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Sample records for elements flanking human

  1. Interaction of HIF and USF signaling pathways in human genes flanked by hypoxia-response elements and E-box palindromes.

    PubMed

    Hu, Junmin; Stiehl, Daniel P; Setzer, Claudia; Wichmann, Daniela; Shinde, Dheeraj A; Rehrauer, Hubert; Hradecky, Pavel; Gassmann, Max; Gorr, Thomas A

    2011-11-01

    Rampant activity of the hypoxia-inducible factor (HIF)-1 in cancer is frequently associated with the malignant progression into a harder-to-treat, increasingly aggressive phenotype. Clearly, anti-HIF strategies in cancer cells are of considerable clinical interest. One way to fine-tune, or inhibit, HIF's transcriptional outflow independently of hydroxylase activities could be through competing transcription factors. A CACGTG-binding activity in human hepatoma cells was previously found to restrict HIF's access to hypoxia response cis-elements (HRE) in a Daphnia globin gene promoter construct (phb2). The CACGTG factor, and its impact on hypoxia-responsive human genes, was analyzed in this study by genome-wide computational scans as well as gene-specific quantitative PCR, reporter and DNA-binding assays in hepatoma (Hep3B), cervical carcinoma (HeLa), and breast carcinoma (MCF7) cells. Among six basic helix-loop-helix transcription factors known to target CACGTG palindromes, we identified upstream stimulatory factor (USF)-1/2 as predominant phb2 CACGTG constituents in Hep3B, HeLa, and MCF7 cells. Human genes with adjacent or overlapping HRE and CACGTG motifs included with lactate dehydrogenase A (LDHA) and Bcl-2/E1B 19 kDa interacting protein 3 (BNIP3) hypoxia-induced HIF-1 targets. Parallel recruitment of HIF-1α and USF1/2a to the respective promoter chromatin was verified for all cell lines investigated. Mutual complementing (LDHA) or moderating (BNIP3) cross-talk was seen upon overexpression or silencing of HIF-1α and USF1/2a. Distinct (LDHA) or overlapping (BNIP3) promoter-binding sites for HIF-1 and USFs were subsequently characterized. We propose that, depending on abundance or activity of its protein constituents, O(2)-independent USF signaling can function to fine-tune or interfere with HIF-mediated transcription in cancer cells. PMID:21984181

  2. Regions flanking exon 1 regulate constitutive expression of the human antithrombin gene.

    PubMed

    Fernandez-Rachubinski, F A; Weiner, J H; Blajchman, M A

    1996-11-15

    We have identified cis-acting elements and trans-acting factors that regulate constitutive expression of the human antithrombin gene. The activity of the sequences flanking the first exon of the gene was investigated using a luciferase-based reporter assay in transiently transfected HepG2, COS1, BSC40, and HeLa cells. Deletion analysis allowed the mapping of two elements able to promote antithrombin gene transcription in HepG2 and COS1 cells. The first element is located upstream of the first exon (-150/+68 nucleotides). The second element is in the first intervening sequence (+300/+700 nucleotides) and functions in an orientation opposite to that of the first. Footprint analysis showed three protected areas in the 5' upstream element at -92/-68 (element A), -14/+37 (element B), and -126/-100 nucleotides (element C). These elements acted as enhancers in luciferase reporter assays. Gel retardation analysis demonstrated that two liver-enriched transcription factors, hepatocyte nuclear factor 4 (HNF4) and CCAAT enhancer-binding protein (C/EBPa), bound to the 5' upstream element. HNF4 bound to elements A and C, whereas C/EBPa bound to element B. Element A also interacted with the ubiquitous nuclear hormone receptors chicken ovalbumin upstream promoter transcription factor 1 (COUP-TF1), thyroid hormone receptor alpha (TRalpha), peroxisome proliferator-activated receptor alpha(PPARalpha), and retinoid X receptor alpha (RXRalpha). In HepG2 and BSC40 cells, HNF4, C/EBPalpha, and RXRalpha activated luciferase expression from a reporter construct containing the 5'-upstream minimal antithrombin gene promoter, while COUP-TF1, TRalpha, and HNF3 (alpha or beta) repressed such expression. Our results show that constitutive expression of the human antithrombin gene depends in part upon the interplay of these transcription factors and suggest that signaling pathways regulated by these factors can modulate antithrombin gene transcription. PMID:8910619

  3. Oestrogens Downregulate Tissue Factor Pathway Inhibitor through Oestrogen Response Elements in the 5'-Flanking Region.

    PubMed

    Ali, Huda Omar; Stavik, Benedicte; Myklebust, Christiane Filion; Andersen, Elisabeth; Dahm, Anders E A; Iversen, Nina; Sandset, Per Morten; Skretting, Grethe

    2016-01-01

    Oestrogens influence the pathology and development of hormone-sensitive breast cancers. Tissue factor pathway inhibitor (TFPI) has been shown to be associated with breast cancer pathogenesis. Recently, we found TFPI mRNA levels to be significantly reduced by oestrogens in a breast cancer cell line (MCF7), a process mediated through the oestrogen receptor alpha (ERα). The aim of the present study was to investigate the mechanism(s) by which oestrogens may regulate TFPI at the transcriptional level. The TFPI 5'-flanking region contains three oestrogen response element (ERE) half-sites at positions -845, -769 and -50. Constructs containing the wild type or mutated ERE half-sites of the TFPI 5'-flanking region were generated in a luciferase reporter gene vector and transiently co-transfected with an ERα expression vector into HEK293 cells and subsequently treated with oestrogens. We found that luciferase activity was significantly downregulated after oestrogen stimulation in cells transfected with the wild type construct, an effect that was abolished by mutating either ERE half-sites. Electrophoretic mobility shift assay suggested direct and specific interaction of ERα with the ERE half-sites in the TFPI 5'-flanking region. Chromatin immunoprecipitation showed that ERα was recruited to the region -899 to -578 of the TFPI 5'-flanking region in vivo, where the ERE half-sites -845 and -769 are located. Our results indicate that ERα can interact with all three ERE half-sites in the TFPI 5'-flanking region and thus participate in the repression of oestrogen mediated TFPI transcription in breast cancer cells. PMID:26999742

  4. Characterization of the 5'-flanking region of the gene for the alpha chain of human fibrinogen.

    PubMed

    Hu, C H; Harris, J E; Davie, E W; Chung, D W

    1995-11-24

    The 5'-flanking region of the gene coding for the alpha chain of human fibrinogen was isolated, sequenced, and characterized. The principal site of transcription initiation was determined by primer extension analysis and the RNase protection assay and shown to be at an adenine residue located 55 nucleotides upstream from the initiator methionine codon, or 13,399 nucleotides down-stream from the polyadenylation site of the gene coding for the gamma chain. Transient expression of constructs containing sequentially deleted 5'-flanking sequences of the alpha chain gene fused to the chloramphenicol acetyltransferase reporter gene showed that the promoter was liver-specific and inducible by interleukin 6 (IL-6). The shortest DNA fragment with significant promoter activity and full response to IL-6 stimulation encompassed the region from -217 to +1 base pairs (bp). Although six potential IL-6 responsive sequences homologous to the type II IL-6 responsive element were present, a single sequence of CTGGGA localized from -122 to -127 bp was shown to be a functional element in IL-6 induction. A hepatocyte nuclear factor 1 (HNF-1) binding site, present from -47 to -59 bp, in combination with other upstream elements, was essential for liver-specific expression of the gene. A functional CCAAT/enhancer binding protein site (C/EBP, -134 to -142 bp) was also identified within 217 bp from the transcription initiation site. An additional positive element (-1393 to -1133 bp) and a negative element (-1133 to -749 bp) were also found in the upstream region of the alpha-fibrinogen gene. PMID:7499335

  5. The 5' flanking region of human epsilon-globin gene.

    PubMed Central

    Baralle, F E; Shoulders, C C; Goodbourn, S; Jeffreys, A; Proudfoot, N J

    1980-01-01

    The structural analysis of the 2.0 kb region upstream from the epsilon-globin gene has been carried out. A genomic DNA map around the gene was worked out in some detail to ensure that the cloned DNA was representative of the actual chromosomal arrangement. Furthermore, a new technique was developed to precisely map a reiterated DNA sequence present 1.5 kb to the 5' side of the gene. The complete nucleotide sequence of the 2.0 kb 5' flanking region was then determined and overlapped with the gene. The sequence included the reiterated DNA sequence which is homologous to the so-called AluI family of repeats. Unusual stretches of sequence 50 nucleotides long, where A + T represent about 90% of the bases, are present at both the 5' and 3' sides of the repeat. Images PMID:6253916

  6. Histology of melanic flank and opercular color pattern elements in the Firemouth Cichlid, Thorichthys meeki.

    PubMed

    Beeching, Simon C; Glass, Brock A; Rehorek, Susan J

    2013-07-01

    Dark melanic color pattern elements, such as bars, stripes, and spots, are common in the skin of fishes, and result from the differential distribution and activity of melanin-containing chromatophores (melanophores). We determined the histological basis of two melanic color pattern elements in the integument of the Firemouth Cichlid, Thorichthys meeki. Vertical bars on the flanks were formed by three layers of dermal melanophores, whereas opercular spots were formed by four layers (two lateral and two medial) in the integument surrounding the opercular bones. Pretreatment of opercular tissue with potassium and sodium salts effectively concentrated or dispersed intracellular melanosomes. Regional differences in epidermal structure, scale distribution, and connective tissues were also identified. PMID:23450665

  7. Capture of flanking DNA by a P element in Drosophila melanogaster: Creation of a transposable element

    SciTech Connect

    Tsubota, Stuart, I.; Huong Dangvu )

    1991-02-01

    A 6.1-kilobase nsertion into the rudimentary (r) gene was cloned and partially sequenced. The insertion consists of a 703-base-pair (bp) P element next to a 5.4-kilobase single-copy sequence. The normal positon of the single-copy sequence is near the tip of the X chromosome. Upon insertion into the r gene, this chimeric element generated an 8-bp target-site duplication, characteristic of P elements. At the non-P-element end of the insertion, the first 8 bp are identical to the first 8 bp of the inverted terminal repeats of the P element. Thus, this element has inverted terminal repeats of 8 bp. This large element can excise from the r gene under conditions of hybrid dysgenesis, which indicates that it behaves like a normal P element. These data support the conclusion that a normally stable single-copy sequence has now become unstable and duplicated within the genome.

  8. Whale phylogeny and rapid radiation events revealed using novel retroposed elements and their flanking sequences

    PubMed Central

    2011-01-01

    Background A diversity of hypotheses have been proposed based on both morphological and molecular data to reveal phylogenetic relationships within the order Cetacea (dolphins, porpoises, and whales), and great progress has been made in the past two decades. However, there is still some controversy concerning relationships among certain cetacean taxa such as river dolphins and delphinoid species, which needs to be further addressed with more markers in an effort to address unresolved portions of the phylogeny. Results An analysis of additional SINE insertions and SINE-flanking sequences supported the monophyly of the order Cetacea as well as Odontocete, Delphinoidea (Delphinidae + Phocoenidae + Mondontidae), and Delphinidae. A sister relationship between Delphinidae and Phocoenidae + Mondontidae was supported, and members of classical river dolphins and the genera Tursiops and Stenella were found to be paraphyletic. Estimates of divergence times revealed rapid divergences of basal Odontocete lineages in the Oligocene and Early Miocene, and a recent rapid diversification of Delphinidae in the Middle-Late Miocene and Pliocene within a narrow time frame. Conclusions Several novel SINEs were found to differentiate Delphinidae from the other two families (Monodontidae and Phocoenidae), whereas the sister grouping of the latter two families with exclusion of Delphinidae was further revealed using the SINE-flanking sequences. Interestingly, some anomalous PCR amplification patterns of SINE insertions were detected, which can be explained as the result of potential ancestral SINE polymorphisms and incomplete lineage sorting. Although a few loci were potentially anomalous, this study demonstrated that the SINE-based approach is a powerful tool in phylogenetic studies. Identifying additional SINE elements that resolve the relationships in the superfamily Delphinoidea and family Delphinidae will be important steps forward in completely resolving cetacean phylogenetic

  9. The splicing regulatory element, UGCAUG, is phylogenetically and spatially conserved in introns that flank tissue-specific alternative exons

    PubMed Central

    Minovitsky, Simon; Gee, Sherry L.; Schokrpur, Shiruyeh; Dubchak, Inna; Conboy, John G.

    2005-01-01

    Previous studies have identified UGCAUG as an intron splicing enhancer that is frequently located adjacent to tissue-specific alternative exons in the human genome. Here, we show that UGCAUG is phylogenetically and spatially conserved in introns that flank brain-enriched alternative exons from fish to man. Analysis of sequence from the mouse, rat, dog, chicken and pufferfish genomes revealed a strongly statistically significant association of UGCAUG with the proximal intron region downstream of brain-enriched alternative exons. The number, position and sequence context of intronic UGCAUG elements were highly conserved among mammals and in chicken, but more divergent in fish. Control datasets, including constitutive exons and non-tissue-specific alternative exons, exhibited a much lower incidence of closely linked UGCAUG elements. We propose that the high sequence specificity of the UGCAUG element, and its unique association with tissue-specific alternative exons, mark it as a critical component of splicing switch mechanism(s) designed to activate a limited repertoire of splicing events in cell type-specific patterns. We further speculate that highly conserved UGCAUG-binding protein(s) related to the recently described Fox-1 splicing factor play a critical role in mediating this specificity. PMID:15691898

  10. Characterization of the 5'-flanking region for the human fibrinogen beta gene.

    PubMed Central

    Huber, P; Dalmon, J; Courtois, G; Laurent, M; Assouline, Z; Marguerie, G

    1987-01-01

    To identify the possible regulatory sequences in the genetic expression of fibrinogen, a human genomic DNA library raised in lambda EMBL 4 phage was screened using cDNA probes coding for the A alpha, B beta and gamma chains of human fibrinogen. The entire fibrinogen locus was characterized and its organization analysed by means of hybridization and restriction mapping. Among the clones identified, a single recombinant lambda phage contained the beta gene and its 5'- and 3'-flanking regions. A 1.5 kb fragment of the immediate 5'-flanking region was sequenced and S1 mapping experiments revealed three transcription start points. Comparison of this sequence with that previously reported for the same region upstream from the human gamma gene revealed no significant homology which suggests that the potential promoting sequences of these genes are different. In contrast, comparison of the 5'-flanking regions of human and rat beta genes revealed a 142 bp sequence of 80% homology situated 16 bp upstream from the human beta gene. This highly conserved region may well represents a potential candidate for a regulatory sequence of the human beta gene. Images PMID:3029722

  11. Analysis of the regions flanking the human insulin gene and sequence of an Alu family member.

    PubMed Central

    Bell, G I; Pictet, R; Rutter, W J

    1980-01-01

    The regions around the human insulin gene have been studied by heteroduplex, hybridization and sequence analysis. These studies indicated that there is a region of heterogeneous length located approximately 700 bp before the 5' end of the gene; and that the 19 kb of cloned DNA which includes the 1430 bp insulin gene as well as 5650 bp before and 11,500 bp after the gene is single copy sequence except for 500 bp located 6000 bp from the 3' end of the gene. This 500 bp segment contains a member of the Alu family of dispersed middle repetitive sequences as well as another less highly repeated homopolymeric segment. The sequence of this region was determined. This Alu repeat is bordered by 19 bp direct repeats and also contains an 83 bp sequence which is present twice. The regions flanking the human and rat I insulin genes were compared by heteroduplex analysis to localize homologous sequences in the flanking regions which could be involved in the regulation of insulin biosynthesis. The homology between the two genes is restricted to the region encoding preproinsulin and a short region of approximately 60 bp flanking the 5' side of the genes. Images PMID:6253909

  12. Oestrogens Downregulate Tissue Factor Pathway Inhibitor through Oestrogen Response Elements in the 5’-Flanking Region

    PubMed Central

    Ali, Huda Omar; Stavik, Benedicte; Myklebust, Christiane Filion; Andersen, Elisabeth; Dahm, Anders E. A.; Iversen, Nina; Sandset, Per Morten; Skretting, Grethe

    2016-01-01

    Oestrogens influence the pathology and development of hormone-sensitive breast cancers. Tissue factor pathway inhibitor (TFPI) has been shown to be associated with breast cancer pathogenesis. Recently, we found TFPI mRNA levels to be significantly reduced by oestrogens in a breast cancer cell line (MCF7), a process mediated through the oestrogen receptor alpha (ERα). The aim of the present study was to investigate the mechanism(s) by which oestrogens may regulate TFPI at the transcriptional level. The TFPI 5’-flanking region contains three oestrogen response element (ERE) half-sites at positions -845, -769 and -50. Constructs containing the wild type or mutated ERE half-sites of the TFPI 5’-flanking region were generated in a luciferase reporter gene vector and transiently co-transfected with an ERα expression vector into HEK293 cells and subsequently treated with oestrogens. We found that luciferase activity was significantly downregulated after oestrogen stimulation in cells transfected with the wild type construct, an effect that was abolished by mutating either ERE half-sites. Electrophoretic mobility shift assay suggested direct and specific interaction of ERα with the ERE half-sites in the TFPI 5’-flanking region. Chromatin immunoprecipitation showed that ERα was recruited to the region -899 to -578 of the TFPI 5’-flanking region in vivo, where the ERE half-sites -845 and -769 are located. Our results indicate that ERα can interact with all three ERE half-sites in the TFPI 5’-flanking region and thus participate in the repression of oestrogen mediated TFPI transcription in breast cancer cells. PMID:26999742

  13. Flank pain

    MedlinePlus

    Pain - side; Side pain ... Flank pain can be a sign of a kidney problem. But, since many organs are in this area, other causes are possible. If you have flank pain and fever , chills, blood in the urine, or ...

  14. Expression of the Human Glucokinase Gene: Important Roles of the 5′ Flanking and Intron 1 Sequences

    PubMed Central

    Li, Zhixin; Mao, Yiqing; Li, Hui; Wang, Xi; Wang, Rong; Xu, Wei; Song, Rongjing; Jin, Ling; Li, Xiuli; Irwin, David M.; Niu, Gang; Tan, Huanran

    2012-01-01

    Background Glucokinase plays important tissue-specific roles in human physiology, where it acts as a sensor of blood glucose levels in the pancreas, and a few other cells of the gut and brain, and as the rate-limiting step in glucose metabolism in the liver. Liver-specific expression is driven by one of the two tissue-specific promoters, and has an absolute requirement for insulin. The sequences that mediate regulation by insulin are incompletely understood. Methodology/Principal Findings To better understand the liver-specific expression of the human glucokinase gene we compared the structures of this gene from diverse mammals. Much of the sequence located between the 5′ pancreatic beta-cell-specific and downstream liver-specific promoters of the glucokinase genes is composed of repetitive DNA elements that were inserted in parallel on different mammalian lineages. The transcriptional activity of the liver-specific promoter 5′ flanking sequences were tested with and without downstream intronic sequences in two human liver cells lines, HepG2 and L-02. While glucokinase liver-specific 5′ flanking sequences support expression in liver cell lines, a sequence located about 2000 bases 3′ to the liver-specific mRNA start site represses gene expression. Enhanced reporter gene expression was observed in both cell lines when cells were treated with fetal calf serum, but only in the L-02 cells was expression enhanced by insulin. Conclusions/Significance Our results suggest that the normal liver L-02 cell line may be a better model to understand the regulation of the liver-specific expression of the human glucokinase gene. Our results also suggest that sequences downstream of the liver-specific mRNA start site have important roles in the regulation of liver-specific glucokinase gene expression. PMID:23029263

  15. Identification and characterization of 5′-flanking region of the human riboflavin transporter 1 gene (SLC52A1)

    PubMed Central

    Sabui, Subrata; Ghosal, Abhisek; Said, Hamid M.

    2014-01-01

    The human SLC52A1 gene encodes the riboflavin transporter-1 (RFVT-1), a plasma membrane protein that transports vitamin B2 (riboflavin, RF) into cells, and thus, plays a role in controlling cellular homeostasis of RF in those tissues that express the carrier protein (e.g. placenta and intestine). Currently, there is nothing known about transcriptional regulation of the SLC52A1 gene, therefore, we aimed to clone and characterize its 5′-flanking region. Using rapid amplification of the cDNA ends (5′-RACE), we identified one transcription start site (TSS). A 579 bp segment of the 5′-flanking region of this gene was cloned which exhibited robust promoter activity upon transfection in human intestinal epithelial cells. Deletion analysis revealed the core promoter activity to be embedded in a region between −234 and −23 that lacked TATA element, was GC-rich, and harbored several putative cis-regulatory sites including KLFs, AP-2, EGRF and Sp-1. Mutating each of these sites led to a significant decrease in promoter activity (which was highest for the Sp-1 site), suggesting their possible involvement in regulating SLC52A1 transcription. Focusing on the Sp-1 site, EMSA, super-shift and ChIP analysis was performed that established the interaction of the Sp-1 transcription factor with the SLC52A1 promoter; also, co-transfection of the minimal SLC52A1 promoter with an Sp-1 containing vector in Drosophila SL-2 cells led to significant promoter activation. These results are the first to reveal the identity of the minimal SLC52A1 promoter and to establish an important role for Sp-1 in its activity. PMID:25284511

  16. Identification and characterization of 5'-flanking region of the human riboflavin transporter 1 gene (SLC52A1).

    PubMed

    Sabui, Subrata; Ghosal, Abhisek; Said, Hamid M

    2014-12-10

    The human SLC52A1 gene encodes the riboflavin transporter-1 (RFVT-1), a plasma membrane protein that transports vitamin B2 (riboflavin, RF) into cells, and thus, plays a role in controlling cellular homeostasis of RF in those tissues that express the carrier protein (e.g. placenta and intestine). Currently, there is nothing known about transcriptional regulation of the SLC52A1 gene, therefore, we aimed to clone and characterize its 5'-flanking region. Using rapid amplification of the cDNA ends (5'-RACE), we identified one transcription start site (TSS). A 579 bp segment of the 5'-flanking region of this gene was cloned which exhibited robust promoter activity upon transfection in human intestinal epithelial cells. Deletion analysis revealed that the core promoter activity to be embedded in a region between -234 and -23 that lacked TATA element, was GC-rich, and harbored several putative cis-regulatory sites including KLFs, AP-2, EGRF and Sp-1. Mutating each of these sites led to a significant decrease in promoter activity (which was highest for the Sp-1 site), suggesting their possible involvement in regulating SLC52A1 transcription. Focusing on the Sp-1 site, EMSA, super-shift and ChIP analysis was performed that established the interaction of the Sp-1 transcription factor with the SLC52A1 promoter; also, co-transfection of the minimal SLC52A1 promoter with an Sp-1 containing vector in Drosophila SL-2 cells led to significant promoter activation. These results are the first to reveal the identity of the minimal SLC52A1 promoter and to establish an important role for Sp-1 in its activity. PMID:25284511

  17. Definition of a lipopolysaccharide-responsive element in the 5'-flanking regions of MuRantes and crg-2.

    PubMed Central

    Shin, H S; Drysdale, B E; Shin, M L; Noble, P W; Fisher, S N; Paznekas, W A

    1994-01-01

    Macrophages are stimulated by lipopolysaccharide (LPS) of gram-negative organisms. The changes in LPS-stimulated macrophages include transcriptional activation of multiple immediate-early genes, which may contribute to the natural immunity to microorganisms. We have defined by deletion and mutational analysis LPS-responsive elements (LREs) in two chemokine genes, MuRantes and crg-2, which are activated in an immediate-early manner. LRE consists of two motifs, TCAYR, which is an AP-1 half site with two flanking bases, and (A/T) (G/C)NTTYC(A/T)NTTY, which resembles in part the interferon-stimulated responsive element (ISRE). The orientation of these two motifs relative to each other in MuRantes differed from that in crg-2. These two motifs are separated by 10 and 6 nonconsensus nucleotides in the MuRantes and crg-2 LREs, respectively. Stimulation of macrophage-like RAW 264.7 cells with alpha/beta interferon did not activate MuRantes, indicating that the ISRE-like motif in MuRantes does not have ISRE activity. Upon stimulation of RAW 264.7 cells with LPS, proteins capable of binding to LRE accumulate in the nuclei as measured by electrophoretic mobility shift assay. These LRE-binding proteins include c-Jun and CREB. Images PMID:7513046

  18. The Complex Genetic Context of blaPER-1 Flanked by Miniature Inverted-Repeat Transposable Elements in Acinetobacter johnsonii

    PubMed Central

    Zong, Zhiyong

    2014-01-01

    On a large plasmid of Acinetobacter johnsonii strain XBB1 from hospital sewage, blaPER-1 and ISCR1 were found in a complex Tn402-like integron carrying an arr3-aacA4 cassette array. The integron was truncated by the same 439-bp miniature inverted-repeat transposable element (MITE) at both ends. blaPER-1 and its complex surroundings might have been mobilized by the MITEst into an orf of unknown function, evidenced by the presence of the characteristic 5-bp direct target repeats. The same 439-bp MITEs have also been found flanking class 1 integrons carrying metallo-β-lactamases genes blaIMP-1, blaIMP-5 and blaVIM-2 before but without ISCR1. Although the cassette arrays are different, integrons have always been truncated by the 439-bp MITEs at the exact same locations. The results suggested that MITEs might be able to mobilize class 1 integrons via transposition or homologous recombination and therefore represent a possible common mechanism for mobilizing antimicrobial resistance determinants. PMID:24587208

  19. Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix

    PubMed Central

    Iarovaia, Olga V.; Akopov, Sergey B.; Nikolaev, Lev G.; Sverdlov, Eugene D.; Razin, Sergey V.

    2005-01-01

    The spatial organization of an ∼170 kb region of human chromosome 19, including CD22 and GPR40–GPR43 genes, was studied using in situ hybridization of a set of cosmid and PAC probes with nuclear halos prepared from proliferating and differentiated HL60 cells. The whole region under study was found to be looped out into the nuclear halo in proliferating cells. It is likely that the loop observed was attached to the nuclear matrix via MAR elements present at the flanks of the area under study. Upon dimethyl sulfoxide-induced differentiation of the cells the looped fragment became associated with the nuclear matrix. This change in the spatial organization correlated with the activation of transcription of at least two (CD22 and GPR43) genes present within the loop. The data obtained are discussed in the framework of the hypothesis postulating that the spatial organization of chromosomal DNA is maintained via constitutive (basic) and facultative (transcription-related) interactions of the latter with the nuclear matrix. PMID:16049024

  20. Induction of transcription within chromosomal DNA loops flanked by MAR elements causes an association of loop DNA with the nuclear matrix.

    PubMed

    Iarovaia, Olga V; Akopov, Sergey B; Nikolaev, Lev G; Sverdlov, Eugene D; Razin, Sergey V

    2005-01-01

    The spatial organization of an approximately 170 kb region of human chromosome 19, including CD22 and GPR40-GPR43 genes, was studied using in situ hybridization of a set of cosmid and PAC probes with nuclear halos prepared from proliferating and differentiated HL60 cells. The whole region under study was found to be looped out into the nuclear halo in proliferating cells. It is likely that the loop observed was attached to the nuclear matrix via MAR elements present at the flanks of the area under study. Upon dimethyl sulfoxide-induced differentiation of the cells the looped fragment became associated with the nuclear matrix. This change in the spatial organization correlated with the activation of transcription of at least two (CD22 and GPR43) genes present within the loop. The data obtained are discussed in the framework of the hypothesis postulating that the spatial organization of chromosomal DNA is maintained via constitutive (basic) and facultative (transcription-related) interactions of the latter with the nuclear matrix. PMID:16049024

  1. Negative and positive regulation by a short segment in the 5'-flanking region of the human cytomegalovirus major immediate-early gene

    SciTech Connect

    Nelson, J.A.; Reynolds-Kohler, C.; Smith, B.A.

    1987-11-01

    To analyze the significance of inducible DNase I-hypersensitive sites occurring in the 5'-flanking sequence of the major immediate-early gene of human cytomegalovirus (HCMV), various deleted portions of the HCMV immediate-early promoter regulatory region were attached to the chloramphenicol acetyltransferase (CAT) gene and assayed for activity in transiently transfected undifferentiated and differentiated human teratocarcinoma cells, Tera-2. Assays of progressive deletions in the promoter regulatory region indicated that removal of a 395-base-pair portion of this element (nucleotides -750 to -1145) containing two inducible DNase I sites which correlate with gene expression resulted in a 7.5-fold increase in CAT activity in undifferentiated cells. However, in permissive differentiated Tera-2, human foreskin fibroblast, and HeLa cells, removal of this regulatory region resulted in decreased activity. In addition, attachment of this HCMV upstream element to a homologous or heterologous promoter increased activity three-to fivefold in permissive cells. Therefore, a cis regulatory element exists 5' to the enhancer of the major immediate-early gene of HCMV. This element negatively modulates expression in nonpermissive cells but positively influences expression in permissive cells.

  2. A CAR-responsive enhancer element locating approximately 31 kb upstream in the 5'-flanking region of rat cytochrome P450 (CYP) 3A1 gene.

    PubMed

    Gamou, Toshie; Habano, Wataru; Terashima, Jun; Ozawa, Shogo

    2015-04-01

    Constitutive androstane receptor (CAR) is one of the principal regulators of hepatic cytochrome P450s (CYPs) 3A (CYP3A). cDNA-mediated expression of a mature rat CAR (rCAR) into rat hepatoma cells induced CYP3A1 and CYP2B mRNAs. Aberrant rCAR failed in these inductions. Three important human CYP3A4 regulatory elements (REs), proximal ER6 (proER6), xenobiotic responsive enhancer module (XREM) and constitutive liver enhancer module (CLEM), support constitutive and inducible expression of CYP3As mediated by CAR and pregnane X receptor (PXR). NHR-scan software predicted proER6, XREM and CLEM at -255 b, -8 kb and -11.5 kb, respectively of CYP3A4, but neither XREM nor CLEM was predicted in rat CYP3A. A luciferase reporter construct carrying a 5'-flanking sequence of CYP3A1 (-31,739 to -31,585 from its transcription initiation site) revealed important for the rCAR-dependent transactivation of CYP3A1. This region includes two putative binding motifs of nuclear receptors (DR4 and DR2), a putative hepatocyte nuclear factor-1 binding motif (HNF1), nuclear factor-kappa B binding motif (NFκB), activator protein 1 binding motif (AP-1), and ecotropic viral integration site 1 binding motif (Evi1). We hereby conclude DR4 and/or DR2 motifs being primarily responsible and HNF1 being synergistically functioning elements for the rCAR-mediated transcription of CYP3A1. PMID:25989892

  3. Characterization of the 5' flanking region of the human D1A dopamine receptor gene.

    PubMed Central

    Minowa, M T; Minowa, T; Monsma, F J; Sibley, D R; Mouradian, M M

    1992-01-01

    To study how the expression of the D1A dopamine receptor gene is regulated, a human genomic clone was isolated by using a rat cDNA as probe. A 2.3-kilobase genomic fragment spanning -2571 through -236 relative to the adenosine of the first methionine codon was sequenced. The gene has an intron of 116 base pairs in the 5' noncoding region, nucleotides -599 through -484 as determined by S1 mapping and reverse transcription-PCR. It has multiple transcription initiation sites located between -1061 and -1040. The promoter region lacks a TATA box and a CAAT box, is rich in G+C content, and has multiple putative binding sites for transcription factor Sp1. Thus, the promoter region of the human D1A gene has features of "housekeeping" genes. However, it also has consensus sequences for AP1 and AP2 binding sites and a putative cAMP response element. The ability of four deletion mutants of the 2.3-kilobase fragment to modulate transcription of the heterologous chloramphenicol acetyltransferase gene in the promoterless plasmid pCAT-Basic was determined. All mutants demonstrated substantial transcriptional activity in the murine neuroblastoma cell line NS20Y, which expresses the D1A gene endogenously. Transient expression assays suggested the presence of a positive modulator between nucleotides -1340 and -1102, and a negative modulator between -1730 and -1341. The four genomic fragments had no or very low transcriptional activity in NB41A3, C6, and Hep G2 cells, which are not known to express this gene. Thus, the human D1A gene belongs to the category of tissue-specific, regulated genes that have housekeeping-type promoters. Images PMID:1557411

  4. Retrotransposons in the flanking regions of normal plant genes: a role for copia-like elements in the evolution of gene structure and expression.

    PubMed Central

    White, S E; Habera, L F; Wessler, S R

    1994-01-01

    The wx-K mutation results from the insertion of a copia-like retrotransposon into exon 12 of the maize waxy gene. This retrotransposon, named Hopscotch, has one long open reading frame encoding all of the domains required for transposition. Computer-assisted database searches using Hopscotch and other plant copia-like retroelements as query sequences have revealed that ancient, degenerate retrotransposon insertions are found in close proximity to 21 previously sequenced plant genes. The data suggest that these elements may be involved in gene duplication and the regulation of gene expression. Similar searches using the Drosophila retrotransposon copia did not reveal any retrotransposon-like sequences in the flanking regions of animal genes. These results, together with the recent finding that reverse-transcriptase sequences characteristic of copia-like elements are ubiquitous and diverse in plants, suggest that copia-like retrotransposons are an ancient component of plant genomes. Images PMID:7991537

  5. A novel PCR technique using Alu-specific primers to identify unknown flanking sequences from the human genome

    SciTech Connect

    Minami, M.; Poussin, K.; Brechot, C.; Paterlini, P.

    1995-09-20

    The rapid and reproducible identification of new cellular DNA sequences is difficult to achieve with the currently available procedures. Here we describe a novel approach based on the polymerase chain reaction (PCR) using a primer specific to the known sequence and another directed to a human Alu repeat. To avoid undesirable amplifications between Alu sequences, primers are constructed with dUTPs and destroyed by uracil DNA glycosylase treatment after 10 initial cycles of amplification. Only desirable fragments are then further amplified with specific primers to the known region and to a tag sequence introduced in the Alu-specific primer. Using this protocol, we have successfully indentified cellular sequences flanking integrated hepatitis B virus DNA from the human genome of three hepatoma tissues. The method enables a direct specific amplification without any ligation or nonspecific annealing steps as required by previous PCR-based protocols. This rapid and straightforward approach will be a powerful tool for the study of viral integration sites, but is also widely applicable to other studies of the human genome. 39 refs., 4 figs.

  6. A/T gap tolerance in the core sequence and flanking sequence requirements of non-canonical p53 response elements.

    PubMed

    Cai, Bi-He; Chao, Chung-Faye; Lin, Hwang-Chi; Huang, Hua-Ying; Kannagi, Reiji; Chen, Jang-Yi

    2016-06-01

    The canonical core sequence of the p53 response element, CATG, has a two-base A/T gap. Previously, we found that p53 can also activate a non-canonical four-base A/T gap CATATG core sequence. In this study, we investigated the possible number of A/T bases used by p53 and showed that a six-base A/T gap CATATATG core sequence was the maximum A/T gap in the p53 response element that could be upregulated by p53 and p63. Canonical and non-canonical p53 response elements also have three-base flanking sequences. A/T bases could be substituted by G/C bases, including CACACG and CGTGTG, but not CGCGCG. We found that the SV40 promoter with functional six- and two-base A/T gap core sequences could be activated by TAp63γ and that TAp63γ could upregulate SV40 small and large T antigens expression in COS7 cells. We also found that the distal region of PUMA promoter with functional two six-base A/T gap core sequences could be activated by TAp63γ in 293T cells. These new findings could provide novel rules for the non-canonical p53 family response element and could extend the entire p53 family regulation network. PMID:26823482

  7. In vitro interaction of uterine estrogen receptor with the estrogen response element present in the 3'-flanking region of the murine c-fos protooncogene.

    PubMed

    Hyder, S M; Stancel, G M

    1994-01-01

    Estradiol treatment rapidly stimulates transcription of the c-fos protooncogene in the rodent uterus, and transfection analysis previously identified an estrogen response element (ERE) in the 3'-flanking region of the murine gene with the sequence GGTCAnnnCAGCC. We now report that endogenous estrogen receptor (ER) obtained from either mouse or rat uterus binds to this 3'-ERE. Unoccupied receptor, receptor occupied with estradiol and receptor occupied with the antiestrogen tamoxifen all bind to this element, and the binding of receptor exhibits strict sequence specificity. By using a competition binding assay, the affinity of the ER for the c-fos-ERE is estimated to be approximately an order of magnitude less than the affinity for the consensus ERE (GGTCAnnnTGACC) found in the Xenopus and chicken vitellogenin genes. Differences in the electrophoretic mobilities of the c-fos and vitellogenin EREs bound to the ER in band-shift assays also suggest subtle structural differences in the two complexes. Mutations in either half-site of the c-fos-ERE destroy ER binding, suggesting that the receptor binds to this sequence as either a homo- or heterodimer. The 3'-fos-ERE region exhibits some homologies to both AP1 and AP2 consensus sites, but neither AP1-like proteins present in uterine extracts nor recombinant AP2 bind this protooncogene sequence. The finding that the ERE present in the 3'-region of the murine c-fos gene interacts with receptors present in the mouse and rat uterus supports a role for this element in the physiological regulation of c-fos expression in the uterus by estrogens. PMID:8136308

  8. A regional inventory of the landslide processes and the elements at risk on the Rift flanks west of Lake Kivu (DRC)

    NASA Astrophysics Data System (ADS)

    Maki Mateso, Jean-Claude; Monsieurs, Elise; Jacobs, Liesbet; Bagalwa Mateso, Luc; Fiama Bondo, Silvanos; Delvaux, Damien; Albino, Fabien; Kervyn, François; Dewitte, Olivier

    2016-04-01

    The Rift flanks west of Lake Kivu (DRC) are one of the Congolese regions most affected by fatal landslides. However, information on the distribution of these processes and their impact on society is still lacking. Here we present a first regional landslide inventory and the associated elements at risk. The inventory was conducted in an area of 5,700 km² in three administrative territories between the cities of Bukavu and Goma. The region is one of the most densely populated area of DRC with a density of up to 200 persons/km². The approach for the inventory relies on visual analysis of Google Earth imagery and a 5 m resolution DEM that we produced from TanDEM-X interferometry. Field validation was performed in target places accounting for 5% of the study area. More than 2,000 landslides were mapped and distinction was made between deep and shallow, and slide and flow processes. Average landslide area is 6 ha (max. = 430 ha). Geomorphological analysis of landslide distribution shows topographic, lithologic, climatic and seismic controls. For 600 randomly-selected landslides, elements at risk (house, road, cultivated land, river) were inventoried in the areas affected and potentially affected by the instabilities; 10% of the landslides are inhabited and 25% do not present any risk. Numerous landslides have caused direct and indirect damage in recent years. In some places, the impact of mining activities on slope stability can be important. Google Earth was the only way to locate the recent shallow failures triggered by known extreme rainfall events. This inventory is a first step towards the understanding of the landslide processes in the region. Further studies are needed to complete and validate the information, to better infer about the triggers, and to compute susceptibility and risk maps.

  9. COL1A1 transgene expression in stably transfected osteoblastic cells. Relative contributions of first intron, 3'-flanking sequences, and sequences derived from the body of the human COL1A1 minigene

    NASA Technical Reports Server (NTRS)

    Breault, D. T.; Lichtler, A. C.; Rowe, D. W.

    1997-01-01

    Collagen reporter gene constructs have be used to identify cell-specific sequences needed for transcriptional activation. The elements required for endogenous levels of COL1A1 expression, however, have not been elucidated. The human COL1A1 minigene is expressed at high levels and likely harbors sequence elements required for endogenous levels of activity. Using stably transfected osteoblastic Py1a cells, we studied a series of constructs (pOBColCAT) designed to characterize further the elements required for high level of expression. pOBColCAT, which contains the COL1A1 first intron, was expressed at 50-100-fold higher levels than ColCAT 3.6, which lacks the first intron. This difference is best explained by improved mRNA processing rather than a transcriptional effect. Furthermore, variation in activity observed with the intron deletion constructs is best explained by altered mRNA splicing. Two major regions of the human COL1A1 minigene, the 3'-flanking sequences and the minigene body, were introduced into pOBColCAT to assess both transcriptional enhancing activity and the effect on mRNA stability. Analysis of the minigene body, which includes the first five exons and introns fused with the terminal six introns and exons, revealed an orientation-independent 5-fold increase in CAT activity. In contrast the 3'-flanking sequences gave rise to a modest 61% increase in CAT activity. Neither region increased the mRNA half-life of the parent construct, suggesting that CAT-specific mRNA instability elements may serve as dominant negative regulators of stability. This study suggests that other sites within the body of the COL1A1 minigene are important for high expression, e.g. during periods of rapid extracellular matrix production.

  10. Insights of ridge-flank hydrothermal processes through minor and trace element geochemistry of sediment pore fluids from IODP Site 1301

    NASA Astrophysics Data System (ADS)

    Hulme, S. M.

    2005-12-01

    The volumetric flux of seawater that flows through the oceanic crust rivals that which flows from rivers into the oceans. As seawater or formation fluid circulates through oceanic basement it is warmed and reacts with basalt and secondary minerals. In addition, diffusive exchange with overlying pore fluids may also impact the composition of the circulating fluid in basement. This interplay among seawater (formation fluid) reaction with basalt, diffusive exchange, and warming continues to the point of egress. How this seawater circulates through the crust and the chemical, mass, and thermal fluxes that it generates was the focus for drilling IODP Leg 301 on the eastern flank of the Juan de Fuca Ridge on 3.5-m.y.-old crust. We have conducted a comprehensive series of chemical analyses on pore waters from IODP Expedition 301 to constrain the composition of the formation fluid within the upper-most basaltic basement and compared it to the composition from nearby springs and borehole data. Sediments were recovered from IODP Holes 1301C (29 samples) and 1301D (9 samples) using the advanced piston coring (APC) technique. Sediments for pore fluid extraction were collected throughout the sediment column with a greater vertical resolution at the sediment-basement contact. Pore fluids were extracted in a nitrogen atmosphere to minimize potential oxidation reactions. Shipboard analyses included Ca, Mg, Alkalinity, pH, chlorinity, ammonium, phosphate, sulfate, K, Si, Li, B, Mn, Fe, Sr, DIC, total C, and Ba. Subsequent sample analysis with a Finnagin Element 2 high-resolution ICP-MS included: the trace elements Rb, Cs, Ba, Y, Cd and U; transition metals Mo, V, Cr, Co, Cu, Ni and Zn; and the complete suite of rare earth elements (REE). These data provide additional constraints to determine diffusive fluxes between the sediment and basement reservoirs, allowing us to refine models that constrain the rate of fluid flow within the crust and re-affirm the directionality of flow along

  11. Identification of an oxygen-responsive element in the 5'-flanking sequence of the rat cytosolic phosphoenolpyruvate carboxykinase-1 gene, modulating its glucagon-dependent activation.

    PubMed Central

    Bratke, J; Kietzmann, T; Jungermann, K

    1999-01-01

    The glucagon-stimulated transcription of the cytosolic phosphoenolpyruvate carboxykinase-1 (PCK1) gene is mediated by cAMP and positively modulated by oxygen in primary hepatocytes. Rat hepatocytes were transfected with constructs containing the first 2500, 493 or 281 bp of the PCK1 5'-flanking region in front of the chloramphenicol acetyltransferase (CAT) reporter gene. With all three constructs glucagon induced CAT activity with decreasing efficiency maximally under arterial pO2 and to about 65% under venous pO2. Rat hepatocytes were then transfected with constructs containing the first 493 bp of the PCK1 5'-flanking region in front of the luciferase (LUC) reporter gene, which were block-mutated at the CRE1 (cAMP-response element-1; -93/-86), putative CRE2 (-146/-139), promoter element (P) 1 (-118/-104), P2 (-193/-181) or P4 (-291/-273) sites. Glucagon induced LUC activity strongly when the P1 and P2 sites were mutated and weakly when the P4 site was mutated; induction of the P1, P2 and P4 mutants was positively modulated by the pO2. Glucagon also induced LUC activity strongly when the putative CRE2 site was altered; however, induction of the CRE2 mutant was not modulated by the pO2. Glucagon did not induce LUC activity when the CRE1 site was modified. These experiments suggested that the CRE1 but not the putative CRE2 was an essential site necessary for the cAMP-mediated PCK1 gene activation by glucagon and that the putative CRE2 site was involved in the oxygen-dependent modulation of PCK1 gene activation. To confirm these conclusions rat hepatocytes were transfected with simian virus 40 (SV40)-promoter-driven LUC-gene constructs containing three CRE1 sequences (-95/-84), three CRE2 sequences (-148/-137) or three CRE1 sequences plus two CRE2 sequences of the PCK1 gene in front of the SV40 promoter. Glucagon induced LUC activity markedly when the CRE1, but not when the CRE2, sites were in front of the SV40-LUC gene; however, induction of the (CRE1)3SV40-LUC

  12. The role of the 5'-flanking sequence of a human tRNA(Glu) gene in modulation of its transcriptional activity in vitro.

    PubMed Central

    Gonos, E S; Goddard, J P

    1990-01-01

    The role of a tRNA-like structure within the 5'-flanking sequence of a human tRNA(Glu) gene in the modulation of its transcription in vitro by HeLa cell extracts has been investigated using several deletion mutants of a recombinant of the gene which lacked part or all of the tRNA-like structure. The transcriptional efficiency of four mutants was the same as that of the wild-type recombinant, two mutants had decreased transcriptional efficiency, one was more efficient, and one, lacking part of the 5' intragenic control region, was inactive. Correlation of the transcriptional efficiencies with the position and the size of the 5'-flanking sequence that was deleted indicated that the tRNA-like structure may be deleted without loss of transcriptional efficiency. Current models for the modulation of tRNA gene transcription by the 5'-flanking sequence are assessed in the light of the results obtained, and a potential model is presented. Images Fig. 2. Fig. 4. PMID:2268303

  13. Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome.

    PubMed Central

    Davies, K E; Pearson, P L; Harper, P S; Murray, J M; O'Brien, T; Sarfarazi, M; Williamson, R

    1983-01-01

    The inheritance of two restriction fragment length polymorphisms (RFLPs) on the short arm of the human X chromosome has been studied relative to Duchenne muscular dystrophy. This provides a partial genetic map of the short arm of the human X chromosome between Xp110 and Xp223. The data were derived from the segregation between a RFLP located at Xp21-Xp223, the DMD locus, and a RFLP located at Xp110-Xp113. The genetic distance from Xp110 to Xp223 was found to be approximately 40 centimorgans (cM). This provides experimental confirmation that 1cM corresponds to approximately 1,000 kilobase pairs of DNA for this region of the human X chromosome. Our data confirm that the DMD mutation lies between Xp223 and Xp110. The availability of flanking probes surrounding the DMD locus will assist in the ordering of further DNA sequences relative to the mutation. Images PMID:6304647

  14. Characterization of the 5′-flanking region of the human DNA helicase B (HELB) gene and its response to trans-Resveratrol

    PubMed Central

    Uchiumi, Fumiaki; Arakawa, Jun; Iwakoshi, Keiko; Ishibashi, Sayaka; Tanuma, Sei-ichi

    2016-01-01

    Human DNA helicase B (HELB/HDHB) regulates DNA replication through association with human DNA polymerase α-primase. In the present study, an 866-base pair (bp) of the 5′-flanking region of the human HELB gene-containing Luciferase (Luc) reporter plasmid, pHDHB-Luc was transfected into various cell lines and Luc activity was analyzed. Deletion analyses revealed that a 121-bp containing the major transcription start site (TSS) was essential for the basal promoter activity in all tested cells. TF-SEARCH analysis indicated that GC-box/Sp1 and duplicated GGAA-motifs containing putative STAT-x and c-ETS binding sites are located close to the TSS. Furthermore, chromatin immunoprecipitation (ChIP) analysis showed that PU.1 and Sp1 bind to the 121-bp region. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analyses showed the HELB gene and protein expression was up-regulated by trans-Resveratrol (Rsv) treatment in HeLa S3 cells. Moreover, transfection experiment indicated that mutations on the GC-boxes and the duplicated GGAA-motif greatly reduced promoter activity and the response to Rsv in HeLa S3 cells. These results suggest that Rsv, which is a natural compound that has been found to elongate the lifespan of various organisms, regulates HELB promoter activity through co-operation of the GC-boxes and the duplicated GGAA-motif in the 121-bp. PMID:27079536

  15. Finite element modeling of the human pelvis

    SciTech Connect

    Carlson, B.

    1995-11-01

    A finite element model of the human pelvis was created using a commercial wire frame image as a template. To test the final mesh, the model`s mechanical behavior was analyzed through finite element analysis and the results were displayed graphically as stress concentrations. In the future, this grid of the pelvis will be integrated with a full leg model and used in side-impact car collision simulations.

  16. Flank solar wind interaction

    NASA Technical Reports Server (NTRS)

    Moses, Stewart L.; Greenstadt, Eugene W.; Coroniti, Ferdinand V.

    1994-01-01

    In this report we will summarize the results of the work performed under the 'Flank Solar Wind Interaction' investigation in support of NASA's Space Physics Guest Investigator Program. While this investigation was focused on the interaction of the Earth's magnetosphere with the solar wind as observed by instruments on the International Sun-Earth Explorer (ISEE) 3 spacecraft, it also represents the culmination of decades of research performed by scientists at TRW on the rich phenomenology of collisionless shocks in space.

  17. Arsia Mons Flank

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This VIS image shows the part of the NE flank of Arsia Mons where it meets the plains. The flank of the volcano is comprised of long flows. Collapse features are present at the flank margin.

    Image information: VIS instrument. Latitude -7.9, Longitude 241.9 East (118.1 West). 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  18. Physical Map of Human 6p21.2–6p21.3: Region Flanking the Centromeric End of the Major Histocompatibility Complex

    PubMed Central

    Tripodis, Nicos; Mason, Ruth; Humphray, Sean J.; Davies, Angela F.; Herberg, Jethro A.; Trowsdale, John; Nizetic, Dean; Senger, Gabriele; Ragoussis, Jiannis

    1998-01-01

    We have physically mapped and cloned a 2.5-Mb chromosomal segment flanking the centromeric end of the major histocompatibility complex (MHC). We characterized in detail 27 YACs, 144 cosmids, 51 PACs, and 5 BACs, which will facilitate the complete genomic sequencing of this region of chromosome 6. The contig contains the genes encoding CSBP, p21, HSU09564 serine kinase, ZNF76, TCP-11, RPS10, HMGI(Y), BAK, and the human homolog of Tctex-7 (HSET). The GLO1 gene was mapped further centromeric in the 6p21.2–6p21.1 region toward TCTE-1. The gene order of the GLO1–HMGI(Y) segment in respect to the centromere is similar to the gene order in the mouse t-chromosome distal inversion, indicating that there is conservation in gene content but not gene order between humans and mice in this region. The close linkage of the BAK and CSBP genes to the MHC is of interest because of their possible involvement in autoimmune disease. PMID:9647638

  19. The human element in technology transfer

    NASA Technical Reports Server (NTRS)

    Peake, H. J.

    1978-01-01

    A transfer model composed of three roles and their linkages was considered. This model and a growing body of experience was analyzed to provide guidance in the human elements of technology transfer. For example, criteria for selection of technology transfer agents was described, and some needed working climate factors were known. These concepts were successfully applied to transfer activities.

  20. Pavonis Mons Flank

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site] Context image for PIA03040 Pavonis Mons Flank

    This image shows a portion of the flank of Pavonis Mons. The collapse features at the bottom of the image are related to subsurface tubes that once contained lava.

    Image information: VIS instrument. Latitude 0.6S, Longitude 247.0E. 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  1. Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth.

    PubMed

    Opoku-Acheampong, Alexander B; Penugonda, Kavitha; Lindshield, Brian L

    2016-01-01

    Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth. PMID:27272436

  2. Effect of Saw Palmetto Supplements on Androgen-Sensitive LNCaP Human Prostate Cancer Cell Number and Syrian Hamster Flank Organ Growth

    PubMed Central

    Opoku-Acheampong, Alexander B.; Penugonda, Kavitha; Lindshield, Brian L.

    2016-01-01

    Saw palmetto supplements (SPS) are commonly consumed by men with prostate cancer. We investigated whether SPS fatty acids and phytosterols concentrations determine their growth-inhibitory action in androgen-sensitive LNCaP cells and hamster flank organs. High long-chain fatty acids-low phytosterols (HLLP) SPS ≥ 750 nM with testosterone significantly increased and ≥500 nM with dihydrotestosterone significantly decreased LNCaP cell number. High long-chain fatty acids-high phytosterols (HLHP) SPS ≥ 500 nM with dihydrotestosterone and high medium-chain fatty acids-low phytosterols (HMLP) SPS ≥ 750 nM or with androgens significantly decreased LNCaP cell number (n = 3; p < 0.05). Five- to six-week-old, castrated male Syrian hamsters were randomized to control (n = 4), HLLP, HLHP, and HMLP SPS (n = 6) groups. Testosterone or dihydrotestosterone was applied topically daily for 21 days to the right flank organ; the left flank organ was treated with ethanol and served as the control. Thirty minutes later, SPS or ethanol was applied to each flank organ in treatment and control groups, respectively. SPS treatments caused a notable but nonsignificant reduction in the difference between left and right flank organ growth in testosterone-treated SPS groups compared to the control. The same level of inhibition was not seen in dihydrotestosterone-treated SPS groups (p < 0.05). Results may suggest that SPS inhibit 5α-reductase thereby preventing hamster flank organ growth. PMID:27272436

  3. Hinf I/Tsp509 I and BsoF I polymorphisms in the flanking regions of the human VNTR locus D1S80.

    PubMed

    Duncan, G T; Balamurugan, K; Budowle, B; Tracey, M L

    1996-11-01

    The minisatellite locus D1S80 (1p35-p36), is a highly polymorphic VNTR that also contains a Hinf I polymorphism in the 5' flanking region. Our data suggest that the Hinf I polymorphism is a G > T transversion 58 bases downstream from the forward primer. This G > T transversion also creates a Tsp509 I restriction site. Additionally, a G > C transversion polymorphism was identified in the 3' flanking region by the creation of a BsoF I restriction site immediately adjacent to the repeat region. PMID:9021400

  4. Finite element analysis of human joints

    SciTech Connect

    Bossart, P.L.; Hollerbach, K.

    1996-09-01

    Our work focuses on the development of finite element models (FEMs) that describe the biomechanics of human joints. Finite element modeling is becoming a standard tool in industrial applications. In highly complex problems such as those found in biomechanics research, however, the full potential of FEMs is just beginning to be explored, due to the absence of precise, high resolution medical data and the difficulties encountered in converting these enormous datasets into a form that is usable in FEMs. With increasing computing speed and memory available, it is now feasible to address these challenges. We address the first by acquiring data with a high resolution C-ray CT scanner and the latter by developing semi-automated method for generating the volumetric meshes used in the FEM. Issues related to tomographic reconstruction, volume segmentation, the use of extracted surfaces to generate volumetric hexahedral meshes, and applications of the FEM are described.

  5. Analysis of sequences flanking the vap regions of Dichelobacter nodosus: evidence for multiple integration events, a killer system, and a new genetic element.

