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Sample records for profiling uncovers plasmid-induced

  1. Investigation of plasmid-induced growth defect in Pseudomonas putida.

    PubMed

    Mi, Jia; Sydow, Anne; Schempp, Florence; Becher, Daniela; Schewe, Hendrik; Schrader, Jens; Buchhaupt, Markus

    2016-08-10

    Genetic engineering in bacteria mainly relies on the use of plasmids. But despite their pervasive use for physiological studies as well as for the design and optimization of industrially used production strains, only limited information about plasmid induced growth defects is available for different replicons and organisms. Here, we present the identification and characterization of such a phenomenon for Pseudomonas putida transformants carrying the pBBR1-derived plasmid pMiS1. We identified the kanamycin resistance gene and the transcription factor encoding rhaR gene to be causal for the growth defect in P. putida. In contrast, this effect was not observed in Escherichia coli. The plasmid-induced growth defect was eliminated after introduction of a mutation in the plasmid-encoded rep gene, thus enabling construction of the non-toxic variant pMiS4. GFP reporters construct analyses and qPCR experiments revealed a distinctly lowered plasmid copy number for pMiS4, which is probably the reason for alleviation of the growth defect by this mutation. Our work expands the knowledge about plasmid-induced growth defects and provides a useful low-copy pBBR1 replicon variant. PMID:27287537

  2. Developing Guidance Material To Uncover a Mathematics Profile of Adult Participants on a Crane Course.

    ERIC Educational Resources Information Center

    Lindenskov, Lena

    This paper reports on a pilot study in the Danish "Profile in Mathematics" project implemented by the Directorate General for Employment, Placement and Vocational Training and the Ministry of Education. The pilot study develops and tests specific guidance materials to guide participants and teachers through a course for crane workers that teaches…

  3. Comparative Epigenomic Profiling of the DNA Methylome in Mouse and Zebrafish Uncovers High Interspecies Divergence

    PubMed Central

    Zhang, Chi; Hoshida, Yujin; Sadler, Kirsten C.

    2016-01-01

    The DNA methylation landscape is dynamically patterned during development and distinct methylation patterns distinguish healthy from diseased cells. However, whether tissue-specific methylation patterns are conserved across species is not known. We used comparative methylome analysis of base-resolution DNA methylation profiles from the liver and brain of mouse and zebrafish generated by reduced representation bisulfite sequencing to identify the conserved and divergent aspects of the methylome in these commonly used vertebrate model organisms. On average, 24% of CpGs are methylated in mouse livers and the pattern of methylation was highly concordant among four male mice from two different strains. The same level of methylation (24.2%) was identified in mouse brain. In striking contrast, zebrafish had 63 and 70% of CpG methylation in the liver and brain, respectively. This is attributed, in part, to the higher percentage of the zebrafish genome occupied by transposable elements (52% vs. 45% in mice). Thus, the species identity was more significant in determining methylome patterning than was the similarity in organ function. Conserved features of the methylome across tissues and species was the exclusion of methylation from promoters and from CpG islands near transcription start sites, and the clustering of methylated CpGs in gene bodies and intragenic regions. These data suggest that DNA methylation reflects species-specific genome structure, and supports the notion that DNA methylation in non-promoter regions may contribute to genome evolution. PMID:27379160

  4. Early changes in gene expression profiles of hepatic GVHD uncovered by oligonucleotide microarrays.

    PubMed

    Ichiba, Tamotsu; Teshima, Takanori; Kuick, Rork; Misek, David E; Liu, Chen; Takada, Yuichiro; Maeda, Yoshinobu; Reddy, Pavan; Williams, Debra L; Hanash, Samir M; Ferrara, James L M

    2003-07-15

    The liver, skin, and gastrointestinal tract are major target organs of acute graft-versus-host disease (GVHD), the major complication of allogeneic bone marrow transplantation (BMT). In order to gain a better understanding of acute GVHD in the liver, we compared the gene expression profiles of livers after experimental allogeneic and syngeneic BMT using oligonucleotide microarray. At 35 days after allogeneic BMT when hepatic GVHD was histologically evident, genes related to cellular effectors and acute-phase proteins were up-regulated, whereas genes largely related to metabolism and endocrine function were down-regulated. At day 7 after BMT before the development of histologic changes in the liver, interferon gamma (IFN-gamma)-inducible genes, major histocompatibility (MHC) class II molecules, and genes related to leukocyte trafficking had been up-regulated. Immunohistochemistry demonstrated that expression of IFN-gamma protein itself was increased in the spleen but not in hepatic tissue. These results suggest that the increased expression of genes associated with the attraction and activation of donor T cells induced by IFN-gamma early after BMT is important in the initiation of hepatic GVHD in this model and provide new potential molecular targets for early detection and intervention of acute GVHD.

  5. Transcriptional Profiles Uncover Aspergillus flavus-Induced Resistance in Maize Kernels

    PubMed Central

    Luo, Meng; Brown, Robert L.; Chen, Zhi-Yuan; Menkir, Abebe; Yu, Jiujiang; Bhatnagar, Deepak

    2011-01-01

    Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and through storage. Previous studies have highlighted the constitutive production of proteins involved in maize kernel resistance against A. flavus’ infection. However, little is known about induced resistance nor about defense gene expression and regulation in kernels. In this study, maize oligonucleotide arrays and a pair of closely-related maize lines varying in aflatoxin accumulation were used to reveal the gene expression network in imbibed mature kernels in response to A. flavus’ challenge. Inoculated kernels were incubated 72 h via the laboratory-based Kernel Screening Assay (KSA), which highlights kernel responses to fungal challenge. Gene expression profiling detected 6955 genes in resistant and 6565 genes in susceptible controls; 214 genes induced in resistant and 2159 genes induced in susceptible inoculated kernels. Defense related and regulation related genes were identified in both treatments. Comparisons between the resistant and susceptible lines indicate differences in the gene expression network which may enhance our understanding of the maize-A. flavus interaction. PMID:22069739

  6. Transcriptional profiles uncover Aspergillus flavus-induced resistance in maize kernels.

    PubMed

    Luo, Meng; Brown, Robert L; Chen, Zhi-Yuan; Menkir, Abebe; Yu, Jiujiang; Bhatnagar, Deepak

    2011-07-01

    Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and through storage. Previous studies have highlighted the constitutive production of proteins involved in maize kernel resistance against A. flavus' infection. However, little is known about induced resistance nor about defense gene expression and regulation in kernels. In this study, maize oligonucleotide arrays and a pair of closely-related maize lines varying in aflatoxin accumulation were used to reveal the gene expression network in imbibed mature kernels in response to A. flavus' challenge. Inoculated kernels were incubated 72 h via the laboratory-based Kernel Screening Assay (KSA), which highlights kernel responses to fungal challenge. Gene expression profiling detected 6955 genes in resistant and 6565 genes in susceptible controls; 214 genes induced in resistant and 2159 genes induced in susceptible inoculated kernels. Defense related and regulation related genes were identified in both treatments. Comparisons between the resistant and susceptible lines indicate differences in the gene expression network which may enhance our understanding of the maize-A. flavus interaction. PMID:22069739

  7. Uncovering the profile of mutations of transforming growth factor beta-induced gene in Chinese corneal dystrophy patients

    PubMed Central

    Hao, Xiao-Dan; Zhang, Yang-Yang; Chen, Peng; Li, Su-Xia; Wang, Ye

    2016-01-01

    AIM To uncover the mutations profile of transforming growth factor beta-induced (TGFBI) gene in Chinese corneal dystrophy patients and further investigate the characteristics of genotype-phenotype correlations. METHODS Forty-two subjects (6 unrelated families including 15 patients and 8 unaffected members, and 19 sporadic patients) of Chinese origin were subjected to phenotypic and genotypic characterization. The corneal phenotypes of patients were documented by slit lamp photography. Mutation screening of the coding regions of TGFBI was performed by direct sequencing. RESULTS We detected four corneal dystrophy types. The most frequent phenotypes were granular corneal dystrophy (GCD) (including 3 families and 8 sporadic patients) and lattice corneal dystrophy (LCD) (including 2 families and 9 sporadic patients). The next phenotypes were corneal dystrophy of Bowman layer (CDB) (1 family and 1 sporadic patient) and epithelial basement membrane dystrophy (EBMD) (1 sporadic patient). Six distinct mutations responsible for TGFBI corneal dystrophies were identified in 30 individuals with corneal dystrophies. Those were, p.R124H mutation in 1 family and 2 sporadic patients with GCD, p.R555W mutation in 2 families and 3 sporadic patients with GCD, p.R124C mutation in 2 families and 7 sporadic patients with LCD, p.A620D mutation in 1 sporadic patient with LCD, p.H626R mutation in 1 sporadic patient with LCD, and p.R555Q in 1 family and 1 sporadic patient with CDB. No mutation was detected in the remaining 3 atypical GCD patients and 1 EBMD patient. CONCLUSION GCD and LCD are the most frequent phenotypes in Chinese population. R555W was the most common mutation for GCD; R124C was the most common mutation for LCD. Our findings extend the mutational spectrum of TFGBI, and this is the extensively delineated TGFBI mutation profile associated with the various corneal dystrophies in the Chinese population. PMID:26949635

  8. Inositol Pyrophosphate Profiling of Two HCT116 Cell Lines Uncovers Variation in InsP8 Levels

    PubMed Central

    Gu, Chunfang; Wilson, Miranda S. C.; Jessen, Henning J.; Saiardi, Adolfo; Shears, Stephen B.

    2016-01-01

    The HCT116 cell line, which has a pseudo-diploid karotype, is a popular model in the fields of cancer cell biology, intestinal immunity, and inflammation. In the current study, we describe two batches of diverged HCT116 cells, which we designate as HCT116NIH and HCT116UCL. Using both gel electrophoresis and HPLC, we show that HCT116UCL cells contain 6-fold higher levels of InsP8 than HCT116NIH cells. This observation is significant because InsP8 is one of a group of molecules collectively known as ‘inositol pyrophosphates’ (PP-InsPs)—highly ‘energetic’ and conserved regulators of cellular and organismal metabolism. Variability in the cellular levels of InsP8 within divergent HCT116 cell lines could have impacted the phenotypic data obtained in previous studies. This difference in InsP8 levels is more remarkable for being specific; levels of other inositol phosphates, and notably InsP6 and 5-InsP7, are very similar in both HCT116NIH and HCT116UCL lines. We also developed a new HPLC procedure to record 1-InsP7 levels directly (for the first time in any mammalian cell line); 1-InsP7 comprised <2% of total InsP7 in HCT116NIH and HCT116UCL lines. The elevated levels of InsP8 in the HCT116UCL lines were not due to an increase in expression of the PP-InsP kinases (IP6Ks and PPIP5Ks), nor to a decrease in the capacity to dephosphorylate InsP8. We discuss how the divergent PP-InsP profiles of the newly-designated HCT116NIH and HCT116UCL lines should be considered an important research opportunity: future studies using these two lines may uncover new features that regulate InsP8 turnover, and may also yield new directions for studying InsP8 function. PMID:27788189

  9. Analysis of microRNA and Gene Expression Profiles in Multiple Sclerosis: Integrating Interaction Data to Uncover Regulatory Mechanisms

    PubMed Central

    Freiesleben, Sherry; Hecker, Michael; Zettl, Uwe Klaus; Fuellen, Georg; Taher, Leila

    2016-01-01

    MicroRNAs (miRNAs) have been reported to contribute to the pathophysiology of multiple sclerosis (MS), an inflammatory disorder of the central nervous system. Here, we propose a new consensus-based strategy to analyse and integrate miRNA and gene expression data in MS as well as other publically available data to gain a deeper understanding of the role of miRNAs in MS and to overcome the challenges posed by studies with limited patient sample sizes. We processed and analysed microarray datasets, and compared the expression of genes and miRNAs in the blood of MS patients and controls. We then used our consensus and integration approach to construct two molecular networks dysregulated in MS: a miRNA- and a gene-based network. We identified 18 differentially expressed (DE) miRNAs and 128 DE genes that may contribute to the regulatory alterations behind MS. The miRNAs were linked to immunological and neurological pathways, and we exposed let-7b-5p and miR-345-5p as promising blood-derived disease biomarkers in MS. The results suggest that DE miRNAs are more informative than DE genes in uncovering pathways potentially involved in MS. Our findings provide novel insights into the regulatory mechanisms and networks underlying MS. PMID:27694855

  10. Gene expression profiling in hearts of diabetic mice uncovers a potential role of estrogen-related receptor γ in diabetic cardiomyopathy.

    PubMed

    Lasheras, Jaime; Vilà, Maria; Zamora, Mònica; Riu, Efrén; Pardo, Rosario; Poncelas, Marcos; Cases, Ildefonso; Ruiz-Meana, Marisol; Hernández, Cristina; Feliu, Juan E; Simó, Rafael; García-Dorado, David; Villena, Josep A

    2016-07-15

    Diabetic cardiomyopathy is characterized by an abnormal oxidative metabolism, but the underlying mechanisms remain to be defined. To uncover potential mechanisms involved in the pathophysiology of diabetic cardiomyopathy, we performed a gene expression profiling study in hearts of diabetic db/db mice. Diabetic hearts showed a gene expression pattern characterized by the up-regulation of genes involved in lipid oxidation, together with an abnormal expression of genes related to the cardiac contractile function. A screening for potential regulators of the genes differentially expressed in diabetic mice found that estrogen-related receptor γ (ERRγ) was increased in heart of db/db mice. Overexpression of ERRγ in cultured cardiomyocytes was sufficient to promote the expression of genes involved in lipid oxidation, increase palmitate oxidation and induce cardiomyocyte hypertrophy. Our findings strongly support a role for ERRγ in the metabolic alterations that underlie the development of diabetic cardiomyopathy. PMID:27062900

  11. Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

    PubMed Central

    Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

    2010-01-01

    Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation

  12. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    PubMed Central

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  13. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

    PubMed

    Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan

    2015-04-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  14. Metabolomic profiling in liver of adiponectin-knockout mice uncovers lysophospholipid metabolism as an important target of adiponectin action

    PubMed Central

    Liu, Ying; Sen, Sanjana; Wannaiampikul, Sivaporn; Palanivel, Rengasamy; Hoo, Ruby L. C.; Isserlin, Ruth; Bader, Gary D.; Tungtrongchitr, Rungsunn; Deshaies, Yves; Xu, Aimin; Sweeney, Gary

    2016-01-01

    Adiponectin mediates anti-diabetic effects via increasing hepatic insulin sensitivity and direct metabolic effects. In the present study, we conducted a comprehensive and unbiased metabolomic profiling of liver tissue from AdKO (adiponectin-knockout) mice, with and without adiponectin supplementation, fed on an HFD (high-fat diet) to derive insight into the mechanisms and consequences of insulin resistance. Hepatic lipid accumulation and insulin resistance induced by the HFD were reduced by adiponectin. The HFD significantly altered levels of 147 metabolites, and bioinformatic analysis indicated that one of the most striking changes was the profile of increased lysophospholipids. These changes were largely corrected by adiponectin, at least in part via direct regulation of PLA2 (phospholipase A2) as palmitate-induced PLA2 activation was attenuated by adiponectin in primary hepatocytes. Notable decreases in several glycerolipids after the HFD were reversed by adiponectin, which also corrected elevations in several diacyglycerol and ceramide species. Our data also indicate that stimulation of ω-oxidation of fatty acids by the HFD is enhanced by adiponectin. In conclusion, this metabolomic profiling approach in AdKO mice identified important targets of adiponectin action, including PLA2, to regulate lysophospholipid metabolism and ω-oxidation of fatty acids. PMID:25915851

  15. Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma.

    PubMed

    Iqbal, Javeed; Shen, Yulei; Huang, Xin; Liu, Yanyan; Wake, Laura; Liu, Cuiling; Deffenbacher, Karen; Lachel, Cynthia M; Wang, Chao; Rohr, Joseph; Guo, Shuangping; Smith, Lynette M; Wright, George; Bhagavathi, Sharathkumar; Dybkaer, Karen; Fu, Kai; Greiner, Timothy C; Vose, Julie M; Jaffe, Elaine; Rimsza, Lisa; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M; Cook, James R; Tubbs, Raymond R; Armitage, James O; Weisenburger, Dennis D; Staudt, Louis M; Gascoyne, Randy D; McKeithan, Timothy W; Chan, Wing C

    2015-02-12

    We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL. PMID:25498913

  16. Global microRNA expression profiling uncovers molecular markers for classification and prognosis in aggressive B-cell lymphoma

    PubMed Central

    Shen, Yulei; Huang, Xin; Liu, Yanyan; Wake, Laura; Liu, Cuiling; Deffenbacher, Karen; Lachel, Cynthia M.; Wang, Chao; Rohr, Joseph; Guo, Shuangping; Smith, Lynette M.; Wright, George; Bhagavathi, Sharathkumar; Dybkaer, Karen; Fu, Kai; Greiner, Timothy C.; Vose, Julie M.; Jaffe, Elaine; Rimsza, Lisa; Rosenwald, Andreas; Ott, German; Delabie, Jan; Campo, Elias; Braziel, Rita M.; Cook, James R.; Tubbs, Raymond R.; Armitage, James O.; Weisenburger, Dennis D.; Staudt, Louis M.; Gascoyne, Randy D.; McKeithan, Timothy W.; Chan, Wing C.

    2015-01-01

    We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naïve B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)–DLBCL compared with activated B-cell (ABC)–DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog (MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the “gold standard” GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL. PMID:25498913

  17. Resveratrol metabolite profiling in clinical nutrition research--from diet to uncovering disease risk biomarkers: epidemiological evidence.

    PubMed

    Rabassa, Montserrat; Zamora-Ros, Raul; Urpi-Sarda, Mireia; Andres-Lacueva, Cristina

    2015-08-01

    Resveratrol is a bioactive plant compound that has drawn scientific and media attention owing to its protective effects against a wide variety of illnesses, including cardiovascular diseases and cancer. In the last two decades, a plethora of preclinical studies have shown these beneficial effects, and some of them have been supported by clinical trials. However, there are few epidemiological studies assessing these relationships, showing mostly inconsistent results among them. This could be partially due to the difficulty of accurately estimating dietary resveratrol exposure. The development of Phenol-Explorer, a database containing resveratrol food-composition data, will facilitate the estimation of resveratrol intake. Moreover, the discovery and validation of a nutritional biomarker of this exposure, urinary resveratrol metabolite profile, will allow a more accurate assessment of dietary resveratrol exposure. Few epidemiological studies have assessed the potential health effects of resveratrol. Resveratrol was not associated with total mortality, cancer, or cardiovascular events, but it was associated with an improvement of serum glucose and triglyceride levels and a decrease in heart rate. Together, these findings suggest a potential cardioprotective effect of resveratrol in epidemiological studies, although the evidence is still scarce.

  18. Gene expression profiles uncover individual identities of gnathal neuroblasts and serial homologies in the embryonic CNS of Drosophila

    PubMed Central

    Urbach, Rolf; Jussen, David; Technau, Gerhard M.

    2016-01-01

    The numbers and types of progeny cells generated by neural stem cells in the developing CNS are adapted to its region-specific functional requirements. In Drosophila, segmental units of the CNS develop from well-defined patterns of neuroblasts. Here we constructed comprehensive neuroblast maps for the three gnathal head segments. Based on the spatiotemporal pattern of neuroblast formation and the expression profiles of 46 marker genes (41 transcription factors), each neuroblast can be uniquely identified. Compared with the thoracic ground state, neuroblast numbers are progressively reduced in labial, maxillary and mandibular segments due to smaller sizes of neuroectodermal anlagen and, partially, to suppression of neuroblast formation and induction of programmed cell death by the Hox gene Deformed. Neuroblast patterns are further influenced by segmental modifications in dorsoventral and proneural gene expression. With the previously published neuroblast maps and those presented here for the gnathal region, all neuroectodermal neuroblasts building the CNS of the fly (ventral nerve cord and brain, except optic lobes) are now individually identified (in total 2×567 neuroblasts). This allows, for the first time, a comparison of the characteristics of segmental populations of stem cells and to screen for serially homologous neuroblasts throughout the CNS. We show that approximately half of the deutocerebral and all of the tritocerebral (posterior brain) and gnathal neuroblasts, but none of the protocerebral (anterior brain) neuroblasts, display serial homology to neuroblasts in thoracic/abdominal neuromeres. Modifications in the molecular signature of serially homologous neuroblasts are likely to determine the segment-specific characteristics of their lineages. PMID:27095493

  19. Transcriptomic profiling of Yersinia pseudotuberculosis reveals reprogramming of the Crp regulon by temperature and uncovers Crp as a master regulator of small RNAs.

    PubMed

    Nuss, Aaron M; Heroven, Ann Kathrin; Waldmann, Barbara; Reinkensmeier, Jan; Jarek, Michael; Beckstette, Michael; Dersch, Petra

    2015-03-01

    One hallmark of pathogenic yersiniae is their ability to rapidly adjust their life-style and pathogenesis upon host entry. In order to capture the range, magnitude and complexity of the underlying gene control mechanisms we used comparative RNA-seq-based transcriptomic profiling of the enteric pathogen Y. pseudotuberculosis under environmental and infection-relevant conditions. We identified 1151 individual transcription start sites, multiple riboswitch-like RNA elements, and a global set of antisense RNAs and previously unrecognized trans-acting RNAs. Taking advantage of these data, we revealed a temperature-induced and growth phase-dependent reprogramming of a large set of catabolic/energy production genes and uncovered the existence of a thermo-regulated 'acetate switch', which appear to prime the bacteria for growth in the digestive tract. To elucidate the regulatory architecture linking nutritional status to virulence we also refined the CRP regulon. We identified a massive remodelling of the CRP-controlled network in response to temperature and discovered CRP as a transcriptional master regulator of numerous conserved and newly identified non-coding RNAs which participate in this process. This finding highlights a novel level of complexity of the regulatory network in which the concerted action of transcriptional regulators and multiple non-coding RNAs under control of CRP adjusts the control of Yersinia fitness and virulence to the requirements of their environmental and virulent life-styles.

  20. TMA Uncovers Medicare Mistakes.

    PubMed

    Sorrel, Amy Lynn

    2015-07-01

    The Texas Medical Association recently uncovered some major Medicare mistakes that show just why some physicians talk about leaving the federal program. Investigations and advocacy by TMA staff put Medicare on the path to a fix. PMID:26201065

  1. TMA Uncovers Medicare Mistakes.

    PubMed

    Sorrel, Amy Lynn

    2015-07-01

    The Texas Medical Association recently uncovered some major Medicare mistakes that show just why some physicians talk about leaving the federal program. Investigations and advocacy by TMA staff put Medicare on the path to a fix.

  2. Integrative Comparative Analyses of Transcript and Metabolite Profiles from Pepper and Tomato Ripening and Development Stages Uncovers Species-Specific Patterns of Network Regulatory Behavior[W][OA

    PubMed Central

    Osorio, Sonia; Alba, Rob; Nikoloski, Zoran; Kochevenko, Andrej; Fernie, Alisdair R.; Giovannoni, James J.

    2012-01-01

    Integrative comparative analyses of transcript and metabolite levels from climacteric and nonclimacteric fruits can be employed to unravel the similarities and differences of the underlying regulatory processes. To this end, we conducted combined gas chromatography-mass spectrometry and heterologous microarray hybridization assays in tomato (Solanum lycopersicum; climacteric) and pepper (Capsicum chilense; nonclimacteric) fruits across development and ripening. Computational methods from multivariate and network-based analyses successfully revealed the difference between the covariance structures of the integrated data sets. Moreover, our results suggest that both fruits have similar ethylene-mediated signaling components; however, their regulation is different and may reflect altered ethylene sensitivity or regulators other than ethylene in pepper. Genes involved in ethylene biosynthesis were not induced in pepper fruits. Nevertheless, genes downstream of ethylene perception such as cell wall metabolism genes, carotenoid biosynthesis genes, and the never-ripe receptor were clearly induced in pepper as in tomato fruit. While signaling sensitivity or actual signals may differ between climacteric and nonclimacteric fruit, the evidence described here suggests that activation of a common set of ripening genes influences metabolic traits. Also, a coordinate regulation of transcripts and the accumulation of key organic acids, including malate, citrate, dehydroascorbate, and threonate, in pepper fruit were observed. Therefore, the integrated analysis allows us to uncover additional information for the comprehensive understanding of biological events relevant to metabolic regulation during climacteric and nonclimacteric fruit development. PMID:22685169

  3. Uncovering the Math Curriculum

    ERIC Educational Resources Information Center

    Burns, Marilyn

    2014-01-01

    Teachers often express to Marulyn Burns their worry about the need to "cover the curriculum." In response, she draws on one of her favorite quotes: "You don't want to cover a subject; you want to uncover it." This quote is from "The Having of Wonderful Ideas and Other Essays on Teaching and Learning" by Eleanor…

  4. Non-targeted profiling of semi-polar metabolites in Arabidopsis root exudates uncovers a role for coumarin secretion and lignification during the local response to phosphate limitation

    PubMed Central

    Ziegler, Jörg; Schmidt, Stephan; Chutia, Ranju; Müller, Jens; Böttcher, Christoph; Strehmel, Nadine; Scheel, Dierk; Abel, Steffen

    2016-01-01

    Plants have evolved two major strategies to cope with phosphate (Pi) limitation. The systemic response, mainly comprising increased Pi uptake and metabolic adjustments for more efficient Pi use, and the local response, enabling plants to explore Pi-rich soil patches by reorganization of the root system architecture. Unlike previous reports, this study focused on root exudation controlled by the local response to Pi deficiency. To approach this, a hydroponic system separating the local and systemic responses was developed. Arabidopsis thaliana genotypes exhibiting distinct sensitivities to Pi deficiency could be clearly distinguished by their root exudate composition as determined by non-targeted reversed-phase ultraperformance liquid chromatography electrospray ionization quadrupole-time-of-flight mass spectrometry metabolite profiling. Compared with wild-type plants or insensitive low phosphate root 1 and 2 (lpr1 lpr2) double mutant plants, the hypersensitive phosphate deficiency response 2 (pdr2) mutant exhibited a reduced number of differential features in root exudates after Pi starvation, suggesting the involvement of PDR2-encoded P5-type ATPase in root exudation. Identification and analysis of coumarins revealed common and antagonistic regulatory pathways between Pi and Fe deficiency-induced coumarin secretion. The accumulation of oligolignols in root exudates after Pi deficiency was inversely correlated with Pi starvation-induced lignification at the root tips. The strongest oligolignol accumulation in root exudates was observed for the insensitive lpr1 lpr2 double mutant, which was accompanied by the absence of Pi deficiency-induced lignin deposition, suggesting a role of LPR ferroxidases in lignin polymerization during Pi starvation. PMID:26685189

  5. Uncovering Sexual Problems

    PubMed Central

    Cohen, May

    1977-01-01

    While patients frequently make it difficult for us to uncover their sexual concerns, a much greater difficulty is due to physicians' unwillingness to deal with this subject. Physicians need to acquire basic knowledge about human sexuality as well as skills in making patients feel comfortable and open. A non-judgmental attitude is essential. The physician will also be able to anticipate and prevent sexual distress by education. Expertise must be developed in differentiating those problems requiring referral for specialized sexual counselling from those which the family physician can handle. PMID:21304865

  6. Tensor GSVD of Patient- and Platform-Matched Tumor and Normal DNA Copy-Number Profiles Uncovers Chromosome Arm-Wide Patterns of Tumor-Exclusive Platform-Consistent Alterations Encoding for Cell Transformation and Predicting Ovarian Cancer Survival

    PubMed Central

    Sankaranarayanan, Preethi; Schomay, Theodore E.; Aiello, Katherine A.; Alter, Orly

    2015-01-01

    The number of large-scale high-dimensional datasets recording different aspects of a single disease is growing, accompanied by a need for frameworks that can create one coherent model from multiple tensors of matched columns, e.g., patients and platforms, but independent rows, e.g., probes. We define and prove the mathematical properties of a novel tensor generalized singular value decomposition (GSVD), which can simultaneously find the similarities and dissimilarities, i.e., patterns of varying relative significance, between any two such tensors. We demonstrate the tensor GSVD in comparative modeling of patient- and platform-matched but probe-independent ovarian serous cystadenocarcinoma (OV) tumor, mostly high-grade, and normal DNA copy-number profiles, across each chromosome arm, and combination of two arms, separately. The modeling uncovers previously unrecognized patterns of tumor-exclusive platform-consistent co-occurring copy-number alterations (CNAs). We find, first, and validate that each of the patterns across only 7p and Xq, and the combination of 6p+12p, is correlated with a patient’s prognosis, is independent of the tumor’s stage, the best predictor of OV survival to date, and together with stage makes a better predictor than stage alone. Second, these patterns include most known OV-associated CNAs that map to these chromosome arms, as well as several previously unreported, yet frequent focal CNAs. Third, differential mRNA, microRNA, and protein expression consistently map to the DNA CNAs. A coherent picture emerges for each pattern, suggesting roles for the CNAs in OV pathogenesis and personalized therapy. In 6p+12p, deletion of the p21-encoding CDKN1A and p38-encoding MAPK14 and amplification of RAD51AP1 and KRAS encode for human cell transformation, and are correlated with a cell’s immortality, and a patient’s shorter survival time. In 7p, RPA3 deletion and POLD2 amplification are correlated with DNA stability, and a longer survival. In Xq

  7. Uncovering Black Womanhood in Engineering

    ERIC Educational Resources Information Center

    Gibson, Sheree L.; Espino, Michelle M.

    2016-01-01

    Despite the growing research that outlines the experiences of Blacks and women undergraduates in engineering, little is known about Black women in this field. The purpose of this qualitative study was to uncover how eight Black undergraduate women in engineering understood their race and gender identities in a culture that can be oppressive to…

  8. Personalized Immunomonitoring Uncovers Molecular Networks that Stratify Lupus Patients.

    PubMed

    Banchereau, Romain; Hong, Seunghee; Cantarel, Brandi; Baldwin, Nicole; Baisch, Jeanine; Edens, Michelle; Cepika, Alma-Martina; Acs, Peter; Turner, Jacob; Anguiano, Esperanza; Vinod, Parvathi; Kahn, Shaheen; Obermoser, Gerlinde; Blankenship, Derek; Wakeland, Edward; Nassi, Lorien; Gotte, Alisa; Punaro, Marilynn; Liu, Yong-Jun; Banchereau, Jacques; Rossello-Urgell, Jose; Wright, Tracey; Pascual, Virginia

    2016-04-21

    Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases. PAPERCLIP. PMID:27040498

  9. Uncovering Beliefs about Learning: Multimethod, Multitrait Research.

    ERIC Educational Resources Information Center

    Muscella, Deborah

    The central theme of this paper is that multimethod, multitrait research is essential to uncover learning beliefs and learning structures. The year-long social-ecological study clearly illustrated the efficacy of such a research process. This was a study of the elements of a kindergarten classroom environment and the beliefs that parents,…

  10. Enhancer modeling uncovers transcriptional signatures of individual cardiac cell states in Drosophila

    PubMed Central

    Busser, Brian W.; Haimovich, Julian; Huang, Di; Ovcharenko, Ivan; Michelson, Alan M.

    2015-01-01

    Here we used discriminative training methods to uncover the chromatin, transcription factor (TF) binding and sequence features of enhancers underlying gene expression in individual cardiac cells. We used machine learning with TF motifs and ChIP data for a core set of cardiogenic TFs and histone modifications to classify Drosophila cell-type-specific cardiac enhancer activity. We show that the classifier models can be used to predict cardiac cell subtype cis-regulatory activities. Associating the predicted enhancers with an expression atlas of cardiac genes further uncovered clusters of genes with transcription and function limited to individual cardiac cell subtypes. Further, the cell-specific enhancer models revealed chromatin, TF binding and sequence features that distinguish enhancer activities in distinct subsets of heart cells. Collectively, our results show that computational modeling combined with empirical testing provides a powerful platform to uncover the enhancers, TF motifs and gene expression profiles which characterize individual cardiac cell fates. PMID:25609699

  11. Lead exposure at uncovered outdoor firing ranges

    SciTech Connect

    Goldberg, R.L.; Hicks, A.M.; O'Leary, L.M.; London, S. )

    1991-06-01

    Excessive lead exposure in shooting instructors at indoor firing ranges and covered outdoor firing ranges has been documented. The City of Los Angeles assessed exposure of its full-time shooting instructors at uncovered outdoor ranges via air monitoring and blood lead-level measurements. Results of these tests revealed that significant lead exposure and absorption can occur at outdoor firing ranges. The use of copper-jacketed ammunition may decrease air lead levels and decrease lead absorption by range instructors.

  12. A Teachable Moment Uncovered by Video Analysis

    NASA Astrophysics Data System (ADS)

    Gates, Joshua

    2011-05-01

    Early in their study of one-dimensional kinematics, my students build an algebraic model that describes the effects of a rolling ball's (perpendicular) collision with a wall. The goal is for the model to predict the ball's velocity when it returns to a fixed point approximately 50-100 cm from the wall as a function of its velocity as it passes this point initially. They are told to assume that the ball's velocity does not change while it rolls to or from the wall—that the velocity change all happens very quickly and only at the wall. In order to evaluate this assumption following the data collection, I have the students analyze one such collision using video analysis. The results uncover an excellent teachable moment about assumptions and their impact on models and error analysis.

  13. Uncovering the Architecture of Action Semantics

    PubMed Central

    Watson, Christine E.; Buxbaum, Laurel J.

    2014-01-01

    Despite research suggesting that stored sensorimotor information about tool use is a component of the semantic representations of tools, little is known about the action features or organizing principles that underlie this knowledge. We used methods similar to those applied in other semantic domains to examine the “architecture” of action semantic knowledge. In Experiment 1, participants sorted photographs of tools into groups according to the similarity of their associated “use” actions and rated tools on dimensions related to action. The results suggest that the magnitude of arm movement, configuration of the hand, and manner of motion during tool use play a role in determining how tools cluster in action “semantic space”. In Experiment 2, we validated the architecture uncovered in Experiment 1 using an implicit semantic task for which tool use knowledge was not ostensibly relevant (blocked cyclic word-picture matching). Using stimuli from Experiment 1, we found that participants performed more poorly during blocks of trials containing tools used with similar versus unrelated actions, and the amount of semantic interference depended on the magnitude of action similarity among tools. Thus, the degree of featural overlap between tool use actions plays a role in determining the overall semantic similarity of tools. PMID:25045905

  14. Uncovering the architecture of action semantics.

    PubMed

    Watson, Christine E; Buxbaum, Laurel J

    2014-10-01

    Despite research suggesting that stored sensorimotor information about tool use is a component of the semantic representations of tools, little is known about the action features or organizing principles that underlie this knowledge. We used methods similar to those applied in other semantic domains to examine the "architecture" of action semantic knowledge. In Experiment 1, participants sorted photographs of tools into groups according to the similarity of their associated "use" actions and rated tools on dimensions related to action. The results suggest that the magnitude of arm movement, configuration of the hand, and manner of motion during tool use play a role in determining how tools cluster in action "semantic space." In Experiment 2, we validated the architecture uncovered in Experiment 1 using an implicit semantic task for which tool use knowledge was not ostensibly relevant (blocked cyclic word-picture matching). Using stimuli from Experiment 1, we found that participants performed more poorly during blocks of trials containing tools used with similar versus unrelated actions, and the amount of semantic interference depended on the magnitude of action similarity among tools. Thus, the degree of featural overlap between tool use actions plays a role in determining the overall semantic similarity of tools.

  15. Uncovering Wolbachia Diversity upon Artificial Host Transfer

    PubMed Central

    Schneider, Daniela I.; Riegler, Markus; Arthofer, Wolfgang; Merçot, Hervé; Stauffer, Christian; Miller, Wolfgang J.

    2013-01-01

    The common endosymbiotic Wolbachia bacteria influence arthropod hosts in multiple ways. They are mostly recognized for their manipulations of host reproduction, yet, more recent studies demonstrate that Wolbachia also impact host behavior, metabolic pathways and immunity. Besides their biological and evolutionary roles, Wolbachia are new potential biological control agents for pest and vector management. Importantly, Wolbachia-based control strategies require controlled symbiont transfer between host species and predictable outcomes of novel Wolbachia-host associations. Theoretically, this artificial horizontal transfer could inflict genetic changes within transferred Wolbachia populations. This could be facilitated through de novo mutations in the novel recipient host or changes of haplotype frequencies of polymorphic Wolbachia populations when transferred from donor to recipient hosts. Here we show that Wolbachia resident in the European cherry fruit fly, Rhagoletis cerasi, exhibit ancestral and cryptic sequence polymorphism in three symbiont genes, which are exposed upon microinjection into the new hosts Drosophila simulans and Ceratitis capitata. Our analyses of Wolbachia in microinjected D. simulans over 150 generations after microinjection uncovered infections with multiple Wolbachia strains in trans-infected lines that had previously been typed as single infections. This confirms the persistence of low-titer Wolbachia strains in microinjection experiments that had previously escaped standard detection techniques. Our study demonstrates that infections by multiple Wolbachia strains can shift in prevalence after artificial host transfer driven by either stochastic or selective processes. Trans-infection of Wolbachia can claim fitness costs in new hosts and we speculate that these costs may have driven the shifts of Wolbachia strains that we saw in our model system. PMID:24376534

  16. 20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON ...

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

    20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON THE WEST SIDE WHERE F-1 ENGINE WAS TESTED. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

  17. Uncovering the nutritional landscape of food.

    PubMed

    Kim, Seunghyeon; Sung, Jaeyun; Foo, Mathias; Jin, Yong-Su; Kim, Pan-Jun

    2015-01-01

    Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food's frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition.

  18. η Carinae Baby Homunculus Uncovered by ALMA

    NASA Astrophysics Data System (ADS)

    Abraham, Zulema; Falceta-Gonçalves, Diego; Beaklini, Pedro P. B.

    2014-08-01

    We report observations of η Carinae obtained with ALMA in the continuum of 100, 230, 280, and 660 GHz in 2012 November, with a resolution that varied from 2.''88 to 0.''45 for the lower and higher frequencies, respectively. The source is not resolved, even at the highest frequency; its spectrum is characteristic of thermal bremsstrahlung of a compact source, but different from the spectrum of optically thin wind. The recombination lines H42α, He42α, H40α, He40α, H50β, H28α, He28α, H21α, and He21α were also detected, and their intensities reveal non-local thermodynamic equilibrium effects. We found that the line profiles could only be fit by an expanding shell of dense and ionized gas, which produces a slow shock in the surroundings of η Carinae. Combined with fittings to the continuum, we were able to constrain the shell size, radius, density, temperature, and velocity. The detection of the He recombination lines is compatible with the high-temperature gas and requires a high-energy ionizing photon flux, which must be provided by the companion star. The mass-loss rate and wind velocity, necessary to explain the formation of the shell, are compatible with an luminous blue variable eruption. The position, velocity, and physical parameters of the shell coincide with those of the Weigelt blobs. The dynamics found for the expanding shell correspond to matter ejected by η Carinae in 1941 in an event similar to that which formed the Little Homunculus; for that reason, we called the new ejecta the "Baby Homunculus."

  19. Uncovering the Nutritional Landscape of Food

    PubMed Central

    Kim, Seunghyeon; Sung, Jaeyun; Foo, Mathias; Jin, Yong-Su; Kim, Pan-Jun

    2015-01-01

    Recent progresses in data-driven analysis methods, including network-based approaches, are revolutionizing many classical disciplines. These techniques can also be applied to food and nutrition, which must be studied to design healthy diets. Using nutritional information from over 1,000 raw foods, we systematically evaluated the nutrient composition of each food in regards to satisfying daily nutritional requirements. The nutrient balance of a food was quantified and termed nutritional fitness; this measure was based on the food’s frequency of occurrence in nutritionally adequate food combinations. Nutritional fitness offers a way to prioritize recommendable foods within a global network of foods, in which foods are connected based on the similarities of their nutrient compositions. We identified a number of key nutrients, such as choline and α-linolenic acid, whose levels in foods can critically affect the nutritional fitness of the foods. Analogously, pairs of nutrients can have the same effect. In fact, two nutrients can synergistically affect the nutritional fitness, although the individual nutrients alone may not have an impact. This result, involving the tendency among nutrients to exhibit correlations in their abundances across foods, implies a hidden layer of complexity when exploring for foods whose balance of nutrients within pairs holistically helps meet nutritional requirements. Interestingly, foods with high nutritional fitness successfully maintain this nutrient balance. This effect expands our scope to a diverse repertoire of nutrient-nutrient correlations, which are integrated under a common network framework that yields unexpected yet coherent associations between nutrients. Our nutrient-profiling approach combined with a network-based analysis provides a more unbiased, global view of the relationships between foods and nutrients, and can be extended towards nutritional policies, food marketing, and personalized nutrition. PMID:25768022

  20. η Carinae Baby Homunculus uncovered by ALMA

    SciTech Connect

    Abraham, Zulema; Beaklini, Pedro P. B.; Falceta-Gonçalves, Diego

    2014-08-20

    We report observations of η Carinae obtained with ALMA in the continuum of 100, 230, 280, and 660 GHz in 2012 November, with a resolution that varied from 2.''88 to 0.''45 for the lower and higher frequencies, respectively. The source is not resolved, even at the highest frequency; its spectrum is characteristic of thermal bremsstrahlung of a compact source, but different from the spectrum of optically thin wind. The recombination lines H42α, He42α, H40α, He40α, H50β, H28α, He28α, H21α, and He21α were also detected, and their intensities reveal non-local thermodynamic equilibrium effects. We found that the line profiles could only be fit by an expanding shell of dense and ionized gas, which produces a slow shock in the surroundings of η Carinae. Combined with fittings to the continuum, we were able to constrain the shell size, radius, density, temperature, and velocity. The detection of the He recombination lines is compatible with the high-temperature gas and requires a high-energy ionizing photon flux, which must be provided by the companion star. The mass-loss rate and wind velocity, necessary to explain the formation of the shell, are compatible with an luminous blue variable eruption. The position, velocity, and physical parameters of the shell coincide with those of the Weigelt blobs. The dynamics found for the expanding shell correspond to matter ejected by η Carinae in 1941 in an event similar to that which formed the Little Homunculus; for that reason, we called the new ejecta the 'Baby Homunculus'.

  1. UNCOVERING THE NUCLEUS CANDIDATE FOR NGC 253

    SciTech Connect

    Günthardt, G. I.; Camperi, J. A.; Agüero, M. P.; Díaz, R. J.; Gomez, P. L.; Schirmer, M.; Bosch, G. E-mail: camperi@oac.uncor.edu E-mail: rdiaz@gemini.edu E-mail: mschirmer@gemini.edu

    2015-11-15

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H{sub 2} rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  2. Uncovering the Nucleus Candidate for NGC 253

    NASA Astrophysics Data System (ADS)

    Günthardt, G. I.; Agüero, M. P.; Camperi, J. A.; Díaz, R. J.; Gomez, P. L.; Bosch, G.; Schirmer, M.

    2015-11-01

    NGC 253 is the nearest spiral galaxy with a nuclear starburst that becomes the best candidate for studying the relationship between starburst and active galactic nucleus activity. However, this central region is veiled by large amounts of dust, and it has been so far unclear which is the true dynamical nucleus to the point that there is no strong evidence that the galaxy harbors a supermassive black hole co-evolving with the starburst as was supposed earlier. Near-infrared (NIR) spectroscopy, especially NIR emission line analysis, could be advantageous in shedding light on the true nucleus identity. Using Flamingos-2 at Gemini South we have taken deep K-band spectra along the major axis of the central structure and through the brightest infrared source. In this work, we present evidence showing that the brightest NIR and mid-infrared source in the central region, already known as radio source TH7 and so far considered just a large stellar supercluster, in fact presents various symptoms of a genuine galactic nucleus. Therefore, it should be considered a valid nucleus candidate. Mentioning some distinctive aspects, it is the most massive compact infrared object in the central region, located at 2.″0 of the symmetry center of the galactic bar, as measured in the K-band emission. Moreover, our data indicate that this object is surrounded by a large circumnuclear stellar disk and it is also located at the rotation center of the large molecular gas disk of NGC 253. Furthermore, a kinematic residual appears in the H2 rotation curve with a sinusoidal shape consistent with an outflow centered in the candidate nucleus position. The maximum outflow velocity is located about 14 pc from TH7, which is consistent with the radius of a shell detected around the nucleus candidate, observed at 18.3 μm (Qa) and 12.8 μm ([Ne ii]) with T-ReCS. Also, the Brγ emission line profile shows a pronounced blueshift and this emission line also has the highest equivalent width at this

  3. Weaving Social Foundations through Dance Pedagogy: A Pedagogy of Uncovering

    ERIC Educational Resources Information Center

    Barr, Sherrie; Risner, Doug

    2014-01-01

    Today's dance educators enter classrooms populated by increasingly diverse students in which teachers' pedagogical knowledge necessitates heightened understandings of race, ethnicity, social class, gender, and sexuality. Uncovering taken-for-granted assumptions, dominant stereotypes, and educational structures that reproduce social…

  4. Uncovering key data points to improve OR profitability.

    PubMed

    Stiefel, Robert A; Greenfield, Howard

    2014-03-01

    Using data analysis to target areas for performance improvement in the operating room (OR) involves: regularly monitoring key OR statistics, such as through use of a dashboard, determining the root causes of problems uncovered by the data analysis, making appropriate corrections and continuing to monitor performance.

  5. Malignant Gastroduodenal Obstruction: Treatment with Self-Expanding Uncovered Wallstent

    SciTech Connect

    Gutzeit, Andreas Binkert, Christoph A.; Schoch, Eric; Sautter, Thomas; Jost, Res; Zollikofer, Christoph L.

    2009-01-15

    Purpose: To retrospectively evaluate the clinical effectiveness of a self-expanding uncovered Wallstent in patients with malignant gastroduodenal obstruction. Materials and Methods: Under combined endoscopic and fluoroscopic guidance, 29 patients with a malignant gastroduodenal stenosis were treated with a self-expanding uncovered metallic Wallstent. A dysphagia score was assessed before and after the intervention to measure the success of this palliative therapy. The dysphagia score ranged between grade 0 to grade 4: grade 0 = able to tolerate solid food, grade 1 = able to tolerate soft food, grade 2 = able to tolerate thick liquids, grade 3 = able to tolerate water or clear fluids, and grade 4 = unable to tolerate anything perorally. Stent patency and patients survival rates were calculated. Results: The insertion of the gastroduodenal stent was technically successful in 28 patients (96.5%). After stenting, 25 patients (86.2%) showed clinical improvement by at least one score point. During follow-up, 22 (78.5%) of 28 patients showed no stent occlusion until death and did not have to undergo any further intervention. In six patients (20.6%), all of whom were treated with secondary stent insertions, occlusion with tumor ingrowth and/or overgrowth was observed after the intervention. The median period of primary stent patency in our study was 240 days. Conclusion: Placement of an uncovered Wallstent is clinically effective in patients with malignant gastroduodenal obstruction. Stent placement is associated with high technical success, good palliation effect, and high durability of stent function.

  6. 76 FR 17107 - Uncovered Innerspring Units From the People's Republic of China: Extension of Preliminary Results...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-28

    ... International Trade Administration Uncovered Innerspring Units From the People's Republic of China: Extension of... time limit for the preliminary results of the new shipper review of uncovered innerspring units... Uncovered Innerspring Units From the People's Republic of China: Initiation of Antidumping Duty New...

  7. High levels of cryptic species diversity uncovered in Amazonian frogs

    PubMed Central

    Funk, W. Chris; Caminer, Marcel; Ron, Santiago R.

    2012-01-01

    One of the greatest challenges for biodiversity conservation is the poor understanding of species diversity. Molecular methods have dramatically improved our ability to uncover cryptic species, but the magnitude of cryptic diversity remains unknown, particularly in diverse tropical regions such as the Amazon Basin. Uncovering cryptic diversity in amphibians is particularly pressing because amphibians are going extinct globally at an alarming rate. Here, we use an integrative analysis of two independent Amazonian frog clades, Engystomops toadlets and Hypsiboas treefrogs, to test whether species richness is underestimated and, if so, by how much. We sampled intensively in six countries with a focus in Ecuador (Engystomops: 252 individuals from 36 localities; Hypsiboas: 208 individuals from 65 localities) and combined mitochondrial DNA, nuclear DNA, morphological, and bioacoustic data to detect cryptic species. We found that in both clades, species richness was severely underestimated, with more undescribed species than described species. In Engystomops, the two currently recognized species are actually five to seven species (a 150–250% increase in species richness); in Hypsiboas, two recognized species represent six to nine species (a 200–350% increase). Our results suggest that Amazonian frog biodiversity is much more severely underestimated than previously thought. PMID:22130600

  8. Phylostratigraphic profiles in zebrafish uncover chordate origins of the vertebrate brain.

    PubMed

    Šestak, Martin Sebastijan; Domazet-Lošo, Tomislav

    2015-02-01

    An elaborated tripartite brain is considered one of the important innovations of vertebrates. Other extant chordate groups have a more basic brain organization. For instance, cephalochordates possess a relatively simple brain possibly homologous to the vertebrate forebrain and hindbrain, whereas tunicates display the tripartite organization, but without the specialized brain centers. The difference in anatomical complexity is even more pronounced if one compares chordates with other deuterostomes that have only a diffuse nerve net or alternatively a rather simple central nervous system. To gain a new perspective on the evolutionary roots of the complex vertebrate brain, we made here a phylostratigraphic analysis of gene expression patterns in the developing zebrafish (Danio rerio). The recovered adaptive landscape revealed three important periods in the evolutionary history of the zebrafish brain. The oldest period corresponds to preadaptive events in the first metazoans and the emergence of the nervous system at the metazoan-eumetazoan transition. The origin of chordates marks the next phase, where we found the overall strongest adaptive imprint in almost all analyzed brain regions. This finding supports the idea that the vertebrate brain evolved independently of the brains within the protostome lineage. Finally, at the origin of vertebrates we detected a pronounced signal coming from the dorsal telencephalon, in agreement with classical theories that consider this part of the cerebrum a genuine vertebrate innovation. Taken together, these results reveal a stepwise adaptive history of the vertebrate brain where most of its extant organization was already present in the chordate ancestor.

  9. Breakpoint analysis of transcriptional and genomic profiles uncovers novel gene fusions spanning multiple human cancer types.

    PubMed

    Giacomini, Craig P; Sun, Steven; Varma, Sushama; Shain, A Hunter; Giacomini, Marilyn M; Balagtas, Jay; Sweeney, Robert T; Lai, Everett; Del Vecchio, Catherine A; Forster, Andrew D; Clarke, Nicole; Montgomery, Kelli D; Zhu, Shirley; Wong, Albert J; van de Rijn, Matt; West, Robert B; Pollack, Jonathan R

    2013-04-01

    Gene fusions, like BCR/ABL1 in chronic myelogenous leukemia, have long been recognized in hematologic and mesenchymal malignancies. The recent finding of gene fusions in prostate and lung cancers has motivated the search for pathogenic gene fusions in other malignancies. Here, we developed a "breakpoint analysis" pipeline to discover candidate gene fusions by tell-tale transcript level or genomic DNA copy number transitions occurring within genes. Mining data from 974 diverse cancer samples, we identified 198 candidate fusions involving annotated cancer genes. From these, we validated and further characterized novel gene fusions involving ROS1 tyrosine kinase in angiosarcoma (CEP85L/ROS1), SLC1A2 glutamate transporter in colon cancer (APIP/SLC1A2), RAF1 kinase in pancreatic cancer (ATG7/RAF1) and anaplastic astrocytoma (BCL6/RAF1), EWSR1 in melanoma (EWSR1/CREM), CDK6 kinase in T-cell acute lymphoblastic leukemia (FAM133B/CDK6), and CLTC in breast cancer (CLTC/VMP1). Notably, while these fusions involved known cancer genes, all occurred with novel fusion partners and in previously unreported cancer types. Moreover, several constituted druggable targets (including kinases), with therapeutic implications for their respective malignancies. Lastly, breakpoint analysis identified new cell line models for known rearrangements, including EGFRvIII and FIP1L1/PDGFRA. Taken together, we provide a robust approach for gene fusion discovery, and our results highlight a more widespread role of fusion genes in cancer pathogenesis. PMID:23637631

  10. Transcriptional profiles uncover Aspergillus flavus-induced resistance in maize kernels

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aflatoxin contamination caused by the opportunistic pathogen A. flavus is a major concern in maize production prior to harvest and during storage, and also a concern in many other crops, such as peanuts, cottonseed, tree nuts, and rice. Although a number of resistant maize lines with low aflatoxin c...

  11. Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques.

    PubMed

    Shalhoub, Joseph; Viiri, Leena E; Cross, Amanda J; Gregan, Scott M; Allin, David M; Astola, Nagore; Franklin, Ian J; Davies, Alun H; Monaco, Claudia

    2016-05-01

    Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours. Supernatants were interrogated for 45 analytes using the Luminex 100 platform. Twenty-nine of the 45 analytes were reproducibly detectable in the majority of donors. The in vitro production of a specific network of mediators was found to be significantly higher in symptomatic than asymptomatic plaques, including: tumour necrosis factor α, interleukin (IL) 1β, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), CCL5, CCL20, CXCL9, matrix metalloproteinase (MMP)-3 and MMP-9. Ingenuity pathway analysis of differentially expressed analytes between symptomatic and asymptomatic patients identified a number of key biological pathways (p< 10(-25)). In conclusion, the carotid artery plaque culprit of ischaemic neurological symptoms is characterised by an inflammatory milieu favouring inflammatory cell recruitment and pro-inflammatory macrophage polarisation. PMID:26763091

  12. Multi-analyte profiling in human carotid atherosclerosis uncovers pro-inflammatory macrophage programming in plaques.

    PubMed

    Shalhoub, Joseph; Viiri, Leena E; Cross, Amanda J; Gregan, Scott M; Allin, David M; Astola, Nagore; Franklin, Ian J; Davies, Alun H; Monaco, Claudia

    2016-05-01

    Molecular characterisation of vulnerable atherosclerosis is necessary for targeting functional imaging and plaque-stabilising therapeutics. Inflammation has been linked to atherogenesis and the development of high-risk plaques. We set to quantify cytokine, chemokine and matrix metalloproteinase (MMP) protein production in cells derived from carotid plaques to map the inflammatory milieu responsible for instability. Carotid endarterectomies from carefully characterised symptomatic (n=35) and asymptomatic (n=32) patients were enzymatically dissociated producing mixed cell type atheroma cell suspensions which were cultured for 24 hours. Supernatants were interrogated for 45 analytes using the Luminex 100 platform. Twenty-nine of the 45 analytes were reproducibly detectable in the majority of donors. The in vitro production of a specific network of mediators was found to be significantly higher in symptomatic than asymptomatic plaques, including: tumour necrosis factor α, interleukin (IL) 1β, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), CCL5, CCL20, CXCL9, matrix metalloproteinase (MMP)-3 and MMP-9. Ingenuity pathway analysis of differentially expressed analytes between symptomatic and asymptomatic patients identified a number of key biological pathways (p< 10(-25)). In conclusion, the carotid artery plaque culprit of ischaemic neurological symptoms is characterised by an inflammatory milieu favouring inflammatory cell recruitment and pro-inflammatory macrophage polarisation.

  13. Uncovering Transcriptional Regulatory Networks by Sparse Bayesian Factor Model

    NASA Astrophysics Data System (ADS)

    Meng, Jia; Zhang, Jianqiu(Michelle); Qi, Yuan(Alan); Chen, Yidong; Huang, Yufei

    2010-12-01

    The problem of uncovering transcriptional regulation by transcription factors (TFs) based on microarray data is considered. A novel Bayesian sparse correlated rectified factor model (BSCRFM) is proposed that models the unknown TF protein level activity, the correlated regulations between TFs, and the sparse nature of TF-regulated genes. The model admits prior knowledge from existing database regarding TF-regulated target genes based on a sparse prior and through a developed Gibbs sampling algorithm, a context-specific transcriptional regulatory network specific to the experimental condition of the microarray data can be obtained. The proposed model and the Gibbs sampling algorithm were evaluated on the simulated systems, and results demonstrated the validity and effectiveness of the proposed approach. The proposed model was then applied to the breast cancer microarray data of patients with Estrogen Receptor positive ([InlineEquation not available: see fulltext.]) status and Estrogen Receptor negative ([InlineEquation not available: see fulltext.]) status, respectively.

  14. Computational biology approach to uncover hepatitis C virus helicase operation.

    PubMed

    Flechsig, Holger

    2014-04-01

    Hepatitis C virus (HCV) helicase is a molecular motor that splits nucleic acid duplex structures during viral replication, therefore representing a promising target for antiviral treatment. Hence, a detailed understanding of the mechanism by which it operates would facilitate the development of efficient drug-assisted therapies aiming to inhibit helicase activity. Despite extensive investigations performed in the past, a thorough understanding of the activity of this important protein was lacking since the underlying internal conformational motions could not be resolved. Here we review investigations that have been previously performed by us for HCV helicase. Using methods of structure-based computational modelling it became possible to follow entire operation cycles of this motor protein in structurally resolved simulations and uncover the mechanism by which it moves along the nucleic acid and accomplishes strand separation. We also discuss observations from that study in the light of recent experimental studies that confirm our findings.

  15. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

    PubMed Central

    Charlier, Caroline; Touchon, Marie; Chenal-Francisque, Viviane; Leclercq, Alexandre; Criscuolo, Alexis; Gaultier, Charlotte; Roussel, Sophie; Brisabois, Anne; Disson, Olivier; Rocha, Eduardo P. C.; Brisse, Sylvain; Lecuit, Marc

    2016-01-01

    Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking microbial intra-species virulence heterogeneity. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated with either food or human central nervous system (CNS) and maternal-neonatal (MN) listeriosis. The latter are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS and MN clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we uncovered multiple novel putative virulence factors and demonstrated experimentally the contribution of the first gene cluster mediating Listeria monocytogenes neural and placental tropisms. This study illustrates the exceptional power of harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes. PMID:26829754

  16. Computational biology approach to uncover hepatitis C virus helicase operation

    PubMed Central

    Flechsig, Holger

    2014-01-01

    Hepatitis C virus (HCV) helicase is a molecular motor that splits nucleic acid duplex structures during viral replication, therefore representing a promising target for antiviral treatment. Hence, a detailed understanding of the mechanism by which it operates would facilitate the development of efficient drug-assisted therapies aiming to inhibit helicase activity. Despite extensive investigations performed in the past, a thorough understanding of the activity of this important protein was lacking since the underlying internal conformational motions could not be resolved. Here we review investigations that have been previously performed by us for HCV helicase. Using methods of structure-based computational modelling it became possible to follow entire operation cycles of this motor protein in structurally resolved simulations and uncover the mechanism by which it moves along the nucleic acid and accomplishes strand separation. We also discuss observations from that study in the light of recent experimental studies that confirm our findings. PMID:24707123

  17. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis

    PubMed Central

    Rosenberg, Alan M.; Yeung, Rae S. M.; Morris, Quaid

    2016-01-01

    Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples. PMID:27244050

  18. Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis.

    PubMed

    Cui, Ang; Quon, Gerald; Rosenberg, Alan M; Yeung, Rae S M; Morris, Quaid

    2016-01-01

    Gene expression-based signatures help identify pathways relevant to diseases and treatments, but are challenging to construct when there is a diversity of disease mechanisms and treatments in patients with complex diseases. To overcome this challenge, we present a new application of an in silico gene expression deconvolution method, ISOpure-S1, and apply it to identify a common gene expression signature corresponding to response to treatment in 33 juvenile idiopathic arthritis (JIA) patients. Using pre- and post-treatment gene expression profiles only, we found a gene expression signature that significantly correlated with a reduction in the number of joints with active arthritis, a measure of clinical outcome (Spearman rho = 0.44, p = 0.040, Bonferroni correction). This signature may be associated with a decrease in T-cells, monocytes, neutrophils and platelets. The products of most differentially expressed genes include known biomarkers for JIA such as major histocompatibility complexes and interleukins, as well as novel biomarkers including α-defensins. This method is readily applicable to expression datasets of other complex diseases to uncover shared mechanistic patterns in heterogeneous samples. PMID:27244050

  19. 77 FR 12227 - Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ... contaminants in uncovered finished water reservoirs; and potential assessment approaches to determine the... AGENCY 40 CFR Parts 141 and 142 Long Term 2 Enhanced Surface Water Treatment Rule: Uncovered Finished Water Reservoirs; Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of...

  20. Uncovering disassortativity in large scale-free networks

    NASA Astrophysics Data System (ADS)

    Litvak, Nelly; van der Hofstad, Remco

    2013-02-01

    Mixing patterns in large self-organizing networks, such as the Internet, the World Wide Web, and social and biological networks, are often characterized by degree-degree dependencies between neighboring nodes. In this paper, we propose a new way of measuring degree-degree dependencies. One of the problems with the commonly used assortativity coefficient is that in disassortative networks its magnitude decreases with the network size. We mathematically explain this phenomenon and validate the results on synthetic graphs and real-world network data. As an alternative, we suggest to use rank correlation measures such as Spearman's ρ. Our experiments convincingly show that Spearman's ρ produces consistent values in graphs of different sizes but similar structure, and it is able to reveal strong (positive or negative) dependencies in large graphs. In particular, we discover much stronger negative degree-degree dependencies in Web graphs than was previously thought. Rank correlations allow us to compare the assortativity of networks of different sizes, which is impossible with the assortativity coefficient due to its genuine dependence on the network size. We conclude that rank correlations provide a suitable and informative method for uncovering network mixing patterns.

  1. Uncovering aberrant mutant PKA function with flow cytometric FRET

    PubMed Central

    Lee, Shin-Rong; Sang, Lingjie; Yue, David T.

