Nordestgaard BG, Røder MA, Nielsen SF, Bojesen SE, Siddiq A, Fitzgerald LM, Kolb S, Kwon EM, Karyadi DM, Blot WJ, Zheng W, Cai Q, McDonnell SK, Rinckleb AE, Drake B, Colditz G, Wokolorczyk D, Stephenson RA, Teerlink C, Muller H, Rothenbacher D, Sellers TA, Lin HY, Slavov C, Mitev V, Lose F, Srinivasan S, Maia S, Paulo P, Lange E, Cooney KA, Antoniou AC, Vincent D, Bacot F, Tessier DC; COGS-Cancer Research UK GWAS-ELLIPSE (part of GAME-ON) Initiative; Australian Prostate Cancer Bioresource; UK Genetic Prostate Cancer Study Collaborators/British Association of Urological Surgeons' Section of Oncology; UK ProtecT (Prostate testing for cancer and Treatment) Study

PubMed

Olumi, Aria F

2014-02-01

Prostate cancer is the most frequently diagnosed cancer in males in developed countries. To identify common prostate cancer susceptibility alleles, we genotyped 211,155 SNPs on a custom Illumina array (iCOGS) in blood DNA from 25,074 prostate cancer cases and 24,272 controls from the international PRACTICAL Consortium. Twenty-three new prostate cancer susceptibility loci were identified at genome-wide significance (P<5×10(-8)). More than 70 prostate cancer susceptibility loci, explaining ~30% of the familial risk for this disease, have now been identified. On the basis of combined risks conferred by the new and previously known risk loci, the top 1% of the risk distribution has a 4.7-fold higher risk than the average of the population being profiled. These results will facilitate population risk stratification for clinical studies. Copyright © 2014 Elsevier Inc. All rights reserved.

A powerful tool for genome analysis in maize: development and evaluation of the high density 600 k SNP genotyping array.

PubMed

Unterseer, Sandra; Bauer, Eva; Haberer, Georg; Seidel, Michael; Knaak, Carsten; Ouzunova, Milena; Meitinger, Thomas; Strom, Tim M; Fries, Ruedi; Pausch, Hubert; Bertani, Christofer; Davassi, Alessandro; Mayer, Klaus Fx; Schön, Chris-Carolin

2014-09-29

High density genotyping data are indispensable for genomic analyses of complex traits in animal and crop species. Maize is one of the most important crop plants worldwide, however a high density SNP genotyping array for analysis of its large and highly dynamic genome was not available so far. We developed a high density maize SNP array composed of 616,201 variants (SNPs and small indels). Initially, 57 M variants were discovered by sequencing 30 representative temperate maize lines and then stringently filtered for sequence quality scores and predicted conversion performance on the array resulting in the selection of 1.2 M polymorphic variants assayed on two screening arrays. To identify high-confidence variants, 285 DNA samples from a broad genetic diversity panel of worldwide maize lines including the samples used for sequencing, important founder lines for European maize breeding, hybrids, and proprietary samples with European, US, semi-tropical, and tropical origin were used for experimental validation. We selected 616 k variants according to their performance during validation, support of genotype calls through sequencing data, and physical distribution for further analysis and for the design of the commercially available Affymetrix® Axiom® Maize Genotyping Array. This array is composed of 609,442 SNPs and 6,759 indels. Among these are 116,224 variants in coding regions and 45,655 SNPs of the Illumina® MaizeSNP50 BeadChip for study comparison. In a subset of 45,974 variants, apart from the target SNP additional off-target variants are detected, which show only a minor bias towards intermediate allele frequencies. We performed principal coordinate and admixture analyses to determine the ability of the array to detect and resolve population structure and investigated the extent of LD within a worldwide validation panel. The high density Affymetrix® Axiom® Maize Genotyping Array is optimized for European and American temperate maize and was developed based on a diverse sample panel by applying stringent quality filter criteria to ensure its suitability for a broad range of applications. With 600 k variants it is the largest currently publically available genotyping array in crop species.

Customizing microarrays for neuroscience drug discovery.

PubMed

Girgenti, Matthew J; Newton, Samuel S

2007-08-01

Microarray-based gene profiling has become the centerpiece of gene expression studies in the biological sciences. The ability to now interrogate the entire genome using a single chip demonstrates the progress in technology and instrumentation that has been made over the last two decades. Although this unbiased approach provides researchers with an immense quantity of data, obtaining meaningful insight is not possible without intensive data analysis and processing. Custom developed arrays have emerged as a viable and attractive alternative that can take advantage of this robust technology and tailor it to suit the needs and requirements of individual investigations. The ability to simplify data analysis, reduce noise and carefully optimize experimental conditions makes it a suitable tool that can be effectively utilized in neuroscience drug discovery efforts. Furthermore, incorporating recent advancements in fine focusing gene profiling to include specific cellular phenotypes can help resolve the complex cellular heterogeneity of the brain. This review surveys the use of microarray technology in neuroscience paying special attention to customized arrays and their potential in drug discovery. Novel applications of microarrays and ancillary techniques, such as laser microdissection, FAC sorting and RNA amplification, have also been discussed. The notion that a hypothesis-driven approach can be integrated into drug development programs is highlighted.

An unreliable group arrival queue with k stages of service, retrial under variant vacation policy

NASA Astrophysics Data System (ADS)

Radha, J.; Indhira, K.; Chandrasekaran, V. M.

2017-11-01

In this research work we considered repairable retrial queue with group arrival and the server utilize the variant vacations. A server gives service in k stages. Any arriving group of units finds the server free, one from the group entering the first stage of service and the rest are joining into the orbit. After completion of the i th stage of service, the customer may have the option to choose (i+1)th stage of service with probability θi , with probability pi may join into orbit as feedback customer or may leave the system with probability {q}i=≤ft\\{\\begin{array}{l}1-{p}i-{θ }i,i=1,2,\\cdots k-1\\ 1-{p}i,i=k\\end{array}\\right\\}. If the orbit is empty at the service completion of each stage service, the server takes modified vacation until at least one customer appears in the orbit on the server returns from a vacation. Busy server may get to breakdown and the service channel will fail for a short interval of time. By using the supplementary variable method, steady state probability generating function for system size, some system performance measures are discussed.

Focal plane subsystem design and performance for atmospheric chemistry from geostationary orbit tropospheric emissions monitoring of pollution

NASA Astrophysics Data System (ADS)

Gilmore, A. S.; Philbrick, R. H.; Funderburg, J.

2017-09-01

Remote sensing of pollutants are enabled from a satellite in a geostationary orbit containing an imaging spectrometer encompassing the wavelength ranges of 290 - 490 nm and 540 - 740 nm. As the first of NASA's Earth Venture Instrument Program, the Tropospheric Emissions: Monitoring of Pollution (TEMPO) program will utilize this instrument to measure hourly air quality over a large portion of North America. The focal plane subsystem (FPS) contains two custom designed and critically aligned full frame transfer charge coupled devices (active area: 1028 x 2048, 18 μm) within a focal plane array package designed for radiation tolerance and space charging rejection. In addition, the FPS contains custom distributed focal plane electronics that provide all necessary clocks and biases to the sensors, receives all analog data from the sensors and performs 14 bit analog to digital conversion for upstream processing. Finally, the FPS encompasses custom low noise cables connecting the focal plane array and associated electronics. This paper discusses the design and performance of this novel focal plane subsystem with particular emphasis on the optical performance achieved including alignment, quantum efficiency, and modulation transfer function.

Focal-plane detector system for the KATRIN experiment

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

Amsbaugh, J. F.; Barrett, J.; Beglarian, A.

Here, the local plane detector system for the KArlsiuhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high vacuum system, a high vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system, It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.

Focal-plane detector system for the KATRIN experiment

DOE PAGES

Amsbaugh, J. F.; Barrett, J.; Beglarian, A.; ...

2015-01-09

Here, the local plane detector system for the KArlsiuhe TRItium Neutrino (KATRIN) experiment consists of a multi-pixel silicon p-i-n-diode array, custom readout electronics, two superconducting solenoid magnets, an ultra high vacuum system, a high vacuum system, calibration and monitoring devices, a scintillating veto, and a custom data-acquisition system, It is designed to detect the low-energy electrons selected by the KATRIN main spectrometer. We describe the system and summarize its performance after its final installation.

Convolutional Neural Network on Embedded Linux(trademark) System-on-Chip: A Methodology and Performance Benchmark

DTIC Science & Technology

2016-05-01

A9 CPU and 15 W for the i7 CPU. A method of accelerating this computation is by using a customized hardware unit called a field- programmable gate...implementation of custom logic to accelerate com- putational workloads. This FPGA fabric, in addition to the standard programmable logic, contains 220...chip; field- programmable gate array Daniel Gebhardt U U U U 18 (619) 553-2786 INITIAL DISTRIBUTION 84300 Library (2) 85300 Archive/Stock (1

Convolutional Neural Network on Embedded Linux System-on-Chip: A Methodology and Performance Benchmark

DTIC Science & Technology

2016-05-01

A9 CPU and 15 W for the i7 CPU. A method of accelerating this computation is by using a customized hardware unit called a field- programmable gate...implementation of custom logic to accelerate com- putational workloads. This FPGA fabric, in addition to the standard programmable logic, contains 220...chip; field- programmable gate array Daniel Gebhardt U U U U 18 (619) 553-2786 INITIAL DISTRIBUTION 84300 Library (2) 85300 Archive/Stock (1

Molecular testing for familial hypercholesterolaemia-associated mutations in a UK-based cohort: development of an NGS-based method and comparison with multiplex polymerase chain reaction and oligonucleotide arrays.

PubMed

Reiman, Anne; Pandey, Sarojini; Lloyd, Kate L; Dyer, Nigel; Khan, Mike; Crockard, Martin; Latten, Mark J; Watson, Tracey L; Cree, Ian A; Grammatopoulos, Dimitris K

2016-11-01

Background Detection of disease-associated mutations in patients with familial hypercholesterolaemia is crucial for early interventions to reduce risk of cardiovascular disease. Screening for these mutations represents a methodological challenge since more than 1200 different causal mutations in the low-density lipoprotein receptor has been identified. A number of methodological approaches have been developed for screening by clinical diagnostic laboratories. Methods Using primers targeting, the low-density lipoprotein receptor, apolipoprotein B, and proprotein convertase subtilisin/kexin type 9, we developed a novel Ion Torrent-based targeted re-sequencing method. We validated this in a West Midlands-UK small cohort of 58 patients screened in parallel with other mutation-targeting methods, such as multiplex polymerase chain reaction (Elucigene FH20), oligonucleotide arrays (Randox familial hypercholesterolaemia array) or the Illumina next-generation sequencing platform. Results In this small cohort, the next-generation sequencing method achieved excellent analytical performance characteristics and showed 100% and 89% concordance with the Randox array and the Elucigene FH20 assay. Investigation of the discrepant results identified two cases of mutation misclassification of the Elucigene FH20 multiplex polymerase chain reaction assay. A number of novel mutations not previously reported were also identified by the next-generation sequencing method. Conclusions Ion Torrent-based next-generation sequencing can deliver a suitable alternative for the molecular investigation of familial hypercholesterolaemia patients, especially when comprehensive mutation screening for rare or unknown mutations is required.

Plenoptic Ophthalmoscopy: A Novel Imaging Technique.

PubMed

Adam, Murtaza K; Aenchbacher, Weston; Kurzweg, Timothy; Hsu, Jason

2016-11-01

This prospective retinal imaging case series was designed to establish feasibility of plenoptic ophthalmoscopy (PO), a novel mydriatic fundus imaging technique. A custom variable intensity LED array light source adapter was created for the Lytro Gen1 light-field camera (Lytro, Mountain View, CA). Initial PO testing was performed on a model eye and rabbit fundi. PO image acquisition was then performed on dilated human subjects with a variety of retinal pathology and images were subjected to computational enhancement. The Lytro Gen1 light-field camera with custom LED array captured fundus images of eyes with diabetic retinopathy, age-related macular degeneration, retinal detachment, and other diagnoses. Post-acquisition computational processing allowed for refocusing and perspective shifting of retinal PO images, resulting in improved image quality. The application of PO to image the ocular fundus is feasible. Additional studies are needed to determine its potential clinical utility. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:1038-1043.]. Copyright 2016, SLACK Incorporated.

An acceleration framework for synthetic aperture radar algorithms

NASA Astrophysics Data System (ADS)

Kim, Youngsoo; Gloster, Clay S.; Alexander, Winser E.

2017-04-01

Algorithms for radar signal processing, such as Synthetic Aperture Radar (SAR) are computationally intensive and require considerable execution time on a general purpose processor. Reconfigurable logic can be used to off-load the primary computational kernel onto a custom computing machine in order to reduce execution time by an order of magnitude as compared to kernel execution on a general purpose processor. Specifically, Field Programmable Gate Arrays (FPGAs) can be used to accelerate these kernels using hardware-based custom logic implementations. In this paper, we demonstrate a framework for algorithm acceleration. We used SAR as a case study to illustrate the potential for algorithm acceleration offered by FPGAs. Initially, we profiled the SAR algorithm and implemented a homomorphic filter using a hardware implementation of the natural logarithm. Experimental results show a linear speedup by adding reasonably small processing elements in Field Programmable Gate Array (FPGA) as opposed to using a software implementation running on a typical general purpose processor.

Characteristics of a semi-custom library development system

NASA Technical Reports Server (NTRS)

Yancey, M.; Cannon, R.

1990-01-01

Standard cell and gate array macro libraries are in common use with workstation computer aided design (CAD) tools for application specific integrated circuit (ASIC) semi-custom application and have resulted in significant improvements in the overall design efficiencies as contrasted with custom design methodologies. Similar design methodology enhancements in providing for the efficient development of the library cells is an important factor in responding to the need for continuous technology improvement. The characteristics of a library development system that provides design flexibility and productivity enhancements for the library development engineer as he provides libraries in the state-of-the-art process technologies are presented. An overview of Gould's library development system ('Accolade') is also presented.

Generation of Custom DSP Transform IP Cores: Case Study Walsh-Hadamard Transform

DTIC Science & Technology

2002-09-01

mathematics and hardware design What I know: Finite state machine Pipelining Systolic array … What I know: Linear algebra Digital signal processing...state machine Pipelining Systolic array … What I know: Linear algebra Digital signal processing Adaptive filter theory … A math guy A hardware engineer...Synthesis Technology Libary Bit-width (8) HF factor (1,2,3,6) VF factor (1,2,4, ... 32) Xilinx FPGA Place&Route Xilinx FPGA Place&Route Performance

High Speed Imaging using Nanoprobe Arrays

DTIC Science & Technology

2010-06-23

Gotsmann and U. Dürig, Appl. Phys. Lett. 87, 194102 2005. 9 W. P. King, S. Saxena, B. A. Nelson, R. Pitchimani, and B. L. Weeks, Nano Lett. 6, 2145...microcantilevers with selective coatings has been applied as an artificial nose to recognize and characterize alcohol vapors either in a static mode...doped resistive heater. Fig. 4(c) shows a custom printed circuit board (PCB) to mount the array chip and a flexible ribbon cable for the electrical

Alignment of sensor arrays in optical instruments using a geometric approach.

PubMed

Sawyer, Travis W

2018-02-01

Alignment of sensor arrays in optical instruments is critical to maximize the instrument's performance. While many commercial systems use standardized mounting threads for alignment, custom systems require specialized equipment and alignment procedures. These alignment procedures can be time-consuming, dependent on operator experience, and have low repeatability. Furthermore, each alignment solution must be considered on a case-by-case basis, leading to additional time and resource cost. Here I present a method to align a sensor array using geometric analysis. By imaging a grid pattern of dots, I show that it is possible to calculate the misalignment for a sensor in five degrees of freedom simultaneously. I first test the approach by simulating different cases of misalignment using Zemax before applying the method to experimentally acquired data of sensor misalignment for an echelle spectrograph. The results show that the algorithm effectively quantifies misalignment in five degrees of freedom for an F/5 imaging system, accurate to within ±0.87  deg in rotation and ±0.86  μm in translation. Furthermore, the results suggest that the method can also be applied to non-imaging systems with a small penalty to precision. This general approach can potentially improve the alignment of sensor arrays in custom instruments by offering an accurate, quantitative approach to calculating misalignment in five degrees of freedom simultaneously.

Evaluation of SNP Data from the Malus Infinium Array Identifies Challenges for Genetic Analysis of Complex Genomes of Polyploid Origin

PubMed Central

Troggio, Michela; Šurbanovski, Nada; Bianco, Luca; Moretto, Marco; Giongo, Lara; Banchi, Elisa; Viola, Roberto; Fernández, Felicdad Fernández; Costa, Fabrizio; Velasco, Riccardo; Cestaro, Alessandro; Sargent, Daniel James

2013-01-01

High throughput arrays for the simultaneous genotyping of thousands of single-nucleotide polymorphisms (SNPs) have made the rapid genetic characterisation of plant genomes and the development of saturated linkage maps a realistic prospect for many plant species of agronomic importance. However, the correct calling of SNP genotypes in divergent polyploid genomes using array technology can be problematic due to paralogy, and to divergence in probe sequences causing changes in probe binding efficiencies. An Illumina Infinium II whole-genome genotyping array was recently developed for the cultivated apple and used to develop a molecular linkage map for an apple rootstock progeny (M432), but a large proportion of segregating SNPs were not mapped in the progeny, due to unexpected genotype clustering patterns. To investigate the causes of this unexpected clustering we performed BLAST analysis of all probe sequences against the ‘Golden Delicious’ genome sequence and discovered evidence for paralogous annealing sites and probe sequence divergence for a high proportion of probes contained on the array. Following visual re-evaluation of the genotyping data generated for 8,788 SNPs for the M432 progeny using the array, we manually re-scored genotypes at 818 loci and mapped a further 797 markers to the M432 linkage map. The newly mapped markers included the majority of those that could not be mapped previously, as well as loci that were previously scored as monomorphic, but which segregated due to divergence leading to heterozygosity in probe annealing sites. An evaluation of the 8,788 probes in a diverse collection of Malus germplasm showed that more than half the probes returned genotype clustering patterns that were difficult or impossible to interpret reliably, highlighting implications for the use of the array in genome-wide association studies. PMID:23826289

CIDR

Science.gov Websites

they have high Illumina design scores or have worked in other experiments. For Golden Gate experiments design files returned by Illumina. Efficient SNP selection: The most efficient way to select your SNPs is to get Illumina design scores on all of your possible SNPs prior to narrowing down your list. You can

Characteristics of microbial community functional structure of a biological coking wastewater treatment system.

PubMed

Joshi, Dev Raj; Zhang, Yu; Zhang, Hong; Gao, Yingxin; Yang, Min

2018-01-01

Nitrogenous heterocyclic compounds are key pollutants in coking wastewater; however, the functional potential of microbial communities for biodegradation of such contaminants during biological treatment is still elusive. Herein, a high throughput functional gene array (GeoChip 5.0) in combination with Illumina HiSeq2500 sequencing was used to compare and characterize the microbial community functional structure in a long run (500days) bench scale bioreactor treating coking wastewater, with a control system treating synthetic wastewater. Despite the inhibitory toxic pollutants, GeoChip 5.0 detected almost all key functional gene (average 61,940 genes) categories in the coking wastewater sludge. With higher abundance, aromatic ring cleavage dioxygenase genes including multi ring1,2diox; one ring2,3diox; catechol represented significant functional potential for degradation of aromatic pollutants which was further confirmed by Illumina HiSeq2500 analysis results. Response ratio analysis revealed that three nitrogenous compound degrading genes- nbzA (nitro-aromatics), tdnB (aniline), and scnABC (thiocyanate) were unique for coking wastewater treatment, which might be strong cause to increase ammonia level during the aerobic process. Additionally, HiSeq2500 elucidated carbozole and isoquinoline degradation genes in the system. These findings expanded our understanding on functional potential of microbial communities to remove organic nitrogenous pollutants; hence it will be useful in optimization strategies for biological treatment of coking wastewater. Copyright © 2017. Published by Elsevier B.V.

A novel ultra high-throughput 16S rRNA gene amplicon sequencing library preparation method for the Illumina HiSeq platform.

PubMed

de Muinck, Eric J; Trosvik, Pål; Gilfillan, Gregor D; Hov, Johannes R; Sundaram, Arvind Y M

2017-07-06

Advances in sequencing technologies and bioinformatics have made the analysis of microbial communities almost routine. Nonetheless, the need remains to improve on the techniques used for gathering such data, including increasing throughput while lowering cost and benchmarking the techniques so that potential sources of bias can be better characterized. We present a triple-index amplicon sequencing strategy to sequence large numbers of samples at significantly lower c ost and in a shorter timeframe compared to existing methods. The design employs a two-stage PCR protocol, incorpo rating three barcodes to each sample, with the possibility to add a fourth-index. It also includes heterogeneity spacers to overcome low complexity issues faced when sequencing amplicons on Illumina platforms. The library preparation method was extensively benchmarked through analysis of a mock community in order to assess biases introduced by sample indexing, number of PCR cycles, and template concentration. We further evaluated the method through re-sequencing of a standardized environmental sample. Finally, we evaluated our protocol on a set of fecal samples from a small cohort of healthy adults, demonstrating good performance in a realistic experimental setting. Between-sample variation was mainly related to batch effects, such as DNA extraction, while sample indexing was also a significant source of bias. PCR cycle number strongly influenced chimera formation and affected relative abundance estimates of species with high GC content. Libraries were sequenced using the Illumina HiSeq and MiSeq platforms to demonstrate that this protocol is highly scalable to sequence thousands of samples at a very low cost. Here, we provide the most comprehensive study of performance and bias inherent to a 16S rRNA gene amplicon sequencing method to date. Triple-indexing greatly reduces the number of long custom DNA oligos required for library preparation, while the inclusion of variable length heterogeneity spacers minimizes the need for PhiX spike-in. This design results in a significant cost reduction of highly multiplexed amplicon sequencing. The biases we characterize highlight the need for highly standardized protocols. Reassuringly, we find that the biological signal is a far stronger structuring factor than the various sources of bias.

A Hermetic Wireless Subretinal Neurostimulator for Vision Prostheses

PubMed Central

Shire, Douglas B.; Chen, Jinghua; Doyle, Patrick; Gingerich, Marcus D.; Cogan, Stuart F.; Drohan, William A.; Behan, Sonny; Theogarajan, Luke; Wyatt, John L.; Rizzo, Joseph F.

2016-01-01

A miniaturized, hermetically encased, wirelessly operated retinal prosthesis has been developed for preclinical studies in the Yucatan minipig, and includes several design improvements over our previously reported device. The prosthesis attaches conformally to the outside of the eye and electrically drives a microfabricated thin-film polyimide array of sputtered iridium oxide film electrodes. This array is implanted into the subretinal space using a customized ab externo surgical technique. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs in the case connect the stimulator chip to secondary power and data receiving coils on the eye and to the electrode array under the retina. Long-term in vitro pulse testing of the electrodes projected a lifetime consistent with typical devices in industry. The final assembly was tested in vitro to verify wireless operation of the system in physiological saline using a custom RF transmitter and primary coils. Stimulation pulse strength, duration, and frequency were programmed wirelessly from a Peripheral Component Interconnect eXtensions for Instrumentation (PXI) computer. Operation of the retinal implant has been verified in two pigs for up to five and a half months by detecting stimulus artifacts generated by the implanted device. PMID:21859595

Optical Fiber Array Assemblies for Space Flight on the Lunar Reconnaissance Orbiter

NASA Technical Reports Server (NTRS)

Ott, Jelanie; Matuszeski, Adam

2011-01-01

Custom fiber optic bundle array assemblies developed by the Photonics Group at NASA Goddard Space Flight Center were an enabling technology for both the Lunar Orbiter Laser Altimeter (LOLA) and the Laser Ranging (LR) Investigation on the Lunar Reconnaissance Orbiter (LRO) currently in operation. The unique assembly array designs provided considerable decrease in size and weight and met stringent system level requirements. This is the first time optical fiber array bundle assemblies were used in a high performance space flight application. This innovation was achieved using customized Diamond Switzerland AVIM optical connectors. For LOLA, a five fiber array was developed for the receiver telescope to maintain precise alignment for each of the 200/220 micron optical fibers collecting 1,064 nm wavelength light being reflected back from the moon. The array splits to five separate detectors replacing the need for multiple telescopes. An image illustration of the LOLA instrument can be found at the top of the figure. For the laser ranging, a seven-optical-fiber array of 400/440 micron fibers was developed to transmit light from behind the LR receiver telescope located on the end of the high gain antenna system (HGAS). The bundle was routed across two moving gimbals, down the HGAS boom arm, over a deployable mandrel and across the spacecraft to a detector on the LOLA instrument. The routing of the optical fiber bundle and its end locations is identified in the figure. The Laser Ranging array and bundle is currently accepting light at a wavelength of 532 nm sent to the moon from laser stations at Greenbelt MD and other stations around the world to gather precision ranging information from the Earth to the LRO spacecraft. The LR bundle assembly is capable of withstanding temperatures down to -55 C at the connectors, and 20,000 mechanical gimbal cycles at temperatures as cold as -20 C along the length of the seven-fiber bundle (that is packaged into the gimbals). The total bundle assembly is 10 meters long with two interconnections requiring precise clocking of the seven-fiber array pattern.

Development and validation of a 20K single nucleotide polymorphism (SNP) whole genome genotyping array for apple (Malus × domestica Borkh).

PubMed

Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

2014-01-01

High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs.

Development and Validation of a 20K Single Nucleotide Polymorphism (SNP) Whole Genome Genotyping Array for Apple (Malus × domestica Borkh)

PubMed Central

Bianco, Luca; Cestaro, Alessandro; Sargent, Daniel James; Banchi, Elisa; Derdak, Sophia; Di Guardo, Mario; Salvi, Silvio; Jansen, Johannes; Viola, Roberto; Gut, Ivo; Laurens, Francois; Chagné, David; Velasco, Riccardo; van de Weg, Eric; Troggio, Michela

2014-01-01

High-density SNP arrays for genome-wide assessment of allelic variation have made high resolution genetic characterization of crop germplasm feasible. A medium density array for apple, the IRSC 8K SNP array, has been successfully developed and used for screens of bi-parental populations. However, the number of robust and well-distributed markers contained on this array was not sufficient to perform genome-wide association analyses in wider germplasm sets, or Pedigree-Based Analysis at high precision, because of rapid decay of linkage disequilibrium. We describe the development of an Illumina Infinium array targeting 20K SNPs. The SNPs were predicted from re-sequencing data derived from the genomes of 13 Malus × domestica apple cultivars and one accession belonging to a crab apple species (M. micromalus). A pipeline for SNP selection was devised that avoided the pitfalls associated with the inclusion of paralogous sequence variants, supported the construction of robust multi-allelic SNP haploblocks and selected up to 11 entries within narrow genomic regions of ±5 kb, termed focal points (FPs). Broad genome coverage was attained by placing FPs at 1 cM intervals on a consensus genetic map, complementing them with FPs to enrich the ends of each of the chromosomes, and by bridging physical intervals greater than 400 Kbps. The selection also included ∼3.7K validated SNPs from the IRSC 8K array. The array has already been used in other studies where ∼15.8K SNP markers were mapped with an average of ∼6.8K SNPs per full-sib family. The newly developed array with its high density of polymorphic validated SNPs is expected to be of great utility for Pedigree-Based Analysis and Genomic Selection. It will also be a valuable tool to help dissect the genetic mechanisms controlling important fruit quality traits, and to aid the identification of marker-trait associations suitable for the application of Marker Assisted Selection in apple breeding programs. PMID:25303088

Monitoring Error Rates In Illumina Sequencing.

PubMed

Manley, Leigh J; Ma, Duanduan; Levine, Stuart S

2016-12-01

Guaranteeing high-quality next-generation sequencing data in a rapidly changing environment is an ongoing challenge. The introduction of the Illumina NextSeq 500 and the depreciation of specific metrics from Illumina's Sequencing Analysis Viewer (SAV; Illumina, San Diego, CA, USA) have made it more difficult to determine directly the baseline error rate of sequencing runs. To improve our ability to measure base quality, we have created an open-source tool to construct the Percent Perfect Reads (PPR) plot, previously provided by the Illumina sequencers. The PPR program is compatible with HiSeq 2000/2500, MiSeq, and NextSeq 500 instruments and provides an alternative to Illumina's quality value (Q) scores for determining run quality. Whereas Q scores are representative of run quality, they are often overestimated and are sourced from different look-up tables for each platform. The PPR's unique capabilities as a cross-instrument comparison device, as a troubleshooting tool, and as a tool for monitoring instrument performance can provide an increase in clarity over SAV metrics that is often crucial for maintaining instrument health. These capabilities are highlighted.

MixHMM: Inferring Copy Number Variation and Allelic Imbalance Using SNP Arrays and Tumor Samples Mixed with Stromal Cells

PubMed Central

Schulz, Vincent; Chen, Min; Tuck, David

2010-01-01

Background Genotyping platforms such as single nucleotide polymorphism (SNP) arrays are powerful tools to study genomic aberrations in cancer samples. Allele specific information from SNP arrays provides valuable information for interpreting copy number variation (CNV) and allelic imbalance including loss-of-heterozygosity (LOH) beyond that obtained from the total DNA signal available from array comparative genomic hybridization (aCGH) platforms. Several algorithms based on hidden Markov models (HMMs) have been designed to detect copy number changes and copy-neutral LOH making use of the allele information on SNP arrays. However heterogeneity in clinical samples, due to stromal contamination and somatic alterations, complicates analysis and interpretation of these data. Methods We have developed MixHMM, a novel hidden Markov model using hidden states based on chromosomal structural aberrations. MixHMM allows CNV detection for copy numbers up to 7 and allows more complete and accurate description of other forms of allelic imbalance, such as increased copy number LOH or imbalanced amplifications. MixHMM also incorporates a novel sample mixing model that allows detection of tumor CNV events in heterogeneous tumor samples, where cancer cells are mixed with a proportion of stromal cells. Conclusions We validate MixHMM and demonstrate its advantages with simulated samples, clinical tumor samples and a dilution series of mixed samples. We have shown that the CNVs of cancer cells in a tumor sample contaminated with up to 80% of stromal cells can be detected accurately using Illumina BeadChip and MixHMM. Availability The MixHMM is available as a Python package provided with some other useful tools at http://genecube.med.yale.edu:8080/MixHMM. PMID:20532221

Genomic analysis using high density SNP based oligonucleotide arrays and MLPA provides a comprehensive analysis of INI1/SMARCB1 in malignant rhabdoid tumors

PubMed Central

Jackson, Eric M.; Sievert, Angela J.; Gai, Xiaowu; Hakonarson, Hakon; Judkins, Alexander R; Tooke, Laura; Perin, Juan Carlos; Xie, Hongbo; Shaikh, Tamim H.; Biegel, Jaclyn A.

2009-01-01

Translational Relevance Previous reports suggested that abnormalities of INI1 could be detected in 70–75% of malignant rhabdoid tumors. The mechanism of inactivation in the other 25% remained unclear. The goal of this study was to perform a high-resolution genomic analysis of a large series of rhabdoid tumors with the expectation of identifying additional loci related to the initiation or progression of these malignancies. We also developed a comprehensive set of assays, including a new MLPA assay, to interrogate the INI1 locus in 22q11.2. Intragenic deletions could be detected using the Illumina 550K Beadchip, whereas single exon deletions could be detected using MLPA. The current study demonstrates that with a multi-platform approach, alterations at the INI1 locus can be detected in almost all cases. Thus, appropriate molecular genetic testing can be used as an aid in the diagnosis and for treatment planning for most patients. Purpose A high-resolution genomic profiling and comprehensive targeted analysis of INI1/SMARCB1 of a large series of pediatric rhabdoid tumors was performed. The aim was to identify regions of copy number change and loss of heterozygosity that might pinpoint additional loci involved in the development or progression of rhabdoid tumors, and define the spectrum of genomic alterations of INI1 in this malignancy. Experimental Design A multi-platform approach, utilizing Illumina single nucleotide polymorphism (SNP) based oligonucleotide arrays, multiplex ligation dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH), and coding sequence analysis was used to characterize genome wide copy number changes, loss of heterozygosity, and genomic alterations of INI1/SMARCB1 in a series of pediatric rhabdoid tumors. Results The bi-allelic alterations of INI1 that led to inactivation were elucidated in 50 of 51 tumors. INI1 inactivation was demonstrated by a variety of mechanisms, including deletions, mutations, and loss of heterozygosity. The results from the array studies highlighted the complexity of rearrangements of chromosome 22, compared to the low frequency of alterations involving the other chromosomes. Conclusions The results from the genome wide SNP-array analysis suggest that INI1 is the primary tumor suppressor gene involved in the development of rhabdoid tumors with no second locus identified. In addition, we did not identify hot spots for the breakpoints in sporadic tumors with deletions of chromosome 22q11.2. By employing a multimodality approach, the wide spectrum of alterations of INI1 can be identified in the majority of patients, which increases the clinical utility of molecular diagnostic testing. PMID:19276269

Performance Analysis of a NASA Integrated Network Array

NASA Technical Reports Server (NTRS)

Nessel, James A.

2012-01-01

The Space Communications and Navigation (SCaN) Program is planning to integrate its individual networks into a unified network which will function as a single entity to provide services to user missions. This integrated network architecture is expected to provide SCaN customers with the capabilities to seamlessly use any of the available SCaN assets to support their missions to efficiently meet the collective needs of Agency missions. One potential optimal application of these assets, based on this envisioned architecture, is that of arraying across existing networks to significantly enhance data rates and/or link availabilities. As such, this document provides an analysis of the transmit and receive performance of a proposed SCaN inter-network antenna array. From the study, it is determined that a fully integrated internetwork array does not provide any significant advantage over an intra-network array, one in which the assets of an individual network are arrayed for enhanced performance. Therefore, it is the recommendation of this study that NASA proceed with an arraying concept, with a fundamental focus on a network-centric arraying.

Taking advantage of modern turbines

NASA Astrophysics Data System (ADS)

Thresher, Robert

2018-06-01

Wind facilities have generally deployed turbines of the same power and height in regular uniform arrays. Now, the modern generation of turbines, with customer-selectable tower heights and larger rotors, can significantly increase wind energy's economic potential using less land to generate cheaper electricity.

Multistage WDM access architecture employing cascaded AWGs

NASA Astrophysics Data System (ADS)

El-Nahal, F. I.; Mears, R. J.

2009-03-01

Here we propose passive/active arrayed waveguide gratings (AWGs) with enhanced performance for system applications mainly in novel access architectures employing cascaded AWG technology. Two technologies were considered to achieve space wavelength switching in these networks. Firstly, a passive AWG with semiconductor optical amplifiers array, and secondly, an active AWG. Active AWG is an AWG with an array of phase modulators on its arrayed-waveguides section, where a programmable linear phase-profile or a phase hologram is applied across the arrayed-waveguide section. This results in a wavelength shift at the output section of the AWG. These architectures can address up to 6912 customers employing only 24 wavelengths, coarsely separated by 1.6 nm. Simulation results obtained here demonstrate that cascaded AWGs access architectures have a great potential in future local area networks. Furthermore, they indicate for the first time that active AWGs architectures are more efficient in routing signals to the destination optical network units than passive AWG architectures.

Development of a 35-MHz piezo-composite ultrasound array for medical imaging.

PubMed

Cannata, Jonathan M; Williams, Jay A; Zhou, Qifa; Ritter, Timothy A; Shung, K Kirk

2006-01-01

This paper discusses the development of a 64-element 35-MHz composite ultrasonic array. This array was designed primarily for ocular imaging applications, and features 2-2 composite elements mechanically diced out of a fine-grain high-density Navy Type VI ceramic. Array elements were spaced at a 50-micron pitch, interconnected via a custom flexible circuit and matched to the 50-ohm system electronics via a 75-ohm transmission line coaxial cable. Elevation focusing was achieved using a cylindrically shaped epoxy lens. One functional 64-element array was fabricated and tested. Bandwidths averaging 55%, 23-dB insertion loss, and crosstalk less than -24 dB were measured. An image of a tungsten wire target phantom was acquired using a synthetic aperture reconstruction algorithm. The results from this imaging test demonstrate resolution exceeding 50 microm axially and 100 microm laterally.

New customizable phased array UT instrument opens door for furthering research and better industrial implementation

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

Dao, Gavin; Ginzel, Robert

2014-02-18

Phased array UT as an inspection technique in itself continues to gain wide acceptance. However, there is much room for improvement in terms of implementation of Phased Array (PA) technology for every unique NDT application across several industries (e.g. oil and petroleum, nuclear and power generation, steel manufacturing, etc.). Having full control of the phased array instrument and customizing a software solution is necessary for more seamless and efficient inspections, from setting the PA parameters, collecting data and reporting, to the final analysis. NDT researchers and academics also need a flexible and open platform to be able to control variousmore » aspects of the phased array process. A high performance instrument with advanced PA features, faster data rates, a smaller form factor, and capability to adapt to specific applications, will be discussed.« less

Clinical prototype of a plastic water-equivalent scintillating fiber dosimeter array for QA applications.

PubMed

Lacroix, Fréderic; Archambault, Louis; Gingras, Luc; Guillot, Mathieu; Beddar, A Sam; Beaulieu, Luc

2008-08-01

A clinical prototype of a scintillating fiber dosimeter array for quality assurance applications is presented. The array consists of a linear array of 29 plastic scintillation detectors embedded in a water-equivalent plastic sheet coupled to optical fibers used to guide optical photons to a charge coupled device (CCD) camera. The CCD is packaged in a light-tight, radiation-shielded housing designed for convenient transport. A custom designed connector is used to ensure reproducible mechanical positioning of the optical fibers relative to the CCD. Profile and depth dose characterization measurements are presented and show that the prototype provides excellent dose measurement reproducibility (+/-0.8%) in-field and good accuracy (+/-1.6% maximum deviation) relative to the dose measured with an IC10 ionization chamber.

Haematobia irritans dataset of raw sequence reads from Illumina and Pac Bio sequencing of genomic DNA

USDA-ARS?s Scientific Manuscript database

The genome of the horn fly, Haematobia irritans, was sequenced using Illumina- and Pac Bio-based protocols. Following quality filtering, the raw reads have been deposited at NCBI under the BioProject and BioSample accession numbers PRJNA30967 and SAMN07830356, respectively. The Illumina reads are un...

Evolutionary multidimensional access architecture featuring cost-reduced components

NASA Astrophysics Data System (ADS)

Farjady, Farsheed; Parker, Michael C.; Walker, Stuart D.

1998-12-01

We describe a three-stage wavelength-routed optical access network, utilizing coarse passband-flattened arrayed- waveguide grating routers. An N-dimensional addressing strategy enables 6912 customers to be bi-directionally addressed with multi-Gb/s data using only 24 wavelengths spaced by 1.6 nm. Coarse wavelength separation allows use of increased tolerance WDM components at the exchange and customer premises. The architecture is designed to map onto standard access network topologies, allowing elegant upgradability from legacy PON infrastructures at low cost. Passband-flattening of the routers is achieved through phase apodization.

Seven-panel solar wing deployment and on-orbit maneuvering analyses

NASA Astrophysics Data System (ADS)

Hwang, Earl

2005-05-01

BSS developed a new generation high power (~20kW) solar array to meet the customer demands. The high power solar array had the north and south solar wings of which designs were identical. Each side of the solar wing consists of three main conventional solar panels and the four-side panel swing-out new design. The fully deployed solar array surface area is 966 ft2. It was a quite challenging task to define the solar array's optimum design parameters and deployment scheme for such a huge solar array's successful deployment and on-orbit maneuvering. Hence, a deployable seven-flex-panel solar wing nonlinear math model and a fully deployed solar array/bus-payload math model were developed with the Dynamic Analysis and Design System (DADS) program codes utilizing the inherited and empirical data. Performing extensive parametric analyses with the math model, the optimum design parameters and the orbit maneuvering /deployment schemes were determined to meet all the design requirements, and for the successful solar wing deployment on-orbit.

Taking advantage of modern turbines

DOE PAGES

Thresher, Robert

2018-05-14

Here, wind facilities have generally deployed turbines of the same power and height in regular uniform arrays. Now, the modern generation of turbines, with customer-selectable tower heights and larger rotors, can significantly increase wind energy's economic potential using less land to generate cheaper electricity.

Taking advantage of modern turbines

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

Thresher, Robert

Here, wind facilities have generally deployed turbines of the same power and height in regular uniform arrays. Now, the modern generation of turbines, with customer-selectable tower heights and larger rotors, can significantly increase wind energy's economic potential using less land to generate cheaper electricity.

High-density single nucleotide polymorphism (SNP) array mapping in Brassica oleracea: identification of QTL associated with carotenoid variation in broccoli florets.

PubMed

Brown, Allan F; Yousef, Gad G; Chebrolu, Kranthi K; Byrd, Robert W; Everhart, Koyt W; Thomas, Aswathy; Reid, Robert W; Parkin, Isobel A P; Sharpe, Andrew G; Oliver, Rebekah; Guzman, Ivette; Jackson, Eric W

2014-09-01

A high-resolution genetic linkage map of B. oleracea was developed from a B. napus SNP array. The work will facilitate genetic and evolutionary studies in Brassicaceae. A broccoli population, VI-158 × BNC, consisting of 150 F2:3 families was used to create a saturated Brassica oleracea (diploid: CC) linkage map using a recently developed rapeseed (Brassica napus) (tetraploid: AACC) Illumina Infinium single nucleotide polymorphism (SNP) array. The map consisted of 547 non-redundant SNP markers spanning 948.1 cM across nine chromosomes with an average interval size of 1.7 cM. As the SNPs are anchored to the genomic reference sequence of the rapid cycling B. oleracea TO1000, we were able to estimate that the map provides 96 % coverage of the diploid genome. Carotenoid analysis of 2 years data identified 3 QTLs on two chromosomes that are associated with up to half of the phenotypic variation associated with the accumulation of total or individual compounds. By searching the genome sequences of the two related diploid species (B. oleracea and B. rapa), we further identified putative carotenoid candidate genes in the region of these QTLs. This is the first description of the use of a B. napus SNP array to rapidly construct high-density genetic linkage maps of one of the constituent diploid species. The unambiguous nature of these markers with regard to genomic sequences provides evidence to the nature of genes underlying the QTL, and demonstrates the value and impact this resource will have on Brassica research.

Genome-wide Association Study for Ovarian Cancer Susceptibility using Pooled DNA

PubMed Central

Lu, Yi; Chen, Xiaoqing; Beesley, Jonathan; Johnatty, Sharon E.; deFazio, Anna; Lambrechts, Sandrina; Lambrechts, Diether; Despierre, Evelyn; Vergotes, Ignace; Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Wang-Gohrke, Shan; Dörk, Thilo; Dürst, Matthias; Antonenkova, Natalia; Bogdanova, Natalia; Goodman, Marc T.; Lurie, Galina; Wilkens, Lynne R.; Carney, Michael E.; Butzow, Ralf; Nevanlinna, Heli; Heikkinen, Tuomas; Leminen, Arto; Kiemeney, Lambertus A.; Massuger, Leon F.A.G.; van Altena, Anne M.; Aben, Katja K.; Kjaer, Susanne Krüger; Høgdall, Estrid; Jensen, Allan; Brooks-Wilson, Angela; Le, Nhu; Cook, Linda; Earp, Madalene; Kelemen, Linda; Easton, Douglas; Pharoah, Paul; Song, Honglin; Tyrer, Jonathan; Ramus, Susan; Menon, Usha; Gentry-Maharaj, Alexandra; Gayther, Simon A.; Bandera, Elisa V.; Olson, Sara H.; Orlow, Irene; Rodriguez-Rodriguez, Lorna

2013-01-01

Recent genome-wide association studies (GWAS) have identified four low-penetrance ovarian cancer susceptibility loci. We hypothesized that further moderate or low penetrance variants exist among the subset of SNPs not well tagged by the genotyping arrays used in the previous studies which would account for some of the remaining risk. We therefore conducted a time- and cost-effective stage 1 GWAS on 342 invasive serous cases and 643 controls genotyped on pooled DNA using the high density Illumina 1M-Duo array. We followed up 20 of the most significantly associated SNPs, which are not well tagged by the lower density arrays used by the published GWAS, and genotyping them on individual DNA. Most of the top 20 SNPs were clearly validated by individually genotyping the samples used in the pools. However, none of the 20 SNPs replicated when tested for association in a much larger stage 2 set of 4,651 cases and 6,966 controls from the Ovarian Cancer Association Consortium. Given that most of the top 20 SNPs from pooling were validated in the same samples by individual genotyping, the lack of replication is likely to be due to the relatively small sample size in our stage 1 GWAS rather than due to problems with the pooling approach. We conclude that there are unlikely to be any moderate or large effects on ovarian cancer risk untagged by the less dense arrays. However our study lacked power to make clear statements on the existence of hitherto untagged small effect variants. PMID:22794196

Photoacoustic Imaging with a Commercial Ultrasound System and a Custom Probe

PubMed Central

Wang, Xueding; Fowlkes, J. Brian; Cannata, Jonathan M.; Hu, Changhong; Carson, Paul L.

2010-01-01

Building photoacoustic imaging (PAI) systems by using stand-alone ultrasound (US) units makes it convenient to take advantage of the state-of-the-art ultrasonic technologies. However, the sometimes limited receiving sensitivity and the comparatively narrow bandwidth of commercial US probes may not be sufficient to acquire high quality photoacoustic images. In this work, a high-speed PAI system has been developed using a commercial US unit and a custom built 128-element piezoelectric-polymer array (PPA) probe using a P(VDF-TrFE) film and flexible circuit to define the elements. Since the US unit supports simultaneous signal acquisition from 64 parallel receive channels, PAI data for synthetic image formation from a 64 or 128 element array aperture can be acquired after a single or dual laser firing, respectively. Therefore, 2D B-scan imaging can be achieved with a maximum frame rate up to 10 Hz, limited only by the laser repetition rate. The uniquely properties of P(VDF-TrFE) facilitated a wide -6 dB receiving bandwidth of over 120 % for the array. A specially designed 128-channel preamplifier board made the connection between the array and the system cable which not only enabled element electrical impedance matching but also further elevated the signal-to-noise ratio (SNR) to further enhance the detection of weak photoacoustic signals. Through the experiments on phantoms and rabbit ears, the good performance of this PAI system was demonstrated. PMID:21276653

Engineering customized TALE nucleases (TALENs) and TALE transcription factors by fast ligation-based automatable solid-phase high-throughput (FLASH) assembly.

PubMed

Reyon, Deepak; Maeder, Morgan L; Khayter, Cyd; Tsai, Shengdar Q; Foley, Jonathan E; Sander, Jeffry D; Joung, J Keith

2013-07-01

Customized DNA-binding domains made using transcription activator-like effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in various organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or downregulate expression of endogenous genes in human cells and plants. This unit describes a detailed protocol for the recently described fast ligation-based automatable solid-phase high-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multichannel pipet. Using the automated approach, a single researcher can construct up to 96 DNA fragments encoding TALE repeat arrays of various lengths in a single day, and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in a week or less. Plasmids required for FLASH are available by request from the Joung lab (http://eGenome.org). This unit also describes improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) web server (http://ZiFiT.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high throughput. © 2013 by John Wiley & Sons, Inc.

Engineering Customized TALE Nucleases (TALENs) and TALE Transcription Factors by Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) Assembly

PubMed Central

Reyon, Deepak; Maeder, Morgan L.; Khayter, Cyd; Tsai, Shengdar Q.; Foley, Jonathan E.; Sander, Jeffry D.; Joung, J. Keith

2013-01-01

Customized DNA-binding domains made using Transcription Activator-Like Effector (TALE) repeats are rapidly growing in importance as widely applicable research tools. TALE nucleases (TALENs), composed of an engineered array of TALE repeats fused to the FokI nuclease domain, have been used successfully for directed genome editing in multiple different organisms and cell types. TALE transcription factors (TALE-TFs), consisting of engineered TALE repeat arrays linked to a transcriptional regulatory domain, have been used to up- or down-regulate expression of endogenous genes in human cells and plants. Here we describe a detailed protocol for practicing the recently described Fast Ligation-based Automatable Solid-phase High-throughput (FLASH) assembly method. FLASH enables automated high-throughput construction of engineered TALE repeats using an automated liquid handling robot or manually using a multi-channel pipet. With the automated version of FLASH, a single researcher can construct up to 96 DNA fragments encoding various length TALE repeat arrays in one day and then clone these to construct sequence-verified TALEN or TALE-TF expression plasmids in one week or less. Plas-mids required to practice FLASH are available by request from the Joung Lab (http://www.jounglab.org/). We also describe here improvements to the Zinc Finger and TALE Targeter (ZiFiT Targeter) webserver (http://ZiFiTBeta.partners.org) that facilitate the design and construction of FLASH TALE repeat arrays in high-throughput. PMID:23821439

High-voltage integrated active quenching circuit for single photon count rate up to 80 Mcounts/s.

PubMed

Acconcia, Giulia; Rech, Ivan; Gulinatti, Angelo; Ghioni, Massimo

2016-08-08

Single photon avalanche diodes (SPADs) have been subject to a fast improvement in recent years. In particular, custom technologies specifically developed to fabricate SPAD devices give the designer the freedom to pursue the best detector performance required by applications. A significant breakthrough in this field is represented by the recent introduction of a red enhanced SPAD (RE-SPAD) technology, capable of attaining a good photon detection efficiency in the near infrared range (e.g. 40% at a wavelength of 800 nm) while maintaining a remarkable timing resolution of about 100ps full width at half maximum. Being planar, the RE-SPAD custom technology opened the way to the development of SPAD arrays particularly suited for demanding applications in the field of life sciences. However, to achieve such excellent performance custom SPAD detectors must be operated with an external active quenching circuit (AQC) designed on purpose. Next steps toward the development of compact and practical multichannel systems will require a new generation of monolithically integrated AQC arrays. In this paper we present a new, fully integrated AQC fabricated in a high-voltage 0.18 µm CMOS technology able to provide quenching pulses up to 50 Volts with fast leading and trailing edges. Although specifically designed for optimal operation of RE-SPAD devices, the new AQC is quite versatile: it can be used with any SPAD detector, regardless its fabrication technology, reaching remarkable count rates up to 80 Mcounts/s and generating a photon detection pulse with a timing jitter as low as 119 ps full width at half maximum. The compact design of our circuit has been specifically laid out to make this IC a suitable building block for monolithically integrated AQC arrays.

Design and Use of Microphone Directional Arrays for Aeroacoustic Measurements

NASA Technical Reports Server (NTRS)

Humphreys, William M., Jr.; Brooks, Thomas F.; Hunter, William W., Jr.; Meadows, Kristine R.

1998-01-01

An overview of the development of two microphone directional arrays for aeroacoustic testing is presented. These arrays were specifically developed to measure airframe noise in the NASA Langley Quiet Flow Facility. A large aperture directional array using 35 flush-mounted microphones was constructed to obtain high resolution noise localization maps around airframe models. This array possesses a maximum diagonal aperture size of 34 inches. A unique logarithmic spiral layout design was chosen for the targeted frequency range of 2-30 kHz. Complementing the large array is a small aperture directional array, constructed to obtain spectra and directivity information from regions on the model. This array, possessing 33 microphones with a maximum diagonal aperture size of 7.76 inches, is easily moved about the model in elevation and azimuth. Custom microphone shading algorithms have been developed to provide a frequency- and position-invariant sensing area from 10-40 kHz with an overall targeted frequency range for the array of 5-60 kHz. Both arrays are employed in acoustic measurements of a 6 percent of full scale airframe model consisting of a main element NACA 632-215 wing section with a 30 percent chord half-span flap. Representative data obtained from these measurements is presented, along with details of the array calibration and data post-processing procedures.

ASIC Readout Circuit Architecture for Large Geiger Photodiode Arrays

NASA Technical Reports Server (NTRS)

Vasile, Stefan; Lipson, Jerold

2012-01-01

The objective of this work was to develop a new class of readout integrated circuit (ROIC) arrays to be operated with Geiger avalanche photodiode (GPD) arrays, by integrating multiple functions at the pixel level (smart-pixel or active pixel technology) in 250-nm CMOS (complementary metal oxide semiconductor) processes. In order to pack a maximum of functions within a minimum pixel size, the ROIC array is a full, custom application-specific integrated circuit (ASIC) design using a mixed-signal CMOS process with compact primitive layout cells. The ROIC array was processed to allow assembly in bump-bonding technology with photon-counting infrared detector arrays into 3-D imaging cameras (LADAR). The ROIC architecture was designed to work with either common- anode Si GPD arrays or common-cathode InGaAs GPD arrays. The current ROIC pixel design is hardwired prior to processing one of the two GPD array configurations, and it has the provision to allow soft reconfiguration to either array (to be implemented into the next ROIC array generation). The ROIC pixel architecture implements the Geiger avalanche quenching, bias, reset, and time to digital conversion (TDC) functions in full-digital design, and uses time domain over-sampling (vernier) to allow high temporal resolution at low clock rates, increased data yield, and improved utilization of the laser beam.

A wideband software reconfigurable modem

NASA Astrophysics Data System (ADS)

Turner, J. H., Jr.; Vickers, H.

A wideband modem is described which provides signal processing capability for four Lx-band signals employing QPSK, MSK and PPM waveforms and employs a software reconfigurable architecture for maximum system flexibility and graceful degradation. The current processor uses a 2901 and two 8086 microprocessors per channel and performs acquisition, tracking, and data demodulation for JITDS, GPS, IFF and TACAN systems. The next generation processor will be implemented using a VHSIC chip set employing a programmable complex array vector processor module, a GP computer module, customized gate array modules, and a digital array correlator. This integrated processor has application to a wide number of diverse system waveforms, and will bring the benefits of VHSIC technology insertion into avionic antijam communications systems.

CMOS gate array characterization procedures

NASA Astrophysics Data System (ADS)

Spratt, James P.

1993-09-01

Present procedures are inadequate for characterizing the radiation hardness of gate array product lines prior to personalization because the selection of circuits to be used, from among all those available in the manufacturer's circuit library, is usually uncontrolled. (Some circuits are fundamentally more radiation resistant than others.) In such cases, differences in hardness can result between different designs of the same logic function. Hardness also varies because many gate arrays feature large custom-designed megacells (e.g., microprocessors and random access memories-MicroP's and RAM's). As a result, different product lines cannot be compared equally. A characterization strategy is needed, along with standardized test vehicle(s), methodology, and conditions, so that users can make informed judgments on which gate arrays are best suited for their needs. The program described developed preferred procedures for the radiation characterization of gate arrays, including a gate array evaluation test vehicle, featuring a canary circuit, designed to define the speed versus hardness envelope of the gate array. A multiplier was chosen for this role, and a baseline multiplier architecture is suggested that could be incorporated into an existing standard evaluation circuit chip.

Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race/ethnicity using imputation and a novel hybrid SNP selection algorithm.

PubMed

Hoffmann, Thomas J; Zhan, Yiping; Kvale, Mark N; Hesselson, Stephanie E; Gollub, Jeremy; Iribarren, Carlos; Lu, Yontao; Mei, Gangwu; Purdy, Matthew M; Quesenberry, Charles; Rowell, Sarah; Shapero, Michael H; Smethurst, David; Somkin, Carol P; Van den Eeden, Stephen K; Walter, Larry; Webster, Teresa; Whitmer, Rachel A; Finn, Andrea; Schaefer, Catherine; Kwok, Pui-Yan; Risch, Neil

2011-12-01

Four custom Axiom genotyping arrays were designed for a genome-wide association (GWA) study of 100,000 participants from the Kaiser Permanente Research Program on Genes, Environment and Health. The array optimized for individuals of European race/ethnicity was previously described. Here we detail the development of three additional microarrays optimized for individuals of East Asian, African American, and Latino race/ethnicity. For these arrays, we decreased redundancy of high-performing SNPs to increase SNP capacity. The East Asian array was designed using greedy pairwise SNP selection. However, removing SNPs from the target set based on imputation coverage is more efficient than pairwise tagging. Therefore, we developed a novel hybrid SNP selection method for the African American and Latino arrays utilizing rounds of greedy pairwise SNP selection, followed by removal from the target set of SNPs covered by imputation. The arrays provide excellent genome-wide coverage and are valuable additions for large-scale GWA studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation

PubMed Central

Chan, D.; McGraw, S.; Klein, K.; Wallock, L.M.; Konermann, C.; Plass, C.; Chan, P.; Robaire, B.; Jacob, R.A.; Greenwood, C.M.T.; Trasler, J.M.