    PubMed

    Bloomfield, G A; Whittle, G; McDonagh, M B; Katz, M E; Cheetham, B F

    1997-02-01

    Dichelobacter nodosus is the causative agent of ovine footrot. The vap regions of the D. nodosus genome may have arisen by the integration of a genetic element and may have a role in virulence. The virulent D. nodosus strain A198 has multiple copies of the vap regions. In the present study, sequences to the left and right of vap regions 1, 2 and 3 of strain A198 were analysed by Southern blotting and DNa sequencing. The results suggest that vap regions 1 and 2 rose by independent integration events into different tRNA genes. The discovery of a second integrase gene (intB), a gene with similarity to bacteriophage repressor proteins (regA), and a gene similar to an ORF from a conjugative transposon (gepA), suggests that a second genetic element, either a bacteriophage or a conjugative transposon, is integrated next to vap region 3 in the D. nodosus genome. The arrangement of intB and the vap regions in three other virulent strains and one benign strain was determined using using Southern blotting and PCR. One strain, H1215, contained vapE' and not vapE, and thus resembles vap region 3, suggesting that vap region 3 also may have arisen by an independent integration event. In all strains, a copy of intB was found next to the vap regions. The vap regions contain two genes, vapA and toxA, with similarity to the hig genes of the killer plasmid Rts1. Evidence is presented that vapA and toxA have a similar function in D. nodosus. PMID:9043132

  6. Arsia Mons Southern Flank

    NASA Technical Reports Server (NTRS)

    2005-01-01

    [figure removed for brevity, see original site]

    The final VIS image of Arsia Mons is located on the southern flank of the volcano adjacent to the NE trending feature. There has been a significant amount of collapse features formed in this region.

    Image information: VIS instrument. Latitude -11.1, Longitude 238.6 East (121.4 West). 17 meter/pixel resolution.

    Note: this THEMIS visual image has not been radiometrically nor geometrically calibrated for this preliminary release. An empirical correction has been performed to remove instrumental effects. A linear shift has been applied in the cross-track and down-track direction to approximate spacecraft and planetary motion. Fully calibrated and geometrically projected images will be released through the Planetary Data System in accordance with Project policies at a later time.

    NASA's Jet Propulsion Laboratory manages the 2001 Mars Odyssey mission for NASA's Office of Space Science, Washington, D.C. The Thermal Emission Imaging System (THEMIS) was developed by Arizona State University, Tempe, in collaboration with Raytheon Santa Barbara Remote Sensing. The THEMIS investigation is led by Dr. Philip Christensen at Arizona State University. Lockheed Martin Astronautics, Denver, is the prime contractor for the Odyssey project, and developed and built the orbiter. Mission operations are conducted jointly from Lockheed Martin and from JPL, a division of the California Institute of Technology in Pasadena.

  7. Human Research Program: Space Human Factors and Habitability Element

    NASA Technical Reports Server (NTRS)

    Russo, Dane M.

    2007-01-01

    The three project areas of the Space Human Factors and Habitability Element work together to achieve a working and living environment that will keep crews healthy, safe, and productive throughout all missions -- from Earth orbit to Mars expeditions. The Advanced Environmental Health (AEH) Project develops and evaluates advanced habitability systems and establishes requirements and health standards for exploration missions. The Space Human Factors Engineering (SHFE) Project s goal is to ensure a safe and productive environment for humans in space. With missions using new technologies at an ever-increasing rate, it is imperative that these advances enhance crew performance without increasing stress or risk. The ultimate goal of Advanced Food Technology (AFT) Project is to develop and deliver technologies for human centered spacecraft that will support crews on missions to the moon, Mars, and beyond.

  8. Finite Element Modeling of Human Placental Tissue

    PubMed Central

    Yu, Mao; Manoogian, Sarah; Duma, Stefan M.; Stitzel, Joel D.

    2009-01-01

    Motor vehicle crashes account for a large portion of placental abruption and fetal losses. To better understand the material properties of the human placenta, a Finite Element (FE) model of human placenta tissue was created and verified using data from uniaxial tension tests. Sixty-four tensile tests at three different strain rates of 7% strain/s, 70% strain/s, and 700% strain/s from six whole human placentas were used for model development. Nominal stresses were calculated by dividing forces at the grips by the original cross-sectional area. Nominal strains were calculated by dividing cross-head displacement by the original gauge length. A detailed methodology for interpreting experimental data for application to material model development is presented. A model of the tension coupon was created in LS-DYNA and stretched in the same manner as the uniaxial tension tests. The behavior of the material was optimized to the uniaxial tension test using a multi-island genetic algorithm. The results demonstrate good correlation between experiments and the model, with an average difference of 2% between the optimized FE and experimental first principal stress at the termination state. The material parameters found in this study can be utilized in FE models of placental tissues for behavior under dynamic loading. PMID:20184849

  9. Tipping elements in the human intestinal ecosystem

    PubMed Central

    Lahti, Leo; Salojärvi, Jarkko; Salonen, Anne; Scheffer, Marten; de Vos, Willem M.

    2014-01-01

    The microbial communities living in the human intestine can have profound impact on our well-being and health. However, we have limited understanding of the mechanisms that control this complex ecosystem. Here, based on a deep phylogenetic analysis of the intestinal microbiota in a thousand western adults, we identify groups of bacteria that exhibit robust bistable abundance distributions. These bacteria are either abundant or nearly absent in most individuals, and exhibit decreased temporal stability at the intermediate abundance range. The abundances of these bimodally distributed bacteria vary independently, and their abundance distributions are not affected by short-term dietary interventions. However, their contrasting alternative states are associated with host factors such as ageing and overweight. We propose that the bistable groups reflect tipping elements of the intestinal microbiota, whose critical transitions may have profound health implications and diagnostic potential. PMID:25003530

  10. The structure of the human peripherin gene (PRPH) and identification of potential regulatory elements

    SciTech Connect

    Foley, J.; Ley, C.A.; Parysek, L.M.

    1994-07-15

    The authors determined the complete nucleotide sequence of the coding region of the human peripherin gene (PRPH), as well as 742 bp 5{prime} to the cap site and 584 bp 3{prime} to the stop codon, and compared its structure and sequence to the rat and mouse genes. The overall structure of 9 exons separated by 8 introns is conserved among these three mammalian species. The nucleotide sequences of the human peripherin gene exons were 90% identical to the rat gene sequences, and the predicted human peripherin protein differed from rat peripherin at only 18 of 475 amino acid residues. Comparison of the 5{prime} flanking regions of the human peripherin gene and rodent genes revealed extensive areas of high homology. Additional conserved segments were found in introns 1 and 2. Within the 5{prime} region, potential regulatory sequences, including a nerve growth factor negative regulatory element, a Hox protein binding site, and a heat shock element, were identified in all peripherin genes. The positional conservation of each element suggests that they may be important in the tissue-specific, developmental-specific, and injury-specific expression of the peripherin gene. 24 refs., 2 figs., 1 tab.

  11. Recycling of trace elements required for humans in CELSS

    NASA Astrophysics Data System (ADS)

    Ashida, A.

    1994-11-01

    Recycle of complete nourishment necessary for human should be constructed in CELSS (Controlled Ecological Life Support Systems). Essential elements necessary for human support are categorized as major elements, semi-major elements and trace elements. Recently, trace elements have been identified from considerations of local diseases, food additive problems, pollution problems and adult diseases, consisting of Fe, Zn, Cu, Se, Co, F, Si, Mn, Cr, I, As, Mo, Ni, V, Sn, Li, Br, Cd, Pb, B. A review of the biogeochemical history of the earth's biosphere and the physiological nature of humans and plants explains some of the requirements. A possible route for intake of trace elements is considered that trace elements are dissolved in some chemical form in water, absorbed by plants through their roots and then transfered to human as foods. There may be a posibility that living things absorb some trace elements from atmosphere. Management and recycling of trace elements in CELSS is discussed.

  12. Volcano Flank Terraces on Mars

    NASA Astrophysics Data System (ADS)

    Byrne, P. K.; van Wyk de Vries, B.; Murray, J. B.; Troll, V. R.

    2008-12-01

    Flank terraces are bulge-like structures that occur on the slopes of at least nine large shield volcanoes on Mars, and three on Earth. Terraces have a convex-upward, convex-outward morphology, with an imbricate "fish scale" stacking pattern in plan. They occur at all elevations, are scale-invariant structures, and have similar proportions to thrust faults on Earth. Suggested mechanisms of formation include elastic self-loading, lithospheric flexure, magma chamber tumescence, flank relaxation, and shallow gravitational slumping. Terrace geometries predicted by most of these mechanisms do not agree with our observations, however. Only lithospheric flexure can fully account for terrace geometry on Mars and Earth, and so is the most likely candidate mechanism for flank terrace formation. To verify this hypothesis, we conducted scaled analogue modelling experiments, and investigated the structures formed during flexure. Cones of a sand-gypsum mix were placed upon a deep layer of silicone gel, to simulate volcanic loads upon viscoelastic Martian crust. Key parameters were varied across our experimental program. In all cases convex topographic structures developed on the cones' flanks, arranged in an imbricate, overlapping plan-view pattern. These structures closely resemble flank terraces observed on Mars, and our results provide for a basic kinematic model of terrace formation. Analogue volcanoes experienced a decrease in upper surface area whilst volume was conserved; the contractional surface strain was accommodated by outward verging, circumferentially striking thrusts. The morphology of experimental structures suggests an orientation of the principal stress axes of σ1 = radial, σ2 = concentric, and σ3 = vertical. Elsewhere (J. B. Murray et al., this volume) we detail the relationship between flank terraces and other structures such as pit craters and gräben, using Ascraeus Mons as a case study. We suggest that terraces may influence the distribution and location

  13. Identification of DNA-binding proteins that interact with the 5'-flanking region of the human D-amino acid oxidase gene by pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry.

    PubMed

    Tran, Diem Hong; Shishido, Yuji; Chung, Seong Pil; Trinh, Huong Thi Thanh; Yorita, Kazuko; Sakai, Takashi; Fukui, Kiyoshi

    2015-12-10

    D-Amino acid oxidase (DAO) is a flavoenzyme that metabolizes D-amino acids and is expected to be a promising therapeutic target of schizophrenia and glioblastoma. The study of DNA-binding proteins has yielded much information in the regulation of transcription and other biological processes. However, proteins interacting with DAO gene have not been elucidated. Our assessment of human DAO promoter activity using luciferase reporter system indicated the 5'-flanking region of this gene (-4289 bp from transcription initiation site) has a regulatory sequence for gene expression, which is regulated by multi-protein complexes interacting with this region. By using pull-down assay coupled with two-dimensional gel electrophoresis and mass spectrometry, we identified six proteins binding to the 5'-flanking region of the human DAO gene (zinc finger C2HC domain-containing protein 1A; histidine-tRNA ligase, cytoplasmic; molybdenum cofactor biosynthesis protein; 60S ribosomal protein L37; calponin-1; calmodulin binding protein and heterogeneous nuclear ribonucleoprotein A2/B1). These preliminary results will contribute to the advance in the understanding of the potential factors associated with the regulatory mechanism of DAO expression. PMID:25749303

  14. West Flank Downhole Temperature Data

    DOE Data Explorer

    Doug Blankenship

    2008-03-01

    Downhole temperature data for the three wells inside the West Flank FORGE footprint; 83-11, TCH 74-2 and TCH 48-11. TCH 74-2 and TCH 48-11 were both collected before 1990 and 83-11 was collected in 2009. The are compiled into one spreadsheet for ease of visualization.

  15. Cyclic AMP regulation of the human glycoprotein hormone. cap alpha. -subunit gene is mediated by an 18-base-pair element

    SciTech Connect

    Silver, B.J.; Bokar, J.A.; Virgin, J.B.; Vallen, E.A.; Milsted, A.; Nilson, J.H.

    1987-04-01

    cAMP regulates transcription of the gene encoding the ..cap alpha..-subunit of human chorionic gonadotropin (hCG) in the choriocarcinoma cells (BeWo). To define the sequences required for regulation by cAMP, the authors inserted fragments from the 5' flanking region of the ..cap alpha..-subunit gene into a test vector containing the simian virus 40 early promoter (devoid of its enhancer) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Results from transient expression assays in BeWo cells indicated that a 1500-base-pair (bp) fragment conferred cAMP responsiveness on the CAT gene regardless of position or orientation of the insert relative to the viral promoter. A subfragment extending from position -169 to position -100 had the same effect on cAMP-induced expression. Furthermore, the entire stimulatory effect could be achieved with an 18-bp synthetic oligodeoxynucleotide corresponding to a direct repeat between position -146 and -111. In the absence of cAMP, the ..cap alpha..-subunit 5' flanking sequence also enhanced transcription from the simian virus 40 early promoter. They localized this enhancer activity to the same -169/-100 fragment containing the cAMP response element. The 18-bp element alone, however, had no effect on basal expression. Thus, this short DNA sequence serves as a cAMP response element and also functions independently of other promoter-regulatory elements located in the 5' flanking sequence of the ..cap alpha..-subunit gene.

  16. Elemental distribution in human femoral head

    NASA Astrophysics Data System (ADS)

    Santos, C.; Fonseca, M.; Corregidor, V.; Silva, H.; Luís, H.; Jesus, A. P.; Branco, J.; Alves, L. C.

    2014-07-01

    Osteoporosis is the most common bone disease with severe symptoms and harmful effects on the patient quality of life. Because abnormal distribution and concentration of the major and trace elements may help to characterize the disease, ion beam analysis is applied to the study of bone samples. Proton Induced X-ray Emission and Elastic Backscattering Spectrometry are applied for qualitative and quantitative analysis of an osteoporotic bone sample, for the determination of the Ca/P ratio and analysis of the distribution of major and trace elements. The analysis was made both in trabecular and cortical bone and the results are in agreement with the information found in literature.

  17. The Human Element in the Virtual Library.

    ERIC Educational Resources Information Center

    Saunders, Laverna M.

    1999-01-01

    Introduces the concept of the virtual library and explores how the increasing reliance on computers and digital information has affected library users and staff. Discusses users' expectations, democratization of access, human issues, organizational change, technostress, ergonomics, assessment, and strategies for success and survival. Contains 35…

  18. Regulatory elements in the first intron contribute to transcriptional control of the human. cap alpha. 1(I) collagen gene

    SciTech Connect

    Bornstein, P.; McKay, J.; Morishima, J.K.; Devarayalu, S.; Gelinas, R.E.

    1987-12-01

    Several lines of evidence have suggested that the regulation of type I collagen gene transcription is complex and that important regulatory elements reside 5' to, and within, the first intron of the ..cap alpha..1(I) gene. The authors therefore sequenced a 2.3-kilobase HindIII fragment that encompasses 804 base pairs of 5' flanking sequence, the first exon, and most of the first intron of the ..cap alpha..1(I) human collagen gene. A 274-base-pair intronic sequence, flanked by Ava I sites (A274), contained a sequence identical to a high-affinity decanucleotide binding site for transcription factor Sp1 and a viral core enhancer sequence. DNase I protection experiments indicated zones of protection that corresponded to these motifs. When A274 was cloned 5' to the chloramphenicol acetyltransferase (CAT) gene, driven by an ..cap alpha..1(I) collagen promoter sequence, and expression was assessed by transfection, significant orientation-specific inhibition of CAT activity was observed. This effect was most apparent in chicken tendon fibroblasts, which modulate their level of collagen synthesis in culture. They propose that normal regulation of ..cap alpha..1(I) collagen gene transcription results from an interplay of positive and negative elements present in the promoter region and within the first intron.

  19. Factors influencing trace element composition in human teeth

    SciTech Connect

    Tandon, L.; Iyengar, G.V.

    1997-12-01

    The authors recently compiled and reviewed the literature published in or after 1978 for 45 major, minor, and trace elements in human teeth as a part of an International Atomic Energy Agency (IAEA) study. The purpose of this paper is to discuss the various factors that influence the concentration levels of certain trace elements in human teeth. The sampling practices and analytical techniques that are applicable for trace element analysis are also discussed. It is also our intention to identify reference range of values, where data permit such conclusions. The scrutiny was designed to identify only the healthy permanent teeth, and values from teeth with fillings, caries, or periodontal diseases were eliminated.

  20. Environmental influence on trace element levels in human hair

    SciTech Connect

    Limic, N.; Valkovic, V.

    1986-12-01

    Trace element content of human hair depends on many factors. It has been shown by a large number of investigators that environmental factors play an important role. Elements from air particulates, water, shampoo or other media get incorporated into the hair structure. Here a model is proposed in which different contributions to trace element levels in human hair are factorized and the environmental contribution to the radial and longitudinal concentration profiles can be calculated. With the proper understanding of environmental contamination, hair analysis has better chances of being used as a diagnostic tool.

  1. Elemental concentration distribution in human fingernails - A 3D study

    NASA Astrophysics Data System (ADS)

    Pineda-Vargas, C. A.; Mars, J. A.; Gihwala, D.

    2012-02-01

    The verification of pathologies has normally been based on analysis of blood (serum and plasma), and physiological tissue. Recently, nails and in particular human fingernails have become an important medium for pathological studies, especially those of environmental origin. The analytical technique of PIXE has been used extensively in the analysis of industrial samples and human tissue specimens. The application of the analytical technique to nails has been mainly to bulk samples. In this study we use micro-PIXE and -RBS, as both complementary and supplementary, to determine the elemental concentration distribution of human fingernails of individuals. We report on the 3D quantitative elemental concentration distributions (QECDs) of various elements that include C, N and O as major elements (10-20%), P, S, Cl, K and Ca as minor elements (1-10%) and Fe, Mn, Zn, Ti, Na, Mg, Cu, Ni, Cr, Rb, Br, Sr and Se as trace elements (less than 1%). For PIXE and RBS the specimens were bombarded with a 3 MeV proton beam. To ascertain any correlations in the quantitative elemental concentration distributions, a linear traverse analysis was performed across the width of the nail. Elemental distribution correlations were also obtained.

  2. Soviet space flight: the human element.

    PubMed

    Garshnek, V

    1988-05-01

    Building on past experience and knowledge, the Soviet manned space flight effort has become broad, comprehensive, and forward-looking. Their long-running space station program has provided the capabilities to investigate long-term effects of microgravity on human physiology and behavior and test various countermeasures against microgravity-induced physiological deconditioning. Since the beginning of Soviet manned space flight, the biomedical training and preparation of cosmonauts has evolved from a process that increased human tolerance to space flight factors, to a system of interrelated measures to prepare cosmonauts physically and psychologically to live and work in space. Currently, the Soviet Union is constructing a multimodular space station, the Mir. With the emergence of dedicated laboratory modules, the Soviets have begun the transition from small-scale experimental research to large-scale production activities and specialized scientific work in space. In the future, additional laboratory modules will be added, including one dedicated to biomedical research, called the "Medilab." The longest manned space flight to date (326 days) has been completed by the Soviets. The biomedical effects of previous long-duration flights, and perhaps those of still greater length, may contribute important insight ito the possibility of extended missions beyond Earth, such as a voyage to Mars. PMID:11589234

  3. Soviet space flight: the human element.

    PubMed

    Garshnek, V

    1989-07-01

    Building on past experience and knowledge, the Soviet manned space flight effort has become broad, comprehensive, and forward-looking. Their long-running space station program has provided the capabilities to investigate long-term effects of microgravity on human physiology and behavior, and test various countermeasures against microgravity-induced physiological deconditioning. Since the beginning of Soviet manned space flight, the biomedical training and preparation of cosmonauts has evolved from a process that increased human tolerance to space flight factors, to a system of interrelated measures to prepare cosmonauts physically and psychologically to live and work in space. Currently, the Soviet Union is constructing a multimodular space station, the Mir. With the emergence of dedicated laboratory modules, the Soviets have begun the transition from small-scale experimental research to large-scale production activities and specialized scientific work in space. In the future, additional laboratory modules will be added, including one dedicated to biomedical research, called the "Medilab." The longest manned space flight to date (326 d) has been completed by the Soviets. The biomedical effects of previous long-duration flights, and perhaps those of still greater length, may contribute important insight into the possibility of extended missions beyond Earth, such as a voyage to Mars. PMID:2764853

  4. Autonomy and the human element in space

    NASA Technical Reports Server (NTRS)

    1985-01-01

    NASA is contemplating the next logical step in the U.S. space program - the permanent presence of humans in space. As currently envisioned, the initial system, planned for the early 1990's, will consist of manned and unmanned platforms situated primarily in low Earth orbit. The manned component will most likely be inhabited by 6-8 crew members performing a variety of tasks such as materials processing, satellite servicing, and life science experiments. The station thus has utility in scientific and commercial enterprises, in national security, and in the development of advanced space technology. The technical foundations for this next step have been firmly established as a result of unmanned spacecraft missions to other planets, the Apollo program, and Skylab. With the shuttle, NASA inaugurates a new era of frequent flights and more routine space operations supporting a larger variety of missions. A permanently manned space system will enable NASA to expand the scope of its activities still further. Since NASA' s inception there has been an intense debate over the relative merits of manned and unmanned space systems. Despite the generally higher costs associated with manned components, astronauts have accomplished numerous essential, complex tasks in space. The unique human talent to evaluate and respond inventively to unanticipated events has been crucial in many missions, and the presence of crews has helped arouse and sustain public interest in the space program. On the other hand, the hostile orbital environment affects astronaut physiology and productivity, is dangerous, and mandates extensive support systems. Safety and cost factors require the entire station complex, both space and ground components, to be highly automated to free people from mundane operational chores. Recent advances in computer technology, artificial intelligence (AI), and robotics have the potential to greatly extend space station operations, offering lower costs and superior

  5. Flank tectonics of Martian volcanoes

    SciTech Connect

    Thomas, P.J. ); Squyres, S.W. ); Carr, M.H. )

    1990-08-30

    On the flanks of Olympus Mons is a series of terraces, concentrically distributed around the caldera. Their morphology and location suggest that they could be thrust faults caused by compressional failure of the cone. In an attempt to understand the mechanism of faulting and the possible influences of the interior structure of Olympus Mons, the authors have constructed a numerical model for elastic stresses within a Martian volcano. In the absence of internal pressurization, the middle slopes of the cone are subjected to compressional stress, appropriate to the formation of thrust faults. These stresses for Olympus Mons are {approximately}250 MPa. If a vacant magma chamber is contained within the cone, the region of maximum compressional stress is extended toward the base of the cone. If the magma chamber is pressurized, extensional stresses occur at the summit and on the upper slopes of the cone. For a filled but unpressurized magma chamber, the observed positions of the faults agree well with the calculated region of high compressional stress. Three other volcanoes on Mars, Ascraeus Mons, Arsia Mons, and Pavonis Mons, possess similar terraces. Extending the analysis to other Martian volcanoes, they find that only these three and Olympus Mons have flank stresses that exceed the compressional failure strength of basalt, lending support to the view that the terraces on all four are thrust faults.

  6. "Reverse Genomics" Predicts Function of Human Conserved Noncoding Elements.

    PubMed

    Marcovitz, Amir; Jia, Robin; Bejerano, Gill

    2016-05-01

    Evolutionary changes in cis-regulatory elements are thought to play a key role in morphological and physiological diversity across animals. Many conserved noncoding elements (CNEs) function as cis-regulatory elements, controlling gene expression levels in different biological contexts. However, determining specific associations between CNEs and related phenotypes is a challenging task. Here, we present a computational "reverse genomics" approach that predicts the phenotypic functions of human CNEs. We identify thousands of human CNEs that were lost in at least two independent mammalian lineages (IL-CNEs), and match their evolutionary profiles against a diverse set of phenotypes recently annotated across multiple mammalian species. We identify 2,759 compelling associations between human CNEs and a diverse set of mammalian phenotypes. We discuss multiple CNEs, including a predicted ear element near BMP7, a pelvic CNE in FBN1, a brain morphology element in UBE4B, and an aquatic adaptation forelimb CNE near EGR2, and provide a full list of our predictions. As more genomes are sequenced and more traits are annotated across species, we expect our method to facilitate the interpretation of noncoding mutations in human disease and expedite the discovery of individual CNEs that play key roles in human evolution and development. PMID:26744417

  7. Trace elements in human hair: an international comparison

    SciTech Connect

    Takagi, Y.; Matsuda, S.; Imai, S.; Ohmori, Y.; Masuda, T.; Vinson, J.A.; Mehra, M.C.; Puri, B.K.; Kaniewski, A.

    1986-06-01

    Hair as a biological tissue is unique in the sense that it serves as an accumulator for trace elements, and in addition, it is formed in relatively short period of time and remains isolated from the metabolic events in the human body. In view of the interest in the distribution of trace elements in human hair an international survey was conducted to study their distribution in populations of different origin. Hair samples drawn from North America (USA, Canada), Europe (Poland) and Asia (Japan and India) were analyzed for 21 trace elements. An attempt was also made to observe a correlation, if any, between elemental concentration, age, sex and living habits of the individuals in a particular country.

  8. Determination of positions of optical elements of the human eye

    SciTech Connect

    Galetskii, S O; Cherezova, T Yu

    2009-02-28

    An original method for noninvasive determining the positions of elements of intraocular optics is proposed. The analytic dependence of the measurement error on the optical-scheme parameters and the restriction in distance from the element being measured are determined within the framework of the method proposed. It is shown that the method can be efficiently used for determining the position of elements in the classical Gullstrand eye model and personalised eye models. The positions of six optical surfaces of the Gullstrand eye model and four optical surfaces of the personalised eye model can be determined with an error of less than 0.25 mm. (human eye optics)

  9. Flank tectonics of Martian volcanoes

    NASA Technical Reports Server (NTRS)

    Thomas, Paul J.; Squyres, Steven W.; Carr, Michael H.

    1990-01-01

    The origin of the numerous terraces on the flanks of the Olympus Mons volcano on Mars, seen on space images to be arranged in a roughly concentric pattern, is investigated. The images of the volcano show that the base of each terrace is marked by a modest but abrupt change in slope, suggesting that these terraces could be thrust faults caused by a compressional failure of the cone. The mechanism of faulting and the possible effect of the interior structure of Olympus Mons was investigated using a numerical model for elastic stresses within a Martian volcano, constructed for that purpose. Results of the analysis supports the view that the terraces on Olympus Mons, as well as on other three Martian volcanoes, including Ascraeus Mons, Arsia Mons, and Pavonis Mons are indeed thrust faults.

  10. Improvement and induction property of radiation-responsive promoter through DNA shuffling of 5′-flanking regions of the human p21 gene

    PubMed Central

    Kagiya, Go; Ogawa, Ryohei; Cook, John A.; Choudhuri, Rajani; Hatashita, Masanori; Tanaka, Yoshikazu; DeGraff, Bill G.; Mitchell, James B.

    2010-01-01

    A promoter that augments gene expression in response to stimulation of ionizing radiation would be a desired tool for radiogenetic therapy, a combination of radiotherapy and gene therapy. Although various promoters occurring naturally or artificially have been used for researches, one showing higher reactivity to ionizing radiation is desirable. In the present study, we attempted to improve a radiation-responsive promoter of the p21 through a technique called DNA shuffling. A library of DNA fragments was constructed by re-ligation of randomly digested promoter fragments and improved promoters were chosen out of the library. We repeated this process twice to obtain a promoter showing 2.6 fold better reactivity to ionizing radiation compared with its parent, p21 promoter after 10 Gy γ-ray irradiation. Nucleotide sequence analyses revealed that the obtained promoter was densely packed with some of the cis-acting elements including binding sites for p53, NF-κB, NRF-2, AP-1 and NF-Y more than p21 promoter. In addition, it was shown that its induction by ionizing radiation was dependent upon p53 status of a cell line, suggesting that the promoter retained properties of the p21 promoter. This technique is simple and efficient to improve a promoter responsive to other stimulus of interest besides IR. PMID:20541129

  11. Lessons Learned Concerning the Human Element in Events and Training

    SciTech Connect

    Michael D. Sandvig

    2006-02-01

    As the number and complexity of responses to hazardous material incidents have increased, government regulators have implemented a national incident command system, bolstered by a host of protective measures and response equipment. Special advanced technical equipment has also been developed and made available to on-scene responders and command staff. Yet with all the investment in organizational and technical advance, the human element of emergency response remains critical and also needs our continued attention to ensure effective operation and success. This paper focuses on lessons learned from radiological events and training exercises that pertain to these human elements.

  12. Oxygen-evoked changes in transcriptional activity of the 5'-flanking region of the human amiloride-sensitive sodium channel (alphaENaC) gene: role of nuclear factor kappaB.

    PubMed Central

    Baines, Deborah L; Janes, Mandy; Newman, David J; Best, Oliver G

    2002-01-01

    Expression of the alpha-subunit of the amiloride-sensitive sodium channel (alphaENaC) is regulated by a number of factors in the lung, including oxygen partial pressure (PO2). As transcriptional activation is a mechanism for raising cellular mRNA levels, we investigated the effect of physiological changes in PO2 on the activity of the redox-sensitive transcription factor nuclear factor kappaB (NF-kappaB) and transcriptional activity of 5'-flanking regions of the human alphaENaC gene using luciferase reporter-gene vectors transiently transfected into human adult alveolar carcinoma A549 cells. By Western blotting we confirmed the presence of NF-kappaB p65 but not p50 in these cells. Transiently increasing PO2 from 23 to 42 mmHg for 24 h evoked a significant increase in NF-kappaB DNA-binding activity and transactivation of a NF-kappaB-driven luciferase construct (pGLNF-kappaBpro), which was blocked by the NF-kappaB activation inhibitor sulphasalazine (5 mM). Transcriptional activity of alphaENaC-luciferase constructs containing 5'-flanking sequences (including the NF-kappaB consensus) were increased by raising PO2 from 23 to 142 mmHg if they contained transcriptional initiation sites (TIS) for exons 1A and 1B (pGL3E2.2) or the 3' TIS of exon 1B alone (pGL3E0.8). Sulphasalazine had no significant effect on the activity of these constructs, suggesting that the PO2-evoked rise in activity was not a direct consequence of NF-kappaB activation. Conversely, the relative luciferase activity of a construct that lacked the 3' TIS, a 3' intron and splice site but still retained the 5' TIS and NF-kappaB consensus sequence was suppressed significantly by raising PO2. This effect was reversed by sulphasalazine, suggesting that activation of NF-kappaB mediated PO2-evoked suppression of transcription from the exon 1A TIS of alphaENaC. PMID:12023897

  13. Human Geophagia, Calabash Chalk and Undongo: Mineral Element Nutritional Implications

    PubMed Central

    Abrahams, Peter W.; Davies, Theo C.; Solomon, Abiye O.; Trow, Amanda J.; Wragg, Joanna

    2013-01-01

    The prime aim of our work is to report and comment on the bioaccessible concentrations – i.e., the soluble content of chemical elements in the gastrointestinal environment that is available for absorption – of a number of essential mineral nutrients and potentially harmful elements (PHEs) associated with the deliberate ingestion of African geophagical materials, namely Calabash chalk and Undongo. The pseudo-total concentrations of 13 mineral nutrients/PHEs were quantified following a nitric-perchloric acid digestion of nine different Calabash chalk samples, and bioaccessible contents of eight of these chemical elements were determined in simulated saliva/gastric and intestinal solutions obtained via use of the Fed ORganic Estimation human Simulation Test (FOREhST) in vitro procedure. The Calabash chalk pseudo-total content of the chemical elements is often below what may be regarded as average for soils/shales, and no concentration is excessively high. The in vitro leachate solutions had concentrations that were often lower than those of the blanks used in our experimental procedure, indicative of effective adsorption: lead, a PHE about which concern has been previously raised in connection with the consumption of Calabash chalk, was one such chemical element where this was evident. However, some concentrations in the leachate solutions are suggestive that Calabash chalk can be a source of chemical elements to humans in bioaccessible form, although generally the materials appear to be only a modest supplier: this applies even to iron, a mineral nutrient that has often been linked to the benefits of geophagia in previous academic literature. Our investigations indicate that at the reported rates of ingestion, Calabash chalk on the whole is not an important source of mineral nutrients or PHEs to humans. Similarly, although Undongo contains elevated pseudo-total concentrations of chromium and nickel, this soil is not a significant source to humans for any of the

  14. Allelic ladder characterization of the short tandem repeat polymorphism located in the 5{prime} flanking region to the human coagulation factor XIII A subunit gene

    SciTech Connect

    Puers, C.; Lins, A.M.; Sprecher, C.J.

    1994-09-01

    The short tandem repeat (STR) polymorphism present within the 5{prime} untranslated region of the human coagulation factor XIII A subunit gene, HUM-F13A01 [AAAG]{sub n}, was evaluated using an allelic ladder, i.e., a standard size marker consisting of amplified alleles from the locus. The allelic ladder was constructed by pooling 12 polymerase chain reaction (PCR)-amplified alleles identified by their differential migration in denaturing polyacrylamide gel electrophoresis. This standard marker was used to distinguish 14 different alleles observed at this locus. Sequence analyses indicate that 13 of the alleles contain 4 through 16 iterations of the tandemly repeated AAAG sequence, respectively. The remaining allele carries four repeats and displays a deletion of two consecutive nucleotides (GT), one base distal to the repeat region. The allelic ladder was employed to type 326 F13A01 chromosomes rapidly and reliably in representatives of a German Caucasian population. Population data were analyzed with respect to Hardy-Weinberg Equilibrium (HWE) and compared with those of a previously studied Houston, Texas, Caucasian population. 27 refs., 2 figs., 1 tab.

  15. Toward the Human Element. Beginning Handbook for Change. Volume I.

    ERIC Educational Resources Information Center

    Prince, Gerald; And Others

    The primary aim of this handbook is to encourage and stimulate growth and renewal of the "human element" within the school environment. Four processes form the objectives that are fundamental to achieving this goal: problem solving, shared decision making, open communications, and accountability. Skills in these four processes are discussed in…

  16. An integrated encyclopedia of DNA elements in the human genome.

    PubMed

    2012-09-01

    The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. PMID:22955616

  17. An Integrated Encyclopedia of DNA Elements in the Human Genome

    PubMed Central

    2012-01-01

    Summary The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure, and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall the project provides new insights into the organization and regulation of our genes and genome, and an expansive resource of functional annotations for biomedical research. PMID:22955616

  18. Human tracking using a two-element antenna array

    NASA Astrophysics Data System (ADS)

    Lin, Adrian; Ling, Hao

    2005-05-01

    We investigate the use of a low-cost, two-element receiving array for tracking human movements in indoor surveillance applications. Conventional direction of arrival (DOA) detection requires the use of an antenna array with multiple elements. Here we investigate the use of only two elements in the receiver array. The concept entails simultaneously resolving the Doppler frequencies of the returned signals from the moving targets and the DOA of the targets. Simulation is performed to demonstrate the concept. Both the monostatic and the bistatic scenario where the transmitter and the receiving array are placed at different locations are investigated. DOA errors and tolerances are analyzed for each scenario. An experimental system is constructed to test the concept. The system consists of a two-element receiver array operating at 2.4 GHz. Measurement results of various collection scenarios are presented.

  19. The human papillomavirus type 16 E2 transcription factor binds with low cooperativity to two flanking sites and represses the E6 promoter through displacement of Sp1 and TFIID.

    PubMed Central

    Tan, S H; Leong, L E; Walker, P A; Bernard, H U

    1994-01-01

    The E6 promoters of all genital human papillomaviruses have a characteristic alignment of transcription factor binding sites. Activation of the basic transcription complex at the TATA box depends upon a sequence-aberrant Sp1 site. Repression of E6 promoters is achieved by two binding sites for the viral E2 protein positioned between the Sp1 site and the TATA box. We have purified the human papillomavirus type 16 E2 protein after expression in Escherichia coli and studied its binding and repression properties with oligonucleotides representing the homologous promoter sequences. A Kd value of 3 x 10(-10) M indicated binding properties expected for a native protein. We found low cooperativity in the binding of two E2 dimers to flanking sites, both when these sites were separated by 3 nucleotides, as in the natural promoter, and when they were further apart. E2 protein, bound close to the distal Sp1 site, displaced the Sp1 factor even when the aberrant sequence was replaced by a typical Sp1 core recognition site. The high affinity of E2 protein for its binding site even led to Sp1 displacement at concentrations of E2 protein nearly 2 orders of magnitude lower than those of Sp1. Functional analyses of mutated E6 promoter sequences showed repression by this distal E2 binding site in the complete absence of binding to the proximal E2 binding site. From our findings and observations published by others, we conclude that each of the E2 binding sites in the E6 promoter of genital human papillomaviruses plays a separate role by displacing the transcription factors Sp1 and TFIID. Images PMID:8083979

  20. Human Exposure and Health Effects of Inorganic and Elemental Mercury

    PubMed Central

    Zheng, Wei

    2012-01-01

    Mercury is a toxic and non-essential metal in the human body. Mercury is ubiquitously distributed in the environment, present in natural products, and exists extensively in items encountered in daily life. There are three forms of mercury, i.e., elemental (or metallic) mercury, inorganic mercury compounds, and organic mercury compounds. This review examines the toxicity of elemental mercury and inorganic mercury compounds. Inorganic mercury compounds are water soluble with a bioavailability of 7% to 15% after ingestion; they are also irritants and cause gastrointestinal symptoms. Upon entering the body, inorganic mercury compounds are accumulated mainly in the kidneys and produce kidney damage. In contrast, human exposure to elemental mercury is mainly by inhalation, followed by rapid absorption and distribution in all major organs. Elemental mercury from ingestion is poorly absorbed with a bioavailability of less than 0.01%. The primary target organs of elemental mercury are the brain and kidney. Elemental mercury is lipid soluble and can cross the blood-brain barrier, while inorganic mercury compounds are not lipid soluble, rendering them unable to cross the blood-brain barrier. Elemental mercury may also enter the brain from the nasal cavity through the olfactory pathway. The blood mercury is a useful biomarker after short-term and high-level exposure, whereas the urine mercury is the ideal biomarker for long-term exposure to both elemental and inorganic mercury, and also as a good indicator of body burden. This review discusses the common sources of mercury exposure, skin lightening products containing mercury and mercury release from dental amalgam filling, two issues that happen in daily life, bear significant public health importance, and yet undergo extensive debate on their safety. PMID:23230464

  1. Computer-integrated finite element modeling of human middle ear.

    PubMed

    Sun, Q; Gan, R Z; Chang, K-H; Dormer, K J

    2002-10-01

    The objective of this study was to produce an improved finite element (FE) model of the human middle ear and to compare the model with human data. We began with a systematic and accurate geometric modeling technique for reconstructing the middle ear from serial sections of a freshly frozen temporal bone. A geometric model of a human middle ear was constructed in a computer-aided design (CAD) environment with particular attention to geometry and microanatomy. Using the geometric model, a working FE model of the human middle ear was created using previously published material properties of middle ear components. This working FE model was finalized by a cross-calibration technique, comparing its predicted stapes footplate displacements with laser Doppler interferometry measurements from fresh temporal bones. The final FE model was shown to be reasonable in predicting the ossicular mechanics of the human middle ear. PMID:14595544

  2. Transposable element insertions have strongly affected human evolution

    PubMed Central

    Britten, Roy J.

    2010-01-01

    Comparison of a full collection of the transposable element (TE) sequences of vertebrates with genome sequences shows that the human genome makes 655 perfect full-length matches. The cause is that the human genome contains many active TEs that have caused TE inserts in relatively recent times. These TE inserts in the human genome are several types of young Alus (AluYa5, AluYb8, AluYc1, etc.). Work in many laboratories has shown that such inserts have many effects including changes in gene expression, increases in recombination, and unequal crossover. The time of these very effective changes in the human lineage genome extends back about 4 million years according to these data and very likely much earlier. Rapid human lineage-specific evolution, including brain size is known to have also occurred in the last few million years. Alu insertions likely underlie rapid human lineage evolution. They are known to have many effects. Examples are listed in which TE sequences have influenced human-specific genes. The proposed model is that the many TE insertions created many potentially effective changes and those selected were responsible for a part of the striking human lineage evolution. The combination of the results of these events that were selected during human lineage evolution was apparently effective in producing a successful and rapidly evolving species. PMID:21041622

  3. Efficient transcription of the human angiotensin II type 2 receptor gene requires intronic sequence elements.

    PubMed Central

    Warnecke, C; Willich, T; Holzmeister, J; Bottari, S P; Fleck, E; Regitz-Zagrosek, V

    1999-01-01

    To investigate mechanisms of human angiotensin II type 2 receptor (hAT2) gene regulation we functionally characterized the promoter and downstream regions of the gene. 5'-Terminal deletion mutants from -1417/+100 to -46/+100 elicited significant but low functional activity in luciferase reporter gene assays with PC12W cells. Inclusion into the promoter constructs of intron 1 and the transcribed region of the hAT2 gene up to the translation start enhanced luciferase activity 6.7+/-1.6-fold and 11.6+/-1.7-fold (means+/-S.E.M.) respectively, whereas fusion of the promoter to the spliced 5' untranslated region of hAT2 cDNA did not, which indicated an enhancement caused by intronic sequence elements. Reverse transcriptase-mediated PCR confirmed that the chimaeric hAT2-luciferase mRNA was regularly spliced in PC12W cells. A Northern blot analysis of transfected cells showed levels of luciferase mRNA expression consistent with the respective enzyme activities. Mapping of intron 1 revealed that a 12 bp sequence in the centre of the intron was required for the increase in promoter activity, whereas the 5' adjacent intronic region mediated a decrease in luciferase activity. Mutation of the 12 bp region led to altered protein binding and markedly decreased luciferase activity. Cloned into a promoterless luciferase vector, a 123 bp intron 1 fragment was able to direct reporter gene expression to the same activity as occurred in conjunction with the 5' flanking region. These results indicate that sequence elements in intron 1 are necessary for efficient transcription of hAT2. In reporter gene assays, intron 1 might by itself function as a promoter and initiate transcription from an alternative start point. PMID:10229654

  4. Essential and toxic elements in seaweeds for human consumption.

    PubMed

    Desideri, D; Cantaluppi, C; Ceccotto, F; Meli, M A; Roselli, C; Feduzi, L

    2016-01-01

    Essential elements (K, Ca, P, S, Cl, Mn, Fe, Cu, Zn, Ni, Br, and I) and nonessential or toxic elements (Al, Ti, Si, Rb, Sr, As, Cd, Sn, and Pb) were determined by energy-dispersive polarized x-ray fluorescence spectrometry in 14 seaweeds purchased in local specialty stores in Italy and consumed by humans. The differences in elements between the algae species reached up to 2-4 orders of magnitude. Lithothamnium calcareum showed the highest levels of Ca, Al, Si, Fe, and Ti. Palmaria palmata showed the highest concentrations of K, Rb, and Cl. The highest content of S was in Chondrus crispus. Laminaria digitata contained the highest concentrations of total As, Cd, Sn, Br, and I. The highest concentration of Zn was in Chlorella pyrenoidosa. Ulva lactuca displayed the highest levels of Cu, Ni, Mn, and Pb. Iodine levels ranged from 3.4 in Chlorella pyrenoidosa to 7316 mg/kg(dry) in Laminaria digitata. The nutrimental importance of essential elements was assessed using nutritional requirements. The results showed that the consumption of algae might serve as an important source of the essential elements. Health risk due to the toxic elements present in seaweed was estimated using risk estimators. Total As, Cd, and Pb concentrations ranged from <1 to 67.6, to 7.2 and to 6.7 mg/kg(dry) respectively; therefore, their contribution to total elemental intake does not appear to pose any threat to the consumers, but the concentrations of these elements should be controlled to protect the consumer against potential adverse health risks. PMID:26817952

  5. Defining functional DNA elements in the human genome

    PubMed Central

    Kellis, Manolis; Wold, Barbara; Snyder, Michael P.; Bernstein, Bradley E.; Kundaje, Anshul; Marinov, Georgi K.; Ward, Lucas D.; Birney, Ewan; Crawford, Gregory E.; Dekker, Job; Dunham, Ian; Elnitski, Laura L.; Farnham, Peggy J.; Feingold, Elise A.; Gerstein, Mark; Giddings, Morgan C.; Gilbert, David M.; Gingeras, Thomas R.; Green, Eric D.; Guigo, Roderic; Hubbard, Tim; Kent, Jim; Lieb, Jason D.; Myers, Richard M.; Pazin, Michael J.; Ren, Bing; Stamatoyannopoulos, John A.; Weng, Zhiping; White, Kevin P.; Hardison, Ross C.

    2014-01-01

    With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease. PMID:24753594

  6. A knowledgebase of the human Alu repetitive elements.

    PubMed

    Mallona, Izaskun; Jordà, Mireia; Peinado, Miguel A

    2016-04-01

    Alu elements are the most abundant retrotransposons in the human genome with more than one million copies. Alu repeats have been reported to participate in multiple processes related with genome regulation and compartmentalization. Moreover, they have been involved in the facilitation of pathological mutations in many diseases, including cancer. The contribution of Alus and other repeats in genomic regulation is often overlooked because their study poses technical and analytical challenges hardly attainable with conventional strategies. Here we propose the integration of ontology-based semantic methods to query a knowledgebase for the human Alus. The knowledgebase for the human Alus leverages Sequence (SO) and Gene Ontologies (GO) and is devoted to address functional and genetic information in the genomic context of the Alus. For each Alu element, the closest gene and transcript are stored, as well their functional annotation according to GO, the state of the chromatin and the transcription factors binding sites inside the Alu. The model uses Web Ontology Language (OWL) and Semantic Web Rule Language (SWRL). As a case of use and to illustrate the utility of the tool, we have evaluated the epigenetic states of Alu repeats associated with gene promoters according to their transcriptional activity. The ontology is easily extendable, offering a scaffold for the inclusion of new experimental data. The RDF/XML formalization is freely available at http://aluontology.sourceforge.net/. PMID:26827622

  7. Have humans lost control: The elusive X-controlling element.

    PubMed

    Peeters, Samantha B; Yang, Christine; Brown, Carolyn J

    2016-08-01

    The process of X-chromosome inactivation (XCI) randomly silences one of two X chromosomes in normal female cells. The ability to predict if there is a preference for one of the two Xs to be chosen (and survive) more often as the active X has important repercussions in human health and X-linked disease. Mice have a genetic component that modulates non-random skewing called the X-controlling element (Xce). Although the nature of the locus and its mechanisms of action are still under investigation, it is clear that different mouse strains carry unique Xce alleles on their X chromosomes, resulting in distinct skewing phenotypes in the F1 progeny of hybrid crosses. Whether a similar mechanism exists in humans is unclear, and challenges to identifying such a locus include the complexity and diversity of the human genome, the restricted time points and tissue(s) of examination in human subjects, and the lack of a model system recapitulating XCI in early development. In this review we consider the evidence for such a controlling locus in humans, in addition to discussing if we have the power to recognize it given the contribution of selective growth in causing skewed patterns of XCI. PMID:26849907

  8. NASA Human Research Program Space Radiation Program Element

    NASA Technical Reports Server (NTRS)

    Chappell, Lori; Huff, Janice; Patel, Janapriya; Wang, Minli; Hu, Shaowwen; Kidane, Yared; Myung-Hee, Kim; Li, Yongfeng; Nounu, Hatem; Plante, Ianik; Ponomarev, Artem; Hada, Megumi

    2013-01-01

    The goal of the NASA Human Research Program's Space Radiation Program Element is to ensure that crews can safely live and work in the space radiation environment. Current work is focused on developing the knowledge base and tools required for accurate assessment of health risks resulting from space radiation exposure including cancer and circulatory and central nervous system diseases, as well as acute risks from solar particle events. Division of Space Life Sciences (DSLS) Space Radiation Team scientists work at multiple levels to advance this goal, with major projects in biological risk research; epidemiology; and physical, biophysical, and biological modeling.

  9. Ubiquitous and neuronal DNA-binding proteins interact with a negative regulatory element of the human hypoxanthine phosphoribosyltransferase gene.

    PubMed Central

    Rincón-Limas, D E; Amaya-Manzanares, F; Niño-Rosales, M L; Yu, Y; Yang, T P; Patel, P I

    1995-01-01

    The hypoxanthine phosphoribosyltransferase (HPRT) gene is constitutively expressed at low levels in all tissues but at higher levels in the brain; the significance and mechanism of this differential expression are unknown. We previously identified a 182-bp element (hHPRT-NE) within the 5'-flanking region of the human HPRT (hHPRT) gene, which is involved not only in conferring neuronal specificity but also in repressing gene expression in nonneuronal tissues. Here we report that this element interacts with different nuclear proteins, some of which are present specifically in neuronal cells (complex I) and others of which are present in cells showing constitutive expression of the gene (complex II). In addition, we found that complex I factors are expressed in human NT2/D1 cells following induction of neuronal differentiation by retinoic acid. This finding correlates with an increase of HPRT gene transcription following neuronal differentiation. We also mapped the binding sites for both complexes to a 60-bp region (Ff; positions -510 to -451) which, when analyzed in transfection assays, functioned as a repressor element analogous to the full-length hHPRT-NE sequence. Methylation interference footprintings revealed a minimal unique DNA motif, 5'-GGAAGCC-3', as the binding site for nuclear proteins from both neuronal and nonneuronal sources. However, site-directed mutagenesis of the footprinted region indicated that different nucleotides are essential for the associations of these two complexes. Moreover, UV cross-linking experiments showed that both complexes are formed by the association of several different proteins. Taken together, these data suggest that differential interaction of DNA-binding factors with this regulatory element plays a crucial role in the brain-preferential expression of the gene, and they should lead to the isolation of transcriptional regulators important in neuronal expression of the HPRT gene. PMID:8524221

  10. Interactions between concentrations of chemical elements in human femoral heads.

    PubMed

    Brodziak-Dopierala, Barbara; Kwapulinski, Jerzy; Kusz, Damian; Gajda, Zbigniew; Sobczyk, Krzysztof

    2009-07-01

    Environmental and occupational exposure to various metals has been a major public health concern and the subject of many studies. With the development of industry and transportation, environmental pollution has markedly worsened. As a result, metals are now ubiquitous and are absorbed into the body with food, drinking water, and polluted air. Exposure to these elements leads to numerous health problems, affecting almost every system of the human body, including the skeletal system. Bone is a specific research material that is difficult to obtain, therefore chemical analyses of metal concentrations in this tissue are rarely found in the literature. Nevertheless, bone, due to its long regeneration period, can serve as a biomarker of a long-term metal accumulation resulting from environmental or occupational exposure. Our study was conducted on bone samples harvested from inhabitants of the Upper Silesia region during hip replacement surgery. Femoral heads removed during surgery were sectioned into slices and further subdivided into samples comprising articular cartilage, cortical bone, and trabecular bone. Concentrations of 12 trace elements were measured with an atomic absorption spectrophotometry method. We found significant correlation between concentrations of these metal elements in the samples of cortical bone. This is determined not only by the physiological functions of these metals in hydroxyapatite, but also by the specific mineral structure of the bone tissue. PMID:18776997

  11. Validation of a finite element model of the human metacarpal.

    PubMed

    Barker, D S; Netherway, D J; Krishnan, J; Hearn, T C

    2005-03-01

    Implant loosening and mechanical failure of components are frequently reported following metacarpophalangeal (MCP) joint replacement. Studies of the mechanical environment of the MCP implant-bone construct are rare. The objective of this study was to evaluate the predictive ability of a finite element model of the intact second human metacarpal to provide a validated baseline for further mechanical studies. A right index human metacarpal was subjected to torsion and combined axial/bending loading using strain gauge (SG) and 3D finite element (FE) analysis. Four different representations of bone material properties were considered. Regression analyses were performed comparing maximum and minimum principal surface strains taken from the SG and FE models. Regression slopes close to unity and high correlation coefficients were found when the diaphyseal cortical shell was modelled as anisotropic and cancellous bone properties were derived from quantitative computed tomography. The inclusion of anisotropy for cortical bone was strongly influential in producing high model validity whereas variation in methods of assigning stiffness to cancellous bone had only a minor influence. The validated FE model provides a tool for future investigations of current and novel MCP joint prostheses. PMID:15642506

  12. The hamster flank organ model: Is it relevant to man

    SciTech Connect

    Franz, T.J.; Lehman, P.A.; Pochi, P.; Odland, G.F.; Olerud, J. )

    1989-10-01

    The critical role that androgens play in the etiology of acne has led to a search for topically active antiandrogens and the frequent use of the flank organ of the golden Syrian hamster as an animal model. 17-alpha-propyltestosterone (17-PT) has been identified as having potent antiandrogenic activity in the hamster model, and this report describes its clinical evaluation. Two double-blind placebo controlled studies comparing 4% 17-PT in 80% alcohol versus vehicle alone were conducted. One study examined 17-PT sebosuppressive activity in 20 subjects. The second study examined its efficacy in 44 subjects having mild to moderate acne. A third study measured in vitro percutaneous absorption of 17-PT through hamster flank and monkey skin, and human face skin in-vivo, using radioactive drug. 17-PT was found to be ineffective in reducing either the sebum excretion rate or the number of inflammatory acne lesions. Failure of 17-PT to show clinical activity was not a result of poor percutaneous absorption. Total absorption in man was 7.7% of the dose and only 1.0% in the hamster. The sebaceous gland of hamster flank organ is apparently more sensitive to antiandrogens than the human sebaceous gland.

  13. Epigenetic regulation of transposable element derived human gene promoters.

    PubMed

    Huda, Ahsan; Bowen, Nathan J; Conley, Andrew B; Jordan, I King

    2011-04-01

    It was previously thought that epigenetic histone modifications of mammalian transposable elements (TEs) serve primarily to defend the genome against deleterious effects associated with their activity. However, we recently showed that, genome-wide, human TEs can also be epigenetically modified in a manner consistent with their ability to regulate host genes. Here, we explore the ability of TE sequences to epigenetically regulate individual human genes by focusing on the histone modifications of promoter sequences derived from TEs. We found 1520 human genes that initiate transcription from within TE-derived promoter sequences. We evaluated the distributions of eight histone modifications across these TE-promoters, within and between the GM12878 and K562 cell lines, and related their modification status with the cell-type specific expression patterns of the genes that they regulate. TE-derived promoters are significantly enriched for active histone modifications, and depleted for repressive modifications, relative to the genomic background. Active histone modifications of TE-promoters peak at transcription start sites and are positively correlated with increasing expression within cell lines. Furthermore, differential modification of TE-derived promoters between cell lines is significantly correlated with differential gene expression. LTR-retrotransposon derived promoters in particular play a prominent role in mediating cell-type specific gene regulation, and a number of these LTR-promoter genes are implicated in lineage-specific cellular functions. The regulation of human genes mediated by histone modifications targeted to TE-derived promoters is consistent with the ability of TEs to contribute to the epigenomic landscape in a way that provides functional utility to the host genome. PMID:21215797

  14. Human T-cell leukemia virus type 1 Tax activates transcription of the human fra-1 gene through multiple cis elements responsive to transmembrane signals.