    2016-01-01

    SUMMARY Biology has been revolutionized by tools that allow the detection and characterization of protein-protein interactions (PPI). Förster resonance energy transfer (FRET)-based methods have become particularly attractive as they allow quantitative studies of PPIs within the convenient and relevant context of living cells. We describe here an approach that allows the rapid construction of live-cell, FRET-based binding curves using a commercially-available flow cytometer. We illustrate a simple method for absolutely calibrating the cytometer, validate our binding assay against the gold-standard isothermal calorimetry (ITC), and use flow cytometric FRET to uncover the structural and functional effects of the Cushing syndrome-causing mutation (L206R) on PKA’s catalytic subunit. We discover that this mutation not only differentially affects PKAcat’s binding to its multiple partners, but also impacts its rate of catalysis. These findings improve our mechanistic understanding of this disease-causing mutation, while illustrating the simplicity, general applicability and power of flow cytometric FRET. PMID:26997269

  2. Charting the Vasculome: Uncovering the Principles of Vascular Organization

    NASA Astrophysics Data System (ADS)

    Oppenheim, Jacob; Magnasco, Marcelo

    2014-03-01

    The efficient distribution of resources in any system requires a carefully designed architecture that is both space filling and efficient. While the principles of such networks are beginning to be uncovered in plants, they remain poorly elucidated in the case of higher animals. We have developed a high-throughput, easily implemented method of mapping vascular networks in mammalian tissue. By combining high resolution, rapid fluorescence blockface imaging with serial sectioning, we are able to map the vasculature of the rat liver at a resolution of 10 microns, revealing the structure above the level of the capillaries, constituting the largest vascular dataset yet assembled. We have developed algorithms for the efficient three-dimensional reconstruction from two-dimensional images, allowing skeletonization and investigation of its geometry and topology. We are able to calculate the scaling properties of these networks as well as the frequency of loops at each level. Using sophisticated topological tools, we are beginning to elucidate the principles of their organization. Ultimately, a greater understanding of vasculature is necessary for the success of efforts in synthetic and regenerative biology along with the better understanding of the growth and development of cancers.

  3. Invisible Milky Way Satellite Uncovered With Help from NERSC

    SciTech Connect

    2011-01-01

    Astronomers predict that large spiral galaxies, like our Milky Way, have hundreds of satellite galaxies orbiting around them. While a few satellites are visible, like the Magellanic Clouds, many other galaxies are too dim to see. Scientists suspect that these faint satellite galaxies are primarily comprised of mysterious "dark matter," which makes up 85 percent of all matter in the universe and so far remains undetected. Using supercomputers at the National Energy Research Scientific Computing Center (NERSC), Sukanya Chakrabarti, an assistant professor of physics at Florida Atlantic University, developed a mathematical method to uncover these "dark" satellites. When she applied this method to our own Milky Way galaxy, Chakrabarti discovered a faint satellite might be lurking on the opposite side of the galaxy from Earth, approximately 300,000 light-years from the galactic center. According to Chakrabarti, the dark satellite galaxies create disturbances in the cold atomic hydrogen gas at the edges of the spiral galaxy's disk, and these perturbations reveal the mass, distance and location of the satellite. With the help of NERSC systems, she successfully validated her method by analyzing the radio observations of the Whirlpool Galaxy, which has a visible satellite one-third of its size, and NGC 1512, which has a satellite one-hundredth its size. Her calculations correctly predicted the mass and location of both of the known satellite galaxies. http://www.lbl.gov/cs/Archive/news031411.html

  4. Uncovering the mechanism(s) of deep brain stimulation

    NASA Astrophysics Data System (ADS)

    Gang, Li; Chao, Yu; Ling, Lin; C-Y Lu, Stephen

    2005-01-01

    Deep brain stimulators, often called `pacemakers for the brain', are implantable devices which continuously deliver impulse stimulation to specific targeted nuclei of deep brain structure, namely deep brain stimulation (DBS). To date, deep brain stimulation (DBS) is the most effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been put forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address our present knowledge of the effects of high-frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS.

  5. Uncovering Cryptic Parasitoid Diversity in Horismenus (Chalcidoidea, Eulophidae)

    PubMed Central

    Hansson, Christer; Alvarez, Nadir; Benrey, Betty

    2015-01-01

    Horismenus parasitoids are an abundant and understudied group of eulophid wasps found mainly in the New World. Recent surveys based on morphological analyses in Costa Rica have quadrupled the number of named taxa, with more than 400 species described so far. This recent revision suggests that there is still a vast number of unknown species to be identified. As Horismenus wasps have been widely described as parasitoids of insect pests associated with crop plants, it is of high importance to properly establish the extant diversity of the genus, in order to provide biological control practitioners with an exhaustive catalog of putative control agents. In this study, we first collected Horismenus wasps from wild Phaseolus bean seeds in Central Mexico and Arizona to assess the genetic relatedness of three morphologically distinct species with overlapping host and geographical ranges. Sequence data from two nuclear and two mitochondrial gene regions uncovered three cryptic species within each of the three focal species (i.e., H. missouriensis, H. depressus and H. butcheri). The monophyly of each cryptic group is statistically supported (except in two of them represented by one single tip in which monophyly cannot be tested). The phylogenetic reconstruction is discussed with respect to differences between gene regions as well as likely reasons for the differences in variability between species. PMID:26352700

  6. Uncovering Cryptic Parasitoid Diversity in Horismenus (Chalcidoidea, Eulophidae).

    PubMed

    Kenyon, Sarah G; Buerki, Sven; Hansson, Christer; Alvarez, Nadir; Benrey, Betty

    2015-01-01

    Horismenus parasitoids are an abundant and understudied group of eulophid wasps found mainly in the New World. Recent surveys based on morphological analyses in Costa Rica have quadrupled the number of named taxa, with more than 400 species described so far. This recent revision suggests that there is still a vast number of unknown species to be identified. As Horismenus wasps have been widely described as parasitoids of insect pests associated with crop plants, it is of high importance to properly establish the extant diversity of the genus, in order to provide biological control practitioners with an exhaustive catalog of putative control agents. In this study, we first collected Horismenus wasps from wild Phaseolus bean seeds in Central Mexico and Arizona to assess the genetic relatedness of three morphologically distinct species with overlapping host and geographical ranges. Sequence data from two nuclear and two mitochondrial gene regions uncovered three cryptic species within each of the three focal species (i.e., H. missouriensis, H. depressus and H. butcheri). The monophyly of each cryptic group is statistically supported (except in two of them represented by one single tip in which monophyly cannot be tested). The phylogenetic reconstruction is discussed with respect to differences between gene regions as well as likely reasons for the differences in variability between species. PMID:26352700

  7. Uncovering patterns of technology use in consumer health informatics.

    PubMed

    Hung, Man; Conrad, Jillian; Hon, Shirley D; Cheng, Christine; Franklin, Jeremy D; Tang, Philip

    2013-11-01

    Internet usage and accessibility has grown at a staggering rate, influencing technology use for healthcare purposes. The amount of health information technology (Health IT) available through the Internet is immeasurable and growing daily. Health IT is now seen as a fundamental aspect of patient care as it stimulates patient engagement and encourages personal health management. It is increasingly important to understand consumer health IT patterns including who is using specific technologies, how technologies are accessed, factors associated with use, and perceived benefits. To fully uncover consumer patterns it is imperative to recognize common barriers and which groups they disproportionately affect. Finally, exploring future demand and predictions will expose significant opportunities for health IT. The most frequently used health information technologies by consumers are gathering information online, mobile health (mHealth) technologies, and personal health records (PHRs). Gathering health information online is the favored pathway for healthcare consumers as it is used by more consumers and more frequently than any other technology. In regard to mHealth technologies, minority Americans, compared with White Americans utilize social media, mobile Internet, and mobile applications more frequently. Consumers believe PHRs are the most beneficial health IT. PHR usage is increasing rapidly due to PHR integration with provider health systems and health insurance plans. Key issues that have to be explicitly addressed in health IT are privacy and security concerns, health literacy, unawareness, and usability. Privacy and security concerns are rated the number one reason for the slow rate of health IT adoption.

  8. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms

    PubMed Central

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-01-01

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)—a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms. PMID:26194911

  9. Losartan ameliorates dystrophic epidermolysis bullosa and uncovers new disease mechanisms.

    PubMed

    Nyström, Alexander; Thriene, Kerstin; Mittapalli, Venugopal; Kern, Johannes S; Kiritsi, Dimitra; Dengjel, Jörn; Bruckner-Tuderman, Leena

    2015-07-20

    Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB)-a severe skin fragility disorder associated with lifelong blistering and disabling progressive soft tissue fibrosis. Causative therapies for this complex disorder face major hurdles, and clinical implementation remains elusive. Here, we report an alternative evidence-based approach to ameliorate fibrosis and relieve symptoms in RDEB. Based on the findings that TGF-β activity is elevated in injured RDEB skin, we targeted TGF-β activity with losartan in a preclinical setting. Long-term treatment of RDEB mice efficiently reduced TGF-β signaling in chronically injured forepaws and halted fibrosis and subsequent fusion of the digits. In addition, proteomics analysis of losartan- vs. vehicle-treated RDEB skin uncovered changes in multiple proteins related to tissue inflammation. In line with this, losartan reduced inflammation and diminished TNF-α and IL-6 expression in injured forepaws. Collectively, the data argue that RDEB fibrosis is a consequence of a cascade encompassing tissue damage, TGF-β-mediated inflammation, and matrix remodeling. Inhibition of TGF-β activity limits these unwanted outcomes and thereby substantially ameliorates long-term symptoms.

  10. Profiling of the cell surface proteome.

    PubMed

    Jang, Jun Ho; Hanash, Samir

    2003-10-01

    The in depth-mining of the proteome necessitates the comprehensive analysis of proteins in individual subcellular compartments to uncover interesting patterns of protein expression that include assessment of protein location, trafficking and of post-translational modifications that are location specific. One of the compartments of substantial interest from a diagnostic and therapeutic point of view is the plasma membrane which contains intrinsic membrane proteins and other proteins expressed on the cell surface. Technologies are currently available for the comprehensive profiling of the cell surface proteome that rely on protein tagging of intact cells. Studies are emerging that point to unexpected patterns of expression of specific proteins on the cell surface, with a common occurrence of proteins previously considered to occur predominantly in other compartments, notably the endoplasmic reticulum. The profiling of the cell surface and plasma membrane proteomes will likely provide novel insights and uncover disease related alterations. PMID:14625857

  11. Management of Complicated Aortic Aneurysms Using Multiple Overlapping Uncovered Stents

    PubMed Central

    Zhang, Yongxue; Teng, Zhongzhao; Lu, Qingsheng; Zhao, Zhiqing; Bao, Junmin; Feng, Xiang; Feng, Rui; Chen, Zengsheng; Huang, Yuan; Sadat, Umar; Gillard, Jonathan H; Jing, Zaiping

    2014-01-01

    Abstract This study sought to report the mid-term outcome of a modified flow-diverting strategy in the treatment of complicated aortic aneurysms of different morphology. Historical data suggested aortic aneurysm expansion and rupture after endovascular treatment with current commercial flow-diverters, indicating the essentiality of further investigation of this technique prior to its large-scale clinical application. An alternative flow-diverting strategy using layer-by-layer assembled multiple overlapping uncovered stents was employed in this study. The treatment outcome in aneurysms of different morphology (saccular, fusiform, and dissecting) was assessed during a mid-term follow-up period. Of 42 patients enrolled in this study (30 male, mean age: 63.3 years), technical success was achieved in 40 cases. During an average follow-up period of 20.9 months, mean aneurysm diameter shrunk from 53.4 ± 13.6 mm to 48.8 ± 13.9 mm (P < 0.001), while stent-induced sac thrombosis ratio increased significantly (18.1 ± 14.9% to 93.6 ± 9.5%, P < 0.001). The majority of side branches (74/76 major visceral branches, 237/244 minor segmental arteries), covered by 3.3 stents on average, maintained their patency after stenting. Saccular aneurysms manifested the highest thrombus deposition speed (18/20 were totally thrombosed within 12 months) and most significant shrinkage (51.4 ± 13.3 mm pre-operatively vs 43.5 ± 10.2 mm during follow-up, P < 0.001) compared with fusiform and dissecting aneurysms. This modified flow-diverting strategy could be a feasible alternative in the management of complicated aortic aneurysms where vital branches need to be preserved. The treatment outcome may depend on the aneurysm type. Further studies with larger patient cohort and longer follow-up are required to substantiate these results. PMID:25501077

  12. Uncovering oral Neisseria tropism and persistence using metagenomic sequencing.

    PubMed

    Donati, Claudio; Zolfo, Moreno; Albanese, Davide; Tin Truong, Duy; Asnicar, Francesco; Iebba, Valerio; Cavalieri, Duccio; Jousson, Olivier; De Filippo, Carlotta; Huttenhower, Curtis; Segata, Nicola

    2016-01-01

    Microbial epidemiology and population genomics have previously been carried out near-exclusively for organisms grown in vitro. Metagenomics helps to overcome this limitation, but it is still challenging to achieve strain-level characterization of microorganisms from culture-independent data with sufficient resolution for epidemiological modelling. Here, we have developed multiple complementary approaches that can be combined to profile and track individual microbial strains. To specifically profile highly recombinant neisseriae from oral metagenomes, we integrated four metagenomic analysis techniques: single nucleotide polymorphisms in the clade's core genome, DNA uptake sequence signatures, metagenomic multilocus sequence typing and strain-specific marker genes. We applied these tools to 520 oral metagenomes from the Human Microbiome Project, finding evidence of site tropism and temporal intra-subject strain retention. Although the opportunistic pathogen Neisseria meningitidis is enriched for colonization in the throat, N. flavescens and N. subflava populate the tongue dorsum, and N. sicca, N. mucosa and N. elongata the gingival plaque. The buccal mucosa appeared as an intermediate ecological niche between the plaque and the tongue. The resulting approaches to metagenomic strain profiling are generalizable and can be extended to other organisms and microbiomes across environments. PMID:27572971

  13. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced... water storage facilities. (a) Systems using uncovered finished water storage facilities must comply...

  14. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced... water storage facilities. (a) Systems using uncovered finished water storage facilities must comply...

  15. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced... water storage facilities. (a) Systems using uncovered finished water storage facilities must comply...

  16. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS Enhanced... water storage facilities. (a) Systems using uncovered finished water storage facilities must comply...

  17. Uncovering phenotypes of poor-pitch singing: the Sung Performance Battery (SPB).

    PubMed

    Berkowska, Magdalena; Dalla Bella, Simone

    2013-01-01

    Singing is as natural as speaking for humans. Increasing evidence shows that the layman can carry a tune (e.g., when asked to sing a well-known song or to imitate single pitches, intervals and short melodies). Yet, important individual differences exist in the general population with regard to singing proficiency. Some individuals are particularly inaccurate or imprecise in producing or imitating pitch information (poor-pitch singers), thus showing a variety of singing phenotypes. Unfortunately, so far there is not a standard set of tasks for assessing singing proficiency in the general population, allowing to uncover and characterize individual profiles of poor-pitch singing. Different tasks and analysis methods are typically used in various experiments, making the comparison of the results across studies arduous. To fill this gap we propose here a new tool for assessing singing proficiency (the Sung Performance Battery, SPB). The SPB starts from the assessment of participants' vocal range followed by five tasks: (1) single-pitch matching, (2) pitch-interval matching, (3) novel-melody matching, (4) singing from memory of familiar melodies (with lyrics and on a syllable), and (5) singing of familiar melodies (with lyrics and on a syllable) at a slow tempo indicated by a metronome. Data analysis via acoustical methods provides objective measures of pitch accuracy and precision in terms of absolute and relative pitch. The SPB has been tested in a group of 50 occasional singers. The results indicate that the battery is useful for characterizing proficient singing and for detecting cases of inaccurate and/or imprecise singing. PMID:24151475

  18. Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

    PubMed

    Loayza-Puch, Fabricio; Rooijers, Koos; Buil, Levi C M; Zijlstra, Jelle; Oude Vrielink, Joachim F; Lopes, Rui; Ugalde, Alejandro Pineiro; van Breugel, Pieter; Hofland, Ingrid; Wesseling, Jelle; van Tellingen, Olaf; Bex, Axel; Agami, Reuven

    2016-02-25

    Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is currently not available. Here we harness ribosome profiling for sensing restrictive amino acids, and develop diricore, a procedure for differential ribosome measurements of codon reading. We first demonstrate the functionality and constraints of diricore using metabolic inhibitors and nutrient deprivation assays. Notably, treatment with L-asparaginase elicited both specific diricore signals at asparagine codons and high levels of asparagine synthetase (ASNS). We then applied diricore to kidney cancer and discover signals indicating restrictive proline. As for asparagine, this observation was linked to high levels of PYCR1, a key enzyme in proline production, suggesting a compensatory mechanism allowing tumour expansion. Indeed, PYCR1 is induced by shortage of proline precursors, and its suppression attenuated kidney cancer cell proliferation when proline was limiting. High PYCR1 is frequently observed in invasive breast carcinoma. In an in vivo model system of this tumour, we also uncover signals indicating restrictive proline. We further show that CRISPR-mediated knockout of PYCR1 impedes tumorigenic growth in this system. Thus, diricore has the potential to reveal unknown amino acid deficiencies, vulnerabilities that can be used to target key metabolic pathways for cancer treatment. PMID:26878238

  19. Uncovering the Role of the Methylome in Dementia and Neurodegeneration.

    PubMed

    Klein, Hans-Ulrich; De Jager, Philip L

    2016-08-01

    Our understanding of the epigenome has advanced dramatically over the past decade, particularly in terms of DNA methylation, a modification found throughout the genome. Studies of the brain and neurons have outlined an increasingly complex architecture involving not just CG dinucleotide methylation but also methylation of other dinucleotides, and modifications of methylated bases such as 5-hydroxymethylcytosine. Different modifications may play an important role in brain development, function and decline; recent descriptions of the effects of aging and neurodegenerative processes such as Alzheimer disease on methylation profiles have ushered in an era of DNA methylome-wide association studies. Rapidly improving technologies and study designs are returning robust results, and investigations of the human brain's epigenome are increasingly feasible, complementing insights gained from genetic studies. PMID:27423266

  20. Deepest Image of Exploded Star Uncovers Bipolar Jets

    NASA Astrophysics Data System (ADS)

    2004-08-01

    A spectacular new image of Cassiopeia A from NASA's Chandra X-ray Observatory released today has nearly 200 times more data than the "First Light" Chandra image of this object made five years ago. The new image reveals clues that the initial explosion caused by the collapse of a massive star was far more complicated than suspected. Chandra Broadband Image of Cassiopeia A Chandra Broadband Image of Cassiopeia A "Although this young supernova remnant has been intensely studied for years, this deep observation is the most detailed ever made of the remains of an exploded star," said Martin Laming of the Naval Research Laboratory in Washington, D.C. Laming is part of a team of scientists led by Una Hwang of the Goddard Space Flight Center in Greenbelt, Maryland. "It is a gold mine of data that astronomers will be panning through for years to come." The one-million-second (about 11.5-day) observation of Cassiopeia A uncovered two large, opposed jet-like structures that extend to about 10 light years from the center of the remnant. Clouds of iron that have remained nearly pure for the approximately 340 years since the explosion were also detected. "The presence of the bipolar jets suggests that jets could be more common in relatively normal supernova explosions than supposed by astronomers," said Hwang. A paper by Hwang, Laming and others on the Cassiopeia A observation will appear in an upcoming issue of The Astrophysical Journal Letters. Chandra Enhanced Silicon Image of Cassiopeia A Chandra Enhanced Silicon Image of Cassiopeia A X-ray spectra show that the jets are rich in silicon atoms and relatively poor in iron atoms. In contrast, fingers of almost pure iron gas extend in a direction nearly perpendicular to the jets. This iron was produced in the central, hottest regions of the star. The high silicon and low iron abundances in the jets indicate that massive, matter-dominated jets were not the immediate cause of the explosion, as these should have carried out large

  1. New incompatibilities uncovered using the Promega DNA IQ™ chemistry.

    PubMed

    Laurin, Nancy; Célestin, Florence; Clark, Meagan; Wilkinson, Della; Yamashita, Brian; Frégeau, Chantal

    2015-12-01

    Over the years, the Promega DNA IQ™ System was proven an effective technology for the production of clean DNA from a wide variety of casework specimens. The capture of DNA using the DNA IQ™ paramagnetic beads, however, was shown to be affected by a few specific chemicals that could be present on exhibits submitted to the laboratory. In this study, various blood and latent fingerprint enhancement reagents/methods, marker pens and adhesive tapes, applied at the crime scene or in the forensic laboratory on casework exhibits or used to collect biological material, were tested for their compatibility with the DNA IQ™ technology. Although no impact on DNA recovery was observed for most reagents, the MAGNA™ Jet Black fingerprint powder and three 3M Scotch(®) adhesive tapes were shown to severely or completely inhibit DNA binding onto the DNA IQ™ beads. The effect of MAGNA™ Jet Black on DNA recovery could be counteracted by separating the magnetic powder from the lysates by centrifugation or filtration, prior to DNA extraction. High quality STR profiles were obtained from samples subjected to MAGNA™ Jet Black suggesting it does not impact DNA integrity.

  2. Towards uncovering the roles of switchgrass peroxidases in plant processes

    PubMed Central

    Saathoff, Aaron J.; Donze, Teresa; Palmer, Nathan A.; Bradshaw, Jeff; Heng-Moss, Tiffany; Twigg, Paul; Tobias, Christian M.; Lagrimini, Mark; Sarath, Gautam

    2013-01-01

    Herbaceous perennial plants selected as potential biofuel feedstocks had been understudied at the genomic and functional genomic levels. Recent investments, primarily by the U.S. Department of Energy, have led to the development of a number of molecular resources for bioenergy grasses, such as the partially annotated genome for switchgrass (Panicum virgatum L.), and some related diploid species. In its current version, the switchgrass genome contains 65,878 gene models arising from the A and B genomes of this tetraploid grass. The availability of these gene sequences provides a framework to exploit transcriptomic data obtained from next-generation sequencing platforms to address questions of biological importance. One such question pertains to discovery of genes and proteins important for biotic and abiotic stress responses, and how these components might affect biomass quality and stress response in plants engineered for a specific end purpose. It can be expected that production of switchgrass on marginal lands will expose plants to diverse stresses, including herbivory by insects. Class III plant peroxidases have been implicated in many developmental responses such as lignification and in the adaptive responses of plants to insect feeding. Here, we have analyzed the class III peroxidases encoded by the switchgrass genome, and have mined available transcriptomic datasets to develop a first understanding of the expression profiles of the class III peroxidases in different plant tissues. Lastly, we have identified switchgrass peroxidases that appear to be orthologs of enzymes shown to play key roles in lignification and plant defense responses to hemipterans. PMID:23802005

  3. Foraminiferal Mn/Ca: Uncovering its Paleoproxy Potential

    NASA Astrophysics Data System (ADS)

    de Baere, B. J.; Klinkhammer, G. P.; Mix, A. C.

    2007-12-01

    College of Oceanic and Atmospheric Sciences, Oregon State University, Ocean Admin Bldg 104, Corvallis, OR 97331, United States of America. The flow-through time-resolved analysis (FT-TRA) technique for foraminiferal proxy work allows for the quantification of pristine biogenic elemental data, such as Mn/Ca, whilst disregarding overgrowth-induced signals. We used this state-of-the-art technique to carry out a core-top survey of the Mn/Ca ratios for surface dwelling foraminifera from across the world's oceans. This study revealed an oceanographically consistent pattern featuring order of magnitude variability, exactly what one would expect from the distribution of dissolved Mn in the mixed layer. Foraminifera at southern hemisphere sites have the lowest Mn/Ca ratios (~ 0.01) while those from the northern hemisphere are distinctly higher (~ 0.2). This pattern is strikingly similar in distribution and scale to variations in the atmospheric iron flux suggesting that foraminiferal Mn/Ca has potential as a paleoproxy for terrestrial input and productivity. The dust-dominated pattern at the surface together with the unique profile of Mn in the water column makes the Mn/Ca ratio of foraminiferal calcite a powerful new paleoproxy.

  4. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations.

    PubMed

    Pugh, Trevor J; Weeraratne, Shyamal Dilhan; Archer, Tenley C; Pomeranz Krummel, Daniel A; Auclair, Daniel; Bochicchio, James; Carneiro, Mauricio O; Carter, Scott L; Cibulskis, Kristian; Erlich, Rachel L; Greulich, Heidi; Lawrence, Michael S; Lennon, Niall J; McKenna, Aaron; Meldrim, James; Ramos, Alex H; Ross, Michael G; Russ, Carsten; Shefler, Erica; Sivachenko, Andrey; Sogoloff, Brian; Stojanov, Petar; Tamayo, Pablo; Mesirov, Jill P; Amani, Vladimir; Teider, Natalia; Sengupta, Soma; Francois, Jessica Pierre; Northcott, Paul A; Taylor, Michael D; Yu, Furong; Crabtree, Gerald R; Kautzman, Amanda G; Gabriel, Stacey B; Getz, Gad; Jäger, Natalie; Jones, David T W; Lichter, Peter; Pfister, Stefan M; Roberts, Thomas M; Meyerson, Matthew; Pomeroy, Scott L; Cho, Yoon-Jae

    2012-08-01

    Medulloblastomas are the most common malignant brain tumours in children. Identifying and understanding the genetic events that drive these tumours is critical for the development of more effective diagnostic, prognostic and therapeutic strategies. Recently, our group and others described distinct molecular subtypes of medulloblastoma on the basis of transcriptional and copy number profiles. Here we use whole-exome hybrid capture and deep sequencing to identify somatic mutations across the coding regions of 92 primary medulloblastoma/normal pairs. Overall, medulloblastomas have low mutation rates consistent with other paediatric tumours, with a median of 0.35 non-silent mutations per megabase. We identified twelve genes mutated at statistically significant frequencies, including previously known mutated genes in medulloblastoma such as CTNNB1, PTCH1, MLL2, SMARCA4 and TP53. Recurrent somatic mutations were newly identified in an RNA helicase gene, DDX3X, often concurrent with CTNNB1 mutations, and in the nuclear co-repressor (N-CoR) complex genes GPS2, BCOR and LDB1. We show that mutant DDX3X potentiates transactivation of a TCF promoter and enhances cell viability in combination with mutant, but not wild-type, β-catenin. Together, our study reveals the alteration of WNT, hedgehog, histone methyltransferase and now N-CoR pathways across medulloblastomas and within specific subtypes of this disease, and nominates the RNA helicase DDX3X as a component of pathogenic β-catenin signalling in medulloblastoma. PMID:22820256

  5. New incompatibilities uncovered using the Promega DNA IQ™ chemistry.

    PubMed

    Laurin, Nancy; Célestin, Florence; Clark, Meagan; Wilkinson, Della; Yamashita, Brian; Frégeau, Chantal

    2015-12-01

    Over the years, the Promega DNA IQ™ System was proven an effective technology for the production of clean DNA from a wide variety of casework specimens. The capture of DNA using the DNA IQ™ paramagnetic beads, however, was shown to be affected by a few specific chemicals that could be present on exhibits submitted to the laboratory. In this study, various blood and latent fingerprint enhancement reagents/methods, marker pens and adhesive tapes, applied at the crime scene or in the forensic laboratory on casework exhibits or used to collect biological material, were tested for their compatibility with the DNA IQ™ technology. Although no impact on DNA recovery was observed for most reagents, the MAGNA™ Jet Black fingerprint powder and three 3M Scotch(®) adhesive tapes were shown to severely or completely inhibit DNA binding onto the DNA IQ™ beads. The effect of MAGNA™ Jet Black on DNA recovery could be counteracted by separating the magnetic powder from the lysates by centrifugation or filtration, prior to DNA extraction. High quality STR profiles were obtained from samples subjected to MAGNA™ Jet Black suggesting it does not impact DNA integrity. PMID:26295931

  6. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity

    PubMed Central

    Alsamarah, Abdelaziz; LaCuran, Alecander E.; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  7. Uncovering the historic environmental hazards of urban brownfields.

    PubMed

    Litt, Jill S; Burke, Thomas A

    2002-12-01

    In Baltimore, over 1,000 vacant industrial sites persist across its urban landscape, yet little is known about the potential environmental health risks that may undermine future cleanup and redevelopment activities and the health of those in communities near these sites. This study examined the characteristics of urban brownfield properties in southeast Baltimore, Maryland, and screened sites for their potential environmental hazards. In addition, demographic and health data were evaluated to profile the social and health status of those in brownfield communities. The results show that brownfields in southeast Baltimore represent a range of historic operations, including metal smelting, oil refining, warehousing, and transportation, as well as paints, plastics, and metals manufacturing. The screening method identified a range of substances associated with these properties, including heavy metals, chlorinated hydrocarbons, and polycyclic aromatic hydrocarbons, all of which are suspected or recognized toxicants, and many of which are persistent in the environment. Spatially, these sites are concentrated in white, working class neighborhoods in which poverty levels exceed and educational attainment lags behind state and national averages. Moreover, these sites are concentrated in communities in which excess mortality rates due to respiratory disease, cancer, and heart disease exist when compared to the city, state, and national averages. This investigation demonstrated the usefulness of historic archives, real estate records, regulatory files, and national hazard-tracking systems based on standard industrial classification (SIC) to screen brownfield properties for their hazard potential. This analysis provides the foundation for further site monitoring and testing, cleanup and redevelopment priority setting, risk management strategies, and neighborhood planning, and it illustrates the need for increased health surveillance and disease prevention strategies in affected

  8. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity.

    PubMed

    Alsamarah, Abdelaziz; LaCuran, Alecander E; Oelschlaeger, Peter; Hao, Jijun; Luo, Yun

    2015-01-01

    Abnormal alteration of bone morphogenetic protein (BMP) signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI) to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2) tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD) simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5) or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2), as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189) will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling. PMID:26133550

  9. Uncovering Influence through Social Network Analysis: The Role of Schools in Education for Sustainable Development

    ERIC Educational Resources Information Center

    Kolleck, Nina

    2016-01-01

    This paper examines the implementation of Education for Sustainable Development (ESD) in Germany and explores the possibilities of Social Network Analysis (SNA) for uncovering influential actors in educational policy innovation processes. From the theoretical perspective, an actor's influence is inferred from its relative position within…

  10. Uncovering the Motivating Factors behind Writing in English in en EFL Context

    ERIC Educational Resources Information Center

    Büyükyavuz, Oya; Çakir, Ismail

    2014-01-01

    Writing in a language, whether the target or native, is regarded as a complex activity operating on multiple cognitive levels. This study aimed to uncover the factors which motivate teacher trainees of English to write in English in an EFL context. The study also investigated the differences in the ways teacher trainees are motivated in terms of…

  11. Using Sociolinguistic Methods to Uncover Speaker Meaning in Teacher Interview Transcripts

    ERIC Educational Resources Information Center

    Olsen, Brad

    2006-01-01

    Given the current popularity of ethnographic methods of researching teaching and teachers, many investigators commonly confront the task of analyzing interview transcripts in order to uncover speakers' meaning systems and the embedded perspectives on knowledge and practice upon which those meaning systems rely. Others have written about conducting…

  12. Feminist Approaches to Triangulation: Uncovering Subjugated Knowledge and Fostering Social Change in Mixed Methods Research

    ERIC Educational Resources Information Center

    Hesse-Biber, Sharlene

    2012-01-01

    This article explores the deployment of triangulation in the service of uncovering subjugated knowledge and promoting social change for women and other oppressed groups. Feminist approaches to mixed methods praxis create a tight link between the research problem and the research design. An analysis of selected case studies of feminist praxis…

  13. Uncovering Pre-Service Teacher Beliefs about Young Children: A Photographic Elicitation Methodology

    ERIC Educational Resources Information Center

    Stockall, Nancy; Davis, Sara

    2011-01-01

    This illustrative paper provides an introduction to using mixed qualitative methods of photo-elicitation, face to face interviews and semiotic analysis to uncover pre-service students' beliefs about young children. The researchers share their experience on conducting a study using photo-elicitation and engaging pre-service teachers in a discussion…

  14. 40 CFR 141.714 - Requirements for uncovered finished water storage facilities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... must cover any uncovered finished water storage facility. (2) Systems must treat the discharge from the... water storage facilities. 141.714 Section 141.714 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS...

  15. Community Mapping in Action: Uncovering Resources and Assets for Young Children and Their Families

    ERIC Educational Resources Information Center

    Ordonez-Jasis, Rosario; Myck-Wayne, Janice

    2012-01-01

    Community mapping is a promising practice that can assist early intervention/early childhood special education (EI/ECSE) professionals uncover the depth and diversity of community needs, resources, and learning opportunities, in the neighborhoods surrounding their schools. Community mapping is an inquiry-based method that situates learning in the…

  16. A Phenomenological Approach to Uncovering the Essence of Grieving Experiences of Undergraduates

    ERIC Educational Resources Information Center

    Bergene, Lisa Beth

    2013-01-01

    Past studies have suggested that during their time on campus, as many as half of all undergraduates will experience the death of a loved one (Balk, 2001; Balk, Walker, & Baker, 2010; Holland & Neimeyer, 2010). The purpose of this study was to use a phenomenological method to uncover a thick, rich description of the lived experience of…

  17. Uncovering One Trilingual Child's Multi-Literacies Development across Informal and Formal Learning Contexts

    ERIC Educational Resources Information Center

    Kim, Mi Song

    2016-01-01

    Due to globalisation and rapid technological change, today's educators need to help students develop multi-literacy competencies to enable them to function successfully in our culturally and linguistically diverse (CLD) and increasingly connected global and digital society. A qualitative, longitudinal case study attempted to uncover the…

  18. Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice1[OPEN

    PubMed Central

    Obertello, Mariana; Shrivastava, Stuti; Katari, Manpreet S.; Coruzzi, Gloria M.

    2015-01-01

    In this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana) to a crop, rice (Oryza sativa), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants. To uncover such conserved N-regulatory network modules, we first generated an N-regulatory network based solely on rice transcriptome and gene interaction data. Next, we enhanced the network knowledge in the rice N-regulatory network using transcriptome and gene interaction data from Arabidopsis and new data from Arabidopsis and rice plants exposed to the same N treatment conditions. This cross-species network analysis uncovered a set of N-regulated transcription factors (TFs) predicted to target the same genes and network modules in both species. Supernode analysis of the TFs and their targets in these conserved network modules uncovered genes directly related to N use (e.g. N assimilation) and to other shared biological processes indirectly related to N. This cross-species network approach was validated with members of two TF families in the supernode network, BASIC-LEUCINE ZIPPER TRANSCRIPTION FACTOR1-TGA and HYPERSENSITIVITY TO LOW PI-ELICITED PRIMARY ROOT SHORTENING1 (HRS1)/HRS1 Homolog family, which have recently been experimentally validated to mediate the N response in Arabidopsis. PMID:26045464

  19. Using Text Mining to Uncover Students' Technology-Related Problems in Live Video Streaming

    ERIC Educational Resources Information Center

    Abdous, M'hammed; He, Wu

    2011-01-01

    Because of their capacity to sift through large amounts of data, text mining and data mining are enabling higher education institutions to reveal valuable patterns in students' learning behaviours without having to resort to traditional survey methods. In an effort to uncover live video streaming (LVS) students' technology related-problems and to…

  20. 76 FR 80337 - Uncovered Innerspring Units From the People's Republic of China: Rescission of Antidumping Duty...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ..., 366 F. Supp. 2d 1246, 1250 (CIT 2005); and Hebei New Donghua Amino Acid Co. v. United States, 374 F... Republic of China: Preliminary Intent to Rescind New Shipper Review, 76 FR 47151 (August 4, 2011... Antidumping Duty New Shipper Review, 76 FR 65695 (October 24, 2011); Uncovered Innerspring Units from...

  1. Thymus cDNA library survey uncovers novel features of immune molecules in Chinese giant salamander Andrias davidianus.

    PubMed

    Zhu, Rong; Chen, Zhong-Yuan; Wang, Jun; Yuan, Jiang-Di; Liao, Xiang-Yong; Gui, Jian-Fang; Zhang, Qi-Ya

    2014-10-01

    A ranavirus-induced thymus cDNA library was constructed from Chinese giant salamander, the largest extant amphibian species. Among the 137 putative immune-related genes derived from this library, these molecules received particular focus: immunoglobulin heavy chains (IgM, IgD, and IgY), IFN-inducible protein 6 (IFI6), and T cell receptor beta chain (TCRβ). Several unusual features were uncovered: IgD displays a structure pattern distinct from those described for other amphibians by having only four constant domains plus a hinge region. A unique IgY form (IgY(ΔFc)), previously undescribed in amphibians, is present in serum. Alternative splicing is observed to generate IgH diversification. IFI6 is newly-identified in amphibians, which occurs in two forms divergent in subcelluar distribution and antiviral activity. TCRβ immunoscope profile follows the typical vertebrate pattern, implying a polyclonal T cell repertoire. Collectively, the pioneering survey of ranavirus-induced thymus cDNA library from Chinese giant salamander reveals immune components and characteristics in this primitive amphibian.

  2. 78 FR 65711 - Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year Reviews

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... orders on imports of uncovered innerspring units from South Africa and Vietnam (73 FR 75390 and 75391... COMMISSION Uncovered Innerspring Units From China, South Africa, and Vietnam Institution of Five-Year Reviews... innerspring units from China, South Africa, and Vietnam would be likely to lead to continuation or...

  3. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion.

    PubMed

    Bibo-Verdugo, Betsaida; O'Donoghue, Anthony J; Rojo-Arreola, Liliana; Craik, Charles S; García-Carreño, Fernando

    2016-04-01

    Crustaceans are a diverse group, distributed in widely variable environmental conditions for which they show an equally extensive range of biochemical adaptations. Some digestive enzymes have been studied by purification/characterization approaches. However, global analysis is crucial to understand how digestive enzymes interplay. Here, we present the first proteomic analysis of the digestive fluid from a crustacean (Homarus americanus) and identify glycosidases and peptidases as the most abundant classes of hydrolytic enzymes. The digestion pathway of complex carbohydrates was predicted by comparing the lobster enzymes to similar enzymes from other crustaceans. A novel and unbiased substrate profiling approach was used to uncover the global proteolytic specificity of gastric juice and determine the contribution of cysteine and aspartic acid peptidases. These enzymes were separated by gel electrophoresis and their individual substrate specificities uncovered from the resulting gel bands. This new technique is called zymoMSP. Each cysteine peptidase cleaves a set of unique peptide bonds and the S2 pocket determines their substrate specificity. Finally, affinity chromatography was used to enrich for a digestive cathepsin D1 to compare its substrate specificity and cold-adapted enzymatic properties to mammalian enzymes. We conclude that the H. americanus digestive peptidases may have useful therapeutic applications, due to their cold-adaptation properties and ability to hydrolyze collagen.

  4. Complementary Proteomic and Biochemical Analysis of Peptidases in Lobster Gastric Juice Uncovers the Functional Role of Individual Enzymes in Food Digestion.

    PubMed

    Bibo-Verdugo, Betsaida; O'Donoghue, Anthony J; Rojo-Arreola, Liliana; Craik, Charles S; García-Carreño, Fernando

    2016-04-01

    Crustaceans are a diverse group, distributed in widely variable environmental conditions for which they show an equally extensive range of biochemical adaptations. Some digestive enzymes have been studied by purification/characterization approaches. However, global analysis is crucial to understand how digestive enzymes interplay. Here, we present the first proteomic analysis of the digestive fluid from a crustacean (Homarus americanus) and identify glycosidases and peptidases as the most abundant classes of hydrolytic enzymes. The digestion pathway of complex carbohydrates was predicted by comparing the lobster enzymes to similar enzymes from other crustaceans. A novel and unbiased substrate profiling approach was used to uncover the global proteolytic specificity of gastric juice and determine the contribution of cysteine and aspartic acid peptidases. These enzymes were separated by gel electrophoresis and their individual substrate specificities uncovered from the resulting gel bands. This new technique is called zymoMSP. Each cysteine peptidase cleaves a set of unique peptide bonds and the S2 pocket determines their substrate specificity. Finally, affinity chromatography was used to enrich for a digestive cathepsin D1 to compare its substrate specificity and cold-adapted enzymatic properties to mammalian enzymes. We conclude that the H. americanus digestive peptidases may have useful therapeutic applications, due to their cold-adaptation properties and ability to hydrolyze collagen. PMID:26613762

  5. Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

    SciTech Connect

    Bradford, Blair U.; O'Connell, Thomas M.; Han, Jun; Kosyk, Oksana; Shymonyak, Svitlana; Ross, Pamela K.; Winnike, Jason; Kono, Hiroshi; Rusyn, Ivan

    2008-10-15

    Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption.

  6. Development stage-specific proteomic profiling uncovers small, lineage specific proteins most abundant in the Aspergillus Fumigatus conidial proteome

    PubMed Central

    2012-01-01

    Background The pathogenic mold Aspergillus fumigatus is the most frequent infectious cause of death in severely immunocompromised individuals such as leukemia and bone marrow transplant patients. Germination of inhaled conidia (asexual spores) in the host is critical for the initiation of infection, but little is known about the underlying mechanisms of this process. Results To gain insights into early germination events and facilitate the identification of potential stage-specific biomarkers and vaccine candidates, we have used quantitative shotgun proteomics to elucidate patterns of protein abundance changes during early fungal development. Four different stages were examined: dormant conidia, isotropically expanding conidia, hyphae in which germ tube emergence has just begun, and pre-septation hyphae. To enrich for glycan-linked cell wall proteins we used an alkaline cell extraction method. Shotgun proteomic resulted in the identification of 375 unique gene products with high confidence, with no evidence for enrichment of cell wall-immobilized and secreted proteins. The most interesting discovery was the identification of 52 proteins enriched in dormant conidia including 28 proteins that have never been detected in the A. fumigatus conidial proteome such as signaling protein Pil1, chaperones BipA and calnexin, and transcription factor HapB. Additionally we found many small, Aspergillus specific proteins of unknown function including 17 hypothetical proteins. Thus, the most abundant protein, Grg1 (AFUA_5G14210), was also one of the smallest proteins detected in this study (M.W. 7,367). Among previously characterized proteins were melanin pigment and pseurotin A biosynthesis enzymes, histones H3 and H4.1, and other proteins involved in conidiation and response to oxidative or hypoxic stress. In contrast, expanding conidia, hyphae with early germ tubes, and pre-septation hyphae samples were enriched for proteins responsible for housekeeping functions, particularly translation, respiratory metabolism, amino acid and carbohydrate biosynthesis, and the tricarboxylic acid cycle. Conclusions The observed temporal expression patterns suggest that the A. fumigatus conidia are dominated by small, lineage-specific proteins. Some of them may play key roles in host-pathogen interactions, signal transduction during conidial germination, or survival in hostile environments. PMID:22545825

  7. Profiling metabolic networks to study cancer metabolism.

    PubMed

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

    Cancer is a disease of unregulated cell growth and survival, and tumors reprogram biochemical pathways to aid these processes. New capabilities in the computational and bioanalytical characterization of metabolism have now emerged, facilitating the identification of unique metabolic dependencies that arise in specific cancers. By understanding the metabolic phenotype of cancers as a function of their oncogenic profiles, metabolic engineering may be applied to design synthetically lethal therapies for some tumors. This process begins with accurate measurement of metabolic fluxes. Here we review advanced methods of quantifying pathway activity and highlight specific examples where these approaches have uncovered potential opportunities for therapeutic intervention.

  8. Pioneer Profile.

    ERIC Educational Resources Information Center

    Butcher, Channa Beth

    1987-01-01

    Profiles Herbert A. Sweet, founder and director of Acorn Farms Day Camp (Indiana) for 44 years. Includes reminiscences about the camp's program, staffing, food, World War II, affiliation with the American Camping Association, and camps/directors of today. (NEC)

  9. Leadership Profiles.

    ERIC Educational Resources Information Center

    Teach, Beverly; And Others

    1994-01-01

    Presents profiles of two leaders in the field of educational media and technology: Carolyn Guss and Mendel Sherman, both retired professors from Indiana University's program in Information Systems Technology. (KRN)

  10. Chemical Analysis: An Indispensable Means for Uncovering Severe Cases of Fraud with Cosmetics and Tattoo Inks.

    PubMed

    Hohl, Christopher; Hauri, Urs

    2016-01-01

    Three cases of fraud with commodities containing illegal stealth compounds are presented, which were uncovered by the State Laboratory Basel-City, Switzerland. All three commodities, grapefruit seed extracts, a phytocosmetical skin cream, and tattoo inks, were produced abroad, had forged declarations of ingredients and, in the case of the extracts and the cream, were marketed with far-reaching health claims. While inspections will identify suspicious products and would be able to eliminate health claims to some extent, only chemical analysis can uncover the illegal agents used and give law enforcement bodies the necessary evidence to immediately clamp down on those brands, where the stealth agent presents a serious health hazard to consumers. PMID:27198815

  11. Integration of small RNAs, degradome and transcriptome sequencing in hyperaccumulator Sedum alfredii uncovers a complex regulatory network and provides insights into cadmium phytoremediation.

    PubMed

    Han, Xiaojiao; Yin, Hengfu; Song, Xixi; Zhang, Yunxing; Liu, Mingying; Sang, Jiang; Jiang, Jing; Li, Jihong; Zhuo, Renying

    2016-06-01

    The hyperaccumulating ecotype of Sedum alfredii Hance is a cadmium (Cd)/zinc/lead co-hyperaccumulating species of Crassulaceae. It is a promising phytoremediation candidate accumulating substantial heavy metal ions without obvious signs of poisoning. However, few studies have focused on the regulatory roles of miRNAs and their targets in the hyperaccumulating ecotype of S. alfredii. Here, we combined analyses of the transcriptomics, sRNAs and the degradome to generate a comprehensive resource focused on identifying key regulatory miRNA-target circuits under Cd stress. A total of 87 721 unigenes and 356 miRNAs were identified by deep sequencing, and 79 miRNAs were differentially expressed under Cd stress. Furthermore, 754 target genes of 194 miRNAs were validated by degradome sequencing. A gene ontology (GO) enrichment analysis of differential miRNA targets revealed that auxin, redox-related secondary metabolism and metal transport pathways responded to Cd stress. An integrated analysis uncovered 39 pairs of miRNA targets that displayed negatively correlated expression profiles. Ten miRNA-target pairs also exhibited negative correlations according to a real-time quantitative PCR analysis. Moreover, a coexpression regulatory network was constructed based on profiles of differentially expressed genes. Two hub genes, ARF4 (auxin response factor 4) and AAP3 (amino acid permease 3), which might play central roles in the regulation of Cd-responsive genes, were uncovered. These results suggest that comprehensive analyses of the transcriptomics, sRNAs and the degradome provided a useful platform for investigating Cd hyperaccumulation in S. alfredii, and may provide new insights into the genetic engineering of phytoremediation. PMID:26801211

  12. Magnetization of uncovered and V-covered ultrathin Fe(100) films on V(100)

    SciTech Connect

    Fritzsche, H.; Liu, Y.T.; Hauschild, J.; Maletta, H.

    2004-12-01

    We used polarized neutron reflectometry (PNR) to determine the absolute magnetic moment of uncovered and V-covered Fe films in the thickness range from 0.3 to 5.5 nm. The films were prepared by molecular beam epitaxy on a V(100) buffer layer grown on a MgO(100) crystal. The magnetic moment shows a linear dependence on the Fe film thickness with a reduction (compared to the Fe bulk value) of the magnetic moment equivalent to 0.1 nm bulk Fe for the V-covered films and a reduction equivalent to 0.03 nm bulk Fe for the uncovered Fe films. For the case of the V/Fe/V samples we observe a much smaller reduction of the magnetic moment than reported for experiments on Fe/V multilayers. As theoretical calculations show a strong decrease of the magnetic moment for an interface alloy we conclude that the larger reduction of the magnetization in Fe/V multilayers is due to an increase in interface roughness with increasing film thickness. For the uncovered Fe(100) films we find a much smaller reduction of the magnetic moment than in earlier in situ PNR experiments on V(110)/Fe(110) where we observed a reduction equivalent to 0.4 nm bulk Fe.

  13. Proteomic analysis of propiconazole responses in mouse liver: comparison of genomic and proteomic profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this fungicide. Utilizing twodimensional...

  14. Proteomic Analysis of Propiconazole Responses in Mouse Liver-Comparison of Genomic and Proteomic Profiles

    EPA Science Inventory

    We have performed for the first time a comprehensive profiling of changes in protein expression of soluble proteins in livers from mice treated with the mouse liver tumorigen, propiconazole, to uncover the pathways and networks altered by this commonly used fungicide. Utilizing t...

  15. Profile summary.

    PubMed

    2003-01-01

    All drugs appearing in the Adis Profile Summary table have been selected based on information contained in R&D Insight trade mark, a proprietary product of Adis International. The information in the profiles is gathered from the world's medical and scientific literature, at international conferences and symposia, and directly from the developing companies themselves. The emphasis of Drugs in R&D is on the clinical potential of new drugs, and selection of agents for inclusion is based on products in late-phase clinical development that have recently had a significant change in status.

  16. The defect level and ideal thermal conductivity of graphene uncovered by residual thermal reffusivity at the 0 K limit

    NASA Astrophysics Data System (ADS)

    Xie, Yangsu; Xu, Zaoli; Xu, Shen; Cheng, Zhe; Hashemi, Nastaran; Deng, Cheng; Wang, Xinwei

    2015-05-01

    Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m-1 K-1 due to different levels of alternations and defects in graphene samples. In this work, the thermal diffusivity of suspended four-layered graphene foam (GF) is characterized from room temperature (RT) down to 17 K. For the first time, we identify the defect level in graphene by evaluating the inverse of thermal diffusivity (termed ``thermal reffusivity'': Θ) at the 0 K limit. By using the Debye model of Θ = Θ0 + C × e-θ/2T and fitting the Θ-T curve to the point of T = 0 K, we identify the defect level (Θ0) and determine the Debye temperature of graphene. Θ0 is found to be 1878 s m-2 for the studied GF and 43-112 s m-2 for three highly crystalline graphite materials. This uncovers a 16-43-fold higher defect level in GF than that in pyrolytic graphite. In GF, the phonon mean free path solely induced by defects and boundary scattering is determined as 166 nm. The Debye temperature of graphene is determined to be 1813 K, which is very close to the average theoretical Debye temperature (1911 K) of the three acoustic phonon modes in graphene. By subtracting the defect effect, we report the ideal thermal diffusivity and conductivity (κideal) of graphene presented in the 3D foam structure in the range of 33-299 K. Detailed physics based on chemical composition and structure analysis are given to explain the κideal-T profile by comparing with those reported for suspended graphene.Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m-1 K-1 due to different levels of alternations and defects in graphene samples. In this work, the thermal

  17. The defect level and ideal thermal conductivity of graphene uncovered by residual thermal reffusivity at the 0 K limit.

    PubMed

    Xie, Yangsu; Xu, Zaoli; Xu, Shen; Cheng, Zhe; Hashemi, Nastaran; Deng, Cheng; Wang, Xinwei

    2015-06-14

    Due to its intriguing thermal and electrical properties, graphene has been widely studied for potential applications in sensor and energy devices. However, the reported value for its thermal conductivity spans from dozens to thousands of W m(-1) K(-1) due to different levels of alternations and defects in graphene samples. In this work, the thermal diffusivity of suspended four-layered graphene foam (GF) is characterized from room temperature (RT) down to 17 K. For the first time, we identify the defect level in graphene by evaluating the inverse of thermal diffusivity (termed "thermal reffusivity": Θ) at the 0 K limit. By using the Debye model of Θ = Θ0 + C× e(-θ/2T) and fitting the Θ-T curve to the point of T = 0 K, we identify the defect level (Θ0) and determine the Debye temperature of graphene. Θ0 is found to be 1878 s m(-2) for the studied GF and 43-112 s m(-2) for three highly crystalline graphite materials. This uncovers a 16-43-fold higher defect level in GF than that in pyrolytic graphite. In GF, the phonon mean free path solely induced by defects and boundary scattering is determined as 166 nm. The Debye temperature of graphene is determined to be 1813 K, which is very close to the average theoretical Debye temperature (1911 K) of the three acoustic phonon modes in graphene. By subtracting the defect effect, we report the ideal thermal diffusivity and conductivity (κideal) of graphene presented in the 3D foam structure in the range of 33-299 K. Detailed physics based on chemical composition and structure analysis are given to explain the κideal-T profile by comparing with those reported for suspended graphene.

  18. Ranking Profiles

    ERIC Educational Resources Information Center

    Van Der Werf, Martin

    2007-01-01

    This article presents the "U.S. News" ranking profiles of four colleges, namely: (1) Smith College; (2) Washington University in St. Louis; (3) Colorado State University at Fort Collins; and (4) Whitman College. Smith College was in the top 10 of the nation's liberal-arts colleges, or just outside it, almost since the "U.S. News" rankings began.…

  19. Uncovering beam position monitor noise at the Relativistic Heavy Ion Collider

    NASA Astrophysics Data System (ADS)

    Shen, X.; Lee, S. Y.; Bai, M.

    2015-01-01

    We apply the independent component analysis (ICA) algorithm to uncover intrinsic noise in the beam position monitor (BPM) system. Numerical simulations found that ICA is efficient in the BPM noise estimation. The ICA algorithm is applied to the turn-by-turn data at the Relativistic Heavy Ion Collider. We found the distribution of the BPM noise level, which is consistent with the Johnson-Nyquist thermal noise model. The ICA analysis of turn-by-turn data can be used in neuronetwork feasibility of monitoring a storage ring parasitically.

  20. Serial insertion of bilateral uncovered metal stents for malignant hilar obstruction using an 8 Fr biliary system: a case series of 17 consecutive patients

    PubMed Central

    Thosani, Amar; Grunwald, Matthew; Nagula, Satish; Bucobo, Juan Carlos; Buscaglia, Jonathan M.

    2015-01-01

    Controversy exists over the need for unilateral versus bilateral stent placement in patients with malignant obstruction at the biliary hilum. Placement of bilateral uncovered self-expanding metal stent (UCSEMS) at this location is technically challenging, and generally associated with lower rates of procedural success. Serial insertion of side-by-side UCSEMS may be especially difficult when simultaneous deployment is not possible using larger stent delivery catheters. In this single-center, retrospective case series of all patients who underwent bilateral placement of uncovered WallflexTM biliary stents between July 2008 and July 2014, we evaluate the feasibility, technical success, and safety of patients undergoing serial insertion of bilateral UCSEMS using the 8 Fr WallflexTM biliary system for malignant hilar obstruction. A total of 17 patients were included. Primary cholangiocarcinoma, Bismuth IV, was the most common diagnosis. Mean procedure time was 54.4 minutes. Overall procedural technical success was achieved in 17/17 patients. Stricture dilation was necessary prior to WallflexTM insertion in 8/17 patients (47.1%). Transpapillary extension of two stents was performed in all patients. There were no cases of stent deployment malfunction, or inability to insert or deploy the 2nd stent. Nine of 17 patients (52.9%) required inpatient hospitalization following ERCP; the most common indications were abdominal pain and need for IV antibiotics. There was one case of ERCP-related cholangitis otherwise; there were no other major complications. Bilateral, serial insertion of UCSEMS using the 8 Fr WallflexTM biliary system in malignant hilar obstruction is feasible with an excellent technical success profile. Using this device for side-by-side deployment of UCSEMS appears to be safe in the majority of patients. PMID:26605283

  1. Uncovering study abroad: foreignness and its relevance to nurse education and cultural competence.

    PubMed

    Greatrex-White, Sheila

    2008-07-01

    This paper reports some of the findings from a hermeneutic phenomenological research project designed to uncover the nature of the phenomenon 'study abroad' in the context of Nursing Higher Education in the United Kingdom. The research question asked was 'How is study abroad manifest in the experience of nursing students?' Informed by the philosophy of Martin Heidegger, the analysis of 26 study abroad students' diary accounts uncovered six general structures, or ways for study abroad to be, namely; leaving behind, escape, foreigner, self-discovery, learning and risk. The focus here is on the general structure 'foreigner' and the far-reaching implications this can have in terms of understanding how study abroad comes to be. The relationship between study abroad, positive disturbance and the development of students who are able to recognise diversity across different cultures is discussed. It is suggested that if one of the major aims of nurse higher education is the development of culturally competent practitioners, study abroad is deserving of far greater attention than is currently the case. PMID:17931751

  2. Uncovering study abroad: foreignness and its relevance to nurse education and cultural competence.

    PubMed

    Greatrex-White, Sheila

    2008-07-01

    This paper reports some of the findings from a hermeneutic phenomenological research project designed to uncover the nature of the phenomenon 'study abroad' in the context of Nursing Higher Education in the United Kingdom. The research question asked was 'How is study abroad manifest in the experience of nursing students?' Informed by the philosophy of Martin Heidegger, the analysis of 26 study abroad students' diary accounts uncovered six general structures, or ways for study abroad to be, namely; leaving behind, escape, foreigner, self-discovery, learning and risk. The focus here is on the general structure 'foreigner' and the far-reaching implications this can have in terms of understanding how study abroad comes to be. The relationship between study abroad, positive disturbance and the development of students who are able to recognise diversity across different cultures is discussed. It is suggested that if one of the major aims of nurse higher education is the development of culturally competent practitioners, study abroad is deserving of far greater attention than is currently the case.

  3. Uncovering Sundanese Values by Analyzing Symbolic Meaning of Ménak Priangan Clothing (1800-1942)

    NASA Astrophysics Data System (ADS)

    Karmila, M.; Suciati; Widiaty, I.

    2016-04-01

    This study investigates symbolic meanings found in the Sunda ethnic clothing, particularly the Menak Priangan clothing. This study aims to uncover and document those symbolic meanings found in the Menak Priangan clothing as an effort to develop Sunda cultural artefacts of West Java. This study on Menak Priangan clothing applies ethnography (visual) and aesthetic methods. The visual method is utilized in order to uncover local cultural (Sunda) values found in Menak Priangan clothing visualization, including: design, model, name, and representing colours, which then directed towards local Sundanese aesthetic concepts living within the Priangan community. Furthermore, aesthetic method is used to explore role of aesthetic values in empowering visual cultural values within certain community, particularly Sunda aesthetic values. The study results show that since the 19th century, Sunda ethnic clothing was limited to Priangan Sunda only, while traditional clothing wearing by Priangan people reflects their social strata, consisting of: a. Menak Gede (Menak pangluhurna: mayor), bearing raden title, b. Menak Leutik/Santana (mayor assistant), titles: asep, mas, agus, ujang, (Nyimas for woman), c. Somah/Cacah: ordinary people/lower class. Clothing is a cultural phenomenon within certain culture reflecting such society experiences. For Menak people, clothing and its accessories have important meanings. They wear such traditional clothing and accessories as a symbol of power they have within bureaucratic structure and as a symbol of social status they bear within traditional community structure.

  4. Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

    PubMed Central

    Korpal, Manav; Feala, Jacob; Puyang, Xiaoling; Zou, Jian; Ramos, Alex H.; Wu, Jeremy; Baumeister, Timm; Yu, Lihua; Warmuth, Markus; Zhu, Ping

    2015-01-01

    Although targeted therapies are initially effective, resistance inevitably emerges. Several methods, such as genetic analysis of resistant clinical specimens, have been applied to uncover these resistance mechanisms to facilitate follow-up care. Although these approaches have led to clinically relevant discoveries, difficulties in attaining the relevant patient material or in deconvoluting the genomic data collected from these specimens have severely hampered the path towards a cure. To this end, we here describe a tool for expeditious discovery that may guide improvement in first-line therapies and alternative clinical management strategies. By coupling preclinical in vitro or in vivo drug selection with next-generation sequencing, it is possible to identify genomic structural variations and/or gene expression alterations that may serve as functional drivers of resistance. This approach facilitates the spontaneous emergence of alterations, enhancing the probability that these mechanisms may be observed in the patients. In this protocol we provide guidelines to maximize the potential for uncovering single nucleotide variants that drive resistance using adherent lines. PMID:26710000

  5. MPI Profiling

    SciTech Connect

    Han, D K; Jones, T R

    2005-02-11

    The Message Passing Interface (MPI) is the de facto message-passing standard for massively parallel programs. It is often the case that application performance is a crucial factor, especially for solving grand challenge problems. While there have been many studies on the scalability of applications, there have not been many focusing on the specific types of MPI calls being made and their impact on application performance. Using a profiling tool called mpiP, a large spectrum of parallel scientific applications were surveyed and their performance results analyzed.

  6. Strategies and approaches in plasmidome studies-uncovering plasmid diversity disregarding of linear elements?

    PubMed

    Dib, Julián R; Wagenknecht, Martin; Farías, María E; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which-despite their frequent occurrence in a large number of bacteria-are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  7. Uncovering brain–heart information through advanced signal and image processing

    PubMed Central

    Toschi, Nicola; Barbieri, Riccardo

    2016-01-01

    Through their dynamical interplay, the brain and the heart ensure fundamental homeostasis and mediate a number of physiological functions as well as their disease-related aberrations. Although a vast number of ad hoc analytical and computational tools have been recently applied to the non-invasive characterization of brain and heart dynamic functioning, little attention has been devoted to combining information to unveil the interactions between these two physiological systems. This theme issue collects contributions from leading experts dealing with the development of advanced analytical and computational tools in the field of biomedical signal and image processing. It includes perspectives on recent advances in 7 T magnetic resonance imaging as well as electroencephalogram, electrocardiogram and cerebrovascular flow processing, with the specific aim of elucidating methods to uncover novel biological and physiological correlates of brain–heart physiology and physiopathology. PMID:27044995

  8. Strategies and approaches in plasmidome studies—uncovering plasmid diversity disregarding of linear elements?

    PubMed Central

    Dib, Julián R.; Wagenknecht, Martin; Farías, María E.; Meinhardt, Friedhelm

    2015-01-01

    The term plasmid was originally coined for circular, extrachromosomal genetic elements. Today, plasmids are widely recognized not only as important factors facilitating genome restructuring but also as vehicles for the dissemination of beneficial characters within bacterial communities. Plasmid diversity has been uncovered by means of culture-dependent or -independent approaches, such as endogenous or exogenous plasmid isolation as well as PCR-based detection or transposon-aided capture, respectively. High-throughput-sequencing made possible to cover total plasmid populations in a given environment, i.e., the plasmidome, and allowed to address the quality and significance of self-replicating genetic elements. Since such efforts were and still are rather restricted to circular molecules, here we put equal emphasis on the linear plasmids which—despite their frequent occurrence in a large number of bacteria—are largely neglected in prevalent plasmidome conceptions. PMID:26074886

  9. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    SciTech Connect

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2012-04-23

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  10. Representations of God uncovered in a spirituality group of borderline inpatients.

