Identification and expression profiling of novel plant cell wall degrading enzymes from a destructive pest of palm trees, Rhynchophorus ferrugineus.

PubMed

Antony, B; Johny, J; Aldosari, S A; Abdelazim, M M

2017-08-01

Plant cell wall degrading enzymes (PCWDEs) from insects were recently identified as a multigene family of proteins that consist primarily of glycoside hydrolases (GHs) and carbohydrate esterases (CEs) and play essential roles in the degradation of the cellulose/hemicellulose/pectin network in the invaded host plant. Here we applied transcriptomic and degenerate PCR approaches to identify the PCWDEs from a destructive pest of palm trees, Rhynchophorus ferrugineus, followed by a gut-specific and stage-specific differential expression analysis. We identified a total of 27 transcripts encoding GH family members and three transcripts of the CE family with cellulase, hemicellulase and pectinase activities. We also identified two GH9 candidates, which have not previously been reported from Curculionidae. The gut-specific quantitative expression analysis identified key cellulases, hemicellulases and pectinases from R. ferrugineus. The expression analysis revealed a pectin methylesterase, RferCE8u02, and a cellulase, GH45c34485, which showed the highest gut enriched expression. Comparison of PCWDE expression patterns revealed that cellulases and pectinases are significantly upregulated in the adult stages, and we observed specific high expression of the hemicellulase RferGH16c4170. Overall, our study revealed the potential of PCWDEs from R. ferrugineus, which may be useful in biotechnological applications and may represent new tools in R. ferrugineus pest management strategies. © 2017 The Royal Entomological Society.

Comparison of Ribotyping, Randomly Amplified Polymorphic DNA Analysis, and Pulsed-Field Gel Electrophoresis in Typing of Lactobacillus rhamnosus and L. casei Strains

PubMed Central

Tynkkynen, Soile; Satokari, Reetta; Saarela, Maria; Mattila-Sandholm, Tiina; Saxelin, Maija

1999-01-01

A total of 24 strains, biochemically identified as members of the Lactobacillus casei group, were identified by PCR with species-specific primers. The same set of strains was typed by randomly amplified polymorphic DNA (RAPD) analysis, ribotyping, and pulsed-field gel electrophoresis (PFGE) in order to compare the discriminatory power of the methods. Species-specific primers for L. rhamnosus and L. casei identified the type strain L. rhamnosus ATCC 7469 and the neotype strain L. casei ATCC 334, respectively, but did not give any signal with the recently revived species L. zeae, which contains the type strain ATCC 15820 and the strain ATCC 393, which was previously classified as L. casei. Our results are in accordance with the suggested new classification of the L. casei group. Altogether, 21 of the 24 strains studied were identified with the species-specific primers. In strain typing, PFGE was the most discriminatory method, revealing 17 genotypes for the 24 strains studied. Ribotyping and RAPD analysis yielded 15 and 12 genotypes, respectively. PMID:10473394

Comparison of ribotyping, randomly amplified polymorphic DNA analysis, and pulsed-field gel electrophoresis in typing of Lactobacillus rhamnosus and L. casei strains.

PubMed

Tynkkynen, S; Satokari, R; Saarela, M; Mattila-Sandholm, T; Saxelin, M

1999-09-01

A total of 24 strains, biochemically identified as members of the Lactobacillus casei group, were identified by PCR with species-specific primers. The same set of strains was typed by randomly amplified polymorphic DNA (RAPD) analysis, ribotyping, and pulsed-field gel electrophoresis (PFGE) in order to compare the discriminatory power of the methods. Species-specific primers for L. rhamnosus and L. casei identified the type strain L. rhamnosus ATCC 7469 and the neotype strain L. casei ATCC 334, respectively, but did not give any signal with the recently revived species L. zeae, which contains the type strain ATCC 15820 and the strain ATCC 393, which was previously classified as L. casei. Our results are in accordance with the suggested new classification of the L. casei group. Altogether, 21 of the 24 strains studied were identified with the species-specific primers. In strain typing, PFGE was the most discriminatory method, revealing 17 genotypes for the 24 strains studied. Ribotyping and RAPD analysis yielded 15 and 12 genotypes, respectively.

[Study on UPLC specific chromatogram of Lily and its specific peaks compositions analysis by QTOF-MS].

PubMed

Nie, Hui; Yan, Hui; Qian, Da-Wei; Duan, Jin-Ao; Ou, Yang-Zhen; Qian, Ye-Fei; Guan, Han-Liang

2013-07-01

To establish the UPLC specific chromatogram of Lily and analyze the specific peaks compositions by ESI-QTOF-MS. The samples were conducted by ACQUITY UPLC BEH C18 Column (2.1 mm x 100 mm, 1.7 microm) and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.4 mL/min. The detection wavelength was set at 320 nm and column temperature was 35 degrees C. Negative ion mode was chosen for qualitative analysis. The capillary voltage was set at 3.0 kV. The nebulization gas was set to 600 L/h at 350 degrees C, and the source temperature was 120 degrees C. The specific chromatogram of Lily was obtained. There were 19 common peaks. Twelve phenylpropenoid glycerides compositions were identified. Among them, 6 compositions were identified by comparison with the reference substances and others were identified by MS and MS2 data. UPLC specific chromatogram can be used for the quality evaluation of Lily, giving support to quality control comprehensively.

Whole genome sequence analysis of unidentified genetically modified papaya for development of a specific detection method.

PubMed

Nakamura, Kosuke; Kondo, Kazunari; Akiyama, Hiroshi; Ishigaki, Takumi; Noguchi, Akio; Katsumata, Hiroshi; Takasaki, Kazuto; Futo, Satoshi; Sakata, Kozue; Fukuda, Nozomi; Mano, Junichi; Kitta, Kazumi; Tanaka, Hidenori; Akashi, Ryo; Nishimaki-Mogami, Tomoko

2016-08-15

Identification of transgenic sequences in an unknown genetically modified (GM) papaya (Carica papaya L.) by whole genome sequence analysis was demonstrated. Whole genome sequence data were generated for a GM-positive fresh papaya fruit commodity detected in monitoring using real-time polymerase chain reaction (PCR). The sequences obtained were mapped against an open database for papaya genome sequence. Transgenic construct- and event-specific sequences were identified as a GM papaya developed to resist infection from a Papaya ringspot virus. Based on the transgenic sequences, a specific real-time PCR detection method for GM papaya applicable to various food commodities was developed. Whole genome sequence analysis enabled identifying unknown transgenic construct- and event-specific sequences in GM papaya and development of a reliable method for detecting them in papaya food commodities. Copyright © 2016 Elsevier Ltd. All rights reserved.

Analysis of the Human Prostate-Specific Proteome Defined by Transcriptomics and Antibody-Based Profiling Identifies TMEM79 and ACOXL as Two Putative, Diagnostic Markers in Prostate Cancer

PubMed Central

O'Hurley, Gillian; Busch, Christer; Fagerberg, Linn; Hallström, Björn M.; Stadler, Charlotte; Tolf, Anna; Lundberg, Emma; Schwenk, Jochen M.; Jirström, Karin; Bjartell, Anders; Gallagher, William M.; Uhlén, Mathias; Pontén, Fredrik

2015-01-01

To better understand prostate function and disease, it is important to define and explore the molecular constituents that signify the prostate gland. The aim of this study was to define the prostate specific transcriptome and proteome, in comparison to 26 other human tissues. Deep sequencing of mRNA (RNA-seq) and immunohistochemistry-based protein profiling were combined to identify prostate specific gene expression patterns and to explore tissue biomarkers for potential clinical use in prostate cancer diagnostics. We identified 203 genes with elevated expression in the prostate, 22 of which showed more than five-fold higher expression levels compared to all other tissue types. In addition to previously well-known proteins we identified two poorly characterized proteins, TMEM79 and ACOXL, with potential to differentiate between benign and cancerous prostatic glands in tissue biopsies. In conclusion, we have applied a genome-wide analysis to identify the prostate specific proteome using transcriptomics and antibody-based protein profiling to identify genes with elevated expression in the prostate. Our data provides a starting point for further functional studies to explore the molecular repertoire of normal and diseased prostate including potential prostate cancer markers such as TMEM79 and ACOXL. PMID:26237329

Targets of perioperative fluid therapy and their effects on postoperative outcome: a systematic review and meta-analysis.

PubMed

Berger, M M; Gradwohl-Matis, I; Brunauer, A; Ulmer, H; Dünser, M W

2015-07-01

Perioperative fluid management plays a fundamental role in maintaining organ perfusion, and is considered to affect morbidity and mortality. Targets according to which fluid therapy should be administered are poorly defined. This systematic review aimed to identify specific targets for perioperative fluid therapy. The PubMed database (January 1993-December 2013) and reference lists were searched to identify clinical trials which evaluated specific targets of perioperative fluid therapy and reported clinically relevant perioperative endpoints in adult patients. Only studies in which targeted fluid therapy was the sole intervention were included into the main data analysis. A pooled data analysis was used to compare mortality between goal-directed fluid therapy and control interventions. Thirty-six clinical studies were selected. Sixteen studies including 1224 patients specifically evaluated targeted fluid therapy and were included into the main data analysis. Three specific targets for perioperative fluid therapy were identified: a systolic or pulse pressure variation <10-12%, an increase in stroke volume <10%, and a corrected flow time of 0.35-0.4 s in combination with an increase in stroke volume <10%. Targeting any one of these goals resulted in less postoperative complications (pooled data analysis: OR 0.53; CI95, 0.34-0.83; P=0.005) and a shorter length of intensive care unit/hospital stay, but no difference in postoperative mortality (pooled data analysis: OR 0.61; CI95, 0.33-1.11; P=0.12). This systematic review identified three goals for perioperative fluid administration, targeting of which appeared to be associated with less postoperative complications and shorter intensive care unit/hospital lengths of stay. Perioperative mortality remained unaffected.

Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation.

PubMed

Godec, Jernej; Tan, Yan; Liberzon, Arthur; Tamayo, Pablo; Bhattacharya, Sanchita; Butte, Atul J; Mesirov, Jill P; Haining, W Nicholas

2016-01-19

Gene-expression profiling has become a mainstay in immunology, but subtle changes in gene networks related to biological processes are hard to discern when comparing various datasets. For instance, conservation of the transcriptional response to sepsis in mouse models and human disease remains controversial. To improve transcriptional analysis in immunology, we created ImmuneSigDB: a manually annotated compendium of ∼5,000 gene-sets from diverse cell states, experimental manipulations, and genetic perturbations in immunology. Analysis using ImmuneSigDB identified signatures induced in activated myeloid cells and differentiating lymphocytes that were highly conserved between humans and mice. Sepsis triggered conserved patterns of gene expression in humans and mouse models. However, we also identified species-specific biological processes in the sepsis transcriptional response: although both species upregulated phagocytosis-related genes, a mitosis signature was specific to humans. ImmuneSigDB enables granular analysis of transcriptomic data to improve biological understanding of immune processes of the human and mouse immune systems. Copyright © 2016 Elsevier Inc. All rights reserved.

Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

PubMed

Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

2017-10-01

Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

Sexual dimorphic floral development in dioecious plants revealed by transcriptome, phytohormone, and DNA methylation analysis in Populus tomentosa.

PubMed

Song, Yuepeng; Ma, Kaifeng; Ci, Dong; Chen, Qingqing; Tian, Jiaxing; Zhang, Deqiang

2013-12-01

Dioecious plants have evolved sex-specific floral development mechanisms. However, the precise gene expression patterns in dioecious plant flower development remain unclear. Here, we used andromonoecious poplar, an exceptional model system, to eliminate the confounding effects of genetic background of dioecious plants. Comparative transcriptome and physiological analysis allowed us to characterize sex-specific development of female and male flowers. Transcriptome analysis identified genes significantly differentially expressed between the sexes, including genes related to floral development, phytohormone synthesis and metabolism, and DNA methylation. Correlation analysis revealed a significant correlation between phytohormone signaling and gene expression, identifying specific phytohormone-responsive genes and their cis-regulatory elements. Two genes related to DNA methylation, METHYLTRANSFERASE1 (MET1) and DECREASED DNA METHYLATION 1 (DDM1), which are located in the sex determination region of Chromosome XIX, have differential expression between female and male flowers. A time-course analysis revealed that MET1 and DDM1 expression may produce different DNA methylation levels in female and male flowers. Understanding the interactions of phytohormone signaling, DNA methylation and target gene expression should lead to a better understanding of sexual differences in floral development. Thus, this study identifies a set of candidate genes for further studies of poplar sexual dimorphism and relates sex-specific floral development to physiological and epigenetic changes.

Comparison of Whole-Cell SELEX Methods for the Identification of Staphylococcus Aureus-Specific DNA Aptamers

PubMed Central

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-01-01

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria. PMID:25884791

Comparison of whole-cell SELEX methods for the identification of Staphylococcus aureus-specific DNA aptamers.

PubMed

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-04-15

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria.

Low levels of serum serotonin and amino acids identified in migraine patients.

PubMed

Ren, Caixia; Liu, Jia; Zhou, Juntuo; Liang, Hui; Wang, Yayun; Sun, Yinping; Ma, Bin; Yin, Yuxin

2018-02-05

Migraine is a highly disabling primary headache associated with a high socioeconomic burden and a generally high prevalence. The clinical management of migraine remains a challenge. This study was undertaken to identify potential serum biomarkers of migraine. Using Liquid Chromatography coupled to Mass Spectrometry (LC-MS), the metabolomic profile of migraine was compared with healthy individuals. Principal component analysis (PCA) and Orthogonal partial least squares-discriminant analysis (orthoPLS-DA) showed the metabolomic profile of migraine is distinguishable from controls. Volcano plot analysis identified 10 serum metabolites significantly decreased during migraine. One of these was serotonin, and the other 9 were amino acids. Pathway analysis and enrichment analysis showed tryptophan metabolism (serotonin metabolism), arginine and proline metabolism, and aminoacyl-tRNA biosynthesis are the three most prominently altered pathways in migraine. ROC curve analysis indicated Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine are potential sensitive and specific biomarkers for migraine. Our results show Glycyl-l-proline, N-Methyl-dl-Alanine and l-Methionine may be as specific or more specific for migraine than serotonin which is the traditional biomarker of migraine. We propose that therapeutic manipulation of these metabolites or metabolic pathways may be helpful in the prevention and treatment of migraine. Copyright © 2018 Elsevier Inc. All rights reserved.

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis

ERIC Educational Resources Information Center

Gonzalez, Oscar; MacKinnon, David P.

2018-01-01

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to…

Identifying States along the Hematopoietic Stem Cell Differentiation Hierarchy with Single Cell Specificity via Raman Spectroscopy.

PubMed

Ilin, Yelena; Choi, Ji Sun; Harley, Brendan A C; Kraft, Mary L

2015-11-17

A major challenge for expanding specific types of hematopoietic cells ex vivo for the treatment of blood cell pathologies is identifying the combinations of cellular and matrix cues that direct hematopoietic stem cells (HSC) to self-renew or differentiate into cell populations ex vivo. Microscale screening platforms enable minimizing the number of rare HSCs required to screen the effects of numerous cues on HSC fate decisions. These platforms create a strong demand for label-free methods that accurately identify the fate decisions of individual hematopoietic cells at specific locations on the platform. We demonstrate the capacity to identify discrete cells along the HSC differentiation hierarchy via multivariate analysis of Raman spectra. Notably, cell state identification is accurate for individual cells and independent of the biophysical properties of the functionalized polyacrylamide gels upon which these cells are cultured. We report partial least-squares discriminant analysis (PLS-DA) models of single cell Raman spectra enable identifying four dissimilar hematopoietic cell populations across the HSC lineage specification. Successful discrimination was obtained for a population enriched for long-term repopulating HSCs (LT-HSCs) versus their more differentiated progeny, including closely related short-term repopulating HSCs (ST-HSCs) and fully differentiated lymphoid (B cells) and myeloid (granulocytes) cells. The lineage-specific differentiation states of cells from these four subpopulations were accurately identified independent of the stiffness of the underlying biomaterial substrate, indicating subtle spectral variations that discriminated these populations were not masked by features from the culture substrate. This approach enables identifying the lineage-specific differentiation stages of hematopoietic cells on biomaterial substrates of differing composition and may facilitate correlating hematopoietic cell fate decisions with the extrinsic cues that elicited them.

Report of sampling and analysis results, Addison Army housing units, Addison, Illinois. Final report

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

Not Available

1990-09-01

The objectives of this sampling and analysis effort include further characterization of environmental contamination identified in an enhanced preliminary assessment carried out in 1989. The specific activities performed at this site were identification, evaluation of the condition, and collection of samples from specific suspected asbestos-containing materials, including floor tiles, pipe run and pipe fitting insulation, dust in the ductwork, and exterior siding, where present. These evaluation were necessary to clarify potential environmental issues identified in the earlier report, prior to the sale or realignment of the property.

Genotyping of Chromobacterium violaceum isolates by recA PCR-RFLP analysis.

PubMed

Scholz, Holger Christian; Witte, Angela; Tomaso, Herbert; Al Dahouk, Sascha; Neubauer, Heinrich

2005-03-15

Intraspecies variation of Chromobacterium violaceum was examined by comparative sequence - and by restriction fragment length polymorphism analysis of the recombinase A gene (recA-PCR-RFLP). Primers deduced from the known recA gene sequence of the type strain C. violaceum ATCC 12472(T) allowed the specific amplification of a 1040bp recA fragment from each of the 13 C. violaceum strains investigated, whereas other closely related organisms tested negative. HindII-PstI-recA RFLP analysis generated from 13 representative C. violaceum strains enabled us to identify at least three different genospecies. In conclusion, analysis of the recA gene provides a rapid and robust nucleotide sequence-based approach to specifically identify and classify C. violaceum on genospecies level.

Preferential Allele Expression Analysis Identifies Shared Germline and Somatic Driver Genes in Advanced Ovarian Cancer

PubMed Central

Halabi, Najeeb M.; Martinez, Alejandra; Al-Farsi, Halema; Mery, Eliane; Puydenus, Laurence; Pujol, Pascal; Khalak, Hanif G.; McLurcan, Cameron; Ferron, Gwenael; Querleu, Denis; Al-Azwani, Iman; Al-Dous, Eman; Mohamoud, Yasmin A.; Malek, Joel A.; Rafii, Arash

2016-01-01

Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients, and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those genes could lead to new therapeutic strategies. PMID:26735499

Identification of Human Lineage-Specific Transcriptional Coregulators Enabled by a Glossary of Binding Modules and Tunable Genomic Backgrounds.

PubMed

Mariani, Luca; Weinand, Kathryn; Vedenko, Anastasia; Barrera, Luis A; Bulyk, Martha L

2017-09-27

Transcription factors (TFs) control cellular processes by binding specific DNA motifs to modulate gene expression. Motif enrichment analysis of regulatory regions can identify direct and indirect TF binding sites. Here, we created a glossary of 108 non-redundant TF-8mer "modules" of shared specificity for 671 metazoan TFs from publicly available and new universal protein binding microarray data. Analysis of 239 ENCODE TF chromatin immunoprecipitation sequencing datasets and associated RNA sequencing profiles suggest the 8mer modules are more precise than position weight matrices in identifying indirect binding motifs and their associated tethering TFs. We also developed GENRE (genomically equivalent negative regions), a tunable tool for construction of matched genomic background sequences for analysis of regulatory regions. GENRE outperformed four state-of-the-art approaches to background sequence construction. We used our TF-8mer glossary and GENRE in the analysis of the indirect binding motifs for the co-occurrence of tethering factors, suggesting novel TF-TF interactions. We anticipate that these tools will aid in elucidating tissue-specific gene-regulatory programs. Copyright © 2017 Elsevier Inc. All rights reserved.

CONDITIONAL PROBABILITY ANALYSIS APPROACH FOR IDENTIFYING BIOLOGICAL THRESHOLD OF IMPACT FOR SEDIMENTATION: APPICATION TO FRESHWATER STREAMS IN OREGON COAST RANGE ECOREGION

EPA Science Inventory

A conditional probability analysis (CPA) approach has been developed for identifying biological thresholds of impact for use in the development of geographic-specific water quality criteria for protection of aquatic life. This approach expresses the threshold as the likelihood ...

Optimizing of MALDI-ToF-based low-molecular-weight serum proteome pattern analysis in detection of breast cancer patients; the effect of albumin removal on classification performance.

PubMed

Pietrowska, M; Marczak, L; Polanska, J; Nowicka, E; Behrent, K; Tarnawski, R; Stobiecki, M; Polanski, A; Widlak, P

2010-01-01

Mass spectrometry-based analysis of the serum proteome allows identifying multi-peptide patterns/signatures specific for blood of cancer patients, thus having high potential value for cancer diagnostics. However, because of problems with optimization and standardization of experimental and computational design, none of identified proteome patterns/signatures was approved for diagnostics in clinical practice as yet. Here we compared two methods of serum sample preparation for mass spectrometry-based proteome pattern analysis aimed to identify biomarkers that could be used in early detection of breast cancer patients. Blood samples were collected in a group of 92 patients diagnosed at early (I and II) stages of the disease before the start of therapy, and in a group of age-matched healthy controls (104 women). Serum specimens were purified and analyzed using MALDI-ToF spectrometry, either directly or after membrane filtration (50 kDa cut-off) to remove albumin and other large serum proteins. Mass spectra of the low-molecular-weight fraction (2-10 kDa) of the serum proteome were resolved using the Gaussian mixture decomposition, and identified spectral components were used to build classifiers that differentiated samples from breast cancer patients and healthy persons. Mass spectra of complete serum and membrane-filtered albumin-depleted samples have apparently different structure and peaks specific for both types of samples could be identified. The optimal classifier built for the complete serum specimens consisted of 8 spectral components, and had 81% specificity and 72% sensitivity, while that built for the membrane-filtered samples consisted of 4 components, and had 80% specificity and 81% sensitivity. We concluded that pre-processing of samples to remove albumin might be recommended before MALDI-ToF mass spectrometric analysis of the low-molecular-weight components of human serum Keywords: albumin removal; breast cancer; clinical proteomics; mass spectrometry; pattern analysis; serum proteome.

Identification of EBP50 as a Specific Biomarker for Carcinogens Via the Analysis of Mouse Lymphoma Cellular Proteome

PubMed Central

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-01-01

To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens. PMID:22434383

Identification of EBP50 as a specific biomarker for carcinogens via the analysis of mouse lymphoma cellular proteome.

PubMed

Lee, Yoen Jung; Choi, In-Kwon; Sheen, Yhun Yhong; Park, Sue Nie; Kwon, Ho Jeong

2012-03-01

To identify specific biomarkers generated upon exposure of L5178Y mouse lymphoma cells to carcinogens, 2-DE and MALDI-TOF MS analysis were conducted using the cellular proteome of L5178Y cells that had been treated with the known carcinogens, 1,2-dibromoethane and O-nitrotoluene and the noncarcinogens, emodin and D-mannitol. Eight protein spots that showed a greater than 1.5-fold increase or decrease in intensity following carcinogen treatment compared with treatment with noncarcinogens were selected. Of the identified proteins, we focused on the candidate biomarker ERM-binding phosphoprotein 50 (EBP50), the expression of which was specifically increased in response to treatment with the carcinogens. The expression level of EBP50 was determined by western analysis using polyclonal rabbit anti-EBP50 antibody. Further, the expression level of EBP50 was increased in cells treated with seven additional carcinogens, verifying that EBP50 could serve as a specific biomarker for carcinogens.

Space Station Furnace Facility. Volume 2: Requirements Definition and Conceptual Design Study. Appendix 3: Environment Analysis. Volume 2; Appendix 3

NASA Technical Reports Server (NTRS)

1992-01-01

A Preliminary Safety Analysis (PSA) is being accomplished as part of the Space Station Furnace Facility (SSFF) contract. This analysis is intended to support SSFF activities by analyzing concepts and designs as they mature to develop essential safety requirements for inclusion in the appropriate specifications, and designs, as early as possible. In addition, the analysis identifies significant safety concerns that may warrant specific trade studies or design definition, etc. The analysis activity to date concentrated on hazard and hazard cause identification and requirements development with the goal of developing a baseline set of detailed requirements to support trade study, specifications development, and preliminary design activities. The analysis activity will continue as the design and concepts mature. Section 2 defines what was analyzed, but it is likely that the SSFF definitions will undergo further changes. The safety analysis activity will reflect these changes as they occur. The analysis provides the foundation for later safety activities. The hazards identified will in most cases have Preliminary Design Review (PDR) applicability. The requirements and recommendations developed for each hazard will be tracked to ensure proper and early resolution of safety concerns.

49 CFR 350.311 - What specific items are eligible for reimbursement under the MCSAP?

Code of Federal Regulations, 2010 CFR

2010-10-01

... data acquisition, storage, and analysis that are specifically identifiable as program-related to develop a data base to coordinate resources and improve efficiency. (e) Clerical and administrative...

49 CFR 350.311 - What specific items are eligible for reimbursement under the MCSAP?

Code of Federal Regulations, 2012 CFR

2012-10-01

... data acquisition, storage, and analysis that are specifically identifiable as program-related to develop a data base to coordinate resources and improve efficiency. (e) Clerical and administrative...

49 CFR 350.311 - What specific items are eligible for reimbursement under the MCSAP?

Code of Federal Regulations, 2013 CFR

2013-10-01

... data acquisition, storage, and analysis that are specifically identifiable as program-related to develop a data base to coordinate resources and improve efficiency. (e) Clerical and administrative...

49 CFR 350.311 - What specific items are eligible for reimbursement under the MCSAP?

Code of Federal Regulations, 2014 CFR

2014-10-01

... data acquisition, storage, and analysis that are specifically identifiable as program-related to develop a data base to coordinate resources and improve efficiency. (e) Clerical and administrative...

49 CFR 350.311 - What specific items are eligible for reimbursement under the MCSAP?

Code of Federal Regulations, 2011 CFR

2011-10-01

... data acquisition, storage, and analysis that are specifically identifiable as program-related to develop a data base to coordinate resources and improve efficiency. (e) Clerical and administrative...

Results of the Lunar Exploration Analysis Group (LEAG) Gap Review: Specific Action Team (SAT), Examination of Strategic Knowledge Gaps (SKGs) for Human Exploration of the Moon

NASA Technical Reports Server (NTRS)

Shearer, C. K.; Eppler, D.; Farrell, W.; Gruener, J.; Lawrence, S.; Pellis, N.; Spudis, P. D.; Stopar, J.; Zeigler, R.; Neal, C;

The DACUM Job Analysis Process.

ERIC Educational Resources Information Center

Dofasco, Inc., Hamilton (Ontario).

This document explains the DACUM (Developing A Curriculum) process for analyzing task-based jobs to: identify where standard operating procedures are required; identify duplicated low value added tasks; develop performance standards; create job descriptions; and identify the elements that must be included in job-specific training programs. The…

Genomic Inventory and Transcriptional Analysis of Medicago truncatula Transporters1[W][OA

PubMed Central

Benedito, Vagner A.; Li, Haiquan; Dai, Xinbin; Wandrey, Maren; He, Ji; Kaundal, Rakesh; Torres-Jerez, Ivone; Gomez, S. Karen; Harrison, Maria J.; Tang, Yuhong; Zhao, Patrick X.; Udvardi, Michael K.

2010-01-01

Transporters move hydrophilic substrates across hydrophobic biological membranes and play key roles in plant nutrition, metabolism, and signaling and, consequently, in plant growth, development, and responses to the environment. To initiate and support systematic characterization of transporters in the model legume Medicago truncatula, we identified 3,830 transporters and classified 2,673 of these into 113 families and 146 subfamilies. Analysis of gene expression data for 2,611 of these transporters identified 129 that are expressed in an organ-specific manner, including 50 that are nodule specific and 36 specific to mycorrhizal roots. Further analysis uncovered 196 transporters that are induced at least 5-fold during nodule development and 44 in roots during arbuscular mycorrhizal symbiosis. Among the nodule- and mycorrhiza-induced transporter genes are many candidates for known transport activities in these beneficial symbioses. The data presented here are a unique resource for the selection and functional characterization of legume transporters. PMID:20023147

Identifying Depressed Older Adults in Primary Care: A Secondary Analysis of a Multisite Randomized Controlled Trial

PubMed Central

Voils, Corrine I.; Olsen, Maren K.; Williams, John W.; for the IMPACT Study Investigators

2008-01-01

Objective: To determine whether a subset of depressive symptoms could be identified to facilitate diagnosis of depression in older adults in primary care. Method: Secondary analysis was conducted on 898 participants aged 60 years or older with major depressive disorder and/or dysthymic disorder (according to DSM-IV criteria) who participated in the Improving Mood–Promoting Access to Collaborative Treatment (IMPACT) study, a multisite, randomized trial of collaborative care for depression (recruitment from July 1999 to August 2001). Linear regression was used to identify a core subset of depressive symptoms associated with decreased social, physical, and mental functioning. The sensitivity and specificity, adjusting for selection bias, were evaluated for these symptoms. The sensitivity and specificity of a second subset of 4 depressive symptoms previously validated in a midlife sample was also evaluated. Results: Psychomotor changes, fatigue, and suicidal ideation were associated with decreased functioning and served as the core set of symptoms. Adjusting for selection bias, the sensitivity of these 3 symptoms was 0.012 and specificity 0.994. The sensitivity of the 4 symptoms previously validated in a midlife sample was 0.019 and specificity was 0.997. Conclusion: We identified 3 depression symptoms that were highly specific for major depressive disorder in older adults. However, these symptoms and a previously identified subset were too insensitive for accurate diagnosis. Therefore, we recommend a full assessment of DSM-IV depression criteria for accurate diagnosis. PMID:18311416

Cross-cohort analysis identifies a TEAD4 ↔ MYCN positive-feedback loop as the core regulatory element of high-risk neuroblastoma. | Office of Cancer Genomics

Cancer.gov

High-risk neuroblastomas show a paucity of recurrent somatic mutations at diagnosis. As a result, the molecular basis for this aggressive phenotype remains elusive. Recent progress in regulatory network analysis helped us elucidate disease-driving mechanisms downstream of genomic alterations, including recurrent chromosomal alterations. Our analysis identified three molecular subtypes of high-risk neuroblastomas, consistent with chromosomal alterations, and identified subtype-specific master regulator (MR) proteins that were conserved across independent cohorts.

Temporal analysis and spatial mapping of Lymantria dispar nuclear polyhedrosis virus transcripts and in vitro translation polypeptides

Treesearch

James M. Slavicek

1991-01-01

Genomic expression of the Lymantriu dispar multinucleocapsid nuclear polyhedrosis virus (LdMNPV) was studied. Viral specific transcripts expressed in cell culture at various times from 2 through 72 h postinfection were identified and their genomic origins mapped through Northern analysis. Sixty-five distinct transcripts were identified in this...

Identifying Students' Expectancy-Value Beliefs: A Latent Class Analysis Approach to Analyzing Middle School Students' Science Self-Perceptions

ERIC Educational Resources Information Center

Phelan, Julia; Ing, Marsha; Nylund-Gibson, Karen; Brown, Richard S.

2017-01-01

This study extends current research by organizing information about students' expectancy-value achievement motivation, in a way that helps parents and teachers identify specific entry points to encourage and support students' science aspirations. This study uses latent class analysis to describe underlying differences in ability beliefs, task…

Identification, characterization and expression analysis of lineage-specific genes within sweet orange (Citrus sinensis).

PubMed

Xu, Yuantao; Wu, Guizhi; Hao, Baohai; Chen, Lingling; Deng, Xiuxin; Xu, Qiang

2015-11-23

With the availability of rapidly increasing number of genome and transcriptome sequences, lineage-specific genes (LSGs) can be identified and characterized. Like other conserved functional genes, LSGs play important roles in biological evolution and functions. Two set of citrus LSGs, 296 citrus-specific genes (CSGs) and 1039 orphan genes specific to sweet orange, were identified by comparative analysis between the sweet orange genome sequences and 41 genomes and 273 transcriptomes. With the two sets of genes, gene structure and gene expression pattern were investigated. On average, both the CSGs and orphan genes have fewer exons, shorter gene length and higher GC content when compared with those evolutionarily conserved genes (ECs). Expression profiling indicated that most of the LSGs expressed in various tissues of sweet orange and some of them exhibited distinct temporal and spatial expression patterns. Particularly, the orphan genes were preferentially expressed in callus, which is an important pluripotent tissue of citrus. Besides, part of the CSGs and orphan genes expressed responsive to abiotic stress, indicating their potential functions during interaction with environment. This study identified and characterized two sets of LSGs in citrus, dissected their sequence features and expression patterns, and provided valuable clues for future functional analysis of the LSGs in sweet orange.

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

PubMed

Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

[Sensibility and specificity of cytology and colposcopy exams with the histological evaluation of cervical intraepithelial lesions].

PubMed

Tuon, Felipe Francisco Bondan; Bittencourt, Marcio Sommer; Panichi, Maria Alice; Pinto, Alvaro Piazetta

2002-01-01

To evaluate the correlation of cytopathological and colposcopycal diagnosis with the histopathological analysis from biopsy. 80 patients from the colposcopy ambulatory of the Hospital e Maternidade Santa Brígida de Curitiba, PR, were selected. Those patients were sent to colposcopy under the following criteria: 1) previous abnormal cytopathological exams, 2) Indicative clinical data or, 3) Suspected lesions on gynecological exam. The statistical significance analysis of the results was done using the chi-square test. Sensibility, specificity, positive predictive value (PPV) and negative predictive value (NPV) were also determined. The patients' mean age was 30.2 (+/-10.9). Cytopathological capability of identifying lesions was 50% when compared to histology. Its specificity was 77%, the sensibility 41%, the PPV 74%, and the NPV 45%. Colposcopy capability of identifying lesions was 50%. Its sensibility, specificity, PPV and NPV were 96%, 19%, 65% and 75% respectively. The two methods associated were capable of identifying 63% of the lesions. Cytopathology was a high specificity exam, while colposcopy from those selected patients had a high sensibility. Colposcopy association with cytopathological screening, on those selected patients, significantly raises the diagnostic accuracy of cervical cancer precursor lesions.

Specification Reformulation During Specification Validation

NASA Technical Reports Server (NTRS)

Benner, Kevin M.

1992-01-01

The goal of the ARIES Simulation Component (ASC) is to uncover behavioral errors by 'running' a specification at the earliest possible points during the specification development process. The problems to be overcome are the obvious ones the specification may be large, incomplete, underconstrained, and/or uncompilable. This paper describes how specification reformulation is used to mitigate these problems. ASC begins by decomposing validation into specific validation questions. Next, the specification is reformulated to abstract out all those features unrelated to the identified validation question thus creating a new specialized specification. ASC relies on a precise statement of the validation question and a careful application of transformations so as to preserve the essential specification semantics in the resulting specialized specification. This technique is a win if the resulting specialized specification is small enough so the user my easily handle any remaining obstacles to execution. This paper will: (1) describe what a validation question is; (2) outline analysis techniques for identifying what concepts are and are not relevant to a validation question; and (3) identify and apply transformations which remove these less relevant concepts while preserving those which are relevant.

Microarray Detection Call Methodology as a Means to Identify and Compare Transcripts Expressed within Syncytial Cells from Soybean (Glycine max) Roots Undergoing Resistant and Susceptible Reactions to the Soybean Cyst Nematode (Heterodera glycines)

PubMed Central

Klink, Vincent P.; Overall, Christopher C.; Alkharouf, Nadim W.; MacDonald, Margaret H.; Matthews, Benjamin F.

2010-01-01

Background. A comparative microarray investigation was done using detection call methodology (DCM) and differential expression analyses. The goal was to identify genes found in specific cell populations that were eliminated by differential expression analysis due to the nature of differential expression methods. Laser capture microdissection (LCM) was used to isolate nearly homogeneous populations of plant root cells. Results. The analyses identified the presence of 13,291 transcripts between the 4 different sample types. The transcripts filtered down into a total of 6,267 that were detected as being present in one or more sample types. A comparative analysis of DCM and differential expression methods showed a group of genes that were not differentially expressed, but were expressed at detectable amounts within specific cell types. Conclusion. The DCM has identified patterns of gene expression not shown by differential expression analyses. DCM has identified genes that are possibly cell-type specific and/or involved in important aspects of plant nematode interactions during the resistance response, revealing the uniqueness of a particular cell population at a particular point during its differentiation process. PMID:20508855

Business Process Modelling is an Essential Part of a Requirements Analysis. Contribution of EFMI Primary Care Working Group.

PubMed

de Lusignan, S; Krause, P; Michalakidis, G; Vicente, M Tristan; Thompson, S; McGilchrist, M; Sullivan, F; van Royen, P; Agreus, L; Desombre, T; Taweel, A; Delaney, B

2012-01-01

To perform a requirements analysis of the barriers to conducting research linking of primary care, genetic and cancer data. We extended our initial data-centric approach to include socio-cultural and business requirements. We created reference models of core data requirements common to most studies using unified modelling language (UML), dataflow diagrams (DFD) and business process modelling notation (BPMN). We conducted a stakeholder analysis and constructed DFD and UML diagrams for use cases based on simulated research studies. We used research output as a sensitivity analysis. Differences between the reference model and use cases identified study specific data requirements. The stakeholder analysis identified: tensions, changes in specification, some indifference from data providers and enthusiastic informaticians urging inclusion of socio-cultural context. We identified requirements to collect information at three levels: micro- data items, which need to be semantically interoperable, meso- the medical record and data extraction, and macro- the health system and socio-cultural issues. BPMN clarified complex business requirements among data providers and vendors; and additional geographical requirements for patients to be represented in both linked datasets. High quality research output was the norm for most repositories. Reference models provide high-level schemata of the core data requirements. However, business requirements' modelling identifies stakeholder issues and identifies what needs to be addressed to enable participation.

Identifying the Most Important 21st Century Workforce Competencies: An Analysis of the Occupational Information Network (O*NET). Research Report. ETS RR-13-21

ERIC Educational Resources Information Center

Burrus, Jeremy; Jackson, Teresa; Xi, Nuo; Steinberg, Jonathan

2013-01-01

To identify the most important competencies for college graduates to succeed in the 21st century workforce, we conducted an analysis of the Occupational Information Network (O*NET) database. O*NET is a large job analysis operated and maintained by the U.S. Department of Labor. We specifically analyzed ratings of the importance of abilities (52…

Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

ERIC Educational Resources Information Center

Lum, Jarrad A. G.; Conti-Ramsden, Gina

2013-01-01

This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

Digital transcriptome analysis of putative sex-determination genes in papaya (Carica papaya).

PubMed

Urasaki, Naoya; Tarora, Kazuhiko; Shudo, Ayano; Ueno, Hiroki; Tamaki, Moritoshi; Miyagi, Norimichi; Adaniya, Shinichi; Matsumura, Hideo

2012-01-01

Papaya (Carica papaya) is a trioecious plant species that has male, female and hermaphrodite flowers on different plants. The primitive sex chromosomes genetically determine the sex of the papaya. Although draft sequences of the papaya genome are already available, the genes for sex determination have not been identified, likely due to the complicated structure of its sex-chromosome sequences. To identify the candidate genes for sex determination, we conducted a transcriptome analysis of flower samples from male, female and hermaphrodite plants using high-throughput SuperSAGE for digital gene expression analysis. Among the short sequence tags obtained from the transcripts, 312 unique tags were specifically mapped to the primitive sex chromosome (X or Y(h)) sequences. An annotation analysis revealed that retroelements are the most abundant sequences observed in the genes corresponding to these tags. The majority of tags on the sex chromosomes were located on the X chromosome, and only 30 tags were commonly mapped to both the X and Y(h) chromosome, implying a loss of many genes on the Y(h) chromosome. Nevertheless, candidate Y(h) chromosome-specific female determination genes, including a MADS-box gene, were identified. Information on these sex chromosome-specific expressed genes will help elucidating sex determination in the papaya.

Digital Transcriptome Analysis of Putative Sex-Determination Genes in Papaya (Carica papaya)

PubMed Central

Urasaki, Naoya; Tarora, Kazuhiko; Shudo, Ayano; Ueno, Hiroki; Tamaki, Moritoshi; Miyagi, Norimichi; Adaniya, Shinichi; Matsumura, Hideo

2012-01-01

Papaya (Carica papaya) is a trioecious plant species that has male, female and hermaphrodite flowers on different plants. The primitive sex chromosomes genetically determine the sex of the papaya. Although draft sequences of the papaya genome are already available, the genes for sex determination have not been identified, likely due to the complicated structure of its sex-chromosome sequences. To identify the candidate genes for sex determination, we conducted a transcriptome analysis of flower samples from male, female and hermaphrodite plants using high-throughput SuperSAGE for digital gene expression analysis. Among the short sequence tags obtained from the transcripts, 312 unique tags were specifically mapped to the primitive sex chromosome (X or Yh) sequences. An annotation analysis revealed that retroelements are the most abundant sequences observed in the genes corresponding to these tags. The majority of tags on the sex chromosomes were located on the X chromosome, and only 30 tags were commonly mapped to both the X and Yh chromosome, implying a loss of many genes on the Yh chromosome. Nevertheless, candidate Yh chromosome-specific female determination genes, including a MADS-box gene, were identified. Information on these sex chromosome-specific expressed genes will help elucidating sex determination in the papaya. PMID:22815863

Identifying Ecosystem Services of Rivers and Streams Through Content Analysis

EPA Science Inventory

While much ecosystem services research focuses on analysis such as mapping and/or valuation, fewer research efforts are directed toward in-depth understanding of the specific ecological quantities people value. Ecosystem service monitoring and analysis efforts and communications ...

Identifying Behaviors and Situations Associated With Increased Crash Risk for Older Drivers

DOT National Transportation Integrated Search

2009-06-01

This report reviews published literature and analyzes the most recent Fatality Analysis Reporting : System (FARS) and National Automotive Sampling System (NASS)/General Estimates System : (GES) data to identify specific driving behaviors (performance...

Deep Sequencing to Identify the Causes of Viral Encephalitis

PubMed Central

Chan, Benjamin K.; Wilson, Theodore; Fischer, Kael F.; Kriesel, John D.

2014-01-01

Deep sequencing allows for a rapid, accurate characterization of microbial DNA and RNA sequences in many types of samples. Deep sequencing (also called next generation sequencing or NGS) is being developed to assist with the diagnosis of a wide variety of infectious diseases. In this study, seven frozen brain samples from deceased subjects with recent encephalitis were investigated. RNA from each sample was extracted, randomly reverse transcribed and sequenced. The sequence analysis was performed in a blinded fashion and confirmed with pathogen-specific PCR. This analysis successfully identified measles virus sequences in two brain samples and herpes simplex virus type-1 sequences in three brain samples. No pathogen was identified in the other two brain specimens. These results were concordant with pathogen-specific PCR and partially concordant with prior neuropathological examinations, demonstrating that deep sequencing can accurately identify viral infections in frozen brain tissue. PMID:24699691

Comparative Analysis of Serum Proteins from Patients with Severe and Mild EV-A71-induced HFMD using iTRAQ-Coupled LC-MS/MS Screening.

PubMed

Fan, Peihu; Chen, Wei; Yu, Pin; Bao, Linlin; Xu, Lili; Qin, Chuan

2017-12-01

This study was designed to provide a rationale for monitoring the development of severe hand, foot, and mouth disease (HFMD) and predicting the onset of this disease via global comparative analysis between patients with severe and mild HFMD. The authors collected serum from five groups: mild (E-M) and severe (E-S) EV-A71-induced HFMD; mild (NE-M) and severe (NE-S) non-EV-A71-induced HFMD; and healthy control subjects (CON). The authors then performed comparative analysis and identified specific differentially expressed proteins (DEPs) of E-S using isobaric mass tag (isobaric tags for relative and absolute quantitation, iTRAQ) labeling coupled with multidimensional liquid chromatography-mass spectrometry (LC-MS/MS). Moreover, The authors validated specific DEPs by multiple reaction monitoring (MRM). The authors identified 10 specific proteins that were significantly altered in E-S patients. Bioinformatics analysis revealed that most of these DEPs are primarily involved in the acute response to infection, which was common to all groups. More importantly, up-regulated proteins associated with neural injury were specifically identified in the E-S group. These findings conclude that severe HFMD symptoms may be caused by EV-A71 infection-mediated injury of the neural system and provide a reference for future research on the course and prognosis of severe HFMD. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Participant Interaction in Asynchronous Learning Environments: Evaluating Interaction Analysis Methods

ERIC Educational Resources Information Center

Blanchette, Judith

2012-01-01

The purpose of this empirical study was to determine the extent to which three different objective analytical methods--sequence analysis, surface cohesion analysis, and lexical cohesion analysis--can most accurately identify specific characteristics of online interaction. Statistically significant differences were found in all points of…

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer

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

Pandi, Narayanan Sathiya, E-mail: sathiyapandi@gmail.com; Suganya, Sivagurunathan; Rajendran, Suriliyandi

Highlights: •Identified stomach lineage specific gene set (SLSGS) was found to be under expressed in gastric tumors. •Elevated expression of SLSGS in gastric tumor is a molecular predictor of metabolic type gastric cancer. •In silico pathway scanning identified estrogen-α signaling is a putative regulator of SLSGS in gastric cancer. •Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. -- Abstract: Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However,more » the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC.« less

Bone Mineral Density Variation in Men is influenced by Sex-Specific and Non Sex-Specific Quantitative Trait Loci

PubMed Central

Peacock, Munro; Koller, Daniel L.; Lai, Dongbing; Hui, Siu; Foroud, Tatiana; Econs, Michael J.

2009-01-01

Introduction A major predictor of age-related osteoporotic fracture is peak areal bone mineral density (aBMD) which is a highly heritable trait. However, few linkage and association studies have been performed in men to identify the genes contributing to normal variation in aBMD. The aim of this study was to perform a genome wide scan in healthy men to identify quantitative trait loci (QTL) that were significantly linked to aBMD and to test whether any of these might be sex-specific. Methods aBMD at the spine and hip were measured in 515 pairs of brothers, aged 18-61 (405 white pairs, 110 black pairs). Linkage analysis in the brother sample was compared with results in a previously published sample of 774 sister pairs to identify sex-specific quantitative trait loci (QTL). Results A genome wide scan identified significant QTL (LOD>3.6) for aBMD on chromosomes 4q21 (hip), 7q34 (spine), 14q32 (hip), 19p13 (hip), 21q21 (hip), and 22q13 (hip). Analysis suggested that the QTL on chromosome 7q34, 14q32, and 21q21 were male-specific whereas the others were not sex-specific. Conclusions This study demonstrates that six QTL were significantly linked with aBMD in men. One was linked to spine and five were linked to hip. When compared to published data in women from the same geographical region, the QTL on chromosomes 7, 14 and 21 were male-specific. The occurrence of sex-specific genes in humans for aBMD has important implications for the pathogenesis and treatment of osteoporosis. PMID:19427925

The use of the sexual function questionnaire as a screening tool for women with sexual dysfunction.

PubMed

Quirk, Frances; Haughie, Scott; Symonds, Tara

2005-07-01

To determine if the validated Sexual Function Questionnaire (SFQ), developed to assess efficacy in female sexual dysfunction (FSD) clinical trials, may also have utility in identifying target populations for such studies. Data from five clinical trials and two general population surveys were used to analyze the utility of the SFQ as a tool to discriminate between the presence of specific components of FSD (i.e., hypoactive sexual desire disorder, female sexual arousal disorder, female orgasmic disorder, and dyspareunia). Sensitivity/specificity analysis and logistic regression analysis, using data from all five clinical studies and the general population surveys, confirmed that the SFQ domains have utility in detecting the presence of specific components of FSD and provide scores indicative of the presence of a specific sexual disorder. The SFQ is a valuable new tool for detecting the presence of FSD and identifying the specific components of sexual functions affected (desire, arousal, orgasm, or dyspareunia).

Subcellular proteome profiles of different latex fractions revealed washed solutions from rubber particles contain crucial enzymes for natural rubber biosynthesis.

PubMed

Wang, Dan; Sun, Yong; Chang, Lili; Tong, Zheng; Xie, Quanliang; Jin, Xiang; Zhu, Liping; He, Peng; Li, Hongbin; Wang, Xuchu

2018-06-30

Rubber particle (RP) is a specific organelle for natural rubber biosynthesis (NRB) and storage in rubber tree Hevea brasiliensis. NRB is processed by RP membrane-localized proteins, which were traditionally purified by repeated washing. However, we noticed many proteins in the discarded washing solutions (WS) from RP. Here, we compared the proteome profiles of WS, C-serum (CS) and RP by 2-DE, and identified 233 abundant proteins from WS by mass spectrometry. Many spots on 2-DE gels were identified as different protein species. We further performed shotgun analysis of CS, WS and RP and identified 1837, 1799 and 1020 unique proteins, respectively. Together with 2-DE, we finally identified 1825 proteins from WS, 246 were WS-specific. These WS-specific proteins were annotated in Gene Ontology, indicating most abundant pathways are organic substance metabolic process, protein degradation, primary metabolic process, and energy metabolism. Protein-protein interaction analysis revealed these WS-specific proteins are mainly involved in ribosomal metabolism, proteasome system, vacuolar protein sorting and endocytosis. Label free and Western blotting revealed many WS-specific proteins and protein complexes are crucial for NRB initiation. These findings not only deepen our understanding of WS proteome, but also provide new evidences on the roles of RP membrane proteins in NRB. Natural rubber is stored in rubber particle from the rubber tree. Rubber particles were traditionally purified by repeated washing, but many proteins were identified from the washing solutions (WS). We obtained the first visualization proteome profiles with 1825 proteins from WS, including 246 WS-specific ones. These WS proteins contain almost all enzymes for polyisoprene initiation and may play important roles in rubber biosynthesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of key regulators of pancreatic cancer progression through multidimensional systems-level analysis.

PubMed

Rajamani, Deepa; Bhasin, Manoj K

2016-05-03

Pancreatic cancer is an aggressive cancer with dismal prognosis, urgently necessitating better biomarkers to improve therapeutic options and early diagnosis. Traditional approaches of biomarker detection that consider only one aspect of the biological continuum like gene expression alone are limited in their scope and lack robustness in identifying the key regulators of the disease. We have adopted a multidimensional approach involving the cross-talk between the omics spaces to identify key regulators of disease progression. Multidimensional domain-specific disease signatures were obtained using rank-based meta-analysis of individual omics profiles (mRNA, miRNA, DNA methylation) related to pancreatic ductal adenocarcinoma (PDAC). These domain-specific PDAC signatures were integrated to identify genes that were affected across multiple dimensions of omics space in PDAC (genes under multiple regulatory controls, GMCs). To further pin down the regulators of PDAC pathophysiology, a systems-level network was generated from knowledge-based interaction information applied to the above identified GMCs. Key regulators were identified from the GMC network based on network statistics and their functional importance was validated using gene set enrichment analysis and survival analysis. Rank-based meta-analysis identified 5391 genes, 109 miRNAs and 2081 methylation-sites significantly differentially expressed in PDAC (false discovery rate ≤ 0.05). Bimodal integration of meta-analysis signatures revealed 1150 and 715 genes regulated by miRNAs and methylation, respectively. Further analysis identified 189 altered genes that are commonly regulated by miRNA and methylation, hence considered GMCs. Systems-level analysis of the scale-free GMCs network identified eight potential key regulator hubs, namely E2F3, HMGA2, RASA1, IRS1, NUAK1, ACTN1, SKI and DLL1, associated with important pathways driving cancer progression. Survival analysis on individual key regulators revealed that higher expression of IRS1 and DLL1 and lower expression of HMGA2, ACTN1 and SKI were associated with better survival probabilities. It is evident from the results that our hierarchical systems-level multidimensional analysis approach has been successful in isolating the converging regulatory modules and associated key regulatory molecules that are potential biomarkers for pancreatic cancer progression.

Cluster analysis reveals subclinical subgroups with shared autistic and schizotypal traits.

PubMed

Ford, Talitha C; Apputhurai, Pragalathan; Meyer, Denny; Crewther, David P

2018-07-01

Autism and schizophrenia spectrum research is typically based on coarse diagnostic classification, which overlooks individual variation within clinical groups. This method limits the identification of underlying cognitive, genetic and neural correlates of specific symptom dimensions. This study, therefore, aimed to identify homogenous subclinical subgroups of specific autistic and schizotypal traits dimensions, that may be utilised to establish more effective diagnostic and treatment practices. Latent profile analysis of subscale scores derived from an autism-schizotypy questionnaire, completed by 1678 subclinical adults aged 18-40 years (1250 females), identified a local optimum of eight population clusters: High, Moderate and Low Psychosocial Difficulties; High, Moderate and Low Autism-Schizotypy; High Psychosis-Proneness; and Moderate Schizotypy. These subgroups represent the convergent and discriminant dimensions of autism and schizotypy in the subclinical population, and highlight the importance of examining subgroups of specific symptom characteristics across these spectra in order to identify the underlying genetic and neural correlates that can be utilised to advance diagnostic and treatment practices. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of novel and known oocyte-specific genes using complementary DNA subtraction and microarray analysis in three different species.

PubMed

Vallée, Maud; Gravel, Catherine; Palin, Marie-France; Reghenas, Hélène; Stothard, Paul; Wishart, David S; Sirard, Marc-André

2005-07-01

The main objective of the present study was to identify novel oocyte-specific genes in three different species: bovine, mouse, and Xenopus laevis. To achieve this goal, two powerful technologies were combined: a polymerase chain reaction (PCR)-based cDNA subtraction, and cDNA microarrays. Three subtractive libraries consisting of 3456 clones were established and enriched for oocyte-specific transcripts. Sequencing analysis of the positive insert-containing clones resulted in the following classification: 53% of the clones corresponded to known cDNAs, 26% were classified as uncharacterized cDNAs, and a final 9% were classified as novel sequences. All these clones were used for cDNA microarray preparation. Results from these microarray analyses revealed that in addition to already known oocyte-specific genes, such as GDF9, BMP15, and ZP, known genes with unknown function in the oocyte were identified, such as a MLF1-interacting protein (MLF1IP), B-cell translocation gene 4 (BTG4), and phosphotyrosine-binding protein (xPTB). Furthermore, 15 novel oocyte-specific genes were validated by reverse transcription-PCR to confirm their preferential expression in the oocyte compared to somatic tissues. The results obtained in the present study confirmed that microarray analysis is a robust technique to identify true positives from the suppressive subtractive hybridization experiment. Furthermore, obtaining oocyte-specific genes from three species simultaneously allowed us to look at important genes that are conserved across species. Further characterization of these novel oocyte-specific genes will lead to a better understanding of the molecular mechanisms related to the unique functions found in the oocyte.

Automated drug identification system

NASA Technical Reports Server (NTRS)

Campen, C. F., Jr.

1974-01-01

System speeds up analysis of blood and urine and is capable of identifying 100 commonly abused drugs. System includes computer that controls entire analytical process by ordering various steps in specific sequences. Computer processes data output and has readout of identified drugs.

Exome-chip association analysis reveals an Asian-specific missense variant in PAX4 associated with type 2 diabetes in Chinese individuals.

PubMed

Cheung, Chloe Y Y; Tang, Clara S; Xu, Aimin; Lee, Chi-Ho; Au, Ka-Wing; Xu, Lin; Fong, Carol H Y; Kwok, Kelvin H M; Chow, Wing-Sun; Woo, Yu-Cho; Yuen, Michele M A; Hai, JoJo S H; Jin, Ya-Li; Cheung, Bernard M Y; Tan, Kathryn C B; Cherny, Stacey S; Zhu, Feng; Zhu, Tong; Thomas, G Neil; Cheng, Kar-Keung; Jiang, Chao-Qiang; Lam, Tai-Hing; Tse, Hung-Fat; Sham, Pak-Chung; Lam, Karen S L

2017-01-01

Genome-wide association studies (GWASs) have identified many common type 2 diabetes-associated variants, mostly at the intronic or intergenic regions. Recent advancements of exome-array genotyping platforms have opened up a novel means for detecting the associations of low-frequency or rare coding variants with type 2 diabetes. We conducted an exomechip association analysis to identify additional type 2 diabetes susceptibility variants in the Chinese population. An exome-chip association study was conducted by genotyping 5640 Chinese individuals from Hong Kong, using a custom designed exome array, the Asian Exomechip. Single variant association analysis was conducted on 77,468 single nucleotide polymorphisms (SNPs). Fifteen SNPs were subsequently genotyped for replication analysis in an independent Chinese cohort comprising 12,362 individuals from Guangzhou. A combined analysis involving 7189 cases and 10,813 controls was performed. In the discovery stage, an Asian-specific coding variant rs2233580 (p.Arg192His) in PAX4, and two variants at the known loci, CDKN2B-AS1 and KCNQ1, were significantly associated with type 2 diabetes with exome-wide significance (p discovery  < 6.45 × 10 -7 ). The risk allele (T) of PAX4 rs2233580 was associated with a younger age at diabetes diagnosis. This variant was replicated in an independent cohort and demonstrated a stronger association that reached genome-wide significance (p meta-analysis [p meta ] = 3.74 × 10 -15 ) in the combined analysis. We identified the association of a PAX4 Asian-specific missense variant rs2233580 with type 2 diabetes in an exome-chip association analysis, supporting the involvement of PAX4 in the pathogenesis of type 2 diabetes. Our findings suggest PAX4 is a possible effector gene of the 7q32 locus, previously identified from GWAS in Asians.

Modulating Calcium Signals to Boost AON Exon Skipping for DMD

DTIC Science & Technology

2016-10-01

RNA Seq analysis to identify mechanisms of activity and specificity in order to guide discovery of second-generation skipping drugs or combinations...with greater activity. 15. SUBJECT TERMS Exon skipping, Dantrolene, Calcium, Duchenne, Dytrophy, Dystrophin, anti-sense-oligonucleatide, DMD, RNA ...for a subset of very rare mutations. Finally, we hypothesize that by combining chemical genomics with RNA Seq analysis we can begin to identify

Plan delivery quality assurance for CyberKnife: Statistical process control analysis of 350 film-based patient-specific QAs.

PubMed

Bellec, J; Delaby, N; Jouyaux, F; Perdrieux, M; Bouvier, J; Sorel, S; Henry, O; Lafond, C

2017-07-01

Robotic radiosurgery requires plan delivery quality assurance (DQA) but there has never been a published comprehensive analysis of a patient-specific DQA process in a clinic. We proposed to evaluate 350 consecutive film-based patient-specific DQAs using statistical process control. We evaluated the performance of the process to propose achievable tolerance criteria for DQA validation and we sought to identify suboptimal DQA using control charts. DQAs were performed on a CyberKnife-M6 using Gafchromic-EBT3 films. The signal-to-dose conversion was performed using a multichannel-correction and a scanning protocol that combined measurement and calibration in a single scan. The DQA analysis comprised a gamma-index analysis at 3%/1.5mm and a separate evaluation of spatial and dosimetric accuracy of the plan delivery. Each parameter was plotted on a control chart and control limits were calculated. A capability index (Cpm) was calculated to evaluate the ability of the process to produce results within specifications. The analysis of capability showed that a gamma pass rate of 85% at 3%/1.5mm was highly achievable as acceptance criteria for DQA validation using a film-based protocol (Cpm>1.33). 3.4% of DQA were outside a control limit of 88% for gamma pass-rate. The analysis of the out-of-control DQA helped identify a dosimetric error in our institute for a specific treatment type. We have defined initial tolerance criteria for DQA validations. We have shown that the implementation of a film-based patient-specific DQA protocol with the use of control charts is an effective method to improve patient treatment safety on CyberKnife. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Immune complexome analysis reveals the specific and frequent presence of immune complex antigens in lung cancer patients: A pilot study.

PubMed

Ohyama, Kaname; Yoshimi, Haruka; Aibara, Nozomi; Nakamura, Yoichi; Miyata, Yasuyoshi; Sakai, Hideki; Fujita, Fumihiko; Imaizumi, Yoshitaka; Chauhan, Anil K; Kishikawa, Naoya; Kuroda, Naotaka

2017-01-15

Cancer immunotherapies such as antibodies targeting T cell checkpoints, or adaptive tumor-infiltrating lymphocyte (TIL) transfer, have been developed to boost the endogenous immune response against human malignancies. However, activation of T cells by such antibodies can lead to the risk of autoimmune diseases. Also, the selection of tumor-reactive T cells for TIL relies on information regarding mutated antigens in tumors and does not reflect other factors involved in protein antigenicity. It is therefore essential to engineer therapeutic interventions by which T cell reactivity against tumor cells is selectively enhanced (i.e., "focused cancer immunotherapy") based on tumor antigens that are specifically expressed in the tumor of a certain cancer and in many patients with this cancer. Immune complexes (ICs) are the direct and stable products of immunological recognition by humoral immunity. Here, we searched for tumor-specific IC antigens in each of five cancers (lung (n = 28), colon (n = 20), bladder (n = 20), renal cell (n = 15) and malignant lymphoma (n = 9)), by using immune complexome analysis that comprehensively identifies and profiles the constituent antigens in ICs. This analysis indicated that gelsolin and inter-alpha-trypsin inhibitor heavy chains were specifically and frequently detected (at a frequency higher than 80%), and that phosphoproteins (VENTX, VCIP135) were also specifically present in the ICs of lung cancer patients. Immune complexome analysis successfully identified several tumor-specific IC antigens with high detection frequency in lung cancer patients. These specific antigens are required to validate the clinical benefit by further analysis using a large number of patients. © 2016 UICC.

Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

PubMed Central

Caie, Peter D.; Zhou, Ying; Turnbull, Arran K.; Oniscu, Anca; Harrison, David J.

2016-01-01

A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death. PMID:27322148

Discriminant biomarkers of acute respiratory distress syndrome associated to H1N1 influenza identified by metabolomics HPLC-QTOF-MS/MS platform.

PubMed

Ferrarini, Alessia; Righetti, Laura; Martínez, Ma Paz; Fernández-López, Mariano; Mastrangelo, Annalaura; Horcajada, Juan P; Betbesé, Antoni; Esteban, Andrés; Ordóñez, Jordi; Gea, Joaquín; Cabello, Jesús Ruiz; Pellati, Federica; Lorente, José A; Nin, Nicolás; Rupérez, Francisco J

2017-09-01

Acute respiratory distress syndrome (ARDS) is a serious complication of influenza A (H1N1) virus infection. Its pathogenesis is unknown and biomarkers are lacking. Untargeted metabolomics allows the analysis of the whole metabolome in a biological compartment, identifying patterns associated with specific conditions. We hypothesized that LC-MS could help identify discriminant metabolites able to define the metabolic alterations occurring in patients with influenza A (H1N1) virus infection that developed ARDS. Serum samples from patients diagnosed with 2009 influenza A (H1N1) virus infection with (n = 25) or without (n = 32) ARDS were obtained on the day of hospital admission and analyzed by LC-MS/MS. Metabolite identification was determined by MS/MS analysis and analysis of standards. The specificity of the patterns identified was confirmed in patients without 2009 influenza A(H1N1) virus pneumonia (15 without and 17 with ARDS). Twenty-three candidate biomarkers were found to be significantly different between the two groups, including lysophospholipids and sphingolipids related to inflammation; bile acids, tryptophan metabolites, and thyroxine, related to the metabolism of the gut microflora. Confirmation results demonstrated the specificity of major alterations occurring in ARDS patients with influenza A (H1N1) virus infection. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of Order Sets in Inpatient Computerized Provider Order Entry Systems: A Comparative Analysis of Usage Patterns at Seven Sites

PubMed Central

Wright, Adam; Feblowitz, Joshua C.; Pang, Justine E.; Carpenter, James D.; Krall, Michael A.; Middleton, Blackford; Sittig, Dean F.

2012-01-01

Background Many computerized provider order entry (CPOE) systems include the ability to create electronic order sets: collections of clinically-related orders grouped by purpose. Order sets promise to make CPOE systems more efficient, improve care quality and increase adherence to evidence-based guidelines. However, the development and implementation of order sets can be expensive and time-consuming and limited literature exists about their utilization. Methods Based on analysis of order set usage logs from a diverse purposive sample of seven sites with commercially- and internally-developed inpatient CPOE systems, we developed an original order set classification system. Order sets were categorized across seven non-mutually exclusive axes: admission/discharge/transfer (ADT), perioperative, condition-specific, task-specific, service-specific, convenience, and personal. In addition, 731 unique subtypes were identified within five axes: four in ADT (S=4), three in perioperative, 144 in condition-specific, 513 in task-specific, and 67 in service-specific. Results Order sets (n=1,914) were used a total of 676,142 times at the participating sites during a one-year period. ADT and perioperative order sets accounted for 27.6% and 24.2% of usage respectively. Peripartum/labor, chest pain/Acute Coronary Syndrome/Myocardial Infarction and diabetes order sets accounted for 51.6% of condition-specific usage. Insulin, angiography/angioplasty and arthroplasty order sets accounted for 19.4% of task-specific usage. Emergency/trauma, Obstetrics/Gynecology/Labor Delivery and anesthesia accounted for 32.4% of service-specific usage. Overall, the top 20% of order sets accounted for 90.1% of all usage. Additional salient patterns are identified and described. Conclusion We observed recurrent patterns in order set usage across multiple sites as well as meaningful variations between sites. Vendors and institutional developers should identify high-value order set types through concrete data analysis in order to optimize the resources devoted to development and implementation. PMID:22819199

RFLP and sequence analysis of the cytochrome b gene of selected animals and man: methodology and forensic application.

PubMed

Zehner, R; Zimmermann, S; Mebs, D

1998-01-01

To identify common animal species by analysis of the cytochrome b gene a method has been developed to obtain PCR products of a large domain of the cytochrome b gene (981 bp out of 1140 bp) in humans, selected mammals and birds using the same specifically designed primers. Species-specific RFLP patterns are generated by co-restriction with the restriction endonucleases ALU I and NCO I. The RFLP patterns obtained are conclusive even in mixtures of two or more species. The results were confirmed by sequence analysis which in addition explained intraspecies variations in the RFLP patterns. The method has been applied to forensic casework studies where the origin of roasted meat, stomach contents and a bone sample has been successfully identified.

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

PubMed Central

Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

2016-01-01

Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus.

PubMed

Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S

2016-01-01

Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites.

Meta-QTL analysis of seed iron and zinc concentration and content in common bean (Phaseolus vulgaris L.).

PubMed

Izquierdo, Paulo; Astudillo, Carolina; Blair, Matthew W; Iqbal, Asif M; Raatz, Bodo; Cichy, Karen A

2018-05-11

Twelve meta-QTL for seed Fe and Zn concentration and/or content were identified from 87 QTL originating from seven population grown in sixteen field trials. These meta-QTL include 2 specific to iron, 2 specific to zinc and 8 that co-localize for iron and zinc concentrations and/or content. Common bean (Phaseolus vulgaris L.) is the most important legume for human consumption worldwide and it is an important source of microelements, especially iron and zinc. Bean biofortification breeding programs develop new varieties with high levels of Fe and Zn targeted for countries with human micronutrient deficiencies. Biofortification efforts thus far have relied on phenotypic selection of raw seed mineral concentrations in advanced generations. While numerous quantitative trait loci (QTL) studies have been conducted to identify genomic regions associated with increased Fe and Zn concentration in seeds, these results have yet to be employed for marker-assisted breeding. The objective of this study was to conduct a meta-analysis from seven QTL studies in Andean and Middle American intra- and inter-gene pool populations to identify the regions in the genome that control the Fe and Zn levels in seeds. Two meta-QTL specific to Fe and two meta-QTL specific to Zn were identified. Additionally, eight Meta QTL that co-localized for Fe and Zn concentration and/or content were identified across seven chromosomes. The Fe and Zn shared meta-QTL could be useful candidates for marker-assisted breeding to simultaneously increase seed Fe and Zn. The physical positions for 12 individual meta-QTL were identified and within five of the meta-QTL, candidate genes were identified from six gene families that have been associated with transport of iron and zinc in plants.

Data collection and analysis for local roadway safety assessment.

DOT National Transportation Integrated Search

2014-11-01

The project Data Analysis for Local Roadway : Assessment conducted systematic road-safety : assessment and identified major risks that can be el : iminated or reduced by pr : actical road-improvement : measures. Specifically, the primary task o...