2017-01-01

STUDY QUESTION Do short-term and long-term exposures to low-dose folic acid supplementation alter DNA methylation in sperm? SUMMARY ANSWER No alterations in sperm DNA methylation patterns were found following the administration of low-dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. WHAT IS KNOWN ALREADY Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate's role in one-carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high-dose (5 mg/day) folic acid supplementation. STUDY DESIGN, SIZE, DURATION This is a control versus treatment study where genome-wide sperm DNA methylation patterns were examined prior to fortification of food (1996–1997) in men with no history of infertility at baseline and following 90-day exposure to placebo (n = 9) or supplement containing 400 μg folic acid/day (n = 10). Additionally, pre-fortification sperm DNA methylation profiles (n = 19) were compared with those of a group of post-fortification (post-2004) men (n = 8) who had been exposed for several years to dietary folic acid fortification. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole-genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array. MAIN RESULTS AND THE ROLE OF CHANCE Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first-generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre- and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. LARGE SCALE DATA Illumina HumanMethylation450 BeadChip data from this study have been submitted to the NCBI Gene Expression Omnibus under the accession number GSE89781. LIMITATIONS, REASONS FOR CAUTION This study was limited to the number of participants available in each cohort, in particular those who were not exposed to early (pre-1998) fortification of food with folic acid. While genome-wide DNA methylation was assessed with several techniques that targeted genic and CpG-rich regions, intergenic regions were less well interrogated. WIDER IMPLICATIONS OF THE FINDINGS Overall, our findings provide evidence that short-term exposure to low-dose folic acid supplements of 400 μg/day, over a period of 3 months, a duration of time that might occur during infertility treatments, has no major impact on the sperm DNA methylome. STUDY FUNDING/COMPETING INTERESTS This work was supported by a grant to J.M.T. from the Canadian Institutes of Health Research (CIHR: MOP-89944). The authors have no conflicts of interest to declare. PMID:27994001

Stability of the human sperm DNA methylome to folic acid fortification and short-term supplementation.

PubMed

Chan, D; McGraw, S; Klein, K; Wallock, L M; Konermann, C; Plass, C; Chan, P; Robaire, B; Jacob, R A; Greenwood, C M T; Trasler, J M

2017-02-01

Do short-term and long-term exposures to low-dose folic acid supplementation alter DNA methylation in sperm? No alterations in sperm DNA methylation patterns were found following the administration of low-dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate's role in one-carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor. DNA methylation patterns are established in developing male germ cells and have been suggested to be affected by high-dose (5 mg/day) folic acid supplementation. This is a control versus treatment study where genome-wide sperm DNA methylation patterns were examined prior to fortification of food (1996-1997) in men with no history of infertility at baseline and following 90-day exposure to placebo (n = 9) or supplement containing 400 μg folic acid/day (n = 10). Additionally, pre-fortification sperm DNA methylation profiles (n = 19) were compared with those of a group of post-fortification (post-2004) men (n = 8) who had been exposed for several years to dietary folic acid fortification. Blood and seminal plasma folate levels were measured in participants before and following the 90-day treatment with placebo or supplement. Sperm DNA methylation was assessed using the whole-genome and genome-wide techniques, MassArray epityper, restriction landmark genomic scanning, methyl-CpG immunoprecipitation and Illumina HumanMethylation450 Bead Array. Following treatment, supplemented individuals had significantly higher levels of blood and seminal plasma folates compared to placebo. Initial first-generation genome-wide analyses of sperm DNA methylation showed little evidence of changes when comparing pre- and post-treatment samples. With Illumina HumanMethylation450 BeadChip arrays, no significant changes were observed in individual probes following low-level supplementation; when compared with those of the post-fortification cohort, there were also few differences in methylation despite exposure to years of fortified foods. Illumina HumanMethylation450 BeadChip data from this study have been submitted to the NCBI Gene Expression Omnibus under the accession number GSE89781. This study was limited to the number of participants available in each cohort, in particular those who were not exposed to early (pre-1998) fortification of food with folic acid. While genome-wide DNA methylation was assessed with several techniques that targeted genic and CpG-rich regions, intergenic regions were less well interrogated. Overall, our findings provide evidence that short-term exposure to low-dose folic acid supplements of 400 μg/day, over a period of 3 months, a duration of time that might occur during infertility treatments, has no major impact on the sperm DNA methylome. This work was supported by a grant to J.M.T. from the Canadian Institutes of Health Research (CIHR: MOP-89944). The authors have no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

An alternative method to amplify RNA without loss of signal conservation for expression analysis with a proteinase DNA microarray in the ArrayTube format.

PubMed

Schüler, Susann; Wenz, Ingrid; Wiederanders, B; Slickers, P; Ehricht, R

2006-06-12

Recent developments in DNA microarray technology led to a variety of open and closed devices and systems including high and low density microarrays for high-throughput screening applications as well as microarrays of lower density for specific diagnostic purposes. Beside predefined microarrays for specific applications manufacturers offer the production of custom-designed microarrays adapted to customers' wishes. Array based assays demand complex procedures including several steps for sample preparation (RNA extraction, amplification and sample labelling), hybridization and detection, thus leading to a high variability between several approaches and resulting in the necessity of extensive standardization and normalization procedures. In the present work a custom designed human proteinase DNA microarray of lower density in ArrayTube format was established. This highly economic open platform only requires standard laboratory equipment and allows the study of the molecular regulation of cell behaviour by proteinases. We established a procedure for sample preparation and hybridization and verified the array based gene expression profile by quantitative real-time PCR (QRT-PCR). Moreover, we compared the results with the well established Affymetrix microarray. By application of standard labelling procedures with e.g. Klenow fragment exo-, single primer amplification (SPA) or In Vitro Transcription (IVT) we noticed a loss of signal conservation for some genes. To overcome this problem we developed a protocol in accordance with the SPA protocol, in which we included target specific primers designed individually for each spotted oligomer. Here we present a complete array based assay in which only the specific transcripts of interest are amplified in parallel and in a linear manner. The array represents a proof of principle which can be adapted to other species as well. As the designed protocol for amplifying mRNA starts from as little as 100 ng total RNA, it presents an alternative method for detecting even low expressed genes by microarray experiments in a highly reproducible and sensitive manner. Preservation of signal integrity is demonstrated out by QRT-PCR measurements. The little amounts of total RNA necessary for the analyses make this method applicable for investigations with limited material as in clinical samples from, for example, organ or tumour biopsies. Those are arguments in favour of the high potential of our assay compared to established procedures for amplification within the field of diagnostic expression profiling. Nevertheless, the screening character of microarray data must be mentioned, and independent methods should verify the results.

An externally head-mounted wireless neural recording device for laboratory animal research and possible human clinical use.

PubMed

Yin, Ming; Li, Hao; Bull, Christopher; Borton, David A; Aceros, Juan; Larson, Lawrence; Nurmikko, Arto V

2013-01-01

In this paper we present a new type of head-mounted wireless neural recording device in a highly compact package, dedicated for untethered laboratory animal research and designed for future mobile human clinical use. The device, which takes its input from an array of intracortical microelectrode arrays (MEA) has ninety-seven broadband parallel neural recording channels and was integrated on to two custom designed printed circuit boards. These house several low power, custom integrated circuits, including a preamplifier ASIC, a controller ASIC, plus two SAR ADCs, a 3-axis accelerometer, a 48MHz clock source, and a Manchester encoder. Another ultralow power RF chip supports an OOK transmitter with the center frequency tunable from 3GHz to 4GHz, mounted on a separate low loss dielectric board together with a 3V LDO, with output fed to a UWB chip antenna. The IC boards were interconnected and packaged in a polyether ether ketone (PEEK) enclosure which is compatible with both animal and human use (e.g. sterilizable). The entire system consumes 17mA from a 1.2Ahr 3.6V Li-SOCl2 1/2AA battery, which operates the device for more than 2 days. The overall system includes a custom RF receiver electronics which are designed to directly interface with any number of commercial (or custom) neural signal processors for multi-channel broadband neural recording. Bench-top measurements and in vivo testing of the device in rhesus macaques are presented to demonstrate the performance of the wireless neural interface.

A high-speed trapezoid image sensor design for continuous traffic monitoring at signalized intersection approaches.

DOT National Transportation Integrated Search

2014-10-01

The goal of this project is to monitor traffic flow continuously with an innovative camera system composed of a custom : designed image sensor integrated circuit (IC) containing trapezoid pixel array and camera system that is capable of : intelligent...

Simulation and experimental characterization of the point spread function, pixel saturation, and blooming of a mercury cadmium telluride focal plane array.

PubMed

Soehnel, Grant; Tanbakuchi, Anthony

2012-11-20

A custom IR spot scanning experiment was constructed to project subpixel spots on a mercury cadmium telluride focal plane array (FPA). The hardware consists of an FPA in a liquid nitrogen cooled Dewar, high precision motorized stages, a custom aspheric lens, and a 1.55 and 3.39 μm laser source. By controlling the position and intensity of the spot, characterizations of cross talk, saturation, blooming, and (indirectly) the minority carrier lifetime were performed. In addition, a Monte-Carlo-based charge diffusion model was developed to validate experimental data and make predictions. Results show very good agreement between the model and experimental data. Parameters such as wavelength, reverse bias, and operating temperature were found to have little effect on pixel crosstalk in the absorber layer of the detector. Saturation characterizations show that these FPAs, which do not have antiblooming circuitry, exhibit an increase in cross talk due to blooming at ∼39% beyond the flux required for analog saturation.

High-performance integrated pick-up circuit for SPAD arrays in time-correlated single photon counting

NASA Astrophysics Data System (ADS)

Acconcia, Giulia; Cominelli, Alessandro; Peronio, Pietro; Rech, Ivan; Ghioni, Massimo

2017-05-01

The analysis of optical signals by means of Single Photon Avalanche Diodes (SPADs) has been subject to a widespread interest in recent years. The development of multichannel high-performance Time Correlated Single Photon Counting (TCSPC) acquisition systems has undergone a fast trend. Concerning the detector performance, best in class results have been obtained resorting to custom technologies leading also to a strong dependence of the detector timing jitter from the threshold used to determine the onset of the photogenerated current flow. In this scenario, the avalanche current pick-up circuit plays a key role in determining the timing performance of the TCSPC acquisition system, especially with a large array of SPAD detectors because of electrical crosstalk issues. We developed a new current pick-up circuit based on a transimpedance amplifier structure able to extract the timing information from a 50-μm-diameter custom technology SPAD with a state-of-art timing jitter as low as 32ps and suitable to be exploited with SPAD arrays. In this paper we discuss the key features of this structure and we present a new version of the pick-up circuit that also provides quenching capabilities in order to minimize the number of interconnections required, an aspect that becomes more and more crucial in densely integrated systems.

Custom Array Comparative Genomic Hybridization: the Importance of DNA Quality, an Expert Eye, and Variant Validation

PubMed Central

Lantieri, Francesca; Malacarne, Michela; Gimelli, Stefania; Santamaria, Giuseppe; Coviello, Domenico; Ceccherini, Isabella

2017-01-01

The presence of false positive and false negative results in the Array Comparative Genomic Hybridization (aCGH) design is poorly addressed in literature reports. We took advantage of a custom aCGH recently carried out to analyze its design performance, the use of several Agilent aberrations detection algorithms, and the presence of false results. Our study provides a confirmation that the high density design does not generate more noise than standard designs and, might reach a good resolution. We noticed a not negligible presence of false negative and false positive results in the imbalances call performed by the Agilent software. The Aberration Detection Method 2 (ADM-2) algorithm with a threshold of 6 performed quite well, and the array design proved to be reliable, provided that some additional filters are applied, such as considering only intervals with average absolute log2ratio above 0.3. We also propose an additional filter that takes into account the proportion of probes with log2ratio exceeding suggestive values for gain or loss. In addition, the quality of samples was confirmed to be a crucial parameter. Finally, this work raises the importance of evaluating the samples profiles by eye and the necessity of validating the imbalances detected. PMID:28287439

Customization of the acoustic field produced by a piezoelectric array through interelement delays

PubMed Central

Chitnis, Parag V.; Barbone, Paul E.; Cleveland, Robin O.

2008-01-01

A method for producing a prescribed acoustic pressure field from a piezoelectric array was investigated. The array consisted of 170 elements placed on the inner surface of a 15 cm radius spherical cap. Each element was independently driven by using individual pulsers each capable of generating 1.2 kV. Acoustic field customization was achieved by independently controlling the time when each element was excited. The set of time delays necessary to produce a particular acoustic field was determined by using an optimization scheme. The acoustic field at the focal plane was simulated by using the angular spectrum method, and the optimization searched for the time delays that minimized the least squared difference between the magnitudes of the simulated and desired pressure fields. The acoustic field was shaped in two different ways: the −6 dB focal width was increased to different desired widths and the ring-shaped pressure distributions of various prescribed diameters were produced. For both cases, the set of delays resulting from the respective optimization schemes were confirmed to yield the desired pressure distributions by using simulations and measurements. The simulations, however, predicted peak positive pressures roughly half those obtained from the measurements, which was attributed to the exclusion of nonlinearity in the simulations. PMID:18537369

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

PubMed Central

Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B.; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P.; Southey, Melissa; John, Esther M.; Conner, Thomas A.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L.; Hansen, Thomas V.O.; Osorio, Ana; Weitzel, Jeffrey N.; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D. Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-ren; Walker, Lisa; Side, Lucy E.; Porteous, Mary E.; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K.; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B.M.; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I.; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J.; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A.; Johannsson, Oskar Th.; Barkardottir, Rosa B.; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R.; Pinto, Pedro; Spurdle, Amanda B.; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R.; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y.; Berger, Andreas; Singer, Christian F.; Loud, Jennifer T.; Greene, Mark H.; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L.; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A.; Caligo, Maria A.; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M.; Olopade, Olufunmilayo I.; Nathanson, Katherine L.; Domchek, Susan M.; Lorenchick, Christa; Jankowitz, Rachel C.; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J.; Simard, Jacques; Easton, Douglas F.; Chenevix-Trench, Georgia; Schmutzler, Rita K.; Antoniou, Antonis C.; Ottini, Laura

2017-01-01

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management. PMID:28448241

Extent of Linkage Disequilibrium in the Domestic Cat, Felis silvestris catus, and Its Breeds

PubMed Central

Alhaddad, Hasan; Khan, Razib; Grahn, Robert A.; Gandolfi, Barbara; Mullikin, James C.; Cole, Shelley A.; Gruffydd-Jones, Timothy J.; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A.

2013-01-01

Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r 2) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r2 was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r2 ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r2 ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds’ population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits. PMID:23308248

Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores.

PubMed

Lecarpentier, Julie; Silvestri, Valentina; Kuchenbaecker, Karoline B; Barrowdale, Daniel; Dennis, Joe; McGuffog, Lesley; Soucy, Penny; Leslie, Goska; Rizzolo, Piera; Navazio, Anna Sara; Valentini, Virginia; Zelli, Veronica; Lee, Andrew; Amin Al Olama, Ali; Tyrer, Jonathan P; Southey, Melissa; John, Esther M; Conner, Thomas A; Goldgar, David E; Buys, Saundra S; Janavicius, Ramunas; Steele, Linda; Ding, Yuan Chun; Neuhausen, Susan L; Hansen, Thomas V O; Osorio, Ana; Weitzel, Jeffrey N; Toss, Angela; Medici, Veronica; Cortesi, Laura; Zanna, Ines; Palli, Domenico; Radice, Paolo; Manoukian, Siranoush; Peissel, Bernard; Azzollini, Jacopo; Viel, Alessandra; Cini, Giulia; Damante, Giuseppe; Tommasi, Stefania; Peterlongo, Paolo; Fostira, Florentia; Hamann, Ute; Evans, D Gareth; Henderson, Alex; Brewer, Carole; Eccles, Diana; Cook, Jackie; Ong, Kai-Ren; Walker, Lisa; Side, Lucy E; Porteous, Mary E; Davidson, Rosemarie; Hodgson, Shirley; Frost, Debra; Adlard, Julian; Izatt, Louise; Eeles, Ros; Ellis, Steve; Tischkowitz, Marc; Godwin, Andrew K; Meindl, Alfons; Gehrig, Andrea; Dworniczak, Bernd; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Hahnen, Eric; Hauke, Jan; Rhiem, Kerstin; Kast, Karin; Arnold, Norbert; Ditsch, Nina; Wang-Gohrke, Shan; Wappenschmidt, Barbara; Wand, Dorothea; Lasset, Christine; Stoppa-Lyonnet, Dominique; Belotti, Muriel; Damiola, Francesca; Barjhoux, Laure; Mazoyer, Sylvie; Van Heetvelde, Mattias; Poppe, Bruce; De Leeneer, Kim; Claes, Kathleen B M; de la Hoya, Miguel; Garcia-Barberan, Vanesa; Caldes, Trinidad; Perez Segura, Pedro; Kiiski, Johanna I; Aittomäki, Kristiina; Khan, Sofia; Nevanlinna, Heli; van Asperen, Christi J; Vaszko, Tibor; Kasler, Miklos; Olah, Edith; Balmaña, Judith; Gutiérrez-Enríquez, Sara; Diez, Orland; Teulé, Alex; Izquierdo, Angel; Darder, Esther; Brunet, Joan; Del Valle, Jesús; Feliubadalo, Lidia; Pujana, Miquel Angel; Lazaro, Conxi; Arason, Adalgeir; Agnarsson, Bjarni A; Johannsson, Oskar Th; Barkardottir, Rosa B; Alducci, Elisa; Tognazzo, Silvia; Montagna, Marco; Teixeira, Manuel R; Pinto, Pedro; Spurdle, Amanda B; Holland, Helene; Lee, Jong Won; Lee, Min Hyuk; Lee, Jihyoun; Kim, Sung-Won; Kang, Eunyoung; Kim, Zisun; Sharma, Priyanka; Rebbeck, Timothy R; Vijai, Joseph; Robson, Mark; Lincoln, Anne; Musinsky, Jacob; Gaddam, Pragna; Tan, Yen Y; Berger, Andreas; Singer, Christian F; Loud, Jennifer T; Greene, Mark H; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L; Toland, Amanda Ewart; Senter, Leigha; Bojesen, Anders; Nielsen, Henriette Roed; Skytte, Anne-Bine; Sunde, Lone; Jensen, Uffe Birk; Pedersen, Inge Sokilde; Krogh, Lotte; Kruse, Torben A; Caligo, Maria A; Yoon, Sook-Yee; Teo, Soo-Hwang; von Wachenfeldt, Anna; Huo, Dezheng; Nielsen, Sarah M; Olopade, Olufunmilayo I; Nathanson, Katherine L; Domchek, Susan M; Lorenchick, Christa; Jankowitz, Rachel C; Campbell, Ian; James, Paul; Mitchell, Gillian; Orr, Nick; Park, Sue Kyung; Thomassen, Mads; Offit, Kenneth; Couch, Fergus J; Simard, Jacques; Easton, Douglas F; Chenevix-Trench, Georgia; Schmutzler, Rita K; Antoniou, Antonis C; Ottini, Laura

2017-07-10

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10 -6 ). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10 -9 ). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Extent of linkage disequilibrium in the domestic cat, Felis silvestris catus, and its breeds.

PubMed

Alhaddad, Hasan; Khan, Razib; Grahn, Robert A; Gandolfi, Barbara; Mullikin, James C; Cole, Shelley A; Gruffydd-Jones, Timothy J; Häggström, Jens; Lohi, Hannes; Longeri, Maria; Lyons, Leslie A

2013-01-01

Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.

Mechanical Design and Development of TES Bolometer Detector Arrays for the Advanced ACTPol Experiment

NASA Technical Reports Server (NTRS)

Ward, Jonathan T.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Crowley, Kevin T.; Devlin, Mark J.; Duff, Shannon M.; Gallardo, Patricio M.; Henderson, Shawn W.; Ho, Shuay-Pwu Patty;

Mechanical designs and development of TES bolometer detector arrays for the Advanced ACTPol experiment

NASA Astrophysics Data System (ADS)

Ward, Jonathan T.; Austermann, Jason; Beall, James A.; Choi, Steve K.; Crowley, Kevin T.; Devlin, Mark J.; Duff, Shannon M.; Gallardo, Patricio A.; Henderson, Shawn W.; Ho, Shuay-Pwu Patty; Hilton, Gene; Hubmayr, Johannes; Khavari, Niloufar; Klein, Jeffrey; Koopman, Brian J.; Li, Dale; McMahon, Jeffrey; Mumby, Grace; Nati, Federico; Niemack, Michael D.; Page, Lyman A.; Salatino, Maria; Schillaci, Alessandro; Schmitt, Benjamin L.; Simon, Sara M.; Staggs, Suzanne T.; Thornton, Robert; Ullom, Joel N.; Vavagiakis, Eve M.; Wollack, Edward J.

2016-07-01

The next generation Advanced ACTPol (AdvACT) experiment is currently underway and will consist of four Transition Edge Sensor (TES) bolometer arrays, with three operating together, totaling 5800 detectors on the sky. Building on experience gained with the ACTPol detector arrays, AdvACT will utilize various new technologies, including 150 mm detector wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors includes a feedhorn array of stacked silicon wafers which form a spline profile leading to each pixel. This is then followed by a waveguide interface plate, detector wafer, back short cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured from high purity copper and then gold plated. In addition to the detector array assembly, the array package also encloses cryogenic readout electronics. We present the full mechanical design of the AdvACT high frequency (HF) detector array package along with a detailed look at the detector array stack assemblies. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT arrays with pre-existing ACTPol infrastructure.

A Practical Platform for Blood Biomarker Study by Using Global Gene Expression Profiling of Peripheral Whole Blood

PubMed Central

Schmid, Patrick; Yao, Hui; Galdzicki, Michal; Berger, Bonnie; Wu, Erxi; Kohane, Isaac S.

2009-01-01

Background Although microarray technology has become the most common method for studying global gene expression, a plethora of technical factors across the experiment contribute to the variable of genome gene expression profiling using peripheral whole blood. A practical platform needs to be established in order to obtain reliable and reproducible data to meet clinical requirements for biomarker study. Methods and Findings We applied peripheral whole blood samples with globin reduction and performed genome-wide transcriptome analysis using Illumina BeadChips. Real-time PCR was subsequently used to evaluate the quality of array data and elucidate the mode in which hemoglobin interferes in gene expression profiling. We demonstrated that, when applied in the context of standard microarray processing procedures, globin reduction results in a consistent and significant increase in the quality of beadarray data. When compared to their pre-globin reduction counterparts, post-globin reduction samples show improved detection statistics, lowered variance and increased sensitivity. More importantly, gender gene separation is remarkably clearer in post-globin reduction samples than in pre-globin reduction samples. Our study suggests that the poor data obtained from pre-globin reduction samples is the result of the high concentration of hemoglobin derived from red blood cells either interfering with target mRNA binding or giving the pseudo binding background signal. Conclusion We therefore recommend the combination of performing globin mRNA reduction in peripheral whole blood samples and hybridizing on Illumina BeadChips as the practical approach for biomarker study. PMID:19381341

Novel insights into systemic autoimmune rheumatic diseases using shared molecular signatures and an integrative analysis.

PubMed

Hudson, Marie; Bernatsky, Sasha; Colmegna, Ines; Lora, Maximilien; Pastinen, Tomi; Klein Oros, Kathleen; Greenwood, Celia M T

2017-06-03

We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4 + T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases. We recruited 13 seropositive rheumatoid arthritis, 19 systemic sclerosis, 12 systemic lupus erythematosus subjects, and 8 healthy controls. We identified 33 genes that were both differentially methylated and expressed (26 over- and 7 under-expressed) in SARD cases versus controls. The most highly overexpressed gene was CD1C (log fold change in expression = 1.85, adjusted P value = 0.009). In functional analysis (Ingenuity Pathway Analysis), the top network identified was lipid metabolism, molecular transport, small molecule biochemistry. The top canonical pathways included the mitochondrial L-carnitine shuttle pathway (P = 5E-03) and PTEN signaling (P = 8E-03). The top upstream regulator was HNF4A (P = 3E-05). This novel SARD signature contributes to ongoing work to further our understanding of the molecular mechanisms underlying SARD and provides novel targets of interest.

High-density fiber-optic DNA random microsphere array.

PubMed

Ferguson, J A; Steemers, F J; Walt, D R

2000-11-15

A high-density fiber-optic DNA microarray sensor was developed to monitor multiple DNA sequences in parallel. Microarrays were prepared by randomly distributing DNA probe-functionalized 3.1-microm-diameter microspheres in an array of wells etched in a 500-microm-diameter optical imaging fiber. Registration of the microspheres was performed using an optical encoding scheme and a custom-built imaging system. Hybridization was visualized using fluorescent-labeled DNA targets with a detection limit of 10 fM. Hybridization times of seconds are required for nanomolar target concentrations, and analysis is performed in minutes.

Optimization of a multi-well array SERS chip

NASA Astrophysics Data System (ADS)

Abell, J. L.; Driskell, J. D.; Dluhy, R. A.; Tripp, R. A.; Zhao, Y.-P.

2009-05-01

SERS-active substrates are fabricated by oblique angle deposition and patterned by a polymer-molding technique to provide a uniform array for high throughput biosensing and multiplexing. Using a conventional SERS-active molecule, 1,2-Bis(4-pyridyl)ethylene (BPE), we show that this device provides a uniform Raman signal enhancement from well to well. The patterning technique employed in this study demonstrates a flexibility allowing for patterning control and customization, and performance optimization of the substrate. Avian influenza is analyzed to demonstrate the ability of this multi-well patterned SERS substrate for biosensing.

Microarray Technology for the Diagnosis of Fetal Chromosomal Aberrations: Which Platform Should We Use?

PubMed Central

Karampetsou, Evangelia; Morrogh, Deborah; Chitty, Lyn

2014-01-01

The advantage of microarray (array) over conventional karyotype for the diagnosis of fetal pathogenic chromosomal anomalies has prompted the use of microarrays in prenatal diagnostics. In this review we compare the performance of different array platforms (BAC, oligonucleotide CGH, SNP) and designs (targeted, whole genome, whole genome, and targeted, custom) and discuss their advantages and disadvantages in relation to prenatal testing. We also discuss the factors to consider when implementing a microarray testing service for the diagnosis of fetal chromosomal aberrations. PMID:26237396

Development of advanced micromirror arrays by flip-chip assembly

NASA Astrophysics Data System (ADS)

Michalicek, M. Adrian; Bright, Victor M.

2001-10-01

This paper presents the design, commercial prefabrication, modeling and testing of advanced micromirror arrays fabricated using a novel, simple and inexpensive flip-chip assembly technique. Several polar piston arrays and rectangular cantilever arrays were fabricated using flip-chip assembly by which the upper layers of the array are fabricated on a separate chip and then transferred to a receiving module containing the lower layers. Typical polar piston arrays boast 98.3% active surface area, highly planarized surfaces, low address potentials compatible with CMOS electronics, highly standardized actuation between devices, and complex segmentation of mirror surfaces which allows for custom aberration configurations. Typical cantilever arrays boast large angles of rotation as well as an average surface planarity of only 1.779 nm of RMS roughness across 100 +m mirrors. Continuous torsion devices offer stable operation through as much as six degrees of rotation while binary operation devices offer stable activated positions with as much as 20 degrees of rotation. All arrays have desirable features of costly fabrication services like five structural layers and planarized mirror surfaces, but are prefabricated in the less costly MUMPs process. Models are developed for all devices and used to compare empirical data.

Rethinking mobile delivery: using Quick Response codes to access information at the point of need.

PubMed

Lombardo, Nancy T; Morrow, Anne; Le Ber, Jeanne

2012-01-01

This article covers the use of Quick Response (QR) codes to provide instant mobile access to information, digital collections, educational offerings, library website, subject guides, text messages, videos, and library personnel. The array of uses and the value of using QR codes to push customized information to patrons are explained. A case is developed for using QR codes for mobile delivery of customized information to patrons. Applications in use at the Libraries of the University of Utah will be reviewed to provide readers with ideas for use in their library. Copyright © Taylor & Francis Group, LLC

Charge Coupled Devices in Signal Processing Systems. Volume V. Final Report.

DTIC Science & Technology

1979-12-01

the Phase III program. At that time, mutual customer /contractor interest arose in a unique application area, involving manipulation of lists of...using half adders and "or" circuits. 4-35 3 b 2 b3 01 b *3b, *2 b 1 b2b 1 0 1 b, + + + + + + ++ r T 7 7 r* 7FA +-0j FA 147 7 7 1 77 7 7 TL NO.6 NO. 5...which the cell could be step-and- repeated into an array in the CAD system. In practice we found that the attendent custom skewing delay layout

DNA methylation data analysis and its application to cancer research

PubMed Central

Ma, Xiaotu; Wang, Yi-Wei; Zhang, Michael Q; Gazdar, Adi F

2013-01-01

With the rapid development of genome-wide high-throughput technologies, including expression arrays, SNP arrays and next-generation sequencing platforms, enormous amounts of molecular data have been generated and deposited in the public domain. The application of computational approaches is required to yield biological insights from this enormous, ever-growing resource. A particularly interesting subset of these resources is related to epigenetic regulation, with DNA methylation being the most abundant data type. In this paper, we will focus on the analysis of DNA methylation data and its application to cancer studies. We first briefly review the molecular techniques that generate such data, much of which has been obtained with the use of the most recent version of Infinium HumanMethylation450 BeadChip® technology (Illumina, CA, USA). We describe the coverage of the methylome by this technique. Several examples of data mining are provided. However, it should be understood that reliance on a single aspect of epigenetics has its limitations. In the not too distant future, these defects may be rectified, providing scientists with previously unavailable opportunities to explore in detail the role of epigenetics in cancer and other disease states. PMID:23750645

Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data.

PubMed

Chen, Guo-Bo; Lee, Sang Hong; Brion, Marie-Jo A; Montgomery, Grant W; Wray, Naomi R; Radford-Smith, Graham L; Visscher, Peter M

2014-09-01

As custom arrays are cheaper than generic GWAS arrays, larger sample size is achievable for gene discovery. Custom arrays can tag more variants through denser genotyping of SNPs at associated loci, but at the cost of losing genome-wide coverage. Balancing this trade-off is important for maximizing experimental designs. We quantified both the gain in captured SNP-heritability at known candidate regions and the loss due to imperfect genome-wide coverage for inflammatory bowel disease using immunochip (iChip) and imputed GWAS data on 61,251 and 38.550 samples, respectively. For Crohn's disease (CD), the iChip and GWAS data explained 19 and 26% of variation in liability, respectively, and SNPs in the densely genotyped iChip regions explained 13% of the SNP-heritability for both the iChip and GWAS data. For ulcerative colitis (UC), the iChip and GWAS data explained 15 and 19% of variation in liability, respectively, and the dense iChip regions explained 10 and 9% of the SNP-heritability in the iChip and the GWAS data. From bivariate analyses, estimates of the genetic correlation in risk between CD and UC were 0.75 (SE 0.017) and 0.62 (SE 0.042) for the iChip and GWAS data, respectively. We also quantified the SNP-heritability of genomic regions that did or did not contain the previous 163 GWAS hits for CD and UC, and SNP-heritability of the overlapping loci between the densely genotyped iChip regions and the 163 GWAS hits. For both diseases, over different genomic partitioning, the densely genotyped regions on the iChip tagged at least as much variation in liability as in the corresponding regions in the GWAS data, however a certain amount of tagged SNP-heritability in the GWAS data was lost using the iChip due to the low coverage at unselected regions. These results imply that custom arrays with a GWAS backbone will facilitate more gene discovery, both at associated and novel loci. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Generation of dark hollow beam via coherent combination based on adaptive optics.

PubMed

Zheng, Yi; Wang, Xiaohua; Shen, Feng; Li, Xinyang

2010-12-20

A novel method for generating a dark hollow beam (DHB) is proposed and studied both theoretically and experimentally. A coherent combination technique for laser arrays is implemented based on adaptive optics (AO). A beam arraying structure and an active segmented mirror are designed and described. Piston errors are extracted by a zero-order interference detection system with the help of a custom-made photo-detectors array. An algorithm called the extremum approach is adopted to calculate feedback control signals. A dynamic piston error is imported by LiNbO₃ to test the capability of the AO servo. In a closed loop the stable and clear DHB is obtained. The experimental results confirm the feasibility of the concept.

X-ray photon correlation spectroscopy using a fast pixel array detector with a grid mask resolution enhancer.

PubMed

Hoshino, Taiki; Kikuchi, Moriya; Murakami, Daiki; Harada, Yoshiko; Mitamura, Koji; Ito, Kiminori; Tanaka, Yoshihito; Sasaki, Sono; Takata, Masaki; Jinnai, Hiroshi; Takahara, Atsushi

2012-11-01

The performance of a fast pixel array detector with a grid mask resolution enhancer has been demonstrated for X-ray photon correlation spectroscopy (XPCS) measurements to investigate fast dynamics on a microscopic scale. A detecting system, in which each pixel of a single-photon-counting pixel array detector, PILATUS, is covered by grid mask apertures, was constructed for XPCS measurements of silica nanoparticles in polymer melts. The experimental results are confirmed to be consistent by comparison with other independent experiments. By applying this method, XPCS measurements can be carried out by customizing the hole size of the grid mask to suit the experimental conditions, such as beam size, detector size and sample-to-detector distance.

Development of the New DAQ System for the SD Array of TA×4 and TALE

NASA Astrophysics Data System (ADS)

Takahashi, Yuichi; Sahara, Ryosuke; Konishi, Shogo; Goto, Takashi; Ogio, Shoichi

The data acquisition (DAQ) system for the surface detector (SD) arrays of TA×4 and TALE will be presented. Each SD records digital signals with 50 MHz FADCs and sends the data to a central communication center (of the "communication tower") via a wireless network system. The technique employed here is based on the currently-running DAQ system of the Telescope Array, and there are some improvements including i) replacement of a wireless LAN module with a custom protocol to another with TCP/IP, and ii) replacement of the "tower electronics" to a generic Linux board PC of Raspberry Pi Type II B. The details and performance of the new DAQ system are described below.

Optical Links and RF Distribution for Antenna Arrays

NASA Technical Reports Server (NTRS)

Huang, Shouhua; Calhoun, Malcolm; Tjoelker, Robert

2006-01-01

An array of three antennas has recently been developed at the NASA Jet Propulsion Laboratory capable of detecting signals at X and Ka band. The array requires a common frequency reference and high precision phase alignment to correlate received signals. Frequency and timing references are presently provided from a remotely located hydrogen maser and clock through a combination of commercially and custom developed optical links. The selected laser, photodetector, and fiber components have been tested under anticipated thermal and simulated antenna rotation conditions. The resulting stability limitations due to thermal perturbations or induced stress on the optical fiber have been characterized. Distribution of the X band local oscillator includes a loop back and precision phase monitor to enable correlation of signals received from each antenna.

Adaptation of commercial microscopes for advanced imaging applications

NASA Astrophysics Data System (ADS)

Brideau, Craig; Poon, Kelvin; Stys, Peter

2015-03-01

Today's commercially available microscopes offer a wide array of options to accommodate common imaging experiments. Occasionally, an experimental goal will require an unusual light source, filter, or even irregular sample that is not compatible with existing equipment. In these situations the ability to modify an existing microscopy platform with custom accessories can greatly extend its utility and allow for experiments not possible with stock equipment. Light source conditioning/manipulation such as polarization, beam diameter or even custom source filtering can easily be added with bulk components. Custom and after-market detectors can be added to external ports using optical construction hardware and adapters. This paper will present various examples of modifications carried out on commercial microscopes to address both atypical imaging modalities and research needs. Violet and near-ultraviolet source adaptation, custom detection filtering, and laser beam conditioning and control modifications will be demonstrated. The availability of basic `building block' parts will be discussed with respect to user safety, construction strategies, and ease of use.

Arrays of Miniature Microphones for Aeroacoustic Testing

NASA Technical Reports Server (NTRS)

Shams, Qamar A.; Humphreys, William M.; Sealey, Bradley S.; Bartram, Scott M.; Zuckewar, Allan J.; Comeaux, Toby; Adams, James K.

2007-01-01

A phased-array system comprised of custom-made and commercially available microelectromechanical system (MEMS) silicon microphones and custom ancillary hardware has been developed for use in aeroacoustic testing in hard-walled and acoustically treated wind tunnels. Recent advances in the areas of multi-channel signal processing and beam forming have driven the construction of phased arrays containing ever-greater numbers of microphones. Traditional obstacles to this trend have been posed by (1) the high costs of conventional condenser microphones, associated cabling, and support electronics and (2) the difficulty of mounting conventional microphones in the precise locations required for high-density arrays. The present development overcomes these obstacles. One of the hallmarks of the new system is a series of fabricated platforms on which multiple microphones can be mounted. These mounting platforms, consisting of flexible polyimide circuit-board material (see left side of figure), include all the necessary microphone power and signal interconnects. A single bus line connects all microphones to a common power supply, while the signal lines terminate in one or more data buses on the sides of the circuit board. To minimize cross talk between array channels, ground lines are interposed as shields between all the data bus signal lines. The MEMS microphones are electrically connected to the boards via solder pads that are built into the printed wiring. These flexible circuit boards share many characteristics with their traditional rigid counterparts, but can be manufactured much thinner, as small as 0.1 millimeter, and much lighter with boards weighing as much as 75 percent less than traditional rigid ones. For a typical hard-walled wind-tunnel installation, the flexible printed-circuit board is bonded to the tunnel wall and covered with a face sheet that contains precise cutouts for the microphones. Once the face sheet is mounted, a smooth surface is established over the entire array due to the flush mounting of all microphones (see right side of figure). The face sheet is made from a continuous glass-woven-fabric base impregnated with an epoxy resin binder. This material offers a combination of high mechanical strength and low dielectric loss, making it suitable for withstanding the harsh test section environment present in many wind tunnels, while at the same time protecting the underlying polyimide board. Customized signal-conditioning hardware consisting of line drivers and antialiasing filters are coupled with the array. The line drivers are constructed using low-supply-current, high-gain-bandwidth operational amplifiers designed to transmit the microphone signals several dozen feet from the array to external acquisition hardware. The anti-alias filters consist of individual Chebyshev low-pass filters (one for each microphone channel) housed on small printed-circuit boards mounted on one or more motherboards. The mother/daughter board design results in a modular system, which is easy to debug and service and which enables the filter characteristics to be changed by swapping daughter boards with ones containing different filter parameters. The filter outputs are passed to commercially- available acquisition hardware to digitize and store the conditioned microphone signals. Wind-tunnel testing of the new MEMS microphone polyimide mounting system shows that the array performance is comparable to that of traditional arrays, but with significantly less cost of construction.

Transparent Fingerprint Sensor System for Large Flat Panel Display.

PubMed

Seo, Wonkuk; Pi, Jae-Eun; Cho, Sung Haeung; Kang, Seung-Youl; Ahn, Seong-Deok; Hwang, Chi-Sun; Jeon, Ho-Sik; Kim, Jong-Uk; Lee, Myunghee

2018-01-19

In this paper, we introduce a transparent fingerprint sensing system using a thin film transistor (TFT) sensor panel, based on a self-capacitive sensing scheme. An armorphousindium gallium zinc oxide (a-IGZO) TFT sensor array and associated custom Read-Out IC (ROIC) are implemented for the system. The sensor panel has a 200 × 200 pixel array and each pixel size is as small as 50 μm × 50 μm. The ROIC uses only eight analog front-end (AFE) amplifier stages along with a successive approximation analog-to-digital converter (SAR ADC). To get the fingerprint image data from the sensor array, the ROIC senses a capacitance, which is formed by a cover glass material between a human finger and an electrode of each pixel of the sensor array. Three methods are reviewed for estimating the self-capacitance. The measurement result demonstrates that the transparent fingerprint sensor system has an ability to differentiate a human finger's ridges and valleys through the fingerprint sensor array.

Customizable PCR-microplate array for differential identification of multiple pathogens

PubMed Central

Woubit, Abdela; Yehualaeshet, Teshome; Roberts, Sherrelle; Graham, Martha; Kim, Moonil; Samuel, Temesgen

2014-01-01

Customizable PCR-microplate arrays were developed for the rapid identification of Francisella tularensis subsp. tularensis, Salmonella Typhi, Shigella dysenteriae, Yersinia pestis, Vibrio cholerae Escherichia coli O157:H7, Salmonella Typhimurium, Salmonella Saintpaul, Francisella tularensis subsp. novicida, Vibrio parahaemolyticus, and Yersinia pseudotuberculosis. Previously, we identified highly specific primers targeting each of the pathogens above. Here, we report the development of customizable PCR-microplate arrays for simultaneous identification of the pathogens using the primers. A mixed aliquot of genomic DNA from 38 different strains was used to validate three PCR-microplate array formats. Identical PCR conditions were used to run all the samples on the three formats. Results show specific amplifications on all the three custom plates. In a preliminary test to evaluate the sensitivity of these assays in laboratory-inoculated samples, detection limits as low as 9 cfu/g/ml S. Typhimurium were obtained from beef hot dog, and 78 cfu/ml from milk. Such microplate arrays could serve as valuable tools for initial identification or secondary confirmation of these pathogens. PMID:24215700

Transparent Fingerprint Sensor System for Large Flat Panel Display

PubMed Central

Seo, Wonkuk; Pi, Jae-Eun; Cho, Sung Haeung; Kang, Seung-Youl; Ahn, Seong-Deok; Hwang, Chi-Sun; Jeon, Ho-Sik; Kim, Jong-Uk

2018-01-01

In this paper, we introduce a transparent fingerprint sensing system using a thin film transistor (TFT) sensor panel, based on a self-capacitive sensing scheme. An armorphousindium gallium zinc oxide (a-IGZO) TFT sensor array and associated custom Read-Out IC (ROIC) are implemented for the system. The sensor panel has a 200 × 200 pixel array and each pixel size is as small as 50 μm × 50 μm. The ROIC uses only eight analog front-end (AFE) amplifier stages along with a successive approximation analog-to-digital converter (SAR ADC). To get the fingerprint image data from the sensor array, the ROIC senses a capacitance, which is formed by a cover glass material between a human finger and an electrode of each pixel of the sensor array. Three methods are reviewed for estimating the self-capacitance. The measurement result demonstrates that the transparent fingerprint sensor system has an ability to differentiate a human finger’s ridges and valleys through the fingerprint sensor array. PMID:29351218

Chronic, percutaneous connector for electrical recording and stimulation with microelectrode arrays.

PubMed

Shah, Kedar G; Lee, Kye Young; Tolosa, Vanessa; Tooker, Angela; Felix, Sarah; Benett, William; Pannu, Satinderpall

2014-01-01

The translation of advances in neural stimulation and recording research into clinical practice hinges on the ability to perform chronic experiments in awake and behaving animal models. Advances in microelectrode array technology, most notably flexible polymer arrays, have significantly improved reliability of the neural interface. However, electrical connector technology has lagged and is prone to failure from non-biocompatibility, large size, contamination, corrosion, and difficulty of use. We present a novel chronic, percutaneous electrical connector system that is suitable for neural stimulation and recording. This system features biocompatible materials, low connect and disconnect forces, passive alignment, and a protective cap during non-use. We have successfully designed, assembled, and tested in vitro both a 16-channel system and a high density 64-channel system. Custom, polyimide, 16-channel, microelectrode arrays were electrically assembled with the connector system and tested using cyclic voltammetry and electrochemical impedance spectroscopy. This connector system is versatile and can be used with a variety of microelectrode array technologies for chronic studies.

StrainSeeker: fast identification of bacterial strains from raw sequencing reads using user-provided guide trees.

PubMed

Roosaare, Märt; Vaher, Mihkel; Kaplinski, Lauris; Möls, Märt; Andreson, Reidar; Lepamets, Maarja; Kõressaar, Triinu; Naaber, Paul; Kõljalg, Siiri; Remm, Maido

2017-01-01

Fast, accurate and high-throughput identification of bacterial isolates is in great demand. The present work was conducted to investigate the possibility of identifying isolates from unassembled next-generation sequencing reads using custom-made guide trees. A tool named StrainSeeker was developed that constructs a list of specific k -mers for each node of any given Newick-format tree and enables the identification of bacterial isolates in 1-2 min. It uses a novel algorithm, which analyses the observed and expected fractions of node-specific k -mers to test the presence of each node in the sample. This allows StrainSeeker to determine where the isolate branches off the guide tree and assign it to a clade whereas other tools assign each read to a reference genome. Using a dataset of 100 Escherichia coli isolates, we demonstrate that StrainSeeker can predict the clades of E. coli with 92% accuracy and correct tree branch assignment with 98% accuracy. Twenty-five thousand Illumina HiSeq reads are sufficient for identification of the strain. StrainSeeker is a software program that identifies bacterial isolates by assigning them to nodes or leaves of a custom-made guide tree. StrainSeeker's web interface and pre-computed guide trees are available at http://bioinfo.ut.ee/strainseeker. Source code is stored at GitHub: https://github.com/bioinfo-ut/StrainSeeker.

CIDR

Science.gov Websites

NIH CIDR Program Studies For whole exome sequencing projects, we pretest all samples using a high -density SNP array (>200,000 markers). For custom targeted sequencing, we pretest all samples using a 96 pretest samples using a 96 SNP GoldenGate assay. This extensive pretesting allows us to unambiguously tie

Librarians as Community Partners: An Outreach Handbook

ERIC Educational Resources Information Center

Smallwood, Carol, Ed.

2010-01-01

Including 66 focused snapshots of outreach in action, this resource reflects the creative solutions of librarians searching for new and innovative ways to build programs that meet customer needs while expanding the library's scope into the community. This contributed volume includes: (1) A huge array of program options for partnering with other…

Low-Latency Embedded Vision Processor (LLEVS)

DTIC Science & Technology

2016-03-01

26 3.2.3 Task 3 Projected Performance Analysis of FPGA- based Vision Processor ........... 31 3.2.3.1 Algorithms Latency Analysis ...Programmable Gate Array Custom Hardware for Real- Time Multiresolution Analysis . ............................................... 35...conduct data analysis for performance projections. The data acquired through measurements , simulation and estimation provide the requisite platform for

CIDR

Science.gov Websites

variety of arrays appropriate for a wide breadth of study design needs. Genomic coverage of many of the chromosomal anomalies are services offered at NO ADDITIONAL COST to study investigators with GWAS projects be submitted for both the initial GWAS study as well as replication using our custom SNP service

'FloraArray' for screening of specific DNA probes representing the characteristics of a certain microbial community.

PubMed

Yokoi, Takahide; Kaku, Yoshiko; Suzuki, Hiroyuki; Ohta, Masayuki; Ikuta, Hajime; Isaka, Kazuichi; Sumino, Tatsuo; Wagatsuma, Masako

2007-08-01

To investigate uncharacterized microbial communities, a custom DNA microarray named 'FloraArray' was developed for screening specific probes that would represent the characteristics of a microbial community. The array was prepared by spotting 2000 plasmid DNAs from a genomic shotgun library of a sludge sample on a DNA microarray. By comparative hybridization of the array with two different samples of genomic DNA, one from the activated sludge and the other from a nonactivated sludge sample of an anaerobic ammonium oxidation (anammox) bacterial community, specific spots were visualized as a definite fluctuating profile in an MA (differential intensity ratio vs. spot intensity) plot. About 300 spots of the array accounted for the candidate probes to represent anammox reaction of the activated sludge. After sequence analysis of the probes and examination of the results of blastn searches against the reported anammox reference sequence, complete matches were found for 161 probes (58.3%) and >90% matches were found for 242 probes (87.1%). These results demonstrate that 'FloraArray' could be a useful tool for screening specific DNA molecules of unknown microbial communities.

Biomechanical Characterization of Cardiomyocyte Using PDMS Pillar with Microgrooves

PubMed Central

Oyunbaatar, Nomin-Erdene; Lee, Deok-Hyu; Patil, Swati J.; Kim, Eung-Sam; Lee, Dong-Weon

2016-01-01

This paper describes the surface-patterned polydimethylsiloxane (PDMS) pillar arrays for enhancing cell alignment and contraction force in cardiomyocytes. The PDMS micropillar (μpillar) arrays with microgrooves (μgrooves) were fabricated using a unique micro-mold made using SU-8 double layer processes. The spring constant of the μpillar arrays was experimentally confirmed using atomic force microscopy (AFM). After culturing cardiac cells on the two different types of μpillar arrays, with and without grooves on the top of μpillar, the characteristics of the cardiomyocytes were analyzed using a custom-made image analysis system. The alignment of the cardiomyocytes on the μgrooves of the μpillars was clearly observed using a DAPI staining process. The mechanical force generated by the contraction force of the cardiomyocytes was derived from the displacement of the μpillar arrays. The contraction force of the cardiomyocytes aligned on the μgrooves was 20% higher than that of the μpillar arrays without μgrooves. The experimental results prove that applied geometrical stimulus is an effective method for aligning and improving the contraction force of cardiomyocytes. PMID:27517924

What is a free customer worth? Armchair calculations of nonpaying customers' value can lead to flawed strategies.

PubMed

Gupta, Sunil; Mela, Carl F

2008-11-01

Free customers who are subsidized by paying customers are essential to a vast array of businesses, such as media companies, employment services, and even IT providers. But because they generate revenue only indirectly, figuring out the true value of those customers--and how much attention to devote them--has always been a challenge. Traditional customer-valuation models don't help; they focus exclusively on paying customers and largely ignore network effects, or how customers help draw other customers to a business. Now a new model, devised by professors Gupta, of Harvard Business School, and Mela, of Fuqua School of Business, takes into account not only direct network effects (where buyers attract more buyers or sellers more sellers) but also indirect network effects (where buyers attract more sellers or vice versa) . The model calculates the precise long-term impact of each additional free customer on a company's profits, factoring in the degree to which he or she brings in other customers--whether free or paying--and the ripple effect of those customers. The model helped an online auction house make several critical decisions. The business made its money on fees charged to sellers but recognized that its free customers--its buyers--were valuable, too. As competition heated up, the company worried that it wasn't wooing enough buyers. Using the model, the business discovered that the network effects of buyers were indeed large and that those customers were worth over $1,000 each--much more than had been assumed. Armed with that information, the firm increased its research on buyers, invested more in targeting them with ads, and improved their experience. The model also helped the company identify the effects of various pricing strategies on sellers, showing that they became less price-sensitive over time. As a result, the company raised the fees it charged them as well.

Wafer-level radiometric performance testing of uncooled microbolometer arrays

NASA Astrophysics Data System (ADS)

Dufour, Denis G.; Topart, Patrice; Tremblay, Bruno; Julien, Christian; Martin, Louis; Vachon, Carl

2014-03-01

A turn-key semi-automated test system was constructed to perform on-wafer testing of microbolometer arrays. The system allows for testing of several performance characteristics of ROIC-fabricated microbolometer arrays including NETD, SiTF, ROIC functionality, noise and matrix operability, both before and after microbolometer fabrication. The system accepts wafers up to 8 inches in diameter and performs automated wafer die mapping using a microscope camera. Once wafer mapping is completed, a custom-designed quick insertion 8-12 μm AR-coated Germanium viewport is placed and the chamber is pumped down to below 10-5 Torr, allowing for the evaluation of package-level focal plane array (FPA) performance. The probe card is electrically connected to an INO IRXCAM camera core, a versatile system that can be adapted to many types of ROICs using custom-built interface printed circuit boards (PCBs). We currently have the capability for testing 384x288, 35 μm pixel size and 160x120, 52 μm pixel size FPAs. For accurate NETD measurements, the system is designed to provide an F/1 view of two rail-mounted blackbodies seen through the Germanium window by the die under test. A master control computer automates the alignment of the probe card to the dies, the positioning of the blackbodies, FPA image frame acquisition using IRXCAM, as well as data analysis and storage. Radiometric measurement precision has been validated by packaging dies measured by the automated probing system and re-measuring the SiTF and Noise using INO's pre-existing benchtop system.

Development of a c-scan photoacoutsic imaging probe for prostate cancer detection

NASA Astrophysics Data System (ADS)

Valluru, Keerthi S.; Chinni, Bhargava K.; Rao, Navalgund A.; Bhatt, Shweta; Dogra, Vikram S.

2011-03-01

Prostate cancer is the second leading cause of death in American men after lung cancer. The current screening procedures include Digital Rectal Exam (DRE) and Prostate Specific Antigen (PSA) test, along with Transrectal Ultrasound (TRUS). All suffer from low sensitivity and specificity in detecting prostate cancer in early stages. There is a desperate need for a new imaging modality. We are developing a prototype transrectal photoacoustic imaging probe to detect prostate malignancies in vivo that promises high sensitivity and specificity. To generate photoacoustic (PA) signals, the probe utilizes a high energy 1064 nm laser that delivers light pulses onto the prostate at 10Hz with 10ns duration through a fiber optic cable. The designed system will generate focused C-scan planar images using acoustic lens technology. A 5 MHz custom fabricated ultrasound sensor array located in the image plane acquires the focused PA signals, eliminating the need for any synthetic aperture focusing. The lens and sensor array design was optimized towards this objective. For fast acquisition times, a custom built 16 channel simultaneous backend electronics PCB has been developed. It consists of a low-noise variable gain amplifier and a 16 channel ADC. Due to the unavailability of 2d ultrasound arrays, in the current implementation several B-scan (depth-resolved) data is first acquired by scanning a 1d array, which is then processed to reconstruct either 3d volumetric images or several C-scan planar images. Experimental results on excised tissue using a in-vitro prototype of this technology are presented to demonstrate the system capability in terms of resolution and sensitivity.

SAR processing on the MPP

NASA Technical Reports Server (NTRS)

Batcher, K. E.; Eddey, E. E.; Faiss, R. O.; Gilmore, P. A.

1981-01-01

The processing of synthetic aperture radar (SAR) signals using the massively parallel processor (MPP) is discussed. The fast Fourier transform convolution procedures employed in the algorithms are described. The MPP architecture comprises an array unit (ARU) which processes arrays of data; an array control unit which controls the operation of the ARU and performs scalar arithmetic; a program and data management unit which controls the flow of data; and a unique staging memory (SM) which buffers and permutes data. The ARU contains a 128 by 128 array of bit-serial processing elements (PE). Two-by-four surarrays of PE's are packaged in a custom VLSI HCMOS chip. The staging memory is a large multidimensional-access memory which buffers and permutes data flowing with the system. Efficient SAR processing is achieved via ARU communication paths and SM data manipulation. Real time processing capability can be realized via a multiple ARU, multiple SM configuration.

Performance of the Fully Digital FPGA-Based Front-End Electronics for the GALILEO Array

NASA Astrophysics Data System (ADS)

Barrientos, D.; Bellato, M.; Bazzacco, D.; Bortolato, D.; Cocconi, P.; Gadea, A.; González, V.; Gulmini, M.; Isocrate, R.; Mengoni, D.; Pullia, A.; Recchia, F.; Rosso, D.; Sanchis, E.; Toniolo, N.; Ur, C. A.; Valiente-Dobón, J. J.

2015-12-01

In this work we present the architecture and results of a fully digital Front End Electronics (FEE) read out system developed for the GALILEO array. The FEE system, developed in collaboration with the Advanced Gamma Tracking Array (AGATA) collaboration, is composed of three main blocks: preamplifiers, digitizers and preprocessing electronics. The slow control system contains a custom Linux driver, a dynamic library and a server implementing network services. This work presents the first results of the digital FEE system coupled with a GALILEO germanium detector, which has demonstrated the capability to achieve an energy resolution of 1.530/00 at an energy of 1.33 MeV, similar to the one obtained with a conventional analog system. While keeping a good performance in terms of energy resolution, digital electronics will allow to instrument the full GALILEO array with a versatile system with high integration and low power consumption and costs.