    PubMed Central

    Tsuchiya, H; Fujii, M; Niki, T; Tokuhara, M; Matsui, M; Seiki, M

    1993-01-01

    We have shown that Tax1 of human T-cell leukemia virus type 1 stimulates the expression of several cellular immediate-early genes (M. Fujii, T. Niki, T. Mori, T. Matsuda, M. Matsui, N. Nomura, and M. Seiki, Oncogene 6:1023-1029, 1991). In this study, the 5'-flanking region of the human fra-1 gene, which is a Tax1-inducible fos-related gene, was isolated and Tax1 or serum-responsive cis elements were analyzed to obtain further insight into the mechanism of Tax1 action. The 62-bp sequence starting 46 nucleotides upstream from the translation initiation site showed 71% homology with the sequence surrounding the TATA box of the c-fos promoter. Regulatory motifs identified in the c-fos promoter, such as an Ets-binding site, E boxes, a CArG box, c-fos AP-1 sites, and two retinoblastoma control elements, were also found upstream of the c-fos homology region. A 502-bp fragment containing these motifs mediated transcriptional activation by Tax1 or by serum in a transient transfection assay. Three independent Tax1-responsive regions (TRRs) were identified, and mutations in each revealed that one of the retinoblastoma control elements in TRR1 and the c-fos AP-1 sites in TRR2 and TRR3 were essential for the activation. Although TRR2 contains a CArG box-like sequence, it was a weak binding site for p67SRF, if it bound at all, and was not required for activation. All three TRRs could also mediate the signals stimulated by serum. Thus, Tax1 appears to activate fra-1 gene expression by means of a part of the cellular machinery similar to that which mediates growth signals. Images PMID:8230424

  15. Human Health Countermeasures (HHC) Element Management Plan: Human Research Program. Revision B

    NASA Technical Reports Server (NTRS)

    Norsk, Peter; Baumann, David

    2012-01-01

    NASA s Human Research Program (HRP) is an applied research and technology program within the Human Exploration and Operations Mission Directorate (HEOMD) that addresses human health and performance risk mitigation strategies in support of exploration missions. The HRP research and technology development is focused on the highest priority risks to crew health and safety with the goal of ensuring mission success and maintaining long-term crew health. Crew health and performance standards, defined by the NASA Chief Health and Medical Officer (CHMO), set the acceptable risk level for exploration missions. The HRP conducts research to inform these standards as well as provide deliverables, such as countermeasures, that ensure standards can be met to maximize human performance and mission success. The Human Health Countermeasures (HHC) Element was formed as part of the HRP to develop a scientifically-based, integrated approach to understanding and mitigating the health risks associated with human spaceflight. These health risks have been organized into four research portfolios that group similar or related risks. A fifth portfolio exists for managing technology developments and infrastructure projects. The HHC Element portfolios consist of: a) Vision and Cardiovascular; b) Exercise and Performance; c) Multisystem; d) Bone; and e) Technology and Infrastructure. The HHC identifies gaps associated with the health risks and plans human physiology research that will result in knowledge required to more fully understand risks and will result in validated countermeasures to mitigate risks.

  16. Customized Finite Element Modelling of the Human Cornea

    PubMed Central

    Simonini, Irene; Pandolfi, Anna

    2015-01-01

    Aim To construct patient-specific solid models of human cornea from ocular topographer data, to increase the accuracy of the biomechanical and optical estimate of the changes in refractive power and stress caused by photorefractive keratectomy (PRK). Method Corneal elevation maps of five human eyes were taken with a rotating Scheimpflug camera combined with a Placido disk before and after refractive surgery. Patient-specific solid models were created and discretized in finite elements to estimate the corneal strain and stress fields in preoperative and postoperative configurations and derive the refractive parameters of the cornea. Results Patient-specific geometrical models of the cornea allow for the creation of personalized refractive maps at different levels of IOP. Thinned postoperative corneas show a higher stress gradient across the thickness and higher sensitivity of all geometrical and refractive parameters to the fluctuation of the IOP. Conclusion Patient-specific numerical models of the cornea can provide accurate quantitative information on the refractive properties of the cornea under different levels of IOP and describe the change of the stress state of the cornea due to refractive surgery (PRK). Patient-specific models can be used as indicators of feasibility before performing the surgery. PMID:26098104

  17. Volcano Flank Structures on Earth and Mars

    NASA Astrophysics Data System (ADS)

    van Wyk de Vries, B.; Byrne, P. K.; Mathieu, L.; Murray, J. B.; Troll, V. R.

    2007-12-01

    Shield volcanoes on Earth and Mars share common features, including calderas and pit crater chains. A set of structures present on the sides of several of the large shields on Mars are not regarded as having Earth analogues, however. Flank terraces are topographically subtle structures, characterised by a gentle convex profile and a distinctive "fish scale" imbricate distribution pattern. Magma chamber inflation, lithospheric flexure, flank relaxation, or gravitational slumping have been suggested as terrace formation mechanisms. Terraces on both Mars and Earth are clearly visible only in slope maps, and may thus escape visual detection in the field. We show that both Mauna Loa (Hawaii) and Etna (Sicily) display the same characteristic "fish scale" terrace pattern. This pattern delineates structures that we contend are terrestrial flank terraces. Heterogeneities in volcano geometry, due to buttressing or extension, result in terrace distributions that are not as evenly circumferential as those on Mars. Plan and cross-sectional profiles, however, parallel those of the Martian structures. These structures may also be present on Alayta (Ethiopia), Santa Cruz (Galapagos), and Tendürek Dagi (Turkey). Another type of structure, larger and steeper than flank terraces but sharing a similar plan-view morphology, is also present on Mauna Lau and Etna. These "flank bulges" appear to correlate with structures on Piton de la Fournaise (La Réunion), Cosiguina (Nicaragua), and Karthala (Comoros) on Earth, and Apollinaris Patera and Tharsis Tholus on Mars. Elsewhere (Paul K. Byrne et al., this volume) we argue that lithospheric flexure is a likely formation mechanism for Martian terraces. Flexure is active beneath Mauna Loa, and possibly under Etna, and so may also be responsible for terrestrial flank terraces. Scaled analogue models suggest that the larger flank bulges are due to magma intrusions derived from large chambers within these edifices. There is thus a strong

  18. Trace elements in human physiology and pathology: zinc and metallothioneins.

    PubMed

    Tapiero, Haim; Tew, Kenneth D

    2003-11-01

    Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes. PMID:14652165

  19. Understanding Etna flank instability through numerical models

    NASA Astrophysics Data System (ADS)

    Apuani, Tiziana; Corazzato, Claudia; Merri, Andrea; Tibaldi, Alessandro

    2013-02-01

    As many active volcanoes, Mount Etna shows clear evidence of flank instability, and different mechanisms were suggested to explain this flank dynamics, based on the recorded deformation pattern and character. Shallow and deep deformations, mainly associated with both eruptive and seismic events, are concentrated along recognised fracture and fault systems, mobilising the eastern and south-eastern flank of the volcano. Several interacting causes were postulated to control the phenomenon, including gravity force, magma ascent along the feeding system, and a very complex local and/or regional tectonic activity. Nevertheless, the complexity of such dynamics is still an open subject of research and being the volcano flanks heavily urbanised, the comprehension of the gravitative dynamics is a major issue for public safety and civil protection. The present research explores the effects of the main geological features (in particular the role of the subetnean clays, interposed between the Apennine-Maghrebian flysch and the volcanic products) and the role of weakness zones, identified by fracture and fault systems, on the slope instability process. The effects of magma intrusions are also investigated. The problem is addressed by integrating field data, laboratory tests and numerical modelling. A bi- and tri-dimensional stress-strain analysis was performed by a finite difference numerical code (FLAC and FLAC3D), mainly aimed at evaluating the relationship among geological features, volcano-tectonic structures and magmatic activity in controlling the deformation processes. The analyses are well supported by dedicated structural-mechanical field surveys, which allowed to estimate the rock mass strength and deformability parameters. To take into account the uncertainties which inevitably occur in a so complicated model, many efforts were done in performing a sensitivity analysis along a WNW-ESE section crossing the volcano summit and the Valle del Bove depression. This was

  20. Developmental regulation of the human embryonic beta-like globin gene is mediated by synergistic interactions among multiple tissue- and stage-specific elements.

    PubMed Central

    Trepicchio, W L; Dyer, M A; Baron, M H

    1993-01-01

    The stage-specific regulation of mammalian embryonic globin genes has been an experimentally elusive problem, in part because of the developmentally early timing of their expression. We have carried out a systematic analysis of truncation and internal deletion mutations within the 5'-flanking region of the human embryonic beta-like globin gene (epsilon) in erythroid and nonerythroid cell lines. Within a 670-bp region upstream from the constitutive promoter are multiple positive and negative control elements. Of these, a positive regulatory element (epsilon-PRE II) which is active only in embryonic erythroid cells is of particular interest. Remarkably, although it is inactive on its own, in the presence of other sequences located further upstream, it confers tissue- and developmental stage-specific expression on a constitutive epsilon-globin or heterologous promoter. The activity of epsilon-PRE II is also modulated by another positive regulatory domain located further downstream to direct erythroid cell-specific, but little or no embryonic stage-specific, transcription. A nuclear factor highly enriched in embryonic erythroid cells binds specifically within a 19-bp region of epsilon-PRE II. Nuclei from adult erythroid cells also contain a factor that binds to this region but forms a complex of faster electrophoretic mobility. We speculate that interactions between epsilon-PRE II and other upstream control elements play an important role in the developmental regulation of the human embryonic beta-like globin gene. Images PMID:8246963

  1. HUMAN SCALP HAIR: AN ENVIRONMENTAL EXPOSURE INDEX FOR TRACE ELEMENTS. II. SEVENTEEN TRACE ELEMENTS IN FOUR NEW JERSEY COMMUNITIES (1972)

    EPA Science Inventory

    Seventeen trace elements - arsenic (As), barium (Ba), boron (B), cadmium (Cd), chromium (Cr), copper (Cu), Iron (Fe), lead (Pb), lithium (Li), manganese (Mn), mercury (Hg), nickle (Ni), selenium (Se), silver (Ag), tin (Sn), vanadium (V), and zinc (Zn) - were measured in human sca...

  2. West Flank Coso, CA FORGE Seismic Reflection

    DOE Data Explorer

    Doug Blankenship

    2016-05-16

    PDFs of seismic reflection profiles 101,110, 111 local to the West Flank FORGE site. 45 line kilometers of seismic reflection data are processed data collected in 2001 through the use of vibroseis trucks. The initial analysis and interpretation of these data was performed by Unruh et al. (2001). Optim processed these data by inverting the P-wave first arrivals to create a 2-D velocity structure. Kirchhoff images were then created for each line using velocity tomograms (Unruh et al., 2001).

  3. [Flank pain in renal and ureteral calculus].

    PubMed

    Pedersen, Katja Venborg; Drewes, Asbjørn Mohr; Osther, Palle Jørn Sloth

    2011-02-14

    Flank pain is common and often associated with stone colics. Similar pain characteristics can, however, be observed in other diseases. Stone colics have all the characteristics of visceral pain. The pain is diffuse, often referred to the body wall and accompanied by autonomic reflexes. In patients with recurrent stones, the colics may be more intense due to sensitisation of the nervous system. Furthermore, painful diseases in the reproductive organs can enhance stone colics. Non-steroidal anti-inflammatory drugs are the first choice for stone colics because they act by reducing the renal pelvic pressure. PMID:21320415

  4. PIXE analysis of elemental concentrations in human hair and nails

    NASA Astrophysics Data System (ADS)

    Paschoa, A. S.; Baptista, G. B.; Mauricio, G. M.; Leite, C. V. Barros; Lerner, Y. B.; Issler, P. F.

    1984-04-01

    The PIXE technique was applied to examine the elemental concentrations in scalp hair and nails collected over several months from three subjects living in Rio de Janeiro, Brazil. The results were then compared with data taken from the literature, and with the range and average elemental concentrations obtained by analyzing, using the same technique and laboratory conditions, samples of scalp hair taken from 51 men and 50 women living in another region of Latin America.

  5. Human Research Program Human Health Countermeasures Element Nutrition Risk Standing Review Panel

    NASA Technical Reports Server (NTRS)

    Bistrian, Bruce

    2009-01-01

    The Nutrition Risk Standing Review Panel (SRP) reviewed and discussed the specific gaps and tasks for the Human Health Countermeasures (HHC) Element related to nutrition identified in the Human Research Program (HRP) Integrated Research Plan. There was general consensus that the described gaps and proposed tasks were critical to future NASA mission success. The SRP acknowledged the high scientific quality of the work currently being undertaken by the Nutritional Biochemistry group under the direction of Dr. Scott Smith. In review of the entire HRP, four new gaps were identified that complement the Element's existing research activities. Given the limitations of ground-based analogs for many of the unique physiological and metabolic alterations in space, future studies are needed to quantify nutritional factors that change during actual space flight. In addition, future tasks should seek to better evaluate the time course of physiological and metabolic alterations during flight to better predict alterations during longer duration missions. Finally, given the recent data suggesting a potential role for increased inflammatory responses during space flight, the role of inflammation needs to be explored in detail, including the development of potential countermeasures and new ground based analogs, if this possibility is confirmed.

  6. Investigating the Partitioning of Inorganic Elements Consumed by Humans between the Various Fractions of Human Wastes: An Alternative Approach

    NASA Technical Reports Server (NTRS)

    Wignarajah, Kanapathipillai; Pisharody, Suresh; Fisher, John W.

    2003-01-01

    The elemental composition of food consumed by astronauts is well defined. The major elements carbon, hydrogen, oxygen, nitrogen and sulfur are taken up in large amounts and these are often associated with the organic fraction (carbohydrates, proteins, fats etc) of human tissue. On the other hand, a number of the elements are located in the extracellular fluids and can be accounted for in the liquid and solid waste fraction of humans. These elements fall into three major categories - cationic macroelements (e.g. Ca, K, Na, Mg and Si), anionic macroelements (e.g. P, S and Cl and 17 essential microelements, (e.g. Fe, Mn, Cr, Co, Cu, Zn, Se and Sr). When provided in the recommended concentrations to an adult healthy human, these elements should not normally accumulate in humans and will eventually be excreted in the different human wastes. Knowledge of the partitioning of these elements between the different human waste fractions is important in understanding (a) developing waste separation technologies, (b) decision-making on how these elements can be recovered for reuse in space habitats, and (c) to developing the processors for waste management. Though considerable literature exists on these elements, there is a lack of understanding and often conflicting data. Two major reasons for these problems include the lack of controlled experimental protocols and the inherently large variations between human subjects (Parker and Gallagher, 1988). We have used the existing knowledge of human nutrition and waste from the available literature and NASA documentation to build towards a consensus to typify and chemically characterize the various human wastes. It is our belief, that this could be a building block towards integrating a human life support and waste processing in a closed system.

  7. Characterization of the Nanog 5'-flanking Region in Bovine.

    PubMed

    Choi, Don-Ho; Kim, Duk-Jung; Song, Ki-Duk; Park, Hwan-Hee; Ko, Tae Hyun; Pyao, Yuliya; Chung, Ku-Min; Cha, Seok Ho; Sin, Young-Su; Kim, Nam-Hyung; Lee, Woon-Kyu

    2016-10-01

    Bovine embryonic stem cells have potential for use in research, such as transgenic cattle generation and the study of developmental gene regulation. The Nanog may play a critical role in maintenance of the undifferentiated state of embryonic stem cells in the bovine, as in murine and human. Nevertheless, efforts to study the bovine Nanog for pluripotency-maintaining factors have been insufficient. In this study, in order to understand the mechanisms of transcriptional regulation of the bovine Nanog, the 5'-flanking region of the Nanog was isolated from ear cells of Hanwoo. Results of transient transfection using a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the -134 to -19 region contained the positive regulatory sequences for the transcription of the bovine Nanog. Results from mutagenesis studies demonstrated that the Sp1-binding site that is located in the proximal promoter region plays an important role in transcriptional activity of the bovine Nanog promoter. The electrophoretic mobility shift assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. In addition, significant inhibition of Nanog promoter activity by the Sp1 mutant was observed in murine embryonic stem cells. Furthermore, chromatin-immunoprecipitation assay with the Sp1 specific antibody confirmed the specific binding of Sp1 transcription factor to this site. These results suggest that Sp1 is an essential regulatory factor for bovine Nanog transcriptional activity. PMID:27165025

  8. Human Research Program Human Health Countermeasures Element Extravehicular Activity (EVA) Risk Standing Review Panel (SRP)

    NASA Technical Reports Server (NTRS)

    Norfleet, William; Harris, Bernard

    2009-01-01

    The Extravehicular Activity (EVA) Risk Standing Review Panel (SRP) was favorably impressed by the operational risk management approach taken by the Human Research Program (HRP) Integrated Research Plan (IRP) to address the stated life sciences issues. The life sciences community at the Johnson Space Center (JSC) seems to be focused on operational risk management. This approach is more likely to provide risk managers with the information they need at the time they need it. Concerning the information provided to the SRP by the EVA Physiology, Systems, and Performance Project (EPSP), it is obvious that a great deal of productive activity is under way. Evaluation of this information was hampered by the fact that it often was not organized in a fashion that reflects the "Gaps and Tasks" approach of the overall Human Health Countermeasures (HHC) effort, and that a substantial proportion of the briefing concerned subjects that, while interesting, are not part of the HHC Element (e.g., the pressurized rover presentation). Additionally, no information was provided on several of the tasks or how they related to work underway or already accomplished. This situation left the SRP having to guess at the efforts and relationship to other elements, and made it hard to easily map the EVA Project efforts currently underway, and the data collected thus far, to the gaps and tasks in the IRP. It seems that integration of the EPSP project into the HHC Element could be improved. Along these lines, we were concerned that our SRP was split off from the other participating SRPs at an early stage in the overall agenda for the meeting. In reality, the concerns of EPSP and other projects share much common ground. For example, the commonality of the concerns of the EVA and exercise physiology groups is obvious, both in terms of what reduced exercise capacity can do to EVA capability, and how the exercise performed during an EVA could contribute to an overall exercise countermeasure prescription.

  9. Sequence specific generation of a DNA panhandle permits PCR amplification of unknown flanking DNA.

    PubMed Central

    Jones, D H; Winistorfer, S C

    1992-01-01

    We present a novel method for the PCR amplification of unknown DNA that flanks a known segment directly from human genomic DNA. PCR requires that primer annealing sites be present on each end of the DNA segment that is to be amplified. In this method, known DNA is placed on the uncharacterized side of the sequence of interest via DNA polymerase mediated generation of a PCR template that is shaped like a pan with a handle. Generation of this template permits specific amplification of the unknown sequence. Taq (DNA) polymerase was used to form the original template and to generate the PCR product. 2.2 kb of the beta-globin gene, and 657 bp of the 5' flanking region of the cystic fibrosis transmembrane conductance regulator gene, were amplified directly from human genomic DNA using primers that initially flank only one side of the region amplified. This method will provide a powerful tool for acquiring DNA sequence information. Images PMID:1371352

  10. West Flank Coso, CA FORGE Magnetotelluric Inversion

    DOE Data Explorer

    Doug Blankenship

    2016-05-16

    The Coso Magnetotelluric (MT) dataset of which the West Flank FORGE MT data is a subset, was collected by Schlumberger / WesternGeco and initially processed by the WesternGeco GeoSolutions Integrated EM Center of Excellence in Milan, Italy. The 2011 data was based on 99 soundings that were centered on the West Flank geothermal prospect. The new soundings along with previous data from 2003 and 2006 were incorporated into a 3D inversion. Full impedance tensor data were inverted in the 1-3000 Hz range. The modelling report notes several noise sources, specifically the DC powerline that is 20,000 feet west of the survey area, and may have affected data in the 0.02 to 10 Hz range. Model cell dimensions of 450 x 450 x 65 feet were used to avoid computational instability in the 3D model. The fit between calculated and observed MT values for the final model run had an RMS value of 1.807. The included figure from the WesternGeco report shows the sounding locations from the 2011, 2006 and 2003 surveys.

  11. [Excruciating flank pain: "acute renal colic"].

    PubMed

    Thomas, A; Andrianne, R

    2004-04-01

    The classic presentation of acute renal colic is the sudden onset of very severe pain in the flank primarily caused by the acute ureteral obstruction. The diagnosis is often made on clinical symptoms only, although confirmatory exams are generally performed because many others significant disorders may present with symptom of flank pain that mimics renal colic. Life threatening emergency such as abdominal aortic aneurysm must be ruled out. While non contrast CT has become the standard imaging modality, in some situations, a plain abdominal radiograph associated with a renal ultrasound or a contrast study such as intravenous pyelogram may be preferred. Hematuria is frequently present on urine analysis. The usual therapy represented by analgesic and nonsteroidal anti-inflammatory drugs should be started as soon as possible. Size and location of the stone are the most important predictors of spontaneous passage. Uncontrolled pain by medical therapy, fever, oligo-anuria suggest complicated stone disease. Such conditions require emergency treatment by drainage or stone extraction. Although recurrent stone rate is important, extensive metabolic explorations are not recommended after an uncomplicated first episode. Nevertheless fluid intake is encouraged and a stone chemical analysis should be performed whenever possible. PMID:15182032

  12. A similar 5'-flanking region is required for estrogen and progesterone induction of ovalbumin gene expression.

    PubMed

    Dean, D C; Gope, R; Knoll, B J; Riser, M E; O'Malley, B W

    1984-08-25

    We have previously transferred an ovalbumin-beta-globin fusion gene (ovalglobin) into primary cultures of chick oviduct cells and demonstrated that an ovalbumin gene 5'-flanking sequence between -221 and -95 is necessary for progesterone-mediated transcriptional induction (Dean, D. C., Knoll, B. J., Riser, M. E., and O'Malley, B. W. (1983) Nature (Lond.) 305, 551-554). Here we compare 5'-flanking sequences required for induction of the ovalglobin gene by 17 beta-estradiol and progesterone. The early gene of simian virus 40 was inserted into the same plasmid as the ovalbumin fusion gene to serve as an internal control. Since transcription of the viral early gene was unaffected by the presence of steroid hormone or deletions in the ovalbumin gene 5'-flanking region, the level of its transcripts could be monitored as a reference standard for ovalglobin transcription. Ovalglobin transcripts initiated principally from the ovalbumin cap site in the presence or absence of progesterone and 17 beta-estradiol. Deletion of 5'-flanking sequences to -197 had little effect on the induction with either hormone, while successive deletions to -180, -161, and -143 resulted in a gradual decrease in the level of induction. Deletion to -95 eliminated the induction. The results of this study indicate that DNA control elements for regulation of the ovalbumin gene by estrogen and progesterone either overlap directly or are clustered in close proximity in the 5'-flanking region near the ovalbumin gene promoter. PMID:6088508

  13. Accumulation of potentially toxic elements in plants and element transfer to human food chain

    SciTech Connect

    Dudka, S.; Miller, W.P.

    1995-12-31

    This paper summarizes the biological pathways of cadmium, mercury, and lead into the human food chain; major sources of bioaccumulation; and exposure limits. For occupationally non-exposed persons and non-smokers, food is the main source of cadmium. About one-third of the total Cd burden originates from animal products and two-thirds from plant products. Consumption of fish and other aquatic animals is the main source of Hg intake by humans. The Provisional Tolerable Weekly Intake (PTWI) of Hg is achieved through occupational exposure or by consumption of large amounts of contaminated fish. About half of human Pb intake comes from food, of which more than half originates from plants. Drinking water and ingestion of Pb-rich soil and dust make up the other half of the Pb burden in humans. Cases of cadmium and methylmercury poisoning have been reported in Japan. No acute hazard from lead in the food chain has been determined so far.

  14. Identification of human-specific AluS elements through comparative genomics.

    PubMed

    Lee, Jae; Kim, Yun-Ji; Mun, Seyoung; Kim, Heui-Soo; Han, Kyudong

    2015-01-25

    Mobile elements are responsible for ~45% of the human genome. Among them is the Alu element, accounting for 10% of the human genome (>1.1million copies). Several studies of Alu elements have reported that they are frequently involved in human genetic diseases and genomic rearrangements. In this study, we investigated the AluS subfamily, which is a relatively old Alu subfamily and has the highest copy number in primate genomes. Previously, a set of 263 human-specific AluS insertions was identified in the human genome. To validate these, we compared each of the human-specific AluS loci with its pre-insertion site in other primate genomes, including chimpanzee, gorilla, and orangutan. We obtained 24 putative human-specific AluS candidates via the in silico analysis and manual inspection, and then tried to verify them using PCR amplification and DNA sequencing. Through the PCR product sequencing, we were able to detect two instances of near-parallel Alu insertions in nearby sites that led to computational false negatives. Finally, we computationally and experimentally verified 23 human-specific AluS elements. We reported three alternative Alu insertion events, which are accompanied by filler DNA and/or Alu retrotransposition mediated-deletion. Bisulfite sequencing was carried out to examine DNA methylation levels of human-specific AluS elements. The results showed that fixed AluS elements are hypermethylated compared with polymorphic elements, indicating a possible relation between DNA methylation and Alu fixation in the human genome. PMID:25447892

  15. Dyke and sill injections: what mostly trigger volcano flank collapse?

    NASA Astrophysics Data System (ADS)

    Catry, Thibault; Cayol, Valérie; Michon, Laurent; Famin, Vincent; Romagnoli, Claudia; Chaput, Marie

    2010-05-01

    There is a large number of evidences that the morphostructural evolution of basaltic oceanic volcanoes (e.g. Stromboli, Hawaï and Canary Islands) results of alternating phases of growth and destruction. Among dismantling processes, flank collapses have been largely documented and interpreted as gravitational destabilization triggered by vertical injections of magma (dykes). In most cases, this interpretation has not been sustained by field observations because active volcanoes have poor occurrence of outcropped intrusions. From this point of view, Piton des Neiges volcano (La Réunion Island) represents a case in point because it has been deeply incised by erosion, providing large outcropped surfaces exhibiting the geometrical relationship between intrusions and host volcanic formations. The recent discovery of a highly deformed pile of sills at the interface between a debris avalanche deposit and a fossilized magma chamber brought to light the role of horizontal injections in the triggering of lateral collapses. The validation of this assumption rests on a digital model developed from the Mixed Boundary Element Method of elastic deformation field analysis. In this study, we modelled the intensity and the distribution of deformation and Coulomb stresses perturbation due to the injection of dykes along rift zones and a sill below the flank of a basaltic volcano. We quantified the influence of the intrusions in the mechanical state of the edifice, based on the deformation detected during an intrusion of magma at Piton de la Fournaise volcano. By comparing the deformation generated by sills to that generated by dykes, our modelling approach concludes that the area deformed by a sill injection is much wider than that deformed by a dyke injection. Moreover, we found that sill injection reaches higher intensities of lateral displacements. The combination of field data and our modelling results suggests therefore that repeated sill injection is an underestimated trigger

  16. Patient-specific modeling of human cardiovascular system elements

    NASA Astrophysics Data System (ADS)

    Kossovich, Leonid Yu.; Kirillova, Irina V.; Golyadkina, Anastasiya A.; Polienko, Asel V.; Chelnokova, Natalia O.; Ivanov, Dmitriy V.; Murylev, Vladimir V.

    2016-03-01

    Object of study: The research is aimed at development of personalized medical treatment. Algorithm was developed for patient-specific surgical interventions of the cardiovascular system pathologies. Methods: Geometrical models of the biological objects and initial and boundary conditions were realized by medical diagnostic data of the specific patient. Mechanical and histomorphological parameters were obtained with the help mechanical experiments on universal testing machine. Computer modeling of the studied processes was conducted with the help of the finite element method. Results: Results of the numerical simulation allowed evaluating the physiological processes in the studied object in normal state, in presence of different pathologies and after different types of surgical procedures.

  17. Technology and the Adult Degree Program: The Human Element

    ERIC Educational Resources Information Center

    Rodriquez, Frank G.; Nash, Susan Smith

    2004-01-01

    While technology has for many years been a critical component in programs for adults and calls to mind sophisticated gadgetry with expensive price tags, it is often the nexus where technology and humans intersect that proves most critical to the success and quality of adult degree programs.

  18. Hybridization Capture Using Short PCR Products Enriches Small Genomes by Capturing Flanking Sequences (CapFlank)

    PubMed Central

    Tsangaras, Kyriakos; Wales, Nathan; Sicheritz-Pontén, Thomas; Rasmussen, Simon; Michaux, Johan; Ishida, Yasuko; Morand, Serge; Kampmann, Marie-Louise; Gilbert, M. Thomas P.; Greenwood, Alex D.

    2014-01-01

    Solution hybridization capture methods utilize biotinylated oligonucleotides as baits to enrich homologous sequences from next generation sequencing (NGS) libraries. Coupled with NGS, the method generates kilo to gigabases of high confidence consensus targeted sequence. However, in many experiments, a non-negligible fraction of the resulting sequence reads are not homologous to the bait. We demonstrate that during capture, the bait-hybridized library molecules add additional flanking library sequences iteratively, such that baits limited to targeting relatively short regions (e.g. few hundred nucleotides) can result in enrichment across entire mitochondrial and bacterial genomes. Our findings suggest that some of the off-target sequences derived in capture experiments are non-randomly enriched, and that CapFlank will facilitate targeted enrichment of large contiguous sequences with minimal prior target sequence information. PMID:25275614

  19. Rapid deformation of the south flank of Kilauea Volcano, Hawaii

    USGS Publications Warehouse

    Owen, S.; Segall, P.; Freymueller, Jeffrey T.; Miklius, Asta; Denlinger, R.; Arnadottir, T.; Sako, M.; Burgmann, R.

    1995-01-01

    The south flank of Kilauea volcano has experienced two large [magnitude (M) 7.2 and M 6.1] earthquakes in the past two decades. Global Positioning System measurements conducted between 1990 and 1993 reveal seaward displacements of Kilauea's central south flank at rates of up to about 10 centimeters per year. In contrast, the northern side of the volcano and the distal ends of the south flank did not displace significantly. The observations can be explained by slip on a low-angle fault beneath the south flank combined with dilation deep within Kilauea's rift system, both at rates of at least 15 centimeters per year.

  20. Hypoxia-inducible nuclear factors bind to an enhancer element located 3' to the human erythropoietin gene.

    PubMed Central

    Semenza, G L; Nejfelt, M K; Chi, S M; Antonarakis, S E

    1991-01-01

    Human erythropoietin gene expression in liver and kidney is inducible by anemia or hypoxia. DNase I-hypersensitive sites were identified 3' to the human erythropoietin gene in liver nuclei. A 256-base-pair region of 3' flanking sequence was shown by DNase I protection and electrophoretic mobility-shift assays to bind four or more different nuclear factors, at least two of which are induced by anemia in both liver and kidney, and the region functioned as a hypoxia-inducible enhancer in transient expression assays. These results provide insight into the molecular basis for the regulation of gene expression by a fundamental physiologic stimulus, hypoxia. Images PMID:2062846

  1. Diversity of VanA Glycopeptide Resistance Elements in Enterococci from Humans and Nonhuman Sources

    PubMed Central

    Woodford, Neil; Adebiyi, Antoinette-Mary A.; Palepou, Marie-France I.; Cookson, Barry D.

    1998-01-01

    Elements mediating VanA glycopeptide resistance in 106 diverse enterococci from humans and nonhuman sources were compared with the prototype VanA transposon, Tn1546, in Enterococcus faecium BM4147. The isolates included 64 from individual patients at 15 hospitals in the United Kingdom (isolated between 1987 and 1996) and 42 from nonhuman sources in the United Kingdom (27 from raw meat, 7 from animal feces, and 8 from sewage). VanA elements were assigned to 24 groups (designated groups A to X) with primers that amplified 10 overlapping fragments of Tn1546. Ten groups of elements were found only in human enterococci, eight groups of elements were unique to nonhuman strains, and six groups of elements were common in enterococci from all sources. Elements indistinguishable from Tn1546 (group A) were observed more frequently in enterococci from nonhuman sources (34 versus 9%) but were identified in enterococci that caused outbreaks in hospital patients between 1987 and 1995. The most common group found in human enterococci (group H; 33%) was rarely observed in enterococci from other sources (5%). Group H elements differed from Tn1546 in three regions and included a novel insertion sequence, designated IS1542, between orf2 and vanR. The VanA elements of 14 other groups had a similar insertion at this position and/or distinct insertions at other positions. We conclude that VanA elements in enterococci are heterogeneous, although all show regions of homology with Tn1546. Furthermore, the elements most common among the human and nonhuman enterococci studied were different. This approach may be useful for monitoring the evolution of VanA resistance and may also be applicable in local “snapshot” epidemiological studies. However, as transposition events involving insertion sequences accounted for the differences observed between several groups, the stability of the elements must be assessed before their true epidemiological significance can be determined. PMID:9517923

  2. Determination of element levels in human serum: Total reflection X-ray fluorescence applications

    NASA Astrophysics Data System (ADS)

    Majewska, U.; Łyżwa, P.; Łyżwa, K.; Banaś, D.; Kubala-Kukuś, A.; Wudarczyk-Moćko, J.; Stabrawa, I.; Braziewicz, J.; Pajek, M.; Antczak, G.; Borkowska, B.; Góźdź, S.

    2016-08-01

    Deficiency or excess of elements could disrupt proper functioning of the human body and could lead to several disorders. Determination of their concentrations in different biological human fluids and tissues should become a routine practice in medical treatment. Therefore the knowledge about appropriate element concentrations in human organism is required. The purpose of this study was to determine the concentration of several elements (P, S, Cl, K, Ca, Cr, Fe, Cu, Zn, Se, Br, Rb, Pb) in human serum and to define the reference values of element concentration. Samples of serum were obtained from 105 normal presumably healthy volunteers (66 women aged between 15 and 78 years old; 39 men aged between 15 and 77 years old). Analysis has been done for the whole studied population and for subgroups by sex and age. It is probably first so a wide study of elemental composition of serum performed in the case of Świętokrzyskie region. Total reflection X-ray fluorescence (TXRF) method was used to perform the elemental analysis. Spectrometer S2 Picofox (Bruker AXS Microanalysis GmbH) was used to identify and measure elemental composition of serum samples. Finally, 1st and 3rd quartiles were accepted as minimum and maximum values of concentration reference range.

  3. Transcription activities of human papillomavirus type 11 E6 promoter-proximal elements in raft and submerged cultures of foreskin keratinocytes.

    PubMed Central

    Zhao, W; Chow, L T; Broker, T R

    1997-01-01

    Human papillomaviruses (HPVs) replicate only in differentiated squamous epithelia in warts and in epithelial raft cultures grown at the medium-air interface. Virus-encoded and host transcription factors are thought to be responsible for repressing the viral enhancer and promoter located within the upstream regulatory region (URR) in the undifferentiated basal and parabasal cells while up-regulating their activities in the differentiated spinous cells. Using recombinant retroviruses, we acutely transduced neonatal foreskin keratinocytes (PHKs) with a lacZ reporter gene driven by the wild-type URR of the low-risk HPV type 11 or by a URR with individual mutations in seven promoter-proximal elements, some of which have not been characterized previously. Beta-galactosidase activities were detected in the submerged, proliferating PHKs and also in the differentiated spinous cells, but not in the steady-state proliferating basal cells, of stratified raft cultures. In particular, mutation of an Oct1, an Sp1, or a previously unknown promoter-proximal AP1 site severely reduced the reporter activity, whereas mutation of either of two NF1 sites flanking the Oct1 site had no effect. These results demonstrate changes in cellular transcription factor profiles under different culture conditions and begin to characterize the naturally differentiation-dependent activation of the URR. They provide one molecular explanation for the patterns of HPV expression in warts and help validate epithelial raft cultures as an important experimental system for genetic dissection of HPV regulatory elements. PMID:9343243

  4. Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element.

    PubMed Central

    Barrero, María J; Camarero, Nuria; Marrero, Pedro F; Haro, Diego

    2003-01-01

    The expression of several genes involved in fatty acid metabolism is regulated by peroxisome proliferator-activated receptors (PPARs). To gain more insight into the control of carnitine palmitoyltransferase (CPT) gene expression, we examined the transcriptional regulation of the human CPT II gene. We show that the 5'-flanking region of this gene is transcriptionally active and binds PPARalpha in vivo in a chromatin immunoprecipitation assay. In addition, we characterized the peroxisome proliferator-responsive element (PPRE) in the proximal promoter of the CPT II gene, which appears to be a novel PPRE. The sequence of this PPRE contains one half-site which is a perfect consensus sequence (TGACCT) but no clearly recognizable second half-site (CAGCAC); this part of the sequence contains only one match to the consensus, which seems to be irrelevant for the binding of PPARalpha. As expected, other members of the nuclear receptor superfamily also bind to this element and repress the activation mediated by PPARalpha, thus showing that the interplay between several nuclear receptors may regulate the entry of fatty acids into the mitochondria, a crucial step in their metabolism. PMID:12408750

  5. Human factoring the procedures element in a complex manufacturing system

    SciTech Connect

    Caccamise, D.J.; Mecherikoff, M.

    1993-06-01

    As a result of Human Factors evaluations of procedures associated with incidents at Rocky Flats Plant (RFP) it was determined that the existing procedure format created significant opportunities for confusion in their attempt to convey information about a work process. For instance, there was no mechanism to clearly identify the participants and their roles during the instructions portion of the procedure. In addition, procedure authors frequently used complex logic to convey a series of contingent actions within steps. It was also difficult to discern the actual procedure steps from other types of information in the procedure. These and other inadequacies prompted the Human Factors Engineering (HFE) department to propose solutions to these problems that followed well-researched principles of cognitive psychology, dealing with how humans process information. Format and style contribute to procedure usability, and therefore to safety and efficiency in operations governed by the procedures. Since it was difficult to tie specific performance failures to specific format and style characteristics and thereby dearly define costs and benefits, it was difficult on that basis to sell the idea that changes in procedure format and style were really necessary to improve safety and efficiency. In addition, we found that the socio-political systems governing this process, particularly at the subprocess interface level, were not functioning efficiently. Both the technological aspects of the process and the socio-political aspects were contributing to waste and considerable re-work. Fixing the customer feedback loop to the process owners not only minimized re-work and waste, but also provided the data to persuade subprocess owners to make the necessary changes that heretofore were being met with great resistance.

  6. Positioning the actual interference fringe pattern on the tooth flank in measuring gear tooth flanks by laser interferometry

    NASA Astrophysics Data System (ADS)

    Fang, Suping; Wang, Leijie; Liu, Shiqiao; Komori, Masaharu; Kubo, Aizoh

    2011-05-01

    In measuring form deviation of gear tooth flanks by laser interferometry, the collected interference fringe pattern (IFP) is badly distorted, in the case of shape, relative to the actual tooth flank. Meanwhile, a clear and definite mapping relationship between the collected IFP and the actual tooth flank is indispensable for both transforming phase differences into deviation values and positioning the measurement result on the actual tooth flank. In order to solve these problems, this paper proposes a method using the simulation tooth image as a bridge connecting the actual tooth flank and the collected IFP. The mapping relationship between the simulation tooth image and the actual tooth flank has been obtained by ray tracing methods [Fang et al., Appl. Opt. 49(33), 6409-6415 (2010)]. This paper mainly discusses how to build the relationship between the simulation tooth image and the collected IFP by using a matching algorithm of two characteristic point sets. With the combination of the two above-mentioned assistant mapping relationships, the mapping relationship between the collected IFP and the actual tooth flank can be built; the collected IFP can be positioned on the actual tooth flank. Finally, the proposed method is employed in a measurement of the form deviation of a gear tooth flank and the result proves the feasibility of the proposed method.

  7. Human Research Program Human Health Countermeasures Element Sensorimotor Risk Standing Review Panel (SRP) Final Report

    NASA Technical Reports Server (NTRS)

    Peterson, Barry

    2009-01-01

    The Sensorimotor Risk Standing Review Panel (SRP) met at the NASA Johnson Space Center on October 4-6, 2009 to discuss the areas of future research targeted by the Human Health Countermeasures (HHC) Element of the Human Research Program (HRP). Using evidence-based knowledge as a background for risks, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Sensorimotor Risk SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the SRP's review. The SRP was requested to evaluate the practicality of the proposed efforts in light of the realistic demands placed on the HRP. In short, all tasks presented in the Integrated Research Plan (IRP) should address specific risks related to the challenges faced by the astronauts as a result of prolonged exposure to microgravity. All tasks proposed to fill the gaps in knowledge should provide applied, translational data necessary to address the specific risks. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the panel charge, either as a group or in separate sessions. The SRP made a final debriefing to the HRP Program Scientist. Taking the evidence and the risk as givens, the SRP reached the following conclusions: 1) the panel is very supportive of and endorses the present activities of the Sensorimotor Risk; and the panel is likewise supportive of the gaps and associated tasks in the IRP; 2) overall, the tasks addressed the gaps in the IRP; 3) there were some gaps and tasks that merit further enhancement and some new gaps/tasks that the SRP recommends.

  8. Structural property of regulatory elements in human promoters

    NASA Astrophysics Data System (ADS)

    Cao, Xiao-Qin; Zeng, Jia; Yan, Hong

    2008-04-01

    The capacity of transcription factors to activate gene expression is encoded in the promoter sequences, which are composed of short regulatory motifs that function as transcription factor binding sites (TFBSs) for specific proteins. To the best of our knowledge, the structural property of TFBSs that controls transcription is still poorly understood. Rigidity is one of the important structural properties of DNA, and plays an important role in guiding DNA-binding proteins to the target sites efficiently. After analyzing the rigidity of 2897 TFBSs in 1871 human promoters, we show that TFBSs are generally more flexible than other genomic regions such as exons, introns, 3' untranslated regions, and TFBS-poor promoter regions. Furthermore, we find that the density of TFBSs is consistent with the average rigidity profile of human promoters upstream of the transcription start site, which implies that TFBSs directly influence the promoter structure. We also examine the local rigid regions probably caused by specific TFBSs such as the DNA sequence TATA(A/T)A(A/T) box, which may inhibit nucleosomes and thereby facilitate the access of transcription factors bound nearby. Our results suggest that the structural property of TFBSs accounts for the promoter structure as well as promoter activity.

  9. Dissection of human vitreous body elements for proteomic analysis.

    PubMed

    Skeie, Jessica M; Mahajan, Vinit B

    2011-01-01

    The vitreous is an optically clear, collagenous extracellular matrix that fills the inside of the eye and overlies the retina. (1,2) Abnormal interactions between vitreous substructures and the retina underlie several vitreoretinal diseases, including retinal tear and detachment, macular pucker, macular hole, age-related macular degeneration, vitreomacular traction, proliferative vitreoretinopathy, proliferative diabetic retinopathy, and inherited vitreoretinopathies. (1,2) The molecular composition of the vitreous substructures is not known. Since the vitreous body is transparent with limited surgical access, it has been difficult to study its substructures at the molecular level. We developed a method to separate and preserve these tissues for proteomic and biochemical analysis. The dissection technique in this experimental video shows how to isolate vitreous base, anterior hyaloid, vitreous core, and vitreous cortex from postmortem human eyes. One-dimensional SDS-PAGE analyses of each vitreous component showed that our dissection technique resulted in four unique protein profiles corresponding to each substructure of the human vitreous body. Identification of differentially compartmentalized proteins will reveal candidate molecules underlying various vitreoretinal diseases. PMID:21304469

  10. Sagittal evaluation of elemental geometrical dimensions of human vertebrae.

    PubMed Central

    Gilad, I; Nissan, M

    1985-01-01

    Geometrical configuration and dimensions of the human vertebra were investigated using radiographs of 157 normal healthy adult men. Measurements were based on five bony reference points, which can be defined in radiographs. The measurements permit the determination of nine dimensions that can be used for anthropometrical evaluation of the cervical and lumbar vertebrae. A simplified model of the vertebra in the sagittal plane is presented and serves as a basis for the geometrical measurements. In the cervical region, average width exceeded average height of vertebral bodies C3 to C7, while in C2 the average width was smaller than the average height; C7 was the longest and C3 the shortest cervical vertebra. In the lumbar region, average width exceeded average height of the vertebral bodies. Values for width and height did not differ significantly from L1 to L5; L3 was the longest and L5 the shortest lumbar vertebra. Images Fig. 1 PMID:3870717

  11. West Flank Coso, CA FORGE ArcGIS data 2

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    archive of ArcGIS data from the West Flank FORGE site located in Coso, California. Archive contains: 8 shapefiles polygon of the 3D geologic model polylines of the traces 3D modeled faults polylines of the fault traces from Duffield and Bacon, 1980 polygon of the West Flank FORGE site polylines of the traces of the geologic cross-sections (cross-sections in a separate archive in the GDR) polylines of the traces of the seismic reflection profiles through and adjacent to the West Flank site (seismic reflection profiles in a separate archive in the GDR) points of the well collars in and around the West Flank site polylines of the surface expression of the West Flank well paths

  12. Human Research Program Human Health Countermeasures Element Bone and Muscle Risk Standing Review Panel (SRP)

    NASA Technical Reports Server (NTRS)

    Glowacki, Julie; Gregor, Robert

    2009-01-01

    The Bone and Muscle Risk Standing Review Panel (SRP) met at the NASA Johnson Space Center (JSC) on October 4-6, 2009 to discuss the areas of current and future research targeted by the Human Health Countermeasures (HHC) Element of the Human Research Program (HRP). Using evidence-based knowledge as a background for identified risks to astronaut health and performance, NASA had identified gaps in knowledge to address those risks. Ongoing and proposed tasks were presented to address the gaps. The charge to the Bone and Muscle Risk SRP was to review the gaps, evaluate whether the tasks addressed these gaps and to make recommendations to NASA s HRP Science Management Office regarding the Panel's review. The Bone and Muscle Risk SRP consisted of scientists who are experts in muscle, bone, or both and could evaluate the existing evidence with sufficient knowledge of the potential effects of long duration exposure to microgravity. More important, although expertise in basic science is important, the SRP was requested to evaluate the practicality of the proposed efforts in light of the realistic demands placed on the HRP. In short, all tasks presented in the Integrated Research Plan (IRP) should address specific questions related to the challenges faced by the astronauts as a result of prolonged exposure to microgravity. All tasks proposed to fill the gaps in knowledge should provide applied, translational data necessary to answer the specific questions. Several presentations were made to the SRP during the site visit and the SRP spent sufficient time to address the panel charge, either as a group or in separate sessions for the Bone and Muscle Risk subgroups. The SRP made a final debriefing to the HRP Program Scientist, Dr. John B. Charles, on October 6, 2009. Taking the evidence and identified risks as givens, the SRP concluded that 1) integration of information should lead to a more comprehensive approach to identifying the gaps, 2) not all tasks addressed the gaps as

  13. Cognitive neuroscience in forensic science: understanding and utilizing the human element

    PubMed Central

    Dror, Itiel E.

    2015-01-01

    The human element plays a critical role in forensic science. It is not limited only to issues relating to forensic decision-making, such as bias, but also relates to most aspects of forensic work (some of which even take place before a crime is ever committed or long after the verification of the forensic conclusion). In this paper, I explicate many aspects of forensic work that involve the human element and therefore show the relevance (and potential contribution) of cognitive neuroscience to forensic science. The 10 aspects covered in this paper are proactive forensic science, selection during recruitment, training, crime scene investigation, forensic decision-making, verification and conflict resolution, reporting, the role of the forensic examiner, presentation in court and judicial decisions. As the forensic community is taking on the challenges introduced by the realization that the human element is critical for forensic work, new opportunities emerge that allow for considerable improvement and enhancement of the forensic science endeavour. PMID:26101281

  14. Cognitive neuroscience in forensic science: understanding and utilizing the human element.

    PubMed

    Dror, Itiel E

    2015-08-01

    The human element plays a critical role in forensic science. It is not limited only to issues relating to forensic decision-making, such as bias, but also relates to most aspects of forensic work (some of which even take place before a crime is ever committed or long after the verification of the forensic conclusion). In this paper, I explicate many aspects of forensic work that involve the human element and therefore show the relevance (and potential contribution) of cognitive neuroscience to forensic science. The 10 aspects covered in this paper are proactive forensic science, selection during recruitment, training, crime scene investigation, forensic decision-making, verification and conflict resolution, reporting, the role of the forensic examiner, presentation in court and judicial decisions. As the forensic community is taking on the challenges introduced by the realization that the human element is critical for forensic work, new opportunities emerge that allow for considerable improvement and enhancement of the forensic science endeavour. PMID:26101281

  15. Simulation of the optical performance of refractive elements to mimic the human eye focusing

    NASA Astrophysics Data System (ADS)

    Diaz-Gonzalez, G.; Santiago-Alvarado, Agustín.; Cruz-Félix, Ángel S.

    2015-09-01

    Refractive optics has evolved and incorporated new elements in optical systems every day, such as conventional lenses, tunable lenses, GRIN lenses, diffractive lenses, intraocular lenses, etc. Some of these elements are reported in the literature together with different proposed models of the human eye. In this work, optical properties of some of these lenses will be studied, and simulations of their behavior will be done in order to analyze which one is better for imaging process. Such lenses will be incorporated in an optical system that mimics the human eye behavior. Analysis and obtained results are reported, as well as the proposed optical system. Finally, we present the conclusions of the work.

  16. [Developing a finite element model of human head with true anatomic structure mandible].

    PubMed

    Ma, Chunsheng; Zhang, Haizhong; Du, Huiliang; Huang, Shilin; Zhang, Jinhuan

    2005-02-01

    A finite element model of human mandible is developed from CT scan images by the technologies of three-dimensional reconstruction, image processing and meshing. The mandible model is connected to one modified head model of Hybrid III dummy with joint according to the anatomic structure and mechanical characteristics of the temporomandibular joint. Then a finite element model of the human head with the true anatomic structure mandible is developed. This model has been validated with the cadaver test results. It can be used in researches on the mechanism of craniofacial blunt-impact injury and on the assessment of injury severity. PMID:15762115

  17. Two distinct promoter elements in the human rRNA gene identified by linker scanning mutagenesis.

    PubMed Central

    Haltiner, M M; Smale, S T; Tjian, R

    1986-01-01

    A cell-free RNA polymerase I transcription system was used to evaluate the transcription efficiency of 21 linker scanning mutations that span the human rRNA gene promoter. Our analysis revealed the presence of two major control elements, designated the core and upstream elements, that affect the level of transcription initiation. The core element extends from -45 to +18 relative to the RNA start site, and transcription is severely affected (up to 100-fold) by linker scanning mutations in this region. Linker scanning and deletion mutations in the upstream element, located between nucleotides -156 and -107, cause a three- to fivefold reduction in transcription. Under certain reaction conditions, such as the presence of a high ratio of protein to template or supplementation of the reaction with partially purified protein fractions, sequences upstream of the core element can have an even greater effect (20- to 50-fold) on RNA polymerase I transcription. Primer extension analysis showed that RNA synthesized from all of these mutant templates is initiated at the correct in vivo start site. To examine the functional relationship between the core and the upstream region, mutant promoters were constructed that alter the orientation, distance, or multiplicity of these control elements relative to each other. The upstream control element appears to function in only one orientation, and its position relative to the core is constrained within a fairly narrow region. Moreover, multiple core elements in close proximity to each other have an inhibitory effect on transcription. Images PMID:3785147

  18. Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription.

    PubMed Central

    Carcedo, M T; Iglesias, J M; Bances, P; Morgan, R O; Fernandez, M P

    2001-01-01

    Human annexin A5 is a ubiquitous protein implicated in diverse signal transduction processes associated with cell growth and differentiation, and its gene regulation is an important component of this function. Promoter transcriptional activity was determined for a wide 5' portion of the human annexin A5 gene, from bp -1275 to +79 relative to the most 5' of several discrete transcription start points. Transfection experiments carried out in HeLa cells identified the segment from bp -202 to +79 as the minimal promoter conferring optimal transcriptional activity. Two canonical Sp1 sites in the immediate 5' flanking region of a CpG island were required for significant transcription. Strong repressive activity in the distal promoter region between bp -717 to -1153 was attributed to the presence of an endogenous retroviral long terminal repeat, homologous with long terminal repeat 47B. The downstream sequence from bp position +31 to +79 in untranslated exon 1 was also essential for transcription, as its deletion from any of the plasmid constructs abolished activity in transfection assays. Electrophoretic mobility-shift assays, Southwestern-blot analysis and affinity chromatography were used to identify a protein doublet of relative molecular mass 35 kDa that bound an octanucleotide palindromic sequence in exon 1. The DNA cis-element resembled an E-box, but did not bind higher molecular mass transcription factors, such as upstream stimulatory factor or activator protein 4. The discovery of a downstream element crucial for annexin A5 gene transcription, and its interaction with a potentially novel transcription factor or complex, may provide a clue to understanding the initiation of transcription by TATA-less, multiple start site promoters. PMID:11368787

  19. Integrated study to define the hazard of the unstable flanks of Mt. Etna: the Italian DPC-INGV FLANK Project

    NASA Astrophysics Data System (ADS)

    Acocella, Valerio; Puglisi, Giuseppe

    2010-05-01

    Volcanoes are often characterized by unstable flanks. The eastern and south-eastern flanks of Mt. Etna (Italy) have shown repeated evidence of instability in the recent past. The extent and frequency of these processes varies widely, from nearly continuous creep-like movements of specific portions of the flank to the rarer slip of the entire eastern sector, involving also the off-shore portion. Estimated slip rates may vary enormously, from mm/yr to m/week. The most dramatic instability events are associated with major eruptions and shallow seismic activity, as during 2002-2003, posing a serious hazard to the inhabited flanks of the volcano. The Italian Department of Civil Defense (DPC), with the National Institute of Geophysics and Volcanology (INGV), as well as with the involvement of Italian Universities and other Research Institutes, has launched a 2-years project (may 2008-may 2010) devoted to minimize the hazard deriving from the instability of the Etna flanks. This multidisciplinary project embraces geological, geophysical, volcanological, modeling and hazard studies, both on the on-shore and the off-shore portions of the E and SE flanks of the volcano. Indeed, the main aims are to define: (a) the 3D geometry of the collapsing sector(s); (b) the relationships between flank movement and volcanic and seismic activity; (c) the hazard related to the flank instability. The collected data populate a GIS database implemented according the WoVo rules. This project represents the first attempt, at least in Europe, to use an integrated approach to minimize the hazard deriving from flank instability in a volcano. Here we briefly summarize the state of the art of the project at an advanced stage, highlighting the path of the different Tasks, as well as the main results.

  20. Close sequence comparisons are sufficient to identify human cis-regulatory elements.

    PubMed

    Prabhakar, Shyam; Poulin, Francis; Shoukry, Malak; Afzal, Veena; Rubin, Edward M; Couronne, Olivier; Pennacchio, Len A

    2006-07-01

    Cross-species DNA sequence comparison is the primary method used to identify functional noncoding elements in human and other large genomes. However, little is known about the relative merits of evolutionarily close and distant sequence comparisons. To address this problem, we identified evolutionarily conserved noncoding regions in primate, mammalian, and more distant comparisons using a uniform approach (Gumby) that facilitates unbiased assessment of the impact of evolutionary distance on predictive power. We benchmarked computational predictions against previously identified cis-regulatory elements at diverse genomic loci and also tested numerous extremely conserved human-rodent sequences for transcriptional enhancer activity using an in vivo enhancer assay in transgenic mice. Human regulatory elements were identified with acceptable sensitivity (53%-80%) and true-positive rate (27%-67%) by comparison with one to five other eutherian mammals or six other simian primates. More distant comparisons (marsupial, avian, amphibian, and fish) failed to identify many of the empirically defined functional noncoding elements. Our results highlight the practical utility of close sequence comparisons, and the loss of sensitivity entailed by more distant comparisons. We derived an intuitive relationship between ancient and recent noncoding sequence conservation from whole-genome comparative analysis that explains most of the observations from empirical benchmarking. Lastly, we determined that, in addition to strength of conservation, genomic location and/or density of surrounding conserved elements must also be considered in selecting candidate enhancers for in vivo testing at embryonic time points. PMID:16769978

  1. 6. DETAIL OF SCROLLED CENTRAL PANEL, FLANKED BY ALLEGORICAL STATUES ...