Exploring patterns enriched in a dataset with contrastive principal component analysis.

PubMed

Abid, Abubakar; Zhang, Martin J; Bagaria, Vivek K; Zou, James

2018-05-30

Visualization and exploration of high-dimensional data is a ubiquitous challenge across disciplines. Widely used techniques such as principal component analysis (PCA) aim to identify dominant trends in one dataset. However, in many settings we have datasets collected under different conditions, e.g., a treatment and a control experiment, and we are interested in visualizing and exploring patterns that are specific to one dataset. This paper proposes a method, contrastive principal component analysis (cPCA), which identifies low-dimensional structures that are enriched in a dataset relative to comparison data. In a wide variety of experiments, we demonstrate that cPCA with a background dataset enables us to visualize dataset-specific patterns missed by PCA and other standard methods. We further provide a geometric interpretation of cPCA and strong mathematical guarantees. An implementation of cPCA is publicly available, and can be used for exploratory data analysis in many applications where PCA is currently used.

[A functional analysis of healthcare auditors' skills in Venezuela, 2008].

PubMed

Chirinos-Muñoz, Mónica S

2010-10-01

Using functional analysis for identifying the basic, working, specific and generic skills and values which a health service auditor must have. Implementing the functional analysis technique with 10 experts, identifying specific, basic, generic skills and values by means of deductive logic. A functional map was obtained which started by establishing a key purpose based on improving healthcare and service quality from which three key functions emerged. The main functions and skills' units were then broken down into the competitive elements defining what a health service auditor is able to do. This functional map (following functional analysis methodology) shows in detail the simple and complex tasks which a healthcare auditor should apply in the workplace, adopting a forward management approach for improving healthcare and health service quality. This methodology, expressing logical-deductive awareness raising, provides expert consensual information validating each element regarding overall skills.

Identification of recently handled materials by analysis of latent human fingerprints using infrared spectromicroscopy.

PubMed

Grant, Ashleigh; Wilkinson, T J; Holman, Derek R; Martin, Michael C

2005-09-01

Analysis of fingerprints has predominantly focused on matching the pattern of ridges to a specific person as a form of identification. The present work focuses on identifying extrinsic materials that are left within a person's fingerprint after recent handling of such materials. Specifically, we employed infrared spectromicroscopy to locate and positively identify microscopic particles from a mixture of common materials in the latent human fingerprints of volunteer subjects. We were able to find and correctly identify all test substances based on their unique infrared spectral signatures. Spectral imaging is demonstrated as a method for automating recognition of specific substances in a fingerprint. We also demonstrate the use of attenuated total reflectance (ATR) and synchrotron-based infrared spectromicroscopy for obtaining high-quality spectra from particles that were too thick or too small, respectively, for reflection/absorption measurements. We believe the application of this rapid, nondestructive analytical technique to the forensic study of latent human fingerprints has the potential to add a new layer of information available to investigators. Using fingerprints to not only identify who was present at a crime scene, but also to link who was handling key materials, will be a powerful investigative tool.

Concepts of Cost and Cost Analysis for Higher Education.

ERIC Educational Resources Information Center

Brinkman, Paul T.; Allen, Richard H.

1986-01-01

Concepts of costs and cost analysis in higher education are examined, along with how to prepare for a cost study. Specific cost analysis techniques are identified, along with types of data generated and potential problems. In preparing for cost studies, it is important to consider: purpose, types of cost analysis, types of cost, common…

Serum Biochemical Phenotypes in the Domestic Dog

PubMed Central

Chang, Yu-Mei; Hadox, Erin; Szladovits, Balazs; Garden, Oliver A.

2016-01-01

The serum or plasma biochemical profile is essential in the diagnosis and monitoring of systemic disease in veterinary medicine, but current reference intervals typically take no account of breed-specific differences. Breed-specific hematological phenotypes have been documented in the domestic dog, but little has been published on serum biochemical phenotypes in this species. Serum biochemical profiles of dogs in which all measurements fell within the existing reference intervals were retrieved from a large veterinary database. Serum biochemical profiles from 3045 dogs were retrieved, of which 1495 had an accompanying normal glucose concentration. Sixty pure breeds plus a mixed breed control group were represented by at least 10 individuals. All analytes, except for sodium, chloride and glucose, showed variation with age. Total protein, globulin, potassium, chloride, creatinine, cholesterol, total bilirubin, ALT, CK, amylase, and lipase varied between sexes. Neutering status significantly impacted all analytes except albumin, sodium, calcium, urea, and glucose. Principal component analysis of serum biochemical data revealed 36 pure breeds with distinctive phenotypes. Furthermore, comparative analysis identified 23 breeds with significant differences from the mixed breed group in all biochemical analytes except urea and glucose. Eighteen breeds were identified by both principal component and comparative analysis. Tentative reference intervals were generated for breeds with a distinctive phenotype identified by comparative analysis and represented by at least 120 individuals. This is the first large-scale analysis of breed-specific serum biochemical phenotypes in the domestic dog and highlights potential genetic components of biochemical traits in this species. PMID:26919479

The design analysis of a rechargeable lithium cell for space applications

NASA Technical Reports Server (NTRS)

Subba Rao, S.; Shen, D. H.; Yen, S. P. S.; Somoano, R. B.

1986-01-01

Ambient temperature rechargeable lithium batteries are needed by NASA for advanced space power applications for future missions. Specific energies of not less than 100 Wh/kg and long cycle life are critical performance goals. A design analysis of a 35 Ah Li-TiS2 cell was carried out using literature and experimental data to identify key design parameters governing specific energy. It is found that high specific energies are achievable in prismatic cells, especially with the use of advanced hardware materials. There is a serious need for a greatly expanded engineering database in order to enable more quantitative design analysis.

Statin use and survival in colorectal cancer: Results from a population-based cohort study and an updated systematic review and meta-analysis.

PubMed

Gray, Ronan T; Coleman, Helen G; Hughes, Carmel; Murray, Liam J; Cardwell, Chris R

2016-12-01

The aim of this study was to investigate the association between statin use and survival in a population-based colorectal cancer (CRC) cohort and perform an updated meta-analysis to quantify the magnitude of any association. A cohort of 8391 patients with newly diagnosed Dukes' A-C CRC (2009-2012) was identified from the Scottish Cancer Registry. This cohort was linked to the Prescribing Information System and the National Records of Scotland Death Records (until January 2015) to identify 1064 colorectal cancer-specific deaths. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use were calculated using time dependent Cox regression models. The systematic review included relevant studies published before January 2016. Meta-analysis techniques were used to derive combined HRs for associations between statin use and cancer-specific and overall mortality. In the Scottish cohort, statin use before diagnosis (HR=0.84, 95% CI 0.75-0.94), but not after (HR=0.90, 95% CI 0.77-1.05), was associated with significantly improved cancer-specific mortality. The systematic review identified 15 relevant studies. In the meta-analysis, there was consistent (I 2 =0%,heterogeneity P=0.57) evidence of a reduction in cancer-specific mortality with statin use before diagnosis in 6 studies (n=86,622, pooled HR=0.82, 95% CI 0.79-0.86) but this association was less apparent and more heterogeneous (I 2 =67%,heterogeneity P=0.03) with statin use after diagnosis in 4 studies (n=19,152, pooled HR=0.84, 95% CI 0.68-1.04). In a Scottish CRC cohort and updated meta-analysis there was some evidence that statin use was associated with improved survival. However, these associations were weak in magnitude and, particularly for post-diagnosis use, varied markedly between studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers

PubMed Central

2013-01-01

Background Many large-scale studies analyzed high-throughput genomic data to identify altered pathways essential to the development and progression of specific types of cancer. However, no previous study has been extended to provide a comprehensive analysis of pathways disrupted by copy number alterations across different human cancers. Towards this goal, we propose a network-based method to integrate copy number alteration data with human protein-protein interaction networks and pathway databases to identify pathways that are commonly disrupted in many different types of cancer. Results We applied our approach to a data set of 2,172 cancer patients across 16 different types of cancers, and discovered a set of commonly disrupted pathways, which are likely essential for tumor formation in majority of the cancers. We also identified pathways that are only disrupted in specific cancer types, providing molecular markers for different human cancers. Analysis with independent microarray gene expression datasets confirms that the commonly disrupted pathways can be used to identify patient subgroups with significantly different survival outcomes. We also provide a network view of disrupted pathways to explain how copy number alterations affect pathways that regulate cell growth, cycle, and differentiation for tumorigenesis. Conclusions In this work, we demonstrated that the network-based integrative analysis can help to identify pathways disrupted by copy number alterations across 16 types of human cancers, which are not readily identifiable by conventional overrepresentation-based and other pathway-based methods. All the results and source code are available at http://compbio.cs.umn.edu/NetPathID/. PMID:23822816

PASTA: splice junction identification from RNA-Sequencing data

PubMed Central

2013-01-01

Background Next generation transcriptome sequencing (RNA-Seq) is emerging as a powerful experimental tool for the study of alternative splicing and its regulation, but requires ad-hoc analysis methods and tools. PASTA (Patterned Alignments for Splicing and Transcriptome Analysis) is a splice junction detection algorithm specifically designed for RNA-Seq data, relying on a highly accurate alignment strategy and on a combination of heuristic and statistical methods to identify exon-intron junctions with high accuracy. Results Comparisons against TopHat and other splice junction prediction software on real and simulated datasets show that PASTA exhibits high specificity and sensitivity, especially at lower coverage levels. Moreover, PASTA is highly configurable and flexible, and can therefore be applied in a wide range of analysis scenarios: it is able to handle both single-end and paired-end reads, it does not rely on the presence of canonical splicing signals, and it uses organism-specific regression models to accurately identify junctions. Conclusions PASTA is a highly efficient and sensitive tool to identify splicing junctions from RNA-Seq data. Compared to similar programs, it has the ability to identify a higher number of real splicing junctions, and provides highly annotated output files containing detailed information about their location and characteristics. Accurate junction data in turn facilitates the reconstruction of the splicing isoforms and the analysis of their expression levels, which will be performed by the remaining modules of the PASTA pipeline, still under development. Use of PASTA can therefore enable the large-scale investigation of transcription and alternative splicing. PMID:23557086

Improving Free-Piston Stirling Engine Specific Power

NASA Technical Reports Server (NTRS)

Briggs, Maxwell Henry

2014-01-01

This work uses analytical methods to demonstrate the potential benefits of optimizing piston and/or displacer motion in a Stirling Engine. Isothermal analysis was used to show the potential benefits of ideal motion in ideal Stirling engines. Nodal analysis is used to show that ideal piston and displacer waveforms are not optimal in real Stirling engines. Constrained optimization was used to identify piston and displacer waveforms that increase Stirling engine specific power.

Improving Free-Piston Stirling Engine Specific Power

NASA Technical Reports Server (NTRS)

Briggs, Maxwell H.

2015-01-01

This work uses analytical methods to demonstrate the potential benefits of optimizing piston and/or displacer motion in a Stirling engine. Isothermal analysis was used to show the potential benefits of ideal motion in ideal Stirling engines. Nodal analysis is used to show that ideal piston and displacer waveforms are not optimal in real Stirling engines. Constrained optimization was used to identify piston and displacer waveforms that increase Stirling engine specific power.

Construction of a high-density genetic map by specific locus amplified fragment sequencing (SLAF-seq) and its application to Quantitative Trait Loci (QTL) analysis for boll weight in upland cotton (Gossypium hirsutum.).

PubMed

Zhang, Zhen; Shang, Haihong; Shi, Yuzhen; Huang, Long; Li, Junwen; Ge, Qun; Gong, Juwu; Liu, Aiying; Chen, Tingting; Wang, Dan; Wang, Yanling; Palanga, Koffi Kibalou; Muhammad, Jamshed; Li, Weijie; Lu, Quanwei; Deng, Xiaoying; Tan, Yunna; Song, Weiwu; Cai, Juan; Li, Pengtao; Rashid, Harun or; Gong, Wankui; Yuan, Youlu

2016-04-11

Upland Cotton (Gossypium hirsutum) is one of the most important worldwide crops it provides natural high-quality fiber for the industrial production and everyday use. Next-generation sequencing is a powerful method to identify single nucleotide polymorphism markers on a large scale for the construction of a high-density genetic map for quantitative trait loci mapping. In this research, a recombinant inbred lines population developed from two upland cotton cultivars 0-153 and sGK9708 was used to construct a high-density genetic map through the specific locus amplified fragment sequencing method. The high-density genetic map harbored 5521 single nucleotide polymorphism markers which covered a total distance of 3259.37 cM with an average marker interval of 0.78 cM without gaps larger than 10 cM. In total 18 quantitative trait loci of boll weight were identified as stable quantitative trait loci and were detected in at least three out of 11 environments and explained 4.15-16.70 % of the observed phenotypic variation. In total, 344 candidate genes were identified within the confidence intervals of these stable quantitative trait loci based on the cotton genome sequence. These genes were categorized based on their function through gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and eukaryotic orthologous groups analysis. This research reported the first high-density genetic map for Upland Cotton (Gossypium hirsutum) with a recombinant inbred line population using single nucleotide polymorphism markers developed by specific locus amplified fragment sequencing. We also identified quantitative trait loci of boll weight across 11 environments and identified candidate genes within the quantitative trait loci confidence intervals. The results of this research would provide useful information for the next-step work including fine mapping, gene functional analysis, pyramiding breeding of functional genes as well as marker-assisted selection.

Arrhythmias in Adults with Congenital Heart Disease: What Are Risk Factors for Specific Arrhythmias?

PubMed

Loomba, Rohit S; Buelow, Matthew W; Aggarwal, Saurabh; Arora, Rohit R; Kovach, Joshua; Ginde, Salil

2017-04-01

An increasing number of patients with congenital heart disease are now surviving into adulthood. This has also led to the emergence of complications from the underlying congenital heart disease, related surgical interventions, and associated combordities. While the prevalence of particular arrhythmias with specific congenital heart disease has been previously described, a detailed analysis of all lesions and a large number of comorbidities has not been previously published. Admissions with congenital heart disease were identified in the National Inpatient Sample. Associated comorbidities were also identified for these patients. Univariate analysis was done to compare those risk factors associated with specific arrhythmias in the setting of congenital heart disease. Next, regression analysis was done to identify what patient characteristics and comorbidities were associated with increased risk of specific arrhythmias. A total of 52,725,227 admissions were included in the analysis. Of these, 109,168 (0.21%) had congenital heart disease. Of those with congenital heart disease, 27,088 (25%) had an arrhythmia at some point. The most common arrhythmia in those with congenital heart disease was atrial fibrillation, which was noted in 86% of those with arrhythmia followed by atrial flutter which was noted in 20% of those with congenital heart disease. The largest burden of arrhythmia was found to be in those with tricuspid atresia with a 51% prevalence of arrhythmia in this group followed by Ebstein anomaly which had an arrhythmia prevalence of 39%. Increasing age, male gender, double outlet right ventricle, atrioventricular septal defect, heart failure, obstructive sleep apnea, transposition of the great arteries, congenitally corrected transposition, and tetralogy of Fallot were frequently noted to be independent risk factors of specific arrhythmias. Approximately, 25% of adult admissions with congenital heart disease are associated with arrhythmia. The burden of arrhythmia varies by the specific lesion and other risk factors as well. Understanding of these can help in risk stratification and can help devise strategies to lower this risk. © 2016 Wiley Periodicals, Inc.

Identification of Novel Tissue-Specific Genes by Analysis of Microarray Databases: A Human and Mouse Model

PubMed Central

Suh, Yeunsu; Davis, Michael E.; Lee, Kichoon

2013-01-01

Understanding the tissue-specific pattern of gene expression is critical in elucidating the molecular mechanisms of tissue development, gene function, and transcriptional regulations of biological processes. Although tissue-specific gene expression information is available in several databases, follow-up strategies to integrate and use these data are limited. The objective of the current study was to identify and evaluate novel tissue-specific genes in human and mouse tissues by performing comparative microarray database analysis and semi-quantitative PCR analysis. We developed a powerful approach to predict tissue-specific genes by analyzing existing microarray data from the NCBI′s Gene Expression Omnibus (GEO) public repository. We investigated and confirmed tissue-specific gene expression in the human and mouse kidney, liver, lung, heart, muscle, and adipose tissue. Applying our novel comparative microarray approach, we confirmed 10 kidney, 11 liver, 11 lung, 11 heart, 8 muscle, and 8 adipose specific genes. The accuracy of this approach was further verified by employing semi-quantitative PCR reaction and by searching for gene function information in existing publications. Three novel tissue-specific genes were discovered by this approach including AMDHD1 (amidohydrolase domain containing 1) in the liver, PRUNE2 (prune homolog 2) in the heart, and ACVR1C (activin A receptor, type IC) in adipose tissue. We further confirmed the tissue-specific expression of these 3 novel genes by real-time PCR. Among them, ACVR1C is adipose tissue-specific and adipocyte-specific in adipose tissue, and can be used as an adipocyte developmental marker. From GEO profiles, we predicted the processes in which AMDHD1 and PRUNE2 may participate. Our approach provides a novel way to identify new sets of tissue-specific genes and to predict functions in which they may be involved. PMID:23741331

SFRP1 is a possible candidate for epigenetic therapy in non-small cell lung cancer.

PubMed

Taguchi, Y-H; Iwadate, Mitsuo; Umeyama, Hideaki

2016-08-12

Non-small cell lung cancer (NSCLC) remains a lethal disease despite many proposed treatments. Recent studies have indicated that epigenetic therapy, which targets epigenetic effects, might be a new therapeutic methodology for NSCLC. However, it is not clear which objects (e.g., genes) this treatment specifically targets. Secreted frizzled-related proteins (SFRPs) are promising candidates for epigenetic therapy in many cancers, but there have been no reports of SFRPs targeted by epigenetic therapy for NSCLC. This study performed a meta-analysis of reprogrammed NSCLC cell lines instead of the direct examination of epigenetic therapy treatment to identify epigenetic therapy targets. In addition, mRNA expression/promoter methylation profiles were processed by recently proposed principal component analysis based unsupervised feature extraction and categorical regression analysis based feature extraction. The Wnt/β-catenin signalling pathway was extensively enriched among 32 genes identified by feature extraction. Among the genes identified, SFRP1 was specifically indicated to target β-catenin, and thus might be targeted by epigenetic therapy in NSCLC cell lines. A histone deacetylase inhibitor might reactivate SFRP1 based upon the re-analysis of a public domain data set. Numerical computation validated the binding of SFRP1 to WNT1 to suppress Wnt signalling pathway activation in NSCLC. The meta-analysis of reprogrammed NSCLC cell lines identified SFRP1 as a promising target of epigenetic therapy for NSCLC.

Characterization of Steroid Receptor RNA Activator Protein Function in Modulating the Estrogen Signaling Pathway

DTIC Science & Technology

2007-05-01

Signaling Pathway 5b. GRANT NUMBER W81XWH-05-1-0245 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Yi Yan 5e. TASK NUMBER...negative control to identify proteins non-specifically precipitated. Tandem mass spectrometric analysis of immunoprecipitated samples identified a...immunoprecipitated sample and negative control. It is important to note that, SRAP was present among the remaining specifically precipitated 87 proteins. Using the

Nuclear factors that bind to the enhancer region of nondefective Friend murine leukemia virus.

PubMed Central

Manley, N R; O'Connell, M A; Sharp, P A; Hopkins, N

1989-01-01

Nondefective Friend murine leukemia virus (MuLV) causes erythroleukemia when injected into newborn NFS mice, while Moloney MuLV causes T-cell lymphoma. Exchange of the Friend virus enhancer region, a sequence of about 180 nucleotides including the direct repeat and a short 3'-adjacent segment, for the corresponding region in Moloney MuLV confers the ability to cause erythroid disease on Moloney MuLV. We have used the electrophoretic mobility shift assay and methylation interference analysis to identify cellular factors which bind to the Friend virus enhancer region and compared these with factors, previously identified, that bind to the Moloney virus direct repeat (N. A. Speck and D. Baltimore, Mol. Cell. Biol. 7:1101-1110, 1987). We identified five binding sites for sequence-specific DNA-binding proteins in the Friend virus enhancer region. While some binding sites are present in both the Moloney and Friend virus enhancers, both viruses contain unique sites not present in the other. Although none of the factors identified in this report which bind to these unique sites are present exclusively in T cells or erythroid cells, they bind to three regions of the enhancer shown by genetic analysis to encode disease specificity and thus are candidates to mediate the tissue-specific expression and distinct disease specificities encoded by these virus enhancer elements. Images PMID:2778872

A strategy for evaluating pathway analysis methods.

PubMed

Yu, Chenggang; Woo, Hyung Jun; Yu, Xueping; Oyama, Tatsuya; Wallqvist, Anders; Reifman, Jaques

2017-10-13

Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth, either established or assumed, of the pathways perturbed by a specific clinical or experimental condition. As such, our strategy allows researchers to systematically and objectively evaluate pathway analysis methods by employing any number of datasets for a variety of conditions.

Comparison of Subjective Global Assessment and Protein Energy Wasting Score to Nutrition Evaluations Conducted by Registered Dietitian Nutritionists in Identifying Protein Energy Wasting Risk in Maintenance Hemodialysis Patients.

PubMed

Sum, Simon Siu-Man; Marcus, Andrea F; Blair, Debra; Olejnik, Laura A; Cao, Joyce; Parrott, J Scott; Peters, Emily N; Hand, Rosa K; Byham-Gray, Laura D

2017-09-01

To compare the 7-point subjective global assessment (SGA) and the protein energy wasting (PEW) score with nutrition evaluations conducted by registered dietitian nutritionists in identifying PEW risk in stage 5 chronic kidney disease patients on maintenance hemodialysis. This study is a secondary analysis of a cross-sectional study entitled "Development and Validation of a Predictive energy Equation in Hemodialysis". PEW risk identified by the 7-point SGA and the PEW score was compared against the nutrition evaluations conducted by registered dietitian nutritionists through data examination from the original study (reference standard). A total of 133 patients were included for the analysis. The sensitivity, specificity, positive and negative predictive value (PPV and NPV), positive and negative likelihood ratio (PLR and NLR) of both scoring tools were calculated when compared against the reference standard. The patients were predominately African American (n = 112, 84.2%), non-Hispanic (n = 101, 75.9%), and male (n = 80, 60.2%). Both the 7-point SGA (sensitivity = 78.6%, specificity = 59.1%, PPV = 33.9%, NPV = 91.2%, PLR = 1.9, and NLR = 0.4) and the PEW score (sensitivity = 100%, specificity = 28.6%, PPV = 27.2%, NPV = 100%, PLR = 1.4, and NLR = 0) were more sensitive than specific in identifying PEW risk. The 7-point SGA may miss 21.4% patients having PEW and falsely identify 40.9% of patients who do not have PEW. The PEW score can identify PEW risk in all patients, but 71.4% of patients identified may not have PEW risk. Both the 7-point SGA and the PEW score could identify PEW risk. The 7-point SGA was more specific, and the PEW score was more sensitive. Both scoring tools were found to be clinically confident in identifying patients who were actually not at PEW risk. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Liability risk sharing regime for U.S. commercial space transportation : study and analysis

DOT National Transportation Integrated Search

2002-04-01

The Federal Aviation Administration of the Department of Transportation (DOT), in cooperation with interested federal agencies, has performed a study and analysis of seven issues specifically identified in the Space Competitiveness Act, and provides ...

Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis

PubMed Central

Parker, Robert; Siddiqui, Nazneen; Potiphar, Lee; Goldin, Rob; Timms, John F.; Wells, Athol U.; Kon, Onn M.; Wickremasinghe, Melissa; Mitchell, Donald; Weeks, Mark E.; Lalvani, Ajit

2017-01-01

Background Kveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4–6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins. Methods Kv extracts were separated by 1D-SDS-PAGE and 2D-DIGE and then underwent mass spectrometric analysis for protein identification. Sarcoidosis and control PBMCs were first stimulated with Kv and then with three selected recombinant protein candidates which were identified from the proteomic analysis. PBMC secreted cytokines were subsequently measured by Multiplex Cytokine Assay. Results We observed significantly increased IFN-γ and TNF-α secretion from Kv-stimulated PBMCs of sarcoidosis patients vs. PBMCs from healthy volunteers (IFN-γ: 207.2 pg/mL vs. 3.86 pg/mL, p = 0.0018; TNF-α: 2375 pg/mL vs. 42.82 pg/mL, p = 0.0003). Through proteomic approaches we then identified 74 sarcoidosis tissue-specific proteins. Of these, 3 proteins (vimentin, tubulin and alpha-actinin-4) were identified using both 1D-SDS-PAGE and 2D-DIGE. Data are available via ProteomeXchange with identifier PXD005150. Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001). This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027). No difference was found in cytokine secretion between sarcoidosis and control PBMCs when stimulated with either tubulin or alpha-actinin-4. Conclusions Stimulation with both Kveim reagent and vimentin induces a specific pro-inflammatory cytokine secretion from sarcoidosis PBMCs. Further investigation of cellular immune responses to Kveim-specific proteins may identify novel biomarkers to assist the diagnosis of sarcoidosis. PMID:28114394

Late-Notice HIE Investigation

NASA Technical Reports Server (NTRS)

Hejduk, M. D.

2016-01-01

Provide a response to MOWG action item 1410-01: Analyze close approaches which have required mission team action on short notice. Determine why the approaches were identified later in the process than most other events. Method: Performed an analysis to determine whether there is any correlation between late notice event identification and space weather, sparse tracking, or high drag objects, which would allow preventive action to be taken Examined specific late notice events identified by missions as problematic to try to identify root cause and attempt to relate them to the correlation analysis.

Comparative Analysis of the Orphan CRISPR2 Locus in 242 Enterococcus faecalis Strains

PubMed Central

Hullahalli, Karthik; Rodrigues, Marinelle; Schmidt, Brendan D.; Li, Xiang; Bhardwaj, Pooja; Palmer, Kelli L.

2015-01-01

Clustered, Regularly Interspaced Short Palindromic Repeats and their associated Cas proteins (CRISPR-Cas) provide prokaryotes with a mechanism for defense against mobile genetic elements (MGEs). A CRISPR locus is a molecular memory of MGE encounters. It contains an array of short sequences, called spacers, that generally have sequence identity to MGEs. Three different CRISPR loci have been identified among strains of the opportunistic pathogen Enterococcus faecalis. CRISPR1 and CRISPR3 are associated with the cas genes necessary for blocking MGEs, but these loci are present in only a subset of E. faecalis strains. The orphan CRISPR2 lacks cas genes and is ubiquitous in E. faecalis, although its spacer content varies from strain to strain. Because CRISPR2 is a variable locus occurring in all E. faecalis, comparative analysis of CRISPR2 sequences may provide information about the clonality of E. faecalis strains. We examined CRISPR2 sequences from 228 E. faecalis genomes in relationship to subspecies phylogenetic lineages (sequence types; STs) determined by multilocus sequence typing (MLST), and to a genome phylogeny generated for a representative 71 genomes. We found that specific CRISPR2 sequences are associated with specific STs and with specific branches on the genome tree. To explore possible applications of CRISPR2 analysis, we evaluated 14 E. faecalis bloodstream isolates using CRISPR2 analysis and MLST. CRISPR2 analysis identified two groups of clonal strains among the 14 isolates, an assessment that was confirmed by MLST. CRISPR2 analysis was also used to accurately predict the ST of a subset of isolates. We conclude that CRISPR2 analysis, while not a replacement for MLST, is an inexpensive method to assess clonality among E. faecalis isolates, and can be used in conjunction with MLST to identify recombination events occurring between STs. PMID:26398194

Parallel analysis of tagged deletion mutants efficiently identifies genes involved in endoplasmic reticulum biogenesis.

PubMed

Wright, Robin; Parrish, Mark L; Cadera, Emily; Larson, Lynnelle; Matson, Clinton K; Garrett-Engele, Philip; Armour, Chris; Lum, Pek Yee; Shoemaker, Daniel D

2003-07-30

Increased levels of HMG-CoA reductase induce cell type- and isozyme-specific proliferation of the endoplasmic reticulum. In yeast, the ER proliferations induced by Hmg1p consist of nuclear-associated stacks of smooth ER membranes known as karmellae. To identify genes required for karmellae assembly, we compared the composition of populations of homozygous diploid S. cerevisiae deletion mutants following 20 generations of growth with and without karmellae. Using an initial population of 1,557 deletion mutants, 120 potential mutants were identified as a result of three independent experiments. Each experiment produced a largely non-overlapping set of potential mutants, suggesting that differences in specific growth conditions could be used to maximize the comprehensiveness of similar parallel analysis screens. Only two genes, UBC7 and YAL011W, were identified in all three experiments. Subsequent analysis of individual mutant strains confirmed that each experiment was identifying valid mutations, based on the mutant's sensitivity to elevated HMG-CoA reductase and inability to assemble normal karmellae. The largest class of HMG-CoA reductase-sensitive mutations was a subset of genes that are involved in chromatin structure and transcriptional regulation, suggesting that karmellae assembly requires changes in transcription or that the presence of karmellae may interfere with normal transcriptional regulation. Copyright 2003 John Wiley & Sons, Ltd.

Comparative transcriptome analysis of different chemotypes elucidates withanolide biosynthesis pathway from medicinal plant Withania somnifera

PubMed Central

Gupta, Parul; Goel, Ridhi; Agarwal, Aditya Vikram; Asif, Mehar Hasan; Sangwan, Neelam Singh; Sangwan, Rajender Singh; Trivedi, Prabodh Kumar

2015-01-01

Withania somnifera is one of the most valuable medicinal plants synthesizing secondary metabolites known as withanolides. Despite pharmaceutical importance, limited information is available about the biosynthesis of withanolides. Chemo-profiling of leaf and root tissues of Withania suggest differences in the content and/or nature of withanolides in different chemotypes. To identify genes involved in chemotype and/or tissue-specific withanolide biosynthesis, we established transcriptomes of leaf and root tissues of distinct chemotypes. Genes encoding enzymes for intermediate steps of terpenoid backbone biosynthesis with their alternatively spliced forms and paralogous have been identified. Analysis suggests differential expression of large number genes among leaf and root tissues of different chemotypes. Study also identified differentially expressing transcripts encoding cytochrome P450s, glycosyltransferases, methyltransferases and transcription factors which might be involved in chemodiversity in Withania. Virus induced gene silencing of the sterol ∆7-reductase (WsDWF5) involved in the synthesis of 24-methylene cholesterol, withanolide backbone, suggests role of this enzyme in biosynthesis of withanolides. Information generated, in this study, provides a rich resource for functional analysis of withanolide-specific genes to elucidate chemotype- as well as tissue-specific withanolide biosynthesis. This genomic resource will also help in development of new tools for functional genomics and breeding in Withania. PMID:26688389

Biomarker discovery and transcriptomic responses in Daphnia magna exposed to munitions constituents.

PubMed

Garcia-Reyero, Natalia; Poynton, Helen C; Kennedy, Alan J; Guan, Xin; Escalon, B Lynn; Chang, Bonnie; Varshavsky, Julia; Loguinov, Alex V; Vulpe, Chris D; Perkins, Edward J

2009-06-01

Ecotoxicogenomic approaches are emerging as alternative methods in environmental monitoring because they allow insight into pollutant modes of action and help assess the causal agents and potential toxicity beyond the traditional end points of death, growth, and reproduction. Gene expression analysis has shown particular promise for identifying gene expression biomarkers of chemical exposure that can be further used to monitor specific chemical exposures in the environment. We focused on the development of gene expression markers to detect and discriminate between chemical exposures. Using a custom cDNA microarray for Daphnia magna, we identified distinct expression fingerprints in response to exposure at sublethal concentrations of Cu, Zn, Pb, and munitions constituents. Using the results obtained from microarray analysis, we chose a suite of potential biomarkers for each of the specific exposures. The selected potential biomarkers were tested in independent chemical exposures for specificity using quantitative reverse transcription polymerase chain reaction. Six genes were confirmed as differentially regulated bythe selected chemical exposures. Furthermore, each exposure was identified by response of a unique combination (suite) of individual gene expression biomarkers. These results demonstrate the potential for discovery and validation of novel biomarkers of chemical exposures using gene expression analysis, which could have broad applicability in environmental monitoring.

Genetic Architecture of Aluminum Tolerance in Rice (Oryza sativa) Determined through Genome-Wide Association Analysis and QTL Mapping

PubMed Central

Famoso, Adam N.; Zhao, Keyan; Clark, Randy T.; Tung, Chih-Wei; Wright, Mark H.; Bustamante, Carlos; Kochian, Leon V.; McCouch, Susan R.

2011-01-01

Aluminum (Al) toxicity is a primary limitation to crop productivity on acid soils, and rice has been demonstrated to be significantly more Al tolerant than other cereal crops. However, the mechanisms of rice Al tolerance are largely unknown, and no genes underlying natural variation have been reported. We screened 383 diverse rice accessions, conducted a genome-wide association (GWA) study, and conducted QTL mapping in two bi-parental populations using three estimates of Al tolerance based on root growth. Subpopulation structure explained 57% of the phenotypic variation, and the mean Al tolerance in Japonica was twice that of Indica. Forty-eight regions associated with Al tolerance were identified by GWA analysis, most of which were subpopulation-specific. Four of these regions co-localized with a priori candidate genes, and two highly significant regions co-localized with previously identified QTLs. Three regions corresponding to induced Al-sensitive rice mutants (ART1, STAR2, Nrat1) were identified through bi-parental QTL mapping or GWA to be involved in natural variation for Al tolerance. Haplotype analysis around the Nrat1 gene identified susceptible and tolerant haplotypes explaining 40% of the Al tolerance variation within the aus subpopulation, and sequence analysis of Nrat1 identified a trio of non-synonymous mutations predictive of Al sensitivity in our diversity panel. GWA analysis discovered more phenotype–genotype associations and provided higher resolution, but QTL mapping identified critical rare and/or subpopulation-specific alleles not detected by GWA analysis. Mapping using Indica/Japonica populations identified QTLs associated with transgressive variation where alleles from a susceptible aus or indica parent enhanced Al tolerance in a tolerant Japonica background. This work supports the hypothesis that selectively introgressing alleles across subpopulations is an efficient approach for trait enhancement in plant breeding programs and demonstrates the fundamental importance of subpopulation in interpreting and manipulating the genetics of complex traits in rice. PMID:21829395

Nutrition labelling is a trade policy issue: lessons from an analysis of specific trade concerns at the World Trade Organization.

PubMed

Thow, Anne Marie; Jones, Alexandra; Hawkes, Corinna; Ali, Iqra; Labonté, Ronald

2017-01-12

Interpretive nutrition labels provide simplified nutrient-specific text and/or symbols on the front of pre-packaged foods, to encourage and enable consumers to make healthier choices. This type of labelling has been proposed as part of a comprehensive policy response to the global epidemic of non-communicable diseases. However, regulation of nutrition labelling falls under the remit of not just the health sector but also trade. Specific Trade Concerns have been raised at the World Trade Organization's Technical Barriers to Trade Committee regarding interpretive nutrition labelling initiatives in Thailand, Chile, Indonesia, Peru and Ecuador. This paper presents an analysis of the discussions of these concerns. Although nutrition labelling was identified as a legitimate policy objective, queries were raised regarding the justification of the specific labelling measures proposed, and the scientific evidence for effectiveness of such measures. Concerns were also raised regarding the consistency of the measures with international standards. Drawing on policy learning theory, we identified four lessons for public health policy makers, including: strategic framing of nutrition labelling policy objectives; pro-active policy engagement between trade and health to identify potential trade issues; identifying ways to minimize potential 'practical' trade concerns; and engagement with the Codex Alimentarius Commission to develop international guidance on interpretative labelling. This analysis indicates that while there is potential for trade sector concerns to stifle innovation in nutrition labelling policy, care in how interpretive nutrition labelling measures are crafted in light of trade commitments can minimize such a risk and help ensure that trade policy is coherent with nutrition action. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Integrating Genetic and Gene Co-expression Analysis Identifies Gene Networks Involved in Alcohol and Stress Responses

PubMed Central

Luo, Jie; Xu, Pei; Cao, Peijian; Wan, Hongjian; Lv, Xiaonan; Xu, Shengchun; Wang, Gangjun; Cook, Melloni N.; Jones, Byron C.; Lu, Lu; Wang, Xusheng

2018-01-01

Although the link between stress and alcohol is well recognized, the underlying mechanisms of how they interplay at the molecular level remain unclear. The purpose of this study is to identify molecular networks underlying the effects of alcohol and stress responses, as well as their interaction on anxiety behaviors in the hippocampus of mice using a systems genetics approach. Here, we applied a gene co-expression network approach to transcriptomes of 41 BXD mouse strains under four conditions: stress, alcohol, stress-induced alcohol and control. The co-expression analysis identified 14 modules and characterized four expression patterns across the four conditions. The four expression patterns include up-regulation in no restraint stress and given an ethanol injection (NOE) but restoration in restraint stress followed by an ethanol injection (RSE; pattern 1), down-regulation in NOE but rescue in RSE (pattern 2), up-regulation in both restraint stress followed by a saline injection (RSS) and NOE, and further amplification in RSE (pattern 3), and up-regulation in RSS but reduction in both NOE and RSE (pattern 4). We further identified four functional subnetworks by superimposing protein-protein interactions (PPIs) to the 14 co-expression modules, including γ-aminobutyric acid receptor (GABA) signaling, glutamate signaling, neuropeptide signaling, cAMP-dependent signaling. We further performed module specificity analysis to identify modules that are specific to stress, alcohol, or stress-induced alcohol responses. Finally, we conducted causality analysis to link genetic variation to these identified modules, and anxiety behaviors after stress and alcohol treatments. This study underscores the importance of integrative analysis and offers new insights into the molecular networks underlying stress and alcohol responses. PMID:29674951

Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology.

PubMed

Liu, Tao; Sims, David; Baum, Buzz

2009-01-01

In recent years RNAi screening has proven a powerful tool for dissecting gene functions in animal cells in culture. However, to date, most RNAi screens have been performed in a single cell line, and results then extrapolated across cell types and systems. Here, to dissect generic and cell type-specific mechanisms underlying cell morphology, we have performed identical kinome RNAi screens in six different Drosophila cell lines, derived from two distinct tissues of origin. This analysis identified a core set of kinases required for normal cell morphology in all lines tested, together with a number of kinases with cell type-specific functions. Most significantly, the screen identified a role for minibrain (mnb/DYRK1A), a kinase associated with Down's syndrome, in the regulation of actin-based protrusions in CNS-derived cell lines. This cell type-specific requirement was not due to the peculiarities in the morphology of CNS-derived cells and could not be attributed to differences in mnb expression. Instead, it likely reflects differences in gene expression that constitute the cell type-specific functional context in which mnb/DYRK1A acts. Using parallel RNAi screens and gene expression analyses across cell types we have identified generic and cell type-specific regulators of cell morphology, which include mnb/DYRK1A in the regulation of protrusion morphology in CNS-derived cell lines. This analysis reveals the importance of using different cell types to gain a thorough understanding of gene function across the genome and, in the case of kinases, the difficulties of using the differential gene expression to predict function.

Assessing Group Interaction with Social Language Network Analysis

NASA Astrophysics Data System (ADS)

Scholand, Andrew J.; Tausczik, Yla R.; Pennebaker, James W.

In this paper we discuss a new methodology, social language network analysis (SLNA), that combines tools from social language processing and network analysis to assess socially situated working relationships within a group. Specifically, SLNA aims to identify and characterize the nature of working relationships by processing artifacts generated with computer-mediated communication systems, such as instant message texts or emails. Because social language processing is able to identify psychological, social, and emotional processes that individuals are not able to fully mask, social language network analysis can clarify and highlight complex interdependencies between group members, even when these relationships are latent or unrecognized.

A Novel Collection of snRNA-Like Promoters with Tissue-Specific Transcription Properties

PubMed Central

Garritano, Sonia; Gigoni, Arianna; Costa, Delfina; Malatesta, Paolo; Florio, Tullio; Cancedda, Ranieri; Pagano, Aldo

2012-01-01

We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol) III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III. PMID:23109855

A novel collection of snRNA-like promoters with tissue-specific transcription properties.

PubMed

Garritano, Sonia; Gigoni, Arianna; Costa, Delfina; Malatesta, Paolo; Florio, Tullio; Cancedda, Ranieri; Pagano, Aldo

2012-01-01

We recently identified a novel dataset of snRNA-like trascriptional units in the human genome. The investigation of a subset of these elements showed that they play relevant roles in physiology and/or pathology. In this work we expand our collection of small RNAs taking advantage of a newly developed algorithm able to identify genome sequence stretches with RNA polymerase (pol) III type 3 promoter features thus constituting putative pol III binding sites. The bioinformatic analysis of a subset of these elements that map in introns of protein-coding genes in antisense configuration suggest their association with alternative splicing, similarly to other recently characterized small RNAs. Interestingly, the analysis of the transcriptional activity of these novel promoters shows that they are active in a cell-type specific manner, in accordance with the emerging body of evidence of a tissue/cell-specific activity of pol III.

Microarray analysis reveals overlapping and specific transcriptional responses to different plant hormones in rice

PubMed Central

Garg, Rohini; Tyagi, Akhilesh K.; Jain, Mukesh

2012-01-01

Hormones exert pleiotropic effects on plant growth and development throughout the life cycle. Many of these effects are mediated at molecular level via altering gene expression. In this study, we investigated the exogenous effect of plant hormones, including auxin, cytokinin, abscisic acid, ethylene, salicylic acid and jasmonic acid, on the transcription of rice genes at whole genome level using microarray. Our analysis identified a total of 4171 genes involved in several biological processes, whose expression was altered significantly in the presence of different hormones. Further, 28% of these genes exhibited overlapping transcriptional responses in the presence of any two hormones, indicating crosstalk among plant hormones. In addition, we identified genes showing only a particular hormone-specific response, which can be used as hormone-specific markers. The results of this study will facilitate further studies in hormone biology in rice. PMID:22827941

Teaching community diagnosis to medical students: evaluation of a case study approach.

PubMed

Bair, C W

1980-01-01

A unique case study approach to training medical students in community diagnosis techniques was initiated at the Medical College of Ohio at Toledo. This paper describes the five elements of this teaching method: preliminary specification of target community and data base; group problem-solving requirement; specification of desired output; defined performance objectives; and regularly scheduled time for analysis. Experience with the case study method over two years was evaluated to identify specific strengths and weaknesses. The identified strengths include use of limited educational time to introduce community health problems, development of experience in a collegial team work setting, and specific awareness of the types of data useful to the analysis of community health service problems. Negative evaluations suggested that the method was not conducive to the development of skills in three areas: ability to establish the relative importance of health problems in communities; ability to identify an appropriate health system response to a community health problem from feasible alternatives; and ability to anticipate the community impact of health program modifications or improvements. Potential explanations for these deficiencies include: need for increased didactic support in the classroom for particular skill areas; need to establish a direct field experience in community diagnosis; inappropriateness of the data base used for evaluation of particular skills; and the probability that quantitative analysis, as used in this evaluation, may not be sufficient in and of itself to measure the outcome of a community diagnosis experience.

Comprehensive genome-wide proteomic analysis of human placental tissue for the Chromosome-Centric Human Proteome Project.

PubMed

Lee, Hyoung-Joo; Jeong, Seul-Ki; Na, Keun; Lee, Min Jung; Lee, Sun Hee; Lim, Jong-Sun; Cha, Hyun-Jeong; Cho, Jin-Young; Kwon, Ja-Young; Kim, Hoguen; Song, Si Young; Yoo, Jong Shin; Park, Young Mok; Kim, Hail; Hancock, William S; Paik, Young-Ki

2013-06-07

As a starting point of the Chromosome-Centric Human Proteome Project (C-HPP), we established strategies of genome-wide proteomic analysis, including protein identification, quantitation of disease-specific proteins, and assessment of post-translational modifications, using paired human placental tissues from healthy and preeclampsia patients. This analysis resulted in identification of 4239 unique proteins with high confidence (two or more unique peptides with a false discovery rate less than 1%), covering 21% of approximately 20, 059 (Ensembl v69, Oct 2012) human proteins, among which 28 proteins exhibited differentially expressed preeclampsia-specific proteins. When these proteins are assigned to all human chromosomes, the pattern of the newly identified placental protein population is proportional to that of the gene count distribution of each chromosome. We also identified 219 unique N-linked glycopeptides, 592 unique phosphopeptides, and 66 chromosome 13-specific proteins. In particular, protein evidence of 14 genes previously known to be specifically up-regulated in human placenta was verified by mass spectrometry. With respect to the functional implication of these proteins, 38 proteins were found to be involved in regulatory factor biosynthesis or the immune system in the placenta, but the molecular mechanism of these proteins during pregnancy warrants further investigation. As far as we know, this work produced the highest number of proteins identified in the placenta and will be useful for annotating and mapping all proteins encoded in the human genome.

Quantitative profiling of immune repertoires for minor lymphocyte counts using unique molecular identifiers.

PubMed

Egorov, Evgeny S; Merzlyak, Ekaterina M; Shelenkov, Andrew A; Britanova, Olga V; Sharonov, George V; Staroverov, Dmitriy B; Bolotin, Dmitriy A; Davydov, Alexey N; Barsova, Ekaterina; Lebedev, Yuriy B; Shugay, Mikhail; Chudakov, Dmitriy M

2015-06-15

Emerging high-throughput sequencing methods for the analyses of complex structure of TCR and BCR repertoires give a powerful impulse to adaptive immunity studies. However, there are still essential technical obstacles for performing a truly quantitative analysis. Specifically, it remains challenging to obtain comprehensive information on the clonal composition of small lymphocyte populations, such as Ag-specific, functional, or tissue-resident cell subsets isolated by sorting, microdissection, or fine needle aspirates. In this study, we report a robust approach based on unique molecular identifiers that allows profiling Ag receptors for several hundred to thousand lymphocytes while preserving qualitative and quantitative information on clonal composition of the sample. We also describe several general features regarding the data analysis with unique molecular identifiers that are critical for accurate counting of starting molecules in high-throughput sequencing applications. Copyright © 2015 by The American Association of Immunologists, Inc.

Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage

PubMed Central

2014-01-01

Introduction Cartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Methods The distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance. Results Young, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected. Conclusions MALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved. PMID:24886698

Upgrade and interpersonal skills training at American Airlines

NASA Technical Reports Server (NTRS)

Estridge, W. W.; Mansfield, J. L.

1980-01-01

Segments of the interpersonal skills training audio visual program are presented. The program was developed to train customer contact personnel with specific emphasis on transactional analysis in customer treatment. Concepts of transactional analysis are summarized in terms of the make up of the personality, identified as the three ego states. These ego states are identified as the parent, the adult, and the child. Synopses of four of the tape programs are given.

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

Andersen, Gary L.; Dubinsky, Eric A.

Herein are described 1058 different bacterial taxa that were unique to either human, grazing mammal, or bird fecal wastes. These identified taxa can serve as specific identifier taxa for these sources in environmental waters. Two field tests in marine waters demonstrate the capacity of phylogenetic microarray analysis to track multiple sources with one test.

Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

PubMed

Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

2014-09-05

Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

Using patients’ experiences to identify priorities for quality improvement in breast cancer care: patient narratives, surveys or both?

PubMed Central

2012-01-01

Background Patients’ experiences have become central to assessing the performance of healthcare systems worldwide and are increasingly being used to inform quality improvement processes. This paper explores the relative value of surveys and detailed patient narratives in identifying priorities for improving breast cancer services as part of a quality improvement process. Methods One dataset was collected using a narrative interview approach, (n = 13) and the other using a postal survey (n = 82). Datasets were analyzed separately and then compared to determine whether similar priorities for improving patient experiences were identified. Results There were both similarities and differences in the improvement priorities arising from each approach. Day surgery was specifically identified as a priority in the narrative dataset but included in the survey recommendations only as part of a broader priority around improving inpatient experience. Both datasets identified appointment systems, patients spending enough time with staff, information about treatment and side effects and more information at the end of treatment as priorities. The specific priorities identified by the narrative interviews commonly related to ‘relational’ aspects of patient experience. Those identified by the survey typically related to more ‘functional’ aspects and were not always sufficiently detailed to identify specific improvement actions. Conclusions Our analysis suggests that whilst local survey data may act as a screening tool to identify potential problems within the breast cancer service, they do not always provide sufficient detail of what to do to improve that service. These findings may have wider applicability in other services. We recommend using an initial preliminary survey, with better use of survey open comments, followed by an in-depth qualitative analysis to help deliver improvements to relational and functional aspects of patient experience. PMID:22913525

Integrated microarray and ChIP analysis identifies multiple Foxa2 dependent target genes in the notochord.

PubMed

Tamplin, Owen J; Cox, Brian J; Rossant, Janet

2011-12-15

The node and notochord are key tissues required for patterning of the vertebrate body plan. Understanding the gene regulatory network that drives their formation and function is therefore important. Foxa2 is a key transcription factor at the top of this genetic hierarchy and finding its targets will help us to better understand node and notochord development. We performed an extensive microarray-based gene expression screen using sorted embryonic notochord cells to identify early notochord-enriched genes. We validated their specificity to the node and notochord by whole mount in situ hybridization. This provides the largest available resource of notochord-expressed genes, and therefore candidate Foxa2 target genes in the notochord. Using existing Foxa2 ChIP-seq data from adult liver, we were able to identify a set of genes expressed in the notochord that had associated regions of Foxa2-bound chromatin. Given that Foxa2 is a pioneer transcription factor, we reasoned that these sites might represent notochord-specific enhancers. Candidate Foxa2-bound regions were tested for notochord specific enhancer function in a zebrafish reporter assay and 7 novel notochord enhancers were identified. Importantly, sequence conservation or predictive models could not have readily identified these regions. Mutation of putative Foxa2 binding elements in two of these novel enhancers abrogated reporter expression and confirmed their Foxa2 dependence. The combination of highly specific gene expression profiling and genome-wide ChIP analysis is a powerful means of understanding developmental pathways, even for small cell populations such as the notochord. Copyright © 2011 Elsevier Inc. All rights reserved.

Development of a data independent acquisition mass spectrometry workflow to enable glycopeptide analysis without predefined glycan compositional knowledge.

PubMed

Lin, Chi-Hung; Krisp, Christoph; Packer, Nicolle H; Molloy, Mark P

2018-02-10

Glycoproteomics investigates glycan moieties in a site specific manner to reveal the functional roles of protein glycosylation. Identification of glycopeptides from data-dependent acquisition (DDA) relies on high quality MS/MS spectra of glycopeptide precursors and often requires manual validation to ensure confident assignments. In this study, we investigated pseudo-MRM (MRM-HR) and data-independent acquisition (DIA) as alternative acquisition strategies for glycopeptide analysis. These approaches allow data acquisition over the full MS/MS scan range allowing data re-analysis post-acquisition, without data re-acquisition. The advantage of MRM-HR over DDA for N-glycopeptide detection was demonstrated from targeted analysis of bovine fetuin where all three N-glycosylation sites were detected, which was not the case with DDA. To overcome the duty cycle limitation of MRM-HR acquisition needed for analysis of complex samples such as plasma we trialed DIA. This allowed development of a targeted DIA method to identify N-glycopeptides without pre-defined knowledge of the glycan composition, thus providing the potential to identify N-glycopeptides with unexpected structures. This workflow was demonstrated by detection of 59 N-glycosylation sites from 41 glycoproteins from a HILIC enriched human plasma tryptic digest. 21 glycoforms of IgG1 glycopeptides were identified including two truncated structures that are rarely reported. We developed a data-independent mass spectrometry workflow to identify specific glycopeptides from complex biological mixtures. The novelty is that this approach does not require glycan composition to be pre-defined, thereby allowing glycopeptides carrying unexpected glycans to be identified. This is demonstrated through the analysis of immunoglobulins in human plasma where we detected two IgG1 glycoforms that are rarely observed. Copyright © 2017 Elsevier B.V. All rights reserved.

Ocular findings associated with a Cys39Arg mutation in the Norrie disease gene.

PubMed

Joos, K M; Kimura, A E; Vandenburgh, K; Bartley, J A; Stone, E M

1994-12-01

To diagnose the carriers and noncarriers in a family affected with Norrie disease based on molecular analysis. Family members from three generations, including one affected patient, two obligate carriers, one carrier identified with linkage analysis, one noncarrier identified with linkage analysis, and one female family member with indeterminate carrier status, were examined clinically and electrophysiologically. Linkage analysis had previously failed to determine the carrier status of one female family member in the third generation. Blood samples were screened for mutations in the Norrie disease gene with single-strand conformation polymorphism analysis. The mutation was characterized by dideoxy-termination sequencing. Ophthalmoscopy and electroretinographic examination failed to detect the carrier state. The affected individuals and carriers in this family were found to have a transition from thymidine to cytosine in the first nucleotide of codon 39 of the Norrie disease gene, causing a cysteine-to-arginine mutation. Single-strand conformation polymorphism analysis identified a patient of indeterminate status (by linkage) to be a noncarrier of Norrie disease. Ophthalmoscopy and electroretinography could not identify carriers of this Norrie disease mutation. Single-strand conformation polymorphism analysis was more sensitive and specific than linkage analysis in identifying carriers in this family.

Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

PubMed Central

Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

2012-01-01

Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of “injury" gene predictors that can classify lung injury samples and identify patients at risk for clinically relevant lung injury complications. PMID:23071521

Identification of parental line specific effects of MLF2 on resistance to coccidiosis in chickens

PubMed Central

2011-01-01

Background MLF2 was the candidate gene associated with coccidiosis resistance in chickens. Although single marker analysis supported the association between MLF2 and coccidiosis resistance, causative mutation relevant to coccidiosis was not identified yet. Thus, this study suggested segregation analysis of MLF2 haplotype and the association test of the other candidate genes using improved data transformation. Results A haplotype probably originated from one parental line was found out of 4 major haplotypes of MLF2. Frequency of this haplotype was 0.2 in parental chickens and its offspring in 12 families. Allele substitution effect of the MLF2 haplotype originated from a specific line was associated with increased body weight and fecal egg count explaining coccidiosis resistance. Nevertheless Box-Cox transformation was able to improve normality; association test did not produce obvious different results compared with analysis with log transformed phenotype. Conclusion Allele substitution effect analysis and classification of MLF2 haplotype identified the segregation of haplotype associated with coccidiosis resistance. The haplotype originated from a specific parental line was associated with improving disease resistance. Estimating effect of MLF2 haplotype on coccidiosis resistance will provide useful information for selecting animals or lines for future study. PMID:21645301

Parallel gene analysis with allele-specific padlock probes and tag microarrays

PubMed Central

Banér, Johan; Isaksson, Anders; Waldenström, Erik; Jarvius, Jonas; Landegren, Ulf; Nilsson, Mats

2003-01-01

Parallel, highly specific analysis methods are required to take advantage of the extensive information about DNA sequence variation and of expressed sequences. We present a scalable laboratory technique suitable to analyze numerous target sequences in multiplexed assays. Sets of padlock probes were applied to analyze single nucleotide variation directly in total genomic DNA or cDNA for parallel genotyping or gene expression analysis. All reacted probes were then co-amplified and identified by hybridization to a standard tag oligonucleotide array. The technique was illustrated by analyzing normal and pathogenic variation within the Wilson disease-related ATP7B gene, both at the level of DNA and RNA, using allele-specific padlock probes. PMID:12930977

Identifying influential individuals on intensive care units: using cluster analysis to explore culture.

PubMed

Fong, Allan; Clark, Lindsey; Cheng, Tianyi; Franklin, Ella; Fernandez, Nicole; Ratwani, Raj; Parker, Sarah Henrickson

2017-07-01

The objective of this paper is to identify attribute patterns of influential individuals in intensive care units using unsupervised cluster analysis. Despite the acknowledgement that culture of an organisation is critical to improving patient safety, specific methods to shift culture have not been explicitly identified. A social network analysis survey was conducted and an unsupervised cluster analysis was used. A total of 100 surveys were gathered. Unsupervised cluster analysis was used to group individuals with similar dimensions highlighting three general genres of influencers: well-rounded, knowledge and relational. Culture is created locally by individual influencers. Cluster analysis is an effective way to identify common characteristics among members of an intensive care unit team that are noted as highly influential by their peers. To change culture, identifying and then integrating the influencers in intervention development and dissemination may create more sustainable and effective culture change. Additional studies are ongoing to test the effectiveness of utilising these influencers to disseminate patient safety interventions. This study offers an approach that can be helpful in both identifying and understanding influential team members and may be an important aspect of developing methods to change organisational culture. © 2017 John Wiley & Sons Ltd.

A comparative meta-analysis of QTL between intraspecific Gossypium hirsutum interspecific populations and Gossypium hirsutum x Gossypium barbadense populations

USDA-ARS?s Scientific Manuscript database

Recent Meta-analysis of quantitative trait loci (QTL) in tetraploid cotton (Gossypium spp.) has identified regions of the genome with high concentrations of various trait QTL called clusters, and specific trait QTL called hotspots. The Meta-analysis included all population types of Gossypium mixing ...

Developing the Instructional Specification. Monograph Number 12.

ERIC Educational Resources Information Center

Gerlach, Vernon S.; And Others

Analysis of a film script that makes the learner identify and distinguish between statements of observation and statements of inference leads an instructor (or other program writer) step by step through the processes of preparing an instructional specification--a blue-print for preparing powerful self-instructional materials. There are four parts…

Real-time polymerase chain reaction for diagnosing infectious mononucleosis in pediatric patients: A systematic review and meta-analysis.

PubMed

Jiang, Sha-Yi; Yang, Jing-Wei; Shao, Jing-Bo; Liao, Xue-Lian; Lu, Zheng-Hua; Jiang, Hui

2016-05-01

In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis. © 2015 Wiley Periodicals, Inc.

Targeted deletion and lipidomic analysis identify epithelial cell COX-2 as a major driver of chemically induced skin cancer.

PubMed

Jiao, Jing; Ishikawa, Tomo-O; Dumlao, Darren S; Norris, Paul C; Magyar, Clara E; Mikulec, Carol; Catapang, Art; Dennis, Edward A; Fischer, Susan M; Herschman, Harvey R

2014-11-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX-2) plays a critical role in DMBA/TPA-induced skin tumor induction. Although many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell type-specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared with littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2-expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell type-specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biologic responses. Cox-2 gene deletion demonstrates that intrinsic COX-2 expression in initiated keratinocytes is a principal driver of skin carcinogenesis; lipidomic analysis identifies likely prostanoid effectors. ©2014 American Association for Cancer Research.

Is the Timed Up and Go test a useful predictor of risk of falls in community dwelling older adults: a systematic review and meta- analysis

PubMed Central

2014-01-01

Background The Timed Up and Go test (TUG) is a commonly used screening tool to assist clinicians to identify patients at risk of falling. The purpose of this systematic review and meta-analysis is to determine the overall predictive value of the TUG in community-dwelling older adults. Methods A literature search was performed to identify all studies that validated the TUG test. The methodological quality of the selected studies was assessed using the QUADAS-2 tool, a validated tool for the quality assessment of diagnostic accuracy studies. A TUG score of ≥13.5 seconds was used to identify individuals at higher risk of falling. All included studies were combined using a bivariate random effects model to generate pooled estimates of sensitivity and specificity at ≥13.5 seconds. Heterogeneity was assessed using the variance of logit transformed sensitivity and specificity. Results Twenty-five studies were included in the systematic review and 10 studies were included in meta-analysis. The TUG test was found to be more useful at ruling in rather than ruling out falls in individuals classified as high risk (>13.5 sec), with a higher pooled specificity (0.74, 95% CI 0.52-0.88) than sensitivity (0.31, 95% CI 0.13-0.57). Logistic regression analysis indicated that the TUG score is not a significant predictor of falls (OR = 1.01, 95% CI 1.00-1.02, p = 0.05). Conclusion The Timed Up and Go test has limited ability to predict falls in community dwelling elderly and should not be used in isolation to identify individuals at high risk of falls in this setting. PMID:24484314

Identification and characterization of near-fatal asthma phenotypes by cluster analysis.

PubMed

Serrano-Pariente, J; Rodrigo, G; Fiz, J A; Crespo, A; Plaza, V

2015-09-01

Near-fatal asthma (NFA) is a heterogeneous clinical entity and several profiles of patients have been described according to different clinical, pathophysiological and histological features. However, there are no previous studies that identify in a unbiased way--using statistical methods such as clusters analysis--different phenotypes of NFA. Therefore, the aim of the present study was to identify and to characterize phenotypes of near fatal asthma using a cluster analysis. Over a period of 2 years, 33 Spanish hospitals enrolled 179 asthmatics admitted for an episode of NFA. A cluster analysis using two-steps algorithm was performed from data of 84 of these cases. The analysis defined three clusters of patients with NFA: cluster 1, the largest, including older patients with clinical and therapeutic criteria of severe asthma; cluster 2, with an high proportion of respiratory arrest (68%), impaired consciousness level (82%) and mechanical ventilation (93%); and cluster 3, which included younger patients, characterized by an insufficient anti-inflammatory treatment and frequent sensitization to Alternaria alternata and soybean. These results identify specific asthma phenotypes involved in NFA, confirming in part previous findings observed in studies with a clinical approach. The identification of patients with a specific NFA phenotype could suggest interventions to prevent future severe asthma exacerbations. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Widespread occurrence of lysine methylation in Plasmodium falciparum proteins at asexual blood stages.

PubMed

Kaur, Inderjeet; Zeeshan, Mohammad; Saini, Ekta; Kaushik, Abhinav; Mohmmed, Asif; Gupta, Dinesh; Malhotra, Pawan

2016-10-20

Post-transcriptional and post-translational modifications play a major role in Plasmodium life cycle regulation. Lysine methylation of histone proteins is well documented in several organisms, however in recent years lysine methylation of proteins outside histone code is emerging out as an important post-translational modification (PTM). In the present study we have performed global analysis of lysine methylation of proteins in asexual blood stages of Plasmodium falciparum development. We immunoprecipitated stage specific Plasmodium lysates using anti-methyl lysine specific antibodies that immunostained the asexual blood stage parasites. Using liquid chromatography and tandem mass spectrometry analysis, 570 lysine methylated proteins at three different blood stages were identified. Analysis of the peptide sequences identified 605 methylated sites within 422 proteins. Functional classification of the methylated proteins revealed that the proteins are mainly involved in nucleotide metabolic processes, chromatin organization, transport, homeostatic processes and protein folding. The motif analysis of the methylated lysine peptides reveals novel motifs. Many of the identified lysine methylated proteins are also interacting partners/substrates of PfSET domain proteins as revealed by STRING database analysis. Our findings suggest that the protein methylation at lysine residues is widespread in Plasmodium and plays an important regulatory role in diverse set of the parasite pathways.

CAPER 3.0: A Scalable Cloud-Based System for Data-Intensive Analysis of Chromosome-Centric Human Proteome Project Data Sets.

PubMed

Yang, Shuai; Zhang, Xinlei; Diao, Lihong; Guo, Feifei; Wang, Dan; Liu, Zhongyang; Li, Honglei; Zheng, Junjie; Pan, Jingshan; Nice, Edouard C; Li, Dong; He, Fuchu

2015-09-04

The Chromosome-centric Human Proteome Project (C-HPP) aims to catalog genome-encoded proteins using a chromosome-by-chromosome strategy. As the C-HPP proceeds, the increasing requirement for data-intensive analysis of the MS/MS data poses a challenge to the proteomic community, especially small laboratories lacking computational infrastructure. To address this challenge, we have updated the previous CAPER browser into a higher version, CAPER 3.0, which is a scalable cloud-based system for data-intensive analysis of C-HPP data sets. CAPER 3.0 uses cloud computing technology to facilitate MS/MS-based peptide identification. In particular, it can use both public and private cloud, facilitating the analysis of C-HPP data sets. CAPER 3.0 provides a graphical user interface (GUI) to help users transfer data, configure jobs, track progress, and visualize the results comprehensively. These features enable users without programming expertise to easily conduct data-intensive analysis using CAPER 3.0. Here, we illustrate the usage of CAPER 3.0 with four specific mass spectral data-intensive problems: detecting novel peptides, identifying single amino acid variants (SAVs) derived from known missense mutations, identifying sample-specific SAVs, and identifying exon-skipping events. CAPER 3.0 is available at http://prodigy.bprc.ac.cn/caper3.

Assessing host-specificity of Escherichia coli using a supervised learning logic-regression-based analysis of single nucleotide polymorphisms in intergenic regions.

PubMed

Zhi, Shuai; Li, Qiaozhi; Yasui, Yutaka; Edge, Thomas; Topp, Edward; Neumann, Norman F

2015-11-01

Host specificity in E. coli is widely debated. Herein, we used supervised learning logic-regression-based analysis of intergenic DNA sequence variability in E. coli in an attempt to identify single nucleotide polymorphism (SNP) biomarkers of E. coli that are associated with natural selection and evolution toward host specificity. Seven-hundred and eighty strains of E. coli were isolated from 15 different animal hosts. We utilized logic regression for analyzing DNA sequence data of three intergenic regions (flanked by the genes uspC-flhDC, csgBAC-csgDEFG, and asnS-ompF) to identify genetic biomarkers that could potentially discriminate E. coli based on host sources. Across 15 different animal hosts, logic regression successfully discriminated E. coli based on animal host source with relatively high specificity (i.e., among the samples of the non-target animal host, the proportion that correctly did not have the host-specific marker pattern) and sensitivity (i.e., among the samples from a given animal host, the proportion that correctly had the host-specific marker pattern), even after fivefold cross validation. Permutation tests confirmed that for most animals, host specific intergenic biomarkers identified by logic regression in E. coli were significantly associated with animal host source. The highest level of biomarker sensitivity was observed in deer isolates, with 82% of all deer E. coli isolates displaying a unique SNP pattern that was 98% specific to deer. Fifty-three percent of human isolates displayed a unique biomarker pattern that was 98% specific to humans. Twenty-nine percent of cattle isolates displayed a unique biomarker that was 97% specific to cattle. Interestingly, even within a related host group (i.e., Family: Canidae [domestic dogs and coyotes]), highly specific SNP biomarkers (98% and 99% specificity for dog and coyotes, respectively) were observed, with 21% of dog E. coli isolates displaying a unique dog biomarker and 61% of coyote isolates displaying a unique coyote biomarker. Application of a supervised learning method, such as logic regression, to DNA sequence analysis at certain intergenic regions demonstrates that some E. coli strains may evolve to become host-specific. Copyright © 2015 Elsevier Inc. All rights reserved.

Profiles of Reactivity in Cocaine-Exposed Children

ERIC Educational Resources Information Center

Schuetze, Pamela; Molnar, Danielle S.; Eiden, Rina D.

2012-01-01

This study explored the possibility that specific, theoretically consistent profiles of reactivity could be identified in a sample of cocaine-exposed infants and whether these profiles were associated with a range of infant and/or maternal characteristics. Cluster analysis was used to identify distinct groups of infants based on physiological,…

Analysis of stable isotopes in fish to identify habitat use and switching

EPA Science Inventory

In our isotopic studies of fish in Oregon Coast Range streams we have found stable isotopes of carbon, oxygen and sulfur to be surprisingly useful in identifying and discriminating specific habitat or tributary use by a variety of fish species. Stable isotopes of carbon can be u...

A Serological Biopsy Using Five Stomach-Specific Circulating Biomarkers for Gastric Cancer Risk Assessment: A Multi-Phase Study.