Testing Microshutter Arrays Using Commercial FPGA Hardware

NASA Technical Reports Server (NTRS)

Rapchun, David

2008-01-01

NASA is developing micro-shutter arrays for the Near Infrared Spectrometer (NIRSpec) instrument on the James Webb Space Telescope (JWST). These micro-shutter arrays allow NIRspec to do Multi Object Spectroscopy, a key part of the mission. Each array consists of 62414 individual 100 x 200 micron shutters. These shutters are magnetically opened and held electrostatically. Individual shutters are then programmatically closed using a simple row/column addressing technique. A common approach to provide these data/clock patterns is to use a Field Programmable Gate Array (FPGA). Such devices require complex VHSIC Hardware Description Language (VHDL) programming and custom electronic hardware. Due to JWST's rapid schedule on the development of the micro-shutters, rapid changes were required to the FPGA code to facilitate new approaches being discovered to optimize the array performance. Such rapid changes simply could not be made using conventional VHDL programming. Subsequently, National Instruments introduced an FPGA product that could be programmed through a Labview interface. Because Labview programming is considerably easier than VHDL programming, this method was adopted and brought success. The software/hardware allowed the rapid change the FPGA code and timely results of new micro-shutter array performance data. As a result, numerous labor hours and money to the project were conserved.

Massively parallel sequencing of 68 insertion/deletion markers identifies novel microhaplotypes for utility in human identity testing.

PubMed

Wendt, Frank R; Warshauer, David H; Zeng, Xiangpei; Churchill, Jennifer D; Novroski, Nicole M M; Song, Bing; King, Jonathan L; LaRue, Bobby L; Budowle, Bruce

2016-11-01

Short tandem repeat (STR) loci are the traditional markers used for kinship, missing persons, and direct comparison human identity testing. These markers hold considerable value due to their highly polymorphic nature, amplicon size, and ability to be multiplexed. However, many STRs are still too large for use in analysis of highly degraded DNA. Small bi-allelic polymorphisms, such as insertions/deletions (INDELs), may be better suited for analyzing compromised samples, and their allele size differences are amenable to analysis by capillary electrophoresis. The INDEL marker allelic states range in size from 2 to 6 base pairs, enabling small amplicon size. In addition, heterozygote balance may be increased by minimizing preferential amplification of the smaller allele, as is more common with STR markers. Multiplexing a large number of INDELs allows for generating panels with high discrimination power. The Nextera™ Rapid Capture Custom Enrichment Kit (Illumina, Inc., San Diego, CA) and massively parallel sequencing (MPS) on the Illumina MiSeq were used to sequence 68 well-characterized INDELs in four major US population groups. In addition, the STR Allele Identification Tool: Razor (STRait Razor) was used in a novel way to analyze INDEL sequences and detect adjacent single nucleotide polymorphisms (SNPs) and other polymorphisms. This application enabled the discovery of unique allelic variants, which increased the discrimination power and decreased the single-locus random match probabilities (RMPs) of 22 of these well-characterized INDELs which can be considered as microhaplotypes. These findings suggest that additional microhaplotypes containing human identification (HID) INDELs may exist elsewhere in the genome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

BEAT: Bioinformatics Exon Array Tool to store, analyze and visualize Affymetrix GeneChip Human Exon Array data from disease experiments

PubMed Central

2012-01-01

Background It is known from recent studies that more than 90% of human multi-exon genes are subject to Alternative Splicing (AS), a key molecular mechanism in which multiple transcripts may be generated from a single gene. It is widely recognized that a breakdown in AS mechanisms plays an important role in cellular differentiation and pathologies. Polymerase Chain Reactions, microarrays and sequencing technologies have been applied to the study of transcript diversity arising from alternative expression. Last generation Affymetrix GeneChip Human Exon 1.0 ST Arrays offer a more detailed view of the gene expression profile providing information on the AS patterns. The exon array technology, with more than five million data points, can detect approximately one million exons, and it allows performing analyses at both gene and exon level. In this paper we describe BEAT, an integrated user-friendly bioinformatics framework to store, analyze and visualize exon arrays datasets. It combines a data warehouse approach with some rigorous statistical methods for assessing the AS of genes involved in diseases. Meta statistics are proposed as a novel approach to explore the analysis results. BEAT is available at http://beat.ba.itb.cnr.it. Results BEAT is a web tool which allows uploading and analyzing exon array datasets using standard statistical methods and an easy-to-use graphical web front-end. BEAT has been tested on a dataset with 173 samples and tuned using new datasets of exon array experiments from 28 colorectal cancer and 26 renal cell cancer samples produced at the Medical Genetics Unit of IRCCS Casa Sollievo della Sofferenza. To highlight all possible AS events, alternative names, accession Ids, Gene Ontology terms and biochemical pathways annotations are integrated with exon and gene level expression plots. The user can customize the results choosing custom thresholds for the statistical parameters and exploiting the available clinical data of the samples for a multivariate AS analysis. Conclusions Despite exon array chips being widely used for transcriptomics studies, there is a lack of analysis tools offering advanced statistical features and requiring no programming knowledge. BEAT provides a user-friendly platform for a comprehensive study of AS events in human diseases, displaying the analysis results with easily interpretable and interactive tables and graphics. PMID:22536968

C%2B%2B tensor toolbox user manual.

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

Plantenga, Todd D.; Kolda, Tamara Gibson

2012-04-01

The C++ Tensor Toolbox is a software package for computing tensor decompositions. It is based on the Matlab Tensor Toolbox, and is particularly optimized for sparse data sets. This user manual briefly overviews tensor decomposition mathematics, software capabilities, and installation of the package. Tensors (also known as multidimensional arrays or N-way arrays) are used in a variety of applications ranging from chemometrics to network analysis. The Tensor Toolbox provides classes for manipulating dense, sparse, and structured tensors in C++. The Toolbox compiles into libraries and is intended for use with custom applications written by users.

High temperature, high intensity solar array. [for Venus Radar Mapper mission

NASA Technical Reports Server (NTRS)

Smith, B. S.; Brooks, G. R.; Pinkerton, R.

1985-01-01

The solar array for the Venus Radar Mapper mission will operate in the high temperature, high intensity conditions of a low Venus orbit environment. To fulfill the performance requirements in this environment at minimum cost and mass while maximizing power density and packing factor on the panel surface, several features were introduced into the design. These features included the use of optical surface reflectors (OSR's) to reduce the operating temperature; new adhesives for conductive bonding of OSR's to avoid electrostatic discharges; custom-designed large area cells and novel shunt diode circuit and panel power harness configurations.

The effect of algorithms on copy number variant detection.

PubMed

Tsuang, Debby W; Millard, Steven P; Ely, Benjamin; Chi, Peter; Wang, Kenneth; Raskind, Wendy H; Kim, Sulgi; Brkanac, Zoran; Yu, Chang-En

2010-12-30

The detection of copy number variants (CNVs) and the results of CNV-disease association studies rely on how CNVs are defined, and because array-based technologies can only infer CNVs, CNV-calling algorithms can produce vastly different findings. Several authors have noted the large-scale variability between CNV-detection methods, as well as the substantial false positive and false negative rates associated with those methods. In this study, we use variations of four common algorithms for CNV detection (PennCNV, QuantiSNP, HMMSeg, and cnvPartition) and two definitions of overlap (any overlap and an overlap of at least 40% of the smaller CNV) to illustrate the effects of varying algorithms and definitions of overlap on CNV discovery. We used a 56 K Illumina genotyping array enriched for CNV regions to generate hybridization intensities and allele frequencies for 48 Caucasian schizophrenia cases and 48 age-, ethnicity-, and gender-matched control subjects. No algorithm found a difference in CNV burden between the two groups. However, the total number of CNVs called ranged from 102 to 3,765 across algorithms. The mean CNV size ranged from 46 kb to 787 kb, and the average number of CNVs per subject ranged from 1 to 39. The number of novel CNVs not previously reported in normal subjects ranged from 0 to 212. Motivated by the availability of multiple publicly available genome-wide SNP arrays, investigators are conducting numerous analyses to identify putative additional CNVs in complex genetic disorders. However, the number of CNVs identified in array-based studies, and whether these CNVs are novel or valid, will depend on the algorithm(s) used. Thus, given the variety of methods used, there will be many false positives and false negatives. Both guidelines for the identification of CNVs inferred from high-density arrays and the establishment of a gold standard for validation of CNVs are needed.

Biomimetic cell wall model studies to identify new lignin bioengineering targets for improving biomass susceptibility to pretreatment and enzymatic saccharification

USDA-ARS?s Scientific Manuscript database

Increasingly, bioengineering of lignin to contain atypical building blocks from other metabolic pathways is being pursued to custom-design lignin that is easier to remove by chemical pretreatments and less inhibitory toward polysaccharide saccharification. Because plants produce such a diverse array...

Microlens frames for laser diode arrays

DOEpatents

Skidmore, J.A.; Freitas, B.L.

1999-07-13

Monolithic microlens frames enable the fabrication of monolithic laser diode arrays and are manufactured inexpensively with high registration, and with inherent focal length compensation for any lens diameter variation. A monolithic substrate is used to fabricate a low-cost microlens array. The substrate is wet-etched or sawed with a series of v-grooves. The v-grooves can be created by wet-etching, by exploiting the large etch-rate selectivity of different crystal planes. The v-grooves provide a support frame for either cylindrical or custom-shaped microlenses. Because the microlens frames are formed by photolithographic semiconductor batch-processing techniques, they can be formed inexpensively over large areas with precise lateral and vertical registration. The v-groove has an important advantage for preserving the correct focus for lenses of varying diameter. 12 figs.

Microlens frames for laser diode arrays

DOEpatents

Skidmore, Jay A.; Freitas, Barry L.

1999-01-01

Monolithic microlens frames enable the fabrication of monolithic laser diode arrays and are manufactured inexpensively with high registration, and with inherent focal length compensation for any lens diameter variation. A monolithic substrate is used to fabricate a low-cost microlens array. The substrate is wet-etched or sawed with a series of v-grooves. The v-grooves can be created by wet-etching, by exploiting the large etch-rate selectivity of different crystal planes. The v-grooves provide a support frame for either cylindrical or custom-shaped microlenses. Because the microlens frames are formed by photolithographic semiconductor batch-processing techniques, they can be formed inexpensively over large areas with precise lateral and vertical registration. The v-groove has an important advantage for preserving the correct focus for lenses of varying diameter.

Fiber-optic hydrophone array for acoustic surveillance in the littoral

NASA Astrophysics Data System (ADS)

Hill, David; Nash, Phillip

2005-05-01

We describe a fibre-optic hydrophone array system architecture that can be tailored to meet the underwater acoustic surveillance requirements of the military, counter terrorist and customs authorities in protecting ports and harbours, offshore production facilities or coastal approaches. Physically the fibre-optic hydrophone array is in the form of a lightweight cable, enabling rapid deployment from a small vessel. Based upon an optical architecture of time and wavelength multiplexed interferometric hydrophones, the array is comprised of a series of hydrophone sub-arrays. Using multiple sub-arrays, extended perimeters many tens of kilometres in length can be monitored. Interrogated via a long (~50km) optical fibre data link, the acoustic date is processed using the latest open architecture sonar processing platform, ensuring that acoustic targets below, on and above the surface are detected, tracked and classified. Results obtained from an at sea trial of a 96-channel hydrophone array are given, showing the passive detection and tracking of a diver, small surface craft and big ocean going ships beyond the horizon. Furthermore, we describe how the OptaMarine fibre-optic hydrophone array fits into an integrated multi-layered approach to port and harbour security consisting of active sonar for diver detection and hull imaging, as well as thermal imaging and CCTV for surface monitoring. Finally, we briefly describe a complimentary land perimeter intruder detection system consisting of an array of fibre optic accelerometers.

Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome.

PubMed

Arai, Eri; Sakamoto, Hiromi; Ichikawa, Hitoshi; Totsuka, Hirohiko; Chiku, Suenori; Gotoh, Masahiro; Mori, Taisuke; Nakatani, Tamao; Ohnami, Sumiko; Nakagawa, Tohru; Fujimoto, Hiroyuki; Wang, Linghua; Aburatani, Hiroyuki; Yoshida, Teruhiko; Kanai, Yae

2014-09-15

The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Illumina Infinium HumanMethylation27 BeadArray and Agilent SurePrint Human Gene Expression microarray, respectively. Sanger sequencing and quantitative reverse transcription-PCR were performed for technical verification. MetaCore software was used for pathway analysis. Somatic nonsynonymous single-nucleotide mutations, insertions/deletions and intragenic breaks of 2,153, 359 and 8 genes were detected, respectively. Mutations of GCN1L1, MED12 and CCNC, which are members of CDK8 mediator complex directly regulating β-catenin-driven transcription, were identified in 16% of the RCCs. Mutations of MACF1, which functions in the Wnt/β-catenin signaling pathway, were identified in 4% of the RCCs. A combination of methylome and transcriptome analyses further highlighted the significant role of the Wnt/β-catenin signaling pathway in renal carcinogenesis. Genetic aberrations and reduced expression of ERC2 and ABCA13 were frequent in RCCs, and MTOR mutations were identified as one of the major disrupters of cell signaling during renal carcinogenesis. Our results confirm that multilayer-omics analysis can be a powerful tool for revealing pathways that play a significant role in carcinogenesis. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Multilayer-omics analysis of renal cell carcinoma, including the whole exome, methylome and transcriptome

PubMed Central

Arai, Eri; Sakamoto, Hiromi; Ichikawa, Hitoshi; Totsuka, Hirohiko; Chiku, Suenori; Gotoh, Masahiro; Mori, Taisuke; Nakatani, Tamao; Ohnami, Sumiko; Nakagawa, Tohru; Fujimoto, Hiroyuki; Wang, Linghua; Aburatani, Hiroyuki; Yoshida, Teruhiko; Kanai, Yae

2014-01-01

The aim of this study was to identify pathways that have a significant impact during renal carcinogenesis. Sixty-seven paired samples of both noncancerous renal cortex tissue and cancerous tissue from patients with clear cell renal cell carcinomas (RCCs) were subjected to whole-exome, methylome and transcriptome analyses using Agilent SureSelect All Exon capture followed by sequencing on an Illumina HiSeq 2000 platform, Illumina Infinium HumanMethylation27 BeadArray and Agilent SurePrint Human Gene Expression microarray, respectively. Sanger sequencing and quantitative reverse transcription-PCR were performed for technical verification. MetaCore software was used for pathway analysis. Somatic nonsynonymous single-nucleotide mutations, insertions/deletions and intragenic breaks of 2,153, 359 and 8 genes were detected, respectively. Mutations of GCN1L1, MED12 and CCNC, which are members of CDK8 mediator complex directly regulating β-catenin-driven transcription, were identified in 16% of the RCCs. Mutations of MACF1, which functions in the Wnt/β-catenin signaling pathway, were identified in 4% of the RCCs. A combination of methylome and transcriptome analyses further highlighted the significant role of the Wnt/β-catenin signaling pathway in renal carcinogenesis. Genetic aberrations and reduced expression of ERC2 and ABCA13 were frequent in RCCs, and MTOR mutations were identified as one of the major disrupters of cell signaling during renal carcinogenesis. Our results confirm that multilayer-omics analysis can be a powerful tool for revealing pathways that play a significant role in carcinogenesis. PMID:24504440

Performance comparison of two microarray platforms to assess differential gene expression in human monocyte and macrophage cells

PubMed Central

Maouche, Seraya; Poirier, Odette; Godefroy, Tiphaine; Olaso, Robert; Gut, Ivo; Collet, Jean-Phillipe; Montalescot, Gilles; Cambien, François

2008-01-01

Background In this study we assessed the respective ability of Affymetrix and Illumina microarray methodologies to answer a relevant biological question, namely the change in gene expression between resting monocytes and macrophages derived from these monocytes. Five RNA samples for each type of cell were hybridized to the two platforms in parallel. In addition, a reference list of differentially expressed genes (DEG) was generated from a larger number of hybridizations (mRNA from 86 individuals) using the RNG/MRC two-color platform. Results Our results show an important overlap of the Illumina and Affymetrix DEG lists. In addition, more than 70% of the genes in these lists were also present in the reference list. Overall the two platforms had very similar performance in terms of biological significance, evaluated by the presence in the DEG lists of an excess of genes belonging to Gene Ontology (GO) categories relevant for the biology of monocytes and macrophages. Our results support the conclusion of the MicroArray Quality Control (MAQC) project that the criteria used to constitute the DEG lists strongly influence the degree of concordance among platforms. However the importance of prioritizing genes by magnitude of effect (fold change) rather than statistical significance (p-value) to enhance cross-platform reproducibility recommended by the MAQC authors was not supported by our data. Conclusion Functional analysis based on GO enrichment demonstrates that the 2 compared technologies delivered very similar results and identified most of the relevant GO categories enriched in the reference list. PMID:18578872

Epigenome-wide DNA methylation analysis in siblings and monozygotic twins discordant for sporadic Parkinson's disease revealed different epigenetic patterns in peripheral blood mononuclear cells.

PubMed

Kaut, Oliver; Schmitt, Ina; Tost, Jörg; Busato, Florence; Liu, Yi; Hofmann, Per; Witt, Stephanie H; Rietschel, Marcella; Fröhlich, Holger; Wüllner, Ullrich

2017-01-01

Numerous studies have elucidated the genetics of Parkinson's disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs. 227 healthy individuals (cohort 1) applying Illumina's VeraCode and 472 PD patients vs. 487 controls (cohort 2) using pyrosequencing. We choose a delta beta of >15 % and selected 62 differentially methylated CpGs in 51 genes from the discordant siblings. Among them, three displayed multiple CpGs per gene: microRNA 886 (MIR886, 10 CpGs), phosphodiesterase 4D (PDE4D, 2 CpGs) and tripartite motif-containing 34 (TRIM34, 2 CpGs). PDE4D was confirmed in both cohorts (p value 2.44e-05). In addition, for biomarker construction, we used the penalized logistic regression model, resulting in a signature of eight CpGs with an AUC of 0.77. Our findings suggest that a distinct level of PD susceptibility stems from individual, epigenetic modifications of specific genes. We identified a signature of CpGs in blood cells that could separate control from disease with a reasonable discriminatory power, holding promise for future epigenetically based biomarker development.

Design methodology: edgeless 3D ASICs with complex in-pixel processing for pixel detectors

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

Fahim Farah, Fahim Farah; Deptuch, Grzegorz W.; Hoff, James R.

The design methodology for the development of 3D integrated edgeless pixel detectors with in-pixel processing using Electronic Design Automation (EDA) tools is presented. A large area 3 tier 3D detector with one sensor layer and two ASIC layers containing one analog and one digital tier, is built for x-ray photon time of arrival measurement and imaging. A full custom analog pixel is 65μm x 65μm. It is connected to a sensor pixel of the same size on one side, and on the other side it has approximately 40 connections to the digital pixel. A 32 x 32 edgeless array withoutmore » any peripheral functional blocks constitutes a sub-chip. The sub-chip is an indivisible unit, which is further arranged in a 6 x 6 array to create the entire 1.248cm x 1.248cm ASIC. Each chip has 720 bump-bond I/O connections, on the back of the digital tier to the ceramic PCB. All the analog tier power and biasing is conveyed through the digital tier from the PCB. The assembly has no peripheral functional blocks, and hence the active area extends to the edge of the detector. This was achieved by using a few flavors of almost identical analog pixels (minimal variation in layout) to allow for peripheral biasing blocks to be placed within pixels. The 1024 pixels within a digital sub-chip array have a variety of full custom, semi-custom and automated timing driven functional blocks placed together. The methodology uses a modified mixed-mode on-top digital implementation flow to not only harness the tool efficiency for timing and floor-planning but also to maintain designer control over compact parasitically aware layout. The methodology uses the Cadence design platform, however it is not limited to this tool.« less

Design methodology: edgeless 3D ASICs with complex in-pixel processing for pixel detectors

NASA Astrophysics Data System (ADS)

Fahim, Farah; Deptuch, Grzegorz W.; Hoff, James R.; Mohseni, Hooman

2015-08-01

The design methodology for the development of 3D integrated edgeless pixel detectors with in-pixel processing using Electronic Design Automation (EDA) tools is presented. A large area 3 tier 3D detector with one sensor layer and two ASIC layers containing one analog and one digital tier, is built for x-ray photon time of arrival measurement and imaging. A full custom analog pixel is 65μm x 65μm. It is connected to a sensor pixel of the same size on one side, and on the other side it has approximately 40 connections to the digital pixel. A 32 x 32 edgeless array without any peripheral functional blocks constitutes a sub-chip. The sub-chip is an indivisible unit, which is further arranged in a 6 x 6 array to create the entire 1.248cm x 1.248cm ASIC. Each chip has 720 bump-bond I/O connections, on the back of the digital tier to the ceramic PCB. All the analog tier power and biasing is conveyed through the digital tier from the PCB. The assembly has no peripheral functional blocks, and hence the active area extends to the edge of the detector. This was achieved by using a few flavors of almost identical analog pixels (minimal variation in layout) to allow for peripheral biasing blocks to be placed within pixels. The 1024 pixels within a digital sub-chip array have a variety of full custom, semi-custom and automated timing driven functional blocks placed together. The methodology uses a modified mixed-mode on-top digital implementation flow to not only harness the tool efficiency for timing and floor-planning but also to maintain designer control over compact parasitically aware layout. The methodology uses the Cadence design platform, however it is not limited to this tool.

Identification of a deep intronic mutation in the COL6A2 gene by a novel custom oligonucleotide CGH array designed to explore allelic and genetic heterogeneity in collagen VI-related myopathies

PubMed Central

2010-01-01

Background Molecular characterization of collagen-VI related myopathies currently relies on standard sequencing, which yields a detection rate approximating 75-79% in Ullrich congenital muscular dystrophy (UCMD) and 60-65% in Bethlem myopathy (BM) patients as PCR-based techniques tend to miss gross genomic rearrangements as well as copy number variations (CNVs) in both the coding sequence and intronic regions. Methods We have designed a custom oligonucleotide CGH array in order to investigate the presence of CNVs in the coding and non-coding regions of COL6A1, A2, A3, A5 and A6 genes and a group of genes functionally related to collagen VI. A cohort of 12 patients with UCMD/BM negative at sequencing analysis and 2 subjects carrying a single COL6 mutation whose clinical phenotype was not explicable by inheritance were selected and the occurrence of allelic and genetic heterogeneity explored. Results A deletion within intron 1A of the COL6A2 gene, occurring in compound heterozygosity with a small deletion in exon 28, previously detected by routine sequencing, was identified in a BM patient. RNA studies showed monoallelic transcription of the COL6A2 gene, thus elucidating the functional effect of the intronic deletion. No pathogenic mutations were identified in the remaining analyzed patients, either within COL6A genes, or in genes functionally related to collagen VI. Conclusions Our custom CGH array may represent a useful complementary diagnostic tool, especially in recessive forms of the disease, when only one mutant allele is detected by standard sequencing. The intronic deletion we identified represents the first example of a pure intronic mutation in COL6A genes. PMID:20302629

An Array Library for Microsoft SQL Server with Astrophysical Applications

NASA Astrophysics Data System (ADS)

Dobos, L.; Szalay, A. S.; Blakeley, J.; Falck, B.; Budavári, T.; Csabai, I.

2012-09-01

Today's scientific simulations produce output on the 10-100 TB scale. This unprecedented amount of data requires data handling techniques that are beyond what is used for ordinary files. Relational database systems have been successfully used to store and process scientific data, but the new requirements constantly generate new challenges. Moving terabytes of data among servers on a timely basis is a tough problem, even with the newest high-throughput networks. Thus, moving the computations as close to the data as possible and minimizing the client-server overhead are absolutely necessary. At least data subsetting and preprocessing have to be done inside the server process. Out of the box commercial database systems perform very well in scientific applications from the prospective of data storage optimization, data retrieval, and memory management but lack basic functionality like handling scientific data structures or enabling advanced math inside the database server. The most important gap in Microsoft SQL Server is the lack of a native array data type. Fortunately, the technology exists to extend the database server with custom-written code that enables us to address these problems. We present the prototype of a custom-built extension to Microsoft SQL Server that adds array handling functionality to the database system. With our Array Library, fix-sized arrays of all basic numeric data types can be created and manipulated efficiently. Also, the library is designed to be able to be seamlessly integrated with the most common math libraries, such as BLAS, LAPACK, FFTW, etc. With the help of these libraries, complex operations, such as matrix inversions or Fourier transformations, can be done on-the-fly, from SQL code, inside the database server process. We are currently testing the prototype with two different scientific data sets: The Indra cosmological simulation will use it to store particle and density data from N-body simulations, and the Milky Way Laboratory project will use it to store galaxy simulation data.

Characterization of Custom-Designed Charge-Coupled Devices for Applications to Gas and Aerosol Monitoring Sensorcraft Instrument

NASA Technical Reports Server (NTRS)

Refaat, Tamer F.; Abedin, M. Nurul; Farnsworth, Glenn R.; Garcia, Christopher S.; Zawodny, Joseph M.

2005-01-01

Custom-designed charge-coupled devices (CCD) for Gas and Aerosols Monitoring Sensorcraft instrument were developed. These custom-designed CCD devices are linear arrays with pixel format of 512x1 elements and pixel size of 10x200 sq m. These devices were characterized at NASA Langley Research Center to achieve a full well capacity as high as 6,000,000 e-. This met the aircraft flight mission requirements in terms of signal-to-noise performance and maximum dynamic range. Characterization and analysis of the electrical and optical properties of the CCDs were carried out at room temperature. This includes measurements of photon transfer curves, gain coefficient histograms, read noise, and spectral response. Test results obtained on these devices successfully demonstrated the objectives of the aircraft flight mission. In this paper, we describe the characterization results and also discuss their applications to future mission.

ICE: A Scalable, Low-Cost FPGA-Based Telescope Signal Processing and Networking System

NASA Astrophysics Data System (ADS)

Bandura, K.; Bender, A. N.; Cliche, J. F.; de Haan, T.; Dobbs, M. A.; Gilbert, A. J.; Griffin, S.; Hsyu, G.; Ittah, D.; Parra, J. Mena; Montgomery, J.; Pinsonneault-Marotte, T.; Siegel, S.; Smecher, G.; Tang, Q. Y.; Vanderlinde, K.; Whitehorn, N.

2016-03-01

We present an overview of the ‘ICE’ hardware and software framework that implements large arrays of interconnected field-programmable gate array (FPGA)-based data acquisition, signal processing and networking nodes economically. The system was conceived for application to radio, millimeter and sub-millimeter telescope readout systems that have requirements beyond typical off-the-shelf processing systems, such as careful control of interference signals produced by the digital electronics, and clocking of all elements in the system from a single precise observatory-derived oscillator. A new generation of telescopes operating at these frequency bands and designed with a vastly increased emphasis on digital signal processing to support their detector multiplexing technology or high-bandwidth correlators — data rates exceeding a terabyte per second — are becoming common. The ICE system is built around a custom FPGA motherboard that makes use of an Xilinx Kintex-7 FPGA and ARM-based co-processor. The system is specialized for specific applications through software, firmware and custom mezzanine daughter boards that interface to the FPGA through the industry-standard FPGA mezzanine card (FMC) specifications. For high density applications, the motherboards are packaged in 16-slot crates with ICE backplanes that implement a low-cost passive full-mesh network between the motherboards in a crate, allow high bandwidth interconnection between crates and enable data offload to a computer cluster. A Python-based control software library automatically detects and operates the hardware in the array. Examples of specific telescope applications of the ICE framework are presented, namely the frequency-multiplexed bolometer readout systems used for the South Pole Telescope (SPT) and Simons Array and the digitizer, F-engine, and networking engine for the Canadian Hydrogen Intensity Mapping Experiment (CHIME) and Hydrogen Intensity and Real-time Analysis eXperiment (HIRAX) radio interferometers.

Genome-wide comparison of paired fresh frozen and formalin-fixed paraffin-embedded gliomas by custom BAC and oligonucleotide array comparative genomic hybridization: facilitating analysis of archival gliomas

PubMed Central

Mohapatra, Gayatry; Engler, David A.; Starbuck, Kristen D.; Kim, James C.; Bernay, Derek C.; Scangas, George A.; Rousseau, Audrey; Batchelor, Tracy T.; Betensky, Rebecca A.; Louis, David N.

2010-01-01

Molecular genetic analysis of cancer is rapidly evolving as a result of improvement in genomic technologies and the growing applicability of such analyses to clinical oncology. Array based comparative genomic hybridization (aCGH) is a powerful tool for detecting DNA copy number alterations (CNA), particularly in solid tumors, and has been applied to the study of malignant gliomas. In the clinical setting, however, gliomas are often sampled by small biopsies and thus formalin-fixed paraffin-embedded (FFPE) blocks are often the only tissue available for genetic analysis, especially for rare types of gliomas. Moreover, the biological basis for the marked intratumoral heterogeneity in gliomas is most readily addressed in FFPE material. Therefore, for gliomas, the ability to use DNA from FFPE tissue is essential for both clinical and research applications. In this study, we have constructed a custom bacterial artificial chromosome (BAC) array and show excellent sensitivity and specificity for detecting CNAs in a panel of paired frozen and FFPE glioma samples. Our study demonstrates a high concordance rate between CNAs detected in FFPE compared to frozen DNA. We have also developed a method of labeling DNA from FFPE tissue that allows efficient hybridization to oligonucleotide arrays. This labeling technique was applied to a panel of biphasic anaplastic oligoastrocytomas (AOA) to identify genetic changes unique to each component. Together, results from these studies suggest that BAC and oligonucleotide aCGH are sensitive tools for detecting CNAs in FFPE DNA, and can enable genome-wide analysis of rare, small and/or histologically heterogeneous gliomas. PMID:21080181

Identification of a novel NHS mutation in a Chinese family with Nance-Horan syndrome.

PubMed

Li, Aijun; Li, Bingzhen; Wu, Lemeng; Yang, Liping; Chen, Ningning; Ma, Zhizhong

2015-04-01

To identiy the disease causing mutation in a Chinese family presenting with early-onset cataract and dental anomalies. A specific Hereditary Eye Disease Enrichment Panel (HEDEP) (personalized customization by MyGenostics, Baltimore, MD) based on targeted exome capture technology was used to collect the protein coding regions of 30 early-onset cataract associated genes, and high throughput sequencing was done with Illumina HiSeq 2000 platform. The identified variant was confirmed with Sanger sequencing. A novel deletion in exon 4 (c.852delG) of NHS gene was identified; the identified 1 bp deletion altered the reading frame and was predicted to result in a premature stop codon after the addition of twelve novel amino acid (p.S285PfsX13). This mutation co-segregated in affected males and obligate female carriers, but was absent in 100 matched controls. Our findings broaden the spectrum of NHS mutations causing Nance-Horan syndrome and phenotypic spectrum of the disease in Chinese patients.

Exome sequencing and arrayCGH detection of gene sequence and copy number variation between ILS and ISS mouse strains.

PubMed

Dumas, Laura; Dickens, C Michael; Anderson, Nathan; Davis, Jonathan; Bennett, Beth; Radcliffe, Richard A; Sikela, James M

2014-06-01

It has been well documented that genetic factors can influence predisposition to develop alcoholism. While the underlying genomic changes may be of several types, two of the most common and disease associated are copy number variations (CNVs) and sequence alterations of protein coding regions. The goal of this study was to identify CNVs and single-nucleotide polymorphisms that occur in gene coding regions that may play a role in influencing the risk of an individual developing alcoholism. Toward this end, two mouse strains were used that have been selectively bred based on their differential sensitivity to alcohol: the Inbred long sleep (ILS) and Inbred short sleep (ISS) mouse strains. Differences in initial response to alcohol have been linked to risk for alcoholism, and the ILS/ISS strains are used to investigate the genetics of initial sensitivity to alcohol. Array comparative genomic hybridization (arrayCGH) and exome sequencing were conducted to identify CNVs and gene coding sequence differences, respectively, between ILS and ISS mice. Mouse arrayCGH was performed using catalog Agilent 1 × 244 k mouse arrays. Subsequently, exome sequencing was carried out using an Illumina HiSeq 2000 instrument. ArrayCGH detected 74 CNVs that were strain-specific (38 ILS/36 ISS), including several ISS-specific deletions that contained genes implicated in brain function and neurotransmitter release. Among several interesting coding variations detected by exome sequencing was the gain of a premature stop codon in the alpha-amylase 2B (AMY2B) gene specifically in the ILS strain. In total, exome sequencing detected 2,597 and 1,768 strain-specific exonic gene variants in the ILS and ISS mice, respectively. This study represents the most comprehensive and detailed genomic comparison of ILS and ISS mouse strains to date. The two complementary genome-wide approaches identified strain-specific CNVs and gene coding sequence variations that should provide strong candidates to contribute to the alcohol-related phenotypic differences associated with these strains.

Customizable PCR-microplate array for differential identification of multiple pathogens.

PubMed

Woubit, Abdela; Yehualaeshet, Teshome; Roberts, Sherrelle; Graham, Martha; Kim, Moonil; Samuel, Temesgen

2013-11-01

Customizable PCR-microplate arrays were developed for the rapid identification of Salmonella Typhimurium, Salmonella Saintpaul, Salmonella Typhi, Shigella dysenteriae, Escherichia coli O157:H7, Francisella tularensis subsp. tularensis, Francisella tularensis subsp. novicida, Vibrio cholerae, Vibrio parahaemolyticus, Yersinia pestis, and Yersinia pseudotuberculosis. Previously, we identified highly specific primers targeting each of these pathogens. Here, we report the development of customizable PCR-microplate arrays for simultaneous identification of the pathogens using the primers identified. A mixed aliquot of genomic DNA from 38 strains was used to validate three PCR-microplate array formats. Identical PCR conditions were used to run all the samples on the three formats. Specific amplifications were obtained on all three custom plates. In preliminary tests performed to evaluate the sensitivity of these assays in samples inoculated in the laboratory with Salmonella Typhimurium, amplifications were obtained from 1 g of beef hot dog inoculated at as low as 9 CFU/ml or from milk inoculated at as low as 78 CFU/ml. Such microplate arrays could be valuable tools for initial identification or secondary confirmation of contamination by these pathogens.

Preliminary Concept of Operations for the Deep Space Array-Based Network

NASA Astrophysics Data System (ADS)

Bagri, D. S.; Statman, J. I.

2004-05-01

The Deep Space Array-Based Network (DSAN) will be an array-based system, part of a greater than 1000 times increase in the downlink/telemetry capability of the Deep Space Network. The key function of the DSAN is provision of cost-effective, robust telemetry, tracking, and command services to the space missions of NASA and its international partners. This article presents an expanded approach to the use of an array-based system. Instead of using the array as an element in the existing Deep Space Network (DSN), relying to a large extent on the DSN infrastructure, we explore a broader departure from the current DSN, using fewer elements of the existing DSN, and establishing a more modern concept of operations. For example, the DSAN will have a single 24 x 7 monitor and control (M&C) facility, while the DSN has four 24 x 7 M&C facilities. The article gives the architecture of the DSAN and its operations philosophy. It also briefly describes the customer's view of operations, operations management, logistics, anomaly analysis, and reporting.

Photoacoustics and speed-of-sound dual mode imaging with a long depth-of-field by using annular ultrasound array.

PubMed

Ding, Qiuning; Tao, Chao; Liu, Xiaojun

2017-03-20

Speed-of-sound and optical absorption reflect the structure and function of tissues from different aspects. A dual-mode microscopy system based on a concentric annular ultrasound array is proposed to simultaneously acquire the long depth-of-field images of speed-of-sound and optical absorption of inhomogeneous samples. First, speed-of-sound is decoded from the signal delay between each element of the annular array. The measured speed-of-sound could not only be used as an image contrast, but also improve the resolution and accuracy of spatial location of photoacoustic image in inhomogeneous acoustic media. Secondly, benefitting from dynamic focusing of annular array and the measured speed-of-sound, it is achieved an advanced acoustic-resolution photoacoustic microscopy with a precise position and a long depth-of-field. The performance of the dual-mode imaging system has been experimentally examined by using a custom-made annular array. The proposed dual-mode microscopy might have the significances in monitoring the biological physiological and pathological processes.

Investigation of Implantable Multi-Channel Electrode Array in Rat Cerebral Cortex Used for Recording

NASA Astrophysics Data System (ADS)

Taniguchi, Noriyuki; Fukayama, Osamu; Suzuki, Takafumi; Mabuchi, Kunihiko

There have recently been many studies concerning the control of robot movements using neural signals recorded from the brain (usually called the Brain-Machine interface (BMI)). We fabricated implantable multi-electrode arrays to obtain neural signals from the rat cerebral cortex. As any multi-electrode array should have electrode alignment that minimizes invasion, it is necessary to customize the recording site. We designed three types of 22-channel multi-electrode arrays, i.e., 1) wide, 2) three-layered, and 3) separate. The first extensively covers the cerebral cortex. The second has a length of 2 mm, which can cover the area of the primary motor cortex. The third array has a separate structure, which corresponds to the position of the forelimb and hindlimb areas of the primary motor cortex. These arrays were implanted into the cerebral cortex of a rat. We estimated the walking speed from neural signals using our fabricated three-layered array to investigate its feasibility for BMI research. The neural signal of the rat and its walking speed were simultaneously recorded. The results revealed that evaluation using either the anterior electrode group or posterior group provided accurate estimates. However, two electrode groups around the center yielded poor estimates although it was possible to record neural signals.

Fabrication of five-level ultraplanar micromirror arrays by flip-chip assembly

NASA Astrophysics Data System (ADS)

Michalicek, M. Adrian; Bright, Victor M.

2001-10-01

This paper reports a detailed study of the fabrication of various piston, torsion, and cantilever style micromirror arrays using a novel, simple, and inexpensive flip-chip assembly technique. Several rectangular and polar arrays were commercially prefabricated in the MUMPs process and then flip-chip bonded to form advanced micromirror arrays where adverse effects typically associated with surface micromachining were removed. These arrays were bonded by directly fusing the MUMPs gold layers with no complex preprocessing. The modules were assembled using a computer-controlled, custom-built flip-chip bonding machine. Topographically opposed bond pads were designed to correct for slight misalignment errors during bonding and typically result in less than 2 micrometers of lateral alignment error. Although flip-chip micromirror performance is briefly discussed, the means used to create these arrays is the focus of the paper. A detailed study of flip-chip process yield is presented which describes the primary failure mechanisms for flip-chip bonding. Studies of alignment tolerance, bonding force, stress concentration, module planarity, bonding machine calibration techniques, prefabrication errors, and release procedures are presented in relation to specific observations in process yield. Ultimately, the standard thermo-compression flip-chip assembly process remains a viable technique to develop highly complex prototypes of advanced micromirror arrays.

Volumetric Real-Time Imaging Using a CMUT Ring Array

PubMed Central

Choe, Jung Woo; Oralkan, Ömer; Nikoozadeh, Amin; Gencel, Mustafa; Stephens, Douglas N.; O’Donnell, Matthew; Sahn, David J.; Khuri-Yakub, Butrus T.

2012-01-01

A ring array provides a very suitable geometry for forward-looking volumetric intracardiac and intravascular ultrasound imaging. We fabricated an annular 64-element capacitive micromachined ultrasonic transducer (CMUT) array featuring a 10-MHz operating frequency and a 1.27-mm outer radius. A custom software suite was developed to run on a PC-based imaging system for real-time imaging using this device. This paper presents simulated and experimental imaging results for the described CMUT ring array. Three different imaging methods—flash, classic phased array (CPA), and synthetic phased array (SPA)—were used in the study. For SPA imaging, two techniques to improve the image quality—Hadamard coding and aperture weighting—were also applied. The results show that SPA with Hadamard coding and aperture weighting is a good option for ring-array imaging. Compared with CPA, it achieves better image resolution and comparable signal-to-noise ratio at a much faster image acquisition rate. Using this method, a fast frame rate of up to 463 volumes per second is achievable if limited only by the ultrasound time of flight; with the described system we reconstructed three cross-sectional images in real-time at 10 frames per second, which was limited by the computation time in synthetic beamforming. PMID:22718870

Volumetric real-time imaging using a CMUT ring array.

PubMed

Choe, Jung Woo; Oralkan, Ömer; Nikoozadeh, Amin; Gencel, Mustafa; Stephens, Douglas N; O'Donnell, Matthew; Sahn, David J; Khuri-Yakub, Butrus T

2012-06-01

A ring array provides a very suitable geometry for forward-looking volumetric intracardiac and intravascular ultrasound imaging. We fabricated an annular 64-element capacitive micromachined ultrasonic transducer (CMUT) array featuring a 10-MHz operating frequency and a 1.27-mm outer radius. A custom software suite was developed to run on a PC-based imaging system for real-time imaging using this device. This paper presents simulated and experimental imaging results for the described CMUT ring array. Three different imaging methods--flash, classic phased array (CPA), and synthetic phased array (SPA)--were used in the study. For SPA imaging, two techniques to improve the image quality--Hadamard coding and aperture weighting--were also applied. The results show that SPA with Hadamard coding and aperture weighting is a good option for ring-array imaging. Compared with CPA, it achieves better image resolution and comparable signal-to-noise ratio at a much faster image acquisition rate. Using this method, a fast frame rate of up to 463 volumes per second is achievable if limited only by the ultrasound time of flight; with the described system we reconstructed three cross-sectional images in real-time at 10 frames per second, which was limited by the computation time in synthetic beamforming.

EzArray: A web-based highly automated Affymetrix expression array data management and analysis system

PubMed Central

Zhu, Yuerong; Zhu, Yuelin; Xu, Wei

2008-01-01

Background Though microarray experiments are very popular in life science research, managing and analyzing microarray data are still challenging tasks for many biologists. Most microarray programs require users to have sophisticated knowledge of mathematics, statistics and computer skills for usage. With accumulating microarray data deposited in public databases, easy-to-use programs to re-analyze previously published microarray data are in high demand. Results EzArray is a web-based Affymetrix expression array data management and analysis system for researchers who need to organize microarray data efficiently and get data analyzed instantly. EzArray organizes microarray data into projects that can be analyzed online with predefined or custom procedures. EzArray performs data preprocessing and detection of differentially expressed genes with statistical methods. All analysis procedures are optimized and highly automated so that even novice users with limited pre-knowledge of microarray data analysis can complete initial analysis quickly. Since all input files, analysis parameters, and executed scripts can be downloaded, EzArray provides maximum reproducibility for each analysis. In addition, EzArray integrates with Gene Expression Omnibus (GEO) and allows instantaneous re-analysis of published array data. Conclusion EzArray is a novel Affymetrix expression array data analysis and sharing system. EzArray provides easy-to-use tools for re-analyzing published microarray data and will help both novice and experienced users perform initial analysis of their microarray data from the location of data storage. We believe EzArray will be a useful system for facilities with microarray services and laboratories with multiple members involved in microarray data analysis. EzArray is freely available from . PMID:18218103

Rapid microsatellite identification from Illumina paired-end genomic sequencing in two birds and a snake

USGS Publications Warehouse

Castoe, Todd A.; Poole, Alexander W.; de Koning, A. P. Jason; Jones, Kenneth L.; Tomback, Diana F.; Oyler-McCance, Sara J.; Fike, Jennifer A.; Lance, Stacey L.; Streicher, Jeffrey W.; Smith, Eric N.; Pollock, David D.

2012-01-01

Identification of microsatellites, or simple sequence repeats (SSRs), can be a time-consuming and costly investment requiring enrichment, cloning, and sequencing of candidate loci. Recently, however, high throughput sequencing (with or without prior enrichment for specific SSR loci) has been utilized to identify SSR loci. The direct "Seq-to-SSR" approach has an advantage over enrichment-based strategies in that it does not require a priori selection of particular motifs, or prior knowledge of genomic SSR content. It has been more expensive per SSR locus recovered, however, particularly for genomes with few SSR loci, such as bird genomes. The longer but relatively more expensive 454 reads have been preferred over less expensive Illumina reads. Here, we use Illumina paired-end sequence data to identify potentially amplifiable SSR loci (PALs) from a snake (the Burmese python, Python molurus bivittatus), and directly compare these results to those from 454 data. We also compare the python results to results from Illumina sequencing of two bird genomes (Gunnison Sage-grouse, Centrocercus minimus, and Clark's Nutcracker, Nucifraga columbiana), which have considerably fewer SSRs than the python. We show that direct Illumina Seq-to-SSR can identify and characterize thousands of potentially amplifiable SSR loci for as little as $10 per sample – a fraction of the cost of 454 sequencing. Given that Illumina Seq-to-SSR is effective, inexpensive, and reliable even for species such as birds that have few SSR loci, it seems that there are now few situations for which prior hybridization is justifiable.

Rapid microsatellite identification from illumina paired-end genomic sequencing in two birds and a snake

USGS Publications Warehouse

Castoe, T.A.; Poole, A.W.; de Koning, A. P. J.; Jones, K.L.; Tomback, D.F.; Oyler-McCance, S.J.; Fike, J.A.; Lance, S.L.; Streicher, J.W.; Smith, E.N.; Pollock, D.D.

2012-01-01

Identification of microsatellites, or simple sequence repeats (SSRs), can be a time-consuming and costly investment requiring enrichment, cloning, and sequencing of candidate loci. Recently, however, high throughput sequencing (with or without prior enrichment for specific SSR loci) has been utilized to identify SSR loci. The direct "Seq-to-SSR" approach has an advantage over enrichment-based strategies in that it does not require a priori selection of particular motifs, or prior knowledge of genomic SSR content. It has been more expensive per SSR locus recovered, however, particularly for genomes with few SSR loci, such as bird genomes. The longer but relatively more expensive 454 reads have been preferred over less expensive Illumina reads. Here, we use Illumina paired-end sequence data to identify potentially amplifiable SSR loci (PALs) from a snake (the Burmese python, Python molurus bivittatus), and directly compare these results to those from 454 data. We also compare the python results to results from Illumina sequencing of two bird genomes (Gunnison Sage-grouse, Centrocercus minimus, and Clark's Nutcracker, Nucifraga columbiana), which have considerably fewer SSRs than the python. We show that direct Illumina Seq-to-SSR can identify and characterize thousands of potentially amplifiable SSR loci for as little as $10 per sample - a fraction of the cost of 454 sequencing. Given that Illumina Seq-to-SSR is effective, inexpensive, and reliable even for species such as birds that have few SSR loci, it seems that there are now few situations for which prior hybridization is justifiable. ?? 2012 Castoe et al.

Rapid microsatellite identification from Illumina paired-end genomic sequencing in two birds and a snake.

PubMed

Castoe, Todd A; Poole, Alexander W; de Koning, A P Jason; Jones, Kenneth L; Tomback, Diana F; Oyler-McCance, Sara J; Fike, Jennifer A; Lance, Stacey L; Streicher, Jeffrey W; Smith, Eric N; Pollock, David D

2012-01-01

Identification of microsatellites, or simple sequence repeats (SSRs), can be a time-consuming and costly investment requiring enrichment, cloning, and sequencing of candidate loci. Recently, however, high throughput sequencing (with or without prior enrichment for specific SSR loci) has been utilized to identify SSR loci. The direct "Seq-to-SSR" approach has an advantage over enrichment-based strategies in that it does not require a priori selection of particular motifs, or prior knowledge of genomic SSR content. It has been more expensive per SSR locus recovered, however, particularly for genomes with few SSR loci, such as bird genomes. The longer but relatively more expensive 454 reads have been preferred over less expensive Illumina reads. Here, we use Illumina paired-end sequence data to identify potentially amplifiable SSR loci (PALs) from a snake (the Burmese python, Python molurus bivittatus), and directly compare these results to those from 454 data. We also compare the python results to results from Illumina sequencing of two bird genomes (Gunnison Sage-grouse, Centrocercus minimus, and Clark's Nutcracker, Nucifraga columbiana), which have considerably fewer SSRs than the python. We show that direct Illumina Seq-to-SSR can identify and characterize thousands of potentially amplifiable SSR loci for as little as $10 per sample--a fraction of the cost of 454 sequencing. Given that Illumina Seq-to-SSR is effective, inexpensive, and reliable even for species such as birds that have few SSR loci, it seems that there are now few situations for which prior hybridization is justifiable.

Childhood and Children: A Compendium of Customs, Superstitions, Theories, Profiles, and Facts.

ERIC Educational Resources Information Center

Bel Geddes, Joan

Children and childhood are almost completely ignored in most history books, encyclopedias, anthologies, and almanacs, which concentrate on the achievement of the adult half of the world's population. This book is intended to fill the gap by focusing on childhood, and presents an array of facts, anecdotes, profiles, and observations about children…

Genome-wide association study for birth, weaning and yearling weight in Colombian Brahman cattle

PubMed Central

Martínez, Rodrigo; Bejarano, Diego; Gómez, Yolanda; Dasoneville, Romain; Jiménez, Ariel; Even, Gael; Sölkner, Johann; Mészáros, Gabor

2017-01-01

Abstract Genotypic and phenotypic data of 1,562 animals were analyzed to find genomic regions that potentially influence the birth weight (BW), weaning weight at seven months of age (WW) and yearling weight (YW) of Colombian Brahman cattle, with genotyping conducted using Illumina Bead chip array with 74,669 SNPs. A Single Step Genomic BLUP (ssGBLP), approach was used to estimate the proportion of variance explained by each marker. Multiple regions scattered across the genome were found to influence weights at different ages, also dependent on the trait component (direct or maternal). The most interesting regions were connected to previously identified QTLs and genes, such as ADAMTSL3, CAPN2, CAPN2, FABP6, ZEB2 influencing growth and weight traits. The identified regions will contribute to the development and refinement of genomic selection programs for Zebu Brahman cattle in Colombia. PMID:28534927

Effects of soluble and particulate Cr(VI) on genome-wide DNA methylation in human B lymphoblastoid cells.

PubMed

Lou, Jianlin; Wang, Yu; Chen, Junqiang; Ju, Li; Yu, Min; Jiang, Zhaoqiang; Feng, Lingfang; Jin, Lingzhi; Zhang, Xing

2015-10-01

Several previous studies highlighted the potential epigenetic effects of Cr(VI), especially DNA methylation. However, few studies have compared the effects of Cr(VI) on DNA methylation profiles between soluble and particulate chromate in vitro. Accordingly, Illumina Infinium Human Methylation 450K BeadChip array was used to analyze DNA methylation profiles of human B lymphoblastoid cells exposed to potassium dichromate or lead chromate, and the cell viability was also studied. Array based DNA methylation analysis showed that the impacts of Cr(VI) on DNA methylation were limited, only about 40 differentially methylated CpG sites, with an overlap of 15CpG sites, were induced by both potassium dichromate and lead chromate. The results of mRNA expression showed that after Cr(VI) treatment, mRNA expression changes of four genes (TBL1Y, FZD5, IKZF2, and KIAA1949) were consistent with their DNA methylation alteration, but DNA methylation changes of other six genes did not correlate with mRNA expression. In conclusion, both of soluble and particulate Cr(VI) could induce a small amount of differentially methylated sites in human B lymphoblastoid cells, and the correlations between DNA methylation changes and mRNA expression varied between different genes. Copyright © 2015 Elsevier B.V. All rights reserved.

Performance of the Versatile Array of Neutron Detectors at Low Energy (VANDLE)

DOE PAGES

Peters, W. A.; Ilyushkin, S.; Madurga, M.; ...

2016-08-26

The Versatile Array of Neutron Detectors at Low Energy (VANDLE) is a new, highly efficient plastic-scintillator array constructed for decay and transfer reaction experimental setups that require neutron detection. The versatile and modular design allows for customizable experimental setups including beta-delayed neutron spectroscopy and (d,n) transfer reactions in normal and inverse kinematics. The neutron energy and prompt-photon discrimination is determined through the time of flight technique. Fully digital data acquisition electronics and integrated triggering logic enables some VANDLE modules to achieve an intrinsic efficiency over 70% for 300-keV neutrons, measured through two different methods. A custom Geant4 simulation models aspectsmore » of the detector array and the experimental setups to determine efficiency and detector response. Lastly, a low detection threshold, due to the trigger logic and digitizing data acquisition, allowed us to measure the light-yield response curve from elastically scattered carbon nuclei inside the scintillating plastic from incident neutrons with kinetic energies below 2 MeV.« less

Note: Development of a multichannel magnetic probe array for magnetohydrodynamic activity studies in Sino-United Spherical Tokamak

NASA Astrophysics Data System (ADS)

Zhong, H.; Tan, Y.; Gao, Z.

2018-02-01

A 30-channel movable magnetic probe radial array measuring the poloidal magnetic field's time derivative B˙ θ has been developed and installed on the Sino-United Spherical Tokamak to investigate the magnetohydrodynamic (MHD) activities in ohmic discharges. The probe array consists of thirty identical commercial chip inductors mounted on a slim printed circuit board and shielded by a customized quartz tube of 14 mm in outer diameter. With the application of instrumentation amplifiers, the system exhibits a good signal to noise ratio and the measured vertical field spatial distribution agrees well with the simulation result. The measured spatial and temporal distribution of B˙ θ during the MHD activities exhibits a clear phase reversal layer, which is a direct proof of tearing mode and provides a reliable indication of the magnetic island chain position.

A Wireless Implantable Switched-Capacitor Based Optogenetic Stimulating System

PubMed Central

Lee, Hyung-Min; Kwon, Ki-Yong; Li, Wen

2015-01-01

This paper presents a power-efficient implantable optogenetic interface using a wireless switched-capacitor based stimulating (SCS) system. The SCS efficiently charges storage capacitors directly from an inductive link and periodically discharges them into an array of micro-LEDs, providing high instantaneous power without affecting wireless link and system supply voltage. A custom-designed computer interface in LabVIEW environment wirelessly controls stimulation parameters through the inductive link, and an optrode array enables simultaneous neural recording along with optical stimulation. The 4-channel SCS system prototype has been implemented in a 0.35-μm CMOS process and combined with the optrode array. In vivo experiments involving light-induced local field potentials verified the efficacy of the SCS system. An implantable version of the SCS system with flexible hermetic sealing is under development for chronic experiments. PMID:25570099

Annular and Cylindrical Phased Array Geometries for Transrectal High-Intensity Focused Ultrasound (HIFU) using PZT and Piezocomposite Materials

NASA Astrophysics Data System (ADS)

Seip, Ralf; Chen, Wohsing; Carlson, Roy; Frizzell, Leon; Warren, Gary; Smith, Nadine; Saleh, Khaldon; Gerber, Gene; Shung, Kirk; Guo, Hongkai; Sanghvi, Narendra T.

2005-03-01

This paper presents engineering progress and the latest in-vitro and in-vivo results obtained with a 4.0 MHz, 20 element, PZT annular transrectal HIFU array and several 4.0 MHz, 211 element, PZT and piezocomposite cylindrical transrectal HIFU arrays for the treatment of prostate cancer. The geometries of both arrays were designed and analyzed to steer the HIFU beams to the desired sites in the prostate volume using multi-channel electronic drivers, with the intent to increase treatment efficiency and reliability for the next generation of HIFU systems. The annular array is able to focus in depth from 25 mm to 50 mm, generate total acoustic powers in excess of 60W, and has been integrated into a modified Sonablate®500 HIFU system capable of controlling such an applicator through custom treatment planning and execution software. Both PZT- and piezocomposite cylindrical arrays were constructed and their characteristics were compared for the transrectal applications. These arrays have been installed into appropriate transducer housings, and have undergone characterization tests to determine their total acoustic power output, focusing range (in depth and laterally), focus quality, efficiency, and comparison tests to determine the material and technology of choice (PZT or piezocomposite) for intra-cavity HIFU applications. Array descriptions, characterization results, in-vitro and in-vivo results, and an overview of their intended use through the application software is shown.

Design and Application of Combined 8-Channel Transmit and 10-Channel Receive Arrays and Radiofrequency Shimming for 7-T Shoulder Magnetic Resonance Imaging

PubMed Central

Brown, Ryan; Deniz, Cem Murat; Zhang, Bei; Chang, Gregory; Sodickson, Daniel K.; Wiggins, Graham C.