    PubMed

    Goodman, Geoff; Manierre, Amy

    2008-01-01

    We present aspects of a psychoanalytically-oriented, exploratory spirituality group for nine female psychiatric inpatients diagnosed with borderline personality disorder. Through drawings and group process, the patients uncovered and elaborated on their representations of God. Two patterns of representations were identified: (1) representations of a punitive, judgmental, rigid God that seemed directly to reflect and correspond with parental representations and (2) representations of a depersonified, inanimate, abstract God entailing aspects of idealization that seemed to compensate for parental representations. Interestingly, the second pattern was associated with comorbid narcissistic features in the patients. Those patients who presented punitive God representations were able to begin the process of re-creating these representations toward more benign or benevolent images in the context of this group, while those participants who presented depersonified God representations seemed unable to do so.

  11. Lipidomics Analyses Reveal Temporal and Spatial Lipid Organization and Uncover Daily Oscillations in Intracellular Organelles.

    PubMed

    Aviram, Rona; Manella, Gal; Kopelman, Naama; Neufeld-Cohen, Adi; Zwighaft, Ziv; Elimelech, Meytar; Adamovich, Yaarit; Golik, Marina; Wang, Chunyan; Han, Xianlin; Asher, Gad

    2016-05-19

    Cells have evolved mechanisms to handle incompatible processes through temporal organization by circadian clocks and by spatial compartmentalization within organelles defined by lipid bilayers. Recent advances in lipidomics have led to identification of plentiful lipid species, yet our knowledge regarding their spatiotemporal organization is lagging behind. In this study, we quantitatively characterized the nuclear and mitochondrial lipidome in mouse liver throughout the day, upon different feeding regimens, and in clock-disrupted mice. Our analyses revealed potential connections between lipid species within and between lipid classes. Remarkably, we uncovered diurnal oscillations in lipid accumulation in the nucleus and mitochondria. These oscillations exhibited opposite phases and readily responded to feeding time. Furthermore, we found that the circadian clock coordinates the phase relation between the organelles. In summary, our study provides temporal and spatial depiction of lipid organization and reveals the presence and coordination of diurnal rhythmicity in intracellular organelles. PMID:27161994

  12. An organ boundary-enriched gene regulatory network uncovers regulatory hierarchies underlying axillary meristem initiation

    PubMed Central

    Tian, Caihuan; Zhang, Xiaoni; He, Jun; Yu, Haopeng; Wang, Ying; Shi, Bihai; Han, Yingying; Wang, Guoxun; Feng, Xiaoming; Zhang, Cui; Wang, Jin; Qi, Jiyan; Yu, Rong; Jiao, Yuling

    2014-01-01

    Gene regulatory networks (GRNs) control development via cell type-specific gene expression and interactions between transcription factors (TFs) and regulatory promoter regions. Plant organ boundaries separate lateral organs from the apical meristem and harbor axillary meristems (AMs). AMs, as stem cell niches, make the shoot a ramifying system. Although AMs have important functions in plant development, our knowledge of organ boundary and AM formation remains rudimentary. Here, we generated a cellular-resolution genomewide gene expression map for low-abundance Arabidopsis thaliana organ boundary cells and constructed a genomewide protein–DNA interaction map focusing on genes affecting boundary and AM formation. The resulting GRN uncovers transcriptional signatures, predicts cellular functions, and identifies promoter hub regions that are bound by many TFs. Importantly, further experimental studies determined the regulatory effects of many TFs on their targets, identifying regulators and regulatory relationships in AM initiation. This systems biology approach thus enhances our understanding of a key developmental process. PMID:25358340

  13. Health Detectives: Uncovering the Mysteries of Disease (LBNL Science at the Theater)

    ScienceCinema

    Bissell, Mina; Canaria, Christie; Celnicker, Susan; Karpen, Gary

    2016-07-12

    In this April 23, 2012 Science at the Theater event, Berkeley Lab scientists discuss how they uncover the mysteries of disease in unlikely places. Speakers and topics include: World-renowned cancer researcher Mina Bissell's pioneering research on the role of the cellular microenvironment in breast cancer has changed the conversation about the disease. How does DNA instability cause disease? To find out, Christie Canaria images neural networks to study disorders such as Huntington's disease. Fruit flies can tell us a lot about ourselves. Susan Celniker explores the fruit fly genome to learn how our genome works. DNA is not destiny. Gary Karpen explores how environmental factors shape genome function and disease through epigenetics.

  14. Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers

    PubMed Central

    Almeida, Alexandre; Villain, Adrien; Joubrel, Caroline; Touak, Gérald; Sauvage, Elisabeth; Rosinski-Chupin, Isabelle

    2015-01-01

    ABSTRACT Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence-associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease. IMPORTANCE Group B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we

  15. Uncovering novel 3-hydroxy-4-pyridinone metal ion complexes with potential anti-inflammatory properties.

    PubMed

    Chisté, Renan Campos; Ribeiro, Daniela; Freitas, Marisa; Leite, Andreia; Moniz, Tânia; Rangel, Maria; Fernandes, Eduarda

    2016-02-01

    Ligands of the 3-hydroxy-4-pyridinone (3,4-HPO) type, with one (Hmpp) or two methyl groups (Hdmpp), have been reported to possess biomedical, chemical and analytical applications. In this first screening study aiming to uncover new promising agents to mitigate the oxidative damage highly present in several metabolic disorders, such as diabetes mellitus, we assessed the potential of twelve 3,4-HPO metal ion complexes to modulate oxidative burst in human neutrophils. Metal ion 3,4-HPO complexes of Ni, Fe, V, Co, Cu and Zn were synthesized and tested up to 15μM. Among all the compounds, [Cu(mpp)2] and [Cu(dmpp)2] exhibited the highest scavenging capacity against superoxide radical (O2(-)) (IC50=0.36±0.07 and 0.30±0.06μM, respectively) and against hypochlorous acid (HOCl) (IC50=0.6±0.3 and 0.4±0.1μM, respectively). In the particular case of O2(-), [Fe(mpp)3] and [Fe(dmpp)3] (both at 15μM) presented 35% and 22% of inhibition, respectively, while all the other compounds were neither able to scavenge O2(-) nor stimulate its production. Regarding the scavenging capacity against hydrogen peroxide (H2O2), all the compounds showed low efficiency (from 6-39%). Finally, with exception of [VO(mpp)2] and [VO(dmpp)2], all compounds exhibited scavenging activity against HOCl (39-81%) and the most efficient compounds were Cu(II) and Zn(II) complexes. Thus, these preliminary results uncover promising new metal ion complexes, inhibitors of neutrophil's oxidative burst, with potential anti-inflammatory properties, which may be seen as an useful strategy for further studies in the treatment of a number of diseases where oxidative damage is a serious issue.

  16. Uncovering the role of p53 splice variants in human malignancy: a clinical perspective

    PubMed Central

    Surget, Sylvanie; Khoury, Marie P; Bourdon, Jean-Christophe

    2014-01-01

    Thirty-five years of research on p53 gave rise to more than 68,000 articles and reviews, but did not allow the uncovering of all the mysteries that this major tumor suppressor holds. How p53 handles the different signals to decide the appropriate cell fate in response to a stress and its implication in tumorigenesis and cancer progression remains unclear. Nevertheless, the uncovering of p53 isoforms has opened new perspectives in the cancer research field. Indeed, the human TP53 gene encodes not only one but at least twelve p53 protein isoforms, which are produced in normal tissues through alternative initiation of translation, usage of alternative promoters, and alternative splicing. In recent years, it became obvious that the different p53 isoforms play an important role in regulating cell fate in response to different stresses in normal cells by differentially regulating gene expression. In cancer cells, abnormal expression of p53 isoforms contributes actively to cancer formation and progression, regardless of TP53 mutation status. They can also be associated with response to treatment, depending on the cell context. The determination of p53 isoform expression and p53 mutation status helps to define different subtypes within a particular cancer type, which would have different responses to treatment. Thus, the understanding of the regulation of p53 isoform expression and their biological activities in relation to the cellular context would constitute an important step toward the improvement of the diagnostic, prognostic, and predictive values of p53 in cancer treatment. This review aims to summarize the involvement of p53 isoforms in cancer and to highlight novel potential therapeutic targets. PMID:24379683

  17. Molecular profiling of breast cancer: transcriptomic studies and beyond.

    PubMed

    Culhane, A C; Howlin, J

    2007-12-01

    Utilisation of 'omics' technologies, in particular gene expression profiling, has increased dramatically in recent years. In basic research, high-throughput profiling applications are increasingly used and may now even be considered standard research tools. In the clinic, there is a need for better and more accurate diagnosis, prognosis and treatment response indicators. As such, clinicians have looked to omics technologies for potential biomarkers. These prediction profiling studies have in turn attracted the attention of basic researchers eager to uncover biological mechanisms underlying clinically useful signatures. Here we highlight some of the seminal work establishing the arrival of the omics, in particular transcriptomics, in breast cancer research and discuss a sample of the most current applications. We also discuss the challenges of data analysis and integrated data analysis with emphasis on utilising the current publicly available gene expression datasets. (Part of a Multi-author Review). PMID:17957338

  18. Combining data mining and machine learning for effective user profiling

    SciTech Connect

    Fawcett, T.; Provost, F.

    1996-12-31

    This paper describes the automatic design of methods for detecting fraudulent behavior. Much of the design is accomplished using a series of machine learning methods. In particular, we combine data mining and constructive induction with more standard machine learning techniques to design methods for detecting fraudulent usage of cellular telephones based on profiling customer behavior. Specifically, we use a rule-learning program to uncover indicators of fraudulent behavior from a large database of cellular calls. These indicators are used to create profilers, which then serve as features to a system that combines evidence from multiple profilers to generate high-confidence alarms. Experiments indicate that this automatic approach performs nearly as well as the best hand-tuned methods for detecting fraud.

  19. Uncovering the Links between Prospective Teachers' Personal Responsibility, Academic Optimism, Hope, and Emotions about Teaching: A Mediation Analysis

    ERIC Educational Resources Information Center

    Eren, Altay

    2014-01-01

    Prospective teachers' sense of personal responsibility has not been examined together with their academic optimism, hope, and emotions about teaching in a single study to date. However, to consider hope, academic optimism, and emotions about teaching together with personal responsibility is important to uncover the factors affecting…

  20. Application of Synthetic Peptide Arrays To Uncover Cyclic Di-GMP Binding Motifs

    PubMed Central

    Düvel, Juliane; Bense, Sarina; Möller, Stefan; Bertinetti, Daniela; Schwede, Frank; Morr, Michael; Eckweiler, Denitsa; Genieser, Hans-Gottfried; Jänsch, Lothar; Herberg, Friedrich W.; Frank, Ronald

    2015-01-01

    ABSTRACT High levels of the universal bacterial second messenger cyclic di-GMP (c-di-GMP) promote the establishment of surface-attached growth in many bacteria. Not only can c-di-GMP bind to nucleic acids and directly control gene expression, but it also binds to a diverse array of proteins of specialized functions and orchestrates their activity. Since its development in the early 1990s, the synthetic peptide array technique has become a powerful tool for high-throughput approaches and was successfully applied to investigate the binding specificity of protein-ligand interactions. In this study, we used peptide arrays to uncover the c-di-GMP binding site of a Pseudomonas aeruginosa protein (PA3740) that was isolated in a chemical proteomics approach. PA3740 was shown to bind c-di-GMP with a high affinity, and peptide arrays uncovered LKKALKKQTNLR to be a putative c-di-GMP binding motif. Most interestingly, different from the previously identified c-di-GMP binding motif of the PilZ domain (RXXXR) or the I site of diguanylate cyclases (RXXD), two leucine residues and a glutamine residue and not the charged amino acids provided the key residues of the binding sequence. Those three amino acids are highly conserved across PA3740 homologs, and their singular exchange to alanine reduced c-di-GMP binding within the full-length protein. IMPORTANCE In many bacterial pathogens the universal bacterial second messenger c-di-GMP governs the switch from the planktonic, motile mode of growth to the sessile, biofilm mode of growth. Bacteria adapt their intracellular c-di-GMP levels to a variety of environmental challenges. Several classes of c-di-GMP binding proteins have been structurally characterized, and diverse c-di-GMP binding domains have been identified. Nevertheless, for several c-di-GMP receptors, the binding motif remains to be determined. Here we show that the use of a synthetic peptide array allowed the identification of a c-di-GMP binding motif of a putative c

  1. Effect of early exposure on the integration of dental implants in the baboon: Part 1--Clinical findings at uncovering.

    PubMed

    Severson, S; Vernino, A R; Caudill, R; Holt, R; Church, C; Davis, A

    2000-04-01

    There has been increased discussion on the advantages of a one- versus a two-stage surgical approach in the placement of dental endosseous implants. This study evaluated the influence of early implant exposure on crestal bone height adjacent to the implant surface and Periotest values at uncovering in the baboon. Forty-eight implants (24 commercially pure titanium, 24 titanium alloy) were placed in maxillary and mandibular posterior sites in 6 baboons. Implant exposure was evaluated weekly for 3 weeks after implant placement. The level of bone adjacent to the dental implants was measured at placement from the top of the implant collar to the crest of the bone at the mesial, distal, buccal, and lingual surfaces. The maxillary sites were measured again at a 6-month uncovering, while the mandibular sites were measured at a 3-month uncovering. Periotest readings were also recorded at uncovering. Early implant exposure was more common in the mandible, with the majority occurring by the second week postplacement. There were no significant differences in the crestal bone height changes at uncovering between the pure titanium and alloy implants in either arch. In the maxilla, the changes in crestal bone height were not statistically different between exposed and nonexposed implants at any aspect. In the mandible, the difference in 3-month changes between exposed and nonexposed implants was significant for the distal, buccal, and lingual aspects. The overall percentage of implants with a Periotest reading in the "good" category was greater for the nonexposed sites as compared to exposed sites. The results of this study suggest that the two-stage surgical approach results in a better clinical outcome as compared to the one-stage approach in the baboon model.

  2. DNA Identification of Skeletal Remains from World War II Mass Graves Uncovered in Slovenia

    PubMed Central

    Marjanović, Damir; Durmić-Pašić, Adaleta; Bakal, Narcisa; Haverić, Sanin; Kalamujić, Belma; Kovačević, Lejla; Ramić, Jasmin; Pojskić, Naris; Škaro, Vedrana; Projić, Petar; Bajrović, Kasim; Hadžiselimović, Rifat; Drobnič, Katja; Huffine, Ed; Davoren, Jon; Primorac, Dragan

    2007-01-01

    Aim To present the joint effort of three institutions in the identification of human remains from the World War II found in two mass graves in the area of Škofja Loka, Slovenia. Methods The remains of 27 individuals were found in two small and closely located mass graves. The DNA was isolated from bone and teeth samples using either standard phenol/chloroform alcohol extraction or optimized Qiagen DNA extraction procedure. Some recovered samples required the employment of additional DNA purification methods, such as N-buthanol treatment. QuantifilerTM Human DNA Quantification Kit was used for DNA quantification. PowerPlex 16 kit was used to simultaneously amplify 15 short tandem repeat (STR) loci. Matching probabilities were estimated using the DNA View program. Results Out of all processed samples, 15 remains were fully profiled at all 15 STR loci. The other 12 profiles were partial. The least successful profile included 13 loci. Also, 69 referent samples (buccal swabs) from potential living relatives were collected and profiled. Comparison of victims' profile against referent samples database resulted in 4 strong matches. In addition, 5 other profiles were matched to certain referent samples with lower probability. Conclusion Our results show that more than 6 decades after the end of the World War II, DNA analysis may significantly contribute to the identification of the remains from that period. Additional analysis of Y-STRs and mitochondrial DNA (mtDNA) markers will be performed in the second phase of the identification project. PMID:17696306

  3. Characterizing inactive ribosomes in translational profiling.

    PubMed

    Liu, Botao; Qian, Shu-Bing

    2016-01-01

    The broad impact of translational regulation has emerged explosively in the last few years in part due to the technological advance in genome-wide interrogation of gene expression. During mRNA translation, the majority of actively translating ribosomes exist as polysomes in cells with multiple ribosomes loaded on a single transcript. The importance of the monosome, however, has been less appreciated in translational profiling analysis. Here we report that the monosome fraction isolated by sucrose sedimentation contains a large quantity of inactive ribosomes that do not engage on mRNAs to direct translation. We found that the elongation factor eEF2, but not eEF1A, stably resides in these non-translating ribosomes. This unique feature permits direct evaluation of ribosome status under various stress conditions and in the presence of translation inhibitors. Ribosome profiling reveals that the monosome has a similar but not identical pattern of ribosome footprints compared to the polysome. We show that the association of free ribosomal subunits minimally contributes to ribosome occupancy outside of the coding region. Our results not only offer a quantitative method to monitor ribosome availability, but also uncover additional layers of ribosome status needed to be considered in translational profiling analysis. PMID:27335722

  4. Quantitative profiling of initiating ribosomes in vivo.

    PubMed

    Gao, Xiangwei; Wan, Ji; Liu, Botao; Ma, Ming; Shen, Ben; Qian, Shu-Bing

    2015-02-01

    Cells have evolved exquisite mechanisms to fine-tune the rate of protein synthesis in response to stress. Systemic mapping of start-codon positions and precise measurement of the corresponding initiation rate would transform our understanding of translational control. Here we present quantitative translation initiation sequencing (QTI-seq), with which the initiating ribosomes can be profiled in real time at single-nucleotide resolution. Resultant initiation maps not only delineated variations of start-codon selection but also highlighted a dynamic range of initiation rates in response to nutrient starvation. The integrated data set provided unique insights into principles of alternative translation and mechanisms controlling different aspects of translation initiation. With RiboTag mice, QTI-seq permitted tissue-specific profiling of initiating ribosomes in vivo. Liver cell-specific ribosome profiling uncovered a robust translational reprogramming of the proteasome system in fasted mice. Our findings illuminated the prevalence and dynamic nature of translational regulation pivotal to physiological adaptation in vivo.

  5. Advanced interferometric profile measurements through refractive media

    SciTech Connect

    Koev, Stephan T.; Ghodssi, Reza

    2008-09-15

    Optical profilers are valuable tools for the characterization of microelectromechanical systems (MEMSs). They use phase sifting interferometry (PSI) or vertical scanning interferometry to measure the topography of microscale structures with nanometer resolution. However, for many emerging MEMS applications, the sample needs to be imaged while placed in a liquid or in a package with a glass window. The increased refractive index of the transparent medium degrades the interference image contrast and prevents any measurement of the sample. We report on the modification of a Veeco NT1100 optical profiler to enable PSI measurements through refractive media. This approach can be applied to any other optical profiler with PSI capability. The modification consists in replacing the original illumination source with a custom-built narrow linewidth source, which increases the coherence length of the light and the contrast of the interference image. We present measurements taken with the modified configuration on samples covered with 3 mm water or 500 {mu}m glass, and we compare them to measurements of uncovered samples. We show that the measurement precision is only slightly reduced by the water and glass, and that it is still sufficiently high for typical MEMS applications. The described method can be readily used for measuring through other types and thicknesses of refractive materials.

  6. Profiling and Racial Profiling: An Interactive Exercise

    ERIC Educational Resources Information Center

    Semple, Philip

    2013-01-01

    Racial Profiling has been recognized as a serious problem that affects many segments of our society and is especially notable in law enforcement. Governments and police services have pronounced that racial profiling is not acceptable and will not be tolerated. They have gone to great lengths in trying to eradicate racial profiling through…

  7. COMPENDEX Profiling Guide.

    ERIC Educational Resources Information Center

    Standera, Oldrich

    This manual provides instructions for completing the COMPENDEX (Computerized Engineering Index) Profile Submission Form used to prepare Current Information Selection (CIS) profiles. An annotated bibliography lists nine items useful in searching for proper profile words. (AB)

  8. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants

    PubMed Central

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we “wordify” the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  9. Uncovering major genomic features of essential genes in Bacteria and a methanogenic Archaea.

    PubMed

    Grazziotin, Ana Laura; Vidal, Newton M; Venancio, Thiago M

    2015-09-01

    Identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. Although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. Here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for growth in vivo, encompassing 15 Bacteria and one Archaea. We refine and generalize important theories proposed using Escherichia coli. Essential genes are typically monogenic and more conserved than nonessential genes. Genes required in vivo are less conserved than those essential in vitro, suggesting that more divergent strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. We identified essential analogous pathways that would probably be missed by orthology-based essentiality prediction strategies. For example, Streptococcus sanguinis carries horizontally transferred isoprenoid biosynthesis genes that are widespread in Archaea. Genes specifically essential in Mycobacterium tuberculosis and Burkholderia pseudomallei are reported as potential drug targets. Moreover, essential genes are not only preferentially located in operons, but also occupy the first position therein, supporting the influence of their regulatory regions in driving transcription of whole operons. Finally, these important genomic features are shared between Bacteria and at least one Archaea, suggesting that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the prokaryotic domains. PMID:26084810

  10. Online tools for uncovering data quality issues in satellite-based global precipitation products

    NASA Astrophysics Data System (ADS)

    Liu, Z.; Heo, G.

    2015-12-01

    Accurate and timely available global precipitation products are important to many applications such as flood forecasting, hydrological modeling, vector-borne disease research, crop yield estimates, etc. However, data quality issues such as biases and uncertainties are common in satellite-based precipitation products and it is important to understand these issues in applications. In recent years, algorithms using multi-satellites and multi-sensors for satellite-based precipitation estimates have become popular, such as the TRMM (Tropical Rainfall Measuring Mission) Multi-satellite Precipitation Analysis (TMPA) and the latest Integrated Multi-satellitE Retrievals for GPM (IMERG). Studies show that data quality issues for multi-satellite and multi-sensor products can vary with space and time and can be difficult to summarize. Online tools can provide customized results for a given area of interest, allowing customized investigation or comparison on several precipitation products. Because downloading data and software is not required, online tools can facilitate precipitation product evaluation and comparison. In this presentation, we will present online tools to uncover data quality issues in satellite-based global precipitation products. Examples will be presented as well.

  11. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma.

    PubMed

    Zhang, Xindong; Gao, Lin; Liu, Zhi-Ping; Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  12. Uncovering a new role for peroxidase enzymes as drivers of angiogenesis.

    PubMed

    Panagopoulos, Vasilios; Zinonos, Irene; Leach, Damien A; Hay, Shelley J; Liapis, Vasilios; Zysk, Aneta; Ingman, Wendy V; DeNichilo, Mark O; Evdokiou, Andreas

    2015-11-01

    Peroxidases are heme-containing enzymes released by activated immune cells at sites of inflammation. To-date their functional role in human health has mainly been limited to providing a mechanism for oxidative defence against invading bacteria and other pathogenic microorganisms. Our laboratory has recently identified a new functional role for peroxidase enzymes in stimulating fibroblast migration and collagen biosynthesis, offering a new insight into the causative association between inflammation and the pro-fibrogenic events that mediate tissue repair and regeneration. Peroxidases are found at elevated levels within and near blood vessels however, their direct involvement in angiogenesis has never been reported. Here we report for the first time that myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are readily internalised by human umbilical vein endothelial cells (HUVEC) where they promote cellular proliferation, migration, invasion, and stimulate angiogenesis both in vitro and in vivo. These pro-angiogenic effects were attenuated using the specific peroxidase inhibitor 4-ABAH, indicating the enzyme's catalytic activity is essential in mediating this response. Mechanistically, we provide evidence that MPO and EPO regulate endothelial FAK, Akt, p38 MAPK, ERK1/2 phosphorylation and stabilisation of HIF-2α, culminating in transcriptional regulation of key angiogenesis pathways. These findings uncover for the first time an important and previously unsuspected role for peroxidases as drivers of angiogenesis, and suggest that peroxidase inhibitors may have therapeutic potential for the treatment of angiogenesis related diseases driven by inflammation.

  13. Cryptic no more: soil macrofossils uncover Pleistocene forest microrefugia within a periglacial desert.

    PubMed

    de Lafontaine, Guillaume; Amasifuen Guerra, Carlos Alberto; Ducousso, Alexis; Petit, Rémy J

    2014-11-01

    Despite their critical importance for understanding the local effects of global climate change on biodiversity, glacial microrefugia are not well studied because they are difficult to detect by using classical palaeoecological or population genetics approaches. We used soil macrofossil charcoal analysis to uncover the presence of cryptic glacial refugia for European beech (Fagus sylvatica) and other tree species in the Landes de Gascogne (southwestern France). Using botanical identification and direct radiocarbon dating (140 (14) C-dates) of macrofossil charcoal extracted from mineral soils, we reconstructed the glacial and postglacial history of all extant beech stands in the region (n = 11). Soil charcoal macrofossils were found in all sites, allowing the identification of up to at least 14 distinct fire events per site. There was direct evidence of the presence of beech during the last glacial period at three sites. Beech was detected during Heinrich stadial-1, one of the coldest and driest intervals of the last glacial period in Western Europe. Together with previous results on the genetic structure of the species in the region, these findings suggest that beech persisted in situ in several microrefugia through full glacial and interglacial periods up to the present day.

  14. The characteristic blue spectra of accretion disks in quasars as uncovered in the infrared.

    PubMed

    Kishimoto, Makoto; Antonucci, Robert; Blaes, Omer; Lawrence, Andy; Boisson, Catherine; Albrecht, Marcus; Leipski, Christian

    2008-07-24

    Quasars are thought to be powered by supermassive black holes accreting surrounding gas. Central to this picture is a putative accretion disk which is believed to be the source of the majority of the radiative output. It is well known, however, that the most extensively studied disk model-an optically thick disk which is heated locally by the dissipation of gravitational binding energy-is apparently contradicted by observations in a few major respects. In particular, the model predicts a specific blue spectral shape asymptotically from the visible to the near-infrared, but this is not generally seen in the visible wavelength region where the disk spectrum is observable. A crucial difficulty has been that, towards the infrared, the disk spectrum starts to be hidden under strong, hot dust emission from much larger but hitherto unresolved scales, and thus has essentially been impossible to observe. Here we report observations of polarized light interior to the dust-emitting region that enable us to uncover this near-infrared disk spectrum in several quasars. The revealed spectra show that the near-infrared disk spectrum is indeed as blue as predicted. This indicates that, at least for the outer near-infrared-emitting radii, the standard picture of the locally heated disk is approximately correct.

  15. Uncovering compounds by synergy of cluster expansion and high-throughput methods.

    PubMed

    Levy, Ohad; Hart, Gus L W; Curtarolo, Stefano

    2010-04-01

    Predicting from first-principles calculations whether mixed metallic elements phase-separate or form ordered structures is a major challenge of current materials research. It can be partially addressed in cases where experiments suggest the underlying lattice is conserved, using cluster expansion (CE) and a variety of exhaustive evaluation or genetic search algorithms. Evolutionary algorithms have been recently introduced to search for stable off-lattice structures at fixed mixture compositions. The general off-lattice problem is still unsolved. We present an integrated approach of CE and high-throughput ab initio calculations (HT) applicable to the full range of compositions in binary systems where the constituent elements or the intermediate ordered structures have different lattice types. The HT method replaces the search algorithms by direct calculation of a moderate number of naturally occurring prototypes representing all crystal systems and guides CE calculations of derivative structures. This synergy achieves the precision of the CE and the guiding strengths of the HT. Its application to poorly characterized binary Hf systems, believed to be phase-separating, defines three classes of alloys where CE and HT complement each other to uncover new ordered structures.

  16. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    PubMed

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  17. Uncovering stem-cell heterogeneity in the microniche with label-free microfluidics

    NASA Astrophysics Data System (ADS)

    Sohn, Lydia L.

    2013-03-01

    Better suited for large number of cells from bulk tissue, traditional cell-screening techniques, such as fluorescence-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS), cannot easily screen stem or progenitor cells from minute populations found in their physiological niches. Furthermore, they rely upon irreversible antibody binding, potentially altering cell properties, including gene expression and regenerative capacity. We have developed a label-free, single-cell analysis microfluidic platform capable of quantifying cell-surface marker expression of functional organ stem cells directly isolated from their micro-anatomical niche. With this platform, we have screened single quiescent muscle stem (satellite) cells derived from single myofibers, and we have uncovered an important heterogeneity in the surface-marker expression of these cells. By sorting the screened cells with our microfluidic device, we have determined what this heterogeneity means in terms of muscle stem-cell functionality. For instance, we show that the levels of beta1-integrin can predict the differentiation capacity of quiescent satellite cells, and in contrast to recent literature, that some CXCR4 + cells are not myogenic. Our results provide the first direct demonstration of a microniche-specific variation in gene expression in stem cells of the same lineage. Overall, our label-free, single-cell analysis and cell-sorting platform could be extended to other systems involving rare-cell subsets. This work was funded by the W. M. Keck Foundation, NIH, and California Institute of Regenerative Medicine

  18. UNCOVERING THE ORIGINS OF SPIRAL STRUCTURE BY MEASURING RADIAL VARIATION IN PATTERN SPEEDS

    SciTech Connect

    Meidt, Sharon E.; Rand, Richard J.; Merrifield, Michael R.

    2009-09-01

    Current theories of spiral and bar structure predict a variety of pattern speed behaviors, calling for detailed, direct measurement of the radial variation of pattern speeds. Our recently developed Radial Tremaine-Weinberg (TWR) method allows this goal to be achieved for the first time. Here, we present TWR spiral pattern speed estimates for M101, IC 342, NGC 3938, and NGC 3344 in order to investigate whether spiral structure is steady or winding, whether spirals are described by multiple pattern speeds, and the relation between bar and spiral speeds. Where possible, we interpret our pattern speeds estimates according to the resonance radii associated with each (established with the disk angular rotation), and compare these to previous determinations. By analyzing the high-quality H I and CO data cubes available for these galaxies, we show that it is possible to determine directly multiple pattern speeds within these systems, and hence identify the characteristic signatures of the processes that drive the spiral structure. Even this small sample of galaxies reveals a surprisingly complex taxonomy, with the first direct evidence for the presence of resonant coupling of multiple patterns found in some systems, and the measurement of a simple single-pattern speed in others. Overall, this study demonstrates that we are now in a position to uncover more of the apparently complex physics that lies behind spiral structure.

  19. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    DOE PAGES

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method frommore » being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.« less

  20. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging.

    PubMed

    Rose, P B; Erickson, A S; Mayer, M; Nattress, J; Jovanovic, I

    2016-04-18

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as "searching for a needle in a haystack" because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material's areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  1. Novel resistance functions uncovered using functional metagenomic investigations of resistance reservoirs

    PubMed Central

    Pehrsson, Erica C.; Forsberg, Kevin J.; Gibson, Molly K.; Ahmadi, Sara; Dantas, Gautam

    2013-01-01

    Rates of infection with antibiotic-resistant bacteria have increased precipitously over the past several decades, with far-reaching healthcare and societal costs. Recent evidence has established a link between antibiotic resistance genes in human pathogens and those found in non-pathogenic, commensal, and environmental organisms, prompting deeper investigation of natural and human-associated reservoirs of antibiotic resistance. Functional metagenomic selections, in which shotgun-cloned DNA fragments are selected for their ability to confer survival to an indicator host, have been increasingly applied to the characterization of many antibiotic resistance reservoirs. These experiments have demonstrated that antibiotic resistance genes are highly diverse and widely distributed, many times bearing little to no similarity to known sequences. Through unbiased selections for survival to antibiotic exposure, functional metagenomics can improve annotations by reducing the discovery of false-positive resistance and by allowing for the identification of previously unrecognizable resistance genes. In this review, we summarize the novel resistance functions uncovered using functional metagenomic investigations of natural and human-impacted resistance reservoirs. Examples of novel antibiotic resistance genes include those highly divergent from known sequences, those for which sequence is entirely unable to predict resistance function, bifunctional resistance genes, and those with unconventional, atypical resistance mechanisms. Overcoming antibiotic resistance in the clinic will require a better understanding of existing resistance reservoirs and the dissemination networks that govern horizontal gene exchange, informing best practices to limit the spread of resistance-conferring genes to human pathogens. PMID:23760651

  2. Uncovering cryptic species diversity of a termite community in a West African savanna.

    PubMed

    Hausberger, Barbara; Kimpel, Dorothea; van Neer, Abbo; Korb, Judith

    2011-12-01

    To uncover the termite species diversity of a natural African savanna ecosystem, we combined morphological analyses and sequencing of three gene fragments (cytochrome oxidase I, cytochrome oxidase II and 28SrDNA, total length about 2450 bp) to infer putative species from phylogenetic trees. We identified 18 putative species clusters with high support values and which we retrieved consistently. Samples from two genera (Ancistrotermes and Microcerotermes) were excluded from the mitochondrial phylogenetic analyses as they might represent nuclear mitochondrial sequences (NUMTs). In total, our data suggest a species richness of at least 20 species, all but one belonging to the Termitidae (higher termites), and among them the fungus-growing Macrotermitinae were most prevalent with at least nine putative species. Within the fungus-growers the most species-rich genus was Microtermes and its four putative species were all cryptic species. Their abundance in the samples suggests that they play an important ecological role which is completely unstudied also due to the lack of reliable identification means. Our study shows that morphological traits are unreliable means of species identification for several termite taxa. Yet reliable and consistent identification is necessary for studying the functional role of termites in ecosystem and global processes.

  3. Percutaneous Treatment of Malignant Jaundice Due to Extrahepatic Cholangiocarcinoma: Covered Viabil Stent Versus Uncovered Wallstents

    SciTech Connect

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Bezzi, Mario; Passariello, Roberto; Hatzidakis, Adam

    2010-02-15

    To compare clinical effectiveness of Viabil-covered stents versus uncovered metallic Wallstents, for palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, 60 patients were enrolled in a prospective and randomized study. In half of the patients a bare Wallstent was used, and in the other half a Viabil biliary stent. Patients were followed up until death. Primary patency, survival, complication rates, and mean cost were calculated in both groups. Stent dysfunction occurred in 9 (30%) patients in the bare stent group after a mean period of 133.1 days and in 4 (13.3%) patients in the covered stent group after a mean of 179.5 days. The incidence of stent dysfunction was significantly lower in the covered stent group (P = 0.046). Tumor ingrowth occurred exclusively in the bare stent group (P = 0.007). Median survival was 180.5 days for the Wallstent and 243.5 days for the Viabil group (P = 0.039). Complications and mean cost were similar in the two groups. Viabil stent-grafts proved to be significantly superior to Wallstents for the palliation of malignant jaundice due to extrahepatic cholangiocarcinoma, with comparable cost and complication rates. Appropriate patient selection should be performed prior to stent placement.

  4. Uncovering novel mobile genetic elements and their dynamics through an extra-chromosomal sequencing approach.

    PubMed

    Deutsch, Douglas R; Utter, Bryan; Fischetti, Vincent A

    2016-01-01

    Staphylococcus aureus is a major clinically important pathogen with well-studied phage contributions to its virulence potential. In this commentary, we describe our method to enrich and sequence stealth extra-chromosomal DNA elements in the bacterial cell, allowing the identification of novel extra-chromosomal prophages in S. aureus clinical strains. Extra-chromosomal sequencing is a useful and broadly applicable tool to study bacterial genomics, giving a temporal glance at the extra-chromosomal compartment of the cell and allowing researchers to uncover lower-copy plasmidial elements (e.g., prophages) as well as gain a greater understanding of mobile genetic elements that shuffle on and off the chromosome. Here, we describe how episomal and plasmidial DNA elements can have profound downstream effects on the host cell and surrounding bacterial population, and discuss specific examples of their importance in Gram-positive bacteria. We also offer potential avenues of future research where extra-chromosomal sequencing may play a key role in our understanding of the complete virulence potential of infectious bacteria. PMID:27581613

  5. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

    PubMed

    Kilpeläinen, Tuomas O; Carli, Jayne F Martin; Skowronski, Alicja A; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K; Drong, Alexander W; Hayes, James E; Zhao, Jinghua; Pers, Tune H; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Del Greco M, Fabiola; Pasko, Dorota; Renström, Frida; Willems, Sara M; Mahajan, Anubha; Rose, Lynda M; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S; Ju Sung, Yun; Ramos, Yolande F; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J N; Crosslin, David R; Dale, Caroline E; Dastani, Zari; Day, Felix R; Deelen, Joris; Delgado, Graciela E; Demirkan, Ayse; Finucane, Francis M; Ford, Ian; Garcia, Melissa E; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A; Hunter, David J; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S; Jørgensen, Marit E; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P; Myers, Richard H; Männistö, Satu; Nalls, Mike A; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D; Rankinen, Tuomo; Rasmussen-Torvik, Laura J; Rathmann, Wolfgang; Rice, Treva K; Brent Richards, J; Ridker, Paul M; Sattar, Naveed; Savage, David B; Söderberg, Stefan; Timpson, Nicholas J; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I A; Sarzynski, Mark A; Rao, D C; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G; Heliövaara, Markku; Knekt, Paul B; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K; Viikari, Jorma S; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W; van Duijn, Cornelia M; Harris, Tamara B; Bouchard, Claude; Allison, Matthew A; Chasman, Daniel I; Ohlsson, Claes; Lind, Lars; Scott, Robert A; Langenberg, Claudia; Wareham, Nicholas J; Ferrucci, Luigi; Frayling, Timothy M; Pramstaller, Peter P; Borecki, Ingrid B; Waterworth, Dawn M; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B; Eline Slagboom, P; Grallert, Harald; Spector, Tim D; Jukema, J W; Klein, Robert J; Schadt, Erik E; Franks, Paul W; Lindgren, Cecilia M; Leibel, Rudolph L; Loos, Ruth J F

    2016-02-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

  6. Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus

    PubMed Central

    Wiemann, Philipp; Lechner, Beatrix E.; Baccile, Joshua A.; Velk, Thomas A.; Yin, Wen-Bing; Bok, Jin Woo; Pakala, Suman; Losada, Liliana; Nierman, William C.; Schroeder, Frank C.; Haas, Hubertus; Keller, Nancy P.

    2014-01-01

    Iron plays a critical role in survival and virulence of the opportunistic pathogen Aspergillus fumigatus. Two transcription factors, the GATA-factor SreA and the bZip-factor HapX oppositely monitor iron homeostasis with HapX activating iron acquisition pathways (e.g., siderophores) and shutting down iron consumptive pathways (and SreA) during iron starvation conditions whereas SreA negatively regulates HapX and corresponding pathways during iron sufficiency. Recently the non-ribosomal peptide, hexadehydroastechrome (HAS; a tryptophan-derived iron (III)-complex), has been found important in A. fumigatus virulence. We found that HAS overproduction caused an iron starvation phenotype, from alteration of siderophore pools to regulation of iron homeostasis gene expression including sreA. Moreover, we uncovered an iron dependent secondary metabolism network where both SreA and HapX oppositely regulate multiple other secondary metabolites including HAS. This circuitry links iron-acquisition and consumption pathways with secondary metabolism—thus placing HAS as part of a metabolic feedback circuitry designed to balance iron pools in the fungus and presenting iron availability as one environmental trigger of secondary metabolism. PMID:25386169

  7. Structural phylogenomics uncovers the early and concurrent origins of cysteine biosynthesis and iron-sulfur proteins.

    PubMed

    Zhang, Hong-Yu; Qin, Tao; Jiang, Ying-Ying; Caetano-Anollés, Gustavo

    2012-01-01

    Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ~3.5 billion years ago while the tRNA-independent counterpart emerged ~500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history.

  8. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging.

    PubMed

    Rose, P B; Erickson, A S; Mayer, M; Nattress, J; Jovanovic, I

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as "searching for a needle in a haystack" because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material's areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  9. Uncovering major genomic features of essential genes in Bacteria and a methanogenic Archaea.

    PubMed

    Grazziotin, Ana Laura; Vidal, Newton M; Venancio, Thiago M

    2015-09-01

    Identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. Although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. Here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for growth in vivo, encompassing 15 Bacteria and one Archaea. We refine and generalize important theories proposed using Escherichia coli. Essential genes are typically monogenic and more conserved than nonessential genes. Genes required in vivo are less conserved than those essential in vitro, suggesting that more divergent strategies are deployed when the organism is stressed by the host immune system and unstable nutrient availability. We identified essential analogous pathways that would probably be missed by orthology-based essentiality prediction strategies. For example, Streptococcus sanguinis carries horizontally transferred isoprenoid biosynthesis genes that are widespread in Archaea. Genes specifically essential in Mycobacterium tuberculosis and Burkholderia pseudomallei are reported as potential drug targets. Moreover, essential genes are not only preferentially located in operons, but also occupy the first position therein, supporting the influence of their regulatory regions in driving transcription of whole operons. Finally, these important genomic features are shared between Bacteria and at least one Archaea, suggesting that high order properties of gene essentiality and genome architecture were probably present in the last universal common ancestor or evolved independently in the prokaryotic domains.

  10. Uncovering system-specific stress signatures in primate teeth with multimodal imaging

    PubMed Central

    Austin, Christine; Smith, Tanya M.; Farahani, Ramin M. Z.; Hinde, Katie; Carter, Elizabeth A.; Lee, Joonsup; Lay, Peter A.; Kennedy, Brendan J.; Sarrafpour, Babak; Wright, Rosalind J.; Wright, Robert O.; Arora, Manish

    2016-01-01

    Early life stress can disrupt development and negatively impact long-term health trajectories. Reconstructing histories of early life exposure to external stressors is hampered by the absence of retrospective time-specific biomarkers. Defects in tooth enamel have been used to reconstruct stress but the methods used are subjective and do not identify the specific biological systems impacted by external stressors. Here we show that external physical and social stressors impart biochemical signatures in primate teeth that can be retrieved to objectively reconstruct the timing of early life developmental disruptions. Using teeth from captive macaques, we uncovered elemental imprints specific to disruptions of skeletal growth, including major disruptions in body weight trajectory and moderate to severe illnesses. Discrete increases in heat shock protein-70 expression in dentine coincided with elemental signatures, confirming that elemental signals were associated with activation of stress-related pathways. To overcome limitations of conventional light-microscopic analysis, we used high resolution Raman microspectral imaging to identify structural and compositional alterations in enamel and dentine that coincided with elemental signatures and with detailed medical and behavioural data. Integrating these objective biochemical markers with temporal mapping of teeth enables the retrospective study of early life developmental disruptions and their ensuing health sequelae. PMID:26727334

  11. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data. PMID:27610367

  12. Uncovering DELLA-Independent Gibberellin Responses by Characterizing New Tomato procera Mutants

    PubMed Central

    Livne, Sivan; Lor, Vai S.; Nir, Ido; Eliaz, Natanella; Aharoni, Asaph; Olszewski, Neil E.; Eshed, Yuval; Weiss, David

    2015-01-01

    Gibberellin (GA) regulates plant development primarily by triggering the degradation/deactivation of the DELLA proteins. However, it remains unclear whether all GA responses are regulated by DELLAs. Tomato (Solanum lycopersicum) has a single DELLA gene named PROCERA (PRO), and its recessive pro allele exhibits constitutive GA activity but retains responsiveness to external GA. In the loss-of-function mutant proΔGRAS, all examined GA developmental responses were considerably enhanced relative to pro and a defect in seed desiccation tolerance was uncovered. As pro, but not proΔGRAS, elongation was promoted by GA treatment, pro may retain residual DELLA activity. In agreement with homeostatic feedback regulation of the GA biosynthetic pathway, we found that GA20oxidase1 expression was suppressed in proΔGRAS and was not affected by exogenous GA3. In contrast, expression of GA2oxidase4 was not affected by the elevated GA signaling in proΔGRAS but was strongly induced by exogenous GA3. Since a similar response was found in Arabidopsis thaliana plants with impaired activity of all five DELLA genes, we suggest that homeostatic GA responses are regulated by both DELLA-dependent and -independent pathways. Transcriptome analysis of GA-treated proΔGRAS leaves suggests that 5% of all GA-regulated genes in tomato are DELLA independent. PMID:26036254

  13. Chirally modified platinum generated by adsorption of cinchonidine ether derivatives: towards uncovering the chiral sites.

    PubMed

    Bonalumi, Norberto; Vargas, Angelo; Ferri, Davide; Baiker, Alfons

    2007-01-01

    The adsorption behavior of O-methyl and O-trimethylsilyl derivatives of cinchonidine (CD), employed as chiral modifiers for heterogeneous enantioselective hydrogenations on supported Pt catalysts, has been investigated by using attenuated total reflection infrared spectroscopy (ATR-IR) and density functional theory (DFT) electronic structure calculations. The ATR-IR spectroscopic investigation provided detailed insight of the adsorbed modifiers under conditions close to those employed during catalytic processes, and electronic structure calculations were used as a complement to the experiments to uncover the implications of conformational changes in generating the topology of the surface chiral site. The structural investigation of the adsorbed modifiers revealed a relationship between the spatial positions of the ether substituents and the enantiodifferentiation induced by the modified catalyst observed in the hydrogenation of alpha-activated ketones. Experiments and calculations corroborate a model, according to which the addition of a bulky ether group to CD reshapes the chiral sites, thus generating catalytic chiral surfaces with different and, in some cases (e.g. hydrogenation of ketopantolactone), even opposite enantioselective properties to those obtained with CD without altering the absolute configuration of the modifier. The study also confirms that active surface conformations of cinchona modifiers are markedly different from those existing in vacuum and in solution, thus underlying the necessity of investigating the surface-modifier interaction in order to understand enantioselectivity.

  14. Cryptic no more: soil macrofossils uncover Pleistocene forest microrefugia within a periglacial desert.

    PubMed

    de Lafontaine, Guillaume; Amasifuen Guerra, Carlos Alberto; Ducousso, Alexis; Petit, Rémy J

    2014-11-01

    Despite their critical importance for understanding the local effects of global climate change on biodiversity, glacial microrefugia are not well studied because they are difficult to detect by using classical palaeoecological or population genetics approaches. We used soil macrofossil charcoal analysis to uncover the presence of cryptic glacial refugia for European beech (Fagus sylvatica) and other tree species in the Landes de Gascogne (southwestern France). Using botanical identification and direct radiocarbon dating (140 (14) C-dates) of macrofossil charcoal extracted from mineral soils, we reconstructed the glacial and postglacial history of all extant beech stands in the region (n = 11). Soil charcoal macrofossils were found in all sites, allowing the identification of up to at least 14 distinct fire events per site. There was direct evidence of the presence of beech during the last glacial period at three sites. Beech was detected during Heinrich stadial-1, one of the coldest and driest intervals of the last glacial period in Western Europe. Together with previous results on the genetic structure of the species in the region, these findings suggest that beech persisted in situ in several microrefugia through full glacial and interglacial periods up to the present day. PMID:25312611

  15. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    NASA Astrophysics Data System (ADS)

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-04-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications.

  16. Microarray data mining: A novel optimization-based approach to uncover biologically coherent structures

    PubMed Central

    Tan, Meng P; Smith, Erin N; Broach, James R; Floudas, Christodoulos A

    2008-01-01

    Background DNA microarray technology allows for the measurement of genome-wide expression patterns. Within the resultant mass of data lies the problem of analyzing and presenting information on this genomic scale, and a first step towards the rapid and comprehensive interpretation of this data is gene clustering with respect to the expression patterns. Classifying genes into clusters can lead to interesting biological insights. In this study, we describe an iterative clustering approach to uncover biologically coherent structures from DNA microarray data based on a novel clustering algorithm EP_GOS_Clust. Results We apply our proposed iterative algorithm to three sets of experimental DNA microarray data from experiments with the yeast Saccharomyces cerevisiae and show that the proposed iterative approach improves biological coherence. Comparison with other clustering techniques suggests that our iterative algorithm provides superior performance with regard to biological coherence. An important consequence of our approach is that an increasing proportion of genes find membership in clusters of high biological coherence and that the average cluster specificity improves. Conclusion The results from these clustering experiments provide a robust basis for extracting motifs and trans-acting factors that determine particular patterns of expression. In addition, the biological coherence of the clusters is iteratively assessed independently of the clustering. Thus, this method will not be severely impacted by functional annotations that are missing, inaccurate, or sparse. PMID:18538024

  17. Plant Phenotyping using Probabilistic Topic Models: Uncovering the Hyperspectral Language of Plants.

    PubMed

    Wahabzada, Mirwaes; Mahlein, Anne-Katrin; Bauckhage, Christian; Steiner, Ulrike; Oerke, Erich-Christian; Kersting, Kristian

    2016-01-01

    Modern phenotyping and plant disease detection methods, based on optical sensors and information technology, provide promising approaches to plant research and precision farming. In particular, hyperspectral imaging have been found to reveal physiological and structural characteristics in plants and to allow for tracking physiological dynamics due to environmental effects. In this work, we present an approach to plant phenotyping that integrates non-invasive sensors, computer vision, as well as data mining techniques and allows for monitoring how plants respond to stress. To uncover latent hyperspectral characteristics of diseased plants reliably and in an easy-to-understand way, we "wordify" the hyperspectral images, i.e., we turn the images into a corpus of text documents. Then, we apply probabilistic topic models, a well-established natural language processing technique that identifies content and topics of documents. Based on recent regularized topic models, we demonstrate that one can track automatically the development of three foliar diseases of barley. We also present a visualization of the topics that provides plant scientists an intuitive tool for hyperspectral imaging. In short, our analysis and visualization of characteristic topics found during symptom development and disease progress reveal the hyperspectral language of plant diseases. PMID:26957018

  18. Uncovering secrets behind low-resistance planing craft hull forms through optimization

    NASA Astrophysics Data System (ADS)

    Mohamad Ayob, Ahmad F.; Ray, Tapabrata; Smith, Warren F.

    2011-11-01

    There has always been significant interest within the naval architectural research community to identify ship hull forms with low resistance. While numerous design optimization frameworks have been proposed over the years to support the activity, very little attention has been paid towards the process of gaining an understanding of 'what makes a good ship design superior?'. Furthermore, there have been limited attempts to identify computationally cheap indicators that can be used to distinguish between good and poor designs. A recent technique named discovery of innovative design principles, which is aimed at understanding the relationship between the design variables, is incorporated in this work. In this article, optimal high-speed planing craft hull forms with minimum calm-water resistance are identified through the use of three state-of-the-art optimization algorithms. Collections of such designs are then used to uncover insights into the underlying relationships between the variables. The importance of such relationships is further analysed to identify computationally cheap performance indicators that can be used in lieu of detailed calm-water resistance calculations. Such indicators are useful at the concept and preliminary design stages, where one needs to sieve efficiently through a number of candidate designs to identify the better ones for further analysis.

  19. Uncovering Special Nuclear Materials by Low-energy Nuclear Reaction Imaging

    PubMed Central

    Rose, P. B.; Erickson, A. S.; Mayer, M.; Nattress, J.; Jovanovic, I.

    2016-01-01

    Weapons-grade uranium and plutonium could be used as nuclear explosives with extreme destructive potential. The problem of their detection, especially in standard cargo containers during transit, has been described as “searching for a needle in a haystack” because of the inherently low rate of spontaneous emission of characteristic penetrating radiation and the ease of its shielding. Currently, the only practical approach for uncovering well-shielded special nuclear materials is by use of active interrogation using an external radiation source. However, the similarity of these materials to shielding and the required radiation doses that may exceed regulatory limits prevent this method from being widely used in practice. We introduce a low-dose active detection technique, referred to as low-energy nuclear reaction imaging, which exploits the physics of interactions of multi-MeV monoenergetic photons and neutrons to simultaneously measure the material’s areal density and effective atomic number, while confirming the presence of fissionable materials by observing the beta-delayed neutron emission. For the first time, we demonstrate identification and imaging of uranium with this novel technique using a simple yet robust source, setting the stage for its wide adoption in security applications. PMID:27087555

  20. Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels

    PubMed Central

    Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.; Sun, Qi; Kriebel, Jennifer; Feitosa, Mary F; Hedman, Åsa K.; Drong, Alexander W.; Hayes, James E.; Zhao, Jinghua; Pers, Tune H.; Schick, Ursula; Grarup, Niels; Kutalik, Zoltán; Trompet, Stella; Mangino, Massimo; Kristiansson, Kati; Beekman, Marian; Lyytikäinen, Leo-Pekka; Eriksson, Joel; Henneman, Peter; Lahti, Jari; Tanaka, Toshiko; Luan, Jian'an; Greco M, Fabiola Del; Pasko, Dorota; Renström, Frida; Willems, Sara M.; Mahajan, Anubha; Rose, Lynda M.; Guo, Xiuqing; Liu, Yongmei; Kleber, Marcus E.; Pérusse, Louis; Gaunt, Tom; Ahluwalia, Tarunveer S.; Ju Sung, Yun; Ramos, Yolande F.; Amin, Najaf; Amuzu, Antoinette; Barroso, Inês; Bellis, Claire; Blangero, John; Buckley, Brendan M.; Böhringer, Stefan; I Chen, Yii-Der; de Craen, Anton J. N.; Crosslin, David R.; Dale, Caroline E.; Dastani, Zari; Day, Felix R.; Deelen, Joris; Delgado, Graciela E.; Demirkan, Ayse; Finucane, Francis M.; Ford, Ian; Garcia, Melissa E.; Gieger, Christian; Gustafsson, Stefan; Hallmans, Göran; Hankinson, Susan E.; Havulinna, Aki S; Herder, Christian; Hernandez, Dena; Hicks, Andrew A.; Hunter, David J.; Illig, Thomas; Ingelsson, Erik; Ioan-Facsinay, Andreea; Jansson, John-Olov; Jenny, Nancy S.; Jørgensen, Marit E.; Jørgensen, Torben; Karlsson, Magnus; Koenig, Wolfgang; Kraft, Peter; Kwekkeboom, Joanneke; Laatikainen, Tiina; Ladwig, Karl-Heinz; LeDuc, Charles A.; Lowe, Gordon; Lu, Yingchang; Marques-Vidal, Pedro; Meisinger, Christa; Menni, Cristina; Morris, Andrew P.; Myers, Richard H.; Männistö, Satu; Nalls, Mike A.; Paternoster, Lavinia; Peters, Annette; Pradhan, Aruna D.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rathmann, Wolfgang; Rice, Treva K.; Brent Richards, J; Ridker, Paul M.; Sattar, Naveed; Savage, David B.; Söderberg, Stefan; Timpson, Nicholas J.; Vandenput, Liesbeth; van Heemst, Diana; Uh, Hae-Won; Vohl, Marie-Claude; Walker, Mark; Wichmann, Heinz-Erich; Widén, Elisabeth; Wood, Andrew R.; Yao, Jie; Zeller, Tanja; Zhang, Yiying; Meulenbelt, Ingrid; Kloppenburg, Margreet; Astrup, Arne; Sørensen, Thorkild I. A.; Sarzynski, Mark A.; Rao, D. C.; Jousilahti, Pekka; Vartiainen, Erkki; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Kajantie, Eero; Osmond, Clive; Palotie, Aarno; Eriksson, Johan G.; Heliövaara, Markku; Knekt, Paul B.; Koskinen, Seppo; Jula, Antti; Perola, Markus; Huupponen, Risto K.; Viikari, Jorma S.; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli T.; Mellström, Dan; Lorentzon, Mattias; Casas, Juan P.; Bandinelli, Stefanie; März, Winfried; Isaacs, Aaron; van Dijk, Ko W.; van Duijn, Cornelia M.; Harris, Tamara B.; Bouchard, Claude; Allison, Matthew A.; Chasman, Daniel I.; Ohlsson, Claes; Lind, Lars; Scott, Robert A.; Langenberg, Claudia; Wareham, Nicholas J.; Ferrucci, Luigi; Frayling, Timothy M.; Pramstaller, Peter P.; Borecki, Ingrid B.; Waterworth, Dawn M.; Bergmann, Sven; Waeber, Gérard; Vollenweider, Peter; Vestergaard, Henrik; Hansen, Torben; Pedersen, Oluf; Hu, Frank B.; Eline Slagboom, P; Grallert, Harald; Spector, Tim D.; Jukema, J.W.; Klein, Robert J.; Schadt, Erik E; Franks, Paul W.; Lindgren, Cecilia M.; Leibel, Rudolph L.; Loos, Ruth J. F.

    2016-01-01

    Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10−6 in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10−8) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID:26833098

  1. Structural phylogenomics uncovers the early and concurrent origins of cysteine biosynthesis and iron-sulfur proteins.

    PubMed

    Zhang, Hong-Yu; Qin, Tao; Jiang, Ying-Ying; Caetano-Anollés, Gustavo

    2012-01-01

    Cysteine (Cys) has unique chemical properties of catalysis, metal chelation, and protein stabilization. While Cys biosynthesis is assumed to be very ancient, the actual time of origin of these metabolic pathways remains unknown. Here, we use the molecular clocks of protein folds and fold superfamilies to time the origin of Cys biosynthesis. We find that the tRNA-dependent biosynthetic pathway appeared ~3.5 billion years ago while the tRNA-independent counterpart emerged ~500 million years later. A deep analysis of the origins of Cys biosynthesis in the context of emerging biochemistry uncovers some intriguing features of the planetary environment of early Earth. Results suggest that iron-sulfur (Fe-S) proteins that use cysteinyl sulfur to bind iron atoms were not the first to arise in evolution. Instead, their origin coincides with the appearance of the first Cys biosynthetic pathway. It is therefore likely that Cys did not play an important role in the make up of primordial protein molecules and that Fe-S clusters were not part of active sites at the beginning of biological history. PMID:22731683

  2. Uncovering the connectivity of coral reef systems via Lagrangian Coherent Structures

    NASA Astrophysics Data System (ADS)

    Leclair, Matthieu; Lowe, Ryan; Zang, Zhenlin; Ivey, Gregory; Peacock, Thomas

    2015-04-01

    There has been a staggering decline in the health of coral reef ecosystems worldwide over the past century, driven by anthropogenic influences, natural processes, and overall climate change. The future of coral reefs depends largely on their ability to recover from catastrophic events, which in turn crucially relies on the ability of reef larval populations to supply and restore damaged reefs. Improving quantitative predictions of reef larval transport and connectivity has thus emerged as a high priority research area in coral reef science. Ocean circulation models are being increasingly utilized in conjunction with particle tracking methods to provide spatially explicit predictions of larval transport within reef systems. The current major drawback of this approach is that it does not elucidate the underlying yet dynamic flow structures that drive reef connectivity. Recently, however, novel Lagrangian-based analysis approaches have been developed to identify the hidden coherent structures that govern material transport in spatiotemporally complex flow fields. Here we apply these methods to investigate the connectivity within a complex coral reef system, using the UNESCO World Heritage Ningaloo Reef in Australia as a case study. Our study demonstrates how this new approach identifies the dominant flow structures present on the reef, thereby uncovering connectivity and advocating a new practical framework for investigating and understanding how ocean processes shape the ecological transport in and around coral reefs. The technique can prove particularly valuable in supporting the design of Marine Protected Areas that are intended to safeguard the future of coral reefs and other ocean ecosystems.

  3. Using comparative genomics to uncover new kinds of protein-based metabolic organelles in bacteria

    PubMed Central

    Jorda, Julien; Lopez, David; Wheatley, Nicole M; Yeates, Todd O

    2013-01-01

    Bacterial microcompartment (MCP) organelles are cytosolic, polyhedral structures consisting of a thin protein shell and a series of encapsulated, sequentially acting enzymes. To date, different microcompartments carrying out three distinct types of metabolic processes have been characterized experimentally in various bacteria. In the present work, we use comparative genomics to explore the existence of yet uncharacterized microcompartments encapsulating a broader set of metabolic pathways. A clustering approach was used to group together enzymes that show a strong tendency to be encoded in chromosomal proximity to each other while also being near genes for microcompartment shell proteins. The results uncover new types of putative microcompartments, including one that appears to encapsulate B12-independent, glycyl radical-based degradation of 1,2-propanediol, and another potentially involved in amino alcohol metabolism in mycobacteria. Preliminary experiments show that an unusual shell protein encoded within the glycyl radical-based microcompartment binds an iron-sulfur cluster, hinting at complex mechanisms in this uncharacterized system. In addition, an examination of the computed microcompartment clusters suggests the existence of specific functional variations within certain types of MCPs, including the alpha carboxysome and the glycyl radical-based microcompartment. The findings lead to a deeper understanding of bacterial microcompartments and the pathways they sequester. PMID:23188745

  4. Uncovering the role of hypoxia inducible factor-1α in skin carcinogenesis.

    PubMed

    Nys, Kris; Maes, Hannelore; Dudek, Aleksandra Maria; Agostinis, Patrizia

    2011-08-01

    The hypoxia inducible factor-1α (HIF-1α) is a pleiotropic transcription factor typically activated in response to low oxygen tension as well as other stress factors in normoxic conditions. Upon activation HIF-1α mediates the transcriptional activation of target genes involved in a variety of processes comprising stress adaptation, metabolism, growth and invasion, but also apoptotic cell death. The molecular mechanisms, signaling pathways and downstream targets evoked by the activation of HIF-1α in epidermal cells are becoming increasingly understood and underscore the participation of HIF-1α in crucial processes including malignant transformation and cancer progression. Recent studies have implicated HIF-1α as an integral part of the multifaceted signal transduction initiated by the exposure of keratinocytes to ultraviolet radiation B (UVB), which represents the most ubiquitous hazard for human skin and the principal risk factor for skin cancer. HIF-1α activation by UVB exposure contributes to either repair or the removal of UVB-damaged keratinocytes by inducing apoptosis, thus revealing a tumor suppressor role for HIF-1α in these cells. On the other hand, the constitutive expression of HIF-1α evoked by the mild hypoxic state of the skin has been implicated as a positive factor in the transformation of normal melanocytes into malignant melanoma, one of the most aggressive types of human cancers. Here we review the uncovered and complex role of HIF-1α in skin carcinogenesis. PMID:21338656

  5. Genome-wide analysis uncovers novel recurrent alterations in primary central nervous system lymphomas

    PubMed Central

    Braggio, Esteban; Van Wier, Scott; Ojha, Juhi; McPhail, Ellen; Asmann, Yan W.; Egan, Jan; da Silva, Jackline Ayres; Schiff, David; Lopes, M Beatriz; Decker, Paul A; Valdez, Riccardo; Tibes, Raoul; Eckloff, Bruce; Witzig, Thomas E.; Stewart, A Keith; Fonseca, Rafael; O’Neill, Brian Patrick

    2015-01-01

    Purpose Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin lymphoma confined to the CNS. Whether there is a PCNSL-specific genomic signature and, if so, how it differs from systemic diffuse large B-cell lymphoma (DLBCL) is uncertain. Experimental design We performed a comprehensive genomic study of tumor samples from 19 immunocompetent PCNSL patients. Testing comprised array-comparative genomic hybridization and whole exome sequencing. Results Biallelic inactivation of TOX and PRKCD were recurrently found in PCNSL but not in systemic DLBCL, suggesting a specific role in PCNSL pathogenesis. Additionally, we found a high prevalence of MYD88 mutations (79%) and CDKN2A biallelic loss (60%). Several genes recurrently affected in PCNSL were common with systemic DLBCL, including loss of TNFAIP3, PRDM1, GNA13, TMEM30A, TBL1XR1, B2M, CD58, activating mutations of CD79B, CARD11 and translocations IgH-BCL6. Overall, BCR/TLR/NF-κB pathways were altered in >90% of PNCSL, highlighting its value for targeted therapeutic approaches. Furthermore, integrated analysis showed enrichment of pathways associated with immune response, proliferation, apoptosis, and lymphocyte differentiation. Conclusions In summary, genome-wide analysis uncovered novel recurrent alterations, including TOX and PRKCD, helping to differentiate PCNSL from systemic DLBCL and related lymphomas. PMID:25991819

  6. Uncovering Driver DNA Methylation Events in Nonsmoking Early Stage Lung Adenocarcinoma

    PubMed Central

    Jia, Songwei; Chen, Luonan

    2016-01-01

    As smoking rates decrease, proportionally more cases with lung adenocarcinoma occur in never-smokers, while aberrant DNA methylation has been suggested to contribute to the tumorigenesis of lung adenocarcinoma. It is extremely difficult to distinguish which genes play key roles in tumorigenic processes via DNA methylation-mediated gene silencing from a large number of differentially methylated genes. By integrating gene expression and DNA methylation data, a pipeline combined with the differential network analysis is designed to uncover driver methylation genes and responsive modules, which demonstrate distinctive expressions and network topology in tumors with aberrant DNA methylation. Totally, 135 genes are recognized as candidate driver genes in early stage lung adenocarcinoma and top ranked 30 genes are recognized as driver methylation genes. Functional annotation and the differential network analysis indicate the roles of identified driver genes in tumorigenesis, while literature study reveals significant correlations of the top 30 genes with early stage lung adenocarcinoma in never-smokers. The analysis pipeline can also be employed in identification of driver epigenetic events for other cancers characterized by matched gene expression data and DNA methylation data.