PubMed

Tu, Huakang; Sun, Liping; Dong, Xiao; Gong, Yuehua; Xu, Qian; Jing, Jingjing; Bostick, Roberd M; Wu, Xifeng; Yuan, Yuan

2017-05-01

We aimed to assess a serological biopsy using five stomach-specific circulating biomarkers-pepsinogen I (PGI), PGII, PGI/II ratio, anti-Helicobacter pylori (H. pylori) antibody, and gastrin-17 (G-17)-for identifying high-risk individuals and predicting risk of developing gastric cancer (GC). Among 12,112 participants with prospective follow-up from an ongoing population-based screening program using both serology and gastroscopy in China, we conducted a multi-phase study involving a cross-sectional analysis, a follow-up analysis, and an integrative risk prediction modeling analysis. In the cross-sectional analysis, the five biomarkers (especially PGII, the PGI/II ratio, and H. pylori sero-positivity) were associated with the presence of precancerous gastric lesions or GC at enrollment. In the follow-up analysis, low PGI levels and PGI/II ratios were associated with higher risk of developing GC, and both low (<0.5 pmol/l) and high (>4.7 pmol/l) G-17 levels were associated with higher risk of developing GC, suggesting a J-shaped association. In the risk prediction modeling analysis, the five biomarkers combined yielded a C statistic of 0.803 (95% confidence interval (CI)=0.789-0.816) and improved prediction beyond traditional risk factors (C statistic from 0.580 to 0.811, P<0.001) for identifying precancerous lesions at enrollment, and higher serological biopsy scores based on the five biomarkers at enrollment were associated with higher risk of developing GC during follow-up (P for trend <0.001). A serological biopsy composed of the five stomach-specific circulating biomarkers could be used to identify high-risk individuals for further diagnostic gastroscopy, and to stratify individuals' risk of developing GC and thus to guide targeted screening and precision prevention.

Fault Tree Analysis Application for Safety and Reliability

NASA Technical Reports Server (NTRS)

Wallace, Dolores R.

2003-01-01

Many commercial software tools exist for fault tree analysis (FTA), an accepted method for mitigating risk in systems. The method embedded in the tools identifies a root as use in system components, but when software is identified as a root cause, it does not build trees into the software component. No commercial software tools have been built specifically for development and analysis of software fault trees. Research indicates that the methods of FTA could be applied to software, but the method is not practical without automated tool support. With appropriate automated tool support, software fault tree analysis (SFTA) may be a practical technique for identifying the underlying cause of software faults that may lead to critical system failures. We strive to demonstrate that existing commercial tools for FTA can be adapted for use with SFTA, and that applied to a safety-critical system, SFTA can be used to identify serious potential problems long before integrator and system testing.

Identification of suitable genes contributes to lung adenocarcinoma clustering by multiple meta-analysis methods.

PubMed

Yang, Ze-Hui; Zheng, Rui; Gao, Yuan; Zhang, Qiang

2016-09-01

With the widespread application of high-throughput technology, numerous meta-analysis methods have been proposed for differential expression profiling across multiple studies. We identified the suitable differentially expressed (DE) genes that contributed to lung adenocarcinoma (ADC) clustering based on seven popular multiple meta-analysis methods. Seven microarray expression profiles of ADC and normal controls were extracted from the ArrayExpress database. The Bioconductor was used to perform the data preliminary preprocessing. Then, DE genes across multiple studies were identified. Hierarchical clustering was applied to compare the classification performance for microarray data samples. The classification efficiency was compared based on accuracy, sensitivity and specificity. Across seven datasets, 573 ADC cases and 222 normal controls were collected. After filtering out unexpressed and noninformative genes, 3688 genes were remained for further analysis. The classification efficiency analysis showed that DE genes identified by sum of ranks method separated ADC from normal controls with the best accuracy, sensitivity and specificity of 0.953, 0.969 and 0.932, respectively. The gene set with the highest classification accuracy mainly participated in the regulation of response to external stimulus (P = 7.97E-04), cyclic nucleotide-mediated signaling (P = 0.01), regulation of cell morphogenesis (P = 0.01) and regulation of cell proliferation (P = 0.01). Evaluation of DE genes identified by different meta-analysis methods in classification efficiency provided a new perspective to the choice of the suitable method in a given application. Varying meta-analysis methods always present varying abilities, so synthetic consideration should be taken when providing meta-analysis methods for particular research. © 2015 John Wiley & Sons Ltd.

Tissue-enriched expression profiles in Aedes aegypti identify hemocyte-specific transcriptome responses to infection

PubMed Central

Choi, Young-Jun; Fuchs, Jeremy F.; Mayhew, George F.; Yu, Helen E.; Christensen, Bruce M.

2012-01-01

Hemocytes are integral components of mosquito immune mechanisms such as phagocytosis, melanization, and production of antimicrobial peptides. However, our understanding of hemocyte-specific molecular processes and their contribution to shaping the host immune response remains limited. To better understand the immunophysiological features distinctive of hemocytes, we conducted genome-wide analysis of hemocyte-enriched transcripts, and examined how tissue-enriched expression patterns change with the immune status of the host. Our microarray data indicate that the hemocyte-enriched trascriptome is dynamic and context-dependent. Analysis of transcripts enriched after bacterial challenge in circulating hemocytes with respect to carcass added a dimension to evaluating infection-responsive genes and immune-related gene families. We resolved patterns of transcriptional change unique to hemocytes from those that are likely shared by other immune responsive tissues, and identified clusters of genes preferentially induced in hemocytes, likely reflecting their involvement in cell type specific functions. In addition, the study revealed conserved hemocyte-enriched molecular repertoires which might be implicated in core hemocyte function by cross-species meta-analysis of microarray expression data from Anopheles gambiae and Drosophila melanogaster. PMID:22796331

Smelling the Diagnosis: The Electronic Nose as Diagnostic Tool in Inflammatory Arthritis. A Case-Reference Study.

PubMed

Brekelmans, Marjolein P; Fens, Niki; Brinkman, Paul; Bos, Lieuwe D; Sterk, Peter J; Tak, Paul P; Gerlag, Daniëlle M

2016-01-01

To investigate whether exhaled breath analysis using an electronic nose can identify differences between inflammatory joint diseases and healthy controls. In a cross-sectional study, the exhaled breath of 21 rheumatoid arthritis (RA) and 18 psoriatic arthritis (PsA) patients with active disease was compared to 21 healthy controls using an electronic nose (Cyranose 320; Smiths Detection, Pasadena, CA, USA). Breathprints were analyzed with principal component analysis, discriminant analysis, and area under curve (AUC) of receiver operating characteristics (ROC) curves. Volatile organic compounds (VOCs) were identified by gas chromatography and mass spectrometry (GC-MS), and relationships between breathprints and markers of disease activity were explored. Breathprints of RA patients could be distinguished from controls with an accuracy of 71% (AUC 0.75, 95% CI 0.60-0.90, sensitivity 76%, specificity 67%). Breathprints from PsA patients were separated from controls with 69% accuracy (AUC 0.77, 95% CI 0.61-0.92, sensitivity 72%, specificity 71%). Distinction between exhaled breath of RA and PsA patients exhibited an accuracy of 69% (AUC 0.72, 95% CI 0.55-0.89, sensitivity 71%, specificity 72%). There was a positive correlation in RA patients of exhaled breathprints with disease activity score (DAS28) and number of painful joints. GC-MS identified seven key VOCs that significantly differed between the groups. Exhaled breath analysis by an electronic nose may play a role in differential diagnosis of inflammatory joint diseases. Data from this study warrant external validation.

A Systems Biology Framework Identifies Molecular Underpinnings of Coronary Heart Disease

PubMed Central

Huan, Tianxiao; Zhang, Bin; Wang, Zhi; Joehanes, Roby; Zhu, Jun; Johnson, Andrew D.; Ying, Saixia; Munson, Peter J.; Raghavachari, Nalini; Wang, Richard; Liu, Poching; Courchesne, Paul; Hwang, Shih-Jen; Assimes, Themistocles L.; McPherson, Ruth; Samani, Nilesh J.; Schunkert, Heribert; Meng, Qingying; Suver, Christine; O'Donnell, Christopher J.; Derry, Jonathan; Yang, Xia; Levy, Daniel

2013-01-01

Objective Genetic approaches have identified numerous loci associated with coronary heart disease (CHD). The molecular mechanisms underlying CHD gene-disease associations, however, remain unclear. We hypothesized that genetic variants with both strong and subtle effects drive gene subnetworks that in turn affect CHD. Approach and Results We surveyed CHD-associated molecular interactions by constructing coexpression networks using whole blood gene expression profiles from 188 CHD cases and 188 age- and sex-matched controls. 24 coexpression modules were identified including one case-specific and one control-specific differential module (DM). The DMs were enriched for genes involved in B-cell activation, immune response, and ion transport. By integrating the DMs with altered gene expression associated SNPs (eSNPs) and with results of GWAS of CHD and its risk factors, the control-specific DM was implicated as CHD-causal based on its significant enrichment for both CHD and lipid eSNPs. This causal DM was further integrated with tissue-specific Bayesian networks and protein-protein interaction networks to identify regulatory key driver (KD) genes. Multi-tissue KDs (SPIB and TNFRSF13C) and tissue-specific KDs (e.g. EBF1) were identified. Conclusions Our network-driven integrative analysis not only identified CHD-related genes, but also defined network structure that sheds light on the molecular interactions of genes associated with CHD risk. PMID:23539213

Does beer, wine or liquor consumption correlate with the risk of renal cell carcinoma? A dose-response meta-analysis of prospective cohort studies

PubMed Central

Xu, Xin; Zhu, Yi; Zheng, Xiangyi; Xie, Liping

2015-01-01

Despite plenty of evidence supports an inverse association between alcohol drinking and risk of renal cell carcinoma (RCC), sex-specific and beverage-specific dose-response relationships have not been well established. We examined this association by performing a systematic review and meta-analysis of prospective studies. Studies were identified by comprehensively searching PubMed and EMBASE databases through February 21, 2015. Categorical and dose-response meta-analyses were conducted to identify the effects of alcohol on RCC. A total of eight publications (including seven cohort studies and one pooled analysis of 12 cohort studies) were eligible for this meta-analysis. Dose-response analysis showed that each 5 g/day increment of alcohol intake corresponded to a 5% decrease in risk of RCC for males and 9% for females. Alcohol intakes from wine, beer, and liquor were each associated with a reduced risk of RCC. When these associations were examined separately by gender, statistically significant inverse associations were restricted to alcohol from wine among females (RR = 0.82, 95% CI 0.73–0.91) and to alcohol from beer and from liquor among males (RR = 0.87, 95% CI 0.83–0.91 and RR = 0.95, 95% CI 0.92–0.99, respectively). In conclusion, there exist gender-specific and beverage-specific differences in the association between alcohol intake and RCC risk. PMID:25965820

Sparse Feature Selection Identifies H2A.Z as a Novel, Pattern-Specific Biomarker for Asymmetrically Self-Renewing Distributed Stem Cells

PubMed Central

Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R.; Chen, Jennifer C.; Winkler, David A.; Sherley, James L.

2015-01-01

There is a long-standing unmet clinical need for biomarkers with high specificity for distributed stem cells (DSCs) in tissues, or for use in diagnostic and therapeutic cell preparations (e.g., bone marrow). Although DSCs are essential for tissue maintenance and repair, accurate determination of their numbers for medical applications has been problematic. Previous searches for biomarkers expressed specifically in DSCs were hampered by difficulty obtaining pure DSCs and by the challenges in mining complex molecular expression data. To identify DSC such useful and specific biomarkers, we combined a novel sparse feature selection method with combinatorial molecular expression data focused on asymmetric self-renewal, a conspicuous property of DSCs. The analysis identified reduced expression of the histone H2A variant H2A.Z as a superior molecular discriminator for DSC asymmetric self-renewal. Subsequent molecular expression studies showed H2A.Z to be a novel “pattern-specific biomarker” for asymmetrically self-renewing cells with sufficient specificity to count asymmetrically self-renewing DSCs in vitro and potentially in situ. PMID:25636161

Comment on 'Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets' by Lam et al.

PubMed

Hill, W David

2018-04-01

Intelligence and educational attainment are strongly genetically correlated. This relationship can be exploited by Multi-Trait Analysis of GWAS (MTAG) to add power to Genome-wide Association Studies (GWAS) of intelligence. MTAG allows the user to meta-analyze GWASs of different phenotypes, based on their genetic correlations, to identify association's specific to the trait of choice. An MTAG analysis using GWAS data sets on intelligence and education was conducted by Lam et al. (2017). Lam et al. (2017) reported 70 loci that they described as 'trait specific' to intelligence. This article examines whether the analysis conducted by Lam et al. (2017) has resulted in genetic information about a phenotype that is more similar to education than intelligence.

Sex-dependent difference in the effect of metformin on colorectal cancer-specific mortality of diabetic colorectal cancer patients

PubMed Central

Park, Jung Won; Lee, Jin Ha; Park, Ye Hyun; Park, Soo Jung; Cheon, Jae Hee; Kim, Won Ho; Kim, Tae Il

2017-01-01

AIM To assess factors associated with the higher effect of metformin on mortality in diabetic colorectal cancer (CRC) patients, since the factors related to the effectiveness of metformin have not been identified yet. METHODS Between January 2000 and December 2010, 413 patients diagnosed with both stage 3/4 CRC and diabetes mellitus were identified. Patients’ demographics and clinical characteristics were analyzed. The effect of metformin on CRC-specific mortality and the interactions between metformin and each adjusted factor were evaluated. RESULTS Total follow-up duration was median 50 mo (range: 1-218 mo). There were 85 deaths (45.9%) and 72 CRC-specific deaths (38.9%) among 185 patients who used metformin, compared to 130 total deaths (57.0%) and 107 CRC-specific deaths (46.9%) among 228 patients who did not use metformin. In multivariate analysis, survival benefit associated with metformin administration was identified (HR = 0.985, 95%CI: 0.974-0.997, P = 0.012). Interaction test between metformin and sex after adjustment for relevant factors revealed that female CRC patients taking metformin exhibited a significantly lower CRC-specific mortality rate than male CRC patients taking metformin (HR = 0.369, 95%CI: 0.155-0.881, P = 0.025). Furthermore, subgroup analysis revealed significant differences in CRC-specific mortality between the metformin and non-metformin groups in female patients (HR = 0.501, 95%CI: 0.286-0.879, P = 0.013) but not male patients (HR = 0.848, 95%CI: 0.594-1.211, P = 0.365). There were no significant interactions between metformin and other adjusted factors on CRC-specific mortality. CONCLUSION We showed a strong sex-dependent difference in the effect of metformin on CRC-specific mortality in advanced stage CRC patients with diabetes. PMID:28811714

Molecular characterization and intermolecular interaction of coat protein of Prunus necrotic ringspot virus: implications for virus assembly.

PubMed

Kulshrestha, Saurabh; Hallan, Vipin; Sharma, Anshul; Seth, Chandrika Attri; Chauhan, Anjali; Zaidi, Aijaz Asghar

2013-09-01

Coat protein (CP) and RNA3 from Prunus necrotic ringspot virus (PNRSV-rose), the most prevalent virus infecting rose in India, were characterized and regions in the coat protein important for self-interaction, during dimer formation were identified. The sequence analysis of CP and partial RNA 3 revealed that the rose isolate of PNRSV in India belongs to PV-32 group of PNRSV isolates. Apart from the already established group specific features of PV-32 group member's additional group-specific and host specific features were also identified. Presence of methionine at position 90 in the amino acid sequence alignment of PNRSV CP gene (belonging to PV-32 group) was identified as the specific conserved feature for the rose isolates of PNRSV. As protein-protein interaction plays a vital role in the infection process, an attempt was made to identify the portions of PNRSV CP responsible for self-interaction using yeast two-hybrid system. It was found (after analysis of the deletion clones) that the C-terminal region of PNRSV CP (amino acids 153-226) plays a vital role in this interaction during dimer formation. N-terminal of PNRSV CP is previously known to be involved in CP-RNA interactions, but our results also suggested that N-terminal of PNRSV CP represented by amino acids 1-77 also interacts with C-terminal (amino acids 153-226) in yeast two-hybrid system, suggesting its probable involvement in the CP-CP interaction.

Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

PubMed Central

Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

2009-01-01

Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE.

PubMed

Bowes Rickman, Catherine; Ebright, Jessica N; Zavodni, Zachary J; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P; Wistow, Graeme; Boon, Kathy; Hauser, Michael A

2006-06-01

To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. The EyeSAGE database, combining three different gene-profiling platforms including the authors' multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions.

Regional differences in mitochondrial DNA methylation in human post-mortem brain tissue.

PubMed

Devall, Matthew; Smith, Rebecca G; Jeffries, Aaron; Hannon, Eilis; Davies, Matthew N; Schalkwyk, Leonard; Mill, Jonathan; Weedon, Michael; Lunnon, Katie

2017-01-01

DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions ( p  < 0.05) in the mitochondrial genome, between anatomically separate cortical regions and the cerebellum in matched samples ( N  = 3 matched donors). Further analysis identified eight significant differentially methylated regions between the total cortex and cerebellum after correcting for multiple testing. Using unsupervised hierarchical clustering analysis of the mitochondrial DNA methylome, we were able to identify tissue-specific patterns of mitochondrial DNA methylation between blood, cerebellum and cortex. Our study represents a comprehensive analysis of the mitochondrial methylome using pre-existing Methylated DNA Immunoprecipitation Sequencing data to identify brain region-specific patterns of mitochondrial DNA methylation.

ISSLS PRIZE IN CLINICAL SCIENCE 2017: Is infection the possible initiator of disc disease? An insight from proteomic analysis.

PubMed

Rajasekaran, S; Tangavel, Chitraa; Aiyer, Siddharth N; Nayagam, Sharon Miracle; Raveendran, M; Demonte, Naveen Luke; Subbaiah, Pramela; Kanna, Rishi; Shetty, Ajoy Prasad; Dharmalingam, K

2017-05-01

Proteomic and 16S rDNA analysis of disc tissues obtained in vivo. To address the controversy of infection as an aetiology for disc disorders through protein profiling. There is raging controversy over the presence of bacteria in human lumbar discs in vivo, and if they represent contamination or infection. Proteomics can provide valuable insight by identifying proteins signifying bacterial presence and, also host defence response proteins (HDRPs), which will confirm infection. 22 discs (15-disc herniations (DH), 5-degenerate (DD), 2-normal in MRI (NM) were harvested intraoperatively and immediately snap frozen. Samples were pooled into three groups and proteins extracted were analysed with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Post identification, data analysis was performed using Uniprotdb, Pantherdb, Proteome discoverer and STRING network. Authentication for bacterial presence was performed by PCR amplification of 16S rDNA. LC-MS/MS analysis using Orbitrap showed 1103 proteins in DH group, compared to 394 in NM and 564 in DD. 73 bacterial specific proteins were identified (56 specific for Propionibacterium acnes; 17 for Staphylococcus epidermidis). In addition, 67 infection-specific HDRPs, unique or upregulated, such as Defensin, Lysozyme, Dermcidin, Cathepsin-G, Prolactin-Induced Protein, and Phospholipase-A2, were identified confirming presence of infection. Species-specific primers for P. acnes exhibited amplicons at 946 bp (16S rDNA) and 515 bp (Lipase) confirming presence of P. acnes in both NM discs, 11 of 15 DH discs, and all five DD discs. Bioinformatic search for protein-protein interactions (STRING) documented 169 proteins with close interactions (protein clustering co-efficient 0.7) between host response and degenerative proteins implying that infection may initiate degradation through Ubiquitin C. Our study demonstrates bacterial specific proteins and host defence proteins to infection which strengthen the hypothesis of infection as a possible initiator of disc disease. These results can lead to a paradigm shift in our understanding and management of disc disorders.

13C-DEPLETED MICROBIAL LIPIDS INDICATE SEASONAL METHANOTROPHIC ACTIVITY IN SHALLOW ESTUARINE SEDIMENTS

EPA Science Inventory

Compound specific isotope analysis was combined with phospholipid fatty acid (PLFA) analysis to identify methanotrophic activity in members of the sedimentary microbial community in the Altamaha and Savannah River estuaries in Georgia. 13C-depleted PLFAs indicate methane utilizat...

Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways

PubMed Central

Kaushik, Abhinav; Ali, Shakir; Gupta, Dinesh

2017-01-01

Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA. PMID:28084397

A graph-based network-vulnerability analysis system

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

Swiler, L.P.; Phillips, C.; Gaylor, T.

1998-05-03

This paper presents a graph based approach to network vulnerability analysis. The method is flexible, allowing analysis of attacks from both outside and inside the network. It can analyze risks to a specific network asset, or examine the universe of possible consequences following a successful attack. The analysis system requires as input a database of common attacks, broken into atomic steps, specific network configuration and topology information, and an attacker profile. The attack information is matched with the network configuration information and an attacker profile to create a superset attack graph. Nodes identify a stage of attack, for example themore » class of machines the attacker has accessed and the user privilege level he or she has compromised. The arcs in the attack graph represent attacks or stages of attacks. By assigning probabilities of success on the arcs or costs representing level of effort for the attacker, various graph algorithms such as shortest path algorithms can identify the attack paths with the highest probability of success.« less

A graph-based network-vulnerability analysis system

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

Swiler, L.P.; Phillips, C.; Gaylor, T.

1998-01-01

This report presents a graph-based approach to network vulnerability analysis. The method is flexible, allowing analysis of attacks from both outside and inside the network. It can analyze risks to a specific network asset, or examine the universe of possible consequences following a successful attack. The analysis system requires as input a database of common attacks, broken into atomic steps, specific network configuration and topology information, and an attacker profile. The attack information is matched with the network configuration information and an attacker profile to create a superset attack graph. Nodes identify a stage of attack, for example the classmore » of machines the attacker has accessed and the user privilege level he or she has compromised. The arcs in the attack graph represent attacks or stages of attacks. By assigning probabilities of success on the arcs or costs representing level-of-effort for the attacker, various graph algorithms such as shortest-path algorithms can identify the attack paths with the highest probability of success.« less

Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution

PubMed Central

Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

2016-01-01

AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening. PMID:26733055

Genome-wide analysis of the AP2/ERF family in Musa species reveals divergence and neofunctionalisation during evolution.

PubMed

Lakhwani, Deepika; Pandey, Ashutosh; Dhar, Yogeshwar Vikram; Bag, Sumit Kumar; Trivedi, Prabodh Kumar; Asif, Mehar Hasan

2016-01-06

AP2/ERF domain containing transcription factor super family is one of the important regulators in the plant kingdom. The involvement of AP2/ERF family members has been elucidated in various processes associated with plant growth, development as well as in response to hormones, biotic and abiotic stresses. In this study, we carried out genome-wide analysis to identify members of AP2/ERF family in Musa acuminata (A genome) and Musa balbisiana (B genome) and changes leading to neofunctionalisation of genes. Analysis identified 265 and 318 AP2/ERF encoding genes in M. acuminata and M. balbisiana respectively which were further classified into ERF, DREB, AP2, RAV and Soloist groups. Comparative analysis indicated that AP2/ERF family has undergone duplication, loss and divergence during evolution and speciation of the Musa A and B genomes. We identified nine genes which are up-regulated during fruit ripening and might be components of the regulatory machinery operating during ethylene-dependent ripening in banana. Tissue-specific expression analysis of the genes suggests that different regulatory mechanisms might be involved in peel and pulp ripening process through recruiting specific ERFs in these tissues. Analysis also suggests that MaRAV-6 and MaERF026 have structurally diverged from their M. balbisiana counterparts and have attained new functions during ripening.

Sub-grouping patients with non-specific low back pain based on cluster analysis of discriminatory clinical items.

PubMed

Billis, Evdokia; McCarthy, Christopher J; Roberts, Chris; Gliatis, John; Papandreou, Maria; Gioftsos, George; Oldham, Jacqueline A

2013-02-01

To identify potential subgroups amongst patients with non-specific low back pain based on a consensus list of potentially discriminatory examination items. Exploratory study. A convenience sample of 106 patients with non-specific low back pain (43 males, 63 females, mean age 36 years, standard deviation 15.9 years) and 7 physiotherapists. Based on 3 focus groups and a two-round Delphi involving 23 health professionals and a random stratified sample of 150 physiotherapists, respectively, a comprehensive examination list comprising the most "discriminatory" items was compiled. Following reliability analysis, the most reliable clinical items were assessed with a sample of patients with non-specific low back pain. K-means cluster analysis was conducted for 2-, 3- and 4-cluster options to explore for meaningful homogenous subgroups. The most clinically meaningful cluster was a two-subgroup option, comprising a small group (n = 24) with more severe clinical presentation (i.e. more widespread pain, functional and sleeping problems, other symptoms, increased investigations undertaken, more severe clinical signs, etc.) and a larger less dysfunctional group (n = 80). A number of potentially discriminatory clinical items were identified by health professionals and sub-classified, based on a sample of patients with non-specific low back pain, into two subgroups. However, further work is needed to validate this classification process.

Use of principal components analysis and protein microarray to explore the association of HIV-1-specific IgG responses with disease progression.

PubMed

Gerns Storey, Helen L; Richardson, Barbra A; Singa, Benson; Naulikha, Jackie; Prindle, Vivian C; Diaz-Ochoa, Vladimir E; Felgner, Phil L; Camerini, David; Horton, Helen; John-Stewart, Grace; Walson, Judd L

2014-01-01

The role of HIV-1-specific antibody responses in HIV disease progression is complex and would benefit from analysis techniques that examine clusterings of responses. Protein microarray platforms facilitate the simultaneous evaluation of numerous protein-specific antibody responses, though excessive data are cumbersome in analyses. Principal components analysis (PCA) reduces data dimensionality by generating fewer composite variables that maximally account for variance in a dataset. To identify clusters of antibody responses involved in disease control, we investigated the association of HIV-1-specific antibody responses by protein microarray, and assessed their association with disease progression using PCA in a nested cohort design. Associations observed among collections of antibody responses paralleled protein-specific responses. At baseline, greater antibody responses to the transmembrane glycoprotein (TM) and reverse transcriptase (RT) were associated with higher viral loads, while responses to the surface glycoprotein (SU), capsid (CA), matrix (MA), and integrase (IN) proteins were associated with lower viral loads. Over 12 months greater antibody responses were associated with smaller decreases in CD4 count (CA, MA, IN), and reduced likelihood of disease progression (CA, IN). PCA and protein microarray analyses highlighted a collection of HIV-specific antibody responses that together were associated with reduced disease progression, and may not have been identified by examining individual antibody responses. This technique may be useful to explore multifaceted host-disease interactions, such as HIV coinfections.

Analysis of Phosphorylation of the Receptor-Like Protein Kinase HAESA during Arabidopsis Floral Abscission

PubMed Central

Taylor, Isaiah; Wang, Ying; Seitz, Kati; Baer, John; Bennewitz, Stefan; Mooney, Brian P.; Walker, John C.

2016-01-01

Receptor-like protein kinases (RLKs) are the largest family of plant transmembrane signaling proteins. Here we present functional analysis of HAESA, an RLK that regulates floral organ abscission in Arabidopsis. Through in vitro and in vivo analysis of HAE phosphorylation, we provide evidence that a conserved phosphorylation site on a region of the HAE protein kinase domain known as the activation segment positively regulates HAE activity. Additional analysis has identified another putative activation segment phosphorylation site common to multiple RLKs that potentially modulates HAE activity. Comparative analysis suggests that phosphorylation of this second activation segment residue is an RLK specific adaptation that may regulate protein kinase activity and substrate specificity. A growing number of RLKs have been shown to exhibit biologically relevant dual specificity toward serine/threonine and tyrosine residues, but the mechanisms underlying dual specificity of RLKs are not well understood. We show that a phospho-mimetic mutant of both HAE activation segment residues exhibits enhanced tyrosine auto-phosphorylation in vitro, indicating phosphorylation of this residue may contribute to dual specificity of HAE. These results add to an emerging framework for understanding the mechanisms and evolution of regulation of RLK activity and substrate specificity. PMID:26784444

Immunoaffinity Enrichment and Mass Spectrometry Analysis of Protein Methylation

PubMed Central

Guo, Ailan; Gu, Hongbo; Zhou, Jing; Mulhern, Daniel; Wang, Yi; Lee, Kimberly A.; Yang, Vicky; Aguiar, Mike; Kornhauser, Jon; Jia, Xiaoying; Ren, Jianmin; Beausoleil, Sean A.; Silva, Jeffrey C.; Vemulapalli, Vidyasiri; Bedford, Mark T.; Comb, Michael J.

2014-01-01

Protein methylation is a common posttranslational modification that mostly occurs on arginine and lysine residues. Arginine methylation has been reported to regulate RNA processing, gene transcription, DNA damage repair, protein translocation, and signal transduction. Lysine methylation is best known to regulate histone function and is involved in epigenetic regulation of gene transcription. To better study protein methylation, we have developed highly specific antibodies against monomethyl arginine; asymmetric dimethyl arginine; and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS analysis to identify and quantify arginine and lysine methylation sites in several model studies. Overall, we identified over 1000 arginine methylation sites in human cell line and mouse tissues, and ∼160 lysine methylation sites in human cell line HCT116. The number of methylation sites identified in this study exceeds those found in the literature to date. Detailed analysis of arginine-methylated proteins observed in mouse brain compared with those found in mouse embryo shows a tissue-specific distribution of arginine methylation, and extends the types of proteins that are known to be arginine methylated to include many new protein types. Many arginine-methylated proteins that we identified from the brain, including receptors, ion channels, transporters, and vesicle proteins, are involved in synaptic transmission, whereas the most abundant methylated proteins identified from mouse embryo are transcriptional regulators and RNA processing proteins. PMID:24129315

Cross-disease transcriptomics: Unique IL-17A signaling in psoriasis lesions and an autoimmune PBMC signature

PubMed Central

Sarkar, Mrinal K.; Liang, Yun; Xing, Xianying; Gudjonsson, Johann E.

2016-01-01

Transcriptome studies of psoriasis have identified robust changes in mRNA expression through large-scale analysis of patient cohorts. These studies, however, have analyzed all mRNA changes in aggregate, without distinguishing between disease-specific and non-specific differentially expressed genes (DEGs). In this study, RNA-seq meta-analysis was used to identify (1) psoriasis-specific DEGs altered in few diseases besides psoriasis and (2) non-specific DEGs similarly altered in many other skin conditions. We show that few cutaneous DEGs are psoriasis-specific and that the two DEG classes differ in their cell type and cytokine associations. Psoriasis-specific DEGs are expressed by keratinocytes and induced by IL-17A, whereas non-specific DEGs are expressed by inflammatory cells and induced by IFN-gamma and TNF. PBMC-derived DEGs were more psoriasis-specific than cutaneous DEGs. Nonetheless, PBMC DEGs associated with MHC class I and NK cells were commonly downregulated in psoriasis and other autoimmune diseases (e.g., multiple sclerosis, sarcoidosis and juvenile rheumatoid arthritis). These findings demonstrate “cross-disease” transcriptomics as an approach to gain insights into the cutaneous and non-cutaneous psoriasis transcriptomes. This highlighted unique contributions of IL-17A to the cytokine network and uncovered a blood-based gene signature that links psoriasis to other diseases of autoimmunity. PMID:27206706

OpenCyto: An Open Source Infrastructure for Scalable, Robust, Reproducible, and Automated, End-to-End Flow Cytometry Data Analysis

PubMed Central

Finak, Greg; Frelinger, Jacob; Jiang, Wenxin; Newell, Evan W.; Ramey, John; Davis, Mark M.; Kalams, Spyros A.; De Rosa, Stephen C.; Gottardo, Raphael

2014-01-01

Flow cytometry is used increasingly in clinical research for cancer, immunology and vaccines. Technological advances in cytometry instrumentation are increasing the size and dimensionality of data sets, posing a challenge for traditional data management and analysis. Automated analysis methods, despite a general consensus of their importance to the future of the field, have been slow to gain widespread adoption. Here we present OpenCyto, a new BioConductor infrastructure and data analysis framework designed to lower the barrier of entry to automated flow data analysis algorithms by addressing key areas that we believe have held back wider adoption of automated approaches. OpenCyto supports end-to-end data analysis that is robust and reproducible while generating results that are easy to interpret. We have improved the existing, widely used core BioConductor flow cytometry infrastructure by allowing analysis to scale in a memory efficient manner to the large flow data sets that arise in clinical trials, and integrating domain-specific knowledge as part of the pipeline through the hierarchical relationships among cell populations. Pipelines are defined through a text-based csv file, limiting the need to write data-specific code, and are data agnostic to simplify repetitive analysis for core facilities. We demonstrate how to analyze two large cytometry data sets: an intracellular cytokine staining (ICS) data set from a published HIV vaccine trial focused on detecting rare, antigen-specific T-cell populations, where we identify a new subset of CD8 T-cells with a vaccine-regimen specific response that could not be identified through manual analysis, and a CyTOF T-cell phenotyping data set where a large staining panel and many cell populations are a challenge for traditional analysis. The substantial improvements to the core BioConductor flow cytometry packages give OpenCyto the potential for wide adoption. It can rapidly leverage new developments in computational cytometry and facilitate reproducible analysis in a unified environment. PMID:25167361

OpenCyto: an open source infrastructure for scalable, robust, reproducible, and automated, end-to-end flow cytometry data analysis.

PubMed

Finak, Greg; Frelinger, Jacob; Jiang, Wenxin; Newell, Evan W; Ramey, John; Davis, Mark M; Kalams, Spyros A; De Rosa, Stephen C; Gottardo, Raphael

2014-08-01

Flow cytometry is used increasingly in clinical research for cancer, immunology and vaccines. Technological advances in cytometry instrumentation are increasing the size and dimensionality of data sets, posing a challenge for traditional data management and analysis. Automated analysis methods, despite a general consensus of their importance to the future of the field, have been slow to gain widespread adoption. Here we present OpenCyto, a new BioConductor infrastructure and data analysis framework designed to lower the barrier of entry to automated flow data analysis algorithms by addressing key areas that we believe have held back wider adoption of automated approaches. OpenCyto supports end-to-end data analysis that is robust and reproducible while generating results that are easy to interpret. We have improved the existing, widely used core BioConductor flow cytometry infrastructure by allowing analysis to scale in a memory efficient manner to the large flow data sets that arise in clinical trials, and integrating domain-specific knowledge as part of the pipeline through the hierarchical relationships among cell populations. Pipelines are defined through a text-based csv file, limiting the need to write data-specific code, and are data agnostic to simplify repetitive analysis for core facilities. We demonstrate how to analyze two large cytometry data sets: an intracellular cytokine staining (ICS) data set from a published HIV vaccine trial focused on detecting rare, antigen-specific T-cell populations, where we identify a new subset of CD8 T-cells with a vaccine-regimen specific response that could not be identified through manual analysis, and a CyTOF T-cell phenotyping data set where a large staining panel and many cell populations are a challenge for traditional analysis. The substantial improvements to the core BioConductor flow cytometry packages give OpenCyto the potential for wide adoption. It can rapidly leverage new developments in computational cytometry and facilitate reproducible analysis in a unified environment.

Comparative transcriptome analysis of papilla and skin in the sea cucumber, Apostichopus japonicus.

PubMed

Zhou, Xiaoxu; Cui, Jun; Liu, Shikai; Kong, Derong; Sun, He; Gu, Chenlei; Wang, Hongdi; Qiu, Xuemei; Chang, Yaqing; Liu, Zhanjiang; Wang, Xiuli

2016-01-01

Papilla and skin are two important organs of the sea cucumber. Both tissues have ectodermic origin, but they are morphologically and functionally very different. In the present study, we performed comparative transcriptome analysis of the papilla and skin from the sea cucumber (Apostichopus japonicus) in order to identify and characterize gene expression profiles by using RNA-Seq technology. We generated 30.6 and 36.4 million clean reads from the papilla and skin and de novo assembled in 156,501 transcripts. The Gene Ontology (GO) analysis indicated that cell part, metabolic process and catalytic activity were the most abundant GO category in cell component, biological process and molecular funcation, respectively. Comparative transcriptome analysis between the papilla and skin allowed the identification of 1,059 differentially expressed genes, of which 739 genes were expressed at higher levels in papilla, while 320 were expressed at higher levels in skin. In addition, 236 differentially expressed unigenes were not annotated with any database, 160 of which were apparently expressed at higher levels in papilla, 76 were expressed at higher levels in skin. We identified a total of 288 papilla-specific genes, 171 skin-specific genes and 600 co-expressed genes. Also, 40 genes in papilla-specific were not annotated with any database, 2 in skin-specific. Development-related genes were also enriched, such as fibroblast growth factor, transforming growth factor-β, collagen-α2 and Integrin-α2, which may be related to the formation of the papilla and skin in sea cucumber. Further pathway analysis identified ten KEGG pathways that were differently enriched between the papilla and skin. The findings on expression profiles between two key organs of the sea cucumber should be valuable to reveal molecular mechanisms involved in the development of organs that are related but with morphological differences in the sea cucumber.

Risk analysis of hematopoietic stem cell transplant process: failure mode, effect, and criticality analysis and hazard analysis critical control point methods integration based on guidelines to good manufacturing practice for medicinal product ANNEX 20 (February 2008).

PubMed

Gianassi, S; Bisin, S; Bindi, B; Spitaleri, I; Bambi, F

2010-01-01

The collection and handling of hematopoietic stem cells (HSCs) must meet high quality requirements. An integrated Quality Risk Management can help to identify and contain potential risks related to HSC production. Risk analysis techniques allow one to "weigh" identified hazards, considering the seriousness of their effects, frequency, and detectability, seeking to prevent the most harmful hazards. The Hazard Analysis Critical Point, recognized as the most appropriate technique to identify risks associated with physical, chemical, and biological hazards for cellular products, consists of classifying finished product specifications and limits of acceptability, identifying all off-specifications, defining activities that can cause them, and finally establishing both a monitoring system for each Critical Control Point and corrective actions for deviations. The severity of possible effects on patients, as well as the occurrence and detectability of critical parameters, are measured on quantitative scales (Risk Priority Number [RPN]). Risk analysis was performed with this technique on manipulation process of HPC performed at our blood center. The data analysis showed that hazards with higher values of RPN with greater impact on the process are loss of dose and tracking; technical skills of operators and manual transcription of data were the most critical parameters. Problems related to operator skills are handled by defining targeted training programs, while other critical parameters can be mitigated with the use of continuous control systems. The blood center management software was completed by a labeling system with forms designed to be in compliance with standards in force and by starting implementation of a cryopreservation management module. Copyright 2010 Elsevier Inc. All rights reserved.

OEXP Analysis Tools Workshop

NASA Technical Reports Server (NTRS)

Garrett, L. Bernard; Wright, Robert L.; Badi, Deborah; Findlay, John T.

1988-01-01

This publication summarizes the software needs and available analysis tools presented at the OEXP Analysis Tools Workshop held at the NASA Langley Research Center, Hampton, Virginia on June 21 to 22, 1988. The objective of the workshop was to identify available spacecraft system (and subsystem) analysis and engineering design tools, and mission planning and analysis software that could be used for various NASA Office of Exploration (code Z) studies, specifically lunar and Mars missions.

A comparative analysis of transcriptomic, biochemical and physiological responses to elevated ozone identifies species-specific mechanisms of resilience in legume crops

USDA-ARS?s Scientific Manuscript database

Current concentrations of tropospheric ozone (O3) pollution negatively impact plant metabolism, which can result in decreased crop yields. Interspecific variation in the physiological response of plants to elevated [O3] exists; however, the underlying cellular responses explaining species-specific d...

Training School Psychologists to Identify Specific Learning Disabilities: A Content Analysis of Syllabi

ERIC Educational Resources Information Center

Barrett, Courtenay A.; Cottrell, Joseph M.; Newman, Daniel S.; Pierce, Benjamin G.; Anderson, Alisha

2015-01-01

Approximately 2.4 million children receive special education services for specific learning disabilities (SLDs), and school psychologists are key contributors to the SLD eligibility decision-making process. The Individuals with Disabilities Education Act (2004) enabled local education agencies to use response to intervention (RTI) instead of the…

Sex differences in gut microbiota in patients with major depressive disorder.

PubMed

Chen, Jian-Jun; Zheng, Peng; Liu, Yi-Yun; Zhong, Xiao-Gang; Wang, Hai-Yang; Guo, Yu-Jie; Xie, Peng

2018-01-01

Our previous studies found that disturbances in gut microbiota might have a causative role in the onset of major depressive disorder (MDD). The aim of this study was to investigate whether there were sex differences in gut microbiota in patients with MDD. First-episode drug-naïve MDD patients and healthy controls were included. 16S rRNA gene sequences extracted from the fecal samples of the included subjects were analyzed. Principal-coordinate analysis and partial least squares-discriminant analysis were used to assess whether there were sex-specific gut microbiota. A random forest algorithm was used to identify the differential operational taxonomic units. Linear discriminant-analysis effect size was further used to identify the dominant sex-specific phylotypes responsible for the differences between MDD patients and healthy controls. In total, 57 and 74 differential operational taxonomic units responsible for separating female and male MDD patients from their healthy counterparts were identified. Compared with their healthy counterparts, increased Actinobacteria and decreased Bacteroidetes levels were found in female and male MDD patients, respectively. The most differentially abundant bacterial taxa in female and male MDD patients belonged to phyla Actinobacteria and Bacteroidia, respectively. Meanwhile, female and male MDD patients had different dominant phylotypes. These results demonstrated that there were sex differences in gut microbiota in patients with MDD. The suitability of Actinobacteria and Bacteroidia as the sex-specific biomarkers for diagnosing MDD should be further explored.

Seizure semiology identifies patients with bilateral temporal lobe epilepsy.

PubMed

Loesch, Anna Mira; Feddersen, Berend; Tezer, F Irsel; Hartl, Elisabeth; Rémi, Jan; Vollmar, Christian; Noachtar, Soheyl

2015-01-01

Laterality in temporal lobe epilepsy is usually defined by EEG and imaging results. We investigated whether the analysis of seizure semiology including lateralizing seizure phenomena identifies bilateral independent temporal lobe seizure onset. We investigated the seizure semiology in 17 patients in whom invasive EEG-video-monitoring documented bilateral temporal seizure onset. The results were compared to 20 left and 20 right consecutive temporal lobe epilepsy (TLE) patients who were seizure free after anterior temporal lobe resection. The seizure semiology was analyzed using the semiological seizure classification with particular emphasis on the sequence of seizure phenomena over time and lateralizing seizure phenomena. Statistical analysis included chi-square test or Fisher's exact test. Bitemporal lobe epilepsy patients had more frequently different seizure semiology (100% vs. 40%; p<0.001) and significantly more often lateralizing seizure phenomena pointing to bilateral seizure onset compared to patients with unilateral TLE (67% vs. 11%; p<0.001). The sensitivity of identical vs. different seizure semiology for the identification of bilateral TLE was high (100%) with a specificity of 60%. Lateralizing seizure phenomena had a low sensitivity (59%) but a high specificity (89%). The combination of lateralizing seizure phenomena and different seizure semiology showed a high specificity (94%) but a low sensitivity (59%). The analysis of seizure semiology including lateralizing seizure phenomena adds important clinical information to identify patients with bilateral TLE. Copyright © 2014 Elsevier B.V. All rights reserved.

Structural analysis consultation using artificial intelligence

NASA Technical Reports Server (NTRS)

Melosh, R. J.; Marcal, P. V.; Berke, L.

1978-01-01

The primary goal of consultation is definition of the best strategy to deal with a structural engineering analysis objective. The knowledge base to meet the need is designed to identify the type of numerical analysis, the needed modeling detail, and specific analysis data required. Decisions are constructed on the basis of the data in the knowledge base - material behavior, relations between geometry and structural behavior, measures of the importance of time and temperature changes - and user supplied specifics characteristics of the spectrum of analysis types, the relation between accuracy and model detail on the structure, its mechanical loadings, and its temperature states. Existing software demonstrated the feasibility of the approach, encompassing the 36 analysis classes spanning nonlinear, temperature affected, incremental analyses which track the behavior of structural systems.

Allergenicity and cross-reactivity of booklice (Liposcelis bostrichophila): a common household insect pest in Japan.

PubMed

Fukutomi, Yuma; Kawakami, Yuji; Taniguchi, Masami; Saito, Akemi; Fukuda, Azumi; Yasueda, Hiroshi; Nakazawa, Takuya; Hasegawa, Maki; Nakamura, Hiroyuki; Akiyama, Kazuo

2012-01-01

Booklice (Liposcelis bostrichophila) are a common household insect pest distributed worldwide. Particularly in Japan, they infest 'tatami' mats and are the most frequently detected insect among all detectable insects, present at a frequency of about 90% in dust samples. Although it has been hypothesized that they are an important indoor allergen, studies on their allergenicity have been limited. To clarify the allergenicity of booklice and the cross-reactivity of this insect allergen with allergens of other insects, patients sensitized to booklice were identified from 185 Japanese adults with allergic asthma using skin tests and IgE-ELISA. IgE-inhibition analysis, immunoblotting and immunoblotting-inhibition analysis were performed using sera from these patients. Allergenic proteins contributing to specific sensitization to booklice were identified by two-dimensional electrophoresis and two-dimensional immunoblotting. The booklouse-specific IgE antibody was detected in sera from 41 patients (22% of studied patients). IgE inhibition analysis revealed that IgE reactivity to the booklouse allergen in the sera from one third of booklouse-sensitized patients was not inhibited by preincubation with extracts from any other environmental insects in this study. Immunoblotting identified a 26-kD protein from booklouse extract as the allergenic protein contributing to specific sensitization to booklice. The amino acid sequence of peptide fragments of this protein showed no homology to those of previously described allergenic proteins, indicating that this protein is a new allergen. Sensitization to booklice was relatively common and specific sensitization to this insect not related to insect panallergy was indicated in this population. Copyright © 2011 S. Karger AG, Basel.

Quantitative DNA Methylation Analysis Identifies a Single CpG Dinucleotide Important for ZAP-70 Expression and Predictive of Prognosis in Chronic Lymphocytic Leukemia

PubMed Central

Claus, Rainer; Lucas, David M.; Stilgenbauer, Stephan; Ruppert, Amy S.; Yu, Lianbo; Zucknick, Manuela; Mertens, Daniel; Bühler, Andreas; Oakes, Christopher C.; Larson, Richard A.; Kay, Neil E.; Jelinek, Diane F.; Kipps, Thomas J.; Rassenti, Laura Z.; Gribben, John G.; Döhner, Hartmut; Heerema, Nyla A.; Marcucci, Guido; Plass, Christoph; Byrd, John C.

2012-01-01

Purpose Increased ZAP-70 expression predicts poor prognosis in chronic lymphocytic leukemia (CLL). Current methods for accurately measuring ZAP-70 expression are problematic, preventing widespread application of these tests in clinical decision making. We therefore used comprehensive DNA methylation profiling of the ZAP-70 regulatory region to identify sites important for transcriptional control. Patients and Methods High-resolution quantitative DNA methylation analysis of the entire ZAP-70 gene regulatory regions was conducted on 247 samples from patients with CLL from four independent clinical studies. Results Through this comprehensive analysis, we identified a small area in the 5′ regulatory region of ZAP-70 that showed large variability in methylation in CLL samples but was universally methylated in normal B cells. High correlation with mRNA and protein expression, as well as activity in promoter reporter assays, revealed that within this differentially methylated region, a single CpG dinucleotide and neighboring nucleotides are particularly important in ZAP-70 transcriptional regulation. Furthermore, by using clustering approaches, we identified a prognostic role for this site in four independent data sets of patients with CLL using time to treatment, progression-free survival, and overall survival as clinical end points. Conclusion Comprehensive quantitative DNA methylation analysis of the ZAP-70 gene in CLL identified important regions responsible for transcriptional regulation. In addition, loss of methylation at a specific single CpG dinucleotide in the ZAP-70 5′ regulatory sequence is a highly predictive and reproducible biomarker of poor prognosis in this disease. This work demonstrates the feasibility of using quantitative specific ZAP-70 methylation analysis as a relevant clinically applicable prognostic test in CLL. PMID:22564988

Matrix Assisted Laser Desorption Ionization Mass Spectrometric Analysis of Bacillus anthracis: From Fingerprint Analysis of the Bacterium to Quantification of its Toxins in Clinical Samples

NASA Astrophysics Data System (ADS)

Woolfitt, Adrian R.; Boyer, Anne E.; Quinn, Conrad P.; Hoffmaster, Alex R.; Kozel, Thomas R.; de, Barun K.; Gallegos, Maribel; Moura, Hercules; Pirkle, James L.; Barr, John R.

A range of mass spectrometry-based techniques have been used to identify, characterize and differentiate Bacillus anthracis, both in culture for forensic applications and for diagnosis during infection. This range of techniques could usefully be considered to exist as a continuum, based on the degrees of specificity involved. We show two examples here, a whole-organism fingerprinting method and a high-specificity assay for one unique protein, anthrax lethal factor.

Dynamics explorer: Interface definition study, volume 1

NASA Technical Reports Server (NTRS)

1978-01-01

Work done in response to the work statement wherein a specific deliverable was not identified but where design and analysis tasks were identified is reported. The summary and baseline change list is included along with design notes for the spacecraft system, thermal subsystem, power subsystem, communications subsystem, plasma wave instrument interface definition, and the structure.

Statistical Coupling Analysis-Guided Library Design for the Discovery of Mutant Luciferases.

PubMed

Liu, Mira D; Warner, Elliot A; Morrissey, Charlotte E; Fick, Caitlyn W; Wu, Taia S; Ornelas, Marya Y; Ochoa, Gabriela V; Zhang, Brendan S; Rathbun, Colin M; Porterfield, William B; Prescher, Jennifer A; Leconte, Aaron M

2018-02-06

Directed evolution has proven to be an invaluable tool for protein engineering; however, there is still a need for developing new approaches to continue to improve the efficiency and efficacy of these methods. Here, we demonstrate a new method for library design that applies a previously developed bioinformatic method, Statistical Coupling Analysis (SCA). SCA uses homologous enzymes to identify amino acid positions that are mutable and functionally important and engage in synergistic interactions between amino acids. We use SCA to guide a library of the protein luciferase and demonstrate that, in a single round of selection, we can identify luciferase mutants with several valuable properties. Specifically, we identify luciferase mutants that possess both red-shifted emission spectra and improved stability relative to those of the wild-type enzyme. We also identify luciferase mutants that possess a >50-fold change in specificity for modified luciferins. To understand the mutational origin of these improved mutants, we demonstrate the role of mutations at N229, S239, and G246 in altered function. These studies show that SCA can be used to guide library design and rapidly identify synergistic amino acid mutations from a small library.

Structural and mechanistic analysis of a β-glycoside phosphorylase identified by screening a metagenomic library.

PubMed

Macdonald, Spencer S; Patel, Ankoor; Larmour, Veronica L C; Morgan-Lang, Connor; Hallam, Steven J; Mark, Brian L; Withers, Stephen G

2018-03-02

Glycoside phosphorylases have considerable potential as catalysts for the assembly of useful glycans for products ranging from functional foods and prebiotics to novel materials. However, the substrate diversity of currently identified phosphorylases is relatively small, limiting their practical applications. To address this limitation, we developed a high-throughput screening approach using the activated substrate 2,4-dinitrophenyl β-d-glucoside (DNPGlc) and inorganic phosphate for identifying glycoside phosphorylase activity and used it to screen a large insert metagenomic library. The initial screen, based on release of 2,4-dinitrophenyl from DNPGlc in the presence of phosphate, identified the gene bglP, encoding a retaining β-glycoside phosphorylase from the CAZy GH3 family. Kinetic and mechanistic analysis of the gene product, BglP, confirmed a double displacement ping-pong mechanism involving a covalent glycosyl-enzyme intermediate. X-ray crystallographic analysis provided insights into the phosphate-binding mode and identified a key glutamine residue in the active site important for substrate recognition. Substituting this glutamine for a serine swapped the substrate specificity from glucoside to N -acetylglucosaminide. In summary, we present a high-throughput screening approach for identifying β-glycoside phosphorylases, which was robust, simple to implement, and useful in identifying active clones within a metagenomics library. Implementation of this screen enabled discovery of a new glycoside phosphorylase class and has paved the way to devising simple ways in which enzyme specificity can be encoded and swapped, which has implications for biotechnological applications. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

The performance of blood pressure-to-height ratio as a screening measure for identifying children and adolescents with hypertension: a meta-analysis.

PubMed

Ma, Chunming; Liu, Yue; Lu, Qiang; Lu, Na; Liu, Xiaoli; Tian, Yiming; Wang, Rui; Yin, Fuzai

2016-02-01

The blood pressure-to-height ratio (BPHR) has been shown to be an accurate index for screening hypertension in children and adolescents. The aim of the present study was to perform a meta-analysis to assess the performance of BPHR for the assessment of hypertension. Electronic and manual searches were performed to identify studies of the BPHR. After methodological quality assessment and data extraction, pooled estimates of the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the receiver operating characteristic curve and summary receiver operating characteristics were assessed systematically. The extent of heterogeneity for it was assessed. Six studies were identified for analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio and diagnostic odds ratio values of BPHR, for assessment of hypertension, were 96% [95% confidence interval (CI)=0.95-0.97], 90% (95% CI=0.90-0.91), 10.68 (95% CI=8.03-14.21), 0.04 (95% CI=0.03-0.07) and 247.82 (95% CI=114.50-536.34), respectively. The area under the receiver operating characteristic curve was 0.9472. The BPHR had higher diagnostic accuracies for identifying hypertension in children and adolescents.

In silico genome-wide identification and characterization of the glutathione S-transferase gene family in Vigna radiata.

PubMed

Vaish, Swati; Awasthi, Praveen; Tiwari, Siddharth; Tiwari, Shailesh Kumar; Gupta, Divya; Basantani, Mahesh Kumar

2018-05-01

Plant glutathione S-transferases (GSTs) are integral to normal plant metabolism and biotic and abiotic stress tolerance. The GST gene family has been characterized in diverse plant species using molecular biology and bioinformatics approaches. In the current study, in silico analysis identified 44 GSTs in Vigna radiata. Of the total 44 GSTs identified, chromosomal locations of 31 GSTs were confirmed. The pI value of GST proteins ranged from 5.10 to 9.40. The predicted molecular weights ranged from 13.12 to 50 kDa. Subcellular localization analysis revealed that all GSTs were predominantly localized in the cytoplasm. The active site amino acids were confirmed to be serine in tau, phi, theta, zeta, and TCHQD; cysteine in lambda, DHAR, and omega; and tyrosine in EF1G. The gene architecture conformed to the two-exon/one-intron and three-exon/two-intron organization in the case of tau and phi classes, respectively. MEME analysis identified 10 significantly conserved motifs with the width of 8-50 amino acids. The motifs identified were either specific to a specific GST class or were shared by multiple GST classes. The results of the current study will be of potential importance in the characterization of the GST gene family in V. radiata, an economically important leguminous crop.

Structural analysis of photosystem I polypeptides using chemical crosslinking

NASA Technical Reports Server (NTRS)

Armbrust, T. S.; Odom, W. R.; Guikema, J. A.; Spooner, B. S. (Principal Investigator)

1994-01-01

Thylakoid membranes, obtained from leaves of 14 d soybean (Glycine max L. cv. Williams) plants, were treated with the chemical crosslinkers glutaraldehyde or 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC) to investigate the structural organization of photosystem I. Polypeptides were resolved using lithium dodecyl sulfate polyacrylamide gel electrophoresis, and were identified by western blot analysis using a library of polyclonal antibodies specific for photosystem I subunits. An electrophoretic examination of crosslinked thylakoids revealed numerous crosslinked products, using either glutaraldehyde or EDC. However, only a few of these could be identified by western blot analysis using subunit-specific polyclonal antibodies. Several glutaraldehyde dependent crosslinked species were identified. A single band was identified minimally composed of PsaC and PsaD, documenting the close interaction between these two subunits. The most interesting aspect of these studies was a crosslinked species composed of the PsaB subunit observed following EDC treatment of thylakoids. This is either an internally crosslinked species, which will provide structural information concerning the topology of the complex PsaB protein, a linkage with a polypeptide for which we do not yet have an immunological probe, or a masking of epitopes by the EDC linkage at critical locations in the peptide which is linked to PsaB.

A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia.

PubMed

Wu, Chung Wah; Evans, Jared M; Huang, Shengbing; Mahoney, Douglas W; Dukek, Brian A; Taylor, William R; Yab, Tracy C; Smyrk, Thomas C; Jen, Jin; Kisiel, John B; Ahlquist, David A

2018-05-25

MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation. We introduce a comprehensive approach to sequence-oriented isomiR annotation (CASMIR) to allow unbiased identification of global isomiRs from small RNA sequencing data. In this approach, small RNA reads are maintained as independent sequences instead of being summarized under miRNA names. IsomiR features are identified through step-wise local alignment against canonical forms and precursor sequences. Through customizing the reference database, CASMIR is applicable to isomiR annotation across species. To demonstrate its application, we investigated isomiR profiles in normal and neoplastic human colorectal epithelia. We also ran miRDeep2, a popular miRNA analysis algorithm to validate isomiRs annotated by CASMIR. With CASMIR, specific and biologically relevant isomiR patterns could be identified. We note that specific isomiRs are often more abundant than their canonical forms. We identify isomiRs that are commonly up-regulated in both colorectal cancer and advanced adenoma, and illustrate advantages in targeting isomiRs as potential biomarkers over canonical forms. Studying miRNAs at the isomiR level could reveal new insight into miRNA biology and inform assay design for specific isomiRs. CASMIR facilitates comprehensive annotation of isomiR features in small RNA sequencing data for isomiR profiling and differential expression analysis.

Identification of milling and baking quality QTL in multiple soft wheat mapping populations.

PubMed

Cabrera, Antonio; Guttieri, Mary; Smith, Nathan; Souza, Edward; Sturbaum, Anne; Hua, Duc; Griffey, Carl; Barnett, Marla; Murphy, Paul; Ohm, Herb; Uphaus, Jim; Sorrells, Mark; Heffner, Elliot; Brown-Guedira, Gina; Van Sanford, David; Sneller, Clay

2015-11-01

Two mapping approaches were use to identify and validate milling and baking quality QTL in soft wheat. Two LG were consistently found important for multiple traits and we recommend the use marker-assisted selection on specific markers reported here. Wheat-derived food products require a range of characteristics. Identification and understanding of the genetic components controlling end-use quality of wheat is important for crop improvement. We assessed the underlying genetics controlling specific milling and baking quality parameters of soft wheat including flour yield, softness equivalent, flour protein, sucrose, sodium carbonate, water absorption and lactic acid, solvent retention capacities in a diversity panel and five bi-parental mapping populations. The populations were genotyped with SSR and DArT markers, with markers specific for the 1BL.1RS translocation and sucrose synthase gene. Association analysis and composite interval mapping were performed to identify quantitative trait loci (QTL). High heritability was observed for each of the traits evaluated, trait correlations were consistent over populations, and transgressive segregants were common in all bi-parental populations. A total of 26 regions were identified as potential QTL in the diversity panel and 74 QTL were identified across all five bi-parental mapping populations. Collinearity of QTL from chromosomes 1B and 2B was observed across mapping populations and was consistent with results from the association analysis in the diversity panel. Multiple regression analysis showed the importance of the two 1B and 2B regions and marker-assisted selection for the favorable alleles at these regions should improve quality.

Identification of genes associated with the long-gut-persistence phenotype of the probiotic Lactobacillus johnsonii strain NCC533 using a combination of genomics and transcriptome analysis.

PubMed

Denou, Emmanuel; Pridmore, Raymond David; Berger, Bernard; Panoff, Jean-Michel; Arigoni, Fabrizio; Brüssow, Harald

2008-05-01

Lactobacillus johnsonii strains NCC533 and ATCC 33200 (the type strain of this species) differed significantly in gut residence time (12 versus 5 days) after oral feeding to mice. Genes affecting the long gut residence time of the probiotic strain NCC533 were targeted for analysis. We hypothesized that genes specific for this strain, which are expressed during passage of the bacterium through the gut, affect the phenotype. When the DNA of the type strain was hybridized against a microarray of the sequenced NCC533 strain, we identified 233 genes that were specific for the long-gut-persistence isolate. Whole-genome transcription analysis of the NCC533 strain using the microarray format identified 174 genes that were strongly and consistently expressed in the jejunum of mice monocolonized with this strain. Fusion of the two microarray data sets identified three gene loci that were both expressed in vivo and specific to the long-gut-persistence isolate. The identified genes included LJ1027 and LJ1028, two glycosyltransferase genes in the exopolysaccharide synthesis operon; LJ1654 to LJ1656, encoding a sugar phosphotransferase system (PTS) transporter annotated as mannose PTS; and LJ1680, whose product shares 30% amino acid identity with immunoglobulin A proteases from pathogenic bacteria. Knockout mutants were tested in vivo. The experiments revealed that deletion of LJ1654 to LJ1656 and LJ1680 decreased the gut residence time, while a mutant with a deleted exopolysaccharide biosynthesis cluster had a slightly increased residence time.

A Neural Basis of Facial Action Recognition in Humans

PubMed Central

Srinivasan, Ramprakash; Golomb, Julie D.

2016-01-01

By combining different facial muscle actions, called action units, humans can produce an extraordinarily large number of facial expressions. Computational models and studies in cognitive science and social psychology have long hypothesized that the brain needs to visually interpret these action units to understand other people's actions and intentions. Surprisingly, no studies have identified the neural basis of the visual recognition of these action units. Here, using functional magnetic resonance imaging and an innovative machine learning analysis approach, we identify a consistent and differential coding of action units in the brain. Crucially, in a brain region thought to be responsible for the processing of changeable aspects of the face, multivoxel pattern analysis could decode the presence of specific action units in an image. This coding was found to be consistent across people, facilitating the estimation of the perceived action units on participants not used to train the multivoxel decoder. Furthermore, this coding of action units was identified when participants attended to the emotion category of the facial expression, suggesting an interaction between the visual analysis of action units and emotion categorization as predicted by the computational models mentioned above. These results provide the first evidence for a representation of action units in the brain and suggest a mechanism for the analysis of large numbers of facial actions and a loss of this capacity in psychopathologies. SIGNIFICANCE STATEMENT Computational models and studies in cognitive and social psychology propound that visual recognition of facial expressions requires an intermediate step to identify visible facial changes caused by the movement of specific facial muscles. Because facial expressions are indeed created by moving one's facial muscles, it is logical to assume that our visual system solves this inverse problem. Here, using an innovative machine learning method and neuroimaging data, we identify for the first time a brain region responsible for the recognition of actions associated with specific facial muscles. Furthermore, this representation is preserved across subjects. Our machine learning analysis does not require mapping the data to a standard brain and may serve as an alternative to hyperalignment. PMID:27098688

Prospective identification of adolescent suicide ideation using classification tree analysis: Models for community-based screening.

PubMed

Hill, Ryan M; Oosterhoff, Benjamin; Kaplow, Julie B

2017-07-01

Although a large number of risk markers for suicide ideation have been identified, little guidance has been provided to prospectively identify adolescents at risk for suicide ideation within community settings. The current study addressed this gap in the literature by utilizing classification tree analysis (CTA) to provide a decision-making model for screening adolescents at risk for suicide ideation. Participants were N = 4,799 youth (Mage = 16.15 years, SD = 1.63) who completed both Waves 1 and 2 of the National Longitudinal Study of Adolescent to Adult Health. CTA was used to generate a series of decision rules for identifying adolescents at risk for reporting suicide ideation at Wave 2. Findings revealed 3 distinct solutions with varying sensitivity and specificity for identifying adolescents who reported suicide ideation. Sensitivity of the classification trees ranged from 44.6% to 77.6%. The tree with greatest specificity and lowest sensitivity was based on a history of suicide ideation. The tree with moderate sensitivity and high specificity was based on depressive symptoms, suicide attempts or suicide among family and friends, and social support. The most sensitive but least specific tree utilized these factors and gender, ethnicity, hours of sleep, school-related factors, and future orientation. These classification trees offer community organizations options for instituting large-scale screenings for suicide ideation risk depending on the available resources and modality of services to be provided. This study provides a theoretically and empirically driven model for prospectively identifying adolescents at risk for suicide ideation and has implications for preventive interventions among at-risk youth. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

PubMed Central

van Dam, Peter A.; van Dam, Pieter-Jan H. H.; Rolfo, Christian; Giallombardo, Marco; van Berckelaer, Christophe; Trinh, Xuan Bich; Altintas, Sevilay; Huizing, Manon; Papadimitriou, Kostas; Tjalma, Wiebren A. A.; van Laere, Steven

2016-01-01

An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expression2Kinases (E2K). In the CCSs a total of 1,547 probe sets were identified that were overexpressed (FDR < 0.1). Comparing to CCCLs 560 probe sets (481 unique genes) had a cancer cell-specific expression profile, and 315 of these genes (65%) were validated. GSEA identified 5 cancer hallmarks enriched in CCSs (P < 0.01 and FDR < 0.25) showing that deregulation of the cell cycle is a major component of cervical cancer biology. E2K identified a protein-protein interaction (PPI) network of 162 nodes (including 20 drugable kinases) and 1626 edges. This PPI-network consists of 5 signaling modules associated with MYC signaling (Module 1), cell cycle deregulation (Module 2), TGFβ-signaling (Module 3), MAPK signaling (Module 4) and chromatin modeling (Module 5). Potential targets for treatment which could be identified were CDK1, CDK2, ABL1, ATM, AKT1, MAPK1, MAPK3 among others. The present study identified important driver pathways in cervical carcinogenesis which should be assessed for their potential therapeutic drugability. PMID:26701206

Identification of MicroRNAs in Helicoverpa armigera and Spodoptera litura Based on Deep Sequencing and Homology Analysis

PubMed Central

Ge, Xie; Zhang, Yong; Jiang, Jianhao; Zhong, Yi; Yang, Xiaonan; Li, Zhiqian; Huang, Yongping; Tan, Anjiang

2013-01-01

The current identification of microRNAs (miRNAs) in insects is largely dependent on genome sequences. However, the lack of available genome sequences inhibits the identification of miRNAs in various insect species. In this study, we used a miRNA database of the silkworm Bombyx mori as a reference to identify miRNAs in Helicoverpa armigera and Spodoptera litura using deep sequencing and homology analysis. Because all three species belong to the Lepidoptera, the experiment produced reliable results. Our study identified 97 and 91 conserved miRNAs in H. armigera and S. litura, respectively. Using the genome of B. mori and BAC sequences of H. armigera as references, 1 novel miRNA and 8 novel miRNA candidates were identified in H. armigera, and 4 novel miRNA candidates were identified in S. litura. An evolutionary analysis revealed that most of the identified miRNAs were insect-specific, and more than 20 miRNAs were Lepidoptera-specific. The investigation of the expression patterns of miR-2a, miR-34, miR-2796-3p and miR-11 revealed their potential roles in insect development. miRNA target prediction revealed that conserved miRNA target sites exist in various genes in the 3 species. Conserved miRNA target sites for the Hsp90 gene among the 3 species were validated in the mammalian 293T cell line using a dual-luciferase reporter assay. Our study provides a new approach with which to identify miRNAs in insects lacking genome information and contributes to the functional analysis of insect miRNAs. PMID:23289012

Coupling Genetics and Proteomics To Identify Aphid Proteins Associated with Vector-Specific Transmission of Polerovirus (Luteoviridae)▿

PubMed Central

Yang, Xiaolong; Thannhauser, T. W.; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E.; Gray, Stewart M.

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F2 progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F2 genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission. PMID:17959668

Coupling genetics and proteomics to identify aphid proteins associated with vector-specific transmission of polerovirus (luteoviridae).

PubMed

Yang, Xiaolong; Thannhauser, T W; Burrows, Mary; Cox-Foster, Diana; Gildow, Fred E; Gray, Stewart M

2008-01-01

Cereal yellow dwarf virus-RPV (CYDV-RPV) is transmitted specifically by the aphids Rhopalosiphum padi and Schizaphis graminum in a circulative nonpropagative manner. The high level of vector specificity results from the vector aphids having the functional components of the receptor-mediated endocytotic pathways to allow virus to transverse the gut and salivary tissues. Studies of F(2) progeny from crosses of vector and nonvector genotypes of S. graminum showed that virus transmission efficiency is a heritable trait regulated by multiple genes acting in an additive fashion and that gut- and salivary gland-associated factors are not genetically linked. Utilizing two-dimensional difference gel electrophoresis to compare the proteomes of vector and nonvector parental and F(2) genotypes, four aphid proteins (S4, S8, S29, and S405) were specifically associated with the ability of S. graminum to transmit CYDV-RPV. The four proteins were coimmunoprecipitated with purified RPV, indicating that the aphid proteins are capable of binding to virus. Analysis by mass spectrometry identified S4 as a luciferase and S29 as a cyclophilin, both of which have been implicated in macromolecular transport. Proteins S8 and S405 were not identified from available databases. Study of this unique genetic system coupled with proteomic analysis indicated that these four virus-binding aphid proteins were specifically inherited and conserved in different generations of vector genotypes and suggests that they play a major role in regulating polerovirus transmission.