2014-01-01

Objective The objective of the study was to investigate the feasibility of 7-T shoulder magnetic resonance imaging by developing transmit and receive radiofrequency (RF) coil arrays and exploring RF shim methods. Materials and Methods A mechanically flexible 8-channel transmit array and an anatomically conformable 10-channel receive array were designed and implemented. The transmit performance of various RF shim methods was assessed through local flip angle measurements in the right and left shoulders of 6 subjects. The receive performance was assessed through signal-to-noise ratio measurements using the developed 7-T coil and a baseline commercial 3-T coil. Results The 7-T transmit array driven with phase-coherent RF shim weights provided adequate B1+ efficiency and uniformity for turbo spin echo shoulder imaging. B1+ twisting that is characteristic of high-field loop coils necessitates distinct RF shim weights in the right and left shoulders. The 7-T receive array provided a 2-fold signal-to-noise ratio improvement over the 3-T array in the deep articular shoulder cartilage. Conclusions Shoulder imaging at 7-T is feasible with a custom transmit/receive array either in a single-channel transmit mode with a fixed RF shim or in a parallel transmit mode with a subject-specific RF shim. PMID:24056112

Combined array CGH plus SNP genome analyses in a single assay for optimized clinical testing

PubMed Central

Wiszniewska, Joanna; Bi, Weimin; Shaw, Chad; Stankiewicz, Pawel; Kang, Sung-Hae L; Pursley, Amber N; Lalani, Seema; Hixson, Patricia; Gambin, Tomasz; Tsai, Chun-hui; Bock, Hans-Georg; Descartes, Maria; Probst, Frank J; Scaglia, Fernando; Beaudet, Arthur L; Lupski, James R; Eng, Christine; Wai Cheung, Sau; Bacino, Carlos; Patel, Ankita

2014-01-01

In clinical diagnostics, both array comparative genomic hybridization (array CGH) and single nucleotide polymorphism (SNP) genotyping have proven to be powerful genomic technologies utilized for the evaluation of developmental delay, multiple congenital anomalies, and neuropsychiatric disorders. Differences in the ability to resolve genomic changes between these arrays may constitute an implementation challenge for clinicians: which platform (SNP vs array CGH) might best detect the underlying genetic cause for the disease in the patient? While only SNP arrays enable the detection of copy number neutral regions of absence of heterozygosity (AOH), they have limited ability to detect single-exon copy number variants (CNVs) due to the distribution of SNPs across the genome. To provide comprehensive clinical testing for both CNVs and copy-neutral AOH, we enhanced our custom-designed high-resolution oligonucleotide array that has exon-targeted coverage of 1860 genes with 60 000 SNP probes, referred to as Chromosomal Microarray Analysis – Comprehensive (CMA-COMP). Of the 3240 cases evaluated by this array, clinically significant CNVs were detected in 445 cases including 21 cases with exonic events. In addition, 162 cases (5.0%) showed at least one AOH region >10 Mb. We demonstrate that even though this array has a lower density of SNP probes than other commercially available SNP arrays, it reliably detected AOH events >10 Mb as well as exonic CNVs beyond the detection limitations of SNP genotyping. Thus, combining SNP probes and exon-targeted array CGH into one platform provides clinically useful genetic screening in an efficient manner. PMID:23695279

Characteristics of High Latitude Ionosphere Scintillations

NASA Astrophysics Data System (ADS)

Morton, Y.

2012-12-01

As we enter a new solar maximum period, global navigation satellite systems (GNSS) receivers, especially the ones operating in high latitude and equatorial regions, are facing an increasing threat from ionosphere scintillations. The increased solar activities, however, also offer a great opportunity to collect scintillation data to characterize scintillation signal parameters and ionosphere irregularities. While there are numerous GPS receivers deployed around the globe to monitor ionosphere scintillations, most of them are commercial receivers whose signal processing mechanisms are not designed to operate under ionosphere scintillation. As a result, they may distort scintillation signal parameters or lose lock of satellite signals under strong scintillations. Since 2008, we have established and continuously improved a unique GNSS receiver array at HAARP, Alaska. The array contains high ends commercial receivers and custom RF front ends which can be automatically triggered to collect high quality GPS and GLONASS satellite signals during controlled heating experiments and natural scintillation events. Custom designed receiver signal tracking algorithms aim to preserve true scintillation signatures are used to process the raw RF samples. Signal strength, carrier phase, and relative TEC measurements generated by the receiver array since its inception have been analyzed to characterize high latitude scintillation phenomena. Daily, seasonal, and solar events dependency of scintillation occurrence, spectral contents of scintillation activities, and plasma drifts derived from these measurements will be presented. These interesting results demonstrate the feasibility and effectiveness of our experimental data collection system in providing insightful details of ionosphere responses to active perturbations and natural disturbances.

Illumina Unamplified Indexed Library Construction: An Automated Approach

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

Hack, Christopher A.; Sczyrba, Alexander; Cheng, Jan-Fang

Manual library construction is a limiting factor in Illumina sequencing. Constructing libraries by hand is costly, time-consuming, low-throughput, and ergonomically hazardous, and constructing multiple libraries introduces risk of library failure due to pipetting errors. The ability to construct multiple libraries simultaneously in automated fashion represents significant cost and time savings. Here we present a strategy to construct up to 96 unamplified indexed libraries using Illumina TruSeq reagents and a Biomek FX robotic platform. We also present data to indicate that this library construction method has little or no risk of cross-contamination between samples.

Maternal blood contamination of collected cord blood can be identified using DNA methylation at three CpGs.

PubMed

Morin, Alexander M; Gatev, Evan; McEwen, Lisa M; MacIsaac, Julia L; Lin, David T S; Koen, Nastassja; Czamara, Darina; Räikkönen, Katri; Zar, Heather J; Koenen, Karestan; Stein, Dan J; Kobor, Michael S; Jones, Meaghan J

2017-01-01

Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability and potential to inform on a sensitive period of human development. However, the introduction of maternal blood during labor or cross-contamination during sample collection may complicate downstream analyses. After discovering maternal contamination of cord blood in a cohort study of 150 neonates using Illumina 450K DNA methylation (DNAm) data, we used a combination of linear regression and random forest machine learning to create a DNAm-based screening method. We identified a panel of DNAm sites that could discriminate between contaminated and non-contaminated samples, then designed pyrosequencing assays to pre-screen DNA prior to being assayed on an array. Maternal contamination of cord blood was initially identified by unusual X chromosome DNA methylation patterns in 17 males. We utilized our DNAm panel to detect contaminated male samples and a proportional amount of female samples in the same cohort. We validated our DNAm screening method on an additional 189 sample cohort using both pyrosequencing and DNAm arrays, as well as 9 publically available cord blood 450K data sets. The rate of contamination varied from 0 to 10% within these studies, likely related to collection specific methods. Maternal blood can contaminate cord blood during sample collection at appreciable levels across multiple studies. We have identified a panel of markers that can be used to identify this contamination, either post hoc after DNAm arrays have been completed, or in advance using a targeted technique like pyrosequencing.

Best Practices and Joint Calling of the HumanExome BeadChip: The CHARGE Consortium

PubMed Central

Grove, Megan L.; Yu, Bing; Cochran, Barbara J.; Haritunians, Talin; Bis, Joshua C.; Taylor, Kent D.; Hansen, Mark; Borecki, Ingrid B.; Cupples, L. Adrienne; Fornage, Myriam; Gudnason, Vilmundur; Harris, Tamara B.; Kathiresan, Sekar; Kraaij, Robert; Launer, Lenore J.; Levy, Daniel; Liu, Yongmei; Mosley, Thomas; Peloso, Gina M.; Psaty, Bruce M.; Rich, Stephen S.; Rivadeneira, Fernando; Siscovick, David S.; Smith, Albert V.; Uitterlinden, Andre; van Duijn, Cornelia M.; Wilson, James G.; O’Donnell, Christopher J.; Rotter, Jerome I.; Boerwinkle, Eric

2013-01-01

Genotyping arrays are a cost effective approach when typing previously-identified genetic polymorphisms in large numbers of samples. One limitation of genotyping arrays with rare variants (e.g., minor allele frequency [MAF] <0.01) is the difficulty that automated clustering algorithms have to accurately detect and assign genotype calls. Combining intensity data from large numbers of samples may increase the ability to accurately call the genotypes of rare variants. Approximately 62,000 ethnically diverse samples from eleven Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium cohorts were genotyped with the Illumina HumanExome BeadChip across seven genotyping centers. The raw data files for the samples were assembled into a single project for joint calling. To assess the quality of the joint calling, concordance of genotypes in a subset of individuals having both exome chip and exome sequence data was analyzed. After exclusion of low performing SNPs on the exome chip and non-overlap of SNPs derived from sequence data, genotypes of 185,119 variants (11,356 were monomorphic) were compared in 530 individuals that had whole exome sequence data. A total of 98,113,070 pairs of genotypes were tested and 99.77% were concordant, 0.14% had missing data, and 0.09% were discordant. We report that joint calling allows the ability to accurately genotype rare variation using array technology when large sample sizes are available and best practices are followed. The cluster file from this experiment is available at www.chargeconsortium.com/main/exomechip. PMID:23874508

Toward a comprehensive and systematic methylome signature in colorectal cancers.

PubMed

Ashktorab, Hassan; Rahi, Hamed; Wansley, Daniel; Varma, Sudhir; Shokrani, Babak; Lee, Edward; Daremipouran, Mohammad; Laiyemo, Adeyinka; Goel, Ajay; Carethers, John M; Brim, Hassan

2013-08-01

CpG Island Methylator Phenotype (CIMP) is one of the underlying mechanisms in colorectal cancer (CRC). This study aimed to define a methylome signature in CRC through a methylation microarray analysis and a compilation of promising CIMP markers from the literature. Illumina HumanMethylation27 (IHM27) array data was generated and analyzed based on statistical differences in methylation data (1st approach) or based on overall differences in methylation percentages using lower 95% CI (2nd approach). Pyrosequencing was performed for the validation of nine genes. A meta-analysis was used to identify CIMP and non-CIMP markers that were hypermethylated in CRC but did not yet make it to the CIMP genes' list. Our 1st approach for array data analysis demonstrated the limitations in selecting genes for further validation, highlighting the need for the 2nd bioinformatics approach to adequately select genes with differential aberrant methylation. A more comprehensive list, which included non-CIMP genes, such as APC, EVL, CD109, PTEN, TWIST1, DCC, PTPRD, SFRP1, ICAM5, RASSF1A, EYA4, 30ST2, LAMA1, KCNQ5, ADHEF1, and TFPI2, was established. Array data are useful to categorize and cluster colonic lesions based on their global methylation profiles; however, its usefulness in identifying robust methylation markers is limited and rely on the data analysis method. We have identified 16 non-CIMP-panel genes for which we provide rationale for inclusion in a more comprehensive characterization of CIMP+ CRCs. The identification of a definitive list for methylome specific genes in CRC will contribute to better clinical management of CRC patients.

Genome-wide association study for feed efficiency and growth traits in U.S. beef cattle.

PubMed

Seabury, Christopher M; Oldeschulte, David L; Saatchi, Mahdi; Beever, Jonathan E; Decker, Jared E; Halley, Yvette A; Bhattarai, Eric K; Molaei, Maral; Freetly, Harvey C; Hansen, Stephanie L; Yampara-Iquise, Helen; Johnson, Kristen A; Kerley, Monty S; Kim, JaeWoo; Loy, Daniel D; Marques, Elisa; Neibergs, Holly L; Schnabel, Robert D; Shike, Daniel W; Spangler, Matthew L; Weaber, Robert L; Garrick, Dorian J; Taylor, Jeremy F

2017-05-18

Single nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations. Moderate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but < 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained). Fourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species.

Genome-Wide Association Meta-Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci.

PubMed

McIntosh, Laura A; Marion, Miranda C; Sudman, Marc; Comeau, Mary E; Becker, Mara L; Bohnsack, John F; Fingerlin, Tasha E; Griffin, Thomas A; Haas, J Peter; Lovell, Daniel J; Maier, Lisa A; Nigrovic, Peter A; Prahalad, Sampath; Punaro, Marilynn; Rosé, Carlos D; Wallace, Carol A; Wise, Carol A; Moncrieffe, Halima; Howard, Timothy D; Langefeld, Carl D; Thompson, Susan D

2017-11-01

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)-negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. Three cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. Meta-analysis showed evidence of association (P < 1 × 10 -6 ) at 9 regions: PRR9_LOR (P = 5.12 × 10 -8 ), ILDR1_CD86 (P = 6.73 × 10 -8 ), WDFY4 (P = 1.79 × 10 -7 ), PTH1R (P = 1.87 × 10 -7 ), RNF215 (P = 3.09 × 10 -7 ), AHI1_LINC00271 (P = 3.48 × 10 -7 ), JAK1 (P = 4.18 × 10 -7 ), LINC00951 (P = 5.80 × 10 -7 ), and HBP1 (P = 7.29 × 10 -7 ). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22. This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF-negative polyarticular JIA. © 2017, American College of Rheumatology.

Independent assessment and improvement of wheat genome sequence assemblies using Fosill jumping libraries.

PubMed

Lu, Fu-Hao; McKenzie, Neil; Kettleborough, George; Heavens, Darren; Clark, Matthew D; Bevan, Michael W

2018-05-01

The accurate sequencing and assembly of very large, often polyploid, genomes remains a challenging task, limiting long-range sequence information and phased sequence variation for applications such as plant breeding. The 15-Gb hexaploid bread wheat (Triticum aestivum) genome has been particularly challenging to sequence, and several different approaches have recently generated long-range assemblies. Mapping and understanding the types of assembly errors are important for optimising future sequencing and assembly approaches and for comparative genomics. Here we use a Fosill 38-kb jumping library to assess medium and longer-range order of different publicly available wheat genome assemblies. Modifications to the Fosill protocol generated longer Illumina sequences and enabled comprehensive genome coverage. Analyses of two independent Bacterial Artificial Chromosome (BAC)-based chromosome-scale assemblies, two independent Illumina whole genome shotgun assemblies, and a hybrid Single Molecule Real Time (SMRT-PacBio) and short read (Illumina) assembly were carried out. We revealed a surprising scale and variety of discrepancies using Fosill mate-pair mapping and validated several of each class. In addition, Fosill mate-pairs were used to scaffold a whole genome Illumina assembly, leading to a 3-fold increase in N50 values. Our analyses, using an independent means to validate different wheat genome assemblies, show that whole genome shotgun assemblies based solely on Illumina sequences are significantly more accurate by all measures compared to BAC-based chromosome-scale assemblies and hybrid SMRT-Illumina approaches. Although current whole genome assemblies are reasonably accurate and useful, additional improvements will be needed to generate complete assemblies of wheat genomes using open-source, computationally efficient, and cost-effective methods.

Identification of Biomarkers Associated with the Healing of Chronic Wounds

DTIC Science & Technology

2010-06-01

and iTRAQ findings and the final set of custom antibody arrays included calreticulin, ENO1, Gelsolin, Progranulin , sRAGE. S100A12/ENRAGE, S100A6...Gelsolin 29.47 .0872 -13.04 .5660 .20 .7444 -.40 .6368 Progranulin 3.67 .0282 -1.80 .4151 .068 .2398 -.019 .8153 sRAGE 3.10 .2720 .44 .9052 -.01 .8842

High-throughput live-imaging of embryos in microwell arrays using a modular specimen mounting system.

PubMed

Donoughe, Seth; Kim, Chiyoung; Extavour, Cassandra G

2018-04-30

High-throughput live-imaging of embryos is an essential technique in developmental biology, but it is difficult and costly to mount and image embryos in consistent conditions. Here, we present OMMAwell, a simple, reusable device to easily mount dozens of embryos in arrays of agarose microwells with customizable dimensions and spacing. OMMAwell can be configured to mount specimens for upright or inverted microscopes, and includes a reservoir to hold live-imaging medium to maintain constant moisture and osmolarity of specimens during time-lapse imaging. All device components can be fabricated by cutting pieces from a sheet of acrylic using a laser cutter or by making them with a 3D printer. We demonstrate how to design a custom mold and use it to live-image dozens of embryos at a time. We include descriptions, schematics, and design files for 13 additional molds for nine animal species, including most major traditional laboratory models and a number of emerging model systems. Finally, we provide instructions for researchers to customize OMMAwell inserts for embryos or tissues not described herein. © 2018. Published by The Company of Biologists Ltd.

High sensitivity broadband 360GHz passive receiver for TeraSCREEN

NASA Astrophysics Data System (ADS)

Wang, Hui; Oldfield, Matthew; Maestrojuán, Itziar; Platt, Duncan; Brewster, Nick; Viegas, Colin; Alderman, Byron; Ellison, Brian N.

2016-05-01

TeraSCREEN is an EU FP7 Security project aimed at developing a combined active, with frequency channel centered at 360 GHz, and passive, with frequency channels centered at 94, 220 and 360 GHz, imaging system for border controls in airport and commercial ferry ports. The system will include automatic threat detection and classification and has been designed with a strong focus on the ethical, legal and practical aspects of operating in these environments and with the potential threats in mind. Furthermore, both the passive and active systems are based on array receivers with the active system consisting of a 16 element MIMO FMCW radar centered at 360 GHz with a bandwidth of 30 GHz utilizing a custom made direct digital synthesizer. The 16 element passive receiver system at 360 GHz uses commercial Gunn diode oscillators at 90 GHz followed by custom made 90 to 180 GHz frequency doublers supplying the local oscillator for 360 GHz sub-harmonic mixers. This paper describes the development of the passive antenna module, local oscillator chain, frequency mixers and detectors used in the passive receiver array of this system. The complete passive receiver chain is characterized in this paper.

Lithographic manufacturing of adaptive optics components

NASA Astrophysics Data System (ADS)

Scott, R. Phillip; Jean, Madison; Johnson, Lee; Gatlin, Ridley; Bronson, Ryan; Milster, Tom; Hart, Michael

2017-09-01

Adaptive optics systems and their laboratory test environments call for a number of unusual optical components. Examples include lenslet arrays, pyramids, and Kolmogorov phase screens. Because of their specialized application, the availability of these parts is generally limited, with high cost and long lead time, which can also significantly drive optical system design. These concerns can be alleviated by a fast and inexpensive method of optical fabrication. To that end, we are exploring direct-write lithographic techniques to manufacture three different custom elements. We report results from a number of prototype devices including 1, 2, and 3 wave Multiple Order Diffractive (MOD) lenslet arrays with 0.75 mm pitch and phase screens with near Kolmogorov structure functions with a Fried length r0 around 1 mm. We also discuss plans to expand our research to include a diffractive pyramid that is smaller, lighter, and more easily manufactured than glass versions presently used in pyramid wavefront sensors. We describe how these components can be produced within the limited dynamic range of the lithographic process, and with a rapid prototyping and manufacturing cycle. We discuss exploratory manufacturing methods, including replication, and potential observing techniques enabled by the ready availability of custom components.

Improved Protocols for Illumina Sequencing

PubMed Central

Bronner, Iraad F.; Quail, Michael A.; Turner, Daniel J.; Swerdlow, Harold

2013-01-01

In this unit, we describe a set of improvements we have made to the standard Illumina protocols to make the sequencing process more reliable in a high-throughput environment, reduce amplification bias, narrow the distribution of insert sizes, and reliably obtain high yields of data. PMID:19582764

Smart customers, dumb companies.

PubMed

Locke, C

2000-01-01

Customers today are being bombarded with an overwhelming array of choices. To alleviate customer frustration, say Steven Cristol and Peter Sealey in Simplicity Marketing, companies should stop creating new brands and product extensions. Better to consolidate product and service functions by following a four R approach: replace, repackage, reposition, and replenish. That's an outmoded, dictatorial view of markets, says Christopher Locke. Far from being stymied by choices, customers are rapidly becoming smarter than the companies that pretend to serve them. In this networked economy, people are talking among themselves, and that changes everything. Locke predicts we'll see a growing number of well-defined micromarkets--groups of customers converging in real time around entertaining and knowledgeable voices--such as NPR's car guys and the Motley Fool investment site. "Micromedia" Web sites will replace traditional advertising because they'll provide credible user-supplied news about products and services. Locke contends that an open exchange of information solves the "problem" of choice much better than manipulative strategies like simplicity or even permission marketing. Companies can participate in micromarkets through what Locke dubs "gonzo marketing." If Ford, for example, discovers that a subset of its employees are organic gardeners, it may offer support to a big independent organic-gardening Web site with donations and employee volunteers. This marketing effort would be driven not by advertising managers but by people with genuine interest in each micromarket, so it would have credibility with customers. With gonzo marketing, both companies and their markets will benefit.

De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes.

PubMed

Ashrafi, Hamid; Hill, Theresa; Stoffel, Kevin; Kozik, Alexander; Yao, Jiqiang; Chin-Wo, Sebastian Reyes; Van Deynze, Allen

2012-10-30

Molecular breeding of pepper (Capsicum spp.) can be accelerated by developing DNA markers associated with transcriptomes in breeding germplasm. Before the advent of next generation sequencing (NGS) technologies, the majority of sequencing data were generated by the Sanger sequencing method. By leveraging Sanger EST data, we have generated a wealth of genetic information for pepper including thousands of SNPs and Single Position Polymorphic (SPP) markers. To complement and enhance these resources, we applied NGS to three pepper genotypes: Maor, Early Jalapeño and Criollo de Morelos-334 (CM334) to identify SNPs and SSRs in the assembly of these three genotypes. Two pepper transcriptome assemblies were developed with different purposes. The first reference sequence, assembled by CAP3 software, comprises 31,196 contigs from >125,000 Sanger-EST sequences that were mainly derived from a Korean F1-hybrid line, Bukang. Overlapping probes were designed for 30,815 unigenes to construct a pepper Affymetrix GeneChip® microarray for whole genome analyses. In addition, custom Python scripts were used to identify 4,236 SNPs in contigs of the assembly. A total of 2,489 simple sequence repeats (SSRs) were identified from the assembly, and primers were designed for the SSRs. Annotation of contigs using Blast2GO software resulted in information for 60% of the unigenes in the assembly. The second transcriptome assembly was constructed from more than 200 million Illumina Genome Analyzer II reads (80-120 nt) using a combination of Velvet, CLC workbench and CAP3 software packages. BWA, SAMtools and in-house Perl scripts were used to identify SNPs among three pepper genotypes. The SNPs were filtered to be at least 50 bp from any intron-exon junctions as well as flanking SNPs. More than 22,000 high-quality putative SNPs were identified. Using the MISA software, 10,398 SSR markers were also identified within the Illumina transcriptome assembly and primers were designed for the identified markers. The assembly was annotated by Blast2GO and 14,740 (12%) of annotated contigs were associated with functional proteins. Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project.

Code-modulated interferometric imaging system using phased arrays

NASA Astrophysics Data System (ADS)

Chauhan, Vikas; Greene, Kevin; Floyd, Brian

2016-05-01

Millimeter-wave (mm-wave) imaging provides compelling capabilities for security screening, navigation, and bio- medical applications. Traditional scanned or focal-plane mm-wave imagers are bulky and costly. In contrast, phased-array hardware developed for mass-market wireless communications and automotive radar promise to be extremely low cost. In this work, we present techniques which can allow low-cost phased-array receivers to be reconfigured or re-purposed as interferometric imagers, removing the need for custom hardware and thereby reducing cost. Since traditional phased arrays power combine incoming signals prior to digitization, orthogonal code-modulation is applied to each incoming signal using phase shifters within each front-end and two-bit codes. These code-modulated signals can then be combined and processed coherently through a shared hardware path. Once digitized, visibility functions can be recovered through squaring and code-demultiplexing operations. Pro- vided that codes are selected such that the product of two orthogonal codes is a third unique and orthogonal code, it is possible to demultiplex complex visibility functions directly. As such, the proposed system modulates incoming signals but demodulates desired correlations. In this work, we present the operation of the system, a validation of its operation using behavioral models of a traditional phased array, and a benchmarking of the code-modulated interferometer against traditional interferometer and focal-plane arrays.

Transcriptome sequencing and microarray development for the woodrat (Neotoma spp.): custom genetic tools for exploring herbivore ecology.

PubMed

Malenke, J R; Milash, B; Miller, A W; Dearing, M D

2013-07-01

Massively parallel sequencing has enabled the creation of novel, in-depth genetic tools for nonmodel, ecologically important organisms. We present the de novo transcriptome sequencing, analysis and microarray development for a vertebrate herbivore, the woodrat (Neotoma spp.). This genus is of ecological and evolutionary interest, especially with respect to ingestion and hepatic metabolism of potentially toxic plant secondary compounds. We generated a liver transcriptome of the desert woodrat (Neotoma lepida) using the Roche 454 platform. The assembled contigs were well annotated using rodent references (99.7% annotation), and biotransformation function was reflected in the gene ontology. The transcriptome was used to develop a custom microarray (eArray, Agilent). We tested the microarray with three experiments: one across species with similar habitat (thus, dietary) niches, one across species with different habitat niches and one across populations within a species. The resulting one-colour arrays had high technical and biological quality. Probes designed from the woodrat transcriptome performed significantly better than functionally similar probes from the Norway rat (Rattus norvegicus). There were a multitude of expression differences across the woodrat treatments, many of which related to biotransformation processes and activities. The pattern and function of the differences indicate shared ecological pressures, and not merely phylogenetic distance, play an important role in shaping gene expression profiles of woodrat species and populations. The quality and functionality of the woodrat transcriptome and custom microarray suggest these tools will be valuable for expanding the scope of herbivore biology, as well as the exploration of conceptual topics in ecology. © 2013 John Wiley & Sons Ltd.

Genomic and transcriptomic predictors of triglyceride response to regular exercise

PubMed Central

Sarzynski, Mark A; Davidsen, Peter K; Sung, Yun Ju; Hesselink, Matthijs K C; Schrauwen, Patrick; Rice, Treva K; Rao, D C; Falciani, Francesco; Bouchard, Claude

2015-01-01

Aim We performed genome-wide and transcriptome-wide profiling to identify genes and single nucleotide polymorphisms (SNPs) associated with the response of triglycerides (TG) to exercise training. Methods Plasma TG levels were measured before and after a 20-week endurance training programme in 478 white participants from the HERITAGE Family Study. Illumina HumanCNV370-Quad v3.0 BeadChips were genotyped using the Illumina BeadStation 500GX platform. Affymetrix HG-U133+2 arrays were used to quantitate gene expression levels from baseline muscle biopsies of a subset of participants (N=52). Genome-wide association study (GWAS) analysis was performed using MERLIN, while transcriptomic predictor models were developed using the R-package GALGO. Results The GWAS results showed that eight SNPs were associated with TG training-response (ΔTG) at p<9.9×10−6, while another 31 SNPs showed p values <1×10−4. In multivariate regression models, the top 10 SNPs explained 32.0% of the variance in ΔTG, while conditional heritability analysis showed that four SNPs statistically accounted for all of the heritability of ΔTG. A molecular signature based on the baseline expression of 11 genes predicted 27% of ΔTG in HERITAGE, which was validated in an independent study. A composite SNP score based on the top four SNPs, each from the genomic and transcriptomic analyses, was the strongest predictor of ΔTG (R2=0.14, p=3.0×10−68). Conclusions Our results indicate that skeletal muscle transcript abundance at 11 genes and SNPs at a number of loci contribute to TG response to exercise training. Combining data from genomics and transcriptomics analyses identified a SNP-based gene signature that should be further tested in independent samples. PMID:26491034

Association analysis for udder index and milking speed with imputed whole-genome sequence variants in Nordic Holstein cattle.

PubMed

Jardim, Júlia Gazzoni; Guldbrandtsen, Bernt; Lund, Mogens Sandø; Sahana, Goutam

2018-03-01

Genome-wide association testing facilitates the identification of genetic variants associated with complex traits. Mapping genes that promote genetic resistance to mastitis could reduce the cost of antibiotic use and enhance animal welfare and milk production by improving outcomes of breeding for udder health. Using imputed whole-genome sequence variants, we carried out association studies for 2 traits related to udder health, udder index, and milking speed in Nordic Holstein cattle. A total of 4,921 bulls genotyped with the BovineSNP50 BeadChip array were imputed to high-density genotypes (Illumina BovineHD BeadChip, Illumina, San Diego, CA) and, subsequently, to whole-genome sequence variants. An association analysis was carried out using a linear mixed model. Phenotypes used in the association analyses were deregressed breeding values. Multitrait meta-analysis was carried out for these 2 traits. We identified 10 and 8 chromosomes harboring markers that were significantly associated with udder index and milking speed, respectively. Strongest association signals were observed on chromosome 20 for udder index and chromosome 19 for milking speed. Multitrait meta-analysis identified 13 chromosomes harboring associated markers for the combination of udder index and milking speed. The associated region on chromosome 20 overlapped with earlier reported quantitative trait loci for similar traits in other cattle populations. Moreover, this region was located close to the FYB gene, which is involved in platelet activation and controls IL-2 expression; FYB is a strong candidate gene for udder health and worthy of further investigation. Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Correcting for intra-experiment variation in Illumina BeadChip data is necessary to generate robust gene-expression profiles.

PubMed

Kitchen, Robert R; Sabine, Vicky S; Sims, Andrew H; Macaskill, E Jane; Renshaw, Lorna; Thomas, Jeremy S; van Hemert, Jano I; Dixon, J Michael; Bartlett, John M S

2010-02-24

Microarray technology is a popular means of producing whole genome transcriptional profiles, however high cost and scarcity of mRNA has led many studies to be conducted based on the analysis of single samples. We exploit the design of the Illumina platform, specifically multiple arrays on each chip, to evaluate intra-experiment technical variation using repeated hybridisations of universal human reference RNA (UHRR) and duplicate hybridisations of primary breast tumour samples from a clinical study. A clear batch-specific bias was detected in the measured expressions of both the UHRR and clinical samples. This bias was found to persist following standard microarray normalisation techniques. However, when mean-centering or empirical Bayes batch-correction methods (ComBat) were applied to the data, inter-batch variation in the UHRR and clinical samples were greatly reduced. Correlation between replicate UHRR samples improved by two orders of magnitude following batch-correction using ComBat (ranging from 0.9833-0.9991 to 0.9997-0.9999) and increased the consistency of the gene-lists from the duplicate clinical samples, from 11.6% in quantile normalised data to 66.4% in batch-corrected data. The use of UHRR as an inter-batch calibrator provided a small additional benefit when used in conjunction with ComBat, further increasing the agreement between the two gene-lists, up to 74.1%. In the interests of practicalities and cost, these results suggest that single samples can generate reliable data, but only after careful compensation for technical bias in the experiment. We recommend that investigators appreciate the propensity for such variation in the design stages of a microarray experiment and that the use of suitable correction methods become routine during the statistical analysis of the data.

Correcting for intra-experiment variation in Illumina BeadChip data is necessary to generate robust gene-expression profiles

PubMed Central

2010-01-01

Background Microarray technology is a popular means of producing whole genome transcriptional profiles, however high cost and scarcity of mRNA has led many studies to be conducted based on the analysis of single samples. We exploit the design of the Illumina platform, specifically multiple arrays on each chip, to evaluate intra-experiment technical variation using repeated hybridisations of universal human reference RNA (UHRR) and duplicate hybridisations of primary breast tumour samples from a clinical study. Results A clear batch-specific bias was detected in the measured expressions of both the UHRR and clinical samples. This bias was found to persist following standard microarray normalisation techniques. However, when mean-centering or empirical Bayes batch-correction methods (ComBat) were applied to the data, inter-batch variation in the UHRR and clinical samples were greatly reduced. Correlation between replicate UHRR samples improved by two orders of magnitude following batch-correction using ComBat (ranging from 0.9833-0.9991 to 0.9997-0.9999) and increased the consistency of the gene-lists from the duplicate clinical samples, from 11.6% in quantile normalised data to 66.4% in batch-corrected data. The use of UHRR as an inter-batch calibrator provided a small additional benefit when used in conjunction with ComBat, further increasing the agreement between the two gene-lists, up to 74.1%. Conclusion In the interests of practicalities and cost, these results suggest that single samples can generate reliable data, but only after careful compensation for technical bias in the experiment. We recommend that investigators appreciate the propensity for such variation in the design stages of a microarray experiment and that the use of suitable correction methods become routine during the statistical analysis of the data. PMID:20181233

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer.

PubMed

Rohan, Thomas; Ye, Kenny; Wang, Yihong; Glass, Andrew G; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC.

MicroRNA expression in benign breast tissue and risk of subsequent invasive breast cancer

PubMed Central

Ye, Kenny; Wang, Yihong; Ginsberg, Mindy; Loudig, Olivier

2018-01-01

MicroRNAs are endogenous, small non-coding RNAs that control gene expression by directing their target mRNAs for degradation and/or posttranscriptional repression. Abnormal expression of microRNAs is thought to contribute to the development and progression of cancer. A history of benign breast disease (BBD) is associated with increased risk of subsequent breast cancer. However, no large-scale study has examined the association between microRNA expression in BBD tissue and risk of subsequent invasive breast cancer (IBC). We conducted discovery and validation case-control studies nested in a cohort of 15,395 women diagnosed with BBD in a large health plan between 1971 and 2006 and followed to mid-2015. Cases were women with BBD who developed subsequent IBC; controls were matched 1:1 to cases on age, age at diagnosis of BBD, and duration of plan membership. The discovery stage (316 case-control pairs) entailed use of the Illumina MicroRNA Expression Profiling Assay (in duplicate) to identify breast cancer-associated microRNAs. MicroRNAs identified at this stage were ranked by the strength of the correlation between Illumina array and quantitative PCR results for 15 case-control pairs. The top ranked 14 microRNAs entered the validation stage (165 case-control pairs) which was conducted using quantitative PCR (in triplicate). In both stages, linear regression was used to evaluate the association between the mean expression level of each microRNA (response variable) and case-control status (independent variable); paired t-tests were also used in the validation stage. None of the 14 validation stage microRNAs was associated with breast cancer risk. The results of this study suggest that microRNA expression in benign breast tissue does not influence the risk of subsequent IBC. PMID:29432432

Strain Library Imaging Protocol for high-throughput, automated single-cell microscopy of large bacterial collections arrayed on multiwell plates.

PubMed

Shi, Handuo; Colavin, Alexandre; Lee, Timothy K; Huang, Kerwyn Casey

2017-02-01

Single-cell microscopy is a powerful tool for studying gene functions using strain libraries, but it suffers from throughput limitations. Here we describe the Strain Library Imaging Protocol (SLIP), which is a high-throughput, automated microscopy workflow for large strain collections that requires minimal user involvement. SLIP involves transferring arrayed bacterial cultures from multiwell plates onto large agar pads using inexpensive replicator pins and automatically imaging the resulting single cells. The acquired images are subsequently reviewed and analyzed by custom MATLAB scripts that segment single-cell contours and extract quantitative metrics. SLIP yields rich data sets on cell morphology and gene expression that illustrate the function of certain genes and the connections among strains in a library. For a library arrayed on 96-well plates, image acquisition can be completed within 4 min per plate.

Electron lithography STAR design guidelines. Part 3: The mosaic transistor array applied to custom microprocessors. Part 4: Stores logic arrays, SLAs implemented with clocked CMOS

NASA Technical Reports Server (NTRS)

Trotter, J. D.

1982-01-01

The Mosaic Transistor Array is an extension of the STAR system developed by NASA which has dedicated field cells designed to be specifically used in semicustom microprocessor applications. The Sandia radiation hard bulk CMOS process is utilized in order to satisfy the requirements of space flights. A design philosophy is developed which utilizes the strengths and recognizes the weaknesses of the Sandia process. A style of circuitry is developed which incorporates the low power and high drive capability of CMOS. In addition the density achieved is better than that for classic CMOS, although not as good as for NMOS. The basic logic functions for a data path are designed with compatible interface to the STAR grid system. In this manner either random logic or PLA type structures can be utilized for the control logic.

Sequencing the Genome of the Heirloom Watermelon Cultivar Charleston Gray

USDA-ARS?s Scientific Manuscript database

The genome of the watermelon cultivar Charleston Gray, a major heirloom which has been used in breeding programs of many watermelon cultivars, was sequenced. Our strategy involved a hybrid approach using the Illumina and 454/Titanium next-generation sequencing technologies. For Illumina, shotgun g...

High Throughput Plasmid Sequencing with Illumina and CLC Bio (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

ScienceCinema

Athavale, Ajay

2018-01-04

Ajay Athavale (Monsanto) presents "High Throughput Plasmid Sequencing with Illumina and CLC Bio" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

Development and Applications of a Bovine 50,000 SNP Chip

USDA-ARS?s Scientific Manuscript database

To develop an Illumina iSelect high density single nucleotide polymorphism (SNP) assay for cattle, the collaborative iBMC (Illumina, USDA ARS Beltsville, University of Missouri, USDA ARS Clay Center) Consortium first performed a de novo SNP discovery project in which genomic reduced representation l...

High frequency copolymer ultrasonic transducer array of size-effective elements

NASA Astrophysics Data System (ADS)

Decharat, Adit; Wagle, Sanat; Habib, Anowarul; Jacobsen, Svein; Melandsø, Frank

2018-02-01

A layer-by-layer deposition method for producing dual-layer ultrasonic transducers from piezoelectric copolymers has been developed. The method uses a combination of customized and standard processing to obtain 2D array transducers with electrical connection of the individual elements routed directly to the rear of the substrate. A numerical model was implemented to study basic parameters effecting the transducer characteristics. Key elements of the array were characterized and evaluated, demonstrating its viability of 2D imaging. Signal reproducibility of the prototype array was studied by characterizing the variations of the center frequency (≈42 MHz) and bandwidth (≈25 MHz) of the acoustic. Object identification was also tested and parameterized by acoustic-field beamwidth as well as proper scan step size. Simple tests to illustrate a benefit of multi-element scan on lowering the inspection time were conducted. Structural imaging of the test structure underneath multi-layered wave media (glass plate and distilled water) was also performed. The prototype presented in this work is an important step towards realizing an inexpensive, compact array of individually operated copolymer transducers that can serve in a fast/volumetric high frequency (HF) ultrasonic scanning platform.

Arbitrary beam control using passive lossless metasurfaces enabled by orthogonally polarized custom surface waves

NASA Astrophysics Data System (ADS)

Kwon, Do-Hoon; Tretyakov, Sergei A.

2018-01-01

For passive, lossless impenetrable metasurfaces, a design technique for arbitrary beam control of receiving, guiding, and launching is presented. Arbitrary control is enabled by a custom surface wave in an orthogonal polarization such that its addition to the incident (input) and the desired scattered (output) fields is supported by a reactive surface impedance everywhere on the reflecting surface. Such a custom surface wave (SW) takes the form of an evanescent wave propagating along the surface with a spatially varying envelope. A growing SW appears when an illuminating beam is received. The SW amplitude stays constant when power is guided along the surface. The amplitude diminishes as a propagating wave (PW) is launched from the surface as a leaky wave. The resulting reactive tensor impedance profile may be realized as an array of anisotropic metallic resonators printed on a grounded dielectric substrate. Illustrative design examples of a Gaussian beam translator-reflector, a probe-fed beam launcher, and a near-field focusing lens are provided.

Early results from the Array of Things

NASA Astrophysics Data System (ADS)

Jacob, R. L.; Catlett, C.; Beckman, P. H.; Sankaran, R.

2017-12-01

The Array of Things (AoT) is an experimental sensor and edge-computing network being deployed in the City of Chicago. An AoT node contains sensors for temperature, pressure, humidty and several trace gases as well as 4-core CPU and full Linux operating system. Custom software called "Waggle" controls the hardware and provides the data collection and transmission services. Each node is attached to a traffic signal light and has power 24/7. Data is sent over the cellular network in near realtime. With Chicago's Department of Transportation, we have been making test deployments of AoT nodes, evaluating their capabilities and comparing collected data with that from other observing systems in the Chicago area.

Methodology for testing infrared focal plane arrays in simulated nuclear radiation environments

NASA Astrophysics Data System (ADS)

Divita, E. L.; Mills, R. E.; Koch, T. L.; Gordon, M. J.; Wilcox, R. A.; Williams, R. E.

1992-07-01

This paper summarizes test methodology for focal plane array (FPA) testing that can be used for benign (clear) and radiation environments, and describes the use of custom dewars and integrated test equipment in an example environment. The test methodology, consistent with American Society for Testing Materials (ASTM) standards, is presented for the total accumulated gamma dose, transient dose rate, gamma flux, and neutron fluence environments. The merits and limitations of using Cobalt 60 for gamma environment simulations and of using various fast-neutron reactors and neutron sources for neutron simulations are presented. Test result examples are presented to demonstrate test data acquisition and FPA parameter performance under different measurement conditions and environmental simulations.

Chromothripsis Detection and Characterization Using the CTLPScanner Web Server.

PubMed

Yang, Jian; Liu, Bo; Cai, Haoyang

2018-01-01

Accurate detection of chromothripsis event is important to study the mechanisms underlying this phenomenon. CTLPScanner ( http://cgma.scu.edu.cn/CTLPScanner/ ) is a web-based tool for identification and annotation of chromothripsis-like pattern (CTLP) in genomic array data. In this chapter, we illustrate the utility of CTLPScanner for screening chromosome pulverization regions and give interpretation of the results. The web interface offers a set of parameters and thresholds for customized screening. We also provide practical recommendations for effective chromothripsis detection. In addition to the user data processing module, CTLPScanner contains more than 50,000 preprocessed oncogenomic arrays, which allow users to explore the presence of chromothripsis signatures from public data resources.

High-throughput illumina strand-specific RNA sequencing library preparation

USDA-ARS?s Scientific Manuscript database

Conventional Illumina RNA-Seq does not have the resolution to decode the complex eukaryote transcriptome due to the lack of RNA polarity information. Strand-specific RNA sequencing (ssRNA-Seq) can overcome these limitations and as such is better suited for genome annotation, de novo transcriptome as...

Development of genomic microsatellites in Gleditsia triacanthos (Fabaceae) using illumina sequencing

Treesearch

Sandra A. Owusu; Margaret Staton; Tara N. Jennings; Scott Schlarbaum; Mark V. Coggeshall; Jeanne Romero-Severson; John E. Carlson; Oliver Gailing

2013-01-01

Premise of the study: Fourteen genomic microsatellite markers were developed and characterized in honey locust, Gleditsia triacanthos, using Illumina sequencing. Due to their high variability, these markers can be applied in analyses of genetic diversity and structure, and in mating system and gene flow studies.

Additional annotation of the pig transcriptome using integrated Iso-seq and Illumina RNA-seq analysis

USDA-ARS?s Scientific Manuscript database

Alternative splicing is a well-known phenomenon that dramatically increases eukaryotic transcriptome diversity. The extent of mRNA isoform diversity among porcine tissues was assessed using Pacific Biosciences single-molecule long-read isoform sequencing (Iso-Seq) and Illumina short read sequencing ...

Identification of a BRCA2-Specific Modifier Locus at 6p24 Related to Breast Cancer Risk

PubMed Central

Vijai, Joseph; Klein, Robert J.; Kirchhoff, Tomas; McGuffog, Lesley; Barrowdale, Daniel; Dunning, Alison M.; Lee, Andrew; Dennis, Joe; Healey, Sue; Dicks, Ed; Soucy, Penny; Sinilnikova, Olga M.; Pankratz, Vernon S.; Wang, Xianshu; Eldridge, Ronald C.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Hogervorst, Frans B. L.; Peock, Susan; Stoppa-Lyonnet, Dominique; Peterlongo, Paolo; Schmutzler, Rita K.; Nathanson, Katherine L.; Piedmonte, Marion; Singer, Christian F.; Thomassen, Mads; Hansen, Thomas v. O.; Neuhausen, Susan L.; Blanco, Ignacio; Greene, Mark H.; Garber, Judith; Weitzel, Jeffrey N.; Andrulis, Irene L.; Goldgar, David E.; D'Andrea, Emma; Caldes, Trinidad; Nevanlinna, Heli; Osorio, Ana; van Rensburg, Elizabeth J.; Arason, Adalgeir; Rennert, Gad; van den Ouweland, Ans M. W.; van der Hout, Annemarie H.; Kets, Carolien M.; Aalfs, Cora M.; Wijnen, Juul T.; Ausems, Margreet G. E. M.; Frost, Debra; Ellis, Steve; Fineberg, Elena; Platte, Radka; Evans, D. Gareth; Jacobs, Chris; Adlard, Julian; Tischkowitz, Marc; Porteous, Mary E.; Damiola, Francesca; Golmard, Lisa; Barjhoux, Laure; Longy, Michel; Belotti, Muriel; Ferrer, Sandra Fert; Mazoyer, Sylvie; Spurdle, Amanda B.; Manoukian, Siranoush; Barile, Monica; Genuardi, Maurizio; Arnold, Norbert; Meindl, Alfons; Sutter, Christian; Wappenschmidt, Barbara; Domchek, Susan M.; Pfeiler, Georg; Friedman, Eitan; Jensen, Uffe Birk; Robson, Mark; Shah, Sohela; Lazaro, Conxi; Mai, Phuong L.; Benitez, Javier; Southey, Melissa C.; Schmidt, Marjanka K.; Fasching, Peter A.; Peto, Julian; Humphreys, Manjeet K.; Wang, Qin; Michailidou, Kyriaki; Sawyer, Elinor J.; Burwinkel, Barbara; Guénel, Pascal; Bojesen, Stig E.; Milne, Roger L.; Brenner, Hermann; Lochmann, Magdalena; Aittomäki, Kristiina; Dörk, Thilo; Margolin, Sara; Mannermaa, Arto; Lambrechts, Diether; Chang-Claude, Jenny; Radice, Paolo; Giles, Graham G.; Haiman, Christopher A.; Winqvist, Robert; Devillee, Peter; García-Closas, Montserrat; Schoof, Nils; Hooning, Maartje J.; Cox, Angela; Pharoah, Paul D. P.; Jakubowska, Anna; Orr, Nick; González-Neira, Anna; Pita, Guillermo; Alonso, M. Rosario; Hall, Per; Couch, Fergus J.; Simard, Jacques; Altshuler, David; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Offit, Kenneth

2013-01-01

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80–0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer. PMID:23544012

Fiber optic systems for colorimetry and scattered colorimetry

NASA Astrophysics Data System (ADS)

Mignani, Anna G.; Mencaglia, Andrea A.; Ciaccheri, Leonardo

2005-09-01

An innovative series of optical fiber sensors based on spectroscopic interrogation is presented. The sensors are custom-designed for a wide range of applications, including gasoline colorimetry, chromium monitoring of sewage, museum lighting control, for use with a platform for interrogating an array of absorption-based chemical sensors, as well as for color and turbidity measurements. Two types of custom-design instrumentation have been developed, both making use of LED light sources and a low-cost optical fiber spectrometer to perform broadband spectral measurements in the visible spectral range. The first was designed especially to address color-based sensors, while the second assessed the combined color and turbidity of edible liquids such as olive oil. Both are potentially exploitable in other industrial and environmental applications.

Development and Calibration of a Field-Deployable Microphone Phased Array for Propulsion and Airframe Noise Flyover Measurements

NASA Technical Reports Server (NTRS)

Humphreys, William M., Jr.; Lockard, David P.; Khorrami, Mehdi R.; Culliton, William G.; McSwain, Robert G.; Ravetta, Patricio A.; Johns, Zachary

2016-01-01

A new aeroacoustic measurement capability has been developed consisting of a large channelcount, field-deployable microphone phased array suitable for airframe noise flyover measurements for a range of aircraft types and scales. The array incorporates up to 185 hardened, weather-resistant sensors suitable for outdoor use. A custom 4-mA current loop receiver circuit with temperature compensation was developed to power the sensors over extended cable lengths with minimal degradation of the signal to noise ratio and frequency response. Extensive laboratory calibrations and environmental testing of the sensors were conducted to verify the design's performance specifications. A compact data system combining sensor power, signal conditioning, and digitization was assembled for use with the array. Complementing the data system is a robust analysis system capable of near real-time presentation of beamformed and deconvolved contour plots and integrated spectra obtained from array data acquired during flyover passes. Additional instrumentation systems needed to process the array data were also assembled. These include a commercial weather station and a video monitoring / recording system. A detailed mock-up of the instrumentation suite (phased array, weather station, and data processor) was performed in the NASA Langley Acoustic Development Laboratory to vet the system performance. The first deployment of the system occurred at Finnegan Airfield at Fort A.P. Hill where the array was utilized to measure the vehicle noise from a number of sUAS (small Unmanned Aerial System) aircraft. A unique in-situ calibration method for the array microphones using a hovering aerial sound source was attempted for the first time during the deployment.

The sonic window: second generation results

NASA Astrophysics Data System (ADS)

Walker, William F.; Fuller, Michael I.; Brush, Edward V.; Eames, Matthew D. C.; Owen, Kevin; Ranganathan, Karthik; Blalock, Travis N.; Hossack, John A.

2006-03-01

Medical Ultrasound Imaging is widely used clinically because of its relatively low cost, portability, lack of ionizing radiation, and real-time nature. However, even with these advantages ultrasound has failed to permeate the broad array of clinical applications where its use could be of value. A prime example of this untapped potential is the routine use of ultrasound to guide intravenous access. In this particular application existing systems lack the required portability, low cost, and ease-of-use required for widespread acceptance. Our team has been working for a number of years to develop an extremely low-cost, pocket-sized, and intuitive ultrasound imaging system that we refer to as the "Sonic Window." We have previously described the first generation Sonic Window prototype that was a bench-top device using a 1024 element, fully populated array operating at a center frequency of 3.3 MHz. Through a high degree of custom front-end integration combined with multiplexing down to a 2 channel PC based digitizer this system acquired a full set of RF data over a course of 512 transmit events. While initial results were encouraging, this system exhibited limitations resulting from low SNR, relatively coarse array sampling, and relatively slow data acquisition. We have recently begun assembling a second-generation Sonic Window system. This system uses a 3600 element fully sampled array operating at 5.0 MHz with a 300 micron element pitch. This system extends the integration of the first generation system to include front-end protection, pre-amplification, a programmable bandpass filter, four sample and holds, and four A/D converters for all 3600 channels in a set of custom integrated circuits with a combined area smaller than the 1.8 x 1.8 cm footprint of the transducer array. We present initial results from this front-end and present benchmark results from a software beamformer implemented on the Analog Devices BF-561 DSP. We discuss our immediate plans for further integration and testing. This second prototype represents a major reduction in size and forms the foundation of a fully functional, fully integrated, pocket sized prototype.

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

Microelectronic Stimulator Array

DTIC Science & Technology

2000-08-09

narrow, flexible micro-cable 36. The micro-cable 36 is approximately six inches in length and is custom made using gold leads patterned on polyimide ...neural prosthesis device is biocompatibility and safety. Because the duration of any tests with the retinal prosthesis test device 30 are very short...less than an hour), biocompatibility issues are primarily reduced to acute effects of the testing and need not address the more difficult chronic

3D-Printed Biodegradable Polymeric Vascular Grafts.

PubMed

Melchiorri, A J; Hibino, N; Best, C A; Yi, T; Lee, Y U; Kraynak, C A; Kimerer, L K; Krieger, A; Kim, P; Breuer, C K; Fisher, J P

2016-02-04

Congenital heart defect interventions may benefit from the fabrication of patient-specific vascular grafts because of the wide array of anatomies present in children with cardiovascular defects. 3D printing is used to establish a platform for the production of custom vascular grafts, which are biodegradable, mechanically compatible with vascular tissues, and support neotissue formation and growth. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effective temperature in an interacting vertex system: theory and experiment on artificial spin ice.

PubMed

Nisoli, Cristiano; Li, Jie; Ke, Xianglin; Garand, D; Schiffer, Peter; Crespi, Vincent H

2010-07-23

Frustrated arrays of interacting single-domain nanomagnets provide important model systems for statistical mechanics, as they map closely onto well-studied vertex models and are amenable to direct imaging and custom engineering. Although these systems are manifestly athermal, we demonstrate that an effective temperature, controlled by an external magnetic drive, describes their microstates and therefore their full statistical properties.

Integrated Microfluidic Devices for Automated Microarray-Based Gene Expression and Genotyping Analysis

NASA Astrophysics Data System (ADS)

Liu, Robin H.; Lodes, Mike; Fuji, H. Sho; Danley, David; McShea, Andrew

Microarray assays typically involve multistage sample processing and fluidic handling, which are generally labor-intensive and time-consuming. Automation of these processes would improve robustness, reduce run-to-run and operator-to-operator variation, and reduce costs. In this chapter, a fully integrated and self-contained microfluidic biochip device that has been developed to automate the fluidic handling steps for microarray-based gene expression or genotyping analysis is presented. The device consists of a semiconductor-based CustomArray® chip with 12,000 features and a microfluidic cartridge. The CustomArray was manufactured using a semiconductor-based in situ synthesis technology. The micro-fluidic cartridge consists of microfluidic pumps, mixers, valves, fluid channels, and reagent storage chambers. Microarray hybridization and subsequent fluidic handling and reactions (including a number of washing and labeling steps) were performed in this fully automated and miniature device before fluorescent image scanning of the microarray chip. Electrochemical micropumps were integrated in the cartridge to provide pumping of liquid solutions. A micromixing technique based on gas bubbling generated by electrochemical micropumps was developed. Low-cost check valves were implemented in the cartridge to prevent cross-talk of the stored reagents. Gene expression study of the human leukemia cell line (K562) and genotyping detection and sequencing of influenza A subtypes have been demonstrated using this integrated biochip platform. For gene expression assays, the microfluidic CustomArray device detected sample RNAs with a concentration as low as 0.375 pM. Detection was quantitative over more than three orders of magnitude. Experiment also showed that chip-to-chip variability was low indicating that the integrated microfluidic devices eliminate manual fluidic handling steps that can be a significant source of variability in genomic analysis. The genotyping results showed that the device identified influenza A hemagglutinin and neuraminidase subtypes and sequenced portions of both genes, demonstrating the potential of integrated microfluidic and microarray technology for multiple virus detection. The device provides a cost-effective solution to eliminate labor-intensive and time-consuming fluidic handling steps and allows microarray-based DNA analysis in a rapid and automated fashion.

The ICT monitoring system of the ASTRI SST-2M prototype proposed for the Cherenkov Telescope Array

NASA Astrophysics Data System (ADS)

Gianotti, F.; Bruno, P.; Tacchini, A.; Conforti, V.; Fioretti, V.; Tanci, C.; Grillo, A.; Leto, G.; Malaguti, G.; Trifoglio, M.

2016-08-01

In the framework of the international Cherenkov Telescope Array (CTA) observatory, the Italian National Institute for Astrophysics (INAF) has developed a dual mirror, small sized, telescope prototype (ASTRI SST-2M), installed in Italy at the INAF observing station located at Serra La Nave, Mt. Etna. The ASTRI SST-2M prototype is the basis of the ASTRI telescopes that will form the mini-array proposed to be installed at the CTA southern site during its preproduction phase. This contribution presents the solutions implemented to realize the monitoring system for the Information and Communication Technology (ICT) infrastructure of the ASTRI SST-2M prototype. The ASTRI ICT monitoring system has been implemented by integrating traditional tools used in computer centers, with specific custom tools which interface via Open Platform Communication Unified Architecture (OPC UA) to the Alma Common Software (ACS) that is used to operate the ASTRI SST-2M prototype. The traditional monitoring tools are based on Simple Network Management Protocol (SNMP) and commercial solutions and features embedded in the devices themselves. They generate alerts by email and SMS. The specific custom tools convert the SNMP protocol into the OPC UA protocol and implement an OPC UA server. The server interacts with an OPC UA client implemented in an ACS component that, through the ACS Notification Channel, sends monitor data and alerts to the central console of the ASTRI SST-2M prototype. The same approach has been proposed also for the monitoring of the CTA onsite ICT infrastructures.

Piezoresistive pressure sensor array for robotic skin

NASA Astrophysics Data System (ADS)

Mirza, Fahad; Sahasrabuddhe, Ritvij R.; Baptist, Joshua R.; Wijesundara, Muthu B. J.; Lee, Woo H.; Popa, Dan O.