  7. Uncovering buffered pleiotropy: a genome-scale screen for mel-28 genetic interactors in Caenorhabditis elegans.

    PubMed

    Fernandez, Anita G; Mis, Emily K; Lai, Allison; Mauro, Michael; Quental, Angela; Bock, Carly; Piano, Fabio

    2014-01-10

    mel-28 (maternal-effect-lethal-28) encodes a conserved protein required for nuclear envelope function and chromosome segregation in Caenorhabditis elegans. Because mel-28 is a strict maternal-effect lethal gene, its function is required in the early embryo but appears to be dispensable for larval development. We wanted to test the idea that mel-28 has postembryonic roles that are buffered by the contributions of other genes. To find genes that act coordinately with mel-28, we did an RNA interference-based genetic interaction screen using mel-28 and wild-type larvae. We screened 18,364 clones and identified 65 genes that cause sterility in mel-28 but not wild-type worms. Some of these genes encode components of the nuclear pore. In addition we identified genes involved in dynein and dynactin function, vesicle transport, and cell-matrix attachments. By screening mel-28 larvae we have bypassed the requirement for mel-28 in the embryo, uncovering pleiotropic functions for mel-28 later in development that are normally provided by other genes. This work contributes toward revealing the gene networks that underlie cellular processes and reveals roles for a maternal-effect lethal gene later in development.

  8. Uncovering paradoxes from physicians' experiences of patient-centered ward-round.

    PubMed

    Bååthe, Fredrik; Ahlborg, Gunnar; Edgren, Lars; Lagström, Annica; Nilsson, Kerstin

    2016-05-01

    Purpose The purpose of this paper is to uncover paradoxes emerging from physicians' experiences of a patient-centered and team-based ward round, in an internal medicine department. Design/methodology/approach Abductive reasoning relates empirical material to complex responsive processes theory in a dialectical process to further understandings. Findings This paper found the response from physicians, to a patient-centered and team-based ward round, related to whether the new demands challenged or confirmed individual physician's professional identity. Two empirically divergent perspectives on enacting the role of physician during ward round emerged: We-perspective and I-perspective, based on where the physician's professional identity was centered. Physicians with more of a We-perspective experienced challenges with the new round, while physicians with more of an I-perspective experienced alignment with their professional identity and embraced the new round. When identity is challenged, anxiety is aroused, and if anxiety is not catered to, then resistance is likely to follow and changes are likely to be hampered. Practical implications For change processes affecting physicians' professional identity, it is important for managers and change leaders to acknowledge paradox and find a balance between new knowledge that needs to be learnt and who the physician is becoming in this new procedure. Originality/value This paper provides increased understanding about how physicians' professional identity is interacting with a patient-centered ward round. It adds to the knowledge about developing health care in line with recent societal requests and with sustainable physician engagement. PMID:27198705

  9. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds

    PubMed Central

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-01-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal–habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities. PMID:25558353

  10. Uncovering multiple populations with washington photometry. I. The globular cluster NGC 1851

    SciTech Connect

    Cummings, Jeffrey D.; Geisler, D.; Villanova, S.; Carraro, G.

    2014-08-01

    The analysis of multiple populations (MPs) in globular clusters (GCs) has become a forefront area of research in astronomy. Multiple red giant branches (RGBs), subgiant branches (SGBs), and even main sequences (MSs) have now been observed photometrically in many GCs, while broad abundance distributions of certain elements have been detected spectroscopically in most, if not all, GCs. UV photometry has been crucial in discovering and analyzing these MPs, but the Johnson U and the Stromgren and Sloan u filters that have generally been used are relatively inefficient and very sensitive to reddening and atmospheric extinction. In contrast, the Washington C filter is much broader and redder than these competing UV filters, making it far more efficient at detecting MPs and much less sensitive to reddening and extinction. Here, we investigate the use of the Washington system to uncover MPs using only a 1 m telescope. Our analysis of the well-studied GC NGC 1851 finds that the C filter is both very efficient and effective at detecting its previously discovered MPs in the RGB and SGB. Remarkably, we have also detected an intrinsically broad MS best characterized by two distinct but heavily overlapping populations that cannot be explained by binaries, field stars, or photometric errors. The MS distribution is in very good agreement with that seen on the RGB, with ∼30% of the stars belonging to the second population. There is also evidence for two sequences in the red horizontal branch, but this appears to be unrelated to the MPs in this cluster. Neither of these latter phenomena have been observed previously in this cluster. The redder MS stars are also more centrally concentrated than the blue MS. This is the first time MPs in an MS have been discovered from the ground, and using only a 1 m telescope. The Washington system thus proves to be a very powerful tool for investigating MPs, and holds particular promise for extragalactic objects where photons are limited.

  11. Step selection techniques uncover the environmental predictors of space use patterns in flocks of Amazonian birds.

    PubMed

    Potts, Jonathan R; Mokross, Karl; Stouffer, Philip C; Lewis, Mark A

    2014-12-01

    Understanding the behavioral decisions behind animal movement and space use patterns is a key challenge for behavioral ecology. Tools to quantify these patterns from movement and animal-habitat interactions are vital for transforming ecology into a predictive science. This is particularly important in environments undergoing rapid anthropogenic changes, such as the Amazon rainforest, where animals face novel landscapes. Insectivorous bird flocks are key elements of avian biodiversity in the Amazonian ecosystem. Therefore, disentangling and quantifying the drivers behind their movement and space use patterns is of great importance for Amazonian conservation. We use a step selection function (SSF) approach to uncover environmental drivers behind movement choices. This is used to construct a mechanistic model, from which we derive predicted utilization distributions (home ranges) of flocks. We show that movement decisions are significantly influenced by canopy height and topography, but depletion and renewal of resources do not appear to affect movement significantly. We quantify the magnitude of these effects and demonstrate that they are helpful for understanding various heterogeneous aspects of space use. We compare our results to recent analytic derivations of space use, demonstrating that the analytic approximation is only accurate when assuming that there is no persistence in the animals' movement. Our model can be translated into other environments or hypothetical scenarios, such as those given by proposed future anthropogenic actions, to make predictions of spatial patterns in bird flocks. Furthermore, our approach is quite general, so could potentially be used to understand the drivers of movement and spatial patterns for a wide variety of animal communities.

  12. RNA shotgun metagenomic sequencing of northern California (USA) mosquitoes uncovers viruses, bacteria, and fungi.

    PubMed

    Chandler, James Angus; Liu, Rachel M; Bennett, Shannon N

    2015-01-01

    Mosquitoes, most often recognized for the microbial agents of disease they may carry, harbor diverse microbial communities that include viruses, bacteria, and fungi, collectively called the microbiota. The composition of the microbiota can directly and indirectly affect disease transmission through microbial interactions that could be revealed by its characterization in natural populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing (SMS) approaches could allow the discovery of unknown members of the microbiota. In this study, we use RNA SMS to characterize the microbiota of seven individual mosquitoes (species include Culex pipiens, Culiseta incidens, and Ochlerotatus sierrensis) collected from a variety of habitats in California, USA. Sequencing was performed on the Illumina HiSeq platform and the resulting sequences were quality-checked and assembled into contigs using the A5 pipeline. Sequences related to single stranded RNA viruses of the Bunyaviridae and Rhabdoviridae were uncovered, along with an unclassified genus of double-stranded RNA viruses. Phylogenetic analysis finds that in all three cases, the closest relatives of the identified viral sequences are other mosquito-associated viruses, suggesting widespread host-group specificity among disparate viral taxa. Interestingly, we identified a Narnavirus of fungi, also reported elsewhere in mosquitoes, that potentially demonstrates a nested host-parasite association between virus, fungi, and mosquito. Sequences related to 8 bacterial families and 13 fungal families were found across the seven samples. Bacillus and Escherichia/Shigella were identified in all samples and Wolbachia was identified in all Cx. pipiens samples, while no single fungal genus was found in more than two samples. This study exemplifies the utility of RNA SMS in the characterization of the natural microbiota of mosquitoes and, in particular, the value of identifying all microbes associated with a specific host.

  13. RNA shotgun metagenomic sequencing of northern California (USA) mosquitoes uncovers viruses, bacteria, and fungi

    PubMed Central

    Chandler, James Angus; Liu, Rachel M.; Bennett, Shannon N.

    2015-01-01

    Mosquitoes, most often recognized for the microbial agents of disease they may carry, harbor diverse microbial communities that include viruses, bacteria, and fungi, collectively called the microbiota. The composition of the microbiota can directly and indirectly affect disease transmission through microbial interactions that could be revealed by its characterization in natural populations of mosquitoes. Furthermore, the use of shotgun metagenomic sequencing (SMS) approaches could allow the discovery of unknown members of the microbiota. In this study, we use RNA SMS to characterize the microbiota of seven individual mosquitoes (species include Culex pipiens, Culiseta incidens, and Ochlerotatus sierrensis) collected from a variety of habitats in California, USA. Sequencing was performed on the Illumina HiSeq platform and the resulting sequences were quality-checked and assembled into contigs using the A5 pipeline. Sequences related to single stranded RNA viruses of the Bunyaviridae and Rhabdoviridae were uncovered, along with an unclassified genus of double-stranded RNA viruses. Phylogenetic analysis finds that in all three cases, the closest relatives of the identified viral sequences are other mosquito-associated viruses, suggesting widespread host-group specificity among disparate viral taxa. Interestingly, we identified a Narnavirus of fungi, also reported elsewhere in mosquitoes, that potentially demonstrates a nested host-parasite association between virus, fungi, and mosquito. Sequences related to 8 bacterial families and 13 fungal families were found across the seven samples. Bacillus and Escherichia/Shigella were identified in all samples and Wolbachia was identified in all Cx. pipiens samples, while no single fungal genus was found in more than two samples. This study exemplifies the utility of RNA SMS in the characterization of the natural microbiota of mosquitoes and, in particular, the value of identifying all microbes associated with a specific host

  14. Using metaphorical techniques in focus groups to uncover mothers' feelings about family meals

    PubMed Central

    Kling, Leslie; Snider, Sue; Peterson, P. Michael

    2009-01-01

    Traditional nutrition education has not been shown to consistently produce behavior change. While it has been suggested that using emotion-based messages may be a better way to influence nutrition behavior change, this has not been well tested. Producing emotion-based messages is a multi-step process that begins with exploring subconscious barriers to behavior change rather than the more obvious and typically reported barriers. The purpose of this research was to uncover the emotional reasons, sometimes referred to as emotional pulse points, for mothers' choosing or not choosing to have more family meals. This would then serve as the first step to developing emotion-based messages promoting the benefits of family meals. Five focus group interviews were conducted with 51 low-income Black (n=28) and white (n=23) mothers. Metaphorical techniques were used to determine underlying feelings toward family and family meals. Discussions were video-taped, transcribed, and manually analyzed using a content-driven, immersion/crystallization approach to qualitative data analysis. Four themes emerged around the definition of family: acceptance, sharing, chaos, and protective/loyal. Some mothers felt mealtime was merely obligatory, and described it as stressful. Some reported a preference for attending to their own needs instead of sitting down with their children, while others felt that mealtime should be used to interact with and educate children and felt guilty when they were not able to provide family meals. Three themes emerged around feelings towards having or not having family meals: unimportant, important, and guilty. When explored further, mothers indicated that using the feeling of guilt to encourage family meals might be effective. Data obtained are being used to develop innovative, emotion-based messages that will be tested for effectiveness in promoting family meals. PMID:20090889

  15. Uncovering protein interaction in abstracts and text using a novel linear model and word proximity networks

    PubMed Central

    Abi-Haidar, Alaa; Kaur, Jasleen; Maguitman, Ana; Radivojac, Predrag; Rechtsteiner, Andreas; Verspoor, Karin; Wang, Zhiping; Rocha, Luis M

    2008-01-01

    Background: We participated in three of the protein-protein interaction subtasks of the Second BioCreative Challenge: classification of abstracts relevant for protein-protein interaction (interaction article subtask [IAS]), discovery of protein pairs (interaction pair subtask [IPS]), and identification of text passages characterizing protein interaction (interaction sentences subtask [ISS]) in full-text documents. We approached the abstract classification task with a novel, lightweight linear model inspired by spam detection techniques, as well as an uncertainty-based integration scheme. We also used a support vector machine and singular value decomposition on the same features for comparison purposes. Our approach to the full-text subtasks (protein pair and passage identification) includes a feature expansion method based on word proximity networks. Results: Our approach to the abstract classification task (IAS) was among the top submissions for this task in terms of measures of performance used in the challenge evaluation (accuracy, F-score, and area under the receiver operating characteristic curve). We also report on a web tool that we produced using our approach: the Protein Interaction Abstract Relevance Evaluator (PIARE). Our approach to the full-text tasks resulted in one of the highest recall rates as well as mean reciprocal rank of correct passages. Conclusion: Our approach to abstract classification shows that a simple linear model, using relatively few features, can generalize and uncover the conceptual nature of protein-protein interactions from the bibliome. Because the novel approach is based on a rather lightweight linear model, it can easily be ported and applied to similar problems. In full-text problems, the expansion of word features with word proximity networks is shown to be useful, although the need for some improvements is discussed. PMID:18834489

  16. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe

    NASA Astrophysics Data System (ADS)

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns.

  17. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe.

    PubMed

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns.

  18. Multivariate weighted recurrence network inference for uncovering oil-water transitional flow behavior in a vertical pipe.

    PubMed

    Gao, Zhong-Ke; Yang, Yu-Xuan; Cai, Qing; Zhang, Shan-Shan; Jin, Ning-De

    2016-06-01

    Exploring the dynamical behaviors of high water cut and low velocity oil-water flows remains a contemporary and challenging problem of significant importance. This challenge stimulates us to design a high-speed cycle motivation conductance sensor to capture spatial local flow information. We systematically carry out experiments and acquire the multi-channel measurements from different oil-water flow patterns. Then we develop a novel multivariate weighted recurrence network for uncovering the flow behaviors from multi-channel measurements. In particular, we exploit graph energy and weighted clustering coefficient in combination with multivariate time-frequency analysis to characterize the derived complex networks. The results indicate that the network measures are very sensitive to the flow transitions and allow uncovering local dynamical behaviors associated with water cut and flow velocity. These properties render our method particularly useful for quantitatively characterizing dynamical behaviors governing the transition and evolution of different oil-water flow patterns. PMID:27368782

  19. Self-Efficacy Beliefs and Mental Time Travel Ability: Uncovering a Hidden Relationship in Educational Settings

    ERIC Educational Resources Information Center

    Eren, Altay

    2009-01-01

    The aim of this study was threefold: first, it was to explore the profiles of student teachers' mental time travel ability; second, it was to examine the relationship between student teachers' mental time travel ability and self-efficacy beliefs; and third, it was to investigate the role of self-efficacy beliefs in relationship between the past…

  20. Successful treatment of endoleak Type I with uncovered EX-L stent after thoracic endovascular aneurysm repair†

    PubMed Central

    Buz, Semih; Zipfel, Burkhart; D'Ancona, Guiseppe; Hetzer, Roland

    2013-01-01

    Treatment of endoleaks after thoracic endovascular repair remains challenging, particularly when the proximal landing zone is small and partly includes the origin of the neck vessels. We report a Type Ia endoleak, occurring after thoracic endovascular aneurysm repair, which was successfully treated with a novel uncovered nitinol stent. With this success, we were able to avoid a conventional surgery to treat the endoleak. PMID:23255527

  1. Optical coherence tomography derived cut-off value of uncovered stent struts to predict adverse clinical outcomes after drug-eluting stent implantation.

    PubMed

    Won, Hoyoun; Shin, Dong-Ho; Kim, Byeong-Keuk; Mintz, Gary S; Kim, Jung-Sun; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2013-08-01

    Although the presence of uncovered struts may be associated with occurrence of stent thrombosis, the impact of uncovered struts detected routinely by optical coherence tomography (OCT) on subsequent long-term clinical outcomes remains unclear. The objective of this study was to determine the cut-off value of uncovered struts that predicted adverse clinical outcomes after drug eluting stent (DES) implantation. Major safety events (MSEs, a composite occurrence of cardiovascular death, myocardial infarction, and stent thrombosis) were evaluated in 489 DES-treated patients (535 lesions) during the median 851 days after follow-up OCT. MSEs occurred in six patients (four definite stent thrombosis and two sudden cardiac death). The best cut-off value of percentage of uncovered struts for predicting MSE was 5.9 % using the maximal χ(2) method: area under the receiver-operating characteristic curve = 0.779, 95 % confidence interval (CI) = 0.648-0.910, p = 0.019, a sensitivity of 83.3 % and a specificity of 70.3 %. Independent predictors for MSE were post-intervention minimal lumen diameter (odds ratio 0.019, 95 % CI = 0.001-0.513, p = 0.018) and percentage of uncovered struts ≥5.9 % (odds ratio 19.781, 95 % CI = 2.071-188.968, p = 0.010). A greater percentage of uncovered struts (the cut-off value of ≥5.9 % uncovered struts) might be significantly associated with occurrence of MSE after DES implantation. PMID:23615849

  2. Panoramic view of a superfamily of phosphatases through substrate profiling.

    PubMed

    Huang, Hua; Pandya, Chetanya; Liu, Chunliang; Al-Obaidi, Nawar F; Wang, Min; Zheng, Li; Toews Keating, Sarah; Aono, Miyuki; Love, James D; Evans, Brandon; Seidel, Ronald D; Hillerich, Brandan S; Garforth, Scott J; Almo, Steven C; Mariano, Patrick S; Dunaway-Mariano, Debra; Allen, Karen N; Farelli, Jeremiah D

    2015-04-21

    Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process. PMID:25848029

  3. Panoramic view of a superfamily of phosphatases through substrate profiling

    PubMed Central

    Huang, Hua; Pandya, Chetanya; Liu, Chunliang; Al-Obaidi, Nawar F.; Wang, Min; Zheng, Li; Toews Keating, Sarah; Aono, Miyuki; Love, James D.; Evans, Brandon; Seidel, Ronald D.; Hillerich, Brandan S.; Garforth, Scott J.; Almo, Steven C.; Mariano, Patrick S.; Dunaway-Mariano, Debra; Allen, Karen N.; Farelli, Jeremiah D.

    2015-01-01

    Large-scale activity profiling of enzyme superfamilies provides information about cellular functions as well as the intrinsic binding capabilities of conserved folds. Herein, the functional space of the ubiquitous haloalkanoate dehalogenase superfamily (HADSF) was revealed by screening a customized substrate library against >200 enzymes from representative prokaryotic species, enabling inferred annotation of ∼35% of the HADSF. An extremely high level of substrate ambiguity was revealed, with the majority of HADSF enzymes using more than five substrates. Substrate profiling allowed assignment of function to previously unannotated enzymes with known structure, uncovered potential new pathways, and identified iso-functional orthologs from evolutionarily distant taxonomic groups. Intriguingly, the HADSF subfamily having the least structural elaboration of the Rossmann fold catalytic domain was the most specific, consistent with the concept that domain insertions drive the evolution of new functions and that the broad specificity observed in HADSF may be a relic of this process. PMID:25848029

  4. Personal Omics Profiling Reveals Dynamic Molecular and Medical Phenotypes

    PubMed Central

    Chen, Rui; Mias, George I.; Li-Pook-Than, Jennifer; Jiang, Lihua; Lam, Hugo Y. K.; Chen, Rong; Miriami, Elana; Karczewski, Konrad J.; Hariharan, Manoj; Dewey, Frederick E.; Cheng, Yong; Clark, Michael J.; Im, Hogune; Habegger, Lukas; Balasubramanian, Suganthi; O'Huallachain, Maeve; Dudley, Joel T.; Hillenmeyer, Sara; Haraksingh, Rajini; Sharon, Donald; Euskirchen, Ghia; Lacroute, Phil; Bettinger, Keith; Boyle, Alan P.; Kasowski, Maya; Grubert, Fabian; Seki, Scott; Garcia, Marco; Whirl-Carrillo, Michelle; Gallardo, Mercedes; Blasco, Maria A.; Greenberg, Peter L.; Snyder, Phyllis; Klein, Teri E.; Altman, Russ B.; Butte, Atul; Ashley, Euan A.; Nadeau, Kari C.; Gerstein, Mark; Tang, Hua; Snyder, Michael

    2012-01-01

    SUMMARY Personalized medicine is expected to benefit from combining genomic information with regular monitoring of physiological states by multiple high-throughput methods. Here we present an integrative Personal Omics Profile (iPOP), an analysis that combines genomic, transcriptomic, proteomic, metabolomic, and autoantibody profiles from a single individual over a 14-month period. Our iPOP analysis revealed various medical risks, including Type II diabetes. It also uncovered extensive, dynamic changes in diverse molecular components and biological pathways across healthy and diseased conditions. Extremely high coverage genomic and transcriptomic data, which provide the basis of our iPOP, discovered extensive heteroallelic changes during healthy and diseased states and an unexpected RNA editing mechanism. This study demonstrates that longitudinal iPOP can be used to interpret healthy and disease states by connecting genomic information with additional dynamic omics activity. PMID:22424236

  5. Heterogeneity revealed by integrated genomic analysis uncovers a molecular switch in malignant uveal melanoma.

    PubMed

    de Lange, Mark J; van Pelt, Sake I; Versluis, Mieke; Jordanova, Ekaterina S; Kroes, Wilma G M; Ruivenkamp, Claudia; van der Burg, Sjoerd H; Luyten, Grégorius P M; van Hall, Thorbald; Jager, Martine J; van der Velden, Pieter A

    2015-11-10

    Gene expression profiles as well as genomic imbalances are correlated with disease progression in uveal melanoma (UM). We integrated expression and genomic profiles to obtain insight into the oncogenic mechanisms in development and progression of UM. We used tumor tissue from 64 enucleated eyes of UM patients for profiling. Mutations and genomic imbalances were quantified with digital PCR to study tumor heterogeneity and molecular pathogenesis. Gene expression analysis divided the UM panel into three classes. Class I presented tumors with a good prognosis and a distinct genomic make up that is characterized by 6p gain. The UM with a bad prognosis were subdivided into class IIa and class IIb. These classes presented similar survival risks but could be distinguished by tumor heterogeneity. Class IIa presented homogeneous tumors while class IIb tumors, on average, contained 30% of non-mutant cells. Tumor heterogeneity coincided with expression of a set of immune genes revealing an extensive immune infiltrate in class IIb tumors. Molecularly, class IIa and IIb presented the same genomic configuration and could only be distinguished by 8q copy number. Moreover, UM establish in the void of the immune privileged eye indicating that in IIb tumors the infiltrate is attracted by the UM. Combined our data show that chromosome 8q contains the locus that causes the immune phentotype of UM. UM thereby provides an unique opportunity to study immune attraction by tumors. PMID:26462151

  6. Primary School Teachers’ Assessment Profiles in Mathematics Education

    PubMed Central

    Veldhuis, Michiel; van den Heuvel-Panhuizen, Marja

    2014-01-01

    The aim of this study was to contribute to knowledge about classroom assessment by identifying profiles of teachers’ assessment of their students’ understanding of mathematics. For carrying out this study we used data of a nationwide teacher survey (N = 960) in the Netherlands. The data were collected by an online questionnaire. Through exploratory factor analyses the underlying structure of what is measured by this questionnaire was uncovered as consisting of five factors: Goal centeredness of assessment, Authentic nature of assessment, Perceived usefulness of assessment, Diversity of assessment problem format, and Allocated importance of assessing skills and knowledge. By using a latent class analysis four different assessment profiles of teachers were identified: Enthusiastic assessors, Mainstream assessors, Non-enthusiastic assessors, and Alternative assessors. The findings suggest that teachers with particular assessment profiles have qualitatively different assessment practices. The paper concludes with discussing theoretical implications of these assessment profiles and indications these profiles can offer both for designing material for professional development in classroom assessment and for evaluating changes in teachers’ classroom assessment practice. PMID:24466255

  7. DNA profiles from fingermarks.

    PubMed

    Templeton, Jennifer E L; Linacre, Adrian

    2014-11-01

    Criminal investigations would be considerably improved if DNA profiles could be routinely generated from single fingermarks. Here we report a direct DNA profiling method that was able to generate interpretable profiles from 71% of 170 fingermarks. The data are based on fingermarks from all 5 digits of 34 individuals. DNA was obtained from the fingermarks using a swab moistened with Triton-X, and the fibers were added directly to one of two commercial DNA profiling kits. All profiles were obtained without increasing the number of amplification cycles; therefore, our method is ideally suited for adoption by the forensic science community. We indicate the use of the technique in a criminal case in which a DNA profile was generated from a fingermark on tape that was wrapped around a drug seizure. Our direct DNA profiling approach is rapid and able to generate profiles from touched items when current forensic practices have little chance of success.

  8. Profiles in Action.

    ERIC Educational Resources Information Center

    Mortimore, Jo, Ed.

    This publication traces developments in the use of profiles produced over the last two years and attempts to face some difficult and controversial issues raised repeatedly in any consideration of profiling. The introduction addresses assessment issues. Section 2 discusses the technical issues surrounding profiles, or records of achievement, and…

  9. No Place to Hide: Missing Primitive Stars Outside Milky Way Uncovered

    NASA Astrophysics Data System (ADS)

    2010-02-01

    After years of successful concealment, the most primitive stars outside our Milky Way galaxy have finally been unmasked. New observations using ESO's Very Large Telescope have been used to solve an important astrophysical puzzle concerning the oldest stars in our galactic neighbourhood - which is crucial for our understanding of the earliest stars in the Universe. "We have, in effect, found a flaw in the forensic methods used until now," says Else Starkenburg, lead author of the paper reporting the study. "Our improved approach allows us to uncover the primitive stars hidden among all the other, more common stars." Primitive stars are thought to have formed from material forged shortly after the Big Bang, 13.7 billion years ago. They typically have less than one thousandth the amount of chemical elements heavier than hydrogen and helium found in the Sun and are called "extremely metal-poor stars" [1]. They belong to one of the first generations of stars in the nearby Universe. Such stars are extremely rare and mainly observed in the Milky Way. Cosmologists think that larger galaxies like the Milky Way formed from the merger of smaller galaxies. Our Milky Way's population of extremely metal-poor or "primitive" stars should already have been present in the dwarf galaxies from which it formed, and similar populations should be present in other dwarf galaxies. "So far, evidence for them has been scarce," says co-author Giuseppina Battaglia. "Large surveys conducted in the last few years kept showing that the most ancient populations of stars in the Milky Way and dwarf galaxies did not match, which was not at all expected from cosmological models." Element abundances are measured from spectra, which provide the chemical fingerprints of stars [2]. The Dwarf galaxies Abundances and Radial-velocities Team [3] used the FLAMES instrument on ESO's Very Large Telescope to measure the spectra of over 2000 individual giant stars in four of our galactic neighbours, the Fornax

  10. Uncovering microRNA-mediated response to SO2 stress in Arabidopsis thaliana by deep sequencing.

    PubMed

    Li, Lihong; Xue, Meizhao; Yi, Huilan

    2016-10-01

    Sulfur dioxide (SO2) is a major air pollutant and has significant impacts on plants. MicroRNAs (miRNAs) are a class of gene expression regulators that play important roles in response to environmental stresses. In this study, deep sequencing was used for genome-wide identification of miRNAs and their expression profiles in response to SO2 stress in Arabidopsis thaliana shoots. A total of 27 conserved miRNAs and 5 novel miRNAs were found to be differentially expressed under SO2 stress. qRT-PCR analysis showed mostly negative correlation between miRNA accumulation and target gene mRNA abundance, suggesting regulatory roles of these miRNAs during SO2 exposure. The target genes of SO2-responsive miRNAs encode transcription factors and proteins that regulate auxin signaling and stress response, and the miRNAs-mediated suppression of these genes could improve plant resistance to SO2 stress. Promoter sequence analysis of genes encoding SO2-responsive miRNAs showed that stress-responsive and phytohormone-related cis-regulatory elements occurred frequently, providing additional evidence of the involvement of miRNAs in adaption to SO2 stress. This study represents a comprehensive expression profiling of SO2-responsive miRNAs in Arabidopsis and broads our perspective on the ubiquitous regulatory roles of miRNAs under stress conditions.

  11. Uncovering Hidden Layers of Cell Cycle Regulation through Integrative Multi-omic Analysis

    PubMed Central

    Aviner, Ranen; Shenoy, Anjana; Elroy-Stein, Orna; Geiger, Tamar

    2015-01-01

    Studying the complex relationship between transcription, translation and protein degradation is essential to our understanding of biological processes in health and disease. The limited correlations observed between mRNA and protein abundance suggest pervasive regulation of post-transcriptional steps and support the importance of profiling mRNA levels in parallel to protein synthesis and degradation rates. In this work, we applied an integrative multi-omic approach to study gene expression along the mammalian cell cycle through side-by-side analysis of mRNA, translation and protein levels. Our analysis sheds new light on the significant contribution of both protein synthesis and degradation to the variance in protein expression. Furthermore, we find that translation regulation plays an important role at S-phase, while progression through mitosis is predominantly controlled by changes in either mRNA levels or protein stability. Specific molecular functions are found to be co-regulated and share similar patterns of mRNA, translation and protein expression along the cell cycle. Notably, these include genes and entire pathways not previously implicated in cell cycle progression, demonstrating the potential of this approach to identify novel regulatory mechanisms beyond those revealed by traditional expression profiling. Through this three-level analysis, we characterize different mechanisms of gene expression, discover new cycling gene products and highlight the importance and utility of combining datasets generated using different techniques that monitor distinct steps of gene expression. PMID:26439921

  12. High-resolution genomic profiling of thyroid lesions uncovers preferential copy number gains affecting mitochondrial biogenesis loci in the oncocytic variants

    PubMed Central

    Kurelac, Ivana; de Biase, Dario; Calabrese, Claudia; Ceccarelli, Claudio; Ng, Charlotte KY; Lim, Raymond; MacKay, Alan; Weigelt, Britta; Porcelli, Anna Maria; Reis-Filho, Jorge S; Tallini, Giovanni; Gasparre, Giuseppe

    2015-01-01

    Oncocytic change is the result of aberrant mitochondrial hyperplasia, which may occur in both neoplastic and non-neoplastic cells and is not infrequent in the thyroid. Despite being a well-characterized histologic phenotype, the molecular causes underlying such a distinctive cellular change are poorly understood. To identify potential genetic causes for the oncocytic phenotype in thyroid, we analyzed copy number alterations in a set of oncocytic (n=21) and non-oncocytic (n=20) thyroid lesions by high-resolution microarray-based comparative genomic hybridization (aCGH). Each group comprised lesions of diverse histologic types, including hyperplastic nodules, adenomas and carcinomas. Unsupervised hierarchical clustering of categorical aCGH data resulted in two distinct branches, one of which was significantly enriched for samples with the oncocytic phenotype, regardless of histologic type. Analysis of aCGH events showed that the oncocytic group harbored a significantly higher number of genes involved in copy number gains, when compared to that of conventional thyroid lesions. Functional annotation demonstrated an enrichment for copy number gains that affect genes encoding activators of mitochondrial biogenesis in oncocytic cases but not in their non-oncocytic counterparts. Taken together, our data suggest that genomic alterations may represent additional/alternative mechanisms underlying the development of the oncocytic phenotype in the thyroid. PMID:26269756

  13. Genome-Wide Transcriptional Profiling and Metabolic Analysis Uncover Multiple Molecular Responses of the Grass Species Lolium perenne Under Low-Intensity Xenobiotic Stress

    PubMed Central

    Serra, Anne-Antonella; Couée, Ivan; Heijnen, David; Michon-Coudouel, Sophie; Sulmon, Cécile; Gouesbet, Gwenola

    2015-01-01

    Lolium perenne, which is a major component of pastures, lawns, and grass strips, can be exposed to xenobiotic stresses due to diffuse and residual contaminations of soil. L. perenne was recently shown to undergo metabolic adjustments in response to sub-toxic levels of xenobiotics. To gain insight in such chemical stress responses, a de novo transcriptome analysis was carried out on leaves from plants subjected at the root level to low levels of xenobiotics, glyphosate, tebuconazole, and a combination of the two, leading to no adverse physiological effect. Chemical treatments influenced significantly the relative proportions of functional categories and of transcripts related to carbohydrate processes, to signaling, to protein-kinase cascades, such as Serine/Threonine-protein kinases, to transcriptional regulations, to responses to abiotic or biotic stimuli and to responses to phytohormones. Transcriptomics-based expressions of genes encoding different types of SNF1 (sucrose non-fermenting 1)-related kinases involved in sugar and stress signaling or encoding key metabolic enzymes were in line with specific qRT-PCR analysis or with the important metabolic and regulatory changes revealed by metabolomic analysis. The effects of pesticide treatments on metabolites and gene expression strongly suggest that pesticides at low levels, as single molecule or as mixture, affect cell signaling and functioning even in the absence of major physiological impact. This global analysis of L. perenne therefore highlighted the interactions between molecular regulation of responses to xenobiotics, and also carbohydrate dynamics, energy dysfunction, phytohormones and calcium signaling. PMID:26734031

  14. Integrative comparative analyses of transcript and metabolite profiles from pepper and tomato ripening and development stages uncovers species-specific patterns of network regulatory behavior

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Integrative comparative analyses of transcript and metabolite levels from climacteric and nonclimacteric fruits can be employed to unravel the similarities and differences of the underlying regulatory processes. To this end, we conducted combined gas chromatography-mass spectrometry, and heterologou...

  15. Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis

    PubMed Central

    Cao, Song; Liu, Yun; Sun, Wenting; Zhao, Li; Zhang, Lin; Liu, Xinkui; Yu, Tian

    2015-01-01

    Mitochondrial ATP-sensitive potassium channel (mitoKATP) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoKATP status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoKATP opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoKATP opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoKATP opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI. PMID:26171116

  16. Genome-Wide Expression Profiling of Anoxia/Reoxygenation in Rat Cardiomyocytes Uncovers the Role of MitoKATP in Energy Homeostasis.

    PubMed

    Cao, Song; Liu, Yun; Sun, Wenting; Zhao, Li; Zhang, Lin; Liu, Xinkui; Yu, Tian

    2015-01-01

    Mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) is a common end effector of many protective stimuli in myocardial ischemia-reperfusion injury (MIRI). However, the specific molecular mechanism underlying its myocardial protective effect is not well elucidated. We characterized an anoxia/reoxygenation (A/R) model using freshly isolated adult rat cardiomyocytes. MitoK(ATP) status was interfered with its specific opener diazoxide (DZ) or blocker 5-hydroxydecanote (5-HD). Digital gene expression (DGE) and bioinformatic analysis were deployed. Three energy metabolism related genes (MT-ND6, Idh2, and Acadl) were upregulated when mitoK(ATP) opened. In addition, as many as 20 differentially expressed genes (DEGs) were significantly enriched in five energy homeostasis correlated pathways (PPAR, TCA cycle, fatty acid metabolism, and peroxisome). These findings indicated that mitoK(ATP) opening in MIRI resulted in energy mobilization, which was confirmed by measuring ATP content in cardiomyocytes. These causal outcomes could be a molecular mechanism of myocardial protection of mitoKATP and suggested that the mitoK(ATP) opening plays a physiologic role in triggering cardiomyocytes' energy homeostasis during MIRI. Strategies of modulating energy expenditure during myocardial ischemia-reperfusion may be promising approaches to reduce MIRI.

  17. Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

    PubMed Central

    Rachidi, Saleh M.; Qin, Tingting; Sun, Shaoli; Zheng, W. Jim; Li, Zihai

    2013-01-01

    Background Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated. Methods and Findings Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high CXCL13 and low level of GREM1, LOX, TNFAIP6, CD36, and EDNRA. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers. Conclusion This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications. PMID:23536776

  18. Uncovering the mechanism behind quasi-periodic oscillations in black holes

    NASA Astrophysics Data System (ADS)

    Ingram, Adam

    2012-10-01

    We propose a triggered 200ks XMM-Newton observation of a high inclination black hole binary in the hard intermediate state. This will allow us to constrain a characteristic shift in the iron line profile between the rising and falling phases of the quasi-periodic oscillations (QPOs) observed in these objects. Such a property is a necessary and sufficient condition of a QPO driven by precession in the inner regions of the accretion flow and is predicted by our model which invokes the relativistic effect of frame dragging. The model predicts the QPO phase dependence of the iron line to be stronger for high inclination sources displaying intermediate hardness ratios, leaving the hard intermediate state as the ideal configuration. We will trigger the observation from Swift monitoring throughout the outburst.

  19. Uncovering a Dual Regulatory Role for Caspases During Endoplasmic Reticulum Stress-induced Cell Death

    PubMed Central

    Anania, Veronica G.; Yu, Kebing; Gnad, Florian; Pferdehirt, Rebecca R.; Li, Han; Ma, Taylur P.; Jeon, Diana; Fortelny, Nikolaus; Forrest, William; Ashkenazi, Avi; Overall, Christopher M.; Lill, Jennie R.

    2016-01-01

    Many diseases are associated with endoplasmic reticulum (ER) stress, which results from an accumulation of misfolded proteins. This triggers an adaptive response called the “unfolded protein response” (UPR), and prolonged exposure to ER stress leads to cell death. Caspases are reported to play a critical role in ER stress-induced cell death but the underlying mechanisms by which they exert their effect continue to remain elusive. To understand the role caspases play during ER stress, a systems level approach integrating analysis of the transcriptome, proteome, and proteolytic substrate profile was employed. This quantitative analysis revealed transcriptional profiles for most human genes, provided information on protein abundance for 4476 proteins, and identified 445 caspase substrates. Based on these data sets many caspase substrates were shown to be downregulated at the protein level during ER stress suggesting caspase activity inhibits their cellular function. Additionally, RNA sequencing revealed a role for caspases in regulation of ER stress-induced transcriptional pathways and gene set enrichment analysis showed expression of multiple gene targets of essential transcription factors to be upregulated during ER stress upon inhibition of caspases. Furthermore, these transcription factors were degraded in a caspase-dependent manner during ER stress. These results indicate that caspases play a dual role in regulating the cellular response to ER stress through both post-translational and transcriptional regulatory mechanisms. Moreover, this study provides unique insight into progression of the unfolded protein response into cell death, which may help identify therapeutic strategies to treat ER stress-related diseases. PMID:27125827

  20. Realizing full coverage of perovskite film on substrate surface during solution processing: Characterization and elimination of uncovered surface

    NASA Astrophysics Data System (ADS)

    Li, Yan; He, Xue-Long; Ding, Bin; Gao, Li-Li; Yang, Guan-Jun; Li, Cheng-Xin; Li, Chang-Jiu

    2016-07-01

    The full coverage of the perovskite film on the substrate surface is of significant importance for the high performance perovskite solar cells. In order to obtain full coverage perovskite films by one-step deposition method, the microstructures of both uncovered areas and covered areas of the CH3NH3PbI3 film are comparatively investigated. Results show that the uncovered area indeed has an ultra-thin layer of CH3NH3PbI3 film which is too thin to cover the rough surface morphology of the substrate, and the localized solute accumulation due to long crystal growth time is responsible for the non-full coverage of the perovskite film. Then by decreasing the crystal growth time, the localized solute accumulation is eliminated gradually and subsequently a full coverage of perovskite film on substrate surface is realized. As a result, the perovskite solar cells show a conversion efficiency of ∼13% with the uniform and full coverage perovskite film.

  1. Biliary self-expandable metallic stent for unresectable malignant distal biliary obstruction: which is better: covered or uncovered?

    PubMed

    Isayama, Hiroyuki; Nakai, Yousuke; Kogure, Hirofumi; Yamamoto, Natsuyo; Koike, Kazuhiko

    2013-05-01

    Self-expandable metallic stents (SEMS) are a widely accepted biliary endoprosthesis for patients with unresectable malignant distal biliary obstruction. There are two types of SEMS: covered and uncovered. Uncovered SEMS (UCSEMS) embed into the biliary wall due to their mesh structure and self-expandability, and are resistant to migration. However, the disadvantage of UCSEMS is occlusion due to tumor ingrowth (TI) via the stent mesh, and TI is the main cause of UCSEMS occlusion. To overcome this, covered SEMS (CSEMS) were developed and showed longer patency than UCSEMS. However, migration due to the non-embedded stent body is the main cause of CSEMS dysfunction. There are some randomized studies comparing CSEMS and UCSEMS; however, the results are different according to each study. From one meta-analysis, CSEMS showed longer patency than UCSEMS. A literature review revealed that covered SEMS showed longer patency than UCSEMS. Some studies cannot clearly demonstrate the superiority of CSEMS, as the CSEMS used did not prevent TI or migration. Mechanical properties of SEMS may influence the occurrence of complications. A recent clinical study comparing the Covered Wallstent and the Covered WallFlex revealed superiority of the WallFlex for the prevention of migration. Reducing the axial force and increasing the radial force may lead to good results. Migration of CSEMS should be prevented by taking into consideration the mechanical properties of stents and development of anti-migration systems.

  2. Contribution of the Nurses’ Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

    PubMed Central

    Ley, Sylvia H.; Ardisson Korat, Andres V.; Sun, Qi; Tobias, Deirdre K.; Zhang, Cuilin; Qi, Lu; Willett, Walter C.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. Methods. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. Results. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene–environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Conclusions. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes. PMID:27459454

  3. Covered stents versus uncovered stents for the palliation of malignant extrahepatic biliary obstruction caused by direct tumor invasion: a cohort comparative study.

    PubMed

    Li, Feng; Wang, Feng; Yang, Xinshun; Ji, Donghua; Li, Jun; Wang, Ningfang; Liu, Yongsheng; Li, Cheng; Zhang, Tao; Li, Ke

    2012-12-01

    Biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. The aim of the present study was to compare clinical outcomes of covered and uncovered stents in patients with malignant extrahepatic biliary obstruction caused by direct tumor invasion. Patients diagnosed with malignant extrahepatic biliary obstruction caused by direct tumor invasion were enrolled in this study. Of these patients, 37 received ePTFE-covered stent placement and were prospectively studied, and 47 received uncovered stent placement and were retrospectively studied. The technical success rate, tumor ingrowth rate, complication rate, stent patency, and patient survival were evaluated for both groups. Stent placement was successful in all cases except one in the covered group due to stent kinking. Tumor ingrowth occurred exclusively in the uncovered group. No significant differences were observed for the complication rate and patient survival between the two groups. Three patients in the covered group experienced stent migration, whereas no patients did in the uncovered group. A significant difference was found regarding stent patency, which was greater for the covered group compared to the uncovered group. The placement of ePTFE-covered stents for the treatment of malignant biliary obstruction caused by direct tumor invasion was a safe and an effective method characterized by greater stent patency.

  4. A Comparison of a Fully Covered and an Uncovered Segmented Biodegradable Esophageal Stent in a Porcine Model: Preclinical Evaluation of Degradation, Complications, and Tissue Reactions

    PubMed Central

    Feng, Yadong; Jiao, Chunhua; Cao, Yang; Zhao, Ye; Chen, Yanfang; Fang, Lin; Shi, Ruihua

    2016-01-01

    Aims. This study was to compare the degradation, complications, and tissue reactions of two segmented biodegradable esophageal stents in a porcine model. Methods. Uncovered biodegradable segmented stents and fully covered biodegradable segmented stents (FCBDS) were transplanted into the porcine esophagus lumen. Data on biodegradation, complications, and tissue reactions were collected and compared. Results. All animals kept good general conditions. No severe complications and stents migration occurred. Stents degradation commenced at week 3. Compared with uncovered stents, stents structure breakage and complete stents absorption in FCBDS were postponed for 1-2 weeks. Hyperplasia was prominent at early stage and ameliorated at late stage after stents insertion. Tissue reactions in FCBDS were milder than those in uncovered stents in the early stage. A longer degradation period was present in FCBDS than in uncovered stents, while FCBDS induced tissue reaction at late stage was mild. Conclusions. Biodegradable esophageal stents with a segmented trunk may be further evaluated in refractory benign esophagus strictures. This FCBDS may be advantageous compared with uncovered stents for a longer degradation period. PMID:27022391

  5. Integrating multi-omics for uncovering the architecture of cross-talking pathways in breast cancer.

    PubMed

    Wang, Li; Xiao, Yun; Ping, Yanyan; Li, Jing; Zhao, Hongying; Li, Feng; Hu, Jing; Zhang, Hongyi; Deng, Yulan; Tian, Jiawei; Li, Xia

    2014-01-01

    Cross-talk among abnormal pathways widely occurs in human cancer and generally leads to insensitivity to cancer treatment. Moreover, alterations in the abnormal pathways are not limited to single molecular level. Therefore, we proposed a strategy that integrates a large number of biological sources at multiple levels for systematic identification of cross-talk among risk pathways in cancer by random walk on protein interaction network. We applied the method to multi-Omics breast cancer data from The Cancer Genome Atlas (TCGA), including somatic mutation, DNA copy number, DNA methylation and gene expression profiles. We identified close cross-talk among many known cancer-related pathways with complex change patterns. Furthermore, we identified key genes (linkers) bridging these cross-talks and showed that these genes carried out consistent biological functions with the linked cross-talking pathways. Through identification of leader genes in each pathway, the architecture of cross-talking pathways was built. Notably, we observed that linkers cooperated with leaders to form the fundamentation of cross-talk of pathways which play core roles in deterioration of breast cancer. As an example, we observed that KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub. In summary, we offer an effective way to characterize complex cross-talk among disease pathways, which can be applied to other diseases and provide useful information for the treatment of cancer.

  6. RNA sequencing uncovers antisense RNAs and novel small RNAs in Streptococcus pyogenes

    PubMed Central

    Le Rhun, Anaïs; Beer, Yan Yan; Reimegård, Johan; Chylinski, Krzysztof; Charpentier, Emmanuelle

    2016-01-01

    ABSTRACT Streptococcus pyogenes is a human pathogen responsible for a wide spectrum of diseases ranging from mild to life-threatening infections. During the infectious process, the temporal and spatial expression of pathogenicity factors is tightly controlled by a complex network of protein and RNA regulators acting in response to various environmental signals. Here, we focus on the class of small RNA regulators (sRNAs) and present the first complete analysis of sRNA sequencing data in S. pyogenes. In the SF370 clinical isolate (M1 serotype), we identified 197 and 428 putative regulatory RNAs by visual inspection and bioinformatics screening of the sequencing data, respectively. Only 35 from the 197 candidates identified by visual screening were assigned a predicted function (T-boxes, ribosomal protein leaders, characterized riboswitches or sRNAs), indicating how little is known about sRNA regulation in S. pyogenes. By comparing our list of predicted sRNAs with previous S. pyogenes sRNA screens using bioinformatics or microarrays, 92 novel sRNAs were revealed, including antisense RNAs that are for the first time shown to be expressed in this pathogen. We experimentally validated the expression of 30 novel sRNAs and antisense RNAs. We show that the expression profile of 9 sRNAs including 2 predicted regulatory elements is affected by the endoribonucleases RNase III and/or RNase Y, highlighting the critical role of these enzymes in sRNA regulation. PMID:26580233

  7. PAR-CLIP analysis uncovers AUF1 impact on target RNA fate and genome integrity

    PubMed Central

    Yoon, Je-Hyun; De, Supriyo; Srikantan, Subramanya; Abdelmohsen, Kotb; Grammatikakis, Ioannis; Kim, Jiyoung; Kim, Kyoung Mi; Noh, Ji Heon; White, Elizabeth J.F.; Martindale, Jennifer L.; Yang, Xiaoling; Kang, Min-Ju; Wood, William H.; Hooten, Nicole Noren; Evans, Michele K.; Becker, Kevin G.; Tripathi, Vidisha; Prasanth, Kannanganattu V.; Wilson, Gerald M.; Tuschl, Thomas; Ingolia, Nicholas T.; Hafner, Markus; Gorospe, Myriam

    2015-01-01

    Post-transcriptional gene regulation is robustly regulated by RNA-binding proteins (RBPs). Here we describe the collection of RNAs regulated by AUF1 (AU-binding factor 1), an RBP linked to cancer, inflammation and aging. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis reveals that AUF1 primarily recognizes U-/GU-rich sequences in mRNAs and noncoding RNAs and influences target transcript fate in three main directions. First, AUF1 lowers the steady-state levels of numerous target RNAs, including long noncoding RNA NEAT1, in turn affecting the organization of nuclear paraspeckles. Second, AUF1 does not change the abundance of many target RNAs, but ribosome profiling reveals that AUF1 promotes the translation of numerous mRNAs in this group. Third, AUF1 unexpectedly enhances the steady-state levels of several target mRNAs encoding DNA-maintenance proteins. Through its actions on target RNAs, AUF1 preserves genomic integrity, in agreement with the AUF1-elicited prevention of premature cellular senescence. PMID:25366541

  8. ATP-sensitive potassium channels: uncovering novel targets for treating depression.

    PubMed

    Fan, Yi; Kong, Hui; Ye, Xinhai; Ding, Jianhua; Hu, Gang

    2016-07-01

    ATP-sensitive potassium (K-ATP) channels have been shown to couple membrane electrical activity to energy metabolism in a variety of cells and are important in several physiological systems. In the brain, K-ATP channels are strongly expressed in the neuronal circuitry. The distributional profile and functional significance of K-ATP channels suggest that they may be involved in stress-induced depression. First, we showed that chronic mild stress (CMS) significantly increased the expression of hippocampal Kir6.2 and Kir6.1 subunits of K-ATP channels. Next, using Kir6.2 knockout (Kir6.2(-/-)) mice, we presented that Kir6.2 deficiency resulted in antidepressant-like behaviors under non-stress conditions, but aggravated depressive behaviors accompanied by the loss of CA3 neuron and the reduction of brain-derived neurotrophic factor in hippocampus under chronic stress. Finally, we demonstrated that the K-ATP channel opener iptakalim, as well as a classical antidepressant fluoxetine, can reverse CMS-induced depression-related behaviors and counteract the deleterious effects of stress on hippocampus in wild-type mice, but only partially alleviate these symptoms in Kir6.2(-/-) mice. Collectively, our findings demonstrate that K-ATP channels are involved in the pathogenesis of depression and may be a promising target for the therapy of depression.

  9. Uncovering the genetic basis for early isogamete differentiation: a case study of Ectocarpus siliculosus

    PubMed Central

    2013-01-01

    Background The phenomenon of sexual reproduction characterizes nearly all eukaryotes, with anisogamy being the most prevalent form of gamete discrimination. Since dimorphic gametes most likely descend from equal-sized specialized germ cells, identifying the genetic bases of the early functional diversification in isogametes can provide better understanding of the evolution of sexual dimorphism. However, despite the potential importance to the evolutionary biology field, no comprehensive survey of the transcriptome profiling in isomorphic gametes has been reported hitherto. Results Gamete differentiation on the genomic level was investigated using Ectocarpus siliculosus, a model organism for brown algal lineage which displays an isogamous sexual reproduction cycle. Transcriptome libraries of male and female gametes were generated using Next Generation Sequencing technology (SOLiD) and analyzed to identify differentially regulated genes and pathways with potential roles in fertilization and gamete specialization. Gamete transcriptomes showed a high level of complexity with a large portion of gender specific gene expression. Our results indicate that over 4,000 of expressed genes are differentially regulated between male and female, including sequences related to cell movement, carbohydrate and lipid metabolism, signaling, transport and RNA processing. Conclusions This first comprehensive transcriptomic study of protist isogametes describes considerable adaptation to distinct sexual roles, suggesting that functional anisogamy precedes morphological differentiation. Several sex-biased genes and pathways with a putative role in reproduction were identified, providing the basis for more detailed investigations of the mechanisms underlying evolution of mating types and sexual dimorphism. PMID:24359479

  10. Functional genomics of the brain: uncovering networks in the CNS using a systems approach.

    PubMed

    Konopka, Genevieve

    2011-01-01

    The central nervous system (CNS) is undoubtedly the most complex human organ system in terms of its diverse functions, cellular composition, and connections. Attempts to capture this diversity experimentally were the foundation on which the field of neurobiology was built. Until now though, techniques were either painstakingly slow or insufficient in capturing this heterogeneity. In addition, the combination of multiple layers of information needed for a complete picture of neuronal diversity from the epigenome to the proteome requires an even more complex compilation of data. In this era of high-throughput genomics though, the ability to isolate and profile neurons and brain tissue has increased tremendously and now requires less effort. Both microarrays and next-generation sequencing have identified neuronal transcriptomes and signaling networks involved in normal brain development, as well as in disease. However, the expertise needed to organize and prioritize the resultant data remains substantial. A combination of supervised organization and unsupervised analyses are needed to fully appreciate the underlying structure in these datasets. When utilized effectively, these analyses have yielded striking insights into a number of fundamental questions in neuroscience on topics ranging from the evolution of the human brain to neuropsychiatric and neurodegenerative disorders. Future studies will incorporate these analyses with behavioral and physiological data from patients to more efficiently move toward personalized therapeutics.

  11. Transcriptome sequencing uncovers a three–long noncoding RNA signature in predicting breast cancer survival

    PubMed Central

    Guo, Wenna; Wang, Qiang; Zhan, Yueping; Chen, Xijia; Yu, Qi; Zhang, Jiawei; Wang, Yi; Xu, Xin-jian; Zhu, Liucun

    2016-01-01

    Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan–Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified. The Kaplan–Meier analysis and ROC curves proved that the model could predict the prognostic survival with good sensitivity and specificity in both the validation set (AUC = 0.752, 95% confidence intervals (CI): 0.651–0.854) and the microarray dataset (AUC = 0.714, 95%CI: 0.615–0.814). Further study showed the three-lncRNA signature was not only pervasive in different breast cancer stages, subtypes and age groups, but also provides more accurate prognostic information than some widely known biomarkers. The results suggested that RNA-seq transcriptome profiling provides that the three-lncRNA signature is an independent prognostic biomarker, and have clinical significance. In addition, lncRNA, miRNA, and mRNA interaction network indicated lncRNAs may intervene in breast cancer pathogenesis by binding to miR-190b, acting as competing endogenous RNAs. PMID:27338266

  12. Laser Microdissection of Narrow Sheath Mutant Maize Uncovers Novel Gene Expression in the Shoot Apical Meristem

    PubMed Central

    Zhang, Xiaolan; Madi, Shahinez; Borsuk, Lisa; Nettleton, Dan; Elshire, Robert J; Buckner, Brent; Janick-Buckner, Diane; Beck, Jon; Timmermans, Marja; Schnable, Patrick S; Scanlon, Michael J

    2007-01-01

    Microarrays enable comparative analyses of gene expression on a genomic scale, however these experiments frequently identify an abundance of differentially expressed genes such that it may be difficult to identify discrete functional networks that are hidden within large microarray datasets. Microarray analyses in which mutant organisms are compared to nonmutant siblings can be especially problematic when the gene of interest is expressed in relatively few cells. Here, we describe the use of laser microdissection microarray to perform transcriptional profiling of the maize shoot apical meristem (SAM), a ~100-μm pillar of organogenic cells that is required for leaf initiation. Microarray analyses compared differential gene expression within the SAM and incipient leaf primordium of nonmutant and narrow sheath mutant plants, which harbored mutations in the duplicate genes narrow sheath1 (ns1) and narrow sheath2 (ns2). Expressed in eight to ten cells within the SAM, ns1 and ns2 encode paralogous WUSCHEL1-like homeobox (WOX) transcription factors required for recruitment of leaf initials that give rise to a large lateral domain within maize leaves. The data illustrate the utility of laser microdissection-microarray analyses to identify a relatively small number of genes that are differentially expressed within the SAM. Moreover, these analyses reveal potentially conserved WOX gene functions and implicate specific hormonal and signaling pathways during early events in maize leaf development. PMID:17571927

  13. Uncovering a Macrophage Transcriptional Program by Integrating Evidence from Motif Scanning and Expression Dynamics

    PubMed Central

    Ramsey, Stephen A.; Klemm, Sandy L.; Zak, Daniel E.; Kennedy, Kathleen A.; Thorsson, Vesteinn; Li, Bin; Gilchrist, Mark; Gold, Elizabeth S.; Johnson, Carrie D.; Litvak, Vladimir; Navarro, Garnet; Roach, Jared C.; Rosenberger, Carrie M.; Rust, Alistair G.; Yudkovsky, Natalya; Aderem, Alan; Shmulevich, Ilya

    2008-01-01

    Macrophages are versatile immune cells that can detect a variety of pathogen-associated molecular patterns through their Toll-like receptors (TLRs). In response to microbial challenge, the TLR-stimulated macrophage undergoes an activation program controlled by a dynamically inducible transcriptional regulatory network. Mapping a complex mammalian transcriptional network poses significant challenges and requires the integration of multiple experimental data types. In this work, we inferred a transcriptional network underlying TLR-stimulated murine macrophage activation. Microarray-based expression profiling and transcription factor binding site motif scanning were used to infer a network of associations between transcription factor genes and clusters of co-expressed target genes. The time-lagged correlation was used to analyze temporal expression data in order to identify potential causal influences in the network. A novel statistical test was developed to assess the significance of the time-lagged correlation. Several associations in the resulting inferred network were validated using targeted ChIP-on-chip experiments. The network incorporates known regulators and gives insight into the transcriptional control of macrophage activation. Our analysis identified a novel regulator (TGIF1) that may have a role in macrophage activation. PMID:18369420

  14. Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei

    PubMed Central

    Dejung, Mario; Subota, Ines; Bucerius, Ferdinand; Dindar, Gülcin; Freiwald, Anja; Engstler, Markus; Boshart, Michael; Butter, Falk; Janzen, Christian J.

    2016-01-01

    Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes. PMID:26910529

  15. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE.

    PubMed

    Van de Wouwer, Dorien; Vanholme, Ruben; Decou, Raphaël; Goeminne, Geert; Audenaert, Dominique; Nguyen, Long; Höfer, René; Pesquet, Edouard; Vanholme, Bartel; Boerjan, Wout

    2016-09-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  16. Detecting and profiling tissue-selective genes.

    PubMed

    Liang, Shuang; Li, Yizheng; Be, Xiaobing; Howes, Steve; Liu, Wei

    2006-07-12

    The widespread use of DNA microarray technologies has generated large amounts of data from various tissue and/or cell types. These data set the stage to answer the question of tissue specificity of human transcriptome in a comprehensive manner. Our focus is to uncover the tissue-gene relationship by identifying genes that are preferentially expressed in a small number of tissue types. The tissue selectivity would shed light on the potential physiological functions of these genes and provides an indispensable reference to compare against disease pathophysiology and to identify or validate tissue-specific drug targets. Here we describe a systematic computational and statistical approach to profile gene expression data to identify tissue-selective genes with the use of a more extensive data set and a well-established multiple-comparison procedure with error rate control. Expression data of 35,152 probe sets in 97 normal human tissue types were analyzed, and 3,919 genes were identified to be selective to one or a few tissue types. We presented results of these tissue-selective genes and compared them to those identified by other studies.