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

    6. DETAIL OF SCROLLED CENTRAL PANEL, FLANKED BY ALLEGORICAL STATUES (OF LEARNING) AND FESTOONS, ABOVE MAIN ENTRANCE OF THE ROEBLING SCHOOL. - John A. Roebling's Sons Company, Kinkora Works, Village of Roebling, Roebling, Burlington County, NJ

  2. DETAIL OF FENCE FLANKING GATE AT ENTRANCE TO MEMORIAL WALK. ...

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

    DETAIL OF FENCE FLANKING GATE AT ENTRANCE TO MEMORIAL WALK. VIEW TO NORTHEAST. - Rock Island National Cemetery, Rock Island Arsenal, 0.25 mile north of southern tip of Rock Island, Rock Island, Rock Island County, IL

  3. GATE AND FLANKING FENCE AT ENTRANCE TO MEMORIAL WALK. VIEW ...

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

    GATE AND FLANKING FENCE AT ENTRANCE TO MEMORIAL WALK. VIEW TO NORTHEAST. - Rock Island National Cemetery, Rock Island Arsenal, 0.25 mile north of southern tip of Rock Island, Rock Island, Rock Island County, IL

  4. East side detail, showing later wings flanking original entrance on ...

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

    East side detail, showing later wings flanking original entrance on east side. - Fitzsimons General Hospital, Red Cross Building, South Eighth Street Bounded by West McAfee Avenue on South & West Harlow Avenue on North, Aurora, Adams County, CO

  5. View looking northeast of console table and mirror flanked by ...

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

    View looking northeast of console table and mirror flanked by 18th century French chairs in the first floor Reception Hall - Perry Belmont House, 1618 New Hampshire Avenue, NW, Washington, District of Columbia, DC

  6. 1. FRONT (NORTH) SIDE; SMOKESTACKS FLANK PROTECTING BAY THAT CONTAINS ...

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

    1. FRONT (NORTH) SIDE; SMOKESTACKS FLANK PROTECTING BAY THAT CONTAINS COAL ELEVATING EQUIPMENT - Rath Packing Company, Boiler Room, Sycamore Street between Elm & Eighteenth Streets, Waterloo, Black Hawk County, IA

  7. Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders.

    PubMed

    Wakabayashi, Aoi; Ulirsch, Jacob C; Ludwig, Leif S; Fiorini, Claudia; Yasuda, Makiko; Choudhuri, Avik; McDonel, Patrick; Zon, Leonard I; Sankaran, Vijay G

    2016-04-19

    Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptionalcis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders. PMID:27044088

  8. Insight into GATA1 transcriptional activity through interrogation of cis elements disrupted in human erythroid disorders

    PubMed Central

    Wakabayashi, Aoi; Ulirsch, Jacob C.; Ludwig, Leif S.; Fiorini, Claudia; Yasuda, Makiko; Choudhuri, Avik; McDonel, Patrick; Zon, Leonard I.; Sankaran, Vijay G.

    2016-01-01

    Whole-exome sequencing has been incredibly successful in identifying causal genetic variants and has revealed a number of novel genes associated with blood and other diseases. One limitation of this approach is that it overlooks mutations in noncoding regulatory elements. Furthermore, the mechanisms by which mutations in transcriptional cis-regulatory elements result in disease remain poorly understood. Here we used CRISPR/Cas9 genome editing to interrogate three such elements harboring mutations in human erythroid disorders, which in all cases are predicted to disrupt a canonical binding motif for the hematopoietic transcription factor GATA1. Deletions of as few as two to four nucleotides resulted in a substantial decrease (>80%) in target gene expression. Isolated deletions of the canonical GATA1 binding motif completely abrogated binding of the cofactor TAL1, which binds to a separate motif. Having verified the functionality of these three GATA1 motifs, we demonstrate strong evolutionary conservation of GATA1 motifs in regulatory elements proximal to other genes implicated in erythroid disorders, and show that targeted disruption of such elements results in altered gene expression. By modeling transcription factor binding patterns, we show that multiple transcription factors are associated with erythroid gene expression, and have created predictive maps modeling putative disruptions of their binding sites at key regulatory elements. Our study provides insight into GATA1 transcriptional activity and may prove a useful resource for investigating the pathogenicity of noncoding variants in human erythroid disorders. PMID:27044088

  9. Human Learning of Elemental Category Structures: Revising the Classic Result of Shepard, Hovland, and Jenkins (1961)

    ERIC Educational Resources Information Center

    Kurtz, Kenneth J.; Levering, Kimery R.; Stanton, Roger D.; Romero, Joshua; Morris, Steven N.

    2013-01-01

    The findings of Shepard, Hovland, and Jenkins (1961) on the relative ease of learning 6 elemental types of 2-way classifications have been deeply influential 2 times over: 1st, as a rebuke to pure stimulus generalization accounts, and again as the leading benchmark for evaluating formal models of human category learning. The litmus test for models…

  10. Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue.

    PubMed

    Pemmer, B; Roschger, A; Wastl, A; Hofstaetter, J G; Wobrauschek, P; Simon, R; Thaler, H W; Roschger, P; Klaushofer, K; Streli, C

    2013-11-01

    Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. PMID:23932972

  11. Spatial distribution of the trace elements zinc, strontium and lead in human bone tissue☆

    PubMed Central

    Pemmer, B.; Roschger, A.; Wastl, A.; Hofstaetter, J.G.; Wobrauschek, P.; Simon, R.; Thaler, H.W.; Roschger, P.; Klaushofer, K.; Streli, C.

    2013-01-01

    Trace elements are chemical elements in minute quantities, which are known to accumulate in the bone. Cortical and trabecular bones consist of bone structural units (BSUs) such as osteons and bone packets of different mineral content and are separated by cement lines. Previous studies investigating trace elements in bone lacked resolution and therefore very little is known about the local concentration of zinc (Zn), strontium (Sr) and lead (Pb) in BSUs of human bone. We used synchrotron radiation induced micro X-ray fluorescence analysis (SR μ-XRF) in combination with quantitative backscattered electron imaging (qBEI) to determine the distribution and accumulation of Zn, Sr, and Pb in human bone tissue. Fourteen human bone samples (10 femoral necks and 4 femoral heads) from individuals with osteoporotic femoral neck fractures as well as from healthy individuals were analyzed. Fluorescence intensity maps were matched with BE images and correlated with calcium (Ca) content. We found that Zn and Pb had significantly increased levels in the cement lines of all samples compared to the surrounding mineralized bone matrix. Pb and Sr levels were found to be correlated with the degree of mineralization. Interestingly, Zn intensities had no correlation with Ca levels. We have shown for the first time that there is a differential accumulation of the trace elements Zn, Pb and Sr in BSUs of human bone indicating different mechanisms of accumulation. PMID:23932972

  12. Automated volumetric grid generation for finite element modeling of human hand joints

    SciTech Connect

    Hollerbach, K.; Underhill, K.; Rainsberger, R.

    1995-02-01

    We are developing techniques for finite element analysis of human joints. These techniques need to provide high quality results rapidly in order to be useful to a physician. The research presented here increases model quality and decreases user input time by automating the volumetric mesh generation step.

  13. Examining the Impact of Culture and Human Elements on OLAP Tools Usefulness

    ERIC Educational Resources Information Center

    Sharoupim, Magdy S.

    2010-01-01

    The purpose of the present study was to examine the impact of culture and human-related elements on the On-line Analytical Processing (OLAP) usability in generating decision-making information. The use of OLAP technology has evolved rapidly and gained momentum, mainly due to the ability of OLAP tools to examine and query large amounts of data sets…

  14. Fractality and entropic scaling in the chromosomal distribution of conserved noncoding elements in the human genome.

    PubMed

    Polychronopoulos, Dimitris; Athanasopoulou, Labrini; Almirantis, Yannis

    2016-06-15

    Conserved non-coding elements (CNEs) are defined using various degrees of sequence identity and thresholds of minimal length. Their conservation frequently exceeds the one observed for protein-coding sequences. We explored the chromosomal distribution of different classes of CNEs in the human genome. We employed two methodologies: the scaling of block entropy and box-counting, with the aim to assess fractal characteristics of different CNE datasets. Both approaches converged to the conclusion that well-developed fractality is characteristic of elements that are either extremely conserved between species or are of ancient origin, i.e. conserved between distant organisms across evolution. Given that CNEs are often clustered around genes, we verified by appropriate gene masking that fractal-like patterns emerge even when elements found in proximity or inside genes are excluded. An evolutionary scenario is proposed, involving genomic events that might account for fractal distribution of CNEs in the human genome as indicated through numerical simulations. PMID:26899868

  15. Correlations of trace elements in breast human tissues: Evaluation of spatial distribution using μ-XRF

    NASA Astrophysics Data System (ADS)

    Silva, Marina Piacenti da; Silva, Deisy Mara da; Ribeiro-Silva, Alfredo; Poletti, Martin Eduardo

    2012-05-01

    The aim of this work is to investigate microscopic correlations between trace elements in breast human tissues. A synchrotron X-ray fluorescence microprobe system (μ-XRF) was used to obtain two-dimensional distribution of trace element Ca, Fe, Cu and Zn in normal (6 samples) and malignant (14 samples) breast tissues. The experiment was performed in X-ray Fluorescence beam line at Laboratório Nacional de Luz Síncrotron (LNLS), Campinas, Brazil. The white microbeam was generated with a fine conical capillary with a 20 μm output diameter. The samples were supported on a XYZ table. An optical microscope with motorized zoom was used for sample positioning and choice the area to be scanned. Automatic two-dimensional scans were programmed and performed with steps of 30 μm in each direction (x, y) on the selected area. The fluorescence signals were recorded using a Si(Li) detector, positioned at 90 degrees with respect to the incident beam, with a collection time of 10 s per point. The elemental maps obtained from each sample were overlap to observe correlation between trace elements. Qualitative results showed that the pairs of elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman correlation tests, indicate that there is a spatial correlation between these pairs of elements (p < 0.001) suggesting the importance of these elements in metabolic processes associated with the development of the tumor.

  16. Urinary stones as a novel matrix for human biomonitoring of toxic and essential elements.

    PubMed

    Kuta, J; Smetanová, S; Benová, D; Kořistková, T; Machát, J

    2016-02-01

    Monitoring of body burden of toxic elements is usually based on analysis of concentration of particular elements in blood, urine and/or hair. Analysis of these matrices, however, predominantly reflects short- or medium-term exposure to trace elements or pollutants. In this work, urinary stones were investigated as a matrix for monitoring long-term exposure to toxic and essential elements. A total of 431 samples of urinary calculi were subjected to mineralogical and elemental analysis by infrared spectroscopy and inductively coupled plasma mass spectrometry. The effect of mineralogical composition of the stones and other parameters such as sex, age and geographical location on contents of trace and minor elements is presented. Our results demonstrate the applicability of such approach and confirm that the analysis of urinary calculi can be helpful in providing complementary information on human exposure to trace metals and their excretion. Analysis of whewellite stones (calcium oxalate monohydrate) with content of phosphorus <0.6 % has been proved to be a promising tool for biomonitoring of trace and minor elements. PMID:25736734

  17. Correlations of trace elements in breast human tissues: Evaluation of spatial distribution using {mu}-XRF

    SciTech Connect

    Piacenti da Silva, Marina; Silva, Deisy Mara da; Ribeiro-Silva, Alfredo; Poletti, Martin Eduardo

    2012-05-17

    The aim of this work is to investigate microscopic correlations between trace elements in breast human tissues. A synchrotron X-ray fluorescence microprobe system ({mu}-XRF) was used to obtain two-dimensional distribution of trace element Ca, Fe, Cu and Zn in normal (6 samples) and malignant (14 samples) breast tissues. The experiment was performed in X-ray Fluorescence beam line at Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, Brazil. The white microbeam was generated with a fine conical capillary with a 20 {mu}m output diameter. The samples were supported on a XYZ table. An optical microscope with motorized zoom was used for sample positioning and choice the area to be scanned. Automatic two-dimensional scans were programmed and performed with steps of 30 {mu}m in each direction (x, y) on the selected area. The fluorescence signals were recorded using a Si(Li) detector, positioned at 90 degrees with respect to the incident beam, with a collection time of 10 s per point. The elemental maps obtained from each sample were overlap to observe correlation between trace elements. Qualitative results showed that the pairs of elements Ca-Zn and Fe-Cu could to be correlated in malignant breast tissues. Quantitative results, achieved by Spearman correlation tests, indicate that there is a spatial correlation between these pairs of elements (p < 0.001) suggesting the importance of these elements in metabolic processes associated with the development of the tumor.

  18. Active muscle response using feedback control of a finite element human arm model.

    PubMed

    Östh, Jonas; Brolin, Karin; Happee, Riender

    2012-01-01

    Mathematical human body models (HBMs) are important research tools that are used to study the human response in car crash situations. Development of automotive safety systems requires the implementation of active muscle response in HBM, as novel safety systems also interact with vehicle occupants in the pre-crash phase. In this study, active muscle response was implemented using feedback control of a nonlinear muscle model in the right upper extremity of a finite element (FE) HBM. Hill-type line muscle elements were added, and the active and passive properties were assessed. Volunteer tests with low impact loading resulting in elbow flexion motions were performed. Simulations of posture maintenance in a gravity field and the volunteer tests were successfully conducted. It was concluded that feedback control of a nonlinear musculoskeletal model can be used to obtain posture maintenance and human-like reflexive responses in an FE HBM. PMID:21294008

  19. Finite-element simulation of firearm injury to the human cranium

    NASA Astrophysics Data System (ADS)

    Mota, A.; Klug, W. S.; Ortiz, M.; Pandolfi, A.

    An advanced physics-based simulation of firearms injury to the human cranium is presented, modeling by finite elements the collision of a firearm projectile into a human parietal bone. The space-discretized equations of motion are explicitly integrated in time with Newmark's time-stepping algorithm. The impact of the projectile on the skull, as well as the collisions between flying fragments, are controlled through a nonsmooth contact algorithm. Cohesive theories of fracture, in conjunction with adaptive remeshing, control the nucleation and the propagation of fractures. The progressive opening of fracture surfaces is governed by a thermodynamically irreversible cohesive law embedded into cohesive-interface elements. Numerical results compare well with forensic data of actual firearm wounds to human crania.

  20. Surety of human elements of high consequence systems: An organic model

    SciTech Connect

    FORSYTHE,JAMES C.; WENNER,CAREN A.

    2000-04-25

    Despite extensive safety analysis and application of safety measures, there is a frequent lament, ``Why do we continue to have accidents?'' Two breakdowns are prevalent in risk management and prevention. First, accidents result from human actions that engineers, analysts and management never envisioned and second, controls, intended to preclude/mitigate accident sequences, prove inadequate. This paper addresses the first breakdown, the inability to anticipate scenarios involving human action/inaction. The failure of controls has been addressed in a previous publication (Forsythe and Grose, 1998). Specifically, this paper presents an approach referred to as surety. The objective of this approach is to provide high levels of assurance in situations where potential system failure paths cannot be fully characterized. With regard to human elements of complex systems, traditional approaches to human reliability are not sufficient to attain surety. Consequently, an Organic Model has been developed to account for the organic properties exhibited by engineered systems that result from human involvement in those systems.

  1. Uptake of Elements From Aerosols by Humans ~ A Case Study From Delhi & Bangalore Cities

    NASA Astrophysics Data System (ADS)

    Anand, S.; Yadav, S.; Jain, V. K.

    2006-05-01

    Aerosol research has gained tremendous importance globally due to the cumulative effects of increasing industrialization and urbanization on aerosol production which can have an alarming impact on the climate of the planet as well as the health of its inhabitants. Therefore, there is an increasing need to study aerosols for all of their physicochemical and biological aspects on both local and global scales. World over extensive research has gone into studying the physical and the chemical aspects of aerosols. However, little information is yet available on the health impacts of aerosols particularly in the Asian context. Here we report uptake of various elements that are concentrated in aerosols by the human body in Delhi and Bangalore cities and their possible health effects. In many urban areas, for example in Delhi, inhalable fractions of aerosols are known to have high concentrations of elements such as Cu, Zn, Pb, Ba, Ni and Cr (Yadav and Rajamani 2004). Also aerosols in the North West part of India seem to be particularly enriched in these elements. If so, there is a high possibility of these elements getting into the human system either directly or indirectly through water and food. To determine the concentrations of these elements that are present in significant concentrations in the inhalable fractions of aerosols, human hair and blood samples are used as proxies. Both these regions have contrasting geographic and climatic conditions. Delhi (altitude : 213-305m above MSL) located on the fringes of the Thar desert which supplies considerable amount of dust, is semi-arid with annual rainfall of 60-80 cms & temperatures varying between 1° - 45°. Bangalore (altitude of 900m above MSL) receives a high annual rainfall of 80-100 cms and being located on the fringes of tropical forests of the Sahyadri Mountains (Western Ghats) receives little crustal contribution to the aerosols. Samples from least polluted mountainous areas of Himalayas (Gangothri) and Sahyadri

  2. Spatial distribution of dust-bound trace elements in Pakistan and their implications for human exposure.

    PubMed

    Eqani, Syed Ali Musstjab Akber Shah; Kanwal, Ayesha; Bhowmik, Avit Kumar; Sohail, Mohammad; Ullah, Rizwan; Ali, Syeda Maria; Alamdar, Ambreen; Ali, Nadeem; Fasola, Mauro; Shen, Heqing

    2016-06-01

    This study aims to assess the spatial patterns of selected dust-borne trace elements alongside the river Indus Pakistan, their relation with anthropogenic and natural sources, and the potential risk posed to human health. The studied elements were found in descending concentrations: Mn, Zn, Pb, Cu, Ni, Cr, Co, and Cd. The Index of Geo-accumulation indicated that pollution of trace metals were higher in lower Indus plains than on mountain areas. In general, the toxic elements Cr, Mn, Co and Ni exhibited altitudinal trends (P < 0.05). The few exceptions to this trend were the higher values for all studied elements from the northern wet mountainous zone (low lying Himalaya). Spatial PCA/FA highlighted that the sources of different trace elements were zone specific, thus pointing to both geological influences and anthropogenic activities. The Hazard Index for Co and for Mn in children exceeded the value of 1 only in the riverine delta zone and in the southern low lying zone, whereas the Hazard Index for Pb was above the bench mark for both children and adults (with few exceptions) in all regions, thus indicating potential non-carcinogenic health risks. These results will contribute towards the environmental management of trace metal(s) with potential risk for human health throughout Pakistan. PMID:26901073

  3. Metastatic seminoma presenting as flank pain

    PubMed Central

    Smyth, Lisa G.; Davis, Niall F.; Forde, James C.; O’Kelly, Olive; Gupta, Rrajnish K.; Flood, Hugh

    2013-01-01

    Seminoma is the most common single histological sub-type of testicular carcinoma. Patients usually present with a painless lump and stage I disease. We describe a case of an incidental meta-static seminoma in a 28-year-old man post-renal trauma with a dramatically elevated β-human chorionic gonadotropin (βHCG). His βHCG level has returned to normal post-orchidectomy and chemotherapy. PMID:24475006

  4. The effect of transposable elements on phenotypic variation: insights from plants to humans.

    PubMed

    Wei, Liya; Cao, Xiaofeng

    2016-01-01

    Transposable elements (TEs), originally discovered in maize as controlling elements, are the main components of most eukaryotic genomes. TEs have been regarded as deleterious genomic parasites due to their ability to undergo massive amplification. However, TEs can regulate gene expression and alter phenotypes. Also, emerging findings demonstrate that TEs can establish and rewire gene regulatory networks by genetic and epigenetic mechanisms. In this review, we summarize the key roles of TEs in fine-tuning the regulation of gene expression leading to phenotypic plasticity in plants and humans, and the implications for adaption and natural selection. PMID:26753674

  5. Development of a finite element model of a finger pad for biomechanics of human tactile sensations.

    PubMed

    Vodlak, Teja; Vidrih, Zlatko; Fetih, Dusan; Peric, Djordje; Rodic, Tomaz

    2015-08-01

    The aim of ongoing research is to develop a multi-scale multi-physics computational framework for modelling of human touch in order to provide understanding of fundamental biophysical mechanisms responsible for tactile sensation. The paper presents the development of a macro-scale global finite element model of the finger pad and calibration of applied material models against experimental results using inverse method. The developed macro model serves as a basis for down-scaling to micro finite element models of mechanoreceptors and further implementations and applications as a virtual tool in scientific or industrial applications related to neuroscience, haptics, prosthetics, virtual touch and packaging. PMID:26736410

  6. Assessing land-use change using the trace element chemistry of human bones (Invited)

    NASA Astrophysics Data System (ADS)

    Hannigan, R. E.; Darrah, T. H.; Prutsman-Pfeiffer, J.

    2009-12-01

    Reconstruction of environmental life histories using the elemental chemistry of biominerals is becoming common in ecological research. Less common is the application of these approaches to reconstruct environmental records from human bones. Here we present trace element data from human long bone of various ages and environments. Specifically samples from poorhouse burials in Rochester, NY (1750’s) and Buffalo, NY (1855) and a pioneer burial site in Mt. Morris, NY (1810) and associated soil samples were analyzed by ICP-MS. Based on differences in soil type, geology, groundwater chemistry, diet, bone pathology, life style at time of death (diet etc.) we reconstructed environmental life histories of the three populations as well as identified differences between individuals attributable to life style. These data reveal the potential of human bone trace element chemistry to provide retrospective information regarding land-use. Using human bone chemistry of populations within a single area is it possible to assess long-term changes in land-use as reflective of diet, occupation, etc.

  7. Genomic leftovers: identifying novel microsatellites, over-represented motifs and functional elements in the human genome.

    PubMed

    Fonville, Natalie C; Velmurugan, Karthik Raja; Tae, Hongseok; Vaksman, Zalman; McIver, Lauren J; Garner, Harold R

    2016-01-01

    The human genome is 99% complete. This study contributes to filling the 1% gap by enriching previously unknown repeat regions called microsatellites (MST). We devised a Global MST Enrichment (GME) kit to enrich and nextgen sequence 2 colorectal cell lines and 16 normal human samples to illustrate its utility in identifying contigs from reads that do not map to the genome reference. The analysis of these samples yielded 790 novel extra-referential concordant contigs that are observed in more than one sample. We searched for evidence of functional elements in the concordant contigs in two ways: (1) BLAST-ing each contig against normal RNA-Seq samples, (2) Checking for predicted functional elements using GlimmerHMM. Of the 790 concordant contigs, 37 had an exact match to at least one RNA-Seq read; 15 aligned to more than 100 RNA-Seq reads. Of the 249 concordant contigs predicted by GlimmerHMM to have functional elements, 6 had at least one exact RNA-Seq match. BLAST-ing these novel contigs against all publically available sequences confirmed that they were found in human and chimpanzee BAC and FOSMID clones sequenced as part of the original human genome project. These extra-referential contigs predominantly contained pentameric repeats, especially two motifs: AATGG and GTGGA. PMID:27278669

  8. Evidence of extensive non-allelic gene conversion among LTR elements in the human genome.

    PubMed

    Trombetta, Beniamino; Fantini, Gloria; D'Atanasio, Eugenia; Sellitto, Daniele; Cruciani, Fulvio

    2016-01-01

    Long Terminal Repeats (LTRs) are nearly identical DNA sequences found at either end of Human Endogenous Retroviruses (HERVs). The high sequence similarity that exists among different LTRs suggests they could be substrate of ectopic gene conversion events. To understand the extent to which gene conversion occurs and to gain new insights into the evolutionary history of these elements in humans, we performed an intra-species phylogenetic study of 52 LTRs on different unrelated Y chromosomes. From this analysis, we obtained direct evidence that demonstrates the occurrence of ectopic gene conversion in several LTRs, with donor sequences located on both sex chromosomes and autosomes. We also found that some of these elements are characterized by an extremely high density of polymorphisms, showing one of the highest nucleotide diversities in the human genome, as well as a complex patchwork of sequences derived from different LTRs. Finally, we highlighted the limits of current short-read NGS studies in the analysis of genetic diversity of the LTRs in the human genome. In conclusion, our comparative re-sequencing analysis revealed that ectopic gene conversion is a common event in the evolution of LTR elements, suggesting complex genetic links among LTRs from different chromosomes. PMID:27346230

  9. Evidence of extensive non-allelic gene conversion among LTR elements in the human genome

    PubMed Central

    Trombetta, Beniamino; Fantini, Gloria; D’Atanasio, Eugenia; Sellitto, Daniele; Cruciani, Fulvio

    2016-01-01

    Long Terminal Repeats (LTRs) are nearly identical DNA sequences found at either end of Human Endogenous Retroviruses (HERVs). The high sequence similarity that exists among different LTRs suggests they could be substrate of ectopic gene conversion events. To understand the extent to which gene conversion occurs and to gain new insights into the evolutionary history of these elements in humans, we performed an intra-species phylogenetic study of 52 LTRs on different unrelated Y chromosomes. From this analysis, we obtained direct evidence that demonstrates the occurrence of ectopic gene conversion in several LTRs, with donor sequences located on both sex chromosomes and autosomes. We also found that some of these elements are characterized by an extremely high density of polymorphisms, showing one of the highest nucleotide diversities in the human genome, as well as a complex patchwork of sequences derived from different LTRs. Finally, we highlighted the limits of current short-read NGS studies in the analysis of genetic diversity of the LTRs in the human genome. In conclusion, our comparative re-sequencing analysis revealed that ectopic gene conversion is a common event in the evolution of LTR elements, suggesting complex genetic links among LTRs from different chromosomes. PMID:27346230

  10. Genomic leftovers: identifying novel microsatellites, over-represented motifs and functional elements in the human genome

    PubMed Central

    Fonville, Natalie C.; Velmurugan, Karthik Raja; Tae, Hongseok; Vaksman, Zalman; McIver, Lauren J.; Garner, Harold R.

    2016-01-01

    The human genome is 99% complete. This study contributes to filling the 1% gap by enriching previously unknown repeat regions called microsatellites (MST). We devised a Global MST Enrichment (GME) kit to enrich and nextgen sequence 2 colorectal cell lines and 16 normal human samples to illustrate its utility in identifying contigs from reads that do not map to the genome reference. The analysis of these samples yielded 790 novel extra-referential concordant contigs that are observed in more than one sample. We searched for evidence of functional elements in the concordant contigs in two ways: (1) BLAST-ing each contig against normal RNA-Seq samples, (2) Checking for predicted functional elements using GlimmerHMM. Of the 790 concordant contigs, 37 had an exact match to at least one RNA-Seq read; 15 aligned to more than 100 RNA-Seq reads. Of the 249 concordant contigs predicted by GlimmerHMM to have functional elements, 6 had at least one exact RNA-Seq match. BLAST-ing these novel contigs against all publically available sequences confirmed that they were found in human and chimpanzee BAC and FOSMID clones sequenced as part of the original human genome project. These extra-referential contigs predominantly contained pentameric repeats, especially two motifs: AATGG and GTGGA. PMID:27278669

  11. STAT5 plays a critical role in regulating the 5'-flanking region of the porcine whey acidic protein gene in transgenic mice.

    PubMed

    Ji, Mi-Ran; Lee, Sang In; Jang, Ye-Jin; Jeon, Mi-Hyang; Kim, Jeom Sun; Kim, Kyung-Woon; Park, Jin-Ki; Yoo, Jae Gyu; Jeon, Ik-Soo; Kwon, Dae-Jin; Park, Choon-Keun; Byun, Sung June

    2015-12-01

    The mammary gland serves as a valuable bioreactor system for the production of recombinant proteins in lactating animals. Pharmaceutical-grade recombinant protein can be harvested from the milk of transgenic animals that carry a protein of interest under the control of promoter regions genes encoding milk proteins. Whey acidic protein (WAP), for example, is predominantly expressed in the mammary gland and is regulated by lactating hormones during pregnancy. We cloned the 5'-flanking region of the porcine WAP gene (pWAP) to confirm the sequence elements in its promoter that are required for gene-expression activity. In the present study, we investigated how lactogenic hormones--including prolactin, hydrocortisone, and insulin--contribute to the transcriptional activation of the pWAP promoter region in mammalian cells, finding that these hormones activate STAT5 signaling, which in turn induce gene expression via STAT5 binding sites in its 5'-flanking region. To confirm the expression and hormonal regulation of the 5'-flanking region of pWAP in vivo, we generated transgenic mice expressing human recombinant granulocyte colony stimulating factor (hCSF2) in the mammary gland under the control of the pWAP promoter. These mice secreted hCSF2 protein in their milk at levels ranging from 242 to 1,274.8 ng/ml. Collectively, our findings show that the pWAP promoter may be useful for confining the expression of foreign proteins to the mammary gland, where they can be secreted along with milk. PMID:26256125

  12. The Implications of Flank Vents on Olympus Mons

    NASA Astrophysics Data System (ADS)

    Peters, S.; Christensen, P. R.

    2014-12-01

    Flank vents are a common feature on polygenetic volcanoes. They indicate that magma has propagated away from the main conduit and/or magma chamber. Flank vents and flank eruptions have been documented and studied on a number of terrestrial volcanoes and to a lesser degree on Mars. The distribution of volcanic vents about a central caldera can provide information on radial dikes and tectonic stresses acting on the volcano, and can constrain models involving the emplacement and flexure of the edifice (e.g. Nakamura, 1976; McGovern and Solomon, 1993). In the absence of spectral data (due to optically thick dust cover) and in situ observations, morphology is a powerful tool for ascertaining the eruptive and tectonic history of Olympus Mons. Approximately 190 high-resolution CTX (Context Camera) images covering Olympus Mons have been mosaicked together. The analysis of a CTX mosaic reveals Mars's largest shield volcano in stunning detail and allows for a thorough analysis of the targeted features. Preliminary results show numerous flank vents some of which produce leveed channels on the slopes of Olympus Mons. Some vents display varying morphologies, suggesting that the style of volcanism has evolved over time. Flank vents are observed to occur over a range of elevations, although a paucity of vents is observed on the lower flank. Analyses are ongoing and include mapping the spatial and elevation distribution of flank vents on the shield. Once mapped, the distribution of flank vents will define the orientation of tectonic stresses acting on Olympus Mons and help determine whether they are influenced by underlying topography, regional scale processes or a combination of both. In addition, these vents act as a window into the subsurface which can help characterize dike emplacement within the shield. Furthermore, the morphology of flank vents will provide information on the evolution of their eruptive styles. All of this information is crucial to help understand the

  13. Cloning and characterization of the 5'-flanking region of the Ehox gene

    SciTech Connect

    Lee, Woon Kyu . E-mail: wklee@yumc.yonsei.ac.kr; Kim, Yong-Man; Malik, Nasir; Ma Chang; Westphal, Heiner

    2006-03-03

    The paired-like homeobox-containing gene Ehox plays a role in embryonic stem cell differentiation and is highly expressed in the developing placenta and thymus. To understand the mechanisms of regulation of Ehox gene expression, the 5'-flanking region of the Ehox gene was isolated from a mouse BAC library. 5'-RACE analysis revealed a single transcriptional start site 130 nucleotides upstream of the translation initiation codon. Transient transfection with a luciferase reporter gene under the control of serially deleted 5'-flanking sequences revealed that the nt -84 to -68 region contained a positive cis-acting element for efficient expression of the Ehox gene. Mutational analysis of this region and oligonucleotide competition in the electrophoretic mobility shift assay revealed the presence of a CCAAT box, which is a target for transcription nuclear factor Y (NFY). NFY is essential for positive gene regulation. No tissue-specific enhancer was identified in the 1.9-kb 5'-flanking region of the Ehox gene. Ehox is expressed during the early stages of embryo development, specifically in Brain at 9.5 dpc, as well as during the late stages of embryo development. These results suggest that NFY is an essential regulatory factor for Ehox transcriptional activity, which is important for the post-implantation stage of the developing embryo.

  14. Identification of the principal promoter sequence of the c-H-ras transforming oncogene: deletion analysis of the 5'-flanking region by focus formation assay.

    PubMed Central

    Honkawa, H; Masahashi, W; Hashimoto, S; Hashimoto-Gotoh, T

    1987-01-01

    A number of deletion mutants were isolated, including 5', 3', and internal deletions in the 5'-flanking region of the human cellular oncogene related to the Harvey sarcoma virus (c-H-ras), and their transforming activities were examined in NIH 3T3 cells. DNA sequences which could not be detected without losing transforming activity were localized to a relatively short stretch upstream of the region which showed homology to the 5'-flanking region of v-H-ras oncogene. S1 nuclease analysis indicated that there were two clusters of mRNA start sites at positions that were about 1,371 and 1,298 base pairs upstream of the first coding ATG. The minimum region required for promoter function was estimated to be a 51-base-pair-long (or less) DNA segment. The promoter was GC rich (78%) and did not contain the consensus sequences that are usually observed in PolII-directed promoters but contained a GC box within which one of the mRNA start sites was included. In addition, two sets of positive and negative elements seemed to be located between the promoter and the protein-coding region, which appeared to influence positively and negatively, respectively, the efficiency of transformation with the c-H-ras oncogene. Images PMID:3670300

  15. Distribution of trace elements in the human body determined by neutron activation analysis

    SciTech Connect

    Yukawa, M.; Suzuki-Yasumoto, M.; Amano, K.; Terai, M.

    1980-01-01

    Neutron activation analysis and instrumental semiconductor gamma-ray spectrometry were used for analysis of 20 trace elements in 10 autopsied human organs and tissues (liver, kidney, cerebrum, cerebellum, heart, muscle, pancreas, spleen, lung, and aorta) from 63 Japanese persons, whose ages ranged from 15 days to 85 yr. Distributions of aluminum, bromine, magnesium, manganese, rubidium, selenium, and vanadium in human body were almost uniform. High concentrations of cadmium were found in kidney and liver samples. There was a high mercury concentration in the liver, kidney, and brain samples. Concentrations of other elements (arsenic, gold, cobalt, chromium, copper, iron, indium, antimony, selenium, titanium, and zinc) in each organ or tissue are also presented in this paper.

  16. Investigating the functionality of an OCT4-short response element in human induced pluripotent stem cells

    PubMed Central

    Vega-Crespo, Agustin; Truong, Brian; Hermann, Kip J; Awe, Jason P; Chang, Katherine M; Lee, Patrick C; Schoenberg, Benjamen E; Wu, Lily; Byrne, James A; Lipshutz, Gerald S

    2016-01-01

    Pluripotent stem cells offer great therapeutic promise for personalized treatment platforms for numerous injuries, disorders, and diseases. Octamer-binding transcription factor 4 (OCT4) is a key regulatory gene maintaining pluripotency and self-renewal of mammalian cells. With site-specific integration for gene correction in cellular therapeutics, use of the OCT4 promoter may have advantages when expressing a suicide gene if pluripotency remains. However, the human OCT4 promoter region is 4 kb in size, limiting the capacity of therapeutic genes and other regulatory components for viral vectors, and decreasing the efficiency of homologous recombination. The purpose of this investigation was to characterize the functionality of a novel 967bp OCT4-short response element during pluripotency and to examine the OCT4 titer-dependent response during differentiation to human derivatives not expressing OCT4. Our findings demonstrate that the OCT4-short response element is active in pluripotency and this activity is in high correlation with transgene expression in vitro, and the OCT4-short response element is inactivated when pluripotent cells differentiate. These studies demonstrate that this shortened OCT4 regulatory element is functional and may be useful as part of an optimized safety component in a site-specific gene transferring system that could be used as an efficient and clinically applicable safety platform for gene transfer in cellular therapeutics. PMID:27500178

  17. Minimizing Human Risk: Human Performance Models in the Space Human Factors and Habitability and Behavioral Health and Performance Elements

    NASA Technical Reports Server (NTRS)

    Gore, Brian F.

    2016-01-01

    Human space exploration has never been more exciting than it is today. Human presence to outer worlds is becoming a reality as humans are leveraging much of our prior knowledge to the new mission of going to Mars. Exploring the solar system at greater distances from Earth than ever before will possess some unique challenges, which can be overcome thanks to the advances in modeling and simulation technologies. The National Aeronautics and Space Administration (NASA) is at the forefront of exploring our solar system. NASA's Human Research Program (HRP) focuses on discovering the best methods and technologies that support safe and productive human space travel in the extreme and harsh space environment. HRP uses various methods and approaches to answer questions about the impact of long duration missions on the human in space including: gravity's impact on the human body, isolation and confinement on the human, hostile environments impact on the human, space radiation, and how the distance is likely to impact the human. Predictive models are included in the HRP research portfolio as these models provide valuable insights into human-system operations. This paper will provide an overview of NASA's HRP and will present a number of projects that have used modeling and simulation to provide insights into human-system issues (e.g. automation, habitat design, schedules) in anticipation of space exploration.

  18. New invMED1 element cis-activates human multidrug-related MDR1 and MVP genes, involving the LRP130 protein.

    PubMed

    Labialle, Stéphane; Dayan, Guila; Gayet, Landry; Rigal, Dominique; Gambrelle, Joël; Baggetto, Loris G

    2004-01-01

    The MDR1 gene is a key component of the cytotoxic defense network and its overexpression results in the multidrug resistance (MDR) phenotype. However, the molecular mechanisms that regulate the MDR1 gene and coordinate multiple MDR-related genes expression are poorly understood. In a previous study, we identified a new 12 bp cis-activating region in the 5'-flanking region of the human MDR1 gene, which we called inverted MED1. In the present study, we characterized the precise binding element, which we named invMED1, and revealed the presence of the LRP130 protein as the nuclear factor. Its binding intensity increases with the endogenous MDR1 geneexpression and with the MDR level of CEM leukemia cells. Interestingly, the LRP130 level did not vary with the chemoresistance level. We observed the involvement of LRP130 in the transcriptional activity of the MDR1 gene promoter, and moreover, in that of the MDR-related, invMED1-containing, MVP gene promoter. We used siRNAs and transcriptional decoys in two unrelated human cancer cell lines to show the role of the invMED1/LRP130 couple in both MDR1 and MVP endogenous genes activities. We showed that invMED1 was localized in the -105/-100 and -148/-143 regions of the MDR1 and MVP gene promoters, respectively. In addition, since the invMED1 sequence is primarily located in the -160/-100 bp region of mammalian MDR-related genes, our results present the invMED1/LRP130 couple as a potential central regulator of the transcription of these genes. PMID:15272088

  19. My patient has abdominal and flank pain: Identifying renal causes.

    PubMed

    Cox, Christopher; MacDonald, Scott; Henneberry, Ryan; Atkinson, Paul R

    2015-11-01

    Acute flank and abdominal pain are common presenting complaints in the emergency department. With increasing access to point-of-care ultrasound (PoCUS), emergency physicians have an added tool to help identify renal problems as a cause of a patient's pain. PoCUS for hydronephrosis has a sensitivity of 72-83.3% and a varying specificity, similar to radiology-performed ultrasonography. In addition to assessment for hydronephrosis, PoCUS can help emergency physicians to exclude other serious causes of flank and abdominal pain such as the presence of an abdominal aortic aneurysm, or free fluid in the intraperitoneal space, which could represent hemorrhage. Use of PoCUS for the assessment of flank pain has resulted in more rapid diagnosis, decreased use of computed tomography, and shorter emergency department length of stay. PMID:27433264

  20. Trace elements contamination and human health risk assessment in drinking water from Shenzhen, China.

    PubMed

    Lu, Shao-You; Zhang, Hui-Min; Sojinu, Samuel O; Liu, Gui-Hua; Zhang, Jian-Qing; Ni, Hong-Gang

    2015-01-01

    The levels of seven essential trace elements (Mn, Co, Ni, Cu, Zn, Se, and Mo) and six non-essential trace elements (Cr, As, Cd, Sb, Hg, and Pb) in a total of 89 drinking water samples collected in Shenzhen, China were determined using inductively coupled plasma mass spectrometry (ICP-MS) in the present study. Both the essential and non-essential trace elements were frequently detectable in the different kinds of drinking waters assessed. Remarkable temporal and spatial variations were observed among most of the trace elements in the tap water collected from two tap water treatment plants. Meanwhile, potential human health risk from these non-essential trace elements in the drinking water for local residents was also assessed. The median values of cancer risks associated with exposure to carcinogenic metals via drinking water consumption were estimated to be 6.1 × 10(-7), 2.1 × 10(-8), and 2.5 × 10(-7) for As, Cd, and Cr, respectively; the median values of incremental lifetime for non-cancer risks were estimated to be 6.1 × 10(-6), 4.4 × 10(-5), and 2.2 × 10(-5) for Hg, Pb, and Sb, respectively. The median value of total incremental lifetime health risk induced by the six non-essential trace elements for the population was 3.5 × 10(-5), indicating that the potential health risks from non-carcinogenic trace elements in drinking water also require some attention. Sensitivity analysis indicates that the most important factor for health risk assessment should be the levels of heavy metal in drinking water. PMID:25514858

  1. Integration of Expressed Sequence Tag Data Flanking Predicted RNA Secondary Structures Facilitates Novel Non-Coding RNA Discovery

    PubMed Central

    Krzyzanowski, Paul M.; Price, Feodor D.; Muro, Enrique M.; Rudnicki, Michael A.; Andrade-Navarro, Miguel A.

    2011-01-01

    Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation. PMID:21698286

  2. Integration of expressed sequence tag data flanking predicted RNA secondary structures facilitates novel non-coding RNA discovery.

    PubMed

    Krzyzanowski, Paul M; Price, Feodor D; Muro, Enrique M; Rudnicki, Michael A; Andrade-Navarro, Miguel A

    2011-01-01

    Many computational methods have been used to predict novel non-coding RNAs (ncRNAs), but none, to our knowledge, have explicitly investigated the impact of integrating existing cDNA-based Expressed Sequence Tag (EST) data that flank structural RNA predictions. To determine whether flanking EST data can assist in microRNA (miRNA) prediction, we identified genomic sites encoding putative miRNAs by combining functional RNA predictions with flanking ESTs data in a model consistent with miRNAs undergoing cleavage during maturation. In both human and mouse genomes, we observed that the inclusion of flanking ESTs adjacent to and not overlapping predicted miRNAs significantly improved the performance of various methods of miRNA prediction, including direct high-throughput sequencing of small RNA libraries. We analyzed the expression of hundreds of miRNAs predicted to be expressed during myogenic differentiation using a customized microarray and identified several known and predicted myogenic miRNA hairpins. Our results indicate that integrating ESTs flanking structural RNA predictions improves the quality of cleaved miRNA predictions and suggest that this strategy can be used to predict other non-coding RNAs undergoing cleavage during maturation. PMID:21698286

  3. Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence.

    PubMed

    Scott, A F; Schmeckpeper, B J; Abdelrazik, M; Comey, C T; O'Hara, B; Rossiter, J P; Cooley, T; Heath, P; Smith, K D; Margolet, L

    1987-10-01

    A consensus sequence for the human long interspersed repeated DNA element, L1Hs (LINE or KpnI sequence), is presented. The sequence contains two open reading frames (ORFs) which are homologous to ORFs in corresponding regions of L1 elements in other species. The L1Hs ORFs are separated by a small evolutionarily nonconserved region. The 5' end of the consensus contains frequent terminators in all three reading frames and has a relatively high GC content with numerous stretches of weak homology with AluI repeats. The 5' ORF extends for a minimum of 723 bp (241 codons). The 3' ORF is 3843 bp (1281 codons) and predicts a protein of 149 kD which has regions of weak homology to the polymerase domain of various reverse transcriptases. The 3' end of the consensus has a 208-bp nonconserved region followed by an adenine-rich end. The organization of the L1Hs consensus sequence resembles the structure of eukaryotic mRNAs except for the noncoding region between ORFs. However, due to base substitutions or truncation most elements appear incapable of producing mRNA that can be translated. Our observation that individual elements cluster into subfamilies on the basis of the presence or absence of blocks of sequence, or by the linkage of alternative bases at multiple positions, suggests that most L1 sequences were derived from a small number of structural genes. An estimate of the mammalian L1 substitution rate was derived and used to predict the age of individual human elements. From this it follows that the majority of human L1 sequences have been generated within the last 30 million years. The human elements studied here differ from each other, yet overall the L1Hs sequences demonstrate a pattern of species-specificity when compared to the L1 families of other mammals. Possible mechanisms that may account for the origin and evolution of the L1 family are discussed. These include pseudogene formation (retroposition), transposition, gene conversion, and RNA recombination. PMID

  4. West Flank Coso FORGE Magnetotelluric 3D Data

    SciTech Connect

    Doug Blankenship

    2016-01-01

    This is the 3D version of the MT data for the West Flank FORGE area.The Coso geothermal field has had three Magnetotelluric (MT) datasets collected including surveys in 2003, 2006, and 2011. The final collection, in 2011, expanded the survey to the west and covers the West Flank of FORGE area.This most recent data set was collected by Schlumberger/WesternGeco and inverted by the WesternGeco GeoSolutions Integrated EM Center of Excellence in Milan, Italy; the 2003 and 2006 data were integrated for these inversions in the present study.

  5. Transducer model produces facilitation from opposite-sign flanks

    NASA Technical Reports Server (NTRS)

    Solomon, J. A.; Watson, A. B.; Morgan, M. J.

    1999-01-01

    Small spots, lines and Gabor patterns can be easier to detect when they are superimposed upon similar spots, lines and Gabor patterns. Traditionally, such facilitation has been understood to be a consequence of nonlinear contrast transduction. Facilitation has also been reported to arise from non-overlapping patterns with opposite sign. We point out that this result does not preclude the traditional explanation for superimposed targets. Moreover, we find that facilitation from opposite-sign flanks is weaker than facilitation from same-sign flanks. Simulations with a transducer model produce opposite-sign facilitation.

  6. Stability analysis of Western flank of Cumbre Vieja volcano (La Palma) using numerical modelling

    NASA Astrophysics Data System (ADS)

    Bru, Guadalupe; Gonzalez, Pablo J.; Fernandez-Merodo, Jose A.; Fernandez, Jose

    2016-04-01

    La Palma volcanic island is one of the youngest of the Canary archipelago, being a composite volcano formed by three overlapping volcanic centers. There are clear onshore and offshore evidences of past giant landslides that have occurred during its evolution. Currently, the active Cumbre Vieja volcano is in an early development state (Carracedo et al., 2001). The study of flank instability processes aim to assess, among other hazards, catastrophic collapse and potential tsunami generation. Early studies of the potential instability of Cumbre Vieja volcano western flank have focused on the use of sparse geodetic networks (Moss et al. 1999), surface geological mapping techniques (Day et al. 1999) and offshore bathymetry (Urgeles et al. 1999). Recently, a dense GNSS network and satellite radar interferometry results indicate ground motion consistent with deep-seated creeping processes (Prieto et al. 2009, Gonzalez et al. 2010). In this work, we present a geomechanical advanced numerical model that captures the ongoing deformation processes at Cumbre Vieja. We choose the Finite Elements Method (FEM) which is based in continuum mechanics and is the most used for geotechnical applications. FEM has the ability of using arbitrary geometry, heterogeneities, irregular boundaries and different constitutive models representative of the geotechnical units involved. Our main contribution is the introduction of an inverse approach to constrain the geomechanical parameters using satellite radar interferometry displacements. This is the first application of such approach on a large volcano flank study. We suggest that the use of surface displacements and inverse methods to rigorously constrain the geomechanical model parameter space is a powerful tool to understand volcano flank instability. A particular important result of the studied case is the estimation of displaced rock volume, which is a parameter of critical importance for simulations of Cumbre Vieja tsunamigenic hazard

  7. Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements

    PubMed Central

    Moisan, Stéphanie; Berlivet, Soizik; Ka, Chandran; Gac, Gérald Le; Dostie, Josée; Férec, Claude

    2016-01-01

    A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory ‘chromatin looping’ systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation of CFTR is responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations. CFTR is a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at the CFTR locus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of the CFTR locus in expressing and non-expressing human primary cells, we identified several new contact points between the CFTR promoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increase CFTR expression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin looping via CTCF. PMID:26615198

  8. Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements.

    PubMed

    Moisan, Stéphanie; Berlivet, Soizik; Ka, Chandran; Gac, Gérald Le; Dostie, Josée; Férec, Claude

    2016-04-01

    A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory 'chromatin looping' systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation ofCFTRis responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations.CFTRis a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at theCFTRlocus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of theCFTRlocus in expressing and non-expressing human primary cells, we identified several new contact points between theCFTRpromoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increaseCFTRexpression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin loopingviaCTCF. PMID:26615198

  9. Composition of pore and spring waters from Baby Bare: global implications of geochemical fluxes from a ridge flank hydrothermal system

    NASA Astrophysics Data System (ADS)

    Wheat, C. Geoffrey; Mottl, Michael J.

    2000-02-01

    Warm hydrothermal springs were discovered on Baby Bare, which is an isolated basement outcrop on 3.5 Ma-old crust on the eastern flank of the Juan de Fuca Ridge. We have sampled these spring waters from a manned submersible, along with associated sediment pore waters from 48 gravity and piston cores. Systematic variations in the chemical composition of these waters indicate that hydrothermal reactions in basement at moderate temperatures (63°C in uppermost basement at this site) remove Na, K, Li, Rb, Mg, TCO 2, alkalinity, and phosphate from the circulating seawater and leach Ca, Sr, Si, B, and Mn from the oceanic crust; and that reactions with the turbidite sediment surrounding Baby Bare remove Na, Li, Mg, Ca, Sr, and sulfate from the pore water while producing ammonium and Si and both producing and consuming phosphate, nitrate, alkalinity, Mn, and Fe. K, Rb, and B are relatively unreactive in the sediment column. These data confirm the earlier inference that sediment pore waters from areas of upwelling can be used to estimate the composition of altered seawater in the underlying basement, even for those elements that are reactive in the sediment column or are affected by sampling artifacts. The composition of altered seawater in basement at Baby Bare is similar to the inferred composition of 58°C formation water from crust nearly twice as old (5.9 Ma) on the southern flank of the Costa Rica Rift. The Baby Bare fluids also exhibit the same directions of net elemental transfer between basalt and seawater as solutions produced in laboratory experiments at a similar temperature, and complement compositional changes from seawater observed in seafloor basalts altered at cool to moderate temperatures. The common parameter among the two ridge flanks and experiments is temperature, suggesting that the residence time of seawater in basement at the two ridge-flank sites is sufficiently long for the solutions to equilibrate with altered basalt. This conclusion is supported

  10. 10. INTERIOR OF LIVING ROOM SHOWING FRONT DOOR FLANKED BY ...

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

    10. INTERIOR OF LIVING ROOM SHOWING FRONT DOOR FLANKED BY SLIDING GLASS WINDOWS AND ELECTRICAL WALL HEATER. ORIGINAL 1-LIGHT OVER 1-LIGHT, DOUBLE-HUNG WINDOW AT PHOTO RIGHT. CEILING VENT TO CHIMNEY AT RIGHT UPPER PHOTO CENTER. VIEW TO SOUTHEAST. - Bishop Creek Hydroelectric System, Plant 4, Worker Cottage, Bishop Creek, Bishop, Inyo County, CA

  11. FACILITY 713, LIVING ROOM SHOWING DIAMONDPANED WINDOWS FLANKING THE FIREPLACE, ...

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

    FACILITY 713, LIVING ROOM SHOWING DIAMOND-PANED WINDOWS FLANKING THE FIREPLACE, AND LEADED-GLASS WINDOWS IN DINING ROOM IN RIGHT BACKGROUND, VIEW FACING SOUTHEAST. - Schofield Barracks Military Reservation, Central-Entry Single-Family Housing Type, Between Bragg & Grime Streets near Ayres Avenue, Wahiawa, Honolulu County, HI

  12. An efficient method for flanking sequence isolation in barley

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An adapter ligation method was developed to determine native barley (Hordeum vulgare) sequences flanking Ds insertions and barley ESTs. This method is simple and efficient, with the majority of queries returning valid sequence information. This report describes the protocol in detail, quantifies its...

  13. West Flank Coso, CA FORGE Natural Fracture data

    DOE Data Explorer

    Doug Blankenship

    2016-05-16

    Natural fracture data from wells 33-7, 33A-7,52A-7, 52B-7 and 83-11 at West Flank. Fracture orientations were determined from image logs of these wells (see accompanying submissions). Data files contain depth, apparent (in wellbore reference frame) and true (in geographic reference frame) azimuth and dip, respectively.

  14. Nature of thrusting along western flank of Bighorn Mountains, Wyoming

    SciTech Connect

    Noggle, K.S.

    1986-08-01

    The northern portion of the Bighorn Mountains is characterized by opposed mountain-front thrusts, of which the southwest direction is dominant. Blind basement thrusts along the northeastern flank do not pierce the folded Paleozoic cover; whereas on the western flank, southwest-directed thrust segments expose Precambrian rocks along a 24-km (14-mi) extent. Field studies on the western flank show evidence of four major southwest-directed thrust segments delineated by tear-fault boundaries, which include from northwest to southeast: (1) the Five Springs thrust, a low-angle, out-of-the-syncline fault mainly involving the sedimentary sequence; (2) the Bear Creek thrust, a continuation of the Five Springs out-of-the-syncline fault; (3) the South Beaver Creek thrust, which juxtaposes Precambrian rocks against a tectonically thinned, overturned anticlinal limb of Mississippian through Jurassic rocks and which is inward from an out-of-the-syncline thrust involving little displacement of Jurassic formations; and (4) a mountain-front reentrant that coincides with the zone where the South Beaver Creek thrust continues beneath Paleozoic cover, causing the upper flexure of a double monocline. The central portion of the Bighorn Mountains is thrust eastward, whereas the northern portion is thrust southwestward with much less displacement. The segmented association of southwest-directed basement thrusts along the western flank of the northern Bighorns is indicative of the major transport direction for that portion of the Bighorn uplift.

  15. Erosion of the submarine flanks of the Canary Islands

    NASA Astrophysics Data System (ADS)

    Mitchell, Neil C.; Dade, W. Brian; Masson, Douglas G.

    2003-12-01

    Surveying with multibeam echo sounders around old (≫1 Ma) volcanic ocean islands reveals that their submarine flanks contain a strong downslope-oriented ridge-and-valley corrugation, which modifies the original volcanic morphology of lava terraces and cones. By analogy with canyons in other settings, this corrugation was probably caused by channel incision by erosive sedimentary mass flows such as turbidity currents and debris flows. We adapt a method first used in subaerial geomorphology to isolate the erosion depth (exhumation) and apply it to the eroded flanks of the 6-8 Ma Anaga massif of Tenerife. The channels formed around this massif divert around local topographic highs. These highs, which are probably original volcanic cones, are therefore preferentially preserved during erosion, so that their elevations can be used to construct an artificial reference surface. Terrain depth was calculated by subtracting this reference surface from measured bathymetry. Comparison of the terrain depth of the old, eroded submarine flank of Anaga with that of the young, mostly unaltered submarine flank of El Hierro allows us to infer the mean depth of Anaga's submarine erosion, which is ˜100 m. Volcanic terrains can be dated by radiometric methods, so they also provide a way of quantifying long-term denudation rates. We infer that submarine denudation of Anaga has occurred at comparable rates to that of subaerial lowlands and much slower than denudation of highlands, illustrated locally by the more extensive erosion of the subaerial Anaga edifice.