2016-05-01

Robots are starting to transition from the confines of the manufacturing floor to homes, schools, hospitals, and highly dynamic environments. As, a result, it is impossible to foresee all the probable operational situations of robots, and preprogram the robot behavior in those situations. Among human-robot interaction technologies, haptic communication is an intuitive physical interaction method that can help define operational behaviors for robots cooperating with humans. Multimodal robotic skin with distributed sensors can help robots increase perception capabilities of their surrounding environments. Electro-Hydro-Dynamic (EHD) printing is a flexible multi-modal sensor fabrication method because of its direct printing capability of a wide range of materials onto substrates with non-uniform topographies. In past work we designed interdigitated comb electrodes as a sensing element and printed piezoresistive strain sensors using customized EHD printable PEDOT:PSS based inks. We formulated a PEDOT:PSS derivative ink, by mixing PEDOT:PSS and DMSO. Bending induced characterization tests of prototyped sensors showed high sensitivity and sufficient stability. In this paper, we describe SkinCells, robot skin sensor arrays integrated with electronic modules. 4x4 EHD-printed arrays of strain sensors was packaged onto Kapton sheets and silicone encapsulant and interconnected to a custom electronic module that consists of a microcontroller, Wheatstone bridge with adjustable digital potentiometer, multiplexer, and serial communication unit. Thus, SkinCell's electronics can be used for signal acquisition, conditioning, and networking between sensor modules. Several SkinCells were loaded with controlled pressure, temperature and humidity testing apparatuses, and testing results are reported in this paper.

Photopatterned free-standing polyacrylamide gels for microfluidic protein electrophoresis.

PubMed

Duncombe, Todd A; Herr, Amy E

2013-06-07

Designed for compatibility with slab-gel polyacrylamide gel electrophoresis (PAGE) reagents and instruments, we detail development of free-standing polyacrylamide gel (fsPAG) microstructures supporting electrophoretic performance rivalling that of microfluidic platforms. For the protein electrophoresis study described here, fsPAGE lanes are comprised of a sample reservoir and contiguous separation gel. No enclosed microfluidic channels are employed. The fsPAG devices (120 μm tall) are directly photopatterned atop of and covalently attached to planar polymer or glass surfaces. Leveraging the fast <1 h design-prototype-test cycle - significantly faster than mold based fabrication techniques - we optimize the fsPAG architecture to minimize injection dispersion for rapid (<1 min) and short (1 mm) protein separations. The facile fabrication and prototyping of the fsPAGE provides researchers a powerful tool for developing custom analytical assays. We highlight the utility of assay customization by fabricating a polyacrylamide gel with a spatial pore-size distribution and demonstrate the resulting enhancement in separation performance over a uniform gel. Further, we up-scale from a unit separation to an array of 96 concurrent fsPAGE assays in 10 min run time driven by one electrode pair. The fsPAG array layout matches that of a 96-well plate to facilitate integration of the planar free standing gel array with multi-channel pipettes while remaining compatible with conventional slab-gel PAGE reagents, such as staining for label-free protein detection. Notably, the entire fsPAGE workflow from fabrication, to operation, and readout uses readily available materials and instruments - making this technique highly accessible.

Fully Tunable Silicon Nanowire Arrays Fabricated by Soft Nanoparticle Templating.

PubMed

Rey, By Marcel; Elnathan, Roey; Ditcovski, Ran; Geisel, Karen; Zanini, Michele; Fernandez-Rodriguez, Miguel-Angel; Naik, Vikrant V; Frutiger, Andreas; Richtering, Walter; Ellenbogen, Tal; Voelcker, Nicolas H; Isa, Lucio

2016-01-13

We demonstrate a fabrication breakthrough to produce large-area arrays of vertically aligned silicon nanowires (VA-SiNWs) with full tunability of the geometry of the single nanowires and of the whole array, paving the way toward advanced programmable designs of nanowire platforms. At the core of our fabrication route, termed "Soft Nanoparticle Templating", is the conversion of gradually compressed self-assembled monolayers of soft nanoparticles (microgels) at a water-oil interface into customized lithographical masks to create VA-SiNW arrays by means of metal-assisted chemical etching (MACE). This combination of bottom-up and top-down techniques affords excellent control of nanowire etching site locations, enabling independent control of nanowire spacing, diameter and height in a single fabrication route. We demonstrate the fabrication of centimeter-scale two-dimensional gradient photonic crystals exhibiting continuously varying structural colors across the entire visible spectrum on a single silicon substrate, and the formation of tunable optical cavities supported by the VA-SiNWs, as unambiguously demonstrated through numerical simulations. Finally, Soft Nanoparticle Templating is combined with optical lithography to create hierarchical and programmable VA-SiNW patterns.

A 15-MHz 1-3 Piezocomposite Concave Array Transducer for Ophthalmic Imaging.

PubMed

Cha, Jung Hyui; Kang, Byungwoo; Jang, Jihun; Chang, Jin Ho

2015-11-01

Because of the spherical shape of the human eye, the anterior segments of the eye, particularly the cornea and the lens, create high levels of refraction and reflection of ultrasound which negatively affect the performance of linear and convex arrays. To minimize the ultrasound energy loss, a 15-MHz concave array transducer was designed, fabricated, and characterized; its footprint is able to mesh well with the shape of the cornea. The concave array has a curvature with a radius of 15 mm and 128 elements with a 1.44- pitch. Its elevational focus and view angle are 30 mm and 72.3°, respectively, thus allowing the imaging area to cover the retinal region of interest in the posterior segment. As an active layer, a 1-3 piezocomposite was designed and fabricated in response to the bidirectional (i.e., azimuthal and elevational) curvature of the concave array and the high coupling coefficient. From the performance evaluation, it was found that the completed concave array is able to provide a center frequency of 15.95 MHz and a -6-dB fractional bandwidth of 67.8% after electrical tuning has been conducted. The crosstalk level was measured to be less than -25 dB. It was verified that the concave array is robust to the refraction and reflection from the cornea through pulse-echo testing using a custom-made eye-mimicking phantom. Furthermore, images of both the wire-target phantom and the ex vivo porcine eye were acquired by the finished concave array, which was connected to a commercial ultrasound scanner equipped with a research package. The evaluation results demonstrated that the developed concave array transducer is a possible alternative to conventional arrays for effectively imaging the posterior segment of the eye.

Transcriptome sequencing of newly molted adult female cattle ticks, Rhipicephalus microplus: Raw Illumina reads.

USDA-ARS?s Scientific Manuscript database

Illumina paired end oligo-dT sequencing technology was used to sequence the transcriptome from newly molted adult females from the cattle tick, Rhipicephalus microplus. These samples include newly molted unfed whole adult females, newly molted whole adult females feeding for 2 hours on a bovine host...

OTG-snpcaller: An Optimized Pipeline Based on TMAP and GATK for SNP Calling from Ion Torrent Data

PubMed Central

Huang, Wenpan; Xi, Feng; Lin, Lin; Zhi, Qihuan; Zhang, Wenwei; Tang, Y. Tom; Geng, Chunyu; Lu, Zhiyuan; Xu, Xun

2014-01-01

Because the new Proton platform from Life Technologies produced markedly different data from those of the Illumina platform, the conventional Illumina data analysis pipeline could not be used directly. We developed an optimized SNP calling method using TMAP and GATK (OTG-snpcaller). This method combined our own optimized processes, Remove Duplicates According to AS Tag (RDAST) and Alignment Optimize Structure (AOS), together with TMAP and GATK, to call SNPs from Proton data. We sequenced four sets of exomes captured by Agilent SureSelect and NimbleGen SeqCap EZ Kit, using Life Technology’s Ion Proton sequencer. Then we applied OTG-snpcaller and compared our results with the results from Torrent Variants Caller. The results indicated that OTG-snpcaller can reduce both false positive and false negative rates. Moreover, we compared our results with Illumina results generated by GATK best practices, and we found that the results of these two platforms were comparable. The good performance in variant calling using GATK best practices can be primarily attributed to the high quality of the Illumina sequences. PMID:24824529

OTG-snpcaller: an optimized pipeline based on TMAP and GATK for SNP calling from ion torrent data.

PubMed

Zhu, Pengyuan; He, Lingyu; Li, Yaqiao; Huang, Wenpan; Xi, Feng; Lin, Lin; Zhi, Qihuan; Zhang, Wenwei; Tang, Y Tom; Geng, Chunyu; Lu, Zhiyuan; Xu, Xun

2014-01-01

Because the new Proton platform from Life Technologies produced markedly different data from those of the Illumina platform, the conventional Illumina data analysis pipeline could not be used directly. We developed an optimized SNP calling method using TMAP and GATK (OTG-snpcaller). This method combined our own optimized processes, Remove Duplicates According to AS Tag (RDAST) and Alignment Optimize Structure (AOS), together with TMAP and GATK, to call SNPs from Proton data. We sequenced four sets of exomes captured by Agilent SureSelect and NimbleGen SeqCap EZ Kit, using Life Technology's Ion Proton sequencer. Then we applied OTG-snpcaller and compared our results with the results from Torrent Variants Caller. The results indicated that OTG-snpcaller can reduce both false positive and false negative rates. Moreover, we compared our results with Illumina results generated by GATK best practices, and we found that the results of these two platforms were comparable. The good performance in variant calling using GATK best practices can be primarily attributed to the high quality of the Illumina sequences.

HumanMethylation450K Array–Identified Biomarkers Predict Tumour Recurrence/Progression at Initial Diagnosis of High-risk Non-muscle Invasive Bladder Cancer

PubMed Central

Kitchen, Mark O; Bryan, Richard T; Emes, Richard D; Luscombe, Christopher J; Cheng, KK; Zeegers, Maurice P; James, Nicholas D; Gommersall, Lyndon M; Fryer, Anthony A

2018-01-01

Background: High-risk non-muscle invasive bladder cancer (HR-NMIBC) is a clinically unpredictable disease. Despite clinical risk estimation tools, many patients are undertreated with intra-vesical therapies alone, whereas others may be over-treated with early radical surgery. Molecular biomarkers, particularly DNA methylation, have been reported as predictive of tumour/patient outcomes in numerous solid organ and haematologic malignancies; however, there are few reports in HR-NMIBC and none using genome-wide array assessment. We therefore sought to identify novel DNA methylation markers of HR-NMIBC clinical outcomes that might predict tumour behaviour at initial diagnosis and help guide patient management. Patients and methods: A total of 21 primary initial diagnosis HR-NMIBC tumours were analysed by Illumina HumanMethylation450 BeadChip arrays and subsequently bisulphite Pyrosequencing. In all, 7 had not recurred at 1 year after resection and 14 had recurred and/or progressed despite intra-vesical BCG. A further independent cohort of 32 HR-NMIBC tumours (17 no recurrence and 15 recurrence and/or progression despite BCG) were also assessed by bisulphite Pyrosequencing. Results: Array analyses identified 206 CpG loci that segregated non-recurrent HR-NMIBC tumours from clinically more aggressive recurrence/progression tumours. Hypermethylation of CpG cg11850659 and hypomethylation of CpG cg01149192 in combination predicted HR-NMIBC recurrence and/or progression within 1 year of diagnosis with 83% sensitivity, 79% specificity, and 83% positive and 79% negative predictive values. Conclusions: This is the first genome-wide DNA methylation analysis of a unique HR-NMIBC tumour cohort encompassing known 1-year clinical outcomes. Our analyses identified potential novel epigenetic markers that could help guide individual patient management in this clinically unpredictable disease. PMID:29343995

Exome Array Analysis of Nuclear Lens Opacity.

PubMed

Loomis, Stephanie J; Klein, Alison P; Lee, Kristine E; Chen, Fei; Bomotti, Samantha; Truitt, Barbara; Iyengar, Sudha K; Klein, Ronald; Klein, Barbara E K; Duggal, Priya

2018-06-01

Nuclear cataract is the most common subtype of age-related cataract, the leading cause of blindness worldwide. It results from advanced nuclear sclerosis, or opacity in the center of the optic lens, and is affected by both genetic and environmental risk factors, including smoking. We sought to understand the genetic factors associated with nuclear sclerosis through interrogation of rare and low frequency coding variants using exome array data. We analyzed Illumina Human Exome Array data for 1,488 participants of European ancestry in the Beaver Dam Eye Study who were without cataract surgery for association with nuclear sclerosis grade, controlling for age and sex. We performed single-variant regression analysis for 32,138 variants with minor allele frequency (MAF) ≥0.003. In addition, gene-based analysis of 11,844 genes containing at least two variants with MAF < 0.05 was performed using a gene-based unified burden and non-burden sequence kernel association test (SKAT-O). Additionally, both single-variant and gene-based analyses were analyzed stratified by smoking status. No single-variant test was statistically significant after Bonferroni correction (p < 1.6 × 10 -6 ; top single nucleotide polymorphism (SNP): rs144458991, p = 2.83 × 10 -5 ). Gene-based tests were suggestively associated with the gene RNF149 overall (p = 8.29 × 10 -6 ) and among never smokers (N = 790, p = 2.67 × 10 -6 ). This study did not find a significant genetic association with nuclear sclerosis, the possible association with the RNF149 gene highlights a potential candidate gene for future studies that aim to understand the genetic architecture of nuclear sclerosis.

A Metagenome-Wide Association Study and Arrayed Mutant Library Confirm Acetobacter Lipopolysaccharide Genes Are Necessary for Association with Drosophila melanogaster.

PubMed

White, K Makay; Matthews, Melinda K; Hughes, Rachel C; Sommer, Andrew J; Griffitts, Joel S; Newell, Peter D; Chaston, John M

2018-03-28

A metagenome wide association (MGWA) study of bacterial host association determinants in Drosophila predicted that LPS biosynthesis genes are significantly associated with host colonization. We were unable to create site-directed mutants for each of the predicted genes in Acetobacter , so we created an arrayed transposon insertion library using Acetobacter fabarum DsW_054 isolated from Drosophila Creation of the A. fabarum DsW_054 gene knock-out library was performed by combinatorial mapping and Illumina sequencing of random transposon insertion mutants. Transposon insertion locations for 6,418 mutants were successfully mapped, including hits within 63% of annotated genes in the A. fabarum DsW_054 genome. For 45/45 members of the library, insertion sites were verified by arbitrary PCR and Sanger sequencing. Mutants with insertions in four different LPS biosynthesis genes were selected from the library to validate the MGWA predictions. Insertion mutations in two genes biosynthetically upstream of Lipid-A formation, lpxC and lpxB , show significant differences in host association, whereas mutations in two genes encoding LPS biosynthesis functions downstream of Lipid-A biosynthesis had no effect. These results suggest an impact of bacterial cell surface molecules on the bacterial capacity for host association. Also, the transposon insertion mutant library will be a useful resource for ongoing research on the genetic basis for Acetobacter traits. Copyright © 2018 White et al.

Quantitative assessment of RNA-protein interactions with high-throughput sequencing-RNA affinity profiling.

PubMed

Ozer, Abdullah; Tome, Jacob M; Friedman, Robin C; Gheba, Dan; Schroth, Gary P; Lis, John T

2015-08-01

Because RNA-protein interactions have a central role in a wide array of biological processes, methods that enable a quantitative assessment of these interactions in a high-throughput manner are in great demand. Recently, we developed the high-throughput sequencing-RNA affinity profiling (HiTS-RAP) assay that couples sequencing on an Illumina GAIIx genome analyzer with the quantitative assessment of protein-RNA interactions. This assay is able to analyze interactions between one or possibly several proteins with millions of different RNAs in a single experiment. We have successfully used HiTS-RAP to analyze interactions of the EGFP and negative elongation factor subunit E (NELF-E) proteins with their corresponding canonical and mutant RNA aptamers. Here we provide a detailed protocol for HiTS-RAP that can be completed in about a month (8 d hands-on time). This includes the preparation and testing of recombinant proteins and DNA templates, clustering DNA templates on a flowcell, HiTS and protein binding with a GAIIx instrument, and finally data analysis. We also highlight aspects of HiTS-RAP that can be further improved and points of comparison between HiTS-RAP and two other recently developed methods, quantitative analysis of RNA on a massively parallel array (RNA-MaP) and RNA Bind-n-Seq (RBNS), for quantitative analysis of RNA-protein interactions.

The epigenetic landscape of oral squamous cell carcinoma

PubMed Central

Jithesh, P V; Risk, J M; Schache, A G; Dhanda, J; Lane, B; Liloglou, T; Shaw, R J

2013-01-01

Background: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. Methods: DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. Results: Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between ‘CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. Conclusion: Although OSCC seems as much an ‘epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC. PMID:23287992

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.

Detection of Turner syndrome using X-chromosome inactivation specific differentially methylated CpG sites: A pilot study.

PubMed

Zhang, Qiang; Guo, Xiaohong; Tian, Tian; Wang, Teng; Li, Qiaoli; Wang, Lei; Liu, Yun; Xing, Qinghe; He, Lin; Zhao, Xinzhi

2017-05-01

Early diagnosis of Turner syndrome (TS) may improve preventive measures and treatment. X-chromosome inactivation specific differentially methylated CpG sites (XIDMSs) that are high methylated in inactive X chromosomes (Xi) and unmethylated in active X chromosomes (Xa) may be potential makers for TS detection. The candidate XIDMSs were screened from 9 male and 12 female DNA samples with normal karyotypes using the Illumina 450k array and validated by bisulfite sequencing PCR and pyrosequencing assay. X chromosome dosage was calculated according to the methylation level of multiple XIDMSs. Overall, 108 candidate XIDMSs were screened by the 450k array. Validations indicated that XIDMSs gathered and formed the X-chromosome inactivation specific differentially methylated regions (XIDMRs). Using 3 XIDMRs at SAT1, UXT and UTP14A loci, 36 TS, 22 normal female and 6 male samples were analyzed. Methylation levels of the 20 XIDMSs in the XIDMRs could distinguish between TS and normal female DNA samples, the X chromosome dosage was consistent with karyotyping data. Analyzing samples of 2 triple X syndrome and 3 Klinefelter syndrome patients suggested that this method could be used to detect X chromosome aneuploids other than TS. XIDMSs are widely spread along the X chromosome and might be effective markers for detection of TS and other X chromosome aneuploids. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigation of bacterial and archaeal communities: novel protocols using modern sequencing by Illumina MiSeq and traditional DGGE-cloning.

PubMed

Kraková, Lucia; Šoltys, Katarína; Budiš, Jaroslav; Grivalský, Tomáš; Ďuriš, František; Pangallo, Domenico; Szemes, Tomáš

2016-09-01

Different protocols based on Illumina high-throughput DNA sequencing and denaturing gradient gel electrophoresis (DGGE)-cloning were developed and applied for investigating hot spring related samples. The study was focused on three target genes: archaeal and bacterial 16S rRNA and mcrA of methanogenic microflora. Shorter read lengths of the currently most popular technology of sequencing by Illumina do not allow analysis of the complete 16S rRNA region, or of longer gene fragments, as was the case of Sanger sequencing. Here, we demonstrate that there is no need for special indexed or tailed primer sets dedicated to short variable regions of 16S rRNA since the presented approach allows the analysis of complete bacterial 16S rRNA amplicons (V1-V9) and longer archaeal 16S rRNA and mcrA sequences. Sample augmented with transposon is represented by a set of approximately 300 bp long fragments that can be easily sequenced by Illumina MiSeq. Furthermore, a low proportion of chimeric sequences was observed. DGGE-cloning based strategies were performed combining semi-nested PCR, DGGE and clone library construction. Comparing both investigation methods, a certain degree of complementarity was observed confirming that the DGGE-cloning approach is not obsolete. Novel protocols were created for several types of laboratories, utilizing the traditional DGGE technique or using the most modern Illumina sequencing.

Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

PubMed Central

Patel, Sanjay R.; Goodloe, Robert; De, Gourab; Kowgier, Matthew; Weng, Jia; Buxbaum, Sarah G.; Cade, Brian; Fulop, Tibor; Gharib, Sina A.; Gottlieb, Daniel J.; Hillman, David; Larkin, Emma K.; Lauderdale, Diane S.; Li, Li; Mukherjee, Sutapa; Palmer, Lyle; Zee, Phyllis; Zhu, Xiaofeng; Redline, Susan

2012-01-01

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×10−6. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis. PMID:23155414

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

MuffinInfo: HTML5-Based Statistics Extractor from Next-Generation Sequencing Data.

PubMed

Alic, Andy S; Blanquer, Ignacio

2016-09-01

Usually, the information known a priori about a newly sequenced organism is limited. Even resequencing the same organism can generate unpredictable output. We introduce MuffinInfo, a FastQ/Fasta/SAM information extractor implemented in HTML5 capable of offering insights into next-generation sequencing (NGS) data. Our new tool can run on any software or hardware environment, in command line or graphically, and in browser or standalone. It presents information such as average length, base distribution, quality scores distribution, k-mer histogram, and homopolymers analysis. MuffinInfo improves upon the existing extractors by adding the ability to save and then reload the results obtained after a run as a navigable file (also supporting saving pictures of the charts), by supporting custom statistics implemented by the user, and by offering user-adjustable parameters involved in the processing, all in one software. At the moment, the extractor works with all base space technologies such as Illumina, Roche, Ion Torrent, Pacific Biosciences, and Oxford Nanopore. Owing to HTML5, our software demonstrates the readiness of web technologies for mild intensive tasks encountered in bioinformatics.

An efficient approach to BAC based assembly of complex genomes.

PubMed

Visendi, Paul; Berkman, Paul J; Hayashi, Satomi; Golicz, Agnieszka A; Bayer, Philipp E; Ruperao, Pradeep; Hurgobin, Bhavna; Montenegro, Juan; Chan, Chon-Kit Kenneth; Staňková, Helena; Batley, Jacqueline; Šimková, Hana; Doležel, Jaroslav; Edwards, David

2016-01-01

There has been an exponential growth in the number of genome sequencing projects since the introduction of next generation DNA sequencing technologies. Genome projects have increasingly involved assembly of whole genome data which produces inferior assemblies compared to traditional Sanger sequencing of genomic fragments cloned into bacterial artificial chromosomes (BACs). While whole genome shotgun sequencing using next generation sequencing (NGS) is relatively fast and inexpensive, this method is extremely challenging for highly complex genomes, where polyploidy or high repeat content confounds accurate assembly, or where a highly accurate 'gold' reference is required. Several attempts have been made to improve genome sequencing approaches by incorporating NGS methods, to variable success. We present the application of a novel BAC sequencing approach which combines indexed pools of BACs, Illumina paired read sequencing, a sequence assembler specifically designed for complex BAC assembly, and a custom bioinformatics pipeline. We demonstrate this method by sequencing and assembling BAC cloned fragments from bread wheat and sugarcane genomes. We demonstrate that our assembly approach is accurate, robust, cost effective and scalable, with applications for complete genome sequencing in large and complex genomes.

SMEX-Lite Modular Solar Array Architecture

NASA Technical Reports Server (NTRS)

Lyons, John

2002-01-01

For the most part, Goddard solar arrays have been custom designs that are unique to each mission. The solar panel design has been frozen prior to issuing an RFP for their procurement. There has typically been 6-9 months between RFP release and contract award, followed by an additional 24 months for performance of the contract. For Small Explorer (SMEX) missions, with three years between mission definition and launch, this has been a significant problem. The SMEX solar panels have been sufficiently small that the contract performance period has been reduced to 12-15 months. The bulk of this time is used up in the final design definition and fabrication of flight solar cell assemblies. Even so, it has been virtually impossible to have the spacecraft design at a level of maturity sufficient to freeze the solar panel geometry and release the RFP in time to avoid schedule problems with integrating the solar panels to the spacecraft. With that in mind, the SMEX-Lite project team developed a modular architecture for the assembly of solar arrays to greatly reduce the cost and schedule associated with the development of a mission- specific solar array. In the modular architecture, solar cells are fabricated onto small substrate panels. This modular panel (approximately 8.5" x 17" in this case) becomes the building block for constructing solar arrays for multiple missions with varying power requirements and geometrical arrangements. The mechanical framework that holds these modules together as a solar array is the only mission-unique design, changing in size and shape as required for each mission. There are several advantages to this approach. First, the typical solar array development cycle requires a mission unique design, procurement, and qualification including a custom qualification panel. With the modular architecture, a single qualification of the SMEX-Lite modules and the associated mechanical framework in a typical configuration provided a qualification by similarity to multiple missions. It then becomes possible to procure solar array modules in advance of mission definition and respond quickly and inexpensively to a selected mission's unique requirements. The solar array modular architecture allows the procurement of solar array modules before the array geometry has been frozen. This reduces the effect of procurement lead-time on the mission integration and test flow by as much as 50%. Second, by spreading the non-recurring costs over multiple missions, the cost per unit area is also reduced. In the case of the SMEX-Lite procurement, this reduction was by about one third of the cost per unit area compared to previous SMEX mission-unique procurements. Third, the modular architecture greatly facilitates the infusion of new solar cell technologies into flight programs as these technologies become available. New solar cell technologies need only be fabricated onto a standard-sized module to be incorporated into the next available mission. The modular solar array can be flown in a mixed configuration with some new and some standard cell technologies. Since each module has its own wiring terminals, the array can be arranged as desired electrically with little impact to cost and schedule. The solar array modular architecture does impose some additional constraints on systems and subsystem engineers. First, they must work with discrete solar array modules rather than size the array to fit exactly within an available envelope. The array area is constrained to an integer multiple of the module area. Second, the modular design is optimized for space radiation and thermal environments not greatly different from a typical SMEX LEO environment. For example, a mission with a highly elliptical orbit (e.g., Polar, SMEX/FAST) would require thicker coverglasses to protect the solar cells from the more intense radiation environment.

Performance and characterization of new micromachined high-frequency linear arrays.

PubMed

Lukacs, Marc; Yin, Jianhua; Pang, Guofeng; Garcia, Richard C; Cherin, Emmanuel; Williams, Ross; Mehi, Jim; Foster, F Stuart

2006-10-01

A new approach for fabricating high frequency (> 20 MHz) linear array transducers, based on laser micromachining, has been developed. A 30 MHz, 64-element, 74-microm pitch, linear array design is presented. The performance of the device is demonstrated by comparing electrical and acoustic measurements with analytical, equivalent circuit, and finite-element analysis (FEA) simulations. All FEA results for array performance have been generated using one global set of material parameters. Each fabricated array has been integrated onto a flex circuit for ease of handling, and the flex has been integrated onto a custom printed circuit board test card for ease of testing. For a fully assembled array, with an acoustic lens, the center frequency was 28.7 MHz with a one-way -3 dB and -6 dB bandwidth of 59% and 83%, respectively, and a -20 dB pulse width of -99 ns. The per-element peak acoustic power, for a +/- 30 V single cycle pulse, measured at the 10 mm focal length of the lens was 590 kPa with a -6 dB directivity span of about 30 degrees. The worst-case total cross talk of the combined array and flex assembly is for nearest neighboring elements and was measured to have an average level -40 dB across the -6 dB bandwidth of the device. Any significant deviation from simulation can be explained through limitations in apparatus calibration and in device packaging.

Micromirror array nanostructures for anticounterfeiting applications

NASA Astrophysics Data System (ADS)

Lee, Robert A.

2004-06-01

The optical characteristics of pixellated passive micro mirror arrays are derived and applied in the context of their use as reflective optically variable device (OVD) nanostructures for the protection of documents from counterfeiting. The traditional design variables of foil based diffractive OVDs are shown to be able to be mapped to a corresponding set of design parameters for reflective optical micro mirror array (OMMA) devices. The greatly increased depth characteristics of micro mirror array OVDs provides an opportunity for directly printing the OVD microstructure onto the security document in-line with the normal printing process. The micro mirror array OVD architecture therefore eliminates the need for hot stamping foil as the carrier of the OVD information, thereby reducing costs. The origination of micro mirror array devices via a palette based data format and a combination electron beam lithography and photolithography techniques is discussed via an artwork example and experimental tests. Finally the application of the technology to the design of a generic class of devices which have the interesting property of allowing for both application and customer specific OVD image encoding and data encoding at the end user stage of production is described. Because of the end user nature of the image and data encoding process these devices are particularly well suited to ID document applications and for this reason we refer this new OVD concept as biometric OVD technology.

Genome-wide comparison of paired fresh frozen and formalin-fixed paraffin-embedded gliomas by custom BAC and oligonucleotide array comparative genomic hybridization: facilitating analysis of archival gliomas.

PubMed

Mohapatra, Gayatry; Engler, David A; Starbuck, Kristen D; Kim, James C; Bernay, Derek C; Scangas, George A; Rousseau, Audrey; Batchelor, Tracy T; Betensky, Rebecca A; Louis, David N

2011-04-01

Array comparative genomic hybridization (aCGH) is a powerful tool for detecting DNA copy number alterations (CNA). Because diffuse malignant gliomas are often sampled by small biopsies, formalin-fixed paraffin-embedded (FFPE) blocks are often the only tissue available for genetic analysis; FFPE tissues are also needed to study the intratumoral heterogeneity that characterizes these neoplasms. In this paper, we present a combination of evaluations and technical advances that provide strong support for the ready use of oligonucleotide aCGH on FFPE diffuse gliomas. We first compared aCGH using bacterial artificial chromosome (BAC) arrays in 45 paired frozen and FFPE gliomas, and demonstrate a high concordance rate between FFPE and frozen DNA in an individual clone-level analysis of sensitivity and specificity, assuring that under certain array conditions, frozen and FFPE DNA can perform nearly identically. However, because oligonucleotide arrays offer advantages to BAC arrays in genomic coverage and practical availability, we next developed a method of labeling DNA from FFPE tissue that allows efficient hybridization to oligonucleotide arrays. To demonstrate utility in FFPE tissues, we applied this approach to biphasic anaplastic oligoastrocytomas and demonstrate CNA differences between DNA obtained from the two components. Therefore, BAC and oligonucleotide aCGH can be sensitive and specific tools for detecting CNAs in FFPE DNA, and novel labeling techniques enable the routine use of oligonucleotide arrays for FFPE DNA. In combination, these advances should facilitate genome-wide analysis of rare, small and/or histologically heterogeneous gliomas from FFPE tissues.

Accuracy of genotype imputation in Swiss cattle breeds

USDA-ARS?s Scientific Manuscript database

The objective of this study was to evaluate the accuracy of imputation from Illumina Bovine3k Bead Chip (3k) and Illumina BovineLD (6k) to 54k chip information in Swiss dairy cattle breeds. Genotype data comprised of 54k SNP chip data of Original Braunvieh (OB), Brown Swiss (BS), Swiss Fleckvieh (SF...

Illumina sequencing of green stink bug nymph and adult cdna to identify potential rnai gene targets

USDA-ARS?s Scientific Manuscript database

Whole-body transcriptomes for nymphs and adults of the green stink bug, Acrosternum hilare (Say), were sequenced on an Illumina® Genome Analyzer IIx sequencer. The insects were collected from sites in North Carolina and Virginia, USA. The cDNA library for each sample was sequenced on one lane of an...

Haematobia irritans dataset of raw sequence reads from Illumina-based transcriptome sequencing of specific tissues and life stages

USDA-ARS?s Scientific Manuscript database

Illumina HiSeq technology was used to sequence the transcriptome from various dissected tissues and life stages from the horn fly, Haematobia irritans. These samples include eggs (0, 2, 4, and 9 hours post-oviposition), adult fly gut, adult fly legs, adult fly malpighian tubule, adult fly ovary, adu...

New features to the night sky radiance model illumina: Hyperspectral support, improved obstacles and cloud reflection

NASA Astrophysics Data System (ADS)

Aubé, M.; Simoneau, A.

2018-05-01

Illumina is one of the most physically detailed artificial night sky brightness model to date. It has been in continuous development since 2005 [1]. In 2016-17, many improvements were made to the Illumina code including an overhead cloud scheme, an improved blocking scheme for subgrid obstacles (trees and buildings), and most importantly, a full hyperspectral modeling approach. Code optimization resulted in significant reduction in execution time enabling users to run the model on standard personal computers for some applications. After describing the new schemes introduced in the model, we give some examples of applications for a peri-urban and a rural site both located inside the International Dark Sky reserve of Mont-Mégantic (QC, Canada).

ANTS — a simulation package for secondary scintillation Anger-camera type detector in thermal neutron imaging

NASA Astrophysics Data System (ADS)

Morozov, A.; Defendi, I.; Engels, R.; Fraga, F. A. F.; Fraga, M. M. F. R.; Guerard, B.; Jurkovic, M.; Kemmerling, G.; Manzin, G.; Margato, L. M. S.; Niko, H.; Pereira, L.; Petrillo, C.; Peyaud, A.; Piscitelli, F.; Raspino, D.; Rhodes, N. J.; Sacchetti, F.; Schooneveld, E. M.; Van Esch, P.; Zeitelhack, K.

2012-08-01

A custom and fully interactive simulation package ANTS (Anger-camera type Neutron detector: Toolkit for Simulations) has been developed to optimize the design and operation conditions of secondary scintillation Anger-camera type gaseous detectors for thermal neutron imaging. The simulation code accounts for all physical processes related to the neutron capture, energy deposition pattern, drift of electrons of the primary ionization and secondary scintillation. The photons are traced considering the wavelength-resolved refraction and transmission of the output window. Photo-detection accounts for the wavelength-resolved quantum efficiency, angular response, area sensitivity, gain and single-photoelectron spectra of the photomultipliers (PMTs). The package allows for several geometrical shapes of the PMT photocathode (round, hexagonal and square) and offers a flexible PMT array configuration: up to 100 PMTs in a custom arrangement with the square or hexagonal packing. Several read-out patterns of the PMT array are implemented. Reconstruction of the neutron capture position (projection on the plane of the light emission) is performed using the center of gravity, maximum likelihood or weighted least squares algorithm. Simulation results reproduce well the preliminary results obtained with a small-scale detector prototype. ANTS executables can be downloaded from http://coimbra.lip.pt/~andrei/.

High-power LED package requirements

NASA Astrophysics Data System (ADS)

Wall, Frank; Martin, Paul S.; Harbers, Gerard

2004-01-01

Power LEDs have evolved from simple indicators into illumination devices. For general lighting applications, where the objective is to light up an area, white LED arrays have been utilized to serve that function. Cost constraints will soon drive the industry to provide a discrete lighting solution. Early on, that will mean increasing the power densities while quantum efficiencies are addressed. For applications such as automotive headlamps & projection, where light needs to be tightly collimated, or controlled, arrays of die or LEDs will not be able to satisfy the requirements & limitations defined by etendue. Ultimately, whether a luminaire requires a small source with high luminance, or light spread over a general area, economics will force the evolution of the illumination LED into a compact discrete high power package. How the customer interfaces with this new package should be an important element considered early on in the design cycle. If an LED footprint of adequate size is not provided, it may prove impossible for the customer, or end user, to get rid of the heat in a manner sufficient to prevent premature LED light output degradation. Therefore it is critical, for maintaining expected LED lifetime & light output, that thermal performance parameters be defined, by design, at the system level, which includes heat sinking methods & interface materials or methdology.

A small, portable, battery-powered brain-computer interface system for motor rehabilitation.

PubMed

McCrimmon, Colin M; Ming Wang; Silva Lopes, Lucas; Wang, Po T; Karimi-Bidhendi, Alireza; Liu, Charles Y; Heydari, Payam; Nenadic, Zoran; Do, An H

2016-08-01

Motor rehabilitation using brain-computer interface (BCI) systems may facilitate functional recovery in individuals after stroke or spinal cord injury. Nevertheless, these systems are typically ill-suited for widespread adoption due to their size, cost, and complexity. In this paper, a small, portable, and extremely cost-efficient (<;$200) BCI system has been developed using a custom electroencephalographic (EEG) amplifier array, and a commercial microcontroller and touchscreen. The system's performance was tested using a movement-related BCI task in 3 able-bodied subjects with minimal previous BCI experience. Specifically, subjects were instructed to alternate between relaxing and dorsiflexing their right foot, while their EEG was acquired and analyzed in real-time by the BCI system to decode their underlying movement state. The EEG signals acquired by the custom amplifier array were similar to those acquired by a commercial amplifier (maximum correlation coefficient ρ=0.85). During real-time BCI operation, the average correlation between instructional cues and decoded BCI states across all subjects (ρ=0.70) was comparable to that of full-size BCI systems. Small, portable, and inexpensive BCI systems such as the one reported here may promote a widespread adoption of BCI-based movement rehabilitation devices in stroke and spinal cord injury populations.

In vivo operation of the Boston 15-channel wireless subretinal visual prosthesis

NASA Astrophysics Data System (ADS)

Shire, Douglas B.; Doyle, Patrick; Kelly, Shawn K.; Gingerich, Marcus D.; Chen, Jinghua; Cogan, Stuart F.; Drohan, William A.; Mendoza, Oscar; Theogarajan, Luke; Wyatt, John; Rizzo, Joseph F.

2010-02-01

This presentation concerns the engineering development of the Boston visual prosthesis for restoring useful vision to patients blind with degenerative retinal disease. A miniaturized, hermetically-encased, 15-channel wirelessly-operated retinal prosthetic was developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array having sputtered iridium oxide electrodes. This array is implanted into the subretinal space using a specially-designed ab externo surgical technique; the bulk of the prosthesis is on the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip; secondary power/data receiving coils surround the cornea. Long-term in vitro pulse testing was also performed on the electrodes to ensure their stability over years of operation. Assemblies were first tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a computer with a custom graphical user interface. Operation of the retinal implant was verified in vivo in 3 minipigs for more than three months by measuring stimulus artifacts on the eye surface using contact lens electrodes.

Comparative analytical evaluation of the respiratory TaqMan Array Card with real-time PCR and commercial multi-pathogen assays.

PubMed

Harvey, John J; Chester, Stephanie; Burke, Stephen A; Ansbro, Marisela; Aden, Tricia; Gose, Remedios; Sciulli, Rebecca; Bai, Jing; DesJardin, Lucy; Benfer, Jeffrey L; Hall, Joshua; Smole, Sandra; Doan, Kimberly; Popowich, Michael D; St George, Kirsten; Quinlan, Tammy; Halse, Tanya A; Li, Zhen; Pérez-Osorio, Ailyn C; Glover, William A; Russell, Denny; Reisdorf, Erik; Whyte, Thomas; Whitaker, Brett; Hatcher, Cynthia; Srinivasan, Velusamy; Tatti, Kathleen; Tondella, Maria Lucia; Wang, Xin; Winchell, Jonas M; Mayer, Leonard W; Jernigan, Daniel; Mawle, Alison C

2016-02-01

In this study, a multicenter evaluation of the Life Technologies TaqMan(®) Array Card (TAC) with 21 custom viral and bacterial respiratory assays was performed on the Applied Biosystems ViiA™ 7 Real-Time PCR System. The goal of the study was to demonstrate the analytical performance of this platform when compared to identical individual pathogen specific laboratory developed tests (LDTs) designed at the Centers for Disease Control and Prevention (CDC), equivalent LDTs provided by state public health laboratories, or to three different commercial multi-respiratory panels. CDC and Association of Public Health Laboratories (APHL) LDTs had similar analytical sensitivities for viral pathogens, while several of the bacterial pathogen APHL LDTs demonstrated sensitivities one log higher than the corresponding CDC LDT. When compared to CDC LDTs, TAC assays were generally one to two logs less sensitive depending on the site performing the analysis. Finally, TAC assays were generally more sensitive than their counterparts in three different commercial multi-respiratory panels. TAC technology allows users to spot customized assays and design TAC layout, simplify assay setup, conserve specimen, dramatically reduce contamination potential, and as demonstrated in this study, analyze multiple samples in parallel with good reproducibility between instruments and operators. Copyright © 2015 Elsevier B.V. All rights reserved.

Variability-aware compact modeling and statistical circuit validation on SRAM test array

NASA Astrophysics Data System (ADS)

Qiao, Ying; Spanos, Costas J.

2016-03-01

Variability modeling at the compact transistor model level can enable statistically optimized designs in view of limitations imposed by the fabrication technology. In this work we propose a variability-aware compact model characterization methodology based on stepwise parameter selection. Transistor I-V measurements are obtained from bit transistor accessible SRAM test array fabricated using a collaborating foundry's 28nm FDSOI technology. Our in-house customized Monte Carlo simulation bench can incorporate these statistical compact models; and simulation results on SRAM writability performance are very close to measurements in distribution estimation. Our proposed statistical compact model parameter extraction methodology also has the potential of predicting non-Gaussian behavior in statistical circuit performances through mixtures of Gaussian distributions.

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Chauveau, J.; Del Buono, L.; Genat, J. F.; Lebbolo, H.; Roos, L.; Zhang, B.; Beigbeder, C.; Bernier, R.; Breton, D.; Caceres, T.; Chase, R.; Ducorps, A.; Hrisoho, A.; Imbert, P.; Sen, S.; Tocut, V.; Truong, K.; Wormser, G.; Zomer, F.; Bonneaud, G.; Dohou, F.; Gastaldi, F.; Matricon, P.; Renard, C.; Thiebaux, C.; Vasileiadis, G.; Verderi, M.; Oxoby, G.; Va'Vra, J.; Warner, D.; Wilson, R. J.

1999-08-01

The detector of Internally Reflected Cherenkov light (DIRC) of the BaBar detector (SLAC Stanford, USA) measures better than 1 ns the arrival time of Cherenkov photoelectrons, detected in a 11 000 phototubes array and their amplitude spectra. It mainly comprises of 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom Analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom Digital TDC chips for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected from up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test of the pre-production chips have been performed as well as system tests.

Mechanical Designs and Developement of Advanced ACT: A Transfomative Upgrade to the ACTPol Receiver on the Atacama Cosmology Telescope.

NASA Astrophysics Data System (ADS)

Ward, Jonathan; Advanced ACT Collaboration, NASA Space Technology Research Fellowship

2017-06-01

The Atacama Cosmology Telescope is a six-meter diameter telescope located at 17,000 feet (5,200 meters) on Cerro Toco in the Andes Mountains of northern Chile. The next generation Advanced ACT (AdvACT) experiment is currently underway and will consist of three multichroic TES bolometer arrays operating together, totaling 5800 detectors on the sky. Each array will be sensitive to two frequency bands: a high frequency (HF) array at 150 and 230 GHz, two middle frequency (MF) arrays at 90 and 150 GHz, and a low frequency (LF) array at 28 and 41 GHz. The AdACT detector arrays will feature a revamped design when compared to ACTPol, including a transition to 150mm wafers equipped with multichroic pixels, allowing for a more densely packed focal plane. Each set of detectors consists of a feedhorn array of stacked silicon wafers which form a corrugated profile leading to each pixel. This is then followed by a four-piece detector stack assembly of silicon wafers which includes a waveguide interface plate, detector wafer, backshort cavity plate, and backshort cap. Each array is housed in a custom designed structure manufactured out of gold-plated, high purity copper. In addition to the detector array assembly, the array package also encloses the majority of our readout electronics. We present the full mechanical design of the AdvACT HF and MF detector array packages along with a detailed look at the detector array assemblies. We also highlight the use of continuously rotating warm half-wave plates (HWPs) at the front of the AdvACT receiver. We review the design of the rotation system and also early pipeline data analysis results. This experiment will also make use of extensive hardware and software previously developed for ACT, which will be modified to incorporate the new AdvACT instruments. Therefore, we discuss the integration of all AdvACT instruments with pre-existing ACTPol infrastructure.

In vitro biocompatibility and electrical stability of thick-film platinum/gold alloy electrodes printed on alumina

NASA Astrophysics Data System (ADS)

Carnicer-Lombarte, Alejandro; Lancashire, Henry T.; Vanhoestenberghe, Anne

2017-06-01

Objective. High-density electrode arrays are a powerful tool in both clinical neuroscience and basic research. However, current manufacturing techniques require the use of specialised techniques and equipment, which are available to few labs. We have developed a high-density electrode array with customisable design, manufactured using simple printing techniques and with commercially available materials. Approach. Electrode arrays were manufactured by thick-film printing a platinum-gold alloy (Pt/Au) and an insulating dielectric on 96% alumina ceramic plates. Arrays were conditioned in serum and serum-free conditions, with and without 1 kHz, 200 µA, charge balanced stimulation for up to 21 d. Array biocompatibility was assessed using an extract assay and a PC-12 cell contact assay. Electrode impedance, charge storage capacity and charge injection capacity were before and after array conditioning. Main results. The manufactured Pt/Au electrodes have a highly porous surface and exhibit electrical properties comparable to arrays manufactured using alternative techniques. Materials used in array manufacture were found to be non-toxic to L929 fibroblasts by extract assay, and neuronal-like PC-12 cells adhered and extended neurites on the array surfaces. Arrays remained functional after long-term delivery of electrical pulses while exposed to protein-rich environments. Charge storage capacities and charge injection capacities increased following stimulation accounted for by an increase in surface index (real surface area) observed by vertical scanning interferometry. Further, we observed accumulation of proteins at the electrode sites following conditioning in the presence of serum. Significance. This study demonstrates the in vitro biocompatibility of commercially available thick-film printing materials. The printing technique is both simple and versatile, with layouts readily modified to produce customized electrode arrays. Thick-film electrode arrays are an attractive tool that may be implemented for general tissue engineering and neuroscience research.

Two Siblings with Alternate Unbalanced Recombinants Derived from a Large Cryptic Maternal Pericentric Inversion of Chromosome 20

PubMed Central

DeScipio, Cheryl; Morrissette, Jennifer J.D.; Conlin, Laura K.; Clark, Dinah; Kaur, Maninder; Coplan, James; Riethman, Harold; Spinner, Nancy B.; Krantz, Ian D.

2009-01-01

Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologues, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially-available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, ~900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, ~1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e. between RP11-93B14 and proximal BAC RP11-765G16). PMID:20101690

Two siblings with alternate unbalanced recombinants derived from a large cryptic maternal pericentric inversion of chromosome 20.

PubMed

Descipio, Cheryl; Morrissette, Jennifer D; Conlin, Laura K; Clark, Dinah; Kaur, Maninder; Coplan, James; Riethman, Harold; Spinner, Nancy B; Krantz, Ian D

2010-02-01

Two brothers, with dissimilar clinical features, were each found to have different abnormalities of chromosome 20 by subtelomere fluorescence in situ hybridization (FISH). The proband had deletion of 20p subtelomere and duplication of 20q subtelomere, while his brother was found to have a duplication of 20p subtelomere and deletion of 20q subtelomere. Parental cytogenetic studies were initially thought to be normal, both by G-banding and by subtelomere FISH analysis. Since chromosome 20 is a metacentric chromosome and an inversion was suspected, we used anchored FISH to assist in identifying a possible inversion. This approach employed concomitant hybridization of a FISH probe to the short (p) arm of chromosome 20 with the 20q subtelomere probe. We identified a cytogenetically non-visible, mosaic pericentric inversion of one of the maternal chromosome 20 homologs, providing a mechanistic explanation for the chromosomal abnormalities present in these brothers. Array comparative genomic hybridization (CGH) with both a custom-made BAC and cosmid-based subtelomere specific array (TEL array) and a commercially available SNP-based array confirmed and further characterized these rearrangements, identifying this as the largest pericentric inversion of chromosome 20 described to date. TEL array data indicate that the 20p breakpoint is defined by BAC RP11-978M13, approximately 900 kb from the pter; SNP array data reveal this breakpoint to occur within BAC RP11-978M13. The 20q breakpoint is defined by BAC RP11-93B14, approximately 1.7 Mb from the qter, by TEL array; SNP array data refine this breakpoint to within a gap between BACs on the TEL array (i.e., between RP11-93B14 and proximal BAC RP11-765G16). Copyright 2010 Wiley-Liss, Inc.

A common variant near TGFBR3 is associated with primary open angle glaucoma.

PubMed

Li, Zheng; Allingham, R Rand; Nakano, Masakazu; Jia, Liyun; Chen, Yuhong; Ikeda, Yoko; Mani, Baskaran; Chen, Li-Jia; Kee, Changwon; Garway-Heath, David F; Sripriya, Sarangapani; Fuse, Nobuo; Abu-Amero, Khaled K; Huang, Chukai; Namburi, Prasanthi; Burdon, Kathryn; Perera, Shamira A; Gharahkhani, Puya; Lin, Ying; Ueno, Morio; Ozaki, Mineo; Mizoguchi, Takanori; Krishnadas, Subbiah Ramasamy; Osman, Essam A; Lee, Mei Chin; Chan, Anita S Y; Tajudin, Liza-Sharmini A; Do, Tan; Goncalves, Aurelien; Reynier, Pascal; Zhang, Hong; Bourne, Rupert; Goh, David; Broadway, David; Husain, Rahat; Negi, Anil K; Su, Daniel H; Ho, Ching-Lin; Blanco, Augusto Azuara; Leung, Christopher K S; Wong, Tina T; Yakub, Azhany; Liu, Yutao; Nongpiur, Monisha E; Han, Jong Chul; Hon, Do Nhu; Shantha, Balekudaru; Zhao, Bowen; Sang, Jinghong; Zhang, NiHong; Sato, Ryuichi; Yoshii, Kengo; Panda-Jonas, Songhomita; Ashley Koch, Allison E; Herndon, Leon W; Moroi, Sayoko E; Challa, Pratap; Foo, Jia Nee; Bei, Jin-Xin; Zeng, Yi-Xin; Simmons, Cameron P; Bich Chau, Tran Nguyen; Sharmila, Philomenadin Ferdinamarie; Chew, Merwyn; Lim, Blanche; Tam, Pansy O S; Chua, Elaine; Ng, Xiao Yu; Yong, Victor H K; Chong, Yaan Fun; Meah, Wee Yang; Vijayan, Saravanan; Seongsoo, Sohn; Xu, Wang; Teo, Yik Ying; Cooke Bailey, Jessica N; Kang, Jae H; Haines, Jonathan L; Cheng, Ching Yu; Saw, Seang-Mei; Tai, E-Shyong; Richards, Julia E; Ritch, Robert; Gaasterland, Douglas E; Pasquale, Louis R; Liu, Jianjun; Jonas, Jost B; Milea, Dan; George, Ronnie; Al-Obeidan, Saleh A; Mori, Kazuhiko; Macgregor, Stuart; Hewitt, Alex W; Girkin, Christopher A; Zhang, Mingzhi; Sundaresan, Periasamy; Vijaya, Lingam; Mackey, David A; Wong, Tien Yin; Craig, Jamie E; Sun, Xinghuai; Kinoshita, Shigeru; Wiggs, Janey L; Khor, Chiea-Chuen; Yang, Zhenglin; Pang, Chi Pui; Wang, Ningli; Hauser, Michael A; Tashiro, Kei; Aung, Tin; Vithana, Eranga N

2015-07-01

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10(-33)), we observed one SNP showing significant association to POAG (CDC7-TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10(-8)). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis. © The Author 2015. Published by Oxford University Press.

A common variant near TGFBR3 is associated with primary open angle glaucoma

PubMed Central

Li, Zheng; Allingham, R. Rand; Nakano, Masakazu; Jia, Liyun; Chen, Yuhong; Ikeda, Yoko; Mani, Baskaran; Chen, Li-Jia; Kee, Changwon; Garway-Heath, David F.; Sripriya, Sarangapani; Fuse, Nobuo; Abu-Amero, Khaled K.; Huang, Chukai; Namburi, Prasanthi; Burdon, Kathryn; Perera, Shamira A.; Gharahkhani, Puya; Lin, Ying; Ueno, Morio; Ozaki, Mineo; Mizoguchi, Takanori; Krishnadas, Subbiah Ramasamy; Osman, Essam A.; Lee, Mei Chin; Chan, Anita S.Y.; Tajudin, Liza-Sharmini A.; Do, Tan; Goncalves, Aurelien; Reynier, Pascal; Zhang, Hong; Bourne, Rupert; Goh, David; Broadway, David; Husain, Rahat; Negi, Anil K.; Su, Daniel H; Ho, Ching-Lin; Blanco, Augusto Azuara; Leung, Christopher K.S.; Wong, Tina T.; Yakub, Azhany; Liu, Yutao; Nongpiur, Monisha E.; Han, Jong Chul; Hon, Do Nhu; Shantha, Balekudaru; Zhao, Bowen; Sang, Jinghong; Zhang, NiHong; Sato, Ryuichi; Yoshii, Kengo; Panda-Jonas, Songhomita; Ashley Koch, Allison E.; Herndon, Leon W.; Moroi, Sayoko E.; Challa, Pratap; Foo, Jia Nee; Bei, Jin-Xin; Zeng, Yi-Xin; Simmons, Cameron P.; Bich Chau, Tran Nguyen; Sharmila, Philomenadin Ferdinamarie; Chew, Merwyn; Lim, Blanche; Tam, Pansy O.S.; Chua, Elaine; Ng, Xiao Yu; Yong, Victor H.K.; Chong, Yaan Fun; Meah, Wee Yang; Vijayan, Saravanan; Seongsoo, Sohn; Xu, Wang; Teo, Yik Ying; Cooke Bailey, Jessica N.; Kang, Jae H.; Haines, Jonathan L.; Cheng, Ching Yu; Saw, Seang-Mei; Tai, E-Shyong; Richards, Julia E.; Ritch, Robert; Gaasterland, Douglas E.; Pasquale, Louis R.; Liu, Jianjun; Jonas, Jost B.; Milea, Dan; George, Ronnie; Al-Obeidan, Saleh A.; Mori, Kazuhiko; Macgregor, Stuart; Hewitt, Alex W.; Girkin, Christopher A.; Zhang, Mingzhi; Sundaresan, Periasamy; Vijaya, Lingam; Mackey, David A.; Wong, Tien Yin; Craig, Jamie E.; Sun, Xinghuai; Kinoshita, Shigeru; Wiggs, Janey L.; Khor, Chiea-Chuen; Yang, Zhenglin; Pang, Chi Pui; Wang, Ningli; Hauser, Michael A.; Tashiro, Kei; Aung, Tin; Vithana, Eranga N.

2015-01-01

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis. PMID:25861811

Ancestry Informative Marker Sets for Determining Continental Origin and Admixture Proportions in Common Populations in America

PubMed Central

Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M.; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E.; Gregersen, Peter K.; Belmont, John W.; De La Vega, Francisco M.; Seldin, Michael F.

2011-01-01

To provide a resource for assessing continental ancestry in a wide variety of genetic studies we identified, validated and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan® assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations. PMID:18683858

A 32 x 32 capacitive micromachined ultrasonic transducer array manufactured in standard CMOS.

PubMed

Lemmerhirt, David F; Cheng, Xiaoyang; White, Robert; Rich, Collin A; Zhang, Man; Fowlkes, J Brian; Kripfgans, Oliver D

2012-07-01

As ultrasound imagers become increasingly portable and lower cost, breakthroughs in transducer technology will be needed to provide high-resolution, real-time 3-D imaging while maintaining the affordability needed for portable systems. This paper presents a 32 x 32 ultrasound array prototype, manufactured using a CMUT-in-CMOS approach whereby ultrasonic transducer elements and readout circuits are integrated on a single chip using a standard integrated circuit manufacturing process in a commercial CMOS foundry. Only blanket wet-etch and sealing steps are added to complete the MEMS devices after the CMOS process. This process typically yields better than 99% working elements per array, with less than ±1.5 dB variation in receive sensitivity among the 1024 individually addressable elements. The CMUT pulseecho frequency response is typically centered at 2.1 MHz with a -6 dB fractional bandwidth of 60%, and elements are arranged on a 250 μm hexagonal grid (less than half-wavelength pitch). Multiplexers and CMOS buffers within the array are used to make on-chip routing manageable, reduce the number of physical output leads, and drive the transducer cable. The array has been interfaced to a commercial imager as well as a set of custom transmit and receive electronics, and volumetric images of nylon fishing line targets have been produced.

A z-gradient array for simultaneous multi-slice excitation with a single-band RF pulse.