  17. Floral Transcriptomes in Woodland Strawberry Uncover Developing Receptacle and Anther Gene Networks.

    PubMed

    Hollender, Courtney A; Kang, Chunying; Darwish, Omar; Geretz, Aviva; Matthews, Benjamin F; Slovin, Janet; Alkharouf, Nadim; Liu, Zhongchi

    2014-05-14

    Flowers are reproductive organs and precursors to fruits and seeds. While the basic tenets of the ABCE model of flower development are conserved in angiosperms, different flowering plants exhibit different and sometimes unique characteristics. A distinct feature of strawberry (Fragaria spp.) flowers is the development of several hundreds of individual apocarpous (unfused) carpels. These individual carpels are arranged in a spiral pattern on the subtending stem tip, the receptacle. Therefore, the receptacle is an integral part of the strawberry flower and is of significant agronomic importance, being the precursor to strawberry fruit. Taking advantage of next-generation sequencing and laser capture microdissection, we generated different tissue- and stage-transcriptomic profiling of woodland strawberry (Fragaria vesca) flower development. Using pairwise comparisons and weighted gene coexpression network analysis, we identified modules of coexpressed genes and hub genes of tissue-specific networks. Of particular importance is the discovery of a developing receptacle-specific module exhibiting similar molecular features to those of young floral meristems. The strawberry homologs of a number of meristem regulators, including LOST MERISTEM and WUSCHEL, are identified as hub genes operating in the developing receptacle network. Furthermore, almost 25% of the F-box genes in the genome are transiently induced in developing anthers at the meiosis stage, indicating active protein degradation. Together, this work provides important insights into the molecular networks underlying strawberry's unique reproductive developmental processes. This extensive floral transcriptome data set is publicly available and can be readily queried at the project Web site, serving as an important genomic resource for the plant biology research community.

  18. Uncovering the Prevalence and Diversity of Integrating Conjugative Elements in Actinobacteria

    PubMed Central

    Beaudin, Julie; Brzezinski, Ryszard; Roy, Sébastien; Burrus, Vincent

    2011-01-01

    Horizontal gene transfer greatly facilitates rapid genetic adaptation of bacteria to shifts in environmental conditions and colonization of new niches by allowing one-step acquisition of novel functions. Conjugation is a major mechanism of horizontal gene transfer mediated by conjugative plasmids and integrating conjugative elements (ICEs). While in most bacterial conjugative systems DNA translocation requires the assembly of a complex type IV secretion system (T4SS), in Actinobacteria a single DNA FtsK/SpoIIIE-like translocation protein is required. To date, the role and diversity of ICEs in Actinobacteria have received little attention. Putative ICEs were searched for in 275 genomes of Actinobacteria using HMM-profiles of proteins involved in ICE maintenance and transfer. These exhaustive analyses revealed 144 putative FtsK/SpoIIIE-type ICEs and 17 putative T4SS-type ICEs. Grouping of the ICEs based on the phylogenetic analyses of maintenance and transfer proteins revealed extensive exchanges between different sub-families of ICEs. 17 ICEs were found in Actinobacteria from the genus Frankia, globally important nitrogen-fixing microorganisms that establish root nodule symbioses with actinorhizal plants. Structural analysis of ICEs from Frankia revealed their unexpected diversity and a vast array of predicted adaptive functions. Frankia ICEs were found to excise by site-specific recombination from their host's chromosome in vitro and in planta suggesting that they are functional mobile elements whether Frankiae live as soil saprophytes or plant endosymbionts. Phylogenetic analyses of proteins involved in ICEs maintenance and transfer suggests that active exchange between ICEs cargo-borne and chromosomal genes took place within the Actinomycetales order. Functionality of Frankia ICEs in vitro as well as in planta lets us anticipate that conjugation and ICEs could allow the development of genetic manipulation tools for this challenging microorganism and for many

  19. Nuclear translocation uncovers the amyloid peptide Aβ42 as a regulator of gene transcription.

    PubMed

    Barucker, Christian; Harmeier, Anja; Weiske, Joerg; Fauler, Beatrix; Albring, Kai Frederik; Prokop, Stefan; Hildebrand, Peter; Lurz, Rudi; Heppner, Frank L; Huber, Otmar; Multhaup, Gerhard

    2014-07-18

    Although soluble species of the amyloid-β peptide Aβ42 correlate with disease symptoms in Alzheimer disease, little is known about the biological activities of amyloid-β (Aβ). Here, we show that Aβ peptides varying in lengths from 38 to 43 amino acids are internalized by cultured neuroblastoma cells and can be found in the nucleus. By three independent methods, we demonstrate direct detection of nuclear Aβ42 as follows: (i) biochemical analysis of nuclear fractions; (ii) detection of biotin-labeled Aβ in living cells by confocal laser scanning microscopy; and (iii) transmission electron microscopy of Aβ in cultured cells, as well as brain tissue of wild-type and transgenic APPPS1 mice (overexpression of amyloid precursor protein and presenilin 1 with Swedish and L166P mutations, respectively). Also, this study details a novel role for Aβ42 in nuclear signaling, distinct from the amyloid precursor protein intracellular domain. Chromatin immunoprecipitation showed that Aβ42 specifically interacts as a repressor of gene transcription with LRP1 and KAI1 promoters. By quantitative RT-PCR, we confirmed that mRNA levels of the examined candidate genes were exclusively decreased by the potentially neurotoxic Aβ42 wild-type peptide. Shorter peptides (Aβ38 or Aβ40) and other longer peptides (nontoxic Aβ42 G33A substitution or Aβ43) did not affect mRNA levels. Overall, our data indicate that the nuclear translocation of Aβ42 impacts gene regulation, and deleterious effects of Aβ42 in Alzheimer disease pathogenesis may be influenced by altering the expression profiles of disease-modifying genes.

  20. Campus Profile 98.

    ERIC Educational Resources Information Center

    Glendale Community Coll., CA. Planning and Research Office.

    Glendale Community College's Campus Profile is designed to assist faculty, staff, and students in understanding the college's diverse operations. Organized around an outline from the state accountability model, this statistical report focuses on the academic years 1995-1997. "Campus Profile '98" includes more accountability performance measures…

  1. Uncovering large-scale coherent structures in natural and forced turbulent wakes by combining PIV, POD, and FTLE

    NASA Astrophysics Data System (ADS)

    Kourentis, L.; Konstantinidis, E.

    2012-03-01

    Planar velocity data of the unsteady separated flow in the turbulent wake of a circular cylinder obtained by particle image velocimetry (PIV) are analyzed in order to visualize the large-scale coherent structures associated with alternating vortex shedding at a Reynolds number of 2,150. Two different cases are examined: unforced vortex shedding in the natural wake and vortex lock-on incited by forced perturbations superimposed in the inflow velocity. Proper orthogonal decomposition (POD) is employed to reconstruct the low-order wake dynamics from randomly sampled snapshots of the velocity field. The reconstructed flow is subsequently used to determine the evolution of the finite-time Lyapunov exponent (FTLE) fields which identify the Lagrangian coherent structures. The results demonstrate that the combination of methods employed offers a powerful visualization tool to uncover large-scale coherent structures and to exemplify vortex dynamics in natural and forced bluff-body wakes.

  2. A chemical family-based strategy for uncovering hidden bioactive molecules and multicomponent interactions in herbal medicines

    PubMed Central

    Song, Hui-Peng; Wu, Si-Qi; Hao, Haiping; Chen, Jun; Lu, Jun; Xu, Xiaojun; Li, Ping; Yang, Hua

    2016-01-01

    Two concepts involving natural products were proposed and demonstrated in this paper. (1) Natural product libraries (e.g. herbal extract) are not perfect for bioactivity screening because of the vast complexity of compound compositions, and thus a library reconstruction procedure is necessary before screening. (2) The traditional mode of “screening single compound” could be improved to “screening single compound, drug combination and multicomponent interaction” due to the fact that herbal medicines work by integrative effects of multi-components rather than single effective constituents. Based on the two concepts, we established a novel strategy aiming to make screening easier and deeper. Using thrombin as the model enzyme, we firstly uncovered the minor lead compounds, potential drug combinations and multicomponent interactions in an herbal medicine of Dan-Qi pair, showing a significant advantage over previous methods. This strategy was expected to be a new and promising mode for investigation of herbal medicines. PMID:27025397

  3. Using zebrafish to uncover the genetic and neural basis of aggression, a frequent comorbid symptom of psychiatric disorders.

    PubMed

    Jones, Lauren J; Norton, William H J

    2015-01-01

    Aggression is an important adaptive behavior that can be used to monopolize resources such as mates or food, acquire and defend territory and establish dominant hierarchies in social groups. It is also a symptom of several psychiatric disorders including attention-deficit/hyperactivity disorder and schizophrenia. The frequent comorbidity of aggression and psychiatric diseases suggests that common genes and neural circuits may link these disorders. Research using animal models has the potential to uncover these genes and neural circuits despite the difficulty of fully modeling human behavioral disorders. In this review we propose that zebrafish may be a suitable model organism for aggression research with the potential to shed light upon the aggressive symptoms of human diseases.

  4. Atmospheric pollution history at Linfen (China) uncovered by magnetic and chemical parameters of sediments from a water reservoir.

    PubMed

    Ma, Mingming; Hu, Shouyun; Cao, Liwan; Appel, Erwin; Wang, Longsheng

    2015-09-01

    We studied magnetic and chemical parameters of sediments from sediments of a water reservoir at Linfen (China) in order to quantitatively reconstruct the atmospheric pollution history in this region. The results show that the main magnetic phases are magnetite and maghemite originating from the surrounding catchment and from anthropogenic activities, and there is a significant positive relationship between magnetic concentration parameters and heavy metals concentrations, indicating that magnetic proxies can be used to monitor the anthropogenic pollution. In order to uncover the atmospheric pollution history, we combined the known events of environmental improvement with variations of magnetic susceptibility (χ) and heavy metals along the cores to obtain a detailed chronological framework. In addition, air comprehensive pollution index (ACPI) was reconstructed from regression equation among magnetic and chemical parameters as well as atmospheric monitoring data. Based on these results, the atmospheric pollution history was successfully reconstructed.

  5. Computing the origin and evolution of the ribosome from its structure — Uncovering processes of macromolecular accretion benefiting synthetic biology

    PubMed Central

    Caetano-Anollés, Gustavo; Caetano-Anollés, Derek

    2015-01-01

    Accretion occurs pervasively in nature at widely different timeframes. The process also manifests in the evolution of macromolecules. Here we review recent computational and structural biology studies of evolutionary accretion that make use of the ideographic (historical, retrodictive) and nomothetic (universal, predictive) scientific frameworks. Computational studies uncover explicit timelines of accretion of structural parts in molecular repertoires and molecules. Phylogenetic trees of protein structural domains and proteomes and their molecular functions were built from a genomic census of millions of encoded proteins and associated terminal Gene Ontology terms. Trees reveal a ‘metabolic-first’ origin of proteins, the late development of translation, and a patchwork distribution of proteins in biological networks mediated by molecular recruitment. Similarly, the natural history of ancient RNA molecules inferred from trees of molecular substructures built from a census of molecular features shows patchwork-like accretion patterns. Ideographic analyses of ribosomal history uncover the early appearance of structures supporting mRNA decoding and tRNA translocation, the coevolution of ribosomal proteins and RNA, and a first evolutionary transition that brings ribosomal subunits together into a processive protein biosynthetic complex. Nomothetic structural biology studies of tertiary interactions and ancient insertions in rRNA complement these findings, once concentric layering assumptions are removed. Patterns of coaxial helical stacking reveal a frustrated dynamics of outward and inward ribosomal growth possibly mediated by structural grafting. The early rise of the ribosomal ‘turnstile’ suggests an evolutionary transition in natural biological computation. Results make explicit the need to understand processes of molecular growth and information transfer of macromolecules. PMID:27096056

  6. Clinical exome sequencing for cerebellar ataxia and spastic paraplegia uncovers novel gene–disease associations and unanticipated rare disorders

    PubMed Central

    van de Warrenburg, Bart P; Schouten, Meyke I; de Bot, Susanne T; Vermeer, Sascha; Meijer, Rowdy; Pennings, Maartje; Gilissen, Christian; Willemsen, Michèl AAP; Scheffer, Hans; Kamsteeg, Erik-Jan

    2016-01-01

    Cerebellar ataxia (CA) and hereditary spastic paraplegia (HSP) are two of the most prevalent motor disorders with extensive locus and allelic heterogeneity. We implemented clinical exome sequencing, followed by filtering data for a ‘movement disorders' gene panel, as a generic test to increase variant detection in 76 patients with these disorders. Segregation analysis or phenotypic re-evaluation was utilized to substantiate findings. Disease-causing variants were identified in 9 of 28 CA patients, and 8 of 48 HSP patients. In addition, possibly disease-causing variants were identified in 1 and 8 of the remaining CA and HSP patients, respectively. In 10 patients with CA, the total disease-causing or possibly disease-causing variants were detected in 8 different genes, whereas 16 HSP patients had such variants in 12 different genes. In the majority of cases, the identified variants were compatible with the patient phenotype. Interestingly, in some patients variants were identified in genes hitherto related to other movement disorders, such as TH variants in two siblings with HSP. In addition, rare disorders were uncovered, for example, a second case of HSP caused by a VCP variant. For some patients, exome sequencing results had implications for treatment, exemplified by the favorable L-DOPA treatment in a patient with HSP due to ATP13A2 variants (Parkinson type 9). Thus, clinical exome sequencing in this cohort of CA and HSP patients suggests broadening of disease spectra, revealed novel gene–disease associations, and uncovered unanticipated rare disorders. In addition, clinical exome sequencing results have shown their value in guiding practical patient management. PMID:27165006

  7. Microbiological study of fresh herbs from retail premises uncovers an international outbreak of salmonellosis.

    PubMed

    Elviss, N C; Little, C L; Hucklesby, L; Sagoo, S; Surman-Lee, S; de Pinna, E; Threlfall, E J

    2009-08-31

    This Local Authorities Co-ordinators of Regulatory Services/Health Protection Agency study was prompted by the increasing concern regarding the microbiological safety of ready-to-eat salad vegetable products, particularly fresh herbs. During May to October 2007, 3760 ready-to-eat fresh herbs, of different varieties, were sampled across the UK to assess their microbiological safety in relation to salmonella contamination and levels of Escherichia coli. Sixty (1.6%) herb samples were found to be of unsatisfactory quality according to Regulation (EC) No. 2073/2005 on the microbiological criteria of foodstuffs, i.e. contaminated with Salmonella spp. and/or containing E. coli at >10(3) cfu/g. When criteria in the PHLS Microbiological Guidelines for some ready-to-eat foods (2000) were used, 117 (3.9%) of herb samples were of unsatisfactory quality due to the presence of salmonella and/or E. coli at > or = 10(2) cfu/g. Eighteen (0.5%) samples of six different herb types were contaminated with Salmonella spp.: identified as serotypes Senftenberg (8), Agona (2), Anatum (1), Durban (1), Javiana (1), Mgulani (1), Montevideo (1), Unnamed (I 16:g, t: z42) (1), Virchow (1) and mixed Newport & Virchow (1). In each case the retailer and the UK Food Standards Agency were immediately informed and remedial action taken. Samples contaminated with S. Senftenberg were specifically associated with basil grown in Israel. Thirty-two human cases of S. Senftenberg infection were subsequently identified throughout England and Wales and a further 19 in Scotland, Denmark, The Netherlands and the USA. The strain of S. Senftenberg identified from the basil and that from cases had an indistinguishable molecular profile, suggesting a likely connection between consumption of basil and human infection. The presence of Salmonella spp. is unacceptable in ready-to-foods such as fresh herbs. This study highlights the necessity of applying good agricultural and hygiene practices pre-, during and post

  8. Label-free proteomics uncovers energy metabolism and focal adhesion regulations responsive for endometrium receptivity.

    PubMed

    Chen, Qian; Zhang, Aijun; Yu, Feng; Gao, Jing; Liu, Yue; Yu, Chengli; Zhou, Hu; Xu, Chen

    2015-04-01

    The menstrual cycle of the female uterus leads to periodic changes of the endometrium. These changes are important for developing the endometrial receptivity and for achieving competency of embryo implantation. However, the molecular events underlying the endometrial receptivity process remain poorly understood. Here we applied an LC-MS-based label-free quantitative proteomic approach to compare the endometrial tissues in the midsecretory (receptive) phase with the endometrial tissues in the proliferative phase from age-matched woman (n = 6/group). The proteomes of endometrial tissues were extracted using an SDS-based detergent, digested by the filter-aided sample preparation procedures, and subsequently analyzed by nano-LC-MS/MS (Orbitrap XL) with a 4 h gradient. Reliable protein expression profiles were reproducibly obtained from the endometrial tissues in the receptive and proliferative phases. A total of 2138 protein groups were quantified under highly stringent criteria with a false discovery rate of <1% for peptide and protein groups. Among these proteins, 317 proteins had differences in expression that were statistically significant between the receptive and proliferative phases. Direct protein-protein interaction network analyses of these significantly changed proteins showed that the up-regulation of creatine kinase B-type (CKB) in the receptive phase may be related to endometrium receptivity. The interaction network also showed that proteins related to cell-cell adhesion were down-regulated. Moreover, the results from KEGG pathway analyses are consistent with the protein-protein interaction results. The proteins, including alpha-actinin (ACTN), extracellular matrix proteins, integrin alpha-V, and so on, that are involved in the focal adhesion pathway were down-regulated in the receptive phase compared with the proliferative phase, which may facilitate the implantation of the fertilized ovum. Selected proteins were validated by Western blot analysis and

  9. Contaminated Sediment Core Profiling

    EPA Science Inventory

    Evaluating the environmental risk of sites containing contaminated sediments often poses major challenges due in part to the absence of detailed information available for a given location. Sediment core profiling is often utilized during preliminary environmental investigations ...

  10. Attitude profile design program

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Attitude Profile Design (APD) Program was designed to be used as a stand-alone addition to the Simplex Computation of Optimum Orbital Trajectories (SCOOT). The program uses information from a SCOOT output file and the user defined attitude profile to produce time histories of attitude, angular body rates, and accelerations. The APD program is written in standard FORTRAN77 and should be portable to any machine that has an appropriate compiler. The input and output are through formatted files. The program reads the basic flight data, such as the states of the vehicles, acceleration profiles, and burn information, from the SCOOT output file. The user inputs information about the desired attitude profile during coasts in a high level manner. The program then takes these high level commands and executes the maneuvers, outputting the desired information.

  11. Profiles in Cancer Research

    Cancer.gov

    These articles put a face to some of the thousands of individuals who contribute to NCI’s cancer research efforts. The profiles highlight the work of scientists and clinicians and describe the circumstances and motivation behind their work.

  12. Expedition 29 Crew Profile

    NASA Video Gallery

    The six members of Expedition 29 are profiled and interviewed. NASA astronauts Mike Fossum and Dan Burbank; JAXA astronaut Satoshi Furukawa; and cosmonauts Anton Shkaplerov and Anatoly Ivanishin di...

  13. BWR AXIAL PROFILE

    SciTech Connect

    J. Huffer

    2004-09-28

    The purpose of this calculation is to develop axial profiles for estimating the axial variation in burnup of a boiling water reactor (BWR) assembly spent nuclear fuel (SNF) given the average burnup of an assembly. A discharged fuel assembly typically exhibits higher burnup in the center and lower burnup at the ends of the assembly. Criticality safety analyses taking credit for SNF burnup must account for axially varying burnup relative to calculations based on uniformly distributed assembly average burnup due to the under-burned tips. Thus, accounting for axially varying burnup in criticality analyses is also referred to as accounting for the ''end effect'' reactivity. The magnitude of the reactivity change due to ''end effect'' is dependent on the initial assembly enrichment, the assembly average burnup, and the particular axial profile characterizing the burnup distribution. The set of bounding axial profiles should incorporate multiple BWR core designs and provide statistical confidence (95 percent confidence that 95 percent of the population is bound by the profile) that end nodes are conservatively represented. The profiles should also conserve the overall burnup of the fuel assembly. More background on BWR axial profiles is provided in Attachment I.

  14. Histone profiles in cancer.

    PubMed

    Riedel, Simone S; Neff, Tobias; Bernt, Kathrin M

    2015-10-01

    While DNA abnormalities have long been recognized as the cause of cancer, the contribution of chromatin is a relatively recent discovery. Excitement in the field of cancer epigenetics is driven by 3 key elements: 1. Chromatin may play an active and often critical role in controlling gene expression, DNA stability and cell identity. 2. Chromatin modifiers are frequent targets of DNA aberrations, in some cancers reaching near 100%. Particularly in cancers with low rates of DNA mutations, the key "driver" of malignancy is often a chromatin modifier. 3. Cancer-associated aberrant chromatin is amenable to pharmacologic modulation. This has sparked the rapidly expanding development of small molecules targeting chromatin modifiers or reader domains, several of which have shown promise in clinical trials. In parallel, technical advances have greatly enhanced our ability to perform comprehensive chromatin/histone profiling. Despite the discovery that distinct histone profiles are associated with prognostic subgroups, and in some instances may point towards an underlying aberration that can be targeted, histone profiling has not entered clinical diagnostics. Even eligibility for clinical trials targeting chromatin hinges on traditional histologic or DNA-based molecular criteria rather than chromatin profiles. This review will give an overview of the philosophical debate around the role of histones in controlling or modulating gene expression and discuss the most common techniques for histone profiling. In addition, we will provide prominent examples of aberrantly expressed or mutated chromatin modifiers that result in either globally or locally aberrant histone profiles, and that may be promising therapeutic targets.

  15. What Studying Problems Are Faced by the Adolescent Grade Repeaters in Macao: Uncovering Underlying Mechanisms Based on Evidences from the PISA 2012 Study

    ERIC Educational Resources Information Center

    Sit, Pou-seong; Cheung, Kwok-cheung; Cheong, Wai-cheong; Mak, Soi-kei; Soh, Kay-cheng; Ieong, Man-kai

    2015-01-01

    Most schools in Macao are private schools, and there is a variety of grade repetition policy practiced in the 45 secondary schools. The policies are translated into school-based accountability of some kind of minimum competency standards. The objective of this study is to uncover the mediation mechanisms accounting for the influences of grade…

  16. Intercomparison of stratospheric ozone and temperature profiles during the October 2005 Hohenpeissenberg Ozone Profiling Experiment (HOPE)

    NASA Astrophysics Data System (ADS)

    Steinbrecht, W.; McGee, T. J.; Twigg, L. W.; Claude, H.; Schönenborn, F.; Sumnicht, G. K.; Silbert, D.

    2009-01-01

    Thirteen clear nights in October 2005 allowed successful intercomparison of the stationary lidar operated since 1987 by the German Weather Service (DWD) at Hohenpeissenberg (47.8° N, 11.0° E) with the Network for the Detection of Atmospheric Composition Change (NDACC) travelling standard lidar operated by NASA's Goddard Space Flight Center. Both lidars provide ozone profiles in the stratosphere, and temperature profiles in the strato- and mesosphere. Additional ozone profiles came from on-site Brewer/Mast ozonesondes, additional temperature profiles from Vaisala RS92 radiosondes launched at Munich (65 km north-east), and from operational analyses by the US National Centers for Environmental Prediction (NCEP). The intercomparison confirmed a low bias for ozone from the DWD lidar in the 33 to 43 km region, by up to 10%. This bias is caused by the DWD ozone algorithm. It will be removed in a future version. Between 20 and 33 km, agreement between both lidars, and ozonesondes below 30 km, is good with ozone differences less than 3 to 5%. Results are consistent with previous comparisons of the DWD lidar with SAGE, GOMOS and other satellite instruments. The intercomparison did uncover a 290 m upward shift of the DWD lidar data. When this shift is removed, agreement with ozone from the NASA lidar improves below 20 km, with remaining differences usually less than 5%, and not statistically significant. Precision (repeatability) for the lidar ozone data is better than 5% between 20 and 40 km altitude, dropping to 10% near 45 km, and 50% near 50 km. Temperature from the DWD lidar has a 1 to 2 K cold bias from 30 to 65 km against the NASA lidar, and a 2 to 4 K cold bias against radiosondes and NCEP. This is consistent with previous intercomparisons against NCEP or radiosondes. The cold bias against the NASA lidar disappears when the DWD lidar data are corrected for the afore-mentioned 290 m range error, and more appropriate values for the Earth's gravity acceleration are

  17. Effective resist profile control

    NASA Astrophysics Data System (ADS)

    Liu, Chen-Yu; Wang, Chien-Wei; Huang, Chun-Ching; Chang, Ching-Yu; Ku, Yao-Ching

    2014-03-01

    To meet Moore's law, resist resolution improvement has become more and more important. However, it is difficult to improve resist resolution and keep vertical sidewall profile. For example, a high contrast hole resist may cause trench scum, due to very T-top profile. This paper reports several concepts for resist profile tuning without losing performance for lithographic factor , including mask error enhancement factor (MEEF), depth of focus (DOF), and critical dimension uniformity (CDU). To quantitative analysis the resist profile improvement, we define a new factor, Scum fail ratio (F/R%) for new techniques evaluation. The new techniques, including floatable additive, floatable PAG, and new monomer, are discussed. From X-SEM and CD-SEM data, former three concepts could improve resist sidewall profile quantitatively evaluated by Scum fail F/R% and keep lithographic factors. In addition, another key factor, resist residue defect, is also discussed. The high contrast resist with higher receding contact angle (RCA) easily generates more residue defect after development. With the new monomer composition, RCA of Resist E is decreased from 54 to 48 degree after development. Therefore, the residue defect is improved one order.

  18. Genome-wide screen uncovers novel pathways for tRNA processing and nuclear-cytoplasmic dynamics.

    PubMed

    Wu, Jingyan; Bao, Alicia; Chatterjee, Kunal; Wan, Yao; Hopper, Anita K

    2015-12-15

    Transfer ribonucleic acids (tRNAs) are essential for protein synthesis. However, key gene products involved in tRNA biogenesis and subcellular movement remain to be discovered. We conducted the first comprehensive unbiased analysis of the role of nearly an entire proteome in tRNA biology and describe 162 novel and 12 previously known Saccharomyces cerevisiae gene products that function in tRNA processing, turnover, and subcellular movement. tRNA nuclear export is of particular interest because it is essential, but the known tRNA exporters (Los1 [exportin-t] and Msn5 [exportin-5]) are unessential. We report that mutations of CRM1 (Exportin-1), MEX67/MTR2 (TAP/p15), and five nucleoporins cause accumulation of unspliced tRNA, a hallmark of defective tRNA nuclear export. CRM1 mutation genetically interacts with los1Δ and causes altered tRNA nuclear-cytoplasmic distribution. The data implicate roles for the protein and mRNA nuclear export machineries in tRNA nuclear export. Mutations of genes encoding actin cytoskeleton components and mitochondrial outer membrane proteins also cause accumulation of unspliced tRNA, likely due to defective splicing on mitochondria. Additional gene products, such as chromatin modification enzymes, have unanticipated effects on pre-tRNA end processing. Thus, this genome-wide screen uncovered putative novel pathways for tRNA nuclear export and extensive links between tRNA biology and other aspects of cell physiology. PMID:26680305

  19. An uncovered XIII century icon: particular use of organic pigments and gilding techniques highlighted by analytical methods.

    PubMed

    Daveri, Alessia; Doherty, Brenda; Moretti, Patrizia; Grazia, Chiara; Romani, Aldo; Fiorin, Enrico; Brunetti, Brunetto Giovanni; Vagnini, Manuela

    2015-01-25

    The restoration of a panel painting depicting a Madonna and Child listed as an unknown Tuscan artist of the nineteenth century, permitted the hidden original version, a XIII century Medieval icon to be uncovered. It is discovery provided the opportunity for an extensive in situ campaign of non-invasive analytical investigations by portable imaging and spectroscopic techniques (infrared, X-ray fluorescence and diffraction, UV-Vis absorption and emission), followed by aimed micro-destructive investigations (Raman and SEM-EDS). This approach permitted characterization of the original ground and paint layers by complementary techniques. Furthermore, this protocol allowed supplementary particularities of great interest to be highlighted. Namely, numerous original gilding techniques have been accentuated in diverse areas and include the use of surrogate gold (disulphur tin), orpiment as a further false gold and an area with an original silver rich layer. Moreover, pigments including azurite mixed with indigo have been non-invasively identified. Micro-invasive analyses also allowed the diagnosis of organic colorants, namely, an animal anthraquinone lake, kermes and an unusual vegetal chalcone pigment, possibly safflower. The identification of the latter is extremely rare as a painting pigment and has been identified using an innovative adaption to surface enhanced Raman techniques on a cross-section. The resulting data contributes new hypotheses to the historic and artistic knowledge of materials and techniques utilized in XIII century icon paintings and ultimately provides scientific technical support of the recent restoration. PMID:25105261

  20. Uncovering myths and transforming realities among low-SES African-American men: implications for reducing prostate cancer disparities.

    PubMed Central

    Richardson, Joann T.; Webster, J. DeWitt; Fields, Norma J.

    2004-01-01

    PURPOSE: Prostate cancer provides the most dramatic evidence of cancer disparities based on race and ethnicity among U.S. men. African-American men still hold a commanding lead in both prostate cancer incidence and mortality, particularly among those of low socioeconomic status (SES) and the medically underserved. Therefore, the need for early intervention persists. The purpose of this exploratory pilot study was to: a) assess the knowledge of a cohort of low-SES African-American men regarding prostate health/prostate cancer, and b) uncover myths/misinformation as barriers to prostate health decisions and behaviors. PROCEDURES: Asymptomatic African-American men participated in focus groups to candidly discuss: a) health concerns, b) prostate health, c) prostate cancer screening, diagnosis and treatment, and d) factors influencing prostate health decisions/behaviors. FINDINGS: Participants revealed sociocultural and psychological barriers: myths and lack of accurate/adequate knowledge about prostate health and cancer, fear, denial and apathy. CONCLUSIONS: These findings suggest factors that may explain the reluctance and limited participation in prostate health and prostate cancer services among medically underserved, socioeconomically disadvantaged, African-American men. Lack of knowledge, which affects all barriers to care, is amenable to change. Therefore, improvements in prostate cancer outcomes are achievable through culturally and linguistically appropriate health education tailored to their specific needs. PMID:15540880

  1. Systems dynamic modeling of a guard cell Cl- channel mutant uncovers an emergent homeostatic network regulating stomatal transpiration.

    PubMed

    Wang, Yizhou; Papanatsiou, Maria; Eisenach, Cornelia; Karnik, Rucha; Williams, Mary; Hills, Adrian; Lew, Virgilio L; Blatt, Michael R

    2012-12-01

    Stomata account for much of the 70% of global water usage associated with agriculture and have a profound impact on the water and carbon cycles of the world. Stomata have long been modeled mathematically, but until now, no systems analysis of a plant cell has yielded detail sufficient to guide phenotypic and mutational analysis. Here, we demonstrate the predictive power of a systems dynamic model in Arabidopsis (Arabidopsis thaliana) to explain the paradoxical suppression of channels that facilitate K(+) uptake, slowing stomatal opening, by mutation of the SLAC1 anion channel, which mediates solute loss for closure. The model showed how anion accumulation in the mutant suppressed the H(+) load on the cytosol and promoted Ca(2+) influx to elevate cytosolic pH (pH(i)) and free cytosolic Ca(2+) concentration ([Ca(2+)](i)), in turn regulating the K(+) channels. We have confirmed these predictions, measuring pH(i) and [Ca(2+)](i) in vivo, and report that experimental manipulation of pH(i) and [Ca(2+)](i) is sufficient to recover K(+) channel activities and accelerate stomatal opening in the slac1 mutant. Thus, we uncover a previously unrecognized signaling network that ameliorates the effects of the slac1 mutant on transpiration by regulating the K(+) channels. Additionally, these findings underscore the importance of H(+)-coupled anion transport for pH(i) homeostasis.

  2. Cryptic diversity in flathead fishes (Scorpaeniformes: Platycephalidae) across the Indo-West Pacific uncovered by DNA barcoding.

    PubMed

    Puckridge, Melody; Andreakis, Nikos; Appleyard, Sharon A; Ward, Robert D

    2013-01-01

    Identification of taxonomical units underpins most biological endeavours ranging from accurate biodiversity estimates to the effective management of sustainably harvested, protected or endangered species. Successful species identification is now frequently based on a combination of approaches including morphometrics and DNA markers. Sequencing of the mitochondrial COI gene is an established methodology with an international campaign directed at barcoding all fishes. We employed COI sequencing alongside traditional taxonomic identification methods and uncovered instances of deep intraspecific genetic divergences among flathead species. Sixty-five operational taxonomic units (OTUs) were observed across the Indo-West Pacific from just 48 currently recognized species. The most comprehensively sampled taxon, Platycephalus indicus, exhibited the highest levels of genetic diversity with eight lineages separated by up to 16.37% genetic distance. Our results clearly indicate a thorough reappraisal of the current taxonomy of P. indicus (and its three junior synonyms) is warranted in conjunction with detailed taxonomic work on the other additional Platycephalidae OTUs detected by DNA barcoding. PMID:23006488

  3. An uncovered XIII century icon: Particular use of organic pigments and gilding techniques highlighted by analytical methods

    NASA Astrophysics Data System (ADS)

    Daveri, Alessia; Doherty, Brenda; Moretti, Patrizia; Grazia, Chiara; Romani, Aldo; Fiorin, Enrico; Brunetti, Brunetto Giovanni; Vagnini, Manuela

    2015-01-01

    The restoration of a panel painting depicting a Madonna and Child listed as an unknown Tuscan artist of the nineteenth century, permitted the hidden original version, a XIII century Medieval icon to be uncovered. It is discovery provided the opportunity for an extensive in situ campaign of non-invasive analytical investigations by portable imaging and spectroscopic techniques (infrared, X-ray fluorescence and diffraction, UV-Vis absorption and emission), followed by aimed micro-destructive investigations (Raman and SEM-EDS). This approach permitted characterization of the original ground and paint layers by complementary techniques. Furthermore, this protocol allowed supplementary particularities of great interest to be highlighted. Namely, numerous original gilding techniques have been accentuated in diverse areas and include the use of surrogate gold (disulphur tin), orpiment as a further false gold and an area with an original silver rich layer. Moreover, pigments including azurite mixed with indigo have been non-invasively identified. Micro-invasive analyses also allowed the diagnosis of organic colorants, namely, an animal anthraquinone lake, kermes and an unusual vegetal chalcone pigment, possibly safflower. The identification of the latter is extremely rare as a painting pigment and has been identified using an innovative adaption to surface enhanced Raman techniques on a cross-section. The resulting data contributes new hypotheses to the historic and artistic knowledge of materials and techniques utilized in XIII century icon paintings and ultimately provides scientific technical support of the recent restoration.

  4. Uncovering temporal transitions and self-organization during slow aging of dense granular media in the absence of shear bands

    NASA Astrophysics Data System (ADS)

    Walker, David M.; Tordesillas, Antoinette; Ren, Jie; Dijksman, Joshua A.; Behringer, Robert P.

    2014-07-01

    We present a method for discovering temporal transitions in the macroscopic response of two granular assemblies of photoelastic disks, subject to prolonged symmetric cyclic pure shear —under uniform deformation. A distance-matrix-based analysis is used in a reconstructed state space formed from the macroscopic stress ratio time series, with the technique of quadrant scans applied to extract transition times from the recurrence plots. Macroscopic measures of pressure and shear stress exhibit limit cycle behavior with respect to the applied cyclic strain. The contact network and the strong force filamentary network, however, show a gradual change across shear cycles. A quantitative characterization of the self-organization process at the mesoscale reveals that the observed transition in system dynamics at the macroscale is consistent with the process of aging. A distinct and consistent pattern of self-organization with respect to the contact topology and the structural stability of force chains is uncovered. The contact topology evolves to a more densely connected and stable truss-laced lattice, embodying force chain columns endowed with higher levels of triangular and rectangular bracing. This results in an increase in the structural stability of force chains, consistent with the prevailing conjecture on the structural mechanism behind the observed increase in shear strength and shear stiffness in an aging sand.

  5. Uncovering the Genome-Wide Transcriptional Responses of the Filamentous Fungus Aspergillus niger to Lignocellulose Using RNA Sequencing

    PubMed Central

    Gaddipati, Sanyasi; Kokolski, Matthew; Malla, Sunir; Blythe, Martin J.; Ibbett, Roger; Campbell, Maria; Liddell, Susan; Aboobaker, Aziz; Tucker, Gregory A.; Archer, David B.

    2012-01-01

    A key challenge in the production of second generation biofuels is the conversion of lignocellulosic substrates into fermentable sugars. Enzymes, particularly those from fungi, are a central part of this process, and many have been isolated and characterised. However, relatively little is known of how fungi respond to lignocellulose and produce the enzymes necessary for dis-assembly of plant biomass. We studied the physiological response of the fungus Aspergillus niger when exposed to wheat straw as a model lignocellulosic substrate. Using RNA sequencing we showed that, 24 hours after exposure to straw, gene expression of known and presumptive plant cell wall–degrading enzymes represents a huge investment for the cells (about 20% of the total mRNA). Our results also uncovered new esterases and surface interacting proteins that might form part of the fungal arsenal of enzymes for the degradation of plant biomass. Using transcription factor deletion mutants (xlnR and creA) to study the response to both lignocellulosic substrates and low carbon source concentrations, we showed that a subset of genes coding for degradative enzymes is induced by starvation. Our data support a model whereby this subset of enzymes plays a scouting role under starvation conditions, testing for available complex polysaccharides and liberating inducing sugars, that triggers the subsequent induction of the majority of hydrolases. We also showed that antisense transcripts are abundant and that their expression can be regulated by growth conditions. PMID:22912594

  6. Transcriptome-wide studies uncover the diversity of modes of mRNA recruitment to eukaryotic ribosomes.

    PubMed

    Shatsky, Ivan N; Dmitriev, Sergey E; Andreev, Dmitri E; Terenin, Ilya M

    2014-01-01

    The conventional paradigm of translation initiation in eukaryotes states that the cap-binding protein complex eIF4F (consisting of eIF4E, eIF4G and eIF4A) plays a central role in the recruitment of capped mRNAs to ribosomes. However, a growing body of evidence indicates that this paradigm should be revised. This review summarizes the data which have been mostly accumulated in a post-genomic era owing to revolutionary techniques of transcriptome-wide analysis. Unexpectedly, these techniques have uncovered remarkable diversity in the recruitment of cellular mRNAs to eukaryotic ribosomes. These data enable a preliminary classification of mRNAs into several groups based on their requirement for particular components of eIF4F. They challenge the widely accepted concept which relates eIF4E-dependence to the extent of secondary structure in the 5' untranslated regions of mRNAs. Moreover, some mRNA species presumably recruit ribosomes to their 5' ends without the involvement of either the 5' m(7)G-cap or eIF4F but instead utilize eIF4G or eIF4G-like auxiliary factors. The long-standing concept of internal ribosome entry site (IRES)-elements in cellular mRNAs is also discussed.

  7. A POPULATION OF VERY HOT SUPER-EARTHS IN MULTIPLE-PLANET SYSTEMS SHOULD BE UNCOVERED BY KEPLER

    SciTech Connect

    Schlaufman, Kevin C.; Lin, D. N. C.; Ida, S. E-mail: lin@ucolick.or

    2010-11-20

    We simulate a Kepler-like observation of a theoretical exoplanet population and show that the observed orbital period distribution of the Kepler giant planet candidates is best matched by an average stellar specific dissipation function Q'{sub *} in the interval 10{sup 6} {approx_lt} Q'{sub *} {approx_lt} 10{sup 7}. In that situation, the few super-Earths that are driven to orbital periods of P < 1 day by dynamical interactions in multiple-planet systems will survive tidal disruption for a significant fraction of the main-sequence lifetimes of their stellar hosts. Consequently, though these very hot super-Earths are not characteristic of the overall super-Earth population, their substantial transit probability implies that they should be significant contributors to the full super-Earth population uncovered by Kepler. As a result, the CoRoT-7 system may be the first representative of a population of very hot super-Earths that we suggest should be found in multiple-planet systems preferentially orbiting the least-dissipative stellar hosts in the Kepler sample.

  8. Endoscopic management of unresectable malignant gastroduodenal obstruction with a nitinol uncovered metal stent: A prospective Japanese multicenter study

    PubMed Central

    Sasaki, Reina; Sakai, Yuji; Tsuyuguchi, Toshio; Nishikawa, Takao; Fujimoto, Tatsuya; Mikami, Shigeru; Sugiyama, Harutoshi; Yokosuka, Osamu

    2016-01-01

    AIM: To determine the safety and efficacy of endoscopic duodenal stent placement in patients with malignant gastric outlet obstruction. METHODS: This prospective, observational, multicenter study included 39 consecutive patients with malignant gastric outlet obstruction. All patients underwent endoscopic placement of a nitinol, uncovered, self-expandable metal stent. The primary outcome was clinical success at 2 wk after stent placement that was defined as improvement in the Gastric Outlet Obstruction Scoring System score relative to the baseline. RESULTS: Technical success was achieved in all duodenal stent procedures. Procedure-related complications occurred in 4 patients (10.3%) in the form of mild pneumonitis. No other morbidities or mortalities were observed. The clinical success rate was 92.3%. The mean survival period after stent placement was 103 d. The mean period of stent patency was 149 d and the patency remained acceptable for the survival period. Stent dysfunction occurred in 3 patients (7.7%) on account of tumor growth. CONCLUSION: Endoscopic management using duodenal stents for patients with incurable malignant gastric outlet obstruction is safe and improved patients’ quality of life. PMID:27076769

  9. Analysis of functional abnormalities uncovered during preoperative evaluation of donor candidates for living-related liver transplantation.

    PubMed

    Morimoto, T; Awane, M; Tanaka, A; Ikai, I; Nakamura, Y; Yamamoto, Y; Takada, Y; Honda, K; Inamoto, T; Uemoto, S

    1995-02-01

    Functional abnormalities of the liver uncovered during preoperative routine evaluation were analyzed in 109 donor candidates for 100 cases of living-related liver transplantation (LRLT) performed during the period from June, 1990 to May, 1994 at the Second Department of Surgery, Kyoto University Hospital. High serum transaminase (GOT, GPT) levels were noted in 10 (9.2%) cases among 109 candidates, high alkaline phosphatase in 4 (3.7%), hyperbilirubinemia in 3 (2.8%), anemia in 3 and high choline esterase in 3 cases. Positive hepatitis C antibody (HCV) was also noted in 1 case. Fatty liver was detected in 10 (9.2%) cases, cholecystitis in 2 cases, 1 case each of cyst and calcification in the liver by diagnostic imaging (ultra sonograph and/or computed tomography). These abnormalities of the liver necessitated replacing the initial candidate with the other parent in 9 cases, including 1 case without any functional abnormality whose graft liver was too large to fit the recipient abdominal cavity. There were 14 cases of ABO blood type incompatible combination. Switching the initial candidate due to these abnormalities mentioned above resulted in incompatible combinations in 4 of these 14 cases. Although the advantages of the LRLT are the superior viability of the donor graft and the genetic histocompatibility between recipient and donor, to optimize the advantage of LRLT, all donor candidates should be strongly advised to make every effort preoperatively to improve their physical condition in preparation for the LRLT protocol, since many of these abnormalities are typically reversible.

  10. Uncovering the composition of microbial community structure and metagenomics among three gut locations in pigs with distinct fatness

    PubMed Central

    Yang, Hui; Huang, Xiaochang; Fang, Shaoming; Xin, Wenshui; Huang, Lusheng; Chen, Congying

    2016-01-01

    Uncovering the phylogenetic composition of microbial community and the potential functional capacity of microbiome in different gut locations is of great importance to pig production. Here we performed a comparative analysis of gut microbiota and metagenomics among jejunum, ileum and cecum in pigs with distinct fatness. 16S rRNA gene sequencing revealed dramatic differences of microbial composition, diversity and species abundance between small intestine and cecum. Clostridium and SMB53 were enriched in the small intestine, while Prevotella, Treponema, Ruminococcus and Faecalibacterium showed a higher abundance in the cecum. Functional capacity analysis of gut microbiome revealed that the microbiome of small intestine plays important roles in the metabolism of small molecule nutrients, while the microbiome of cecum has the stronger ability to degrade xylan, pectin and cellulose. We identified tens of fatness associated-bacterial species including Escherichia spp. that showed a notable increase of relative abundance in all three gut locations of high fatness pigs. We further suggested that the potential pathogens, inflammation process, and microbial metabolism and nutrient sensing are involved in the high fatness of pigs. These results improve our knowledge about microbiota compositions in different gut locations, and give an insight into the effect of gut microbiota on porcine fatness. PMID:27255518

  11. Classification of protein motifs based on subcellular localization uncovers evolutionary relationships at both sequence and functional levels

    PubMed Central

    2013-01-01

    Background Most proteins have evolved in specific cellular compartments that limit their functions and potential interactions. On the other hand, motifs define amino acid arrangements conserved between protein family members and represent powerful tools for assigning function to protein sequences. The ideal motif would identify all members of a protein family but in practice many motifs identify both family members and unrelated proteins, referred to as True Positive (TP) and False Positive (FP) sequences, respectively. Results To address the relationship between protein motifs, protein function and cellular localization, we systematically assigned subcellular localization data to motif sequences from the comprehensive PROSITE sequence motif database. Using this data we analyzed relationships between localization and function. We find that TPs and FPs have a strong tendency to localize in different compartments. When multiple localizations are considered, TPs are usually distributed between related cellular compartments. We also identified cases where FPs are concentrated in particular subcellular regions, indicating possible functional or evolutionary relationships with TP sequences of the same motif. Conclusions Our findings suggest that the systematic examination of subcellular localization has the potential to uncover evolutionary and functional relationships between motif-containing sequences. We believe that this type of analysis complements existing motif annotations and could aid in their interpretation. Our results shed light on the evolution of cellular organelles and potentially establish the basis for new subcellular localization and function prediction algorithms. PMID:23865897

  12. Detonation Wave Profile

    SciTech Connect

    Menikoff, Ralph

    2015-12-14

    The Zel’dovich-von Neumann-Doering (ZND) profile of a detonation wave is derived. Two basic assumptions are required: i. An equation of state (EOS) for a partly burned explosive; P(V, e, λ). ii. A burn rate for the reaction progress variable; d/dt λ = R(V, e, λ). For a steady planar detonation wave the reactive flow PDEs can be reduced to ODEs. The detonation wave profile can be determined from an ODE plus algebraic equations for points on the partly burned detonation loci with a specified wave speed. Furthermore, for the CJ detonation speed the end of the reaction zone is sonic. A solution to the reactive flow equations can be constructed with a rarefaction wave following the detonation wave profile. This corresponds to an underdriven detonation wave, and the rarefaction is know as a Taylor wave.

  13. Country profile: Hungary

    SciTech Connect

    Not Available

    1991-09-01

    Country Profile: Hungary has been prepared as a background document for use by US Government agencies and US businesses interested in becoming involved with the new democracies of Eastern Europe as they pursue sustainable economic development. The focus of the Profile is on energy and highlights information on Hungary's energy supply, demand, and utilization. It identifies patterns of energy usage in the important economic sectors, especially industry, and provides a preliminary assessment for opportunities to improve efficiencies in energy production, distribution and use by introducing more efficient technologies. The use of more efficient technologies would have the added benefit of reducing the environmental impact which, although is not the focus of the report, is an issue that effects energy choices. The Profile also presents considerable economic information, primarily in the context of how economic restructuring may affect energy supply, demand, and the introduction of more efficient technologies.

  14. Country profile: Hungary

    SciTech Connect

    Not Available

    1991-09-01

    Country Profile: Hungary has been prepared as a background document for use by US Government agencies and US businesses interested in becoming involved with the new democracies of Eastern Europe as they pursue sustainable economic development. The focus of the Profile is on energy and highlights information on Hungary`s energy supply, demand, and utilization. It identifies patterns of energy usage in the important economic sectors, especially industry, and provides a preliminary assessment for opportunities to improve efficiencies in energy production, distribution and use by introducing more efficient technologies. The use of more efficient technologies would have the added benefit of reducing the environmental impact which, although is not the focus of the report, is an issue that effects energy choices. The Profile also presents considerable economic information, primarily in the context of how economic restructuring may affect energy supply, demand, and the introduction of more efficient technologies.

  15. Practical Differential Profiling

    SciTech Connect

    Schulz, M; De Supinski, B R

    2007-02-04

    Comparing performance profiles from two runs is an essential performance analysis step that users routinely perform. In this work we present eGprof, a tool that facilitates these comparisons through differential profiling inside gprof. We chose this approach, rather than designing a new tool, since gprof is one of the few performance analysis tools accepted and used by a large community of users. eGprof allows users to 'subtract' two performance profiles directly. It also includes callgraph visualization to highlight the differences in graphical form. Along with the design of this tool, we present several case studies that show how eGprof can be used to find and to study the differences of two application executions quickly and hence can aid the user in this most common step in performance analysis. We do this without requiring major changes on the side of the user, the most important factor in guaranteeing the adoption of our tool by code teams.

  16. Temperamental Profiles of Dysregulated Children

    ERIC Educational Resources Information Center

    Althoff, Robert R.; Ayer, Lynsay A.; Crehan, Eileen T.; Rettew, David C.; Baer, Julie R.; Hudziak, James J.

    2012-01-01

    It is crucial to characterize self-regulation in children. We compared the temperamental profiles of children with the Child Behavior Checklist (CBCL) Dysregulation Profile (CBCL-DP) to profiles associated with other CBCL-derived syndromes. 382 children (204 boys; aged 5-18) from a large family study were examined. Temperamental profiles were…

  17. Gaussian-profile beams

    SciTech Connect

    Lee, E.P.

    1982-11-03

    The growth rate of the hose instability is derived for a beam with Gaussian radial profile, using the spread mass model of phase mix damping. It is found that the maximum growth rate of a convecting wave packet is 49% larger than that derived for a beam with the Bennett profile, and the inverse group velocity (dz/d tau) is also increased by about this amount. A general discussion of spread mass models is presented along with an explanation of the regurgitation phenomena seen in their numerical treatment.

  18. DNA polymerase profiling.

    PubMed

    Summerer, Daniel

    2008-01-01

    We report a simple homogeneous fluorescence assay for quantification of DNA polymerase function in high throughput. The fluorescence signal is generated by the DNA polymerase triggering opening of a molecular beacon extension of the template strand. A resulting distance alteration is reported by fluorescence resonance energy transfer between two dyes introduced into the molecular beacon stem. We describe real-time reaction profiling of two model DNA polymerases. We demonstrate kinetic characterization, rapid optimization of reaction conditions, and inhibitor profiling using the presented assay. Furthermore, to supersede purification steps in screening procedures of DNA polymerase mutant libraries, detection of enzymatic activity in bacterial expression lysates is described.

  19. Country Education Profiles: Algeria.

    ERIC Educational Resources Information Center

    International Bureau of Education, Geneva (Switzerland).

    One of a series of profiles prepared by the Cooperative Educational Abstracting Service, this brief outline provides basic background information on educational principles, system of administration, structure and organization, curricula, and teacher training in Algeria. Statistics provided by the Unesco Office of Statistics show enrollment at all…

  20. Teaching with Stratigraphic Profiles

    ERIC Educational Resources Information Center

    Stefanich, Greg P.

    1974-01-01

    Presents two exercises modeled after the ice age puzzle described in the ESCP textbook, including formation of terminal moraines and kettle lakes and intersection of normal faults with gold-quartz veins. Indicates that the stratigraphic profiles are usable in teaching earth science, geography, general science, and topographic problems. (CC)

  1. Profiles of Discourse Recognition

    ERIC Educational Resources Information Center

    Singer, Murray

    2013-01-01

    A discourse recognition theory derived from more general memory formulations would be broad in its psychological implications. This study compared discourse recognition with some established profiles of item recognition. Participants read 10 stories either once or twice each. They then rated their confidence in recognizing explicit, paraphrased,…

  2. International Student Profile.

    ERIC Educational Resources Information Center

    Baldwin, Anne

    In an effort to augment the information needed for decisions regarding policy, funding, programs, and services, Miami-Dade Community College (M-DCC) conducts periodic studies of its foreign student population. This report profiles international students at M-DCC for closing fall term 1990-91, and provides national data comparisons among…

  3. Profiling Bad Apples.

    ERIC Educational Resources Information Center

    LaFee, Scott

    2000-01-01

    Many school administrators want to develop profiling procedures to identify violence-prone students before bullets start flying. Warning signs (chronic depression, anger, abusive home conditions, violent history) are a staring point. Two FBI agents recommend visiting classrooms, identifying troubled kids, and ensuring that they get help. (MLH)

  4. Profiles of Algebraic Competence

    ERIC Educational Resources Information Center

    Humberstone, J.; Reeve, R.A.

    2008-01-01

    The algebraic competence of 72 12-year-old female students was examined to identify profiles of understanding reflecting different algebraic knowledge states. Beginning algebraic competence (mapping abilities: word-to-symbol and vice versa, classifying, and solving equations) was assessed. One week later, the nature of assistance required to map…

  5. Country Profiles, Iran.

    ERIC Educational Resources Information Center

    Friesen, John K.; Moore, Richard V.

    A profile of Iran is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population--size, number of households, women of reproductive age, growth patterns, role of women, urban/rural distribution,…

  6. English Teaching Profile: Bahrain

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    A profile of the state of English and English instruction in Bahrain covers the following topics: description of the role and status of English language use in industry and commerce, government, and education; the role of English at all levels of the educational system; the availability, characteristics, and qualifications of teachers of English;…

  7. The Moral Capacity Profile

    ERIC Educational Resources Information Center

    Wilks, Duffy; Ratheal, Juli D'Ann

    2011-01-01

    Effective counseling practice continues to be inevitably linked to underlying theories of behavioral causality. In this article, the authors present the Moral Capacity Profile of an individual from the perspective of the Amoral, Moral, Quasi-Moral/Quasi-Immoral, and Immoral Model of Behavior, a model that uniquely expands counseling's theoretical…

  8. PSI Member Profile.

    ERIC Educational Resources Information Center

    Professional Secretaries International, Kansas City, MO.

    A survey of 2,700 of the 27,000 members of Professional Secretaries International received 755 responses yielding the following profile of secretarial workers: (1) the average member is female, about 45 years old, married with no dependents living at home, and owns a single-family home in the suburbs; (2) most respondents have worked in office or…

  9. Profile of a Dropout

    ERIC Educational Resources Information Center

    Hammontree, Tom

    1978-01-01

    At Coral Gables Senior High, Dade County, Florida, a profile of the average student dropout was composed on the basis of school records to serve as a guide to identifying potential dropouts, who are given special remedial and counseling attention. Dropout rates have decreased from 10 percent to 4.4 over three years. (DTT)

  10. Profiles of Adult Learners.

    ERIC Educational Resources Information Center

    Illinois State Library, Springfield.

    Since January 1986, when the Illinois Secretary of State Literacy Grant Program began funding a wide variety of adult literacy programs, more than 30,000 students have sought help with reading. They have been matched with 25,000 tutors who have provided more than 2 million hours of volunteer instruction. The profiles in this booklet are stories of…

  11. Simple beam profile monitor

    SciTech Connect

    Gelbart, W.; Johnson, R. R.; Abeysekera, B.

    2012-12-19

    An inexpensive beam profile monitor is based on the well proven rotating wire method. The monitor can display beam position and shape in real time for particle beams of most energies and beam currents up to 200{mu}A. Beam shape, position cross-section and other parameters are displayed on a computer screen.

  12. Smart laser profiler

    NASA Astrophysics Data System (ADS)

    Martin, Francois; Laurent, John

    2004-05-01

    In order to meet the needs of many diverse industrial 3D inspection tasks, INO has developed a new concept for the design of a smart and modular 3D laser profiler. This stand-alone sensor which we call Smart Laser Profiler (SLP) is composed of a laser line projector, collection optics, a high frame rate camera and a digital signal processor (DSP). The on-board DSP is the key to this technology. The SLP sensor has been designed to be both compact and rugged and it is enclosed in a water resistant NEMA 4 class housing that is easy to install on a production line. The Smart Laser Profiler has several preprogrammed functions on the DSP that implement basic shape analysis algorithms like volume measurement and shape conformance. For more complex shape analysis, the sensor can transfer the raw 3D profiles to a PC through a high-speed communication link. The present article will describe both the unique hardware, electronics and optical architecture of the sensor and the software tools that were developed.

  13. PROFILE user's guide

    NASA Technical Reports Server (NTRS)

    Collins, L.; Saunders, D.

    1986-01-01

    User information for program PROFILE, an aerodynamics design utility for refining, plotting, and tabulating airfoil profiles is provided. The theory and implementation details for two of the more complex options are also presented. These are the REFINE option, for smoothing curvature in selected regions while retaining or seeking some specified thickness ratio, and the OPTIMIZE option, which seeks a specified curvature distribution. REFINE uses linear techniques to manipulate ordinates via the central difference approximation to second derivatives, while OPTIMIZE works directly with curvature using nonlinear least squares techniques. Use of programs QPLOT and BPLOT is also described, since all of the plots provided by PROFILE (airfoil coordinates, curvature distributions) are achieved via the general purpose QPLOT utility. BPLOT illustrates (again, via QPLOT) the shape functions used by two of PROFILE's options. The programs were designed and implemented for the Applied Aerodynamics Branch at NASA Ames Research Center, Moffett Field, California, and written in FORTRAN and run on a VAX-11/780 under VMS.

  14. Origins of metabolic profiling.

    PubMed

    Robinson, Arthur B; Robinson, Noah E

    2011-01-01

    Quantitative metabolic profiling originated as a 10-year project carried out between 1968 and 1978 in California. It was hypothesized and then demonstrated that quantitative analysis of a large number of metabolites - selected by analytical convenience and evaluated by computerized pattern recognition - could serve as a useful method for the quantitative measurement of human health. Using chromatographic and mass spectrometric methods to measure between 50 and 200 metabolites in more than 15,000 human specimens, statistically significant and diagnostically useful profiles for several human diseases and for other systematic variables including age, diet, fasting, sex, and other variables were demonstrated. It was also shown that genetically distinct metabolic profiles for each individual are present in both newborn infants and adults. In the course of this work, the many practical and conceptual problems involved in sampling, analysis, evaluation of results, and medical use of quantitative metabolic profiling were considered and, for the most part, solved. This article is an account of that research project. PMID:21207281

  15. Profiles in Measurement.

    ERIC Educational Resources Information Center

    Ludlow, Larry H.; Wright, Benjamin Drake; Linacre, John Michael; Webster, Linda; Andrich, David

    1998-01-01

    Four of the articles in this section profile major figures in measurement: (1) Sir Francis Galton (Larry Ludlow); (2) Georg Rasch (Benjamin Wright); (3) Benjamin Wright (John Michael Linacre); and (4) David Andrich (Linda Webster). The fifth article, by David Andrich, presents insights gained into the Rasch model. (SLD)

  16. 1991 corporate profiles.

    PubMed

    1991-01-01

    We feel a very important part of the career development of any healthcare supply manager is knowing the companies you do business with. The following Corporate Profiles, which contain information about the mission, structure, background and products of leading companies in the healthcare field, are an excellent way to achieve this knowledge.

  17. Rural Incubator Profile.

    ERIC Educational Resources Information Center

    Weinberg, Mark L.

    This profile summarizes the responses of 20 managers of rural business incubators, reporting on their operations, entry and exit policies, facility promotion, service arrangements and economic development outcomes. Incubators assist small businesses in the early stages of growth by providing them with rental space, shared services, management and…

  18. Country Profiles. France.

    ERIC Educational Resources Information Center

    Bourgeois-Pichat, Jean

    A profile of France is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: (1) location and description of the country; (2) population--size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, education,…

  19. COMPENDEX Profile Adjustment Manual.

    ERIC Educational Resources Information Center

    Standera, Oldrich

    If an information system is to survive, the users must be satisfied that it meets their needs promptly and consistently. It is essential to react quickly to any undesired result such as an extemely high or low output, too low a relevance or recall, or both. The search editor should feel responsbile not only for the profile setup but also for its…

  20. Country Profiles, The Philippines.

    ERIC Educational Resources Information Center

    Concepcion, Mercedes B.

    A profile of the Philippines is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition,…

  1. Country Profiles, Sweden.

    ERIC Educational Resources Information Center

    Svala, Gertrud

    A profile of Sweden is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population--size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  2. Country Profiles, Malaysia.

    ERIC Educational Resources Information Center

    Marzuki, Ariffin Bin; Peng, J. Y.

    A profile of Malaysia is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  3. Country Profiles, Mauritius.

    ERIC Educational Resources Information Center

    Xenos, Christos

    A profile of Mauritius is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  4. Country Profiles, Sierra Leone.

    ERIC Educational Resources Information Center

    Dow, Thomas E., Jr.

    A profile of Sierra Leone is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  5. Country Profiles, Ghana.

    ERIC Educational Resources Information Center

    Gaisie, S. K.; And Others

    A profile of Ghana is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  6. Country Profiles, Nepal.

    ERIC Educational Resources Information Center

    Taylor, Daniel; Thapa, Rita

    A profile of Nepal is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population--size, growth patterns, age/sex structure, geographical distribution, topographical obstacles, ethnic and religious…

  7. Country Profiles, Pakistan.

    ERIC Educational Resources Information Center

    Hardee, J. Gilbert; Satterthwaite, Adaline P.

    A profile of Pakistan is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  8. Country Profiles, Thailand.

    ERIC Educational Resources Information Center

    Perkin, Gordon W.; And Others

    A profile of Thailand is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  9. Country Profiles, Indonesia.

    ERIC Educational Resources Information Center

    Population Council, New York, NY.

    A profile of Indonesia is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population - size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  10. Country Profiles, Hong Kong.

    ERIC Educational Resources Information Center

    Population Council, New York, NY.

    A profile of Hong Kong is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  11. Country Profiles, Chile.

    ERIC Educational Resources Information Center

    Goldsmith, Alfredo; And Others

    A profile of Chile is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  12. Country Profiles, Turkey.

    ERIC Educational Resources Information Center

    Anderson, Lewis S.

    A profile of Turkey is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  13. Country Profiles, Taiwan.

    ERIC Educational Resources Information Center

    Keeny, S. M.; And Others

    A profile of Taiwan is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition, migration,…

  14. A Curriculum Orientation Profile.

    ERIC Educational Resources Information Center

    Babin, Patrick

    The Curriculum Orientation Profile was designed to assist in the identification of individual perspectives on curriculum and curricular decision-making. It contains 57 items, with which one agrees or disagrees. Each item is also given a code to be used in interpreting the score. Items with which one agrees are assigned to one of five codes,…

  15. English Teaching Profile: Turkey.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    A profile of the state of English and English instruction in Turkey covers the following topics: a description of the role and status of English language use in industry and commerce, government, and education; the role of English at all levels of the educational system; the availability, characteristics, and training of teachers of English; the…

  16. Low profile thermite igniter

    DOEpatents

    Halcomb, Danny L.; Mohler, Jonathan H.