  16. Urolithiasis presenting as right flank pain: a case report

    PubMed Central

    Chung, Chadwick; Stern, Paula J.; Dufton, John

    2013-01-01

    Background: Urolithiasis refers to renal or ureteral calculi referred to in lay terminology as a kidney stone. Utolithiasis is a potential emergency often resulting in acute abdominal, low back, flank or groin pain. Chiropractors may encounter patients when they are in acute pain or after they have recovered from the acute phase and should be knowledgeable about the signs, symptoms, potential complications and appropriate recommendations for management. Case presentation: A 52 year old male with acute right flank pain presented to the emergency department. A ureteric calculus with associated hydronephrosis was identified and he was prescribed pain medications and discharged to pass the stone naturally. One day later, he returned to the emergency department with severe pain and was referred to urology. He was managed with a temporary ureteric stent and antibiotics. Conclusion: This case describes a patient with acute right flank and lower quadrant pain which was diagnosed as an obstructing ureteric calculus. Acute management and preventive strategies in patients with visceral pathology such as renal calculi must be considered in patients with severe back and flank pain as it can progress to hydronephrosis and kidney failure. PMID:23483000

  17. Application of synchrotron radiation for elemental microanalysis of human central nervous System tissue

    NASA Astrophysics Data System (ADS)

    Szczerbowska-Boruchowska, M.; Lankosz, M.; Ostachowicz, J.; Adamek, D.; Krygowska-Wajs, A.; Tomik, B.; Szczudlik, A.; Simionovici, A.; Bohic, S.

    2003-03-01

    The pathogenesis of two neurodegenerative diseases i.e. Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS) are still not known. It is supposed that disturbance of metal ions homeostasis may promote degeneration and atrophy of neurones. As a preliminary study. the quantitative and topographic elemental analysis of selected parts of human brain and spinal cord was performed using synchrotron microbeam-X ray fluorescence (μ-SXRF) technique. The samples were taken during the autopsy from patients with PD, ALS and from patients died due to non-neurological conditions events. X-ray fluorescence imaging showed that increased concentration of selected elements are observed in neurons perikarial parts in compare with surrounding area. Moreover, comparable analysis showed significant differences in accumulation of selected elements between the pathological and control cases. The investigations indicate that micro-beam of synchrotron radiation can be satisfactory applied for analysis of central nervous System tissue providing useful information about distribution and contents of elements at the single cell level.

  18. Retrotransposition creates sloping shores: a graded influence of hypomethylated CpG islands on flanking CpG sites

    PubMed Central

    Grandi, Fiorella C.; Rosser, James M.; Newkirk, Simon J.; Yin, Jun; Jiang, Xiaoling; Xing, Zhuo; Whitmore, Leanne; Bashir, Sanum; Ivics, Zoltán; Izsvák, Zsuzsanna; Ye, Ping; Yu, Y. Eugene; An, Wenfeng

    2015-01-01

    Long interspersed elements (LINEs), through both self-mobilization and trans-mobilization of short interspersed elements and processed pseudogenes, have made an indelible impact on the structure and function of the human genome. One consequence is the creation of new CpG islands (CGIs). In fact, more than half of all CGIs in the genome are associated with repetitive DNA, three-quarters of which are derived from retrotransposons. However, little is known about the epigenetic impact of newly inserted CGIs. We utilized a transgenic LINE-1 mouse model and tracked DNA methylation dynamics of individual germline insertions during mouse development. The retrotransposed GFP marker sequence, a strong CGI, is hypomethylated in male germ cells but hypermethylated in somatic tissues, regardless of genomic location. The GFP marker is similarly methylated when delivered into the genome via the Sleeping Beauty DNA transposon, suggesting that the observed methylation pattern may be independent of the mode of insertion. Comparative analyses between insertion- and non-insertion-containing alleles further reveal a graded influence of the retrotransposed CGI on flanking CpG sites, a phenomenon that we described as “sloping shores.” Computational analyses of human and mouse methylomic data at single-base resolution confirm that sloping shores are universal for hypomethylated CGIs in sperm and somatic tissues. Additionally, the slope of a hypomethylated CGI can be affected by closely positioned CGI neighbors. Finally, by tracing sloping shore dynamics through embryonic and germ cell reprogramming, we found evidence of bookmarking, a mechanism that likely determines which CGIs will be eventually hyper- or hypomethylated. PMID:25995269

  19. Finite element modeling and modal analysis of the human spine vibration configuration.

    PubMed

    Guo, Li-Xin; Zhang, Yi-Min; Zhang, Ming

    2011-10-01

    This study was designed to investigate the modal characteristics of the human spine. A 3-D finite element model of the spine T12-Pelvis segment was used to extract resonant frequencies and modal modes of the human spine. By finite element modal analysis and harmonic response analysis, several lower vibration modes in the flexion-extension, lateral bending, and vertical directions were obtained and its vibration configurations were shown in this paper. The results indicate that the lowest resonant frequency of the model is in the flexion-extension direction. The second-order resonant frequency is in the lateral bending direction and the third-order resonant frequency of the T12-Pelvis model is in the vertical direction. The results also show that lumbar spinal vertebrae conduct the rotation action during whole body vibration (WBV). The vibration configurations of the lumbar spine can explore the motion mechanism of different lumbar components under WBV and make us to understand the vibration-induced spine diseases. The findings in this study will be helpful to understand WBV-related injury of the spine in clinics and the ergonomics design and development of mechanical production to protect human spine safety. PMID:21693412

  20. Partitioning of Inorganic Elements Consumed by Humans Between the Various Fractions of Human Wastes: A Review and Analysis of Existing Literature

    NASA Technical Reports Server (NTRS)

    Wignarajah, K.; Fisher, John W.; Pisharody, Suresh A.

    2003-01-01

    The nutritional requirements of humans and astronauts are well defined and show consistency, but the same cannot be said of human wastes. Nutrients taken up by humans can be considered to fall into two major categories - organic and inorganic fractions. Carbon, hydrogen, oxygen, nitrogen and sulfur are elements that are associated with the organic fraction. These elements are taken up in large amounts by humans and when metabolized released in wastes often in gaseous forms or as water. On the other hand, a large number of the elements are simply exchanged and can be accounted for in the liquid and solid wastes of humans. These elements fall into three major categories - cationic macroelements (e.g. Ca, K, Na, Mg and Si), anionic macroelements (e.g P, S and Cl), 17 essential microelements, (e.g. Fe, Mn, Cr, Co, Cu, Zn, Se and Sr). When provided in the recommended concentrations to an adult human, these elements should not normally accumulate in humans, but will be excreted in the different human wastes. Knowledge of the partitioning of these elements between the different human waste fractions is fundamental to understanding (a) how these elements can be recovered for reuse in space habitats, and (b) to developing the processors for waste management. The current literature is exhaustive but sometimes also conflicting. We have used the existing knowledge of nutrition and waste from medical literature and NASA documentation to develop a consensus to typify and chemically characterize the various human wastes. The partitioning of these elements has been developed into a functional model.

  1. A paradigm for human body finite element model integration from a set of regional models.

    PubMed

    Thompson, A B; Gayzik, F S; Moreno, D P; Rhyne, A C; Vavalle, N A; Stitzel, J D

    2012-01-01

    Computational modeling offers versatility, scalability, and cost advantages to researchers in the trauma and injury biomechanics communities. The Global Human Body Models Consortium (GHBMC) is a group of government, industry, and academic researchers developing human body models (HBMs) that aim to become the standard tool to meet this growing research need. The objective of this study is to present the methods used to develop the average seated male occupant model (M50, weight = 78 kg, height = 175 cm) from five separately validated body region models (BRMs). BRMs include the head, neck, thorax, abdomen, and a combined pelvis and lower extremity model. Modeling domains were split at the atlanto-occipital joint, C7-T1 boundary, diaphragm, abdominal cavity (peritoneum/retroperitoneum), and the acetabulum respectively. BRM meshes are based on a custom CAD model of the seated male built from a multi-modality imaging protocol of a volunteer subject found in literature.[1] Various meshing techniques were used to integrate the full body model (FBM) including 1-D beam and discrete element connections (e.g. ligamentous structures), 2D shell nodal connections (e.g. inferior vena cava to right atrium), 3D hexahedral nodal connections (e.g. soft tissue envelope connections between regions), and contact definitions varying from tied (muscle insertions) to sliding (liver and diaphragm contact). The model was developed in a general-purpose finite element code, LS-Dyna (LTSC, Livermore, CA) R4.2.1., and consists of 1.95 million elements and 1.3 million nodes. The element breakdown by type is 41% hexahedral, 33.7% tetrahedral, 19.5% quad shells and 5% tria shell. The integration methodology presented highlights the viability of using a collaborative development paradigm for the construction of HBMs, and will be used as template for expanding the suite of GHBMC models. PMID:22846315

  2. Influence of trace elements in human tissue in low-energy photon brachytherapy dosimetry

    NASA Astrophysics Data System (ADS)

    White, Shane A.; Landry, Guillaume; van Gils, Francis; Verhaegen, Frank; Reniers, Brigitte

    2012-06-01

    The aim of this paper is to determine the dosimetric impact of trace elements in human tissues for low-energy photon sources used in brachytherapy. Monte Carlo dose calculations were used to investigate the dosimetric effect of trace elements present in normal or cancerous human tissues. The effect of individual traces (atomic number Z = 11-30) was studied in soft tissue irradiated by low-energy brachytherapy sources. Three other tissue types (prostate, adipose and mammary gland) were also simulated with varying trace concentrations to quantify the contribution of each trace to the dose distribution. The dose differences between cancerous and healthy prostate tissues were calculated in single- and multi-source geometries. The presence of traces in a tissue produces a difference in the dose distribution that is dependent on Z and the concentration of the trace. Low-Z traces (Na) have a negligible effect (<0.3%) in all tissues, while higher Z (K) had a larger effect (>3%). There is a potentially significant difference in the dose distribution between cancerous and healthy prostate tissues (4%) and even larger if compared to the trace-free composition (15%) in both single- and multi-sourced geometries. Trace elements have a non-negligible (up to 8% in prostate D90) effect on the dose in tissues irradiated with low-energy photon sources. This study underlines the need for further investigation into accurate determination of the trace composition of tissues associated with low-energy brachytherapy. Alternatively, trace elements could be incorporated as a source of uncertainty in dose calculations. This work was part of an invited presentation at the ‘International Workshop on Recent Advances in Monte Carlo Techniques for Radiation Therapy’, held in Montreal, June 8-10, 2011.

  3. Characterization of Bovine NANOG5′-flanking Region during Differentiation of Mouse Embryonic Stem Cells

    PubMed Central

    Jang, Hye-Jeong; Park, Hwan Hee; Linh, Tran Thi Thuy; Lee, Hak-Kyo; Song, Ki-Duk; Lee, Woon Kyu

    2015-01-01

    Embryonic stem cells (ESCs) have been used as a powerful tool for research including gene manipulated animal models and the study of developmental gene regulation. Among the critical regulatory factors that maintain the pluripotency and self-renewal of undifferentiated ESCs, NANOG plays a very important role. Nevertheless, because pluripotency maintaining factors and specific markers for livestock ESCs have not yet been probed, few studies of the NANOG gene from domestic animals including bovine have been reported. Therefore, we chose mouse ESCs in order to understand and compare NANOG expression between bovine, human, and mouse during ESCs differentiation. We cloned a 600 bp (−420/+181) bovine NANOG 5′-flanking region, and tagged it with humanized recombinant green fluorescent protein (hrGFP) as a tracing reporter. Very high GFP expression for bovine NANOG promoter was observed in the mouse ESC line. GFP expression was monitored upon ESC differentiation and was gradually reduced along with differentiation toward neurons and adipocyte cells. Activity of bovine NANOG (−420/+181) promoter was compared with already known mouse and human NANOG promoters in mouse ESC and they were likely to show a similar pattern of regulation. In conclusion, bovine NANOG 5-flanking region functions in mouse ES cells and has characteristics similar to those of mouse and human. These results suggest that bovine gene function studied in mouse ES cells should be evaluated and extrapolated for application to characterization of bovine ES cells. PMID:26580439

  4. Human Xq28 Inversion Polymorphism: From Sex Linkage to Genomics--A Genetic Mother Lode

    ERIC Educational Resources Information Center

    Kirby, Cait S.; Kolber, Natalie; Salih Almohaidi, Asmaa M.; Bierwert, Lou Ann; Saunders, Lori; Williams, Steven; Merritt, Robert

    2016-01-01

    An inversion polymorphism of the filamin and emerin genes at the tip of the long arm of the human X-chromosome serves as the basis of an investigative laboratory in which students learn something new about their own genomes. Long, nearly identical inverted repeats flanking the filamin and emerin genes illustrate how repetitive elements can lead to…

  5. Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome.

    PubMed

    Gu, Zhuoya; Jin, Ke; Crabbe, M James C; Zhang, Yang; Liu, Xiaolin; Huang, Yanyan; Hua, Mengyi; Nan, Peng; Zhang, Zhaolei; Zhong, Yang

    2016-04-01

    Transposable elements (TEs) have no longer been totally considered as "junk DNA" for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C (chromosome conformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r = 0.9, P < 2.2 × 10(16); IMR90 fibroblasts: r = 0.94, P < 2.2 × 10(16)) and also have a significant positive correlation with some remote functional DNA elements like enhancers and promoters (Enhancer: hESC: r = 0.997, P = 2.3 × 10(-4); IMR90: r = 0.934, P = 2 × 10(-2); Promoter: hESC: r = 0.995, P = 3.8 × 10(-4); IMR90: r = 0.996, P = 3.2 × 10(-4)). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes. PMID:26861146

  6. HUMAN SCALP HAIR: AN ENVIRONMENTAL EXPOSURE INDEX FOR TRACE ELEMENTS. III. SEVENTEEN TRACE ELEMENTS IN BIRMINGHAM, ALABAMA AND CHARLOTTE, NORTH CAROLINA (1972)

    EPA Science Inventory

    Seventeen trace elements - arsenic (As), barium (Ba), boron, (B), cadmium, (Cd), chromium (Cr), copper (Cu), Iron (Fe), lead (Pb), lithium (Li), manganese (Mn), mercury (Hg), nickel (Ni), selenium (Se), silver (Ag), tin (Sn), vanadium (V), and Zinc (Zn) - were measured in human s...

  7. Functional analysis of the promoter of the mitochondrial phosphate carrier human gene: identification of activator and repressor elements and their transcription factors

    PubMed Central

    2005-01-01

    The phosphate carrier (PiC) catalyses the import of phosphate into mitochondria where it is needed for ATP synthesis. We have analysed the 5′-flanking region of the human PiC gene and found that it has a single transcriptional initiation site and lacks a TATA box. Through deletion analysis of the −1213/−25 nt region, we identified an activation domain (−223/−25) and an inhibition domain (−1017/−814). The most effective promoter activity in transfected HeLa cells corresponded to the region containing putative binding sites for Sp1 (−163/−142; where Sp1 stands for stimulating protein-1) and CREB (−138/−116; where CREB stands for cAMP-response-element-binding protein). These DNA sequences were active in gel-shift assays in the presence of HeLa cell nuclear extracts or recombinant Sp1 and CREB respectively. Forskolin increased PiC promoter activity via the CREB site. Both footprinting and transfection of deletion constructs of the inhibition region (−1017/−814) showed that PiC silencer activity extends over 25 nt (−943/−919), which specifically binds two proteins present in HeLa cell nuclear extracts. These transcription factors were purified by DNA affinity, analysed by MS and identified as p54nrb/NonO (nuclear RNA binding protein) and PSF (protein-associated splicing factor). The PiC silencer region cloned in front of the ferritin promoter conferred a strong inhibition to the heterologous promoter. These findings may provide insight into control of PiC gene expression in different cell types and under different growth conditions. To our knowledge, this is the first study to analyse the regulation of the PiC gene expression in any cell. PMID:15984930

  8. Structure of Proximal and Distant Regulatory Elements in the Human Genome

    NASA Astrophysics Data System (ADS)

    Ovcharenko, Ivan

    Clustering of multiple transcription factor binding sites (TFBSs) for the same transcription factor (TF) is a common feature of cis-regulatory modules in invertebrate animals, but the occurrence of such homotypic clusters of TFBSs (HCTs) in the human genome has remained largely unknown. To explore whether HCTs are also common in human and other vertebrates, we used known binding motifs for vertebrate TFs and a hidden Markov model-based approach to detect HCTs in the human, mouse, chicken, and fugu genomes, and examined their association with cis-regulatory modules. We found that evolutionarily conserved HCTs occupy nearly 2% of the human genome, with experimental evidence for individual TFs supporting their binding to predicted HCTs. More than half of promoters of human genes contain HCTs, with a distribution around the transcription start site in agreement with the experimental data from the ENCODE project. In addition, almost half of 487 experimentally validated developmental enhancers contain them as well - a number more than 25-fold larger than expected by chance. We also found evidence of negative selection acting on TFBSs within HCTs, as the conservation of TFBSs is stronger than the conservation of sequences separating them. The important role of HCTs as components of developmental enhancers is additionally supported by a strong correlation between HCTs and the binding of the enhancer-associated co-activator protein p300. Experimental validation of HCT-containing elements in both zebrafish and mouse suggest that HCTs could be used to predict both the presence of enhancers and their tissue specificity, and are thus a feature that can be effectively used in deciphering the gene regulatory code. In conclusion, our results indicate that HCTs are a pervasive feature of human cis-regulatory modules and suggest that they play an important role in gene regulation in the human and other vertebrate genomes.

  9. The Plasmodium Export Element Revisited

    PubMed Central

    Hiss, Jan Alexander; Przyborski, Jude Marek; Schwarte, Florian; Lingelbach, Klaus; Schneider, Gisbert

    2008-01-01

    We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide. PMID:18253504

  10. The Plasmodium export element revisited.

    PubMed

    Hiss, Jan Alexander; Przyborski, Jude Marek; Schwarte, Florian; Lingelbach, Klaus; Schneider, Gisbert

    2008-01-01

    We performed a bioinformatical analysis of protein export elements (PEXEL) in the putative proteome of the malaria parasite Plasmodium falciparum. A protein family-specific conservation of physicochemical residue profiles was found for PEXEL-flanking sequence regions. We demonstrate that the family members can be clustered based on the flanking regions only and display characteristic hydrophobicity patterns. This raises the possibility that the flanking regions may contain additional information for a family-specific role of PEXEL. We further show that signal peptide cleavage results in a positional alignment of PEXEL from both proteins with, and without, a signal peptide. PMID:18253504

  11. Two Dimensional Finite Element Analysis for the Effect of a Pressure Wave in the Human Brain

    NASA Astrophysics Data System (ADS)

    Ponce L., Ernesto; Ponce S., Daniel

    2008-11-01

    Brain injuries in people of all ages is a serious, world-wide health problem, with consequences as varied as attention or memory deficits, difficulties in problem-solving, aggressive social behavior, and neuro degenerative diseases such as Alzheimer's and Parkinson's. Brain injuries can be the result of a direct impact, but also pressure waves and direct impulses. The aim of this work is to develop a predictive method to calculate the stress generated in the human brain by pressure waves such as high power sounds. The finite element method is used, combined with elastic wave theory. The predictions of the generated stress levels are compared with the resistance of the arterioles that pervade the brain. The problem was focused to the Chilean mining where there are some accidents happen by detonations and high sound level. There are not formal medical investigation, however these pressure waves could produce human brain damage.

  12. Finite Element Approach for the Study of Thermoregulation in Human Head Exposed to Cold Environment

    NASA Astrophysics Data System (ADS)

    Khanday, M. A.; Saxena, V. P.

    2009-07-01

    The temperature of outer parts of human head exposed to cold environment shows large variations. In this paper a theoretical model has been envisaged for the comprehensive analysis of thermoregulation in human head which is taken as a divided heterogeneous medium surrounded by natural tissue layers. The model incorporates biochemical reactions concerning heat generation, blood circulation and other biophysical activities. The model obtained in terms of partial differential equations has been treated with the help of finite element method. This results in the estimation of temperature distribution under the influence of (i) atmospheric conditions (ii) cerebral blood circulation with fluctuating flow in scalp. This study leads to the estimation of risk factor analysis in cold environment.

  13. Computing interaural differences through finite element modeling of idealized human heads

    PubMed Central

    Cai, Tingli; Rakerd, Brad; Hartmann, William M.

    2015-01-01

    Acoustical interaural differences were computed for a succession of idealized shapes approximating the human head-related anatomy: sphere, ellipsoid, and ellipsoid with neck and torso. Calculations were done as a function of frequency (100–2500 Hz) and for source azimuths from 10 to 90 degrees using finite element models. The computations were compared to free-field measurements made with a manikin. Compared to a spherical head, the ellipsoid produced greater large-scale variation with frequency in both interaural time differences and interaural level differences, resulting in better agreement with the measurements. Adding a torso, represented either as a large plate or as a rectangular box below the neck, further improved the agreement by adding smaller-scale frequency variation. The comparisons permitted conjectures about the relationship between details of interaural differences and gross features of the human anatomy, such as the height of the head, and length of the neck. PMID:26428792

  14. Viscoelastic properties of the human tympanic membrane studied with stroboscopic holography and finite element modeling.

    PubMed

    De Greef, Daniel; Aernouts, Jef; Aerts, Johan; Cheng, Jeffrey Tao; Horwitz, Rachelle; Rosowski, John J; Dirckx, Joris J J

    2014-06-01

    A new anatomically-accurate Finite Element (FE) model of the tympanic membrane (TM) and malleus was combined with measurements of the sound-induced motion of the TM surface and the bony manubrium, in an isolated TM-malleus preparation. Using the results, we were able to address two issues related to how sound is coupled to the ossicular chain: (i) Estimate the viscous damping within the tympanic membrane itself, the presence of which may help smooth the broadband response of a potentially highly resonant TM, and (ii) Investigate the function of a peculiar feature of human middle-ear anatomy, the thin mucosal epithelial fold that couples the mid part of the human manubrium to the TM. Sound induced motions of the surface of ex vivo human eardrums and mallei were measured with stroboscopic holography, which yields maps of the amplitude and phase of the displacement of the entire membrane surface at selected frequencies. The results of these measurements were similar, but not identical to measurements made in intact ears. The holography measurements were complemented by laser-Doppler vibrometer measurements of sound-induced umbo velocity, which were made with fine-frequency resolution. Comparisons of these measurements to predictions from a new anatomically accurate FE model with varied membrane characteristics suggest the TM contains viscous elements, which provide relatively low damping, and that the epithelial fold that connects the central section of the human manubrium to the TM only loosely couples the TM to the manubrium. The laser-Doppler measurements in two preparations also suggested the presence of significant variation in the complex modulus of the TM between specimens. Some animations illustrating the model results are available at our website (www.uantwerp.be/en/rg/bimef/downloads/tympanic-membrane-motion). PMID:24657621

  15. Evaluation of Human and Anthropomorphic Test Device Finite Element Models under Spaceflight Loading Conditions

    NASA Technical Reports Server (NTRS)

    Putnam, Jacob P.; Untaroiu, Costin; Somers. Jeffrey

    2014-01-01

    In an effort to develop occupant protection standards for future multipurpose crew vehicles, the National Aeronautics and Space Administration (NASA) has looked to evaluate the test device for human occupant restraint with the modification kit (THOR-K) anthropomorphic test device (ATD) in relevant impact test scenarios. With the allowance and support of the National Highway Traffic Safety Administration, NASA has performed a series of sled impact tests on the latest developed THOR-K ATD. These tests were performed to match test conditions from human volunteer data previously collected by the U.S. Air Force. The objective of this study was to evaluate the THOR-K finite element (FE) model and the Total HUman Model for Safety (THUMS) FE model with respect to the tests performed. These models were evaluated in spinal and frontal impacts against kinematic and kinetic data recorded in ATD and human testing. Methods: The FE simulations were developed based on recorded pretest ATD/human position and sled acceleration pulses measured during testing. Predicted responses by both human and ATD models were compared to test data recorded under the same impact conditions. The kinematic responses of the models were quantitatively evaluated using the ISO-metric curve rating system. In addition, ATD injury criteria and human stress/strain data were calculated to evaluate the risk of injury predicted by the ATD and human model, respectively. Results: Preliminary results show well-correlated response between both FE models and their physical counterparts. In addition, predicted ATD injury criteria and human model stress/strain values are shown to positively relate. Kinematic comparison between human and ATD models indicates promising biofidelic response, although a slightly stiffer response is observed within the ATD. Conclusion: As a compliment to ATD testing, numerical simulation provides efficient means to assess vehicle safety throughout the design process and further improve the

  16. Large-scale discovery of insertion hotspots and preferential integration sites of human transposed elements

    PubMed Central

    Levy, Asaf; Schwartz, Schraga; Ast, Gil

    2010-01-01

    Throughout evolution, eukaryotic genomes have been invaded by transposable elements (TEs). Little is known about the factors leading to genomic proliferation of TEs, their preferred integration sites and the molecular mechanisms underlying their insertion. We analyzed hundreds of thousands nested TEs in the human genome, i.e. insertions of TEs into existing ones. We first discovered that most TEs insert within specific ‘hotspots’ along the targeted TE. In particular, retrotransposed Alu elements contain a non-canonical single nucleotide hotspot for insertion of other Alu sequences. We next devised a method for identification of integration sequence motifs of inserted TEs that are conserved within the targeted TEs. This method revealed novel sequences motifs characterizing insertions of various important TE families: Alu, hAT, ERV1 and MaLR. Finally, we performed a global assessment to determine the extent to which young TEs tend to nest within older transposed elements and identified a 4-fold higher tendency of TEs to insert into existing TEs than to insert within non-TE intergenic regions. Our analysis demonstrates that TEs are highly biased to insert within certain TEs, in specific orientations and within specific targeted TE positions. TE nesting events also reveal new characteristics of the molecular mechanisms underlying transposition. PMID:20008508

  17. Functional elements in the minimal promoter of the human proton-coupled folate transporter

    SciTech Connect

    Stark, Michal; Gonen, Nitzan; Assaraf, Yehuda G.

    2009-10-09

    The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1 kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157 bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 and AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements.

  18. A transcriptional regulatory element in the coding sequence of the human Bcl-2 gene

    PubMed Central

    Lang, Georgina; Gombert, Wendy M; Gould, Hannah J

    2005-01-01

    We investigated the protein-binding sites in a DNAse I hypersensitive site associated with bcl-2 gene expression in human B cells. We mapped this hypersensitive site to the coding sequence of exon 2 of the bcl-2 gene in the bcl-2-expressing REH B-cell line. Electrophoretic mobility shift assays (EMSAs) with extracts from REH cells revealed three previously unrecognized B-Myb-binding sites in this sequence. The protein was identified as B-Myb by using a specific antibody and EMSAs. Accordingly, the levels of B-Myb and bcl-2 proteins, and of Myb EMSA activity, were correlated over a wide range of cell lines, representing different stages of B-cell development. Transfection of REH cells with antisense B-myb down-regulated EMSA activity and the level of bcl-2, and led to the apoptosis of REH cells. Transfection of the bcl-2-non-expressing RPMI 8226 cell line with a B-Myb expression vector induced B-Myb EMSA activity and the expression of bcl-2. Reporter assays indicated that the HSS8 sequence containing the three B-Myb sites may act as an enhancer when it is linked to the bcl-2 gene promoter. Interaction of B-Myb with HSS8 may enhance bcl-2 gene expression by co-operating with positive regulatory elements (e.g. previously identified B-Myb response elements) or silencing negative response elements in the bcl-2 gene promoter. PMID:15606792

  19. Long Interspersed Element-1 Protein Expression Is a Hallmark of Many Human Cancers

    PubMed Central

    Rodić, Nemanja; Sharma, Reema; Sharma, Rajni; Zampella, John; Dai, Lixin; Taylor, Martin S.; Hruban, Ralph H.; Iacobuzio-Donahue, Christine A.; Maitra, Anirban; Torbenson, Michael S.; Goggins, Michael; Shih, Ie-Ming; Duffield, Amy S.; Montgomery, Elizabeth A.; Gabrielson, Edward; Netto, George J.; Lotan, Tamara L.; De Marzo, Angelo M.; Westra, William; Binder, Zev A.; Orr, Brent A.; Gallia, Gary L.; Eberhart, Charles G.; Boeke, Jef D.; Harris, Chris R.; Burns, Kathleen H.

    2014-01-01

    Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1–encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1–encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen. PMID:24607009

  20. Finite element implementation of a multiscale model of the human lens capsule.

    PubMed

    Burd, H J; Regueiro, R A

    2015-11-01

    An axisymmetric finite element implementation of a previously described structural constitutive model for the human lens capsule (Burd in Biomech Model Mechanobiol 8(3):217-231, 2009) is presented. This constitutive model is based on a hyperelastic approach in which the network of collagen IV within the capsule is represented by an irregular hexagonal planar network of hyperelastic bars, embedded in a hyperelastic matrix. The paper gives a detailed specification of the model and the periodic boundary conditions adopted for the network component. Momentum balance equations for the network are derived in variational form. These balance equations are used to develop a nonlinear solution scheme to enable the equilibrium configuration of the network to be computed. The constitutive model is implemented within a macroscopic finite element framework to give a multiscale model of the lens capsule. The possibility of capsule wrinkling is included in the formulation. To achieve this implementation, values of the first and second derivatives of the strain energy density with respect to the in-plane stretch ratios need to be computed at the local, constitutive model, level. Procedures to determine these strain energy derivatives at equilibrium configurations of the network are described. The multiscale model is calibrated against previously published experimental data on isolated inflation and uniaxial stretching of ex vivo human capsule samples. Two independent example lens capsule inflation analyses are presented. PMID:25957261

  1. Element distribution is altered in a zone surrounding human glioblastoma multiforme.

    PubMed

    Dehnhardt, Markus; Zoriy, Myroslav V; Khan, Zahidul; Reifenberger, Guido; Ekström, Tomas J; Sabine Becker, J; Zilles, Karl; Bauer, Andreas

    2008-01-01

    Recent data indicate that A(1) adenosine receptor (A(1)AR) density is increased in a zone surrounding human and experimental gliomas. On the contrary, tumor tissue and adjacent brain tissue show low to intermediate A(1)AR densities. In order to assess whether changes in A(1)AR expression are indicating further processes of a chemical reorganization of the peritumoral zone, we investigated element concentrations and distribution patterns of copper and zinc in six human glioblastoma multiforme (GBM) specimens by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS). Uranium and lead were used as external standards. Copper and zinc levels were increased in a peritumoral zone corresponding to the region of elevated A(1)AR density. They showed a lower density in the solid tumor in comparison to surrounding brain tissue, although the cellular density was higher within GBM. Our findings suggest that the immediate vicinity of GBM is characterized by increased levels of copper and zinc supporting the view that higher A(1)AR density surrounding GBM is not an isolated alteration of peritumoral tissue but an indicator of complex changes in the vicinity of infiltrative tumors. Further research is needed to explore the pathophysiological consequences of altered peritumoral element distribution. PMID:18319136

  2. Rapid detection and sequencing of alleles in the 3' flanking region of the interleukin-6 gene.

    PubMed Central

    Bowcock, A M; Ray, A; Erlich, H; Sehgal, P B

    1989-01-01

    The 3' flanking region of the interleukin 6 gene is polymorphic due to insertions of different size. Within this region lies a sequence of approximately 500 base pairs that is AT rich. Based on flanking sequence information we have constructed oligonucleotides which prime the polymerase chain reaction (PCR) and amplify this AT rich region. The amplification products visualized by agarose gel electrophoresis gave fragment sizes for both homozygous and heterozygous individuals that were concordant with those observed by conventional genomic blotting techniques. Alleles that could not be typed by Southern analysis were resolved with this approach. These results illustrate the value of PCR for the rapid detection of length polymorphisms such as those due to variable numbers of tandem repeats. In contrast to RFLP analysis this procedure takes less than a day to perform, is cheaper, avoids the use of radioactivity and requires far less substrate DNA. Three different human alleles were sequenced, and differences were detected that were due to both large duplications and loss of one or two bases, suggesting that AT rich regions identify highly polymorphic loci. The same primers also amplified non-human primate DNA, allowing a comparison of the human sequence with that of the common chimpanzee and baboon. Images PMID:2789373

  3. A Dynamic Finite Element Analysis of Human Foot Complex in the Sagittal Plane during Level Walking

    PubMed Central

    Qian, Zhihui; Ren, Lei; Ding, Yun; Hutchinson, John R.; Ren, Luquan

    2013-01-01

    The objective of this study is to develop a computational framework for investigating the dynamic behavior and the internal loading conditions of the human foot complex during locomotion. A subject-specific dynamic finite element model in the sagittal plane was constructed based on anatomical structures segmented from medical CT scan images. Three-dimensional gait measurements were conducted to support and validate the model. Ankle joint forces and moment derived from gait measurements were used to drive the model. Explicit finite element simulations were conducted, covering the entire stance phase from heel-strike impact to toe-off. The predicted ground reaction forces, center of pressure, foot bone motions and plantar surface pressure showed reasonably good agreement with the gait measurement data over most of the stance phase. The prediction discrepancies can be explained by the assumptions and limitations of the model. Our analysis showed that a dynamic FE simulation can improve the prediction accuracy in the peak plantar pressures at some parts of the foot complex by 10%–33% compared to a quasi-static FE simulation. However, to simplify the costly explicit FE simulation, the proposed model is confined only to the sagittal plane and has a simplified representation of foot structure. The dynamic finite element foot model proposed in this study would provide a useful tool for future extension to a fully muscle-driven dynamic three-dimensional model with detailed representation of all major anatomical structures, in order to investigate the structural dynamics of the human foot musculoskeletal system during normal or even pathological functioning. PMID:24244500

  4. Relationship between elemental distribution in soil and human impact in Majuro Atoll

    NASA Astrophysics Data System (ADS)

    Ito, L.; Takahashi, Y.; Yoneda, M.; Omori, T.; Yamazaki, K.; Yoshida, H.; Tamenori, Y.; Suga, H.; Yamaguchi, T.

    2015-12-01

    Majuro Atoll is one of islands of the Marshall Islands, located in the central Pacific Ocean. Reef-building corals and biological remains such as foraminifera have formed the islands under the influence of sea-level changes in the Holocene. Since the altitude of the general coral reef island tends to be very low, it is believed that the islands are vulnerable to natural disasters and climate change. However, people have lived in the Majuro Atoll in Marshall Islands for more than 2000 years. Reef islands in the same atoll are often considered to have same tendencies in the developing process; however, (i) there are possibilities that each geography produces different condition in habitat and (ii) human activities have changed the original nature in the island. In this study, we focus on the changes of physico-chemical conditions of soil depending on the depth according to time series variation in three islands in Majuro Atoll. Dating of each depth was conducted by radiocarbon (14C) measurement for foraminifera using accelerator mass spectrometry (AMS) and Bayesian age-depth Models. X-ray fluorescence (XRF) and ICP-MS analyses were employed to measure major and trace elements at different depth, respectively. Among them, phosphorus (P) is considered to play an important role in soil development; therefore X-ray absorption fine structure (XAFS) analysis was also conducted to examine the chemical form of P. Scanning electron microscope (SEM) was used to examine the elemental distribution in the soil particles, while X-ray computed tomography (CT) was used to calculate the rate of porosity of foraminifera at each depth. Concentrations of Fe, Mn, and P decrease with depth and vice versa for Mg. As a result of the μ-XAFS analysis, P in the soil exists as organic phosphorus and apatite. Phosphorous detected from the upper layer was found to distribute heterogeneously in the particles, which was observed as punctate pattern by the SEM observation. The ICP-MS results showed

  5. Modelling of the acoustic field of a multi-element HIFU array scattered by human ribs

    NASA Astrophysics Data System (ADS)

    Gélat, Pierre; ter Haar, Gail; Saffari, Nader

    2011-09-01

    The efficacy of high-intensity focused ultrasound (HIFU) for the treatment of a range of different cancers, including those of the liver, prostate and breast, has been demonstrated. As a non-invasive focused therapy, HIFU offers considerable advantages over techniques such as chemotherapy and surgical resection in terms of reduced risk of harmful side effects. Despite this, there are a number of significant challenges which currently hinder its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the rib cage to induce tissue necrosis in the required volume whilst minimizing the formation of side lobes. Multi-element random-phased arrays are currently showing great promise in overcoming the limitations of single-element transducers. Nevertheless, successful treatment of a patient with liver tumours requires a thorough understanding of the way in which the ultrasonic pressure field from a HIFU array is scattered by the rib cage. In order to address this, a boundary element approach based on a generalized minimal residual (GMRES) implementation of the Burton-Miller formulation was used in conjunction with phase conjugation techniques to focus the field of a 256-element random HIFU array behind human ribs at locations requiring intercostal and transcostal treatment. Simulations were carried out on a 3D mesh of quadratic pressure patches generated using CT scan anatomical data for adult ribs 9-12 on the right side. The methodology was validated on spherical and cylindrical scatterers. Field calculations were also carried out for idealized ribs, consisting of arrays of strip-like scatterers, demonstrating effects of splitting at the focus. This method has the advantage of fully accounting for the effect of scattering and diffraction in 3D under continuous wave excitation.

  6. Trace element landscape of resting and activated human neutrophils on the sub-micrometer level.

    PubMed

    Niemiec, M J; De Samber, B; Garrevoet, J; Vergucht, E; Vekemans, B; De Rycke, R; Björn, E; Sandblad, L; Wellenreuther, G; Falkenberg, G; Cloetens, P; Vincze, L; Urban, C F

    2015-06-01

    Every infection is a battle for trace elements. Neutrophils migrate first to the infection site and accumulate quickly to high numbers. They fight pathogens by phagocytosis and intracellular toxication. Additionally, neutrophils form neutrophil extracellular traps (NETs) to inhibit extracellular microbes. Yet, neutrophil trace element characteristics are largely unexplored. We investigated unstimulated and phorbol myristate acetate-stimulated neutrophils using synchrotron radiation X-ray fluorescence (SR-XRF) on the sub-micron spatial resolution level. PMA activates pinocytosis, cytoskeletal rearrangements and the release of NETs, all mechanisms deployed by neutrophils to combat infection. By analyzing Zn, Fe, Cu, Mn, P, S, and Ca, not only the nucleus but also vesicular granules were identifiable in the elemental maps. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) revealed a neutrophil-specific composition of Zn, Fe, Cu, and Mn in comparison with J774 and HeLa cells, indicating a neutrophil-specific metallome complying with their designated functions. When investigating PMA-activated neutrophils, the SR-XRF analysis depicted typical subcellular morphological changes: the transformation of nucleus and granules and the emergence of void vacuoles. Mature NETs were evenly composed of Fe, P, S, and Ca with occasional hot spots containing Zn, Fe, and Ca. An ICP-MS-based quantification of NET supernatants revealed a NETosis-induced decrease of soluble Zn, whereas Fe, Cu, and Mn concentrations were only slightly affected. In summary, we present a combination of SR-XRF and ICP-MS as a powerful tool to analyze trace elements in human neutrophils. The approach will be applicable and valuable to numerous aspects of nutritional immunity. PMID:25832493

  7. Acoustic and Elastodynamic Redatuming for VSP Salt Dome Flank Imaging

    NASA Astrophysics Data System (ADS)

    Lu, R.; Willis, M.; Toksoz, N.

    2007-12-01

    We apply an extension of the concept of Time Reversed Acoustics (TRA) for imaging salt dome flanks using Vertical Seismic Profile (VSP) data. We demonstrate its performance and capabilities on both synthetic acoustic and elastic seismic data from a Gulf of Mexico (GOM) model. This target-oriented strategy eliminates the need for the traditional complex process of velocity estimation, model building, and iterative depth migration to remove the effects of the salt canopy and surrounding overburden. In this study, we use data from surface shots recorded in a well from a walkaway VSP survey. The method, called redatuming, creates a geometry as if the source and receiver pairs had been located in the borehole at the positions of the receivers. This process generates effective downhole shot gathers without any knowledge of the overburden velocity structure. The resulting shot gathers are less complex since the VSP ray paths from the surface source are shortened and moved to be as if they started in the borehole, then reflected off the salt flank region and captured in the borehole. After redatuming, we apply multiple passes of prestack migration from the reference datum of the borehole. In our example, the first pass migration, using only simple vertical velocity gradient model, reveals the outline of the salt edge. A second pass of reverse-time prestack depth migration using the full, two-way wave equation, is performed with an updated velocity model that now consists of the velocity gradient and the salt dome. The second pass migration brings out the dipping sediments abutting the salt flank because these reflectors were illuminated by energy that bounced off the salt flank forming prismatic reflections.

  8. Flexural analysis of uplifted rift flanks on Venus

    NASA Technical Reports Server (NTRS)

    Evans, Susan A.; Simons, Mark; Solomon, Sean C.

    1992-01-01

    Knowledge of the thermal structure of a planet is vital to a thorough understanding of its general scheme of tectonics. Since no direct measurements of heat flow or thermal gradient are available for Venus, most estimates have been derived from theoretical considerations or by analog with the Earth. The flexural response of the lithosphere to applied loads is sensitive to regional thermal structure. Under the assumption that the yield strength as a function of depth can be specified, the temperature gradient can be inferred from the effective elastic plate thickness. Previous estimates of the effective elastic plate thickness of Venus range from 11-18 km for the foredeep north of Uorsar Rupes to 30-60 km for the annular troughs around several coronae. Thermal gradients inferred for these regions are 14-23 K km(exp -1) and 4-9 K km(exp -1) respectively. In this study, we apply the same techniques to investigate the uplifted flanks of an extensional rift. Hypotheses for the origin of uplifted rift flanks on Earth include lateral transport of heat from the center of the rift, vertical transport of heat by small-scale convection, differential thinning of the lithosphere, dynamical uplift, and isostatic response to mechanical uploading of the lithosphere. The 1st hypothesis is considered the dominant contributor to terrestrial rift flanks lacking evidence for volcanic activity, particularly for rift structures that are no longer active. In this study, we model the uplifted flanks of a venusian rift as the flexural response to a vertical end load.

  9. A new family of retroviral long terminal repeat elements in the human genome identified by their homologies to an element 5{prime} to the spider monkey haptoglobin gene

    SciTech Connect

    Erickson, L.M.; Maeda, N.

    1995-06-10

    A new family of retroviral long terminal repeats that we name Spm-LTR has been identified as a result of DNA sequence comparisons between the entire Gen-Bank databank and an element, SPHP, located 5{prime} to the haptoglobin gene of spider monkeys. The 18 human Spm-LTR sequences so identified fall into three subtypes. There is no sequence similarity between Spm-LTR elements and any endogenous retroviral LTR sequences previously reported except for general features that define LTRs. However, a previously described repeated sequence (MER-4) forms a portion of the Spm-LTR sequence. 13 refs., 1 fig., 1 tab.

  10. Renal infarction: an uncommon mimic presenting with flank pain.

    PubMed

    Manfredini, R; La Cecilia, O; Ughi, G; Kuwornu, H; Bressan, S; Regoli, F; Orzincolo, C; Daniele, C; Gallerani, M

    2000-05-01

    A 39-year-old woman arrived to the emergency department complaining of a constant, progressive, left flank pain, with no beneficial effect from spasmolytic and nonsteroidal antiinflammatory drugs. Two years before, she suffered another episode of right flank pain and stranguria, but instrumental examinations (ultrasonography, urography) remained negative. Besides a mild tenderness in the left flank, physical examination was normal. Blood chemistry panel showed leukocytosis (17.2 x 10(3) mL, neutrophils 82.8%) and a slight increase of serum lactate dehydrogenase (LDH) (543 U/L versus 230 to 460 U/L). Urinanalysis showed a slight hemoglobinuria (0.5 mg/dL), and sediment contained some red cells and leukocytes. Diagnostic examinations (ultrasonography, computed tomography) showed a left renal nonhomogeneous space-occupying lesion, orientative for renal malignancy. She was transferred to the urology department and operated. Both intraoperatory and histological diagnosis was ischemic infarction and, after exclusion of all possible underlying causes, final diagnosis was idiopathic renal infarction. Diagnostic procedures and literature reports are discussed. PMID:10830691

  11. Analysis of Response Elements Involved in the Regulation of the Human Neonatal Fc Receptor Gene (FCGRT)

    PubMed Central

    Mikulska, Joanna E.

    2015-01-01

    Human epithelial, endothelial and PMA-differentiated THP-1 cell lines were used as model systems to study the transcriptional regulation of the human FCGRT gene encoding the alpha chain of hFcRn. The data obtained from site-directed mutagenesis in transient transfection experiments indicate that the Sp1 sites at positions -641, -635, and -313, CF1/YY1 elements at positions -586 and -357, and the AP-1 motif at -276 within the-660/-233 fragment of the human FCGRT promoter (hFCGRT) participate in the regulation of human FCGRT in all selected cell lines. However, their individual contribution to promoter activity is not equivalent. The Sp1 binding site at -313 and the AP-1 site at -276 are critical for the activity of the hFCGRT promoter in epithelial and endothelial cells. Moreover, the CF1/YY1 site at -586 in differentiated THP-1 cells, plays an essential role in the transcriptional activity of the promoter. In addition, the C/EBPbeta binding site at -497 of the hFCGRT promoter in epithelial and endothelial cells, and the C/EBPbeta motif located at -497 and -233 within the hFCGRT promoter in differentiated THP-1 cells may function as positive regulatory sequences in response to LPS or PMA stimulation. EMSA and supershift analyses showed that the functionally identified binding motifs in the hFCGRT promoter were able to specifically interact with their corresponding (Sp1, Sp2, Sp3, c-Fos, c-Jun, YY1, and C/EBPbeta or C/EBPdelta) transcription factors (TFs), suggesting their possible involvement in the regulation of the human FCGRT gene expression. PMID:26252948

  12. Finite element method-simulation of the human lens during accommodation

    NASA Astrophysics Data System (ADS)

    Breitenfeld, P.; Ripken, T.; Lubatschowski, H.

    2005-08-01

    A finite-element-method model with ANSYS 8.0 of a 29 year old human lens during accommodation will be presented. The required data, to draw and calculate a two dimensional, axis-symmetric model of the human lens is inherited from various sources. Furthermore the analysis premises all lens materials to be linear elastic and allows large displacements. A first analysis of a possible method for the treatment of presbyopia by fs-laser induced microcuts is accomplished. Therefore a mechanical analysis of an untreated and a treated lens are compared. As a result an improvement of the flexibility of the lens tissue is found and as its consequence a change of the lens' radii of curvature is established. After a suitable processing of the output data a linear Gaussian ray trace is performed and a minor change in the optical power between the untreated and treaded human lens is perceived. By calculation of the discrete optical power of the anterior and posterior surface on the one hand and the overall optical power on the other hand an interpretation of the effectiveness resulting from the treatment is offered. It is ascertained that the change in optical power of the anterior lens surface is increased while the optical power of the posterior lens surface is decreased, almost compensating each other. A possible explanation for this phenomenon is given and a suggestion of how to increase the effectiveness of the treatment is discussed.

  13. Conservative site-specific and single-copy transgenesis in human LINE-1 elements

    PubMed Central

    Vijaya Chandra, Shree Harsha; Makhija, Harshyaa; Peter, Sabrina; Myint Wai, Cho Mar; Li, Jinming; Zhu, Jindong; Ren, Zhonglu; D'Alcontres, Martina Stagno; Siau, Jia Wei; Chee, Sharon; Ghadessy, Farid John; Dröge, Peter

    2016-01-01

    Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termed attH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis through attH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional in LINE1-targeted hESCs and differentiated progenies. Furthermore, LINE-1 targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes. PMID:26673710

  14. Restless Genomes: Humans as a Model Organism for Understanding Host-Retrotransposable Element Dynamics

    PubMed Central

    Hedges, Dale J.; Belancio, Victoria P.

    2015-01-01

    Since their initial discovery in maize, there have been various attempts to categorize the relationship between transposable elements (TEs) and their host organisms. These have ranged from TEs being selfish parasites to their role as essential, functional components of organismal biology. Research over the past several decades has, in many respects, only served to complicate the issue even further. On the one hand, investigators have amassed substantial evidence concerning the negative effects that TE-mutagenic activity can have on host genomes and organismal fitness. On the other hand, we find an increasing number of examples, across several taxa, of TEs being incorporated into functional biological roles for their host organism. Some 45% of our own genomes are comprised of TE copies. While many of these copies are dormant, having lost their ability to mobilize, several lineages continue to actively proliferate in modern human populations. With its complement of ancestral and active TEs, the human genome exhibits key aspects of the host–TE dynamic that has played out since early on in organismal evolution. In this review, we examine what insights the particularly well-characterized human system can provide regarding the nature of the host–TE interaction. PMID:21310298

  15. Conservative site-specific and single-copy transgenesis in human LINE-1 elements.

    PubMed

    Vijaya Chandra, Shree Harsha; Makhija, Harshyaa; Peter, Sabrina; Myint Wai, Cho Mar; Li, Jinming; Zhu, Jindong; Ren, Zhonglu; D'Alcontres, Martina Stagno; Siau, Jia Wei; Chee, Sharon; Ghadessy, Farid John; Dröge, Peter

    2016-04-01

    Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, termedattH4X, found in 1000 human Long INterspersed Elements-1 (LINE-1). We demonstrate single-copy transgenesis throughattH4X-targeting in various cell lines including hESCs, with the flexibility of selecting clones according to transgene performance and downstream applications. This is exemplified with pluripotency reporter cassettes and constitutively expressed payloads that remain functional inLINE1-targeted hESCs and differentiated progenies. Furthermore,LINE-1targeting does not induce DNA damage-response or chromosomal aberrations, and neither global nor localized endogenous gene expression is substantially affected. Hence, this simple transgene addition tool should become particularly useful for applications that require engineering of the human genome with multi-transgenes. PMID:26673710

  16. Efficient expression of the human papillomavirus type 16 L1 protein in epithelial cells by using Rev and the Rev-responsive element of human immunodeficiency virus or the cis-acting transactivation element of simian retrovirus type 1.

    PubMed Central

    Tan, W; Felber, B K; Zolotukhin, A S; Pavlakis, G N; Schwartz, S

    1995-01-01

    Production of the human papillomavirus (HPV) late gene products L1 and L2 is limited to terminally differentiated keratinocytes. Here, we demonstrate that mRNA encoding the HPV-16 L1 capsid protein contains cis-acting RNA elements that inhibit expression at the posttranscriptional level. While cytoplasmic L1 mRNA is detectable in transfected HeLa cells, L1 protein is not produced. We have identified at least one major inhibitory element that is located within the L1 open reading frame, whereas another negative element had been reported to lie in the 3'-untranslated region of L1. The presence of these elements may explain the lack of HPV late gene expression in undifferentiated epithelial cells. Efficient production of HPV-16 L1 could be achieved with posttranscriptional regulatory elements of human immunodeficiency virus type 1 or simian retrovirus type 1. L1 protein was expressed in the presence of human immunodeficiency virus type 1 Rev from hybrid mRNAs containing the RNA binding site for Rev (Rev-responsive element). In addition, we have achieved efficient expression of L1 from hybrid mRNAs containing a cis-acting transactivation element from simian retrovirus type 1. Our data show that HPV-16 L1 protein production is regulated posttranscriptionally. This regulated expression may allow virus production in terminally differentiated epithelial cells and is probably a conserved and important mechanism for HPV expression. PMID:7637007

  17. Palagonitization of Basalt Glass in the Flanks of Mid-Ocean Ridges: Implications for the Bioenergetics of Oceanic Intracrustal Ecosystems.

    PubMed

    Türke, Andreas; Nakamura, Kentaro; Bach, Wolfgang

    2015-10-01

    When basalt is exposed to oxygenated aqueous solutions, rims of palagonite form along fractures at the expense of glass. We employed electron microprobe and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) analyses of fresh glass and adjacent palagonite crusts to determine the geochemical changes involved in palagonite formation. Samples were retrieved from drill cores taken in the North Pond Area, located on the western flank of the Mid-Atlantic Ridge at 22°45'N and 46°05'W. We also analyzed whole rock powders to determine the overall crust-seawater exchange in a young ridge flank. Radioactive elements are enriched in palagonite relative to fresh glass, reaching concentrations where radiolytic production of molecular hydrogen (H2) may be a significant energy source. Based on these results, we hypothesize that microbial ecosystems in ridge flank habitats undergo a transition in the principal energy carrier, fueling carbon fixation from Fe oxidation in very young crust to H2 consumption in older crust. Unless the H2 is swept away by rapid fluid flow (i.e., in young flanks), it may easily accumulate to levels high enough to support chemolithoautotrophic life. In older flanks, crustal sealing and sediment accumulation have slowed down seawater circulation, and the significance of radiolytically produced H2 for catalytic energy supply is expected to increase greatly. Similar habitats on other planetary surfaces are theoretically possible, as accumulation of radiolytically produced hydrogen merely requires the presence of H2O molecules and a porous medium, from which the hydrogen is not lost. PMID:26426282

  18. The role of viscous magma mush spreading in volcanic flank motion at Kīlauea Volcano, Hawai‘i

    USGS Publications Warehouse

    Plattner, C.; Amelung, F.; Baker, S.; Govers, R.; Poland, M.

    2013-01-01

    Multiple mechanisms have been suggested to explain seaward motion of the south flank of Kīlauea Volcano, Hawai‘i. The consistency of flank motion during both waxing and waning magmatic activity at Kīlauea suggests that a continuously acting force, like gravity body force, plays a substantial role. Using finite element models, we test whether gravity is the principal driver of long-term motion of Kīlauea's flank. We compare our model results to geodetic data from Global Positioning System and interferometric synthetic aperture radar during a time period with few magmatic and tectonic events (2000-2003), when deformation of Kīlauea was dominated by summit subsidence and seaward motion of the south flank. We find that gravity-only models can reproduce the horizontal surface velocities if we incorporate a regional décollement fault and a deep, low-viscosity magma mush zone. To obtain quasi steady state horizontal surface velocities that explain the long-term seaward motion of the flank, we find that an additional weak zone is needed, which is an extensional rift zone above the magma mush. The spreading rate in our model is mainly controlled by the magma mush viscosity, while its density plays a less significant role. We find that a viscosity of 2.5 × 1017–2.5 × 1019 Pa s for the magma mush provides an acceptable fit to the observed horizontal surface deformation. Using high magma mush viscosities, such as 2.5 × 1019 Pa s, the deformation rates remain more steady state over longer time scales. These models explain a significant amount of the observed subsidence at Kīlauea's summit. Some of the remaining subsidence is probably a result of magma withdrawal from subsurface reservoirs

  19. Different cis-acting DNA elements control expression of the human apolipoprotein AI gene in different cell types

    SciTech Connect

    Sastry, K.; Seedorf, U.; Karathanasis, S.K.

    1988-02-01

    In mammals, the gene coding for apolipoprotein AI (apoAI), a protein of the plasma lipid transport system, is expressed only in the liver and the intestine. A series of plasmids containing various lengths of sequences flanking the 5' end of the human apoAI gene were constructed and assayed for transient expression after introduction into cultured human hepatoma 9HepG2), colon carcinoma (Caco-2), and epithelial (HeLa) cells. The results showed that while most of these constructs are expressed in HepG2 and Caco-2 cells, none of them is expressed in HeLa cells. In addition, the results indicated that a DNA segment located between nucleotides -256 and -41 upstream from the transcription start site of this gene is necessary and sufficient for maximal levels of expression in HepG2 but not in Caco-2 cells, while a DNA segment located between nucleotides -2052 and -192 is required for maximal levels of expression in Caco-2 cells. Moreover, it was shown that the -256 to -41 DNA segment functions as a hepatoma cell-specific transcriptional enhancer with both homologous and heterologous promoters. These results indicate that different cis- and possibly trans-acting factors are involved in the establishment and subsequent regulation of expression of the apoAI gene in the mammalian liver and intestine.

  20. Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity.