PubMed

Ertan, Koray; Taraghinia, Soheil; Sadeghi, Alireza; Atalar, Ergin

2018-07-01

Multi-slice radiofrequency (RF) pulses have higher specific absorption rates, more peak RF power, and longer pulse durations than single-slice RF pulses. Gradient field design techniques using a z-gradient array are investigated for exciting multiple slices with a single-band RF pulse. Two different field design methods are formulated to solve for the required current values of the gradient array elements for the given slice locations. The method requirements are specified, optimization problems are formulated for the minimum current norm and an analytical solution is provided. A 9-channel z-gradient coil array driven by independent, custom-designed gradient amplifiers is used to validate the theory. Performance measures such as normalized slice thickness error, gradient strength per unit norm current, power dissipation, and maximum amplitude of the magnetic field are provided for various slice locations and numbers of slices. Two and 3 slices are excited by a single-band RF pulse in simulations and phantom experiments. The possibility of multi-slice excitation with a single-band RF pulse using a z-gradient array is validated in simulations and phantom experiments. Magn Reson Med 80:400-412, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Robust Sub-nanomolar Library Preparation for High Throughput Next Generation Sequencing.

PubMed

Wu, Wells W; Phue, Je-Nie; Lee, Chun-Ting; Lin, Changyi; Xu, Lai; Wang, Rong; Zhang, Yaqin; Shen, Rong-Fong

2018-05-04

Current library preparation protocols for Illumina HiSeq and MiSeq DNA sequencers require ≥2 nM initial library for subsequent loading of denatured cDNA onto flow cells. Such amounts are not always attainable from samples having a relatively low DNA or RNA input; or those for which a limited number of PCR amplification cycles is preferred (less PCR bias and/or more even coverage). A well-tested sub-nanomolar library preparation protocol for Illumina sequencers has however not been reported. The aim of this study is to provide a much needed working protocol for sub-nanomolar libraries to achieve outcomes as informative as those obtained with the higher library input (≥ 2 nM) recommended by Illumina's protocols. Extensive studies were conducted to validate a robust sub-nanomolar (initial library of 100 pM) protocol using PhiX DNA (as a control), genomic DNA (Bordetella bronchiseptica and microbial mock community B for 16S rRNA gene sequencing), messenger RNA, microRNA, and other small noncoding RNA samples. The utility of our protocol was further explored for PhiX library concentrations as low as 25 pM, which generated only slightly fewer than 50% of the reads achieved under the standard Illumina protocol starting with > 2 nM. A sub-nanomolar library preparation protocol (100 pM) could generate next generation sequencing (NGS) results as robust as the standard Illumina protocol. Following the sub-nanomolar protocol, libraries with initial concentrations as low as 25 pM could also be sequenced to yield satisfactory and reproducible sequencing results.

Evaluation of Multiplexed 16S rRNA Microbial Population Surveys Using Illumina MiSeq Platform (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

ScienceCinema

Tremblay, Julien

2018-01-22

Julien Tremblay from DOE JGI presents "Evaluation of Multiplexed 16S rRNA Microbial Population Surveys Using Illumina MiSeq Platorm" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

Evaluation of Multiplexed 16S rRNA Microbial Population Surveys Using Illumina MiSeq Platform (Seventh Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting 2012)

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

Tremblay, Julien

2012-06-01

Julien Tremblay from DOE JGI presents "Evaluation of Multiplexed 16S rRNA Microbial Population Surveys Using Illumina MiSeq Platorm" at the 7th Annual Sequencing, Finishing, Analysis in the Future (SFAF) Meeting held in June, 2012 in Santa Fe, NM.

Design of the Illumina Porcine 50K+ SNP Iselect(TM) Beadchip and Characterization of the Porcine HapMap Population

USDA-ARS?s Scientific Manuscript database

Using next generation sequencing technology the International Swine SNP Consortium has identified 500,000 SNPs and used these to design an Illumina Infinium iSelect™ SNP BeadChip with a selection of 60,218 SNPs. The selected SNPs include previously validated SNPs and SNPs identified de novo using se...

Evaluation of Different Normalization and Analysis Procedures for Illumina Gene Expression Microarray Data Involving Small Changes

PubMed Central

Johnstone, Daniel M.; Riveros, Carlos; Heidari, Moones; Graham, Ross M.; Trinder, Debbie; Berretta, Regina; Olynyk, John K.; Scott, Rodney J.; Moscato, Pablo; Milward, Elizabeth A.

2013-01-01

While Illumina microarrays can be used successfully for detecting small gene expression changes due to their high degree of technical replicability, there is little information on how different normalization and differential expression analysis strategies affect outcomes. To evaluate this, we assessed concordance across gene lists generated by applying different combinations of normalization strategy and analytical approach to two Illumina datasets with modest expression changes. In addition to using traditional statistical approaches, we also tested an approach based on combinatorial optimization. We found that the choice of both normalization strategy and analytical approach considerably affected outcomes, in some cases leading to substantial differences in gene lists and subsequent pathway analysis results. Our findings suggest that important biological phenomena may be overlooked when there is a routine practice of using only one approach to investigate all microarray datasets. Analytical artefacts of this kind are likely to be especially relevant for datasets involving small fold changes, where inherent technical variation—if not adequately minimized by effective normalization—may overshadow true biological variation. This report provides some basic guidelines for optimizing outcomes when working with Illumina datasets involving small expression changes. PMID:27605185

Reduced-vibration tube array

DOEpatents

Bruck, Gerald J.; Bartolomeo, Daniel R.

2004-07-20

A reduced-vibration tube array is disclosed. The array includes a plurality of tubes in a fixed arrangement and a plurality of damping members positioned within the tubes. The damping members include contoured interface regions characterized by bracing points that selectively contact the inner surface of an associated tube. Each interface region is sized and shaped in accordance with the associated tube, so that the damping member bracing points are spaced apart a vibration-reducing distance from the associated tube inner surfaces at equilibrium. During operation, mechanical interaction between the bracing points and the tube inner surfaces reduces vibration by a damage-reducing degree. In one embodiment, the interface regions are serpentine shaped. In another embodiment, the interface regions are helical in shape. The interface regions may be simultaneously helical and serpentine in shape. The damping members may be fixed within the associated tubes, and damping member may be customized several interference regions having attributes chosen in accordance with desired flow characteristics and associated tube properties.

Compact multispectral photodiode arrays using micropatterned dichroic filters

NASA Astrophysics Data System (ADS)

Chandler, Eric V.; Fish, David E.

2014-05-01

The next generation of multispectral instruments requires significant improvements in both spectral band customization and portability to support the widespread deployment of application-specific optical sensors. The benefits of spectroscopy are well established for numerous applications including biomedical instrumentation, industrial sorting and sensing, chemical detection, and environmental monitoring. In this paper, spectroscopic (and by extension hyperspectral) and multispectral measurements are considered. The technology, tradeoffs, and application fits of each are evaluated. In the majority of applications, monitoring 4-8 targeted spectral bands of optimized wavelength and bandwidth provides the necessary spectral contrast and correlation. An innovative approach integrates precision spectral filters at the photodetector level to enable smaller sensors, simplify optical designs, and reduce device integration costs. This method supports user-defined spectral bands to create application-specific sensors in a small footprint with scalable cost efficiencies. A range of design configurations, filter options and combinations are presented together with typical applications ranging from basic multi-band detection to stringent multi-channel fluorescence measurement. An example implementation packages 8 narrowband silicon photodiodes into a 9x9mm ceramic LCC (leadless chip carrier) footprint. This package is designed for multispectral applications ranging from portable color monitors to purpose- built OEM industrial and scientific instruments. Use of an eight-channel multispectral photodiode array typically eliminates 10-20 components from a device bill-of-materials (BOM), streamlining the optical path and shrinking the footprint by 50% or more. A stepwise design approach for multispectral sensors is discussed - including spectral band definition, optical design tradeoffs and constraints, and device integration from prototype through scalable volume production. Additional customization options are explored for application-specific OEM sensors integrated into portable devices using multispectral photodiode arrays.

Aerosol sampling system for collection of Capstone depleted uranium particles in a high-energy environment.

PubMed

Holmes, Thomas D; Guilmette, Raymond A; Cheng, Yung Sung; Parkhurst, Mary Ann; Hoover, Mark D

2009-03-01

The Capstone Depleted Uranium (DU) Aerosol Study was undertaken to obtain aerosol samples resulting from a large-caliber DU penetrator striking an Abrams or Bradley test vehicle. The sampling strategy was designed to (1) optimize the performance of the samplers and maintain their integrity in the extreme environment created during perforation of an armored vehicle by a DU penetrator, (2) collect aerosols as a function of time post perforation, and (3) obtain size-classified samples for analysis of chemical composition, particle morphology, and solubility in lung fluid. This paper describes the experimental setup and sampling methodologies used to achieve these objectives. Custom-designed arrays of sampling heads were secured to the inside of the target in locations approximating the breathing zones of the crew locations in the test vehicles. Each array was designed to support nine filter cassettes and nine cascade impactors mounted with quick-disconnect fittings. Shielding and sampler placement strategies were used to minimize sampler loss caused by the penetrator impact and the resulting fragments of eroded penetrator and perforated armor. A cyclone train was used to collect larger quantities of DU aerosol for measurement of chemical composition and solubility. A moving filter sample was used to obtain semicontinuous samples for DU concentration determination. Control for the air samplers was provided by five remotely located valve control and pressure monitoring units located inside and around the test vehicle. These units were connected to a computer interface chassis and controlled using a customized LabVIEW engineering computer control program. The aerosol sampling arrays and control systems for the Capstone study provided the needed aerosol samples for physicochemical analysis, and the resultant data were used for risk assessment of exposure to DU aerosol.

Aerosol Sampling System for Collection of Capstone Depleted Uranium Particles in a High-Energy Environment

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

Holmes, Thomas D.; Guilmette, Raymond A.; Cheng, Yung-Sung

2009-03-01

The Capstone Depleted Uranium Aerosol Study was undertaken to obtain aerosol samples resulting from a kinetic-energy cartridge with a large-caliber depleted uranium (DU) penetrator striking an Abrams or Bradley test vehicle. The sampling strategy was designed to (1) optimize the performance of the samplers and maintain their integrity in the extreme environment created during perforation of an armored vehicle by a DU penetrator, (2) collect aerosols as a function of time post-impact, and (3) obtain size-classified samples for analysis of chemical composition, particle morphology, and solubility in lung fluid. This paper describes the experimental setup and sampling methodologies used tomore » achieve these objectives. Custom-designed arrays of sampling heads were secured to the inside of the target in locations approximating the breathing zones of the vehicle commander, loader, gunner, and driver. Each array was designed to support nine filter cassettes and nine cascade impactors mounted with quick-disconnect fittings. Shielding and sampler placement strategies were used to minimize sampler loss caused by the penetrator impact and the resulting fragments of eroded penetrator and perforated armor. A cyclone train was used to collect larger quantities of DU aerosol for chemical composition and solubility. A moving filter sample was used to obtain semicontinuous samples for depleted uranium concentration determination. Control for the air samplers was provided by five remotely located valve control and pressure monitoring units located inside and around the test vehicle. These units were connected to a computer interface chassis and controlled using a customized LabVIEW engineering computer control program. The aerosol sampling arrays and control systems for the Capstone study provided the needed aerosol samples for physicochemical analysis, and the resultant data were used for risk assessment of exposure to DU aerosol.« less

A Multipurpose CMOS Platform for Nanosensing

PubMed Central

Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L.; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

2016-01-01

This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μm × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW–229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus. PMID:27916911

A Multipurpose CMOS Platform for Nanosensing.

PubMed

Bonanno, Alberto; Sanginario, Alessandro; Marasso, Simone L; Miccoli, Beatrice; Bejtka, Katarzyna; Benetto, Simone; Demarchi, Danilo

2016-11-30

This paper presents a customizable sensing system based on functionalized nanowires (NWs) assembled onto complementary metal oxide semiconductor (CMOS) technology. The Micro-for-Nano (M4N) chip integrates on top of the electronics an array of aluminum microelectrodes covered with gold by means of a customized electroless plating process. The NW assembly process is driven by an array of on-chip dielectrophoresis (DEP) generators, enabling a custom layout of different nanosensors on the same microelectrode array. The electrical properties of each assembled NW are singularly sensed through an in situ CMOS read-out circuit (ROC) that guarantees a low noise and reliable measurement. The M4N chip is directly connected to an external microcontroller for configuration and data processing. The processed data are then redirected to a workstation for real-time data visualization and storage during sensing experiments. As proof of concept, ZnO nanowires have been integrated onto the M4N chip to validate the approach that enables different kind of sensing experiments. The device has been then irradiated by an external UV source with adjustable power to measure the ZnO sensitivity to UV-light exposure. A maximum variation of about 80% of the ZnO-NW resistance has been detected by the M4N system when the assembled 5 μ m × 500 nm single ZnO-NW is exposed to an estimated incident radiant UV-light flux in the range of 1 nW-229 nW. The performed experiments prove the efficiency of the platform conceived for exploiting any kind of material that can change its capacitance and/or resistance due to an external stimulus.

Design of a Custom RT-qPCR Array for Assignment of Abiotic Stress Tolerance in Traditional Portuguese Grapevine Varieties

PubMed Central

Carvalho, Luísa C.; Silva, Marília; Coito, João L.; Rocheta, Margarida P.; Amâncio, Sara

2017-01-01

Widespread agricultural losses attributed to drought, often combined with high temperatures, frequently occur in the field, namely in Mediterranean climate areas, where the existing scenarios for climate change indicate an increase in the frequency of heat waves and severe drought events in summer. Grapevine (Vitis vinifera L.) is the most cultivated fruit species in the world and the most valuable one and is a traditional Mediterranean species. Currently, viticulture must adjust to impending climate changes that are already pushing vine-growers toward the use of ancient and resilient varieties. Portugal is very rich in grapevine biodiversity, however, currently, 90% of the total producing area is planted with only 16 varieties. There is a pressing need to understand the existing genetic diversity and the physiological potential of the varieties/genotypes available to be able to respond to climate changes. With the above scenario in mind, an assembly of 65 differentially expresses genes (DEGs) previously identified as responsive to abiotic stresses in two well studied genotypes, ‘Touriga Nacional’ and ‘Trincadeira,’ was designed to scan the gene expression of leaf samples from 10 traditional Portuguese varieties growing in two regions with distinct environmental conditions. Forty-five of those DEGs proved to be associated to “abiotic stress” and were chosen to build a custom qPCR array to identify uncharacterized genotypes as sensitive or tolerant to abiotic stress. According to the experimental set-up behind the array design these DEGs can also be used as indicators of the main abiotic stress that the plant is subjected and responding to (drought, heat, or excess light). PMID:29118776

Experimental study of a depth-encoding PET detector inserting horizontal-striped glass between crystal layers

NASA Astrophysics Data System (ADS)

Yang, J.; Kim, K. B.; Choi, Y.; Kang, J.

2018-04-01

A depth-encoding positron emission tomography (PET) detector inserting a horizontal-striped glass between pixilated scintillation crystal layers was developed and experimentally evaluated. The detector consists of 2-layers of 4×4 LYSO array arranged with a 3.37 mm pitch. Horizontal-striped glasses with 1×4 array with different thickness of 3, 4 and 5 mm were inserted between top- and bottom-crystal layers. Bottom surface of bottom-layer was optically coupled to a 4×4 GAPD array. Sixteen output signals from DOI-PET detector were multiplexed by modified resistive charge division (RCD) networks and multiplexed signals were fed into custom-made charge-sensitive preamplifiers. The four amplified signals were digitized and recorded by the custom-made DAQ system based on FPGA. The four digitized outputs were post-processed and converted to flood histograms for each interaction event. Experimental results revealed that all crystal pixels were clearly identified on the 2D flood histogram without overlapping. Patterns of the 2D flood histogram were constituted with arrangements of [bottom–top–bottom–top–\\ldots–top–bottom–top–bottom] crystal responses in X-direction. These could be achieved by employing horizontal-striped glass that controlled the extent of light dispersion towards the X-direction in crystal layers for generation of a different position mapping for each layer and the modified RCD network that controls degree of charge sharing in readout electronics for reduction of identification error. This study demonstrated the proposed DOI-PET detector can extract the 3D γ-ray interaction position without considerable performance degradation of PET detector from the 2D flood histogram.

A Customized Quantitative PCR MicroRNA Panel Provides a Technically Robust Context for Studying Neurodegenerative Disease Biomarkers and Indicates a High Correlation Between Cerebrospinal Fluid and Choroid Plexus MicroRNA Expression.

PubMed

Wang, Wang-Xia; Fardo, David W; Jicha, Gregory A; Nelson, Peter T

2017-12-01

MicroRNA (miRNA) expression varies in association with different tissue types and in diseases. Having been found in body fluids including blood and cerebrospinal fluid (CSF), miRNAs constitute potential biomarkers. CSF miRNAs have been proposed as biomarkers for neurodegenerative diseases; however, there is a lack of consensus about the best candidate miRNA biomarkers and there has been variability in results from different research centers, perhaps due to technical factors. Here, we sought to optimize technical parameters for CSF miRNA studies. We examined different RNA isolation methods and performed miRNA expression profiling with TaqMan® miRNA Arrays. More specifically, we developed a customized CSF-miRNA low-density array (TLDA) panel that contains 47 targets: miRNAs shown previously to be relevant to neurodegenerative disease, miRNAs that are abundant in CSF, data normalizers, and controls for potential blood and tissue contamination. The advantages of using this CSF-miRNA TLDA panel include specificity, sensitivity, fast processing and data analysis, and cost effectiveness. We optimized technical parameters for this assay. Further, the TLDA panel can be tailored to other specific purposes. We tested whether the profile of miRNAs in the CSF resembled miRNAs isolated from brain tissue (hippocampus or cerebellum), blood, or the choroid plexus. We found that the CSF miRNA expression profile most closely resembles that of choroid plexus tissue, underscoring the potential importance of choroid plexus-derived signaling through CSF miRNAs. In summary, the TLDA miRNA array panel will enable evaluation and discovery of CSF miRNA biomarkers and can potentially be utilized in clinical diagnosis and disease stage monitoring.

Design of a Customized Multipurpose Nano-Enabled Implantable System for In-Vivo Theranostics

PubMed Central

Juanola-Feliu, Esteve; Miribel-Català, Pere Ll.; Páez Avilés, Cristina; Colomer-Farrarons, Jordi; González-Piñero, Manel; Samitier, Josep

2014-01-01

The first part of this paper reviews the current development and key issues on implantable multi-sensor devices for in vivo theranostics. Afterwards, the authors propose an innovative biomedical multisensory system for in vivo biomarker monitoring that could be suitable for customized theranostics applications. At this point, findings suggest that cross-cutting Key Enabling Technologies (KETs) could improve the overall performance of the system given that the convergence of technologies in nanotechnology, biotechnology, micro&nanoelectronics and advanced materials permit the development of new medical devices of small dimensions, using biocompatible materials, and embedding reliable and targeted biosensors, high speed data communication, and even energy autonomy. Therefore, this article deals with new research and market challenges of implantable sensor devices, from the point of view of the pervasive system, and time-to-market. The remote clinical monitoring approach introduced in this paper could be based on an array of biosensors to extract information from the patient. A key contribution of the authors is that the general architecture introduced in this paper would require minor modifications for the final customized bio-implantable medical device. PMID:25325336

Requirements for a transformerless power conditioning system

NASA Technical Reports Server (NTRS)

Klein, J.; Koerner, T.; Rippel, W.; Kalbach, J.

1984-01-01

Requirements for development of a Transformerless Power Conditioning Subsystem (TPCS) that will meet utility, manufacturer, and customer needs are detailed. Issues analyzed include current utility guidelines, safety and grounding issues that appear as local codes, various kinds of TPCS connections that can be developed, dc injection, and a brief survey of TPCS circuit topologies that will meet requirements. The major result is that a finite time exists for control operation before dc injection into the distribution transformer causes customer outage (on the order of seconds). This time permits the control system to sense a dc injection condition and remove the TPCS from the utility system. Requirements for such a control system are specified. A three wire connection will ensure balanced operation for customer loads and two wire connections caused average value dc to be injected into single phase loads. This type of connection also allows for the lowest array voltage. The conclusion is that requirements for a TPCS can be determined and that there are not showstopping issues preventing implementation. The actual design and topology of the TPCS was left for further study.

Volumetric visualization algorithm development for an FPGA-based custom computing machine

NASA Astrophysics Data System (ADS)

Sallinen, Sami J.; Alakuijala, Jyrki; Helminen, Hannu; Laitinen, Joakim

1998-05-01

Rendering volumetric medical images is a burdensome computational task for contemporary computers due to the large size of the data sets. Custom designed reconfigurable hardware could considerably speed up volume visualization if an algorithm suitable for the platform is used. We present an algorithm and speedup techniques for visualizing volumetric medical CT and MR images with a custom-computing machine based on a Field Programmable Gate Array (FPGA). We also present simulated performance results of the proposed algorithm calculated with a software implementation running on a desktop PC. Our algorithm is capable of generating perspective projection renderings of single and multiple isosurfaces with transparency, simulated X-ray images, and Maximum Intensity Projections (MIP). Although more speedup techniques exist for parallel projection than for perspective projection, we have constrained ourselves to perspective viewing, because of its importance in the field of radiotherapy. The algorithm we have developed is based on ray casting, and the rendering is sped up by three different methods: shading speedup by gradient precalculation, a new generalized version of Ray-Acceleration by Distance Coding (RADC), and background ray elimination by speculative ray selection.

SNAVA-A real-time multi-FPGA multi-model spiking neural network simulation architecture.

PubMed

Sripad, Athul; Sanchez, Giovanny; Zapata, Mireya; Pirrone, Vito; Dorta, Taho; Cambria, Salvatore; Marti, Albert; Krishnamourthy, Karthikeyan; Madrenas, Jordi

2018-01-01

Spiking Neural Networks (SNN) for Versatile Applications (SNAVA) simulation platform is a scalable and programmable parallel architecture that supports real-time, large-scale, multi-model SNN computation. This parallel architecture is implemented in modern Field-Programmable Gate Arrays (FPGAs) devices to provide high performance execution and flexibility to support large-scale SNN models. Flexibility is defined in terms of programmability, which allows easy synapse and neuron implementation. This has been achieved by using a special-purpose Processing Elements (PEs) for computing SNNs, and analyzing and customizing the instruction set according to the processing needs to achieve maximum performance with minimum resources. The parallel architecture is interfaced with customized Graphical User Interfaces (GUIs) to configure the SNN's connectivity, to compile the neuron-synapse model and to monitor SNN's activity. Our contribution intends to provide a tool that allows to prototype SNNs faster than on CPU/GPU architectures but significantly cheaper than fabricating a customized neuromorphic chip. This could be potentially valuable to the computational neuroscience and neuromorphic engineering communities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Library preparation and data analysis packages for rapid genome sequencing.

PubMed

Pomraning, Kyle R; Smith, Kristina M; Bredeweg, Erin L; Connolly, Lanelle R; Phatale, Pallavi A; Freitag, Michael

2012-01-01

High-throughput sequencing (HTS) has quickly become a valuable tool for comparative genetics and genomics and is now regularly carried out in laboratories that are not connected to large sequencing centers. Here we describe an updated version of our protocol for constructing single- and paired-end Illumina sequencing libraries, beginning with purified genomic DNA. The present protocol can also be used for "multiplexing," i.e. the analysis of several samples in a single flowcell lane by generating "barcoded" or "indexed" Illumina sequencing libraries in a way that is independent from Illumina-supported methods. To analyze sequencing results, we suggest several independent approaches but end users should be aware that this is a quickly evolving field and that currently many alignment (or "mapping") and counting algorithms are being developed and tested.

TIGRESS: TRIUMF-ISAC gamma-ray escape-suppressed spectrometer

NASA Astrophysics Data System (ADS)

Svensson, C. E.; Amaudruz, P.; Andreoiu, C.; Andreyev, A.; Austin, R. A. E.; Ball, G. C.; Bandyopadhyay, D.; Boston, A. J.; Chakrawarthy, R. S.; Chen, A. A.; Churchman, R.; Drake, T. E.; Finlay, P.; Garrett, P. E.; Grinyer, G. F.; Hackman, G.; Hyland, B.; Jones, B.; Kanungo, R.; Maharaj, R.; Martin, J. P.; Morris, D.; Morton, A. C.; Pearson, C. J.; Phillips, A. A.; Ressler, J. J.; Roy, R.; Sarazin, F.; Schumaker, M. A.; Scraggs, H. C.; Smith, M. B.; Starinsky, N.; Valiente-Dobón, J. J.; Waddington, J. C.; Watters, L. M.

2005-10-01

The TRIUMF-ISAC gamma-ray escape-suppressed spectrometer (TIGRESS) is a new γ-ray detector array being developed for use at TRIUMF's Isotope Separator and Accelerator (ISAC) radioactive ion beam facility. TIGRESS will comprise 12 32-fold segmented clover-type HPGe detectors coupled with 20-fold segmented modular Compton suppression shields and custom digital signal processing electronics. This paper provides an overview of the TIGRESS project and progress in its development to date.

MEqTrees Telescope and Radio-sky Simulations and CPU Benchmarking

NASA Astrophysics Data System (ADS)

Shanmugha Sundaram, G. A.

2009-09-01

MEqTrees is a Python-based implementation of the classical Measurement Equation, wherein the various 2×2 Jones matrices are parametrized representations in the spatial and sky domains for any generic radio telescope. Customized simulations of radio-source sky models and corrupt Jones terms are demonstrated based on a policy framework, with performance estimates derived for array configurations, ``dirty''-map residuals and processing power requirements for such computations on conventional platforms.

The Use, Evolution and Lessons Learnt of Deployable Static Solar Array Mechanisms

NASA Technical Reports Server (NTRS)

Ferris, Mark; Haslehurst, Andrew

2014-01-01

This paper focuses on the mechanisms incorporated into SSTL's static deployable arrays; namely the sprung-hinges and hold down and release mechanism (HDRM). Combined, the HDRM and hinges form the hold down release system (HDRS). The deployable static solar array HDRS has been successfully used on several missions, first launched upon the DMC-CFESAT spacecraft in 2007 for a U.S. customer (Figure 1), and later used on DMC-UK2 and EXACTVIEW-1 launched in 2009 and 2012, respectively. The simple, robust and low-cost solution HDRS has been evident in allowing missions to satisfy an ever increasing power demand, allowing the solar arrays to increase in size and have a preferable sun angle for increased cell efficiency. The system is now being employed on the first mission out of SSTL's U.S. office (SST-US) on the Orbital Test Bed platform. This paper shall cover details of the original design and development program, problems incurred on latter missions, and evolution of the HDRS for the present Orbital Test Bed mission. Both the original development and recent evolutions have taken place in rapid timescales, to satisfy the high-turnaround of SSTL missions.

Best face forward.

PubMed

Rayport, Jeffrey F; Jaworski, Bernard J

2004-12-01

Most companies serve customers through a broad array of interfaces, from retail sales clerks to Web sites to voice-response telephone systems. But while the typical company has an impressive interface collection, it doesn't have an interface system. That is, the whole set does not add up to the sum of its parts in its ability to provide service and build customer relationships. Too many people and too many machines operating with insufficient coordination (and often at cross-purposes) mean rising complexity, costs, and customer dissatisfaction. In a world where companies compete not on what they sell but on how they sell it, turning that liability into an asset is what separates winners from losers. In this adaptation of their forthcoming book by the same title, Jeffrey Rayport and Bernard Jaworski explain how companies must reengineer their customer interface systems for optimal efficiency and effectiveness. Part of that transformation, they observe, will involve a steady encroachment by machine interfaces into areas that have long been the sacred province of humans. Managers now have opportunities unprecedented in the history of business to use machines, not just people, to credibly manage their interactions with customers. Because people and machines each have their strengths and weaknesses, company executives must identify what people do best, what machines do best, and how to deploy them separately and together. Front-office reengineering subjects every current and potential service interface to an analysis of opportunities for substitution (using machines instead of people), complementarity (using a mix of machines and people), and displacement (using networks to shift physical locations of people and machines), with the twin objectives of compressing costs and driving top-line growth through increased customer value.

De novo assembly of the pepper transcriptome (Capsicum annuum): a benchmark for in silico discovery of SNPs, SSRs and candidate genes

PubMed Central

2012-01-01

Background Molecular breeding of pepper (Capsicum spp.) can be accelerated by developing DNA markers associated with transcriptomes in breeding germplasm. Before the advent of next generation sequencing (NGS) technologies, the majority of sequencing data were generated by the Sanger sequencing method. By leveraging Sanger EST data, we have generated a wealth of genetic information for pepper including thousands of SNPs and Single Position Polymorphic (SPP) markers. To complement and enhance these resources, we applied NGS to three pepper genotypes: Maor, Early Jalapeño and Criollo de Morelos-334 (CM334) to identify SNPs and SSRs in the assembly of these three genotypes. Results Two pepper transcriptome assemblies were developed with different purposes. The first reference sequence, assembled by CAP3 software, comprises 31,196 contigs from >125,000 Sanger-EST sequences that were mainly derived from a Korean F1-hybrid line, Bukang. Overlapping probes were designed for 30,815 unigenes to construct a pepper Affymetrix GeneChip® microarray for whole genome analyses. In addition, custom Python scripts were used to identify 4,236 SNPs in contigs of the assembly. A total of 2,489 simple sequence repeats (SSRs) were identified from the assembly, and primers were designed for the SSRs. Annotation of contigs using Blast2GO software resulted in information for 60% of the unigenes in the assembly. The second transcriptome assembly was constructed from more than 200 million Illumina Genome Analyzer II reads (80–120 nt) using a combination of Velvet, CLC workbench and CAP3 software packages. BWA, SAMtools and in-house Perl scripts were used to identify SNPs among three pepper genotypes. The SNPs were filtered to be at least 50 bp from any intron-exon junctions as well as flanking SNPs. More than 22,000 high-quality putative SNPs were identified. Using the MISA software, 10,398 SSR markers were also identified within the Illumina transcriptome assembly and primers were designed for the identified markers. The assembly was annotated by Blast2GO and 14,740 (12%) of annotated contigs were associated with functional proteins. Conclusions Before availability of pepper genome sequence, assembling transcriptomes of this economically important crop was required to generate thousands of high-quality molecular markers that could be used in breeding programs. In order to have a better understanding of the assembled sequences and to identify candidate genes underlying QTLs, we annotated the contigs of Sanger-EST and Illumina transcriptome assemblies. These and other information have been curated in a database that we have dedicated for pepper project. PMID:23110314

An efficient annotation and gene-expression derivation tool for Illumina Solexa datasets.

PubMed

Hosseini, Parsa; Tremblay, Arianne; Matthews, Benjamin F; Alkharouf, Nadim W

2010-07-02

The data produced by an Illumina flow cell with all eight lanes occupied, produces well over a terabyte worth of images with gigabytes of reads following sequence alignment. The ability to translate such reads into meaningful annotation is therefore of great concern and importance. Very easily, one can get flooded with such a great volume of textual, unannotated data irrespective of read quality or size. CASAVA, a optional analysis tool for Illumina sequencing experiments, enables the ability to understand INDEL detection, SNP information, and allele calling. To not only extract from such analysis, a measure of gene expression in the form of tag-counts, but furthermore to annotate such reads is therefore of significant value. We developed TASE (Tag counting and Analysis of Solexa Experiments), a rapid tag-counting and annotation software tool specifically designed for Illumina CASAVA sequencing datasets. Developed in Java and deployed using jTDS JDBC driver and a SQL Server backend, TASE provides an extremely fast means of calculating gene expression through tag-counts while annotating sequenced reads with the gene's presumed function, from any given CASAVA-build. Such a build is generated for both DNA and RNA sequencing. Analysis is broken into two distinct components: DNA sequence or read concatenation, followed by tag-counting and annotation. The end result produces output containing the homology-based functional annotation and respective gene expression measure signifying how many times sequenced reads were found within the genomic ranges of functional annotations. TASE is a powerful tool to facilitate the process of annotating a given Illumina Solexa sequencing dataset. Our results indicate that both homology-based annotation and tag-count analysis are achieved in very efficient times, providing researchers to delve deep in a given CASAVA-build and maximize information extraction from a sequencing dataset. TASE is specially designed to translate sequence data in a CASAVA-build into functional annotations while producing corresponding gene expression measurements. Achieving such analysis is executed in an ultrafast and highly efficient manner, whether the analysis be a single-read or paired-end sequencing experiment. TASE is a user-friendly and freely available application, allowing rapid analysis and annotation of any given Illumina Solexa sequencing dataset with ease.

Multi-segment detector array for hybrid reflection-mode ultrasound and optoacoustic tomography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Merčep, Elena; Burton, Neal C.; Deán-Ben, Xosé Luís.; Razansky, Daniel

2017-02-01

The complementary contrast of the optoacoustic (OA) and pulse-echo ultrasound (US) modalities makes the combined usage of these imaging technologies highly advantageous. Due to the different physical contrast mechanisms development of a detector array optimally suited for both modalities is one of the challenges to efficient implementation of a single OA-US imaging device. We demonstrate imaging performance of the first hybrid detector array whose novel design, incorporating array segments of linear and concave geometry, optimally supports image acquisition in both reflection-mode ultrasonography and optoacoustic tomography modes. Hybrid detector array has a total number of 256 elements and three segments of different geometry and variable pitch size: a central 128-element linear segment with pitch of 0.25mm, ideally suited for pulse-echo US imaging, and two external 64-elements segments with concave geometry and 0.6mm pitch optimized for OA image acquisition. Interleaved OA and US image acquisition with up to 25 fps is facilitated through a custom-made multiplexer unit. Spatial resolution of the transducer was characterized in numerical simulations and validated in phantom experiments and comprises 230 and 300 μm in the respective OA and US imaging modes. Imaging performance of the multi-segment detector array was experimentally shown in a series of imaging sessions with healthy volunteers. Employing mixed array geometries allows at the same time achieving excellent OA contrast with a large field of view, and US contrast for complementary structural features with reduced side-lobes and improved resolution. The newly designed hybrid detector array that comprises segments of linear and concave geometries optimally fulfills requirements for efficient US and OA imaging and may expand the applicability of the developed hybrid OPUS imaging technology and accelerate its clinical translation.

QWIP focal plane arrays performances from MWIR up to VLWIR

NASA Astrophysics Data System (ADS)

Robo, J. A.; Costard, E.; Truffer, J. P.; Nedelcu, A.; Marcadet, X.; Bois, P.

2009-05-01

Since 2002, the THALES Group has been manufacturing sensitive arrays using QWIP technology based on GaAs and related III-V compounds, at the Alcatel-Thales-III-V Lab (formerly part of THALES Research and Technology Laboratory). In the past researchers claimed many advantages of QWIPs. Uniformity was one of these and has been the key parameter for the production to start. Another widely claimed advantage for QWIPs was the so-called band-gap engineering and versatility of the III-V processing allowing the custom design of quantum structures at various wavelengths in MWIR, LWIR and VLWIR. An overview of the available performances of QWIPs in the whole infrared spectrum is presented here. We also discuss about the under-development products such as dual band and polarimetric structures.

Seven newly identified loci for autoimmune thyroid disease.

PubMed

Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

2012-12-01

Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

The future of automation for high-volume wafer fabrication and ASIC manufacturing

NASA Astrophysics Data System (ADS)

Hughes, Randall A.; Shott, John D.

1986-12-01

A framework is given to analyze the future trends in semiconductor manufacturing automation systems, focusing specifically on the needs of ASIC (application-specific integrated circuit) or custom integrated circuit manufacturing. Advances in technologies such as gate arrays and standard cells now make it significantly easier to obtain system cost and performance advantages by integrating nonstandard functions on silicon. ASICs are attractive to U.S. manufacturers because they place a premium on sophisticated design tools, familiarity with customer needs and applications, and fast turn-around fabrication. These are areas where U.S. manufacturers believe they have an advantage and, consequently, will not suffer from the severe price/manufacturing competition encountered in conventional high-volume semiconductor products. Previously, automation was often considered viable only for high-volume manufacturing, but automation becomes a necessity in the new ASIC environment.

Night vision in Thales Angenieux: custom solutions for hand-held devices

NASA Astrophysics Data System (ADS)

Rollin, Joel; Teszner, Jean Louis

2005-01-01

Thales Anenieux has been manufacturing for two decades flexible light intensifier goggles that have been popular over numerous countries: thanks to the advent of uncooled microbolometer arrays, further outlooks are settled. Army Forces can have now at their command a multi-purpose and cost effective set of devices that answer most of the battlefield mission profiles. Thales Angenieux move from light intensifier goggles to low cost infared imagers and this smooth change is sketched out: our erlier experience on compact and user-friendly L.I equipment, especially in the field of the opto-mechanical design, has helped us to push forward the best compromises. Our product line policy is displayed: really, we have made a point of addressing many potential customers demands by singling out a modular approach. Further developments are now going on.

Next-Generation Sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations.

PubMed

Balendran, S; Liebmann-Reindl, S; Berghoff, A S; Reischer, T; Popitsch, N; Geier, C B; Kenner, L; Birner, P; Streubel, B; Preusser, M

2017-07-01

Ovarian cancer represents the most common gynaecological malignancy and has the highest mortality of all female reproductive cancers. It has a rare predilection to develop brain metastases (BM). In this study, we evaluated the mutational profile of ovarian cancer metastases through Next-Generation Sequencing (NGS) with the aim of identifying potential clinically actionable genetic alterations with options for small molecule targeted therapy. Library preparation was conducted using Illumina TruSight Rapid Capture Kit in combination with a cancer specific enrichment kit covering 94 genes. BRCA-mutations were confirmed by using TruSeq Custom Amplicon Low Input Kit in combination with a custom-designed BRCA gene panel. In our cohort all eight sequenced BM samples exhibited a multitude of variant alterations, each with unique molecular profiles. The 37 identified variants were distributed over 22 cancer-related genes (23.4%). The number of mutated genes per sample ranged from 3 to 7 with a median of 4.5. The most commonly altered genes were BRCA1/2, TP53, and ATM. In total, 7 out of 8 samples revealed either a BRCA1 or a BRCA2 pathogenic mutation. Furthermore, all eight BM samples showed mutations in at least one DNA repair gene. Our NGS study of BM of ovarian carcinoma revealed a significant number of BRCA-mutations beside TP53, ATM and CHEK2 mutations. These findings strongly suggest the implication of BRCA and DNA repair malfunction in ovarian cancer metastasizing to the brain. Based on these findings, pharmacological PARP inhibition could be one potential targeted therapeutic for brain metastatic ovarian cancer patients.

Complete Genome Sequence of a Streptococcus pyogenes Serotype M12 Scarlet Fever Outbreak Isolate from China, Compiled Using Oxford Nanopore and Illumina Sequencing

PubMed Central

You, Yuanhai; Kou, Yongjun; Niu, Longfei; Jia, Qiong; Liu, Yahui; Walker, Mark J.; Zhu, Jiaqiang

2018-01-01

ABSTRACT The incidence of scarlet fever cases remains high in China. Here, we report the complete genome sequence of a Streptococcus pyogenes isolate of serotype M12, which has been confirmed as the predominant serotype in recent outbreaks. Genome sequencing was achieved by a combination of Oxford Nanopore MinION and Illumina methodologies. PMID:29724853

Pediatric Glioblastoma Therapies Based on Patient-Derived Stem Cell Resources

DTIC Science & Technology

2014-11-01

genomic DNA and then subjected to Illumina high-throughput sequencing . In this analysis, shRNAs lost in the GSC population represent candidate gene...and genomic DNA and then subjected to Illumina high-throughput sequencing . In this analysis, shRNAs lost in the GSC population represent candidate...PRISM 7900 Sequence Detection System ( Genomics Resource, FHCRC). Relative transcript abundance was analyzed using the 2−ΔΔCt method. TRIzol (Invitrogen

Dissection of the Octoploid Strawberry Genome by Deep Sequencing of the Genomes of Fragaria Species

PubMed Central

Hirakawa, Hideki; Shirasawa, Kenta; Kosugi, Shunichi; Tashiro, Kosuke; Nakayama, Shinobu; Yamada, Manabu; Kohara, Mistuyo; Watanabe, Akiko; Kishida, Yoshie; Fujishiro, Tsunakazu; Tsuruoka, Hisano; Minami, Chiharu; Sasamoto, Shigemi; Kato, Midori; Nanri, Keiko; Komaki, Akiko; Yanagi, Tomohiro; Guoxin, Qin; Maeda, Fumi; Ishikawa, Masami; Kuhara, Satoru; Sato, Shusei; Tabata, Satoshi; Isobe, Sachiko N.

2014-01-01

Cultivated strawberry (Fragaria x ananassa) is octoploid and shows allogamous behaviour. The present study aims at dissecting this octoploid genome through comparison with its wild relatives, F. iinumae, F. nipponica, F. nubicola, and F. orientalis by de novo whole-genome sequencing on an Illumina and Roche 454 platforms. The total length of the assembled Illumina genome sequences obtained was 698 Mb for F. x ananassa, and ∼200 Mb each for the four wild species. Subsequently, a virtual reference genome termed FANhybrid_r1.2 was constructed by integrating the sequences of the four homoeologous subgenomes of F. x ananassa, from which heterozygous regions in the Roche 454 and Illumina genome sequences were eliminated. The total length of FANhybrid_r1.2 thus created was 173.2 Mb with the N50 length of 5137 bp. The Illumina-assembled genome sequences of F. x ananassa and the four wild species were then mapped onto the reference genome, along with the previously published F. vesca genome sequence to establish the subgenomic structure of F. x ananassa. The strategy adopted in this study has turned out to be successful in dissecting the genome of octoploid F. x ananassa and appears promising when applied to the analysis of other polyploid plant species. PMID:24282021

Illumina MiSeq Sequencing for Preliminary Analysis of Microbiome Causing Primary Endodontic Infections in Egypt

PubMed Central

Azab, Marwa Mohamed; Fayyad, Dalia Mukhtar

2018-01-01

The use of high throughput next generation technologies has allowed more comprehensive analysis than traditional Sanger sequencing. The specific aim of this study was to investigate the microbial diversity of primary endodontic infections using Illumina MiSeq sequencing platform in Egyptian patients. Samples were collected from 19 patients in Suez Canal University Hospital (Endodontic Department) using sterile # 15K file and paper points. DNA was extracted using Mo Bio power soil DNA isolation extraction kit followed by PCR amplification and agarose gel electrophoresis. The microbiome was characterized on the basis of the V3 and V4 hypervariable region of the 16S rRNA gene by using paired-end sequencing on Illumina MiSeq device. MOTHUR software was used in sequence filtration and analysis of sequenced data. A total of 1858 operational taxonomic units at 97% similarity were assigned to 26 phyla, 245 families, and 705 genera. Four main phyla Firmicutes, Bacteroidetes, Proteobacteria, and Synergistetes were predominant in all samples. At genus level, Prevotella, Bacillus, Porphyromonas, Streptococcus, and Bacteroides were the most abundant. Illumina MiSeq platform sequencing can be used to investigate oral microbiome composition of endodontic infections. Elucidating the ecology of endodontic infections is a necessary step in developing effective intracanal antimicrobials. PMID:29849646

Three-layered radio frequency coil arrangement for sodium MRI of the human brain at 9.4 Tesla.

PubMed

Shajan, G; Mirkes, Christian; Buckenmaier, Kai; Hoffmann, Jens; Pohmann, Rolf; Scheffler, Klaus

2016-02-01

A multinuclei imaging setup with the capability to acquire both sodium ((23) Na) and proton ((1) H) signals at 9.4 Tesla is presented. The main objective was to optimize coil performance at the (23) Na frequency while still having the ability to acquire satisfactory (1) H images. The setup consisted of a combination of three radio frequency (RF) coils arranged in three layers: the innermost layer was a 27-channel (23) Na receive helmet which was surrounded by a four-channel (23) Na transceiver array. The outer layer consisted of a four-channel (1) H dipole array for B0 shimming and anatomical localization. Transmit and receive performance of the (23) Na arrays was compared to a single-tuned (23) Na birdcage resonator. While the transmit efficiency of the (23) Na transceiver array was comparable to the birdcage, the (23) Na receive array provided substantial signal-to-noise ratio (SNR) gain near the surface and comparable SNR in the center. The utility of this customized setup was demonstrated by (23) Na images of excellent quality. High SNR, efficient transmit excitation and B0 shimming capability can be achieved for (23) Na MRI at 9.4T using novel coil combination. This RF configuration is easily adaptable to other multinuclei applications at ultra high field (≥ 7T). © 2015 Wiley Periodicals, Inc.

Two color QWIP and extended wavebands

NASA Astrophysics Data System (ADS)

Costard, Eric; Truffer, Jean P.; Huet, Odile; Dua, Lydie; Nedelcu, Alexandru; Robo, J. A.; Marcadet, Xavier; Briere de l'Isle, Nadia; Bois, Philippe; Manissadjian, A.; Gohier, D.

2007-04-01

Since 2002, the THALES Group has been manufacturing sensitive arrays using QWIP technology based on GaAs and related III-V compounds, at THALES Research and Technology Laboratory. The QWIP technology allows the realization of large staring arrays for Thermal Imagers (TI) working in the long-wave infrared (LWIR) band (8-12 μm). In the past researchers claimed many advantages of QWIPs. Uniformity was one of these and has been the key parameter for the production to start. The 640x512 LWIR focal plane arrays (FPAs) with 20μm pitch was the demonstration that state of the art performances can be achieved even with small pixels. This opened the field for the realization of usable and affordable megapixel FPAs. Thales Research & Technology (TRT) has been developing third generation GaAs LWIR QWIP arrays for volume manufacture of high performance low cost thermal imaging cameras. In the past, another widely claimed advantage for QWIPs was the so-called band-gap engineering and versatility of the III-V processing allowing the custom design of quantum structures to fulfil the requirements of specific applications such as very long wavelength (VLWIR) or multispectral detection. In this presentation, we present the performances of both our first 384x288, 25 μm pitch, MWIR (3-5μm) / LWIR (8-9 μm) dual-band FPAs, and the current status of QWIPs for MWIR (< 5μm) and VLWIR (>15μm) arrays.

Design and Performance of a Miniature Radar L-Band Transceiver

NASA Technical Reports Server (NTRS)

McWatters, D.; Price, D.; Edelstein, W.

2004-01-01

Radar electronics developed for past JPL space missions historically had been custom designed and as such, given budgetary, time, and risk constraints, had not been optimized for maximum flexibility or miniaturization. To help reduce cost and risk of future radar missions, a generic radar module was conceived. The module includes a 1.25-GHz (L-band) transceiver and incorporates miniature high-density packaging of integrated circuits in die/chip form. The technology challenges include overcoming the effect of miniaturization and high packaging density to achieve the performance, reliability, and environmental ruggedness required for space missions. The module was chosen to have representative (generic) functionality most likely required from an L-band radar. For very large aperture phased-array spaceborne radar missions, the large dimensions of the array suggest the benefit of distributing the radar electronics into the antenna array. For such applications, this technology is essential in order to bring down the cost, mass, and power of the radar electronics module replicated in each panel of the array. For smaller sized arrays, a single module can be combined with the central radar controller and still provide the bene.ts of configuration .exibility, low power, and low mass. We present the design approach for the radar electronics module and the test results for its radio frequency (RF) portion: a miniature, low-power, radiation-hard L-band transceiver.

Quantum-Well Infrared Photodetector (QWIP) Focal Plane Assembly

NASA Technical Reports Server (NTRS)

Jhabvala, Murzy; Jhabvala, Christine A.; Ewin, Audrey J.; Hess, Larry A.; Hartmann, Thomas M.; La, Anh T.

2012-01-01

A paper describes the Thermal Infrared Sensor (TIRS), a QWIP-based instrument intended to supplement the Operational Land Imager (OLI) for the Landsat Data Continuity Mission (LDCM). The TIRS instrument is a far-infrared imager operating in the pushbroom mode with two IR channels: 10.8 and 12 microns. The focal plane will contain three 640x512 QWIP arrays mounted on a silicon substrate. The silicon substrate is a custom-fabricated carrier board with a single layer of aluminum interconnects. The general fabrication process starts with a 4-in. (approx.10-cm) diameter silicon wafer. The wafer is oxidized, a single substrate contact is etched, and aluminum is deposited, patterned, and alloyed. This technology development is aimed at incorporating three large-format infrared detecting arrays based on GaAs QWIP technology onto a common focal plane with precision alignment of all three arrays. This focal plane must survive the rigors of flight qualification and operate at a temperature of 43 K (-230 C) for five years while orbiting the Earth. The challenges presented include ensuring thermal compatibility among all the components, designing and building a compact, somewhat modular system and ensuring alignment to very tight levels. The multi-array focal plane integrated onto a single silicon substrate is a new application of both QWIP array development and silicon wafer scale integration. The Invar-based assembly has been tested to ensure thermal reliability.

Dual-mode intracranial catheter integrating 3D ultrasound imaging and hyperthermia for neuro-oncology: feasibility study.

PubMed

Herickhoff, Carl D; Light, Edward D; Bing, Kristin F; Mukundan, Srinivasan; Grant, Gerald A; Wolf, Patrick D; Smith, Stephen W

2009-04-01

In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm x 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom, electrical impedance-matching circuits to achieve a temperature rise over 4 degrees C in excised pork muscle, and second, by designing and constructing a 12 Fr, integrated matrix and linear-array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm x 2.3 mm. This 3.64 MHz array achieved a 3.5 degrees C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav catheter as a gold standard in experiments assessing image quality and therapeutic potential and both probes were used in an in vivo canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.

Dual-mode Intracranial Catheter Integrating 3D Ultrasound Imaging & Hyperthermia for Neuro-oncology: Feasibility Study

PubMed Central

Herickhoff, Carl D.; Light, Edward D.; Bing, Kristin F.; Mukundan, Srinivasan; Grant, Gerald A.; Wolf, Patrick D.; Smith, Stephen W.

2010-01-01

In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm × 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom electrical impedance matching circuits to achieve a temperature rise over 4°C in excised pork muscle, and second by designing and constructing a 12 Fr, integrated matrix and linear array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm × 2.3 mm. This array achieved a 3.5°C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav™ catheter as a gold standard in experiments assessing image quality and therapeutic potential, and both probes were used in a canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating. PMID:19630251

Analysis of Stress Distributions Under Lightweight Wheeled Vehicles

DTIC Science & Technology

2013-10-09

For a balanced analysis it is important at examine the full scale error ε f . Sinkage error, although large in a relative sense is typically on the...director of the Edgerton Center at MIT, to Thuan Doan, and to Meccanotecnica Riesi SRL for collaborating on manufacturing the custom sensing array...a pulling/braking force at the vehicle axle. Fx = T −Rc (33) The importance of drawbar force is obvious, since a positive drawbar force implies that

Multisensory architectures for action-oriented perception

NASA Astrophysics Data System (ADS)

Alba, L.; Arena, P.; De Fiore, S.; Listán, J.; Patané, L.; Salem, A.; Scordino, G.; Webb, B.

2007-05-01

In order to solve the navigation problem of a mobile robot in an unstructured environment a versatile sensory system and efficient locomotion control algorithms are necessary. In this paper an innovative sensory system for action-oriented perception applied to a legged robot is presented. An important problem we address is how to utilize a large variety and number of sensors, while having systems that can operate in real time. Our solution is to use sensory systems that incorporate analog and parallel processing, inspired by biological systems, to reduce the required data exchange with the motor control layer. In particular, as concerns the visual system, we use the Eye-RIS v1.1 board made by Anafocus, which is based on a fully parallel mixed-signal array sensor-processor chip. The hearing sensor is inspired by the cricket hearing system and allows efficient localization of a specific sound source with a very simple analog circuit. Our robot utilizes additional sensors for touch, posture, load, distance, and heading, and thus requires customized and parallel processing for concurrent acquisition. Therefore a Field Programmable Gate Array (FPGA) based hardware was used to manage the multi-sensory acquisition and processing. This choice was made because FPGAs permit the implementation of customized digital logic blocks that can operate in parallel allowing the sensors to be driven simultaneously. With this approach the multi-sensory architecture proposed can achieve real time capabilities.

Reflectance confocal microscope for imaging oral tissues in vivo, potentially with line scanning as a low-cost approach for clinical use

NASA Astrophysics Data System (ADS)

Peterson, Gary; Abeytunge, Sanjeewa; Eastman, Zachary; Rajadhyaksha, Milind

2012-02-01

Reflectance confocal microscopy with a line scanning approach potentially offers a smaller, simpler and less expensive approach than traditional methods of point scanning for imaging in living tissues. With one moving mechanical element (galvanometric scanner), a linear array detector and off-the-shelf optics, we designed a compact (102x102x76mm) line scanning confocal reflectance microscope (LSCRM) for imaging human tissues in vivo in a clinical setting. Custom-designed electronics, based on field programmable gate array (FPGA) logic has been developed. With 405 nm illumination and a custom objective lens of numerical aperture 0.5, lateral resolution was measured to be 0.8 um (calculated 0.64 um). The calculated optical sectioning is 3.2 um. Preliminary imaging shows nuclear and cellular detail in human skin and oral epithelium in vivo. Blood flow is also visualized in the deeper connective tissue (lamina propria) in oral mucosa. Since a line is confocal only in one dimension (parallel) but not in the other, the detection is more sensitive to multiply scattered out of focus background noise than in the traditional point scanning configuration. Based on the results of our translational studies thus far, a simpler, smaller and lower-cost approach based on a LSCRM appears to be promising for clinical imaging.

Delivery of video-on-demand services using local storages within passive optical networks.

PubMed

Abeywickrama, Sandu; Wong, Elaine

2013-01-28

At present, distributed storage systems have been widely studied to alleviate Internet traffic build-up caused by high-bandwidth, on-demand applications. Distributed storage arrays located locally within the passive optical network were previously proposed to deliver Video-on-Demand services. As an added feature, a popularity-aware caching algorithm was also proposed to dynamically maintain the most popular videos in the storage arrays of such local storages. In this paper, we present a new dynamic bandwidth allocation algorithm to improve Video-on-Demand services over passive optical networks using local storages. The algorithm exploits the use of standard control packets to reduce the time taken for the initial request communication between the customer and the central office, and to maintain the set of popular movies in the local storage. We conduct packet level simulations to perform a comparative analysis of the Quality-of-Service attributes between two passive optical networks, namely the conventional passive optical network and one that is equipped with a local storage. Results from our analysis highlight that strategic placement of a local storage inside the network enables the services to be delivered with improved Quality-of-Service to the customer. We further formulate power consumption models of both architectures to examine the trade-off between enhanced Quality-of-Service performance versus the increased power requirement from implementing a local storage within the network.

Assessing the use of an infrared spectrum hyperpixel array imager to measure temperature during additive and subtractive manufacturing

NASA Astrophysics Data System (ADS)

Whitenton, Eric; Heigel, Jarred; Lane, Brandon; Moylan, Shawn

2016-05-01

Accurate non-contact temperature measurement is important to optimize manufacturing processes. This applies to both additive (3D printing) and subtractive (material removal by machining) manufacturing. Performing accurate single wavelength thermography suffers numerous challenges. A potential alternative is hyperpixel array hyperspectral imaging. Focusing on metals, this paper discusses issues involved such as unknown or changing emissivity, inaccurate greybody assumptions, motion blur, and size of source effects. The algorithm which converts measured thermal spectra to emissivity and temperature uses a customized multistep non-linear equation solver to determine the best-fit emission curve. Emissivity dependence on wavelength may be assumed uniform or have a relationship typical for metals. The custom software displays residuals for intensity, temperature, and emissivity to gauge the correctness of the greybody assumption. Initial results are shown from a laser powder-bed fusion additive process, as well as a machining process. In addition, the effects of motion blur are analyzed, which occurs in both additive and subtractive manufacturing processes. In a laser powder-bed fusion additive process, the scanning laser causes the melt pool to move rapidly, causing a motion blur-like effect. In machining, measuring temperature of the rapidly moving chip is a desirable goal to develop and validate simulations of the cutting process. A moving slit target is imaged to characterize how the measured temperature values are affected by motion of a measured target.

Using 3D Printing (Additive Manufacturing) to Produce Low-Cost Simulation Models for Medical Training.