Identification of a novel Gig2 gene family specific to non-amniote vertebrates.

PubMed

Zhang, Yi-Bing; Liu, Ting-Kai; Jiang, Jun; Shi, Jun; Liu, Ying; Li, Shun; Gui, Jian-Fang

2013-01-01

Gig2 (grass carp reovirus (GCRV)-induced gene 2) is first identified as a novel fish interferon (IFN)-stimulated gene (ISG). Overexpression of a zebrafish Gig2 gene can protect cultured fish cells from virus infection. In the present study, we identify a novel gene family that is comprised of genes homologous to the previously characterized Gig2. EST/GSS search and in silico cloning identify 190 Gig2 homologous genes in 51 vertebrate species ranged from lampreys to amphibians. Further large-scale search of vertebrate and invertebrate genome databases indicate that Gig2 gene family is specific to non-amniotes including lampreys, sharks/rays, ray-finned fishes and amphibians. Phylogenetic analysis and synteny analysis reveal lineage-specific expansion of Gig2 gene family and also provide valuable evidence for the fish-specific genome duplication (FSGD) hypothesis. Although Gig2 family proteins exhibit no significant sequence similarity to any known proteins, a typical Gig2 protein appears to consist of two conserved parts: an N-terminus that bears very low homology to the catalytic domains of poly(ADP-ribose) polymerases (PARPs), and a novel C-terminal domain that is unique to this gene family. Expression profiling of zebrafish Gig2 family genes shows that some duplicate pairs have diverged in function via acquisition of novel spatial and/or temporal expression under stresses. The specificity of this gene family to non-amniotes might contribute to a large extent to distinct physiology in non-amniote vertebrates.

VASP-E: Specificity Annotation with a Volumetric Analysis of Electrostatic Isopotentials

PubMed Central

Chen, Brian Y.

2014-01-01

Algorithms for comparing protein structure are frequently used for function annotation. By searching for subtle similarities among very different proteins, these algorithms can identify remote homologs with similar biological functions. In contrast, few comparison algorithms focus on specificity annotation, where the identification of subtle differences among very similar proteins can assist in finding small structural variations that create differences in binding specificity. Few specificity annotation methods consider electrostatic fields, which play a critical role in molecular recognition. To fill this gap, this paper describes VASP-E (Volumetric Analysis of Surface Properties with Electrostatics), a novel volumetric comparison tool based on the electrostatic comparison of protein-ligand and protein-protein binding sites. VASP-E exploits the central observation that three dimensional solids can be used to fully represent and compare both electrostatic isopotentials and molecular surfaces. With this integrated representation, VASP-E is able to dissect the electrostatic environments of protein-ligand and protein-protein binding interfaces, identifying individual amino acids that have an electrostatic influence on binding specificity. VASP-E was used to examine a nonredundant subset of the serine and cysteine proteases as well as the barnase-barstar and Rap1a-raf complexes. Based on amino acids established by various experimental studies to have an electrostatic influence on binding specificity, VASP-E identified electrostatically influential amino acids with 100% precision and 83.3% recall. We also show that VASP-E can accurately classify closely related ligand binding cavities into groups with different binding preferences. These results suggest that VASP-E should prove a useful tool for the characterization of specific binding and the engineering of binding preferences in proteins. PMID:25166865

A metabolomics approach to the identification of biomarkers of sugar-sweetened beverage intake.

PubMed

Gibbons, Helena; McNulty, Breige A; Nugent, Anne P; Walton, Janette; Flynn, Albert; Gibney, Michael J; Brennan, Lorraine

2015-03-01

The association between sugar-sweetened beverages (SSBs) and health risks remains controversial. To clarify proposed links, reliable and accurate dietary assessment methods of food intakes are essential. The aim of this present work was to use a metabolomics approach to identify a panel of urinary biomarkers indicative of SSB consumption from a national food consumption survey and subsequently validate this panel in an acute intervention study. Heat map analysis was performed to identify correlations between ¹H nuclear magnetic resonance (NMR) spectral regions and SSB intakes in participants of the National Adult Nutrition Survey (n = 565). Metabolites were identified and receiver operating characteristic (ROC) analysis was performed to assess sensitivity and specificity of biomarkers. The panel of biomarkers was validated in an acute study (n = 10). A fasting first-void urine sample and postprandial samples (2, 4, 6 h) were collected after SSB consumption. After NMR spectroscopic profiling of the urine samples, multivariate data analysis was applied. A panel of 4 biomarkers-formate, citrulline, taurine, and isocitrate-were identified as markers of SSB intake. This panel of biomarkers had an area under the curve of 0.8 for ROC analysis and a sensitivity and specificity of 0.7 and 0.8, respectively. All 4 biomarkers were identified in the SSB sample. After acute consumption of an SSB drink, all 4 metabolites increased in the urine. The present metabolomics-based strategy proved to be successful in the identification of SSB biomarkers. Future work will ascertain how to translate this panel of markers for use in nutrition epidemiology. © 2015 American Society for Nutrition.

The reliability and validity of video analysis for the assessment of the clinical signs of concussion in Australian football.

PubMed

Makdissi, Michael; Davis, Gavin

2016-10-01

The objective of this study was to determine the reliability and validity of identifying clinical signs of concussion using video analysis in Australian football. Prospective cohort study. All impacts and collisions potentially resulting in a concussion were identified during 2012 and 2013 Australian Football League seasons. Consensus definitions were developed for clinical signs associated with concussion. For intra- and inter-rater reliability analysis, two experienced clinicians independently assessed 102 randomly selected videos on two occasions. Sensitivity, specificity, positive and negative predictive values were calculated based on the diagnosis provided by team medical staff. 212 incidents resulting in possible concussion were identified in 414 Australian Football League games. The intra-rater reliability of the video-based identification of signs associated with concussion was good to excellent. Inter-rater reliability was good to excellent for impact seizure, slow to get up, motor incoordination, ragdoll appearance (2 of 4 analyses), clutching at head and facial injury. Inter-rater reliability for loss of responsiveness and blank and vacant look was only fair and did not reach statistical significance. The feature with the highest sensitivity was slow to get up (87%), but this sign had a low specificity (19%). Other video signs had a high specificity but low sensitivity. Blank and vacant look (100%) and motor incoordination (81%) had the highest positive predictive value. Video analysis may be a useful adjunct to the side-line assessment of a possible concussion. Video analysis however should not replace the need for a thorough multimodal clinical assessment. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

A parallel genome-wide RNAi screening strategy to identify host proteins important for entry of Marburg virus and H5N1 influenza virus.

PubMed

Cheng, Han; Koning, Katie; O'Hearn, Aileen; Wang, Minxiu; Rumschlag-Booms, Emily; Varhegyi, Elizabeth; Rong, Lijun

2015-11-24

Genome-wide RNAi screening has been widely used to identify host proteins involved in replication and infection of different viruses, and numerous host factors are implicated in the replication cycles of these viruses, demonstrating the power of this approach. However, discrepancies on target identification of the same viruses by different groups suggest that high throughput RNAi screening strategies need to be carefully designed, developed and optimized prior to the large scale screening. Two genome-wide RNAi screens were performed in parallel against the entry of pseudotyped Marburg viruses and avian influenza virus H5N1 utilizing an HIV-1 based surrogate system, to identify host factors which are important for virus entry. A comparative analysis approach was employed in data analysis, which alleviated systematic positional effects and reduced the false positive number of virus-specific hits. The parallel nature of the strategy allows us to easily identify the host factors for a specific virus with a greatly reduced number of false positives in the initial screen, which is one of the major problems with high throughput screening. The power of this strategy is illustrated by a genome-wide RNAi screen for identifying the host factors important for Marburg virus and/or avian influenza virus H5N1 as described in this study. This strategy is particularly useful for highly pathogenic viruses since pseudotyping allows us to perform high throughput screens in the biosafety level 2 (BSL-2) containment instead of the BSL-3 or BSL-4 for the infectious viruses, with alleviated safety concerns. The screening strategy together with the unique comparative analysis approach makes the data more suitable for hit selection and enables us to identify virus-specific hits with a much lower false positive rate.

A global analysis of protein expression profiles in Sinorhizobium meliloti: discovery of new genes for nodule occupancy and stress adaptation.

PubMed

Djordjevic, Michael A; Chen, Han Cai; Natera, Siria; Van Noorden, Giel; Menzel, Christian; Taylor, Scott; Renard, Clotilde; Geiger, Otto; Weiller, Georg F

2003-06-01

A proteomic examination of Sinorhizobium meliloti strain 1021 was undertaken using a combination of 2-D gel electrophoresis, peptide mass fingerprinting, and bioinformatics. Our goal was to identify (i) putative symbiosis- or nutrient-stress-specific proteins, (ii) the biochemical pathways active under different conditions, (iii) potential new genes, and (iv) the extent of posttranslational modifications of S. meliloti proteins. In total, we identified the protein products of 810 genes (13.1% of the genome's coding capacity). The 810 genes generated 1,180 gene products, with chromosomal genes accounting for 78% of the gene products identified (18.8% of the chromosome's coding capacity). The activity of 53 metabolic pathways was inferred from bioinformatic analysis of proteins with assigned Enzyme Commission numbers. Of the remaining proteins that did not encode enzymes, ABC-type transporters composed 12.7% and regulatory proteins 3.4% of the total. Proteins with up to seven transmembrane domains were identified in membrane preparations. A total of 27 putative nodule-specific proteins and 35 nutrient-stress-specific proteins were identified and used as a basis to define genes and describe processes occurring in S. meliloti cells in nodules and under stress. Several nodule proteins from the plant host were present in the nodule bacteria preparations. We also identified seven potentially novel proteins not predicted from the DNA sequence. Post-translational modifications such as N-terminal processing could be inferred from the data. The posttranslational addition of UMP to the key regulator of nitrogen metabolism, PII, was demonstrated. This work demonstrates the utility of combining mass spectrometry with protein arraying or separation techniques to identify candidate genes involved in important biological processes and niche occupations that may be intransigent to other methods of gene expression profiling.

Writing Characteristics of Students with Attention Deficit Hyperactive Disorder: A Meta-Analysis

ERIC Educational Resources Information Center

Graham, Steve; Fishman, Evan J.; Reid, Robert; Hebert, Michael

2016-01-01

Students with Attention Deficit Hyperactivity Disorders (ADHD) frequently experience significant difficulty mastering basic academic skills. This meta-analysis focuses on one specific potential area of learning difficulties for these students: namely, writing. To identify the extent and depth of the potential writing challenges faced by students…

Computational Identification of Tissue-Specific Splicing Regulatory Elements in Human Genes from RNA-Seq Data.

PubMed

Badr, Eman; ElHefnawi, Mahmoud; Heath, Lenwood S

2016-01-01

Alternative splicing is a vital process for regulating gene expression and promoting proteomic diversity. It plays a key role in tissue-specific expressed genes. This specificity is mainly regulated by splicing factors that bind to specific sequences called splicing regulatory elements (SREs). Here, we report a genome-wide analysis to study alternative splicing on multiple tissues, including brain, heart, liver, and muscle. We propose a pipeline to identify differential exons across tissues and hence tissue-specific SREs. In our pipeline, we utilize the DEXSeq package along with our previously reported algorithms. Utilizing the publicly available RNA-Seq data set from the Human BodyMap project, we identified 28,100 differentially used exons across the four tissues. We identified tissue-specific exonic splicing enhancers that overlap with various previously published experimental and computational databases. A complicated exonic enhancer regulatory network was revealed, where multiple exonic enhancers were found across multiple tissues while some were found only in specific tissues. Putative combinatorial exonic enhancers and silencers were discovered as well, which may be responsible for exon inclusion or exclusion across tissues. Some of the exonic enhancers are found to be co-occurring with multiple exonic silencers and vice versa, which demonstrates a complicated relationship between tissue-specific exonic enhancers and silencers.

Weighted gene co-expression network analysis of expression data of monozygotic twins identifies specific modules and hub genes related to BMI.

PubMed

Wang, Weijing; Jiang, Wenjie; Hou, Lin; Duan, Haiping; Wu, Yili; Xu, Chunsheng; Tan, Qihua; Li, Shuxia; Zhang, Dongfeng

2017-11-13

The therapeutic management of obesity is challenging, hence further elucidating the underlying mechanisms of obesity development and identifying new diagnostic biomarkers and therapeutic targets are urgent and necessary. Here, we performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify significant genes and specific modules related to BMI based on gene expression profile data of 7 discordant monozygotic twins. In the differential gene expression analysis, it appeared that 32 differentially expressed genes (DEGs) were with a trend of up-regulation in twins with higher BMI when compared to their siblings. Categories of positive regulation of nitric-oxide synthase biosynthetic process, positive regulation of NF-kappa B import into nucleus, and peroxidase activity were significantly enriched within GO database and NF-kappa B signaling pathway within KEGG database. DEGs of NAMPT, TLR9, PTGS2, HBD, and PCSK1N might be associated with obesity. In the WGCNA, among the total 20 distinct co-expression modules identified, coral1 module (68 genes) had the strongest positive correlation with BMI (r = 0.56, P = 0.04) and disease status (r = 0.56, P = 0.04). Categories of positive regulation of phospholipase activity, high-density lipoprotein particle clearance, chylomicron remnant clearance, reverse cholesterol transport, intermediate-density lipoprotein particle, chylomicron, low-density lipoprotein particle, very-low-density lipoprotein particle, voltage-gated potassium channel complex, cholesterol transporter activity, and neuropeptide hormone activity were significantly enriched within GO database for this module. And alcoholism and cell adhesion molecules pathways were significantly enriched within KEGG database. Several hub genes, such as GAL, ASB9, NPPB, TBX2, IL17C, APOE, ABCG4, and APOC2 were also identified. The module eigengene of saddlebrown module (212 genes) was also significantly correlated with BMI (r = 0.56, P = 0.04), and hub genes of KCNN1 and AQP10 were differentially expressed. We identified significant genes and specific modules potentially related to BMI based on the gene expression profile data of monozygotic twins. The findings may help further elucidate the underlying mechanisms of obesity development and provide novel insights to research potential gene biomarkers and signaling pathways for obesity treatment. Further analysis and validation of the findings reported here are important and necessary when more sample size is acquired.

Sensitivity and Specificity of Polysomnographic Criteria for Defining Insomnia

PubMed Central

Edinger, Jack D.; Ulmer, Christi S.; Means, Melanie K.

2013-01-01

Study Objectives: In recent years, polysomnography-based eligibility criteria have been increasingly used to identify candidates for insomnia research, and this has been particularly true of studies evaluating pharmacologic therapy for primary insomnia. However, the sensitivity and specificity of PSG for identifying individuals with insomnia is unknown, and there is no consensus on the criteria sets which should be used for participant selection. In the current study, an archival data set was used to test the sensitivity and specificity of PSG measures for identifying individuals with primary insomnia in both home and lab settings. We then evaluated the sensitivity and specificity of the eligibility criteria employed in a number of recent insomnia trials for identifying primary insomnia sufferers in our sample. Design: Archival data analysis. Settings: Study participants' homes and a clinical sleep laboratory. Participants: Adults: 76 with primary insomnia and 78 non-complaining normal sleepers. Measurements and Results: ROC and cross-tabs analyses were used to evaluate the sensitivity and specificity of PSG-derived total sleep time, latency to persistent sleep, wake after sleep onset, and sleep efficiency for discriminating adults with primary insomnia from normal sleepers. None of the individual criteria accurately discriminated PI from normal sleepers, and none of the criteria sets used in recent trials demonstrated acceptable sensitivity and specificity for identifying primary insomnia. Conclusions: The use of quantitative PSG-based selection criteria in insomnia research may exclude many who meet current diagnostic criteria for an insomnia disorder. Citation: Edinger JD; Ulmer CS; Means MK. Sensitivity and specificity of polysomnographic criteria for defining insomnia. J Clin Sleep Med 2013;9(5):481-491. PMID:23674940

A graph-based system for network-vulnerability analysis

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

Swiler, L.P.; Phillips, C.

1998-06-01

This paper presents a graph-based approach to network vulnerability analysis. The method is flexible, allowing analysis of attacks from both outside and inside the network. It can analyze risks to a specific network asset, or examine the universe of possible consequences following a successful attack. The graph-based tool can identify the set of attack paths that have a high probability of success (or a low effort cost) for the attacker. The system could be used to test the effectiveness of making configuration changes, implementing an intrusion detection system, etc. The analysis system requires as input a database of common attacks,more » broken into atomic steps, specific network configuration and topology information, and an attacker profile. The attack information is matched with the network configuration information and an attacker profile to create a superset attack graph. Nodes identify a stage of attack, for example the class of machines the attacker has accessed and the user privilege level he or she has compromised. The arcs in the attack graph represent attacks or stages of attacks. By assigning probabilities of success on the arcs or costs representing level-of-effort for the attacker, various graph algorithms such as shortest-path algorithms can identify the attack paths with the highest probability of success.« less

Comparative genomic and phylogenetic analysis of short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity.

PubMed

Belyaeva, Olga V; Kedishvili, Natalia Y

2006-12-01

Human short-chain dehydrogenases/reductases with dual retinol/sterol substrate specificity (RODH-like enzymes) are thought to contribute to the oxidation of retinol for retinoic acid biosynthesis and to the metabolism of androgenic and neuroactive 3alpha-hydroxysteroids. Here, we investigated the phylogeny and orthology of these proteins to understand better their origins and physiological roles. Phylogenetic and genomic analysis showed that two proteins (11-cis-RDH and RDHL) are highly conserved, and their orthologs can be identified in the lower taxa, such as amphibians and fish. Two other proteins (RODH-4 and 3alpha-HSD) are significantly less conserved. Orthologs for 3alpha-HSD are present in all mammals analyzed, whereas orthologs for RODH-4 can be identified in some mammalian species but not in others due to species-specific gene duplications. Understanding the evolution and divergence of RODH-like enzymes in various vertebrate species should facilitate further investigation of their in vivo functions using animal models.

A novel unsupervised analysis of electrophysiological signals reveals new sleep substages in mice.

PubMed

Katsageorgiou, Vasiliki-Maria; Sona, Diego; Zanotto, Matteo; Lassi, Glenda; Garcia-Garcia, Celina; Tucci, Valter; Murino, Vittorio

2018-05-01

Sleep science is entering a new era, thanks to new data-driven analysis approaches that, combined with mouse gene-editing technologies, show a promise in functional genomics and translational research. However, the investigation of sleep is time consuming and not suitable for large-scale phenotypic datasets, mainly due to the need for subjective manual annotations of electrophysiological states. Moreover, the heterogeneous nature of sleep, with all its physiological aspects, is not fully accounted for by the current system of sleep stage classification. In this study, we present a new data-driven analysis approach offering a plethora of novel features for the characterization of sleep. This novel approach allowed for identifying several substages of sleep that were hidden to standard analysis. For each of these substages, we report an independent set of homeostatic responses following sleep deprivation. By using our new substages classification, we have identified novel differences among various genetic backgrounds. Moreover, in a specific experiment with the Zfhx3 mouse line, a recent circadian mutant expressing both shortening of the circadian period and abnormal sleep architecture, we identified specific sleep states that account for genotypic differences at specific times of the day. These results add a further level of interaction between circadian clock and sleep homeostasis and indicate that dissecting sleep in multiple states is physiologically relevant and can lead to the discovery of new links between sleep phenotypes and genetic determinants. Therefore, our approach has the potential to significantly enhance the understanding of sleep physiology through the study of single mutations. Moreover, this study paves the way to systematic high-throughput analyses of sleep.

"It still haunts me whether we did the right thing": a qualitative analysis of free text survey data on the bereavement experiences and support needs of family caregivers.

PubMed

Harrop, Emily; Morgan, Fiona; Byrne, Anthony; Nelson, Annmarie

2016-11-08

Research suggests that there may be bereavement experiences and support needs which are specific to family caregivers providing end of life care (EoLC), although this remains an under-researched area. This paper focuses on themes relating to bereavement which were derived from an analysis of free text survey responses collected in a research priority setting exercise for palliative and EoLC. The priority setting exercise involved a public survey, designed to generate research priorities. Rather than identify research topics, many people instead described their experiences and raised more general questions relating to palliative and end of life care. To explore these experiences and perspectives a supplementary thematic analysis was conducted on the survey responses. 1403 respondents took part, including patients, current and bereaved carers, health and social care professionals, volunteers and members of the public. Several grief issues were identified, which seem specific to the experiences of family caregivers. Responses demonstrated a relationship between death experiences, feelings of guilt and bereavement outcomes for some family caregivers, as well as caregiver experiences of a "void" created by the withdrawal of professional support after death. Communication and support needs were also identified by participants. This analysis provides further evidence of some of the specific effects that caring for a loved one at the end of life can have on bereavement experiences. Finding ways of improving communication around the time of death and effective follow up approaches post death could help to address some of these issues.

PSEA: Kinase-specific prediction and analysis of human phosphorylation substrates

NASA Astrophysics Data System (ADS)

Suo, Sheng-Bao; Qiu, Jian-Ding; Shi, Shao-Ping; Chen, Xiang; Liang, Ru-Ping

2014-03-01

Protein phosphorylation catalysed by kinases plays crucial regulatory roles in intracellular signal transduction. With the increasing number of kinase-specific phosphorylation sites and disease-related phosphorylation substrates that have been identified, the desire to explore the regulatory relationship between protein kinases and disease-related phosphorylation substrates is motivated. In this work, we analysed the kinases' characteristic of all disease-related phosphorylation substrates by using our developed Phosphorylation Set Enrichment Analysis (PSEA) method. We evaluated the efficiency of our method with independent test and concluded that our approach is reliable for identifying kinases responsible for phosphorylated substrates. In addition, we found that Mitogen-activated protein kinase (MAPK) and Glycogen synthase kinase (GSK) families are more associated with abnormal phosphorylation. It can be anticipated that our method might be helpful to identify the mechanism of phosphorylation and the relationship between kinase and phosphorylation related diseases. A user-friendly web interface is now freely available at http://bioinfo.ncu.edu.cn/PKPred_Home.aspx.

Gene expression atlas of pigeonpea and its application to gain insights into genes associated with pollen fertility implicated in seed formation

PubMed Central

Pazhamala, Lekha T.; Purohit, Shilp; Saxena, Rachit K.; Garg, Vanika; Krishnamurthy, L.; Verdier, Jerome

2017-01-01

Abstract Pigeonpea (Cajanus cajan) is an important grain legume of the semi-arid tropics, mainly used for its protein rich seeds. To link the genome sequence information with agronomic traits resulting from specific developmental processes, a Cajanus cajan gene expression atlas (CcGEA) was developed using the Asha genotype. Thirty tissues/organs representing developmental stages from germination to senescence were used to generate 590.84 million paired-end RNA-Seq data. The CcGEA revealed a compendium of 28 793 genes with differential, specific, spatio-temporal and constitutive expression during various stages of development in different tissues. As an example to demonstrate the application of the CcGEA, a network of 28 flower-related genes analysed for cis-regulatory elements and splicing variants has been identified. In addition, expression analysis of these candidate genes in male sterile and male fertile genotypes suggested their critical role in normal pollen development leading to seed formation. Gene network analysis also identified two regulatory genes, a pollen-specific SF3 and a sucrose–proton symporter, that could have implications for improvement of agronomic traits such as seed production and yield. In conclusion, the CcGEA provides a valuable resource for pigeonpea to identify candidate genes involved in specific developmental processes and to understand the well-orchestrated growth and developmental process in this resilient crop. PMID:28338822

Space science technology: In-situ science. Sample Acquisition, Analysis, and Preservation Project summary

NASA Technical Reports Server (NTRS)

Aaron, Kim

1991-01-01

The Sample Acquisition, Analysis, and Preservation Project is summarized in outline and graphic form. The objective of the project is to develop component and system level technology to enable the unmanned collection, analysis and preservation of physical, chemical and mineralogical data from the surface of planetary bodies. Technology needs and challenges are identified and specific objectives are described.

PCR-enzyme-linked immunosorbent assay and partial rRNA gene sequencing: a rational approach to identifying mycobacteria.

PubMed Central

Patel, S; Yates, M; Saunders, N A

1997-01-01

A PCR-enzyme-linked immunosorbent assay (ELISA) for amplification and rapid identification of mycobacterial DNA coding for 16S rRNA was developed. The PCR selectively targeted and amplified part of the 16S rRNA gene from all mycobacteria while simultaneously labelling one strand of the amplified product with a 5' fluorescein-labelled primer. The identity of the labelled strand was subsequently determined by hybridization to a panel of mycobacterial species-specific capture probes, which were immobilized via their 5' biotin ends to a streptavidin-coated microtiter plate. Specific hybridization of a 5' fluorescein-labelled strand to a species probe was detected colorimetrically with an anti-fluorescein enzyme conjugate. The assay was able to identify 10 Mycobacterium spp. A probe able to hybridize to all Mycobacterium species (All1) was also included. By a heminested PCR, the assay was sensitive enough to detect as little as 10 fg of DNA, which is equivalent to approximately three bacilli. The assay was able to detect and identify mycobacteria directly from sputa. The specificities of the capture probes were assessed by analysis of 60 mycobacterial strains corresponding to 18 species. Probes Avi1, Int1, Kan1, Xen1, Che1, For1, Mal1, Ter1, and Gor1 were specific. The probe Tbc1 cross-hybridized with the Mycobacterium terrae amplicon. Analysis of 35 strains tested blind resulted in 34 strains being correctly identified. This method could be used for rapid identification of early cultures and may be suitable for the detection and concurrent identification of mycobacteria within clinical specimens. PMID:9276419

A Novel Feature-Map Based ICA Model for Identifying the Individual, Intra/Inter-Group Brain Networks across Multiple fMRI Datasets.

PubMed

Wang, Nizhuan; Chang, Chunqi; Zeng, Weiming; Shi, Yuhu; Yan, Hongjie

2017-01-01

Independent component analysis (ICA) has been widely used in functional magnetic resonance imaging (fMRI) data analysis to evaluate functional connectivity of the brain; however, there are still some limitations on ICA simultaneously handling neuroimaging datasets with diverse acquisition parameters, e.g., different repetition time, different scanner, etc. Therefore, it is difficult for the traditional ICA framework to effectively handle ever-increasingly big neuroimaging datasets. In this research, a novel feature-map based ICA framework (FMICA) was proposed to address the aforementioned deficiencies, which aimed at exploring brain functional networks (BFNs) at different scales, e.g., the first level (individual subject level), second level (intragroup level of subjects within a certain dataset) and third level (intergroup level of subjects across different datasets), based only on the feature maps extracted from the fMRI datasets. The FMICA was presented as a hierarchical framework, which effectively made ICA and constrained ICA as a whole to identify the BFNs from the feature maps. The simulated and real experimental results demonstrated that FMICA had the excellent ability to identify the intergroup BFNs and to characterize subject-specific and group-specific difference of BFNs from the independent component feature maps, which sharply reduced the size of fMRI datasets. Compared with traditional ICAs, FMICA as a more generalized framework could efficiently and simultaneously identify the variant BFNs at the subject-specific, intragroup, intragroup-specific and intergroup levels, implying that FMICA was able to handle big neuroimaging datasets in neuroscience research.

Rhetorical Motives of Identity, Consubstantiality, and Hierarchy: An Analysis of Community College Program Documents

ERIC Educational Resources Information Center

Parkis Pettit, Angela G.

2011-01-01

The dissertation focuses on three academic programs at Tarrant County College, Northeast Campus, specifically the documents used to create and sustain these programs. The purpose of this study includes the following: first, to identify the terminology specific to each program and/or the documents used within the program; second and third to…

A Genre-Specific Reading Comprehension Strategy to Enhance Struggling Fifth-Grade Readers' Ability to Critically Analyze Argumentative Text

ERIC Educational Resources Information Center

Haria, Priti D.; Midgette, Ekaterina

2014-01-01

This study examined the effectiveness of instruction in a genre-specific reading comprehension strategy, "critical analysis of argumentative text," which was designed to help students to identify, summarize, and critically analyze parts of an argumentative text. The investigators hypothesized that reading instruction would improve the…

Past Tense Production in Children with and without Specific Language Impairment across Germanic Languages: A Meta-Analysis

ERIC Educational Resources Information Center

Krok, Windi C.; Leonard, Laurence B.

2015-01-01

Purpose: This study examined the extent to which children with specific language impairment (SLI) across Germanic languages differ from their typically developing (TD) peers in the use of past tense morphology. Method: A systematic literature search identified empirical studies examining regular and/or irregular past tense production by English…

Cloning and characterization of a novel oocyte-specific gene encoding an F-Box protein in rainbow trout (Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

Oocyte-specific genes play critical roles in oogenesis, folliculogenesis and early embryonic development. Through analysis of expressed sequence tags (ESTs) from a rainbow trout oocyte cDNA library, we identified a novel transcript which is represented by multiple ESTs derived only from the oocyte c...

Cloning and characterization of a novel oocyte-specific gene encoding an F-Box protein in rainbow trout (Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

Oocyte-specific genes play critical roles in oogenesis, folliculogenesis and early embryonic development. Through analysis of expressed sequence tags (ESTs) from a rainbow trout oocyte cDNA library, we identified a novel transcript which is represented by ESTs only from the oocyte library. The novel...

Genome-wide identification and quantification of cis- and trans-regulated genes responding to Marek's disease virus infection via analysis of allele-specific expression

USDA-ARS?s Scientific Manuscript database

Background Marek’s disease (MD) is a commercially important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), a naturally-occurring oncogenic alphaherpesvirus. We attempted to identify genes conferring MD resistance, by completing a genome-wide screen for allele-specific expr...

Classification Agreement Analysis of Cross-Battery Assessment in the Identification of Specific Learning Disorders in Children and Youth

ERIC Educational Resources Information Center

Kranzler, John H.; Floyd, Randy G.; Benson, Nicholas; Zaboski, Brian; Thibodaux, Lia

2016-01-01

The Cross-Battery Assessment (XBA) approach to identifying a specific learning disorder (SLD) is based on the postulate that deficits in cognitive abilities in the presence of otherwise average general intelligence are causally related to academic achievement weaknesses. To examine this postulate, we conducted a classification agreement analysis…

A retrospective analysis to identify the factors affecting infection in patients undergoing chemotherapy.

PubMed

Park, Ji Hyun; Kim, Hyeon-Young; Lee, Hanna; Yun, Eun Kyoung

2015-12-01

This study compares the performance of the logistic regression and decision tree analysis methods for assessing the risk factors for infection in cancer patients undergoing chemotherapy. The subjects were 732 cancer patients who were receiving chemotherapy at K university hospital in Seoul, Korea. The data were collected between March 2011 and February 2013 and were processed for descriptive analysis, logistic regression and decision tree analysis using the IBM SPSS Statistics 19 and Modeler 15.1 programs. The most common risk factors for infection in cancer patients receiving chemotherapy were identified as alkylating agents, vinca alkaloid and underlying diabetes mellitus. The logistic regression explained 66.7% of the variation in the data in terms of sensitivity and 88.9% in terms of specificity. The decision tree analysis accounted for 55.0% of the variation in the data in terms of sensitivity and 89.0% in terms of specificity. As for the overall classification accuracy, the logistic regression explained 88.0% and the decision tree analysis explained 87.2%. The logistic regression analysis showed a higher degree of sensitivity and classification accuracy. Therefore, logistic regression analysis is concluded to be the more effective and useful method for establishing an infection prediction model for patients undergoing chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Proteomic Identification and Analysis of Arginine-Methylated Proteins of Plasmodium falciparum at Asexual Blood Stages.

PubMed

Zeeshan, Mohammad; Kaur, Inderjeet; Joy, Joseph; Saini, Ekta; Paul, Gourab; Kaushik, Abhinav; Dabral, Surbhi; Mohmmed, Asif; Gupta, Dinesh; Malhotra, Pawan

2017-02-03

Plasmodium falciparum undergoes a tightly regulated developmental process in human erythrocytes, and recent studies suggest an important regulatory role of post-translational modifications (PTMs). As compared with Plasmodium phosphoproteome, little is known about other PTMs in the parasite. In the present study, we performed a global analysis of asexual blood stages of Plasmodium falciparum to identify arginine-methylated proteins. Using two different methyl arginine-specific antibodies, we immunoprecipitated the arginine-methylated proteins from the stage-specific parasite lysates and identified 843 putative arginine-methylated proteins by LC-MS/MS. Motif analysis of the protein sequences unveiled that the methylation sites are associated with the previously known methylation motifs such as GRx/RGx, RxG, GxxR, or WxxxR. We identified Plasmodium homologues of known arginine-methylated proteins in trypanosomes, yeast, and human. Hydrophilic interaction liquid chromatography (HILIC) was performed on the immunoprecipitates from the trophozoite stage to enrich arginine-methylated peptides. Mass spectrometry analysis of immunoprecipitated and HILIC fractions identified 55 arginine-methylated peptides having 62 methylated arginine sites. Functional classification revealed that the arginine-methylated proteins are involved in RNA metabolism, protein synthesis, intracellular protein trafficking, proteolysis, protein folding, chromatin organization, hemoglobin metabolic process, and several other functions. Summarily, the findings suggest that protein methylation of arginine residues is a widespread phenomenon in Plasmodium, and the PTM may play an important regulatory role in a diverse set of biological pathways, including host-pathogen interactions.

Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing

PubMed Central

Tsioris, Konstantinos; Gupta, Namita T.; Ogunniyi, Adebola O.; Zimnisky, Ross M.; Qian, Feng; Yao, Yi; Wang, Xiaomei; Stern, Joel N. H.; Chari, Raj; Briggs, Adrian W.; Clouser, Christopher R.; Vigneault, Francois; Church, George M.; Garcia, Melissa N.; Murray, Kristy O.; Montgomery, Ruth R.; Kleinstein, Steven H.; Love, J. Christopher

2015-01-01

West Nile virus infection (WNV) is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases. PMID:26481611

Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing.

PubMed

Tsioris, Konstantinos; Gupta, Namita T; Ogunniyi, Adebola O; Zimnisky, Ross M; Qian, Feng; Yao, Yi; Wang, Xiaomei; Stern, Joel N H; Chari, Raj; Briggs, Adrian W; Clouser, Christopher R; Vigneault, Francois; Church, George M; Garcia, Melissa N; Murray, Kristy O; Montgomery, Ruth R; Kleinstein, Steven H; Love, J Christopher

2015-12-01

West Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV - recently infected and post-convalescent subjects - and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases.

An Examination of High School Graduates Who Identify Teachers as Influential in Their Choice of College

ERIC Educational Resources Information Center

Mozie-Ross, Yvette D.

2011-01-01

This exploratory study contributes to what is known about the college choice process by providing a quantitative comparative analysis to determine how high school graduates who identify teachers as influential in their choice of college differ from graduates who do not. Specifically, this study answers the following research question: How do…

Pharmacogenomic identification of small molecules for lineage specific manipulation of subventricular zone germinal activity.

PubMed

Azim, Kasum; Angonin, Diane; Marcy, Guillaume; Pieropan, Francesca; Rivera, Andrea; Donega, Vanessa; Cantù, Claudio; Williams, Gareth; Berninger, Benedikt; Butt, Arthur M; Raineteau, Olivier

2017-03-01

Strategies for promoting neural regeneration are hindered by the difficulty of manipulating desired neural fates in the brain without complex genetic methods. The subventricular zone (SVZ) is the largest germinal zone of the forebrain and is responsible for the lifelong generation of interneuron subtypes and oligodendrocytes. Here, we have performed a bioinformatics analysis of the transcriptome of dorsal and lateral SVZ in early postnatal mice, including neural stem cells (NSCs) and their immediate progenies, which generate distinct neural lineages. We identified multiple signaling pathways that trigger distinct downstream transcriptional networks to regulate the diversity of neural cells originating from the SVZ. Next, we used a novel in silico genomic analysis, searchable platform-independent expression database/connectivity map (SPIED/CMAP), to generate a catalogue of small molecules that can be used to manipulate SVZ microdomain-specific lineages. Finally, we demonstrate that compounds identified in this analysis promote the generation of specific cell lineages from NSCs in vivo, during postnatal life and adulthood, as well as in regenerative contexts. This study unravels new strategies for using small bioactive molecules to direct germinal activity in the SVZ, which has therapeutic potential in neurodegenerative diseases.

GoIFISH: a system for the quantification of single cell heterogeneity from IFISH images.

PubMed

Trinh, Anne; Rye, Inga H; Almendro, Vanessa; Helland, Aslaug; Russnes, Hege G; Markowetz, Florian

2014-08-26

Molecular analysis has revealed extensive intra-tumor heterogeneity in human cancer samples, but cannot identify cell-to-cell variations within the tissue microenvironment. In contrast, in situ analysis can identify genetic aberrations in phenotypically defined cell subpopulations while preserving tissue-context specificity. GoIFISHGoIFISH is a widely applicable, user-friendly system tailored for the objective and semi-automated visualization, detection and quantification of genomic alterations and protein expression obtained from fluorescence in situ analysis. In a sample set of HER2-positive breast cancers GoIFISHGoIFISH is highly robust in visual analysis and its accuracy compares favorably to other leading image analysis methods. GoIFISHGoIFISH is freely available at www.sourceforge.net/projects/goifish/.

New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration

PubMed Central

Ambroset, Chloé; Coluzzi, Charles; Guédon, Gérard; Devignes, Marie-Dominique; Loux, Valentin; Lacroix, Thomas; Payot, Sophie; Leblond-Bourget, Nathalie

2016-01-01

Recent genome analyses suggest that integrative and conjugative elements (ICEs) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. However, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. Even though previous analysis showed the presence of ICEs in some species of Streptococci, the global prevalence and diversity of ICEs was not analyzed in this genus. In this study, we searched for ICEs in the completely sequenced genomes of 124 strains belonging to 27 streptococcal species. These exhaustive analyses revealed 105 putative ICEs and 26 slightly decayed elements whose limits were assessed and whose insertion site was identified. These ICEs were grouped in seven distinct unrelated or distantly related families, according to their conjugation modules. Integration of these streptococcal ICEs is catalyzed either by a site-specific tyrosine integrase, a low-specificity tyrosine integrase, a site-specific single serine integrase, a triplet of site-specific serine integrases or a DDE transposase. Analysis of their integration site led to the detection of 18 target-genes for streptococcal ICE insertion including eight that had not been identified previously (ftsK, guaA, lysS, mutT, rpmG, rpsI, traG, and ebfC). It also suggests that all specificities have evolved to minimize the impact of the insertion on the host. This overall analysis of streptococcal ICEs emphasizes their prevalence and diversity and demonstrates that exchanges or acquisitions of conjugation and recombination modules are frequent. PMID:26779141

New Insights into the Classification and Integration Specificity of Streptococcus Integrative Conjugative Elements through Extensive Genome Exploration.

PubMed

Ambroset, Chloé; Coluzzi, Charles; Guédon, Gérard; Devignes, Marie-Dominique; Loux, Valentin; Lacroix, Thomas; Payot, Sophie; Leblond-Bourget, Nathalie

2015-01-01

Recent genome analyses suggest that integrative and conjugative elements (ICEs) are widespread in bacterial genomes and therefore play an essential role in horizontal transfer. However, only a few of these elements are precisely characterized and correctly delineated within sequenced bacterial genomes. Even though previous analysis showed the presence of ICEs in some species of Streptococci, the global prevalence and diversity of ICEs was not analyzed in this genus. In this study, we searched for ICEs in the completely sequenced genomes of 124 strains belonging to 27 streptococcal species. These exhaustive analyses revealed 105 putative ICEs and 26 slightly decayed elements whose limits were assessed and whose insertion site was identified. These ICEs were grouped in seven distinct unrelated or distantly related families, according to their conjugation modules. Integration of these streptococcal ICEs is catalyzed either by a site-specific tyrosine integrase, a low-specificity tyrosine integrase, a site-specific single serine integrase, a triplet of site-specific serine integrases or a DDE transposase. Analysis of their integration site led to the detection of 18 target-genes for streptococcal ICE insertion including eight that had not been identified previously (ftsK, guaA, lysS, mutT, rpmG, rpsI, traG, and ebfC). It also suggests that all specificities have evolved to minimize the impact of the insertion on the host. This overall analysis of streptococcal ICEs emphasizes their prevalence and diversity and demonstrates that exchanges or acquisitions of conjugation and recombination modules are frequent.

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.

Longitudinal Metagenomic Analysis of Hospital Air Identifies Clinically Relevant Microbes.

PubMed

King, Paula; Pham, Long K; Waltz, Shannon; Sphar, Dan; Yamamoto, Robert T; Conrad, Douglas; Taplitz, Randy; Torriani, Francesca; Forsyth, R Allyn

2016-01-01

We describe the sampling of sixty-three uncultured hospital air samples collected over a six-month period and analysis using shotgun metagenomic sequencing. Our primary goals were to determine the longitudinal metagenomic variability of this environment, identify and characterize genomes of potential pathogens and determine whether they are atypical to the hospital airborne metagenome. Air samples were collected from eight locations which included patient wards, the main lobby and outside. The resulting DNA libraries produced 972 million sequences representing 51 gigabases. Hierarchical clustering of samples by the most abundant 50 microbial orders generated three major nodes which primarily clustered by type of location. Because the indoor locations were longitudinally consistent, episodic relative increases in microbial genomic signatures related to the opportunistic pathogens Aspergillus, Penicillium and Stenotrophomonas were identified as outliers at specific locations. Further analysis of microbial reads specific for Stenotrophomonas maltophilia indicated homology to a sequenced multi-drug resistant clinical strain and we observed broad sequence coverage of resistance genes. We demonstrate that a shotgun metagenomic sequencing approach can be used to characterize the resistance determinants of pathogen genomes that are uncharacteristic for an otherwise consistent hospital air microbial metagenomic profile.

The low-abundance transcriptome reveals novel biomarkers, specific intracellular pathways and targetable genes associated with advanced gastric cancer.

PubMed

Bizama, Carolina; Benavente, Felipe; Salvatierra, Edgardo; Gutiérrez-Moraga, Ana; Espinoza, Jaime A; Fernández, Elmer A; Roa, Iván; Mazzolini, Guillermo; Sagredo, Eduardo A; Gidekel, Manuel; Podhajcer, Osvaldo L

2014-02-15

Studies on the low-abundance transcriptome are of paramount importance for identifying the intimate mechanisms of tumor progression that can lead to novel therapies. The aim of the present study was to identify novel markers and targetable genes and pathways in advanced human gastric cancer through analyses of the low-abundance transcriptome. The procedure involved an initial subtractive hybridization step, followed by global gene expression analysis using microarrays. We observed profound differences, both at the single gene and gene ontology levels, between the low-abundance transcriptome and the whole transcriptome. Analysis of the low-abundance transcriptome led to the identification and validation by tissue microarrays of novel biomarkers, such as LAMA3 and TTN; moreover, we identified cancer type-specific intracellular pathways and targetable genes, such as IRS2, IL17, IFNγ, VEGF-C, WISP1, FZD5 and CTBP1 that were not detectable by whole transcriptome analyses. We also demonstrated that knocking down the expression of CTBP1 sensitized gastric cancer cells to mainstay chemotherapeutic drugs. We conclude that the analysis of the low-abundance transcriptome provides useful insights into the molecular basis and treatment of cancer. © 2013 UICC.

Automatic Identification and Quantification of Extra-Well Fluorescence in Microarray Images.

PubMed

Rivera, Robert; Wang, Jie; Yu, Xiaobo; Demirkan, Gokhan; Hopper, Marika; Bian, Xiaofang; Tahsin, Tasnia; Magee, D Mitchell; Qiu, Ji; LaBaer, Joshua; Wallstrom, Garrick

2017-11-03

In recent studies involving NAPPA microarrays, extra-well fluorescence is used as a key measure for identifying disease biomarkers because there is evidence to support that it is better correlated with strong antibody responses than statistical analysis involving intraspot intensity. Because this feature is not well quantified by traditional image analysis software, identification and quantification of extra-well fluorescence is performed manually, which is both time-consuming and highly susceptible to variation between raters. A system that could automate this task efficiently and effectively would greatly improve the process of data acquisition in microarray studies, thereby accelerating the discovery of disease biomarkers. In this study, we experimented with different machine learning methods, as well as novel heuristics, for identifying spots exhibiting extra-well fluorescence (rings) in microarray images and assigning each ring a grade of 1-5 based on its intensity and morphology. The sensitivity of our final system for identifying rings was found to be 72% at 99% specificity and 98% at 92% specificity. Our system performs this task significantly faster than a human, while maintaining high performance, and therefore represents a valuable tool for microarray image analysis.

Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

NASA Technical Reports Server (NTRS)

Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

1995-01-01

A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.

PubMed

Chang, Kai-Wei; Huang, Nancy A; Liu, I-Hsuan; Wang, Yi-Hui; Wu, Ping; Tseng, Yen-Tzu; Hughes, Michael W; Jiang, Ting Xin; Tsai, Mong-Hsun; Chen, Chien-Yu; Oyang, Yen-Jen; Lin, En-Chung; Chuong, Cheng-Ming; Lin, Shau-Ping

2015-01-23

Regional specificity allows different skin regions to exhibit different characteristics, enabling complementary functions to make effective use of the integumentary surface. Chickens exhibit a high degree of regional specificity in the skin and can serve as a good model for when and how these regional differences begin to emerge. We used developing feather and scale regions in embryonic chickens as a model to gauge the differences in their molecular pathways. We employed cosine similarity analysis to identify the differentially regulated and co-regulated genes. We applied low cell techniques for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer identification to overcome limited cell availabilities from embryonic chicken skin. We identified a specific set of genes demonstrating a high correlation as being differentially expressed during feather and scale development and maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be involved in feathering skin differentiation were found to be differentially regulated. Interestingly, we also found genes along calcium channel pathways that are differentially regulated. From the analysis of differentially regulated pathways, we used calcium signaling pathways as an example for further verification. Some voltage-gated calcium channel subunits, particularly CACNA1D, are expressed spatio-temporally in the skin epithelium. These calcium signaling pathway members may be involved in developmental decisions, morphogenesis, or epithelial maturation. We further characterized enhancers associated with histone modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel-related genes and identified signature intensive hotspots that may be correlated with certain voltage-gated calcium channel genes. We demonstrated the applicability of cosine similarity analysis for identifying novel regulatory pathways that are differentially regulated during development. Our study concerning the effects of signaling pathways and histone signatures on enhancers suggests that voltage-gated calcium signaling may be involved in early skin development. This work lays the foundation for studying the roles of these gene pathways and their genomic regulation during the establishment of skin regional specificity.

Understanding identifiability as a crucial step in uncertainty assessment

NASA Astrophysics Data System (ADS)

Jakeman, A. J.; Guillaume, J. H. A.; Hill, M. C.; Seo, L.

2016-12-01

The topic of identifiability analysis offers concepts and approaches to identify why unique model parameter values cannot be identified, and can suggest possible responses that either increase uniqueness or help to understand the effect of non-uniqueness on predictions. Identifiability analysis typically involves evaluation of the model equations and the parameter estimation process. Non-identifiability can have a number of undesirable effects. In terms of model parameters these effects include: parameters not being estimated uniquely even with ideal data; wildly different values being returned for different initialisations of a parameter optimisation algorithm; and parameters not being physically meaningful in a model attempting to represent a process. This presentation illustrates some of the drastic consequences of ignoring model identifiability analysis. It argues for a more cogent framework and use of identifiability analysis as a way of understanding model limitations and systematically learning about sources of uncertainty and their importance. The presentation specifically distinguishes between five sources of parameter non-uniqueness (and hence uncertainty) within the modelling process, pragmatically capturing key distinctions within existing identifiability literature. It enumerates many of the various approaches discussed in the literature. Admittedly, improving identifiability is often non-trivial. It requires thorough understanding of the cause of non-identifiability, and the time, knowledge and resources to collect or select new data, modify model structures or objective functions, or improve conditioning. But ignoring these problems is not a viable solution. Even simple approaches such as fixing parameter values or naively using a different model structure may have significant impacts on results which are too often overlooked because identifiability analysis is neglected.

Isomer-specific profiling of N-glycans derived from human serum for potential biomarker discovery in pancreatic cancer.

PubMed

Liu, Yufei; Wang, Chang; Wang, Ran; Wu, Yike; Zhang, Liang; Liu, Bi-Feng; Cheng, Liming; Liu, Xin

2018-06-15

Glycosylation is one of the most important post-translational modifications of protein. Recently, global profiling of human serum glycomics has become a noninvasive method for cancer-related biomarker discovery and many studies have focused on compositional glycan profiling. In contrast, structure-specific glycan profiling may provide more potential biomarkers with higher specificity than compositional profiling. In this work, N-glycans released from human serum were neutralized with methylamine and reduced by ammonia-borane complex prior to profiling using nanoLC-ESI-MS with porous graphitized carbon (PGC) and relative abundances of over 280 isomers were compared between pancreatic cancer (PC) cases (n = 32) and healthy controls (n = 32). Statistical analysis identified 25 specific-isomeric biomarkers with significant differences (p-value < 0.05). ROC and PCA analysis were performed to assess the potential biomarkers which were identified as being significantly altered in cancer. The AUCs of the significantly changed specific-isomers were ranging from 0.712 to 0.949. In addition, with the combination of all potential biomarkers, a higher AUC of 0.976 with sensitivity (93.5%) and specificity (90.6%) was obtained. Overall, the proposed strategy coupled to relative quantitative analysis of isomeric glycans make it possible to discover new biomarkers for the diagnosis of PC. Pancreatic cancer (PC) has a poor prognosis with a five-year survival rate <5%. Therefore, a strategy for accurate diagnosis of PC is indeed required. In this paper, a dual-derivatized strategy for structure-specific glycan profiling has been used and according to our best knowledge, this is the first application of this strategy for PC biomarker discovery, in which the separation, identification and relative quantification of isomeric glycans can be simultaneously obtained. In addition, by in-depth analysis of isomeric glycans, the full description of the stereo- and region- diversity of glycans can also be achieved, which might provide more potential information for PC biomarker discovery. Copyright © 2018 Elsevier B.V. All rights reserved.

A case study in nonconformance and performance trend analysis

NASA Technical Reports Server (NTRS)

Maloy, Joseph E.; Newton, Coy P.

1990-01-01

As part of NASA's effort to develop an agency-wide approach to trend analysis, a pilot nonconformance and performance trending analysis study was conducted on the Space Shuttle auxiliary power unit (APU). The purpose of the study was to (1) demonstrate that nonconformance analysis can be used to identify repeating failures of a specific item (and the associated failure modes and causes) and (2) determine whether performance parameters could be analyzed and monitored to provide an indication of component or system degradation prior to failure. The nonconformance analysis of the APU did identify repeating component failures, which possibly could be reduced if key performance parameters were monitored and analyzed. The performance-trending analysis verified that the characteristics of hardware parameters can be effective in detecting degradation of hardware performance prior to failure.

Learning contextual gene set interaction networks of cancer with condition specificity

PubMed Central

2013-01-01

Background Identifying similarities and differences in the molecular constitutions of various types of cancer is one of the key challenges in cancer research. The appearances of a cancer depend on complex molecular interactions, including gene regulatory networks and gene-environment interactions. This complexity makes it challenging to decipher the molecular origin of the cancer. In recent years, many studies reported methods to uncover heterogeneous depictions of complex cancers, which are often categorized into different subtypes. The challenge is to identify diverse molecular contexts within a cancer, to relate them to different subtypes, and to learn underlying molecular interactions specific to molecular contexts so that we can recommend context-specific treatment to patients. Results In this study, we describe a novel method to discern molecular interactions specific to certain molecular contexts. Unlike conventional approaches to build modular networks of individual genes, our focus is to identify cancer-generic and subtype-specific interactions between contextual gene sets, of which each gene set share coherent transcriptional patterns across a subset of samples, termed contextual gene set. We then apply a novel formulation for quantitating the effect of the samples from each subtype on the calculated strength of interactions observed. Two cancer data sets were analyzed to support the validity of condition-specificity of identified interactions. When compared to an existing approach, the proposed method was much more sensitive in identifying condition-specific interactions even in heterogeneous data set. The results also revealed that network components specific to different types of cancer are related to different biological functions than cancer-generic network components. We found not only the results that are consistent with previous studies, but also new hypotheses on the biological mechanisms specific to certain cancer types that warrant further investigations. Conclusions The analysis on the contextual gene sets and characterization of networks of interaction composed of these sets discovered distinct functional differences underlying various types of cancer. The results show that our method successfully reveals many subtype-specific regions in the identified maps of biological contexts, which well represent biological functions that can be connected to specific subtypes. PMID:23418942

Social Network Analysis to Evaluate an Interdisciplinary Research Center

ERIC Educational Resources Information Center

Aboelela, Sally W.; Merrill, Jacqueline A.; Carley, Kathleen M.; Larson, Elaine

2007-01-01

We sought to examine the growth of an interdisciplinary center using social network analysis techniques. Specific aims were to examine the patterns of growth and interdisciplinary connectedness of the Center and to identify the social network characteristics of its productive members. The setting for this study was The Center for Interdisciplinary…

How to Conduct a Good Meta-Analysis in Gifted Education

ERIC Educational Resources Information Center

Steenbergen-Hu, Saiying; Olszewski-Kubilius, Paula

2016-01-01

This methodological brief introduces basic procedures and issues for conducting a high-quality meta-analysis in gifted education. Specifically, we discuss issues such as how to select a topic and formulate research problems, search for and identify qualified studies, code studies and extract data, choose and calculate effect sizes, analyze data,…

Public and Private School Costs. A Local Analysis, 1994.

ERIC Educational Resources Information Center

Public Policy Forum, Inc., Milwaukee, WI.

This document presents findings of a study that identified key factors of cost-per-pupil differences between public and private school spending among selected Milwaukee area public and private schools. The analysis was limited to cost factors only, specifically, to per-pupil spending. Methodology included a review of the school budgets of 7 public…

40 CFR 270.310 - What equipment information must I keep at my facility?

Code of Federal Regulations, 2010 CFR

2010-07-01

... (e.g., identify the hazardous waste management unit on a facility plot plan). (3) Type of equipment... compliance test required by 40 CFR 264.1033(j). (3) A design analysis, specifications, drawings, schematics... acceptable to the Director that present basic control device design information. The design analysis must...

Meta-Analysis of Biofeedback for Tension-Type Headache: Efficacy, Specificity, and Treatment Moderators

ERIC Educational Resources Information Center

Nestoriuc, Yvonne; Rief, Winfried; Martin, Alexandra

2008-01-01

The aims of the present meta-analysis were to investigate the short- and long-term efficacy, multidimensional outcome, and treatment moderators of biofeedback as a behavioral treatment option for tension-type headache. A literature search identified 74 outcome studies, of which 53 were selected according to predefined inclusion criteria.…

What Satisfies Students?: Mining Student-Opinion Data with Regression and Decision Tree Analysis

ERIC Educational Resources Information Center

Thomas, Emily H.; Galambos, Nora

2004-01-01

To investigate how students' characteristics and experiences affect satisfaction, this study uses regression and decision tree analysis with the CHAID algorithm to analyze student-opinion data. A data mining approach identifies the specific aspects of students' university experience that most influence three measures of general satisfaction. The…

Patient complaints as a means to improve quality of hospital care. Results of a qualitative content analysis

PubMed

Hoffmann, Susanne; Dreher-Hummel, Thomas; Dollinger, Claudia; Frei, Irena Anna

2018-04-01

Background: Many hospitals have defined procedures for a complaint management. A systematic analysis of patient complaints helps to identify similar complaints and patterns so that targeted improvement measures can be derived (Gallagher & Mazor, 2015). Aim: Our three-month, nurse-led practice development project aimed 1) to identify complaints regarding communication issues, 2) to systemise and prioritise complaints regarding communication issues, and 3) to derive clinic-specific recommendations for improvement. Method: We analysed 273 complaints of patients documented by the quality management (secondary data analysis). Using content analysis and applying the coding taxonomy for inpatient complaints by Reader, Gillespie and Roberts (2014), we distinguished communication-related complaints. By further inductive differentiation of these complaints, we identified patterns and prioritised fields of action. Results: We identified 186 communication-related complaints divided into 16 subcategories. For each subcategory, improvement interventions were derived, discussed and prioritised. Conclusions: Thus, patient complaints provided an excellent opportunity for reflection and workplace learning for nurses. The analysis gave impulse to exemplify the subject “person-centered care” for nurses.

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies.

PubMed

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P =0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4 , were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients ( P =0.03). Four variants were identified in LEMD3 , and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified.

Combined approach for finding susceptibility genes in DISH/chondrocalcinosis families: whole-genome-wide linkage and IBS/IBD studies

PubMed Central

Couto, Ana Rita; Parreira, Bruna; Thomson, Russell; Soares, Marta; Power, Deborah M; Stankovich, Jim; Armas, Jácome Bruges; Brown, Matthew A

2017-01-01

Twelve families with exuberant and early-onset calcium pyrophosphate dehydrate chondrocalcinosis (CC) and diffuse idiopathic skeletal hyperostosis (DISH), hereafter designated DISH/CC, were identified in Terceira Island, the Azores, Portugal. Ninety-two (92) individuals from these families were selected for whole-genome-wide linkage analysis. An identity-by-descent (IBD) analysis was performed in 10 individuals from 5 of the investigated pedigrees. The chromosome area with the maximal logarithm of the odds score (1.32; P=0.007) was not identified using the IBD/identity-by-state (IBS) analysis; therefore, it was not investigated further. From the IBD/IBS analysis, two candidate genes, LEMD3 and RSPO4, were identified and sequenced. Nine genetic variants were identified in the RSPO4 gene; one regulatory variant (rs146447064) was significantly more frequent in control individuals than in DISH/CC patients (P=0.03). Four variants were identified in LEMD3, and the rs201930700 variant was further investigated using segregation analysis. None of the genetic variants in RSPO4 or LEMD3 segregated within the studied families. Therefore, although a major genetic effect was shown to determine DISH/CC occurrence within these families, the specific genetic variants involved were not identified. PMID:29104755

Clonal Analysis of the Microbiota of Severe Early Childhood Caries

PubMed Central

Kanasi, E.; Dewhirst, F.E.; Chalmers, N.I.; Kent, R.; Moore, A.; Hughes, C.V.; Pradhan, N.; Loo, C.Y.; Tanner, A.C.R.

2010-01-01

Background/Aims Severe early childhood caries is a microbial infection that severely compromises the dentition of young children. The aim of this study was to characterize the microbiota of severe early childhood caries. Methods Dental plaque samples from 2- to 6-year-old children were analyzed using 16S rRNA gene cloning and sequencing, and by specific PCR amplification for Streptococcus mutans and Bifidobacteriaceae species. Results Children with severe caries (n = 39) had more dental plaque and gingival inflammation than caries-free children (n = 41). Analysis of phylotypes from operational taxonomic unit analysis of 16S rRNA clonal metalibraries from severe caries and caries-free children indicated that while libraries differed significantly (p < 0.0001), there was increased diversity than detected in this clonal analysis. Using the Human Oral Microbiome Database, 139 different taxa were identified. Within the limits of this study, caries-associated taxa included Granulicatella elegans (p < 0.01) and Veillonella sp. HOT-780 (p < 0.01). The species associated with caries-free children included Capnocytophaga gingivalis (p < 0.01), Abiotrophia defectiva (p < 0.01), Lachnospiraceae sp. HOT-100 (p < 0.05), Streptococcus sanguinis (p < 0.05) and Streptococcus cristatus (p < 0.05). By specific PCR, S. mutans (p < 0.005) and Bifidobacteriaceae spp. (p < 0.0001) were significantly associated with severe caries. Conclusion Clonal analysis of 80 children identified a diverse microbiota that differed between severe caries and caries-free children, but the association of S. mutans with caries was from specific PCR analysis, not from clonal analysis, of samples. PMID:20861633

Food purchase patterns: empirical identification and analysis of their association with diet quality, socio-economic factors, and attitudes.

PubMed

Thiele, Silke; Peltner, Jonas; Richter, Almut; Mensink, Gert B M

2017-10-12

Empirically derived food purchase patterns provide information about which combinations of foods were purchased from households. The objective of this study was to identify what kinds of patterns exist, which level of diet quality they represent and which factors are associated with the patterns. The study made use of representative German consumption data in which approximately 12 million food purchases from 13,125 households are recorded. In accordance with healthy diet criteria the food purchases were assigned to 18 food groups of the German Food Pyramid. Based on these groups a factor analysis with a principal component technique was applied to identify food patterns. For these patterns nutrient and energy densities were examined. Using regression analysis, associations between pattern scores and socio-economic as well as attitude variables, reflecting personal statements about healthy eating, were analyzed. In total, three food purchase patterns could be identified: a natural, a processed and a traditional one. The first one was characterized by a higher purchasing of natural foods, the second by an increased purchasing of processed foods and the third by a meat-oriented diet. In each pattern there were specific diet quality criteria that could be improved whereas others were in line with actual dietary guidelines. In addition to socio-demographic factors, attitudes were significantly associated with the purchase patterns. The findings of this study are interesting from a public health perspective, as it can be assumed that measures focusing on specific aspects of diet quality are more promising than general ones. However, it is a major challenge to identify the population groups with their specific needs of improvement. As the patterns were associated with both socio-economic and attitude variables these grouping criteria could be used to define target groups.

Quantifying site-specific physical heterogeneity within an estuarine seascape

USGS Publications Warehouse

Kennedy, Cristina G.; Mather, Martha E.; Smith, Joseph M.

2017-01-01

Quantifying physical heterogeneity is essential for meaningful ecological research and effective resource management. Spatial patterns of multiple, co-occurring physical features are rarely quantified across a seascape because of methodological challenges. Here, we identified approaches that measured total site-specific heterogeneity, an often overlooked aspect of estuarine ecosystems. Specifically, we examined 23 metrics that quantified four types of common physical features: (1) river and creek confluences, (2) bathymetric variation including underwater drop-offs, (3) land features such as islands/sandbars, and (4) major underwater channel networks. Our research at 40 sites throughout Plum Island Estuary (PIE) provided solutions to two problems. The first problem was that individual metrics that measured heterogeneity of a single physical feature showed different regional patterns. We solved this first problem by combining multiple metrics for a single feature using a within-physical feature cluster analysis. With this approach, we identified sites with four different types of confluences and three different types of underwater drop-offs. The second problem was that when multiple physical features co-occurred, new patterns of total site-specific heterogeneity were created across the seascape. This pattern of total heterogeneity has potential ecological relevance to structure-oriented predators. To address this second problem, we identified sites with similar types of total physical heterogeneity using an across-physical feature cluster analysis. Then, we calculated an additive heterogeneity index, which integrated all physical features at a site. Finally, we tested if site-specific additive heterogeneity index values differed for across-physical feature clusters. In PIE, the sites with the highest additive heterogeneity index values were clustered together and corresponded to sites where a fish predator, adult striped bass (Morone saxatilis), aggregated in a related acoustic tracking study. In summary, we have shown general approaches to quantifying site-specific heterogeneity.

Truck characteristics analysis

DOT National Transportation Integrated Search

1998-01-01

This report documents the early observations from the Long-Term Pavement Performance (LTPP) Specific Pavement Studies (SPS) conducted as part of the LTPP Program Data Insight conducted to identify initial findings from the test sections established f...

SUPERFUND INNOVATIVE TECHNOLOGIES EVALUATION ...

EPA Pesticide Factsheets

This task seeks to identify high priority needs of the Regions and Program Offices for innovative field sampling, characterization, monitoring, and measurement technologies. When an appropriate solution to a specific problem is identified, a field demonstration is conducted to document the performance and cost of the proposed technologies. The use of field analysis almost always provides a savings in time and cost over the usual sample and ship to a conventional laboratory for analysis approach to site characterization and monitoring. With improvements in technology and appropriate quality assurance/quality control, field analysis has been shown to provide high quality data, useful for most environmental monitoring or characterization projects. An emphasis of the program is to seek out innovative solutions to existing problems and to provide the cost and performance data a user would require to make an informed decision regarding the adequacy of a technology to address a specific environmental problem. The objective of this program is to promote the acceptance and use of innovative field technologies by providing well-documented performance and cost data obtained from field demonstrations.

Paired Exome Analysis Reveals Clonal Evolution and Potential Therapeutic Targets in Urothelial Carcinoma.

PubMed

Lamy, Philippe; Nordentoft, Iver; Birkenkamp-Demtröder, Karin; Thomsen, Mathilde Borg Houlberg; Villesen, Palle; Vang, Søren; Hedegaard, Jakob; Borre, Michael; Jensen, Jørgen Bjerggaard; Høyer, Søren; Pedersen, Jakob Skou; Ørntoft, Torben F; Dyrskjøt, Lars

2016-10-01

Greater knowledge concerning tumor heterogeneity and clonality is needed to determine the impact of targeted treatment in the setting of bladder cancer. In this study, we performed whole-exome, transcriptome, and deep-focused sequencing of metachronous tumors from 29 patients initially diagnosed with early-stage bladder tumors (14 with nonprogressive disease and 15 with progressive disease). Tumors from patients with progressive disease showed a higher variance of the intrapatient mutational spectrum and a higher frequency of APOBEC-related mutations. Allele-specific expression was also higher in these patients, particularly in tumor suppressor genes. Phylogenetic analysis revealed a common origin of the metachronous tumors, with a higher proportion of clonal mutations in the ancestral branch; however, 19 potential therapeutic targets were identified as both ancestral and tumor-specific alterations. Few subclones were present based on PyClone analysis. Our results illuminate tumor evolution and identify candidate therapeutic targets in bladder cancer. Cancer Res; 76(19); 5894-906. ©2016 AACR. ©2016 American Association for Cancer Research.

Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility.

PubMed

Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J; Krueger, Gerald G; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T S; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L; Qureshi, Abrar A; de Bakker, Paul I W; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

2015-04-23

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations.

Dcode.org anthology of comparative genomic tools.

PubMed

Loots, Gabriela G; Ovcharenko, Ivan

2005-07-01

Comparative genomics provides the means to demarcate functional regions in anonymous DNA sequences. The successful application of this method to identifying novel genes is currently shifting to deciphering the non-coding encryption of gene regulation across genomes. To facilitate the practical application of comparative sequence analysis to genetics and genomics, we have developed several analytical and visualization tools for the analysis of arbitrary sequences and whole genomes. These tools include two alignment tools, zPicture and Mulan; a phylogenetic shadowing tool, eShadow for identifying lineage- and species-specific functional elements; two evolutionary conserved transcription factor analysis tools, rVista and multiTF; a tool for extracting cis-regulatory modules governing the expression of co-regulated genes, Creme 2.0; and a dynamic portal to multiple vertebrate and invertebrate genome alignments, the ECR Browser. Here, we briefly describe each one of these tools and provide specific examples on their practical applications. All the tools are publicly available at the http://www.dcode.org/ website.