    PubMed

    Schöne, Stefanie; Jurk, Marcel; Helabad, Mahdi Bagherpoor; Dror, Iris; Lebars, Isabelle; Kieffer, Bruno; Imhof, Petra; Rohs, Remo; Vingron, Martin; Thomas-Chollier, Morgane; Meijsing, Sebastiaan H

    2016-01-01

    The glucocorticoid receptor (GR) binds as a homodimer to genomic response elements, which have particular sequence and shape characteristics. Here we show that the nucleotides directly flanking the core-binding site, differ depending on the strength of GR-dependent activation of nearby genes. Our study indicates that these flanking nucleotides change the three-dimensional structure of the DNA-binding site, the DNA-binding domain of GR and the quaternary structure of the dimeric complex. Functional studies in a defined genomic context show that sequence-induced changes in GR activity cannot be explained by differences in GR occupancy. Rather, mutating the dimerization interface mitigates DNA-induced changes in both activity and structure, arguing for a role of DNA-induced structural changes in modulating GR activity. Together, our study shows that DNA sequence identity of genomic binding sites modulates GR activity downstream of binding, which may play a role in achieving regulatory specificity towards individual target genes. PMID:27581526

  1. Final report for CCQM-K107: total elements and selenomethionine in human serum

    NASA Astrophysics Data System (ADS)

    Goenaga Infante, Heidi

    2016-01-01

    Routine tests that measure the concentration of electrolytes in serum are needed for diagnosis and management of renal, endocrine, acid-base, water balance and other conditions such as screening D- and A-vitamin disorders, kidney insufficiency, bone diseases and leukaemia. The diagnostic concentration ranges for many such markers are narrow, requiring reference methods with small uncertainty. Serum concentration of total selenium (Se) is important in health studies but there is increasing interest in the speciation of selenium compounds in clinical samples such as serum and individual Se- Species are bio-indicators of Se status. The last CCQM IAWG key comparison for elements in the clinical area (CCQM-K14: Ca in human serum) was organized in 2003 and the previous key comparison (CCQM-K60) for Se and Se species used a wheat flour sample. Therefore, the CCQM IAWG agreed that CCQM-K107 and a parallel pilot study CCQM-P146 should be carried out. The candidate human serum sample used for both CCQM-K107 and P146 is of high complexity and contains approximately 1000-fold lower concentrations of selenium methionine (SeMet) than those encountered in the CCQM-K60 wheat flour. This significantly broadens the scope and degree of difficulty of earlier measurements in this field. A total of eleven institutes participated in CCQM-K107 (11 participants for total elements and 7 for SeMet). The performance of the majority of the K107 participants for all the measurands was very good, illustrating their ability to obtain accurate results for analytes such as electrolytes at mg kg-1 level, essential elements at µg kg-1 level and selenium species at µg kg-1 level in a complex biological fluid. The range of agreement between participants was within the interval of ± 0.1% for Ca and up to ± 1.8% for Fe. CMC claims based on total elements in this study may include other elements with similar core competencies (e.g. Se, Cu, Zn) in a wide range of biological materials (including liquids

  2. Generating anatomically accurate finite element meshes for electrical impedance tomography of the human head

    NASA Astrophysics Data System (ADS)

    Yang, Bin; Xu, Canhua; Dai, Meng; Fu, Feng; Dong, Xiuzhen

    2013-07-01

    For electrical impedance tomography (EIT) of brain, the use of anatomically accurate and patient-specific finite element (FE) mesh has been shown to confer significant improvements in the quality of image reconstruction. But, given the lack of a rapid method to achieve the accurate anatomic geometry of the head, the generation of patient-specifc mesh is time-comsuming. In this paper, a modified fuzzy c-means algorithm based on non-local means method is performed to implement the segmentation of different layers in the head based on head CT images. This algorithm showed a better effect, especially an accurate recognition of the ventricles and a suitable performance dealing with noise. And the FE mesh established according to the segmentation results is validated in computational simulation. So a rapid practicable method can be provided for the generation of patient-specific FE mesh of the human head that is suitable for brain EIT.

  3. Suspicious Behavior Detection System for an Open Space Parking Based on Recognition of Human Elemental Actions

    NASA Astrophysics Data System (ADS)

    Inomata, Teppei; Kimura, Kouji; Hagiwara, Masafumi

    Studies for video surveillance applications for preventing various crimes such as stealing and violence have become a hot topic. This paper proposes a new video surveillance system that can detect suspicious behaviors such as a car break-in and vandalization in an open space parking, and that is based on image processing. The proposed system has the following features: it 1)deals time series data flow, 2)recognizes “human elemental actions” using statistic features, and 3)detects suspicious behavior using Subspace method and AdaBoost. We conducted the experiments to test the performance of the proposed system using open space parking scenes. As a result, we obtained about 10.0% for false positive rate, and about 4.6% for false negative rate.

  4. Regulation of human PTCH1b expression by different 5' untranslated region cis-regulatory elements

    PubMed Central

    Ozretić, Petar; Bisio, Alessandra; Musani, Vesna; Trnski, Diana; Sabol, Maja; Levanat, Sonja; Inga, Alberto

    2015-01-01

    PTCH1 gene codes for a 12-pass transmembrane receptor with a negative regulatory role in the Hedgehog-Gli signaling pathway. PTCH1 germline mutations cause Gorlin syndrome, a disorder characterized by developmental abnormalities and tumor susceptibility. The autosomal dominant inheritance, and the evidence for PTCH1 haploinsufficiency, suggests that fine-tuning systems of protein patched homolog 1 (PTC1) levels exist to properly regulate the pathway. Given the role of 5' untranslated region (5'UTR) in protein expression, our aim was to thoroughly explore cis-regulatory elements in the 5'UTR of PTCH1 transcript 1b. The (CGG)n polymorphism was the main potential regulatory element studied so far but with inconsistent results and no clear association between repeat number and disease risk. Using luciferase reporter constructs in human cell lines here we show that the number of CGG repeats has no strong impact on gene expression, both at mRNA and protein levels. We observed variability in the length of 5'UTR and changes in abundance of the associated transcripts after pathway activation. We show that upstream AUG codons (uAUGs) present only in longer 5'UTRs could negatively regulate the amount of PTC1 isoform L (PTC1-L). The existence of an internal ribosome entry site (IRES) observed using different approaches and mapped in the region comprising the CGG repeats, would counteract the effect of the uAUGs and enable synthesis of PTC1-L under stressful conditions, such as during hypoxia. Higher relative translation efficiency of PTCH1b mRNA in HEK 293T cultured hypoxia was observed by polysomal profiling and Western blot analyses. All our results point to an exceptionally complex and so far unexplored role of 5'UTR PTCH1b cis-element features in the regulation of the Hedgehog-Gli signaling pathway. PMID:25826662

  5. Identification and Validation of a Putative Polycomb Responsive Element in the Human Genome

    PubMed Central

    Bengani, Hemant; Mendiratta, Shweta; Maini, Jayant; Vasanthi, Dasari; Sultana, Hina; Ghasemi, Mohsen; Ramachandran, Sowmya; Mishra, Rakesh K.; Brahmachari, Vani

    2013-01-01

    Epigenetic cellular memory mechanisms that involve polycomb and trithorax group of proteins are well conserved across metazoans. The cis-acting elements interacting with these proteins, however, are poorly understood in mammals. In a directed search we identified a potential polycomb responsive element with 25 repeats of YY1 binding motifthatwe designate PRE-PIK3C2B as it occurs in the first intron of human PIK3C2B gene. It down regulates reporter gene expression in HEK cells and the repression is dependent on polycomb group of proteins (PcG). We demonstrate that PRE-PIK3C2B interacts directly with YY1 in vitro and recruits PRC2 complex in vivo. The localization of PcG proteins including YY1 to PRE-PIK3C2B in HEK cells is decreased on knock-down of either YY1 or SUZ12. Endogenous PRE-PIK3C2B shows bivalent marking having H3K27me3 and H3K4me3 for repressed and active state respectively. In transgenic Drosophila, PRE-PIK3C2B down regulates mini-white expression, exhibits variegation and pairing sensitive silencing (PSS), which has not been previously demonstrated for mammalian PRE. Taken together, our results strongly suggest that PRE-PIK3C2B functions as a site of interaction for polycomb proteins. PMID:23805300

  6. Configural and elemental coding of natural odor mixture components in the human brain

    PubMed Central

    Howard, James D.; Gottfried, Jay A.

    2014-01-01

    SUMMARY Most real-world odors are complex mixtures of distinct molecular components. Olfactory systems can adopt different strategies to contend with this stimulus complexity. In elemental processing, odor perception is derived from the sum of its parts; in configural processing, the parts are integrated into unique perceptual wholes. Here we used gas-chromatography/mass-spectrometry techniques to deconstruct a complex natural food smell and assess whether olfactory salience is confined to the whole odor or is also embodied in its parts. By implementing an fMRI sensory-specific satiety paradigm, we identified reward-based changes in orbitofrontal cortex (OFC) for the whole odor and for a small subset of components. Moreover, component-specific changes in OFC-amygdala connectivity correlated with perceived value. Our findings imply that the human brain has direct access to the elemental content of a natural food odor, and highlight the dynamic capacity of the olfactory system to engage both object-level and component-level mechanisms to subserve behavior. PMID:25453843

  7. Regional distribution of potassium, calcium, and six trace elements in normal human brain

    SciTech Connect

    Duflou, H.; Maenhaut, W.; De Reuck, J. )

    1989-11-01

    Eight elements (i.e. K, Ca, Mn, Fe, Cu, Zn, Se, and Rb) were measured in 50 different regions of 12 normal human brains by particle-induced X-ray emission (PIXE) analysis. The dry weight concentrations of K, Fe, Cu, Zn, Se, and Rb were consistently higher for gray than for white matter areas. The K, Zn and Se concentrations for the regions of mixed composition and, to some extent, also the Rb concentrations, were intermediate between the gray and white matter values, and they tended to decrease with decreasing neuron density. The mean dry weight concentrations of K, Ca, Zn, Se, and Rb in the various brain regions were highly correlated with the mean wet-to-dry weight ratios of these regions. For Mn, Fe, and Cu, however, such a correlation was not observed, and these elements exhibited elevated levels in several structures of the basal ganglia. For K, Fe, and Se the concentrations seemed to change with age. A hierarchical cluster analysis indicated that the structures clustered into two large groups, one comprising gray and mixed matter regions, the other white and mixed matter areas. Brain structures involved in the same physiological function or morphologically similar regions often conglomerated in a single subcluster.

  8. Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter

    SciTech Connect

    Jiang, S.-Y.; Wu, M.-S.; Chen, L.-M.; Hung, M.-W.; Lin, H.-E.; Chang, G.-G.; Chang, T.-C. . E-mail: tcchang@ndmctsgh.edu.tw

    2005-06-03

    The expression of retinoic acid-induced gene 1 (RIG1), a class II tumor suppressor gene, is induced in cells treated with retinoids. RIG1 has been shown to express ubiquitously and the increased expression of this gene appears to suppress cell proliferation. Recent studies also demonstrated that this gene may play an important role in cell differentiation and the progression of cancer. In spite of the remarkable regulatory role of this protein, the molecular mechanism of RIG1 expression induced by retinoids remains to be clarified. The present study was designed to study the molecular mechanism underlying the all-trans retinoic acid (atRA)-mediated induction of RIG1 gene expression. Polymerase chain reaction was used to generate a total of 10 luciferase constructs that contain various fragments of the RIG1 5'-genomic region. These constructs were then transfected into human gastric cancer SC-M1 and breast cancer T47D cells for transactivation analysis. atRA exhibited a significant induction in luciferase activity only through the -4910/-5509 fragment of the 5'-genomic region of RIG1 gene relative to the translation initiation site. Further analysis of this promoter fragment indicated that the primary atRA response region is located in between -5048 and -5403 of the RIG1 gene. Within this region, a direct repeat sequence with five nucleotide spacing, 5'-TGACCTctattTGCCCT-3' (DR5, -5243/-5259), and an inverted repeat sequence with six nucleotide spacing, 5'-AGGCCAtggtaaTGGCCT-3' (IR6, -5323/-5340), were identified. Deletion and mutation of the DR5, but not the IR6 element, abolished the atRA-mediated activity. Electrophoretic mobility shift assays with nuclear extract from atRA-treated cells indicated the binding of retinoic acid receptor (RAR) and retinoid X receptor (RXR) heterodimers specifically to this response element. In addition to the functional DR5, the region contains many other potential sequence elements that are required to maximize the at

  9. Transposable elements, polydactyl proteins and the genesis of human-specific transcription networks

    PubMed Central

    Trono, Didier

    2016-01-01

    Transposable elements (TEs) may account for up to two-thirds of the human genome, and as genomic threats they are subjected to epigenetic control mechanisms engaged from the earliest stages of embryonic development. We previously determined that an important component of this process is the sequence-specific recognition of TEs by KRAB-containing zinc finger proteins (KRAB-ZFPs), a large family of tetrapod-restricted transcription factors that act by recruiting inducers of heterochromatin formation and DNA methylation. We further demonstrated that KRAB-ZFPs and their cofactor KAP1 exert a marked influence on the transcription dynamics of embryonic stem cells via their docking of repressor complexes at TE-contained regulatory sequences. It is generally held that, beyond this early embryonic period, TEs become permanently silenced, and that the evolutionary selection of KRAB-ZFPs and other TE controllers is the result of a simple evolutionary arms race between the host and these genetics invaders. Here, I discuss recent evidence that invalidates this dual assumption, and instead suggests that KRAB-ZFPs are the instruments of a massive enterprise of TE domestication, whereby transposon-based regulatory sequences and their cellular ligands establish species-specific transcription regulation networks that influence multiple aspects of human development and physiology. PMID:26763983

  10. A novel mosaic protein containing LDL receptor elements is highly conserved in humans and chickens.

    PubMed

    Mörwald, S; Yamazaki, H; Bujo, H; Kusunoki, J; Kanaki, T; Seimiya, K; Morisaki, N; Nimpf, J; Schneider, W J; Saito, Y

    1997-05-01

    Certain receptors belonging to the LDL receptor (LDLR) gene family appear to constitute a newly identified branch whose members are expressed in brain, in addition to other tissues. In support of this concept, we have now discovered the expression and delineated the molecular structures of a representative of this emerging branch from two such diverse species as human and chicken. This membrane receptor, called LR11 and thus far only known to exist in the rabbit, is a complex seven-domain mosaic protein containing, among other structural elements, a cluster of 11 LDLR ligand-binding repeats and a domain with homology to VPS10, a yeast receptor for vacuolar protein sorting. Cytoplasmic signature sequences define the receptor as competent for endocytosis. The most striking properties of LR11s are their (1) high degree of structural conservation (>80% identity among mammals and birds), with 100% identity in the membrane-spanning and cytoplasmic domains of rabbit and human; (2) lack of regulation by cholesterol and estrogen; and (3) expression in brain. The features of LR11 suggest important roles in intercellular and intracellular ligand transport processes, some of which it may share with other brain-specific LDLR family members. PMID:9157966

  11. Finite element modeling of human brain response to football helmet impacts.

    PubMed

    Darling, T; Muthuswamy, J; Rajan, S D

    2016-10-01

    The football helmet is used to help mitigate the occurrence of impact-related traumatic (TBI) and minor traumatic brain injuries (mTBI) in the game of American football. While the current helmet design methodology may be adequate for reducing linear acceleration of the head and minimizing TBI, it however has had less effect in minimizing mTBI. The objectives of this study are (a) to develop and validate a coupled finite element (FE) model of a football helmet and the human body, and (b) to assess responses of different regions of the brain to two different impact conditions - frontal oblique and crown impact conditions. The FE helmet model was validated using experimental results of drop tests. Subsequently, the integrated helmet-human body FE model was used to assess the responses of different regions of the brain to impact loads. Strain-rate, strain, and stress measures in the corpus callosum, midbrain, and brain stem were assessed. Results show that maximum strain-rates of 27 and 19 s(-1) are observed in the brain-stem and mid-brain, respectively. This could potentially lead to axonal injuries and neuronal cell death during crown impact conditions. The developed experimental-numerical framework can be used in the study of other helmet-related impact conditions. PMID:26867124

  12. Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment.

    PubMed

    Rovira, Joaquim; Nadal, Martí; Schuhmacher, Marta; Domingo, José L

    2015-07-01

    Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10(-6)) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. PMID:25889781

  13. Human learning of elemental category structures: revising the classic result of Shepard, Hovland, and Jenkins (1961).

    PubMed

    Kurtz, Kenneth J; Levering, Kimery R; Stanton, Roger D; Romero, Joshua; Morris, Steven N

    2013-03-01

    The findings of Shepard, Hovland, and Jenkins (1961) on the relative ease of learning 6 elemental types of 2-way classifications have been deeply influential 2 times over: 1st, as a rebuke to pure stimulus generalization accounts, and again as the leading benchmark for evaluating formal models of human category learning. The litmus test for models is the ability to simulate an observed advantage in learning a category structure based on an exclusive-or (XOR) rule over 2 relevant dimensions (Type II) relative to category structures that have no perfectly predictive cue or cue combination (including the linearly-separable Type IV). However, a review of the literature reveals that a Type II advantage over Type IV is found only under highly specific experimental conditions. We investigate when and why a Type II advantage exists to determine the appropriate benchmark for models and the psychological theories they represent. A series of 8 experiments link particular conditions of learning to outcomes ranging from a traditional Type II advantage to compelling non-differences and reversals (i.e., Type IV advantage). Common interpretations of the Type II advantage as either a broad-based phenomenon of human learning or as strong evidence for an attention-mediated similarity-based account are called into question by our findings. Finally, a role for verbalization in the category learning process is supported. PMID:22799282

  14. West Flank Coso, CA FORGE 3D geologic model

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    This is an x,y,z file of the West Flank FORGE 3D geologic model. Model created in Earthvision by Dynamic Graphic Inc. The model was constructed with a grid spacing of 100 m. Geologic surfaces were extrapolated from the input data using a minimum tension gridding algorithm. The data file is tabular data in a text file, with lithology data associated with X,Y,Z grid points. All the relevant information is in the file header (the spatial reference, the projection etc.) In addition all the fields in the data file are identified in the header.

  15. Analysis of cis-elements that facilitate extrachromosomal persistence of human papillomavirus genomes

    SciTech Connect

    Pittayakhajonwut, Daraporn; Angeletti, Peter C.

    2008-05-10

    Human papillomaviruses (HPVs) are maintained latently in dividing epithelial cells as nuclear plasmids. Two virally encoded proteins, E1, a helicase, and E2, a transcription factor, are important players in replication and stable plasmid maintenance in host cells. Recent experiments in yeast have demonstrated that viral genomes retain replication and maintenance function independently of E1 and E2 [Angeletti, P.C., Kim, K., Fernandes, F.J., and Lambert, P.F. (2002). Stable replication of papillomavirus genomes in Saccharomyces cerevisiae. J. Virol. 76(7), 3350-8; Kim, K., Angeletti, P.C., Hassebroek, E.C., and Lambert, P.F. (2005). Identification of cis-acting elements that mediate the replication and maintenance of human papillomavirus type 16 genomes in Saccharomyces cerevisiae. J. Virol. 79(10), 5933-42]. Flow cytometry studies of EGFP-reporter vectors containing subgenomic HPV fragments with or without a human ARS (hARS), revealed that six fragments located in E6-E7, E1-E2, L1, and L2 regions showed a capacity for plasmid stabilization in the absence of E1 and E2 proteins. Interestingly, four fragments within E7, the 3' end of L2, and the 5' end of L1 exhibited stability in plasmids that lacked an hARS, indicating that they possess both replication and maintenance functions. Two fragments lying in E1-E2 and the 3' region of L1 were stable only in the presence of hARS, that they contained only maintenance function. Mutational analyses of HPV16-GFP reporter constructs provided evidence that genomes lacking E1 and E2 could replicate to an extent similar to wild type HPV16. Together these results support the concept that cellular factors influence HPV replication and maintenance, independently, and perhaps in conjunction with E1 and E2, suggesting a role in the persistent phase of the viral lifecycle.

  16. Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

    PubMed Central

    Bengochea, A; de Souza, M M; Lefrançois, L; Le Roux, E; Galy, O; Chemin, I; Kim, M; Wands, J R; Trepo, C; Hainaut, P; Scoazec, J-Y; Vitvitski, L; Merle, P

    2008-01-01

    Dysregulation of growth factors and their receptors is central to human hepatocellular carcinoma (HCC). We previously demonstrated that the Frizzled-7 membrane receptor mediating the Wnt signalling can activate the β-catenin pathway and promotes malignancy in human hepatitis B virus-related HCCs. Expression patterns of all the 10 Frizzled receptors, and their extracellular soluble autoparacrine regulators (19 Wnt activators and 4 sFRP inhibitors) were assessed by real-time RT–PCR in 62 human HCC of different etiologies and their matched peritumorous areas. Immunostaining was performed to localise Frizzled on cell types in liver tissues. Regulation of three known Frizzled-dependent pathways (β-catenin, protein kinase C, and C-Jun NH2-terminal kinase) was measured in tissues by western blot. We found that eight Frizzled-potentially activating events were pleiotropically dysregulated in 95% HCC and 68% peritumours as compared to normal livers (upregulations of Frizzled-3/6/7 and Wnt3/4/5a, or downregulation of sFRP1/5), accumulating gradually with severity of fibrosis in peritumours and loss of differentiation status in tumours. The hepatocytes supported the Wnt/Frizzled signalling since specifically overexpressing Frizzled receptors in liver tissues. Dysregulation of the eight Frizzled-potentially activating events was associated with differential activation of the three known Frizzled-dependent pathways. This study provides an extensive analysis of the Wnt/Frizzled receptor elements and reveals that the dysregulation may be one of the most common and earliest events described thus far during hepatocarcinogenesis. PMID:18577996

  17. Viral protein R of human immunodeficiency virus type-1 induces retrotransposition of long interspersed element-1

    PubMed Central

    2013-01-01

    Background Viral protein R (Vpr), a protein of human immunodeficiency virus type-1 (HIV-1) with various biological functions, was shown to be present in the blood of HIV-1-positive patients. However, it remained unclear whether circulating Vpr in patients’ blood is biologically active. Here, we examined the activity of blood Vpr using an assay system by which retrotransposition of long interspersed element-1 (L1-RTP) was detected. We also investigated the in vivo effects of recombinant Vpr (rVpr) by administrating it to transgenic mice harboring human L1 as a transgene (hL1-Tg mice). Based on our data, we discuss the involvement of blood Vpr in the clinical symptoms of acquired immunodeficiency syndrome (AIDS). Results We first discovered that rVpr was active in induction of L1-RTP. Biochemical analyses revealed that rVpr-induced L1-RTP depended on the aryl hydrocarbon receptor, mitogen-activated protein kinases, and CCAAT/enhancer-binding protein β. By using a sensitive L1-RTP assay system, we showed that 6 of the 15 blood samples from HIV-1 patients examined were positive for induction of L1-RTP. Of note, the L1-RTP-inducing activity was blocked by a monoclonal antibody specific for Vpr. Moreover, L1-RTP was reproducibly induced in various organs, including the kidney, when rVpr was administered to hL1-Tg mice. Conclusions Blood Vpr is biologically active, suggesting that its monitoring is worthwhile for clarification of the roles of Vpr in the pathogenesis of AIDS. This is the first report to demonstrate a soluble factor in patients’ blood active for L1-RTP activity, and implies the involvement of L1-RTP in the development of human diseases. PMID:23915234

  18. HIV-1 and Human PEG10 Frameshift Elements Are Functionally Distinct and Distinguished by Novel Small Molecule Modulators

    PubMed Central

    Sleebs, Brad E.; Lackovic, Kurt; Parisot, John P.; Moss, Rebecca M.; Crowe-McAuliffe, Caillan; Mathew, Suneeth F.; Edgar, Christina D.; Kleffmann, Torsten; Tate, Warren P.

    2015-01-01

    Frameshifting during translation of viral or in rare cases cellular mRNA results in the synthesis of proteins from two overlapping reading frames within the same mRNA. In HIV-1 the protease, reverse transcriptase, and integrase enzymes are in a second reading frame relative to the structural group-specific antigen (gag), and their synthesis is dependent upon frameshifting. This ensures that a strictly regulated ratio of structural proteins and enzymes, which is critical for HIV-1 replication and viral infectivity, is maintained during protein synthesis. The frameshift element in HIV-1 RNA is an attractive target for the development of a new class of anti HIV-1 drugs. However, a number of examples are now emerging of human genes using −1 frameshifting, such as PEG10 and CCR5. In this study we have compared the HIV-1 and PEG10 frameshift elements and shown they have distinct functional characteristics. Frameshifting occurs at several points within each element. Moreover, frameshift modulators that were isolated by high-throughput screening of a library of 114,000 lead-like compounds behaved differently with the PEG10 frameshift element. The most effective compounds affecting the HIV-1 element enhanced frameshifting by 2.5-fold at 10 μM in two different frameshift reporter assay systems. HIV-1 protease:gag protein ratio was affected by a similar amount in a specific assay of virally-infected cultured cell, but the modulation of frameshifting of the first-iteration compounds was not sufficient to show significant effects on viral infectivity. Importantly, two compounds did not affect frameshifting with the human PEG10 element, while one modestly inhibited rather than enhanced frameshifting at the human element. These studies indicate that frameshift elements have unique characteristics that may allow targeting of HIV-1 and of other viruses specifically for development of antiviral therapeutic molecules without effect on human genes like PEG10 that use the same

  19. Identification of cis-acting repressive sequences within the negative regulatory element of human immunodeficiency virus type 1.

    PubMed Central

    Lu, Y C; Touzjian, N; Stenzel, M; Dorfman, T; Sodroski, J G; Haseltine, W A

    1990-01-01

    The negative regulatory element of human immunodeficiency virus type 1 is a 260-nucleotide-long sequence that decreases the rate of RNA transcription initiation specified by the long terminal repeat. This region has the potential to bind several cellular transcription factors. Here it is shown that sequences which recognize the NFAT-1 and USF cellular transcription factors contribute to this negative regulatory effect. The sequences within the negative regulatory element which resemble the AP-1 site and the URS do not negatively regulate human immunodeficiency virus long terminal repeat transcription initiation. PMID:2398545

  20. Estimation of percentage body fat by dual-energy x-ray absorptiometry: evaluation by in vivo human elemental composition.

    PubMed

    Wang, ZiMian; Heymsfield, Steven B; Chen, Zhao; Zhu, Shankuan; Pierson, Richard N

    2010-05-01

    Dual-energy x-ray absorptiometry (DXA) is widely applied for estimating body fat. The percentage of body mass as fat (%fat) is predicted from a DXA-estimated R(ST) value defined as the ratio of soft tissue attenuation at two photon energies (e.g., 40 keV and 70 keV). Theoretically, the R(ST) concept depends on the mass of each major element in the human body. The DXA R(ST) values, however, have never been fully evaluated by measured human elemental composition. The present investigation evaluated the DXA R(ST) value by the total body mass of 11 major elements and the DXA %fat by the five-component (5C) model, respectively. Six elements (i.e. C, N, Na, P, Cl and Ca) were measured by in vivo neutron activation analysis, and potassium (i.e. K) by whole-body (40)K counting in 27 healthy adults. Models were developed for predicting the total body mass of four additional elements (i.e. H, O, Mg and S). The elemental content of soft tissue, after correction for bone mineral elements, was used to predict the R(ST) values. The DXA R(ST) values were strongly associated with the R(ST) values predicted from elemental content (r = 0.976, P < 0.001), although there was a tendency for the elemental-predicted R(ST) to systematically exceed the DXA-measured R(ST) (mean +/- SD, 1.389 +/- 0.024 versus 1.341 +/- 0.024). DXA-estimated %fat was strongly associated with 5C %fat (24.4 +/- 12.0% versus 24.9 +/- 11.1%, r = 0.983, P < 0.001). DXA R(ST) is evaluated by in vivo elemental composition, and the present study supports the underlying physical concept and accuracy of the DXA method for estimating %fat. PMID:20393230

  1. Estimation of percentage body fat by dual-energy x-ray absorptiometry: evaluation by in vivo human elemental composition

    NASA Astrophysics Data System (ADS)

    Wang, ZiMian; Heymsfield, Steven B.; Chen, Zhao; Zhu, Shankuan; Pierson, Richard N.

    2010-05-01

    Dual-energy x-ray absorptiometry (DXA) is widely applied for estimating body fat. The percentage of body mass as fat (%fat) is predicted from a DXA-estimated RST value defined as the ratio of soft tissue attenuation at two photon energies (e.g., 40 keV and 70 keV). Theoretically, the RST concept depends on the mass of each major element in the human body. The DXA RST values, however, have never been fully evaluated by measured human elemental composition. The present investigation evaluated the DXA RST value by the total body mass of 11 major elements and the DXA %fat by the five-component (5C) model, respectively. Six elements (i.e. C, N, Na, P, Cl and Ca) were measured by in vivo neutron activation analysis, and potassium (i.e. K) by whole-body 40K counting in 27 healthy adults. Models were developed for predicting the total body mass of four additional elements (i.e. H, O, Mg and S). The elemental content of soft tissue, after correction for bone mineral elements, was used to predict the RST values. The DXA RST values were strongly associated with the RST values predicted from elemental content (r = 0.976, P < 0.001), although there was a tendency for the elemental-predicted RST to systematically exceed the DXA-measured RST (mean ± SD, 1.389 ± 0.024 versus 1.341 ± 0.024). DXA-estimated %fat was strongly associated with 5C %fat (24.4 ± 12.0% versus 24.9 ± 11.1%, r = 0.983, P < 0.001). DXA RST is evaluated by in vivo elemental composition, and the present study supports the underlying physical concept and accuracy of the DXA method for estimating %fat.

  2. Estimation of percentage body fat by dual-energy x-ray absorptiometry: evaluation by in vivo human elemental composition

    PubMed Central

    Wang, ZiMian; Heymsfield, Steven B; Chen, Zhao; Zhu, Shankuan; Pierson, Richard N

    2010-01-01

    Dual-energy x-ray absorptiometry (DXA) is widely applied for estimating body fat. The percentage of body mass as fat (%fat) is predicted from a DXA-estimated RST value defined as the ratio of soft tissue attenuation at two photon energies (e.g., 40 keV and 70 keV). Theoretically, the RST concept depends on the mass of each major element in the human body. The DXA RST values, however, have never been fully evaluated by measured human elemental composition. The present investigation evaluated the DXA RST value by the total body mass of 11 major elements and the DXA %fat by the five-component (5C) model, respectively. Six elements (i.e. C, N, Na, P, Cl and Ca) were measured by in vivo neutron activation analysis, and potassium (i.e. K) by whole-body 40K counting in 27 healthy adults. Models were developed for predicting the total body mass of four additional elements (i.e. H, O, Mg and S). The elemental content of soft tissue, after correction for bone mineral elements, was used to predict the RST values. The DXA RST values were strongly associated with the RST values predicted from elemental content (r = 0.976, P < 0.001), although there was a tendency for the elemental-predicted RST to systematically exceed the DXA-measured RST (mean ± SD, 1.389 ± 0.024 versus 1.341 ± 0.024). DXA-estimated %fat was strongly associated with 5C %fat (24.4 ± 12.0% versus 24.9 ± 11.1%, r = 0.983, P < 0.001). DXA RST evaluated by in vivo elemental composition, and the present study supports the underlying physical concept and accuracy of the DXA method for estimating %fat. PMID:20393230

  3. Plasma Transport at the Magnetospheric Flank Boundary. Final report

    SciTech Connect

    Otto, Antonius

    2012-04-23

    Progress is highlighted in these areas: 1. Model of magnetic reconnection induced by three-dimensional Kelvin Helmholtz (KH) modes at the magnetospheric flank boundary; 2. Quantitative evaluation of mass transport from the magnetosheath onto closed geomagnetic field for northward IMF; 3. Comparison of mass transfer by cusp reconnection and Flank Kelvin Helmholtz modes; 4. Entropy constraint and plasma transport in the magnetotail - a new mechanism for current sheet thinning; 5. Test particle model for mass transport onto closed geomagnetic field for northward IMF; 6. Influence of density asymmetry and magnetic shear on (a) the linear and nonlinear growth of 3D Kelvin Helmholtz (KH) modes, and (b) three-dimensional KH mediated mass transport; 7. Examination of entropy and plasma transport in the magnetotail; 8. Entropy change and plasma transport by KH mediated reconnection - mixing and heating of plasma; 9. Entropy and plasma transport in the magnetotail - tail reconnection; and, 10. Wave coupling at the magnetospheric boundary and generation of kinetic Alfven waves.

  4. Comparative Evaluation of Midventral and Flank Laparotomy Approaches in Goat

    PubMed Central

    Abubakar, A. A.; Andeshi, R. A.; Yakubu, A. S.; Lawal, F. M.; Adamu, U.

    2014-01-01

    The aim of the study was to compare two laparotomy approaches (flank and midventral). Ten (n = 10) apparently healthy goats of different breeds and sex, average age of 12 ± 2.1 months, and average weight of 13.4 ± 2 kg were used for the investigation. The goats were randomly divided into flank and midventral groups, each group comprising five goats (n = 5). Standard aseptic laparotomy was performed under lumbosacral epidural anaesthesia with mild sedation. Postsurgical wound score showed significant difference (P < 0.05) in erythema at 18–24 hours and 10–14 days after surgery between the two approaches; significant difference of dehiscence between the two groups was also recorded at 10–14 days after surgery. Total white blood cells (WBC) and lymphocytes counts were significantly different (P < 0.05) at the first and second week after surgery. There was significant difference of platelets critical value and platelets dimension width at the first and second week after surgery. Significant difference of packed cells volume between the two approaches was also recorded one week after surgery. It was concluded that midventral laparotomy approach can be conveniently and safely performed under aseptic precautions without fear of intra- and postoperative clinical problems. PMID:26464943

  5. Comparative Evaluation of Midventral and Flank Laparotomy Approaches in Goat.

    PubMed

    Abubakar, A A; Andeshi, R A; Yakubu, A S; Lawal, F M; Adamu, U

    2014-01-01

    The aim of the study was to compare two laparotomy approaches (flank and midventral). Ten (n = 10) apparently healthy goats of different breeds and sex, average age of 12 ± 2.1 months, and average weight of 13.4 ± 2 kg were used for the investigation. The goats were randomly divided into flank and midventral groups, each group comprising five goats (n = 5). Standard aseptic laparotomy was performed under lumbosacral epidural anaesthesia with mild sedation. Postsurgical wound score showed significant difference (P < 0.05) in erythema at 18-24 hours and 10-14 days after surgery between the two approaches; significant difference of dehiscence between the two groups was also recorded at 10-14 days after surgery. Total white blood cells (WBC) and lymphocytes counts were significantly different (P < 0.05) at the first and second week after surgery. There was significant difference of platelets critical value and platelets dimension width at the first and second week after surgery. Significant difference of packed cells volume between the two approaches was also recorded one week after surgery. It was concluded that midventral laparotomy approach can be conveniently and safely performed under aseptic precautions without fear of intra- and postoperative clinical problems. PMID:26464943

  6. Development of a finite element human head model partially validated with thirty five experimental cases.

    PubMed

    Mao, Haojie; Zhang, Liying; Jiang, Binhui; Genthikatti, Vinay V; Jin, Xin; Zhu, Feng; Makwana, Rahul; Gill, Amandeep; Jandir, Gurdeep; Singh, Amrinder; Yang, King H

    2013-11-01

    This study is aimed to develop a high quality, extensively validated finite element (FE) human head model for enhanced head injury prediction and prevention. The geometry of the model was based on computed tomography (CT) and magnetic resonance imaging scans of an adult male who has the average height and weight of an American. A feature-based multiblock technique was adopted to develop hexahedral brain meshes including the cerebrum, cerebellum, brainstem, corpus callosum, ventricles, and thalamus. Conventional meshing methods were used to create the bridging veins, cerebrospinal fluid, skull, facial bones, flesh, skin, and membranes-including falx, tentorium, pia, arachnoid, and dura. The head model has 270,552 elements in total. Thirty five loading cases were selected from a range of experimental head impacts to check the robustness of the model predictions based on responses including the brain pressure, relative skull-brain motion, skull response, and facial response. The brain pressure was validated against intracranial pressure data reported by Nahum et al. (1977, "Intracranial Pressure Dynamics During Head Impact," Proc. 21st Stapp Car Crash Conference, SAE Technical Paper No. 770922) and Trosseille et al. (1992, "Development of a F.E.M. of the Human Head According to a Specific Test Protocol," Proc. 36th Stapp Car Crash Conference, SAE Technical Paper No. 922527). The brain motion was validated against brain displacements under sagittal, coronal, and horizontal blunt impacts performed by Hardy et al. (2001, "Investigation of Head Injury Mechanisms Using Neutral Density Technology and High-Speed Biplanar X-Ray," Stapp Car Crash Journal, 45, pp. 337-368; and 2007, "A Study of the Response of the Human Cadaver Head to Impact," Stapp Car Crash Journal, 51, pp. 17-80). The facial bone responses were validated under nasal impact (Nyquist et al. 1986, "Facial Impact Tolerance and Response," Proc. 30th Stapp Car Crash Conference, SAE Technical Paper No. 861896

  7. Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment

    SciTech Connect

    Rovira, Joaquim; Nadal, Martí; Schuhmacher, Marta; Domingo, José L.

    2015-07-15

    Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10{sup −6}) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. - Highlights: • We determined in skin-contact clothes the concentrations of a number of metals. • Dermal contact exposure and health risks for adults and for 1-year-old children were assessed. • Carcinogenic risks were considered as acceptable (<10{sup −6}). • For non-carcinogenic risks, only Sb exceeded a 10% of the HQ for dermal contact with clothes.

  8. Finite element comparison of human and Hybrid III responses in a frontal impact.

    PubMed

    Danelson, Kerry A; Golman, Adam J; Kemper, Andrew R; Gayzik, F Scott; Clay Gabler, H; Duma, Stefan M; Stitzel, Joel D

    2015-12-01

    The improvement of finite element (FE) Human Body Models (HBMs) has made them valuable tools for investigating restraint interactions compared to anthropomorphic test devices (ATDs). The objective of this study was to evaluate the effect of various combinations of safety restraint systems on the sensitivity of thoracic injury criteria using matched ATD and Human Body Model (HBM) simulations at two crash severities. A total of seven (7) variables were investigated: 3-point belt with two (2) load limits, frontal airbag, knee bolster airbag, a buckle pretensioner, and two (2) delta-v's - 40kph and 50kph. Twenty four (24) simulations were conducted for the Hybrid III ATD FE model and repeated with a validated HBM for 48 total simulations. Metrics tested in these conditions included sternum deflection, chest acceleration, chest excursion, Viscous Criteria (V*C) criteria, pelvis acceleration, pelvis excursion, and femur forces. Additionally, chest band deflection and rib strain distribution were measured in the HBM for additional restraint condition discrimination. The addition of a frontal airbag had the largest effect on the occupant chest metrics with an increase in chest compression and acceleration but a decrease in excursion. While the THUMS and Hybrid III occupants demonstrated the same trend in the chest compression measurements, there were conflicting results in the V*C, acceleration, and displacement metrics. Similarly, the knee bolster airbag had the largest effect on the pelvis with a decrease in acceleration and excursion. With a knee bolster airbag the simulated occupants gave conflicting results, the THUMS had a decrease in femur force and the ATD had an increase. Preferential use of dummies or HBM's is not debated; however, this study highlights the ability of HBM metrics to capture additional chest response metrics. PMID:26432065

  9. Isoniazid suppresses antioxidant response element activities and impairs adipogenesis in mouse and human preadipocytes

    SciTech Connect

    Chen, Yanyan; Xue, Peng; Hou, Yongyong; Zhang, Hao; Zheng, Hongzhi; Zhou, Tong; Qu, Weidong; Teng, Weiping; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2013-12-15

    Transcriptional signaling through the antioxidant response element (ARE), orchestrated by the Nuclear factor E2-related factor 2 (Nrf2), is a major cellular defense mechanism against oxidative or electrophilic stress. Here, we reported that isoniazid (INH), a widely used antitubercular drug, displays a substantial inhibitory property against ARE activities in diverse mouse and human cells. In 3T3-L1 preadipocytes, INH concentration-dependently suppressed the ARE-luciferase reporter activity and mRNA expression of various ARE-dependent antioxidant genes under basal and oxidative stressed conditions. In keeping with our previous findings that Nrf2-ARE plays a critical role in adipogenesis by regulating expression of CCAAT/enhancer-binding protein β (C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ), suppression of ARE signaling by INH hampered adipogenic differentiation of 3T3-L1 cells and human adipose-derived stem cells (ADSCs). Following adipogenesis induced by hormonal cocktails, INH-treated 3T3-L1 cells and ADSCs displayed significantly reduced levels of lipid accumulation and attenuated expression of C/EBPα and PPARγ. Time-course studies in 3T3-L1 cells revealed that inhibition of adipogenesis by INH occurred in the early stage of terminal adipogenic differentiation, where reduced expression of C/EBPβ and C/EBPδ was observed. To our knowledge, the present study is the first to demonstrate that INH suppresses ARE signaling and interrupts with the transcriptional network of adipogenesis, leading to impaired adipogenic differentiation. The inhibition of ARE signaling may be a potential underlying mechanism by which INH attenuates cellular antioxidant response contributing to various complications. - Highlights: • Isoniazid suppresses ARE-mediated transcriptional activity. • Isoniazid inhibits adipogenesis in preadipocytes. • Isoniazid suppresses adipogenic gene expression during adipogenesis.

  10. Modeling sound transmission of human middle ear and its clinical applications using finite element analysis.

    PubMed

    Chen, Shou-I; Lee, Ming-Hsiao; Yao, Chih-Min; Chen, Peir-Rong; Chou, Yuan-Fang; Liu, Tien-Chen; Song, Yu-Lin; Lee, Chia-Fone

    2013-03-01

    We have developed a new finite element (FE) model of human right ear, including the accurate geometry of middle ear ossicles, external ear canal, tympanic cavity, and mastoid cavity. The FE model would be suitable to study the dynamic behaviors of pathological middle ear conditions, including changes of stapedial ligament stiffness, tensor tympani ligament (TTL), and tympanic membrane (TM) stiffness and thickness. Increasing stiffness of stapedial ligament has substantial effect on stapes footplate movement, especially at low frequencies, but less effect on umbo movement. Softer TTL will result in increasing umbo and stapes footplate displacement, especially at low frequencies (f<1000Hz). When the TTL was detached, the vibration amplitude of umbo increased by 6dB at 600Hz and two peaks (300 and 600Hz) were found in the vibration amplitude of stapes footplate. Increasing the stiffness of tensor tympani resulted in a slightly decreased umbo amplitude at very low frequencies (f<500Hz) and significantly decreased displacement up to 12dB at middle frequencies (1000Hz1500Hz. As (TM) thickness was increased, the umbo displacement was reduced, especially at very low frequencies (f<600Hz). Otherwise, the stapes displacement was reduced at all frequencies. PMID:23465416

  11. Sensitivity analysis of a validated subject-specific finite element model of the human craniofacial skeleton.

    PubMed

    Szwedowski, T D; Fialkov, J; Whyne, C M

    2011-01-01

    Developing a more complete understanding of the mechanical response of the craniofacial skeleton (CFS) to physiological loads is fundamental to improving treatment for traumatic injuries, reconstruction due to neoplasia, and deformities. Characterization of the biomechanics of the CFS is challenging due to its highly complex structure and heterogeneity, motivating the utilization of experimentally validated computational models. As such, the objective of this study was to develop, experimentally validate, and parametrically analyse a patient-specific finite element (FE) model of the CFS to elucidate a better understanding of the factors that are of intrinsic importance to the skeletal structural behaviour of the human CFS. An FE model of a cadaveric craniofacial skeleton was created from subject-specific computed tomography data. The model was validated based on bone strain measurements taken under simulated physiological-like loading through the masseter and temporalis muscles (which are responsible for the majority of craniofacial physiologic loading due to mastication). The baseline subject-specific model using locally defined cortical bone thicknesses produced the strongest correlation to the experimental data (r2 = 0.73). Large effects on strain patterns arising from small parametric changes in cortical thickness suggest that the very thin bony structures present in the CFS are crucial to characterizing the local load distribution in the CFS accurately. PMID:21381488

  12. A 2D Electromechanical Model of Human Atrial Tissue Using the Discrete Element Method

    PubMed Central

    Brocklehurst, Paul; Adeniran, Ismail; Yang, Dongmin; Sheng, Yong; Zhang, Henggui; Ye, Jianqiao

    2015-01-01

    Cardiac tissue is a syncytium of coupled cells with pronounced intrinsic discrete nature. Previous models of cardiac electromechanics often ignore such discrete properties and treat cardiac tissue as a continuous medium, which has fundamental limitations. In the present study, we introduce a 2D electromechanical model for human atrial tissue based on the discrete element method (DEM). In the model, single-cell dynamics are governed by strongly coupling the electrophysiological model of Courtemanche et al. to the myofilament model of Rice et al. with two-way feedbacks. Each cell is treated as a viscoelastic body, which is physically represented by a clump of nine particles. Cell aggregations are arranged so that the anisotropic nature of cardiac tissue due to fibre orientations can be modelled. Each cell is electrically coupled to neighbouring cells, allowing excitation waves to propagate through the tissue. Cell-to-cell mechanical interactions are modelled using a linear contact bond model in DEM. By coupling cardiac electrophysiology with mechanics via the intracellular Ca2+ concentration, the DEM model successfully simulates the conduction of cardiac electrical waves and the tissue's corresponding mechanical contractions. The developed DEM model is numerically stable and provides a powerful method for studying the electromechanical coupling problem in the heart. PMID:26583141

  13. Quantitative Validation of a Human Body Finite Element Model Using Rigid Body Impacts.

    PubMed

    Vavalle, Nicholas A; Davis, Matthew L; Stitzel, Joel D; Gayzik, F Scott

    2015-09-01

    Validation is a critical step in finite element model (FEM) development. This study focuses on the validation of the Global Human Body Models Consortium full body average male occupant FEM in five localized loading regimes-a chest impact, a shoulder impact, a thoracoabdominal impact, an abdominal impact, and a pelvic impact. Force and deflection outputs from the model were compared to experimental traces and corridors scaled to the 50th percentile male. Predicted fractures and injury severity measures were compared to evaluate the model's injury prediction capabilities. The methods of ISO/TS 18571 were used to quantitatively assess the fit of model outputs to experimental force and deflection traces. The model produced peak chest, shoulder, thoracoabdominal, abdominal, and pelvis forces of 4.8, 3.3, 4.5, 5.1, and 13.0 kN compared to 4.3, 3.2, 4.0, 4.0, and 10.3 kN in the experiments, respectively. The model predicted rib and pelvic fractures related to Abbreviated Injury Scale scores within the ranges found experimentally all cases except the abdominal impact. ISO/TS 18571 scores for the impacts studied had a mean score of 0.73 with a range of 0.57-0.83. Well-validated FEMs are important tools used by engineers in advancing occupant safety. PMID:25739950

  14. Characterization of human glucocorticoid receptor complexes formed with DNA fragments containing or lacking glucocorticoid response elements

    SciTech Connect

    Tully, D.B.; Cidlowski, J.A. )

    1989-03-07

    Sucrose density gradient shift assays were used to study the interactions of human glucocorticoid receptors (GR) with small DNA fragments either containing or lacking glucocorticoid response element (GRE) DNA consensus sequences. When crude cytoplasmic extracts containing ({sup 3}H)triamcinolone acetonide (({sup 3}H)TA) labeled GR were incubated with unlabeled DNA under conditions of DNA excess, a GRE-containing DNA fragment obtained from the 5' long terminal repeat of mouse mammary tumor virus (MMTV LTR) formed a stable 12-16S complex with activated, but not nonactivated, ({sup 3}H)TA receptor. By contrast, if the cytosols were treated with calf thymus DNA-cellulose to deplete non-GR-DNA-binding proteins prior to heat activation, a smaller 7-10S complex was formed with the MMTV LTR DNA fragment. Activated ({sup 3}H)TA receptor from DNA-cellulose pretreated cytosols also interacted with two similarly sized fragments from pBR322 DNA. Stability of the complexes formed between GR and these three DNA fragments was strongly affected by even moderate alterations in either the salt concentration or the pH of the gradient buffer. Under all conditions tested, the complex formed with the MMTV LTR DNA fragment was more stable than the complexes formed with either of the pBR322 DNA fragments. Together these observations indicate that the formation of stable complexes between activated GR and isolated DNA fragments requires the presence of GRE consensus sequences in the DNA.

  15. A new technique for analyzing trace element uptake by human enamel.

    PubMed

    Funato, Yoshiki; Matsuda, Yasuhiro; Okuyama, Katsushi; Yamamoto, Hiroko; Komatsu, Hisanori; Sano, Hidehiko

    2015-01-01

    Fluorine (F) and strontium (Sr) are key elements in the de- and remineralization of teeth. To quantitatively analyze the distribution of F and Sr, micro-particle-induced gamma/X-ray emission (PIGE/PIXE) technique was used. The cavities were prepared and filled with the fluoride- and Sr-containing restorative materials (FSCMs) in extracted human molars. The single-section enamel specimens were prepared by slicing from the buccal to lingual surface including the FSCMs. After 5 weeks of automatic pH cycling, the demineralization was calculated by integrated mineral loss (ΔIML) from transverse-microradiography. The distributions of F and Sr were analyzed by the PIGE/PIXE technique. The micro-PIGE/PIXE technique indicated a fluorine uptake difference between the enamel surface and enamel cavity wall. ΔIML of FSCMs were significantly lower than intact enamel. The micro-PIGE/PIXE technique enables measurement of F and Sr uptake from FSCMs into enamel, which would be beneficial for research on caries development and prevention. PMID:25740308

  16. Projections of specialist physicians in Mexico: a key element in planning human resources for health.

    PubMed

    Nigenda, Gustavo; Muños, José Alberto

    2015-01-01

    Projections are considered a useful tool in the planning of human resources for health. In Mexico, the supply and demand of specialist doctors are clearly disconnected, and decisions must be made to reduce labour market imbalances. Thus, it is critical to produce reliable projections to assess future interactions between supply and demand. Using a service demand approach, projections of the number of specialist physicians required by the three main public institutions were calculated using the following variables: a) recent recruitment of specialists, b) physician productivity and c) retirement rates. Two types of scenarios were produced: an inertial one with no changes made to current production levels and an alternative scenario adjusted by recommended productivity levels. Results show that institutions must address productivity as a major policy element to act upon in future contracting of specialist physicians. The projections that adjusted for productivity suggest that the hiring trends for surgeons and internists should be maintained or increased to compensate for the increase in demand for services. In contrast, due to the decline in demand for obstetric and paediatric services, the hiring of new obstetrician-gynaecologists and paediatricians should be reduced to align with future demand. PMID:26391878

  17. Transcriptional regulatory elements in the noncoding region of human papillomavirus type 6

    SciTech Connect

    Wu, Tzyy-Choou.

    1989-01-01

    The structure and function of the transcriptional regulatory region of human papillomavirus type 6 (HPV-6) has been investigated. To investigate tissue specific gene expression, a sensitive method to detect and localize HPV-6 viral DNA, mRNA and protein in plastic-embedded tissue sections of genital and respiratory tract papillomata by using in situ hybridization and immunoperoxidase assays has been developed. This method, using ultrathin sections and strand-specific {sup 3}H labeled riboprobes, offers the advantages of superior morphological preservation and detection of viral genomes at low copy number with good resolution, and the modified immunocytochemistry provides better sensitivity. The results suggest that genital tract epithelium is more permissive for HPV-6 replication than respiratory tract epithelium. To study the tissue tropism of HPV-6 at the level of regulation of viral gene expression, the polymerase chain reaction was used to isolate the noncoding region (NCR) of HPV-6 in independent isolates. Nucleotide sequence analysis of molecularly cloned DNA identified base substitutions, deletions/insertions and tandem duplications. Transcriptional regulatory elements in the NCR were assayed in recombinant plasmids containing the bacterial gene for chloramphenicol acetyl transferase.

  18. COST action TD1407: network on technology-critical elements (NOTICE)--from environmental processes to human health threats.

    PubMed

    Cobelo-García, A; Filella, M; Croot, P; Frazzoli, C; Du Laing, G; Ospina-Alvarez, N; Rauch, S; Salaun, P; Schäfer, J; Zimmermann, S

    2015-10-01

    The current socio-economic, environmental and public health challenges that countries are facing clearly need common-defined strategies to inform and support our transition to a sustainable economy. Here, the technology-critical elements (which includes Ga, Ge, In, Te, Nb, Ta, Tl, the Platinum Group Elements and most of the rare-earth elements) are of great relevance in the development of emerging key technologies-including renewable energy, energy efficiency, electronics or the aerospace industry. In this context, the increasing use of technology-critical elements (TCEs) and associated environmental impacts (from mining to end-of-life waste products) is not restricted to a national level but covers most likely a global scale. Accordingly, the European COST Action TD1407: Network on Technology-Critical Elements (NOTICE)-from environmental processes to human health threats, has an overall objective for creating a network of scientists and practitioners interested in TCEs, from the evaluation of their environmental processes to understanding potential human health threats, with the aim of defining the current state of knowledge and gaps, proposing priority research lines/activities and acting as a platform for new collaborations and joint research projects. The Action is focused on three major scientific areas: (i) analytical chemistry, (ii) environmental biogeochemistry and (iii) human exposure and (eco)-toxicology. PMID:26286804

  19. West Flank Coso, CA FORGE 3D temperature model

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

    x,y,z data of the 3D temperature model for the West Flank Coso FORGE site. Model grid spacing is 250m. The temperature model for the Coso geothermal field used over 100 geothermal production sized wells and intermediate-depth temperature holes. At the near surface of this model, two boundary temperatures were assumed: (1) areas with surface manifestations, including fumaroles along the northeast striking normal faults and northwest striking dextral faults with the hydrothermal field, a temperature of ~104˚C was applied to datum at +1066 meters above sea level elevation, and (2) a near-surface temperature at about 10 meters depth, of 20˚C was applied below the diurnal and annual conductive temperature perturbations. These assumptions were based on heat flow studies conducted at the CVF and for the Mojave Desert. On the edges of the hydrothermal system, a 73˚C/km (4˚F/100’) temperature gradient contour was established using conductive gradient data from shallow and intermediate-depth temperature holes. This contour was continued to all elevation datums between the 20˚C surface and -1520 meters below mean sea level. Because the West Flank is outside of the geothermal field footprint, during Phase 1, the three wells inside the FORGE site were incorporated into the preexisting temperature model. To ensure a complete model was built based on all the available data sets, measured bottom-hole temperature gradients in certain wells were downward extrapolated to the next deepest elevation datum (or a maximum of about 25% of the well depth where conductive gradients are evident in the lower portions of the wells). After assuring that the margins of the geothermal field were going to be adequately modelled, the data was contoured using the Kriging method algorithm. Although the extrapolated temperatures and boundary conditions are not rigorous, the calculated temperatures are anticipated to be within ~6˚C (20˚F), or one contour interval, of the

  20. Introducing the "Human Element" in Chemistry by Synthesizing Blue Pigments and Creating Cyanotypes in a First-Year Chemistry Course

    ERIC Educational Resources Information Center

    Morizot, Olivier; Audureau, Eric; Briend, Jean-Yves; Hagel, Gaetan; Boulc'h, Florence

    2015-01-01

    In this article, we present two concrete applications of the concept of the human element to chemistry education; starting with a course and experimental project on blue pigment synthesis and concluding with cross-disciplinary lessons and experiments on blue photography. In addition to the description of the content of these courses, we explore…

  1. Implications of Flexural Flanks at the Valles Marineris, Mars

    NASA Technical Reports Server (NTRS)

    Anderson, F. S.; Banerdt, W. B.; Golombek, M. P.