PubMed

Lichtenberger, John P; Tatum, Peter S; Gada, Satyen; Wyn, Mark; Ho, Vincent B; Liacouras, Peter

2018-03-01

This work describes customized, task-specific simulation models derived from 3D printing in clinical settings and medical professional training programs. Simulation models/task trainers have an array of purposes and desired achievements for the trainee, defining that these are the first step in the production process. After this purpose is defined, computer-aided design and 3D printing (additive manufacturing) are used to create a customized anatomical model. Simulation models then undergo initial in-house testing by medical specialists followed by a larger scale beta testing. Feedback is acquired, via surveys, to validate effectiveness and to guide or determine if any future modifications and/or improvements are necessary. Numerous custom simulation models have been successfully completed with resulting task trainers designed for procedures, including removal of ocular foreign bodies, ultrasound-guided joint injections, nerve block injections, and various suturing and reconstruction procedures. These task trainers have been frequently utilized in the delivery of simulation-based training with increasing demand. 3D printing has been integral to the production of limited-quantity, low-cost simulation models across a variety of medical specialties. In general, production cost is a small fraction of a commercial, generic simulation model, if available. These simulation and training models are customized to the educational need and serve an integral role in the education of our military health professionals.

Identification, Replication, and Functional Fine-Mapping of Expression Quantitative Trait Loci in Primary Human Liver Tissue

PubMed Central

Stanaway, Ian B.; Gamazon, Eric R.; Smith, Joshua D.; Mirkov, Snezana; Ramirez, Jacqueline; Liu, Wanqing; Lin, Yvonne S.; Moloney, Cliona; Aldred, Shelly Force; Trinklein, Nathan D.; Schuetz, Erin; Nickerson, Deborah A.; Thummel, Ken E.; Rieder, Mark J.; Rettie, Allan E.; Ratain, Mark J.; Cox, Nancy J.; Brown, Christopher D.

2011-01-01

The discovery of expression quantitative trait loci (“eQTLs”) can help to unravel genetic contributions to complex traits. We identified genetic determinants of human liver gene expression variation using two independent collections of primary tissue profiled with Agilent (n = 206) and Illumina (n = 60) expression arrays and Illumina SNP genotyping (550K), and we also incorporated data from a published study (n = 266). We found that ∼30% of SNP-expression correlations in one study failed to replicate in either of the others, even at thresholds yielding high reproducibility in simulations, and we quantified numerous factors affecting reproducibility. Our data suggest that drug exposure, clinical descriptors, and unknown factors associated with tissue ascertainment and analysis have substantial effects on gene expression and that controlling for hidden confounding variables significantly increases replication rate. Furthermore, we found that reproducible eQTL SNPs were heavily enriched near gene starts and ends, and subsequently resequenced the promoters and 3′UTRs for 14 genes and tested the identified haplotypes using luciferase assays. For three genes, significant haplotype-specific in vitro functional differences correlated directly with expression levels, suggesting that many bona fide eQTLs result from functional variants that can be mechanistically isolated in a high-throughput fashion. Finally, given our study design, we were able to discover and validate hundreds of liver eQTLs. Many of these relate directly to complex traits for which liver-specific analyses are likely to be relevant, and we identified dozens of potential connections with disease-associated loci. These included previously characterized eQTL contributors to diabetes, drug response, and lipid levels, and they suggest novel candidates such as a role for NOD2 expression in leprosy risk and C2orf43 in prostate cancer. In general, the work presented here will be valuable for future efforts to precisely identify and functionally characterize genetic contributions to a variety of complex traits. PMID:21637794

Transcriptomic Identification of ADH1B as a Novel Candidate Gene for Obesity and Insulin Resistance in Human Adipose Tissue in Mexican Americans from the Veterans Administration Genetic Epidemiology Study (VAGES)

PubMed Central

Winnier, Deidre A.; Fourcaudot, Marcel; Norton, Luke; Abdul-Ghani, Muhammad A.; Hu, Shirley L.; Farook, Vidya S.; Coletta, Dawn K.; Kumar, Satish; Puppala, Sobha; Chittoor, Geetha; Dyer, Thomas D.; Arya, Rector; Carless, Melanie; Lehman, Donna M.; Curran, Joanne E.; Cromack, Douglas T.; Tripathy, Devjit; Blangero, John; Duggirala, Ravindranath; Göring, Harald H. H.; DeFronzo, Ralph A.; Jenkinson, Christopher P.

2015-01-01

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10-9), BMI (5.4 x 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits. PMID:25830378

CNV analysis in the Lithuanian population.

PubMed

Urnikyte, A; Domarkiene, I; Stoma, S; Ambrozaityte, L; Uktveryte, I; Meskiene, R; Kasiulevičius, V; Burokiene, N; Kučinskas, V

2016-05-04

Although copy number variation (CNV) has received much attention, knowledge about the characteristics of CNVs such as occurrence rate and distribution in the genome between populations and within the same population is still insufficient. In this study, Illumina 770 K HumanOmniExpress-12 v1.0 (and v1.1) arrays were used to examine the diversity and distribution of CNVs in 286 unrelated individuals from the two main ethnolinguistic groups of the Lithuanian population (Aukštaičiai and Žemaičiai) (see Additional file 3). For primary data analysis, the Illumina GenomeStudio™ Genotyping Module v1.9 and two algorithms, cnvPartition 3.2.0 and QuantiSNP 2.0, were used to identify high-confidence CNVs. A total of 478 autosomal CNVs were detected by both algorithms, and those were clustered in 87 copy number variation regions (CNVRs), spanning ~12.5 Mb of the genome (see Table 1). At least 8.6 % of the CNVRs were unique and had not been reported in the Database of Genomic Variants. Most CNVRs (57.5 %) were rare, with a frequency of <1 %, whereas common CNVRs with at least 5 % frequency made up only 1.1 % of all CNVRs identified. About 49 % of non-singleton CNVRs were shared between Aukštaičiai and Žemaičiai, and the remaining CNVRs were specific to each group. Many of the CNVs detected (66 %) overlapped with known UCSC gene regions. The ethnolinguistic groups of the Lithuanian population could not be differentiated based on CNV profiles, which may reflect their geographical proximity and suggest the homogeneity of the Lithuanian population. In addition, putative novel CNVs unique to the Lithuanian population were identified. The results of our study enhance the CNV map of the Lithuanian population.

The Development of a High Density Linkage Map for Black Tiger Shrimp (Penaeus monodon) Based on cSNPs

PubMed Central

Baranski, Matthew; Gopikrishna, Gopalapillay; Robinson, Nicholas A.; Katneni, Vinaya Kumar; Shekhar, Mudagandur S.; Shanmugakarthik, Jayakani; Jothivel, Sarangapani; Gopal, Chavali; Ravichandran, Pitchaiyappan; Kent, Matthew; Arnyasi, Mariann; Ponniah, Alphis G.

2014-01-01

Transcriptome sequencing using Illumina RNA-seq was performed on populations of black tiger shrimp from India. Samples were collected from (i) four landing centres around the east coastline (EC) of India, (ii) survivors of a severe WSSV infection during pond culture (SUR) and (iii) the Andaman Islands (AI) in the Bay of Bengal. Equal quantities of purified total RNA from homogenates of hepatopancreas, muscle, nervous tissue, intestinal tract, heart, gonad, gills, pleopod and lymphoid organs were combined to create AI, EC and SUR pools for RNA sequencing. De novo transcriptome assembly resulted in 136,223 contigs (minimum size 100 base pairs, bp) with a total length 61 Mb, an average length of 446 bp and an average coverage of 163× across all pools. Approximately 16% of contigs were annotated with BLAST hit information and gene ontology annotations. A total of 473,620 putative SNPs/indels were identified. An Illumina iSelect genotyping array containing 6,000 SNPs was developed and used to genotype 1024 offspring belonging to seven full-sibling families. A total of 3959 SNPs were mapped to 44 linkage groups. The linkage groups consisted of between 16–129 and 13–130 markers, of length between 139–10.8 and 109.1–10.5 cM and with intervals averaging between 1.2 and 0.9 cM for the female and male maps respectively. The female map was 28% longer than the male map (4060 and 2917 cM respectively) with a 1.6 higher recombination rate observed for female compared to male meioses. This approach has substantially increased expressed sequence and DNA marker resources for tiger shrimp and is a useful resource for QTL mapping and association studies for evolutionarily and commercially important traits. PMID:24465553

Complete Genome Sequence of a Streptococcus pyogenes Serotype M12 Scarlet Fever Outbreak Isolate from China, Compiled Using Oxford Nanopore and Illumina Sequencing.

PubMed

You, Yuanhai; Kou, Yongjun; Niu, Longfei; Jia, Qiong; Liu, Yahui; Davies, Mark R; Walker, Mark J; Zhu, Jiaqiang; Zhang, Jianzhong

2018-05-03

The incidence of scarlet fever cases remains high in China. Here, we report the complete genome sequence of a Streptococcus pyogenes isolate of serotype M12, which has been confirmed as the predominant serotype in recent outbreaks. Genome sequencing was achieved by a combination of Oxford Nanopore MinION and Illumina methodologies. Copyright © 2018 You et al.

Analysis of Illumina Microbial Assemblies

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

Clum, Alicia; Foster, Brian; Froula, Jeff

2010-05-28

Since the emerging of second generation sequencing technologies, the evaluation of different sequencing approaches and their assembly strategies for different types of genomes has become an important undertaken. Next generation sequencing technologies dramatically increase sequence throughput while decreasing cost, making them an attractive tool for whole genome shotgun sequencing. To compare different approaches for de-novo whole genome assembly, appropriate tools and a solid understanding of both quantity and quality of the underlying sequence data are crucial. Here, we performed an in-depth analysis of short-read Illumina sequence assembly strategies for bacterial and archaeal genomes. Different types of Illumina libraries as wellmore » as different trim parameters and assemblers were evaluated. Results of the comparative analysis and sequencing platforms will be presented. The goal of this analysis is to develop a cost-effective approach for the increased throughput of the generation of high quality microbial genomes.« less

A flexible and economical barcoding approach for highly multiplexed amplicon sequencing of diverse target genes

PubMed Central

Herbold, Craig W.; Pelikan, Claus; Kuzyk, Orest; Hausmann, Bela; Angel, Roey; Berry, David; Loy, Alexander

2015-01-01

High throughput sequencing of phylogenetic and functional gene amplicons provides tremendous insight into the structure and functional potential of complex microbial communities. Here, we introduce a highly adaptable and economical PCR approach to barcoding and pooling libraries of numerous target genes. In this approach, we replace gene- and sequencing platform-specific fusion primers with general, interchangeable barcoding primers, enabling nearly limitless customized barcode-primer combinations. Compared to barcoding with long fusion primers, our multiple-target gene approach is more economical because it overall requires lower number of primers and is based on short primers with generally lower synthesis and purification costs. To highlight our approach, we pooled over 900 different small-subunit rRNA and functional gene amplicon libraries obtained from various environmental or host-associated microbial community samples into a single, paired-end Illumina MiSeq run. Although the amplicon regions ranged in size from approximately 290 to 720 bp, we found no significant systematic sequencing bias related to amplicon length or gene target. Our results indicate that this flexible multiplexing approach produces large, diverse, and high quality sets of amplicon sequence data for modern studies in microbial ecology. PMID:26236305

Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese.

PubMed

Tang, Clara S; Zhang, He; Cheung, Chloe Y Y; Xu, Ming; Ho, Jenny C Y; Zhou, Wei; Cherny, Stacey S; Zhang, Yan; Holmen, Oddgeir; Au, Ka-Wing; Yu, Haiyi; Xu, Lin; Jia, Jia; Porsch, Robert M; Sun, Lijie; Xu, Weixian; Zheng, Huiping; Wong, Lai-Yung; Mu, Yiming; Dou, Jingtao; Fong, Carol H Y; Wang, Shuyu; Hong, Xueyu; Dong, Liguang; Liao, Yanhua; Wang, Jiansong; Lam, Levina S M; Su, Xi; Yan, Hua; Yang, Min-Lee; Chen, Jin; Siu, Chung-Wah; Xie, Gaoqiang; Woo, Yu-Cho; Wu, Yangfeng; Tan, Kathryn C B; Hveem, Kristian; Cheung, Bernard M Y; Zöllner, Sebastian; Xu, Aimin; Eugene Chen, Y; Jiang, Chao Qiang; Zhang, Youyi; Lam, Tai-Hing; Ganesh, Santhi K; Huo, Yong; Sham, Pak C; Lam, Karen S L; Willer, Cristen J; Tse, Hung-Fat; Gao, Wei

2015-12-22

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

ReSeqTools: an integrated toolkit for large-scale next-generation sequencing based resequencing analysis.

PubMed

He, W; Zhao, S; Liu, X; Dong, S; Lv, J; Liu, D; Wang, J; Meng, Z

2013-12-04

Large-scale next-generation sequencing (NGS)-based resequencing detects sequence variations, constructs evolutionary histories, and identifies phenotype-related genotypes. However, NGS-based resequencing studies generate extraordinarily large amounts of data, making computations difficult. Effective use and analysis of these data for NGS-based resequencing studies remains a difficult task for individual researchers. Here, we introduce ReSeqTools, a full-featured toolkit for NGS (Illumina sequencing)-based resequencing analysis, which processes raw data, interprets mapping results, and identifies and annotates sequence variations. ReSeqTools provides abundant scalable functions for routine resequencing analysis in different modules to facilitate customization of the analysis pipeline. ReSeqTools is designed to use compressed data files as input or output to save storage space and facilitates faster and more computationally efficient large-scale resequencing studies in a user-friendly manner. It offers abundant practical functions and generates useful statistics during the analysis pipeline, which significantly simplifies resequencing analysis. Its integrated algorithms and abundant sub-functions provide a solid foundation for special demands in resequencing projects. Users can combine these functions to construct their own pipelines for other purposes.

Comparative Transcriptomics Among Four White Pine Species

PubMed Central

Baker, Ethan A. G.; Wegrzyn, Jill L.; Sezen, Uzay U.; Falk, Taylor; Maloney, Patricia E.; Vogler, Detlev R.; Delfino-Mix, Annette; Jensen, Camille; Mitton, Jeffry; Wright, Jessica; Knaus, Brian; Rai, Hardeep; Cronn, Richard; Gonzalez-Ibeas, Daniel; Vasquez-Gross, Hans A.; Famula, Randi A.; Liu, Jun-Jun; Kueppers, Lara M.; Neale, David B.

2018-01-01

Conifers are the dominant plant species throughout the high latitude boreal forests as well as some lower latitude temperate forests of North America, Europe, and Asia. As such, they play an integral economic and ecological role across much of the world. This study focused on the characterization of needle transcriptomes from four ecologically important and understudied North American white pines within the Pinus subgenus Strobus. The populations of many Strobus species are challenged by native and introduced pathogens, native insects, and abiotic factors. RNA from the needles of western white pine (Pinus monticola), limber pine (Pinus flexilis), whitebark pine (Pinus albicaulis), and sugar pine (Pinus lambertiana) was sampled, Illumina short read sequenced, and de novo assembled. The assembled transcripts and their subsequent structural and functional annotations were processed through custom pipelines to contend with the challenges of non-model organism transcriptome validation. Orthologous gene family analysis of over 58,000 translated transcripts, implemented through Tribe-MCL, estimated the shared and unique gene space among the four species. This revealed 2025 conserved gene families, of which 408 were aligned to estimate levels of divergence and reveal patterns of selection. Specific candidate genes previously associated with drought tolerance and white pine blister rust resistance in conifers were investigated. PMID:29559535

Characterization of Large-Area SiPM Array for PET Applications

NASA Astrophysics Data System (ADS)

Du, Junwei; Yang, Yongfeng; Bai, Xiaowei; Judenhofer, Martin S.; Berg, Eric; Di, Kun; Buckley, Steve; Jackson, Carl; Cherry, Simon R.

2016-02-01

The performance of an 8 ×8 array of 6.0 ×6.0 mm2 (active area) SiPMs was evaluated for PET applications using crystal arrays with different pitch sizes (3.4, 1.5, 1.35, and 1.2 mm) and custom designed five-channel front-end readout electronics (four channels for position information and one channel for timing information). The total area of this SiPM array is 57.4 ×57.4 mm2, and the pitch size is 7.2 mm. It was fabricated using enhanced blue sensitivity SiPMs (MicroFB-60035-SMT) with peak spectral sensitivity at 420 nm. The performance of the SiPM array was characterized by measuring flood histogram decoding quality, energy resolution, timing resolution and saturation at several bias voltages (from 25.0 to 30.0 V in 0.5 V intervals) and two different temperatures ( 5° C and 20°C). Results show that the best flood histogram was obtained at a bias voltage of 28.0 V and 5°C and an array of polished LSO crystals with a pitch as small as 1.2 mm can be resolved. No saturation was observed up to a bias voltage of 29.5 V during the experiments, due to adequate light sharing between SiPMs. Energy resolution and timing resolution at 5°C ranged from 12.7 ±0.8% to 14.6 ±1.4% and 1.58 ±0.13 ns to 2.50 ±0.44 ns, for crystal array pitch sizes of 3.4 and 1.2 mm, respectively. Superior flood histogram quality, energy resolution and timing resolution were obtained with larger crystal array pitch sizes and at lower temperature. Based on our findings, we conclude that this large-area SiPM array can serve as a suitable photodetector for high-resolution small-animal PET or dedicated human brain PET scanners.

Development of a Medium Density Combined-Species SNP Array for Pacific and European Oysters (Crassostrea gigas and Ostrea edulis).

PubMed

Gutierrez, Alejandro P; Turner, Frances; Gharbi, Karim; Talbot, Richard; Lowe, Natalie R; Peñaloza, Carolina; McCullough, Mark; Prodöhl, Paulo A; Bean, Tim P; Houston, Ross D

2017-07-05

SNP arrays are enabling tools for high-resolution studies of the genetic basis of complex traits in farmed and wild animals. Oysters are of critical importance in many regions from both an ecological and economic perspective, and oyster aquaculture forms a key component of global food security. The aim of our study was to design a combined-species, medium density SNP array for Pacific oyster ( Crassostrea gigas ) and European flat oyster ( Ostrea edulis ), and to test the performance of this array on farmed and wild populations from multiple locations, with a focus on European populations. SNP discovery was carried out by whole-genome sequencing (WGS) of pooled genomic DNA samples from eight C. gigas populations, and restriction site-associated DNA sequencing (RAD-Seq) of 11 geographically diverse O. edulis populations. Nearly 12 million candidate SNPs were discovered and filtered based on several criteria, including preference for SNPs segregating in multiple populations and SNPs with monomorphic flanking regions. An Affymetrix Axiom Custom Array was created and tested on a diverse set of samples ( n = 219) showing ∼27 K high quality SNPs for C. gigas and ∼11 K high quality SNPs for O. edulis segregating in these populations. A high proportion of SNPs were segregating in each of the populations, and the array was used to detect population structure and levels of linkage disequilibrium (LD). Further testing of the array on three C. gigas nuclear families ( n = 165) revealed that the array can be used to clearly distinguish between both families based on identity-by-state (IBS) clustering parental assignment software. This medium density, combined-species array will be publicly available through Affymetrix, and will be applied for genome-wide association and evolutionary genetic studies, and for genomic selection in oyster breeding programs. Copyright © 2017 Gutierrez et al.

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar).

PubMed

Houston, Ross D; Taggart, John B; Cézard, Timothé; Bekaert, Michaël; Lowe, Natalie R; Downing, Alison; Talbot, Richard; Bishop, Stephen C; Archibald, Alan L; Bron, James E; Penman, David J; Davassi, Alessandro; Brew, Fiona; Tinch, Alan E; Gharbi, Karim; Hamilton, Alastair

2014-02-06

Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection.

Patterning pallet arrays for cell selection based on high-resolution measurements of fluorescent biosensors

PubMed Central

Shadpour, Hamed; Zawistowski, Jon S.; Herman, Annadele; Hahn, Klaus; Allbritton, Nancy L.

2011-01-01

Pallet arrays enable cells to be separated while they remain adherent to a surface and provide a much greater range of cell selection criteria relative to that of current technologies. However there remains a need to further broaden cell selection criteria to include dynamic intracellular signaling events. To demonstrate the feasibility of measuring cellular protein behavior on the arrays using high resolution microscopy, the surfaces of individual pallets were modified to minimize the impact of scattered light at the pallet edges. The surfaces of the three-dimensional pallets on an array were patterned with a coating such as fibronectin using a customized stamping tool. Micropatterns of varying shape and size were printed in designated regions on the pallets in single or multiple steps to demonstrate the reliability and precision of patterning molecules on the pallet surface. Use of a fibronectin matrix stamped at the center of each pallet permitted the localization of H1299 and mouse embryonic fibroblast (MEF) cells to the pallet centers and away from the edges. Compared to pallet arrays with fibronection coating the entire top surface, arrays with a central fibronectin pattern increased the percentage of cells localized to the pallet center by 3-4 fold. Localization of cells to the pallet center also enabled the physical separation of cells from optical artifacts created by the rough pallet side walls. To demonstrate the measurement of dynamic intracellular signaling on the arrays, fluorescence measurements of high spatial resolution were performed using a RhoA GTPase biosensor. This biosensor utilized fluorescence resonance energy transfer (FRET) between cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP) to measure localized RhoA activity in cellular ruffles at the cell periphery. These results demonstrated the ability to perform spatially resolved measurements of fluorescence-based sensors on the pallet arrays. Thus, the patterned pallet arrays should enable novel cell separations in which cell selection is based on complex cellular signaling properties. PMID:21621038

Development and validation of a high density SNP genotyping array for Atlantic salmon (Salmo salar)

PubMed Central

2014-01-01

Background Dense single nucleotide polymorphism (SNP) genotyping arrays provide extensive information on polymorphic variation across the genome of species of interest. Such information can be used in studies of the genetic architecture of quantitative traits and to improve the accuracy of selection in breeding programs. In Atlantic salmon (Salmo salar), these goals are currently hampered by the lack of a high-density SNP genotyping platform. Therefore, the aim of the study was to develop and test a dense Atlantic salmon SNP array. Results SNP discovery was performed using extensive deep sequencing of Reduced Representation (RR-Seq), Restriction site-Associated DNA (RAD-Seq) and mRNA (RNA-Seq) libraries derived from farmed and wild Atlantic salmon samples (n = 283) resulting in the discovery of > 400 K putative SNPs. An Affymetrix Axiom® myDesign Custom Array was created and tested on samples of animals of wild and farmed origin (n = 96) revealing a total of 132,033 polymorphic SNPs with high call rate, good cluster separation on the array and stable Mendelian inheritance in our sample. At least 38% of these SNPs are from transcribed genomic regions and therefore more likely to include functional variants. Linkage analysis utilising the lack of male recombination in salmonids allowed the mapping of 40,214 SNPs distributed across all 29 pairs of chromosomes, highlighting the extensive genome-wide coverage of the SNPs. An identity-by-state clustering analysis revealed that the array can clearly distinguish between fish of different origins, within and between farmed and wild populations. Finally, Y-chromosome-specific probes included on the array provide an accurate molecular genetic test for sex. Conclusions This manuscript describes the first high-density SNP genotyping array for Atlantic salmon. This array will be publicly available and is likely to be used as a platform for high-resolution genetics research into traits of evolutionary and economic importance in salmonids and in aquaculture breeding programs via genomic selection. PMID:24524230

Zoom‐in comparative genomic hybridisation arrays for the characterisation of variable breakpoint contiguous gene syndromes

PubMed Central

Johnston, Jennifer J; Walker, Robert L; Davis, Sean; Facio, Flavia; Turner, Joyce T; Bick, David P; Daentl, Donna L; Ellison, Jay W; Meltzer, Paul S; Biesecker, Leslie G

2007-01-01

Contiguous gene syndromes cause disorders via haploinsufficiency for adjacent genes. Some contiguous gene syndromes (CGS) have stereotypical breakpoints, but others have variable breakpoints. In CGS that have variable breakpoints, the extent of the deletions may be correlated with severity. The Greig cephalopolysyndactyly contiguous gene syndrome (GCPS‐CGS) is a multiple malformation syndrome caused by haploinsufficiency of GLI3 and adjacent genes. In addition, non‐CGS GCPS can be caused by deletions or duplications in GLI3. Although fluorescence in situ hybridisation (FISH) can identify large deletion mutations in patients with GCPS or GCPS‐CGS, it is not practical for identification of small intragenic deletions or insertions, and it is difficult to accurately characterise the extent of the large deletions using this technique. We have designed a custom comparative genomic hybridisation (CGH) array that allows identification of deletions and duplications at kilobase resolution in the vicinity of GLI3. The array averages one probe every 730 bp for a total of about 14 000 probes over 10 Mb. We have analysed 16 individuals with known or suspected deletions or duplications. In 15 of 16 individuals (14 deletions and 1 duplication), the array confirmed the prior results. In the remaining patient, the normal CGH array result was correct, and the prior assessment was a false positive quantitative polymerase chain reaction result. We conclude that high‐density CGH array analysis is more sensitive than FISH analysis for detecting deletions and provides clinically useful results on the extent of the deletion. We suggest that high‐density CGH array analysis should replace FISH analysis for assessment of deletions and duplications in patients with contiguous gene syndromes caused by variable deletions. PMID:17098889

Design and performance of SiPM-based readout of PbF 2 crystals for high-rate, precision timing applications

DOE PAGES

Kaspar, J.; Fienberg, A. T.; Hertzog, D. W.; ...

2017-01-11

Here, we have developed a custom amplifier board coupled to a large-format 16-channel Hamamatsu silicon photomultiplier device for use as the light sensor for the electromagnetic calorimeters in the Muon g-2 experiment at Fermilab. The calorimeter absorber is an array of lead-fluoride crystals, which produces short-duration Cherenkov light. The detector sits in the high magnetic field of the muon storage ring. The SiPMs selected, and their accompanying custom electronics, must preserve the short pulse shape, have high quantum efficiency, be non-magnetic, exhibit gain stability under varying rate conditions, and cover a fairly large fraction of the crystal exit surface area.more » We describe an optimized design that employs the new-generation of thru-silicon via devices. As a result, the performance is documented in a series of bench and beam tests.« less

A Primer for Telemetry Interfacing in Accordance with NASA Standards Using Low Cost FPGAs

NASA Astrophysics Data System (ADS)

McCoy, Jake; Schultz, Ted; Tutt, James; Rogers, Thomas; Miles, Drew; McEntaffer, Randall

2016-03-01

Photon counting detector systems on sounding rocket payloads often require interfacing asynchronous outputs with a synchronously clocked telemetry (TM) stream. Though this can be handled with an on-board computer, there are several low cost alternatives including custom hardware, microcontrollers and field-programmable gate arrays (FPGAs). This paper outlines how a TM interface (TMIF) for detectors on a sounding rocket with asynchronous parallel digital output can be implemented using low cost FPGAs and minimal custom hardware. Low power consumption and high speed FPGAs are available as commercial off-the-shelf (COTS) products and can be used to develop the main component of the TMIF. Then, only a small amount of additional hardware is required for signal buffering and level translating. This paper also discusses how this system can be tested with a simulated TM chain in the small laboratory setting using FPGAs and COTS specialized data acquisition products.

Hardware for dynamic quantum computing.

PubMed

Ryan, Colm A; Johnson, Blake R; Ristè, Diego; Donovan, Brian; Ohki, Thomas A

2017-10-01

We describe the hardware, gateware, and software developed at Raytheon BBN Technologies for dynamic quantum information processing experiments on superconducting qubits. In dynamic experiments, real-time qubit state information is fed back or fed forward within a fraction of the qubits' coherence time to dynamically change the implemented sequence. The hardware presented here covers both control and readout of superconducting qubits. For readout, we created a custom signal processing gateware and software stack on commercial hardware to convert pulses in a heterodyne receiver into qubit state assignments with minimal latency, alongside data taking capability. For control, we developed custom hardware with gateware and software for pulse sequencing and steering information distribution that is capable of arbitrary control flow in a fraction of superconducting qubit coherence times. Both readout and control platforms make extensive use of field programmable gate arrays to enable tailored qubit control systems in a reconfigurable fabric suitable for iterative development.

Angular Positioning Sensor for Space Mechanisms

NASA Astrophysics Data System (ADS)

Steiner, Nicolas; Chapuis, Dominique

2013-09-01

Angular position sensors are used on various rotating mechanisms such as solar array drive mechanisms, antenna pointing mechanisms, scientific instruments, motors or actuators.Now a days, potentiometers and encoders are mainly used for angular measurement purposes. Both of them have their own pros and cons.As alternative, Ruag Space Switzerland Nyon (RSSN) is developing and qualifying two innovative technologies of angular position sensors which offer easy implementation, medium to very high lifetime and high flexibility with regards to the output signal shape/type.The Brushed angular position sensor uses space qualified processes which are already flying on RSSN's sliprings for many years. A large variety of output signal shape can be implemented to fulfill customer requirements (digital, analog, customized, etc.).The contactless angular position sensor consists in a new radiation hard Application Specific Integrated Circuit (ASIC) based on the Hall effect and providing the angular position without complex processing algorithm.

Open-Source 3-D Platform for Low-Cost Scientific Instrument Ecosystem.

PubMed

Zhang, C; Wijnen, B; Pearce, J M

2016-08-01

The combination of open-source software and hardware provides technically feasible methods to create low-cost, highly customized scientific research equipment. Open-source 3-D printers have proven useful for fabricating scientific tools. Here the capabilities of an open-source 3-D printer are expanded to become a highly flexible scientific platform. An automated low-cost 3-D motion control platform is presented that has the capacity to perform scientific applications, including (1) 3-D printing of scientific hardware; (2) laboratory auto-stirring, measuring, and probing; (3) automated fluid handling; and (4) shaking and mixing. The open-source 3-D platform not only facilities routine research while radically reducing the cost, but also inspires the creation of a diverse array of custom instruments that can be shared and replicated digitally throughout the world to drive down the cost of research and education further. © 2016 Society for Laboratory Automation and Screening.

The DIRC front-end electronics chain for BaBar

NASA Astrophysics Data System (ADS)

Bailly, P.; Beigbeder, C.; Bernier, R.; Breton, D.; Bonneaud, G.; Caceres, T.; Chase, R.; Chauveau, J.; Del Buono, L.; Dohou, F.; Ducorps, A.; Gastaldi, F.; Genat, J. F.; Hrisoho, A.; Imbert, P.; Lebbolo, H.; Matricon, P.; Oxoby, G.; Renard, C.; Roos, L.; Sen, S.; Thiebaux, C.; Truong, K.; Tocut, V.; Vasileiadis, G.; Va'Vra, J.; Verderi, M.; Warner, D.; Wilson, R. J.; Wormser, G.; Zhang, B.; Zomer, F.

2000-12-01

Recent results from the Front-End electronics of the Detector of Internally Reflected Cerenkov light (DIRC) for the BaBar experiment at SLAC (Stanford, USA) are presented. It measures to better than 1 ns the arrival time of Cerenkov photoelectrons detected in a 11000 phototubes array and their amplitude spectra. It mainly comprises 64-channel DIRC Front-End Boards (DFB) equipped with eight full-custom analog chips performing zero-cross discrimination with 2 mV threshold and pulse shaping, four full-custom digital time to digital chips (TDC) for timing measurements with 500 ps binning and a readout logic selecting hits in the trigger window, and DIRC Crate Controller cards (DCC) serializing the data collected front up to 16 DFBs onto a 1.2 Gb/s optical link. Extensive test results of the pre-production chips are presented, as well as system tests.

Aerosol Optical Properties at the Ground Sites during the 2010 CARES Field Campaign

NASA Astrophysics Data System (ADS)

Atkinson, D. B.; Radney, J. G.; Harworth, J. W.

2010-12-01

Preliminary results from the ground sites at the 2010 CARES field campaign (T0 near Sacramento, CA and T1 near Cool, CA) will be presented. A number of aerosol optical properties were measured at high time resolution for the four week study period using custom instruments. The aerosol extinction coefficient was measured at T0 using a cavity ring-down transmissometer (CRDT) at two wavelengths (532 and 1064 nm) and the aerosol scattering coefficient was measured at 532 nm using a Radiance Research M903 nephelometer. At T1, a new CRDT instrument was deployed that measured the extinction coefficient at three wavelengths (355, 532, and 1064 nm) for sub-10 μm (nominal) and sub-2.5 μm aerosols at ambient, elevated, and reduced relative humidity. A new type of custom nephelometer that measures the aerosol scattering coefficient at 532 nm using an array detector was also deployed at T1.

Co-fabrication of chitosan and epoxy photoresist to form microwell arrays with permeable hydrogel bottoms

PubMed Central

Ornoff, Douglas M.; Wang, Yuli; Proctor, Angela; Shah, Akash S.; Allbritton, Nancy L.

2015-01-01

Microfabrication technology offers the potential to create biological platforms with customizable patterns and surface chemistries, allowing precise control over the biochemical microenvironment to which a cell or group of cells is exposed. However, most microfabricated platforms grow cells on impermeable surfaces. This report describes the co-fabrication of a micropatterned epoxy photoresist film with a chitosan film to create a freestanding array of permeable, hydrogel-bottomed microwells. These films possess optical properties ideal for microscopy applications, and the chitosan layers are semi-permeable with a molecular exclusion of 9.9 ± 2.1 kDa. By seeding cells into the microwells, overlaying inert mineral oil, and supplying media via the bottom surface, this hybrid film permits cells to be physically isolated from one another but maintained in culture for at least 4 days. Arrays co-fabricated using these materials reduce both large-molecular-weight biochemical crosstalk between cells and mixing of different clonal populations, and will enable high-throughput studies of cellular heterogeneity with increased ability to customize dynamic interrogations compared to materials in currently available technologies. PMID:26447557

Focal plane arrays from UV up to VLWIR

NASA Astrophysics Data System (ADS)

Costard, E.; Nedelcu, A.; Achouche, M.; Reverchon, J. L.; Truffer, J. P.; Huet, O.; Dua, L.; Robo, J. A.; Marcadet, X.; Brière de l'Isle, N.; Facoetti, H.; Bois, P.

2007-10-01

Since 2002, the THALES Group has been manufacturing sensitive arrays using QWIP technology based on GaAs and related III-V compounds, at the Alcatel-Thales-III-V Lab (formerly part of THALES Research and Technology Laboratory). In the past researchers claimed many advantages of QWIPs. Uniformity was one of these and has been the key parameter for the production to start. Another widely claimed advantage for QWIPs was the so-called band-gap engineering and versatility of the III-V processing allowing the custom design of quantum structures to fulfil the requirements of specific applications such as very long wavelength (VLWIR) or multispectral detection. In this presentation, we give the status of our LWIR QWIP production line, and also the current status of QWIPs for MWIR (<5μm) and VLWIR (>15μm) arrays. As the QWIP technology cannot cover the full electromagnetic spectrum, we develop other semiconductor compounds for SWIR and UV applications. We present here the status of our first FPA realization in UV with GaN alloy, and at 1.5μm with InGaAs photodiodes.

In Vivo Validation of Custom-Designed Silicon-Based Microelectrode Arrays for Long-Term Neural Recording and Stimulation

PubMed Central

Manoonkitiwongsa, Panya S.; Wang, Cindy X.; McCreery, Douglas B.

2012-01-01

We developed and validated silicon-based neural probes for neural stimulating and recording in long-term implantation in the brain. The probes combine the deep reactive ion etching process and mechanical shaping of their tip region, yielding a mechanically sturdy shank with a sharpened tip to reduce insertion force into the brain and spinal cord, particularly, with multiple shanks in the same array. The arrays’ insertion forces have been quantified in vitro. Five consecutive chronically-implanted devices were fully functional from 3 to 18 months. The microelectrode sites were electroplated with iridium oxide, and the charge injection capacity measurements were performed both in vitro and after implantation in the adult feline brain. The functionality of the chronic array was validated by stimulating in the cochlear nucleus and recording the evoked neuronal activity in the central nucleus of the inferior colliculus. The arrays’ recording quality has also been quantified in vivo with neuronal spike activity recorded up to 566 days after implantation. Histopathology evaluation of neurons and astrocytes using immunohistochemical stains indicated minimal alterations of tissue architecture after chronic implantation. PMID:22020666

Flexible-Device Injector with a Microflap Array for Subcutaneously Implanting Flexible Medical Electronics.

PubMed

Song, Kwangsun; Kim, Juho; Cho, Sungbum; Kim, Namyun; Jung, Dongwuk; Choo, Hyuck; Lee, Jongho

2018-06-25

Implantable electronics in soft and flexible forms can reduce undesired outcomes such as irritations and chronic damages to surrounding biological tissues due to the improved mechanical compatibility with soft tissues. However, the same mechanical flexibility also makes it difficult to insert such implants through the skin because of reduced stiffness. In this paper, a flexible-device injector that enables the subcutaneous implantation of flexible medical electronics is reported. The injector consists of a customized blade at the tip and a microflap array which holds the flexible implant while the injector penetrates through soft tissues. The microflap array eliminates the need of additional materials such as adhesives that require an extended period to release a flexible medical electronic implant from an injector inside the skin. The mechanical properties of the injection system during the insertion process are experimentally characterized, and the injection of a flexible optical pulse sensor and electrocardiogram sensor is successfully demonstrated in vivo in live pig animal models to establish the practical feasibility of the concept. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The single mirror small size telescope (SST-1M) of the Cherenkov Telescope Array

NASA Astrophysics Data System (ADS)

Aguilar, J. A.; Bilnik, W.; Borkowski, J.; Cadoux, F.; Christov, A.; della Volpe, D.; Favre, Y.; Heller, M.; Kasperek, J.; Lyard, E.; Marszałek, A.; Moderski, R.; Montaruli, T.; Porcelli, A.; Prandini, E.; Rajda, P.; Rameez, M.; Schioppa, E., Jr.; Troyano Pujadas, I.; Zietara, K.; Blocki, J.; Bogacz, L.; Bulik, T.; Frankowski, A.; Grudzinska, M.; Idźkowski, B.; Jamrozy, M.; Janiak, M.; Lalik, K.; Mach, E.; Mandat, D.; Michałowski, J.; Neronov, A.; Niemiec, J.; Ostrowski, M.; Paśko, P.; Pech, M.; Schovanek, P.; Seweryn, K.; Skowron, K.; Sliusar, V.; Stawarz, L.; Stodulska, M.; Stodulski, M.; Toscano, S.; Walter, R.; WiÈ©cek, M.; Zagdański, A.

2016-07-01

The Small Size Telescope with Single Mirror (SST-1M) is one of the proposed types of Small Size Telescopes (SST) for the Cherenkov Telescope Array (CTA). The CTA south array will be composed of about 100 telescopes, out of which about 70 are of SST class, which are optimized for the detection of gamma rays in the energy range from 5 TeV to 300 TeV. The SST-1M implements a Davies-Cotton optics with a 4 m dish diameter with a field of view of 9°. The Cherenkov light produced in atmospheric showers is focused onto a 88 cm wide hexagonal photo-detection plane, composed of 1296 custom designed large area hexagonal silicon photomultipliers (SiPM) and a fully digital readout and trigger system. The SST-1M camera has been designed to provide high performance in a robust as well as compact and lightweight design. In this contribution, we review the different steps that led to the realization of the telescope prototype and its innovative camera.

Polarization-tuned Dynamic Color Filters Incorporating a Dielectric-loaded Aluminum Nanowire Array

PubMed Central

Raj Shrestha, Vivek; Lee, Sang-Shin; Kim, Eun-Soo; Choi, Duk-Yong

2015-01-01

Nanostructured spectral filters enabling dynamic color-tuning are saliently attractive for implementing ultra-compact color displays and imaging devices. Realization of polarization-induced dynamic color-tuning via one-dimensional periodic nanostructures is highly challenging due to the absence of plasmonic resonances for transverse-electric polarization. Here we demonstrate highly efficient dynamic subtractive color filters incorporating a dielectric-loaded aluminum nanowire array, providing a continuum of customized color according to the incident polarization. Dynamic color filtering was realized relying on selective suppression in transmission spectra via plasmonic resonance at a metal-dielectric interface and guided-mode resonance for a metal-clad dielectric waveguide, each occurring at their characteristic wavelengths for transverse-magnetic and electric polarizations, respectively. A broad palette of colors, including cyan, magenta, and yellow, has been attained with high transmission beyond 80%, by tailoring the period of the nanowire array and the incident polarization. Thanks to low cost, high durability, and mass producibility of the aluminum adopted for the proposed devices, they are anticipated to be diversely applied to color displays, holographic imaging, information encoding, and anti-counterfeiting. PMID:26211625

An efficient annotation and gene-expression derivation tool for Illumina Solexa datasets

PubMed Central

2010-01-01

Background The data produced by an Illumina flow cell with all eight lanes occupied, produces well over a terabyte worth of images with gigabytes of reads following sequence alignment. The ability to translate such reads into meaningful annotation is therefore of great concern and importance. Very easily, one can get flooded with such a great volume of textual, unannotated data irrespective of read quality or size. CASAVA, a optional analysis tool for Illumina sequencing experiments, enables the ability to understand INDEL detection, SNP information, and allele calling. To not only extract from such analysis, a measure of gene expression in the form of tag-counts, but furthermore to annotate such reads is therefore of significant value. Findings We developed TASE (Tag counting and Analysis of Solexa Experiments), a rapid tag-counting and annotation software tool specifically designed for Illumina CASAVA sequencing datasets. Developed in Java and deployed using jTDS JDBC driver and a SQL Server backend, TASE provides an extremely fast means of calculating gene expression through tag-counts while annotating sequenced reads with the gene's presumed function, from any given CASAVA-build. Such a build is generated for both DNA and RNA sequencing. Analysis is broken into two distinct components: DNA sequence or read concatenation, followed by tag-counting and annotation. The end result produces output containing the homology-based functional annotation and respective gene expression measure signifying how many times sequenced reads were found within the genomic ranges of functional annotations. Conclusions TASE is a powerful tool to facilitate the process of annotating a given Illumina Solexa sequencing dataset. Our results indicate that both homology-based annotation and tag-count analysis are achieved in very efficient times, providing researchers to delve deep in a given CASAVA-build and maximize information extraction from a sequencing dataset. TASE is specially designed to translate sequence data in a CASAVA-build into functional annotations while producing corresponding gene expression measurements. Achieving such analysis is executed in an ultrafast and highly efficient manner, whether the analysis be a single-read or paired-end sequencing experiment. TASE is a user-friendly and freely available application, allowing rapid analysis and annotation of any given Illumina Solexa sequencing dataset with ease. PMID:20598141

Robotic radiosurgery system patient-specific QA for extracranial treatments using the planar ion chamber array and the cylindrical diode array.

PubMed

Lin, Mu-Han; Veltchev, Iavor; Koren, Sion; Ma, Charlie; Li, Jinsgeng

2015-07-08

Robotic radiosurgery system has been increasingly employed for extracranial treatments. This work is aimed to study the feasibility of a cylindrical diode array and a planar ion chamber array for patient-specific QA with this robotic radiosurgery system and compare their performance. Fiducial markers were implanted in both systems to enable image-based setup. An in-house program was developed to postprocess the movie file of the measurements and apply the beam-by-beam angular corrections for both systems. The impact of noncoplanar delivery was then assessed by evaluating the angles created by the incident beams with respect to the two detector arrangements and cross-comparing the planned dose distribution to the measured ones with/without the angular corrections. The sensitivity of detecting the translational (1-3 mm) and the rotational (1°-3°) delivery errors were also evaluated for both systems. Six extracranial patient plans (PTV 7-137 cm³) were measured with these two systems and compared with the calculated doses. The plan dose distributions were calculated with ray-tracing and the Monte Carlo (MC) method, respectively. With 0.8 by 0.8 mm² diodes, the output factors measured with the cylindrical diode array agree better with the commissioning data. The maximum angular correction for a given beam is 8.2% for the planar ion chamber array and 2.4% for the cylindrical diode array. The two systems demonstrate a comparable sensitivity of detecting the translational targeting errors, while the cylindrical diode array is more sensitive to the rotational targeting error. The MC method is necessary for dose calculations in the cylindrical diode array phantom because the ray-tracing algorithm fails to handle the high-Z diodes and the acrylic phantom. For all the patient plans, the cylindrical diode array/ planar ion chamber array demonstrate 100% / > 92% (3%/3 mm) and > 96% / ~ 80% (2%/2 mm) passing rates. The feasibility of using both systems for robotic radiosurgery system patient-specific QA has been demonstrated. For gamma evaluation, 2%/2 mm criteria for cylindrical diode array and 3%/3 mm criteria for planar ion chamber array are suggested. The customized angular correction is necessary as proven by the improved passing rate, especially with the planar ion chamber array system.

The ARA Mark 3 solar array design and development

NASA Technical Reports Server (NTRS)

vanHassel, Rob H. A.

1996-01-01

The ARA (Advanced Rigid Array) Mark3 solar array of Fokker Space BV is currently in its final stages of qualification (wing tests to be completed in March, 1996; unit/part tests in April, 1996). With regard to its predecessor, the ARA Mark2, the design has not only been improved in terms of mechanical and electrical performance, but also with regard to production cost and throughput time. This 'state of the art' array is designed to fit the needs of a wide variety of geostationary telecommunications satellites and is qualified for launch on the complete range of medium/large size commercial launchers (Ariane IV & V, Atlas, Delta, Proton, Long March, H2). The first mission to fly the new ARA Mk3 array is Hot Bird 2 (customer: Eutelsat, prime contractor: Matra Marconi Space; launch: mid-1996). In this configuration, its end of life (EOL) power-to-mass ratio is 42 W/kg, with an operational life of more than 12 years. The main mechanisms on a solar array are typically found in the deployment system and in the hold down and release system. During the design and development phase of these mechanisms, extensive engineering and qualification tests have been performed. This paper presents the key design features of these mechanisms and the improvements that were made with regard to their predecessors. It also describes the qualification philosophy on unit/part and wing level. Finally, some of the development items that turned out to be critical, as well as the lessons learned from them, are discussed.

Big-Data Perspective to Operating an SKA-Type Synthesis Array Radio Telescope

NASA Astrophysics Data System (ADS)

Shanmugha Sundaram, GA

2015-08-01

Of the two forerunner sites, viz. Australia and South Africa, where pioneering advancements to state-of-the-art in synthesis array radio astronomy instrumentation are being attempted in the form of pathfinders to the Square Kilometer Array (SKA), for its eventual deployment, a diversity of site-dependent topology and design metrics exists. Towards addressing some of the fundamental mysteries in physics at the micro- and macro-cosm levels, that form the Key Science Projects (KSPs) for the SKA, and interfacing them to an optimally designed array conguration, a critical evaluation of their radio imaging capabilities and metrics becomes paramount. Here, the various KSPs and instrument design specifications are discussed, for relative merits and adaptability to either site, from invoking well-founded and established array-design and optimization principles designed into a customized software tool. Since the problem of array design is one that encompasses variables on several scales such as separation distances between the radio interferometric pair (termed the baseline), factors such as redundancy, flux and phase calibration, bandwidth, integration time, clock synchronization for the correlation process at the detector, and many other ambient-defined parameters, there is a significant component of big data involved in the complex visibilities that are to be Fourier transformed from the spatial to the radio-sky domain (to generate a radio sky map) using vast computational infrastructure, with robust data connectivity and data handling facilities to support this. A crucial requirement exists to make the general public aware of the implications of such a massive scale scientific and technological venture, which shall be the focus of this presentation.

Development of a Real-Time Hardware-in-the-Loop Power Systems Simulation Platform to Evaluate Commercial Microgrid Controllers

DTIC Science & Technology

2016-02-19

power converter, a solar photovoltaic ( PV ) system with inverter, and eighteen breakers. (Future work will require either validation of these models...custom control software. (For this project, this was done for the energy storage, solar PV , and breakers.) Implement several relay protection functions...for the PV array is given in Section A.3. This profile was generated by applying a decimation/interpolation filter to the signal from a solar flux

Resonant Cavity Enhanced On-Chip Raman Spectrometer Array with Precisely Positioned Metallic Nano-Gaps for Single Molecule Detection

DTIC Science & Technology

2011-03-22

the nanogaps are engraved on. Simulations show that smaller diameters of the nanowires should provide higher enhancement factors for SERS signal...Inverted Microscope with lasers of wavelengths of 512 to 633 nm as the excitation source. The signal was collected and analyzed by a 50cm Spectrometer...the optical path which can selectively pass the Raman signals and reject the excitation lasers . Figure 2.12 Custom built Raman microscope for the

Next-generation laser retroreflectors for GNSS, solar system exploration, geodesy, gravitational physics and earth observation

NASA Astrophysics Data System (ADS)

Dell'Agnello, S.; Boni, A.; Cantone, C.; Ciocci, E.; Martini, M.; Patrizi, G.; Tibuzzi, M.; Delle Monache, G.; Vittori, R.; Bianco, G.; Currie, D.; Intaglietta, N.; Salvatori, L.; Lops, C.; Contessa, S.; Porcelli, L.; Mondaini, C.; Tuscano, P.; Maiello, M.

2017-11-01

The SCF_Lab (Satellite/lunar/gnss laser ranging and altimetry Characterization Facility Laboratory) of INFNLNF is designed to cover virtually LRAs (Laser Retroreflector Arrays) of CCRs (Cube Corner Retroreflectors) for missions in the whole solar system, with a modular organization of its instrumentation, two redundant SCF (SCF_Lab Characterization Facilities), and an evolutionary measurement approach, including customization and potentially upgrade on-demand. See http://www.lnf.infn.it/esperimenti/etrusco/ for a general description.

Analysis of Multiplexed Nanosensor Arrays Based on Near-Infrared Fluorescent Single-Walled Carbon Nanotubes.

PubMed

Dong, Juyao; Salem, Daniel P; Sun, Jessica H; Strano, Michael S

2018-04-24

The high-throughput, label-free detection of biomolecules remains an important challenge in analytical chemistry with the potential of nanosensors to significantly increase the ability to multiplex such assays. In this work, we develop an optical sensor array, printable from a single-walled carbon nanotube/chitosan ink and functionalized to enable a divalent ion-based proximity quenching mechanism for transducing binding between a capture protein or an antibody with the target analyte. Arrays of 5 × 6, 200 μm near-infrared (nIR) spots at a density of ≈300 spots/cm 2 are conjugated with immunoglobulin-binding proteins (proteins A, G, and L) for the detection of human IgG, mouse IgM, rat IgG2a, and human IgD. Binding kinetics are measured in a parallel, multiplexed fashion from each sensor spot using a custom laser scanning imaging configuration with an nIR photomultiplier tube detector. These arrays are used to examine cross-reactivity, competitive and nonspecific binding of analyte mixtures. We find that protein G and protein L functionalized sensors report selective responses to mouse IgM on the latter, as anticipated. Optically addressable platforms such as the one examined in this work have potential to significantly advance the real-time, multiplexed biomolecular detection of complex mixtures.

Killer whale caller localization using a hydrophone array in an oceanarium pool

NASA Astrophysics Data System (ADS)

Bowles, Ann E.; Greenlaw, Charles F.; McGehee, Duncan E.; van Holliday, D.

2004-05-01

A system to localize calling killer whales was designed around a ten-hydrophone array in a pool at SeaWorld San Diego. The array consisted of nine ITC 8212 and one ITC 6050H hydrophones mounted in recessed 30×30 cm2 niches. Eight of the hydrophones were connected to a Compaq Armada E500 laptop computer through a National Instruments DAQ 6024E PCMCIA A/D data acquisition card and a BNC-2120 signal conditioner. The system was calibrated with a 139-dB, 4.5-kHz pinger. Acoustic data were collected during four 48-72 h recording sessions, simultaneously with video recorded from a four-camera array. Calling whales were localized by one of two methods, (1) at the hydrophone reporting the highest sound exposure level and (2) using custom-designed 3-D localization software based on time-of-arrival (ORCA). Complex reverberations in the niches and pool made locations based on time of arrival difficult to collect. Based on preliminary analysis of data from four sessions (400+ calls/session), the hydrophone reporting the highest level reliably attributed callers 51%-100% of the time. This represents a substantial improvement over attribution rates of 5%-15% obtained with single hydrophone recordings. [Funding provided by Hubbs-SeaWorld Research Institute and the Hubbs Society.

Frontend Receiver Electronics for High Frequency Monolithic CMUT-on-CMOS Imaging Arrays

PubMed Central

Gurun, Gokce; Hasler, Paul; Degertekin, F. Levent

2012-01-01

This paper describes the design of CMOS receiver electronics for monolithic integration with capacitive micromachined ultrasonic transducer (CMUT) arrays for high-frequency intravascular ultrasound imaging. A custom 8-inch wafer is fabricated in a 0.35 μm two-poly, four-metal CMOS process and then CMUT arrays are built on top of the application specific integrated circuits (ASICs) on the wafer. We discuss advantages of the single-chip CMUT-on-CMOS approach in terms of receive sensitivity and SNR. Low-noise and high-gain design of a transimpedance amplifier (TIA) optimized for a forward-looking volumetric-imaging CMUT array element is discussed as a challenging design example. Amplifier gain, bandwidth, dynamic range and power consumption trade-offs are discussed in detail. With minimized parasitics provided by the CMUT-on-CMOS approach, the optimized TIA design achieves a 90 fA/√Hz input referred current noise, which is less than the thermal-mechanical noise of the CMUT element. We show successful system operation with a pulse-echo measurement. Transducer noise-dominated detection in immersion is also demonstrated through output noise spectrum measurement of the integrated system at different CMUT bias voltages. A noise figure of 1.8 dB is obtained in the designed CMUT bandwidth of 10 MHz to 20 MHz. PMID:21859585

Front-end receiver electronics for high-frequency monolithic CMUT-on-CMOS imaging arrays.

PubMed

Gurun, Gokce; Hasler, Paul; Degertekin, F

2011-08-01

This paper describes the design of CMOS receiver electronics for monolithic integration with capacitive micromachined ultrasonic transducer (CMUT) arrays for highfrequency intravascular ultrasound imaging. A custom 8-inch (20-cm) wafer is fabricated in a 0.35-μm two-poly, four-metal CMOS process and then CMUT arrays are built on top of the application specific integrated circuits (ASICs) on the wafer. We discuss advantages of the single-chip CMUT-on-CMOS approach in terms of receive sensitivity and SNR. Low-noise and high-gain design of a transimpedance amplifier (TIA) optimized for a forward-looking volumetric-imaging CMUT array element is discussed as a challenging design example. Amplifier gain, bandwidth, dynamic range, and power consumption trade-offs are discussed in detail. With minimized parasitics provided by the CMUT-on-CMOS approach, the optimized TIA design achieves a 90 fA/√Hz input-referred current noise, which is less than the thermal-mechanical noise of the CMUT element. We show successful system operation with a pulseecho measurement. Transducer-noise-dominated detection in immersion is also demonstrated through output noise spectrum measurement of the integrated system at different CMUT bias voltages. A noise figure of 1.8 dB is obtained in the designed CMUT bandwidth of 10 to 20 MHz.

Control of the external photoluminescent quantum yield of emitters coupled to nanoantenna phased arrays

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

Guo, Ke; Verschuuren, Marc A.; Lozano, Gabriel

2015-08-21

Optical losses in metals represent the largest limitation to the external quantum yield of emitters coupled to plasmonic antennas. These losses can be at the emission wavelength, but they can be more important at shorter wavelengths, i.e., at the excitation wavelength of the emitters, where the conductivity of metals is usually lower. We present accurate measurements of the absolute external photoluminescent quantum yield of a thin layer of emitting material deposited over a periodic nanoantenna phased array. Emission and absorptance measurements of the sample are performed using a custom-made setup including an integrating sphere and variable angle excitation. The measurementsmore » reveal a strong dependence of the external quantum yield on the angle at which the optical field excites the sample. Such behavior is attributed to the coupling between far-field illumination and near-field excitation mediated by the collective resonances supported by the array. Numerical simulations confirm that the inherent losses associated with the metal can be greatly reduced by selecting an optimum angle of illumination, which boosts the light conversion efficiency in the emitting layer. This combined experimental and numerical characterization of the emission from plasmonic arrays reveals the need to carefully design the illumination to achieve the maximum external quantum yield.« less

A dual-mode hemispherical sparse array for 3D passive acoustic mapping and skull localization within a clinical MRI guided focused ultrasound device

NASA Astrophysics Data System (ADS)

Crake, Calum; Brinker, Spencer T.; Coviello, Christian M.; Livingstone, Margaret S.; McDannold, Nathan J.