Genome-wide meta-analysis identifies multiple novel associations and ethnic heterogeneity of psoriasis susceptibility

PubMed Central

Yin, Xianyong; Low, Hui Qi; Wang, Ling; Li, Yonghong; Ellinghaus, Eva; Han, Jiali; Estivill, Xavier; Sun, Liangdan; Zuo, Xianbo; Shen, Changbing; Zhu, Caihong; Zhang, Anping; Sanchez, Fabio; Padyukov, Leonid; Catanese, Joseph J.; Krueger, Gerald G.; Duffin, Kristina Callis; Mucha, Sören; Weichenthal, Michael; Weidinger, Stephan; Lieb, Wolfgang; Foo, Jia Nee; Li, Yi; Sim, Karseng; Liany, Herty; Irwan, Ishak; Teo, Yikying; Theng, Colin T. S.; Gupta, Rashmi; Bowcock, Anne; De Jager, Philip L.; Qureshi, Abrar A.; de Bakker, Paul I. W.; Seielstad, Mark; Liao, Wilson; Ståhle, Mona; Franke, Andre; Zhang, Xuejun; Liu, Jianjun

2015-01-01

Psoriasis is a common inflammatory skin disease with complex genetics and different degrees of prevalence across ethnic populations. Here we present the largest trans-ethnic genome-wide meta-analysis (GWMA) of psoriasis in 15,369 cases and 19,517 controls of Caucasian and Chinese ancestries. We identify four novel associations at LOC144817, COG6, RUNX1 and TP63, as well as three novel secondary associations within IFIH1 and IL12B. Fine-mapping analysis of MHC region demonstrates an important role for all three HLA class I genes and a complex and heterogeneous pattern of HLA associations between Caucasian and Chinese populations. Further, trans-ethnic comparison suggests population-specific effect or allelic heterogeneity for 11 loci. These population-specific effects contribute significantly to the ethnic diversity of psoriasis prevalence. This study not only provides novel biological insights into the involvement of immune and keratinocyte development mechanism, but also demonstrates a complex and heterogeneous genetic architecture of psoriasis susceptibility across ethnic populations. PMID:25903422

Microarray-based analysis of gene expression in lycopersicon esculentum seedling roots in response to cadmium, chromium, mercury, and lead.

PubMed

Hou, Jing; Liu, Xinhui; Wang, Juan; Zhao, Shengnan; Cui, Baoshan

2015-02-03

The effects of heavy metals in agricultural soils have received special attention due to their potential for accumulation in crops, which can affect species at all trophic levels. Therefore, there is a critical need for reliable bioassays for assessing risk levels due to heavy metals in agricultural soil. In the present study, we used microarrays to investigate changes in gene expression of Lycopersicon esculentum in response to Cd-, Cr-, Hg-, or Pb-spiked soil. Exposure to (1)/10 median lethal concentrations (LC50) of Cd, Cr, Hg, or Pb for 7 days resulted in expression changes in 29 Cd-specific, 58 Cr-specific, 192 Hg-specific and 864 Pb-specific genes as determined by microarray analysis, whereas conventional morphological and physiological bioassays did not reveal any toxicant stresses. Hierarchical clustering analysis showed that the characteristic gene expression profiles induced by Cd, Cr, Hg, and Pb were distinct from not only the control but also one another. Furthermore, a total of three genes related to "ion transport" for Cd, 14 genes related to "external encapsulating structure organization", "reproductive developmental process", "lipid metabolic process" and "response to stimulus" for Cr, 11 genes related to "cellular metabolic process" and "cellular response to stimulus" for Hg, 78 genes related to 20 biological processes (e.g., DNA metabolic process, monosaccharide catabolic process, cell division) for Pb were identified and selected as their potential biomarkers. These findings demonstrated that microarray-based analysis of Lycopersicon esculentum was a sensitive tool for the early detection of potential toxicity of heavy metals in agricultural soil, as well as an effective tool for identifying the heavy metal-specific genes, which should be useful for assessing risk levels due to heavy metals in agricultural soil.

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

How healthcare states matter: comparing the introduction of clinical standards in Britain and Germany.

PubMed

Burau, Viola; Fenton, Laura

2009-01-01

This paper aims to identify variation in the introduction of New Public Management reforms in healthcare and how this variation is related to country-specific healthcare states. The analysis uses the introduction of clinical standards in Britain and Germany as cases. The two countries are characterised by interesting differences in relation to the institutional set-up of healthcare states and as such present ideal cases to explore the specific ways of how healthcare states filter clinical standards as tools of a generic managerialism. Both countries have introduced clinical standards but, importantly, the substantive nature of clinical standards differs, reflecting differences in initial institutional conditions. More specifically, in Britain clinical standards have taken the form of two parallel policies, which strengthen hierarchy-based governing and redefine professional self-regulation. In Germany, by contrast, clinical standards come in one single policy, which strengthens the hybrid of network- and hierarchy-based governing and to some extent also pure hierarchy-based forms of governing. First, with its cross-country comparative focus, the analysis is able to identify systematic variations across healthcare states and the specific ways in which they impact on the introduction of New Public Management. Second, with its focus on clinical standards, the analysis deals with the governance of medical practice as one of the central areas of healthcare states.

In silico analysis of stomach lineage specific gene set expression pattern in gastric cancer.

PubMed

Pandi, Narayanan Sathiya; Suganya, Sivagurunathan; Rajendran, Suriliyandi

2013-10-04

Stomach lineage specific gene products act as a protective barrier in the normal stomach and their expression maintains the normal physiological processes, cellular integrity and morphology of the gastric wall. However, the regulation of stomach lineage specific genes in gastric cancer (GC) is far less clear. In the present study, we sought to investigate the role and regulation of stomach lineage specific gene set (SLSGS) in GC. SLSGS was identified by comparing the mRNA expression profiles of normal stomach tissue with other organ tissue. The obtained SLSGS was found to be under expressed in gastric tumors. Functional annotation analysis revealed that the SLSGS was enriched for digestive function and gastric epithelial maintenance. Employing a single sample prediction method across GC mRNA expression profiles identified the under expression of SLSGS in proliferative type and invasive type gastric tumors compared to the metabolic type gastric tumors. Integrative pathway activation prediction analysis revealed a close association between estrogen-α signaling and SLSGS expression pattern in GC. Elevated expression of SLSGS in GC is associated with an overall increase in the survival of GC patients. In conclusion, our results highlight that estrogen mediated regulation of SLSGS in gastric tumor is a molecular predictor of metabolic type GC and prognostic factor in GC. Copyright © 2013 Elsevier Inc. All rights reserved.

Phylogeny of isolates of Prunus necrotic ringspot virus from the Ilarvirus Ringtest and identification of group-specific features.

PubMed

Hammond, R W

2003-06-01

Isolates of Prunus necrotic ringspot virus (PNRSV) were examined to establish the level of naturally occurring sequence variation in the coat protein (CP) gene and to identify group-specific genome features that may prove valuable for the generation of diagnostic reagents. Phylogenetic analysis of a 452 bp sequence of 68 virus isolates, 20 obtained from the European Union Ilarvirus Ringtest held in October 1998, confirmed the clustering of the isolates into three distinct groups. Although no correlation was found between the sequence and host or geographic origin, there was a general trend for severe isolates to cluster into one group. Group-specific features have been identified for discrimination between virus strains.

NAC transcription factor genes: genome-wide identification, phylogenetic, motif and cis-regulatory element analysis in pigeonpea (Cajanus cajan (L.) Millsp.).

PubMed

Satheesh, Viswanathan; Jagannadham, P Tej Kumar; Chidambaranathan, Parameswaran; Jain, P K; Srinivasan, R

2014-12-01

The NAC (NAM, ATAF and CUC) proteins are plant-specific transcription factors implicated in development and stress responses. In the present study 88 pigeonpea NAC genes were identified from the recently published draft genome of pigeonpea by using homology based and de novo prediction programmes. These sequences were further subjected to phylogenetic, motif and promoter analyses. In motif analysis, highly conserved motifs were identified in the NAC domain and also in the C-terminal region of the NAC proteins. A phylogenetic reconstruction using pigeonpea, Arabidopsis and soybean NAC genes revealed 33 putative stress-responsive pigeonpea NAC genes. Several stress-responsive cis-elements were identified through in silico analysis of the promoters of these putative stress-responsive genes. This analysis is the first report of NAC gene family in pigeonpea and will be useful for the identification and selection of candidate genes associated with stress tolerance.

Are nutrition messages lost in transmission? Assessing the quality and consistency of diabetes guideline recommendations on the delivery of nutrition therapy.

PubMed

Hale, Kelli; Capra, Sandra; Bauer, Judy

2016-12-01

To provide an overview of (1) the consistency of Type 2 Diabetes Clinical Practice Guidelines recommendations on the delivery of nutrition therapy and (2) Clinical Practice Guideline quality. Large international clinical practice guideline repositories, diabetes organisation websites, and electronic databases (Pubmed, Scopus), were searched to identify Clinical Practice Guidelines for adults with type 2 diabetes published 2005 to August 2014. Recommendations on the delivery of nutrition therapy were extracted and inductive content analysis was used to analyse consistency. Two researchers independently assessed guideline quality using the AGREE II tool. Nine topics were identified from the recommendations. Overall the consistency of the recommendations was related to guideline type. Compared with nutrition-specific guidelines, the broad ones had a broader focus and included more patient-focused recommendations. The ten Clinical Practice Guidelines assessed included six broad guidelines and four nutrition specific guidelines. Based on AGREE II analysis, the broad guidelines were higher quality than nutrition-specific ones. Broad Clinical Practice Guidelines were higher quality and included more patient-focused recommendations than nutrition-specific ones. Our findings suggest a need for nutrition-specific guidelines to be modified to include greater patient-focus, or for practitioners delivering nutrition therapy to adopt broad Clinical Practice Guidelines. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Active and passive surveillance of enoxaparin generics: a case study relevant to biosimilars.

PubMed

Grampp, Gustavo; Bonafede, Machaon; Felix, Thomas; Li, Edward; Malecki, Michael; Sprafka, J Michael

2015-03-01

This retrospective analysis assessed the capability of active and passive safety surveillance systems to track product-specific safety events in the USA for branded and generic enoxaparin, a complex injectable subject to immune-related and other adverse events (AEs). Analysis of heparin-induced thrombocytopenia (HIT) incidence was performed on benefit claims for commercial and Medicare supplemental-insured individuals newly treated with enoxaparin under pharmacy benefit (1 January 2009 - 30 June 2012). Additionally, spontaneous reports from the FDA AE Reporting System were reviewed to identify incidence and attribution of enoxaparin-related reports to specific manufacturers. Specific, dispensed products were identifiable from National Drug Codes only in pharmacy-benefit databases, permitting sensitive comparison of HIT incidence in nearly a third of patients treated with brand or generic enoxaparin. After originator medicine's loss of exclusivity, only 5% of spontaneous reports were processed by generic manufacturers; reports attributable to specific generics were approximately ninefold lower than expected based on market share. Claims data were useful for active surveillance of enoxaparin generics dispensed under pharmacy benefits but not for products administered under medical benefits. These findings suggest that the current spontaneous reporting system will not distinguish product-specific safety signals for products distributed by multiple manufacturers, including biosimilars.

[Psychosocial and developmental outcomes of TYAs with cancer: Are there any specific characteristics for the young adults?

PubMed

Leprince, Tanguy; Sauveplane, Dominique; Ricadat, Elise; Seigneur, Étienne; Marioni, Gabrielle

2016-12-01

During the last few years, specific support devices and even dedicated units for teenagers and young adults (TYAs - patients grouped in the 15-25 years age group) appeared in oncology. If the existing literature review allows identifying many written work related to the experience of cancer during adolescence, resources about "young adults" are not only far less abundant, but rarely give the definition of what is a "young adult". Based on this observation, it appears necessary, at this stage of our practice, to question the definition and psychosocial outcomes of those psychiatrists and psychologists also call "young adults". Are they so different compared to teenagers? Do they have their own specificities? Based on the analysis of the general literature, we will seek to define the highlights of this moment of life and to identify their specific psychosocial and developmental outcomes. Thus, we will be able to study more accurately the experience of young adults facing cancer and the associated psychological side effects. Based on this analysis, we will present the issues which seemed to be specific in the psychological support of young adults and their relatives. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Characterization of the Proteome of Theobroma cacao Beans by Nano-UHPLC-ESI MS/MS.

PubMed

Scollo, Emanuele; Neville, David; Oruna-Concha, M Jose; Trotin, Martine; Cramer, Rainer

2018-02-01

Cocoa seed storage proteins play an important role in flavour development as aroma precursors are formed from their degradation during fermentation. Major proteins in the beans of Theobroma cacao are the storage proteins belonging to the vicilin and albumin classes. Although both these classes of proteins have been extensively characterized, there is still limited information on the expression and abundance of other proteins present in cocoa beans. This work is the first attempt to characterize the whole cocoa bean proteome by nano-UHPLC-ESI MS/MS analysis using tryptic digests of cocoa bean protein extracts. The results of this analysis show that >1000 proteins could be identified using a species-specific Theobroma cacao database. The majority of the identified proteins were involved with metabolism and energy. Additionally, a significant number of the identified proteins were linked to protein synthesis and processing. Several proteins were also involved with plant response to stress conditions and defence. Albumin and vicilin storage proteins showed the highest intensity values among all detected proteins, although only seven entries were identified as storage proteins. A comparison of MS/MS data searches carried out against larger non-specific databases confirmed that using a species-specific database can increase the number of identified proteins, and at the same time reduce the number of false positives. The results of this work will be useful in developing tools that can allow the comparison of the proteomic profile of cocoa beans from different genotypes and geographic origins. Data are available via ProteomeXchange with identifier PXD005586. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM.

PubMed

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-07

O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

PubMed Central

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-01

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting. PMID:21249131

Cleaning up contaminated wood-treating sites. Background paper

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

NONE

This report identifies technologies available for organic hazardous waste cleanup at woodtreating sites throughout the country. OTA has identified a range of such technologies that have been selected in the past and could be applied to other sites in the future. The applicability of a technology to a particular Superfund site has to be based on many site-specific factors. Nevertheless, it is clear that a number of the approaches identified by OTA may be appropriate and could prove useful if more detailed site-specific studies and tests were done. Although this study focused on the Texarkana site, decisionmakers and the publicmore » could benefit from this analysis in selecting future cleanup strategies for other sites.« less

Territorial energy assessment. Phase I

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

Not Available

1981-07-31

The goal of the project is to provide a current perspective on territorial energy problems, to identify existing energy supply and demand data, and to identify energy resources that might be developed and appropriate technology options. The cost of the technical assessment and economic analysis activities required to support the development of specific energy plans is defined and estimated. Information is summarized for the US Territories, the Pacific Trust Territories, and Puerto Rico. An overview and analysis of the the Pacific Island Entities; profiles of the Pacifc Island Entities; and the Caribbean Island Entities are presented. (MCW)

Genetic Screening Identifies Cyanogenesis-Deficient Mutants of Lotus japonicus and Reveals Enzymatic Specificity in Hydroxynitrile Glucoside Metabolism[W][OA

PubMed Central

Takos, Adam; Lai, Daniela; Mikkelsen, Lisbeth; Abou Hachem, Maher; Shelton, Dale; Motawia, Mohammed Saddik; Olsen, Carl Erik; Wang, Trevor L.; Martin, Cathie; Rook, Fred

2010-01-01

Cyanogenesis, the release of hydrogen cyanide from damaged plant tissues, involves the enzymatic degradation of amino acid–derived cyanogenic glucosides (α-hydroxynitrile glucosides) by specific β-glucosidases. Release of cyanide functions as a defense mechanism against generalist herbivores. We developed a high-throughput screening method and used it to identify cyanogenesis deficient (cyd) mutants in the model legume Lotus japonicus. Mutants in both biosynthesis and catabolism of cyanogenic glucosides were isolated and classified following metabolic profiling of cyanogenic glucoside content. L. japonicus produces two cyanogenic glucosides: linamarin (derived from Val) and lotaustralin (derived from Ile). Their biosynthesis may involve the same set of enzymes for both amino acid precursors. However, in one class of mutants, accumulation of lotaustralin and linamarin was uncoupled. Catabolic mutants could be placed in two complementation groups, one of which, cyd2, encoded the β-glucosidase BGD2. Despite the identification of nine independent cyd2 alleles, no mutants involving the gene encoding a closely related β-glucosidase, BGD4, were identified. This indicated that BGD4 plays no role in cyanogenesis in L. japonicus in vivo. Biochemical analysis confirmed that BGD4 cannot hydrolyze linamarin or lotaustralin and in L. japonicus is specific for breakdown of related hydroxynitrile glucosides, such as rhodiocyanoside A. By contrast, BGD2 can hydrolyze both cyanogenic glucosides and rhodiocyanosides. Our genetic analysis demonstrated specificity in the catabolic pathways for hydroxynitrile glucosides and implied specificity in their biosynthetic pathways as well. In addition, it has provided important tools for elucidating and potentially modifying cyanogenesis pathways in plants. PMID:20453117

Alternative splicing and trans-splicing events revealed by analysis of the Bombyx mori transcriptome

PubMed Central

Shao, Wei; Zhao, Qiong-Yi; Wang, Xiu-Ye; Xu, Xin-Yan; Tang, Qing; Li, Muwang; Li, Xuan; Xu, Yong-Zhen

2012-01-01

Alternative splicing and trans-splicing events have not been systematically studied in the silkworm Bombyx mori. Here, the silkworm transcriptome was analyzed by RNA-seq. We identified 320 novel genes, modified 1140 gene models, and found thousands of alternative splicing and 58 trans-splicing events. Studies of three SR proteins show that both their alternative splicing patterns and mRNA products are conserved from insect to human, and one isoform of Srsf6 with a retained intron is expressed sex-specifically in silkworm gonads. Trans-splicing of mod(mdg4) in silkworm was experimentally confirmed. We identified integrations from a common 5′-gene with 46 newly identified alternative 3′-exons that are located on both DNA strands over a 500-kb region. Other trans-splicing events in B. mori were predicted by bioinformatic analysis, in which 12 events were confirmed by RT-PCR, six events were further validated by chimeric SNPs, and two events were confirmed by allele-specific RT-PCR in F1 hybrids from distinct silkworm lines of JS and L10, indicating that trans-splicing is more widespread in insects than previously thought. Analysis of the B. mori transcriptome by RNA-seq provides valuable information of regulatory alternative splicing events. The conservation of splicing events across species and newly identified trans-splicing events suggest that B. mori is a good model for future studies. PMID:22627775

Identification and Functional Analysis of Healing Regulators in Drosophila

PubMed Central

Álvarez-Fernández, Carmen; Tamirisa, Srividya; Prada, Federico; Chernomoretz, Ariel; Podhajcer, Osvaldo; Blanco, Enrique; Martín-Blanco, Enrique

2015-01-01

Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the overall steps in wound healing, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process. However, they do allow the less understood aspects of the healing response to be explored, e.g., which signal(s) are responsible for initiating tissue remodeling? How is sealing of the epithelia achieved? Or, what inhibitory cues cancel the healing machinery upon completion? Answering these and other questions first requires the identification and functional analysis of wound specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method that is healing-permissive and that allows live imaging and biochemical analysis of cultured imaginal discs. We performed comparative genome-wide profiling between Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. Sets of potential wound-specific genes were subsequently identified. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in healing assays. This non-saturated analysis defines a relevant set of genes whose changes in expression level are functionally significant for proper tissue repair. Amongst these we identified the TCP1 chaperonin complex as a key regulator of the actin cytoskeleton essential for the wound healing response. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound healing response. PMID:25647511

Genome-wide association study in East Asians suggests UHMK1 as a novel bone mineral density susceptibility gene.

PubMed

Choi, Hyung Jin; Park, Hyojung; Zhang, Lei; Kim, Jung Hee; Kim, Ye An; Yang, Jae-Yeon; Pei, Yu-Fang; Tian, Qing; Shen, Hui; Hwang, Joo-Yeon; Deng, Hong-Wen; Cho, Nam H; Shin, Chan Soo

2016-10-01

To identify genetic variants that influence bone mineral density (BMD) in East Asians, we performed a quantitative trait analysis of lumbar spine, total hip and femoral neck BMD in a Korean population-based cohort (N=2729) and follow-up replication analysis in a Chinese Han population and two Caucasian populations (N=1547, 2250 and 987, respectively). From the meta-analysis of the stage 1 discovery analysis and stage 2 replication analysis, we identified four BMD loci that reached near-genome-wide significance level (P<5×10(-7)). One locus on 1q23 (UHMK1, rs16863247, P=4.1×10(-7) for femoral neck BMD and P=3.2×10(-6) for total hip BMD) was a novel BMD signal. Interestingly, rs16863247 was very rare in Caucasians (minor allele frequency<0.01), indicating that this association could be specific to East Asians. In gender specific analysis, rs1160574 on 1q32 (KCNH1) was associated with femoral neck BMD (P=2.1×10(-7)) in female subjects. rs9371538 in the known BMD region on 6q25 ESR1 was associated with lumbar spine BMD (P=5.6×10(-9)). rs7776725 in the known BMD region on 7q31 WTN16 was associated with total hip BMD (P=8.6×10(-9)). In osteoblasts, endogenous UHMK1 expression was increased during differentiation and UHMK1 knockdown decreased its differentiation, while UHMK1 overexpression increased its differentiation. In osteoclasts, endogenous UHMK1 expression was decreased during differentiation and UHMK1 knockdown increased its differentiation, while UHMK1 overexpression decreased its differentiation. In conclusion, our genome-wide association study identified the UHMK1 gene as a novel BMD locus specific to East Asians. Functional studies suggest a role of UHMK1 on regulation of osteoblasts and osteoclasts. Copyright © 2016 Elsevier Inc. All rights reserved.

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

PubMed Central

Zhang, Shujun

2018-01-01

Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci

PubMed Central

Tromp, Gerard; Kuivaniemi, Helena; Gretarsdottir, Solveig; Baas, Annette F.; Giusti, Betti; Strauss, Ewa; van‘t Hof, Femke N.G.; Webb, Thomas R.; Erdman, Robert; Ritchie, Marylyn D.; Elmore, James R.; Verma, Anurag; Pendergrass, Sarah; Kullo, Iftikhar J.; Ye, Zi; Peissig, Peggy L.; Gottesman, Omri; Verma, Shefali S.; Malinowski, Jennifer; Rasmussen-Torvik, Laura J.; Borthwick, Kenneth M.; Smelser, Diane T.; Crosslin, David R.; de Andrade, Mariza; Ryer, Evan J.; McCarty, Catherine A.; Böttinger, Erwin P.; Pacheco, Jennifer A.; Crawford, Dana C.; Carrell, David S.; Gerhard, Glenn S.; Franklin, David P.; Carey, David J.; Phillips, Victoria L.; Williams, Michael J.A.; Wei, Wenhua; Blair, Ross; Hill, Andrew A.; Vasudevan, Thodor M.; Lewis, David R.; Thomson, Ian A.; Krysa, Jo; Hill, Geraldine B.; Roake, Justin; Merriman, Tony R.; Oszkinis, Grzegorz; Galora, Silvia; Saracini, Claudia; Abbate, Rosanna; Pulli, Raffaele; Pratesi, Carlo; Saratzis, Athanasios; Verissimo, Ana R.; Bumpstead, Suzannah; Badger, Stephen A.; Clough, Rachel E.; Cockerill, Gillian; Hafez, Hany; Scott, D. Julian A.; Futers, T. Simon; Romaine, Simon P.R.; Bridge, Katherine; Griffin, Kathryn J.; Bailey, Marc A.; Smith, Alberto; Thompson, Matthew M.; van Bockxmeer, Frank M.; Matthiasson, Stefan E.; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Blankensteijn, Jan D.; Teijink, Joep A.W.; Wijmenga, Cisca; de Graaf, Jacqueline; Kiemeney, Lambertus A.; Lindholt, Jes S.; Hughes, Anne; Bradley, Declan T.; Stirrups, Kathleen; Golledge, Jonathan; Norman, Paul E.; Powell, Janet T.; Humphries, Steve E.; Hamby, Stephen E.; Goodall, Alison H.; Nelson, Christopher P.; Sakalihasan, Natzi; Courtois, Audrey; Ferrell, Robert E.; Eriksson, Per; Folkersen, Lasse; Franco-Cereceda, Anders; Eicher, John D.; Johnson, Andrew D.; Betsholtz, Christer; Ruusalepp, Arno; Franzén, Oscar; Schadt, Eric E.; Björkegren, Johan L.M.; Lipovich, Leonard; Drolet, Anne M.; Verhoeven, Eric L.; Zeebregts, Clark J.; Geelkerken, Robert H.; van Sambeek, Marc R.; van Sterkenburg, Steven M.; de Vries, Jean-Paul; Stefansson, Kari; Thompson, John R.; de Bakker, Paul I.W.; Deloukas, Panos; Sayers, Robert D.; Harrison, Seamus C.; van Rij, Andre M.; Samani, Nilesh J.

2017-01-01

Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease. PMID:27899403

Waist circumference cut-off points for identification of abdominal obesity among the tunisian adult population.

PubMed

Bouguerra, R; Alberti, H; Smida, H; Salem, L B; Rayana, C B; El Atti, J; Achour, A; Gaigi, S; Slama, C B; Zouari, B; Alberti, K G M M

2007-11-01

Waist circumference (WC) is a convenient measure of abdominal adipose tissue. It itself is a cardiovascular disease (CVD) and diabetes-risk factor and is strongly linked to other CVD risk factors. There are, however, ethnic differences in the relationship of WC to the other risk factors. The aim of this study was to determine the optimal cut-off points of WC and body mass index (BMI) at which cardiovascular risk factors can be identified with maximum sensitivity and specificity in a representative sample of the Tunisian adult population and to investigate any correlation between WC and BMI. We used a sample of the Tunisian National Nutrition Survey, a cross-sectional population-based survey, conducted in 1996 on a large nationally representative sample, which included 3435 adults (1244 men and 2191 women) of 20 years or older. WC, BMI, blood pressure and fasting blood measurements (plasma glucose, total cholesterol, triglycerides) were recorded. Receiver operating characteristic (ROC) curve analysis was used to identify optimal cut-off values of WC and BMI to identify with maximum sensitivity and specificity the detection of high blood pressure, hyperglycaemia, high blood cholesterol and hypertriglyceridaemia. ROC curve analysis suggested WC cut-off points of 85 cm in men and 85 cm in women for the optimum detection of high blood pressure, diabetes and dyslipidaemia. The optimum BMI cut-off points for predicting cardiovascular risk factors were 24 kg/m(2) in men and 27 kg/m(2) in women. The cut-off points recommended for the Caucasian population differ from those appropriate for the Tunisian population. The data show a continuous increase in odds ratios of each cardiovascular risk factor, with increasing level of WC and BMI. WC exceeding 85 cm in men and 79 cm in women correctly identified subjects with a BMI of >/=25 kg/m(2), sensitivity of >90% and specificity of >83%. Based on the ROC analysis, we suggest a WC of 85 cm for both men and women as appropriate cut-off points to identify central obesity for the purposes of CVD and diabetes-risk detection among Tunisians. WCs of 85 cm in men and 79 cm in women were the most sensitive and specific to identify most subjects with a BMI >/=25 kg/m(2).

Construct and Predictive Validity of the Core Phonics Survey: A Diagnostic Assessment for Students with Specific Learning Disabilities

ERIC Educational Resources Information Center

Park, Yujeong; Benedict, Amber E.; Brownell, Mary T.

2014-01-01

The factor structure of the CORE Phonics Survey was analyzed using a sample of 165 students in upper elementary school with specific learning disabilities. Confirmatory factor analysis was used to identify the hypothesized constructs of the CORE Phonics Survey and predictive validity of the CORE Phonics Survey to predict students' success in word…

Presence and Image of Women in the Information Media Aimed at Adolescents Aged 10 to 16.

ERIC Educational Resources Information Center

Dansereau, Stephanie; Maranda, Jeanne

An exploratory study identified the areas of information most commonly featured in the printed and electronic media designed specifically for adolescents aged 10-16 and also identified the presence and role of women in the information targeted to this age group. A content analysis was made of both French- and English-language television programs…

A Comparative Needs Analysis of Supportive Services for Non-Handicapped and Handicapped Persons Seeking Post-Secondary Education from the Community College System.

ERIC Educational Resources Information Center

Graham, Gary L.; And Others

This study was concerned with identifying the specific information needs and personal needs of handicapped students and comparing the selected needs with needs of general students. The study hypothesis was that there is no significant difference between identified needs of handicapped students and those of general students. The significance…

An Analysis of the Financial and Political Consequences Experienced by School Corporations when Closing a School or Consolidating Schools

ERIC Educational Resources Information Center

Morikis, Peter

2010-01-01

The purpose of this study was to identify the common consequences experienced by school corporations when closing or consolidating schools. The primary focus of the study was to identify the financial and political consequences experienced by school corporations when closing a school closing or consolidating schools. Specific questions regarding…

Mission Analysis for High Specific Impulse Deep Space Exploration

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Polsgrove, Tara; Brady, Hugh J. (Technical Monitor)

2002-01-01

This paper describes trajectory calculations for high specific impulse engines. Specific impulses on the order of 10,000 to 100,000 sec are predicted in a variety of fusion powered propulsion systems. This paper and its companion paper seek to build on analyses in the literature to yield an analytical routine for determining time of flight and payload fraction to a predetermined destination. The companion paper will compare the results of this analysis to the trajectories determined by several trajectory codes. The major parameters that affect time of flight and payload fraction will be identified and their sensitivities quantified. A review of existing fusion propulsion concepts and their capabilities will also be tabulated.

De novo assembly and analysis of the Artemisia argyi transcriptome and identification of genes involved in terpenoid biosynthesis.

PubMed

Liu, Miaomiao; Zhu, Jinhang; Wu, Shengbing; Wang, Chenkai; Guo, Xingyi; Wu, Jiawen; Zhou, Meiqi

2018-04-11

Artemisia argyi Lev. et Vant. (A. argyi) is widely utilized for moxibustion in Chinese medicine, and the mechanism underlying terpenoid biosynthesis in its leaves is suggested to play an important role in its medicinal use. However, the A. argyi transcriptome has not been sequenced. Herein, we performed RNA sequencing for A. argyi leaf, root and stem tissues to identify as many as possible of the transcribed genes. In total, 99,807 unigenes were assembled by analysing the expression profiles generated from the three tissue types, and 67,446 of those unigenes were annotated in public databases. We further performed differential gene expression analysis to compare leaf tissue with the other two tissue types and identified numerous genes that were specifically expressed or up-regulated in leaf tissue. Specifically, we identified multiple genes encoding significant enzymes or transcription factors related to terpenoid synthesis. This study serves as a valuable resource for transcriptome information, as many transcribed genes related to terpenoid biosynthesis were identified in the A. argyi transcriptome, providing a functional genomic basis for additional studies on molecular mechanisms underlying the medicinal use of A. argyi.

Behavioural Difficulties That Co‐occur With Specific Word Reading Difficulties: A UK Population‐ Based Cohort Study

PubMed Central

Ryder, Denise; Norwich, Brahm; Ford, Tamsin

2015-01-01

This study aimed to examine the association between specific word reading difficulties (SWRD) identified at age 7 years using a discrepancy approach and subsequent dimensional measures of behavioural difficulties reported by teachers and parents at age 11 years. Behavioural problems were assessed using the Strengths and Difficulties Questionnaire. Secondary analysis of a UK representative population‐based sample of children (n = 12 631) was conducted using linear regression models. There were 284 children (2.2%) identified with SWRD at age 7 years. Children with SWRD had significantly higher scores on all measures of behavioural difficulties in unadjusted analysis. SWRD was associated with elevated behavioural difficulties at age 11 years according to parent report, and with greater emotional problems, hyperactivity and conduct issues according to teachers, even after having controlled for baseline difficulties. These results were replicated for children with low reading attainment, but no cognitive ability discrepancy. Categories of special educational need into which children with SWRD were classed at school were varied. Given high rates of co‐occurring behavioural difficulties, assessment that identifies each individual child's specific functional, rather than categorical, difficulties is likely to be the most effective way of providing classroom support. © 2015 The Authors. Dyslexia published by John Wiley & Sons Ltd. PMID:25693052

Dlx1 and Rgs5 in the Ductus Arteriosus: Vessel-Specific Genes Identified by Transcriptional Profiling of Laser-Capture Microdissected Endothelial and Smooth Muscle Cells

PubMed Central

Bökenkamp, Regina; van Brempt, Ronald; van Munsteren, Jacoba Cornelia; van den Wijngaert, Ilse; de Hoogt, Ronald; Finos, Livio; Goeman, Jelle; Groot, Adriana Cornelia Gittenberger-de; Poelmann, Robert Eugen; Blom, Nicolaas Andreas; DeRuiter, Marcus Cornelis

2014-01-01

Closure of the ductus arteriosus (DA) is a crucial step in the transition from fetal to postnatal life. Patent DA is one of the most common cardiovascular anomalies in children with significant clinical consequences especially in premature infants. We aimed to identify genes that specify the DA in the fetus and differentiate it from the aorta. Comparative microarray analysis of laser-captured microdissected endothelial (ECs) and vascular smooth muscle cells (SMCs) from the DA and aorta of fetal rats (embryonic day 18 and 21) identified vessel-specific transcriptional profiles. We found a strong age-dependency of gene expression. Among the genes that were upregulated in the DA the regulator of the G-protein coupled receptor 5 (Rgs5) and the transcription factor distal-less homeobox 1 (Dlx1) exhibited the highest and most significant level of differential expression. The aorta showed a significant preferential expression of the Purkinje cell protein 4 (Pcp4) gene. The results of the microarray analysis were validated by real-time quantitative PCR and immunohistochemistry. Our study confirms vessel-specific transcriptional profiles in ECs and SMCs of rat DA and aorta. Rgs5 and Dlx1 represent novel molecular targets for the regulation of DA maturation and closure. PMID:24489801

Rapid detection of peptide markers for authentication purposes in raw and cooked meat using ambient liquid extraction surface analysis mass spectrometry.

PubMed

Montowska, Magdalena; Alexander, Morgan R; Tucker, Gregory A; Barrett, David A

2014-10-21

In this Article, our previously developed ambient LESA-MS methodology is implemented to analyze five types of thermally treated meat species, namely, beef, pork, horse, chicken, and turkey meat, to select and identify heat-stable and species-specific peptide markers. In-solution tryptic digests of cooked meats were deposited onto a polymer surface, followed by LESA-MS analysis and evaluation using multivariate data analysis and tandem electrospray MS. The five types of cooked meat were clearly discriminated using principal component analysis and orthogonal partial least-squares discriminant analysis. 23 heat stable peptide markers unique to species and muscle protein were identified following data-dependent tandem LESA-MS analysis. Surface extraction and direct ambient MS analysis of mixtures of cooked meat species was performed for the first time and enabled detection of 10% (w/w) of pork, horse, and turkey meat and 5% (w/w) of chicken meat in beef, using the developed LESA-MS/MS analysis. The study shows, for the first time, that ambient LESA-MS methodology displays specificity sufficient to be implemented effectively for the analysis of processed and complex peptide digests. The proposed approach is much faster and simpler than other measurement tools for meat speciation; it has potential for application in other areas of meat science or food production.

The Long Noncoding RNA Landscape of the Mouse Eye.

PubMed

Chen, Weiwei; Yang, Shuai; Zhou, Zhonglou; Zhao, Xiaoting; Zhong, Jiayun; Reinach, Peter S; Yan, Dongsheng

2017-12-01

Long noncoding RNAs (lncRNAs) are important regulators of diverse biological functions. However, an extensive in-depth analysis of their expression profile and function in mammalian eyes is still lacking. Here we describe comprehensive landscapes of stage-dependent and tissue-specific lncRNA expression in the mouse eye. Affymetrix transcriptome array profiled lncRNA signatures from six different ocular tissue subsets (i.e., cornea, lens, retina, RPE, choroid, and sclera) in newborn and 8-week-old mice. Quantitative RT-PCR analysis validated array findings. Cis analyses and Gene Ontology (GO) annotation of protein-coding genes adjacent to signature lncRNA loci clarified potential lncRNA roles in maintaining tissue identity and regulating eye maturation during the aforementioned phase. In newborn and 8-week-old mice, we identified 47,332 protein-coding and noncoding gene transcripts. LncRNAs comprise 19,313 of these transcripts annotated in public data banks. During this maturation phase of these six different tissue subsets, more than 1000 lncRNAs expression levels underwent ≥2-fold changes. qRT-PCR analysis confirmed part of the gene microarray analysis results. K-means clustering identified 910 lncRNAs in the P0 groups and 686 lncRNAs in the postnatal 8-week-old groups, suggesting distinct tissue-specific lncRNA clusters. GO analysis of protein-coding genes proximal to lncRNA signatures resolved close correlations with their tissue-specific functional maturation between P0 and 8 weeks of age in the 6 tissue subsets. Characterizating maturational changes in lncRNA expression patterns as well as tissue-specific lncRNA signatures in six ocular tissues suggest important contributions made by lncRNA to the control of developmental processes in the mouse eye.

PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing

PubMed Central

Dasa, Siva Sai Krishna; Kelly, Kimberly A.

2016-01-01

Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective—targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer-associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use. PMID:27186887

Politics and the Movie

ERIC Educational Resources Information Center

Funderburk, Charles

1978-01-01

Explains how the use of feature-length motion pictures, combined with interesting readings, can generate enthusiasm, discussion, and analysis of basic political ideas, concepts, and values. Reviews costs and identifies specific movies and readings on various political topics. (AV)

Test plan : Branson TRIP system/historical data analysis

DOT National Transportation Integrated Search

2000-06-28

The focus of this data collection effort centers around the following six factors specifically articulated by the Federal Lands Highway, Executive Quality Council. They are as follows: Level of Contracting Out--identify what Preiliminary Engineering ...

The information filter: how dentists use diet diary information to give patients clear and simple advice.

PubMed

Arheiam, Arheiam; Brown, Stephen L; Higham, Susan M; Albadri, Sondos; Harris, Rebecca V

2016-12-01

Diet diaries are recommended for dentists to monitor children's sugar consumption. Diaries provide multifaceted dietary information, but patients respond better to simpler advice. We explore how dentists integrate information from diet diaries to deliver useable advice to patients. As part of a questionnaire study of general dental practitioners (GDPs) in Northwest England, we asked dentists to specify the advice they would give a hypothetical patient based upon a diet diary case vignette. A sequential mixed method approach was used for data analysis: an initial inductive content analysis (ICA) to develop coding system to capture the complexity of dietary assessment and delivered advice. Using these codes, a quantitative analysis was conducted to examine correspondences between identified dietary problems and advice given. From these correspondences, we inferred how dentists reduced problems to give simple advice. A total of 229 dentists' responses were analysed. ICA on 40 questionnaires identified two distinctive approaches of developing diet advice: a summative (summary of issues into an all-encompassing message) and a selective approach (selection of a main message approach). In the quantitative analysis of all responses, raw frequencies indicated that dentists saw more problems than they advised on and provided highly specific advice on a restricted number of problems (e.g. not eating sugars before bedtime 50.7% or harmful items 42.4%, rather than simply reducing the amount of sugar 9.2%). Binary logistic regression models indicate that dentists provided specific advice that was tailored to the key problems that they identified. Dentists provided specific recommendations to address what they felt were key problems, whilst not intervening to address other problems that they may have felt less pressing. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Methylated site display (MSD)-AFLP, a sensitive and affordable method for analysis of CpG methylation profiles.

PubMed

Aiba, Toshiki; Saito, Toshiyuki; Hayashi, Akiko; Sato, Shinji; Yunokawa, Harunobu; Maruyama, Toru; Fujibuchi, Wataru; Kurita, Hisaka; Tohyama, Chiharu; Ohsako, Seiichiroh

2017-03-09

It has been pointed out that environmental factors or chemicals can cause diseases that are developmental in origin. To detect abnormal epigenetic alterations in DNA methylation, convenient and cost-effective methods are required for such research, in which multiple samples are processed simultaneously. We here present methylated site display (MSD), a unique technique for the preparation of DNA libraries. By combining it with amplified fragment length polymorphism (AFLP) analysis, we developed a new method, MSD-AFLP. Methylated site display libraries consist of only DNAs derived from DNA fragments that are CpG methylated at the 5' end in the original genomic DNA sample. To test the effectiveness of this method, CpG methylation levels in liver, kidney, and hippocampal tissues of mice were compared to examine if MSD-AFLP can detect subtle differences in the levels of tissue-specific differentially methylated CpGs. As a result, many CpG sites suspected to be tissue-specific differentially methylated were detected. Nucleotide sequences adjacent to these methyl-CpG sites were identified and we determined the methylation level by methylation-sensitive restriction endonuclease (MSRE)-PCR analysis to confirm the accuracy of AFLP analysis. The differences of the methylation level among tissues were almost identical among these methods. By MSD-AFLP analysis, we detected many CpGs showing less than 5% statistically significant tissue-specific difference and less than 10% degree of variability. Additionally, MSD-AFLP analysis could be used to identify CpG methylation sites in other organisms including humans. MSD-AFLP analysis can potentially be used to measure slight changes in CpG methylation level. Regarding the remarkable precision, sensitivity, and throughput of MSD-AFLP analysis studies, this method will be advantageous in a variety of epigenetics-based research.

Integrated multi-cohort transcriptional meta-analysis of neurodegenerative diseases.

PubMed

Li, Matthew D; Burns, Terry C; Morgan, Alexander A; Khatri, Purvesh

2014-09-04

Neurodegenerative diseases share common pathologic features including neuroinflammation, mitochondrial dysfunction and protein aggregation, suggesting common underlying mechanisms of neurodegeneration. We undertook a meta-analysis of public gene expression data for neurodegenerative diseases to identify a common transcriptional signature of neurodegeneration. Using 1,270 post-mortem central nervous system tissue samples from 13 patient cohorts covering four neurodegenerative diseases, we identified 243 differentially expressed genes, which were similarly dysregulated in 15 additional patient cohorts of 205 samples including seven neurodegenerative diseases. This gene signature correlated with histologic disease severity. Metallothioneins featured prominently among differentially expressed genes, and functional pathway analysis identified specific convergent themes of dysregulation. MetaCore network analyses revealed various novel candidate hub genes (e.g. STAU2). Genes associated with M1-polarized macrophages and reactive astrocytes were strongly enriched in the meta-analysis data. Evaluation of genes enriched in neurons revealed 70 down-regulated genes, over half not previously associated with neurodegeneration. Comparison with aging brain data (3 patient cohorts, 221 samples) revealed 53 of these to be unique to neurodegenerative disease, many of which are strong candidates to be important in neuropathogenesis (e.g. NDN, NAP1L2). ENCODE ChIP-seq analysis predicted common upstream transcriptional regulators not associated with normal aging (REST, RBBP5, SIN3A, SP2, YY1, ZNF143, IKZF1). Finally, we removed genes common to neurodegeneration from disease-specific gene signatures, revealing uniquely robust immune response and JAK-STAT signaling in amyotrophic lateral sclerosis. Our results implicate pervasive bioenergetic deficits, M1-type microglial activation and gliosis as unifying themes of neurodegeneration, and identify numerous novel genes associated with neurodegenerative processes.

Prototype Development of a Tradespace Analysis Tool for Spaceflight Medical Resources.

PubMed

Antonsen, Erik L; Mulcahy, Robert A; Rubin, David; Blue, Rebecca S; Canga, Michael A; Shah, Ronak

2018-02-01

The provision of medical care in exploration-class spaceflight is limited by mass, volume, and power constraints, as well as limitations of available skillsets of crewmembers. A quantitative means of exploring the risks and benefits of inclusion or exclusion of onboard medical capabilities may help to inform the development of an appropriate medical system. A pilot project was designed to demonstrate the utility of an early tradespace analysis tool for identifying high-priority resources geared toward properly equipping an exploration mission medical system. Physician subject matter experts identified resources, tools, and skillsets required, as well as associated criticality scores of the same, to meet terrestrial, U.S.-specific ideal medical solutions for conditions concerning for exploration-class spaceflight. A database of diagnostic and treatment actions and resources was created based on this input and weighed against the probabilities of mission-specific medical events to help identify common and critical elements needed in a future exploration medical capability. Analysis of repository data demonstrates the utility of a quantitative method of comparing various medical resources and skillsets for future missions. Directed database queries can provide detailed comparative estimates concerning likelihood of resource utilization within a given mission and the weighted utility of tangible and intangible resources. This prototype tool demonstrates one quantitative approach to the complex needs and limitations of an exploration medical system. While this early version identified areas for refinement in future version development, more robust analysis tools may help to inform the development of a comprehensive medical system for future exploration missions.Antonsen EL, Mulcahy RA, Rubin D, Blue RS, Canga MA, Shah R. Prototype development of a tradespace analysis tool for spaceflight medical resources. Aerosp Med Hum Perform. 2018; 89(2):108-114.

Soldier caste-specific gene expression in the mandibular glands of Hodotermopsis japonica (Isoptera: Termopsidae)

PubMed Central

Miura, Toru; Kamikouchi, Azusa; Sawata, Miyuki; Takeuchi, Hideaki; Natori, Syunji; Kubo, Takeo; Matsumoto, Tadao

1999-01-01

Although “polymorphic castes” in social insects are well known as one of the most important phenomena of polyphenism, few studies of caste-specific gene expressions have been performed in social insects. To identify genes specifically expressed in the soldier caste of the Japanese damp-wood termite Hodotermopsis japonica, we employed the differential-display method using oligo(dT) and arbitrary primers, compared mRNA from the heads of mature soldiers and pseudergates (worker caste), and identified a clone (PCR product) 329 bp in length termed SOL1. Northern blot analysis showed that the SOL1 mRNA is about 1.0 kb in length and is expressed specifically in mature soldiers, but not in pseudergates, even in the presoldier induction by juvenile hormone analogue, suggesting that the product is specific for terminally differentiated soldiers. By using the method of 5′- and 3′-rapid amplification of cDNA ends, we isolated the full length of SOL1 cDNA, which contained an ORF with a putative signal peptide at the N terminus. The sequence showed no significant homology with any other known protein sequences. In situ hybridization analysis showed that SOL1 is expressed specifically in the mandibular glands. These results strongly suggest that the SOL1 gene encodes a secretory protein specifically synthesized in the mandibular glands of the soldiers. Histological observations revealed that the gland actually develops during the differentiation into the soldier caste. PMID:10570166

Worldwide wind/diesel hybrid power system study: Potential applications and technical issues

NASA Astrophysics Data System (ADS)

King, W. R.; Johnson, B. L., III

1991-04-01

The world market potential for wind/diesel hybrid technology is a function of the need for electric power, the availability of sufficient wind resource to support wind/diesel power, and the existence of buyers with the financial means to invest in the technology. This study includes data related to each of these three factors. This study does not address market penetration, which would require analysis of application specific wind/diesel economics. Buyer purchase criteria, which are vital to assessing market penetration, are discussed only generally. Countries were screened for a country-specific market analysis based on indicators of need and wind resource. Both developed countries and less developed countries (LDCs) were screened for wind/diesel market potential. Based on the results of the screening, ten countries showing high market potential were selected for more extensive market analyses. These analyses provide country-specific market data to guide wind/diesel technology developers in making design decisions that will lead to a competitive product. Section 4 presents the country-specific data developed for these analyses, including more extensive wind resource characterization, application-specific market opportunities, business conditions, and energy market characterizations. An attempt was made to identify the potential buyers with ability to pay for wind/diesel technology required to meet the application-specific market opportunities identified for each country. Additionally, the country-specific data are extended to corollary opportunities in countries not covered by the study. Section 2 gives recommendations for wind/diesel research based on the findings of the study.

Identification of Stmm3 locus Conferring Resistance to Late-stage Chemically Induced Skin Papillomas on Mouse Chromosome 4 by Congenic Mappingand Allele-specific Alteration Analysis

PubMed Central

Saito, Megumi; Okumura, Kazuhiro; Miura, Ikuo; Wakana, Shigeharu; Kominami, Ryo; Wakabayashi, Yuichi

2014-01-01

Genome-wide association studies have revealed that many low-penetrance cancer susceptibility loci are located throughout the genome; however, a very limited number of genes have been identified so far. Using a forward genetics approach to map such loci in a mouse skin cancer model, we previously identified strong genetic loci conferring resistance to chemically induced skin papillomas on chromosome 4 and 7 with a large number of [(FVB/N × MSM/Ms) F1 × FVB/N] backcross mice. In this report, we describe a combination of congenic mapping and allele-specific alteration analysis of the loci on chromosome 4. We used linkage analysis and a congenic mouse strain, FVB.MSM-Stmm3 to refine the location of Stmm3 (Skin tumor modifier of MSM 3) locus within a physical interval of about 34 Mb on distal chromosome 4. In addition, we used patterns of allele-specific imbalances in tumors from N2 and N10 congenic mice to narrow down further the region of Stmm3 locus to a physical distance of about 25 Mb. Furthermore, immunohistochemical analysis showed papillomas from congenic mice had less proliferative activity. These results suggest that Stmm3 responsible genes may have an influence on papilloma formation in the two-stage skin carcinogenesis by regulating papilloma growth rather than development. PMID:25077764

3M™ Molecular detection system versus MALDI-TOF mass spectrometry and molecular techniques for the identification of Escherichia coli 0157:H7, Salmonella spp. &Listeria spp.

PubMed

Loff, Marché; Mare, Louise; de Kwaadsteniet, Michele; Khan, Wesaal

2014-06-01

The aim of this study was to compare standard selective plating, conventional PCR (16S rRNA and species specific primers), MALDI-TOF MS and the 3M™ Molecular Detection System for the routine detection of the pathogens Listeria, Salmonella and Escherichia coli 0157:H7 in wastewater and river water samples. MALDI-TOF MS was able to positively identify 20/21 (95%) of the E. coli isolates obtained at genus and species level, while 16S rRNA sequencing only correctly identified 6/21 (28%) as E. coli strains. None of the presumptive positive Listeria spp. and Salmonella spp. isolates obtained by culturing on selective media were positively identified by MALDI-TOF and 16S rRNA analysis. The species-specific E. coli 0157:H7 PCR described in this present study, was not able to detect any E. coli 0157:H7 strains in the wastewater and river water samples analysed. However, E. coli strains, Listeria spp., L. monocytogenes and Salmonella spp. were detected using species specific PCR. Escherichia coli 0157:H7, Listeria spp. and Salmonella spp. were also sporadically detected throughout the sampling period in the wastewater and river water samples analysed by the 3M™ Molecular Detection System. MALDI-TOF MS, which is a simple, accurate and cost-effective detection method, efficiently identified the culturable organisms, while in the current study both species specific PCR (Listeria spp. and Salmonella spp.) and 3M™ Molecular Detection System could be utilised for the direct routine analysis of pathogens in water sources. Copyright © 2014 Elsevier B.V. All rights reserved.

Evolution of the eukaryotic ARP2/3 activators of the WASP family: WASP, WAVE, WASH, and WHAMM, and the proposed new family members WAWH and WAML

PubMed Central

2012-01-01

Background WASP family proteins stimulate the actin-nucleating activity of the ARP2/3 complex. They include members of the well-known WASP and WAVE/Scar proteins, and the recently identified WASH and WHAMM proteins. WASP family proteins contain family specific N-terminal domains followed by proline-rich regions and C-terminal VCA domains that harbour the ARP2/3-activating regions. Results To reveal the evolution of ARP2/3 activation by WASP family proteins we performed a "holistic" analysis by manually assembling and annotating all homologs in most of the eukaryotic genomes available. We have identified two new families: the WAML proteins (WASP and MIM like), which combine the membrane-deforming and actin bundling functions of the IMD domains with the ARP2/3-activating VCA regions, and the WAWH protein (WASP without WH1 domain) that have been identified in amoebae, Apusozoa, and the anole lizard. Surprisingly, with one exception we did not identify any alternative splice forms for WASP family proteins, which is in strong contrast to other actin-binding proteins like Ena/VASP, MIM, or NHS proteins that share domains with WASP proteins. Conclusions Our analysis showed that the last common ancestor of the eukaryotes must have contained a homolog of WASP, WAVE, and WASH. Specific families have subsequently been lost in many taxa like the WASPs in plants, algae, Stramenopiles, and Euglenozoa, and the WASH proteins in fungi. The WHAMM proteins are metazoa specific and have most probably been invented by the Eumetazoa. The diversity of WASP family proteins has strongly been increased by many species- and taxon-specific gene duplications and multimerisations. All data is freely accessible via http://www.cymobase.org. PMID:22316129

Identifying the Role of National Digital Cadastral Database (ndcdb) in Malaysia and for Land-Based Analysis

NASA Astrophysics Data System (ADS)

Halim, N. Z. A.; Sulaiman, S. A.; Talib, K.; Yusof, O. M.; Wazir, M. A. M.; Adimin, M. K.

2017-10-01

This paper explains the process carried out in identifying the significant role of NDCDB in Malaysia specifically in the land-based analysis. The research was initially a part of a larger research exercise to identify the significance of NDCDB from the legal, technical, role and land-based analysis perspectives. The research methodology of applying the Delphi technique is substantially discussed in this paper. A heterogeneous panel of 14 experts was created to determine the importance of NDCDB from the role standpoint. Seven statements pertaining the significant role of NDCDB in Malaysia and land-based analysis were established after three rounds of consensus building. The agreed statements provided a clear definition to describe the important role of NDCDB in Malaysia and for land-based analysis, which was limitedly studied that lead to unclear perception to the general public and even the geospatial community. The connection of the statements with disaster management is discussed concisely at the end of the research.

Gene expression atlas of pigeonpea and its application to gain insights into genes associated with pollen fertility implicated in seed formation.

PubMed

Pazhamala, Lekha T; Purohit, Shilp; Saxena, Rachit K; Garg, Vanika; Krishnamurthy, L; Verdier, Jerome; Varshney, Rajeev K

2017-04-01

Pigeonpea (Cajanus cajan) is an important grain legume of the semi-arid tropics, mainly used for its protein rich seeds. To link the genome sequence information with agronomic traits resulting from specific developmental processes, a Cajanus cajan gene expression atlas (CcGEA) was developed using the Asha genotype. Thirty tissues/organs representing developmental stages from germination to senescence were used to generate 590.84 million paired-end RNA-Seq data. The CcGEA revealed a compendium of 28 793 genes with differential, specific, spatio-temporal and constitutive expression during various stages of development in different tissues. As an example to demonstrate the application of the CcGEA, a network of 28 flower-related genes analysed for cis-regulatory elements and splicing variants has been identified. In addition, expression analysis of these candidate genes in male sterile and male fertile genotypes suggested their critical role in normal pollen development leading to seed formation. Gene network analysis also identified two regulatory genes, a pollen-specific SF3 and a sucrose-proton symporter, that could have implications for improvement of agronomic traits such as seed production and yield. In conclusion, the CcGEA provides a valuable resource for pigeonpea to identify candidate genes involved in specific developmental processes and to understand the well-orchestrated growth and developmental process in this resilient crop. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Optimal Hemoglobin A1c Levels for Screening of Diabetes and Prediabetes in the Japanese Population.

PubMed

Shimodaira, Masanori; Okaniwa, Shinji; Hanyu, Norinao; Nakayama, Tomohiro

2015-01-01

The aim of this study was to evaluate the utility of hemoglobin A1c (HbA1c) to identify individuals with diabetes and prediabetes in the Japanese population. A total of 1372 individuals without known diabetes were selected for this study. A 75 g oral glucose tolerance test (OGTT) was used to diagnose diabetes and prediabetes. The ability of HbA1c to detect diabetes and prediabetes was investigated using receiver operating characteristic (ROC) analysis. The kappa (κ) coefficient was used to test the agreement between HbA1c categorization and OGTT-based diagnosis. ROC analysis demonstrated that HbA1c was a good test to identify diabetes and prediabetes, with areas under the curve of 0.918 and 0.714, respectively. Optimal HbA1c cutoffs for diagnosing diabetes and prediabetes were 6.0% (sensitivity 83.7%, specificity 87.6%) and 5.7% (sensitivity 60.6%, specificity 72.1%), respectively, although the cutoff for prediabetes showed low accuracy (67.6%) and a high false-negative rate (39.4%). Agreement between HbA1c categorization and OGTT-based diagnosis was low in diabetes (κ = 0.399) and prediabetes (κ = 0.324). In Japanese subjects, the HbA1c cutoff of 6.0% had appropriate sensitivity and specificity for diabetes screening, whereas the cutoff of 5.7% had modest sensitivity and specificity in identifying prediabetes. Thus, HbA1c may be inadequate as a screening tool for prediabetes.

Muscle MRI findings in facioscapulohumeral muscular dystrophy.

PubMed

Gerevini, Simonetta; Scarlato, Marina; Maggi, Lorenzo; Cava, Mariangela; Caliendo, Giandomenico; Pasanisi, Barbara; Falini, Andrea; Previtali, Stefano Carlo; Morandi, Lucia

2016-03-01

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. Muscle MRI identifies a specific pattern of muscle involvement in FSHD patients. Muscle MRI may predict FSHD in asymptomatic and severely affected patients. Muscle MRI of upper girdle better predicts FSHD. Muscle MRI may differentiate FSHD from other forms of muscular dystrophy. Muscle MRI may show the involvement of non-clinical testable muscles.

Transcriptome-wide analysis of WRKY transcription factors in wheat and their leaf rust responsive expression profiling.

PubMed

Satapathy, Lopamudra; Singh, Dharmendra; Ranjan, Prashant; Kumar, Dhananjay; Kumar, Manish; Prabhu, Kumble Vinod; Mukhopadhyay, Kunal

2014-12-01

WRKY, a plant-specific transcription factor family, has important roles in pathogen defense, abiotic cues and phytohormone signaling, yet little is known about their roles and molecular mechanism of function in response to rust diseases in wheat. We identified 100 TaWRKY sequences using wheat Expressed Sequence Tag database of which 22 WRKY sequences were novel. Identified proteins were characterized based on their zinc finger motifs and phylogenetic analysis clustered them into six clades consisting of class IIc and class III WRKY proteins. Functional annotation revealed major functions in metabolic and cellular processes in control plants; whereas response to stimuli, signaling and defense in pathogen inoculated plants, their major molecular function being binding to DNA. Tag-based expression analysis of the identified genes revealed differential expression between mock and Puccinia triticina inoculated wheat near isogenic lines. Gene expression was also performed with six rust-related microarray experiments at Gene Expression Omnibus database. TaWRKY10, 15, 17 and 56 were common in both tag-based and microarray-based differential expression analysis and could be representing rust specific WRKY genes. The obtained results will bestow insight into the functional characterization of WRKY transcription factors responsive to leaf rust pathogenesis that can be used as candidate genes in molecular breeding programs to improve biotic stress tolerance in wheat.

Association of transforming growth-factor alpha gene polymorphisms with nonsyndromic cleft palate only (CPO)

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

Shiang, R.; Lidral, A.C.; Ardinger, H.H.

1993-10-01

Genetic analysis and tissue-specific expression studies support a role for transforming growth-factor alpha (TGFA) in craniofacial development. Previous studies have confirmed an association of alleles for TGFA with nonsyndromic cleft lip with or without cleft palate (CL/P) in humans. The authors carried out a retrospective association study to determine whether specific allelic variants of the TGFA gene are also associated with cleft palate only (CPO). The PCR products from 12 overlapping sets of primers to the TGFA cDNA were examined by using single-strand conformational polymorphism analysis. Four DNA polymorphic sites for TGFA were identified in the 3[prime] untranslated region ofmore » the TGFA gene. These variants, as well as previously identified RFLPs for TGFA, were characterized in case and control populations for CPO by using X[sup 2] analysis. A significant association between alleles of TGFA and CPO was identified which further supports a role for this gene as one of the genetic determinants of craniofacial development. Sequence analysis of the variants disclosed a cluster of three variable sites within 30 bp of each other in the 3[prime] untranslated region previously associated with an antisense transcript. These studies extend the role for TGFA in craniofacial morphogenesis and support an interrelated mechanism underlying nonsyndromic forms of CL/P. 46 refs., 3 figs., 3 tabs.« less

Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects, and tissue-specific enrichment of eQTLs

PubMed Central

Below, Jennifer E.; Parra, Esteban J.; Gamazon, Eric R.; Torres, Jason; Krithika, S.; Candille, Sophie; Lu, Yingchang; Manichakul, Ani; Peralta-Romero, Jesus; Duan, Qing; Li, Yun; Morris, Andrew P.; Gottesman, Omri; Bottinger, Erwin; Wang, Xin-Qun; Taylor, Kent D.; Ida Chen, Y.-D.; Rotter, Jerome I.; Rich, Stephen S.; Loos, Ruth J. F.; Tang, Hua; Cox, Nancy J.; Cruz, Miguel; Hanis, Craig L.; Valladares-Salgado, Adan

2016-01-01

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals, and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol, and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci. PMID:26780889

Specification and estimation of sources of bias affecting neurological studies in PET/MR with an anatomical brain phantom

NASA Astrophysics Data System (ADS)

Teuho, J.; Johansson, J.; Linden, J.; Saunavaara, V.; Tolvanen, T.; Teräs, M.

2014-01-01

Selection of reconstruction parameters has an effect on the image quantification in PET, with an additional contribution from a scanner-specific attenuation correction method. For achieving comparable results in inter- and intra-center comparisons, any existing quantitative differences should be identified and compensated for. In this study, a comparison between PET, PET/CT and PET/MR is performed by using an anatomical brain phantom, to identify and measure the amount of bias caused due to differences in reconstruction and attenuation correction methods especially in PET/MR. Differences were estimated by using visual, qualitative and quantitative analysis. The qualitative analysis consisted of a line profile analysis for measuring the reproduction of anatomical structures and the contribution of the amount of iterations to image contrast. The quantitative analysis consisted of measurement and comparison of 10 anatomical VOIs, where the HRRT was considered as the reference. All scanners reproduced the main anatomical structures of the phantom adequately, although the image contrast on the PET/MR was inferior when using a default clinical brain protocol. Image contrast was improved by increasing the amount of iterations from 2 to 5 while using 33 subsets. Furthermore, a PET/MR-specific bias was detected, which resulted in underestimation of the activity values in anatomical structures closest to the skull, due to the MR-derived attenuation map that ignores the bone. Thus, further improvements for the PET/MR reconstruction and attenuation correction could be achieved by optimization of RAMLA-specific reconstruction parameters and implementation of bone to the attenuation template.

Comparative genome analysis of Pseudomonas genomes including Populus-associated isolates

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

Jun, Se Ran; Wassenaar, Trudy; Nookaew, Intawat

The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches including the rhizosphere and endosphere of many plants influencing phylogenetic diversity and heterogeneity. In this study, comparative genome analysis was performed on over one thousand Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides. Based on average amino acid identity, genomic clusters were identified within the Pseudomonas genus, which showed agreements with clades by NCBI and cliques by IMG. The P. fluorescens group was organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. The speciesmore » P. aeruginosa showed clear distinction in their genomic relatedness compared to other Pseudomonas species groups based on the pan and core genome analysis. The 19 isolates of our 21 Populus-associated isolates formed three distinct subgroups within the P. fluorescens major group, supported by pathway profiles analysis, while two isolates were more closely related to P. chlororaphis and P. putida. The specific genes to Populus-associated subgroups were identified where genes specific to subgroup 1 include several sensory systems such as proteins which act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor; specific genes to subgroup 2 contain unique hypothetical genes; and genes specific to subgroup 3 organisms have a different hydrolase activity. IMPORTANCE The comparative genome analyses of the genus Pseudomonas that included Populus-associated isolates resulted in novel insights into high diversity of Pseudomonas. Consistent and robust genomic clusters with phylogenetic homogeneity were identified, which resolved species-clades that are not clearly defined by 16S rRNA gene sequence analysis alone. The genomic clusters may be reflective of distinct ecological niches to which the organisms have adapted, but this needs to be experimentally characterized with ecologically relevant phenotype properties. This study justifies the need to sequence multiple isolates, especially from P. fluorescens group in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.« less

Comparative genome analysis of Pseudomonas genomes including Populus-associated isolates

DOE PAGES

Jun, Se Ran; Wassenaar, Trudy; Nookaew, Intawat; ...

2016-01-01

The Pseudomonas genus contains a metabolically versatile group of organisms that are known to occupy numerous ecological niches including the rhizosphere and endosphere of many plants influencing phylogenetic diversity and heterogeneity. In this study, comparative genome analysis was performed on over one thousand Pseudomonas genomes, including 21 Pseudomonas strains isolated from the roots of native Populus deltoides. Based on average amino acid identity, genomic clusters were identified within the Pseudomonas genus, which showed agreements with clades by NCBI and cliques by IMG. The P. fluorescens group was organized into 20 distinct genomic clusters, representing enormous diversity and heterogeneity. The speciesmore » P. aeruginosa showed clear distinction in their genomic relatedness compared to other Pseudomonas species groups based on the pan and core genome analysis. The 19 isolates of our 21 Populus-associated isolates formed three distinct subgroups within the P. fluorescens major group, supported by pathway profiles analysis, while two isolates were more closely related to P. chlororaphis and P. putida. The specific genes to Populus-associated subgroups were identified where genes specific to subgroup 1 include several sensory systems such as proteins which act in two-component signal transduction, a TonB-dependent receptor, and a phosphorelay sensor; specific genes to subgroup 2 contain unique hypothetical genes; and genes specific to subgroup 3 organisms have a different hydrolase activity. IMPORTANCE The comparative genome analyses of the genus Pseudomonas that included Populus-associated isolates resulted in novel insights into high diversity of Pseudomonas. Consistent and robust genomic clusters with phylogenetic homogeneity were identified, which resolved species-clades that are not clearly defined by 16S rRNA gene sequence analysis alone. The genomic clusters may be reflective of distinct ecological niches to which the organisms have adapted, but this needs to be experimentally characterized with ecologically relevant phenotype properties. This study justifies the need to sequence multiple isolates, especially from P. fluorescens group in order to study functional capabilities from a pangenomic perspective. This information will prove useful when choosing Pseudomonas strains for use to promote growth and increase disease resistance in plants.« less

Site-specific O-Glycosylation Analysis of Human Blood Plasma Proteins*

PubMed Central

Hoffmann, Marcus; Marx, Kristina; Reichl, Udo; Wuhrer, Manfred; Rapp, Erdmann

2016-01-01

Site-specific glycosylation analysis is key to investigate structure-function relationships of glycoproteins, e.g. in the context of antigenicity and disease progression. The analysis, though, is quite challenging and time consuming, in particular for O-glycosylated proteins. In consequence, despite their clinical and biopharmaceutical importance, many human blood plasma glycoproteins have not been characterized comprehensively with respect to their O-glycosylation. Here, we report on the site-specific O-glycosylation analysis of human blood plasma glycoproteins. To this end pooled human blood plasma of healthy donors was proteolytically digested using a broad-specific enzyme (Proteinase K), followed by a precipitation step, as well as a glycopeptide enrichment and fractionation step via hydrophilic interaction liquid chromatography, the latter being optimized for intact O-glycopeptides carrying short mucin-type core-1 and -2 O-glycans, which represent the vast majority of O-glycans on human blood plasma proteins. Enriched O-glycopeptide fractions were subjected to mass spectrometric analysis using reversed-phase liquid chromatography coupled online to an ion trap mass spectrometer operated in positive-ion mode. Peptide identity and glycan composition were derived from low-energy collision-induced dissociation fragment spectra acquired in multistage mode. To pinpoint the O-glycosylation sites glycopeptides were fragmented using electron transfer dissociation. Spectra were annotated by database searches as well as manually. Overall, 31 O-glycosylation sites and regions belonging to 22 proteins were identified, the majority being acute-phase proteins. Strikingly, also 11 novel O-glycosylation sites and regions were identified. In total 23 O-glycosylation sites could be pinpointed. Interestingly, the use of Proteinase K proved to be particularly beneficial in this context. The identified O-glycan compositions most probably correspond to mono- and disialylated core-1 mucin-type O-glycans (T-antigen). The developed workflow allows the identification and characterization of the major population of the human blood plasma O-glycoproteome and our results provide new insights, which can help to unravel structure-function relationships. The data were deposited to ProteomeXchange PXD003270. PMID:26598643

Noninvasive Tests Do Not Accurately Differentiate Nonalcoholic Steatohepatitis From Simple Steatosis: A Systematic Review and Meta-analysis.