    1999-01-01

    The presence or absence of flexural flanks at the Valles Marineris (VM), Mars, have strong implications for the properties of the lithosphere, information which is critical for models of compensation state and formation of the troughs. Two hypotheses are favored for the formation of the VM, tectonic extension or subsurface withdrawal potentially related to dike emplacement; in either case, the formation of the large troughs at the VM requires a flexural response. After discussing preliminary models of flexure for VM from released Mars Global Surveyor (MGS) Mars Orbiting Laser Altimeter (MOLA) topography, this abstract considers the implications of flexure for gravity modeling and the lithosphere at VM. With future MGS topography and gravity data, and constraints on T(sub e) from this study, significantly better gravity modeling can be done to understand the state of the lithosphere at VM. Additional information is contained in the original extended abstract.

  2. Bathymetry of the southwest flank of Mauna Loa Volcano, Hawaii

    USGS Publications Warehouse

    Chadwick, William W.; Moore, James G.; Fox, Christopher G.

    1994-01-01

    Much of the seafloor topography in the map area is on the southwest submarine flank of the currently active Mauna Loa Volcano. The benches and blocky hills shown on the map were shaped by giant landslides that resulted from instability of the rapidly growing volcano. These landslides were imagined during a 1986 to 1991 swath sonar program of the United States Hawaiian Exclusive Economic Zone, a cooperative venture by the U.S. Geological Survey and the British Institute of Oceanographic Sciences (Lipman and others, 1988; Moore and others, 1989). Dana Seamount (and probably also the neighboring Day Seamount) are apparently Cretaceous in age, based on paleomagnetic studies, and predate the growth of the Hawaiian Ridge volcanoes (Sager and Pringle, 1990).

  3. Evidence of Multiple Flank Collapse at Volcan Baru, Panama

    NASA Astrophysics Data System (ADS)

    Herrick, J. A.; Rose, W. I.

    2009-12-01

    Michigan Tech's Peace Corps Master's International program (PCMI) in Geological Hazards has enabled several long-term investigations of active volcanoes in Latin America. To contribute to volcanic hazard assessments in Panama and achieve the goals defined by the PCMI program, we developed this debris avalanche project to address outstanding questions regarding Volcan Baru's most devastating event - massive slope failure of the western flank. Relying on basic mapping tools as well as the 2007 USGS Open-File Report focusing on hazard assessments of Panama's youngest and potentially active volcano, identification of the debris avalanche deposits (DAD) required detailed field investigations to determine the limits of the units. Extending across an area larger than 600 km2, field strategies were developed based on outcrop exposures within drainages and road-cuts. Aerial photos and DEMs of Baru's nested craters were interpreted by earlier scientists as the remains of two collapsed flanks. The results from in-depth field traverses provide several important discoveries: paleosols and sharp contacts within the stratigraphy indicate multiple DAD, deeply weathered hummocks red-flag the deposits more than 50-km away from Baru's crater, and high-quality radiocarbon samples (up to 45-cm long fragments of entrained wood) lie in the distal reaches of the debris flow area. During the 2008-2009 field seasons, we received assistance from the University of Panama, Civil Protection, and Panama's National Institute of Geography. Support from local experts and feedback from professional scientists of the Smithsonian Institution and Costa Rica's Institute of Electricity were invaluable. The 2-year investment in volcanic hazard studies has brought together resources from several countries as well as fresh data that will benefit the residents and emergency management officials of Panama. Jigsaw fractured clasts lie within Volcan Baru's debris avalanche deposits more than 28 km south of the

  4. Erosion of Terrestrial Rift Flank Topography: A Quantitative Study

    NASA Technical Reports Server (NTRS)

    Weissel, Jeffrey K.

    1999-01-01

    Many rifted or passive continental margins feature a seaward-facing erosional escarpment which abruptly demarcates deeply weathered, low relief, interior uplands from a deeply incised, high relief coastal zone. It is generally accepted that these escarpments originate at the time of continental rifting and propagate inland through the elevated rift flank topography at rates on the order of 1 km/Myr over the course of a margin's history. Considering the length of passive margins worldwide and an average rift flank plateau height of several hundred meters, it is clear that sediment eroded from passive margins is an important component of the mass flux from continents to oceans through geologic time. The overall goal of the research reported here is to develop a quantitative understanding of the kinematics of escarpment propagation across passive margins and the underlying geological processes responsible for this behavior. Plateau-bounding escarpments in general exhibit two basic forms depending on the direction of surface water drainage on the plateau interior relative to the escarpment. Where surface water flows away from the escarpment, the escarpment takes the form of subdued embayments and promontories, such that its overall trend remains fairly straight as it evolves with time. Where upland streams flow across the escarpment, it takes the form of dramatic, narrow gorges whose heads appear to propagate up the plateau drainage systems as large-scale knickpoints. From work on the Colorado Plateau, Schmidt (1987) noted that the Colorado River is located much closer to the Grand Canyon's south rim, a drainage divide escarpment, than to the north rim, which is a gorge-like escarpment. The main implication is that the gorge-like form might be associated with higher long-term average erosion rates compared to the drainage divide escarpment type.

  5. Composition of pore and spring waters from Baby Bare: Global implications of geochemical fluxes from a ridge flank hydrothermal system

    SciTech Connect

    Wheat, C.G.; Mottl, M.J.

    2000-02-01

    Warm hydrothermal springs were discovered on Baby Bare, which is an isolated basement outcrop on 3.5 Ma-old crust on the eastern flank of the Juan de Fuca Ridge. The authors have sampled these spring waters from a manned submersible, along with associated sediment pore waters from 48 gravity and piston cores. Systematic variations in the chemical composition of these waters indicate that hydrothermal reactions in basement at moderate temperatures remove Na, K, Li, Rb, Mg, TCO{sub 2}, alkalinity, and phosphate from the circulating seawater and leach Ca, Sr, Si, B, and Mn from the oceanic crust; and that reactions with the turbidite sediment surrounding Baby Bare remove Na, Li, Mg, Ca, Sr, and sulfate from the pore water while producing ammonium and Si and both producing and consuming phosphate, nitrate, alkalinity, Mn, and Fe. K, Rb, and B are relatively unreactive in the sediment column. The composition of altered seawater in basement at Baby Bare is similar to the inferred composition of 58 C formation water from crust nearly twice as old (5.9 Ma) on the southern flank of the Costa Rica Rift. The Baby Bare fluids also exhibit the same directions of net elemental transfer between basalt and seawater as solutions produced in laboratory experiments at a similar temperature, and complement compositional changes form seawater observed in seafloor basalts altered at cool to moderate temperatures. The common parameter among the two ridge flanks and experiments is temperature, suggesting that the residence time of seawater in the two ridge-flank sites is sufficiently long for the solutions to equilibrate with altered basalt. The authors use the Baby Bare spring water to estimate upper limits on the global fluxes of 14 elements at warm ridge-flank sites such as Baby Bare. Maximum calculated fluxes of Mg, Ca, sulfate, B, and K may equal or exceed 25% of the riverine flux, and such sites may represent the missing, high K/Rb sink required for the K budget.

  6. Risk of human exposure to arsenic and other toxic elements from geophagy: trace element analysis of baked clay using inductively coupled plasma mass spectrometry

    PubMed Central

    2010-01-01

    Background Geophagy or earth-eating is common amongst some Bangladeshi women, especially those who are pregnant, both in Bangladesh and in the United Kingdom. A large proportion of the population in Bangladesh is already exposed to high concentrations of arsenic (As) and other toxic elements from drinking contaminated groundwater. Additional exposure to As and other toxic elements from non-food sources has not been adequately addressed and here we present the first study to monitor As levels in baked clay (known as sikor). Methods Sikor samples originating from Bangladesh were digested using a microwave digester and analysed for their As, Pb, Cd, Mn, Fe and Zn levels using ICP-MS. Detailed As speciation analysis was performed using HPLC-ICP-MS. Results Of particular concern were the levels of As (3.8-13.1 mg kg-1), Cd (0.09-0.4 mg kg-1) and Pb (21-26.7 mg kg-1) present in the sikor samples and their possible impact on human health. Speciation analysis revealed that sikor samples contained mainly inorganic As. Modest consumption of 50 g of sikor is equivalent to ingesting 370 μg of As and 1235 μg of Pb per day, based on median concentration values. This level of sikor consumption exceeds the permitted maximum tolerable daily intake (PMTDI) of inorganic As by almost 2-fold. Conclusion We conclude that sikor can be a significant source of As, Cd and Pb exposure for the Bangladeshi population consuming large quantities of this material. Of particular concern in this regard is geophagy practiced by pregnant women concurrently exposed to As contaminated drinking water. Future studies needs to evaluate the bioavailability of As and other elements from sikor and their impact on human health. PMID:21182763

  7. RENAL RETENTION OF LIPID MICROBUBBLES: A POTENTIAL MECHANISM FOR FLANK DISCOMFORT DURING ULTRASOUND CONTRAST ADMINISTRATION

    PubMed Central

    Liu, Ya Ni; Khangura, Jaspreet; Xie, Aris; Belcik, J. Todd; Qi, Yue; Davidson, Brian P.; Zhao, Yan; Kim, Sajeevani; Inaba, Yoichi; Lindner, Jonathan R.

    2013-01-01

    Background The etiology for flank pain sometimes experienced during administration of ultrasound contrast agents is unknown. We investigated whether microbubble ultrasound contrast agents are retained within the renal microcirculation which could lead to either flow disturbance or local release of vasoactive and pain mediators downstream from complement activation. Methods Retention of lipid-shelled microbubbles in the renal microcirculation of mice was assessed by confocal fluorescent microscopy and contrast-enhanced ultrasound (CEU) imaging with dose-escalating intravenous injection. Studies were performed with size-segregated microbubbles to investigate physical entrapment, after glycocalyx degradation, and in wild-type and C3-deficient mice to investigate complement-mediated retention. Urinary bradykinin was measured before and after microbubbles. Renal CEU in human subjects (n=13) was performed 7–10 min after completion of lipid microbubble administration. Results In both mice and humans, microbubble retention was detected in the renal cortex by persistent CEU signal enhancement. Microbubble retention in mice was linearly related to dose and occurred almost exclusively in cortical glomerular microvessels. Microbubble retention did not affect microsphere-derived renal blood flow. Microbubble retention was not influenced by glycocalyx degradation nor by microbubble size, thereby excluding lodging, but was reduced by 90% (p<0.01) in C3-deficient mice. Urinary bradykinin increased by 65% five minutes after microbubble injection. Conclusion Lipid-shelled microbubbles are retained in the renal cortex due to complement-mediated interactions with glomerular microvascular endothelium. Microbubble retention does not adversely affect renal perfusion but does generate complement-related intermediates that are known to mediate nociception and could be responsible for flank pain. PMID:24035699

  8. The rise flank trails left by migrating offsets of the equatorial East Pacific Rise axis

    SciTech Connect

    Lonsdale, P. )

    1989-01-10

    Sea Beam and magnetic surveys of the young (<1 Ma) rise flank around nontransform rise crest offsets at 5.5{degree}N, 4.9{degree}N, 3.4{degree}, 2.0{degree}N, and 2.8{degree}S mapped distinctive trails of obliquely lineated, highly magnetic crust that spreads from the characteristically curving overlapping rift zones. A Deep Tow survey around the small (1.5 km) 3.9{degree}N offset and the large (27 km) 2.0{degree}N offset provided more detailed infromation on the formation of crust in the offset trails, and of the structure of tectoniclly modified crust at interrift rise crest sites. Patches of interrift crust, which forms deep overlap basins at medium size offsets and basins and plateaus of rotated abyssal hills at large offsets, are periodically shed from the axial zone, together with abandoned portions of overlapped rift zone, to become important elements of the rise flank trails. The oblique aximuths of the paired 'fracture zone' trails that diverge from the rise crest offsets show that most have migrated along the rise crest at average speeds of 25-125 mm/yr. Net movement of the 27-km 2.8{degree}S offset has been slower, with alternating periods of rapid northward and southward migration. Information on the migration history of the surveyed offsets was supplemented by inferring the migration direction of another eight offsets on the equatorial East Pacific Rise (EPR) whose trails were less throughly mapped. Most offsets of the southern Pacific-Cocos boundary have migrated south, and most on the northern Pacific-Nazca boundary have migrated south, and most on the northern Pacific-Nazca boundary have migrated north; the patterns are not readily explained by the inferred distribution of mantle upwellings along the EPR axis.

  9. Using occlusal wear information and finite element analysis to investigate stress distributions in human molars

    PubMed Central

    Benazzi, Stefano; Kullmer, Ottmar; Grosse, Ian R; Weber, Gerhard W

    2011-01-01

    Simulations based on finite element analysis (FEA) have attracted increasing interest in dentistry and dental anthropology for evaluating the stress and strain distribution in teeth under occlusal loading conditions. Nonetheless, FEA is usually applied without considering changes in contacts between antagonistic teeth during the occlusal power stroke. In this contribution we show how occlusal information can be used to investigate the stress distribution with 3D FEA in lower first molars (M1). The antagonistic crowns M1 and P2–M1 of two dried modern human skulls were scanned by μCT in maximum intercuspation (centric occlusion) contact. A virtual analysis of the occlusal power stroke between M1 and P2–M1 was carried out in the Occlusal Fingerprint Analyser (OFA) software, and the occlusal trajectory path was recorded, while contact areas per time-step were visualized and quantified. Stress distribution of the M1 in selected occlusal stages were analyzed in strand7, considering occlusal information taken from OFA results for individual loading direction and loading area. Our FEA results show that the stress pattern changes considerably during the power stroke, suggesting that wear facets have a crucial influence on the distribution of stress on the whole tooth. Grooves and fissures on the occlusal surface are seen as critical locations, as tensile stresses are concentrated at these features. Properly accounting for the power stroke kinematics of occluding teeth results in quite different results (less tensile stresses in the crown) than usual loading scenarios based on parallel forces to the long axis of the tooth. This leads to the conclusion that functional studies considering kinematics of teeth are important to understand biomechanics and interpret morphological adaptation of teeth. PMID:21615398

  10. Airborne particulate matter, platinum group elements and human health: a review of recent evidence.

    PubMed

    Wiseman, Clare L S; Zereini, Fathi

    2009-04-01

    Environmental concentrations of the platinum group elements (PGE) platinum (Pt), palladium (Pd) and rhodium (Rh) have been on the rise, due largely to the use of automobile catalytic converters which employ these metals as exhaust catalysts. It has generally been assumed that the health risks associated with environmental exposures to PGE are minimal. More recent studies on PGE toxicity, environmental bioavailability and concentrations in biologically relevant media indicate however that environmental exposures to these metals may indeed pose a health risk, especially at a chronic, subclinical level. The purpose of this paper is to review the most recent evidence and provide an up-to-date assessment of the risks related to environmental exposures of PGE, particularly in airborne particulate matter (PM). This review concludes that these metals may pose a greater health risk than once thought for several reasons. First, emitted PGE may be easily mobilised and solubilised by various compounds commonly present in the environment, thereby enhancing their bioavailability. Second, PGE may be transformed into more toxic species upon uptake by organisms. The presence of chloride in lung fluids, for instance, may lead to the formation of halogenated PGE complexes that have a greater potential to induce cellular damage. Third, a significant proportion of PGE found in airborne PM is present in the fine fraction that been found to be associated with increases in morbidity and mortality. PGE are also a concern to the extent that they contribute to the suite of metals found in fine PM suspected of eliciting a variety of health effects, especially in vulnerable populations. All these factors highlight the need to monitor environmental levels of PGE and continue research on their bioavailability, behaviour, speciation and associated toxicity to enable us to better assess their potential to elicit health effects in humans. PMID:19181366

  11. The effect of strain rate on fracture toughness of human cortical bone: a finite element study.

    PubMed

    Ural, Ani; Zioupos, Peter; Buchanan, Drew; Vashishth, Deepak

    2011-10-01

    Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0.08-18 s(-1)). In addition, the effect of porosity in combination with strain rate was assessed using three-dimensional models of micro-computed tomography-based compact tension specimens. The simulation results showed that bone's resistance against the propagation of a crack decreased sharply with increase in strain rates up to 1 s(-1) and attained an almost constant value for strain rates larger than 1 s(-1). On the other hand, initiation fracture toughness exhibited a more gradual decrease throughout the strain rates. There was a significant positive correlation between the experimentally measured number of microcracks and the fracture toughness found in the simulations. Furthermore, the simulation results showed that the amount of porosity did not affect the way initiation fracture toughness decreased with increasing strain rates, whereas it exacerbated the same strain rate effect when propagation fracture toughness was considered. These results suggest that strain rates associated with falls lead to a dramatic reduction in bone's resistance against crack propagation. The compromised fracture resistance of bone at loads exceeding normal activities indicates a sharp reduction and/or absence of toughening mechanisms in bone during high strain conditions associated with traumatic fracture. PMID:21783112

  12. THE EFFECT OF STRAIN RATE ON FRACTURE TOUGHNESS OF HUMAN CORTICAL BONE: A FINITE ELEMENT STUDY

    PubMed Central

    Ural, Ani; Zioupos, Peter; Buchanan, Drew; Vashishth, Deepak

    2011-01-01

    Evaluating the mechanical response of bone under high loading rates is crucial to understanding fractures in traumatic accidents or falls. In the current study, a computational approach based on cohesive finite element modeling was employed to evaluate the effect of strain rate on fracture toughness of human cortical bone. Two-dimensional compact tension specimen models were simulated to evaluate the change in initiation and propagation fracture toughness with increasing strain rate (range: 0.08 to 18 s−1). In addition, the effect of porosity in combination with strain rate was assessed using three-dimensional models of microcomputed tomography-based compact tension specimens. The simulation results showed that bone’s resistance against the propagation of fracture decreased sharply with increase in strain rates up to 1 s−1 and attained an almost constant value for strain rates larger than 1 s−1. On the other hand, initiation fracture toughness exhibited a more gradual decrease throughout the strain rates. There was a significant positive correlation between the experimentally measured number of microcracks and the fracture toughness found in the simulations. Furthermore, the simulation results showed that the amount of porosity did not affect the way initiation fracture toughness decreased with increasing strain rates, whereas it exacerbated the same strain rate effect when propagation fracture toughness was considered. These results suggest that strain rates associated with falls lead to a dramatic reduction in bone’s resistance against crack propagation. The compromised fracture resistance of bone at loads exceeding normal activities indicates a sharp reduction and/or absence of toughening mechanisms in bone during high strain conditions associated with traumatic fracture. PMID:21783112

  13. Role of trabecular microfractures in failure of human vertebrae estimated by the finite element method

    NASA Astrophysics Data System (ADS)

    Sidorenko, Irina N.; Bauer, Jan; Monetti, Roberto; Müller, Dirk; Rummeny, Ernst J.; Eckstein, Felix; Matsuura, Maiko; Lochmüller, Eva-Maria; Zysset, Philippe K.; Räth, Christoph W.

    2009-02-01

    Spine fractures are the most frequent complication of osteoporosis, a disease characterized by low bone mass and structural deterioration of bone tissue. In case of the spine, the trabecular network plays the main role in load carrying and distribution. A correct description of mechanical properties of this bone structure helps to differentiate between strong and weak bones and can be useful for fracture prediction and treatment monitoring. By means of the finite element method (FEM), applied to μCT images, we modelled biomechanical processes in probes during loading and correlated the estimated failure load with the maximum compressive strength (MCS), obtained in real biomechanical tests. We studied a sample of 151 specimens taken from the trabecular part of human vertebrae in vitro, visualised using μCT imaging at an isotropic resolution of 26μm and tested by uniaxial compression. Besides the standard way of estimating failure load, which takes into account only strong micro-fractures, we also included small micro-fractures, what improved the correlation with MCS (Pearson's correlation coefficient r=0.78 vs. r=0.58). This correlation coefficient was larger than that for both the standard morphometric parameters (r=0.73 for bone volume fraction) and for texture measures defined by the local (an-) isotropic scaling indices method (r=0.55) and Minkowski Functionals (r=0.61). However, the performance of the FEM was different for subsamples selected according to the MCS value. The correlation increased for strong specimens (r=0.88), slightly decreased for weak specimens (r=0.68) and markedly dropped for specimens with medium MCS, e.g. between 60

  14. Determination of Rare Earth Elements in Human Sperm and Association with Semen Quality.

    PubMed

    Marzec-Wróblewska, Urszula; Kamiński, Piotr; Łakota, Paweł; Ludwikowski, Grzegorz; Szymański, Marek; Wasilow, Karolina; Stuczyński, Tomasz; Buciński, Adam; Jerzak, Leszek

    2015-08-01

    The aim of the present study was to measure lanthanum (La), cerium (Ce), europium (Eu), and gadolinium (Gd) concentrations in human semen and correlate the results with sperm quality. The median semen content of La was 19.5 µg kg(-1) dry weight (dw) (range 2.27-269), of Ce was 41.9 µg kg(-1) dw (range 4.52 to 167), of Eu was 0.68 µg kg(-1) dw (range 0.06-1.95), of Gd was 3.19 µg kg(-1) dw (range 0.38-12.0), and of calcium (Ca) was 4063 mg kg(-1) dw (range 484-17,191). Concentrations of La, Ce, Eu, Gd, and Ca were significantly lower in nondrinkers' semen than in semen from drinkers. Significant differences were detected between La, Ce, Eu, Gd, and Ca concentrations in semen from nondrinkers and moderate drinkers. Concentrations of La, Ce, and Gd in semen of short-term smokers were significantly lower than those in extremely long-term smokers. Significant differences were also detected between La concentration in semen from a group of short-term smokers and that of a group of long-term smokers. Positive correlations were found between La, Ce, Eu, Gd, and Ca concentrations in semen. La, Ce, Gd, and Ca concentrations in semen were positively associated with progressive motility and percentage of normal spermatozoa. Positive correlations were found between Ca and sperm concentration. Concentrations of La, Ce, and Gd were negatively associated with sperm concentration, whilst Ca concentration was negatively associated with volume of ejaculate. At the examined level, La, Ce, Eu, and Gd did not affect sperm quality, whereas alcohol consumption and smoking might have increased the level of rare earth elements in semen. PMID:25762379

  15. Numerical evaluation of implantable hearing devices using a finite element model of human ear considering viscoelastic properties.

    PubMed

    Zhang, Jing; Tian, Jiabin; Ta, Na; Huang, Xinsheng; Rao, Zhushi

    2016-08-01

    Finite element method was employed in this study to analyze the change in performance of implantable hearing devices due to the consideration of soft tissues' viscoelasticity. An integrated finite element model of human ear including the external ear, middle ear and inner ear was first developed via reverse engineering and analyzed by acoustic-structure-fluid coupling. Viscoelastic properties of soft tissues in the middle ear were taken into consideration in this model. The model-derived dynamic responses including middle ear and cochlea functions showed a better agreement with experimental data at high frequencies above 3000 Hz than the Rayleigh-type damping. On this basis, a coupled finite element model consisting of the human ear and a piezoelectric actuator attached to the long process of incus was further constructed. Based on the electromechanical coupling analysis, equivalent sound pressure and power consumption of the actuator corresponding to viscoelasticity and Rayleigh damping were calculated using this model. The analytical results showed that the implant performance of the actuator evaluated using a finite element model considering viscoelastic properties gives a lower output above about 3 kHz than does Rayleigh damping model. Finite element model considering viscoelastic properties was more accurate to numerically evaluate implantable hearing devices. PMID:27276992

  16. Synchrotron Radiation and Energy Dispersive X-Ray Fluorescence Applications on Elemental Distribution in Human Hair and Bones

    SciTech Connect

    Carvalho, M.L.; Marques, A.F.; Brito, J.

    2003-01-24

    This work is an application of synchrotron microprobe X- Ray fluorescence in order to study elemental distribution along human hair samples of contemporary citizens. Furthermore, X-Ray fluorescence spectrometry is also used to analyse human bones of different historical periods: Neolithic and contemporary subjects. The elemental content in the bones allowed us to conclude about environmental contamination, dietary habits and health status influence in the corresponding citizens. All samples were collected post-mortem. Quantitative analysis was performed for Mn, Fe, Co, Ni, Cu, Zn, Br, Rb, Sr and Pb. Mn and Fe concentration were much higher in bones from pre-historic periods. On the contrary, Pb bone concentrations of contemporary subjects are much higher than in pre-historical ones, reaching 100 {mu}g g-1, in some cases. Very low concentrations for Co, Ni, Br and Rb were found in all the analysed samples. Cu concentrations, allows to distinguish Chalcolithic bones from the Neolithic ones. The distribution of trace elements along human hair was studied for Pb and the obtained pattern was consistent with the theoretical model, based on the diffusion of this element from the root and along the hair. Therefore, the higher concentrations in hair for Pb of contemporary individuals were also observed in the bones of citizens of the same sampling sites. All samples were analysed directly without any chemical treatment.

  17. LRE2, an active human L1 element, has low level transcriptional activity and extremely low reverse transcriptase activity

    SciTech Connect

    Holmes, S.E.; Dombroski, B.A.; Sassaman, D.M.

    1994-09-01

    Previously, we found a 2 kb insertion containing a rearranged L1 element plus a unique sequence component (USC) within exon 48 of the dystrophin gene of a patient with muscular dystrophy. We used the USC to clone the precursor of this insertion, the second known {open_quotes}active{close_quotes} human L1 element. The locus LRE2 (L1 Retrotransposable Element 2) has an allele derived from the patient which matches the insertion sequence exactly. LRE2 has a perfect 13-15 bp target site duplication, 2 open reading frames (ORFs), and an unusual 21 bp truncation of the 5{prime} end in a region known to be important for L1 transcription. The truncated LRE2 promoter has about 20% of the transcriptional activity of a previously studied L1 promoter after transfection into NTera2D1 cells of a construct in which the L1 promoter drives the expression of a lacZ gene. In addition, the reverse transcriptase (RT) encoded by LRE2 is active in an in vivo pseudogene assay in yeast and an in vitro assay. However, in both assays the RT of LRE2 is 1-5% as active as that of LRE1. These data demonstrate that multiple {open_quotes}active{close_quotes} L1 elements exist in the human genome, and that active elements can have highly variable rates of transcription and reverse transcriptase activity. That the RT of LRE2 has extremely low activity suggests the possibility that retrotransposition of an L1 element may in some cases involve an RT encoded by another L1 element.

  18. Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse

    PubMed Central

    Tyas, David A; Simpson, T Ian; Carr, Catherine B; Kleinjan, Dirk A; van Heyningen, Veronica; Mason, John O; Price, David J

    2006-01-01

    Background The Pax6 transcription factor is expressed during development in the eyes and in specific CNS regions, where it is essential for normal cell proliferation and differentiation. Mice lacking one or both copies of the Pax6 gene model closely humans with loss-of-function mutations in the PAX6 locus. The sequence of the Pax6/PAX6 protein is identical in mice and humans and previous studies have shown structural conservation of the gene's regulatory regions. Results We generated a transgenic mouse expressing green fluorescent protein (GFP) and neomycin resistance under the control of the entire complement of human PAX6 regulatory elements using a modified yeast artificial chromosome (YAC). Expression of GFP was studied in embryos from 9.5 days on and was confined to cells known to express Pax6. GFP expression was sufficiently strong that expressing cells could be distinguished from non-expressing cells using flow cytometry. Conclusion This work demonstrates the functional conservation of the regulatory elements controlling Pax6/PAX6 expression in mice and humans. The transgene provides an excellent tool for studying the functions of different Pax6/PAX6 regulatory elements in controlling Pax6 expression in animals that are otherwise normal. It will allow the analysis and isolation of cells in which Pax6 is activated, irrespective of the status of the endogenous locus. PMID:16674807

  19. Lead Exposure during Early Human Development and DNA Methylation of Imprinted Gene Regulatory Elements in Adulthood

    PubMed Central

    Li, Yue; Xie, Changchun; Murphy, Susan K.; Skaar, David; Nye, Monica; Vidal, Adriana C.; Cecil, Kim M.; Dietrich, Kim N.; Puga, Alvaro; Jirtle, Randy L.; Hoyo, Cathrine

    2015-01-01

    30 to 78 months. Conclusions: Our findings provide evidence that early childhood lead exposure results in sex-dependent and gene-specific DNA methylation differences in the DMRs of PEG3, IGF2/H19, and PLAGL1/HYMAI in adulthood. Citation: Li Y, Xie C, Murphy SK, Skaar D, Nye M, Vidal AC, Cecil KM, Dietrich KN, Puga A, Jirtle RL, Hoyo C. 2016. Lead exposure during early human development and DNA methylation of imprinted gene regulatory elements in adulthood. Environ Health Perspect 124:666–673; http://dx.doi.org/10.1289/ehp.1408577 PMID:26115033

  20. Linear Amplification Mediated PCR – Localization of Genetic Elements and Characterization of Unknown Flanking DNA

    PubMed Central

    Gabriel, Richard; Kutschera, Ina; Bartholomae, Cynthia C; von Kalle, Christof; Schmidt, Manfred

    2014-01-01

    Linear-amplification mediated PCR (LAM-PCR) has been developed to study hematopoiesis in gene corrected cells of patients treated by gene therapy with integrating vector systems. Due to the stable integration of retroviral vectors, integration sites can be used to study the clonal fate of individual cells and their progeny. LAM- PCR for the first time provided evidence that leukemia in gene therapy treated patients originated from provirus induced overexpression of a neighboring proto-oncogene. The high sensitivity and specificity of LAM-PCR compared to existing methods like inverse PCR and ligation mediated (LM)-PCR is achieved by an initial preamplification step (linear PCR of 100 cycles) using biotinylated vector specific primers which allow subsequent reaction steps to be carried out on solid phase (magnetic beads). LAM-PCR is currently the most sensitive method available to identify unknown DNA which is located in the proximity of known DNA. Recently, a variant of LAM-PCR has been developed that circumvents restriction digest thus abrogating retrieval bias of integration sites and enables a comprehensive analysis of provirus locations in host genomes. The following protocol explains step-by-step the amplification of both 3’- and 5’- sequences adjacent to the integrated lentiviral vector. PMID:24998871

  1. A review of the elements of human well-being with an emphasis on the contribution of ecosystem services.

    PubMed

    Summers, J K; Smith, L M; Case, J L; Linthurst, R A

    2012-06-01

    Natural ecosystems perform fundamental life-support services upon which human civilization depends. However, many people believe that nature provides these services for free and therefore, they are of little or no value. While we do not pay for them, we pay significantly for their loss in terms of wastewater treatment facilities, moratoriums on greenhouse gases, increased illnesses, reduced soil fertility and losses in those images of nature that contribute to our basic happiness. Little is understood about the well-being benefits of the natural environment and its ecosystem services. The interwoven relationship of ecosystems and human well-being is insufficiently acknowledged in the wider philosophical, social, and economic well-being literature. In this article, we discuss an approach to examine human well-being and the interactions of its four primary elements-basic human needs, economic needs, environmental needs, and subjective well-being-and ecosystem services. PMID:22581385

  2. Parametric Comparisons of Intracranial Mechanical Responses from Three Validated Finite Element Models of the Human Head

    PubMed Central

    Ji, Songbai; Ghadyani, Hamidreza; Bolander, Richard P.; Beckwith, Jonathan G.; Ford, James C.; Mcallister, Thomas W.; Flashman, Laura A.; Paulsen, Keith D.; Ernstrom, Karin; Jain, Sonia; Raman, Rema; Zhang, Liying; Greenwald, Richard M.

    2015-01-01

    A number of human head finite element (FE) models have been developed from different research groups over the years to study the mechanisms of traumatic brain injury. These models can vary substantially in model features and parameters, making it important to evaluate whether simulation results from one model are readily comparable with another, and whether response-based injury thresholds established from a specific model can be generalized when a different model is employed. The purpose of this study is to parametrically compare regional brain mechanical responses from three validated head FE models to test the hypothesis that regional brain responses are dependent on the specific head model employed as well as the region of interest (ROI). The Dartmouth Scaled and Normalized Model (DSNM), the Simulated Injury Monitor (SIMon), and the Wayne State University Head Injury Model (WSUHIM) were selected for comparisons. For model input, 144 unique kinematic conditions were created to represent the range of head impacts sustained by male collegiate hockey players during play. These impacts encompass the 50th, 95th, and 99th percentile peak linear and rotational accelerations at 16 impact locations around the head. Five mechanical variables (strain, strain rate, strain × strain rate, stress, and pressure) in seven ROIs reported from the FE models were compared using Generalized Estimating Equation statistical models. Highly significant differences existed among FE models for nearly all output variables and ROIs. The WSUHIM produced substantially higher peak values for almost all output variables regardless of the ROI compared to the DSNM and SIMon models (p < 0.05). DSNM also produced significantly different stress and pressure compared with SIMon for all ROIs (p < 0.05), but such differences were not consistent across ROIs for other variables. Regardless of FE model, most output variables were highly correlated with linear and rotational peak accelerations. The

  3. Validation of Finite Element Predictions of Cartilage Contact Pressure in the Human Hip Joint

    PubMed Central

    Anderson, Andrew E.; Ellis, Benjamin J.; Maas, Steve A.; Peters, Christopher L.; Weiss, Jeffrey A.

    2010-01-01

    Methods to predict contact stresses in the hip can provide an improved understanding of load distribution in the normal and pathologic joint. The objectives of this study were to develop and validate a three-dimensional finite element (FE) model for predicting cartilage contact stresses in the human hip using subject-specific geometry from computed tomography image data, and to assess the sensitivity of model predictions to boundary conditions, cartilage geometry, and cartilage material properties. Loads based on in vivo data were applied to a cadaveric hip joint to simulate walking, descending stairs and stair-climbing. Contact pressures and areas were measured using pressure sensitive film. CT image data were segmented and discretized into FE meshes of bone and cartilage. FE boundary and loading conditions mimicked the experimental testing. Fair to good qualitative correspondence was obtained between FE predictions and experimental measurements for simulated walking and descending stairs, while excellent agreement was obtained for stair-climbing. Experimental peak pressures, average pressures, and contact areas were 10.0 MPa (limit of film detection), 4.4-5.0 MPa and 321.9-425.1 mm2, respectively, while FE predicted peak pressures, average pressures and contact areas were 10.8-12.7 MPa, 5.1-6.2 MPa and 304.2-366.1 mm2, respectively. Misalignment errors, determined as the difference in root mean squared error before and after alignment of FE results, were less than 10%. Magnitude errors, determined as the residual error following alignment, were approximately 30% but decreased to 10-15% when the regions of highest pressure were compared. Alterations to the cartilage shear modulus, bulk modulus, or thickness resulted in ±25% change in peak pressures, while changes in average pressures and contact areas were minor (±10%). When the pelvis and proximal femur were represented as rigid, there were large changes, but the effect depended on the particular loading

  4. Sequence elements in the human osteocalcin gene confer basal activation and inducible response to hormonal vitamin D sub 3

    SciTech Connect

    Kerner, S.A.; Scott, R.A.; Pike, J.W. )

    1989-06-01

    Osteoblast-specific expression of the bone protein osteocalcin is controlled at the transcriptional level by the steroid hormone 1{alpha},25-dihydroxyvitamin D{sub 3}. As this protein may represent a marker for bone activity in human disease, the authors examined the regulation of its expression at the molecular level by evaluating human osteocalcin gene promoter function. They describe regions within the promoter that contribute to basal expression of the gene in osteoblast-like cells in culture. Further, they define a 21-base-pair DNA element with the sequence 5{prime}-GTGACTCACCGGGTGAACGGG-3{prime}, which acts in cis to mediate 1{alpha},25-dihydroxyvitamin D{sub 3} inducibility of the osteocalcin gene. This response element bears sequence similarity with other short DNA segments, particularly those for estrogen and thyroid hormone, which act together with their respective trans-acting receptors to modulate gene transcription.

  5. Mars - The relationship of robotic and human elements in the IAA International Exploration of Mars study

    NASA Astrophysics Data System (ADS)

    Marov, Mikhail Ya.; Duke, Michael B.

    1993-10-01

    The roles of human and robotic missions in Mars exploration are defined in the context of the short- and long-term Mars programs. In particular, it is noted that the currently implemented and planned missions to Mars can be regarded as robotic precursor missions to human exploration. Attention is given to factors that must be considered in formulating the rationale for human flights to Mars and future human Mars settlements and justifying costly projects.

  6. Mars - The relationship of robotic and human elements in the IAA International Exploration of Mars study

    NASA Technical Reports Server (NTRS)

    Marov, Mikhail YA.; Duke, Michael B.

    1993-01-01

    The roles of human and robotic missions in Mars exploration are defined in the context of the short- and long-term Mars programs. In particular, it is noted that the currently implemented and planned missions to Mars can be regarded as robotic precursor missions to human exploration. Attention is given to factors that must be considered in formulating the rationale for human flights to Mars and future human Mars settlements and justifying costly projects.

  7. Mass spectrometric methods for studying nutrient mineral and trace element absorption and metabolism in humans using stable isotopes. A review.

    PubMed

    Crews, H M; Ducros, V; Eagles, J; Mellon, F A; Kastenmayer, P; Luten, J B; McGaw, B A

    1994-11-01

    Mass spectrometric methods for determining stable isotopes of nutrient minerals and trace elements in human metabolic studies are described and discussed. The advantages and disadvantages of the techniques of electron ionization, fast atom bombardment, thermal ionization, and inductively coupled plasma and gas chromatography mass spectrometry are evaluated with reference to their accuracy, precision, sensitivity, and convenience, and the demands of human nutrition research. Examples of specific applications are described and the significance of current developments in mass spectrometry are discussed with reference to present and probable future research needs. PMID:7872491

  8. Construction and evaluation of thoracic injury risk curves for a finite element human body model in frontal car crashes.

    PubMed

    Mendoza-Vazquez, Manuel; Davidsson, Johan; Brolin, Karin

    2015-12-01

    There is a need to improve the protection to the thorax of occupants in frontal car crashes. Finite element human body models are a more detailed representation of humans than anthropomorphic test devices (ATDs). On the other hand, there is no clear consensus on the injury criteria and the thresholds to use with finite element human body models to predict rib fractures. The objective of this study was to establish a set of injury risk curves to predict rib fractures using a modified Total HUman Model for Safety (THUMS). Injury criteria at the global, structural and material levels were computed with a modified THUMS in matched Post Mortem Human Subjects (PMHSs) tests. Finally, the quality of each injury risk curve was determined. For the included PMHS tests and the modified THUMS, DcTHOR and shear stress were the criteria at the global and material levels that reached an acceptable quality. The injury risk curves at the structural level did not reach an acceptable quality. PMID:26397197

  9. 3D FEM Simulation of Flank Wear in Turning

    NASA Astrophysics Data System (ADS)

    Attanasio, Aldo; Ceretti, Elisabetta; Giardini, Claudio

    2011-05-01

    This work deals with tool wear simulation. Studying the influence of tool wear on tool life, tool substitution policy and influence on final part quality, surface integrity, cutting forces and power consumption it is important to reduce the global process costs. Adhesion, abrasion, erosion, diffusion, corrosion and fracture are some of the phenomena responsible of the tool wear depending on the selected cutting parameters: cutting velocity, feed rate, depth of cut, …. In some cases these wear mechanisms are described by analytical models as a function of process variables (temperature, pressure and sliding velocity along the cutting surface). These analytical models are suitable to be implemented in FEM codes and they can be utilized to simulate the tool wear. In the present paper a commercial 3D FEM software has been customized to simulate the tool wear during turning operations when cutting AISI 1045 carbon steel with uncoated tungsten carbide tip. The FEM software was improved by means of a suitable subroutine able to modify the tool geometry on the basis of the estimated tool wear as the simulation goes on. Since for the considered couple of tool-workpiece material the main phenomena generating wear are the abrasive and the diffusive ones, the tool wear model implemented into the subroutine was obtained as combination between the Usui's and the Takeyama and Murata's models. A comparison between experimental and simulated flank tool wear curves is reported demonstrating that it is possible to simulate the tool wear development.

  10. Flank crack detection in locomotive wheels with NDE techniques

    NASA Astrophysics Data System (ADS)

    Laczynski, Marie; Jayaraman, Subash B.; Halter, Ryan; Tittmann, Bernhard R.

    2001-08-01

    There is a need to analyze locomotive wheels for flank cracks in a non-destructive manner in order to prevent catastrophic failures. Flaw, shape, and size are desired parameters in establishing the quality of commercial tires. A variety of defects such as voids, inclusions, surface and internal cracks, or the like, must be discerned in order to prevent failure. This paper exhibits and compares the benefits of a number of different techniques used for flaw detection. Non-destructive evaluation techniques used consist of a magnetic particle, dye penetrant, eddy current, electro-magnetic acoustic transducer (EMAT), and longitudinal and shear wave ultrasonic inspection. The techniques vary in their ability to ascertain the flaw characteristics. Surface, sub-surface, and internal defects were visualized using the various methodologies. Magnetic particle, dye penetrant, and eddy current inspection techniques are viable methods for looking at surface flaws. Depending on the penetration depth, sub- surface flaws were also detectable via these methods. EMAT and ultrasonic transducer methods can be used to find surface, subsurface, and internal flaws based on the configuration utilized.

  11. Open Mini-Flank Partial Nephrectomy: An Essential Contemporary Operation

    PubMed Central

    Mano, Roy

    2014-01-01

    Secondary to the widespread use of the modern imaging techniques of computed tomography, magnetic resonance imaging, and ultrasound, 70% of renal tumors today are detected incidentally with a median tumor size of less than 4 cm. Twenty years ago, all renal tumors, regardless of size were treated with radical nephrectomy (RN). Elective partial nephrectomy (PN) has emerged as the treatment of choice for small renal tumors. The basis of this paradigm shift is three major factors: (1) cancer specific survival is equivalent for T1 tumors (7 cm or less) whether treated by PN or RN; (2) approximately 45% of renal tumors have indolent or benign pathology; and (3) PN prevents or delays the onset of chronic kidney disease, a condition associated with increased cardiovascular morbidity and mortality. Although PN can be technically demanding and associated with potential complications of bleeding, infection, and urinary fistula, the patient derived benefits of this operation far outweigh the risks. We have developed a "mini-flank" open surgical approach that is highly effective and, coupled with rapid recovery postoperative care pathways associated with a 2-day length of hospital stay. PMID:25237456

  12. Incorporation of Trace Elements in Ancient and Modern Human Bone: An X-Ray Absorption Spectroscopy Study

    NASA Astrophysics Data System (ADS)

    Pingitore, N. E.; Cruz-Jimenez, G.; Price, T. D.

    2001-12-01

    X-ray absorption spectroscopy (XAS) affords the opportunity to probe the atomic environment of trace elements in human bone. We are using XAS to investigate the mode(s) of incorporation of Sr, Zn, Pb, and Ba in both modern and ancient (and thus possibly altered) human and animal bone. Because burial and diagenesis may add trace elements to bone, we performed XAS analysis on samples of pristine contemporary and ancient, buried human and animal bone. We assume that deposition of these elements during burial occurs by processes distinct from those in vivo, and this will be reflected in their atomic environments. Archaeologists measure strontium in human and animal bone as a guide to diet. Carnivores show lower Sr/Ca ratios than their herbivore prey due to discrimination against Sr relative to Ca up the food chain. In an initial sample suite no difference was observed between modern and buried bone. Analysis of additional buried samples, using a more sensitive detector, revealed significant differences in the distance to the second and third neighbors of the Sr in some of the buried samples. Distances to the first neighbor, oxygen, were similar in all samples. Zinc is also used in paleo-diet studies. Initial x-ray absorption spectroscopy of a limited suite of bones did not reveal any differences between modern and buried samples. This may reflect the limited number of samples examined or the low levels of Zn in typical aqueous solutions in soils. Signals from barium and lead were too low to record useful XAS spectra. Additional samples will be studied for Zn, Ba, and Pb. We conducted our XAS experiments on beam lines 4-1 and 4-3 at the Stanford Synchrotron Radiation Laboratory. Data were collected in the fluorescence mode, using a Lytle detector and appropriate filter, and a solid state, 13-element Ge-detector.

  13. International project on human daily dietary intake of minor and trace elements

    SciTech Connect

    Iyengar, V.

    1986-01-01

    A coordinate research program on dietary intake of nutrient and other elements initiated by the International Atomic Energy Agency (IAEA) is currently under way. The purpose of the core program of this project is to obtain reliable data on the average daily intakes of several important minor and trace elements in diets consumed in a number of developed and developing countries such as Brazil, Canada, China, Iran, Italy, Spain, Sudan, Sweden, Thailand, and Turkey. In the core program which will be collected for determination of the nutrient elements such as calcium, magnesium, copper, iron, iodine, selenium, and zinc, among others. The project also provides for the measurement of aluminum, arsenic, cadmium, mercury, and lead in view of the biological significance of these elements as toxicants in the diet and includes estimation of the energy, phytate, and fiber components of the diet.

  14. The MYC 3' Wnt-Responsive Element Drives Oncogenic MYC Expression in Human Colorectal Cancer Cells.

    PubMed

    Rennoll, Sherri A; Eshelman, Melanie A; Raup-Konsavage, Wesley M; Kawasawa, Yuka Imamura; Yochum, Gregory S

    2016-01-01

    Mutations in components of the Wnt/β-catenin signaling pathway drive colorectal cancer (CRC) by deregulating expression of downstream target genes including the c-MYC proto-oncogene (MYC). The critical regulatory DNA enhancer elements that control oncogenic MYC expression in CRC have yet to be fully elucidated. In previous reports, we correlated T-cell factor (TCF) and β-catenin binding to the MYC 3' Wnt responsive DNA element (MYC 3' WRE) with MYC expression in HCT116 cells. Here we used CRISPR/Cas9 to determine whether this element is a critical driver of MYC. We isolated a clonal population of cells that contained a deletion of a single TCF binding element (TBE) within the MYC 3' WRE. This deletion reduced TCF/β-catenin binding to this regulatory element and decreased MYC expression. Using RNA-Seq analysis, we found altered expression of genes that regulate metabolic processes, many of which are known MYC target genes. We found that 3' WRE-Mut cells displayed a reduced proliferative capacity, diminished clonogenic growth, and a decreased potential to form tumors in vivo. These findings indicate that the MYC 3' WRE is a critical driver of oncogenic MYC expression and suggest that this element may serve as a therapeutic target for CRC. PMID:27223305

  15. Human prion protein sequence elements impede cross-species chronic wasting disease transmission

    PubMed Central

    Kurt, Timothy D.; Jiang, Lin; Fernández-Borges, Natalia; Bett, Cyrus; Liu, Jun; Yang, Tom; Spraker, Terry R.; Castilla, Joaquín; Eisenberg, David; Kong, Qingzhong; Sigurdson, Christina J.

    2015-01-01

    Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165–175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165–175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission. PMID:25705888

  16. TM6, a Novel Nuclear Matrix Attachment Region, Enhances Its Flanking Gene Expression through Influencing Their Chromatin Structure

    PubMed Central

    Ji, Lusha; Xu, Rui; Lu, Longtao; Zhang, Jiedao; Yang, Guodong; Huang, Jinguang; Wu, Changai; Zheng, Chengchao

    2013-01-01

    Nuclear matrix attachment regions (MARs) regulate the higher-order organization of chromatin and affect the expression of their flanking genes. In this study, a tobacco MAR, TM6, was isolated and demonstrated to remarkably increase the expression of four different promoters that drive gusA gene and adjacent nptII gene. In turn, this expression enhanced the transformation frequency of transgenic tobacco. Deletion analysis of topoisomerase II-binding site, AT-rich element, and MAR recognition signature (MRS) showed that MRS has the highest contribution (61.7%) to the TM6 sequence-mediated transcription activation. Micrococcal nuclease (MNase) accessibility assay showed that 35S and NOS promoter regions with TM6 are more sensitive than those without TM6. The analysis also revealed that TM6 reduces promoter DNA methylation which can affect the gusA expression. In addition, two tobacco chromatin-associated proteins, NtMBP1 and NtHMGB, isolated using a yeast one-hybrid system, specifically bound to the TM6II-1 region (761 bp to 870 bp) and to the MRS element in the TM6II-2 (934 bp to 1,021 bp) region, respectively. We thus suggested that TM6 mediated its chromatin opening and chromatin accessibility of its flanking promoters with consequent enhancement of transcription. PMID:23852133

  17. Human contribution to trace elements in urban areas as measured in holm oak (Quercus ilex L.) bark.

    PubMed

    Minganti, Vincenzo; Drava, Giuliana; Giordani, Paolo; Malaspina, Paola; Modenesi, Paolo

    2016-06-01

    The effect of human activities on the presence of trace elements in the atmosphere was evaluated by analyzing samples of holm oak bark, collected in Italy in a large city, in a small town, and in a reference area, scarcely inhabited. In all cases, point sources of pollution were excluded (e.g., industries and incinerators). The concentrations of As, Cd, Co, Cu, Fe, Mn, Ni, Pb, V, and Zn were measured using inductively coupled plasma optical emission spectrometry (ICP-OES). The element concentrations in the small town are not different from the reference area, except for Pb and Cu, while the samples collected in the large city show higher concentrations of Co, Cu, Fe, Ni, Pb, V, and Zn with respect to the rural area. In particular, the Pb levels in the large city are approximately 16 times higher than in the reference site, and five times higher than in the small town. Most element concentrations are correlated in the large city, while in the reference site, only a few significant correlations between elements were found. Even in the absence of specific sources of pollution, populations living in big cities are exposed to higher concentrations of trace elements than those living in rural environments or in small urban centers. PMID:27000118

  18. Mass fractions of 52 trace elements and zinc/trace element content ratios in intact human prostates investigated by inductively coupled plasma mass spectrometry.

    PubMed

    Zaichick, Sofia; Zaichick, Vladimir; Nosenko, Sergey; Moskvina, Irina

    2012-11-01

    Contents of 52 trace elements in intact prostate of 64 apparently healthy 13-60-year-old men (mean age 36.5 years) were investigated by inductively coupled plasma mass spectrometry. Mean values (M ± SΕΜ) for mass fraction (in milligrams per kilogram, on dry-weight basis) of trace elements were as follows: Ag 0.041 ± 0.005, Al 36 ± 4, Au 0.0039 ± 0.0007, B 0.97 ± 0.13, Be 0.00099 ± 0.00006, Bi 0.021 ± 0.008, Br 29 ± 3, Cd 0.78 ± 0.09, Ce 0.028 ± 0.004, Co 0.035 ± 0.003, Cs 0.034 ± 0.003, Dy 0.0031 ± 0.0005, Er 0.0018 ± 0.0004, Gd 0.0030 ± 0.0005, Hg 0.046 ± 0.006, Ho 0.00056 ± 0.00008, La 0.074 ± 0.015, Li 0.040 ± 0.004, Mn 1.53 ± 0.09, Mo 0.30 ± 0.03, Nb 0.0051 ± 0.0009, Nd 0.013 ± 0.002, Ni 4.3 ± 0.7, Pb 1.8 ± 0.4, Pr 0.0033 ± 0.0004, Rb 15.9 ± 0.6, Sb 0.040 ± 0.005, Se 0.73 ± 0.03, Sm 0.0027 ± 0.0004, Sn 0.25 ± 0.05, Tb 0.00043 ± 0.00009, Th 0.0024 ± 0.0005, Tl 0.0014 ± 0.0001, Tm 0.00030 ± 0.00006, U 0.0049 ± 0.0014, Y 0.019 ± 0.003, Yb 0.0015 ± 0.0002, Zn 782 ± 97, and Zr 0.044 ± 0.009, respectively. The upper limit of mean contents of As, Cr, Eu, Ga, Hf, Ir, Lu, Pd, Pt, Re, Ta, and Ti were the following: As ≤ 0.018, Cr ≤ 0.64, Eu ≤ 0.0006, Ga ≤ 0.08, Hf ≤ 0.02, Ir ≤ 0.0004, Lu ≤ 0.00028, Pd ≤ 0.007, Pt ≤ 0.0009, Re ≤ 0.0015, Ta ≤ 0.005, and Ti ≤ 2.6. In all prostate samples, the content of Te was under detection limit (<0.003). Additionally, ratios of the Zn content to other trace element contents as well as correlations between Zn and trace elements were calculated. Our data indicate that the human prostate accumulates such trace elements as Al, Au, B, Br, Cd, Cr, Ga, Li, Mn, Ni, Pb, U, and Zn. No special relationship between Zn and other trace elements was found. PMID:22549701

  19. Investigating the potential for volcano flank instability triggered by recent dike intrusions at Fogo volcano, Cape Verde

    NASA Astrophysics Data System (ADS)

    Bagnardi, Marco; González, Pablo; Hooper, Andrew; Wright, Tim

    2015-04-01

    Gravitational flank-collapses at volcanoes are rare but catastrophic events that have rarely been witnessed by humans (e.g., Mount St. Helens in 1980). It has been proposed that gravitationally unstable volcanic flanks can be classified in two different types based on the flanks slope: volcanoes characterized by gentle slopes (Hawaiian-like) and that have very dynamic flanks exhibiting high rates of deformation and, conversely, steep-sided volcanoes (Macaronesian-like) showing minimal ground deformation. The two types of volcanoes could therefore reach the stable-state through different mechanisms and experience different mass-wasting processes. Numerous giant debris-avalanche deposits have been identified offshore the volcanoes of the Canary Islands and Cape Verde. Given the steep slopes of these volcanoes, the mass-wasting events may have occurred suddenly and with minimal precursory signals. Several mechanisms have been proposed as potential triggers and among these the intrusion of shallow dikes feeding fissure eruptions is one of the best candidates. In this work, we investigate this hypothesis in the light of new and revised results derived from the analysis of geodetic observations at Fogo volcano (Cape Verde). Fogo has erupted twice in the last 20 years (1995 and 2014-2015) and in both occasions the volcano erupted along fissures that seem to be fed by dykes intruding the shallow crust and the volcanic edifice. We re-process radar data from the ERS satellite to obtain state-of-the-art deformation maps spanning the 1995 eruption and revisit previously proposed models of the magmatic system. Our results indicate that both eruptions were fed by sub-vertical dikes, steeply dipping to the SE, and radiating from the Pico do Fogo volcanic cone to the SW. We also study the effect of such magmatic intrusions in terms of the stress regime that they generate and analyze whether the 1995 and 2014 intrusions could potentially destabilize the structures along which a

  20. Prediction and analysis of human thoracic impact responses and injuries in cadaver impacts using a full human body finite element model.