2018-03-01

Previous work has demonstrated that passive acoustic imaging may be used alongside MRI for monitoring of focused ultrasound therapy. However, past implementations have generally made use of either linear arrays originally designed for diagnostic imaging or custom narrowband arrays specific to in-house therapeutic transducer designs, neither of which is fully compatible with clinical MR-guided focused ultrasound (MRgFUS) devices. Here we have designed an array which is suitable for use within an FDA-approved MR-guided transcranial focused ultrasound device, within the bore of a 3 Tesla clinical MRI scanner. The array is constructed from 5  ×  0.4 mm piezoceramic disc elements arranged in pseudorandom fashion on a low-profile laser-cut acrylic frame designed to fit between the therapeutic elements of a 230 kHz InSightec ExAblate 4000 transducer. By exploiting thickness and radial resonance modes of the piezo discs the array is capable of both B-mode imaging at 5 MHz for skull localization, as well as passive reception at the second harmonic of the therapy array for detection of cavitation and 3D passive acoustic imaging. In active mode, the array was able to perform B-mode imaging of a human skull, showing the outer skull surface with good qualitative agreement with MR imaging. Extension to 3D showed the array was able to locate the skull within  ±2 mm/2° of reference points derived from MRI, which could potentially allow registration of a patient to the therapy system without the expense of real-time MRI. In passive mode, the array was able to resolve a point source in 3D within a  ±10 mm region about each axis from the focus, detect cavitation (SNR ~ 12 dB) at burst lengths from 10 cycles to continuous wave, and produce 3D acoustic maps in a flow phantom. Finally, the array was used to detect and map cavitation associated with microbubble activity in the brain in nonhuman primates.

Developing cDNA Libraries of Receptors Involved in the Recruitment of the Biofouling Tubeworm Hydroides elegans

DTIC Science & Technology

2014-06-12

Transcriptome, Hydroides elegans, Next Generation Sequencing, Illumina HiSeq, PacBio SMRT, Biofilm , Metamorphosis 16. SECURITY CLASSIFICATION OF: a...to a bacterial cue from a bacterial biofilm . Recently, this cue has been identified to be a phage-tail like bacteriocin produced by the bacterium...submitted to the Huntsman Cancer Institute at the University of Utah and the subsequent isolation of mRNA was used for Illumina HiSeq 101 paired end

Estimating genotype error rates from high-coverage next-generation sequence data.

PubMed

Wall, Jeffrey D; Tang, Ling Fung; Zerbe, Brandon; Kvale, Mark N; Kwok, Pui-Yan; Schaefer, Catherine; Risch, Neil

2014-11-01

Exome and whole-genome sequencing studies are becoming increasingly common, but little is known about the accuracy of the genotype calls made by the commonly used platforms. Here we use replicate high-coverage sequencing of blood and saliva DNA samples from four European-American individuals to estimate lower bounds on the error rates of Complete Genomics and Illumina HiSeq whole-genome and whole-exome sequencing. Error rates for nonreference genotype calls range from 0.1% to 0.6%, depending on the platform and the depth of coverage. Additionally, we found (1) no difference in the error profiles or rates between blood and saliva samples; (2) Complete Genomics sequences had substantially higher error rates than Illumina sequences had; (3) error rates were higher (up to 6%) for rare or unique variants; (4) error rates generally declined with genotype quality (GQ) score, but in a nonlinear fashion for the Illumina data, likely due to loss of specificity of GQ scores greater than 60; and (5) error rates increased with increasing depth of coverage for the Illumina data. These findings, especially (3)-(5), suggest that caution should be taken in interpreting the results of next-generation sequencing-based association studies, and even more so in clinical application of this technology in the absence of validation by other more robust sequencing or genotyping methods. © 2014 Wall et al.; Published by Cold Spring Harbor Laboratory Press.

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

PubMed Central

2014-01-01

Introduction We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. Methods We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. Results We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (Ptrend = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (Ptrend = 0.005) but not cases (Ptrend = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (Phet = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (ORhet = 0.84, 95% CI 0.75, 0.94; ORhom = 0.81, 95% CI 0.51, 1.30; Ptrend = 0.002) but not for those who had their menarche age ≤11 years (ORhet = 1.06, 95% CI 0.95, 1.19, ORhom = 1.07, 95% CI 0.67, 1.72; Ptrend = 0.29). Conclusions To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels. PMID:24887515

Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study.

PubMed

Johnson, Nichola; Dudbridge, Frank; Orr, Nick; Gibson, Lorna; Jones, Michael E; Schoemaker, Minouk J; Folkerd, Elizabeth J; Haynes, Ben P; Hopper, John L; Southey, Melissa C; Dite, Gillian S; Apicella, Carmel; Schmidt, Marjanka K; Broeks, Annegien; Van't Veer, Laura J; Atsma, Femke; Muir, Kenneth; Lophatananon, Artitaya; Fasching, Peter A; Beckmann, Matthias W; Ekici, Arif B; Renner, Stefan P; Sawyer, Elinor; Tomlinson, Ian; Kerin, Michael; Miller, Nicola; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Guénel, Pascal; Truong, Therese; Cordina, Emilie; Menegaux, Florence; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Milne, Roger; Zamora, M Pilar; Arias Perez, Jose Ignacio; Benitez, Javier; Bernstein, Leslie; Anton-Culver, Hoda; Ziogas, Argyrios; Clarke Dur, Christina; Brenner, Hermann; Müller, Heiko; Arndt, Volker; Dieffenbach, Aida Karina; Meindl, Alfons; Heil, Joerg; Bartram, Claus R; Schmutzler, Rita K; Brauch, Hiltrud; Justenhoven, Christina; Ko, Yon-Dschun; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Matsuo, Keitaro; Dörk, Thilo; Bogdanova, Natalia V; Antonenkova, Natalia N; Lindblom, Annika; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Chenevix-Trench, Georgia; Beesley, Jonathan; Wu, Anna H; Van den Berg, David; Tseng, Chiu-Chen; Lambrechts, Diether; Smeets, Dominiek; Neven, Patrick; Wildiers, Hans; Chang-Claude, Jenny; Rudolph, Anja; Nickels, Stefan; Flesch-Janys, Dieter; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Pensotti, Valeria; Couch, Fergus J; Olson, Janet E; Wang, Xianshu; Fredericksen, Zachary; Pankratz, Vernon S; Giles, Graham G; Severi, Gianluca; Baglietto, Laura; Haiman, Chris; Simard, Jacques; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Soucy, Penny; Teo, Soo; Yip, Cheng Har; Phuah, Sze Yee; Cornes, Belinda K; Kristensen, Vessela N; Grenaker Alnæs, Grethe; Børresen-Dale, Anne-Lise; Zheng, Wei; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Devillee, Peter; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Sherman, Mark E; Hall, Per; Schoof, Nils; Hooning, Maartje; Hollestelle, Antoinette; Oldenburg, Rogier A; Tilanus-Linthorst, Madeleine; Liu, Jianjun; Cox, Angie; Brock, Ian W; Reed, Malcolm W R; Cross, Simon S; Blot, William; Signorello, Lisa B; Pharoah, Paul D P; Dunning, Alison M; Shah, Mitul; Kang, Daehee; Noh, Dong-Young; Park, Sue K; Choi, Ji-Yeob; Hartman, Mikael; Miao, Hui; Lim, Wei Yen; Tang, Anthony; Hamann, Ute; Försti, Asta; Rüdiger, Thomas; Ulmer, Hans Ulrich; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Vachon, Celine; Yannoukakos, Drakoulis; Shen, Chen-Yang; Yu, Jyh-Cherng; Huang, Chiun-Sheng; Hou, Ming-Feng; González-Neira, Anna; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Luccarini, Craig; Dennis, Joe; Michailidou, Kyriaki; Bolla, Manjeet K; Wang, Jean; Easton, Douglas F; García-Closas, Montserrat; Dowsett, Mitch; Ashworth, Alan; Swerdlow, Anthony J; Peto, Julian; dos Santos Silva, Isabel; Fletcher, Olivia

2014-05-26

We have previously shown that a tag single nucleotide polymorphism (rs10235235), which maps to the CYP3A locus (7q22.1), was associated with a reduction in premenopausal urinary estrone glucuronide levels and a modest reduction in risk of breast cancer in women age ≤50 years. We further investigated the association of rs10235235 with breast cancer risk in a large case control study of 47,346 cases and 47,570 controls from 52 studies participating in the Breast Cancer Association Consortium. Genotyping of rs10235235 was conducted using a custom Illumina Infinium array. Stratified analyses were conducted to determine whether this association was modified by age at diagnosis, ethnicity, age at menarche or tumor characteristics. We confirmed the association of rs10235235 with breast cancer risk for women of European ancestry but found no evidence that this association differed with age at diagnosis. Heterozygote and homozygote odds ratios (ORs) were OR = 0.98 (95% CI 0.94, 1.01; P = 0.2) and OR = 0.80 (95% CI 0.69, 0.93; P = 0.004), respectively (P(trend) = 0.02). There was no evidence of effect modification by tumor characteristics. rs10235235 was, however, associated with age at menarche in controls (P(trend) = 0.005) but not cases (P(trend) = 0.97). Consequently the association between rs10235235 and breast cancer risk differed according to age at menarche (P(het) = 0.02); the rare allele of rs10235235 was associated with a reduction in breast cancer risk for women who had their menarche age ≥15 years (OR(het) = 0.84, 95% CI 0.75, 0.94; OR(hom) = 0.81, 95% CI 0.51, 1.30; P(trend) = 0.002) but not for those who had their menarche age ≤11 years (OR(het) = 1.06, 95% CI 0.95, 1.19, OR(hom) = 1.07, 95% CI 0.67, 1.72; P(trend) = 0.29). To our knowledge rs10235235 is the first single nucleotide polymorphism to be associated with both breast cancer risk and age at menarche consistent with the well-documented association between later age at menarche and a reduction in breast cancer risk. These associations are likely mediated via an effect on circulating hormone levels.

Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas.

PubMed

Johncilla, Melanie; Stachler, Matthew; Misdraji, Joseph; Lisovsky, Mikhail; Yozu, Masato; Lindeman, Neal; Lauwers, Gregory Y; Odze, Robert D; Srivastava, Amitabh

2018-02-08

There is limited data on the spectrum of molecular alterations in goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix. We used next generation sequencing to determine mutations of potential pathogenetic and therapeutic significance in this rare group of tumors. Adequate DNA was successfully extracted in 34/46 cases and the final group included 18 goblet cell carcinoids and 16 adenocarcinoma ex goblet cell carcinoids. Illumina TruSeq™ was used for sequencing exons of a custom 282 gene panel using an Illumina HiSeq 2000. All cases had a minimum coverage depth of at least 50 reads. After filtering through the Exome Sequencing Project, the number of mutations per case ranged from 0-9 (mean:3). The mutational burden in adenocarcinoma ex goblet cell carcinoids was significantly higher than goblet cell carcinoids (mean 5 vs. 3; p < 0.05) but the spectrum of alterations overlapped between the two groups. The most frequent mutations included ARID1A (4/34), ARID2 (4/34), CDH1 (4/34), RHPN2 (4/34), and MLL2 (3/34). Some mutations typically seen in conventional colorectal adenocarcinomas were also identified but with much lower frequency (APC :4/34; KRAS :2/34). MLL2 and KRAS mutations were only seen in adenocarcinoma ex goblet cell carcinoids and TP53 mutations were limited to poorly differentiated adenocarcinoma ex goblet cell carcinoids (2/34). Copy number changes could be evaluated in 15/34 cases and showed low copy number gains in CDKN1B (6/15) and NFKBIA (6/15), among others. The overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered two grades of differentiation of the same tumor rather than two distinct histological types. Mutations in TP53, CDH1 and MLL2 mutations were predominantly present in the adenocarcinoma ex goblet cell carcinoid group consistent with transformation to a higher grade lesion. The unique mutational profile also offers an explanation for the poor chemosensitivity in these tumors and highlights the need for developing new targeted therapies.

Exome Array Analysis Identifies a Common Variant in IL27 Associated with Chronic Obstructive Pulmonary Disease

PubMed Central

Parker, Margaret M.; Chen, Han; Lao, Taotao; Hardin, Megan; Qiao, Dandi; Hawrylkiewicz, Iwona; Sliwinski, Pawel; Yim, Jae-Joon; Kim, Woo Jin; Kim, Deog Kyeom; Castaldi, Peter J.; Hersh, Craig P.; Morrow, Jarrett; Celli, Bartolome R.; Pinto-Plata, Victor M.; Criner, Gerald J.; Marchetti, Nathaniel; Bueno, Raphael; Agustí, Alvar; Make, Barry J.; Crapo, James D.; Calverley, Peter M.; Donner, Claudio F.; Lomas, David A.; Wouters, Emiel F. M.; Vestbo, Jorgen; Paré, Peter D.; Levy, Robert D.; Rennard, Stephen I.; Zhou, Xiaobo; Laird, Nan M.; Lin, Xihong; Beaty, Terri H.; Silverman, Edwin K.

2016-01-01

Rationale: Chronic obstructive pulmonary disease (COPD) susceptibility is in part related to genetic variants. Most genetic studies have been focused on genome-wide common variants without a specific focus on coding variants, but common and rare coding variants may also affect COPD susceptibility. Objectives: To identify coding variants associated with COPD. Methods: We tested nonsynonymous, splice, and stop variants derived from the Illumina HumanExome array for association with COPD in five study populations enriched for COPD. We evaluated single variants with a minor allele frequency greater than 0.5% using logistic regression. Results were combined using a fixed effects meta-analysis. We replicated novel single-variant associations in three additional COPD cohorts. Measurements and Main Results: We included 6,004 control subjects and 6,161 COPD cases across five cohorts for analysis. Our top result was rs16969968 (P = 1.7 × 10−14) in CHRNA5, a locus previously associated with COPD susceptibility and nicotine dependence. Additional top results were found in AGER, MMP3, and SERPINA1. A nonsynonymous variant, rs181206, in IL27 (P = 4.7 × 10−6) was just below the level of exome-wide significance but attained exome-wide significance (P = 5.7 × 10−8) when combined with results from other cohorts. Gene expression datasets revealed an association of rs181206 and the surrounding locus with expression of multiple genes; several were differentially expressed in COPD lung tissue, including TUFM. Conclusions: In an exome array analysis of COPD, we identified nonsynonymous variants at previously described loci and a novel exome-wide significant variant in IL27. This variant is at a locus previously described in genome-wide associations with diabetes, inflammatory bowel disease, and obesity and appears to affect genes potentially related to COPD pathogenesis. PMID:26771213

Dose Response and Prediction Characteristics of a Methylation Sensitive Digital PCR Assay for Cigarette Consumption in Adults.

PubMed

Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D; Beach, Steven R H; Black, Donald W

2018-01-01

The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated ( R 2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year ( R 2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality.

Dose Response and Prediction Characteristics of a Methylation Sensitive Digital PCR Assay for Cigarette Consumption in Adults

PubMed Central

Philibert, Robert; Dogan, Meesha; Noel, Amanda; Miller, Shelly; Krukow, Brianna; Papworth, Emma; Cowley, Joseph; Long, Jeffrey D.; Beach, Steven R. H.; Black, Donald W.

2018-01-01

The tobacco use disorders are the largest preventable cause of morbidity and mortality in the world. A substantial barrier to the development of better intervention and screening measures is the lack of clinically employable biomarkers to detect the existence and extent of tobacco consumption. In prior work, we and others have shown that array based assessment of DNA methylation status at cg05575921 is a sensitive and quantitative method for assessing cigarette consumption. Unfortunately, in general, arrays are not practical clinical tools. Herein, we detail the prediction performance metrics and dose dependency of a clinically implementable droplet digital PCR (ddPCR) assay for cigarette consumption in adults. First, we demonstrate that measurements of cg05575921 as determined by Illumina array and ddPCR are highly correlated (R2 = 0.98, n = 92). Second, using clinical data and biomaterial from 177 subjects ranging from 18 to 78 years of age, we show that the Receiver Operating Characteristic (ROC) area under the curve (AUC) for classifying smoking status using methylation status at cg05575921 is 0.99. Finally, we conduct modeling analyses of cigarette consumption over discrete time periods to show that methylation status is best correlated with mean cigarette consumption over the past year (R2 = 0.5) and that demethylation at cg05575921 is dose dependent with a demethylation (delta beta) of 1% being equivalent to 1.2 cigarettes per day. But we do not find a relationship between Fagerstrom score and DNA methylation. We conclude that ddPCR assessment of cg05575921 methylation is an accurate method for assessing the presence and extent of cigarette consumption in adult subjects. We suggest that skillful clinical implementation of this approach alone or in combination with other assessment methods could lead to substantial reduction of cigarette consumption related morbidity and mortality. PMID:29740475

A gene expression signature of confinement in peripheral blood of red wolves (Canis rufus).

PubMed

Kennerly, Erin; Ballmann, Anne; Martin, Stanton; Wolfinger, Russ; Gregory, Simon; Stoskopf, Michael; Gibson, Greg

2008-06-01

The stresses that animals experience as a result of modification of their ecological circumstances induce physiological changes that leave a signature in profiles of gene expression. We illustrate this concept in a comparison of free range and confined North American red wolves (Canis rufus). Transcription profiling of peripheral blood samples from 13 red wolf individuals in the Alligator River region of North Carolina revealed a strong signal of differentiation. Four hundred eighty-two out of 2980 transcripts detected on Illumina HumanRef8 oligonucleotide bead arrays were found to differentiate free range and confined wolves at a false discovery rate of 12.8% and P < 0.05. Over-representation of genes in focal adhesion, insulin signalling, proteasomal, and tryptophan metabolism pathways suggests the activation of pro-inflammatory and stress responses in confined animals. Consequently, characterization of differential transcript abundance in an accessible tissue such as peripheral blood identifies biomarkers that could be useful in animal management practices and for evaluating the impact of habitat changes on population health, particularly as attention turns to the impact of climate change on physiology and in turn species distributions.

[Analysis of tissue-specific differentially methylated genes with differential gene expression in non-small cell lung cancer].

PubMed

Yin, L G; Zou, Z Q; Zhao, H Y; Zhang, C L; Shen, J G; Qi, L; Qi, M; Xue, Z Q

2014-01-01

Adenocarcinoma (ADC) and squamous cell carcinomas (SCC) are two subtypes of non-small cell lung carcinomas which are regarded as the leading cause of cancer-related malignancy worldwide. The aim of this study is to detect the differentially methylated loci (DMLs) and differentially methylated genes (DMGs) of these two tumor sets, and then to illustrate the different expression level of specific methylated genes. Using TCGA database and Illumina HumanMethylation 27 arrays, we first screened the DMGs and DMLs in tumor samples. Then, we explored the BiologicalProcess terms of hypermethylated and hypomethylated genes using Functional Gene Ontology (GO) catalogues. Hypermethylation intensively occurred in CpG-island, whereas hypomethylation was located in non-CpG-island. Most SCC and ADC hypermethylated genes involved GO function of DNA dependenit regulation of transcription, and hypomethylated genes mainly 'enriched in the term of immune responses. Additionally, the expression level of specific differentially methylated genesis distinctbetween ADC and SCC. It is concluded that ADC and SCC have different methylated status that might play an important role in carcinogenesis.

Report on the Infinium 450k methylation array analysis workshop: April 20, 2012 UCL, London, UK.

PubMed

Morris, Tiffany; Lowe, Robert

2012-08-01

A new platform for DNA methylome analysis is Illumina's Infinium HumanMethylation450. This technology is an extension of the previous HumanMethylation27 BeadChip and allows the methylation status of 12 samples per chip and 4 to 8 chips (total of 48 to 96 samples) to be assessed simultaneously for more than 480,000 cytosines across the genome. The platform incorporates two different probe types using different assay designs (InfiniumI and InfiniumII). Although this has allowed the assessment of more CpG sites, it has also introduced technical variation between the two probe types, which has complicated the analysis process. Many groups are working on normalization methods and analysis pipelines while many others are struggling to make sense of their new data sets. This motivated the organization of a meeting held at University College London that focused solely on the analysis methods and problems related to this new platform. The meeting was attended by 125 computational and bench scientists from 11 countries. There were 10 speakers, a small poster session and a discussion session.

Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America.

PubMed

Kosoy, Roman; Nassir, Rami; Tian, Chao; White, Phoebe A; Butler, Lesley M; Silva, Gabriel; Kittles, Rick; Alarcon-Riquelme, Marta E; Gregersen, Peter K; Belmont, John W; De La Vega, Francisco M; Seldin, Michael F

2009-01-01

To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations. Copyright 2008 Wiley-Liss, Inc.

Diversity and community composition of methanogenic archaea in the rumen of Scottish upland sheep assessed by different methods.

PubMed

Snelling, Timothy J; Genç, Buğra; McKain, Nest; Watson, Mick; Waters, Sinéad M; Creevey, Christopher J; Wallace, R John

2014-01-01

Ruminal archaeomes of two mature sheep grazing in the Scottish uplands were analysed by different sequencing and analysis methods in order to compare the apparent archaeal communities. All methods revealed that the majority of methanogens belonged to the Methanobacteriales order containing the Methanobrevibacter, Methanosphaera and Methanobacteria genera. Sanger sequenced 1.3 kb 16S rRNA gene amplicons identified the main species of Methanobrevibacter present to be a SGMT Clade member Mbb. millerae (≥ 91% of OTUs); Methanosphaera comprised the remainder of the OTUs. The primers did not amplify ruminal Thermoplasmatales-related 16S rRNA genes. Illumina sequenced V6-V8 16S rRNA gene amplicons identified similar Methanobrevibacter spp. and Methanosphaera clades and also identified the Thermoplasmatales-related order as 13% of total archaea. Unusually, both methods concluded that Mbb. ruminantium and relatives from the same clade (RO) were almost absent. Sequences mapping to rumen 16S rRNA and mcrA gene references were extracted from Illumina metagenome data. Mapping of the metagenome data to 16S rRNA gene references produced taxonomic identification to Order level including 2-3% Thermoplasmatales, but was unable to discriminate to species level. Mapping of the metagenome data to mcrA gene references resolved 69% to unclassified Methanobacteriales. Only 30% of sequences were assigned to species level clades: of the sequences assigned to Methanobrevibacter, most mapped to SGMT (16%) and RO (10%) clades. The Sanger 16S amplicon and Illumina metagenome mcrA analyses showed similar species richness (Chao1 Index 19-35), while Illumina metagenome and amplicon 16S rRNA analysis gave lower richness estimates (10-18). The values of the Shannon Index were low in all methods, indicating low richness and uneven species distribution. Thus, although much information may be extracted from the other methods, Illumina amplicon sequencing of the V6-V8 16S rRNA gene would be the method of choice for studying rumen archaeal communities.

Thermal-Mechanical Noise Based CMUT Characterization and Sensing

PubMed Central

Gurun, Gokce; Hochman, Michael; Hasler, Paul; Degertekin, F. Levent

2012-01-01

When capacitive micromachined ultrasonic transducers (CMUTs) are monolithically integrated with custom-designed low-noise electronics, the output noise of the system can be dominated by the CMUT thermal-mechanical noise both in air and in immersion even for devices with low capacitance. Since the thermal-mechanical noise can be related to the electrical admittance of the CMUTs, this provides an effective means of device characterization. This approach yields a novel method to test the functionality and uniformity of CMUT arrays and the integrated electronics where a direct connection to CMUT array element terminals is not available. These measurements can be performed in air at the wafer level, suitable for batch manufacturing and testing. We demonstrate this method on the elements of an 800-μm diameter CMUT-on-CMOS array designed for intravascular imaging in the 10-20 MHz range. Noise measurements in air show the expected resonance behavior and spring softening effects. Noise measurements in immersion for the same array provide useful information on both the acoustic cross talk and radiation properties of the CMUT array elements. The good agreement between a CMUT model based on finite difference and boundary element method and the noise measurements validates the model and indicates that the output noise is indeed dominated by thermal-mechanical noise. The measurement method can be exploited to implement CMUT based passive sensors to measure immersion medium properties, or other parameters affecting the electro-mechanics of the CMUT structure. PMID:22718877

Thermal-mechanical-noise-based CMUT characterization and sensing.

PubMed

Gurun, Gokce; Hochman, Michael; Hasler, Paul; Degertekin, F Levent

2012-06-01

When capacitive micromachined ultrasonic transducers (CMUTs) are monolithically integrated with custom-designed low-noise electronics, the output noise of the system can be dominated by the CMUT thermal-mechanical noise both in air and in immersion even for devices with low capacitance. Because the thermal-mechanical noise can be related to the electrical admittance of the CMUTs, this provides an effective means of device characterization. This approach yields a novel method to test the functionality and uniformity of CMUT arrays and the integrated electronics when a direct connection to CMUT array element terminals is not available. Because these measurements can be performed in air at the wafer level, the approach is suitable for batch manufacturing and testing. We demonstrate this method on the elements of an 800-μm-diameter CMUT-on-CMOS array designed for intravascular imaging in the 10 to 20 MHz range. Noise measurements in air show the expected resonance behavior and spring softening effects. Noise measurements in immersion for the same array provide useful information on both the acoustic cross talk and radiation properties of the CMUT array elements. The good agreement between a CMUT model based on finite difference and boundary element methods and the noise measurements validates the model and indicates that the output noise is indeed dominated by thermal-mechanical noise. The measurement method can be exploited to implement CMUT-based passive sensors to measure immersion medium properties, or other parameters affecting the electro-mechanics of the CMUT structure.

High density processing electronics for superconducting tunnel junction x-ray detector arrays

NASA Astrophysics Data System (ADS)

Warburton, W. K.; Harris, J. T.; Friedrich, S.

2015-06-01

Superconducting tunnel junctions (STJs) are excellent soft x-ray (100-2000 eV) detectors, particularly for synchrotron applications, because of their ability to obtain energy resolutions below 10 eV at count rates approaching 10 kcps. In order to achieve useful solid detection angles with these very small detectors, they are typically deployed in large arrays - currently with 100+ elements, but with 1000 elements being contemplated. In this paper we review a 5-year effort to develop compact, computer controlled low-noise processing electronics for STJ detector arrays, focusing on the major issues encountered and our solutions to them. Of particular interest are our preamplifier design, which can set the STJ operating points under computer control and achieve 2.7 eV energy resolution; our low noise power supply, which produces only 2 nV/√Hz noise at the preamplifier's critical cascode node; our digital processing card that digitizes and digitally processes 32 channels; and an STJ I-V curve scanning algorithm that computes noise as a function of offset voltage, allowing an optimum operating point to be easily selected. With 32 preamplifiers laid out on a custom 3U EuroCard, and the 32 channel digital card in a 3U PXI card format, electronics for a 128 channel array occupy only two small chassis, each the size of a National Instruments 5-slot PXI crate, and allow full array control with simple extensions of existing beam line data collection packages.

Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array.

PubMed

Navruz, Isa; Coskun, Ahmet F; Wong, Justin; Mohammad, Saqib; Tseng, Derek; Nagi, Richie; Phillips, Stephen; Ozcan, Aydogan

2013-10-21

We demonstrate a cellphone based contact microscopy platform, termed Contact Scope, which can image highly dense or connected samples in transmission mode. Weighing approximately 76 grams, this portable and compact microscope is installed on the existing camera unit of a cellphone using an opto-mechanical add-on, where planar samples of interest are placed in contact with the top facet of a tapered fiber-optic array. This glass-based tapered fiber array has ~9 fold higher density of fiber optic cables on its top facet compared to the bottom one and is illuminated by an incoherent light source, e.g., a simple light-emitting-diode (LED). The transmitted light pattern through the object is then sampled by this array of fiber optic cables, delivering a transmission image of the sample onto the other side of the taper, with ~3× magnification in each direction. This magnified image of the object, located at the bottom facet of the fiber array, is then projected onto the CMOS image sensor of the cellphone using two lenses. While keeping the sample and the cellphone camera at a fixed position, the fiber-optic array is then manually rotated with discrete angular increments of e.g., 1-2 degrees. At each angular position of the fiber-optic array, contact images are captured using the cellphone camera, creating a sequence of transmission images for the same sample. These multi-frame images are digitally fused together based on a shift-and-add algorithm through a custom-developed Android application running on the smart-phone, providing the final microscopic image of the sample, visualized through the screen of the phone. This final computation step improves the resolution and also removes spatial artefacts that arise due to non-uniform sampling of the transmission intensity at the fiber optic array surface. We validated the performance of this cellphone based Contact Scope by imaging resolution test charts and blood smears.

Smart-phone based computational microscopy using multi-frame contact imaging on a fiber-optic array

PubMed Central

Navruz, Isa; Coskun, Ahmet F.; Wong, Justin; Mohammad, Saqib; Tseng, Derek; Nagi, Richie; Phillips, Stephen; Ozcan, Aydogan

2013-01-01

We demonstrate a cellphone based contact microscopy platform, termed Contact Scope, which can image highly dense or connected samples in transmission mode. Weighing approximately 76 grams, this portable and compact microscope is installed on the existing camera unit of a cellphone using an opto-mechanical add-on, where planar samples of interest are placed in contact with the top facet of a tapered fiber-optic array. This glass-based tapered fiber array has ∼9 fold higher density of fiber optic cables on its top facet compared to the bottom one and is illuminated by an incoherent light source, e.g., a simple light-emitting-diode (LED). The transmitted light pattern through the object is then sampled by this array of fiber optic cables, delivering a transmission image of the sample onto the other side of the taper, with ∼3× magnification in each direction. This magnified image of the object, located at the bottom facet of the fiber array, is then projected onto the CMOS image sensor of the cellphone using two lenses. While keeping the sample and the cellphone camera at a fixed position, the fiber-optic array is then manually rotated with discrete angular increments of e.g., 1-2 degrees. At each angular position of the fiber-optic array, contact images are captured using the cellphone camera, creating a sequence of transmission images for the same sample. These multi-frame images are digitally fused together based on a shift-and-add algorithm through a custom-developed Android application running on the smart-phone, providing the final microscopic image of the sample, visualized through the screen of the phone. This final computation step improves the resolution and also gets rid of spatial artefacts that arise due to non-uniform sampling of the transmission intensity at the fiber optic array surface. We validated the performance of this cellphone based Contact Scope by imaging resolution test charts and blood smears. PMID:23939637

High-density SNP assay development for genetic analysis in maritime pine (Pinus pinaster).

PubMed

Plomion, C; Bartholomé, J; Lesur, I; Boury, C; Rodríguez-Quilón, I; Lagraulet, H; Ehrenmann, F; Bouffier, L; Gion, J M; Grivet, D; de Miguel, M; de María, N; Cervera, M T; Bagnoli, F; Isik, F; Vendramin, G G; González-Martínez, S C

2016-03-01

Maritime pine provides essential ecosystem services in the south-western Mediterranean basin, where it covers around 4 million ha. Its scattered distribution over a range of environmental conditions makes it an ideal forest tree species for studies of local adaptation and evolutionary responses to climatic change. Highly multiplexed single nucleotide polymorphism (SNP) genotyping arrays are increasingly used to study genetic variation in living organisms and for practical applications in plant and animal breeding and genetic resource conservation. We developed a 9k Illumina Infinium SNP array and genotyped maritime pine trees from (i) a three-generation inbred (F2) pedigree, (ii) the French breeding population and (iii) natural populations from Portugal and the French Atlantic coast. A large proportion of the exploitable SNPs (2052/8410, i.e. 24.4%) segregated in the mapping population and could be mapped, providing the densest ever gene-based linkage map for this species. Based on 5016 SNPs, natural and breeding populations from the French gene pool exhibited similar level of genetic diversity. Population genetics and structure analyses based on 3981 SNP markers common to the Portuguese and French gene pools revealed high levels of differentiation, leading to the identification of a set of highly differentiated SNPs that could be used for seed provenance certification. Finally, we discuss how the validated SNPs could facilitate the identification of ecologically and economically relevant genes in this species, improving our understanding of the demography and selective forces shaping its natural genetic diversity, and providing support for new breeding strategies. © 2015 John Wiley & Sons Ltd.

Rare De Novo Copy Number Variants in Patients with Congenital Pulmonary Atresia

PubMed Central

Xie, Li; Chen, Jin-Lan; Zhang, Wei-Zhi; Wang, Shou-Zheng; Zhao, Tian-Li; Huang, Can; Wang, Jian; Yang, Jin-Fu; Yang, Yi-Feng; Tan, Zhi-Ping

2014-01-01

Background Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Methods and Results Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. Conclusions Rare CNVs contribute to the pathogenesis of PA (9.8%), suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism (FOCM). With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical gene(s) in CHD and may provide novel insights about CHD pathogenesis. PMID:24826987

High-throughput genotyping for species identification and diversity assessment in germplasm collections.

PubMed

Mason, Annaliese S; Zhang, Jing; Tollenaere, Reece; Vasquez Teuber, Paula; Dalton-Morgan, Jessica; Hu, Liyong; Yan, Guijun; Edwards, David; Redden, Robert; Batley, Jacqueline

2015-09-01

Germplasm collections provide an extremely valuable resource for breeders and researchers. However, misclassification of accessions by species often hinders the effective use of these collections. We propose that use of high-throughput genotyping tools can provide a fast, efficient and cost-effective way of confirming species in germplasm collections, as well as providing valuable genetic diversity data. We genotyped 180 Brassicaceae samples sourced from the Australian Grains Genebank across the recently released Illumina Infinium Brassica 60K SNP array. Of these, 76 were provided on the basis of suspected misclassification and another 104 were sourced independently from the germplasm collection. Presence of the A- and C-genomes combined with principle components analysis clearly separated Brassica rapa, B. oleracea, B. napus, B. carinata and B. juncea samples into distinct species groups. Several lines were further validated using chromosome counts. Overall, 18% of samples (32/180) were misclassified on the basis of species. Within these 180 samples, 23/76 (30%) supplied on the basis of suspected misclassification were misclassified, and 9/105 (9%) of the samples randomly sourced from the Australian Grains Genebank were misclassified. Surprisingly, several individuals were also found to be the product of interspecific hybridization events. The SNP (single nucleotide polymorphism) array proved effective at confirming species, and provided useful information related to genetic diversity. As similar genomic resources become available for different crops, high-throughput molecular genotyping will offer an efficient and cost-effective method to screen germplasm collections worldwide, facilitating more effective use of these valuable resources by breeders and researchers. © 2015 John Wiley & Sons Ltd.

A high-density intraspecific SNP linkage map of pigeonpea (Cajanas cajan L. Millsp.)

PubMed Central

Mandal, Paritra; Bhutani, Shefali; Dutta, Sutapa; Kumawat, Giriraj; Singh, Bikram Pratap; Chaudhary, A. K.; Yadav, Rekha; Gaikwad, K.; Sevanthi, Amitha Mithra; Datta, Subhojit; Raje, Ranjeet S.; Sharma, Tilak R.; Singh, Nagendra Kumar

2017-01-01

Pigeonpea (Cajanus cajan (L.) Millsp.) is a major food legume cultivated in semi-arid tropical regions including the Indian subcontinent, Africa, and Southeast Asia. It is an important source of protein, minerals, and vitamins for nearly 20% of the world population. Due to high carbon sequestration and drought tolerance, pigeonpea is an important crop for the development of climate resilient agriculture and nutritional security. However, pigeonpea productivity has remained low for decades because of limited genetic and genomic resources, and sparse utilization of landraces and wild pigeonpea germplasm. Here, we present a dense intraspecific linkage map of pigeonpea comprising 932 markers that span a total adjusted map length of 1,411.83 cM. The consensus map is based on three different linkage maps that incorporate a large number of single nucleotide polymorphism (SNP) markers derived from next generation sequencing data, using Illumina GoldenGate bead arrays, and genotyping with restriction site associated DNA (RAD) sequencing. The genotyping-by-sequencing enhanced the marker density but was met with limited success due to lack of common markers across the genotypes of mapping population. The integrated map has 547 bead-array SNP, 319 RAD-SNP, and 65 simple sequence repeat (SSR) marker loci. We also show here correspondence between our linkage map and published genome pseudomolecules of pigeonpea. The availability of a high-density linkage map will help improve the anchoring of the pigeonpea genome to its chromosomes and the mapping of genes and quantitative trait loci associated with useful agronomic traits. PMID:28654689

Rare de novo copy number variants in patients with congenital pulmonary atresia.

PubMed

Xie, Li; Chen, Jin-Lan; Zhang, Wei-Zhi; Wang, Shou-Zheng; Zhao, Tian-Li; Huang, Can; Wang, Jian; Yang, Jin-Fu; Yang, Yi-Feng; Tan, Zhi-Ping

2014-01-01

Ongoing studies using genomic microarrays and next-generation sequencing have demonstrated that the genetic contributions to cardiovascular diseases have been significantly ignored in the past. The aim of this study was to identify rare copy number variants in individuals with congenital pulmonary atresia (PA). Based on the hypothesis that rare structural variants encompassing key genes play an important role in heart development in PA patients, we performed high-resolution genome-wide microarrays for copy number variations (CNVs) in 82 PA patient-parent trios and 189 controls with an Illumina SNP array platform. CNVs were identified in 17/82 patients (20.7%), and eight of these CNVs (9.8%) are considered potentially pathogenic. Five de novo CNVs occurred at two known congenital heart disease (CHD) loci (16p13.1 and 22q11.2). Two de novo CNVs that may affect folate and vitamin B12 metabolism were identified for the first time. A de novo 1-Mb deletion at 17p13.2 may represent a rare genomic disorder that involves mild intellectual disability and associated facial features. Rare CNVs contribute to the pathogenesis of PA (9.8%), suggesting that the causes of PA are heterogeneous and pleiotropic. Together with previous data from animal models, our results might help identify a link between CHD and folate-mediated one-carbon metabolism (FOCM). With the accumulation of high-resolution SNP array data, these previously undescribed rare CNVs may help reveal critical gene(s) in CHD and may provide novel insights about CHD pathogenesis.

GST-PRIME: an algorithm for genome-wide primer design.

PubMed

Leister, Dario; Varotto, Claudio

2007-01-01

The profiling of mRNA expression based on DNA arrays has become a powerful tool to study genome-wide transcription of genes in a number of organisms. GST-PRIME is a software package created to facilitate large-scale primer design for the amplification of probes to be immobilized on arrays for transcriptome analyses, even though it can be also applied in low-throughput approaches. GST-PRIME allows highly efficient, direct amplification of gene-sequence tags (GSTs) from genomic DNA (gDNA), starting from annotated genome or transcript sequences. GST-PRIME provides a customer-friendly platform for automatic primer design, and despite the relative simplicity of the algorithm, experimental tests in the model plant species Arabidopsis thaliana confirmed the reliability of the software. This chapter describes the algorithm used for primer design, its input and output files, and the installation of the standalone package and its use.

PCI-based WILDFIRE reconfigurable computing engines

NASA Astrophysics Data System (ADS)

Fross, Bradley K.; Donaldson, Robert L.; Palmer, Douglas J.

1996-10-01

WILDFORCE is the first PCI-based custom reconfigurable computer that is based on the Splash 2 technology transferred from the National Security Agency and the Institute for Defense Analyses, Supercomputing Research Center (SRC). The WILDFORCE architecture has many of the features of the WILDFIRE computer, such as field- programmable gate array (FPGA) based processing elements, linear array and crossbar interconnection, and high- performance memory and I/O subsystems. New features introduced in the PCI-based WILDFIRE systems include memory/processor options that can be added to any processing element. These options include static and dynamic memory, digital signal processors (DSPs), FPGAs, and microprocessors. In addition to memory/processor options, many different application specific connectors can be used to extend the I/O capabilities of the system, including systolic I/O, camera input and video display output. This paper also discusses how this new PCI-based reconfigurable computing engine is used for rapid-prototyping, real-time video processing and other DSP applications.

Multigigabit optical transceivers for high-data rate military applications

NASA Astrophysics Data System (ADS)

Catanzaro, Brian E.; Kuznia, Charlie

2012-01-01

Avionics has experienced an ever increasing demand for processing power and communication bandwidth. Currently deployed avionics systems require gigabit communication using opto-electronic transceivers connected with parallel optical fiber. Ultra Communications has developed a series of transceiver solutions combining ASIC technology with flip-chip bonding and advanced opto-mechanical molded optics. Ultra Communications custom high speed ASIC chips are developed using an SoS (silicon on sapphire) process. These circuits are flip chip bonded with sources (VCSEL arrays) and detectors (PIN diodes) to create an Opto-Electronic Integrated Circuit (OEIC). These have been combined with micro-optics assemblies to create transceivers with interfaces to standard fiber array (MT) cabling technology. We present an overview of the demands for transceivers in military applications and how new generation transceivers leverage both previous generation military optical transceivers as well as commercial high performance computing optical transceivers.

Light beam shaping for collimated emission from white organic light-emitting diodes using customized lenticular microlens arrays structure

NASA Astrophysics Data System (ADS)

Zhou, Lei; Bai, Gui-Lin; Guo, Xin; Shen, Su; Ou, Qing-Dong; Fan, Yuan-Yuan

2018-05-01

We present a design approach to realizing a desired collimated planar incoherent light source (CPILS) by incorporating lenticular microlens arrays (LMLAs) onto the substrates of discrete white organic light-emitting diode (WOLED) light sources and demonstrate the effectiveness of this method in collimated light beam shaping and luminance enhancement simultaneously. The obtained collimated WOLED light source shows enhanced luminance by a factor of 2.7 compared with that of the flat conventional device at the normal polar angle and, more importantly, exhibits a narrowed angular emission with a full-width at half-maximum (FWHM) of ˜33.6°. We anticipate that the presented strategy could provide an alternative way for achieving the desired large scale CPILS, thereby opening the door to many potential applications, including LCD backlights, three-dimensional displays, car headlights, and so forth.

Proof of concept of an imaging system demonstrator for PET applications with SiPM

NASA Astrophysics Data System (ADS)

Morrocchi, Matteo; Marcatili, Sara; Belcari, Nicola; Giuseppina Bisogni, Maria; Collazuol, Gianmaria; Ambrosi, Giovanni; Santoni, Cristiano; Corsi, Francesco; Foresta, Maurizio; Marzocca, Cristoforo; Matarrese, Gianvito; Sportelli, Giancarlo; Guerra, Pedro; Santos, Andres; Del Guerra, Alberto

2013-08-01

A PET imaging system demonstrator based on LYSO crystal arrays coupled to SiPM matrices is under construction at the University and INFN of Pisa. Two SiPM matrices, composed of 8×8 SiPM pixels, and 1,5 mm pitch, have been coupled one to one to a LYSO crystals array and read out by a custom electronics system. front-end ASICs were used to read 8 channels of each matrix. Data from each front-end were multiplexed and sent to a DAQ board for the digital conversion; a motherboard collects the data and communicates with a host computer through a USB port for the storage and off-line data processing. In this paper we show the first preliminary tomographic image of a point-like radioactive source acquired with part of the two detection heads in time coincidence.

GLOBECOM '84 - Global Telecommunications Conference, Atlanta, GA, November 26-29, 1984, Conference Record. Volume 1

NASA Astrophysics Data System (ADS)

The subjects discussed are related to LSI/VLSI based subscriber transmission and customer access for the Integrated Services Digital Network (ISDN), special applications of fiber optics, ISDN and competitive telecommunication services, technical preparations for the Geostationary-Satellite Orbit Conference, high-capacity statistical switching fabrics, networking and distributed systems software, adaptive arrays and cancelers, synchronization and tracking, speech processing, advances in communication terminals, full-color videotex, and a performance analysis of protocols. Advances in data communications are considered along with transmission network plans and progress, direct broadcast satellite systems, packet radio system aspects, radio-new and developing technologies and applications, the management of software quality, and Open Systems Interconnection (OSI) aspects of telematic services. Attention is given to personal computers and OSI, the role of software reliability measurement in information systems, and an active array antenna for the next-generation direct broadcast satellite.

Insight into biases and sequencing errors for amplicon sequencing with the Illumina MiSeq platform.

PubMed

Schirmer, Melanie; Ijaz, Umer Z; D'Amore, Rosalinda; Hall, Neil; Sloan, William T; Quince, Christopher

2015-03-31

With read lengths of currently up to 2 × 300 bp, high throughput and low sequencing costs Illumina's MiSeq is becoming one of the most utilized sequencing platforms worldwide. The platform is manageable and affordable even for smaller labs. This enables quick turnaround on a broad range of applications such as targeted gene sequencing, metagenomics, small genome sequencing and clinical molecular diagnostics. However, Illumina error profiles are still poorly understood and programs are therefore not designed for the idiosyncrasies of Illumina data. A better knowledge of the error patterns is essential for sequence analysis and vital if we are to draw valid conclusions. Studying true genetic variation in a population sample is fundamental for understanding diseases, evolution and origin. We conducted a large study on the error patterns for the MiSeq based on 16S rRNA amplicon sequencing data. We tested state-of-the-art library preparation methods for amplicon sequencing and showed that the library preparation method and the choice of primers are the most significant sources of bias and cause distinct error patterns. Furthermore we tested the efficiency of various error correction strategies and identified quality trimming (Sickle) combined with error correction (BayesHammer) followed by read overlapping (PANDAseq) as the most successful approach, reducing substitution error rates on average by 93%. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

SSR_pipeline: a bioinformatic infrastructure for identifying microsatellites from paired-end Illumina high-throughput DNA sequencing data

USGS Publications Warehouse

Miller, Mark P.; Knaus, Brian J.; Mullins, Thomas D.; Haig, Susan M.

2013-01-01

SSR_pipeline is a flexible set of programs designed to efficiently identify simple sequence repeats (e.g., microsatellites) from paired-end high-throughput Illumina DNA sequencing data. The program suite contains 3 analysis modules along with a fourth control module that can automate analyses of large volumes of data. The modules are used to 1) identify the subset of paired-end sequences that pass Illumina quality standards, 2) align paired-end reads into a single composite DNA sequence, and 3) identify sequences that possess microsatellites (both simple and compound) conforming to user-specified parameters. The microsatellite search algorithm is extremely efficient, and we have used it to identify repeats with motifs from 2 to 25bp in length. Each of the 3 analysis modules can also be used independently to provide greater flexibility or to work with FASTQ or FASTA files generated from other sequencing platforms (Roche 454, Ion Torrent, etc.). We demonstrate use of the program with data from the brine fly Ephydra packardi (Diptera: Ephydridae) and provide empirical timing benchmarks to illustrate program performance on a common desktop computer environment. We further show that the Illumina platform is capable of identifying large numbers of microsatellites, even when using unenriched sample libraries and a very small percentage of the sequencing capacity from a single DNA sequencing run. All modules from SSR_pipeline are implemented in the Python programming language and can therefore be used from nearly any computer operating system (Linux, Macintosh, and Windows).

Application of allflex conservation buffer in illumina genotyping.

PubMed

de Groot, M; Ras, T; van Haeringen, W A

2016-12-01

This experiment was designed to study if liquid conservation buffer used in the novel Tissue Sampling Technology (TST) from Allflex can be used for Illumina BeadChip genotyping. Ear punches were collected from 6 bovine samples, using both the Tissue Sampling Unit (TSU) as well as the Total Tagger Universal (TTU) collection system. The stability of the liquid conservation buffer was tested by genotyping samples on Illumina BeadChips, incubated at 0, 3, 15, 24, 48, 72, 168, 336, 720 h after sample collection. Additionally, a replenishment study was designed to test how often the liquid conservation buffer could be completely replenished before a significant call rate drop could be observed. Results from the stability study showed an average call rate of 0.993 for samples collected with the TSU system and 0.953 for samples collected with the TTU system, both exceeding the inclusion threshold call rate of 0.85. As an additional control, the identity of the individual animals was confirmed using the International Society of Animal Genetics (ISAG) recommended SNP panel. The replenishment study revealed a slight drop in the sample call rate after replenishing the conservation buffer for the fourth time for the TSU as well as the TTU samples. In routine analysis, this application allows for multiple experiments to be performed on the liquid conservation buffer, while maintaining the tissue samples for future use. The data collected in this study shows that the liquid conservation buffer used in the TST system can be used for Illumina BeadChip genotyping applications.

Exploring fungal diversity in deep-sea sediments from Okinawa Trough using high-throughput Illumina sequencing

NASA Astrophysics Data System (ADS)

Zhang, Xiao-Yong; Wang, Guang-Hua; Xu, Xin-Ya; Nong, Xu-Hua; Wang, Jie; Amin, Muhammad; Qi, Shu-Hua

2016-10-01

The present study investigated the fungal diversity in four different deep-sea sediments from Okinawa Trough using high-throughput Illumina sequencing of the nuclear ribosomal internal transcribed spacer-1 (ITS1). A total of 40,297 fungal ITS1 sequences clustered into 420 operational taxonomic units (OTUs) with 97% sequence similarity and 170 taxa were recovered from these sediments. Most ITS1 sequences (78%) belonged to the phylum Ascomycota, followed by Basidiomycota (17.3%), Zygomycota (1.5%) and Chytridiomycota (0.8%), and a small proportion (2.4%) belonged to unassigned fungal phyla. Compared with previous studies on fungal diversity of sediments from deep-sea environments by culture-dependent approach and clone library analysis, the present result suggested that Illumina sequencing had been dramatically accelerating the discovery of fungal community of deep-sea sediments. Furthermore, our results revealed that Sordariomycetes was the most diverse and abundant fungal class in this study, challenging the traditional view that the diversity of Sordariomycetes phylotypes was low in the deep-sea environments. In addition, more than 12 taxa accounted for 21.5% sequences were found to be rarely reported as deep-sea fungi, suggesting the deep-sea sediments from Okinawa Trough harbored a plethora of different fungal communities compared with other deep-sea environments. To our knowledge, this study is the first exploration of the fungal diversity in deep-sea sediments from Okinawa Trough using high-throughput Illumina sequencing.

Illuminating choices for library prep: a comparison of library preparation methods for whole genome sequencing of Cryptococcus neoformans using Illumina HiSeq.

PubMed

Rhodes, Johanna; Beale, Mathew A; Fisher, Matthew C

2014-01-01

The industry of next-generation sequencing is constantly evolving, with novel library preparation methods and new sequencing machines being released by the major sequencing technology companies annually. The Illumina TruSeq v2 library preparation method was the most widely used kit and the market leader; however, it has now been discontinued, and in 2013 was replaced by the TruSeq Nano and TruSeq PCR-free methods, leaving a gap in knowledge regarding which is the most appropriate library preparation method to use. Here, we used isolates from the pathogenic fungi Cryptococcus neoformans var. grubii and sequenced them using the existing TruSeq DNA v2 kit (Illumina), along with two new kits: the TruSeq Nano DNA kit (Illumina) and the NEBNext Ultra DNA kit (New England Biolabs) to provide a comparison. Compared to the original TruSeq DNA v2 kit, both newer kits gave equivalent or better sequencing data, with increased coverage. When comparing the two newer kits, we found little difference in cost and workflow, with the NEBNext Ultra both slightly cheaper and faster than the TruSeq Nano. However, the quality of data generated using the TruSeq Nano DNA kit was superior due to higher coverage at regions of low GC content, and more SNPs identified. Researchers should therefore evaluate their resources and the type of application (and hence data quality) being considered when ultimately deciding on which library prep method to use.

Ultra-deep sequencing enables high-fidelity recovery of biodiversity for bulk arthropod samples without PCR amplification

PubMed Central

2013-01-01

Background Next-generation-sequencing (NGS) technologies combined with a classic DNA barcoding approach have enabled fast and credible measurement for biodiversity of mixed environmental samples. However, the PCR amplification involved in nearly all existing NGS protocols inevitably introduces taxonomic biases. In the present study, we developed new Illumina pipelines without PCR amplifications to analyze terrestrial arthropod communities. Results Mitochondrial enrichment directly followed by Illumina shotgun sequencing, at an ultra-high sequence volume, enabled the recovery of Cytochrome c Oxidase subunit 1 (COI) barcode sequences, which allowed for the estimation of species composition at high fidelity for a terrestrial insect community. With 15.5 Gbp Illumina data, approximately 97% and 92% were detected out of the 37 input Operational Taxonomic Units (OTUs), whether the reference barcode library was used or not, respectively, while only 1 novel OTU was found for the latter. Additionally, relatively strong correlation between the sequencing volume and the total biomass was observed for species from the bulk sample, suggesting a potential solution to reveal relative abundance. Conclusions The ability of the new Illumina PCR-free pipeline for DNA metabarcoding to detect small arthropod specimens and its tendency to avoid most, if not all, false positives suggests its great potential in biodiversity-related surveillance, such as in biomonitoring programs. However, further improvement for mitochondrial enrichment is likely needed for the application of the new pipeline in analyzing arthropod communities at higher diversity. PMID:23587339

SSR_pipeline: a bioinformatic infrastructure for identifying microsatellites from paired-end Illumina high-throughput DNA sequencing data.

PubMed

Miller, Mark P; Knaus, Brian J; Mullins, Thomas D; Haig, Susan M

2013-01-01

SSR_pipeline is a flexible set of programs designed to efficiently identify simple sequence repeats (e.g., microsatellites) from paired-end high-throughput Illumina DNA sequencing data. The program suite contains 3 analysis modules along with a fourth control module that can automate analyses of large volumes of data. The modules are used to 1) identify the subset of paired-end sequences that pass Illumina quality standards, 2) align paired-end reads into a single composite DNA sequence, and 3) identify sequences that possess microsatellites (both simple and compound) conforming to user-specified parameters. The microsatellite search algorithm is extremely efficient, and we have used it to identify repeats with motifs from 2 to 25 bp in length. Each of the 3 analysis modules can also be used independently to provide greater flexibility or to work with FASTQ or FASTA files generated from other sequencing platforms (Roche 454, Ion Torrent, etc.). We demonstrate use of the program with data from the brine fly Ephydra packardi (Diptera: Ephydridae) and provide empirical timing benchmarks to illustrate program performance on a common desktop computer environment. We further show that the Illumina platform is capable of identifying large numbers of microsatellites, even when using unenriched sample libraries and a very small percentage of the sequencing capacity from a single DNA sequencing run. All modules from SSR_pipeline are implemented in the Python programming language and can therefore be used from nearly any computer operating system (Linux, Macintosh, and Windows).

Reflectivity quenching of ESR multilayer polymer film reflector in optically bonded scintillator arrays

NASA Astrophysics Data System (ADS)

Loignon-Houle, Francis; Pepin, Catherine M.; Charlebois, Serge A.; Lecomte, Roger

2017-04-01

The 3M-ESR multilayer polymer film is a widely used reflector in scintillation detector arrays. As specified in the datasheet and confirmed experimentally by measurements in air, it is highly reflective (> 98 %) over the entire visible spectrum (400-1000 nm) for all angles of incidence. Despite these outstanding characteristics, it was previously found that light crosstalk between pixels in a bonded LYSO scintillator array with ESR reflector can be as high as ∼30-35%. This unexplained light crosstalk motivated further investigation of ESR optical performance. Analytical simulation of a multilayer structure emulating the ESR reflector showed that the film becomes highly transparent to incident light at large angles when surrounded on both sides by materials of refractive index higher than air. Monte Carlo simulations indicate that a considerable fraction (∼25-35%) of scintillation photons are incident at these leaking angles in high aspect ratio LYSO scintillation crystals. The film transparency was investigated experimentally by measuring the scintillation light transmission through the ESR film sandwiched between a scintillation crystal and a photodetector with or without layers of silicone grease. Strong light leakage, up to nearly 30%, was measured through the reflector when coated on both sides with silicone, thus elucidating the major cause of light crosstalk in bonded arrays. The reflector transparency was confirmed experimentally for angles of incidence larger than 60 ° using a custom designed setup allowing illumination of the bonded ESR film at selected grazing angles. The unsuspected ESR film transparency can be beneficial for detector arrays exploiting light sharing schemes, but it is highly detrimental for scintillator arrays designed for individual pixel readout.