PubMed

Verhaegh, Pauline; Bavalia, Roisin; Winkens, Bjorn; Masclee, Ad; Jonkers, Daisy; Koek, Ger

2018-06-01

Nonalcoholic fatty liver disease is a rapidly increasing health problem. Liver biopsy analysis is the most sensitive test to differentiate between nonalcoholic steatohepatitis (NASH) and simple steatosis (SS), but noninvasive methods are needed. We performed a systematic review and meta-analysis of noninvasive tests for differentiating NASH from SS, focusing on blood markers. We performed a systematic search of the PubMed, Medline and Embase (1990-2016) databases using defined keywords, limited to full-text papers in English and human adults, and identified 2608 articles. Two independent reviewers screened the articles and identified 122 eligible articles that used liver biopsy as reference standard. If at least 2 studies were available, pooled sensitivity (sens p ) and specificity (spec p ) values were determined using the Meta-Analysis Package for R (metafor). In the 122 studies analyzed, 219 different blood markers (107 single markers and 112 scoring systems) were identified to differentiate NASH from simple steatosis, and 22 other diagnostic tests were studied. Markers identified related to several pathophysiological mechanisms. The markers analyzed in the largest proportions of studies were alanine aminotransferase (sens p , 63.5% and spec p , 74.4%) within routine biochemical tests, adiponectin (sensp, 72.0% and spec p , 75.7%) within inflammatory markers, CK18-M30 (sens p , 68.4% and spec p , 74.2%) within markers of cell death or proliferation and homeostatic model assessment of insulin resistance (sens p , 69.0% and spec p , 72.7%) within the metabolic markers. Two scoring systems could also be pooled: the NASH test (differentiated NASH from borderline NASH plus simple steatosis with 22.9% sens p and 95.3% spec p ) and the GlycoNASH test (67.1% sens p and 63.8% spec p ). In the meta-analysis, we found no test to differentiate NASH from SS with a high level of pooled sensitivity and specificity (≥80%). However, some blood markers, when included in scoring systems in single studies, identified patients with NASH with ≥80% sensitivity and specificity. Replication studies and more standardized study designs are urgently needed. At present, no marker or scoring system can be recommended for use in clinical practice to differentiate NASH from simple steatosis. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Global, Regional and Local Influences on Adult Literacy Policy in England

ERIC Educational Resources Information Center

Hamilton, Mary

2014-01-01

This paper explores the relationship between global, regional and local influences on adult literacy policy and practice in the UK through a discourse analysis of policy-related texts. The analysis is framed by theoretical perspectives from literacy studies and socio-material theory. The paper identifies a number of specific features in the UK…

Long-Term Impact of the Farm Financial Analysis Training Curriculum on FSA Borrowers in Pennsylvania

ERIC Educational Resources Information Center

Balliet, Kenneth L.; Douglass, Mark B.; Hanson, Gregory

2010-01-01

The Farm Financial Analysis Training (FFAT) course covers fundamental skills and concepts in liquidity, profitability, solvency, and efficiency. The research reported here identifies and measures the impacts of FFAT on participants including: 1) perceived gains in knowledge, 2) changes in management behavior, 3) changes in specific farm assets and…

Call and Responsibility: Critical Questions for Youth Spoken Word Poetry

ERIC Educational Resources Information Center

Weinstein, Susan; West, Anna

2012-01-01

In this article, Susan Weinstein and Anna West embark on a critical analysis of the maturing field of youth spoken word poetry (YSW). Through a blend of firsthand experience, analysis of YSW-related films and television, and interview data from six years of research, the authors identify specific dynamics that challenge young poets as they…

Needs Analysis in ESP Context: Saudi Engineering Students as a Case Study

ERIC Educational Resources Information Center

Alsamadani, Hashem Ahmed

2017-01-01

Needs analysis can be a vital asset for teachers of English for specific purposes (ESP) to identify their learners' key requirements or needs and determine the areas in which they are lacking skills. Against this background, this study was undertaken during the academic year 2015-16 to define the English language needs of engineering students…

Anxiety Disorders in Williams Syndrome Contrasted with Intellectual Disability and the General Population: A Systematic Review and Meta-Analysis

ERIC Educational Resources Information Center

Royston, R.; Howlin, P.; Waite, J.; Oliver, C.

2017-01-01

Individuals with specific genetic syndromes associated with intellectual disability (ID), such as Williams syndrome (WS), are at increased risk for developing anxiety disorders. A systematic literature review identified sixteen WS papers that could generate pooled prevalence estimates of anxiety disorders for WS. A meta-analysis compared these…

What Satisfies Students? Mining Student-Opinion Data with Regression and Decision-Tree Analysis. AIR 2002 Forum Paper.

ERIC Educational Resources Information Center

Thomas, Emily H.; Galambos, Nora

To investigate how students' characteristics and experiences affect satisfaction, this study used regression and decision-tree analysis with the CHAID algorithm to analyze student opinion data from a sample of 1,783 college students. A data-mining approach identifies the specific aspects of students' university experience that most influence three…

Method and apparatus for enhanced sequencing of complex molecules using surface-induced dissociation in conjunction with mass spectrometric analysis

DOEpatents

Laskin, Julia [Richland, WA; Futrell, Jean H [Richland, WA

2008-04-29

The invention relates to a method and apparatus for enhanced sequencing of complex molecules using surface-induced dissociation (SID) in conjunction with mass spectrometric analysis. Results demonstrate formation of a wide distribution of structure-specific fragments having wide sequence coverage useful for sequencing and identifying the complex molecules.

Specific Proteins in Nontuberculous Mycobacteria: New Potential Tools.

PubMed

Orduña, Patricia; Castillo-Rodal, Antonia I; Mercado, Martha E; Ponce de León, Samuel; López-Vidal, Yolanda

2015-01-01

Nontuberculous mycobacteria (NTM) have been isolated from water, soil, air, food, protozoa, plants, animals, and humans. Although most NTM are saprophytes, approximately one-third of NTM have been associated with human diseases. In this study, we did a comparative proteomic analysis among five NTM strains isolated from several sources. There were different numbers of protein spots from M. gordonae (1,264), M. nonchromogenicum type I (894), M. nonchromogenicum type II (935), M. peregrinum (806), and M. scrofulaceum/Mycobacterium mantenii (1,486) strains, respectively. We identified 141 proteins common to all strains and specific proteins to each NTM strain. A total of 23 proteins were selected for its identification. Two of the common proteins identified (short-chain dehydrogenase/reductase SDR and diguanylate cyclase) did not align with M. tuberculosis complex protein sequences, which suggest that these proteins are found only in the NTM strains. Some of the proteins identified as common to all strains can be used as markers of NTM exposure and for the development of new diagnostic tools. Additionally, the specific proteins to NTM strains identified may represent potential candidates for the diagnosis of diseases caused by these mycobacteria.

Genetic Mapping of Fixed Phenotypes: Disease Frequency as a Breed Characteristic

PubMed Central

Jones, Paul; Martin, Alan; Ostrander, Elaine A.; Lark, Karl G.

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pacreatitis. PMID:19321632

Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic.

PubMed

Chase, Kevin; Jones, Paul; Martin, Alan; Ostrander, Elaine A; Lark, Karl G

2009-01-01

Traits that have been stringently selected to conform to specific criteria in a closed population are phenotypic stereotypes. In dogs, Canis familiaris, such stereotypes have been produced by breeding for conformation, performance (behaviors), etc. We measured phenotypes on a representative sample to establish breed stereotypes. DNA samples from 147 dog breeds were used to characterize single nucleotide polymorphism allele frequencies for association mapping of breed stereotypes. We identified significant size loci (quantitative trait loci [QTLs]), implicating candidate genes appropriate to regulation of size (e.g., IGF1, IGF2BP2 SMAD2, etc.). Analysis of other morphological stereotypes, also under extreme selection, identified many additional significant loci. Behavioral loci for herding, pointing, and boldness implicated candidate genes appropriate to behavior (e.g., MC2R, DRD1, and PCDH9). Significant loci for longevity, a breed characteristic inversely correlated with breed size, were identified. The power of this approach to identify loci regulating the incidence of specific polygenic diseases is demonstrated by the association of a specific IGF1 haplotype with hip dysplasia, patella luxation, and pancreatitis.

Validation of the colour difference plot scoring system analysis of the 103 hexagon multifocal electroretinogram in the evaluation of hydroxychloroquine retinal toxicity.

PubMed

Graves, Gabrielle S; Adam, Murtaza K; Stepien, Kimberly E; Han, Dennis P

2014-08-01

To evaluate sensitivity, specificity and reproducibility of colour difference plot analysis (CDPA) of 103 hexagon multifocal electroretinogram (mfERG) in detecting established hydroxychloroquine (HCQ) retinal toxicity. Twenty-three patients taking HCQ were divided into those with and without retinal toxicity and were compared with a control group without retinal disease and not taking HCQ. CDPA with two masked examiners was performed using age-corrected mfERG responses in the central ring (Rc ; 0-5.5 degrees from fixation) and paracentral ring (Rp ; 5.5-11 degrees from fixation). An abnormal ring was defined as containing any hexagons with a difference in two or more standard deviations from normal (colour blue or black). Categorical analysis (ring involvement or not) showed Rc had 83% sensitivity and 93% specificity. Rp had 89% sensitivity and 82% specificity. Requiring abnormal hexagons in both Rc and Rp yielded sensitivity and specificity of 83% and 95%, respectively. If required in only one ring, they were 89% and 80%, respectively. In this population, there was complete agreement in identifying toxicity when comparing CDPA using Rp with ring ratio analysis using R5/R4 P1 ring responses (89% sensitivity and 95% specificity). Continuous analysis of CDPA with receiver operating characteristic analysis showed optimized detection (83% sensitivity and 96% specificity) when ≥4 abnormal hexagons were present anywhere within the Rp ring outline. Intergrader agreement and reproducibility were good. Colour difference plot analysis had sensitivity and specificity that approached that of ring ratio analysis of R5/R4 P₁ responses. Ease of implementation and reproducibility are notable advantages of CDPA. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Combinations of techniques that effectively change health behavior: evidence from Meta-CART analysis.

PubMed

Dusseldorp, Elise; van Genugten, Lenneke; van Buuren, Stef; Verheijden, Marieke W; van Empelen, Pepijn

2014-12-01

Many health-promoting interventions combine multiple behavior change techniques (BCTs) to maximize effectiveness. Although, in theory, BCTs can amplify each other, the available meta-analyses have not been able to identify specific combinations of techniques that provide synergistic effects. This study overcomes some of the shortcomings in the current methodology by applying classification and regression trees (CART) to meta-analytic data in a special way, referred to as Meta-CART. The aim was to identify particular combinations of BCTs that explain intervention success. A reanalysis of data from Michie, Abraham, Whittington, McAteer, and Gupta (2009) was performed. These data included effect sizes from 122 interventions targeted at physical activity and healthy eating, and the coding of the interventions into 26 BCTs. A CART analysis was performed using the BCTs as predictors and treatment success (i.e., effect size) as outcome. A subgroup meta-analysis using a mixed effects model was performed to compare the treatment effect in the subgroups found by CART. Meta-CART identified the following most effective combinations: Provide information about behavior-health link with Prompt intention formation (mean effect size ḡ = 0.46), and Provide information about behavior-health link with Provide information on consequences and Use of follow-up prompts (ḡ = 0.44). Least effective interventions were those using Provide feedback on performance without using Provide instruction (ḡ = 0.05). Specific combinations of BCTs increase the likelihood of achieving change in health behavior, whereas other combinations decrease this likelihood. Meta-CART successfully identified these combinations and thus provides a viable methodology in the context of meta-analysis.

[Specific placental complications of monochorionic diamniotic twins born after 24 weeks of pregnancies - restrospective analysis].

PubMed

Vlašínová, I; Hruban, L; Janků, P; Gerychová, R; Ventruba, P; Ťápalová, V; Hodická, Z

2015-06-01

Purpose of this study was to determine the frequency of occurence of specific complications of monochorionic diamniotic twins born after 24 weeks of pregnancies and the effect of these complications on perinatal morbidity and mortality. Restrospective analysis. Dpt. of Obstetrics and Gynecology Masaryk University and University Hospital Brno. A retrospective analysis of 175 monochorionic diamniotic pregnancies (mo-bi), which were terminated after the 24th week of pregnancy at the Department of Obstetrics and Gynecology Masaryk University and University Hospital Brno between the years 2008-2013. The specific complications such as twin-to-twin syndrome (TTTs), twin anemia polycytemia sequens (TAPS), selective intrauterine growth restriction (sIUGR), twin-arterial revers perfusion sequence (TRAP), single intrauterine fetal death (IUFD), placental insufficiency with both twins were identified using prenatal ultrasound examinations, perinatal results and the result of pathological anatomical examinations. Perinatal morbidity, neonatal mortality and neurological development were evaluated. The numbers of late detections of specific complications were observed. Specific complications in our group were identified in 50 pregnancies (28.6%). TTTs was diagnosed most often, by 18 pregnancies (10.3%), next most frequent diagnosis were sIUGR (9.7%) and TAPS (3.4%). The placental insufficiency with both twins complicated 2.6% pregnancies. 10 children had abnormal neurological development. Pregnancies with late detection had the worst perinatal results. No acute TTTs during delivery was detected. Specific placental complication reached 29.7% in our file. The most frequent complication was TTTs (10.3%) and selective growth restriction (9.7%). Pregnancies with late diagnosis of these complications had the worst results. The prenatal care by monochorial biamnial pregnancies should be at specialized centres from the 16th week of pregnancy every two weeks.

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study.

PubMed

Mc Menamin, Úna C; Cardwell, Chris R; Hughes, Carmel M; Murray, Liam J

2017-04-01

Preclinical evidence from breast cancer cell lines and animal models suggest that aspirin could have anti-cancer properties. In a large breast cancer patient cohort, we investigated whether post-diagnostic low-dose aspirin use was associated with a reduction in the risk of breast cancer-specific mortality. We identified 15,140 newly diagnosed breast cancer patients within the Scottish Cancer Registry. Linkages to the Scottish Prescribing Information System provided data on dispensed medications and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for breast cancer-specific and all-cause mortality by post-diagnostic low-dose aspirin use. HRs were adjusted for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of statins. Secondary analysis investigated the association between pre-diagnostic low-dose aspirin use and breast cancer-specific and all-cause mortality. Post-diagnostic users of low-dose aspirin appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.44, 95% CI 1.26, 1.65) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.92, 95% CI 0.75, 1.14). Findings were similar in analysis by increasing duration of use and in analysis of pre-diagnostic low-dose aspirin use. In this large nationwide study of breast cancer patients, we found little evidence of an association between post-diagnostic low-dose aspirin use and cancer-specific mortality. Copyright © 2016 Elsevier Ltd. All rights reserved.

Identification of amino acid residues involved in substrate specificity of plant acyl-ACP thioesterases using a bioinformatics-guided approach

PubMed Central

Mayer, Kimberly M; Shanklin, John

2007-01-01

Background The large amount of available sequence information for the plant acyl-ACP thioesterases (TEs) made it possible to use a bioinformatics-guided approach to identify amino acid residues involved in substrate specificity. The Conserved Property Difference Locator (CPDL) program allowed the identification of putative specificity-determining residues that differ between the FatA and FatB TE classes. Six of the FatA residue differences identified by CPDL were incorporated into the FatB-like parent via site-directed mutagenesis and the effect of each on TE activity was determined. Variants were expressed in E. coli strain K27 that allows determination of enzyme activity by GCMS analysis of fatty acids released into the medium. Results Substitutions at four of the positions (74, 86, 141, and 174) changed substrate specificity to varying degrees while changes at the remaining two positions, 110 and 221, essentially inactivated the thioesterase. The effects of substitutions at positions 74, 141, and 174 (3-MUT) or 74, 86, 141, 174 (4-MUT) were not additive with respect to specificity. Conclusion Four of six putative specificity determining positions in plant TEs, identified with the use of CPDL, were validated experimentally; a novel colorimetric screen that discriminates between active and inactive TEs is also presented. PMID:17201914

GEAR: genomic enrichment analysis of regional DNA copy number changes.

PubMed

Kim, Tae-Min; Jung, Yu-Chae; Rhyu, Mun-Gan; Jung, Myeong Ho; Chung, Yeun-Jun

2008-02-01

We developed an algorithm named GEAR (genomic enrichment analysis of regional DNA copy number changes) for functional interpretation of genome-wide DNA copy number changes identified by array-based comparative genomic hybridization. GEAR selects two types of chromosomal alterations with potential biological relevance, i.e. recurrent and phenotype-specific alterations. Then it performs functional enrichment analysis using a priori selected functional gene sets to identify primary and clinical genomic signatures. The genomic signatures identified by GEAR represent functionally coordinated genomic changes, which can provide clues on the underlying molecular mechanisms related to the phenotypes of interest. GEAR can help the identification of key molecular functions that are activated or repressed in the tumor genomes leading to the improved understanding on the tumor biology. GEAR software is available with online manual in the website, http://www.systemsbiology.co.kr/GEAR/.

Quantifiable and objective approach to organizational performance enhancement.

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

Scholand, Andrew Joseph; Tausczik, Yla R.

This report describes a new methodology, social language network analysis (SLNA), that combines tools from social language processing and network analysis to identify socially situated relationships between individuals which, though subtle, are highly influential. Specifically, SLNA aims to identify and characterize the nature of working relationships by processing artifacts generated with computer-mediated communication systems, such as instant message texts or emails. Because social language processing is able to identify psychological, social, and emotional processes that individuals are not able to fully mask, social language network analysis can clarify and highlight complex interdependencies between group members, even when these relationships aremore » latent or unrecognized. This report outlines the philosophical antecedents of SLNA, the mechanics of preprocessing, processing, and post-processing stages, and some example results obtained by applying this approach to a 15-month corporate discussion archive.« less

Nuclear morphology for the detection of alterations in bronchial cells from lung cancer: an attempt to improve sensitivity and specificity.

PubMed

Fafin-Lefevre, Mélanie; Morlais, Fabrice; Guittet, Lydia; Clin, Bénédicte; Launoy, Guy; Galateau-Sallé, Françoise; Plancoulaine, Benoît; Herlin, Paulette; Letourneux, Marc

2011-08-01

To identify which morphologic or densitometric parameters are modified in cell nuclei from bronchopulmonary cancer based on 18 parameters involving shape, intensity, chromatin, texture, and DNA content and develop a bronchopulmonary cancer screening method relying on analysis of sputum sample cell nuclei. A total of 25 sputum samples from controls and 22 bronchial aspiration samples from patients presenting with bronchopulmonary cancer who were professionally exposed to cancer were used. After Feulgen staining, 18 morphologic and DNA content parameters were measured on cell nuclei, via image cytom- etry. A method was developed for analyzing distribution quantiles, compared with simply interpreting mean values, to characterize morphologic modifications in cell nuclei. Distribution analysis of parameters enabled us to distinguish 13 of 18 parameters that demonstrated significant differences between controls and cancer cases. These parameters, used alone, enabled us to distinguish two population types, with both sensitivity and specificity > 70%. Three parameters offered 100% sensitivity and specificity. When mean values offered high sensitivity and specificity, comparable or higher sensitivity and specificity values were observed for at least one of the corresponding quantiles. Analysis of modification in morphologic parameters via distribution analysis proved promising for screening bronchopulmonary cancer from sputum.

In Silico Analysis of Expression Data for Identification of Genes Involved in Spatial Accumulation of Calcium in Developing Seeds of Rice

PubMed Central

Goel, Anshita; Gaur, Vikram S.; Arora, Sandeep; Gupta, Sanjay

2012-01-01

Abstract The calcium (Ca2+) transporters, like Ca2+ channels, Ca2+ ATPases, and Ca2+ exchangers, are instrumental for signaling and transport. However, the mechanism by which they orchestrate the accumulation of Ca2+ in grain filling has not yet been investigated. Hence the present study was designed to identify the potential calcium transporter genes that may be responsible for the spatial accumulation of calcium during grain filling. In silico expression analyses were performed to identify Ca2+ transporters that predominantly express during the different developmental stages of Oryza sativa. A total of 13 unique calcium transporters (7 from massively parallel signature sequencing [MPSS] data analysis, and 9 from microarray analysis) were identified. Analysis of variance (ANOVA) revealed differential expression of the transporters across tissues, and principal component analysis (PCA) exhibited their seed-specific distinctive expression profile. Interestingly, Ca2+ exchanger genes are highly expressed in the initial stages, whereas some Ca2+ ATPase genes are highly expressed throughout seed development. Furthermore, analysis of the cis-elements located in the promoter region of the subset of 13 genes suggested that Dof proteins play essential roles in regulating the expression of Ca2+ transporter genes during rice seed development. Based on these results, we developed a hypothetical model explaining the transport and tissue specific distribution of calcium in developing cereal seeds. The model may be extrapolated to understand the mechanism behind the exceptionally high level of calcium accumulation seen in grains like finger millet. PMID:22734689

Genome-wide organization and expression profiling of the NAC transcription factor family in potato (Solanum tuberosum L.).

PubMed

Singh, Anil Kumar; Sharma, Vishal; Pal, Awadhesh Kumar; Acharya, Vishal; Ahuja, Paramvir Singh

2013-08-01

NAC [no apical meristem (NAM), Arabidopsis thaliana transcription activation factor [ATAF1/2] and cup-shaped cotyledon (CUC2)] proteins belong to one of the largest plant-specific transcription factor (TF) families and play important roles in plant development processes, response to biotic and abiotic cues and hormone signalling. Our genome-wide analysis identified 110 StNAC genes in potato encoding for 136 proteins, including 14 membrane-bound TFs. The physical map positions of StNAC genes on 12 potato chromosomes were non-random, and 40 genes were found to be distributed in 16 clusters. The StNAC proteins were phylogenetically clustered into 12 subgroups. Phylogenetic analysis of StNACs along with their Arabidopsis and rice counterparts divided these proteins into 18 subgroups. Our comparative analysis has also identified 36 putative TNAC proteins, which appear to be restricted to Solanaceae family. In silico expression analysis, using Illumina RNA-seq transcriptome data, revealed tissue-specific, biotic, abiotic stress and hormone-responsive expression profile of StNAC genes. Several StNAC genes, including StNAC072 and StNAC101that are orthologs of known stress-responsive Arabidopsis RESPONSIVE TO DEHYDRATION 26 (RD26) were identified as highly abiotic stress responsive. Quantitative real-time polymerase chain reaction analysis largely corroborated the expression profile of StNAC genes as revealed by the RNA-seq data. Taken together, this analysis indicates towards putative functions of several StNAC TFs, which will provide blue-print for their functional characterization and utilization in potato improvement.

A Semi-parametric Transformation Frailty Model for Semi-competing Risks Survival Data

PubMed Central

Jiang, Fei; Haneuse, Sebastien

2016-01-01

In the analysis of semi-competing risks data interest lies in estimation and inference with respect to a so-called non-terminal event, the observation of which is subject to a terminal event. Multi-state models are commonly used to analyse such data, with covariate effects on the transition/intensity functions typically specified via the Cox model and dependence between the non-terminal and terminal events specified, in part, by a unit-specific shared frailty term. To ensure identifiability, the frailties are typically assumed to arise from a parametric distribution, specifically a Gamma distribution with mean 1.0 and variance, say, σ2. When the frailty distribution is misspecified, however, the resulting estimator is not guaranteed to be consistent, with the extent of asymptotic bias depending on the discrepancy between the assumed and true frailty distributions. In this paper, we propose a novel class of transformation models for semi-competing risks analysis that permit the non-parametric specification of the frailty distribution. To ensure identifiability, the class restricts to parametric specifications of the transformation and the error distribution; the latter are flexible, however, and cover a broad range of possible specifications. We also derive the semi-parametric efficient score under the complete data setting and propose a non-parametric score imputation method to handle right censoring; consistency and asymptotic normality of the resulting estimators is derived and small-sample operating characteristics evaluated via simulation. Although the proposed semi-parametric transformation model and non-parametric score imputation method are motivated by the analysis of semi-competing risks data, they are broadly applicable to any analysis of multivariate time-to-event outcomes in which a unit-specific shared frailty is used to account for correlation. Finally, the proposed model and estimation procedures are applied to a study of hospital readmission among patients diagnosed with pancreatic cancer. PMID:28439147

The establishment of species-specific primers for the molecular identification of ten stored-product psocids based on ITS2 rDNA

PubMed Central

Zhao, Zi-Hua; Cui, Bing-Yi; Li, Zhi-Hong; Jiang, Fan; Yang, Qian-Qian; Kučerová, Zuzana; Stejskal, Václav; Opit, George; Cao, Yang; Li, Fu-Jun

2016-01-01

Psocids are important stored product pests found worldwide that can be spread through grain trade. Most stored-product psocids, including eggs, nymphs, and adults, are very small (~1 mm) and difficult to identify morphologically. Here, we collected 10 economically important stored-product Liposcelis spp. psocids (L. bostrychophila, L. entomophila, L. decolor, L. paeta, L. brunnea, L. corrodens, L. mendax, L. rufa, L. pearmani, and L. tricolor) from 35 geographical locations in 5 countries (China, Czech Republic, Denmark, Germany, and the United States). The ITS2 rDNA gene was extracted and sequenced. The interspecific genetic distance of the stored-product psocids was significantly higher than the intraspecific genetic distance according to the barcoding gap analysis. Ten pairs of species-specific primers based on the ITS2 rDNA were developed for psocid identification. The sensitivity estimation indicated that the species-specific primers could correctly amplify the target ITS2 gene and successfully identify psocids at 1.0 ng/mL. Additionally, these species-specific primers could quantify specificity and identify 10 stored-product psocids; this approach could also be used to accurately identify other stored-product psocids. This work provides a practical approach for the precise examination of 10 stored-product psocid species and also contributes to the development of an identification method using ITS2 rDNA. PMID:26880378

Evaluation of an inpatient fall risk screening tool to identify the most critical fall risk factors in inpatients.

PubMed

Hou, Wen-Hsuan; Kang, Chun-Mei; Ho, Mu-Hsing; Kuo, Jessie Ming-Chuan; Chen, Hsiao-Lien; Chang, Wen-Yin

2017-03-01

To evaluate the accuracy of the inpatient fall risk screening tool and to identify the most critical fall risk factors in inpatients. Variations exist in several screening tools applied in acute care hospitals for examining risk factors for falls and identifying high-risk inpatients. Secondary data analysis. A subset of inpatient data for the period from June 2011-June 2014 was extracted from the nursing information system and adverse event reporting system of an 818-bed teaching medical centre in Taipei. Data were analysed using descriptive statistics, receiver operating characteristic curve analysis and logistic regression analysis. During the study period, 205 fallers and 37,232 nonfallers were identified. The results revealed that the inpatient fall risk screening tool (cut-off point of ≥3) had a low sensitivity level (60%), satisfactory specificity (87%), a positive predictive value of 2·0% and a negative predictive value of 99%. The receiver operating characteristic curve analysis revealed an area under the curve of 0·805 (sensitivity, 71·8%; specificity, 78%). To increase the sensitivity values, the Youden index suggests at least 1·5 points to be the most suitable cut-off point for the inpatient fall risk screening tool. Multivariate logistic regression analysis revealed a considerably increased fall risk in patients with impaired balance and impaired elimination. The fall risk factor was also significantly associated with days of hospital stay and with admission to surgical wards. The findings can raise awareness about the two most critical risk factors for falls among future clinical nurses and other healthcare professionals and thus facilitate the development of fall prevention interventions. This study highlights the needs for redefining the cut-off points of the inpatient fall risk screening tool to effectively identify inpatients at a high risk of falls. Furthermore, inpatients with impaired balance and impaired elimination should be closely monitored by nurses to prevent falling during hospitalisations. © 2016 John Wiley & Sons Ltd.

Omics of Brucella: Species-Specific sRNA-Mediated Gene Ontology Regulatory Networks Identified by Computational Biology.

PubMed

Vishnu, Udayakumar S; Sankarasubramanian, Jagadesan; Gunasekaran, Paramasamy; Sridhar, Jayavel; Rajendhran, Jeyaprakash

2016-06-01

Brucella is an intracellular bacterium that causes the zoonotic infectious disease, brucellosis. Brucella species are currently intensively studied with a view to developing novel global health diagnostics and therapeutics. In this context, small RNAs (sRNAs) are one of the emerging topical areas; they play significant roles in regulating gene expression and cellular processes in bacteria. In the present study, we forecast sRNAs in three Brucella species that infect humans, namely Brucella melitensis, Brucella abortus, and Brucella suis, using a computational biology analysis. We combined two bioinformatic algorithms, SIPHT and sRNAscanner. In B. melitensis 16M, 21 sRNA candidates were identified, of which 14 were novel. Similarly, 14 sRNAs were identified in B. abortus, of which four were novel. In B. suis, 16 sRNAs were identified, and five of them were novel. TargetRNA2 software predicted the putative target genes that could be regulated by the identified sRNAs. The identified mRNA targets are involved in carbohydrate, amino acid, lipid, nucleotide, and coenzyme metabolism and transport, energy production and conversion, replication, recombination, repair, and transcription. Additionally, the Gene Ontology (GO) network analysis revealed the species-specific, sRNA-based regulatory networks in B. melitensis, B. abortus, and B. suis. Taken together, although sRNAs are veritable modulators of gene expression in prokaryotes, there are few reports on the significance of sRNAs in Brucella. This report begins to address this literature gap by offering a series of initial observations based on computational biology to pave the way for future experimental analysis of sRNAs and their targets to explain the complex pathogenesis of Brucella.

Influence of toroidal magnetic field in multiaccreting tori

NASA Astrophysics Data System (ADS)

Pugliese, D.; Montani, G.

2018-06-01

We analysed the effects of a toroidal magnetic field in the formation of several magnetized accretion tori, dubbed as ringed accretion discs (RADs), orbiting around one central Kerr supermassive black hole (SMBH) in active galactic nuclei (AGNs), where both corotating and counterotating discs are considered. Constraints on tori formation and emergence of RADs instabilities, accretion on to the central attractor and tori collision emergence, are investigated. The results of this analysis show that the role of the central BH spin-mass ratio, the magnetic field and the relative fluid rotation and tori rotation with respect the central BH, are crucial elements in determining the accretion tori features, providing ultimately evidence of a strict correlation between SMBH spin, fluid rotation, and magnetic fields in RADs formation and evolution. More specifically, we proved that magnetic field and discs rotation are in fact strongly constrained, as tori formation and evolution in RADs depend on the toroidal magnetic fields parameters. Eventually, this analysis identifies specific classes of tori, for restrict ranges of magnetic field parameter, that can be observed around some specific SMBHs identified by their dimensionless spin.

Hypoxia-induced HIF1α targets in melanocytes reveal a molecular profile associated with poor melanoma prognosis

PubMed Central

Loftus, Stacie K.; Baxter, Laura L.; Cronin, Julia C.; Fufa, Temesgen D.; Pavan, William J.

2017-01-01

Summary Hypoxia and HIF1α signaling direct tissue-specific gene responses regulating tumor progression, invasion and metastasis. By integrating HIF1α knockdown and hypoxia-induced gene expression changes, this study identifies a melanocyte-specific, HIF1α-dependent/hypoxia-responsive gene expression signature. Integration of these gene expression changes with HIF1α ChIP-Seq analysis identifies 81 HIF1α direct target genes in melanocytes. The expression levels for ten of the HIF1α direct targets – GAPDH, PKM, PPAT, DARS, DTWD1, SEH1L, ZNF292, RLF, AGTRAP, and GPC6 – are significantly correlated with reduced time of Disease Free Status (DFS) in melanoma by logistic regression (P-value =0.0013) and ROC curve analysis (AUC= 0.826, P-value<0.0001). This HIF1α-regulated profile defines a melanocyte-specific response under hypoxia, and demonstrates the role of HIF1α as an invasive cell state gatekeeper in regulating cellular metabolism, chromatin and transcriptional regulation, vascularization and invasion. PMID:28168807

A Unique Procedure to Identify Cell Surface Markers Through a Spherical Self-Organizing Map Applied to DNA Microarray Analysis.

PubMed

Sugii, Yuh; Kasai, Tomonari; Ikeda, Masashi; Vaidyanath, Arun; Kumon, Kazuki; Mizutani, Akifumi; Seno, Akimasa; Tokutaka, Heizo; Kudoh, Takayuki; Seno, Masaharu

2016-01-01

To identify cell-specific markers, we designed a DNA microarray platform with oligonucleotide probes for human membrane-anchored proteins. Human glioma cell lines were analyzed using microarray and compared with normal and fetal brain tissues. For the microarray analysis, we employed a spherical self-organizing map, which is a clustering method suitable for the conversion of multidimensional data into two-dimensional data and displays the relationship on a spherical surface. Based on the gene expression profile, the cell surface characteristics were successfully mirrored onto the spherical surface, thereby distinguishing normal brain tissue from the disease model based on the strength of gene expression. The clustered glioma-specific genes were further analyzed by polymerase chain reaction procedure and immunocytochemical staining of glioma cells. Our platform and the following procedure were successfully demonstrated to categorize the genes coding for cell surface proteins that are specific to glioma cells. Our assessment demonstrates that a spherical self-organizing map is a valuable tool for distinguishing cell surface markers and can be employed in marker discovery studies for the treatment of cancer.

Analysis of Transportation and Logistics Challenges Affecting the Deployment of Larger Wind Turbines: Summary of Results

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

J. Cotrell, T. Stehly, J. Johnson, J. O. Roberts, Z. Parker, G. Scott, and D. Heimiller

The objectives of this study were to identify the transportation and logistics challenges, assess the associated impacts, and provide recommendations for strategies and specific actions to address the challenges.

Task analysis of intersection driving scenarios : information processing bottlenecks

DOT National Transportation Integrated Search

2006-08-01

The purpose of this report is to identify the information processing bottlenecks that drivers face in specific intersection driving scenarios. These bottlenecks represent situations in which drivers may become 'overloaded' by driving demands, which c...

40 CFR 1033.625 - Special certification provisions for non-locomotive-specific engines.

Code of Federal Regulations, 2010 CFR

2010-07-01

... and engine family identifier for the engines. (ii) A brief engineering analysis describing how the... engine software. Note that this allowance to separately submit some of the information required by § 1033...

40 CFR 1033.625 - Special certification provisions for non-locomotive-specific engines.

Code of Federal Regulations, 2011 CFR

2011-07-01

... and engine family identifier for the engines. (ii) A brief engineering analysis describing how the... engine software. Note that this allowance to separately submit some of the information required by § 1033...

Optimizing construction quality management of pavements using mechanistic performance analysis.

DOT National Transportation Integrated Search

2004-08-01

This report presents a statistical-based algorithm that was developed to reconcile the results from several pavement performance models used in the state of practice with systematic process control techniques. These algorithms identify project-specif...

A search for specificity in DNA-drug interactions.

PubMed

Cruciani, G; Goodford, P J

1994-06-01

The GRID force field and a principal component analysis have been used in order to predict the interactions of small chemical groups with all 64 different triplet sequences of B-DNA. Factors that favor binding to guanine-cytosine base pairs have been identified, and a dictionary of ligand groups and their locations is presented as a guide to the design of specific DNA ligands.

Modeling and observations of an elevated, moving infrasonic source: Eigenray methods.

PubMed

Blom, Philip; Waxler, Roger

2017-04-01

The acoustic ray tracing relations are extended by the inclusion of auxiliary parameters describing variations in the spatial ray coordinates and eikonal vector due to changes in the initial conditions. Computation of these parameters allows one to define the geometric spreading factor along individual ray paths and assists in identification of caustic surfaces so that phase shifts can be easily identified. A method is developed leveraging the auxiliary parameters to identify propagation paths connecting specific source-receiver geometries, termed eigenrays. The newly introduced method is found to be highly efficient in cases where propagation is non-planar due to horizontal variations in the propagation medium or the presence of cross winds. The eigenray method is utilized in analysis of infrasonic signals produced by a multi-stage sounding rocket launch with promising results for applications of tracking aeroacoustic sources in the atmosphere and specifically to analysis of motor performance during dynamic tests.

Paediatric acid-base disorders: A case-based review of procedures and pitfalls

PubMed Central

Carmody, J Bryan; Norwood, Victoria F

2013-01-01

Acid-base disorders occur frequently in paediatric patients. Despite the perception that their analysis is complex and difficult, a straightforward set of rules is sufficient to interpret even the most complex disorders – provided certain pitfalls are avoided. Using a case-based approach, the present article reviews the fundamental concepts of acid-base analysis and highlights common mistakes and oversights. Specific topics include the proper identification of the primary disorder; distinguishing compensatory changes from additional primary disorders; use of the albumin-corrected anion gap to generate a differential diagnosis for patients with metabolic acidosis; screening for mixed disorders with the delta-delta formula; recognizing the limits of compensation; use of the anion gap to identify ‘hidden’ acidosis; and the importance of using information from the history and physical examination to identify the specific cause of a patient’s acid-base disturbance. PMID:24381489

Information technology and hospice palliative care: social, cultural, ethical and technical implications in a rural setting.

PubMed

Kuziemsky, Craig; Jewers, Heather; Appleby, Brenda; Foshay, Neil; Maccaull, Wendy; Miller, Keith; Macdonald, Madonna

2012-01-01

There is a need to better understand the specific settings in which health information technology (HIT) is used and implemented. Factors that will determine the successful implementation of HIT are context-specific and often reside not at the technical level but rather at the process and people level. This paper provides the results of a needs assessment for HIT to support hospice palliative care (HPC) delivery in rural settings. Roundtable discussions using the nominal group technique were done to identify priority issues regarding HIT usage to support rural HPC delivery. Qualitative content analysis was then used to identify sociotechnical themes from the roundtable data. Twenty priority issues were identified at the roundtable session. Content analysis grouped the priority issues into one central theme and five supporting themes to form a sociotechnical framework for patient-centered care in rural settings. There are several sociotechnical themes and associated issues that need to be considered prior to implementing HIT in rural HPC settings. Proactive evaluation of these issues can enhance HIT implementation and also help to make ethical aspects of HIT design more explicit.

Gender specific analysis of occupational diseases of the low back caused by carrying, lifting or extreme trunk flexion—use of a prevention index to identify occupations with high prevention needs

PubMed Central

Thiede, Markus; Liebers, Falk; Seidler, Andreas; Gravemeyer, Stefan; Latza, Ute

2014-01-01

Background Gender specific analysis of the occupational disease of the lumbar spine caused by carrying, lifting, or extreme trunk flexion in Germany (OD No.2108) with the aim to identify areas of focus for prevention and research with a prevention index (PI). Methods Data from the German Statutory Accident Insurance stratified by gender are shown. Results From 2002 until 2009 there were 2,877 confirmed cases of an OD No. 2108 (40.1% male and 59.1% female). The PI indicated the highest prevention need for female nursing/midwifery associate professionals and male building frame and related trades workers. Patient transfer and working in extremely bent posture were the most frequent exposures. Conclusions The identified occupations with high need for prevention among men come from nearly all major occupational groups whereas women cluster in occupational groups from the health and care sectors. Am. J. Ind. Med. 57:233–244, 2014. © 2013 The Authors. American Journal of Industrial Medicine Published by Wiley Periodicals, Inc. PMID:24243091

Identifying hearing loss by means of iridology.

PubMed

Stearn, Natalie; Swanepoel, De Wet

2006-11-13

Isolated reports of hearing loss presenting as markings on the iris exist, but to date the effectiveness of iridology to identify hearing loss has not been investigated. This study therefore aimed to determine the efficacy of iridological analysis in the identification of moderate to profound sensorineural hearing loss in adolescents. A controlled trial was conducted with an iridologist, blind to the actual hearing status of participants, analyzing the irises of participants with and without hearing loss. Fifty hearing impaired and fifty normal hearing subjects, between the ages of 15 and 19 years, controlled for gender, participated in the study. An experienced iridologist analyzed the randomised set of participants' irises. A 70% correct identification of hearing status was obtained by iridological analyses with a false negative rate of 41% compared to a 19% false positive rate. The respective sensitivity and specificity rates therefore came to 59% and 81%. Iridological analysis of hearing status indicated a statistically significant relationship to actual hearing status (P < 0.05). Although statistically significant sensitivity and specificity rates for identifying hearing loss by iridology were not comparable to those of traditional audiological screening procedures.

Replication of Caucasian Loci Associated with Osteoporosis-related Traits in East Asians

PubMed Central

Kim, Beom-Jun; Ahn, Seong Hee; Kim, Hyeon-Mok; Ikegawa, Shiro; Yang, Tie-Lin; Guo, Yan; Deng, Hong-Wen; Koh, Jung-Min

2016-01-01

Background Most reported genome-wide association studies (GWAS) seeking to identify the loci of osteoporosis-related traits have involved Caucasian populations. We aimed to identify the single nucleotide polymorphisms (SNPs) of osteoporosis-related traits among East Asian populations from the bone mineral density (BMD)-related loci of an earlier GWAS meta-analysis. Methods A total of 95 SNPs, identified at the discovery stage of the largest GWAS meta-analysis of BMD, were tested to determine associations with osteoporosis-related traits (BMD, osteoporosis, or fracture) in Korean subjects (n=1,269). The identified SNPs of osteoporosis-related traits in Korean subjects were included in the replication analysis using Chinese (n=2,327) and Japanese (n=768) cohorts. Results A total of 17 SNPs were associated with low BMD in Korean subjects. Specifically, 9, 6, 9, and 5 SNPs were associated with the presence of osteoporosis, non-vertebral fractures, vertebral fractures, and any fracture, respectively. Collectively, 35 of the 95 SNPs (36.8%) were associated with one or more osteoporosis-related trait in Korean subjects. Of the 35 SNPs, 19 SNPs (54.3%) were also associated with one or more osteoporosis-related traits in East Asian populations. Twelve SNPs were associated with low BMD in the Chinese and Japanese cohorts. Specifically, 3, 4, and 2 SNPs were associated with the presence of hip fractures, vertebral fractures, and any fracture, respectively. Conclusions Our results identified the common SNPs of osteoporosis-related traits in both Caucasian and East Asian populations. These SNPs should be further investigated to assess whether they are true genetic markers of osteoporosis. PMID:27965945

Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients.

PubMed

Gaykalova, Daria A; Vatapalli, Rajita; Wei, Yingying; Tsai, Hua-Ling; Wang, Hao; Zhang, Chi; Hennessey, Patrick T; Guo, Theresa; Tan, Marietta; Li, Ryan; Ahn, Julie; Khan, Zubair; Westra, William H; Bishop, Justin A; Zaboli, David; Koch, Wayne M; Khan, Tanbir; Ochs, Michael F; Califano, Joseph A

2015-01-01

Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC.

What's New in the Site Characterization Tool Box: Molecular Biological Tools to Identify Microorganisms that Degrade Contaminants and Contaminant-Specific Isotope Analysis to Identify Sources and Document Degradation

EPA Science Inventory

In the past, it was necessary to conduct intensive sampling and monitoring of concentrations of contaminants in ground water to trace plumes back to their true source. Now it is possible to determine the ratio of stable isotopes of carbon, hydrogen or chlorine in the contaminan...

Tactical Unit Data and Decision Requirements for Urban Operations

DTIC Science & Technology

2008-10-01

maneuverability, sensor optimization, weapon effects, terrain), and develop rich but lightweight information structures and architecture . Specifically, the goal...tion structure and systemic architecture that enable sharing common data in near real-time, and mission planning and analysis software for U-BE...Building Function Verify mosque and identify possi- ble schools or meeting places Identify types of cinema (stage/theatre) or other similar nearby

Proteomic analysis of human dental cementum and alveolar bone

PubMed Central

Salmon, Cristiane R.; Tomazela, Daniela M.; Ruiz, Karina Gonzales Silvério; Foster, Brian L.; Leme, Adriana Franco Paes; Sallum, Enilson Antonio; Somerman, Martha J.; Nociti, Francisco H.

2013-01-01

Dental cementum (DC) is a bone-like tissue covering the tooth root and responsible for attaching the tooth to the alveolar bone (AB) via the periodontal ligament (PDL). Studies have unsuccessfully tried to identify factors specific to DC versus AB, in an effort to better understand DC development and regeneration. The present study aimed to use matched human DC and AB samples (n=7) to generate their proteomes for comparative analysis. Bone samples were harvested from tooth extraction sites, whereas DC samples were obtained from the apical root portion of extracted third molars. Samples were denatured, followed by protein extraction reduction, alkylation and digestion for analysis by nanoAcquity HPLC system and LTQ-FT Ultra. Data analysis demonstrated that a total of 318 proteins were identified in AB and DC. In addition to shared proteins between these tissues, 105 and 83 proteins exclusive to AB or DC were identified, respectively. This is the first report analyzing the proteomic composition of human DC matrix and identifying putative unique and enriched proteins in comparison to alveolar bone. These findings may provide novel insights into developmental differences between DC and AB, and identify candidate biomarkers that may lead to more efficient and predictable therapies for periodontal regeneration. PMID:24007660

TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

PubMed

Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

2017-02-01

MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

Comparative phylogenomic analysis provides insights into TCP gene functions in Sorghum

PubMed Central

Francis, Aleena; Dhaka, Namrata; Bakshi, Mohit; Jung, Ki-Hong; Sharma, Manoj K.; Sharma, Rita

2016-01-01

Sorghum is a highly efficient C4 crop with potential to mitigate challenges associated with food, feed and fuel. TCP proteins are of particular interest for crop improvement programs due to their well-demonstrated roles in crop domestication and shaping plant architecture thereby, affecting agronomic traits. We identified 20 TCP genes from Sorghum. Except SbTCP8, all are either intronless or contain introns in the untranslated regions. Comparative phylogenetic analysis of Arabidopsis, rice, Brachypodium and Sorghum TCP proteins revealed two distinct classes categorized into ten sub-clades. Sub-clade F is dicot-specific, whereas A2, G1 and I1 groups only contained genes from grasses. Sub-clade B was missing in Sorghum, whereas group A1 was missing in rice indicating species-specific divergence of TCP proteins. TCP proteins of Sorghum are enriched in disorder promoting residues with class I containing higher percent disorder than class II proteins. Seven pairs of paralogous TCP genes were identified from Sorghum, five of which seem to predate Rice-Sorghum divergence. All of them have diverged in their expression. Based on the expression and orthology analysis, five Sorghum genes have been shortlisted for further investigation for their roles in regulating plant morphology. Whereas, three genes have been identified as candidates for engineering abiotic stress tolerance. PMID:27917941

Comparative phylogenomic analysis provides insights into TCP gene functions in Sorghum.

PubMed

Francis, Aleena; Dhaka, Namrata; Bakshi, Mohit; Jung, Ki-Hong; Sharma, Manoj K; Sharma, Rita

2016-12-05

Sorghum is a highly efficient C4 crop with potential to mitigate challenges associated with food, feed and fuel. TCP proteins are of particular interest for crop improvement programs due to their well-demonstrated roles in crop domestication and shaping plant architecture thereby, affecting agronomic traits. We identified 20 TCP genes from Sorghum. Except SbTCP8, all are either intronless or contain introns in the untranslated regions. Comparative phylogenetic analysis of Arabidopsis, rice, Brachypodium and Sorghum TCP proteins revealed two distinct classes categorized into ten sub-clades. Sub-clade F is dicot-specific, whereas A2, G1 and I1 groups only contained genes from grasses. Sub-clade B was missing in Sorghum, whereas group A1 was missing in rice indicating species-specific divergence of TCP proteins. TCP proteins of Sorghum are enriched in disorder promoting residues with class I containing higher percent disorder than class II proteins. Seven pairs of paralogous TCP genes were identified from Sorghum, five of which seem to predate Rice-Sorghum divergence. All of them have diverged in their expression. Based on the expression and orthology analysis, five Sorghum genes have been shortlisted for further investigation for their roles in regulating plant morphology. Whereas, three genes have been identified as candidates for engineering abiotic stress tolerance.

Buffalo cervico-vaginal fluid proteomics with special reference to estrous cycle: heat shock protein (HSP)-70 appears to be an estrus indicator.

PubMed

Muthukumar, Subramanian; Rajkumar, Ramalingam; Karthikeyan, Kandasamy; Liao, Chen-Chung; Singh, Dheer; Akbarsha, Mohammad Abdulkader; Archunan, Govindaraju

2014-05-01

Cervico-vaginal fluid (CVF) plays significant roles in coitus, sperm transport, and implantation. It is believed to be a good noninvasive biomarker for various diagnostic purposes. In this study, a comprehensive proteomic analysis of buffalo CVF was performed during the estrous cycle in order to document the protein expressions, utilizing SDS-PAGE, mass spectrometry, and immunoblot. The main objective was to screen the CVF of buffalo for one or more estrus-specific proteins. A total of 416 proteins were identified in the CVF of both estrus and diestrus phases. Out of these proteins, 68 estrus-specific proteins have been extensively reviewed in the protein database. The major physiological functions of estrus CVF proteins appeared to be stress response, immune response, and metabolic. Eventually, the expression level of heat shock protein-70 in the CVF during the estrus phase, as revealed in SDS-PAGE analysis, was higher than during diestrus. The identity of the protein was confirmed by immunoblot analysis as heat shock protein-70. The findings provide a potential lead for the evaluation of these proteins for estrus detection in buffalo because CVF biomarker detection is a noninvasive technique. The mass spectrometric data of identified proteins have been deposited at the ProteomeXchange with the identifier PXD000620.

Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

PubMed

Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

2015-09-08

Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

Active site specificity profiling datasets of matrix metalloproteinases (MMPs) 1, 2, 3, 7, 8, 9, 12, 13 and 14.

PubMed

Eckhard, Ulrich; Huesgen, Pitter F; Schilling, Oliver; Bellac, Caroline L; Butler, Georgina S; Cox, Jennifer H; Dufour, Antoine; Goebeler, Verena; Kappelhoff, Reinhild; Auf dem Keller, Ulrich; Klein, Theo; Lange, Philipp F; Marino, Giada; Morrison, Charlotte J; Prudova, Anna; Rodriguez, David; Starr, Amanda E; Wang, Yili; Overall, Christopher M

2016-06-01

The data described provide a comprehensive resource for the family-wide active site specificity portrayal of the human matrix metalloproteinase family. We used the high-throughput proteomic technique PICS (Proteomic Identification of protease Cleavage Sites) to comprehensively assay 9 different MMPs. We identified more than 4300 peptide cleavage sites, spanning both the prime and non-prime sides of the scissile peptide bond allowing detailed subsite cooperativity analysis. The proteomic cleavage data were expanded by kinetic analysis using a set of 6 quenched-fluorescent peptide substrates designed using these results. These datasets represent one of the largest specificity profiling efforts with subsequent structural follow up for any protease family and put the spotlight on the specificity similarities and differences of the MMP family. A detailed analysis of this data may be found in Eckhard et al. (2015) [1]. The raw mass spectrometry data and the corresponding metadata have been deposited in PRIDE/ProteomeXchange with the accession number PXD002265.

Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens

PubMed Central

Glinsky, Gennadi V.

2016-01-01

Abstract Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8–10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of divergent sequences of regulatory DNA: (i) recombination-associated exaptation of the highly conserved ancestral regulatory DNA segments; (ii) human-specific insertions of transposable elements. PMID:27503290

Sensory overload: A concept analysis.

PubMed

Scheydt, Stefan; Müller Staub, Maria; Frauenfelder, Fritz; Nielsen, Gunnar H; Behrens, Johann; Needham, Ian

2017-04-01

In the context of mental disorders sensory overload is a widely described phenomenon used in conjunction with psychiatric interventions such as removal from stimuli. However, the theoretical foundation of sensory overload as addressed in the literature can be described as insufficient and fragmentary. To date, the concept of sensory overload has not yet been sufficiently specified or analyzed. The aim of the study was to analyze the concept of sensory overload in mental health care. A literature search was undertaken using specific electronic databases, specific journals and websites, hand searches, specific library catalogues, and electronic publishing databases. Walker and Avant's method of concept analysis was used to analyze the sources included in the analysis. All aspects of the method of Walker and Avant were covered in this concept analysis. The conceptual understanding has become more focused, the defining attributes, influencing factors and consequences are described and empirical referents identified. The concept analysis is a first step in the development of a middle-range descriptive theory of sensory overload based on social scientific and stress-theoretical approaches. This specification may serve as a fundament for further research, for the development of a nursing diagnosis or for guidelines. © 2017 Australian College of Mental Health Nurses Inc.

FLOCK cluster analysis of mast cell event clustering by high-sensitivity flow cytometry predicts systemic mastocytosis.

PubMed

Dorfman, David M; LaPlante, Charlotte D; Pozdnyakova, Olga; Li, Betty

2015-11-01

In our high-sensitivity flow cytometric approach for systemic mastocytosis (SM), we identified mast cell event clustering as a new diagnostic criterion for the disease. To objectively characterize mast cell gated event distributions, we performed cluster analysis using FLOCK, a computational approach to identify cell subsets in multidimensional flow cytometry data in an unbiased, automated fashion. FLOCK identified discrete mast cell populations in most cases of SM (56/75 [75%]) but only a minority of non-SM cases (17/124 [14%]). FLOCK-identified mast cell populations accounted for 2.46% of total cells on average in SM cases and 0.09% of total cells on average in non-SM cases (P < .0001) and were predictive of SM, with a sensitivity of 75%, a specificity of 86%, a positive predictive value of 76%, and a negative predictive value of 85%. FLOCK analysis provides useful diagnostic information for evaluating patients with suspected SM, and may be useful for the analysis of other hematopoietic neoplasms. Copyright© by the American Society for Clinical Pathology.

Monoallelic mutation analysis (MAMA) for identifying germline mutations.

PubMed

Papadopoulos, N; Leach, F S; Kinzler, K W; Vogelstein, B

1995-09-01

Dissection of germline mutations in a sensitive and specific manner presents a continuing challenge. In dominantly inherited diseases, mutations occur in only one allele and are often masked by the normal allele. Here we report the development of a sensitive and specific diagnostic strategy based on somatic cell hybridization termed MAMA (monoallelic mutation analysis). We have demonstrated the utility of this strategy in two different hereditary colorectal cancer syndromes, one caused by a defective tumour suppressor gene on chromosome 5 (familial adenomatous polyposis, FAP) and the other caused by a defective mismatch repair gene on chromosome 2 (hereditary non-polyposis colorectal cancer, HNPCC).

[Differences and similarities between the competencies of a nursing supervisor and an advanced clinical nurse specialist].

PubMed

del Barrio-Linares, M; Pumar-Méndez, M J

2015-01-01

With the aim of contributing to the development of a more specific professional regulation, the present study was to identify differences and similarities between the competencies of the nursing supervisor and clinical nurse specialist in an intensive care unit. A critical analysis of the literature published between 2003 and 2013 was conducted, identified through systematic searches in electronic databases, health management and practitioner journals and reference lists of the 17 items included. «Management and administration» and «direct clinical practice» were identified as specific competencies of nursing supervisor and clinical nurse specialist respectively. «Collaboration», «leadership» and «research» emerged as competencies shared by both profiles, but with different a operationalization way of conducting it. These findings imply that regulation, education and implementation of these profiles must address their specific skills as the distinctive approach taken in operationalizing shared. Copyright © 2014 Elsevier España, S.L.U. y SEEIUC. All rights reserved.

Identification of osteosarcoma-related specific proteins in serum samples using surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry.

PubMed

Gu, Jianli; Li, Jitian; Huang, Manyu; Zhang, Zhiyong; Li, Dongsheng; Song, Guoying; Ding, Xingpo; Li, Wuyin

2014-01-01

Osteosarcoma (OS) is the most common malignant bone tumor. To identify OS-related specific proteins for early diagnosis of OS, a novel approach, surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry (SELDI-TOF-MS) to serum samples from 25 OS patients, 16 osteochondroma, and 26 age-matched normal human volunteers as controls, was performed. Two proteins showed a significantly different expression in OS serum samples from control groups. Proteomic profiles and external leave-one-out cross-validation analysis showed that the correct rate of allocation, the sensitivity, and the specificity of diagnosis were 100%. These two proteins were further identified by searching the EPO-KB database, and one of the proteins identified as Serine rich region profile is involved in various cellular signaling cascades and tumor genesis. The presence of these two proteins in OS patients but absence from premalignant and normal human controls implied that they can be potential biomarkers for early diagnosis of OS.

Sampling and analysis of airborne resin acids and solvent-soluble material derived from heated colophony (rosin) flux: a method to quantify exposure to sensitizing compounds liberated during electronics soldering.

PubMed

Smith, P A; Son, P S; Callaghan, P M; Jederberg, W W; Kuhlmann, K; Still, K R

1996-07-17

Components of colophony (rosin) resin acids are sensitizers through dermal and pulmonary exposure to heated and unheated material. Significant work in the literature identifies specific resin acids and their oxidation products as sensitizers. Pulmonary exposure to colophony sensitizers has been estimated indirectly through formaldehyde exposure. To assess pulmonary sensitization from airborne resin acids, direct measurement is desired, as the degree to which aldehyde exposure correlates with that of resin acids during colophony heating is undefined. Any analytical method proposed should be applicable to a range of compounds and should also identify specific compounds present in a breathing zone sample. This work adapts OSHA Sampling and Analytical Method 58, which is designed to provide airborne concentration data for coal tar pitch volatile solids by air filtration through a glass fiber filter, solvent extraction of the filter, and gravimetric analysis of the non-volatile extract residue. In addition to data regarding total soluble material captured, a portion of the extract may be subjected to compound-specific analysis. Levels of soluble solids found during personal breathing zone sampling during electronics soldering in a Naval Aviation Depot ranged from below the "reliable quantitation limit" reported in the method to 7.98 mg/m3. Colophony-spiked filters analyzed in accordance with the method (modified) produced a limit of detection for total solvent-soluble colophony solids of 10 micrograms/filter. High performance liquid chromatography was used to identify abietic acid present in a breathing zone sample.

Shared molecular pathways and gene networks for cardiovascular disease and type 2 diabetes mellitus in women across diverse ethnicities.

PubMed

Chan, Kei Hang K; Huang, Yen-Tsung; Meng, Qingying; Wu, Chunyuan; Reiner, Alexander; Sobel, Eric M; Tinker, Lesley; Lusis, Aldons J; Yang, Xia; Liu, Simin

2014-12-01

Although cardiovascular disease (CVD) and type 2 diabetes mellitus (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these 2 disorders remain unknown. Using an integrative pathway and network analysis, we performed genome-wide association studies in 8155 blacks, 3494 Hispanic American, and 3697 Caucasian American women who participated in the national Women's Health Initiative single-nucleotide polymorphism (SNP) Health Association Resource and the Genomics and Randomized Trials Network. Eight top pathways and gene networks related to cardiomyopathy, calcium signaling, axon guidance, cell adhesion, and extracellular matrix seemed to be commonly shared between CVD and T2D across all 3 ethnic groups. We also identified ethnicity-specific pathways, such as cell cycle (specific for Hispanic American and Caucasian American) and tight junction (CVD and combined CVD and T2D in Hispanic American). In network analysis of gene-gene or protein-protein interactions, we identified key drivers that included COL1A1, COL3A1, and ELN in the shared pathways for both CVD and T2D. These key driver genes were cross-validated in multiple mouse models of diabetes mellitus and atherosclerosis. Our integrative analysis of American women of 3 ethnicities identified multiple shared biological pathways and key regulatory genes for the development of CVD and T2D. These prospective findings also support the notion that ethnicity-specific susceptibility genes and process are involved in the pathogenesis of CVD and T2D. © 2014 American Heart Association, Inc.

Powerful Identification of Cis-regulatory SNPs in Human Primary Monocytes Using Allele-Specific Gene Expression

PubMed Central

Almlöf, Jonas Carlsson; Lundmark, Per; Lundmark, Anders; Ge, Bing; Maouche, Seraya; Göring, Harald H. H.; Liljedahl, Ulrika; Enström, Camilla; Brocheton, Jessy; Proust, Carole; Godefroy, Tiphaine; Sambrook, Jennifer G.; Jolley, Jennifer; Crisp-Hihn, Abigail; Foad, Nicola; Lloyd-Jones, Heather; Stephens, Jonathan; Gwilliam, Rhian; Rice, Catherine M.; Hengstenberg, Christian; Samani, Nilesh J.; Erdmann, Jeanette; Schunkert, Heribert; Pastinen, Tomi; Deloukas, Panos; Goodall, Alison H.; Ouwehand, Willem H.; Cambien, François; Syvänen, Ann-Christine

2012-01-01

A large number of genome-wide association studies have been performed during the past five years to identify associations between SNPs and human complex diseases and traits. The assignment of a functional role for the identified disease-associated SNP is not straight-forward. Genome-wide expression quantitative trait locus (eQTL) analysis is frequently used as the initial step to define a function while allele-specific gene expression (ASE) analysis has not yet gained a wide-spread use in disease mapping studies. We compared the power to identify cis-acting regulatory SNPs (cis-rSNPs) by genome-wide allele-specific gene expression (ASE) analysis with that of traditional expression quantitative trait locus (eQTL) mapping. Our study included 395 healthy blood donors for whom global gene expression profiles in circulating monocytes were determined by Illumina BeadArrays. ASE was assessed in a subset of these monocytes from 188 donors by quantitative genotyping of mRNA using a genome-wide panel of SNP markers. The performance of the two methods for detecting cis-rSNPs was evaluated by comparing associations between SNP genotypes and gene expression levels in sample sets of varying size. We found that up to 8-fold more samples are required for eQTL mapping to reach the same statistical power as that obtained by ASE analysis for the same rSNPs. The performance of ASE is insensitive to SNPs with low minor allele frequencies and detects a larger number of significantly associated rSNPs using the same sample size as eQTL mapping. An unequivocal conclusion from our comparison is that ASE analysis is more sensitive for detecting cis-rSNPs than standard eQTL mapping. Our study shows the potential of ASE mapping in tissue samples and primary cells which are difficult to obtain in large numbers. PMID:23300628

Dynamic Organization of lncRNA and Circular RNA Regulators Collectively Controlled Cardiac Differentiation in Humans.

PubMed

Li, Yongsheng; Zhang, Jinwen; Huo, Caiqin; Ding, Na; Li, Junyi; Xiao, Jun; Lin, Xiaoyu; Cai, Benzhi; Zhang, Yunpeng; Xu, Juan

2017-10-01

Advances in developmental cardiology have increased our understanding of the early aspects of heart differentiation. However, understanding noncoding RNA (ncRNA) transcription and regulation during this process remains elusive. Here, we constructed transcriptomes for both long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in four important developmental stages ranging from early embryonic to cardiomyocyte based on high-throughput sequencing datasets, which indicate the high stage-specific expression patterns of two ncRNA types. Additionally, higher similarities of samples within each stage were found, highlighting the divergence of samples collected from distinct cardiac developmental stages. Next, we developed a method to identify numerous lncRNA and circRNA regulators whose expression was significantly stage-specific and shifted gradually and continuously during heart differentiation. We inferred that these ncRNAs are important for the stages of cardiac differentiation. Moreover, transcriptional regulation analysis revealed that the expression of stage-specific lncRNAs is controlled by known key stage-specific transcription factors (TFs). In addition, circRNAs exhibited dynamic expression patterns independent from their host genes. Functional enrichment analysis revealed that lncRNAs and circRNAs play critical roles in pathways that are activated specifically during heart differentiation. We further identified candidate TF-ncRNA-gene network modules for each differentiation stage, suggesting the dynamic organization of lncRNAs and circRNAs collectively controlled cardiac differentiation, which may cause heart-related diseases when defective. Our study provides a foundation for understanding the dynamic regulation of ncRNA transcriptomes during heart differentiation and identifies the dynamic organization of novel key lncRNAs and circRNAs to collectively control cardiac differentiation. Copyright © 2017. Published by Elsevier B.V.

Validation of a Low-Cost Paper-Based Screening Test for Sickle Cell Anemia

PubMed Central

Piety, Nathaniel Z.; Yang, Xiaoxi; Kanter, Julie; Vignes, Seth M.; George, Alex; Shevkoplyas, Sergey S.

2016-01-01

Background The high childhood mortality and life-long complications associated with sickle cell anemia (SCA) in developing countries could be significantly reduced with effective prophylaxis and education if SCA is diagnosed early in life. However, conventional laboratory methods used for diagnosing SCA remain prohibitively expensive and impractical in this setting. This study describes the clinical validation of a low-cost paper-based test for SCA that can accurately identify sickle trait carriers (HbAS) and individuals with SCA (HbSS) among adults and children over 1 year of age. Methods and Findings In a population of healthy volunteers and SCA patients in the United States (n = 55) the test identified individuals whose blood contained any HbS (HbAS and HbSS) with 100% sensitivity and 100% specificity for both visual evaluation and automated analysis, and detected SCA (HbSS) with 93% sensitivity and 94% specificity for visual evaluation and 100% sensitivity and 97% specificity for automated analysis. In a population of post-partum women (with a previously unknown SCA status) at a primary obstetric hospital in Cabinda, Angola (n = 226) the test identified sickle cell trait carriers with 94% sensitivity and 97% specificity using visual evaluation (none of the women had SCA). Notably, our test permits instrument- and electricity-free visual diagnostics, requires minimal training to be performed, can be completed within 30 minutes, and costs about $0.07 in test-specific consumable materials. Conclusions Our results validate the paper-based SCA test as a useful low-cost tool for screening adults and children for sickle trait and disease and demonstrate its practicality in resource-limited clinical settings. PMID:26735691

Risk factors for gastric cancer in Latin-America: a meta-analysis

PubMed Central

Bonequi, Patricia; Meneses-González, Fernando; Correa, Pelayo; Rabkin, Charles S.; Camargo, M. Constanza

2013-01-01

Background Latin America has among the highest gastric cancer incidence rates in the world, for reasons that are still unknown. In order to identify region-specific risk factors for gastric cancer, we conducted a meta-analysis summarizing published literature. Methods Searches of PubMed and regional databases for relevant studies published up to December 2011 yielded a total of 29 independent case-control studies. We calculated summary odds ratios (OR) for risk factors reported in at least five studies, including socioeconomic status (education), lifestyle habits (smoking and alcohol use), dietary factors (consumption of fruits, total vegetables, green vegetables, chili pepper, total meat, processed meat, red meat, fish and salt) and host genetic variants (IL1B-511T, IL1B-31C, IL1RN*2, TNFA-308A, TP53 codon 72 Arg and GSTM1 null). Study-specific ORs were extracted and summarized using random-effects models. Results Chili pepper was the only region-specific factor reported in at least five studies. Consistent with multifactorial pathogenesis, smoking, alcohol use, high consumption of red meat or processed meat, excessive salt intake and carriage of IL1RN*2 were each associated with a moderate increase in gastric cancer risk. Conversely, higher levels of education, fruit consumption, and total vegetable consumption were each associated with a moderately decreased risk. The other exposures were not significantly associated. No prospective study data were identified. Conclusion Risk factor associations for gastric cancer in Latin America are based on case-control comparisons that have uncertain reliability, particularly with regard to diet; the specific factors identified and their magnitudes of association are largely similar to those globally recognized. Future studies should emphasize prospective data collection and focus on region-specific exposures that may explain high gastric cancer risk. PMID:23224270

Identifying Group-Specific Sequences for Microbial Communities Using Long k-mer Sequence Signatures

PubMed Central

Wang, Ying; Fu, Lei; Ren, Jie; Yu, Zhaoxia; Chen, Ting; Sun, Fengzhu

2018-01-01

Comparing metagenomic samples is crucial for understanding microbial communities. For different groups of microbial communities, such as human gut metagenomic samples from patients with a certain disease and healthy controls, identifying group-specific sequences offers essential information for potential biomarker discovery. A sequence that is present, or rich, in one group, but absent, or scarce, in another group is considered “group-specific” in our study. Our main purpose is to discover group-specific sequence regions between control and case groups as disease-associated markers. We developed a long k-mer (k ≥ 30 bps)-based computational pipeline to detect group-specific sequences at strain resolution free from reference sequences, sequence alignments, and metagenome-wide de novo assembly. We called our method MetaGO: Group-specific oligonucleotide analysis for metagenomic samples. An open-source pipeline on Apache Spark was developed with parallel computing. We applied MetaGO to one simulated and three real metagenomic datasets to evaluate the discriminative capability of identified group-specific markers. In the simulated dataset, 99.11% of group-specific logical 40-mers covered 98.89% disease-specific regions from the disease-associated strain. In addition, 97.90% of group-specific numerical 40-mers covered 99.61 and 96.39% of differentially abundant genome and regions between two groups, respectively. For a large-scale metagenomic liver cirrhosis (LC)-associated dataset, we identified 37,647 group-specific 40-mer features. Any one of the features can predict disease status of the training samples with the average of sensitivity and specificity higher than 0.8. The random forests classification using the top 10 group-specific features yielded a higher AUC (from ∼0.8 to ∼0.9) than that of previous studies. All group-specific 40-mers were present in LC patients, but not healthy controls. All the assembled 11 LC-specific sequences can be mapped to two strains of Veillonella parvula: UTDB1-3 and DSM2008. The experiments on the other two real datasets related to Inflammatory Bowel Disease and Type 2 Diabetes in Women consistently demonstrated that MetaGO achieved better prediction accuracy with fewer features compared to previous studies. The experiments showed that MetaGO is a powerful tool for identifying group-specific k-mers, which would be clinically applicable for disease prediction. MetaGO is available at https://github.com/VVsmileyx/MetaGO. PMID:29774017

Hotspots in research on the measurement of medical students' clinical competence from 2012-2016 based on co-word analysis.