    1991-03-05

    A thermite igniter/heat source comprising a housing, high-density thermite, and low-density thermite. The housing has a relatively low profile and can focus energy by means of a torch-like ejection of hot reaction products and is externally ignitable.

  17. English Teaching Profile: Colombia.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    This profile of the English language teaching situation in Colombia discusses the role of English in the educational system and in Colombian society. The status of English as the country's first foreign language is examined. It is noted that because Spanish is sufficient for most needs and because there is a relatively small number of Colombians…

  18. Country Education Profiles: Albania.

    ERIC Educational Resources Information Center

    International Bureau of Education, Geneva (Switzerland).

    One of a series of profiles prepared by the Cooperative Educational Abstracting Service, this brief outline provides basic background information on educational principles, system of administration, structure and organization, curricula, and teacher training in Albania. Statistics provided by the Unesco Office of Statistics show enrollment at all…

  19. Uncovering the real Broadmoor.

    PubMed

    2016-09-21

    Can nurses use the example of Broadmoor to enhance their own practice? Stephanie Jones-Berry reports behind the scenes in England's most infamous psychiatric hospital. Contrary to the sensational tabloid stories, she discusses the hospital's supportive ethos. Ms Jones-Berry talks to Broadmoor nurses about how the hospital's inclusive approach helps service users overcome mental health issues and how nurses work collaboratively with patients. She also interviews a former high-risk service user whose experiences at Broadmoor allowed him to transition back into the community and is now involved with mandatory induction training for staff. PMID:27654566

  20. Uncovering Discovery Layer Services

    ERIC Educational Resources Information Center

    Kennedy, Sean P.

    2014-01-01

    Today's electronic information landscape is growing exponentially with no signs of slowing. This poses a significant challenge for academic libraries. Librarians must continually learn and adapt to harness this explosion of resources. To fulfill their claim as the leaders in the information field they must be effective in providing access and…

  1. Charter Schools Uncovered

    ERIC Educational Resources Information Center

    Fowler-Finn, Thomas

    2008-01-01

    In this era of unforgiving accountability and test scores with high-stakes implications, important lessons can be learned from charter school marketing. Scrutiny of the regular public schools has never been more sharp-edged. Charter school proponents are becoming increasingly aggressive in promoting themselves as a viable alternative for…

  2. Uncovering Teacher Leadership

    ERIC Educational Resources Information Center

    Ackerman, Richard; Mackenzie, Sarah V.

    2006-01-01

    Teacher leaders are the pack mules of effective school improvement because they carry the weight of responsibility for ensuring that reforms take root in the classroom and deepen the learning of all students. They continually think about the gap in schools between the real and the ideal, and the discrepancies that they witness compel them to push…

  3. Uncovering Exoplanets using Polarimetry

    NASA Astrophysics Data System (ADS)

    Stam, D. M.

    2012-12-01

    Since the first discovery of a planet around a solar-type star by Mayor & Queloz in 1995, more than 700 of these exoplanets have been detected. Most of these are giant, gaseous planets, but small, presumably solid, exoplanets, that are much harder to detect, have also been found. Among the latter are even some that orbit in their star's habitable zone, where temperatures could be just right to allow liquid water on a planet's surface. Liquid water is generally considered to be essential for the existence of life. Whether liquid water actually exists on a planet depends strongly on the atmosphere's thickness and characteristics, such as the surface pressure and composition. Famous examples in the Solar System are Venus and the Earth, with similar sizes, inner compositions and orbital radii, but wildly different surface conditions. The characterization of the atmospheres of giant, gaseous exoplanets, and of the atmospheres and/or surfaces of small, solid exoplanets will allow a comparison with Solar System planets and it will open up a treasure trove of knowledge about the formation and evolution of planetary atmospheres and surfaces, thanks to the vast range of orbital distances, planet sizes and ages that can be studied. Characterization will also allow studying conditions for life and ultimately the existence of life around other stars. Some information about the upper atmospheric properties has already been derived for a few close-in, hot, giant exoplanets, whose thermal flux can be derived from measurements of the combined flux of the star and the planet. This method has also provided traces of an atmosphere around a large solid planet orbiting red dwarf star GJ1214. Characterization of the atmosphere and/or surface of exoplanets in wide orbits, resembling the cool planets in our Solar System, and in particular of small, solid, Earth-like planets in the habitable zone of Sun-like stars, is virtually impossible with transit observations. Indeed, polarimetry appears to be a strong tool both for the detection and the characterization of such cool exoplanets. Polarimetry helps their detection, because direct starlight is usually unpolarized, while starlight that has been reflected by a planet is usually polarized, especially at the phase angles favorable for observing exoplanets. Polarimetry thus improves the contrast between stars and their planets, and confirms that the detected object is indeed a planet. In my presentation, I will focus on the power of polarimetry for the characterization of exoplanets. This application is known from the derivation of the Venus cloud properties from the planet's polarized phase function by Hansen & Hovenier in 1974. Using numerically simulated flux and polarization phase functions and spectra for both gaseous and solid exoplanets, I will discuss the added value of polarimetry for exoplanet characterization as compared to flux observations, in particular for the retrieval of properties of clouds and hazes. Special attention will be given to the features in polarized phase functions that reveal the existence of liquid water clouds in the atmosphere (rainbows), even in the presence of ice clouds, or liquid water on the surface (glint) of an exoplanet. Using satellite data of the cloud and surface coverage of the Earth, calculated flux and polarization phase functions that should be observable from afar will be presented.

  4. Uncovering Earth's virome.

    PubMed

    Paez-Espino, David; Eloe-Fadrosh, Emiley A; Pavlopoulos, Georgios A; Thomas, Alex D; Huntemann, Marcel; Mikhailova, Natalia; Rubin, Edward; Ivanova, Natalia N; Kyrpides, Nikos C

    2016-08-25

    Viruses are the most abundant biological entities on Earth, but challenges in detecting, isolating, and classifying unknown viruses have prevented exhaustive surveys of the global virome. Here we analysed over 5 Tb of metagenomic sequence data from 3,042 geographically diverse samples to assess the global distribution, phylogenetic diversity, and host specificity of viruses. We discovered over 125,000 partial DNA viral genomes, including the largest phage yet identified, and increased the number of known viral genes by 16-fold. Half of the predicted partial viral genomes were clustered into genetically distinct groups, most of which included genes unrelated to those in known viruses. Using CRISPR spacers and transfer RNA matches to link viral groups to microbial host(s), we doubled the number of microbial phyla known to be infected by viruses, and identified viruses that can infect organisms from different phyla. Analysis of viral distribution across diverse ecosystems revealed strong habitat-type specificity for the vast majority of viruses, but also identified some cosmopolitan groups. Our results highlight an extensive global viral diversity and provide detailed insight into viral habitat distribution and host–virus interactions. PMID:27533034

  5. Uncovering metabolism in rhabdomyosarcoma

    PubMed Central

    Monti, Eugenio; Fanzani, Alessandro

    2016-01-01

    Abstract Rhabdomyosarcoma (RMS) is a myogenic tumor classified as the most frequent soft tissue sarcoma affecting children and adolescents. The histopathological classification includes 5 different histotypes, with 2 most predominant referred as to embryonal and alveolar, the latter being characterized by adverse outcome. The current molecular classification identifies 2 major subsets, those harboring the fused Pax3-Foxo1 transcription factor generating from a recurrent specific translocation (fusion-positive RMS), and those lacking this signature but harboring mutations in the RAS/PI3K/AKT signaling axis (fusion-negative RMS). Since little attention has been devoted to RMS metabolism until now, in this review we summarize the “state of art” of metabolism and discuss how some of the molecular signatures found in this cancer, as observed in other more common tumors, can predict important metabolic challenges underlying continuous cell growth, oxidative stress resistance and metastasis, which could be the subject of future targeted therapies. PMID:26209235

  6. Uncovering the Movement

    ERIC Educational Resources Information Center

    Scruggs, Afi-Odelia E.

    2010-01-01

    Vickie Malone's students see integration when they gather in her classroom at McComb (Mississippi) High School. Black and white youngsters talk and study with peers they've known since elementary school. She doesn't want them to learn history; she wants them to do history. She accomplishes that goal by prodding, poking and challenging her students…

  7. Uncovering foveal crowding?

    PubMed

    Lev, Maria; Yehezkel, Oren; Polat, Uri

    2014-02-12

    Visual crowding, as context modulation, reduce the ability to recognize objects in clutter, sets a fundamental limit on visual perception and object recognition. It's considered that crowding does not exist in the fovea and extensive efforts explored crowding in the periphery revealed various models that consider several aspects of spatial processing. Studies showed that spatial and temporal crowding are correlated, suggesting a tradeoff between spatial and temporal processing of crowding. We hypothesized that limiting stimulus availability should decrease object recognition in clutter. Here we show, for the first time, that robust contour interactions exist in the fovea for much larger target-flanker spacing than reported previously: participants overcome crowded conditions for long presentations times but exhibit contour interaction effects for short presentation times. Thus, by enabling enough processing time in the fovea, contour interactions can be overcome, enabling object recognition. Our results suggest that contemporary models of context modulation should include both time and spatial processing.

  8. [Safety profile of dolutegravir].

    PubMed

    Rivero, Antonio; Domingo, Pere

    2015-03-01

    Integrase inhibitors are the latest drug family to be added to the therapeutic arsenal against human immunodeficiency virus infection. Drugs in this family that do not require pharmacological boosting are characterized by a very good safety profile. The latest integrase inhibitor to be approved for use is dolutegravir. In clinical trials, dolutegravir has shown an excellent tolerability profile, both in antiretroviral-naïve and previously treated patients. Discontinuation rates due to adverse effects were 2% and 3%, respectively. The most frequent adverse effects were nausea, headache, diarrhea and sleep disturbance. A severe hypersensitivity reaction has been reported in only one patient. In patients coinfected with hepatropic viruses, the safety profile is similar to that in patients without coinfection. The lipid profile of dolutegravir is similar to that of raltegravir and superior to those of Atripla® and darunavir/ritonavir. Dolutegravir induces an early, predictable and non-progressive increase in serum creatinine of around 10% of baseline values in treatment-naïve patients and of 14% in treatment-experienced patients. This increase is due to inhibition of tubular creatinine secretion through the OCT2 receptor and does not lead to a real decrease in estimated glomerular filtration rate with algorithms that include serum creatinine. The effect of the combination of dolutegravir plus Kivexa(®) on biomarkers of bone remodeling is lower than that of Atripla(®). Dolutegravir has an excellent tolerability profile with no current evidence of long-term adverse effects. Its use is accompanied by an early and non-progressive increase in serum creatinine due to OCT2 receptor inhibition. In combination with abacavir/lamivudine, dolutegravir has a lower impact than enofovir/emtricitabine/efavirenz on bone remodelling markers. PMID:25858606

  9. Lipidomic profiling of sinus mucosa from patients with chronic rhinosinusitis

    PubMed Central

    Fazlollahi, Farbod; Kongmanas, Kessiri; Tanphaichitr, Nongnuj; Gopen, Quinton; Faull, Kym F.; Suh, Jeffrey D.

    2014-01-01

    Sinusitis is a cause of significant morbidity, substantial healthcare costs, and negative effects on quality of life. The primary objective of this study is to characterize the previously unknown lipid profile of sinonasal mucosa from patients with chronic rhinosinusitis (CRS) and from controls. Sinus mucosa samples were analyzed from 9 CRS patients with concomitant nasal polyps, 11 CRS patients without polyps, and 12 controls. Ten lone polyp samples were also analyzed. Samples were subjected to a modified Bligh/Dyer lipid extraction, then high performance thin layer chromatography (HPTLC), combined gas chromatography/electron impact-mass spectrometry (GC/EI-MS), and flow-injection/electrospray ionization-tandem mass spectrometry (FI/ESI-MS/MS). Data was analyzed for identification and profiling of major components. HPTLC revealed an array of species reflecting the lipid complexity of the samples. GC/EI-MS revealed cholesterol and several fatty acids. FI/ESI-MSMS revealed numerous lipid species, namely a host of phosphatidylcholines, phosphatidylethanolamines, ceramides and cholesteryl esters, but no detectable amounts of phosphatidyinositols or sulfated lipids. These results are a first step to uncover unique molecular biomarkers in CRS. PMID:25588779

  10. Proteomics and transcriptomics analyses of Arabidopsis floral buds uncover important functions of ARABIDOPSIS SKP1-LIKE1

    DOE PAGES

    Lu, Dihong; Ni, Weimin; Stanley, Bruce A.; Ma, Hong

    2016-03-03

    The ARABIDOPSIS SKP1-LIKE1 (ASK1) protein functions as a subunit of SKP1-CUL1-F-box (SCF) E3 ubiquitin ligases. Previous genetic studies showed that ASK1 plays important roles in Arabidopsis flower development and male meiosis. However, the molecular impact of ASK1-containing SCF E3 ubiquitin ligases (ASK1-E3s) on the floral proteome and transcriptome is unknown. Here we identified proteins that are potentially regulated by ASK1-E3s by comparing floral bud proteomes of wild-type and the ask1 mutant plants. More than 200 proteins were detected in the ask1 mutant but not in wild-type and >300 were detected at higher levels in the ask1 mutant than in wild-type,more » but their RNA levels were not significantly different between wild-type and ask1 floral buds as shown by transcriptomics analysis, suggesting that they are likely regulated at the protein level by ASK1-E3s. Integrated analyses of floral proteomics and transcriptomics of ask1 and wild-type uncovered several potential aspects of ASK1-E3 functions, including regulation of transcription regulators, kinases, peptidases, and ribosomal proteins, with implications on possible mechanisms of ASK1-E3 functions in floral development. In conclusion, our results suggested that ASK1-E3s play important roles in Arabidopsis protein degradation during flower development. This study opens up new possibilities for further functional studies of these candidate E3 substrates.« less

  11. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice

    PubMed Central

    Miyata, Haruhiko; Castaneda, Julio M.; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R.; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L.; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M.; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M.

    2016-01-01

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201–12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract–enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the “gold standard” to determine whether a gene’s function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  12. Genome engineering uncovers 54 evolutionarily conserved and testis-enriched genes that are not required for male fertility in mice.

    PubMed

    Miyata, Haruhiko; Castaneda, Julio M; Fujihara, Yoshitaka; Yu, Zhifeng; Archambeault, Denise R; Isotani, Ayako; Kiyozumi, Daiji; Kriseman, Maya L; Mashiko, Daisuke; Matsumura, Takafumi; Matzuk, Ryan M; Mori, Masashi; Noda, Taichi; Oji, Asami; Okabe, Masaru; Prunskaite-Hyyrylainen, Renata; Ramirez-Solis, Ramiro; Satouh, Yuhkoh; Zhang, Qian; Ikawa, Masahito; Matzuk, Martin M

    2016-07-12

    Gene-expression analysis studies from Schultz et al. estimate that more than 2,300 genes in the mouse genome are expressed predominantly in the male germ line. As of their 2003 publication [Schultz N, Hamra FK, Garbers DL (2003) Proc Natl Acad Sci USA 100(21):12201-12206], the functions of the majority of these testis-enriched genes during spermatogenesis and fertilization were largely unknown. Since the study by Schultz et al., functional analysis of hundreds of reproductive-tract-enriched genes have been performed, but there remain many testis-enriched genes for which their relevance to reproduction remain unexplored or unreported. Historically, a gene knockout is the "gold standard" to determine whether a gene's function is essential in vivo. Although knockout mice without apparent phenotypes are rarely published, these knockout mouse lines and their phenotypic information need to be shared to prevent redundant experiments. Herein, we used bioinformatic and experimental approaches to uncover mouse testis-enriched genes that are evolutionarily conserved in humans. We then used gene-disruption approaches, including Knockout Mouse Project resources (targeting vectors and mice) and CRISPR/Cas9, to mutate and quickly analyze the fertility of these mutant mice. We discovered that 54 mutant mouse lines were fertile. Thus, despite evolutionary conservation of these genes in vertebrates and in some cases in all eukaryotes, our results indicate that these genes are not individually essential for male mouse fertility. Our phenotypic data are highly relevant in this fiscally tight funding period and postgenomic age when large numbers of genomes are being analyzed for disease association, and will prevent unnecessary expenditures and duplications of effort by others. PMID:27357688

  13. Percutaneous Palliation of Pancreatic Head Cancer: Randomized Comparison of ePTFE/FEP-Covered Versus Uncovered Nitinol Biliary Stents

    SciTech Connect

    Krokidis, Miltiadis; Fanelli, Fabrizio; Orgera, Gianluigi; Tsetis, Dimitrios; Mouzas, Ioannis; Bezzi, Mario; Kouroumalis, Elias; Pasariello, Roberto; Hatzidakis, Adam

    2011-04-15

    The purpose of this study was to compare the clinical effectiveness of expanded polytetrafluoroethylene/fluorinated-ethylene-propylene (ePTFE/FEP)-covered stents with that of uncovered nitinol stents for the palliation of malignant jaundice caused by inoperable pancreatic head cancer. Eighty patients were enrolled in a prospective randomized study. Bare nitinol stents were used in half of the patients, and ePTFE/FEP-covered stents were used in the remaining patients. Patency, survival, complications, and mean cost were calculated in both groups. Mean patency was 166.0 {+-} 13.11 days for the bare-stent group and 234.0 {+-} 20.87 days for the covered-stent group (p = 0.007). Primary patency rates at 3, 6, and 12 months were 77.5, 69.8, and 69.8% for the bare-stent group and 97.5, 92.2, and 87.6% for the covered-stent group, respectively. Mean secondary patency was 123.7 {+-} 22.5 days for the bare-stent group and 130.3 {+-} 21.4 days for the covered-stent group. Tumour ingrowth occurred exclusively in the bare-stent group in 27.5% of cases (p = 0.002). Median survival was 203.2 {+-} 11.8 days for the bare-stent group and 247.0 {+-} 20 days for the covered-stent group (p = 0.06). Complications and mean cost were similar in both groups. Regarding primary patency and ingrowth rate, ePTFE/FEP-covered stents have shown to be significantly superior to bare nitinol stents for the palliation of malignant jaundice caused by inoperable pancreatic head cancer and pose comparable cost and complications. Use of a covered stent does not significantly influence overall survival rate; nevertheless, the covered endoprosthesis seems to offer result in fewer reinterventions and better quality of patient life.

  14. High Genetic Diversity and Fine-Scale Spatial Structure in the Marine Flagellate Oxyrrhis marina (Dinophyceae) Uncovered by Microsatellite Loci

    PubMed Central

    Lowe, Chris D.; Montagnes, David J. S.; Martin, Laura E.; Watts, Phillip C.

    2010-01-01

    Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites) has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1–6 and 7–23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (He) of 0.00–0.30 and 0.81–0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional FST values indicated weak to moderate population sub-division (0.01–0.12), but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms. PMID:21203414

  15. Human iPS Cell-Derived Neurons Uncover the Impact of Increased Ras Signaling in Costello Syndrome

    PubMed Central

    Rooney, Gemma E.; Goodwin, Alice F.; Depeille, Philippe; Sharir, Amnon; Schofield, Claude M.; Yeh, Erika; Roose, Jeroen P.; Klein, Ophir D.; Rauen, Katherine A.; Weiss, Lauren A.

    2016-01-01

    Increasing evidence implicates abnormal Ras signaling as a major contributor in neurodevelopmental disorders, yet how such signaling causes cortical pathogenesis is unknown. We examined the consequences of aberrant Ras signaling in the developing mouse brain and uncovered several critical phenotypes, including increased production of cortical neurons and morphological deficits. To determine whether these phenotypes are recapitulated in humans, we generated induced pluripotent stem (iPS) cell lines from patients with Costello syndrome (CS), a developmental disorder caused by abnormal Ras signaling and characterized by neurodevelopmental abnormalities, such as cognitive impairment and autism. Directed differentiation toward a neuroectodermal fate revealed an extended progenitor phase and subsequent increased production of cortical neurons. Morphological analysis of mature neurons revealed significantly altered neurite length and soma size in CS patients. This study demonstrates the synergy between mouse and human models and validates the use of iPS cells as a platform to study the underlying cellular pathologies resulting from signaling deficits. SIGNIFICANCE STATEMENT Increasing evidence implicates Ras signaling dysfunction as a major contributor in psychiatric and neurodevelopmental disorders, such as cognitive impairment and autism, but the underlying cortical cellular pathogenesis remains unclear. This study is the first to reveal human neuronal pathogenesis resulting from abnormal Ras signaling and provides insights into how these phenotypic abnormalities likely contribute to neurodevelopmental disorders. We also demonstrate the synergy between mouse and human models, thereby validating the use of iPS cells as a platform to study underlying cellular pathologies resulting from signaling deficits. Recapitulating human cellular pathologies in vitro facilitates the future high throughput screening of potential therapeutic agents that may reverse phenotypic and

  16. Upregulation of glycans containing 3' fucose in a subset of pancreatic cancers uncovered using fusion-tagged lectins.

    PubMed

    Singh, Sudhir; Pal, Kuntal; Yadav, Jessica; Tang, Huiyuan; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Ensink, Elliot; Kc, Birendra; Hostetter, Galen; Xu, H Eric; Bern, Marshall; Smith, David F; Mehta, Anand S; Brand, Randall; Melcher, Karsten; Haab, Brian B

    2015-06-01

    The fucose post-translational modification is frequently increased in pancreatic cancer, thus forming the basis for promising biomarkers, but a subset of pancreatic cancer patients does not elevate the known fucose-containing biomarkers. We hypothesized that such patients elevate glycan motifs with fucose in linkages and contexts different from the known fucose-containing biomarkers. We used a database of glycan array data to identify the lectins CCL2 to detect glycan motifs with fucose in a 3' linkage; CGL2 for motifs with fucose in a 2' linkage; and RSL for fucose in all linkages. We used several practical methods to test the lectins and determine the optimal mode of detection, and we then tested whether the lectins detected glycans in pancreatic cancer patients who did not elevate the sialyl-Lewis A glycan, which is upregulated in ∼75% of pancreatic adenocarcinomas. Patients who did not upregulate sialyl-Lewis A, which contains fucose in a 4' linkage, tended to upregulate fucose in a 3' linkage, as detected by CCL2, but they did not upregulate total fucose or fucose in a 2' linkage. CCL2 binding was high in cancerous epithelia from pancreatic tumors, including areas negative for sialyl-Lewis A and a related motif containing 3' fucose, sialyl-Lewis X. Thus, glycans containing 3' fucose may complement sialyl-Lewis A to contribute to improved detection of pancreatic cancer. Furthermore, the use of panels of recombinant lectins may uncover details about glycosylation that could be important for characterizing and detecting cancer.

  17. High genetic diversity and fine-scale spatial structure in the marine flagellate Oxyrrhis marina (Dinophyceae) uncovered by microsatellite loci.

    PubMed

    Lowe, Chris D; Montagnes, David J S; Martin, Laura E; Watts, Phillip C

    2010-01-01

    Free-living marine protists are often assumed to be broadly distributed and genetically homogeneous on large spatial scales. However, an increasing application of highly polymorphic genetic markers (e.g., microsatellites) has provided evidence for high genetic diversity and population structuring on small spatial scales in many free-living protists. Here we characterise a panel of new microsatellite markers for the common marine flagellate Oxyrrhis marina. Nine microsatellite loci were used to assess genotypic diversity at two spatial scales by genotyping 200 isolates of O. marina from 6 broad geographic regions around Great Britain and Ireland; in one region, a single 2 km shore line was sampled intensively to assess fine-scale genetic diversity. Microsatellite loci resolved between 1-6 and 7-23 distinct alleles per region in the least and most variable loci respectively, with corresponding variation in expected heterozygosities (H(e)) of 0.00-0.30 and 0.81-0.93. Across the dataset, genotypic diversity was high with 183 genotypes detected from 200 isolates. Bayesian analysis of population structure supported two model populations. One population was distributed across all sampled regions; the other was confined to the intensively sampled shore, and thus two distinct populations co-occurred at this site. Whilst model-based analysis inferred a single UK-wide population, pairwise regional F(ST) values indicated weak to moderate population sub-division (0.01-0.12), but no clear correlation between spatial and genetic distance was evident. Data presented in this study highlight extensive genetic diversity for O. marina; however, it remains a substantial challenge to uncover the mechanisms that drive genetic diversity in free-living microorganisms.

  18. Flexible and waterproof micro-sensors to uncover zebrafish circadian rhythms: The next generation of cardiac monitoring for drug screening.

    PubMed

    Zhang, Xiaoxiao; Beebe, Tyler; Jen, Nelson; Lee, Chia-An; Tai, Yuchong; Hsiai, Tzung K

    2015-09-15

    Flexible electronics are the next generation of sensors for mobile health and implantation. Zebrafish (Danio rerio) is an emergent strategy for pre-clinical drug development and toxicity testing. To address the confounding effects from sedation of fish and removal from the aquatic habitat for micro-electrocardiogram (µECG) measurements, we developed waterproof and wearable sensors to uncover the circadian variation in heart rate (HR) and heart rate variability (HRV) (Massin et al., 2000). The parylene-C based ECG sensor consisted of an ultra-soft silicone integrated jacket designed to wrap around the fish during swimming. The Young's modulus of this silicone jacket matched with the fish surface, and an extended parylene cable connected the underwater chest electrodes with the out-of water electronics. In addition, embedded micro-glass spheres in the silicone effectively reduced the effective density of the jacket to ~1 g cm(-3). These innovations enabled physiological ECG telemetry in the fish's natural habitat without the need for sedation. Furthermore, a set of non-linear signal processing techniques filtered out the breathing and electromagnetic artifacts from the recorded signals. We observed a reduction in mean HR and an increase in HRV over 24h at 10 dpa, accompanied by QT prolongation as well as diurnal variations, followed by normalization in mean HR and QT intervals at 26 days post ventricular amputation (dpa). We revealed Amiodarone-mediated QTc prolongation, HR reduction and HRV increase otherwise masked by sedation. The novel features of the flexible silicon jacket for µECG telemetry unraveled the biological clock and normalization of QT intervals at 26 dpa, providing the first evidence of new physiological phenomena during cardiac injury and repair as well as cardiac drug-mediated aberrant rhythms. Thus, the light weight and waterproof design holds promise to advance the next generation of mobile health and drug discovery. PMID:25909335

  19. Uncovering subdominant cytotoxic T-lymphocyte responses in lymphocytic choriomeningitis virus-infected BALB/c mice.

    PubMed Central

    van der Most, R G; Concepcion, R J; Oseroff, C; Alexander, J; Southwood, S; Sidney, J; Chesnut, R W; Ahmed, R; Sette, A

    1997-01-01

    The cytotoxic T-lymphocyte response against lymphocytic choriomeningitis virus (LCMV) in BALB/c mice is predominantly directed against a single, Ld-restricted epitope in the viral nucleoprotein (residues 118 to 126). To investigate whether any Kd/Dd-restricted responses were activated but did not expand during the primary response, we used a BALB/c mutant, BALB/c-H-2dm2, which does not express the Ld molecule. Splenocytes from LCMV-infected BALB/c mice were transferred into irradiated BALB/c-H-2dm2 mice and rechallenged with LCMV. Thus, they were exposed to an antigenic stimulus without the involvement of the immunodominant Ld-restricted epitope. In this adoptive transfer model, the donor splenocytes protected the recipient mice against chronic LCMV infection by mounting a potent Kd- and/or Dd-restricted secondary antiviral response. Analysis of a panel of Kd binding LCMV peptides revealed that residues 283 to 291 from the viral glycoprotein (GP(283-291)) comprise a major new epitope in the adoptive transfer model. Because the donor splenocytes were first activated during the primary infection in BALB/c mice, the GP(283-291) epitope is a subdominant epitope in BALB/c mice that becomes dominant after rechallenge in BALB/c-H-2dm2 mice. This study makes two points. First, it shows that subdominant CTL responses can be protective, and second, it provides a general experimental approach for uncovering subdominant CTL responses in vivo. This strategy can be used to identify subdominant T-cell responses in other systems. PMID:9188577

  20. Temperature profile detector

    DOEpatents

    Tokarz, R.D.

    1983-10-11

    Disclosed is a temperature profile detector shown as a tubular enclosure surrounding an elongated electrical conductor having a plurality of meltable conductive segments surrounding it. Duplicative meltable segments are spaced apart from one another along the length of the enclosure. Electrical insulators surround these elements to confine molten material from the segments in bridging contact between the conductor and a second electrical conductor, which might be the confining tube. The location and rate of growth of the resulting short circuits between the two conductors can be monitored by measuring changes in electrical resistance between terminals at both ends of the two conductors. Additional conductors and separate sets of meltable segments operational at differing temperatures can be monitored simultaneously for measuring different temperature profiles. 8 figs.

  1. Temperature profile detector

    DOEpatents

    Tokarz, Richard D.

    1983-01-01

    A temperature profile detector shown as a tubular enclosure surrounding an elongated electrical conductor having a plurality of meltable conductive segments surrounding it. Duplicative meltable segments are spaced apart from one another along the length of the enclosure. Electrical insulators surround these elements to confine molten material from the segments in bridging contact between the conductor and a second electrical conductor, which might be the confining tube. The location and rate of growth of the resulting short circuits between the two conductors can be monitored by measuring changes in electrical resistance between terminals at both ends of the two conductors. Additional conductors and separate sets of meltable segments operational at differing temperatures can be monitored simultaneously for measuring different temperature profiles.

  2. 1993 corporate profiles.

    PubMed

    1993-01-01

    Some of the companies in this year's Corporate Profiles section you know and use; some may seem familiar; but all of the companies are important to you as healthcare supply managers. This detailed overview of the history, sales and service, product lines, new technology and future plans of each corporation is brought to you as a service from JHMM, to be used as a review, an update and a resource throughout the year. PMID:10130626

  3. Cinnarizine: Comprehensive Profile.

    PubMed

    Haress, Nadia G

    2015-01-01

    Cinnarizine is a piperazine derivative with antihistaminic, antiserotonergic, antidopaminergic, and calcium channel-blocking activities. A comprehensive profile was performed on cinnarizine including its description and the different methods of analysis. The 1H NMR and 13C one- and two-dimensional NMR methods were used. In addition, infrared and mass spectral analyses were performed which all confirmed the structure of cinnarizine. PMID:26051684

  4. Temperature profile detector

    DOEpatents

    Tokarz, Richard D.

    1983-01-01

    Temperature profiles at elevated temperature conditions are monitored by use of an elongated device having two conductors spaced by the minimum distance required to normally maintain an open circuit between them. The melting point of one conductor is selected at the elevated temperature being detected, while the melting point of the other is higher. As the preselected temperature is reached, liquid metal will flow between the conductors, creating short circuits which are detectable as to location.

  5. Temperature-profile detector

    DOEpatents

    Not Available

    1981-01-29

    Temperature profiles at elevated temperature conditions are monitored by use of an elongated device having two conductors spaced by the minimum distance required to normally maintain an open circuit between them. The melting point of one conductor is selected at the elevated temperature being detected, while the melting point of the other is higher. As the preselected temperature is reached, liquid metal will flow between the conductors creating short circuits which are detectable as to location.

  6. Compare Gene Profiles

    SciTech Connect

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linux environment in serial or parallel mode.

  7. Anchorage Kindergarten Profile: Implementing the Alaska Kindergarten Developmental Profile.

    ERIC Educational Resources Information Center

    Fenton, Ray

    This paper discusses the development of the Anchorage Kindergarten Developmental Profile in the context of the Alaska Kindergarten Developmental Profile and presents some evaluation results from studies of the Anchorage measure. Alaska mandated the completion of an Alaska Developmental Profile (ADP) on each kindergarten student and each student…

  8. Surface profiling interferometer

    DOEpatents

    Takacs, Peter Z.; Qian, Shi-Nan

    1989-01-01

    The design of a long-trace surface profiler for the non-contact measurement of surface profile, slope error and curvature on cylindrical synchrotron radiation (SR) mirrors. The optical system is based upon the concept of a pencil-beam interferometer with an inherent large depth-of-field. The key feature of the optical system is the zero-path-difference beam splitter, which separates the laser beam into two colinear, variable-separation probe beams. A linear array detector is used to record the interference fringe in the image, and analysis of the fringe location as a function of scan position allows one to reconstruct the surface profile. The optical head is mounted on an air bearing slide with the capability to measure long aspheric optics, typical of those encountered in SR applications. A novel feature of the optical system is the use of a transverse "outrigger" beam which provides information on the relative alignment of the scan axis to the cylinder optic symmetry axis.

  9. QTL Mapping in Three Rice Populations Uncovers Major Genomic Regions Associated with African Rice Gall Midge Resistance.

    PubMed

    Yao, Nasser; Lee, Cheng-Ruei; Semagn, Kassa; Sow, Mounirou; Nwilene, Francis; Kolade, Olufisayo; Bocco, Roland; Oyetunji, Olumoye; Mitchell-Olds, Thomas; Ndjiondjop, Marie-Noëlle

    2016-01-01

    African rice gall midge (AfRGM) is one of the most destructive pests of irrigated and lowland African ecologies. This study aimed to identify the quantitative trait loci (QTL) associated with AfRGM pest incidence and resistance in three independent bi-parental rice populations (ITA306xBW348-1, ITA306xTOG7106 and ITA306xTOS14519), and to conduct meta QTL (mQTL) analysis to explore whether any genomic regions are conserved across different genetic backgrounds. Composite interval mapping (CIM) conducted on the three populations independently uncovered a total of 28 QTLs associated with pest incidence (12) and pest severity (16). The number of QTLs per population associated with AfRGM resistance varied from three in the ITA306xBW348-1 population to eight in the ITA306xTOG7106 population. Each QTL individually explained 1.3 to 34.1% of the phenotypic variance. The major genomic region for AfRGM resistance had a LOD score and R2 of 60.0 and 34.1% respectively, and mapped at 111 cM on chromosome 4 (qAfrGM4) in the ITA306xTOS14519 population. The meta-analysis reduced the number of QTLs from 28 to 17 mQTLs, each explaining 1.3 to 24.5% of phenotypic variance, and narrowed the confidence intervals by 2.2 cM. There was only one minor effect mQTL on chromosome 1 that was common in the TOS14519 and TOG7106 genetic backgrounds; all other mQTLs were background specific. We are currently fine-mapping and validating the major effect genomic region on chromosome 4 (qAfRGM4). This is the first report in mapping the genomic regions associated with the AfRGM resistance, and will be highly useful for rice breeders. PMID:27508500

  10. QTL Mapping in Three Rice Populations Uncovers Major Genomic Regions Associated with African Rice Gall Midge Resistance

    PubMed Central

    Semagn, Kassa; Sow, Mounirou; Nwilene, Francis; Kolade, Olufisayo; Bocco, Roland; Oyetunji, Olumoye; Mitchell-Olds, Thomas; Ndjiondjop, Marie-Noëlle

    2016-01-01

    African rice gall midge (AfRGM) is one of the most destructive pests of irrigated and lowland African ecologies. This study aimed to identify the quantitative trait loci (QTL) associated with AfRGM pest incidence and resistance in three independent bi-parental rice populations (ITA306xBW348-1, ITA306xTOG7106 and ITA306xTOS14519), and to conduct meta QTL (mQTL) analysis to explore whether any genomic regions are conserved across different genetic backgrounds. Composite interval mapping (CIM) conducted on the three populations independently uncovered a total of 28 QTLs associated with pest incidence (12) and pest severity (16). The number of QTLs per population associated with AfRGM resistance varied from three in the ITA306xBW348-1 population to eight in the ITA306xTOG7106 population. Each QTL individually explained 1.3 to 34.1% of the phenotypic variance. The major genomic region for AfRGM resistance had a LOD score and R2 of 60.0 and 34.1% respectively, and mapped at 111 cM on chromosome 4 (qAfrGM4) in the ITA306xTOS14519 population. The meta-analysis reduced the number of QTLs from 28 to 17 mQTLs, each explaining 1.3 to 24.5% of phenotypic variance, and narrowed the confidence intervals by 2.2 cM. There was only one minor effect mQTL on chromosome 1 that was common in the TOS14519 and TOG7106 genetic backgrounds; all other mQTLs were background specific. We are currently fine-mapping and validating the major effect genomic region on chromosome 4 (qAfRGM4). This is the first report in mapping the genomic regions associated with the AfRGM resistance, and will be highly useful for rice breeders. PMID:27508500

  11. Characterization of the serine acetyltransferase gene family of Vitis vinifera uncovers differences in regulation of OAS synthesis in woody plants

    PubMed Central

    Tavares, Sílvia; Wirtz, Markus; Beier, Marcel P.; Bogs, Jochen; Hell, Rüdiger; Amâncio, Sara

    2015-01-01

    In higher plants cysteine biosynthesis is catalyzed by O-acetylserine(thiol)lyase (OASTL) and represents the last step of the assimilatory sulfate reduction pathway. It is mainly regulated by provision of O-acetylserine (OAS), the nitrogen/carbon containing backbone for fixation of reduced sulfur. OAS is synthesized by Serine acetyltransferase (SERAT), which reversibly interacts with OASTL in the cysteine synthase complex (CSC). In this study we identify and characterize the SERAT gene family of the crop plant Vitis vinifera. The identified four members of the VvSERAT protein family are assigned to three distinct groups upon their sequence similarities to Arabidopsis SERATs. Expression of fluorescently labeled VvSERAT proteins uncover that the sub-cellular localization of VvSERAT1;1 and VvSERAT3;1 is the cytosol and that VvSERAT2;1 and VvSERAT2;2 localize in addition in plastids and mitochondria, respectively. The purified VvSERATs of group 1 and 2 have higher enzymatic activity than VvSERAT3;1, which display a characteristic C-terminal extension also present in AtSERAT3;1. VvSERAT1;1 and VvSERAT2;2 are evidenced to form the CSC. CSC formation activates VvSERAT2;2, by releasing CSC-associated VvSERAT2;2 from cysteine inhibition. Thus, subcellular distribution of SERAT isoforms and CSC formation in cytosol and mitochondria is conserved between Arabidopsis and grapevine. Surprisingly, VvSERAT2;1 lack the canonical C-terminal tail of plant SERATs, does not form the CSC and is almost insensitive to cysteine inhibition (IC50 = 1.9 mM cysteine). Upon sulfate depletion VvSERAT2;1 is strongly induced at the transcriptional level, while transcription of other VvSERATs is almost unaffected in sulfate deprived grapevine cell suspension cultures. Application of abiotic stresses to soil grown grapevine plants revealed isoform-specific induction of VvSERAT2;1 in leaves upon drought, whereas high light- or temperature- stress hardly trigger VvSERAT2;1 transcription. PMID:25741355

  12. Imprints of galaxy evolution on H II regions. Memory of the past uncovered by the CALIFA survey

    NASA Astrophysics Data System (ADS)

    Sánchez, S. F.; Pérez, E.; Rosales-Ortega, F. F.; Miralles-Caballero, D.; López-Sánchez, A. R.; Iglesias-Páramo, J.; Marino, R. A.; Sánchez-Menguiano, L.; García-Benito, R.; Mast, D.; Mendoza, M. A.; Papaderos, P.; Ellis, S.; Galbany, L.; Kehrig, C.; Monreal-Ibero, A.; González Delgado, R.; Mollá, M.; Ziegler, B.; de Lorenzo-Cáceres, A.; Mendez-Abreu, J.; Bland-Hawthorn, J.; Bekeraitė, S.; Roth, M. M.; Pasquali, A.; Díaz, A.; Bomans, D.; van de Ven, G.; Wisotzki, L.

    2015-01-01

    Context. H ii regions in galaxies are the sites of star formation, so they are special places for understanding the build-up of stellar mass in the universe. The line ratios of this ionized gas are frequently used to characterize the ionization conditions. In particular, the oxygen abundances are assumed to trace the chemical enrichment of galaxies. Aims: We explore the connections between the ionization conditions and the properties of the overall underlying stellar population (ionizing or not-ionizing) in H ii regions, in order to uncover the actual physical connection between them. Methods: We use the H ii regions catalog from the CALIFA survey, which is the largest in existence with more than 5000 H ii regions, to explore their distribution across the classical [O iii] λ5007/Hβ vs. [N ii] λ6583/Hα diagnostic diagram, and the way it depends on the oxygen abundance, ionization parameter, electron density, and dust attenuation. The location of H ii regions within this diagram is compared with predictions from photoionization models. Finally, we explore the dependence of the location within the diagnostic diagram on the properties of the host galaxies, the galactocentric distances, and the properties of the underlying stellar population. Results: The H ii regions with weaker ionization strengths and more metal-rich are located in the bottom righthand area of the diagram. In contrast, those regions with stronger ionization strengths and more metal poor are located in the upper lefthand end of the diagram. Photoionization models per se do not predict these correlations between the parameters and the line ratios. The H ii regions located in earlier-type galaxies, closer to the center and formed in older and more metal-rich regions of the galaxies are located in the bottom-right area of the diagram. On the other hand, those regions located in late-type galaxies in the outer regions of the disks and formed on younger and more metal-poor regions lie in the top

  13. Hanford Site Ecological Quality Profile

    SciTech Connect

    Bilyard, Gordon R.; Sackschewsky, Michael R.; Tzemos, Spyridon

    2002-02-17

    This report reviews the ecological quality profile methodology and results for the Hanford Site. It covers critical ecological assets and terrestrial resources, those in Columbia River corridor and those threatened and engdangered, as well as hazards and risks to terrestrial resources. The features of a base habitat value profile are explained, as are hazard and ecological quality profiles.

  14. Competitive Cooperation: The Iceberg Profile.

    ERIC Educational Resources Information Center

    Vaughan, Jerry L.

    Competitive athletes' scores on the Profile of Mood States (POMS) test create an iceberg-like pattern known as the "Iceberg Profile." Their scores for tension, depression, anger, fatigue, and confusion are low while their scores on vigor juts upward creating the "Iceberg Profile." Persons in a cooperative relationship are often competing against…

  15. Safety profile of bevantolol.

    PubMed

    Bray, J S

    1986-03-01

    Double-blind and long-term open-label studies have demonstrated a remarkably favorable safety profile for bevantolol. The drug was associated with a low incidence of adverse experiences similar to that observed with placebo. The adverse experiences were mostly mild to moderate and of the types found previously for other beta-blocking drugs. Very few patients withdrew from clinical studies because of adverse effects. Some patients continued on study for over four years. Bevantolol offers safe beta-blocking activity for the long-term treatment of angina and hypertension.

  16. Profile Interface Generator

    2013-11-09

    The Profile Interface Generator (PIG) is a tool for loosely coupling applications and performance tools. It enables applications to write code that looks like standard C and Fortran functions calls, without requiring that applications link to specific implementations of those function calls. Performance tools can register with PIG in order to listen to only the calls that give information they care about. This interface reduces the build and configuration burden on application developers and allowsmore » semantic instrumentation to live in production codes without interfering with production runs.« less

  17. Compare Gene Profiles

    2014-05-31

    Compare Gene Profiles (CGP) performs pairwise gene content comparisons among a relatively large set of related bacterial genomes. CGP performs pairwise BLAST among gene calls from a set of input genome and associated annotation files, and combines the results to generate lists of common genes, unique genes, homologs, and genes from each genome that differ substantially in length from corresponding genes in the other genomes. CGP is implemented in Python and runs in a Linuxmore » environment in serial or parallel mode.« less

  18. Profile Interface Generator

    SciTech Connect

    2013-11-09

    The Profile Interface Generator (PIG) is a tool for loosely coupling applications and performance tools. It enables applications to write code that looks like standard C and Fortran functions calls, without requiring that applications link to specific implementations of those function calls. Performance tools can register with PIG in order to listen to only the calls that give information they care about. This interface reduces the build and configuration burden on application developers and allows semantic instrumentation to live in production codes without interfering with production runs.

  19. Deflagration Wave Profiles

    SciTech Connect

    Menikoff, Ralph

    2012-04-03

    Shock initiation in a plastic-bonded explosives (PBX) is due to hot spots. Current reactive burn models are based, at least heuristically, on the ignition and growth concept. The ignition phase occurs when a small localized region of high temperature (or hot spot) burns on a fast time scale. This is followed by a growth phase in which a reactive front spreads out from the hot spot. Propagating reactive fronts are deflagration waves. A key question is the deflagration speed in a PBX compressed and heated by a shock wave that generated the hot spot. Here, the ODEs for a steady deflagration wave profile in a compressible fluid are derived, along with the needed thermodynamic quantities of realistic equations of state corresponding to the reactants and products of a PBX. The properties of the wave profile equations are analyzed and an algorithm is derived for computing the deflagration speed. As an illustrative example, the algorithm is applied to compute the deflagration speed in shock compressed PBX 9501 as a function of shock pressure. The calculated deflagration speed, even at the CJ pressure, is low compared to the detonation speed. The implication of this are briefly discussed.

  20. Autoantibody profiling in APS.

    PubMed

    Roggenbuck, D; Somma, V; Schierack, P; Borghi, M O; Meroni, P L

    2014-10-01

    The international consensus for the classification of antiphospholipid syndrome (APS) requires clinical and laboratory criteria to be considered at an equal level for diagnosing APS. Thus, detection of antiphospholipid antibodies (aPL) being a hallmark of APS has been the object of intensive investigation over the past 40 years. However, appropriate detection of aPL still remains a laboratory challenge due to their heterogeneity comprising autoantibodies reactive to different phospholipid-binding plasma proteins, such as beta-2 glycoprotein I (β2GPI) and prothrombin. The relevance of aPL interacting with phospholipids other than cardiolipin (CL, diphosphatidylglycerol), such as phosphatidylserine (PS), remains elusive with regard to the diagnosis of APS. Recently, the concept of aPL profiling has been introduced to assess the risk of thrombotic complications in patients with APS. New assay techniques, apart from enzyme-linked immunosorbent assays (ELISAs) recommended by the international consensus for the classification of APS, have been proposed for multiplexing of aPL testing. Line immunoassays (LIAs) employing a novel hydrophobic solid phase for the simultaneous detection of different aPL seem to be an intriguing alternative. We evaluated a novel multiplex LIA employing a hydrophobic membrane coated with different phospholipid (PL)-binding proteins or PLs. The performance characteristics of this new multiplexing assay technique demonstrated its usefulness for aPL profiling.

  1. Changes in the Distribution of Hepatic Arterial Blood Flow Following TIPS with Uncovered Stent and Stent-Graft: An Experimental Study

    SciTech Connect

    Keussen, Inger; Song, Ho-Young; Bajc, Marika; Cwikiel, Wojciech

    2002-08-15

    Purpose: To evaluate changes in distribution of hepatic arterial blood flow in the liver following insertion of an uncovered stent and subsequently a stent-graft in the transjugular intrahepatic portosystemic shunt (TIPS) channel.Methods: The experiments were performed in eight healthy pigs under general anesthesia. In a pilot study in one pig, scintigraphic evaluation of arterial perfusion to the liver was done before and after inflation of a balloon in the right hepatic vein. In the other pigs, outflow from the right liver vein was checked repeatedly by contrast injection through a percutaneously inserted catheter. The arterial perfusion through the liver was examined by scintigraphy, following selective injection of macro-aggregate of 99Tcm-labeled human serum albumin 99Tcm-HSA) into the hepatic artery. This examination was done before and after creation of a TIPS with an uncovered stent and subsequently after insertion of a covered stent-graft into the cranial portion of the shunt channel. Results: In the pilot study changes in the arterial perfusion to the liver were easily detectable by scintigraphy. One pig died during the procedure and another pig was excluded due to dislodgement of the hepatic artery catheter. The inserted covered stent obstructed venous outflow from part of the right liver lobe. The 99Tcm-HSA activity in this part remained unchanged after TIPS creation with an uncovered stent. A reduction in activity was seen after insertion of a stent-graft (p0.06).Conclusion: The distribution of the hepaticarterial blood flow is affected by creation of a TIPS with a stent-graft, in the experimental pig model.

  2. High-throughput sequencing approach uncovers the miRNome of peritoneal endometriotic lesions and adjacent healthy tissues.

    PubMed

    Saare, Merli; Rekker, Kadri; Laisk-Podar, Triin; Sõritsa, Deniss; Roost, Anne Mari; Simm, Jaak; Velthut-Meikas, Agne; Samuel, Külli; Metsalu, Tauno; Karro, Helle; Sõritsa, Andrei; Salumets, Andres; Peters, Maire

    2014-01-01

    Accumulating data have shown the involvement of microRNAs (miRNAs) in endometriosis pathogenesis. In this study, we used a novel approach to determine the endometriotic lesion-specific miRNAs by high-throughput small RNA sequencing of paired samples of peritoneal endometriotic lesions and matched healthy surrounding tissues together with eutopic endometria of the same patients. We found five miRNAs specific to epithelial cells--miR-34c, miR-449a, miR-200a, miR-200b and miR-141 showing significantly higher expression in peritoneal endometriotic lesions compared to healthy peritoneal tissues. We also determined the expression levels of miR-200 family target genes E-cadherin, ZEB1 and ZEB2 and found that the expression level of E-cadherin was significantly higher in endometriotic lesions compared to healthy tissues. Further evaluation verified that studied miRNAs could be used as diagnostic markers for confirming the presence of endometrial cells in endometriotic lesion biopsy samples. Furthermore, we demonstrated that the miRNA profile of peritoneal endometriotic lesion biopsies is largely masked by the surrounding peritoneal tissue, challenging the discovery of an accurate lesion-specific miRNA profile. Taken together, our findings indicate that only particular miRNAs with a significantly higher expression in endometriotic cells can be detected from lesion biopsies, and can serve as diagnostic markers for endometriosis.

  3. Beam Profile Monitor With Accurate Horizontal And Vertical Beam Profiles

    DOEpatents

    Havener, Charles C [Knoxville, TN; Al-Rejoub, Riad [Oak Ridge, TN

    2005-12-26

    A widely used scanner device that rotates a single helically shaped wire probe in and out of a particle beam at different beamline positions to give a pair of mutually perpendicular beam profiles is modified by the addition of a second wire probe. As a result, a pair of mutually perpendicular beam profiles is obtained at a first beamline position, and a second pair of mutually perpendicular beam profiles is obtained at a second beamline position. The simple modification not only provides more accurate beam profiles, but also provides a measurement of the beam divergence and quality in a single compact device.

  4. Tevatron ionization profile monitoring

    SciTech Connect

    Jansson, A.; Bowie, K.; Fitzpatrick, T.; Kwarciany, R.; Lundberg, C.; Slimmer, D.; Valerio, L.; Zagel, J.; /Fermilab

    2006-06-01

    Ionization Profile monitors have been used in almost all machines at Fermilab. However, the Tevatron presents some particular challenges with its two counter-rotating, small beams, and stringent vacuum requirements. In order to obtain adequate beam size accuracy with the small signals available, custom made electronics from particle physics experiments was employed. This provides a fast (single bunch) and dead-timeless charge integration with a sensitivity in the femto-Coulomb range, bringing the system close to the single ionization electron detection threshold. The detector itself is based on a previous Main Injector prototype, albeit with many modifications and improvements. The first detector was installed at the end of 2005, and the second detector during the spring shutdown. The ultimate goal is to continuously monitor beam size oscillations at injection, as well as the beam size evolution during ramp and squeeze. Initial results are very encouraging.

  5. Near wake velocity profiles

    SciTech Connect

    Porterio, J.L.F.; Page, R.H.; Przirembel, C.E.G.

    1984-02-01

    The development of the wake velocity profile behind a cylindrical blunt based body aligned with a subsonic uniform stream was experimentally investigated as a function of the momentum thickness of the approaching boundary layer and the transfer of mass into the recirculating region. Tests were conducted at M = 0.11 in an interference-free wind tunnel utilizing an upstream support system. Results indicate that the width of the wake increases with the thickness of the boundary layer while the velocity at the centerline decreases. Near wake mass transfer was found to alter centerline velocities while the width of the wake was not significantly altered. Wake centerline velocity development as a function of boundary layer thickness is presented for distances up to three diameters from the base.

  6. Unsupervised Outlier Profile Analysis

    PubMed Central

    Ghosh, Debashis; Li, Song

    2014-01-01

    In much of the analysis of high-throughput genomic data, “interesting” genes have been selected based on assessment of differential expression between two groups or generalizations thereof. Most of the literature focuses on changes in mean expression or the entire distribution. In this article, we explore the use of C(α) tests, which have been applied in other genomic data settings. Their use for the outlier expression problem, in particular with continuous data, is problematic but nevertheless motivates new statistics that give an unsupervised analog to previously developed outlier profile analysis approaches. Some simulation studies are used to evaluate the proposal. A bivariate extension is described that can accommodate data from two platforms on matched samples. The proposed methods are applied to data from a prostate cancer study. PMID:25452686

  7. Losartan: Comprehensive Profile.

    PubMed

    Al-Majed, Abdul-Rahman A; Assiri, Ebrahim; Khalil, Nasr Y; Abdel-Aziz, Hatem A

    2015-01-01

    Losartan (Cozaar™) is an angiotensin II receptor antagonist with antihypertensive activity. It is used in the management of hypertension and heart failure. Nomenclature, formulae, elemental analysis, and appearance of the drug are included in this review. The uses, applications, and the variety of synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum with fragmentation patterns, and NMR (1H and 13C) spectra of losartan together with the corresponding figures and/or tables are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including: spectrophotometric, electrochemical, chromatographic, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior and the pharmacology of the drug are also provided.

  8. Lebanon: country profile.

    PubMed

    Marfleet, P

    1988-05-01

    A brief profile of Lebanon's economy, people, health, culture and political situation is presented. Lebanon has an estimated 3.5 million people, with a Maronite Christian elite, a Muslim Shiite majority, and Muslim Sunnis and Druze groups. The infant mortality is estimated at 41/1000; literacy is 69% among women and 86% among men; life expectancy was 66 years, 10 years ago. The economy, previously thriving on banking, manufacturing and agriculture, is now decimated, and Lebanon's once active tourist industry, based on elegant facilities in Beirut and neighboring beaches and ski slopes, is the victim of 15 years of civil strife. Israel has invaded, supporting Maronite Christians, Syria has invaded in support Muslim and Druze militias, and Iran has aggressively supported Shiite factions.

  9. Profiling the cancer genome.

    PubMed

    Cowin, Prue A; Anglesio, Michael; Etemadmoghadam, Dariush; Bowtell, David D L

    2010-01-01

    Cancer profiling studies have had a profound impact on our understanding of the biology of cancers in a number of ways, including providing insights into the biological heterogeneity of specific cancer types, identification of novel oncogenes and tumor suppressors, and defining pathways that interact to drive the growth of individual cancers. Several large-scale genomic studies are underway that aim to catalog all biologically significant mutational events in each cancer type, and these findings will allow researchers to understand how mutational networks function within individual tumors. The identification of molecular predictive and prognostic tools to facilitate treatment decisions is an important step for individualized patient therapy and, ultimately, in improving patient outcomes. Whereas there are still significant challenges to implementing genomic testing and targeted therapy into routine clinical practice, rapid technological advancements provide hope for overcoming these obstacles.

  10. Staging of biliary atresia at diagnosis by molecular profiling of the liver

    PubMed Central

    2010-01-01

    Background Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte subsets or tissue accumulation of matrix substrates. The groups had no association with traditional markers of liver injury or function, response to surgery, or complications of cirrhosis. However, infants with an inflammation signature were younger, while those with a fibrosis signature had decreased transplant-free survival. Conclusions Molecular profiling at diagnosis of biliary atresia uncovers a signature of inflammation or fibrosis in most livers. This signature may relate to staging of disease at diagnosis and has implications to clinical outcomes. PMID:20465800

  11. Company profile: Sistemic Ltd.

    PubMed

    Reid, Jim

    2013-09-01

    Founded in 2009 and headquartered in Glasgow, Scotland, UK, Sistemic Ltd has developed from a thought in the minds of four scientists into a company working globally to play its part in delivering the exciting opportunities for improvements in human health presented by cell therapies and regenerative medicine products (jointly referred to as the CT industry). Sistemic is now working in all corners of the world with some of the industry's leading companies to ensure that the products that they are developing, which will undoubtedly change the way we treat some of the major diseases and conditions currently placing a large burden on healthcare systems, including diabetes, dementia and cardiovascular disease, are as safe and efficacious as possible. Sistemic is also working to ensure that these products can be produced at a cost that will not lead to potentially transformational treatments being an additional financial burden on our already overburdened healthcare systems. Sistemic is using its revolutionary and IP-protected SistemQC™ (UK) technology to enhance understanding of characterization, process optimization and potency of CT products. The company is using the diagnostic power of miRNAs, a set of approximately 2000 ncRNAs that regulate a large percentage of the total gene expression of a cell. miRNAs are often present in a cell- and tissue-specific way that, at least in some cases, accounts for the phenotypic differences between cell types. These differences in miRNA expression can be interpreted by the miRNA profile and it is interpreting the instructive power of these profiles that underpin Sistemic's knowledge bases, giving CT companies a more comprehensive understanding of their cell populations with respect to their identity and functional capabilities. This knowledge is being used by companies to characterize, process, optimize and assess the efficacy of cell products.

  12. [Metabolic profiling of human blood].

    PubMed

    Trifonova, O P; Lokhov, P G; Archakov, A I

    2014-01-01

    Metabolomics is a novel "omics" branch of science intended for studying a comprehensive set of low molecular weight substances (metabolites) of various biological objects. Metabolite profiles represent a molecular phenotype of biological systems and reflect information encoded at the genome level and realized at the transcriptome and proteome levels. Analysis of human blood metabolic profile is universal and promising tool for clinical applications because it is a sensitive measure of both endogenous and exogenous (environmental) factors affected on the patient's organism. Technical implementation of metabolic profiling of blood and statistic analysis of metabolite profiles for effective diagnostics and risk assessments of diseases are discussed in this review.

  13. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer.

    PubMed

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-01-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured. PMID:27406679

  14. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer

    PubMed Central

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-01-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured. PMID:27406679

  15. A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer

    NASA Astrophysics Data System (ADS)

    Auslander, Noam; Yizhak, Keren; Weinstock, Adam; Budhu, Anuradha; Tang, Wei; Wang, Xin Wei; Ambs, Stefan; Ruppin, Eytan

    2016-07-01

    Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.

  16. The Histone Methyltransferase Inhibitor A-366 Uncovers a Role for G9a/GLP in the Epigenetics of Leukemia

    PubMed Central

    He, Yupeng; Ferguson, Debra; Jagadeeswaran, Sujatha; Osterling, Donald J.; Gao, Wenqing; Spence, Julie K.; Pliushchev, Marina; Sweis, Ramzi F.; Buchanan, Fritz G.; Michaelides, Michael R.; Shoemaker, Alexander R.; Tse, Chris; Chiang, Gary G.

    2015-01-01

    Histone methyltransferases are epigenetic regulators that modify key lysine and arginine residues on histones and are believed to play an important role in cancer development and maintenance. These epigenetic modifications are potentially reversible and as a result this class of enzymes has drawn great interest as potential therapeutic targets of small molecule inhibitors. Previous studies have suggested that the histone lysine methyltransferase G9a (EHMT2) is required to perpetuate malignant phenotypes through multiple mechanisms in a variety of cancer types. To further elucidate the enzymatic role of G9a in cancer, we describe herein the biological activities of a novel peptide-competitive histone methyltransferase inhibitor, A-366, that selectively inhibits G9a and the closely related GLP (EHMT1), but not other histone methyltransferases. A-366 has significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2. Additionally, the selectivity profile of A-366 has aided in the discovery of a potentially important role for G9a/GLP in maintenance of leukemia. Treatment of various leukemia cell lines in vitro resulted in marked differentiation and morphological changes of these tumor cell lines. Furthermore, treatment of a flank xenograft leukemia model with A-366 resulted in growth inhibition in vivo consistent with the profile of H3K9me2 reduction observed. In summary, A-366 is a novel and highly selective inhibitor of G9a/GLP that has enabled the discovery of a role for G9a/GLP enzymatic activity in the growth and differentiation status of leukemia cells. PMID:26147105

  17. Circulating microRNA profiles of Ebola virus infection

    PubMed Central

    Duy, Janice; Koehler, Jeffrey W.; Honko, Anna N.; Schoepp, Randal J.; Wauquier, Nadia; Gonzalez, Jean-Paul; Pitt, M. Louise; Mucker, Eric M.; Johnson, Joshua C.; O’Hearn, Aileen; Bangura, James; Coomber, Moinya; Minogue, Timothy D.

    2016-01-01

    Early detection of Ebola virus (EBOV) infection is essential to halting transmission and adjudicating appropriate treatment. However, current methods rely on viral identification, and this approach can misdiagnose presymptomatic and asymptomatic individuals. In contrast, disease-driven alterations in the host transcriptome can be exploited for pathogen-specific diagnostic biomarkers. Here, we present for the first time EBOV-induced changes in circulating miRNA populations of nonhuman primates (NHPs) and humans. We retrospectively profiled longitudinally-collected plasma samples from rhesus macaques challenged via intramuscular and aerosol routes and found 36 miRNAs differentially present in both groups. Comparison of miRNA abundances to viral loads uncovered 15 highly correlated miRNAs common to EBOV-infected NHPs and humans. As proof of principle, we developed an eight-miRNA classifier that correctly categorized infection status in 64/74 (86%) human and NHP samples. The classifier identified acute infections in 27/29 (93.1%) samples and in 6/12 (50%) presymptomatic NHPs. These findings showed applicability of NHP-derived miRNAs to a human cohort, and with additional research the resulting classifiers could impact the current capability to diagnose presymptomatic and asymptomatic EBOV infections. PMID:27098369

  18. Proteomic profile of Aspergillus flavus in response to water activity.

    PubMed

    Zhang, Feng; Zhong, Hong; Han, Xiaoyun; Guo, Zhenni; Yang, Weiqiang; Liu, Yongfeng; Yang, Kunlong; Zhuang, Zhenhong; Wang, Shihua

    2015-03-01

    Aspergillus flavus, a common contaminant of crops and stored grains, can produce aflatoxins that are harmful to humans and other animals. Water activity (aw) is one of the key factors influencing both fungal growth and mycotoxin production. In this study, we used the isobaric tagging for relative and absolute quantitation (iTRAQ) technique to investigate the effect of aw on the proteomic profile of A. flavus. A total of 3566 proteins were identified, of which 837 were differentially expressed in response to variations in aw. Among these 837 proteins, 403 were over-expressed at 0.99 aw, whereas 434 proteins were over-expressed at 0.93 aw. According to Gene Ontology (GO) analysis, the secretion of extracellular hydrolases increased as aw was raised, suggesting that extracellular hydrolases may play a critical role in induction of aflatoxin biosynthesis. On the basis of Clusters of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) categorizations, we identified an exportin protein, KapK, that may down-regulate aflatoxin biosynthesis by changing the location of NirA. Finally, we considered the role of two osmotic stress-related proteins (Sln1 and Glo1) in the Hog1 pathway and investigated the expression patterns of proteins related to aflatoxin biosynthesis. The data uncovered in this study are critical for understanding the effect of water stress on toxin production and for the development of strategies to control toxin contamination of agricultural products.

  19. Proteomic profile of mouse fibroblasts exposed to pure magnesium extract.

    PubMed

    Zhen, Zhen; Luthringer, Bérengère; Yang, Li; Xi, Tingfei; Zheng, Yufeng; Feyerabend, Frank; Willumeit, Regine; Lai, Chen; Ge, Zigang

    2016-12-01

    Magnesium and its alloys gain wide attention as degradable biomaterials. In order to reveal the molecular mechanism of the influence of biodegradable magnesium on cells, proteomics analysis was performed in this work. After mouse fibroblasts (L929) were cultured with or without Mg degradation products (Mg-extract) for 8, 24, and 48h, changes in protein expression profiles were obtained using isobaric tags for relative and absolute quantitation (iTRAQ) coupled two dimensional liquid chromatography-tandem mass spectrometry (2D LC MS/MS). A total of 867 proteins were identified (relying on at least two peptides). Compared to the control group, 205, 282, and 217 regulated proteins were identified at 8, 24, and 48h, respectively. 65 common proteins were up or down- regulated within all the three time points, which were involved in various physiological and metabolic activities. Consistent with viability, proliferation, and cell cycle analysis, stimulated energy metabolism as well as protein synthesis pathways were discussed, indicating a possible effect of Mg-extract on L929 proliferation. Furthermore, endocytosis and focal adhesion processes were also discussed. This proteomics study uncovers early cellular mechanisms triggered by Mg degradation products and highlights the cytocompatibility of biodegradable metallic materials for biomedical applications such as stents or orthopaedic implants. PMID:27612743

  20. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress.

    PubMed

    Prasad, Kasavajhala V S K; Abdel-Hameed, Amira A E; Xing, Denghui; Reddy, Anireddy S N

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  1. Global gene expression analysis using RNA-seq uncovered a new role for SR1/CAMTA3 transcription factor in salt stress

    PubMed Central

    Prasad, Kasavajhala V. S. K.; Abdel-Hameed, Amira A. E.; Xing, Denghui; Reddy, Anireddy S. N.

    2016-01-01

    Abiotic and biotic stresses cause significant yield losses in all crops. Acquisition of stress tolerance in plants requires rapid reprogramming of gene expression. SR1/CAMTA3, a member of signal responsive transcription factors (TFs), functions both as a positive and a negative regulator of biotic stress responses and as a positive regulator of cold stress-induced gene expression. Using high throughput RNA-seq, we identified ~3000 SR1-regulated genes. Promoters of about 60% of the differentially expressed genes have a known DNA binding site for SR1, suggesting that they are likely direct targets. Gene ontology analysis of SR1-regulated genes confirmed previously known functions of SR1 and uncovered a potential role for this TF in salt stress. Our results showed that SR1 mutant is more tolerant to salt stress than the wild type and complemented line. Improved tolerance of sr1 seedlings to salt is accompanied with the induction of salt-responsive genes. Furthermore, ChIP-PCR results showed that SR1 binds to promoters of several salt-responsive genes. These results suggest that SR1 acts as a negative regulator of salt tolerance by directly repressing the expression of salt-responsive genes. Overall, this study identified SR1-regulated genes globally and uncovered a previously uncharacterized role for SR1 in salt stress response. PMID:27251464

  2. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students.

    PubMed

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-05-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  3. Uncovering Barriers to Teaching Assistants (TAs) Implementing Inquiry Teaching: Inconsistent Facilitation Techniques, Student Resistance, and Reluctance to Share Control over Learning with Students †

    PubMed Central

    Gormally, Cara; Sullivan, Carol Subiño; Szeinbaum, Nadia

    2016-01-01

    Inquiry-based teaching approaches are increasingly being adopted in biology laboratories. Yet teaching assistants (TAs), often novice teachers, teach the majority of laboratory courses in US research universities. This study analyzed the perspectives of TAs and their students and used classroom observations to uncover challenges faced by TAs during their first year of inquiry-based teaching. Our study revealed three insights about barriers to effective inquiry teaching practices: 1) TAs lack sufficient facilitation skills; 2) TAs struggle to share control over learning with students as they reconcile long-standing teaching beliefs with newly learned approaches, consequently undermining their fledgling ability to use inquiry approaches; and 3) student evaluations reinforce teacher-centered behaviors as TAs receive positive feedback conflicting with inquiry approaches. We make recommendations, including changing instructional feedback to focus on learner-centered teaching practices. We urge TA mentors to engage TAs in discussions to uncover teaching beliefs underlying teaching choices and support TAs through targeted feedback and practice. PMID:27158302

  4. Combined Genetic and Genealogic Studies Uncover a Large BAP1 Cancer Syndrome Kindred Tracing Back Nine Generations to a Common Ancestor from the 1700s.

    PubMed

    Carbone, Michele; Flores, Erin G; Emi, Mitsuru; Johnson, Todd A; Tsunoda, Tatsuhiko; Behner, Dusty; Hoffman, Harriet; Hesdorffer, Mary; Nasu, Masaki; Napolitano, Andrea; Powers, Amy; Minaai, Michael; Baumann, Francine; Bryant-Greenwood, Peter; Lauk, Olivia; Kirschner, Michaela B; Weder, Walter; Opitz, Isabelle; Pass, Harvey I; Gaudino, Giovanni; Pastorino, Sandra; Yang, Haining

    2015-12-01

    We recently discovered an inherited cancer syndrome caused by BRCA1-Associated Protein 1 (BAP1) germline mutations, with high incidence of mesothelioma, uveal melanoma and other cancers and very high penetrance by age 55. To identify families with the BAP1 cancer syndrome, we screened patients with family histories of multiple mesotheliomas and melanomas and/or multiple cancers. We identified four families that shared an identical BAP1 mutation: they lived across the US and did not appear to be related. By combining family histories, molecular genetics, and genealogical approaches, we uncovered a BAP1 cancer syndrome kindred of ~80,000 descendants with a core of 106 individuals, whose members descend from a couple born in Germany in the early 1700s who immigrated to North America. Their descendants spread throughout the country with mutation carriers affected by multiple malignancies. Our data show that, once a proband is identified, extended analyses of these kindreds, using genomic and genealogical studies to identify the most recent common ancestor, allow investigators to uncover additional branches of the family that may carry BAP1 mutations. Using this knowledge, we have identified new branches of this family carrying BAP1 mutations. We have also implemented early-detection strategies that help identify cancers at early-stage, when they can be cured (melanomas) or are more susceptible to therapy (MM and other malignancies). PMID:26683624

  5. USGIN ISO metadata profile

    NASA Astrophysics Data System (ADS)

    Richard, S. M.

    2011-12-01

    The USGIN project has drafted and is using a specification for use of ISO 19115/19/39 metadata, recommendations for simple metadata content, and a proposal for a URI scheme to identify resources using resolvable http URI's(see http://lab.usgin.org/usgin-profiles). The principal target use case is a catalog in which resources can be registered and described by data providers for discovery by users. We are currently using the ESRI Geoportal (Open Source), with configuration files for the USGIN profile. The metadata offered by the catalog must provide sufficient content to guide search engines to locate requested resources, to describe the resource content, provenance, and quality so users can determine if the resource will serve for intended usage, and finally to enable human users and sofware clients to obtain or access the resource. In order to achieve an operational federated catalog system, provisions in the ISO specification must be restricted and usage clarified to reduce the heterogeneity of 'standard' metadata and service implementations such that a single client can search against different catalogs, and the metadata returned by catalogs can be parsed reliably to locate required information. Usage of the complex ISO 19139 XML schema allows for a great deal of structured metadata content, but the heterogenity in approaches to content encoding has hampered development of sophisticated client software that can take advantage of the rich metadata; the lack of such clients in turn reduces motivation for metadata producers to produce content-rich metadata. If the only significant use of the detailed, structured metadata is to format into text for people to read, then the detailed information could be put in free text elements and be just as useful. In order for complex metadata encoding and content to be useful, there must be clear and unambiguous conventions on the encoding that are utilized by the community that wishes to take advantage of advanced metadata

  6. Bronchiectasis: a bacteriological profile

    PubMed Central

    Bopaka, Régis Gothard; El Khattabi, Wiam; Janah, Hind; Jabri, Hasna; Afif, Hicham

    2015-01-01

    The occurrence of bronchiectasis can involve a combination of many environmental factors, including infection. The aim of our work is to determine the bacteriological profile of bronchiectasis. This is a retrospective study of 100 patients hospitalized in between January 2010 and July 2013. The average age was 48 years with a 58% female predominance. Symptomatology was by a bronchial syndrome in 90% of cases. Bacteriological examination was able to isolate the microbe in 35% of cases. In our study it was through the examination of sputum cytology in 27% of cases, through the examination of liquid bronchial aspiration in 5% of cases, and through direct examination of sputum in search of Mycobacterium tuberculosis in 3% of cases. Microbes isolated were: Streptococcus pneumonia in 11 cases; Pseudomonas aeruginosa in 10 cases, Klebsiella pneumonia and Mycobacterium tuberculosis in 3 cases each; Moraxella catarrhalis, Haemophilus influenzae, Escherichia coli, Citrobacter spp, Serratia marcescens, Mycoplasma pneumoniae, Acinetobacter baumannii and Staphylococcus aureus in one case each. Through this work, the authors highlight that Streptococcus pneumoniae and Pseudomonas aeruginosa are the most commonly- identified microbes in their patients. It is necessary to have a full bacterial examination and to repeat it regularly over the course of the bronchiectasis. PMID:27047618

  7. Analytical profile of moxidectin.

    PubMed

    Awasthi, Atul; Razzak, Majid; Al-Kassas, Raida; Harvey, Joanne; Garg, Sanjay

    2013-01-01

    Moxidectin or F28249α is a potent endectocide and semisynthetic methoxime derivative of naturally occurring nemadectin. It is well known for the novel mode of action against a broad range of nematode and anthropod animal parasites. In this work, physicochemical and pharmaceutical aspects of moxidectin are described including stability, semisynthesis, purification processes, formulation compositions, impurities, and degradation pathways. Additional experiments such as DSC, XRD, and CHN analysis were carried out to complete the profile of moxidectin. The importance of safety and quality of drug substances was highlighted by chronological developments involving moxidectin and its analogues. The information gathered from the literature was used to trace the origins of moxidectin-related substances presented in the European Pharmacopeia (EP) compendial monograph. During the review, it was noticed that majority of impurities presented in the EP does not have any potential to increase with time in drug substance or formulated products; therefore, they do not require monitoring during stability studies. This also showed the requirement for further characterization of the impurities observed during long-term storage and development of stability indicating methods distinguishing between process impurities and the true degradation products. Furthermore, the stability of moxidectin in formulations is also reviewed in conjunction with known degradation routes and innovative ways to formulate products that are stable and effective at intended shelf life. PMID:23668407

  8. Molecular profiling of chordoma

    PubMed Central

    SCHEIL-BERTRAM, STEFANIE; KAPPLER, ROLAND; VON BAER, ALEXANDRA; HARTWIG, ERICH; SARKAR, MICHAEL; SERRA, MASSIMO; BRÜDERLEIN, SILKE; WESTHOFF, BETTINA; MELZNER, INGO; BASSALY, BIRGIT; HERMS, JOCHEN; HUGO, HEINZ-HERMANN; SCHULTE, MICHAEL; MÖLLER, PETER

    2014-01-01

    The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p<0.001; ≥6-fold change) between chordoma and control (vertebral disc) was identified. Genes with increased expression in chordoma compared to control and chondrosarcoma were most frequently located on chromosomes 2 (11%), 5 (8%), 1 and 7 (each 6%), whereas interphase cytogenetics of 33 chordomas demonstrated gains of chromosomal material most prevalent on 7q (42%), 12q (21%), 17q (21%), 20q (27%) and 22q (21%). The microarray data were confirmed for selected genes by quantitative polymerase chain reaction analysis. As in other studies, we showed the expression of brachyury. We demonstrate the expression of new potential candidates for chordoma tumorigenesis, such as CD24, ECRG4, RARRES2, IGFBP2, RAP1, HAI2, RAB38, osteopontin, GalNAc-T3, VAMP8 and others. Thus, we identified and validated a set of interesting candidate genes whose differential expression likely plays a role in chordoma. PMID:24452533

  9. Transcriptional Profiling of Egg Allergy and Relationship to Disease Phenotype

    PubMed Central

    Kosoy, Roman; Agashe, Charuta; Grishin, Alexander; Leung, Donald Y.; Wood, Robert A.; Sicherer, Scott H.; Jones, Stacie M.; Burks, A. Wesley; Davidson, Wendy F.; Lindblad, Robert W.; Dawson, Peter; Merad, Miriam; Kidd, Brian A.; Dudley, Joel T.; Sampson, Hugh A.

    2016-01-01

    Background Egg allergy is one of the most common food allergies of childhood. There is a lack of information on the immunologic basis of egg allergy beyond the role of IgE. Objective To use transcriptional profiling as a novel approach to uncover immunologic processes associated with different phenotypes of egg allergy. Methods Peripheral blood mononuclear cells (PBMCs) were obtained from egg-allergic children who were defined as reactive (BER) or tolerant (BET) to baked egg, and from food allergic controls (AC) who were egg non-allergic. PBMCs were stimulated with egg white protein. Gene transcription was measured by microarray after 24 h, and cytokine secretion by multiplex assay after 5 days. Results The transcriptional response of PBMCs to egg protein differed between BER and BET versus AC subjects. Compared to the AC group, the BER group displayed increased expression of genes associated with allergic inflammation as well as corresponding increased secretion of IL-5, IL-9 and TNF-α. A similar pattern was observed for the BET group. Further similarities in gene expression patterns between BER and BET groups, as well as some important differences, were revealed using a novel Immune Annotation resource developed for this project. This approach identified several novel processes not previously associated with egg allergy, including positive associations with TLR4-stimulated myeloid cells and activated NK cells, and negative associations with an induced Treg signature. Further pathway analysis of differentially expressed genes comparing BER to BET subjects showed significant enrichment of IFN-α and IFN-γ response genes, as well as genes associated with virally-infected DCs. Conclusions Transcriptional profiling identified several novel pathways and processes that differed when comparing the response to egg allergen in BET, BER, and AC groups. We conclude that this approach is a useful hypothesis-generating mechanism to identify novel immune processes associated

  10. Commitment Profiles and Employee Turnover

    ERIC Educational Resources Information Center

    Stanley, Laura; Vandenberghe, Christian; Vandenberg, Robert; Bentein, Kathleen

    2013-01-01

    We examined how affective (AC), normative (NC), perceived sacrifice (PS), and few alternatives (FA) commitments combine to form profiles and determine turnover intention and turnover. We theorized that three mechanisms account for how profiles operate, i.e., the degree to which membership is internally regulated, the perceived desirability and…

  11. Advanced Multiple Aperture Seeing Profiler

    NASA Astrophysics Data System (ADS)

    Ren, Deqing; Zhao, Gang

    2016-10-01

    Measurements of the seeing profile of the atmospheric turbulence as a function of altitude are crucial for solar astronomical site characterization, as well as the optimized design and performance estimation of solar Multi-Conjugate Adaptive Optics (MCAO). Knowledge of the seeing distribution, up to 30 km, with a potential new solar observation site, is required for future solar MCAO developments. Current optical seeing profile measurement techniques are limited by the need to use a large facility solar telescope for such seeing profile measurements, which is a serious limitation on characterizing a site's seeing conditions in terms of the seeing profile. Based on our previous work, we propose a compact solar seeing profiler called the Advanced Multiple Aperture Seeing Profile (A-MASP). A-MASP consists of two small telescopes, each with a 100 mm aperture. The two small telescopes can be installed on a commercial computerized tripod to track solar granule structures for seeing profile measurement. A-MASP is extreme simple and portable, which makes it an ideal system to bring to a potential new site for seeing profile measurements.

  12. Profiling under UNIX by patching

    NASA Technical Reports Server (NTRS)

    Bishop, Matt

    1986-01-01

    Profiling under UNIX is done by inserting counters into programs either before or during the compilation or assembly phases. A fourth type of profiling involves monitoring the execution of a program, and gathering relevant statistics during the run. This method and an implementation of this method are examined, and its advantages and disadvantages are discussed.

  13. User Profiles in Organizational Environments

    ERIC Educational Resources Information Center

    Teixeira, Claudio; Pinto, Joaquim Sousa; Martins, Joaquim Arnaldo

    2008-01-01

    Purpose: The aim of this paper is to describe a project to provide an online web portal that can be used as a front-end for all university users--students, teachers, staff--and services, library, administration, e-learning, and e-mail. Design/methodology/approach: The profile model proposed is mainly inheritable, defined by profile components with…

  14. Steel Energy and Environmental Profile

    SciTech Connect

    none,

    2000-08-01

    Major steelmaking processes (from ironmaking through fabrication and forming) and their associated energy requirements have been profiled in this 2001 report (PDF 582 KB). This profile by Energetics, Inc. also describes the waste streams generated by each process and estimates annual emissions of CO2 and criteria pollutants.

  15. Excimer laser system Profile-500

    NASA Astrophysics Data System (ADS)

    Atejev, V. V.; Bukreyev, V. S.; Vartapetov, Serge K.; Semenov, A. D.; Sugrobov, V. A.; Turin, V. S.; Fedorov, Sergei N.

    1999-07-01

    The description of ophthalmological excimer laser system 'PROFILE-500' for photorefractive and physiotherapeutic keratectomy is presented. Excimer Laser Systems 'PROFILE- 500' are optical system that use ArF excimer lasers to perform photorefractive keratectomy or LASIK; surgical procedures used to correct myopia, hyperopia and astigmatism.

  16. Interactive Visual Profiling of Musicians.

    PubMed

    Janicke, Stefan; Focht, Josef; Scheuermann, Gerik

    2016-01-01

    Determining similar objects based upon the features of an object of interest is a common task for visual analytics systems. This process is called profiling, if the object of interest is a person with individual attributes. The profiling of musicians similar to a musician of interest with the aid of visual means became an interesting research question for musicologists working with the Bavarian Musicians Encyclopedia Online. This paper illustrates the development of a visual analytics profiling system that is used to address such research questions. Taking musicological knowledge into account, we outline various steps of our collaborative digital humanities project, priority (1) the definition of various measures to determine the similarity of musicians' attributes, and (2) the design of an interactive profiling system that supports musicologists in iteratively determining similar musicians. The utility of the profiling system is emphasized by various usage scenarios illustrating current research questions in musicology. PMID:26529700

  17. Downstream Heat Flux Profile vs. Midplane T Profile in Tokamaks

    SciTech Connect

    Robert J. Goldston

    2009-08-20

    The relationship between the midplane scrape-off-layer electron temperature profile and the parallel heat flux profile at the divertor in tokamaks is investigated. A model is applied which takes into account anisotropic thermal diffusion, in a rectilinear geometry with constant density. Eigenmode analysis is applied to the simplified problem with constant thermal diffusivities. A self-similar nonlinear solution is found for the more realistic problem with anisotropically temperature-dependent thermal diffusivities. Numerical solutions are developed for both cases, with spatially dependent heat flux emerging from the plasma. For both constant and temperature-dependent thermal diffusivities it is found that, below about one-half of its peak, the heat flux profile shape at the divertor, compared with the midplane temperature profile shape, is robustly described by the simplest two-point model. However the physical processes are not those assumed in the simplest two-point model, nor is the numerical coefficient relating q||div to Tmp χ||mp/L|| as predicted. For realistic parameters the peak in the heat flux, moreover, can be reduced by a factor of two or more from the two-point model scaling which fits the remaining profile. For temperature profiles in the SOL region above the x-point set by marginal stability, the heat flux profile to the divertor can be largely decoupled from the prediction of the two-point model. These results suggest caveats for data interpretation, and possibly favorable outcomes for divertor configurations with extended field lines.

  18. Chemoproteomic Strategy to Quantitatively Monitor Transnitrosation Uncovers Functionally Relevant S-Nitrosation Sites on Cathepsin D and HADH2.

    PubMed

    Zhou, Yani; Wynia-Smith, Sarah L; Couvertier, Shalise M; Kalous, Kelsey S; Marletta, Michael A; Smith, Brian C; Weerapana, Eranthie

    2016-06-23

    S-Nitrosoglutathione (GSNO) is an endogenous transnitrosation donor involved in S-nitrosation of a variety of cellular proteins, thereby regulating diverse protein functions. Quantitative proteomic methods are necessary to establish which cysteine residues are most sensitive to GSNO-mediated transnitrosation. Here, a competitive cysteine-reactivity profiling strategy was implemented to quantitatively measure the sensitivity of >600 cysteine residues to transnitrosation by GSNO. This platform identified a subset of cysteine residues with a high propensity for GSNO-mediated transnitrosation. Functional characterization of previously unannotated S-nitrosation sites revealed that S-nitrosation of a cysteine residue distal to the 3-hydroxyacyl-CoA dehydrogenase type 2 (HADH2) active site impaired catalytic activity. Similarly, S-nitrosation of a non-catalytic cysteine residue in the lysosomal aspartyl protease cathepsin D (CTSD) inhibited proteolytic activation. Together, these studies revealed two previously uncharacterized cysteine residues that regulate protein function, and established a chemical-proteomic platform with capabilities to determine substrate specificity of other cellular transnitrosation agents.

  19. Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE1[OPEN

    PubMed Central

    Van de Wouwer, Dorien; Decou, Raphaël; Audenaert, Dominique; Nguyen, Long

    2016-01-01

    Plant secondary-thickened cell walls are characterized by the presence of lignin, a recalcitrant and hydrophobic polymer that provides mechanical strength and ensures long-distance water transport. Exactly the recalcitrance and hydrophobicity of lignin put a burden on the industrial processing efficiency of lignocellulosic biomass. Both forward and reverse genetic strategies have been used intensively to unravel the molecular mechanism of lignin deposition. As an alternative strategy, we introduce here a forward chemical genetic approach to find candidate inhibitors of lignification. A high-throughput assay to assess lignification in Arabidopsis (Arabidopsis thaliana) seedlings was developed and used to screen a 10-k library of structurally diverse, synthetic molecules. Of the 73 compounds that reduced lignin deposition, 39 that had a major impact were retained and classified into five clusters based on the shift they induced in the phenolic profile of Arabidopsis seedlings. One representative compound of each cluster was selected for further lignin-specific assays, leading to the identification of an aromatic compound that is processed in the plant into two fragments, both having inhibitory activity against lignification. One fragment, p-iodobenzoic acid, was further characterized as a new inhibitor of CINNAMATE 4-HYDROXYLASE, a key enzyme of the phenylpropanoid pathway synthesizing the building blocks of the lignin polymer. As such, we provide proof of concept of this chemical biology approach to screen for inhibitors of lignification and present a broad array of putative inhibitors of lignin deposition for further characterization. PMID:27485881

  20. Integrated analysis of phenome, genome, and transcriptome of hybrid rice uncovered multiple heterosis-related loci for yield increase

    PubMed Central

    Li, Dayong; Huang, Zhiyuan; Song, Shuhui; Xin, Yeyun; Mao, Donghai; Lv, Qiming; Zhou, Ming; Tian, Dongmei; Tang, Mingfeng; Wu, Qi; Liu, Xue; Chen, Tingting; Song, Xianwei; Fu, Xiqin; Zhao, Bingran; Liang, Chengzhi; Li, Aihong; Liu, Guozhen; Li, Shigui; Hu, Songnian; Cao, Xiaofeng; Yu, Jun; Yuan, Longping; Chen, Caiyan; Zhu, Lihuang

    2016-01-01

    Hybrid rice is the dominant form of rice planted in China, and its use has extended worldwide since the 1970s. It offers great yield advantages and has contributed greatly to the world’s food security. However, the molecular mechanisms underlying heterosis have remained a mystery. In this study we integrated genetics and omics analyses to determine the candidate genes for yield heterosis in a model two-line rice hybrid system, Liang-you-pei 9 (LYP9) and its parents. Phenomics study revealed that the better parent heterosis (BPH) of yield in hybrid is not ascribed to BPH of all the yield components but is specific to the BPH of spikelet number per panicle (SPP) and paternal parent heterosis (PPH) of effective panicle number (EPN). Genetic analyses then identified multiple quantitative trait loci (QTLs) for these two components. Moreover, a number of differentially expressed genes and alleles in the hybrid were mapped by transcriptome profiling to the QTL regions as possible candidate genes. In parallel, a major QTL for yield heterosis, rice heterosis 8 (RH8), was found to be the DTH8/Ghd8/LHD1 gene. Based on the shared allelic heterozygosity of RH8 in many hybrid rice cultivars, a common mechanism for yield heterosis in the present commercial hybrid rice is proposed. PMID:27663737

  1. Transcriptome landscape of perennial wild Cicer microphyllum uncovers functionally relevant molecular tags regulating agronomic traits in chickpea

    PubMed Central

    Srivastava, Rishi; Bajaj, Deepak; Malik, Ayushi; Singh, Mohar; Parida, Swarup K.

    2016-01-01

    The RNA-sequencing followed by de-novo transcriptome assembly identified 11621 genes differentially xpressed in roots vs. shoots of a wild perennial Cicer microphyllum. Comparative analysis of transcriptomes between microphyllum and cultivated desi cv. ICC4958 detected 12772 including 3242 root- and 1639 shoot-specific microphyllum genes with 85% expression validation success rate. Transcriptional reprogramming of microphyllum root-specific genes implicates their possible role in regulating differential natural adaptive characteristics between wild and cultivated chickpea. The transcript-derived 5698 including 282 in-silico polymorphic SSR and 127038 SNP markers annotated at a genome-wide scale exhibited high amplification and polymorphic potential among cultivated (desi and kabuli) and wild accessions suggesting their utility in chickpea genomics-assisted breeding applications. The functional significance of markers was assessed based on their localization in non-synonymous coding and regulatory regions of microphyllum root-specific genes differentially expressed predominantly in ICC 4958 roots under drought stress. A high-density 490 genic SSR- and SNP markers-anchored genetic linkage map identified six major QTLs regulating drought tolerance-related traits, yield per plant and harvest-index in chickpea. The integration of high-resolution QTL mapping with comparative transcriptome profiling delineated five microphyllum root-specific genes with non-synonymous and regulatory SNPs governing drought-responsive yield traits. Multiple potential key regulators and functionally relevant molecular tags delineated can drive translational research and drought tolerance-mediated chickpea genetic enhancement. PMID:27680662

  2. Uncovering methods for the prevention of protein aggregation and improvement of product quality in a transient expression system.

    PubMed

    Estes, Bram; Hsu, Yueh-Rong; Tam, Lei-Ting; Sheng, Jackie; Stevens, Jennitte; Haldankar, Raj

    2015-01-01

    Mammalian expression systems are used routinely for the production of recombinant proteins as therapeutic molecules as well as research tools. Transient expression has become increasingly popular in recent years due to its rapid timeline and improvements in expression level. While improvements to transient expression systems have focused mainly on the level of protein expression, the aspect of protein quality has received little attention. The removal of undesirable products, such as aggregation, depends primarily on purification, requiring additional cumbersome steps, which can lead to a lower product yield and longer timelines. In this study, we show that reducing the level of transcription by transfecting at a lower gene dose improves the quality of secreted molecules prone to aggregation. For gene dosing to have this effect, it is critical for the carrier DNA to be an empty vector containing the same elements as the gene containing plasmid. This approach can be used in combination with a temperature shift to hypothermic conditions during production to enhance the effect. The observed improvements not only minimized aggregation levels, but also generated products with overall superior quality, including more homogeneous signal peptide cleavage and N-linked glycosylation profiles. These techniques have produced a similar improvement in product quality with a variety of other molecules, suggesting that this may be a general approach to enhance product quality from transient expression systems. PMID:25395220

  3. Chemoproteomic Strategy to Quantitatively Monitor Transnitrosation Uncovers Functionally Relevant S-Nitrosation Sites on Cathepsin D and HADH2.

    PubMed

    Zhou, Yani; Wynia-Smith, Sarah L; Couvertier, Shalise M; Kalous, Kelsey S; Marletta, Michael A; Smith, Brian C; Weerapana, Eranthie

    2016-06-23

    S-Nitrosoglutathione (GSNO) is an endogenous transnitrosation donor involved in S-nitrosation of a variety of cellular proteins, thereby regulating diverse protein functions. Quantitative proteomic methods are necessary to establish which cysteine residues are most sensitive to GSNO-mediated transnitrosation. Here, a competitive cysteine-reactivity profiling strategy was implemented to quantitatively measure the sensitivity of >600 cysteine residues to transnitrosation by GSNO. This platform identified a subset of cysteine residues with a high propensity for GSNO-mediated transnitrosation. Functional characterization of previously unannotated S-nitrosation sites revealed that S-nitrosation of a cysteine residue distal to the 3-hydroxyacyl-CoA dehydrogenase type 2 (HADH2) active site impaired catalytic activity. Similarly, S-nitrosation of a non-catalytic cysteine residue in the lysosomal aspartyl protease cathepsin D (CTSD) inhibited proteolytic activation. Together, these studies revealed two previously uncharacterized cysteine residues that regulate protein function, and established a chemical-proteomic platform with capabilities to determine substrate specificity of other cellular transnitrosation agents. PMID:27291402

  4. Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function.

    PubMed

    Hua, Jing; Davis, Scott P; Hill, Jonathan A; Yamagata, Tetsuya

    2015-10-15

    Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology. PMID:26371251

  5. Laser heterodyne surface profiler

    DOEpatents

    Sommargren, G.E.

    1980-06-16

    A method and apparatus are disclosed for testing the deviation of the face of an object from a flat smooth surface using a beam of coherent light of two plane-polarized components, one of a frequency constantly greater than the other by a fixed amount to produce a difference frequency with a constant phase to be used as a reference, and splitting the beam into its two components. The separate components are directed onto spaced apart points on the face of the object to be tested for smoothness while the face of the object is rotated on an axis normal to one point, thereby passing the other component over a circular track on the face of the object. The two components are recombined after reflection to produce a reflected frequency difference of a phase proportional to the difference in path length of one component reflected from one point to the other component reflected from the other point. The phase of the reflected frequency difference is compared with the reference phase to produce a signal proportional to the deviation of the height of the surface along the circular track with respect to the fixed point at the center, thereby to produce a signal that is plotted as a profile of the surface along the circular track. The phase detector includes a quarter-wave plate to convert the components of the reference beam into circularly polarized components, a half-wave plate to shift the phase of the circularly polarized components, and a polarizer to produce a signal of a shifted phase for comparison with the phase of the frequency difference of the reflected components detected through a second polarizer. Rotation of the half-wave plate can be used for phase adjustment over a full 360/sup 0/ range.

  6. Characterization of the Tomato ARF Gene Family Uncovers a Multi-Levels Post-Transcriptional Regulation Including Alternative Splicing

    PubMed Central

    Chateigner-Boutin, Anne-Laure; Mila, Isabelle; Frasse, Pierre; Wang, Hua; Audran, Corinne; Roustan, Jean-Paul; Bouzayen, Mondher

    2014-01-01

    Background The phytohormone auxin is involved in a wide range of developmental processes and auxin signaling is known to modulate the expression of target genes via two types of transcriptional regulators, namely, Aux/IAA and Auxin Response Factors (ARF). ARFs play a major role in transcriptional activation or repression through direct binding to the promoter of auxin-responsive genes. The present study aims at gaining better insight on distinctive structural and functional features among ARF proteins. Results Building on the most updated tomato (Solanum lycopersicon) reference genome sequence, a comprehensive set of ARF genes was identified, extending the total number of family members to 22. Upon correction of structural annotation inconsistencies, renaming the tomato ARF family members provided a consensus nomenclature for all ARF genes across plant species. In silico search predicted the presence of putative target site for small interfering RNAs within twelve Sl-ARFs while sequence analysis of the 5′-leader sequences revealed the presence of potential small uORF regulatory elements. Functional characterization carried out by transactivation assay partitioned tomato ARFs into repressors and activators of auxin-dependent gene transcription. Expression studies identified tomato ARFs potentially involved in the fruit set process. Genome-wide expression profiling using RNA-seq revealed that at least one third of the gene family members display alternative splicing mode of regulation during the flower to fruit transition. Moreover, the regulation of several tomato ARF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signaling pathways of these two hormones. Conclusion All together, the data bring new insight on the complexity of the expression control of Sl-ARF genes at the transcriptional and post-transcriptional levels supporting the hypothesis that these transcriptional mediators might represent

  7. The Search for Therapeutic Bacteriophages Uncovers One New Subfamily and Two New Genera of Pseudomonas-Infecting Myoviridae

    PubMed Central

    Henry, Marine; Bobay, Louis-Marie; Chevallereau, Anne; Saussereau, Emilie; Ceyssens, Pieter-Jan; Debarbieux, Laurent

    2015-01-01

    In a previous study, six virulent bacteriophages PAK_P1, PAK_P2, PAK_P3, PAK_P4, PAK_P5 and CHA_P1 were evaluated for their in vivo efficacy in treating Pseudomonas aeruginosa infections using a mouse model of lung infection. Here, we show that their genomes are closely related to five other Pseudomonas phages and allow a subdivision into two clades, PAK_P1-like and KPP10-like viruses, based on differences in genome size, %GC and genomic contents, as well as number of tRNAs. These two clades are well delineated, with a mean of 86% and 92% of proteins considered homologous within individual clades, and 25% proteins considered homologous between the two clades. By ESI-MS/MS analysis we determined that their virions are composed of at least 25 different proteins and electron microscopy revealed a morphology identical to the hallmark Salmonella phage Felix O1. A search for additional bacteriophage homologs, using profiles of protein families defined from the analysis of the 11 genomes, identified 10 additional candidates infecting hosts from different species. By carrying out a phylogenetic analysis using these 21 genomes we were able to define a new subfamily of viruses, the Felixounavirinae within the Myoviridae family. The new Felixounavirinae subfamily includes three genera: Felixounalikevirus, PAK_P1likevirus and KPP10likevirus. Sequencing genomes of bacteriophages with therapeutic potential increases the quantity of genomic data on closely related bacteriophages, leading to establishment of new taxonomic clades and the development of strategies for analyzing viral genomes as presented in this article. PMID:25629728

  8. Microbiological study of ready-to-eat salad vegetables from retail establishments uncovers a national outbreak of salmonellosis.

    PubMed

    Sagoo, S K; Little, C L; Ward, L; Gillespie, I A; Mitchell, R T

    2003-03-01

    The increasing availability of bagged prepared salad vegetables reflects consumer demand for fresh, healthy, convenient, and additive-free foods that are safe and nutritious. During May and June 2001 a study of retail bagged prepared ready-to-eat salad vegetables was undertaken to determine the microbiological quality of these vegetables. Examination of the salad vegetables revealed that the vast majority (3,826 of 3,852 samples; 99.3%) were of satisfactory or acceptable microbiological quality according to Public Health Laboratory Service microbiological guidelines, while 20 (0.5%) samples were of unsatisfactory microbiological quality. Unsatisfactory quality was due to Escherichia coli and Listeria spp. (not Listeria monocytogenes) levels in excess of 10(2) CFU/g. However, six (0.2%) samples were of unacceptable microbiological quality because of the presence of Salmonella (Salmonella Newport PT33 [one sample], Salmonella Umbilo [three samples], and Salmonella Durban [one sample]) or because of a L. monocytogenes level of 660 CFU/g, which indicates a health risk. In each case, the retailer involved and the UK Food Standards Agency were immediately informed, and full investigations were undertaken. Nineteen cases of Salmonella Newport PT33 infection were subsequently identified throughout England and Wales. The outbreak strain of Salmonella Newport PT33 isolated from the salad and from humans had a unique plasmid profile. Campylobacter spp. and E. coli O157 were not detected in any of the samples examined. The presence of Salmonella, as well as high levels of L. monocytogenes, is unacceptable. However, minimally processed cut and packaged salad is exposed to a range of conditions during growth, harvest, preparation, and distribution, and it is possible that these conditions may increase the potential for microbial contamination, highlighting the necessity for the implementation of good hygiene practices from farm to fork to prevent contamination and/or bacterial

  9. Differential display system with vertebrate-common degenerate oligonucleotide primers: uncovering genes responsive to dioxin in avian embryonic liver.

    PubMed

    Teraoka, Hiroki; Ito, Shino; Ikeda, Haruki; Kubota, Akira; Abou Elmagd, M M; Kitazawa, Takio; Kim, Eun-Young; Iwata, Hisato; Endoh, Daiji

    2012-01-01

    To assess possible impacts of environmental pollutants on gene expression profiles in a variety of organisms, we developed a novel differential display system with primer sets that are common in seven vertebrate species, based on degenerate oligonucleotide-primed PCR (DOP-PCR). An 8-mer inverse repeat motif was found in most transcripts from the seven vertebrates including fish to primates with detailed transcriptome information; more than 10,000 motifs were recognized in common in the transcripts of the seven species. Among them, we selected 275 common motifs that cover about 40-70% of transcripts throughout these species, and designed 275 DOP-PCR primers that were common to seven vertebrate species (common DOP-PCR primers). To detect genes responsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in developing embryos, differential display with common DOP-PCR primers was applied to embryonic liver of two avian species, the chicken (Gallus gallus) and the common cormorant (Phalacrocorax carbo), which were exposed in ovo to TCDD. The cDNA bands that showed differences between the control and TCDD-treated groups were sequenced and the mRNA expression levels were confirmed by real-time RT-PCR. This approach succeeded in isolating novel dioxin-responsive genes that include 10 coding genes in the chicken, and 1 coding gene and 1 unknown transcript in the cormorant, together with cytochrome P450 1As that have already been well established as dioxin markers. These results highlighted the usefulness of systematically designed novel differential display systems to search genes responsive to chemicals in vertebrates, including wild species, for which transcriptome information is not available. PMID:21786751

  10. SURFACE BRIGHTNESS PROFILES OF DWARF GALAXIES. I. PROFILES AND STATISTICS

    SciTech Connect

    Herrmann, Kimberly A.; Hunter, Deidre A.; Elmegreen, Bruce G. E-mail: dah@lowell.edu

    2013-11-01

    Radial surface brightness profiles of spiral galaxies are classified into three types: (I) single exponential, or the light falls off with one exponential to a break before falling off (II) more steeply, or (III) less steeply. Profile breaks are also found in dwarf disks, but some dwarf Type IIs are flat or increasing out to a break before falling off. Here we re-examine the stellar disk profiles of 141 dwarfs: 96 dwarf irregulars (dIms), 26 Blue Compact Dwarfs (BCDs), and 19 Magellanic-type spirals (Sms). We fit single, double, or even triple exponential profiles in up to 11 passbands: GALEX FUV and NUV, ground-based UBVJHK and Hα, and Spitzer 3.6 and 4.5 μm. We find that more luminous galaxies have brighter centers, larger inner and outer scale lengths, and breaks at larger radii; dwarf trends with M{sub B} extend to spirals. However, the V-band break surface brightness is independent of break type, M{sub B} , and Hubble type. Dwarf Type II and III profiles fall off similarly beyond the breaks but have different interiors and IIs break ∼twice as far as IIIs. Outer Type II and III scale lengths may have weak trends with wavelength, but pure Type II inner scale lengths clearly decrease from the FUV to visible bands whereas Type III inner scale lengths increase with redder bands. This suggests the influence of different star formation histories on profile type, but nonetheless the break location is approximately the same in all passbands. Dwarfs continue trends between profile and Hubble types such that later-type galaxies have more Type II but fewer Type I and III profiles than early-type spirals. BCDs and Sms are over-represented as Types III and II, respectively, compared to dIms.

  11. Wind profiler dedicated in Indonesia

    NASA Astrophysics Data System (ADS)

    Gage, Ken

    A dedication ceremony was recently held in Biak, Indonesia, to commemorate the opening of the Biak VHF wind profiler. The wind profiler, which operates at 50 MHz, was constructed by the National Oceanic and Atmospheric Administration's Aeronomy Laboratory in cooperation with the Indonesian National Institute of Aeronautics and Space (LAPAN). The Biak facility completes the NOAA'Colorado University trans-Pacific wind-profiler network. Other stations in the network, which is sponsored by the National Science Foundation, are Piura, Peru; Pohnpei, Federated States of Micronesia; and Christmas Island in Kirabati. The Christmas Island facility is supported by NOAA's Tropical Ocean and Global Atmosphere (TOGA) Program Project Office.

  12. Profiler/satellite interference analysis

    NASA Astrophysics Data System (ADS)

    Chadwick, R. B.

    1987-02-01

    An engineering analysis of potential radio interference between the Wind Profiler Demonstration Network and three NOAA satellite-based systems is presented. These three systems are: Geostationary Operational Environmental Satellite (GOES) system, the Search and Rescue Satellite (SARSAT) system, and the TIROS series Data Collection System (TDCS). The Profiler considered in this analysis is the UHF Wind Profiler to be supplied by Sperry Corporation under a contract awarded June 1986. The analysis is based on the interference-to-noise ratio at the satellite receiver. Several engineering changes have been made to the original contract to reduce potential interference. The effects of these changes are presented.

  13. Label-free cell profiling.

    PubMed

    Schasfoort, Richard B M; Bentlage, Arthur E H; Stojanovic, Ivan; van der Kooi, Alex; van der Schoot, Ellen; Terstappen, Leon W M M; Vidarsson, Gestur

    2013-08-01

    A surface plasmon resonance (SPR) array imaging method is outlined for label-free cell profiling. Red blood cells (RBCs) were injected into a flow chamber on top of a spotted sensor surface. Spots contained antibodies to various RBC membrane antigens. A typical sensorgram showed an initial response corresponding to cell sedimentation (S) followed by a specific upward response (T) corresponding to specific binding of cells during a critical wash step. The full analysis cycle for RBC profiling was less than 6 min. The sensor surface could be regenerated at least 100 times, allowing the determination of a cell surface antigen profile of RBCs.

  14. VPFIT: Voigt profile fitting program

    NASA Astrophysics Data System (ADS)

    Carswell, R. F.; Webb, J. K.

    2014-08-01

    The VPFIT program fits multiple Voigt profiles (convolved with the instrument profiles) to spectroscopic data that is in FITS or an ASCII file. It requires CFITSIO (ascl:1010.001) and PGPLOT (ascl:1103.002); the tarball includes RDGEN (ascl:1408.017), which can be used with VPFIT to set up the fits, fit the profiles, and examine the result in interactive mode for setting up initial guesses; vpguess (ascl:1408.016) can also be used to set up an initial file.

  15. Genome-Wide Profiling of Yeast DNA:RNA Hybrid Prone Sites with DRIP-Chip

    PubMed Central

    Lu, Phoebe Y. T.; Luo, Zongli; Hamza, Akil; Kobor, Michael S.; Stirling, Peter C.; Hieter, Philip

    2014-01-01

    DNA:RNA hybrid formation is emerging as a significant cause of genome instability in biological systems ranging from bacteria to mammals. Here we describe the genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae by DNA:RNA immunoprecipitation (DRIP) followed by hybridization on tiling microarray. These profiles show that DNA:RNA hybrids preferentially accumulated at rDNA, Ty1 and Ty2 transposons, telomeric repeat regions and a subset of open reading frames (ORFs). The latter are generally highly transcribed and have high GC content. Interestingly, significant DNA:RNA hybrid enrichment was also detected at genes associated with antisense transcripts. The expression of antisense-associated genes was also significantly altered upon overexpression of RNase H, which degrades the RNA in hybrids. Finally, we uncover mutant-specific differences in the DRIP profiles of a Sen1 helicase mutant, RNase H deletion mutant and Hpr1 THO complex mutant compared to wild type, suggesting different roles for these proteins in DNA:RNA hybrid biology. Our profiles of DNA:RNA hybrid prone loci provide a resource for understanding the properties of hybrid-forming regions in vivo, extend our knowledge of hybrid-mitigating enzymes, and contribute to models of antisense-mediated gene regulation. A summary of this paper was presented at the 26th International Conference on Yeast Genetics and Molecular Biology, August 2013. PMID:24743342

  16. Multiplexed In-cell Immunoassay for Same-sample Protein Expression Profiling

    PubMed Central

    Shang, Jing; Zrazhevskiy, Pavel; Postupna, Nadia; Keene, C. Dirk; Montine, Thomas J.; Gao, Xiaohu

    2015-01-01

    In-cell immunoassays have become a valuable tool for protein expression analysis complementary to established assay formats. However, comprehensive molecular characterization of individual specimens has proven challenging and impractical due to, in part, a singleplex nature of reporter enzymes and technical complexity of alternative assay formats. Herein, we describe a simple and robust methodology for multiplexed protein expression profiling on the same intact specimen, employing a well-characterized enzyme alkaline phosphatase for accurate quantification of all targets of interest, while overcoming fundamental limitations of enzyme-based techniques by implementing the DNA-programmed release mechanism for segregation of sub-sets of target-bound reporters. In essence, this methodology converts same-sample multi-target labeling into a set of isolated singleplex measurements performed in a parallel self-consistent fashion. For a proof-of-principle, multiplexed detection of three model proteins was demonstrated on cultured HeLa cells, and two clinically-relevant markers of dementia, β-amyloid and PHF-tau, were profiled in formalin-fixed paraffin embedded brain tissue sections, uncovering correlated increase in abundance of both markers in the “Alzheimer’s disease” cohort. Featuring an analytically powerful yet technically simple and robust methodology, multiplexed in-cell immunoassay is expected to enable insightful same-sample protein profiling studies and become broadly adopted in biomedical research and clinical diagnostics. PMID:26328896

  17. Genome-wide profiling of yeast DNA:RNA hybrid prone sites with DRIP-chip.

    PubMed

    Chan, Yujia A; Aristizabal, Maria J; Lu, Phoebe Y T; Luo, Zongli; Hamza, Akil; Kobor, Michael S; Stirling, Peter C; Hieter, Philip

    2014-04-01

    DNA:RNA hybrid formation is emerging as a significant cause of genome instability in biological systems ranging from bacteria to mammals. Here we describe the genome-wide distribution of DNA:RNA hybrid prone loci in Saccharomyces cerevisiae by DNA:RNA immunoprecipitation (DRIP) followed by hybridization on tiling microarray. These profiles show that DNA:RNA hybrids preferentially accumulated at rDNA, Ty1 and Ty2 transposons, telomeric repeat regions and a subset of open reading frames (ORFs). The latter are generally highly transcribed and have high GC content. Interestingly, significant DNA:RNA hybrid enrichment was also detected at genes associated with antisense transcripts. The expression of antisense-associated genes was also significantly altered upon overexpression of RNase H, which degrades the RNA in hybrids. Finally, we uncover mutant-specific differences in the DRIP profiles of a Sen1 helicase mutant, RNase H deletion mutant and Hpr1 THO complex mutant compared to wild type, suggesting different roles for these proteins in DNA:RNA hybrid biology. Our profiles of DNA:RNA hybrid prone loci provide a resource for understanding the properties of hybrid-forming regions in vivo, extend our knowledge of hybrid-mitigating enzymes, and contribute to models of antisense-mediated gene regulation. A summary of this paper was presented at the 26th International Conference on Yeast Genetics and Molecular Biology, August 2013. PMID:24743342

  18. Epidemiology as discourse: the politics of development institutions in the Epidemiological Profile of El Salvador

    PubMed Central

    Aviles, L

    2001-01-01

    STUDY OBJECTIVE—To determine the ways in which institutions devoted to international development influence epidemiological studies.
DESIGN—This article takes a descriptive epidemiological study of El Salvador, Epidemiological Profile, conducted in 1994 by the US Agency for International Development, as a case study. The methods include discourse analysis in order to uncover the ideological basis of the report and its characteristics as a discourse of development.
SETTING—El Salvador.
RESULTS—The Epidemiological Profile theoretical basis, the epidemiological transition theory, embodies the ethnocentrism of a "colonizer's model of the world." This report follows the logic of a discourse of development by depoliticising development, creating abnormalities, and relying on the development consulting industry. The epidemiological transition theory serves as an ideology that legitimises and dissimulates the international order.
CONCLUSIONS—Even descriptive epidemiological assessments or epidemiological profiles are imbued with theoretical assumptions shaped by the institutional setting under which epidemiological investigations are conducted.


Keywords: El Salvador; politics PMID:11160170

  19. DIANA-mirExTra v2.0: Uncovering microRNAs and transcription factors with crucial roles in NGS expression data.

    PubMed

    Vlachos, Ioannis S; Vergoulis, Thanasis; Paraskevopoulou, Maria D; Lykokanellos, Filopoimin; Georgakilas, Georgios; Georgiou, Penny; Chatzopoulos, Serafeim; Karagkouni, Dimitra; Christodoulou, Foteini; Dalamagas, Theodore; Hatzigeorgiou, Artemis G

    2016-07-01

    Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined DEA of mRNAs and microRNAs (miRNAs) to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server uses as input miRNA/RNA-Seq read count data sets that can be uploaded for analysis. Users can combine their data with 350 small-RNA-Seq and 65 RNA-Seq in-house analyzed libraries which are provided by DIANA-mirExTra v2.0.The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets. More than 450 000 miRNA interactions and 2 000 000 TF binding sites from specific or high-throughput techniques have been incorporated, while accurate miRNA TSS annotation is obtained from microTSS experimental/in silico framework. These comprehensive data sets enable users to perform analyses based solely on experimentally supported information and to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression. The server also supports predicted miRNA:gene interactions from DIANA-microT-CDS for 4 species (human, mouse, nematode and fruit fly). DIANA-mirExTra v2.0 has an intuitive user interface and is freely available to all users without any login requirement. PMID:27207881

  20. Mice Lacking Mannose 6-Phosphate Uncovering Enzyme Activity Have a Milder Phenotype than Mice Deficient for N-Acetylglucosamine-1-Phosphotransferase Activity

    PubMed Central

    Boonen, Marielle; Vogel, Peter; Platt, Kenneth A.; Dahms, Nancy

    2009-01-01

    The mannose 6-phosphate (Man-6-P) lysosomal targeting signal on acid hydrolases is synthesized by the sequential action of uridine 5′-diphosphate-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (GlcNAc-1-phosphotransferase) and GlcNAc-1-phosphodiester α-N-acetylglucosaminidase (“uncovering enzyme” or UCE). Mutations in the two genes that encode GlcNAc-1-phosphotransferase give rise to lysosomal storage diseases (mucolipidosis type II and III), whereas no pathological conditions have been associated with the loss of UCE activity. To analyze the consequences of UCE deficiency, the UCE gene was inactivated via insertional mutagenesis in mice. The UCE −/− mice were viable, grew normally and lacked detectable histologic abnormalities. However, the plasma levels of six acid hydrolases were elevated 1.6- to 5.4-fold over wild-type levels. These values underestimate the degree of hydrolase hypersecretion as these enzymes were rapidly cleared from the plasma by the mannose receptor. The secreted hydrolases contained GlcNAc-P-Man diesters, exhibited a decreased affinity for the cation-independent mannose 6-phosphate receptor and failed to bind to the cation-dependent mannose 6-phosphate receptor. These data demonstrate that UCE accounts for all the uncovering activity in the Golgi. We propose that in the absence of UCE, the weak binding of the acid hydrolases to the cation-independent mannose 6-phosphate receptor allows sufficient sorting to lysosomes to prevent the tissue abnormalities seen with GlcNAc-1-phosphotranferase deficiency. PMID:19710420

  1. DIANA-mirExTra v2.0: Uncovering microRNAs and transcription factors with crucial roles in NGS expression data

    PubMed Central

    Vlachos, Ioannis S.; Vergoulis, Thanasis; Paraskevopoulou, Maria D.; Lykokanellos, Filopoimin; Georgakilas, Georgios; Georgiou, Penny; Chatzopoulos, Serafeim; Karagkouni, Dimitra; Christodoulou, Foteini; Dalamagas, Theodore; Hatzigeorgiou, Artemis G.

    2016-01-01

    Differential expression analysis (DEA) is one of the main instruments utilized for revealing molecular mechanisms in pathological and physiological conditions. DIANA-mirExTra v2.0 (http://www.microrna.gr/mirextrav2) performs a combined DEA of mRNAs and microRNAs (miRNAs) to uncover miRNAs and transcription factors (TFs) playing important regulatory roles between two investigated states. The web server uses as input miRNA/RNA-Seq read count data sets that can be uploaded for analysis. Users can combine their data with 350 small-RNA-Seq and 65 RNA-Seq in-house analyzed libraries which are provided by DIANA-mirExTra v2.0. The web server utilizes miRNA:mRNA, TF:mRNA and TF:miRNA interactions derived from extensive experimental data sets. More than 450 000 miRNA interactions and 2 000 000 TF binding sites from specific or high-throughput techniques have been incorporated, while accurate miRNA TSS annotation is obtained from microTSS experimental/in silico framework. These comprehensive data sets enable users to perform analyses based solely on experimentally supported information and to uncover central regulators within sequencing data: miRNAs controlling mRNAs and TFs regulating mRNA or miRNA expression. The server also supports predicted miRNA:gene interactions from DIANA-microT-CDS for 4 species (human, mouse, nematode and fruit fly). DIANA-mirExTra v2.0 has an intuitive user interface and is freely available to all users without any login requirement. PMID:27207881

  2. Distinguishing ichthyoses by protein profiling.

    PubMed

    Rice, Robert H; Bradshaw, Katie M; Durbin-Johnson, Blythe P; Rocke, David M; Eigenheer, Richard A; Phinney, Brett S; Schmuth, Matthias; Gruber, Robert

    2013-01-01

    To explore the usefulness of protein profiling for characterization of ichthyoses, we here determined the profile of human epidermal stratum corneum by shotgun proteomics. Samples were analyzed after collection on tape circles from six anatomic sites (forearm, palm, lower leg, forehead, abdomen, upper back), demonstrating site-specific differences in profiles. Additional samples were collected from the forearms of subjects with ichthyosis vulgaris (filaggrin (FLG) deficiency), recessive X-linked ichthyosis (steroid sulfatase (STS) deficiency) and autosomal recessive congenital ichthyosis type lamellar ichthyosis (transglutaminase 1 (TGM1) deficiency). The ichthyosis protein expression patterns were readily distinguishable from each other and from phenotypically normal epidermis. In general, the degree of departure from normal was lower from ichthyosis vulgaris than from lamellar ichthyosis, parallel to the severity of the phenotype. Analysis of samples from families with ichthyosis vulgaris and concomitant modifying gene mutations (STS deficiency, GJB2 deficiency) permitted correlation of alterations in protein profile with more complex genetic constellations.

  3. Temperature profile for Poiseuille flow

    NASA Astrophysics Data System (ADS)

    Todd, B. D.; Evans, Denis J.

    1997-03-01

    For planar Poiseuille flow of an atomic fluid in the weak-flow regime, we find that the classical Navier-Stokes prediction of a quartic temperature profile is incorrect. Our results, which confirm a prediction made by Baranyai, Evans, and Daivis (BED) [Phys. Rev. A 46, 7593 (1992)], indicate that near the center of the channel the temperature profile is quadratic. When the temperature profile is fitted to the theoretical predictions of BED we obtain estimates of the thermal conductivity that are in excellent agreement with accurate independent estimates of this transport coefficient. If the presence of the quadratic component of the temperature profile is ignored, the derived value of the thermal conductivity is in error by some 50%.

  4. Planetary Scientist Profile: Noah Petro

    NASA Video Gallery

    Noah Petro is a NASA planetary geologist who studies the surface of airless bodies in space, primarily focusing on the moon. In this video profile, Noah talks about how he was inspired to become a ...

  5. A putative role for amino acid permeases in sink-source communication of barley tissues uncovered by RNA-seq

    PubMed Central

    2012-01-01

    Background The majority of nitrogen accumulating in cereal grains originates from proteins remobilised from vegetative organs. However, interactions between grain filling and remobilisation are poorly understood. We used transcriptome large-scale pyrosequencing of flag leaves, glumes and developing grains to identify cysteine peptidase and N transporter genes playing a role in remobilisation and accumulation of nitrogen in barley. Results Combination of already known and newly derived sequence information reduced redundancy, increased contig length and identified new members of cysteine peptidase and N transporter gene families. The dataset for N transporter genes was aligned with N transporter amino acid sequences of rice and Arabidopsis derived from Aramemnon database. 57 AAT, 45 NRT1/PTR and 22 OPT unigenes identified by this approach cluster to defined subgroups in the respective phylogenetic trees, among them 25 AAT, 8 NRT1/PTR and 5 OPT full-length sequences. Besides, 59 unigenes encoding cysteine peptidases were identified and subdivided into different families of the papain cysteine peptidase clade. Expression profiling of full-length AAT genes highlighted amino acid permeases as the group showing highest transcriptional activity. HvAAP2 and HvAAP6 are highly expressed in vegetative organs whereas HvAAP3 is grain-specific. Sequence similarities cluster HvAAP2 and the putative transporter HvAAP6 together with Arabidopsis transporters, which are involved in long-distance transfer of amino acids. HvAAP3 is closely related to AtAAP1 and AtAAP8 playing a role in supplying N to developing seeds. An important role in amino acid re-translocation can be considered for HvLHT1 and HvLHT2 which are specifically expressed in glumes and flag leaves, respectively. PCA and K-means clustering of AAT transcript data revealed coordinate developmental stages in flag leaves, glumes and grains. Phloem-specific metabolic compounds are proposed that might signal high grain demands

  6. Metropolitan Lima: area profile.

    PubMed

    Hakkert, R

    1986-11-01

    This profile of metropolitan Lima, Peru, covers administrative divisions; population growth; age distribution; ethnicity and religion; housing and households; education and health care; economic activity, income, and consumption; transport and communication; and sources of information. Nearly 30% of Peru's entire population and 42% of its urban population live in Lima. The trend continues, yet Lima's urban primacy is waning due to the growth of some regional centers like Trujillo and Chimbote. Lima is still almost 10 times as large as the country's next ranking cities, Trujillo on the northern coast and Arequipa in the south. Peru's main administrative divisions are the 24 departments, of which the Department of Lima is one. These departments are further divided into 156 provinces. Greater Lima consists of 2 such provinces, the province of Lima and the constitutional province of Callao. Although the population of Lima continues to grow, its rate of growth slowed from about 5.5% during the 1960s to about 3.9% in the 1970s. Current projections estimate a metropolitan population of 6.7 million by 1990. On the whole, Lima's age structure is somewhat older than that of the rest of Peru. The median age of the population is 22.3 years, compared to a national figure of 20.4. The proportion of persons over age 65 is only 3.6%, lower than the national average of 4.1%, due to the tendency of in-migration to concentrate people of intermediate ages in the cities. Almost 400,000 inhabitants of greater Lima are bilingual in Spanish and an indigenous language. As elsewhere in Peru, the dominant religion is Roman Catholicism. Lima is a spread out city with few high rise buildings due to the danger of earthquakes. Only 12% of Lima's households are found in apartment buildings. As in other cities of Latin America, the formal housing market is beyond the reach of a major segment of the population. Consequently, much of the urban settlement has occurred through informal self

  7. Grinding Wheel Profile

    NASA Technical Reports Server (NTRS)

    2004-01-01

    This graphic dubbed by engineers as the 'Grinding Wheel Profile' is the detective's tool used by the Opportunity team to help them understand one of the processes that formed the interior of a rock called 'McKittrick.' Scientists are looking for clues as to how layers, grains and minerals helped create this rock, and the engineers who built the rock abrasion tool (RAT) wanted to ensure that their instrument's handiwork did not get confused with natural processes.

    In the original microscopic image underlaying the graphics, engineers and scientists noticed 'layers' or 'scratches' on the spherical object nicknamed 'blueberry' in the lower right part of the image. The designers of the rock abrasion tool noticed that the arc length and width of the scratches were similar to the shape and size of the rock abrasion tool's grinding wheel, which is made out of a pad of diamond teeth.

    The scrapes on the bottom right blueberry appear to be caused by the fact that the berry got dislodged slightly and its surface was scraped with the grinding pad. In this image, the largest yellow circle is the overall diameter of the hole ground by the rock abrasion tool and the largest yellow rectangular shape is the area of the grinding wheel bit. The smaller yellow semi-circle is the path that the center of the grinding tool follows. The orange arrow arcing around the solid yellow circle (center of grinding tool) indicates the direction that the grinding tool spins around its own center at 3,000 revolutions per minute. The tool simultaneously spins in an orbit around the center of the hole, indicated by the larger orange arrow to the left.

    The grinding tool is 22 millimeters (0.9 inches) in length and the actual grinding surface, which consists of the diamond pad, is 1.5 millimeters (0.06 inches) in length, indicated by the two smaller rectangles. You can see that the smaller bottom rectangle fits exactly the width of the scrape marks.