PubMed

Chang, Xing; Zhou, Xin; Luo, Linzhi; Yang, Chengjia; Pan, Hui; Zhang, Shuyang

2017-09-12

This study aimed to identify hotspots in research on clinical competence measurements from 2012 to 2016. The authors retrieved literature published between 2012 and 2016 from PubMed using selected medical subject headings (MeSH) terms. They used BibExcel software to generate high-frequency MeSH terms and identified hotspots by co-word analysis and cluster analysis. The authors searched 588 related articles and identified 31 high-frequency MeSH terms. In addition, they obtained 6 groups of high-frequency MeSH terms that reflected the domain hotspots. This study identified 6 hotspots of domain research, including studies on influencing factors and perception evaluation, improving and developing measurement tools, feedback measurement, measurement approaches based on computer simulation, the measurement of specific students in different learning phases, and the measurement of students' communication ability. All of these research topics could provide useful information for educators and researchers to continually conduct in-depth studies.

Analysis of Near-field of Circular Aperture Antennas with Application to Study of High Intensity Radio Frequency (HIRF) Hazards to Aviation from JPL/NASA Deep Space Network Antennas

NASA Technical Reports Server (NTRS)

Jamnejad, Vahraz; Statman, Joseph

2013-01-01

This work includes a simplified analysis of the radiated near to mid-field from JPL/NASA Deep Space Network (DSN) reflector antennas and uses an averaging technique over the main beam region and beyond for complying with FAA regulations in specific aviation environments. The work identifies areas that require special attention, including the implications of the very narrow beam of the DSN transmitters. The paper derives the maximum averaged power densities allowed and identifies zones where mitigation measures are required.

Data Mining of Network Logs

NASA Technical Reports Server (NTRS)

Collazo, Carlimar

2011-01-01

The statement of purpose is to analyze network monitoring logs to support the computer incident response team. Specifically, gain a clear understanding of the Uniform Resource Locator (URL) and its structure, and provide a way to breakdown a URL based on protocol, host name domain name, path, and other attributes. Finally, provide a method to perform data reduction by identifying the different types of advertisements shown on a webpage for incident data analysis. The procedures used for analysis and data reduction will be a computer program which would analyze the URL and identify and advertisement links from the actual content links.

Targeted Deletion and Lipidomic Analysis Identify Epithelial Cell COX-2 as a Major Driver of Chemically-induced Skin Cancer

PubMed Central

Jiao, Jing; Ishikawa, Tomo-o; Dumlao, Darren S.; Norris, Paul C.; Magyar, Clara E.; Mikulec, Carol; Catapang, Art; Dennis, Edward A.; Fischer, Susan M.; Herschman, Harvey R.

2014-01-01

Pharmacologic and global gene deletion studies demonstrate that cyclooxygenase-2 (PTGS2/COX2) plays a critical role in DMBA/TPA-induced skin tumor induction. While many cell types in the tumor microenvironment express COX-2, the cell types in which COX-2 expression is required for tumor promotion are not clearly established. Here, cell-type specific Cox-2 gene deletion reveals a vital role for skin epithelial cell COX-2 expression in DMBA/TPA tumor induction. In contrast, myeloid Cox-2 gene deletion has no effect on DMBA/TPA tumorigenesis. The infrequent, small tumors that develop on mice with an epithelial cell-specific Cox-2 gene deletion have decreased proliferation and increased cell differentiation properties. Blood vessel density is reduced in tumors with an epithelial cell-specific Cox-2 gene deletion, compared to littermate control tumors, suggesting a reciprocal relationship in tumor progression between COX-2 expressing tumor epithelial cells and microenvironment endothelial cells. Lipidomics analysis of skin and tumors from DMBA/TPA-treated mice suggests that the prostaglandins PGE2 and PGF2α are likely candidates for the epithelial cell COX-2-dependent eicosanoids that mediate tumor progression. This study both illustrates the value of cell-type specific gene deletions in understanding the cellular roles of signal-generating pathways in complex microenvironments and emphasizes the benefit of a systems-based lipidomic analysis approach to identify candidate lipid mediators of biological responses. PMID:25063587

Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs

PubMed Central

2013-01-01

Background The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations – changes specific to a tumor and not within an individual’s germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. Results We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. Conclusion We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic. PMID:23642077

Identification of somatic mutations in cancer through Bayesian-based analysis of sequenced genome pairs.

PubMed

Christoforides, Alexis; Carpten, John D; Weiss, Glen J; Demeure, Michael J; Von Hoff, Daniel D; Craig, David W

2013-05-04

The field of cancer genomics has rapidly adopted next-generation sequencing (NGS) in order to study and characterize malignant tumors with unprecedented resolution. In particular for cancer, one is often trying to identify somatic mutations--changes specific to a tumor and not within an individual's germline. However, false positive and false negative detections often result from lack of sufficient variant evidence, contamination of the biopsy by stromal tissue, sequencing errors, and the erroneous classification of germline variation as tumor-specific. We have developed a generalized Bayesian analysis framework for matched tumor/normal samples with the purpose of identifying tumor-specific alterations such as single nucleotide mutations, small insertions/deletions, and structural variation. We describe our methodology, and discuss its application to other types of paired-tissue analysis such as the detection of loss of heterozygosity as well as allelic imbalance. We also demonstrate the high level of sensitivity and specificity in discovering simulated somatic mutations, for various combinations of a) genomic coverage and b) emulated heterogeneity. We present a Java-based implementation of our methods named Seurat, which is made available for free academic use. We have demonstrated and reported on the discovery of different types of somatic change by applying Seurat to an experimentally-derived cancer dataset using our methods; and have discussed considerations and practices regarding the accurate detection of somatic events in cancer genomes. Seurat is available at https://sites.google.com/site/seuratsomatic.

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile

PubMed Central

Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

2017-01-01

Purpose To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Methods 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. Results 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. Conclusions CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR. PMID:28042958

A Bifactor Approach to Model Multifaceted Constructs in Statistical Mediation Analysis.

PubMed

Gonzalez, Oscar; MacKinnon, David P

Statistical mediation analysis allows researchers to identify the most important mediating constructs in the causal process studied. Identifying specific mediators is especially relevant when the hypothesized mediating construct consists of multiple related facets. The general definition of the construct and its facets might relate differently to an outcome. However, current methods do not allow researchers to study the relationships between general and specific aspects of a construct to an outcome simultaneously. This study proposes a bifactor measurement model for the mediating construct as a way to parse variance and represent the general aspect and specific facets of a construct simultaneously. Monte Carlo simulation results are presented to help determine the properties of mediated effect estimation when the mediator has a bifactor structure and a specific facet of a construct is the true mediator. This study also investigates the conditions when researchers can detect the mediated effect when the multidimensionality of the mediator is ignored and treated as unidimensional. Simulation results indicated that the mediation model with a bifactor mediator measurement model had unbiased and adequate power to detect the mediated effect with a sample size greater than 500 and medium a - and b -paths. Also, results indicate that parameter bias and detection of the mediated effect in both the data-generating model and the misspecified model varies as a function of the amount of facet variance represented in the mediation model. This study contributes to the largely unexplored area of measurement issues in statistical mediation analysis.

Standardized Index of Shape (DCE-MRI) and Standardized Uptake Value (PET/CT): Two quantitative approaches to discriminate chemo-radiotherapy locally advanced rectal cancer responders under a functional profile.

PubMed

Petrillo, Antonella; Fusco, Roberta; Petrillo, Mario; Granata, Vincenza; Delrio, Paolo; Bianco, Francesco; Pecori, Biagio; Botti, Gerardo; Tatangelo, Fabiana; Caracò, Corradina; Aloj, Luigi; Avallone, Antonio; Lastoria, Secondo

2017-01-31

To investigate dynamic contrast enhanced-MRI (DCE-MRI) in the preoperative chemo-radiotherapy (CRT) assessment for locally advanced rectal cancer (LARC) compared to18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). 75 consecutive patients with LARC were enrolled in a prospective study. DCE-MRI analysis was performed measuring SIS: linear combination of percentage change (Δ) of maximum signal difference (MSD) and wash-out slope (WOS). 18F-FDG PET/CT analysis was performed using SUV maximum (SUVmax). Tumor regression grade (TRG) were estimated after surgery. Non-parametric tests, receiver operating characteristic were evaluated. 55 patients (TRG1-2) were classified as responders while 20 subjects as non responders. ΔSIS reached sensitivity of 93%, specificity of 80% and accuracy of 89% (cut-off 6%) to differentiate responders by non responders, sensitivity of 93%, specificity of 69% and accuracy of 79% (cut-off 30%) to identify pathological complete response (pCR). Therapy assessment via ΔSUVmax reached sensitivity of 67%, specificity of 75% and accuracy of 70% (cut-off 60%) to differentiate responders by non responders and sensitivity of 80%, specificity of 31% and accuracy of 51% (cut-off 44%) to identify pCR. CRT response assessment by DCE-MRI analysis shows a higher predictive ability than 18F-FDG PET/CT in LARC patients allowing to better discriminate significant and pCR.

A confidence building exercise in data and identifiability: Modeling cancer chemotherapy as a case study.

PubMed

Eisenberg, Marisa C; Jain, Harsh V

2017-10-27

Mathematical modeling has a long history in the field of cancer therapeutics, and there is increasing recognition that it can help uncover the mechanisms that underlie tumor response to treatment. However, making quantitative predictions with such models often requires parameter estimation from data, raising questions of parameter identifiability and estimability. Even in the case of structural (theoretical) identifiability, imperfect data and the resulting practical unidentifiability of model parameters can make it difficult to infer the desired information, and in some cases, to yield biologically correct inferences and predictions. Here, we examine parameter identifiability and estimability using a case study of two compartmental, ordinary differential equation models of cancer treatment with drugs that are cell cycle-specific (taxol) as well as non-specific (oxaliplatin). We proceed through model building, structural identifiability analysis, parameter estimation, practical identifiability analysis and its biological implications, as well as alternative data collection protocols and experimental designs that render the model identifiable. We use the differential algebra/input-output relationship approach for structural identifiability, and primarily the profile likelihood approach for practical identifiability. Despite the models being structurally identifiable, we show that without consideration of practical identifiability, incorrect cell cycle distributions can be inferred, that would result in suboptimal therapeutic choices. We illustrate the usefulness of estimating practically identifiable combinations (in addition to the more typically considered structurally identifiable combinations) in generating biologically meaningful insights. We also use simulated data to evaluate how the practical identifiability of the model would change under alternative experimental designs. These results highlight the importance of understanding the underlying mechanisms rather than purely using parsimony or information criteria/goodness-of-fit to decide model selection questions. The overall roadmap for identifiability testing laid out here can be used to help provide mechanistic insight into complex biological phenomena, reduce experimental costs, and optimize model-driven experimentation. Copyright © 2017. Published by Elsevier Ltd.

“We make choices we think are going to save us”: Debate and stance identification for online breast cancer CAM discussions

PubMed Central

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-01-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients’ conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients’ stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members’ stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients’ opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work. PMID:28967000

"We make choices we think are going to save us": Debate and stance identification for online breast cancer CAM discussions.

PubMed

Zhang, Shaodian; Qiu, Lin; Chen, Frank; Zhang, Weinan; Yu, Yong; Elhadad, Noémie

2017-04-01

Patients discuss complementary and alternative medicine (CAM) in online health communities. Sometimes, patients' conflicting opinions toward CAM-related issues trigger debates in the community. The objectives of this paper are to identify such debates, identify controversial CAM therapies in a popular online breast cancer community, as well as patients' stances towards them. To scale our analysis, we trained a set of classifiers. We first constructed a supervised classifier based on a long short-term memory neural network (LSTM) stacked over a convolutional neural network (CNN) to detect automatically CAM-related debates from a popular breast cancer forum. Members' stances in these debates were also identified by a CNN-based classifier. Finally, posts automatically flagged as debates by the classifier were analyzed to explore which specific CAM therapies trigger debates more often than others. Our methods are able to detect CAM debates with F score of 77%, and identify stances with F score of 70%. The debate classifier identified about 1/6 of all CAM-related posts as debate. About 60% of CAM-related debate posts represent the supportive stance toward CAM usage. Qualitative analysis shows that some specific therapies, such as Gerson therapy and usage of laetrile, trigger debates frequently among members of the breast cancer community. This study demonstrates that neural networks can effectively locate debates on usage and effectiveness of controversial CAM therapies, and can help make sense of patients' opinions on such issues under dispute. As to CAM for breast cancer, perceptions of their effectiveness vary among patients. Many of the specific therapies trigger debates frequently and are worth more exploration in future work.

Competency frameworks for advanced practice nursing: a literature review.

PubMed

Sastre-Fullana, P; De Pedro-Gómez, J E; Bennasar-Veny, M; Serrano-Gallardo, P; Morales-Asencio, J M

2014-12-01

This paper describes a literature review that identified common traits in advanced practice nursing that are specific to competency development worldwide. There is a lack of international agreement on the definition of advanced practice nursing and its core competencies. Despite the lack of consensus, there is an ongoing process worldwide to establish and outline the standards and competencies for advanced practice nursing roles. International agencies, such as the International Council of Nurses, have provided general definitions for advanced practice nursing. Additionally, a set of competency standards for this aim has been developed. A literature review and a directed search of institutional websites were performed to identify specific developments in advanced practice nursing competencies and standards of practice. To determine a competency map specific to international advanced practice nursing, key documents were analysed using a qualitative approach based on content analysis to identify common traits among documents and countries. The review process identified 119 relevant journal articles related to advanced practice nursing competencies. Additionally, 97 documents from grey literature that were related to advanced practice nursing competency mapping were identified. From the text analysis, 17 worldwide transversal competency domains emerged. Despite the variety of patterns in international advanced practice nursing development, essential competency domains can be found in most national frameworks for the role development of international advanced practice nursing. These 17 core competencies can be used to further develop instruments that assess the perceived competency of advanced practice nurses. The results of this review can help policy developers and researchers develop instruments to compare advanced practice nursing services in various contexts and to examine their association with related outcomes. © 2014 International Council of Nurses.

Identification of specific metabolites in culture supernatant of Mycobacterium tuberculosis using metabolomics: exploration of potential biomarkers

PubMed Central

Lau, Susanna KP; Lam, Ching-Wan; Curreem, Shirly OT; Lee, Kim-Chung; Lau, Candy CY; Chow, Wang-Ngai; Ngan, Antonio HY; To, Kelvin KW; Chan, Jasper FW; Hung, Ivan FN; Yam, Wing-Cheong; Yuen, Kwok-Yung; Woo, Patrick CY

2015-01-01

Although previous studies have reported the use of metabolomics for Mycobacterium species differentiation, little is known about the potential of extracellular metabolites of Mycobacterium tuberculosis (MTB) as specific biomarkers. Using an optimized ultrahigh performance liquid chromatography–electrospray ionization–quadruple time of flight–mass spectrometry (UHPLC–ESI–Q–TOF–MS) platform, we characterized the extracellular metabolomes of culture supernatant of nine MTB strains and nine non-tuberculous Mycobacterium (NTM) strains (four M. avium complex, one M. bovis Bacillus Calmette–Guérin (BCG), one M. chelonae, one M. fortuitum and two M. kansasii). Principal component analysis readily distinguished the metabolomes between MTB and NTM. Using multivariate and univariate analysis, 24 metabolites with significantly higher levels in MTB were identified. While seven metabolites were identified by tandem mass spectrometry (MS/MS), the other 17 metabolites were unidentified by MS/MS against database matching, suggesting that they may be potentially novel compounds. One metabolite was identified as dexpanthenol, the alcohol analog of pantothenic acid (vitamin B5), which was not known to be produced by bacteria previously. Four metabolites were identified as 1-tuberculosinyladenosine (1-TbAd), a product of the virulence-associated enzyme Rv3378c, and three previously undescribed derivatives of 1-TbAd. Two derivatives differ from 1-TbAd by the ribose group of the nucleoside while the other likely differs by the base. The remaining two metabolites were identified as a tetrapeptide, Val-His-Glu-His, and a monoacylglycerophosphoglycerol, phosphatidylglycerol (PG) (16∶0/0∶0), respectively. Further studies on the chemical structure and biosynthetic pathway of these MTB-specific metabolites would help understand their biological functions. Studies on clinical samples from tuberculosis patients are required to explore for their potential role as diagnostic biomarkers. PMID:26038762

Development of a conceptual framework of health-related quality of life in locally recurrent rectal cancer.

PubMed

Harji, D P; Koh, C; Solomon, M; Velikova, G; Sagar, P M; Brown, J

2015-11-01

The surgical management of locally recurrent rectal cancer (LRRC) has become widely accepted to afford cure and improve quality of life in this subset of patients. Thus far, traditional surgical and oncological markers have been used to highlight the success of surgical intervention. The use of patient-reported outcomes, specifically health-related quality of life (HRQoL), is sparse in these patients. This may be in part due to the lack of well-designed, validated instruments. This study identifies HRQoL issues relevant to patients undergoing surgery for LRRC, with the aim of developing a conceptual framework of HRQoL specific to LRRC to enable measurement of patient-reported outcomes in this cohort of patients. Qualitative focus groups were undertaken at two institutions to identify relevant HRQoL themes. The principles of thematic content analysis were used to analysis data. NViVo10 was used to analyse data. Twenty-one patients participated in six consecutive focus groups. Two patterns of themes emerged related to HRQoL and healthcare service delivery and utilization. Identified themes related to HRQoL included symptoms, sexual function, psychological impact, role and social functioning and future perspective. Under healthcare service and delivery and utilization the subdomain of disease management, treatment expectations and healthcare professionals were identified. This is the first qualitative study undertaken exclusively in patients with LRRC to ascertain relevant HRQoL outcomes. The impact of LRRC on patients is wide-ranging and extends beyond traditional HRQoL outcomes. The study operationalizes the identified outcomes into a conceptual framework, which will provide the basis for the development of a LRRC-specific patient-reported outcome measure. Colorectal Disease © 2015 The Association of Coloproctology of Great Britain and Ireland.

An Introduction to Job Analysis

ERIC Educational Resources Information Center

Boydell, T. H.

1970-01-01

Job training involves preparing a job description and specification, and, if necessary, further analyses of skills, knowledge, and attitudes in order to identify areas of difficulty which will affect the choice of what must be learned and appropriate training techniques. (DM)

Quantitative analyses and transcriptomic profiling of circulating messenger RNAs as biomarkers of rat liver injury.

PubMed

Wetmore, Barbara A; Brees, Dominique J; Singh, Reetu; Watkins, Paul B; Andersen, Melvin E; Loy, James; Thomas, Russell S

2010-06-01

Serum aminotransferases have been the clinical standard for evaluating liver injury for the past 50-60 years. These tissue enzymes lack specificity, also tracking injury to other tissues. New technologies assessing tissue-specific messenger RNA (mRNA) release into blood should provide greater specificity and permit indirect assessment of gene expression status of injured tissue. To evaluate the potential of circulating mRNAs as biomarkers of liver injury, rats were treated either with hepatotoxic doses of D-(+)-galactosamine (DGAL) or acetaminophen (APAP) or a myotoxic dose of bupivacaine HCl (BPVC). Plasma, serum, and liver samples were obtained from each rat. Serum alanine aminotransferase and aspartate aminotransferase were increased by all three compounds, whereas circulating liver-specific mRNAs were only increased by the hepatotoxicants. With APAP, liver-specific mRNAs were significantly increased in plasma at doses that had no effect on serum aminotransferases or liver histopathology. Characterization of the circulating mRNAs by sucrose density gradient centrifugation revealed that the liver-specific mRNAs were associated with both necrotic debris and microvesicles. DGAL treatment also induced a shift in the size of plasma microvesicles, consistent with active release of microvesicles following liver injury. Finally, gene expression microarray analysis of the plasma following DGAL and APAP treatment revealed chemical-specific profiles. The comparative analysis of circulating liver mRNAs with traditional serum transaminases and histopathology indicated that the circulating liver mRNAs were more specific and more sensitive biomarkers of liver injury. Further, the possibility of identifying chemical-specific transcriptional profiles from circulating mRNAs could open a range of possibilities for identifying the etiology of drug/chemical-induced liver injury.

Identifying Multimedia Production Competencies and Skills of Instructional Design and Technology Professionals: An Analysis of Recent Job Postings

ERIC Educational Resources Information Center

Sugar, William; Hoard, Brent; Brown, Abbie; Daniels, Lee

2012-01-01

In an effort to document necessary multimedia production competencies of Instructional Design and Technology graduates, a recent analysis of over 7 months' worth of Instructional Design and Technology job advertisements (n = 615) were conducted. Specific job skills from these postings were categorized and analyzed. The data set includes three job…

Genetic analysis of teat number in pigs reveals some developmental pathways independent of vertebra number and several loci which only affect a specific side

USDA-ARS?s Scientific Manuscript database

Background: Number of functional teats is an important trait in commercial swine production. As litter size increases, the number of teats must also increase to supply nutrition to all piglets. Therefore, a genome-wide association analysis was conducted to identify genomic regions that affect this ...

Does Music Instruction Help Children Learn to Read?: Evidence of a Meta-Analysis

ERIC Educational Resources Information Center

Standley, Jayne M.

2008-01-01

This meta-analysis of 30 studies using a variety of music interventions to affect reading skills resulted in a moderately strong, significant, overall effect size of d = 0.32. When music activities incorporate specific reading skills matched to the needs of identified children (d = 0.44) or contingent music is used to reinforce reading behavior (d…

Software reliability: Application of a reliability model to requirements error analysis

NASA Technical Reports Server (NTRS)

Logan, J.

1980-01-01

The application of a software reliability model having a well defined correspondence of computer program properties to requirements error analysis is described. Requirements error categories which can be related to program structural elements are identified and their effect on program execution considered. The model is applied to a hypothetical B-5 requirement specification for a program module.

Compound-Specific Isotope Analysis of Amino Acids for Stardust-Returned Samples

NASA Technical Reports Server (NTRS)

Cook, Jamie; Elsila, Jamie E.; Stern J. C.; Glavin, D. P.; Dworkin, J. P.

2008-01-01

Significant portions of the early Earth's prebiotic organic inventory , including amino acids, could have been delivered to the Earth's sur face by comets and their fragments. Analysis of comets via spectrosc opic observations has identified many organic molecules, including me thane, ethane, arnmonia, cyanic acid, formaldehyde, formamide, acetal ehyde, acetonitrile, and methanol. Reactions between these identifie d molecules could allow the formation of more complex organics such a s amino acids. Isotopic analysis could reveal whether an extraterrest rial signature is present in the Stardust-exposed amines and amino ac ids. Although bulk isotopic analysis would be dominated by the EACA contaminant's terrestrial signature, compoundspecific isotope analysi s (CSIA) could determine the signature of each of the other individua l amines. Here, we report on progress made towards CSIA of the amino acids glycine and EACA in Stardustreturned samples.

Integrating microarray analysis and the soybean genome to understand the soybeans iron deficiency response

PubMed Central

2009-01-01

Background Soybeans grown in the upper Midwestern United States often suffer from iron deficiency chlorosis, which results in yield loss at the end of the season. To better understand the effect of iron availability on soybean yield, we identified genes in two near isogenic lines with changes in expression patterns when plants were grown in iron sufficient and iron deficient conditions. Results Transcriptional profiles of soybean (Glycine max, L. Merr) near isogenic lines Clark (PI548553, iron efficient) and IsoClark (PI547430, iron inefficient) grown under Fe-sufficient and Fe-limited conditions were analyzed and compared using the Affymetrix® GeneChip® Soybean Genome Array. There were 835 candidate genes in the Clark (PI548553) genotype and 200 candidate genes in the IsoClark (PI547430) genotype putatively involved in soybean's iron stress response. Of these candidate genes, fifty-eight genes in the Clark genotype were identified with a genetic location within known iron efficiency QTL and 21 in the IsoClark genotype. The arrays also identified 170 single feature polymorphisms (SFPs) specific to either Clark or IsoClark. A sliding window analysis of the microarray data and the 7X genome assembly coupled with an iterative model of the data showed the candidate genes are clustered in the genome. An analysis of 5' untranslated regions in the promoter of candidate genes identified 11 conserved motifs in 248 differentially expressed genes, all from the Clark genotype, representing 129 clusters identified earlier, confirming the cluster analysis results. Conclusion These analyses have identified the first genes with expression patterns that are affected by iron stress and are located within QTL specific to iron deficiency stress. The genetic location and promoter motif analysis results support the hypothesis that the differentially expressed genes are co-regulated. The combined results of all analyses lead us to postulate iron inefficiency in soybean is a result of a mutation in a transcription factor(s), which controls the expression of genes required in inducing an iron stress response. PMID:19678937

Transcriptional signature associated with early rheumatoid arthritis and healthy individuals at high risk to develop the disease

PubMed Central

Macías-Segura, N.; Bastian, Y.; Santiago-Algarra, D.; Castillo-Ortiz, J. D.; Alemán-Navarro, A. L.; Jaime-Sánchez, E.; Gomez-Moreno, M.; Saucedo-Toral, C. A.; Lara-Ramírez, Edgar E.; Zapata-Zuñiga, M.; Enciso-Moreno, L.; González-Amaro, R.; Ramos-Remus, C.; Enciso-Moreno, J. A.

2018-01-01

Background Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. Methods Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides. Complementary RNA (cRNA) was synthetized and hybridized to high-density microarrays. Data was analyzed in Genespring Software and functional categories were assigned to a specific transcriptome identified in subjects with RA and FDR ACCP positive. Specific signaling pathways for genes associated to RA were identified. Gene expression was evaluated by qPCR. Receiver operating characteristic (ROC) analysis was used to evaluate these genes as biomarkers. Results A characteristic transcriptome of 551 induced genes and 4,402 repressed genes were identified in early RA patients. Bioinformatics analysis of the data identified a specific transcriptome in RA patients. Moreover, some overlapped transcriptional profiles between patients with RA and ACCP+ were identified, suggesting an up-regulated distinctive transcriptome from the preclinical stages up to progression to an early RA state. A total of 203 pathways have up-regulated genes that are shared between RA and ACCP+. Some of these genes show potential to be used as progression biomarkers for early RA with area under the curve of ROC > 0.92. These genes come from several functional categories associated to inflammation, Wnt signaling and type I interferon pathways. Conclusion The presence of a specific transcriptome in whole blood of RA patients suggests the activation of a specific inflammatory transcriptional signature in early RA development. The set of overexpressed genes in early RA patients that are shared with ACCP+ subjects but not with ACCP- subjects, can represent a transcriptional signature involved with the transition of a preclinical to a clinical RA stage. Some of these particular up-regulated and down-regulated genes are related to inflammatory processes and could be considered as biomarker candidates for disease progression in subjects at risk to develop RA. PMID:29584756

Single-nucleus analysis of accessible chromatin in developing mouse forebrain reveals cell-type-specific transcriptional regulation.

PubMed

Preissl, Sebastian; Fang, Rongxin; Huang, Hui; Zhao, Yuan; Raviram, Ramya; Gorkin, David U; Zhang, Yanxiao; Sos, Brandon C; Afzal, Veena; Dickel, Diane E; Kuan, Samantha; Visel, Axel; Pennacchio, Len A; Zhang, Kun; Ren, Bing

2018-03-01

Analysis of chromatin accessibility can reveal transcriptional regulatory sequences, but heterogeneity of primary tissues poses a significant challenge in mapping the precise chromatin landscape in specific cell types. Here we report single-nucleus ATAC-seq, a combinatorial barcoding-assisted single-cell assay for transposase-accessible chromatin that is optimized for use on flash-frozen primary tissue samples. We apply this technique to the mouse forebrain through eight developmental stages. Through analysis of more than 15,000 nuclei, we identify 20 distinct cell populations corresponding to major neuronal and non-neuronal cell types. We further define cell-type-specific transcriptional regulatory sequences, infer potential master transcriptional regulators and delineate developmental changes in forebrain cellular composition. Our results provide insight into the molecular and cellular dynamics that underlie forebrain development in the mouse and establish technical and analytical frameworks that are broadly applicable to other heterogeneous tissues.

Identifiability of PBPK Models with Applications to ...

EPA Pesticide Factsheets

Any statistical model should be identifiable in order for estimates and tests using it to be meaningful. We consider statistical analysis of physiologically-based pharmacokinetic (PBPK) models in which parameters cannot be estimated precisely from available data, and discuss different types of identifiability that occur in PBPK models and give reasons why they occur. We particularly focus on how the mathematical structure of a PBPK model and lack of appropriate data can lead to statistical models in which it is impossible to estimate at least some parameters precisely. Methods are reviewed which can determine whether a purely linear PBPK model is globally identifiable. We propose a theorem which determines when identifiability at a set of finite and specific values of the mathematical PBPK model (global discrete identifiability) implies identifiability of the statistical model. However, we are unable to establish conditions that imply global discrete identifiability, and conclude that the only safe approach to analysis of PBPK models involves Bayesian analysis with truncated priors. Finally, computational issues regarding posterior simulations of PBPK models are discussed. The methodology is very general and can be applied to numerous PBPK models which can be expressed as linear time-invariant systems. A real data set of a PBPK model for exposure to dimethyl arsinic acid (DMA(V)) is presented to illustrate the proposed methodology. We consider statistical analy

Genome Sequencing and Comparative Analysis of Stenotrophomonas acidaminiphila Reveal Evolutionary Insights Into Sulfamethoxazole Resistance.

PubMed

Huang, Yao-Ting; Chen, Jia-Min; Ho, Bing-Ching; Wu, Zong-Yen; Kuo, Rita C; Liu, Po-Yu

2018-01-01

Stenotrophomonas acidaminiphila is an aerobic, glucose non-fermentative, Gram-negative bacterium that been isolated from various environmental sources, particularly aquatic ecosystems. Although resistance to multiple antimicrobial agents has been reported in S. acidaminiphila , the mechanisms are largely unknown. Here, for the first time, we report the complete genome and antimicrobial resistome analysis of a clinical isolate S. acidaminiphila SUNEO which is resistant to sulfamethoxazole. Comparative analysis among closely related strains identified common and strain-specific genes. In particular, comparison with a sulfamethoxazole-sensitive strain identified a mutation within the sulfonamide-binding site of folP in SUNEO, which may reduce the binding affinity of sulfamethoxazole. Selection pressure analysis indicated folP in SUNEO is under purifying selection, which may be owing to long-term administration of sulfonamide against Stenotrophomonas .

Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño

PubMed Central

González-Segovia, Eric; Ross-Ibarra, Jeffrey; Simpson, June K.

2017-01-01

Background Gene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions. Methods Allele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments. Results A total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates. Discussion Prior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation. PMID:28852597

EPA RE-Powering Mapper: Alternative Energy Potential at Cleanup Sites

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management??s (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

Chemical compounds and mechanisms involved in the formation and stabilization of foam in sparkling wines.

PubMed

Kemp, Belinda; Condé, Bruna; Jégou, Sandrine; Howell, Kate; Vasserot, Yann; Marchal, Richard

2018-02-08

The visual properties of sparkling wine including foam and bubbles are an indicator of sparkling wine quality. Foam properties, particularly foam height (FH) and foam stability (TS), are significantly influenced by the chemical composition of the wine. This review investigates our current knowledge of specific chemical compounds and, the mechanisms by which they influence the foam properties of sparkling wines. Grape and yeast proteins, amino acids, polysaccharides, phenolic compounds, organic acids, fatty acids, ethanol and sugar are examined with respect to their contribution to foam characteristics in sparkling wines made with the Traditional, Transfer, and Charmat and carbonation methods. Contradictory results have been identified that appear to be due to the analytical methods used to measure and quantify compounds and foam. Biopolymer complexes are discussed and absent knowledge with regards to thaumatin-like proteins (TLPs), polysaccharides, amino acids, oak-derived phenolic compounds and organic acids are identified. Future research is also likely to concentrate on visual analysis of sparkling wines by in-depth imaging analysis and specific sensory analysis techniques.

Traumatic injury among drywall installers, 1992 to 1995.

PubMed

Chiou, S S; Pan, C S; Keane, P

2000-11-01

This study examined the traumatic-injury characteristics associated with one of the high-risk occupations in the construction industry--drywall installers--through an analysis of the traumatic-injury data obtained from the Bureau of Labor Statistics. An additional objective was to demonstrate a feasible and economic approach to identify risk factors associated with a specific occupation by using an existing database. An analysis of nonfatal traumatic injuries with days away from work among wage-and-salary drywall installers was performed for 1992 through 1995 using the Occupational Injury and Illness Survey conducted by the Bureau of Labor Statistics. Results from this study indicate that drywall installers are at a high risk of overexertion and falls to a lower level. More than 40% of the injured drywall installers suffered sprains, strains, and/or tears. The most frequently injured body part was the trunk. More than one-third of the trunk injuries occurred while handling solid building materials, mainly drywall. In addition, the database analysis used in this study is valid in identifying overall risk factors for specific occupations.

EPA RE-Powering Mapper Region 10

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 4

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Large Scale

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 2

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 6

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 8

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 7

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 5

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 3

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Solar on Landfills

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 9

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Utility Scale

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Screening Shapefile

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Center for Program Analysis (CPA) initiated the RE-Powering America??s Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

EPA RE-Powering Mapper Region 1

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency (EPA) Office of Land and Emergency Management (OLEM) Office of Communications, Partnerships and Analysis (OCPA) initiated the RE-Powering America's Land Initiative to demonstrate the enormous potential that contaminated lands, landfills, and mine sites provide for developing renewable energy in the United States. EPA developed national level site screening criteria in partnership with the U.S. Department of Energy (DOE) National Renewable Energy Laboratory (NREL) for wind, solar, biomass, and geothermal facilities. While the screening criteria demonstrate the potential to reuse contaminated land for renewable energy facilities, the criteria and data are neither designed to identify the best sites for developing renewable energy nor all-inclusive. Therefore, more detailed, site-specific analysis is necessary to identify or prioritize the best sites for developing renewable energy facilities based on the technical and economic potential. Please note that these sites were only pre-screened for renewable energy potential. The sites were not evaluated for land use constraints or current on the ground conditions. Additional research and site-specific analysis are needed to verify viability for renewable energy potential at a given site.

Development of a bespoke human factors taxonomy for gliding accident analysis and its revelations about highly inexperienced UK glider pilots.

PubMed

Jarvis, Steve; Harris, Don

2010-02-01

Low-hours solo glider pilots have a high risk of accidents compared to more experienced pilots. Numerous taxonomies for causal accident analysis have been produced for powered aviation but none of these is suitable for gliding, so a new taxonomy was required. A human factors taxonomy specifically for glider operations was developed and used to analyse all UK gliding accidents from 2002 to 2006 for their overall causes as well as factors specific to low hours pilots. Fifty-nine categories of pilot-related accident causation emerged, which were formed into progressively larger categories until four overall human factors groups were arrived at: 'judgement'; 'handling'; 'strategy'; 'attention'. 'Handling' accounted for a significantly higher proportion of injuries than other categories. Inexperienced pilots had considerably more accidents in all categories except 'strategy'. Approach control (path judgement, airbrake and speed handling) as well as landing flare misjudgement were chiefly responsible for the high accident rate in early solo glider pilots. Statement of Relevance: This paper uses extant accident data to produce a taxonomy of underlying human factors causes to analyse gliding accidents and identify the specific causes associated with low hours pilots. From this specific, well-targeted remedial measures can be identified.

Flow cytometric purification of Colletotrichum higginsianum biotrophic hyphae from Arabidopsis leaves for stage-specific transcriptome analysis.

PubMed

Takahara, Hiroyuki; Dolf, Andreas; Endl, Elmar; O'Connell, Richard

2009-08-01

Generation of stage-specific cDNA libraries is a powerful approach to identify pathogen genes that are differentially expressed during plant infection. Biotrophic pathogens develop specialized infection structures inside living plant cells, but sampling the transcriptome of these structures is problematic due to the low ratio of fungal to plant RNA, and the lack of efficient methods to isolate them from infected plants. Here we established a method, based on fluorescence-activated cell sorting (FACS), to purify the intracellular biotrophic hyphae of Colletotrichum higginsianum from homogenates of infected Arabidopsis leaves. Specific selection of viable hyphae using a fluorescent vital marker provided intact RNA for cDNA library construction. Pilot-scale sequencing showed that the library was enriched with plant-induced and pathogenicity-related fungal genes, including some encoding small, soluble secreted proteins that represent candidate fungal effectors. The high purity of the hyphae (94%) prevented contamination of the library by sequences derived from host cells or other fungal cell types. RT-PCR confirmed that genes identified in the FACS-purified hyphae were also expressed in planta. The method has wide applicability for isolating the infection structures of other plant pathogens, and will facilitate cell-specific transcriptome analysis via deep sequencing and microarray hybridization, as well as proteomic analyses.

Clinical usefulness of the clock drawing test applying rasch analysis in predicting of cognitive impairment.

PubMed

Yoo, Doo Han; Lee, Jae Shin

2016-07-01

[Purpose] This study examined the clinical usefulness of the clock drawing test applying Rasch analysis for predicting the level of cognitive impairment. [Subjects and Methods] A total of 187 stroke patients with cognitive impairment were enrolled in this study. The 187 patients were evaluated by the clock drawing test developed through Rasch analysis along with the mini-mental state examination of cognitive evaluation tool. An analysis of the variance was performed to examine the significance of the mini-mental state examination and the clock drawing test according to the general characteristics of the subjects. Receiver operating characteristic analysis was performed to determine the cutoff point for cognitive impairment and to calculate the sensitivity and specificity values. [Results] The results of comparison of the clock drawing test with the mini-mental state showed significant differences in according to gender, age, education, and affected side. A total CDT of 10.5, which was selected as the cutoff point to identify cognitive impairement, showed a sensitivity, specificity, Youden index, positive predictive, and negative predicive values of 86.4%, 91.5%, 0.8, 95%, and 88.2%. [Conclusion] The clock drawing test is believed to be useful in assessments and interventions based on its excellent ability to identify cognitive disorders.

Clavibacter michiganensis subsp. phaseoli subsp. nov., pathogenic in bean.

PubMed

González, Ana J; Trapiello, Estefanía

2014-05-01

A yellow Gram-reaction-positive bacterium isolated from bean seeds (Phaseolus vulgaris L.) was identified as Clavibacter michiganensis by 16S rRNA gene sequencing. Molecular methods were employed in order to identify the subspecies. Such methods included the amplification of specific sequences by PCR, 16S amplified rDNA restriction analysis (ARDRA), RFLP and multilocus sequence analysis as well as the analysis of biochemical and phenotypic traits including API 50CH and API ZYM results. The results showed that strain LPPA 982T did not represent any known subspecies of C. michiganensis. Pathogenicity tests revealed that the strain is a bean pathogen causing a newly identified bacterial disease that we name bacterial bean leaf yellowing. On the basis of these results, strain LPPA 982T is regarded as representing a novel subspecies for which the name Clavibacter michiganensis subsp. phaseoli subsp. nov. is proposed. The type strain is LPPA 982T (=CECT 8144T=LMG 27667T).

Moral deliberation and nursing ethics cases: elements of a methodological proposal.

PubMed

Schneider, Dulcinéia Ghizoni; Ramos, Flávia Regina Souza

2012-11-01

A qualitative study with an exploratory, descriptive and documentary design that was conducted with the objective of identifying the elements to constitute a method for the analysis of accusations of and proceedings for professional ethics infringements. The method is based on underlying elements identified inductively during analysis of professional ethics hearings judged by and filed in the archives of the Regional Nursing Board of Santa Catarina, Brazil, between 1999 and 2007. The strategies developed were based on the results of an analysis of the findings of fact (occurrences/infractions, causes and outcomes) contained in the records of 128 professional ethics hearings and on the structural elements (statements, rules and practices) identified in five example professional ethics cases. The strategies suggested for evaluating accusations of ethics infringements and the procedures involved in deliberating on ethics hearings constitute a generic proposal that will require adaptation to the context of specific professional ethics accusations.

Multicolor microRNA FISH effectively differentiates tumor types

PubMed Central

Renwick, Neil; Cekan, Pavol; Masry, Paul A.; McGeary, Sean E.; Miller, Jason B.; Hafner, Markus; Li, Zhen; Mihailovic, Aleksandra; Morozov, Pavel; Brown, Miguel; Gogakos, Tasos; Mobin, Mehrpouya B.; Snorrason, Einar L.; Feilotter, Harriet E.; Zhang, Xiao; Perlis, Clifford S.; Wu, Hong; Suárez-Fariñas, Mayte; Feng, Huichen; Shuda, Masahiro; Moore, Patrick S.; Tron, Victor A.; Chang, Yuan; Tuschl, Thomas

2013-01-01

MicroRNAs (miRNAs) are excellent tumor biomarkers because of their cell-type specificity and abundance. However, many miRNA detection methods, such as real-time PCR, obliterate valuable visuospatial information in tissue samples. To enable miRNA visualization in formalin-fixed paraffin-embedded (FFPE) tissues, we developed multicolor miRNA FISH. As a proof of concept, we used this method to differentiate two skin tumors, basal cell carcinoma (BCC) and Merkel cell carcinoma (MCC), with overlapping histologic features but distinct cellular origins. Using sequencing-based miRNA profiling and discriminant analysis, we identified the tumor-specific miRNAs miR-205 and miR-375 in BCC and MCC, respectively. We addressed three major shortcomings in miRNA FISH, identifying optimal conditions for miRNA fixation and ribosomal RNA (rRNA) retention using model compounds and high-pressure liquid chromatography (HPLC) analyses, enhancing signal amplification and detection by increasing probe-hapten linker lengths, and improving probe specificity using shortened probes with minimal rRNA sequence complementarity. We validated our method on 4 BCC and 12 MCC tumors. Amplified miR-205 and miR-375 signals were normalized against directly detectable reference rRNA signals. Tumors were classified using predefined cutoff values, and all were correctly identified in blinded analysis. Our study establishes a reliable miRNA FISH technique for parallel visualization of differentially expressed miRNAs in FFPE tumor tissues. PMID:23728175

Risk analysis for renewable energy projects due to constraints arising

NASA Astrophysics Data System (ADS)

Prostean, G.; Vasar, C.; Prostean, O.; Vartosu, A.

2016-02-01

Starting from the target of the European Union (EU) to use renewable energy in the area that aims a binding target of 20% renewable energy in final energy consumption by 2020, this article illustrates the identification of risks for implementation of wind energy projects in Romania, which could lead to complex technical implications, social and administrative. In specific projects analyzed in this paper were identified critical bottlenecks in the future wind power supply chain and reasonable time periods that may arise. Renewable energy technologies have to face a number of constraints that delayed scaling-up their production process, their transport process, the equipment reliability, etc. so implementing these types of projects requiring complex specialized team, the coordination of which also involve specific risks. The research team applied an analytical risk approach to identify major risks encountered within a wind farm project developed in Romania in isolated regions with different particularities, configured for different geographical areas (hill and mountain locations in Romania). Identification of major risks was based on the conceptual model set up for the entire project implementation process. Throughout this conceptual model there were identified specific constraints of such process. Integration risks were examined by an empirical study based on the method HAZOP (Hazard and Operability). The discussion describes the analysis of our results implementation context of renewable energy projects in Romania and creates a framework for assessing energy supply to any entity from renewable sources.

Meconium proteins as a source of biomarkers for the assessment of the intrauterine environment of the fetus.

PubMed

Lisowska-Myjak, B; Skarżyńska, E; Bakun, M

2018-06-01

Intrauterine environmental factors can be associated with perinatal complications and long-term health outcomes although the underlying mechanisms remain poorly defined. Meconium formed exclusively in utero and passed naturally by a neonate may contain proteins which characterise the intrauterine environment. The aim of the study was proteomic analysis of the composition of meconium proteins and their classification by biological function. Proteomic techniques combining isoelectrofocussing fractionation and LC-MS/MS analysis were used to study the protein composition of a meconium sample obtained by pooling 50 serial meconium portions from 10 healthy full-term neonates. The proteins were classified by function based on the literature search for each protein in the PubMed database. A total of 946 proteins were identified in the meconium, including 430 proteins represented by two or more peptides. When the proteins were classified by their biological function the following were identified: immunoglobulin fragments and enzymatic, neutrophil-derived, structural and fetal intestine-specific proteins. Meconium is a rich source of proteins deposited in the fetal intestine during its development in utero. A better understanding of their specific biological functions in the intrauterine environment may help to identify these proteins which may serve as biomarkers associated with specific clinical conditions/diseases with the possible impact on the fetal development and further health consequences in infants, older children and adults.

Systematic analysis of molecular mechanisms for HCC metastasis via text mining approach.

PubMed

Zhen, Cheng; Zhu, Caizhong; Chen, Haoyang; Xiong, Yiru; Tan, Junyuan; Chen, Dong; Li, Jin

2017-02-21

To systematically explore the molecular mechanism for hepatocellular carcinoma (HCC) metastasis and identify regulatory genes with text mining methods. Genes with highest frequencies and significant pathways related to HCC metastasis were listed. A handful of proteins such as EGFR, MDM2, TP53 and APP, were identified as hub nodes in PPI (protein-protein interaction) network. Compared with unique genes for HBV-HCCs, genes particular to HCV-HCCs were less, but may participate in more extensive signaling processes. VEGFA, PI3KCA, MAPK1, MMP9 and other genes may play important roles in multiple phenotypes of metastasis. Genes in abstracts of HCC-metastasis literatures were identified. Word frequency analysis, KEGG pathway and PPI network analysis were performed. Then co-occurrence analysis between genes and metastasis-related phenotypes were carried out. Text mining is effective for revealing potential regulators or pathways, but the purpose of it should be specific, and the combination of various methods will be more useful.

Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes

NASA Technical Reports Server (NTRS)

Stolc, Viktor; Samanta, Manoj Pratim; Tongprasit, Waraporn; Marshall, Wallace F.

2005-01-01

The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cells would reveal new flagella-related genes. We have conducted a genome-wide analysis of RNA transcript levels during flagellar regeneration in Chlamydomonas by using maskless photolithography method-produced DNA oligonucleotide microarrays with unique probe sequences for all exons of the 19,803 predicted genes. This analysis represents previously uncharacterized whole-genome transcriptional activity profiling study in this important model organism. Analysis of strongly induced genes reveals a large set of known flagellar components and also identifies a number of important disease-related proteins as being involved with cilia and flagella, including the zebrafish polycystic kidney genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like protein TULP2.

Partial least squares based identification of Duchenne muscular dystrophy specific genes.

PubMed

An, Hui-bo; Zheng, Hua-cheng; Zhang, Li; Ma, Lin; Liu, Zheng-yan

2013-11-01

Large-scale parallel gene expression analysis has provided a greater ease for investigating the underlying mechanisms of Duchenne muscular dystrophy (DMD). Previous studies typically implemented variance/regression analysis, which would be fundamentally flawed when unaccounted sources of variability in the arrays existed. Here we aim to identify genes that contribute to the pathology of DMD using partial least squares (PLS) based analysis. We carried out PLS-based analysis with two datasets downloaded from the Gene Expression Omnibus (GEO) database to identify genes contributing to the pathology of DMD. Except for the genes related to inflammation, muscle regeneration and extracellular matrix (ECM) modeling, we found some genes with high fold change, which have not been identified by previous studies, such as SRPX, GPNMB, SAT1, and LYZ. In addition, downregulation of the fatty acid metabolism pathway was found, which may be related to the progressive muscle wasting process. Our results provide a better understanding for the downstream mechanisms of DMD.

Quantitative proteomic analysis of cultured skin fibroblast cells derived from patients with triglyceride deposit cardiomyovasculopathy

PubMed Central

2013-01-01

Background Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare disease, characterized by the massive accumulation of triglyceride (TG) in multiple tissues, especially skeletal muscle, heart muscle and the coronary artery. TGCV is caused by mutation of adipose triglyceride lipase, which is an essential molecule for the hydrolysis of TG. TGCV is at high risk for skeletal myopathy and heart dysfunction, and therefore premature death. Development of therapeutic methods for TGCV is highly desirable. This study aims to discover specific molecules responsible for TGCV pathogenesis. Methods To identify differentially expressed proteins in TGCV patient cells, the stable isotope labeling with amino acids in cell culture (SILAC) method coupled with LC-MS/MS was performed using skin fibroblast cells derived from two TGCV patients and three healthy volunteers. Altered protein expression in TGCV cells was confirmed using the selected reaction monitoring (SRM) method. Microarray-based transcriptome analysis was simultaneously performed to identify changes in gene expression in TGCV cells. Results Using SILAC proteomics, 4033 proteins were quantified, 53 of which showed significantly altered expression in both TGCV patient cells. Twenty altered proteins were chosen and confirmed using SRM. SRM analysis successfully quantified 14 proteins, 13 of which showed the same trend as SILAC proteomics. The altered protein expression data set was used in Ingenuity Pathway Analysis (IPA), and significant networks were identified. Several of these proteins have been previously implicated in lipid metabolism, while others represent new therapeutic targets or markers for TGCV. Microarray analysis quantified 20743 transcripts, and 252 genes showed significantly altered expression in both TGCV patient cells. Ten altered genes were chosen, 9 of which were successfully confirmed using quantitative RT-PCR. Biological networks of altered genes were analyzed using an IPA search. Conclusions We performed the SILAC- and SRM-based identification-through-confirmation study using skin fibroblast cells derived from TGCV patients, and first identified altered proteins specific for TGCV. Microarray analysis also identified changes in gene expression. The functional networks of the altered proteins and genes are discussed. Our findings will be exploited to elucidate the pathogenesis of TGCV and discover clinically relevant molecules for TGCV in the near future. PMID:24360150

Clinical proteomic analysis of scrub typhus infection.

PubMed

Park, Edmond Changkyun; Lee, Sang-Yeop; Yun, Sung Ho; Choi, Chi-Won; Lee, Hayoung; Song, Hyun Seok; Jun, Sangmi; Kim, Gun-Hwa; Lee, Chang-Seop; Kim, Seung Il

2018-01-01

Scrub typhus is an acute and febrile infectious disease caused by the Gram-negative α-proteobacterium Orientia tsutsugamushi from the family Rickettsiaceae that is widely distributed in Northern, Southern and Eastern Asia. In the present study, we analysed the serum proteome of scrub typhus patients to investigate specific clinical protein patterns in an attempt to explain pathophysiology and discover potential biomarkers of infection. Serum samples were collected from three patients (before and after treatment with antibiotics) and three healthy subjects. One-dimensional sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by liquid chromatography-tandem mass spectrometry was performed to identify differentially abundant proteins using quantitative proteomic approaches. Bioinformatic analysis was then performed using Ingenuity Pathway Analysis. Proteomic analysis identified 236 serum proteins, of which 32 were differentially expressed in normal subjects, naive scrub typhus patients and patients treated with antibiotics. Comparative bioinformatic analysis of the identified proteins revealed up-regulation of proteins involved in immune responses, especially complement system, following infection with O. tsutsugamushi , and normal expression was largely rescued by antibiotic treatment. This is the first proteomic study of clinical serum samples from scrub typhus patients. Proteomic analysis identified changes in protein expression upon infection with O. tsutsugamushi and following antibiotic treatment. Our results provide valuable information for further investigation of scrub typhus therapy and diagnosis.

Molecular Analysis of the Caries Biofilm in Young Permanent Teeth

DTIC Science & Technology

2006-01-01

caries has been the subject of much study. Dental caries results from acid production of bacteria in dental plaque. Clarke was the first to identify...genetically different from the probiotic counterparts, and identify specific oral bacteria distributed on various tooth surfaces. Understanding the...does your child like to have for snack foods ? (cookies, cereal, fruit, chips, candy, fruit snacks) How often do are they snacking on these foods

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

DOE PAGES

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric; ...

2015-03-30

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets

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

Schulze, Kornelius; Imbeaud, Sandrine; Letouzé, Eric

Our genomic analyses promise to improve tumor characterization to optimize personalized treatment for patients with hepatocellular carcinoma (HCC). Exome sequencing analysis of 243 liver tumors identified mutational signatures associated with specific risk factors, mainly combined alcohol and tobacco consumption and exposure to aflatoxin B1. We identified 161 putative driver genes associated with 11 recurrently altered pathways. Associations of mutations defined 3 groups of genes related to risk factors and centered on CTNNB1 (alcohol), TP53 (hepatitis B virus, HBV) and AXIN1. These analyses according to tumor stage progression identified TERT promoter mutation as an early event, whereasFGF3, FGF4, FGF19 or CCND1more » amplification and TP53 and CDKN2A alterations appeared at more advanced stages in aggressive tumors. In 28% of the tumors, we identified genetic alterations potentially targetable by US Food and Drug Administration (FDA)–approved drugs. Finally, we identified risk factor–specific mutational signatures and defined the extensive landscape of altered genes and pathways in HCC, which will be useful to design clinical trials for targeted therapy.« less

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data.

PubMed

Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E; Greenwood, Alex D

2015-11-24

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals.

PeakWorks

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

2016-11-30

The PeakWorks software is designed to assist in the quantitative analysis of atom probe tomography (APT) generated mass spectra. Specifically, through an interactive user interface, mass peaks can be identified automatically (defined by a threshold) and/or identified manually. The software then provides a means to assign specific elemental isotopes (including more than one) to each peak. The software also provides a means for the user to choose background subtraction of each peak based on background fitting functions, the choice of which is left to the users discretion. Peak ranging (the mass range over which peaks are integrated) is also automatedmore » allowing the user to chose a quantitative range (e.g. full-widthhalf- maximum). The software then integrates all identified peaks, providing a background-subtracted composition, which also includes the deconvolution of peaks (i.e. those peaks that happen to have overlapping isotopic masses). The software is also able to output a 'range file' that can be used in other software packages, such as within IVAS. A range file lists the peak identities, the mass range of each identified peak, and a color code for the peak. The software is also able to generate 'dummy' peak ranges within an outputted range file that can be used within IVAS to provide a means for background subtracted proximity histogram analysis.« less

Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic control regions

PubMed Central

2012-01-01

Background Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes, suggesting a general alteration in genome activity. Results Investigation of different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had transgenerational transcriptomes. The microarrays from 11 different tissues were compared with a gene bionetwork analysis. Although each tissue transgenerational transcriptome was unique, common cellular pathways and processes were identified between the tissues. A cluster analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue-specific gene expression and function. A large number of statistically significant over-represented clusters of genes were identified in the genome for both males and females. These gene clusters ranged from 2-5 megabases in size, and a number of them corresponded to the epimutations previously identified in sperm that transmit the epigenetic transgenerational inheritance of disease phenotypes. Conclusions Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome may coordinately regulate these tissue-specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. PMID:23034163

Molecular identification and cluster analysis of homofermentative thermophilic lactobacilli isolated from dairy products.

PubMed

Andrighetto, C; De Dea, P; Lombardi, A; Neviani, E; Rossetti, L; Giraffa, G

1998-10-01

Twenty-five strains of thermophilic lactobacilli isolated from yoghurt and from semi-hard and hard cheeses (in parallel with nine type or reference strains) were identified and grouped according to their genetic relatedness. Strains were identified by sugar fermentation patterns using the "API 50 CHL" galleries, by species-specific DNA probes in dot-blot hybridization experiments, by amplification and restriction analysis of the 16S rRNA gene (ARDRA) and by polymerase chain reaction (PCR) using species-specific oligonucleotide primers. Strains were classified as Lactobacillus delbrueckii subsp. lactis and subsp. bulgaricus, L. helveticus, and L. acidophilus. Strains which were atypical by sugar fermentation patterns were also identified. Most of the strains could not be grouped using carbohydrate fermentation profiles. PCR fingerprinting was used to identify DNA profiles for the 25 lactobacilli. Experimentally obtained PCR profiles enabled discrimination of all strains, which were grouped according to the similarities in their combined patterns. In general, the clustering of the strains corresponded well with species delineation obtained by molecular identification. The dendrogram of genetic relatedness enabled the unambiguous identification of most of the strains which were shown to be atypical by the sugar fermentation profile, except for a discrepancy in one L. delbrueckii subsp. lactis strain and one atypical Lactobacillus sp. strain.

Comparative genomic analysis of Helicobacter pylori from Malaysia identifies three distinct lineages suggestive of differential evolution

PubMed Central

Kumar, Narender; Mariappan, Vanitha; Baddam, Ramani; Lankapalli, Aditya K.; Shaik, Sabiha; Goh, Khean-Lee; Loke, Mun Fai; Perkins, Tim; Benghezal, Mohammed; Hasnain, Seyed E.; Vadivelu, Jamuna; Marshall, Barry J.; Ahmed, Niyaz

2015-01-01

The discordant prevalence of Helicobacter pylori and its related diseases, for a long time, fostered certain enigmatic situations observed in the countries of the southern world. Variation in H. pylori infection rates and disease outcomes among different populations in multi-ethnic Malaysia provides a unique opportunity to understand dynamics of host–pathogen interaction and genome evolution. In this study, we extensively analyzed and compared genomes of 27 Malaysian H. pylori isolates and identified three major phylogeographic lineages: hspEastAsia, hpEurope and hpSouthIndia. The analysis of the virulence genes within the core genome, however, revealed a comparable pathogenic potential of the strains. In addition, we identified four genes limited to strains of East-Asian lineage. Our analyses identified a few strain-specific genes encoding restriction modification systems and outlined 311 core genes possibly under differential evolutionary constraints, among the strains representing different ethnic groups. The cagA and vacA genes also showed variations in accordance with the host genetic background of the strains. Moreover, restriction modification genes were found to be significantly enriched in East-Asian strains. An understanding of these variations in the genome content would provide significant insights into various adaptive and host modulation strategies harnessed by H. pylori to effectively persist in a host-specific manner. PMID:25452339

An Evolutionarily Young Polar Bear (Ursus maritimus) Endogenous Retrovirus Identified from Next Generation Sequence Data

PubMed Central

Tsangaras, Kyriakos; Mayer, Jens; Alquezar-Planas, David E.; Greenwood, Alex D.

2015-01-01

Transcriptome analysis of polar bear (Ursus maritimus) tissues identified sequences with similarity to Porcine Endogenous Retroviruses (PERV). Based on these sequences, four proviral copies and 15 solo long terminal repeats (LTRs) of a newly described endogenous retrovirus were characterized from the polar bear draft genome sequence. Closely related sequences were identified by PCR analysis of brown bear (Ursus arctos) and black bear (Ursus americanus) but were absent in non-Ursinae bear species. The virus was therefore designated UrsusERV. Two distinct groups of LTRs were observed including a recombinant ERV that contained one LTR belonging to each group indicating that genomic invasions by at least two UrsusERV variants have recently occurred. Age estimates based on proviral LTR divergence and conservation of integration sites among ursids suggest the viral group is only a few million years old. The youngest provirus was polar bear specific, had intact open reading frames (ORFs) and could potentially encode functional proteins. Phylogenetic analyses of UrsusERV consensus protein sequences suggest that it is part of a pig, gibbon and koala retrovirus clade. The young age estimates and lineage specificity of the virus suggests UrsusERV is a recent cross species transmission from an unknown reservoir and places the viral group among the youngest of ERVs identified in mammals. PMID:26610552

Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment

PubMed Central

2010-01-01

Background Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. Results We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. Conclusions In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets. PMID:21034488

Structural modelling and comparative analysis of homologous, analogous and specific proteins from Trypanosoma cruzi versus Homo sapiens: putative drug targets for chagas' disease treatment.

PubMed

Capriles, Priscila V S Z; Guimarães, Ana C R; Otto, Thomas D; Miranda, Antonio B; Dardenne, Laurent E; Degrave, Wim M

2010-10-29

Trypanosoma cruzi is the etiological agent of Chagas' disease, an endemic infection that causes thousands of deaths every year in Latin America. Therapeutic options remain inefficient, demanding the search for new drugs and/or new molecular targets. Such efforts can focus on proteins that are specific to the parasite, but analogous enzymes and enzymes with a three-dimensional (3D) structure sufficiently different from the corresponding host proteins may represent equally interesting targets. In order to find these targets we used the workflows MHOLline and AnEnΠ obtaining 3D models from homologous, analogous and specific proteins of Trypanosoma cruzi versus Homo sapiens. We applied genome wide comparative modelling techniques to obtain 3D models for 3,286 predicted proteins of T. cruzi. In combination with comparative genome analysis to Homo sapiens, we were able to identify a subset of 397 enzyme sequences, of which 356 are homologous, 3 analogous and 38 specific to the parasite. In this work, we present a set of 397 enzyme models of T. cruzi that can constitute potential structure-based drug targets to be investigated for the development of new strategies to fight Chagas' disease. The strategies presented here support the concept of structural analysis in conjunction with protein functional analysis as an interesting computational methodology to detect potential targets for structure-based rational drug design. For example, 2,4-dienoyl-CoA reductase (EC 1.3.1.34) and triacylglycerol lipase (EC 3.1.1.3), classified as analogous proteins in relation to H. sapiens enzymes, were identified as new potential molecular targets.

Analysis of a ToxCast™ HTS Toxicity Signature for putative Vascular Disruptor Compounds

EPA Science Inventory

Recent studies have shown the importance of blood vessel formation during embryo development and the strong correlation to developmental toxicity. Several developmental toxicants, such as thalidomide, have been identified which specifically target the forming embryonic vasculatur...

The Objective Identification and Quantification of Interstitial Lung Abnormalities in Smokers.

PubMed

Ash, Samuel Y; Harmouche, Rola; Ross, James C; Diaz, Alejandro A; Hunninghake, Gary M; Putman, Rachel K; Onieva, Jorge; Martinez, Fernando J; Choi, Augustine M; Lynch, David A; Hatabu, Hiroto; Rosas, Ivan O; Estepar, Raul San Jose; Washko, George R

2017-08-01

Previous investigation suggests that visually detected interstitial changes in the lung parenchyma of smokers are highly clinically relevant and predict outcomes, including death. Visual subjective analysis to detect these changes is time-consuming, insensitive to subtle changes, and requires training to enhance reproducibility. Objective detection of such changes could provide a method of disease identification without these limitations. The goal of this study was to develop and test a fully automated image processing tool to objectively identify radiographic features associated with interstitial abnormalities in the computed tomography scans of a large cohort of smokers. An automated tool that uses local histogram analysis combined with distance from the pleural surface was used to detect radiographic features consistent with interstitial lung abnormalities in computed tomography scans from 2257 individuals from the Genetic Epidemiology of COPD study, a longitudinal observational study of smokers. The sensitivity and specificity of this tool was determined based on its ability to detect the visually identified presence of these abnormalities. The tool had a sensitivity of 87.8% and a specificity of 57.5% for the detection of interstitial lung abnormalities, with a c-statistic of 0.82, and was 100% sensitive and 56.7% specific for the detection of the visual subtype of interstitial abnormalities called fibrotic parenchymal abnormalities, with a c-statistic of 0.89. In smokers, a fully automated image processing tool is able to identify those individuals who have interstitial lung abnormalities with moderate sensitivity and specificity. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Proteomic analysis of human dental cementum and alveolar bone.

PubMed

Salmon, Cristiane R; Tomazela, Daniela M; Ruiz, Karina Gonzales Silvério; Foster, Brian L; Paes Leme, Adriana Franco; Sallum, Enilson Antonio; Somerman, Martha J; Nociti, Francisco H

2013-10-08

Dental cementum (DC) is a bone-like tissue covering the tooth root and responsible for attaching the tooth to the alveolar bone (AB) via the periodontal ligament (PDL). Studies have unsuccessfully tried to identify factors specific to DC versus AB, in an effort to better understand DC development and regeneration. The present study aimed to use matched human DC and AB samples (n=7) to generate their proteomes for comparative analysis. Bone samples were harvested from tooth extraction sites, whereas DC samples were obtained from the apical root portion of extracted third molars. Samples were denatured, followed by protein extraction reduction, alkylation and digestion for analysis by nanoAcquity HPLC system and LTQ-FT Ultra. Data analysis demonstrated that a total of 318 proteins were identified in AB and DC. In addition to shared proteins between these tissues, 105 and 83 proteins exclusive to AB or DC were identified, respectively. This is the first report analyzing the proteomic composition of human DC matrix and identifying putative unique and enriched proteins in comparison to alveolar bone. These findings may provide novel insights into developmental differences between DC and AB, and identify candidate biomarkers that may lead to more efficient and predictable therapies for periodontal regeneration. Periodontal disease is a highly prevalent disease affecting the world population, which involves breakdown of the tooth supporting tissues, the periodontal ligament, alveolar bone, and dental cementum. The lack of knowledge on specific factors that differentiate alveolar bone and dental cementum limits the development of more efficient and predictable reconstructive therapies. In order to better understand cementum development and potentially identify factors to improve therapeutic outcomes, we took the unique approach of using matched patient samples of dental cementum and alveolar bone to generate and compare a proteome list for each tissue. A potential biomarker for dental cementum was identified, superoxide dismutase 3 (SOD3), which is found in cementum and cementum-associated cells in mouse, pig, and human tissues. These findings may provide novel insights into developmental differences between alveolar bone and dental cementum, and represent the basis for improved and more predictable therapies. © 2013.

Efficiency of the Bethesda System for Thyroid Cytopathology.

PubMed

Mora-Guzmán, Ismael; Muñoz de Nova, José Luis; Marín-Campos, Cristina; Jiménez-Heffernan, José Antonio; Cuesta Pérez, Juan Julián; Lahera Vargas, Marcos; Torres Mínguez, Emma; Martín-Pérez, Elena

2018-03-28

Fine-needle aspiration biopsies are a key tool for preoperative assessment of thyroid nodules, and the Bethesda system is the preferred method to report cytological analysis. The purpose of this study is to assess the efficiency of the Bethesda system to identify the malignancy risk of thyroid nodules. Patients who underwent thyroid surgery between June 2010 and June 2017 were included. Samples were classified into 6categories according to rates of malignancy associated with each diagnostic category. In order to investigate the correlation between categories, a statistical analysis compared the categories with pathology reports. Diagnostic indicators were calculated as a screening test (categories IV, V, VI as true-positive) and as a method to identify malignancy (V, VI as true-positive). In a series of 522 patients, we found 184 (35.2%) malignant tumours, papillary carcinoma being the most prevalent with 155 cases (84.2%). Malignant rates for diagnostic categories were: I, 0%; II, 1.5%; III, 6.4%; IV, 31%; V, 86.5%; VI, 100%. A robust correlation was identified between categories on statistical analysis. For the «screening test» analysis, sensitivity was 98.9%, specificity 84.4%, positive predictive value 69.6%, negative predictive value 99.5%, and diagnostic accuracy 88.2%. Analysing the accuracy to detect malignancy, values were: sensitivity 98.6%, specificity 97.6%, positive predictive value 93.5%, negative predictive value 99.5%, diagnostic accuracy 97.9%. The Bethesda system is a clear and reliable approach to report thyroid cytology and therefore is an effective tool to identify malignancy risk and guide clinical management. Copyright © 2018 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Specific features of colorectal cancer in patients with metabolic syndrome: a matched case-control analysis of 772 patients.