    The grooves on the blueberry are also the

  8. Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles

    PubMed Central

    Marien, Eyra; Meister, Michael; Muley, Thomas; Fieuws, Steffen; Bordel, Sergio; Derua, Rita; Spraggins, Jeffrey; Van de Plas, Raf; Dehairs, Jonas; Wouters, Jens; Bagadi, Muralidhararao; Dienemann, Hendrik; Thomas, Michael; Schnabel, Philipp A; Caprioli, Richard M; Waelkens, Etienne; Swinnen, Johannes V

    2015-01-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. What’s new? Cellular membranes are subject to extensive modification in cancer, often with marked alterations in phospholipid metabolism. The extent and nature of those changes are not fully known, however, particularly for non-small cell lung cancer (NSCLC). In this study, lipidomics analysis

  9. Refractive turbulence profiling using stellar scintillation and radar wind profiles.

    PubMed

    Churnside, J H; Clifford, S F

    1988-12-01

    The fluctuations of spatially filtered starlight contain information about refractive turbulence strength (C(2)(n)) at the spatial filter wavenumber. If the turbulence at different heights in the atmosphere is moving at different speeds, the contribution to the fluctuations from those heights will occur at different frequencies. Therefore, the C(2)(n) profile can be inferred from the power spectrum of the fluctuations and the wind velocity profile. Vertical resolution is expected to be in the range of several hundred meters to about a kilometer. Turbulence strength measurements to better than 50% should be easily obtainable.

  10. Comparative transcriptome profiling analyses during the lag phase uncover YAP1, PDR1, PDR3, RPN4, and HSF1 as key regulatory genes in genomic adaptation to the lignocellulose derived inhibitor HMF for Saccharomyces cerevisiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The yeast Saccharomyces cerevisiae is able to adapt and in situ detoxify lignocellulose derived inhibitors such as furfural and hydroxymethylfurfural (HMF). The length of lag phase for cell growth in response to the inhibitor challenge has been used to measure tolerance of strain performance. Mechan...

  11. Convex profiles from asteroid lightcurves

    NASA Astrophysics Data System (ADS)

    Ostro, S. J.; Connelly, R.

    1984-03-01

    A lightcurve inversion method that yields a two-dimensional convex profile is introduced. The number of parameters that characterize the profile is limited only by the number of Fourier harmonics used to represent the parent lightcurve. The implementation of the method is outlined by a recursive quadratic programming algorithm, and its application to photoelectric lightcurves and radar measurements is discussed. Special properties of the lightcurves of geometrically scattering ellipsoids are pointed out, and those properties are used to test the inversion method and obtain a criterion for judging whether any lightcurve could actually be due to such an object. Convex profiles for several asteroids are shown, and the method's validity is discussed from a physical as well as purely statistical point of view.

  12. Molecular Profiling of Aggressive Lymphomas

    PubMed Central

    Rossi, Maura; Laginestra, Maria Antonella; Gazzola, Anna; Sapienza, Maria Rosaria; Pileri, Stefano A.; Piccaluga, Pier Paolo

    2012-01-01

    In the last years, several studies of molecular profiling of aggressive lymphomas were performed. In particular, it was shown that DLBCL can be distinguished in two different entities according to GEP. Specifically, ABC and GCB subtypes were characterized by having different pathogenetic and clinical features. In addition, it was demonstrated that DLBCLs are distinct from BL. Indeed, the latter is a unique molecular entity. However, relevant pathological differences emerged among the clinical subtypes. More recently, microRNA profiling provided further information concerning BL-DLBCL distinction as well as for their subclassification. In this paper, the authors based on their own experience and the most updated literature review, the main concept on molecular profiling of aggressive lymphomas. PMID:22190944

  13. Waste product profile: Household batteries

    SciTech Connect

    Miller, C. )

    1994-04-01

    This is the fourteenth in a series of profiles -- brief, factual listings of the solid waste management characteristics of materials in the waste stream. These profiles highlight a product, explain how it fits into integrated waste management systems, and provide current data on recycling and markets for the product. This profile does not cover wet cell lead-acid batteries such as car batteries. Household batteries include primary batteries, which cannot be recharged, and secondary (rechargeable) batteries. Household batteries are available in many sizes including bottom, AAA, AA, C, D, N, and 9-volt. In 1991, 3.8 billion household batteries, or 145,000 tons, were incinerated or landfilled in the US. Due to a limited number of programs collecting batteries, the recycling rate is very small. An EPA study estimated than in 1989, 52% of the cadmium and 88% of the mercury in MSW came from household batteries.

  14. Theoretical solution of profile drag

    NASA Technical Reports Server (NTRS)

    Pretsch, J

    1942-01-01

    After a survey of the customary procedures for appraising the profile drag in which pressure drag was discounted and the methods for computing the laminar and turbulent friction flow, the author proposes a method by which the pressure drag can be computed with the aid of the displacement thickness of the frictional layer. The method is restricted to the case where the effects, caused by separation of frictional layer, are small. Then the total profile drag can be expressed solely by quantities derived from the velocity distribution in the frictional layer immediately at the trailing edge.

  15. A Distinct Fatty Acid Profile Underlies the Reduced Inflammatory State of Metabolically Healthy Obese Individuals

    PubMed Central

    Badoud, Flavia; Stephenson, Susan; Badawi, Alaa; Buchholz, Andrea; Mutch, David M.

    2014-01-01

    Background Obesity is associated with numerous health complications; however, a subgroup of obese individuals (termed the metabolically healthy obese or MHO) appear to have lower risk for complications such as type 2 diabetes and cardiovascular disease. Emerging evidence suggests that MHO individuals have reduced inflammation compared to their metabolically unhealthy obese (MUO) counterparts. As it is recognized that fatty acids (FAs) have a strong relationship with inflammation, the current study aimed to uncover if the reduced inflammation observed in MHO individuals is mirrored by a more favourable FA profile. Methods Fasted serum samples were collected from lean healthy (LH), MHO, and MUO participants (n = 10/group) recruited from the Diabetes Risk Assessment study. A panel of pro- and anti-inflammatory markers were measured by immunoassay. Total serum FA profiling, as well as the FA composition of circulating phospholipids (PL) and triglycerides (TG), was measured by gas chromatography. ANOVA and Mann-Whitney-Wilcoxon tests were used to assess statistical significance between the groups (P<0.05). Results MHO and MUO individuals had similar BMI and body fat %; however, lipid parameters in MHO individuals more closely resembled that of LH individuals. MHO individuals had circulating levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) similar to LH individuals, while levels of platelet derived growth factor-ββ (PDGF-ββ) were intermediate to that of LH and MUO individuals. FA profiling analysis combined with discriminant analysis modelling highlighted a panel of nine FAs (consisting of three saturated, three monounsaturated, and three polyunsaturated FAs) in PL and TG fractions that distinguished the three groups. Specifically, saturated FA (myristic and stearic acids) levels in MHO individuals resembled that of LH individuals. Conclusion Our results suggest that the reduced inflammatory state of MHO individuals compared to MUO

  16. Cognitive Profile of Turner Syndrome

    ERIC Educational Resources Information Center

    Hong, David; Kent, Jamie Scaletta; Kesler, Shelli

    2009-01-01

    Turner syndrome (TS) is a relatively common neurogenetic disorder characterized by complete or partial monosomy-X in a phenotypic female. TS is associated with a cognitive profile that typically includes intact intellectual function and verbal abilities with relative weaknesses in visual-spatial, executive, and social cognitive domains. In this…

  17. Welding. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP), which is one of a series of OCAPs developed to identify the skills that Ohio employers deem necessary to entering a given occupation/occupational area, lists the occupational, academic, and employability skills required of individuals entering the occupation of welder. The introduction explains…

  18. Masonry. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP) for masonry occupations contains a competency list verified by expert workers and developed through a modified DACUM (Developing a Curriculum) involving business, industry, labor, and community agency representatives from Ohio. This OCAP identifies the occupational, academic, and employability…

  19. Teachers' Entrepreneurial Profile: Case Study

    ERIC Educational Resources Information Center

    Stettiner, Caio Flavio; Formigoni, Alexandre; Filho, Mário Pereira Roque; de Camargo, Mauricio Ortiz; Moia, Roberto Padilha

    2015-01-01

    This article was prepared in order to investigate whether the teachers working in a Business Administration BA degree have an entrepreneurial profile, with the aim of finding whether such teachers are able to support the Pedagogical Proposal of the Institution to which they belong to in what concerns the requirement of the course and also the…

  20. Learning Style Profile: Examiner's Manual.

    ERIC Educational Resources Information Center

    Keefe, James W.; Monk, John S.

    This examiner's manual accompanies the Learning Style Profile (LSP), which measures cognitive skills as well as affective and environmental preferences. Charles Letteri's General Operations Model was accepted as the prototype for relating learning styles to cognitive information processing. The LSP was developed from 1983 to 1986; several versions…

  1. Ohio Information Technology Competency Profile.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Education, Columbus.

    This profile includes a comprehensive set of information technology competencies that are grounded in core academic subject areas and built around four occupational clusters (information services and support, network systems, programming and software development, and interactive media) that reflect the job opportunities and skills required for…

  2. Temporal Profiles of SEP events

    NASA Astrophysics Data System (ADS)

    Gomez-Herrero, R.; del Peral, L.; Rodriguez-Frias, M. D.; Sequeiros, J.; Mueller-Mellin, R.; Kunow, H.

    2001-08-01

    This work is a preliminary study of 18 solar energetic particle (SEP) events detected by SOHO/EPHIN between 1996 and 2000. Temporal profiles of Impulsive and Gradual SEP events have been parameterized to determinate differences among SEP events depending on the magnetic connection and Physical conditions of the interplanetary transport.

  3. English Language Teaching Profile: Uruguay.

    ERIC Educational Resources Information Center

    British Council, London (England). English-Teaching Information Centre.

    This profile in outline form of the English language teaching situation in Uruguay discusses the role of English within Uruguayan society and within the educational system. Though English is quite widely used for reading scientific, technical and medical publications, and while it is considered important culturally in higher professions, it is not…

  4. Stream Profiles, An Environmental Investigation.

    ERIC Educational Resources Information Center

    National Wildlife Federation, Washington, DC.

    This environmental unit is one of a series designed for integration within an existing curriculum. The unit is self-contained and requires minimal teacher preparation. The philosophy of the units is based on an experience-oriented process that encourages self-paced independent student work. In this unit, students construct a stream profile based…

  5. ARL Profiles: Research Libraries 2010

    ERIC Educational Resources Information Center

    Potter, William Gray; Cook, Colleen; Kyrillidou, Martha

    2011-01-01

    The current ARL report summarizes a multi-year effort that captures evidence in the form of narrative profiles as it delivers the message of the value and contributions of research libraries during transformative times. When ARL library directors were interviewed in 2005 and asked to describe a research library in the 21st century, there was…

  6. Profiling Mobile English Language Learners

    ERIC Educational Resources Information Center

    Byrne, Jason; Diem, Robert

    2014-01-01

    The purpose of this study was to use an app-embedded survey to profile language learner demographics. A total of 3,759 EFL language learners from primarily eight L1 backgrounds (French, German, Italian, Japanese, Korean, Russian, Spanish and Thai) responded to the survey embedded within a popular English grammar app. This app has over 500,000…

  7. Horticulture. Tech Prep Competency Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Wooster. Agricultural Technical Inst.

    This tech prep competency profile (TCP), which was developed by a consortium of Ohio educators and business/industry representatives, lists the competencies that have been identified as necessary for employment in the following occupations: nursery technician; golf course superintendent; landscape designer/manager; lawn care specialist; tree care…

  8. Electronics. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Occupational Competency Analysis Profile (OCAP) contains a competency list verified by expert workers and developed through a modified DACUM (Developing a Curriculum) involving business, industry, labor, and community agency representatives from Ohio. This OCAP identifies the occupational, academic, and employability skills (competencies)…

  9. Ohio's Competency Analysis Profile. Index.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This index contains the unit titles from all 60 Ohio's Competency Analysis Profile (OCAP) lists. It is intended to facilitate the combination of units from different OCAPs in order to develop curricula that meet specific program needs (e.g., learner differences, labor market demands, and technological developments). OCAP titles are as follows:…

  10. Chinese Converstations: An Intellectual Profile.

    ERIC Educational Resources Information Center

    Cogan, John J.

    1980-01-01

    A profile of how Chinese urban intellectuals view life in their country is presented. Information was obtained through many conversations with Chinese educators and students during the author's visit to China. Discussed are family, education, the cultural revolution, the Gang of Four, the quest for modernization, and the policy toward…

  11. Project Profile Report. Fall 1993.

    ERIC Educational Resources Information Center

    Pennsylvania Coll. of Technology, Williamsport.

    Pennsylvania College of Technology's Project Profile seeks to provide a portrait of all students entering each fall by collecting and analyzing surveys completed at the time of admission and comparing them to previous years. This report presents data on the 4,942 students who applied and matriculated in fall 1993 and includes comparisons by…

  12. English Language Teaching Profile: Canada.

    ERIC Educational Resources Information Center

    British Council, London (England). English-Teaching Information Centre.

    This profile in outline form of the English language teaching situation in Canada discusses the role of English within Canadian society and within the educational systems in the provinces. The discussion takes place within the context of the Official Languages Act of 1969, which declared English and French official languages for all government…

  13. relline: Relativistic line profiles calculation

    NASA Astrophysics Data System (ADS)

    Dauser, Thomas

    2015-05-01

    relline calculates relativistic line profiles; it is compatible with the common X-ray data analysis software XSPEC (ascl:9910.005) and ISIS (ascl:1302.002). The two basic forms are an additive line model (RELLINE) and a convolution model to calculate relativistic smearing (RELCONV).

  14. Drafting. Occupational Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Drafting Occupational Competency Analysis Profile (OCAP) is one of a series of competency lists, verified by expert workers, that have evolved from a modified DACUM (Developing a Curriculum) job analysis process involving business, industry, labor, and community agency representatives from throughout Ohio. This OCAP identifies the…

  15. Welding. Ohio's Competency Analysis Profile.

    ERIC Educational Resources Information Center

    Ohio State Univ., Columbus. Vocational Instructional Materials Lab.

    This Ohio Competency Analysis Profile (OCAP), derived from a modified Developing a Curriculum (DACUM) process, is a comprehensive and verified employer competency list for a welding program. It contains units (with or without subunits), competencies, and competency builders that identify the occupational, academic, and employability skills needed…

  16. Country Profiles, Trinidad and Tobago.

    ERIC Educational Resources Information Center

    Khanna, Sumedha

    A profile of Trinidad and Tobago is sketched in this paper. Although they are now unified into one national whole, their histories and socioeconomic and demographic developments have differed somewhat. Thus, these aspects of the two islands are treated separately where circumstances warrant. Emphasis is placed on the nature, scope, and…

  17. Country Profiles, United Arab Republic.

    ERIC Educational Resources Information Center

    Croley, H. T.

    A profile of the United Arab Republic is sketched in this paper. Emphasis is placed on the nature, scope, and accomplishments of population activities in the country. Topics and sub-topics include: location and description of the country; population (size, growth patterns, age structure, urban/rural distribution, ethnic and religious composition,…

  18. English Teaching Profile (Provisional): Venezuela.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    This profile of the English language teaching situation in Venezuela discusses the status of English in society and in the educational system. It also gives an account of Venezuelan political, economic, and social life. A description is given of the education system and reforms that have been proposed for nursery school through higher education.…

  19. PROFILES Networks: Three International Examples

    ERIC Educational Resources Information Center

    Rauch, F.; Dulle, M.; Namsone, D.; Gorghiu, G.

    2014-01-01

    This paper explores the effectiveness of networking in promoting inquiry-based science education (IBSE) through raising the self-efficacy of science teachers to take ownership of more effective ways of teaching students, supported by stakeholders (Holbrook & Rannikmae, 2010). As PROFILES project (Professional Reflection Oriented Focus on…

  20. Humidity profiles over the ocean

    NASA Technical Reports Server (NTRS)

    Liu, W. T.; Tang, Wenqing; Niiler, Pearn P.

    1991-01-01

    The variabilities of atmospheric humidity profile over oceans from daily to interannual time scales were examined using 9 years of daily and semidaily radiosonde soundings at island stations extending from the Arctic to the South Pacific. The relative humidity profiles were found to have considerable temporal and geographic variabilities, contrary to the prevalent assumption. Principal component analysis on the profiles of specific humidity were used to examine the applicability of a relation between the surface-level humidity and the integrated water vapor; this relation has been used to estimate large-scale evaporation from satellite data. The first principal component was found to correlate almost perfectly with the integrated water vapor. The fractional variance represented by this mode increases with increasing period. It reaches approximately 90 percent at two weeks and decreases sharply, below one week, down to approximately 60 percent at the daily period. At low frequencies, the integrated water vapor appeared to be an adequate estimator of the humidity profile and the surface-level humidity. At periods shorter than a week, more than one independent estimator is needed.

  1. English Teaching Profile: New Zealand.

    ERIC Educational Resources Information Center

    British Council, London (England). English Language and Literature Div.

    A profile of the state of English and English instruction in New Zealand covers the following topics: a description of the role and status of English language use in industry and commerce, government, and education; the role of English at all levels of the educational system; the availability and training of teachers of English, the type of…

  2. Country Energy Profile, South Africa

    SciTech Connect

    1995-08-01

    This country energy profile provides energy and economic information about South Africa. Areas covered include: Economics, demographics, and environment; Energy situation; Energy structure; Energy investment opportunities; Department of Energy (DOE) programs in South Africa; and a listing of International aid to South Africa.

  3. EP Profiles Inventor Mark Sherron

    ERIC Educational Resources Information Center

    Williams, John M.

    2006-01-01

    This article profiles Mark Jerome Sherron, inventor of the ALLIES Line of electronic sensors for blind and visually-impaired people. Featuring the American Liquid Level Indicator electronic sensor (ALLI), Sherron's ALLIES product line also includes the Light Intensity Level Indicator (LILI), a multi-function electronic light sensor for electronic…

  4. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    PubMed

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed.

  5. Genome Reduction Uncovers a Large Dispensable Genome and Adaptive Role for Copy Number Variation in Asexually Propagated Solanum tuberosum[OPEN

    PubMed Central

    Hardigan, Michael A.; Crisovan, Emily; Hamilton, John P.; Laimbeer, Parker; Leisner, Courtney P.; Manrique-Carpintero, Norma C.; Newton, Linsey; Pham, Gina M.; Vaillancourt, Brieanne; Zeng, Zixian; Jiang, Jiming

    2016-01-01

    Clonally reproducing plants have the potential to bear a significantly greater mutational load than sexually reproducing species. To investigate this possibility, we examined the breadth of genome-wide structural variation in a panel of monoploid/doubled monoploid clones generated from native populations of diploid potato (Solanum tuberosum), a highly heterozygous asexually propagated plant. As rare instances of purely homozygous clones, they provided an ideal set for determining the degree of structural variation tolerated by this species and deriving its minimal gene complement. Extensive copy number variation (CNV) was uncovered, impacting 219.8 Mb (30.2%) of the potato genome with nearly 30% of genes subject to at least partial duplication or deletion, revealing the highly heterogeneous nature of the potato genome. Dispensable genes (>7000) were associated with limited transcription and/or a recent evolutionary history, with lower deletion frequency observed in genes conserved across angiosperms. Association of CNV with plant adaptation was highlighted by enrichment in gene clusters encoding functions for environmental stress response, with gene duplication playing a part in species-specific expansions of stress-related gene families. This study revealed unique impacts of CNV in a species with asexual reproductive habits and how CNV may drive adaption through evolution of key stress pathways. PMID:26772996

  6. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    PubMed Central

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  7. A joint modeling approach for uncovering associations between gene expression, bioactivity and chemical structure in early drug discovery to guide lead selection and genomic biomarker development.

    PubMed

    Perualila-Tan, Nolen; Kasim, Adetayo; Talloen, Willem; Verbist, Bie; Göhlmann, Hinrich W H; Shkedy, Ziv

    2016-08-01

    The modern drug discovery process involves multiple sources of high-dimensional data. This imposes the challenge of data integration. A typical example is the integration of chemical structure (fingerprint features), phenotypic bioactivity (bioassay read-outs) data for targets of interest, and transcriptomic (gene expression) data in early drug discovery to better understand the chemical and biological mechanisms of candidate drugs, and to facilitate early detection of safety issues prior to later and expensive phases of drug development cycles. In this paper, we discuss a joint model for the transcriptomic and the phenotypic variables conditioned on the chemical structure. This modeling approach can be used to uncover, for a given set of compounds, the association between gene expression and biological activity taking into account the influence of the chemical structure of the compound on both variables. The model allows to detect genes that are associated with the bioactivity data facilitating the identification of potential genomic biomarkers for compounds efficacy. In addition, the effect of every structural feature on both genes and pIC50 and their associations can be simultaneously investigated. Two oncology projects are used to illustrate the applicability and usefulness of the joint model to integrate multi-source high-dimensional information to aid drug discovery. PMID:27269248

  8. RNA-Seq and Gene Network Analysis Uncover Activation of an ABA-Dependent Signalosome During the Cork Oak Root Response to Drought

    PubMed Central

    Magalhães, Alexandre P.; Verde, Nuno; Reis, Francisca; Martins, Inês; Costa, Daniela; Lino-Neto, Teresa; Castro, Pedro H.; Tavares, Rui M.; Azevedo, Herlânder

    2016-01-01

    Quercus suber (cork oak) is a West Mediterranean species of key economic interest, being extensively explored for its ability to generate cork. Like other Mediterranean plants, Q. suber is significantly threatened by climatic changes, imposing the need to quickly understand its physiological and molecular adaptability to drought stress imposition. In the present report, we uncovered the differential transcriptome of Q. suber roots exposed to long-term drought, using an RNA-Seq approach. 454-sequencing reads were used to de novo assemble a reference transcriptome, and mapping of reads allowed the identification of 546 differentially expressed unigenes. These were enriched in both effector genes (e.g., LEA, chaperones, transporters) as well as regulatory genes, including transcription factors (TFs) belonging to various different classes, and genes associated with protein turnover. To further extend functional characterization, we identified the orthologs of differentially expressed unigenes in the model species Arabidopsis thaliana, which then allowed us to perform in silico functional inference, including gene network analysis for protein function, protein subcellular localization and gene co-expression, and in silico enrichment analysis for TFs and cis-elements. Results indicated the existence of extensive transcriptional regulatory events, including activation of ABA-responsive genes and ABF-dependent signaling. We were then able to establish that a core ABA-signaling pathway involving PP2C-SnRK2-ABF components was induced in stressed Q. suber roots, identifying a key mechanism in this species’ response to drought. PMID:26793200

  9. Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing[OPEN

    PubMed Central

    Wang, Yajun; Hamilton, Michael; Ben-Hur, Asa; Reddy, Anireddy S.N.

    2015-01-01

    Plant SR45 and its metazoan ortholog RNPS1 are serine/arginine-rich (SR)-like RNA binding proteins that function in splicing/postsplicing events and regulate diverse processes in eukaryotes. Interactions of SR45 with both RNAs and proteins are crucial for regulating RNA processing. However, in vivo RNA targets of SR45 are currently unclear. Using RNA immunoprecipitation followed by high-throughput sequencing, we identified over 4000 Arabidopsis thaliana RNAs that directly or indirectly associate with SR45, designated as SR45-associated RNAs (SARs). Comprehensive analyses of these SARs revealed several roles for SR45. First, SR45 associates with and regulates the expression of 30% of abscisic acid (ABA) signaling genes at the postsplicing level. Second, although most SARs are derived from intron-containing genes, surprisingly, 340 SARs are derived from intronless genes. Expression analysis of the SARs suggests that SR45 differentially regulates intronless and intron-containing SARs. Finally, we identified four overrepresented RNA motifs in SARs that likely mediate SR45’s recognition of its targets. Therefore, SR45 plays an unexpected role in mRNA processing of intronless genes, and numerous ABA signaling genes are targeted for regulation at the posttranscriptional level. The diverse molecular functions of SR45 uncovered in this study are likely applicable to other species in view of its conservation across eukaryotes. PMID:26603559

  10. Transcriptome-Wide Identification of RNA Targets of Arabidopsis SERINE/ARGININE-RICH45 Uncovers the Unexpected Roles of This RNA Binding Protein in RNA Processing.

    PubMed

    Xing, Denghui; Wang, Yajun; Hamilton, Michael; Ben-Hur, Asa; Reddy, Anireddy S N

    2015-12-01

    Plant SR45 and its metazoan ortholog RNPS1 are serine/arginine-rich (SR)-like RNA binding proteins that function in splicing/postsplicing events and regulate diverse processes in eukaryotes. Interactions of SR45 with both RNAs and proteins are crucial for regulating RNA processing. However, in vivo RNA targets of SR45 are currently unclear. Using RNA immunoprecipitation followed by high-throughput sequencing, we identified over 4000 Arabidopsis thaliana RNAs that directly or indirectly associate with SR45, designated as SR45-associated RNAs (SARs). Comprehensive analyses of these SARs revealed several roles for SR45. First, SR45 associates with and regulates the expression of 30% of abscisic acid (ABA) signaling genes at the postsplicing level. Second, although most SARs are derived from intron-containing genes, surprisingly, 340 SARs are derived from intronless genes. Expression analysis of the SARs suggests that SR45 differentially regulates intronless and intron-containing SARs. Finally, we identified four overrepresented RNA motifs in SARs that likely mediate SR45's recognition of its targets. Therefore, SR45 plays an unexpected role in mRNA processing of intronless genes, and numerous ABA signaling genes are targeted for regulation at the posttranscriptional level. The diverse molecular functions of SR45 uncovered in this study are likely applicable to other species in view of its conservation across eukaryotes. PMID:26603559

  11. Reverse genetic screen for loss-of-function mutations uncovers a frameshifting deletion in the melanophilin gene accountable for a distinctive coat color in Belgian Blue cattle.

    PubMed

    Li, Wanbo; Sartelet, Arnaud; Tamma, Nico; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2016-02-01

    In the course of a reverse genetic screen in the Belgian Blue cattle breed, we uncovered a 10-bp deletion (c.87_96del) in the first coding exon of the melanophilin gene (MLPH), which introduces a premature stop codon (p.Glu32Aspfs*1) in the same exon, truncating 94% of the protein. Recessive damaging mutations in the MLPH gene are well known to cause skin, hair, coat or plumage color dilution phenotypes in numerous species, including human, mice, dog, cat, mink, rabbit, chicken and quail. Large-scale array genotyping undertaken to identify p.Glu32Aspfs*1 homozygous mutant animals revealed a mutation frequency of 5% in the breed and allowed for the identification of 10 homozygous mutants. As expression of a colored coat requires at least one wild-type allele at the co-dominant Roan locus encoded by the KIT ligand gene (KITLG), homozygous mutants for p.Ala227Asp corresponding with the missense mutation were excluded. The six remaining colored calves displayed a distinctive dilution phenotype as anticipated. This new coat color was named 'cool gray'. It is the first damaging mutation in the MLPH gene described in cattle and extends the already long list of species with diluted color due to recessive mutations in MLPH and broadens the color palette of gray in this breed. PMID:26582259

  12. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs).

    PubMed

    Liu, Xiao; Li, Zesong; Su, Zheng; Zhang, Junjie; Li, Honggang; Xie, Jun; Xu, Hanshi; Jiang, Tao; Luo, Liya; Zhang, Ruifang; Zeng, Xiaojing; Xu, Huaiqian; Huang, Yi; Mou, Lisha; Hu, Jingchu; Qian, Weiping; Zeng, Yong; Zhang, Xiuqing; Xiong, Chengliang; Yang, Huanming; Kristiansen, Karsten; Cai, Zhiming; Wang, Jun; Gui, Yaoting

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome. PMID:26907467

  13. AB039. Novel Y-chromosomal microdeletions associated with non-obstructive azoospermia uncovered by high throughput sequencing of sequence-tagged sites (STSs)

    PubMed Central

    Li, Zesong

    2016-01-01

    Y-chromosomal microdeletion (YCM) serves as an important genetic factor in non-obstructive azoospermia (NOA). Multiplex polymerase chain reaction (PCR) is routinely used to detect YCMs by tracing sequence-tagged sites (STSs) in the Y chromosome. Here we introduce a novel methodology in which we sequence 1,787 (post-filtering) STSs distributed across the entire male-specific Y chromosome (MSY) in parallel to uncover known and novel YCMs. We validated this approach with 766 Chinese men with NOA and 683 ethnically matched healthy individuals and detected 481 and 98 STSs that were deleted in the NOA and control group, representing a substantial portion of novel YCMs which significantly influenced the functions of spermatogenic genes. The NOA patients tended to carry more and rarer deletions that were enriched in nearby intragenic regions. Haplogroup O2* was revealed to be a protective lineage for NOA, in which the enrichment of b1/b3 deletion in haplogroup C was also observed. In summary, our work provides a new high-resolution portrait of deletions in the Y chromosome.

  14. RNA-Seq and Gene Network Analysis Uncover Activation of an ABA-Dependent Signalosome During the Cork Oak Root Response to Drought.

    PubMed

    Magalhães, Alexandre P; Verde, Nuno; Reis, Francisca; Martins, Inês; Costa, Daniela; Lino-Neto, Teresa; Castro, Pedro H; Tavares, Rui M; Azevedo, Herlânder

    2015-01-01

    Quercus suber (cork oak) is a West Mediterranean species of key economic interest, being extensively explored for its ability to generate cork. Like other Mediterranean plants, Q. suber is significantly threatened by climatic changes, imposing the need to quickly understand its physiological and molecular adaptability to drought stress imposition. In the present report, we uncovered the differential transcriptome of Q. suber roots exposed to long-term drought, using an RNA-Seq approach. 454-sequencing reads were used to de novo assemble a reference transcriptome, and mapping of reads allowed the identification of 546 differentially expressed unigenes. These were enriched in both effector genes (e.g., LEA, chaperones, transporters) as well as regulatory genes, including transcription factors (TFs) belonging to various different classes, and genes associated with protein turnover. To further extend functional characterization, we identified the orthologs of differentially expressed unigenes in the model species Arabidopsis thaliana, which then allowed us to perform in silico functional inference, including gene network analysis for protein function, protein subcellular localization and gene co-expression, and in silico enrichment analysis for TFs and cis-elements. Results indicated the existence of extensive transcriptional regulatory events, including activation of ABA-responsive genes and ABF-dependent signaling. We were then able to establish that a core ABA-signaling pathway involving PP2C-SnRK2-ABF components was induced in stressed Q. suber roots, identifying a key mechanism in this species' response to drought.

  15. Long non-coding RNA expression profiling in the NCI60 cancer cell line panel using high-throughput RT-qPCR

    PubMed Central

    Mestdagh, Pieter; Lefever, Steve; Volders, Pieter-Jan; Derveaux, Stefaan; Hellemans, Jan; Vandesompele, Jo

    2016-01-01

    Long non-coding RNAs (lncRNAs) form a new class of RNA molecules implicated in various aspects of protein coding gene expression regulation. To study lncRNAs in cancer, we generated expression profiles for 1707 human lncRNAs in the NCI60 cancer cell line panel using a high-throughput nanowell RT-qPCR platform. We describe how qPCR assays were designed and validated and provide processed and normalized expression data for further analysis. Data quality is demonstrated by matching the lncRNA expression profiles with phenotypic and genomic characteristics of the cancer cell lines. This data set can be integrated with publicly available omics and pharmacological data sets to uncover novel associations between lncRNA expression and mRNA expression, miRNA expression, DNA copy number, protein coding gene mutation status or drug response PMID:27377824

  16. Profiles of human milk oligosaccharides and production of some human milk oligosaccharides in transgenic animals.

    PubMed

    Prieto, Pedro Antonio

    2012-05-01

    During the decade of the 1990s and the first years of the current century, our group embarked on a project to study and synthesize human milk oligosaccharides. This report describes 2 unexpected collateral observations from that endeavor. The first observation was the detection and confirmation of 2 rare neutral human milk oligosaccharides profiles that were uncovered while assessing oligosaccharide content in hundreds of samples of human milk. One of these lacked fucosylated structures altogether, and the other lacked the oligosaccharide 3-fucosyllactose [Galβ1-4(Fucα1-3)Glc]. We used glycoconjugate probes to determine whether the unusual profiles were mirrored by fucosylation of milk glycoproteins. The results show that the lack of fucosylated oligosaccharides in these samples corresponds to the absence of equivalent fucosylated motifs in milk glycoproteins. The second finding was a shortened and distinct lactation process in transgenic rabbits expressing the human fucosyltransferase 1. During the first day of lactation, these animals expressed milk that contained both lactose and 2'-fucosylactose, but on the second day, the production of milk was severely diminished, and by the fourth day, no lactose was detected in their milk. Meanwhile, the concentration of fucosylated glycoproteins increased from the onset of lactation through its premature termination. These 2 findings may shed light on the glycobiology of milk and perhaps on mammary gland differentiation.

  17. Transcriptional profiling at whole population and single cell levels reveals somatosensory neuron molecular diversity

    PubMed Central

    Chiu, Isaac M; Barrett, Lee B; Williams, Erika K; Strochlic, David E; Lee, Seungkyu; Weyer, Andy D; Lou, Shan; Bryman, Gregory S; Roberson, David P; Ghasemlou, Nader; Piccoli, Cara; Ahat, Ezgi; Wang, Victor; Cobos, Enrique J; Stucky, Cheryl L; Ma, Qiufu; Liberles, Stephen D; Woolf, Clifford J

    2014-01-01

    The somatosensory nervous system is critical for the organism's ability to respond to mechanical, thermal, and nociceptive stimuli. Somatosensory neurons are functionally and anatomically diverse but their molecular profiles are not well-defined. Here, we used transcriptional profiling to analyze the detailed molecular signatures of dorsal root ganglion (DRG) sensory neurons. We used two mouse reporter lines and surface IB4 labeling to purify three major non-overlapping classes of neurons: 1) IB4+SNS-Cre/TdTomato+, 2) IB4−SNS-Cre/TdTomato+, and 3) Parv-Cre/TdTomato+ cells, encompassing the majority of nociceptive, pruriceptive, and proprioceptive neurons. These neurons displayed distinct expression patterns of ion channels, transcription factors, and GPCRs. Highly parallel qRT-PCR analysis of 334 single neurons selected by membership of the three populations demonstrated further diversity, with unbiased clustering analysis identifying six distinct subgroups. These data significantly increase our knowledge of the molecular identities of known DRG populations and uncover potentially novel subsets, revealing the complexity and diversity of those neurons underlying somatosensation. DOI: http://dx.doi.org/10.7554/eLife.04660.001 PMID:25525749

  18. Non-small cell lung cancer is characterized by dramatic changes in phospholipid profiles.

    PubMed

    Marien, Eyra; Meister, Michael; Muley, Thomas; Fieuws, Steffen; Bordel, Sergio; Derua, Rita; Spraggins, Jeffrey; Van de Plas, Raf; Dehairs, Jonas; Wouters, Jens; Bagadi, Muralidhararao; Dienemann, Hendrik; Thomas, Michael; Schnabel, Philipp A; Caprioli, Richard M; Waelkens, Etienne; Swinnen, Johannes V

    2015-10-01

    Non-small cell lung cancer (NSCLC) is the leading cause of cancer death globally. To develop better diagnostics and more effective treatments, research in the past decades has focused on identification of molecular changes in the genome, transcriptome, proteome, and more recently also the metabolome. Phospholipids, which nevertheless play a central role in cell functioning, remain poorly explored. Here, using a mass spectrometry (MS)-based phospholipidomics approach, we profiled 179 phospholipid species in malignant and matched non-malignant lung tissue of 162 NSCLC patients (73 in a discovery cohort and 89 in a validation cohort). We identified 91 phospholipid species that were differentially expressed in cancer versus non-malignant tissues. Most prominent changes included a decrease in sphingomyelins (SMs) and an increase in specific phosphatidylinositols (PIs). Also a decrease in multiple phosphatidylserines (PSs) was observed, along with an increase in several phosphatidylethanolamine (PE) and phosphatidylcholine (PC) species, particularly those with 40 or 42 carbon atoms in both fatty acyl chains together. 2D-imaging MS of the most differentially expressed phospholipids confirmed their differential abundance in cancer cells. We identified lipid markers that can discriminate tumor versus normal tissue and different NSCLC subtypes with an AUC (area under the ROC curve) of 0.999 and 0.885, respectively. In conclusion, using both shotgun and 2D-imaging lipidomics analysis, we uncovered a hitherto unrecognized alteration in phospholipid profiles in NSCLC. These changes may have important biological implications and may have significant potential for biomarker development. PMID:25784292

  19. Molecular cloning, structural and expression profiling of DlRan genes during somatic embryogenesis in Dimocarpus longan Lour.

    PubMed

    Fang, Zhizhen; Lai, Chengchun; Zhang, Yaling; Lai, Zhongxiong

    2016-01-01

    To clone and examine expression profiles of DlRan genes during somatic embryogenesis in Dimocarpus longan Lour. Thirty cDNA sequences and two genomic sequences encoding DlRan proteins were isolated from longan embryogenic cultures. Structural analysis of DlRan genes revealed that the longan Ran gene family is more expanded than that of Arabidopsis. Expression analysis of DlRan genes during somatic embryogenesis uncovered a high abundance of DlRan genes in early embryogenic cultures and heart- and torpedo-shaped embryos. The expression of DlRan genes in embryogenic calli was affected by exogenous 2,4-dichlorophenoxyacetic acid treatment. DlRan is involved in 2,4-D induced somatic embryogenesis and development of somatic embryos in longan. PMID:27026877

  20. Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle

    PubMed Central

    Zaccaria, Marco; Ludovici, Matteo; Sanzani, Simona Marianna; Ippolito, Antonio; Aiese Cigliano, Riccardo; Sanseverino, Walter; Scarpari, Marzia; Scala, Valeria; Fanelli, Corrado; Reverberi, Massimo

    2015-01-01

    Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B1, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile) to transcriptional analysis (RNA-seq). There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies. PMID:26512693

  1. Vector wind profile gust model

    NASA Technical Reports Server (NTRS)

    Adelfang, S. I.

    1979-01-01

    Work towards establishing a vector wind profile gust model for the Space Transportation System flight operations and trade studies is reported. To date, all the statistical and computational techniques required were established and partially implemented. An analysis of wind profile gust at Cape Kennedy within the theoretical framework is presented. The variability of theoretical and observed gust magnitude with filter type, altitude, and season is described. Various examples are presented which illustrate agreement between theoretical and observed gust percentiles. The preliminary analysis of the gust data indicates a strong variability with altitude, season, and wavelength regime. An extension of the analyses to include conditional distributions of gust magnitude given gust length, distributions of gust modulus, and phase differences between gust components has begun.

  2. Transcriptome sequencing and profiling of expressed genes in phloem and xylem of ramie (Boehmeria nivea L. Gaud).

    PubMed

    Chen, Jianrong; Liu, Fang; Tang, Yinghong; Yuan, Youmei; Guo, Qingquan

    2014-01-01

    Ramie (Boehmeria nivea L. Gaud) is a highly versatile herbaceous plant which is widely cropped in southern China. The success of this herbaceous plant relies on wide use in modern industry. Understanding the profiling of expressed genes in phloem and xylem of ramie is crucial for improving its industrial performance. Herein, we uncover the transcriptome profile in phloem and xylem in present study. Using Illumina paired-end sequencing technology, 57 million high quality reads were generated. De novo assembly yielded 87,144 unigenes with an average length of 635 bp. By sequence similarity searching for public databases, a total of 32,541 (41.77%) unigenes were annotated for their function. Among these genes, 57,873 (66.4%) and 28,678 (32.9%) unigenes were assigned to categories of Gene Ontology and Orthologous Groups database, respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG), 18,331 (21.0%) unigenes were mapped to 125 pathways. The metabolic pathways were assigned the most unigene (4,793, 26.2%). Furthermore, Pol II and Pol III subunits as well as the genes of Galactose metabolism pathway had higher expression in phloem compared to xylem. In addition, fatty acid metabolism pathway genes showed more abundant in xylem than phloem. These results suggest that high activities of RNA synthesis and Galactose metabolism pathway promises fiber synthesis in phloem. The present study is the initial exploration to uncover the fiber biosynthesis difference between phloem and xylem in ramie through the analysis of deep sequencing data.

  3. Wind profiler signal detection improvements

    NASA Technical Reports Server (NTRS)

    Hart, G. F.; Divis, Dale H.

    1992-01-01

    Research is described on potential improvements to the software used with the NASA 49.25 MHz wind profiler located at Kennedy Space Center. In particular, the analysis and results are provided of a study to (1) identify preferred mathematical techniques for the detection of atmospheric signals that provide wind velocities which are obscured by natural and man-made sources, and (2) to analyze one or more preferred techniques to demonstrate proof of the capability to improve the detection of wind velocities.

  4. Profile of Your Geriatric Patient

    PubMed Central

    Longhurst, Mark F.; Slade, Debra

    1990-01-01

    The family doctor cares for many geriatric patients. Many of these patients enter the family practice for the first time, having either recently moved to the area or to a nearby long-term care facility. Obtaining a meaningful patient profile is essential to the physicians' care, allowing future medical decisions to be made in the best interest of that person. Patients' beliefs motivate their functioning in a system. Any system has its own history, structure, and function. PMID:21234029

  5. Uncovering common bacterial skin infections.

    PubMed

    Napierkowski, Daria

    2013-03-10

    The four most common bacterial skin infections are impetigo, erysipelas, cellulitis, and folliculitis. This article summarizes current information about the etiology, clinical presentation, diagnosis, prevention, treatment, and implications for primary care practice needed to effectively diagnose and treat common bacterial skin infections. PMID:23361375

  6. Shell Games: Uncovering Periodic Properties.

    ERIC Educational Resources Information Center

    Lamb, William G.

    1983-01-01

    Describes activities (demonstrations/experiments) used to introduce history of periodic properties--without electrons, orbitals, filling shells, or any conception of atoms beyond Dalton's model. Activities supplement first chapter in a currently available chemistry text. Indicates potential danger of experiments if proper safety precautions are…

  7. Addiction Science: Uncovering Neurobiological Complexity

    PubMed Central

    Volkow, N. D.; Baler, R. D.

    2013-01-01

    Until very recently addiction-research was limited by existing tools and strategies that were inadequate for studying the inherent complexity at each of the different phenomenological levels. However, powerful new tools (e.g., optogenetics and designer drug receptors) and high throughput protocols are starting to give researchers the potential to systematically interrogate “all” genes, epigenetic marks, and neuronal circuits. These advances, combined with imaging technologies (both for preclinical and clinical studies) and a paradigm shift towards open access have spurred an unlimited growth of datasets transforming the way we investigate the neurobiology of substance use disorders (SUD) and the factors that modulate risk and resilience. PMID:23688927

  8. Uncovering Students' Perceptions of Rubrics

    ERIC Educational Resources Information Center

    Saam, Julie; Sorgman, Margo; Calhoon, Sharon K.

    2007-01-01

    Research regarding rubrics in K-12 classrooms and in higher education has focused on teachers' perceptions and use of them. Rubrics have been found to objectify subjective assignments, ensure accountability, and improve student understanding of teacher expectations (Andrade, 2000; Hall & Salmon, 2003; Walvoord & Anderson, 1998). This study focuses…

  9. Uncovering the Neoproterozoic carbon cycle.

    PubMed

    Johnston, D T; Macdonald, F A; Gill, B C; Hoffman, P F; Schrag, D P

    2012-03-15

    Interpretations of major climatic and biological events in Earth history are, in large part, derived from the stable carbon isotope records of carbonate rocks and sedimentary organic matter. Neoproterozoic carbonate records contain unusual and large negative isotopic anomalies within long periods (10-100 million years) characterized by δ(13)C in carbonate (δ(13)C(carb)) enriched to more than +5 per mil. Classically, δ(13)C(carb) is interpreted as a metric of the relative fraction of carbon buried as organic matter in marine sediments, which can be linked to oxygen accumulation through the stoichiometry of primary production. If a change in the isotopic composition of marine dissolved inorganic carbon is responsible for these excursions, it is expected that records of δ(13)C(carb) and δ(13)C in organic carbon (δ(13)C(org)) will covary, offset by the fractionation imparted by primary production. The documentation of several Neoproterozoic δ(13)C(carb) excursions that are decoupled from δ(13)C(org), however, indicates that other mechanisms may account for these excursions. Here we present δ(13)C data from Mongolia, northwest Canada and Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon isotope anomalies, and use these data in a new quantitative mixing model to examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate and organic carbon isotope data from Mongolia and Canada are tightly coupled through multiple δ(13)C(carb) excursions, quantitatively ruling out previously suggested alternative explanations, such as diagenesis or the presence and terminal oxidation of a large marine dissolved organic carbon reservoir. Our data from Namibia, which do not record isotopic covariance, can be explained by simple mixing with a detrital flux of organic matter. We thus interpret δ(13)C(carb) anomalies as recording a primary perturbation to the surface carbon cycle. This interpretation requires the revisiting of models linking drastic isotope excursions to deep ocean oxygenation and the opening of environments capable of supporting animals. PMID:22388817

  10. ESA uncovers Geminga's `hot spot'

    NASA Astrophysics Data System (ADS)

    2004-07-01

    16 July 2004 Astronomers using ESA’s X-ray observatory XMM-Newton have detected a small, bright ‘hot spot’ on the surface of the neutron star called Geminga, 500 light-years away. The hot spot is the size of a football field and is caused by the same mechanism producing Geminga’s X-ray tails. This discovery identifies the missing link between the X-ray and gamma-ray emission from Geminga. hi-res Size hi-res: 1284 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot This figure shows the effects of charged particles accelerated in the magnetosphere of Geminga. Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (in red) hit the star’s magnetic poles like in an ‘own goal’. Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degrees hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. An animated version of the entire sequence can be found at: Click here for animated GIF [low resolution, animated GIF, 5536 KB] Click here for AVI [high resolution, AVI with DIVX compression, 19128 KB] hi-res Size hi-res: 371 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (a) Panel (a) shows an image taken with the EPIC instrument on board the XMM-Newton observatory. The bright tails, made of particles kicked out by Geminga’s strong magnetic field, trail the neutron star as it moves about in space. hi-res Size hi-res: 377 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (b) Panel (b) shows how electrically charged particles interact with Geminga’s magnetic field. For example, if electrons (blue) are kicked out by the star, positrons (red) hit the star’s magnetic poles like in an ‘own goal’. hi-res Size hi-res: 435 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (c) Panel (c) illustrates the size of Geminga’s magnetic field (blue) compared to that of the star itself at the centre (purple). The magnetic field is tilted with respect to Geminga’s rotation axis (red). hi-res Size hi-res: 121 kb Credits: ESA, P. Caraveo (IASF, Milan) Geminga's hot spot, panel (d) Panel (d) shows the magnetic poles of Geminga, where charged particles hit the surface of the star, creating a two-million degree hot spot, a region much hotter than the surroundings. As the star spins on its rotation axis, the hot spot comes into view and then disappears, causing the periodic colour change seen by XMM-Newton. Neutron stars are the smallest kind of stars known. They are the super-dense remnants of massive stars that died in cataclysmic explosions called supernovae. They have been thrown through space like cannonballs and set spinning at a furious rate, with magnetic fields hundreds of billions of times stronger than Earth’s. In the case of Geminga, this cannonball contains one and a half times the mass of the Sun, squeezed into a sphere just 20 kilometres across and spinning four times every second. A cloud bustling with electrically charged particles surrounds Geminga. These particles are shepherded by its magnetic and electric fields. ESA’s XMM-Newton observatory had already discovered that some of these particles are ejected into space, forming tails that stream behind the neutron star as it hurtles along. Scientists did not know whether Geminga’s tails are formed by electrons or by their twin particles with an opposite electrical charge, called positrons. Nevertheless, they expected that, if for instance electrons are kicked into space, then the positrons should be funnelled down towards the neutron star itself, like in an ‘own goal’. Where these particles strike the surface of the star, they ought to create a hot spot, a region considerably hotter than the surroundings. An international team of astronomers, lead by Patrizia Caraveo, IASF-CNR, Italy, has now reported the detection of such a hot spot on Geminga using ESA’s XMM-Newton observatory. With a temperature of about two million degrees, this hot spot is considerably hotter than the one half million degrees of the surrounding surface. According to this new work, Geminga’s hot spot is just 60 metres in radius. "This hot spot is the size of a football field," said Caraveo, "and is the smallest object ever detected outside of our Solar System." Details of this size can presently be measured only on the Moon and Mars and, even then, only from a spacecraft in orbit around them. The presence of a hot spot was suspected in the late 1990s but only now can we see it ‘live’, emitting X-rays as Geminga rotates, thanks to the superior sensitivity of ESA’s X-ray observatory, XMM-Newton. The team used the European Photon Imaging Cameras (EPIC) to conduct a study of Geminga, lasting about 28 consecutive hours and recording the arrival time and energy of every X-ray photon that Geminga emitted within XMM-Newton’s grasp. "In total, this amounted to 76 850 X-ray counts - twice as many as have been collected by all previous observations of Geminga, since the time of the Roman Empire," said Caraveo. Knowing the rotation rate of Geminga and the time of each photon’s arrival meant that astronomers could identify which photons were coming from each region of the neutron star as it rotates. When they compared photons coming from different regions of the star, they found that the ‘colour’ of the X-rays, which corresponds to their energy, changed as Geminga rotated. In particular, they could clearly see a distinct colour change when the hot spot came into view and then disappeared behind the star. This research closes the gap between the X-ray and gamma-ray emission from neutron stars. XMM-Newton has shown that they both can originate through the same physical mechanism, namely the acceleration of charged particles in the magnetosphere of these degenerate stars. "XMM-Newton’s Geminga observation has been particularly fruitful," said Norbert Schartel, ESA’s Project Scientist for XMM-Newton. "Last year, it yielded the discovery of the source tails and now it has found its rotating hot spot." Caraveo is already applying this new technique to other pulsating neutron stars observed by XMM-Newton looking for hot spots. This research represents an important new tool for understanding the physics of neutron stars. Notes for editors The original paper appeared on 16 July 2004, in Science magazine, under the title 'Phase-resolved spectroscopy of Geminga shows rotating hotspot(s)'. Besides P. Caraveo, the author list includes A. De Luca, S. Mereghetti, A. Pellizzoni and G. Bignami. During the search to track down this elusive celestial object, a co-author on the paper, Giovanni Bignami, named it Geminga almost 30 years ago. He was Principal Investigator of XMM-Newton's EPIC camera from 1987 to 1997 and is now Director of the Centre d'Etude Spatiale des Rayonnements (CESR, Toulouse). Geminga was first glimpsed as a mysterious source of gamma rays, coming from somewhere in the constellation Gemini by NASA's SAS-2 spacecraft in 1973. While searching to pin down its exact location and nature, Bignami named it Geminga because it was a ‘Gemini gamma-ray source’. As an astronomer in Milan, Italy, he was also aware that in his native dialect ‘gh'èminga’ means ‘it is not there’, which he found amusing. It was also remarkably apt, for it was not until 1993 that he succeeded in finally ‘seeing’ and therefore pinpointing Geminga, using optical wavelengths. While it lacked radio emissions, the pulsating X-ray and gamma-ray emissions meant Geminga could only belong to a new class of objects, the radio-quiet neutron stars. The original announcement of the discovery of Geminga’s tails, issued on 25 July 2003, can be found at: http://www.esa.int/esaSC/Pr_11_2003_s_en.html More about XMM-Newton XMM-Newton can detect more X-ray sources than any previous observatory and is helping to solve many cosmic mysteries of the violent Universe, from black holes to the formation of galaxies. It was launched on 10 December 1999, using an Ariane-5 rocket from French Guiana. It is expected to return data for a decade. XMM-Newton’s high-tech design uses over 170 wafer-thin cylindrical mirrors spread over three telescopes. Its orbit takes it almost a third of the way to the Moon, so that astronomers can enjoy long, uninterrupted views of celestial objects. More information on XMM-Newton can be found at: http://www.esa.int/esaSC/SEMM8IGHZTD_1_spk.html

  11. Uncovering Settler Grammars in Curriculum

    ERIC Educational Resources Information Center

    Calderon, Dolores

    2014-01-01

    In this article, I focus on making settler colonialism explicit in education. I turn to social studies curriculum as a clear example of how settler colonialism is deeply embedded in educational knowledge production in the United States that is rooted in a dialectic of Indigenous presence and absence. I argue that the United States, and the…

  12. Uncovering Blue Diffuse Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    James, Bethan; Koposov, Sergey; Stark, Daniel; Belokurov, Vasily; Pettini, Max; Olszewski, Edward W.

    2015-01-01

    Extremely metal-poor galaxies (XMPs) and the star-formation within their chemically pristine environments are fundamental to our understanding of the galaxy formation process at early times. However, traditional emission-line surveys detect only the brightest metal-poor galaxies where star-formation occurs in compact, starbursting environments, and thereby give us only a partial view of the dwarf galaxy population. To avoid such biases, we have developed a new search algorithm based on the morphological, rather then spectral, properties of XMPs and have applied to the Sloan Digital Sky Survey database of images. Using this novel approach, we have discovered ~100 previously undetected, faint blue galaxies, each with isolated HII regions embedded in a diffuse continuum. In this talk I will present the first results from follow-up optical spectroscopy of this sample, which reveals these blue diffuse dwarfs (BDDs) to be young, very metal-poor and actively forming stars despite their intrinsically low luminosities. I will present evidence showing that BDDs appear to bridge the gap between quiescent dwarf irregular (dIrr) galaxies and blue compact galaxies (BCDs) and as such offer an ideal opportunity to assess how star-formation occurs in more `normal' metal-poor systems.

  13. Uncovering the Neoproterozoic carbon cycle.

    PubMed

    Johnston, D T; Macdonald, F A; Gill, B C; Hoffman, P F; Schrag, D P

    2012-03-15

    Interpretations of major climatic and biological events in Earth history are, in large part, derived from the stable carbon isotope records of carbonate rocks and sedimentary organic matter. Neoproterozoic carbonate records contain unusual and large negative isotopic anomalies within long periods (10-100 million years) characterized by δ(13)C in carbonate (δ(13)C(carb)) enriched to more than +5 per mil. Classically, δ(13)C(carb) is interpreted as a metric of the relative fraction of carbon buried as organic matter in marine sediments, which can be linked to oxygen accumulation through the stoichiometry of primary production. If a change in the isotopic composition of marine dissolved inorganic carbon is responsible for these excursions, it is expected that records of δ(13)C(carb) and δ(13)C in organic carbon (δ(13)C(org)) will covary, offset by the fractionation imparted by primary production. The documentation of several Neoproterozoic δ(13)C(carb) excursions that are decoupled from δ(13)C(org), however, indicates that other mechanisms may account for these excursions. Here we present δ(13)C data from Mongolia, northwest Canada and Namibia that capture multiple large-amplitude (over 10 per mil) negative carbon isotope anomalies, and use these data in a new quantitative mixing model to examine the behaviour of the Neoproterozoic carbon cycle. We find that carbonate and organic carbon isotope data from Mongolia and Canada are tightly coupled through multiple δ(13)C(carb) excursions, quantitatively ruling out previously suggested alternative explanations, such as diagenesis or the presence and terminal oxidation of a large marine dissolved organic carbon reservoir. Our data from Namibia, which do not record isotopic covariance, can be explained by simple mixing with a detrital flux of organic matter. We thus interpret δ(13)C(carb) anomalies as recording a primary perturbation to the surface carbon cycle. This interpretation requires the revisiting of models linking drastic isotope excursions to deep ocean oxygenation and the opening of environments capable of supporting animals.

  14. State coal profiles, January 1994

    SciTech Connect

    Not Available

    1994-02-02

    The purpose of State Coal Profiles is to provide basic information about the deposits, production, and use of coal in each of the 27 States with coal production in 1992. Although considerable information on coal has been published on a national level, there is a lack of a uniform overview for the individual States. This report is intended to help fill that gap and also to serve as a framework for more detailed studies. While focusing on coal output, State Coal Profiles shows that the coal-producing States are major users of coal, together accounting for about three-fourths of total US coal consumption in 1992. Each coal-producing State is profiled with a description of its coal deposits and a discussion of the development of its coal industry. Estimates of coal reserves in 1992 are categorized by mining method and sulfur content. Trends, patterns, and other information concerning production, number of mines, miners, productivity, mine price of coal, disposition, and consumption of coal are detailed in statistical tables for selected years from 1980 through 1992. In addition, coal`s contribution to the State`s estimated total energy consumption is given for 1991, the latest year for which data are available. A US summary of all data is provided for comparing individual States with the Nation as a whole. Sources of information are given at the end of the tables.

  15. Developing the CUAHSI Metadata Profile

    NASA Astrophysics Data System (ADS)

    Piasecki, M.; Bermudez, L.; Islam, S.; Beran, B.

    2004-12-01

    The Hydrologic Information System (HIS), of the Consortium of Universities for the Advancement of Hydrologic Science Inc., (CUAHSI), has as one of its goals to improve access to large volume, high quality, and heterogeneous hydrologic data sets. This will be attained in part by adopting a community metadata profile to achieve consistent descriptions that will facilitate data discovery. However, common standards are quite general in nature and typically lack domain specific vocabularies, complicating the adoption of standards for specific communities. We will show and demonstrate the problems encountered in the process of adopting ISO standards to create a CUAHSI metadata profile. The final schema is expressed in a simple metadata format, Metadata Template File (MTF), to leverage metadata annotations/viewer tools already developed by the San Diego Super Computer Center. The steps performed to create an MTF starting from ISO 19115:2003 are the following: 1) creation of ontologies using the Web Ontology Language (OWL) for ISO:19115 2003 and related ISO/TC 211 documents; 2) conceptualization in OWL of related hydrologic vocabularies such as NASA's Global Change Master Directory and units from the Hydrologic Handbook; 3) definition of CUAHSI profile by importing and extending the previous ontologies; 4) explicit creation of CUAHSI core set 5) export of the core set to MTF); 6) definition of metadata blocks for arbitrary digital objects (e.g. time series vs static-spatial data) using ISO's methodology for feature cataloguing; and 7) export of metadata blocks to MTF.

  16. Testing Gravity using Void Profiles

    NASA Astrophysics Data System (ADS)

    Cai, Yan-Chuan; Padilla, Nelson; Li, Baojiu

    2016-10-01

    We investigate void properties in f(R) models using N-body simulations, focusing on their differences from General Relativity (GR) and their detectability. In the Hu-Sawicki f(R) modified gravity (MG) models, the halo number density profiles of voids are not distinguishable from GR. In contrast, the same f(R) voids are more empty of dark matter, and their profiles are steeper. This can in principle be observed by weak gravitational lensing of voids, for which the combination of a spectroscopic redshift and a lensing photometric redshift survey over the same sky is required. Neglecting the lensing shape noise, the f(R) model parameter amplitudes fR0=10-5 and 10-4 may be distinguished from GR using the lensing tangential shear signal around voids by 4 and 8 σ for a volume of 1 (Gpc/h)3. The line-of-sight projection of large-scale structure is the main systematics that limits the significance of this signal for the near future wide angle and deep lensing surveys. For this reason, it is challenging to distinguish fR0=10-6 from GR. We expect that this can be overcome with larger volume. The halo void abundance being smaller and the steepening of dark matter void profiles in f(R) models are unique features that can be combined to break the degeneracy between fR0 and σ8.

  17. Kinetic Profiles in NSTX Plasmas

    SciTech Connect

    R.E. Bell; B.P. LeBlanc; C. Bourdelle; D.R. Ernst; E.D. Fredrickson; D.A. Gates; J.C. Hosea; D.W. Johnson; S.M. Kaye; R. Maingi; S. Medley; J.E. Menard; D. Mueller; M. Ono; F. Paoletti; M. Peng; S.A. Sabbagh; D. Stutman; D.W. Swain; E.J. Synakowski; and J.R. Wilson

    2001-07-10

    The National Spherical Torus Experiment (NSTX) is a low aspect ratio (R/a approximately 1.3) device with auxiliary heating from neutral-beam injection (NBI) and high-harmonic fast-wave heating (HHFW). Typical NSTX parameters are R(subscript ''0'') = 85 cm, a = 67 cm, I(subscript ''p'') = 0.7-1.4 MA, B(subscript ''phi'') = 0.25-0.45 T. Three co-directed deuterium neutral-beam sources have injected P(subscript ''NB'') less than or equal to 4.7 MW. HHFW plasmas typically have delivered P(subscript ''RF'') less than or equal to 3 MW. Important to the understanding of NSTX confinement are the new kinetic profile diagnostics: a multi-pulse Thomson scattering system (MPTS) and a charge-exchange recombination spectroscopy (CHERS) system. The MPTS diagnostic currently measures electron density and temperature profiles at 30 Hz at ten spatial locations. The CHERS system has recently become available to measure carbon ion temperature and toroidal flow at 17 radial positions spanning the outer half of the minor radius with 20 msec time resolution during NBI. Experiments conducted during the last year have produced a wide range of kinetic profiles in NSTX. Some interesting examples are presented below.

  18. Origins of the physical profile.

    PubMed

    Marble, Sanders

    2013-08-01

    This article examines how the U.S. Army came to adopt the physical profile. In 1945, the Army adopted the physical profile system that has, with some changes, survived to this day. Although the profile system does not always work smoothly, it replaced a system that was failing completely to deliver physically fit men to combat units. The World War II problems were the outgrowth of two World War I systems that had been adopted to speed mobilization by (1) accepting physically substandard men and (2) matching men to a noncombat job by their skills. By simply identifying a soldier as "General Service" or "Limited Service" it did not provide enough information about his limitations. In addition, the Army used an intelligence test to grade manpower, but because it lacked information on a man's physical abilities/limitations, that data were misused to allot manpower. These policies interacted with a societal disdain for the "handicapped" and "substandard" and made it hard to use Limited Service men. Adding detail to the information on physical abilities was the Army's solution. PMID:23929050

  19. The line profile variable B stars

    NASA Technical Reports Server (NTRS)

    Smith, M. A.

    1980-01-01

    The observational status of the line profile variable B stars is summarized. The following areas are discussed: recent history; evolutionary status; line profile variations; line strength variations; and photometric variations.

  20. Profiling users in the UNIX os environment

    SciTech Connect

    Dao, V N P; Vemuri, R; Templeton, S J

    2000-09-29

    This paper presents results obtained by using a method of profiling a user based on the login host, the login time, the command set, and the command set execution time of the profiled user. It is assumed that the user is logging onto a UNIX host on a computer network. The paper concentrates on two areas: short-term and long-term profiling. In short-term profiling the focus is on profiling the user at a given session where user characteristics do not change much. In long-term profiling, the duration of observation is over a much longer period of time. The latter is more challenging because of a phenomenon called concept or profile drift. Profile drift occurs when a user logs onto a host for an extended period of time (over several sessions).