PubMed

Zarzavadjian Le Bian, Alban; Denet, Christine; Tabchouri, Nicolas; Donatelli, Gianfranco; Wind, Philippe; Louvet, Christophe; Bennamoun, Mostefa; Christidis, Christos; Perniceni, Thierry; Fuks, David; Gayet, Brice

2018-06-01

Although association between colorectal cancer (CRC) and metabolic syndrome (MetS) is established, specific features of CRC arising in patients presenting with MetS have not been clearly identified. All patients who underwent colectomy for CRC from January 2005 to December 2014 at Institut Mutualiste Montsouris were identified from a prospectively collected database and characteristics were compared in the entire population and in a 1:2 matched case-control analysis [variables on which matching was performed were CRC localization (right- or left-sided) and AJCC stage (0 to IV)]. Out of the 772 identified patients, 98 (12.7%) presented with MetS. Entire population analysis revealed that CRC associated with MetS was more frequent in men (71.4 vs. 47.8%, p < 0.001), more often right-sided (71.4 vs. 50.4%, p < 0.001) and presented with less synchronous liver metastasis (4.1 vs. 8.7%, p = 0.002). Case-control analysis confirmed the gender association (p < 0.001) and showed HNPCC (p < 0.001) and history family of CRC (p = 0.010) to be significantly more frequent in Non-MetS patients. CRC associated with MetS is more frequent in men, more often right-sided, and presents with fewer synchronous metastasis. Further investigations should be designed in order to confirm these results and to enhance our knowledge of carcinogenesis related to MetS.

Bioinformatics analysis and detection of gelatinase encoded gene in Lysinibacillussphaericus

NASA Astrophysics Data System (ADS)

Repin, Rul Aisyah Mat; Mutalib, Sahilah Abdul; Shahimi, Safiyyah; Khalid, Rozida Mohd.; Ayob, Mohd. Khan; Bakar, Mohd. Faizal Abu; Isa, Mohd Noor Mat

2016-11-01

In this study, we performed bioinformatics analysis toward genome sequence of Lysinibacillussphaericus (L. sphaericus) to determine gene encoded for gelatinase. L. sphaericus was isolated from soil and gelatinase species-specific bacterium to porcine and bovine gelatin. This bacterium offers the possibility of enzymes production which is specific to both species of meat, respectively. The main focus of this research is to identify the gelatinase encoded gene within the bacteria of L. Sphaericus using bioinformatics analysis of partially sequence genome. From the research study, three candidate gene were identified which was, gelatinase candidate gene 1 (P1), NODE_71_length_93919_cov_158.931839_21 which containing 1563 base pair (bp) in size with 520 amino acids sequence; Secondly, gelatinase candidate gene 2 (P2), NODE_23_length_52851_cov_190.061386_17 which containing 1776 bp in size with 591 amino acids sequence; and Thirdly, gelatinase candidate gene 3 (P3), NODE_106_length_32943_cov_169.147919_8 containing 1701 bp in size with 566 amino acids sequence. Three pairs of oligonucleotide primers were designed and namely as, F1, R1, F2, R2, F3 and R3 were targeted short sequences of cDNA by PCR. The amplicons were reliably results in 1563 bp in size for candidate gene P1 and 1701 bp in size for candidate gene P3. Therefore, the results of bioinformatics analysis of L. Sphaericus resulting in gene encoded gelatinase were identified.

Imaging modalities for characterising focal pancreatic lesions.

PubMed

Best, Lawrence Mj; Rawji, Vishal; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2017-04-17

Increasing numbers of incidental pancreatic lesions are being detected each year. Accurate characterisation of pancreatic lesions into benign, precancerous, and cancer masses is crucial in deciding whether to use treatment or surveillance. Distinguishing benign lesions from precancerous and cancerous lesions can prevent patients from undergoing unnecessary major surgery. Despite the importance of accurately classifying pancreatic lesions, there is no clear algorithm for management of focal pancreatic lesions. To determine and compare the diagnostic accuracy of various imaging modalities in detecting cancerous and precancerous lesions in people with focal pancreatic lesions. We searched the CENTRAL, MEDLINE, Embase, and Science Citation Index until 19 July 2016. We searched the references of included studies to identify further studies. We did not restrict studies based on language or publication status, or whether data were collected prospectively or retrospectively. We planned to include studies reporting cross-sectional information on the index test (CT (computed tomography), MRI (magnetic resonance imaging), PET (positron emission tomography), EUS (endoscopic ultrasound), EUS elastography, and EUS-guided biopsy or FNA (fine-needle aspiration)) and reference standard (confirmation of the nature of the lesion was obtained by histopathological examination of the entire lesion by surgical excision, or histopathological examination for confirmation of precancer or cancer by biopsy and clinical follow-up of at least six months in people with negative index tests) in people with pancreatic lesions irrespective of language or publication status or whether the data were collected prospectively or retrospectively. Two review authors independently searched the references to identify relevant studies and extracted the data. We planned to use the bivariate analysis to calculate the summary sensitivity and specificity with their 95% confidence intervals and the hierarchical summary receiver operating characteristic (HSROC) to compare the tests and assess heterogeneity, but used simpler models (such as univariate random-effects model and univariate fixed-effect model) for combining studies when appropriate because of the sparse data. We were unable to compare the diagnostic performance of the tests using formal statistical methods because of sparse data. We included 54 studies involving a total of 3,196 participants evaluating the diagnostic accuracy of various index tests. In these 54 studies, eight different target conditions were identified with different final diagnoses constituting benign, precancerous, and cancerous lesions. None of the studies was of high methodological quality. None of the comparisons in which single studies were included was of sufficiently high methodological quality to warrant highlighting of the results. For differentiation of cancerous lesions from benign or precancerous lesions, we identified only one study per index test. The second analysis, of studies differentiating cancerous versus benign lesions, provided three tests in which meta-analysis could be performed. The sensitivities and specificities for diagnosing cancer were: EUS-FNA: sensitivity 0.79 (95% confidence interval (CI) 0.07 to 1.00), specificity 1.00 (95% CI 0.91 to 1.00); EUS: sensitivity 0.95 (95% CI 0.84 to 0.99), specificity 0.53 (95% CI 0.31 to 0.74); PET: sensitivity 0.92 (95% CI 0.80 to 0.97), specificity 0.65 (95% CI 0.39 to 0.84). The third analysis, of studies differentiating precancerous or cancerous lesions from benign lesions, only provided one test (EUS-FNA) in which meta-analysis was performed. EUS-FNA had moderate sensitivity for diagnosing precancerous or cancerous lesions (sensitivity 0.73 (95% CI 0.01 to 1.00) and high specificity 0.94 (95% CI 0.15 to 1.00), the extremely wide confidence intervals reflecting the heterogeneity between the studies). The fourth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (dysplasia) provided three tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing invasive carcinoma were: CT: sensitivity 0.72 (95% CI 0.50 to 0.87), specificity 0.92 (95% CI 0.81 to 0.97); EUS: sensitivity 0.78 (95% CI 0.44 to 0.94), specificity 0.91 (95% CI 0.61 to 0.98); EUS-FNA: sensitivity 0.66 (95% CI 0.03 to 0.99), specificity 0.92 (95% CI 0.73 to 0.98). The fifth analysis, of studies differentiating cancerous (high-grade dysplasia or invasive carcinoma) versus precancerous (low- or intermediate-grade dysplasia) provided six tests in which meta-analysis was performed. The sensitivities and specificities for diagnosing cancer (high-grade dysplasia or invasive carcinoma) were: CT: sensitivity 0.87 (95% CI 0.00 to 1.00), specificity 0.96 (95% CI 0.00 to 1.00); EUS: sensitivity 0.86 (95% CI 0.74 to 0.92), specificity 0.91 (95% CI 0.83 to 0.96); EUS-FNA: sensitivity 0.47 (95% CI 0.24 to 0.70), specificity 0.91 (95% CI 0.32 to 1.00); EUS-FNA carcinoembryonic antigen 200 ng/mL: sensitivity 0.58 (95% CI 0.28 to 0.83), specificity 0.51 (95% CI 0.19 to 0.81); MRI: sensitivity 0.69 (95% CI 0.44 to 0.86), specificity 0.93 (95% CI 0.43 to 1.00); PET: sensitivity 0.90 (95% CI 0.79 to 0.96), specificity 0.94 (95% CI 0.81 to 0.99). The sixth analysis, of studies differentiating cancerous (invasive carcinoma) from precancerous (low-grade dysplasia) provided no tests in which meta-analysis was performed. The seventh analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) provided two tests in which meta-analysis was performed. The sensitivity and specificity for diagnosing cancer were: CT: sensitivity 0.83 (95% CI 0.68 to 0.92), specificity 0.83 (95% CI 0.64 to 0.93) and MRI: sensitivity 0.80 (95% CI 0.58 to 0.92), specificity 0.81 (95% CI 0.53 to 0.95), respectively. The eighth analysis, of studies differentiating precancerous or cancerous (intermediate- or high-grade dysplasia or invasive carcinoma) from precancerous (low-grade dysplasia) or benign lesions provided no test in which meta-analysis was performed.There were no major alterations in the subgroup analysis of cystic pancreatic focal lesions (42 studies; 2086 participants). None of the included studies evaluated EUS elastography or sequential testing. We were unable to arrive at any firm conclusions because of the differences in the way that study authors classified focal pancreatic lesions into cancerous, precancerous, and benign lesions; the inclusion of few studies with wide confidence intervals for each comparison; poor methodological quality in the studies; and heterogeneity in the estimates within comparisons.

atBioNet--an integrated network analysis tool for genomics and biomarker discovery.

PubMed

Ding, Yijun; Chen, Minjun; Liu, Zhichao; Ding, Don; Ye, Yanbin; Zhang, Min; Kelly, Reagan; Guo, Li; Su, Zhenqiang; Harris, Stephen C; Qian, Feng; Ge, Weigong; Fang, Hong; Xu, Xiaowei; Tong, Weida

2012-07-20

Large amounts of mammalian protein-protein interaction (PPI) data have been generated and are available for public use. From a systems biology perspective, Proteins/genes interactions encode the key mechanisms distinguishing disease and health, and such mechanisms can be uncovered through network analysis. An effective network analysis tool should integrate different content-specific PPI databases into a comprehensive network format with a user-friendly platform to identify key functional modules/pathways and the underlying mechanisms of disease and toxicity. atBioNet integrates seven publicly available PPI databases into a network-specific knowledge base. Knowledge expansion is achieved by expanding a user supplied proteins/genes list with interactions from its integrated PPI network. The statistically significant functional modules are determined by applying a fast network-clustering algorithm (SCAN: a Structural Clustering Algorithm for Networks). The functional modules can be visualized either separately or together in the context of the whole network. Integration of pathway information enables enrichment analysis and assessment of the biological function of modules. Three case studies are presented using publicly available disease gene signatures as a basis to discover new biomarkers for acute leukemia, systemic lupus erythematosus, and breast cancer. The results demonstrated that atBioNet can not only identify functional modules and pathways related to the studied diseases, but this information can also be used to hypothesize novel biomarkers for future analysis. atBioNet is a free web-based network analysis tool that provides a systematic insight into proteins/genes interactions through examining significant functional modules. The identified functional modules are useful for determining underlying mechanisms of disease and biomarker discovery. It can be accessed at: http://www.fda.gov/ScienceResearch/BioinformaticsTools/ucm285284.htm.

Real-Time PCR for the Detection and Quantification of Geodermatophilaceae from Stone Samples and Identification of New Members of the Genus Blastococcus†

PubMed Central

Salazar, Oscar; Valverde, Aranzazu; Genilloud, Olga

2006-01-01

Real-time PCR (RT-PCR) technology was used for the specific detection and quantification of members of the family Geodermatophilaceae in stone samples. Differences in the nucleotide sequences of the 16S rRNA gene region were used to design a pair of family-specific primers that were used to detect and quantify by RT-PCR DNA from members of this family in stone samples from different geographical origins in Spain. These primers were applied later to identify by PCR-specific amplification new members of the family Geodermatophilaceae isolated from the same stone samples. The diversity and taxonomic position of the wild-type strains identified from ribosomal sequence analysis suggest the presence of a new lineage within the genus Blastococcus. PMID:16391063

Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations.

PubMed

Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew; Cornwell, MacIntosh; Liu, Weihan; Nardone, Agostina; Xiao, Tengfei; Li, Wei; Qiu, Xintao; Buchwalter, Gilles; Feiglin, Ariel; Abell-Hart, Kayley; Fei, Teng; Rao, Prakash; Long, Henry; Kwiatkowski, Nicholas; Zhang, Tinghu; Gray, Nathanael; Melchers, Diane; Houtman, Rene; Liu, X Shirley; Cohen, Ofir; Wagle, Nikhil; Winer, Eric P; Zhao, Jean; Brown, Myles

2018-02-12

Estrogen receptor α (ER) ligand-binding domain (LBD) mutations are found in a substantial number of endocrine treatment-resistant metastatic ER-positive (ER + ) breast cancers. We investigated the chromatin recruitment, transcriptional network, and genetic vulnerabilities in breast cancer models harboring the clinically relevant ER mutations. These mutants exhibit both ligand-independent functions that mimic estradiol-bound wild-type ER as well as allele-specific neomorphic properties that promote a pro-metastatic phenotype. Analysis of the genome-wide ER binding sites identified mutant ER unique recruitment mediating the allele-specific transcriptional program. Genetic screens identified genes that are essential for the ligand-independent growth driven by the mutants. These studies provide insights into the mechanism of endocrine therapy resistance engendered by ER mutations and potential therapeutic targets. Copyright © 2018 Elsevier Inc. All rights reserved.

Heparin/heparan sulfate 6-O-sulfatase from Flavobacterium heparinum: integrated structural and biochemical investigation of enzyme active site and substrate specificity.

PubMed

Myette, James R; Soundararajan, Venkataramanan; Shriver, Zachary; Raman, Rahul; Sasisekharan, Ram

2009-12-11

Heparin and heparan sulfate glycosaminoglycans (HSGAGs) comprise a chemically heterogeneous class of sulfated polysaccharides. The development of structure-activity relationships for this class of polysaccharides requires the identification and characterization of degrading enzymes with defined substrate specificity and enzymatic activity. Toward this end, we report here the molecular cloning and extensive structure-function analysis of a 6-O-sulfatase from the Gram-negative bacterium Flavobacterium heparinum. In addition, we report the recombinant expression of this enzyme in Escherichia coli in a soluble, active form and identify it as a specific HSGAG sulfatase. We further define the mechanism of action of the enzyme through biochemical and structural studies. Through the use of defined substrates, we investigate the kinetic properties of the enzyme. This analysis was complemented by homology-based molecular modeling studies that sought to rationalize the substrate specificity of the enzyme and mode of action through an analysis of the active-site topology of the enzyme including identifying key enzyme-substrate interactions and assigning key amino acids within the active site of the enzyme. Taken together, our structural and biochemical studies indicate that 6-O-sulfatase is a predominantly exolytic enzyme that specifically acts on N-sulfated or N-acetylated 6-O-sulfated glucosamines present at the non-reducing end of HSGAG oligosaccharide substrates. This requirement for the N-acetyl or N-sulfo groups on the glucosamine substrate can be explained through eliciting favorable interactions with key residues within the active site of the enzyme. These findings provide a framework that enables the use of 6-O-sulfatase as a tool for HSGAG structure-activity studies as well as expand our biochemical and structural understanding of this important class of enzymes.

Comparative and Evolutionary Analysis of Grass Pollen Allergens Using Brachypodium distachyon as a Model System.

PubMed

Sharma, Akanksha; Sharma, Niharika; Bhalla, Prem; Singh, Mohan

2017-01-01

Comparative genomics have facilitated the mining of biological information from a genome sequence, through the detection of similarities and differences with genomes of closely or more distantly related species. By using such comparative approaches, knowledge can be transferred from the model to non-model organisms and insights can be gained in the structural and evolutionary patterns of specific genes. In the absence of sequenced genomes for allergenic grasses, this study was aimed at understanding the structure, organisation and expression profiles of grass pollen allergens using the genomic data from Brachypodium distachyon as it is phylogenetically related to the allergenic grasses. Combining genomic data with the anther RNA-Seq dataset revealed 24 pollen allergen genes belonging to eight allergen groups mapping on the five chromosomes in B. distachyon. High levels of anther-specific expression profiles were observed for the 24 identified putative allergen-encoding genes in Brachypodium. The genomic evidence suggests that gene encoding the group 5 allergen, the most potent trigger of hay fever and allergic asthma originated as a pollen specific orphan gene in a common grass ancestor of Brachypodium and Triticiae clades. Gene structure analysis showed that the putative allergen-encoding genes in Brachypodium either lack or contain reduced number of introns. Promoter analysis of the identified Brachypodium genes revealed the presence of specific cis-regulatory sequences likely responsible for high anther/pollen-specific expression. With the identification of putative allergen-encoding genes in Brachypodium, this study has also described some important plant gene families (e.g. expansin superfamily, EF-Hand family, profilins etc) for the first time in the model plant Brachypodium. Altogether, the present study provides new insights into structural characterization and evolution of pollen allergens and will further serve as a base for their functional characterization in related grass species.

Quantitative phase-digital holographic microscopy: a new imaging modality to identify original cellular biomarkers of diseases

NASA Astrophysics Data System (ADS)

Marquet, P.; Rothenfusser, K.; Rappaz, B.; Depeursinge, C.; Jourdain, P.; Magistretti, P. J.

2016-03-01

Quantitative phase microscopy (QPM) has recently emerged as a powerful label-free technique in the field of living cell imaging allowing to non-invasively measure with a nanometric axial sensitivity cell structure and dynamics. Since the phase retardation of a light wave when transmitted through the observed cells, namely the quantitative phase signal (QPS), is sensitive to both cellular thickness and intracellular refractive index related to the cellular content, its accurate analysis allows to derive various cell parameters and monitor specific cell processes, which are very likely to identify new cell biomarkers. Specifically, quantitative phase-digital holographic microscopy (QP-DHM), thanks to its numerical flexibility facilitating parallelization and automation processes, represents an appealing imaging modality to both identify original cellular biomarkers of diseases as well to explore the underlying pathophysiological processes.

Identifying Emotions on the Basis of Neural Activation

PubMed Central

Kassam, Karim S.; Markey, Amanda R.; Cherkassky, Vladimir L.; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing. PMID:23840392

Identifying Emotions on the Basis of Neural Activation.

PubMed

Kassam, Karim S; Markey, Amanda R; Cherkassky, Vladimir L; Loewenstein, George; Just, Marcel Adam

2013-01-01

We attempt to determine the discriminability and organization of neural activation corresponding to the experience of specific emotions. Method actors were asked to self-induce nine emotional states (anger, disgust, envy, fear, happiness, lust, pride, sadness, and shame) while in an fMRI scanner. Using a Gaussian Naïve Bayes pooled variance classifier, we demonstrate the ability to identify specific emotions experienced by an individual at well over chance accuracy on the basis of: 1) neural activation of the same individual in other trials, 2) neural activation of other individuals who experienced similar trials, and 3) neural activation of the same individual to a qualitatively different type of emotion induction. Factor analysis identified valence, arousal, sociality, and lust as dimensions underlying the activation patterns. These results suggest a structure for neural representations of emotion and inform theories of emotional processing.

Topological, functional, and dynamic properties of the protein interaction networks rewired by benzo(a)pyrene

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

Ba, Qian; Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing; Li, Junyang

2015-03-01

Benzo(a)pyrene is a common environmental and foodborne pollutant that has been identified as a human carcinogen. Although the carcinogenicity of benzo(a)pyrene has been extensively reported, its precise molecular mechanisms and the influence on system-level protein networks are not well understood. To investigate the system-level influence of benzo(a)pyrene on protein interactions and regulatory networks, a benzo(a)pyrene-rewired protein interaction network was constructed based on 769 key proteins derived from more than 500 literature reports. The protein interaction network rewired by benzo(a)pyrene was a scale-free, highly-connected biological system. Ten modules were identified, and 25 signaling pathways were enriched, most of which belong tomore » the human diseases category, especially cancer and infectious disease. In addition, two lung-specific and two liver-specific pathways were identified. Three pathways were specific in short and medium-term networks (< 48 h), and five pathways were enriched only in the medium-term network (6 h–48 h). Finally, the expression of linker genes in the network was validated by Western blotting. These findings establish the overall, tissue- and time-specific benzo(a)pyrene-rewired protein interaction networks and provide insights into the biological effects and molecular mechanisms of action of benzo(a)pyrene. - Highlights: • Benzo(a)pyrene induced scale-free, highly-connected protein interaction networks. • 25 signaling pathways were enriched through modular analysis. • Tissue- and time-specific pathways were identified.« less

R2PL 2005 - Proceedings of the First International Workshop on Reengineering towards Product Lines

DTIC Science & Technology

2006-03-01

thinking. Other domain engineer- ing approaches are FODA [6] and FORM [7]. Typically these approaches are based on the analysis of high-level...November 1998. [6] Kyo C. Kang, Sholom G. Cohen, James A. Hess, William E. Novak, and A. Spencer Peterson. Feature-oriented do- main analysis ( FODA ... Analysis � by Bas Graaf, Bas Cornelissen, and Leon Moonen. © 2006 by Bas Graaf, Bas Cornelissen, and Leon Moonen. �Identifying Domain-Specific

Technology Candidates for Air-to-Air and Air-to-Ground Data Exchange

NASA Technical Reports Server (NTRS)

Haynes, Brian D.

2015-01-01

Technology Candidates for Air-to-Air and Air-to-Ground Data Exchange is a two-year research effort to visualize the U. S. aviation industry at a point 50 years in the future, and to define potential communication solutions to meet those future data exchange needs. The research team, led by XCELAR, was tasked with identifying future National Airspace System (NAS) scenarios, determining requirements and functions (including gaps), investigating technical and business issues for air, ground, & air-to-ground interactions, and reporting on the results. The project was conducted under technical direction from NASA and in collaboration with XCELAR's partner, National Institute of Aerospace, and NASA technical representatives. Parallel efforts were initiated to define the information exchange functional needs of the future NAS, and specific communication link technologies to potentially serve those needs. Those efforts converged with the mapping of each identified future NAS function to potential enabling communication solutions; those solutions were then compared with, and ranked relative to, each other on a technical basis in a structured analysis process. The technical solutions emerging from that process were then assessed from a business case perspective to determine their viability from a real-world adoption and deployment standpoint. The results of that analysis produced a proposed set of future solutions and most promising candidate technologies. Gap analyses were conducted at two points in the process, the first examining technical factors, and the second as part of the business case analysis. In each case, no gaps or unmet needs were identified in applying the solutions evaluated to the requirements identified. The future communication solutions identified in the research comprise both specific link technologies and two enabling technologies that apply to most or all specific links. As a result, the research resulted in a new analysis approach, viewing the underlying architecture of ground-air and air-air communications as a whole, rather than as simple "link to function" paired solutions. For the business case analysis, a number of "reference architectures" were developed for both the future technologies and the current systems, based on three typical configurations of current aircraft. Current and future costs were assigned, and various comparisons made between the current and future architectures. In general, it was assumed that if a future architecture offers lower cost than the current typical architecture, while delivering equivalent or better performance, it is likely that the future solution will gain industry acceptance. Conversely, future architectures presenting higher costs than their current counterparts must present a compelling benefit case in other areas or risk a lack of industry acceptance. The business case analysis consistently indicated lower costs for the proposed future architectures, and in most cases, significantly so. The proposed future solutions were found to offer significantly greater functionality, flexibility, and growth potential over time, at lower cost, than current systems. This was true for overall, fleet-wide equipage for domestic and oceanic air carriers, as well as for single, General Aviation (GA) aircraft. The overall research results indicate that all identified requirements can be met by the proposed solutions with significant capacity for future growth. Results also illustrate that the majority of the future communication needs can be met using currently allocated aviation RF spectrum, if used in more effective ways than it is today. A combination of such optimized aviation-specific links and commercial communication systems meets all identified needs for the 50-year future and beyond, with the caveat that a new, overall function will be needed to manage all information exchange, individual links, security, cost, and other factors. This function was labeled "Delivery Manager" (DM) within this research. DM employs a distributed client/server architecture, for both airborne and ground communications architectures. Final research results included identifying the most promising candidate technologies for the future system, conclusions and recommendations, and identifying areas where further research should be considered.

A quality risk management model approach for cell therapy manufacturing.

PubMed

Lopez, Fabio; Di Bartolo, Chiara; Piazza, Tommaso; Passannanti, Antonino; Gerlach, Jörg C; Gridelli, Bruno; Triolo, Fabio

2010-12-01

International regulatory authorities view risk management as an essential production need for the development of innovative, somatic cell-based therapies in regenerative medicine. The available risk management guidelines, however, provide little guidance on specific risk analysis approaches and procedures applicable in clinical cell therapy manufacturing. This raises a number of problems. Cell manufacturing is a poorly automated process, prone to operator-introduced variations, and affected by heterogeneity of the processed organs/tissues and lot-dependent variability of reagent (e.g., collagenase) efficiency. In this study, the principal challenges faced in a cell-based product manufacturing context (i.e., high dependence on human intervention and absence of reference standards for acceptable risk levels) are identified and addressed, and a risk management model approach applicable to manufacturing of cells for clinical use is described for the first time. The use of the heuristic and pseudo-quantitative failure mode and effect analysis/failure mode and critical effect analysis risk analysis technique associated with direct estimation of severity, occurrence, and detection is, in this specific context, as effective as, but more efficient than, the analytic hierarchy process. Moreover, a severity/occurrence matrix and Pareto analysis can be successfully adopted to identify priority failure modes on which to act to mitigate risks. The application of this approach to clinical cell therapy manufacturing in regenerative medicine is also discussed. © 2010 Society for Risk Analysis.

Frequency-Specific Fractal Analysis of Postural Control Accounts for Control Strategies

PubMed Central

Gilfriche, Pierre; Deschodt-Arsac, Véronique; Blons, Estelle; Arsac, Laurent M.

2018-01-01

Diverse indicators of postural control in Humans have been explored for decades, mostly based on the trajectory of the center-of-pressure. Classical approaches focus on variability, based on the notion that if a posture is too variable, the subject is not stable. Going deeper, an improved understanding of underlying physiology has been gained from studying variability in different frequency ranges, pointing to specific short-loops (proprioception), and long-loops (visuo-vestibular) in neural control. More recently, fractal analyses have proliferated and become useful additional metrics of postural control. They allowed identifying two scaling phenomena, respectively in short and long timescales. Here, we show that one of the most widely used methods for fractal analysis, Detrended Fluctuation Analysis, could be enhanced to account for scalings on specific frequency ranges. By computing and filtering a bank of synthetic fractal signals, we established how scaling analysis can be focused on specific frequency components. We called the obtained method Frequency-specific Fractal Analysis (FsFA) and used it to associate the two scaling phenomena of postural control to proprioceptive-based control loop and visuo-vestibular based control loop. After that, convincing arguments of method validity came from an application on the study of unaltered vs. altered postural control in athletes. Overall, the analysis suggests that at least two timescales contribute to postural control: a velocity-based control in short timescales relying on proprioceptive sensors, and a position-based control in longer timescales with visuo-vestibular sensors, which is a brand-new vision of postural control. Frequency-specific scaling exponents are promising markers of control strategies in Humans. PMID:29643816

Energy transport pathway in proteins: Insights from non-equilibrium molecular dynamics with elastic network model.

PubMed

Wang, Wei Bu; Liang, Yu; Zhang, Jing; Wu, Yi Dong; Du, Jian Jun; Li, Qi Ming; Zhu, Jian Zhuo; Su, Ji Guo

2018-06-22

Intra-molecular energy transport between distant functional sites plays important roles in allosterically regulating the biochemical activity of proteins. How to identify the specific intra-molecular signaling pathway from protein tertiary structure remains a challenging problem. In the present work, a non-equilibrium dynamics method based on the elastic network model (ENM) was proposed to simulate the energy propagation process and identify the specific signaling pathways within proteins. In this method, a given residue was perturbed and the propagation of energy was simulated by non-equilibrium dynamics in the normal modes space of ENM. After that, the simulation results were transformed from the normal modes space to the Cartesian coordinate space to identify the intra-protein energy transduction pathways. The proposed method was applied to myosin and the third PDZ domain (PDZ3) of PSD-95 as case studies. For myosin, two signaling pathways were identified, which mediate the energy transductions form the nucleotide binding site to the 50 kDa cleft and the converter subdomain, respectively. For PDZ3, one specific signaling pathway was identified, through which the intra-protein energy was transduced from ligand binding site to the distant opposite side of the protein. It is also found that comparing with the commonly used cross-correlation analysis method, the proposed method can identify the anisotropic energy transduction pathways more effectively.

Next-generation sequencing-based transcriptomic and proteomic analysis of the common reed, Phragmites australis (Poaceae), reveals genes involved in invasiveness and rhizome specificity.

PubMed

He, Ruifeng; Kim, Min-Jeong; Nelson, William; Balbuena, Tiago S; Kim, Ryan; Kramer, Robin; Crow, John A; May, Greg D; Thelen, Jay J; Soderlund, Carol A; Gang, David R

2012-02-01

The common reed (Phragmites australis), one of the most widely distributed of all angiosperms, uses its rhizomes (underground stems) to invade new territory, making it one of the most successful weedy species worldwide. Characterization of the rhizome transcriptome and proteome is needed to identify candidate genes and proteins involved in rhizome growth, development, metabolism, and invasiveness. We employed next-generation sequencing technologies including 454 and Illumina platforms to characterize the reed rhizome transcriptome and used quantitative proteomics techniques to identify the rhizome proteome. Combining 336514 Roche 454 Titanium reads and 103350802 Illumina paired-end reads in a de novo hybrid assembly yielded 124450 unique transcripts with an average length of 549 bp, of which 54317 were annotated. Rhizome-specific and differentially expressed transcripts were identified between rhizome apical tips (apical meristematic region) and rhizome elongation zones. A total of 1280 nonredundant proteins were identified and quantified using GeLC-MS/MS based label-free proteomics, where 174 and 77 proteins were preferentially expressed in the rhizome elongation zone and apical tip tissues, respectively. Genes involved in allelopathy and in controlling development and potentially invasiveness were identified. In addition to being a valuable sequence and protein data resource for studying plant rhizome species, our results provide useful insights into identifying specific genes and proteins with potential roles in rhizome differentiation, development, and function.

Epigenetic inactivation of VGF associated with Urothelial Cell Carcinoma and its potential as a non-invasive biomarker using urine.

PubMed

Hayashi, Masamichi; Bernert, Heike; Kagohara, Luciane Tsukamoto; Maldonado, Leonel; Brait, Mariana; Schoenberg, Mark; Bivalacqua, Trinity; Netto, George J; Koch, Wayne; Sidransky, David; Hoque, Mohammad O

2014-05-30

To identify new epigenetic markers and further characterize Urothelial Cell Carcinoma (UCC), we tested the promoter methylation (PM) status of 19 genes previously identified as cancer specific methylated genes in other solid tumors. We used bisulfite sequencing, methylation specific PCR and quantitative methylation specific PCR (QMSP) to test the PM status of 19 genes in urothelial cancer cell lines. Among the 19 genes tested, VGF was found to be completely methylated in several UCC cell lines. VGF QMSP analysis showed that methylation values of almost all the primary 19 UCC tissues were higher than the paired normal tissues (P=0.009). In another cohort, 12/35 (34.3%) of low grade UCC cases displayed VGF methylation. As a biomarker for non-invasive detection of UCC, VGF showed a significantly higher frequency of methylation in urine from UCC cases (8/20) compared to controls (1/20) (P=0.020). After treatment of cell lines with 5-Aza-2'-deoxycytidine, VGF was robustly re-expressed. Forced expression of VGF in bladder cancer cell lines inhibited cell growth. Selection of candidates from genome-wide screening approach in other solid tumors successfully identified UCC specific methylated genes.

Experiencing health care service quality: through patients' eyes.

PubMed

Schembri, Sharon

2015-02-01

The primary aim of the present study was to consider health care service quality from the patients' perspective, specifically through the patient's eyes. A narrative analysis was performed on 300 patient stories. This rigorous analysis of patient stories is designed to identify and describe health care service quality through patients' eyes in an authentic and accurate, experiential manner. The findings show that there are variant and complex ways that patients experience health care service quality. Patient stories offer an authentic view of the complex ways that patients experience health care service quality. Narrative analysis is a useful tool to identify and describe how patients experience health care service quality. Patients experience health care service quality in complex and varying ways.

Current and Emerging Technologies for the Analysis of the Genome-Wide and Locus-Specific DNA Methylation Patterns.

PubMed

Tost, Jörg

2016-01-01

DNA methylation is the most studied epigenetic modification, and altered DNA methylation patterns have been identified in cancer and more recently also in many other complex diseases. Furthermore, DNA methylation is influenced by a variety of environmental factors, and the analysis of DNA methylation patterns might allow deciphering previous exposure. Although a large number of techniques to study DNA methylation either genome-wide or at specific loci have been devised, they all are based on a limited number of principles for differentiating the methylation state, viz., methylation-specific/methylation-dependent restriction enzymes, antibodies or methyl-binding proteins, chemical-based enrichment, or bisulfite conversion. Second-generation sequencing has largely replaced microarrays as readout platform and is also becoming more popular for locus-specific DNA methylation analysis. In this chapter, the currently used methods for both genome-wide and locus-specific analysis of 5-methylcytosine and as its oxidative derivatives, such as 5-hydroxymethylcytosine, are reviewed in detail, and the advantages and limitations of each approach are discussed. Furthermore, emerging technologies avoiding PCR amplification and allowing a direct readout of DNA methylation are summarized, together with novel applications, such as the detection of DNA methylation in single cells or in circulating cell-free DNA.

Characterization and identification of ubiquitin conjugation sites with E3 ligase recognition specificities.

PubMed

Nguyen, Van-Nui; Huang, Kai-Yao; Huang, Chien-Hsun; Chang, Tzu-Hao; Bretaña, Neil; Lai, K; Weng, Julia; Lee, Tzong-Yi

2015-01-01

In eukaryotes, ubiquitin-conjugation is an important mechanism underlying proteasome-mediated degradation of proteins, and as such, plays an essential role in the regulation of many cellular processes. In the ubiquitin-proteasome pathway, E3 ligases play important roles by recognizing a specific protein substrate and catalyzing the attachment of ubiquitin to a lysine (K) residue. As more and more experimental data on ubiquitin conjugation sites become available, it becomes possible to develop prediction models that can be scaled to big data. However, no development that focuses on the investigation of ubiquitinated substrate specificities has existed. Herein, we present an approach that exploits an iteratively statistical method to identify ubiquitin conjugation sites with substrate site specificities. In this investigation, totally 6259 experimentally validated ubiquitinated proteins were obtained from dbPTM. After having filtered out homologous fragments with 40% sequence identity, the training data set contained 2658 ubiquitination sites (positive data) and 5532 non-ubiquitinated sites (negative data). Due to the difficulty in characterizing the substrate site specificities of E3 ligases by conventional sequence logo analysis, a recursively statistical method has been applied to obtain significant conserved motifs. The profile hidden Markov model (profile HMM) was adopted to construct the predictive models learned from the identified substrate motifs. A five-fold cross validation was then used to evaluate the predictive model, achieving sensitivity, specificity, and accuracy of 73.07%, 65.46%, and 67.93%, respectively. Additionally, an independent testing set, completely blind to the training data of the predictive model, was used to demonstrate that the proposed method could provide a promising accuracy (76.13%) and outperform other ubiquitination site prediction tool. A case study demonstrated the effectiveness of the characterized substrate motifs for identifying ubiquitination sites. The proposed method presents a practical means of preliminary analysis and greatly diminishes the total number of potential targets required for further experimental confirmation. This method may help unravel their mechanisms and roles in E3 recognition and ubiquitin-mediated protein degradation.

A novel highly divergent protein family identified from a viviparous insect by RNA-seq analysis: a potential target for tsetse fly-specific abortifacients.

PubMed

Benoit, Joshua B; Attardo, Geoffrey M; Michalkova, Veronika; Krause, Tyler B; Bohova, Jana; Zhang, Qirui; Baumann, Aaron A; Mireji, Paul O; Takáč, Peter; Denlinger, David L; Ribeiro, Jose M; Aksoy, Serap

2014-04-01

In tsetse flies, nutrients for intrauterine larval development are synthesized by the modified accessory gland (milk gland) and provided in mother's milk during lactation. Interference with at least two milk proteins has been shown to extend larval development and reduce fecundity. The goal of this study was to perform a comprehensive characterization of tsetse milk proteins using lactation-specific transcriptome/milk proteome analyses and to define functional role(s) for the milk proteins during lactation. Differential analysis of RNA-seq data from lactating and dry (non-lactating) females revealed enrichment of transcripts coding for protein synthesis machinery, lipid metabolism and secretory proteins during lactation. Among the genes induced during lactation were those encoding the previously identified milk proteins (milk gland proteins 1-3, transferrin and acid sphingomyelinase 1) and seven new genes (mgp4-10). The genes encoding mgp2-10 are organized on a 40 kb syntenic block in the tsetse genome, have similar exon-intron arrangements, and share regions of amino acid sequence similarity. Expression of mgp2-10 is female-specific and high during milk secretion. While knockdown of a single mgp failed to reduce fecundity, simultaneous knockdown of multiple variants reduced milk protein levels and lowered fecundity. The genomic localization, gene structure similarities, and functional redundancy of MGP2-10 suggest that they constitute a novel highly divergent protein family. Our data indicates that MGP2-10 function both as the primary amino acid resource for the developing larva and in the maintenance of milk homeostasis, similar to the function of the mammalian casein family of milk proteins. This study underscores the dynamic nature of the lactation cycle and identifies a novel family of lactation-specific proteins, unique to Glossina sp., that are essential to larval development. The specificity of MGP2-10 to tsetse and their critical role during lactation suggests that these proteins may be an excellent target for tsetse-specific population control approaches.

SPARTA: Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis.

PubMed

Johnson, Benjamin K; Scholz, Matthew B; Teal, Tracy K; Abramovitch, Robert B

2016-02-04

Many tools exist in the analysis of bacterial RNA sequencing (RNA-seq) transcriptional profiling experiments to identify differentially expressed genes between experimental conditions. Generally, the workflow includes quality control of reads, mapping to a reference, counting transcript abundance, and statistical tests for differentially expressed genes. In spite of the numerous tools developed for each component of an RNA-seq analysis workflow, easy-to-use bacterially oriented workflow applications to combine multiple tools and automate the process are lacking. With many tools to choose from for each step, the task of identifying a specific tool, adapting the input/output options to the specific use-case, and integrating the tools into a coherent analysis pipeline is not a trivial endeavor, particularly for microbiologists with limited bioinformatics experience. To make bacterial RNA-seq data analysis more accessible, we developed a Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis (SPARTA). SPARTA is a reference-based bacterial RNA-seq analysis workflow application for single-end Illumina reads. SPARTA is turnkey software that simplifies the process of analyzing RNA-seq data sets, making bacterial RNA-seq analysis a routine process that can be undertaken on a personal computer or in the classroom. The easy-to-install, complete workflow processes whole transcriptome shotgun sequencing data files by trimming reads and removing adapters, mapping reads to a reference, counting gene features, calculating differential gene expression, and, importantly, checking for potential batch effects within the data set. SPARTA outputs quality analysis reports, gene feature counts and differential gene expression tables and scatterplots. SPARTA provides an easy-to-use bacterial RNA-seq transcriptional profiling workflow to identify differentially expressed genes between experimental conditions. This software will enable microbiologists with limited bioinformatics experience to analyze their data and integrate next generation sequencing (NGS) technologies into the classroom. The SPARTA software and tutorial are available at sparta.readthedocs.org.

Specific Proteins in Nontuberculous Mycobacteria: New Potential Tools

PubMed Central

Orduña, Patricia; Castillo-Rodal, Antonia I.; Mercado, Martha E.; Ponce de León, Samuel; López-Vidal, Yolanda

2015-01-01

Nontuberculous mycobacteria (NTM) have been isolated from water, soil, air, food, protozoa, plants, animals, and humans. Although most NTM are saprophytes, approximately one-third of NTM have been associated with human diseases. In this study, we did a comparative proteomic analysis among five NTM strains isolated from several sources. There were different numbers of protein spots from M. gordonae (1,264), M. nonchromogenicum type I (894), M. nonchromogenicum type II (935), M. peregrinum (806), and M. scrofulaceum/Mycobacterium mantenii (1,486) strains, respectively. We identified 141 proteins common to all strains and specific proteins to each NTM strain. A total of 23 proteins were selected for its identification. Two of the common proteins identified (short-chain dehydrogenase/reductase SDR and diguanylate cyclase) did not align with M. tuberculosis complex protein sequences, which suggest that these proteins are found only in the NTM strains. Some of the proteins identified as common to all strains can be used as markers of NTM exposure and for the development of new diagnostic tools. Additionally, the specific proteins to NTM strains identified may represent potential candidates for the diagnosis of diseases caused by these mycobacteria. PMID:26106621

Motivators of and Barriers to Engaging in Physical Activity: Perspectives of Low-Income Culturally Diverse Adolescents and Adults.

PubMed

Bragg, Marie A; Tucker, Carolyn M; Kaye, Lily B; Desmond, Frederic

2009-01-01

Obesity rates are rising in the United States, especially among low-income and racial/ethnic minority individuals. Exploring motivators and barriers relative to engaging in physical activity is imperative. The purpose of this study was to identify motivators and barriers relative to engagement in physical activity as reported by culturally diverse low-income adolescents and adults. A total of 91 adolescent (11 to 15 years of age) and adult (18 years of age or older) participants who self-identified as African American, Hispanic, or non-Hispanic White engaged in age group-, race/ethnicity-, and gender-concordant focus groups. Qualitative data analysis indicated that the motivators and barriers most commonly identified among the adolescent and adult focus groups were: social influence; time and priorities; physical environment; fun and enjoyment; inherently physical activities; weight concerns; fatigue, physical discomfort and current fitness level; and immediate positive feelings. Findings were generally similar across age group, gender and race/ethnicity. Age group-specific, gender-specific and race/ethnicity-specific motivators and barriers were related to how commonly the motivators and barriers were identified among each group. Implications for increasing physical activity among low-income culturally diverse adolescents and adults are discussed.

Analysis of evolutionary conservation patterns and their influence on identifying protein functional sites.

PubMed

Fang, Chun; Noguchi, Tamotsu; Yamana, Hayato

2014-10-01

Evolutionary conservation information included in position-specific scoring matrix (PSSM) has been widely adopted by sequence-based methods for identifying protein functional sites, because all functional sites, whether in ordered or disordered proteins, are found to be conserved at some extent. However, different functional sites have different conservation patterns, some of them are linear contextual, some of them are mingled with highly variable residues, and some others seem to be conserved independently. Every value in PSSMs is calculated independently of each other, without carrying the contextual information of residues in the sequence. Therefore, adopting the direct output of PSSM for prediction fails to consider the relationship between conservation patterns of residues and the distribution of conservation scores in PSSMs. In order to demonstrate the importance of combining PSSMs with the specific conservation patterns of functional sites for prediction, three different PSSM-based methods for identifying three kinds of functional sites have been analyzed. Results suggest that, different PSSM-based methods differ in their capability to identify different patterns of functional sites, and better combining PSSMs with the specific conservation patterns of residues would largely facilitate the prediction.

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

Grant, Ashleigh; Wilkinson, T.J.; Holman, Thomas

Analysis of fingerprints has predominantly focused on matching the pattern of ridges to a specific person as a form of identification. The present work focuses on identifying extrinsic materials that are left within a person's fingerprint after recent handling of such materials. Specifically, we employed infrared spectromicroscopy to locate and positively identify microscopic particles from a mixture of common materials in the latent human fingerprints of volunteer subjects. We were able to find and correctly identify all test substances based on their unique infrared spectral signatures. Spectral imaging is demonstrated as a method for automating recognition of specific substances inmore » a fingerprint. We also demonstrate the use of Attenuated Total Reflectance (ATR) and synchrotron-based infrared spectromicroscopy for obtaining high-quality spectra from particles that were too thick or too small, respectively, for reflection/absorption measurements. We believe the application of this rapid, non-destructive analytical technique to the forensic study of latent human finger prints has the potential to add a new layer of information available to investigators. Using fingerprints to not only identify who was present at a crime scene, but also to link who was handling key materials will be a powerful investigative tool.« less

Functional analysis of neuronal microRNAs in Caenorhabditis elegans dauer formation by combinational genetics and Neuronal miRISC immunoprecipitation.

PubMed

Than, Minh T; Kudlow, Brian A; Han, Min

2013-06-01

Identifying the physiological functions of microRNAs (miRNAs) is often challenging because miRNAs commonly impact gene expression under specific physiological conditions through complex miRNA::mRNA interaction networks and in coordination with other means of gene regulation, such as transcriptional regulation and protein degradation. Such complexity creates difficulties in dissecting miRNA functions through traditional genetic methods using individual miRNA mutations. To investigate the physiological functions of miRNAs in neurons, we combined a genetic "enhancer" approach complemented by biochemical analysis of neuronal miRNA-induced silencing complexes (miRISCs) in C. elegans. Total miRNA function can be compromised by mutating one of the two GW182 proteins (AIN-1), an important component of miRISC. We found that combining an ain-1 mutation with a mutation in unc-3, a neuronal transcription factor, resulted in an inappropriate entrance into the stress-induced, alternative larval stage known as dauer, indicating a role of miRNAs in preventing aberrant dauer formation. Analysis of this genetic interaction suggests that neuronal miRNAs perform such a role partly by regulating endogenous cyclic guanosine monophosphate (cGMP) signaling, potentially influencing two other dauer-regulating pathways. Through tissue-specific immunoprecipitations of miRISC, we identified miRNAs and their likely target mRNAs within neuronal tissue. We verified the biological relevance of several of these miRNAs and found that many miRNAs likely regulate dauer formation through multiple dauer-related targets. Further analysis of target mRNAs suggests potential miRNA involvement in various neuronal processes, but the importance of these miRNA::mRNA interactions remains unclear. Finally, we found that neuronal genes may be more highly regulated by miRNAs than intestinal genes. Overall, our study identifies miRNAs and their targets, and a physiological function of these miRNAs in neurons. It also suggests that compromising other aspects of gene expression, along with miRISC, can be an effective approach to reveal miRNA functions in specific tissues under specific physiological conditions.

Sex-specific risk factors for childhood wheeze and longitudinal phenotypes of wheeze.

PubMed

Tse, Sze Man; Rifas-Shiman, Sheryl L; Coull, Brent A; Litonjua, Augusto A; Oken, Emily; Gold, Diane R

2016-12-01

Although sexual dimorphism in wheeze and asthma prevalence are well documented, sex-specific risk factors for wheeze and longitudinal wheeze phenotypes have not been well elucidated. By using a large prebirth cohort, this study aimed to identify sex-specific risk factors for wheeze from birth through midchildhood and identify distinct longitudinal wheeze phenotypes and the sex-specific risk factors associated with these phenotypes. Mothers reported child wheeze symptoms over the past year approximately yearly on 9 occasions starting at age 1 year. We identified sex-specific predictors of wheeze, wheeze phenotypes, and sex-specific predictors of these phenotypes by using generalized estimating equations, latent class mixed models, and multinomial logistic analysis, respectively. A total of 1623 children had information on wheeze at 1 or more time points. Paternal asthma was a stronger predictor of ever wheezing in boys (odds ratio [OR], 2.15; 95% CI, 1.74-2.66) than in girls (OR, 1.53; 95% CI, 1.19-1.96; P for sex by paternal asthma interaction = .03), whereas being black or Hispanic, birth weight for gestational age z score, and breast-feeding duration had stronger associations among girls. We identified 3 longitudinal wheeze phenotypes: never/infrequent wheeze (74.1%), early transient wheeze (12.7%), and persistent wheeze (13.1%). Compared with never/infrequent wheeze, maternal asthma, infant bronchiolitis, and atopic dermatitis were associated with persistent wheeze in both sexes, but paternal asthma was associated with persistent wheeze in boys only (OR, 4.27; 95% CI, 2.33-7.83; P for sex by paternal asthma interaction = .02), whereas being black or Hispanic was a predictor for girls only. We identified sex-specific predictors of wheeze and longitudinal wheeze patterns, which might have important prognostic value and allow for a more personalized approach to wheeze and asthma treatment. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Analysis of tissue-specific region in sericin 1 gene promoter of Bombyx mori

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

Liu Yan; Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031; Yu Lian

The gene encoding sericin 1 (Ser1) of silkworm (Bombyx mori) is specifically expressed in the middle silk gland cells. To identify element involved in this transcription-dependent spatial restriction, truncation of the 5' terminal from the sericin 1 (Ser1) promoter is studied in vivo. A 209 bp DNA sequence upstream of the transcriptional start site (-586 to -378) is found to be responsible for promoting tissue-specific transcription. Analysis of this 209 bp region by overlapping deletion studies showed that a 25 bp region (-500 to -476) suppresses the ectopic expression of the Ser1 promoter. An unknown factor abundant in fat bodymore » nuclear extracts is shown to bind to this 25 bp fragment. These results suggest that this 25 bp region and the unknown factor are necessary for determining the tissue-specificity of the Ser1 promoter.« less

Evidence for specific annexin I-binding proteins on human monocytes.

PubMed Central

Goulding, N J; Pan, L; Wardwell, K; Guyre, V C; Guyre, P M

1996-01-01

Recombinant human annexin I and a monoclonal antibody specific for this protein (mAb 1B) were used to investigate surface binding of this member of the annexin family of proteins to peripheral blood monocytes. Flow cytometric analysis demonstrated trypsin-sensitive, saturable binding of annexin I to human peripheral blood monocytes but not to admixed lymphocytes. A monoclonal antibody that blocks the anti-phospholipase activity of annexin I also blocked its binding to monocytes. These findings suggest the presence of specific binding sites on monocytes. Furthermore, surface iodination, immunoprecipitation and SDS/PAGE analysis were used to identify two annexin I-binding proteins on the surface of monocytes with molecular masses of 15 kDa and 18 kDa respectively. The identification and characterization of these annexin I-binding molecules should help us to better understand the specific interactions of annexin I with monocytes that lead to down-regulation of pro-inflammatory cell functions. PMID:8687405

Ancestry-specific and sex-specific risk alleles identified in a genome-wide gene-by-alcohol dependence interaction study of risky sexual behaviors.

PubMed

Polimanti, Renato; Zhao, Hongyu; Farrer, Lindsay A; Kranzler, Henry R; Gelernter, Joel

2017-12-01

We previously mapped loci for the genome-wide association studies (GWAS) and genome-wide gene-by-alcohol dependence interaction (GW-GxAD) analyses of risky sexual behaviors (RSB). This study extends those findings by analyzing the ancestry- and sex-specific AD-stratified effects on RSB. We examined the concordance of findings for the AD-stratified GWAS and the GW-GxAD analysis of RSB, with concordance defined as genome-wide significance in one analysis and at least nominal significance in the second analysis. A total of 2,173 African-American (AA) and 1,751 European-American (EA) subjects were investigated. Information regarding RSB (lifetime experiences of unprotected sex and multiple sexual partners) and DSM-IV diagnosis of lifetime AD were derived from the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). In our ancestry- and sex-specific analyses, we identified four independent genome-wide significant (GWS) loci (p < 5*10 -8 ) and one suggestive locus (p < 6*10 -8 ). In men, we observed a GWS signal in FAM162A (rs2002594, p = 4.96*10 -8 ). In women, there was a suggestive locus in PLGRKT (rs3824435, p = 5.52*10 -8 ). In AAs, there was a GWS signal in GRK5 (rs1316543, p = 1.25*10 -9 ). In AA men, we observed an intergenic GWS signal (rs12898370, p = 4.49*10 -8 ) near LINGO1. In EA men, there was a GWS signal in CCSER1 (rs62313897; p = 7.93*10 -10 ). The loci identified in this GWAS implicate molecular mechanisms related to psychiatric illness and personality features, suggesting that the interplay between AD and RSB is mediated by alleles associated with behavioral traits. © 2017 Wiley Periodicals, Inc.

An analysis of root cause identification and continuous quality improvement in public health H1N1 after-action reports.

PubMed

Singleton, Christa-Marie; Debastiani, Summer; Rose, Dale; Kahn, Emily B

2014-01-01

To identify the extent to which the Homeland Security Exercise and Evaluation Program's (HSEEP) After Action Report/Improvement Plan (AAR/IP) template was followed by public health entities and facilitated the identification of detailed corrective actions and continuous improvement. Data were drawn from the US H1N1 Public Health Emergency Response (PHER) federal grant awardees (n = 62). After action report/improvement plan text was examined to identify the presence of AAR/IP HSEEP elements and characterized as "minimally complete," "partially complete," or "complete." Corrective actions (CA) and recommendations within the IP focusing on performance deficits were coded as specific, measurable, and time-bound, and whether they were associated with a problem that met root cause criteria and whether the CA/recommendation was intended to address or fix the root cause. A total of 2619 CA/recommendations were identified. More than half (n = 1480, 57%) addressed root causes. Corrective actions/recommendations associated with complete AARs more frequently addressed root cause (58% vs 51%, χ = 9.1, P < 0.003) and were more specific (34% vs 23%, χ = 32.3, P < 0.0001), measurable (30% vs 18%, χ = 37.9, P < 0.0001), and time-bound (38% vs 15%, χ = 115.5, P < 0.0001) than partially complete AARs. The same pattern was not observed with completeness of IPs. Corrective actions and recommendations were similarly specific and measurable. Recommendations significantly addressed root cause more than CAs. Our analysis indicates a possible lack of awardee distinction between CA and recommendations in AARs. As HSEEP adapts to align with the 2011 National Preparedness Goal and National Preparedness System, future HSEEP documents should emphasize the importance of root cause analysis as a required element within AAR documents and templates in the exercise and real incident environment, as well as the need for specific and measurable CAs.

Identification of stress responsive genes by studying specific relationships between mRNA and protein abundance.

PubMed

Morimoto, Shimpei; Yahara, Koji

2018-03-01

Protein expression is regulated by the production and degradation of mRNAs and proteins but the specifics of their relationship are controversial. Although technological advances have enabled genome-wide and time-series surveys of mRNA and protein abundance, recent studies have shown paradoxical results, with most statistical analyses being limited to linear correlation, or analysis of variance applied separately to mRNA and protein datasets. Here, using recently analyzed genome-wide time-series data, we have developed a statistical analysis framework for identifying which types of genes or biological gene groups have significant correlation between mRNA and protein abundance after accounting for potential time delays. Our framework stratifies all genes in terms of the extent of time delay, conducts gene clustering in each stratum, and performs a non-parametric statistical test of the correlation between mRNA and protein abundance in a gene cluster. Consequently, we revealed stronger correlations than previously reported between mRNA and protein abundance in two metabolic pathways. Moreover, we identified a pair of stress responsive genes ( ADC17 and KIN1 ) that showed a highly similar time series of mRNA and protein abundance. Furthermore, we confirmed robustness of the analysis framework by applying it to another genome-wide time-series data and identifying a cytoskeleton-related gene cluster (keratin 18, keratin 17, and mitotic spindle positioning) that shows similar correlation. The significant correlation and highly similar changes of mRNA and protein abundance suggests a concerted role of these genes in cellular stress response, which we consider provides an answer to the question of the specific relationships between mRNA and protein in a cell. In addition, our framework for studying the relationship between mRNAs and proteins in a cell will provide a basis for studying specific relationships between mRNA and protein abundance after accounting for potential time delays.

Cancerouspdomains: comprehensive analysis of cancer type-specific recurrent somatic mutations in proteins and domains.

PubMed

Hashemi, Seirana; Nowzari Dalini, Abbas; Jalali, Adrin; Banaei-Moghaddam, Ali Mohammad; Razaghi-Moghadam, Zahra

2017-08-16

Discriminating driver mutations from the ones that play no role in cancer is a severe bottleneck in elucidating molecular mechanisms underlying cancer development. Since protein domains are representatives of functional regions within proteins, mutations on them may disturb the protein functionality. Therefore, studying mutations at domain level may point researchers to more accurate assessment of the functional impact of the mutations. This article presents a comprehensive study to map mutations from 29 cancer types to both sequence- and structure-based domains. Statistical analysis was performed to identify candidate domains in which mutations occur with high statistical significance. For each cancer type, the corresponding type-specific domains were distinguished among all candidate domains. Subsequently, cancer type-specific domains facilitated the identification of specific proteins for each cancer type. Besides, performing interactome analysis on specific proteins of each cancer type showed high levels of interconnectivity among them, which implies their functional relationship. To evaluate the role of mitochondrial genes, stem cell-specific genes and DNA repair genes in cancer development, their mutation frequency was determined via further analysis. This study has provided researchers with a publicly available data repository for studying both CATH and Pfam domain regions on protein-coding genes. Moreover, the associations between different groups of genes/domains and various cancer types have been clarified. The work is available at http://www.cancerouspdomains.ir .

To Leave or Not to Leave? A Regression Discontinuity Analysis of the Impact of Failing the High School Exit Exam

ERIC Educational Resources Information Center

Ou, Dongshu

2010-01-01

The high school exit exam (HSEE) is rapidly becoming a standardized assessment procedure for educational accountability in the United States. I use a unique, state-specific dataset to identify the effects of failing the HSEE on the likelihood of dropping out of high school based on a regression discontinuity design. The analysis shows that…

Prognostic value of site-specific metastases in pancreatic adenocarcinoma: A Surveillance Epidemiology and End Results database analysis.

PubMed

Oweira, Hani; Petrausch, Ulf; Helbling, Daniel; Schmidt, Jan; Mannhart, Meinrad; Mehrabi, Arianeb; Schöb, Othmar; Giryes, Anwar; Decker, Michael; Abdel-Rahman, Omar

2017-03-14

To evaluate the prognostic value of site-specific metastases among patients with metastatic pancreatic carcinoma registered within the Surveillance, Epidemiology and End Results (SEER) database. SEER database (2010-2013) has been queried through SEER*Stat program to determine the presentation, treatment outcomes and prognostic outcomes of metastatic pancreatic adenocarcinoma according to the site of metastasis. In this study, metastatic pancreatic adenocarcinoma patients were classified according to the site of metastases (liver, lung, bone, brain and distant lymph nodes). We utilized chi-square test to compare the clinicopathological characteristics among different sites of metastases. We used Kaplan-Meier analysis and log-rank testing for survival comparisons. We employed Cox proportional model to perform multivariate analyses of the patient population; and accordingly hazard ratios with corresponding 95%CI were generated. Statistical significance was considered if a two-tailed P value < 0.05 was achieved. A total of 13233 patients with stage IV pancreatic cancer and known sites of distant metastases were identified in the period from 2010-2013 and they were included into the current analysis. Patients with isolated distant nodal involvement or lung metastases have better overall and pancreatic cancer-specific survival compared to patients with isolated liver metastases (for overall survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001) (for pancreatic cancer-specific survival: lung vs liver metastases: P < 0.0001; distant nodal vs liver metastases: P < 0.0001). Multivariate analysis revealed that age < 65 years, white race, being married, female gender; surgery to the primary tumor and surgery to the metastatic disease were associated with better overall survival and pancreatic cancer-specific survival. Pancreatic adenocarcinoma patients with isolated liver metastases have worse outcomes compared to patients with isolated lung or distant nodal metastases. Further research is needed to identify the highly selected subset of patients who may benefit from local treatment of the primary tumor and/or metastatic disease.

Imaging spectroscopy: Earth and planetary remote sensing with the USGS Tetracorder and expert systems

USGS Publications Warehouse

Clark, Roger N.; Swayze, Gregg A.; Livo, K. Eric; Kokaly, Raymond F.; Sutley, Steve J.; Dalton, J. Brad; McDougal, Robert R.; Gent, Carol A.

2003-01-01

Imaging spectroscopy is a tool that can be used to spectrally identify and spatially map materials based on their specific chemical bonds. Spectroscopic analysis requires significantly more sophistication than has been employed in conventional broadband remote sensing analysis. We describe a new system that is effective at material identification and mapping: a set of algorithms within an expert system decision‐making framework that we call Tetracorder. The expertise in the system has been derived from scientific knowledge of spectral identification. The expert system rules are implemented in a decision tree where multiple algorithms are applied to spectral analysis, additional expert rules and algorithms can be applied based on initial results, and more decisions are made until spectral analysis is complete. Because certain spectral features are indicative of specific chemical bonds in materials, the system can accurately identify and map those materials. In this paper we describe the framework of the decision making process used for spectral identification, describe specific spectral feature analysis algorithms, and give examples of what analyses and types of maps are possible with imaging spectroscopy data. We also present the expert system rules that describe which diagnostic spectral features are used in the decision making process for a set of spectra of minerals and other common materials. We demonstrate the applications of Tetracorder to identify and map surface minerals, to detect sources of acid rock drainage, and to map vegetation species, ice, melting snow, water, and water pollution, all with one set of expert system rules. Mineral mapping can aid in geologic mapping and fault detection and can provide a better understanding of weathering, mineralization, hydrothermal alteration, and other geologic processes. Environmental site assessment, such as mapping source areas of acid mine drainage, has resulted in the acceleration of site cleanup, saving millions of dollars and years in cleanup time. Imaging spectroscopy data and Tetracorder analysis can be used to study both terrestrial and planetary science problems. Imaging spectroscopy can be used to probe planetary systems, including their atmospheres, oceans, and land surfaces.

Detection of sialomucin complex (MUC4) in human ocular surface epithelium and tear fluid.

PubMed

Pflugfelder, S C; Liu, Z; Monroy, D; Li, D Q; Carvajal, M E; Price-Schiavi, S A; Idris, N; Solomon, A; Perez, A; Carraway, K L

2000-05-01

To evaluate human ocular surface epithelium and tear fluid for the presence of sialomucin complex (MUC4), a high-molecular-weight heterodimeric glycoprotein composed of mucin (ASGP-1) and transmembrane (ASGP-2) subunits. Reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis assays were used to identify sialomucin complex RNA in ocular surface epithelia. Immunoprecipitation and immunoblot analysis were used to identify immunoreactive species in human tears and in the corneal and conjunctival epithelia using antibodies specific for carbohydrate and peptide epitopes on the sialomucin complex subunits. Immunofluorescence staining was used to detect sialomucin complex in frozen sections and impression cytology specimens of human cornea and conjunctival epithelia. ASGP-1- and ASGP-2-specific sequences were amplified from RNA extracted from both conjunctival and corneal epithelial biopsies by RT-PCR. Sialomucin complex transcripts were also detected in these tissues by Northern blot analysis, with a greater level of RNA detected in the peripheral than the central corneal epithelium. Sialomucin complex was immunoprecipitated from tear fluid samples and both corneal and conjunctival epithelia and detected by immunoblot analysis with specific anti-ASGP-1 and anti-ASGP-2 antibodies. The ASGP-1 peptide antibody HA-1 stained the full thickness of the corneal and conjunctival epithelia. In contrast, antibody 15H10, which reacts against a carbohydrate epitope on ASGP-1, stained only the superficial epithelial layers of these tissues. No staining was observed in the conjunctival goblet cells. Sialomucin complex was originally identified in rat mammary adenocarcinoma cells and has recently been shown to be produced by the ocular surface epithelia of rats. Furthermore, it has been identified as the rat homologue of human MUC4 mucin. The present studies show that it is expressed in the stratified epithelium covering the surface of the human eye and is present in human tear fluid. Expression of a carbohydrate-dependent epitope on the mucin subunit (ASGP-1) of sialomucin complex occurs in a differentiation-dependent fashion. Sialomucin complex joins MUC1 as another membrane mucin produced by the human ocular surface epithelia but is also found in the tear fluid, presumably in a soluble form, as found on the rat ocular surface.

Phylogenomic analysis of UDP glycosyltransferase 1 multigene family in Linum usitatissimum identified genes with varied expression patterns.

PubMed

Barvkar, Vitthal T; Pardeshi, Varsha C; Kale, Sandip M; Kadoo, Narendra Y; Gupta, Vidya S

2012-05-08

The glycosylation process, catalyzed by ubiquitous glycosyltransferase (GT) family enzymes, is a prevalent modification of plant secondary metabolites that regulates various functions such as hormone homeostasis, detoxification of xenobiotics and biosynthesis and storage of secondary metabolites. Flax (Linum usitatissimum L.) is a commercially grown oilseed crop, important because of its essential fatty acids and health promoting lignans. Identification and characterization of UDP glycosyltransferase (UGT) genes from flax could provide valuable basic information about this important gene family and help to explain the seed specific glycosylated metabolite accumulation and other processes in plants. Plant genome sequencing projects are useful to discover complexity within this gene family and also pave way for the development of functional genomics approaches. Taking advantage of the newly assembled draft genome sequence of flax, we identified 137 UDP glycosyltransferase (UGT) genes from flax using a conserved signature motif. Phylogenetic analysis of these protein sequences clustered them into 14 major groups (A-N). Expression patterns of these genes were investigated using publicly available expressed sequence tag (EST), microarray data and reverse transcription quantitative real time PCR (RT-qPCR). Seventy-three per cent of these genes (100 out of 137) showed expression evidence in 15 tissues examined and indicated varied expression profiles. The RT-qPCR results of 10 selected genes were also coherent with the digital expression analysis. Interestingly, five duplicated UGT genes were identified, which showed differential expression in various tissues. Of the seven intron loss/gain positions detected, two intron positions were conserved among most of the UGTs, although a clear relationship about the evolution of these genes could not be established. Comparison of the flax UGTs with orthologs from four other sequenced dicot genomes indicated that seven UGTs were flax diverged. Flax has a large number of UGT genes including few flax diverged ones. Phylogenetic analysis and expression profiles of these genes identified tissue and condition specific repertoire of UGT genes from this crop. This study would facilitate precise selection of candidate genes and their further characterization of substrate specificities and in planta functions.

Phylogenomic analysis of UDP glycosyltransferase 1 multigene family in Linum usitatissimum identified genes with varied expression patterns

PubMed Central

2012-01-01

Background The glycosylation process, catalyzed by ubiquitous glycosyltransferase (GT) family enzymes, is a prevalent modification of plant secondary metabolites that regulates various functions such as hormone homeostasis, detoxification of xenobiotics and biosynthesis and storage of secondary metabolites. Flax (Linum usitatissimum L.) is a commercially grown oilseed crop, important because of its essential fatty acids and health promoting lignans. Identification and characterization of UDP glycosyltransferase (UGT) genes from flax could provide valuable basic information about this important gene family and help to explain the seed specific glycosylated metabolite accumulation and other processes in plants. Plant genome sequencing projects are useful to discover complexity within this gene family and also pave way for the development of functional genomics approaches. Results Taking advantage of the newly assembled draft genome sequence of flax, we identified 137 UDP glycosyltransferase (UGT) genes from flax using a conserved signature motif. Phylogenetic analysis of these protein sequences clustered them into 14 major groups (A-N). Expression patterns of these genes were investigated using publicly available expressed sequence tag (EST), microarray data and reverse transcription quantitative real time PCR (RT-qPCR). Seventy-three per cent of these genes (100 out of 137) showed expression evidence in 15 tissues examined and indicated varied expression profiles. The RT-qPCR results of 10 selected genes were also coherent with the digital expression analysis. Interestingly, five duplicated UGT genes were identified, which showed differential expression in various tissues. Of the seven intron loss/gain positions detected, two intron positions were conserved among most of the UGTs, although a clear relationship about the evolution of these genes could not be established. Comparison of the flax UGTs with orthologs from four other sequenced dicot genomes indicated that seven UGTs were flax diverged. Conclusions Flax has a large number of UGT genes including few flax diverged ones. Phylogenetic analysis and expression profiles of these genes identified tissue and condition specific repertoire of UGT genes from this crop. This study would facilitate precise selection of candidate genes and their further characterization of substrate specificities and in planta functions. PMID:22568875