    PubMed

    Ruan, Jesse; El-Jawahri, Raed; Chai, Li; Barbat, Saeed; Prasad, Priya

    2003-10-01

    Human thoracic dynamic responses and injuries associated with frontal impact, side impact, and belt loading were investigated and predicted using a complete human body finite element model for an average adult male. The human body model was developed to study the impact biomechanics of a vehicular occupant. Its geometry was based on the Visible Human Project (National Library of Medicine) and the topographies from human body anatomical texts. The data was then scaled to an average adult male according to available biomechanical data from the literature. The model includes details of the head, neck, ribcage, abdomen, thoracic and lumbar spine, internal organs of the chest and abdomen, pelvis, and the upper and lower extremities. The present study is focused on the dynamic response and injuries of the thorax. The model was validated at various impact speeds by comparing predicted responses with available experimental cadaver data in frontal and side pendulum impacts, as well as belt loading. Model responses were compared with similar individual cadaver tests instead of using cadaver corridors because the large differences between the upper and lower bounds of the corridors may confound the model validation. The validated model was then used to study thorax dynamic responses and injuries in various simulated impact conditions. Parameters that could induce injuries such as force, deflection, and stress were computed from model simulations and were compared with previously proposed thoracic injury criteria to assess injury potential for the thorax. It has been shown that the model exhibited speed sensitive impact characteristics, and the compressibility of the internal organs significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated FE human body model could be useful for injury assessment in various cadaveric impacts reported in the literature. Internal organ injuries, which are

  1. Oxidative Stress Regulates CFTR Gene Expression in Human Airway Epithelial Cells through a Distal Antioxidant Response Element

    PubMed Central

    Zhang, Zhaolin; Leir, Shih-Hsing

    2015-01-01

    Cystic fibrosis transmembrane conductance regulator gene (CFTR) expression in human airway epithelial cells involves the recruitment of distal cis-regulatory elements, which are associated with airway-selective DNase hypersensitive sites at −44 kb and −35 kb from the gene. The −35-kb site encompasses an enhancer that is regulated by the immune mediators interferon regulatory factor 1 and 2 and by nuclear factor Y. Here we investigate the −44-kb element, which also has enhancer activity in vitro in airway epithelial cells but is inactive in intestinal epithelial cells. This site contains an antioxidant response element (ARE) that plays a critical role in its function in airway cell lines and primary human bronchial epithelial cells. The natural antioxidant sulforaphane (SFN) induces nuclear translocation of nuclear factor, erythroid 2-like 2 (Nrf2), a transcription factor that regulates genes with AREs in their promoters, many of which are involved in response to injury. Under normal conditions, the −44-kb ARE is occupied by the repressor BTB and CNC homology 1, basic leucine zipper transcription factor (Bach1), and v-Maf avian musculoaponeurotic fibrosarcoma oncogene homolog K (MafK) heterodimers. After 2 hours of SFN treatment, Nrf2 displaces these repressive factors and activates CFTR expression. Site-directed mutagenesis shows that both the ARE and an adjacent NF-κB binding site are required for activation of the –44-kb element in airway epithelial cells. Moreover, this element is functionally linked to the −35-kb enhancer in modulating CFTR expression in response to environmental stresses in the airway. PMID:25259561

  2. Determination of thorium and other select trace elements in human tissues by neutron activation analysis

    SciTech Connect

    Glover, S.E.; Grimm, C.A.; Filby, R.H.

    1997-12-01

    Iyengar pointed out the significance of multidisciplinary approaches to biological trace element research and the problems that may be associated with much of the early trace element data (until the early 1970s). Problems identified included the analysis of spurious samples (e.g., hair) based on their availability with no consideration of the biological basis for the investigations and the uncontrolled collection of biological samples by investigators unable to assess the biological integrity of the sample and inadequate quality assurance/quality control. A significant inadequacy is that many trace element analysis studies have been performed on biopsies or samples that may not be representative of the whole organ, or that distribution data have been derived from pooled analyses of organs from many individuals.

  3. Finite element model creation and stability considerations of complex biological articulation: The human wrist joint.

    PubMed

    Gíslason, Magnús K; Stansfield, Benedict; Nash, David H

    2010-06-01

    The finite element method has been used with considerable success to simulate the behaviour of various joints such as the hip, knee and shoulder. It has had less impact on more complicated joints such as the wrist and the ankle. Previously published finite element studies on these multi-bone joints have needed to introduce un-physiological boundary conditions in order to establish numerical convergence of the model simulation. That is necessary since the stabilizing soft tissue mechanism of these joints is usually too elaborate in order to be fully included both anatomically and with regard to material properties. This paper looks at the methodology of creating a finite element model of such a joint focussing on the wrist and the effects additional constraining has on the solution of the model. The study shows that by investigating the effects each of the constraints, a better understanding on the nature of the stabilizing mechanisms of these joints can be achieved. PMID:20303315

  4. Human placenta processed for encapsulation contains modest concentrations of 14 trace minerals and elements.

    PubMed

    Young, Sharon M; Gryder, Laura K; David, Winnie B; Teng, Yuanxin; Gerstenberger, Shawn; Benyshek, Daniel C

    2016-08-01

    Maternal placentophagy has recently emerged as a rare but increasingly popular practice among women in industrialized countries who often ingest the placenta as a processed, encapsulated supplement, seeking its many purported postpartum health benefits. Little scientific research, however, has evaluated these claims, and concentrations of trace micronutrients/elements in encapsulated placenta have never been examined. Because the placenta retains beneficial micronutrients and potentially harmful toxic elements at parturition, we hypothesized that dehydrated placenta would contain detectable concentrations of these elements. To address this hypothesis, we analyzed 28 placenta samples processed for encapsulation to evaluate the concentration of 14 trace minerals/elements using inductively coupled plasma mass spectrometry. Analysis revealed detectable concentrations of arsenic, cadmium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, rubidium, selenium, strontium, uranium, and zinc. Based on one recommended daily intake of placenta capsules (3300 mg/d), a daily dose of placenta supplements contains approximately 0.018 ± 0.004 mg copper, 2.19 ± 0.533 mg iron, 0.005 ± 0.000 mg selenium, and 0.180 ± 0.018 mg zinc. Based on the recommended dietary allowance (RDA) for lactating women, the recommended daily intake of placenta capsules would provide, on average, 24% RDA for iron, 7.1% RDA for selenium, 1.5% RDA for zinc, and 1.4% RDA for copper. The mean concentrations of potentially harmful elements (arsenic, cadmium, lead, mercury, uranium) were well below established toxicity thresholds. These results indicate that the recommended daily intake of encapsulated placenta may provide only a modest source of some trace micronutrients and a minimal source of toxic elements. PMID:27440542

  5. Characteristics of the three ligaments of human spring ligament complex from a viewpoint of elements.

    PubMed

    Tohno, Yoshiyuki; Tohno, Setsuko; Taniguchi, Akira; Azuma, Cho; Minami, Takeshi; Mahakkanukrauh, Pasuk

    2012-06-01

    To elucidate characteristics of the three ligaments constituting the spring ligament complex from a viewpoint of elements, the authors investigated age-related changes of elements, relationships among their elements, relationships among ligaments in the elements, and gender differences in the three ligaments of the spring ligament complex, the superomedial calcaneonavicular (SMCN), inferoplantar longitudinal calcaneonavicular (ICN), and third or medioplantar oblique calcaneonavicular (TCN) ligaments. After ordinary dissection at Nara Medical University was finished, the SMCN, ICN, and TCN ligaments of the spring ligament complex were removed from the subjects. The subjects consisted of 10 men and 12 women, ranging in age from 62 to 99 years (average age = 80.5 ± 9.7 years). After incineration with nitric acid and perchloric acid, the element contents were determined by inductively coupled plasma-atomic emission spectrometry. It was found that although the Ca and P content hardly changed in the SMCN ligament with aging, the Ca and P content in the ICN ligament increased to about three and five times higher in the 80s in comparison with the 60s, respectively, whereas in the TCN ligament, it increased about 40% and 90% higher in the 80s compared with the 60s, respectively. Regarding the relationships among elements, significant direct correlations were found among the contents of Ca, P, and Mg in all the three ligaments of the spring ligament complex. This finding was in agreement with the previous finding obtained with the three ligaments of the anterior cruciate ligament, posterior longitudinal ligament, and ligamentum capitis femoris. Whether there were significant correlations among the three ligaments of the spring ligament complex with regard to the Ca, P, S, Mg, Zn, and Fe contents was examined using Pearson's correlation. It was found that there were significant direct correlations between the SMCN and TCN ligaments in all the Ca, P, Mg, and Zn contents and

  6. A Clinically Oriented Introduction and Review on Finite Element Models of the Human Cochlea

    PubMed Central

    Kikidis, Dimitrios; Bibas, Athanasios

    2014-01-01

    Due to the inaccessibility of the inner ear, direct in vivo information on cochlear mechanics is difficult to obtain. Mathematical modelling is a promising way to provide insight into the physiology and pathology of the cochlea. Finite element method (FEM) is one of the most popular discrete mathematical modelling techniques, mainly used in engineering that has been increasingly used to model the cochlea and its elements. The aim of this overview is to provide a brief introduction to the use of FEM in modelling and predicting the behavior of the cochlea in normal and pathological conditions. It will focus on methodological issues, modelling assumptions, simulation of clinical scenarios, and pathologies. PMID:25530973

  7. DNA sequences of Alu elements indicate a recent replacement of the human autosomal genetic complement

    SciTech Connect

    Knight, A.; Deininger, P.L.; Batzer, M.A.

    1996-04-30

    DNA sequences of neutral nuclear autosomal loci, compared across diverse human populations, provide a previously untapped perspective into the mode and tempo of the emergence of modern humans and a critical comparison with published clonally inherited mitochondrial DNA and Y chromosome measurements of human diversity. We obtained over 55 kilobases of sequence from three autosomal loci encompassing Alu repeats for representatives of diverse human populations as well as orthologous sequences for other hominoid species at one of these loci. Nucleotide diversity was exceedingly low. Most individuals and populations were identical. Only a single nucleotide difference distinguished presumed ancestral alleles from descendants. These results differ from those expected if alleles from divergent archaic populations were maintained through multiregional continuity. The observed virtual lack of sequence polymorphism is the signature of a recent single origin for modern humans, with general replacement of archaic populations. 47 refs., 2 figs., 1 tab.

  8. DNA sequences of Alu elements indicate a recent replacement of the human autosomal genetic complement.

    PubMed Central

    Knight, A; Batzer, M A; Stoneking, M; Tiwari, H K; Scheer, W D; Herrera, R J; Deininger, P L

    1996-01-01

    DNA sequences of neutral nuclear autosomal loci, compared across diverse human populations, provide a previously untapped perspective into the mode and tempo of the emergence of modern humans and a critical comparison with published clonally inherited mitochondrial DNA and Y chromosome measurements of human diversity. We obtained over 55 kilobases of sequence from three autosomal loci encompassing Alu repeats for representatives of diverse human populations as well as orthologous sequences for other hominoid species at one of these loci. Nucleotide diversity was exceedingly low. Most individuals and populations were identical. Only a single nucleotide difference distinguished presumed ancestral alleles from descendants. These results differ from those expected if alleles from divergent archaic populations were maintained through multiregional continuity. The observed virtual lack of sequence polymorphism is the signature of a recent single origin for modern humans, with general replacement of archaic populations. PMID:8633071

  9. Lineage-specific genomics: Frequent birth and death in the human genome: The human genome contains many lineage-specific elements created by both sequence and functional turnover.

    PubMed

    Young, Robert S

    2016-07-01

    Frequent evolutionary birth and death events have created a large quantity of biologically important, lineage-specific DNA within mammalian genomes. The birth and death of DNA sequences is so frequent that the total number of these insertions and deletions in the human population remains unknown, although there are differences between these groups, e.g. transposable elements contribute predominantly to sequence insertion. Functional turnover - where the activity of a locus is specific to one lineage, but the underlying DNA remains conserved - can also drive birth and death. However, this does not appear to be a major driver of divergent transcriptional regulation. Both sequence and functional turnover have contributed to the birth and death of thousands of functional promoters in the human and mouse genomes. These findings reveal the pervasive nature of evolutionary birth and death and suggest that lineage-specific regions may play an important but previously underappreciated role in human biology and disease. PMID:27231054

  10. Investigation of elemental distribution in human femoral head by PIXE and SRXRF microprobe

    NASA Astrophysics Data System (ADS)

    Zhang, Y. X.; Wang, Y. S.; Zhang, Y. P.; Zhang, G. L.; Huang, Y. Y.; He, W.

    2007-07-01

    In order to study the distribution and possible degenerative processes inducing the loss of inorganic substances in bone and to provide a scientific basis for the prevention and therapy of osteoporosis, proton induced X-ray emission (PIXE) method is used for the determination of elemental concentrations in femoral heads from five autopsies and seven patients with femoral neck fractures. Synchrotron radiation X-ray fluorescence (SRXRF) microprobe analysis technique is used to scan a slice of the femoral head from its periphery to its center, via cartilage, compact and spongy zones. The specimen preparation and experiment procedure are described in detail. The results show that the concentrations of P, Ca, Fe, Cu, Sr in the control group are higher than those in the patient group, but the concentrations of S, K, Zn, Mn are not significantly different. The quantitative results of elemental distribution, such as Ca, P, K, Fe, Zn, Sr and Pb in bone slice tissue including cartilage, substantial compact and substantial spongy, are investigated. The data obtained show that the concentrations of Ca, P, K, (the major elements of bone composition), are obviously low in both spongy and cartilage zones in the patient group, but there are no remarkable differences in the compact zone. Combined with the correlations between P, K, Zn, Sr and Ca, the loss mechanism of minerals and the physiological functions of some metal elements in bone are also discussed.

  11. A three-dimensional finite element model of maximal grip loading in the human wrist.

    PubMed

    Gislason, M K; Nash, D H; Nicol, A; Kanellopoulos, A; Bransby-Zachary, M; Hems, T; Condon, B; Stansfield, B

    2009-10-01

    The aim of this work was to create an anatomically accurate three-dimensional finite element model of the wrist, applying subject-specific loading and quantifying the internal load transfer through the joint during maximal grip. For three subjects, representing the anatomical variation at the wrist, loading on each digit was measured during a maximal grip strength test with simultaneous motion capture. The internal metacarpophalangeal joint load was calculated using a biomechanical model. High-resolution magnetic resonance scans were acquired to quantify bone geometry. Finite element analysis was performed, with ligaments and tendons added, to calculate the internal load distribution. It was found that for the maximal grip the thumb carried the highest load, an average of 72.2 +/- 20.1 N in the neutral position. Results from the finite element model suggested that the highest regions of stress were located at the radial aspect of the carpus. Most of the load was transmitted through the radius, 87.5 per cent, as opposed to 12.5 per cent through the ulna with the wrist in a neutral position. A fully three-dimensional finite element analysis of the wrist using subject-specific anatomy and loading conditions was performed. The study emphasizes the importance of modelling a large ensemble of subjects in order to capture the spectrum of the load transfer through the wrist due to anatomical variation. PMID:19908424

  12. Determination of trace element distribution in cancerous and normal human tissues by total reflection X-ray fluorescence analysis

    NASA Astrophysics Data System (ADS)

    von Czarnowski, D.; Denkhaus, E.; Lemke, K.

    1997-07-01

    The intention of this study was to establish a method for cancer diagnosis. For this purpose, different trace element distributions in carcinomas of the digestive tract and in normal tissues of human stomach, colon and rectum in correlation to the type of cancer were determined by total reflection X-ray fluorescence analysis (TXRF). The tissue samples were frozen and cut by a microtome into 10 μm sections, and a modified sample excision technique was introduced according to the aim of this research. After drying and spiking of the tissue sections, more than 20 elements, especially biologically relevant ones, were determined. The repeatabilities of measurements of element concentrations in malignant and normal tissues were calculated to be 10-30% (RSD) depending on the specific element. The concentration of Ca was found to be virtually constant (0.250±0.025 μg per 0.1 mm 3) in normal tissue and in carcinoma of the digestive organs. A significant diminution of Cr, Fe and Ni in carcinoma of the stomach, of Cr and Co in carcinoma of the colon and a significant accumulation of K in cancerous tissue of the colon and of Fe and K in neoplastic tissue of the rectum were discovered for a very limited population of patients.

  13. Multiple single-stranded cis elements are associated with activated chromatin of the human c-myc gene in vivo.

    PubMed Central

    Michelotti, G A; Michelotti, E F; Pullner, A; Duncan, R C; Eick, D; Levens, D

    1996-01-01

    Transcription activation and repression of eukaryotic genes are associated with conformational and topological changes of the DNA and chromatin, altering the spectrum of proteins associated with an active gene. Segments of the human c-myc gene possessing non-B structure in vivo located with enzymatic and chemical probes. Sites hypertensive to cleavage with single-strand-specific S1 nuclease or the single-strand-selective agent potassium permanganate included the major promoters P1 and P2 as well as the far upstream sequence element (FUSE) and CT elements, which bind, respectively, the single-strand-specific factors FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K in vitro. Active and inactive c-myc genes yielded different patterns of S1 nuclease and permanganate sensitivity, indicating alternative chromatin configurations of active and silent genes. The melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally associated torsional strain might assist strand separation and facilitate factor binding. Therefore, the interaction of FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K with supercoiled DNA was studied. Remarkably, both proteins recognize their respective elements torsionally strained but not as liner duplexes. Single-strand- or supercoil-dependent gene regulatory proteins may directly link alterations in DNA conformation and topology with changes in gene expression. PMID:8649373

  14. Shadow enhancers flanking the HoxB cluster direct dynamic Hox expression in early heart and endoderm development.

    PubMed

    Nolte, Christof; Jinks, Tim; Wang, Xinghao; Martinez Pastor, María Teresa; Krumlauf, Robb

    2013-11-01

    The products of Hox genes function in assigning positional identity along the anterior-posterior body axis during animal development. In mouse embryos, Hox genes located at the 3' end of HoxA and HoxB complexes are expressed in nested patterns in the progenitors of the secondary heart field during early cardiogenesis and the combined activities of both of these clusters are required for proper looping of the heart. Using Hox bacterial artificial chromosomes (BACs), transposon reporters, and transgenic analyses in mice, we present the identification of several novel enhancers flanking the HoxB complex which can work over a long range to mediate dynamic reporter expression in the endoderm and embryonic heart during development. These enhancers respond to exogenously added retinoic acid and we have identified two retinoic acid response elements (RAREs) within these control modules that play a role in potentiating their regulatory activity. Deletion analysis in HoxB BAC reporters reveals that these control modules, spread throughout the flanking intergenic region, have regulatory activities that overlap with other local enhancers. This suggests that they function as shadow enhancers to modulate the expression of genes from the HoxB complex during cardiac development. Regulatory analysis of the HoxA complex reveals that it also has enhancers in the 3' flanking region which contain RAREs and have the potential to modulate expression in endoderm and heart tissues. Together, the similarities in their location, enhancer output, and dependence on retinoid signaling suggest that a conserved cis-regulatory cassette located in the 3' proximal regions adjacent to the HoxA and HoxB complexes evolved to modulate Hox gene expression during mammalian cardiac and endoderm development. This suggests a common regulatory mechanism, whereby the conserved control modules act over a long range on multiple Hox genes to generate nested patterns of HoxA and HoxB expression during

  15. Toxic elements in groundwater of Lagos and Ogun States, Southwest, Nigeria and their human health risk assessment.

    PubMed

    Ayedun, H; Gbadebo, A M; Idowu, O A; Arowolo, T A

    2015-06-01

    A good quality drinking water is essential for human survival. However, a large percentage of the populations in most developing countries (Nigeria inclusive) do not have access to potable water. This study was therefore conducted to assess the extent of risk arising from consumption of toxic elements in groundwater samples collected from Lagos and Ogun States, Southwest, Nigeria. Twelve toxic elements concentrations (As, Mn, Cd, Cr, Pb, Ni, Al, Ti, V, Hg, Li, and Sn) were determined from 170 groundwater samples using inductively coupled plasma-mass spectrometry, and the physicochemical parameters were determined using standard methods. The pH results revealed that most of the water samples were slightly acidic. Of the twelve toxic elements, only Mn, Cd, Pb, Ni, and Al have concentrations higher than the WHO recommended limit in drinking water. The average dose of Mn and Al consumed daily from groundwater by an adult in Lagos state is 3.4 and 23.2 (μg/kg body weight), respectively. Similarly, an adult in Ogun State consumed an average daily dose of 6.09 and 25 (μg/kg body weight) Mn and Al, respectively. A greater threat was posed to children and infants. The order for risk of cancer in groundwater from Lagos State was Pb > Cr > As > Cd while the order in Ogun State groundwater was Cr > Cd > As > Pb. The relative high concentrations of Mn, Al, and Pb obtained in this study can be attributed to industrial and anthropogenic activities in the study area. Treatment of groundwater before consumption is recommended to avoid possible adverse cumulative effect. Improved waste disposal methods and regular monitoring of toxic elements in groundwater of the study area should be adopted to safeguard human health. PMID:25971518

  16. Investigating Late Amazonian Volcanotectonic Activity on Olympus Mons, Mars using Flank Vents and Arcuate Graben

    NASA Astrophysics Data System (ADS)

    Peters, S.; Christensen, P. R.

    2015-12-01

    Volcanism, a fundamental process in shaping the Martian surface, is crucial to understanding its evolution. Olympus Mons, the largest volcano on Mars, is one of several large shield volcanoes. Previous studies were technologically limited to large features associated with these constructs. With the advent of high resolution datasets, we are now able to investigate smaller features, such as flank vents and arcuate graben. Flank vents, common on polygenetic volcanoes, indicate that magma has propagated away from the main conduit and/or magma chamber. Vent morphology allows for the characterization of magma properties and eruption rates. Graben indicate extensional deformation. The distribution of graben provides information on stresses that acted on the volcano. In lieu of geophysical, spectral and in-situ data, morphology, morphometry and spatial relationships are powerful tools. We utilized high resolution image data (CTX, HiRISE and THEMIS IR) and topographic data (HRSC DTM, MOLA) to identify and characterize flank vents and graben. We observed 60 flank vents and 84 arcuate graben on Olympus Mons. Flank vents display varying morphologies and morphometries, suggesting different eruption styles and variable magma volatility. Vents occur primarily on the lower flank. This suggests magma has propagated substantial distances from the magma chamber. Observed clustering of vents may also indicate shallow magma sources. Similarly, graben are observed on the lower flank crosscutting young lava flows that have mantled portions of the escarpment. This indicates either gravitational spreading of Olympus Mons or flexure of the lithosphere in response to the load of the edifice. Collectively, the distribution of flank vents and arcuate graben suggests a similar development to that proposed for Ascraeus Mons. Based on superposition relationships and dates from previous studies, the flank vents and graben formed in the Late Amazonian (≤500 Ma).

  17. Scattering of the field of a multi-element phased array by human ribs

    NASA Astrophysics Data System (ADS)

    Gélat, P.; ter Haar, G.; Saffari, N.

    2012-03-01

    The efficacy of high intensity focused ultrasound (HIFU) for the non-invasive treatment of cancer has been demonstrated for a range of different cancers including those of the liver, kidney, prostate and breast. As a non-invasive focused therapy, HIFU offers considerable advantages over other techniques such as chemotherapy and surgical resection, in terms of invasiveness and risk of harmful side effects. Despite its advantages, however, there are a number of significant challenges currently hindering its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the ribcage to induce tissue necrosis at the required foci whilst minimising the formation of side lobes. Multielement random arrays are currently showing great promise in overcoming the limitations of single-element transducers. Nevertheless, successfully treating a patient for liver tumours requires a thorough understanding of the way in which the ultrasonic pressure field from a HIFU array is scattered by the ribcage. A mesh of quadratic pressure patches was generated using CT scan data for ribs nine to twelve on the right side. A boundary element approach based on a Generalised Minimal Residual (GMRES) implementation of the Burton-Miller formulation was used, in conjunction with phase conjugation techniques to focus the field of a 256-element random HIFU array past the ribs at both intercostal and transcostal treatment locations. This method has the advantage of accounting for full effects of scattering and diffraction in three dimensions under continuous wave excitation.

  18. Trace elements in the environment and in human organs. I. Methods and results

    SciTech Connect

    Takacs, S.; Tatar, A.

    1987-04-01

    The authors have determined by spectrophotometry the copper, zinc, lead, and cadmium content of the kidney, liver, lung, and adrenal derived from 1072 autopsies. The metallic content of food and drink was examined and the daily quantity consumed was stated by measuring and calculation. According to the results in Hungary the daily ingestion of these four microelements is small, as reflected by the metal content of the organs. An average 75% of the kidney's whole cadmium content is present in the cortex of the kidney. Lead in the medulla and zinc in the cortex are found in larger quantities. Analyzing the distribution according to sexes it was found that lead in the liver and kidney and cadmium in the kidney and lung of women is significantly lower than in the male. However, the element content in the adrenal is significantly higher for zinc and cadmium in women. The cadmium distribution in the kidney is similar to the essential elements. The correlation of the element pairs is better in the kidney and lung (Zn-Cu is 0.55 in the kidney and 0.51 in the lung).

  19. Does intake of trace elements through urban gardening in Copenhagen pose a risk to human health?

    PubMed

    Warming, Marlies; Hansen, Mette G; Holm, Peter E; Magid, Jakob; Hansen, Thomas H; Trapp, Stefan

    2015-07-01

    This study investigates the potential health risk from urban gardening. The concentrations of the trace elements arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn) in five common garden crops from three garden sites in Copenhagen were measured. Concentrations (mg/kg dw) of As were 0.002-0.21, Cd 0.03-0.25, Cr < 0.09-0.38, Cu 1.8-8.7, Ni < 0.23-0.62, Pb 0.05-1.56, and Zn 10-86. Generally, elemental concentrations in the crops do not reflect soil concentrations, nor exceed legal standards for Cd and Pb in food. Hazard quotients (HQs) were calculated from soil ingestion, vegetable consumption, measured trace element concentrations and tolerable intake levels. The HQs for As, Cd, Cr, Cu, Ni, and Zn do not indicate a health risk through urban gardening in Copenhagen. Exposure to Pb contaminated sites may lead to unacceptable risk not caused by vegetable consumption but by unintentional soil ingestion. PMID:25796073

  20. A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization.

    PubMed

    Vilaboa, Nuria; Bermejo, Rodrigo; Martinez, Pilar; Bornstein, Rafael; Calés, Carmela

    2004-01-01

    Cdc6 is a key regulator of the strict alternation of S and M phases during the mitotic cell cycle. In mammalian and plant cells that physiologically become polyploid, cdc6 is transcriptionally and post-translationally regulated. We have recently reported that Cdc6 levels are maintained in megakaryoblastic HEL cells, but severely downregulated by ectopic expression of transcriptional repressor Drosophila melanogaster escargot. Here, we show that cdc6 promoter activity is upregulated during megakaryocytic differentiation of HEL endoreplicating cells, and that Escargot interferes with such activation. Transactivation experiments showed that a 1.7 kb region located at 2800 upstream cdc6 transcription initiation site behaved as a potent enhancer in endoreplicating cells only. This activity was mainly dependent on a novel cis-regulatory element composed by an E2 box overlapping a GATA motif. Ectopic Escargot could bind this regulatory element in vitro and endogenous GATA-1 and E2A formed specific complexes in megakaryoblastic cells as well as in primary megakaryocytes. Chromatin Immunoprecipitation analysis revealed that both transcription factors were occupying the E2 box/GATA site in vivo. Altogether, these data suggest that cdc6 expression could be actively maintained during megakaryocytic differentiation through transcriptional mechanisms involving specific cis- and trans-regulatory elements. PMID:15590906

  1. A method for amplification of unknown flanking sequences based on touchdown PCR and suppression-PCR.

    PubMed

    Gao, Song; He, Dan; Li, Guangquan; Zhang, Yanhua; Lv, Huiying; Wang, Li

    2016-09-15

    Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample. PMID:27393656

  2. Ovariectomy by left flank approach in prepubertal Nelore (Bos indicus) heifers

    PubMed Central

    Peiró, Juliana R.; Nogueira, Geison M.; Nogueira, Guilherme P.; Perri, Silvia H.V.; Cardoso, Daniel

    2009-01-01

    The main objective of this study was to evaluate a recumbent left flank approach to bilateral ovariectomy in prepubertal heifers and to develop an optimal surgical technique for this procedure. Both ovaries were removed from 6 Nelore heifers by left flank approach without any complications, except in 1 heifer, which was believed to have had only 1 ovary based on ultrasound and exploration during surgery, but was later found to have a remaining functional ovary. Ovariectomy via left flank approach in recumbent prepubertal heifers is feasible and technically easy. This procedure does not involve special instrumentation and, despite the invasive approach, it allows optimal visualization of the ovaries and uterus. PMID:19794897

  3. Determining comparative elemental profile using handheld X-ray fluorescence in humans, elephants, dogs, and dolphins: Preliminary study for species identification.

    PubMed

    Nganvongpanit, Korakot; Buddhachat, Kittisak; Klinhom, Sarisa; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk

    2016-06-01

    Species identification is a crucial step in forensic anthropological studies. The aim of this study was to determine elemental profiles in bones from four mammal species, to be used for species discrimination. Human, elephant, dog, and dolphin bones were scanned by X-ray fluorescence (XRF); the differences in elemental profiles between species were determined using discriminant analysis. Dogs had the greatest number of elements (23), followed by humans (22) and elephants (20). Dolphins had the lowest number of elements (16). The accuracy rate of species identification in humans, elephants, dogs, and dolphins was 98.7%, 100%, 94.9%, and 92.3%, respectively. We conclude that element profiles of bones based on XRF analyses can serve as a tool for determining species. PMID:27093230

  4. The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.

  5. Integrating the human element into the systems engineering process and MBSE methodology.

    SciTech Connect

    Tadros, Michael Samir.

    2013-12-01

    In response to the challenges related to the increasing size and complexity of systems, organizations have recognized the need to integrate human considerations in the beginning stages of systems development. Human Systems Integration (HSI) seeks to accomplish this objective by incorporating human factors within systems engineering (SE) processes and methodologies, which is the focus of this paper. A representative set of HSI methods from multiple sources are organized, analyzed, and mapped to the systems engineering Vee-model. These methods are then consolidated and evaluated against the SE process and Models-Based Systems Engineering (MBSE) methodology to determine where and how they could integrate within systems development activities in the form of specific enhancements. Overall conclusions based on these evaluations are presented and future research areas are proposed.

  6. Leakage of active crater lake brine through the north flank at Rincon de la Vieja volcano, northwest Costa Rica, and implications for crater collapse

    USGS Publications Warehouse

    Kempter, K.A.; Rowe, G.L.

    2000-01-01

    de la Vieja. The distribution of thermal water types at Rincon de la Vieja strongly indicates that formation of the north-flank ACS waters is not due to mixing of shallow, steam-heated AS water with deep-seated NC water. More likely, hyper-acidic brines formed in the Active Crater area are migrating through permeable zones in the volcanic strata that make up the Active Crater's north flank. Dissolution and shallow subsurface alteration of north-flank volcanoclastic material by interaction with acidic lake brine, particularly in the more permeable tephra units, could weaken the already oversteepened north flank of the Active Crater. Sector collapse of the Active Crater, with or without a volcanic eruption, represents a potential threat to human lives, property, and ecosystems at Rincon de la Vieja volcano.

  7. Amino acids flanking the central core of Cu,Zn superoxide dismutase are important in retaining enzyme activity after autoclaving.

    PubMed

    Kumar, Arun; Randhawa, Vinay; Acharya, Vishal; Singh, Kashmir; Kumar, Sanjay

    2016-01-01

    Enzymes are known to be denatured upon boiling, although Cu,Zn superoxide dismutase of Potentilla atrosanguinea (Pot-SOD) retains significant catalytic activity even after autoclaving (heating at 121 °C at a pressure of 1.1 kg per square cm for 20 min). The polypeptide backbone of Pot-SOD consists of 152 amino acids with a central core spanning His45 to Cys145 that is involved in coordination of Cu(2+) and Zn(2+) ions. While the central core is essential for imparting catalytic activity and structural stability to the enzyme, the role of sequences flanking the central core was not understood. Experiments with deletion mutants showed that the amino acid sequences flanking the central core were important in retaining activity of Pot-SOD after autoclaving. Molecular dynamics simulations demonstrated the unfavorable structure of mutants due to increased size of binding pocket and enhanced negative charge on the electrostatic surface, resulting in unavailability of the substrate superoxide radical ([Formula: see text]) to the catalytic pocket. Deletion caused destabilization of structural elements and reduced solvent accessibility that further produced unfavorable structural geometry of the protein. PMID:25990646

  8. Organization and Functional Analysis of the 5′ Flanking Regions of Myostatin-1 and 2 Genes from Larimichthys crocea

    PubMed Central

    Dong, Xiaojing; Zhang, Xiaoju; Diallo, Amadou

    2012-01-01

    Myostatin (MSTN) is a negative regulator of skeletal muscle growth and development. There are two types of MSTNs in fish, but little is known about their gene regulation. Here, the 5′ flanking fragments of 1029 bp from MSTN-1 and 643 bp from MSTN-2 were cloned, sequenced, and analyzed in Larimichthys crocea. Both fragments contained CAAT box and several putative cis-regulatory elements. However, putative TATA box, MyoD, MEF3, SP1, USF, and GH-CSE sites were identified only in the L. crocea MSTN-1 (lcMSTN-1) promoter. Transcriptional activities of four fragments (1013, 841, 514, and 261 bp) truncated from lcMSTN-1 upstream region and two fragments (643 and 296 bp) from lcMSTN-2 upstream region were examined in vitro, using transient transfection in CIK and L6 cells. In CIK cells, the promoter activity correlated positively with the length of truncated fragments in both MSTN-1 and 2. The lcMSTN-2 promoter showed a higher activity than lcMSTN-1 in the corresponding region, which was consistent with MSTN gene expression in vivo. In L6 cells, lcMSTN-2 upstream showed an extremely high luciferase activity. These data indicated that both cloned 5′ flanking sequences contained functional promoters, and that transcription regulation of lcMSTN-1 and 2 promoters was significantly different between mammalian and fish cells. PMID:22149889

  9. Quantitative comparison of ligament formulation and pre-strain in finite element analysis of the human lumbar spine.

    PubMed

    Hortin, Mitchell S; Bowden, Anton E

    2016-11-01

    Data has been published that quantifies the nonlinear, anisotropic material behaviour and pre-strain behaviour of the anterior longitudinal, supraspinous (SSL), and interspinous ligaments of the human lumbar spine. Additionally, data has been published on localized material properties of the SSL. These results have been incrementally incorporated into a previously validated finite element model of the human lumbar spine. Results suggest that the effects of increased ligament model fidelity on bone strain energy were moderate and the effects on disc pressure were slight, and do not justify a change in modelling strategy for most clinical applications. There were significant effects on the ligament stresses of the ligaments that were directly modified, suggesting that these phenomena should be included in FE models where ligament stresses are the desired metric. PMID:27007776

  10. Simulation of bone-conducted sound transmission in a three-dimensional finite-element model of a human skull

    NASA Astrophysics Data System (ADS)

    Chang, You; Kim, Namkeun; Stenfelt, Stefan

    2015-12-01

    Bone conduction (BC) is the transmission of sound to the inner ear through the bones of the skull. This type of transmission is used in humans fitted with BC hearing aids as well as to classify between conductive and sensorineural hearing losses. The objective of the present study is to develop a finite-element (FE) model of the human skull based on cryosectional images of a female cadaver head in order to gain better understanding of the sound transmission. Further, the BC behavior was validated in terms of sound transmission against experimental data published in the literature. Results showed the responses of the simulated skull FE model were consistent with the experimentally reported data.

  11. On the behaviour of a compact antenna system with non-resonant elements in the presence of the human head

    NASA Astrophysics Data System (ADS)

    Leiva, José Luis; Andújar, Aurora; Anguera, Jaume

    2015-11-01

    A novel handset antenna technique to solve the increasing demand of mobile bands, the loading effects (mismatching and efficiency losses) and the power absorption introduced by the head is analysed in terms of bandwidth, efficiency and SAR (specific absorption rate). The technique proposed integrates non-resonant elements and its results are compared with those obtained by a planar inverted-F antenna. The main antenna parameters (bandwidth, efficiency in free-space, efficiency regarding the human head presence and SAR) are compared in terms of electromagnetic simulation and measurements. The study concludes that the novel antenna architecture achieves multiband operation from 824-960 MHz and 1710-2170 MHz and become robust to human loading while occupying a reduced volume of just 250 mm3 in a typical handset phone.

  12. An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Goodman, Allen; Hooley, Becky L.

    2003-01-01

    An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

  13. Numerical study of human vocal folds vibration using Immersed Finite Element Method

    NASA Astrophysics Data System (ADS)

    Wang, Xingshi; Zhang, Lucy; Krane, Michael

    2011-11-01

    The voice production procedure is a self-oscillating, fluid-structure interaction problem. In this study, the vocal folds vibration during phonation will be simulated by self-oscillated layered-structure vocal folds model, using Immersed Finite Element Method. With the numerical results, we will find out the vocal folds vibration pattern, and also show how the lung pressure, stiffness and geometry of vocal folds will affect the vocal folds vibration. With further analysis, we shall get better understanding of the dynamics of voice production. National Institute on Deafness and Other Communication Disorders.

  14. Human polyomavirus JCV late leader peptide region contains important regulatory elements

    SciTech Connect

    Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh |; Khalili, Kamel; Safak, Mahmut . E-mail: msafak@temple.edu

    2006-05-25

    Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader

  15. The elements of human well-being with an emphasis on the contribution of ecosystem services

    EPA Science Inventory

    Natural ecosystems perform fundamental life-support services upon which human civilization depends. However, many people believe that Nature provides these services for free and therefore, they are of little or no value. While we do not pay for them, we pay significantly for th...

  16. Exploring the Human Element of Computer-Assisted Language Learning: An Iranian Context

    ERIC Educational Resources Information Center

    Fatemi Jahromi, Seyed Abolghasseminits; Salimi, Farimah

    2013-01-01

    Based on various theories of human agency (Ajzen, I. (2005). "Attitudes, personality and behavior" (2nd ed.). London: Open University Press; Davis, F.D. (1989). Perceived usefulness, perceived ease of use, and user acceptance of information technology. "MIS Quarterly", 13, 319-340; Rogers, E.M. (1983). "Diffusion of innovations" (3rd ed.). New…

  17. Humanism, Feminism, and Multiculturalism: Essential Elements of Social Justice in Counseling, Education, and Advocacy

    ERIC Educational Resources Information Center

    Brady-Amoon, Peggy

    2011-01-01

    This article explores the association between and among humanism, feminism, multiculturalism, and social justice in counseling, education, and advocacy. In so doing, it shows how these theoretical forces, individually and collectively, are essential to professional counseling, client welfare, education, and the promotion of social justice. The…

  18. Aortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive disease

    SciTech Connect

    Dubick, M.A.; Hunter, G.C.; Casey, S.M.; Keen, C.L.

    1987-02-01

    Altered trace elements and ascorbic acid metabolism have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. However, their role in the disease process, or the effect of atherosclerosis on their tissue levels within plaque, is poorly understood. The presence study analyzes the concentrations of Fe, Cu, Zn, and Mn, and ascorbic acid and superoxide dismutase (SOD) activity in tissue samples from 29 patients with abdominal aortic aneurysms (AAA) and 14 patients with atherosclerotic occlusive disease (AOD). It was observed that the Fe and Mn concentrations in AAA and AOD tissue were higher than the levels in nondiseased control aorta, whereas Cu and Zn levels in AAA and AOD tissue were similar to the levels in controls. The Zn:Cu ratio was significantly lower in the AAA tissue in comparison to both AOD and control tissue. In addition, AAA and AOD tissue had low ascorbic acid levels and low Cu, Zn-SOD activity with Cu,Zn-SOD:Mn-SOD ratios of 0.27 and 0.19, respectively, compared to a ratio of 3.20 in control aorta. These data indicate that aorta affected by aneurysms and occlusive disease have altered trace element and ascorbic acid concentrations, as well as low Cu,Zn-SOD activity. Although these observations do not directly support the hypothesis that AAA is associated with aortic Cu deficiency they do suggest a role for oxygen radicals or increased lipid peroxidation in occlusive and aneurysmal disease of the aorta.

  19. Window type: 2x3 fixed multipaned steel window flanked by 1x3 ...

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

    Window type: 2x3 fixed multipaned steel window flanked by 1x3 multipaned steel casements. Concrete sill and spandrel also illustrated. Building 43, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  20. Olympus Mons Aureole Deposits: New Evidence for a Flank Failure Origin

    NASA Technical Reports Server (NTRS)

    McGovern, P. J.; Smith, J. R.; Morgan, J. K.; Bulmer, M. H.

    2004-01-01

    The origin of the rough-textured aureoles that surround the immense Olympus Mons volcano on Mars is controversial. We present data from the Mars Global Surveyor and Mars Odyssey missions to demonstrate that at least two of the aureole lobes are derived from the volcano's flanks in large and probably catastrophic mass movement events, leaving behind headwalls that constitute the basal scarp. This evidence stems from the morphology and internal structure of aureole blocks, which exhibit remnants of volcanic flow units on their surfaces. Our claim is supported by plausible reconstructions of the prefailure flanks. Structural analogs to known flank failure events at Hawaiian volcanoes suggest that repeated cycles of flank growth and collapse at Olympus Mons allow generation of the observed aureoles from a protoedifice similar in size and shape to the present one.

  1. Complete mitochondrial genome sequence of Chestnut-flanked white-eye (Zosterops erythropleurus).

    PubMed

    Li, Yumei; Yao, Jiyuan; Zhao, Xin; Li, Lingyu; Yan, Shouqing

    2016-09-01

    The Chestnut-flanked white-eye (Zosterops erythropleurus) is a species of family Zosteropidae, which is distributed widely in the world. In the present study, the complete mitochondrial genome sequence of Chestnut-flanked white-eye was determined. It has a total length of 17 811 bp, and contains 13 protein-coding genes, 22 tRNA genes, 2 ribosome RNA genes and 2 control regions. The total base composition was 30.2% for A, 31.0% for C, 14.2% for G and 24.6% for T. The phylogenetic tree of Chestnut-flanked white-eye and 13 other species belonging to the order Passeriformes was built. The molecular data presented here will be useful to study the evolutionary relationships and genetic diversity of Chestnut-flanked white-eye. PMID:26260179

  2. Element content analysis by WDXRF in pistachios grown under organic and conventional farming regimes for human nutrition and health.

    PubMed

    Akbaba, Ugur; Sahin, Yusuf; Türkez, Hasan

    2012-10-01

    In this investigation, the elemental composition of various Antep pistachios (Pistacia vera L.) samples was determined using a sensitive method called wavelength dispersive x-ray fluorescence (WDXRF). A total of 27 elements, such as Al, As, Bi, Ca, Cd, Cu, Fe, Mn, Ni, P, S, Sr, Zn, Cl, Pb, K, Mg, Na, Ba, Rb, Si, Br, Sn, Au, La, Ti and Zr, were determined in pistachios samples (n = 10) grown under organic and conventional farming regimes. The obtained results from each group were analyzed statistically using SPSS statistic program. It was observed that the concentration and peak intensity values of Ca, Fe, Mn, P, Mg, Cl, Na and K elements were higher in the pistachios samples grown under organic farming regime. Similarly, Al was found in higher level in the samples grown under conventional farming regime. As, Bi, Cd, Pb, Ti, La, Sn and Zr contents were measured. Their contents were below the detection limits. Our findings clearly revealed that organic pistachios are likely to have higher nutritional mineral content. The pistachios samples grown under conventional farming regime could contain harmful metals like Al that might damage various systems and/or organs of humans and animals. PMID:22042769

  3. A Three-Dimensional Finite-Element Model of a Human Dry Skull for Bone-Conduction Hearing

    PubMed Central

    2014-01-01

    A three-dimensional finite-element (FE) model of a human dry skull was devised for simulation of human bone-conduction (BC) hearing. Although a dry skull is a simplification of the real complex human skull, such model is valuable for understanding basic BC hearing processes. For validation of the model, the mechanical point impedance of the skull as well as the acceleration of the ipsilateral and contralateral cochlear bone was computed and compared to experimental results. Simulation results showed reasonable consistency between the mechanical point impedance and the experimental measurements when Young's modulus for skull and polyurethane was set to be 7.3 GPa and 1 MPa with 0.01 and 0.1 loss factors at 1 kHz, respectively. Moreover, the acceleration in the medial-lateral direction showed the best correspondence with the published experimental data, whereas the acceleration in the inferior-superior direction showed the largest discrepancy. However, the results were reasonable considering that different geometries were used for the 3D FE skull and the skull used in the published experimental study. The dry skull model is a first step for understanding BC hearing mechanism in a human head and simulation results can be used to predict vibration pattern of the bone surrounding the middle and inner ear during BC stimulation. PMID:25243148

  4. Use of a finite element model of heat transport in the human eye to predict time of death.

    PubMed

    Smart, Jimmy L; Kaliszan, Michal

    2013-01-01

    The goal of this work was to compare human temperature decay curves generated from execution of a COMSOL Multiphysics(®) finite element software model with that of experimental postmortem temperature decay curves. Experiments were performed in 10 human cadavers. The postmortem temperature was continuously measured in human eyeballs and rectums from c. 3 h up to 15 h postmortem. Model-generated curves reflected experimental curves for 10 cases with coefficients of determination ranging from 0.9448 to 0.9953. From modeling efforts, normalized temperature decay curves were generated to aid first responders to estimate time of death within the early postmortem period of 0-24 h. This proposed model has advantages over other models in that it is applied to the human eyeball, where temperature plateau effects are minimal to nonexistent. Nevertheless, the proposed model can be adjusted to compensate for any temperature plateau effects that do exist. It also can take account of antemortem hyperthermia conditions that are known to have occurred. The current model only applies to natural environmental conditions, with no forced convection, no direct sunlight, immersion in water, or other unusual conditions. PMID:23181434

  5. RNA Folding Affects the Recruitment of SR Proteins by Mouse and Human Polypurinic Enhancer Elements in the Fibronectin EDA Exon

    PubMed Central

    Buratti, Emanuele; Muro, Andrés F.; Giombi, Maurizio; Gherbassi, Daniel; Iaconcig, Alessandra; Baralle, Francisco E.

    2004-01-01

    In humans, inclusion or exclusion of the fibronectin EDA exon is mainly regulated by a polypurinic enhancer element (exonic splicing enhancer [ESE]) and a nearby silencer element (exonic splicing silencer [ESS]). While human and mouse ESEs behave identically, mutations introduced into the homologous mouse ESS sequence result either in no change in splicing efficiency or in complete exclusion of the exon. Here, we show that this apparently contradictory behavior cannot be simply accounted for by a localized sequence variation between the two species. Rather, the nucleotide differences as a whole determine several changes in the respective RNA secondary structures. By comparing how the two different structures respond to homologous deletions in their putative ESS sequences, we show that changes in splicing behavior can be accounted for by a differential ESE display in the two RNAs. This is confirmed by RNA-protein interaction analysis of levels of SR protein binding to each exon. The immunoprecipitation patterns show the presence of complex multi-SR protein-RNA interactions that are lost with secondary-structure variations after the introduction of ESE and ESS variations. Taken together, our results demonstrate that the sequence context, in addition to the primary sequence identity, can heavily contribute to the making of functional units capable of influencing pre-mRNA splicing. PMID:14729981

  6. Electron probe microanalysis of the chemical elemental content of human follicular fluid.

    PubMed

    Chong, A P; Taymor, M L; Lechene, C P

    1977-05-15

    Follicular fluid samples were obtained by puncturing follicles of ovaries in situ from patients undergoing laparotomy. Sodium, potassium, chloride, magnesium, calcium, phosphorus, and sulfur concentrations measured by electron probe microanalysis were similar to those of blood, with minimal differences. This suggested that culture media in which these electrolytes are added in concentrations similar to those of serum are appropriate for culture of the human oocyte. PMID:855870

  7. Identification of human TERT elements necessary for telomerase recruitment to telomeres.

    PubMed

    Schmidt, Jens C; Dalby, Andrew B; Cech, Thomas R

    2014-01-01

    Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease. PMID:25271372

  8. Identification of human TERT elements necessary for telomerase recruitment to telomeres

    PubMed Central

    Schmidt, Jens C; Dalby, Andrew B; Cech, Thomas R

    2014-01-01

    Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease. DOI: http://dx.doi.org/10.7554/eLife.03563.001 PMID:25271372

  9. Tables for the metric evaluation of pair-matching of human skeletal elements.

    PubMed

    Thomas, Richard M; Ubelaker, Douglas H; Byrd, John E

    2013-07-01

    A common task in forensic anthropology involves pair-matching of left and right skeletal elements. This can be achieved through visual pair-matching by evaluating similarities in morphology, and through osteometric sorting, a quantitative technique. To simplify the process of osteometric sorting, this article explains the use of a statistic (M), which captures the amount of size variation found between homologous bones from single individuals. A database of skeletal measurements for all major paired postcranial bones is used to calculate values of M from a variety of sources. The maximum value and the 90th and 95th percentiles of M are provided in tabular format, and values of M from forensic cases can be compared to these tables as an objective means for determining whether homologous bones could have originated from the same individual. This simple technique can be combined with visual pair-matching to be particularly effective in cases involving commingling of skeletons. PMID:23682771

  10. Rift zone reorganization through flank instability in ocean island volcanoes: an example from Tenerife, Canary Islands

    NASA Astrophysics Data System (ADS)

    Walter, T. R.; Troll, V. R.; Cailleau, B.; Belousov, A.; Schmincke, H.-U.; Amelung, F.; Bogaard, P.

    2005-04-01

    The relationship between rift zones and flank instability in ocean island volcanoes is often inferred but rarely documented. Our field data, aerial image analysis, and 40Ar/39Ar chronology from Anaga basaltic shield volcano on Tenerife, Canary Islands, support a rift zone—flank instability relationship. A single rift zone dominated the early stage of the Anaga edifice (~6-4.5 Ma). Destabilization of the northern sector led to partial seaward collapse at about ~4.5 Ma, resulting in a giant landslide. The remnant highly fractured northern flank is part of the destabilized sector. A curved rift zone developed within and around this unstable sector between 4.5 and 3.5 Ma. Induced by the dilatation of the curved rift, a further rift-arm developed to the south, generating a three-armed rift system. This evolutionary sequence is supported by elastic dislocation models that illustrate how a curved rift zone accelerates flank instability on one side of a rift, and facilitates dike intrusions on the opposite side. Our study demonstrates a feedback relationship between flank instability and intrusive development, a scenario probably common in ocean island volcanoes. We therefore propose that ocean island rift zones represent geologically unsteady structures that migrate and reorganize in response to volcano flank instability.

  11. A three-dimensional finite element analysis of the osseointegration progression in the human mandible

    NASA Astrophysics Data System (ADS)

    Esmail, Enas; Hassan, Noha; Kadah, Yasser

    2010-02-01

    In this study, three-dimensional (3D) finite element analysis was used to model the effect of the peri-implant bone geometry and thickness on the biomechanical behavior of a dental implant/supporting bone system. The 3D finite element model of the jaw bone, cancellous and cortical, was developed based on computerized tomography (CT) scan technology while the dental implant model was created based on a commercially available implant design. Two models, cylindrical and threaded, representing the peri-implant bone region were simulated. In addition, various thicknesses (0.1 mm, 0.3 mm, 0.5 mm) of the peri-implant bone region were modeled to account for the misalingnment during the drilling process. Different biomechanical properties of the peri-implant bone region were used to simulate the progression of the osseointegration process with time. Four stages of osseointegration were modeled to mimic different phases of tissue healing of the peri- implant region starting with soft connective tissue and ending with complete bone maturation. For the realistic threaded model of the peri-implant bone region, the maximum von Mises stress and displacement in the dental implant and jaw bone were higher than those computed for the simple cylindrical peri-implant bone region model. The average von Mises stress and displacement in the dental implant and the jaw bone decreased as the oseeointegration progressed with time for all thicknesses of the peri-implant bone region. On the other hand, the maximum absolute vertical displacement of the dental implant increased as the drilled thickness of the peri-implant bone region increased.

  12. Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency.

    PubMed

    Ustav, Mart; Castaneda, Fernando Rodriguez; Reinson, Tormi; Männik, Andres; Ustav, Mart

    2015-01-01

    Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5'-CGGG-3' spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters. PMID:26288015

  13. Human Papillomavirus Type 18 cis-Elements Crucial for Segregation and Latency

    PubMed Central

    Ustav, Mart; Castaneda, Fernando Rodriguez; Reinson, Tormi; Männik, Andres; Ustav, Mart

    2015-01-01

    Stable maintenance replication is characteristic of the latency phase of HPV infection, during which the viral genomes are actively maintained as extrachromosomal genetic elements in infected proliferating basal keratinocytes. Active replication in the S-phase and segregation of the genome into daughter cells in mitosis are required for stable maintenance replication. Most of our knowledge about papillomavirus genome segregation has come from studies of bovine papillomavirus type 1 (BPV-1), which have demonstrated that the E2 protein cooperates with cellular trans-factors and that E2 binding sites act as cis-regulatory elements in the viral genome that are essential for the segregation process. However, the genomic organization of the regulatory region in HPVs, and the properties of the viral proteins are different from those of their BPV-1 counterparts. We have designed a segregation assay for HPV-18 and used it to demonstrate that the E2 protein performs segregation in combination with at least two E2 binding sites. The cooperative binding of the E2 protein to two E2 binding sites is a major determinant of HPV-18 genome segregation, as demonstrated by the change in spacing between adjacent binding sites #1 and #2 in the HPV-18 Upstream Regulatory Region (URR). Duplication or triplication of the natural 4 bp 5’-CGGG-3’ spacer between the E2 binding sites increased the cooperative binding of the E2 molecules as well as E2-dependent segregation. Removal of any spacing between these sites eliminated cooperative binding of the E2 protein and disabled segregation of the URR and HPV-18 genome. Transfer of these configurations of the E2 binding sites into viral genomes confirmed the role of the E2 protein and binding sites #1 and #2 in the segregation process. Additional analysis demonstrated that these sites also play an important role in the transcriptional regulation of viral gene expression from different HPV-18 promoters. PMID:26288015

  14. Human exposure to lead and other potentially harmful elements associated with galena mining at New Zurak, central Nigeria

    NASA Astrophysics Data System (ADS)

    Lar, U. A.; Ngozi-Chika, C. S.; Ashano, E. C.

    2013-08-01

    Galena mining in New Zurak, central Nigeria is currently increasing in intensity, with widespread artisanal mining taking place alongside mechanised mining. These activities are causing immeasurable damage to the environment. The prolonged human exposure and ingestion of Pb and other potentially harmful elements (PHEs) such as U, Cd, Se, Zn and As that are released from ores during these (mining) activities is a cause of great concern to populations that live in the vicinity of these mine fields. Many of the communities make their living from subsistence farming, growing food from the surroundings, and obtaining drinking water from nearby surface and sub-surface water resources. An overall assessment of the degree of contamination or toxicity of Pb and other PHEs was carried out using the indices of geoaccumulation (Igeo) and contamination factors (CFs), in the different media sampled - farmland soils, uncultivated lands, mine tailings/dumps, natural waters and vegetables. Results reveal that the mine tailings and dumps are highly contaminated with Pb and other PHEs followed in decreasing degree of contamination by the uncultivated lands, farmlands and natural waters. These findings suggest that release of Pb and other PHEs from the galena mining activity has contributed significantly to the enrichment of these elements in the surrounding environment, including the natural water bodies, and are disposed to subsequent entry into the human body through the food chain. As such these PHE accumulations pose significant risks to the environment and human health, especially of children and pregnant women who are the most vulnerable groups in the area. In order to forestall a reoccurrence of the Zamfara Pb poisoning episode in northwestern Nigeria in 2010, where more than 400 children died, the authorities concerned should ensure that mining in New Zurak is done in a more environmentally friendly manner, ensuring the maintenance of an environmental quality adequate for

  15. Control of human PLP1 expression through transcriptional regulatory elements and alternatively spliced exons in intron 1.

    PubMed

    Hamdan, Hamdan; Kockara, Neriman T; Jolly, Lee Ann; Haun, Shirley; Wight, Patricia A

    2015-01-01

    Although the myelin proteolipid protein gene (PLP1) encodes the most abundant protein in central nervous system (CNS) myelin, not much is known about the mechanisms that govern expression of the human gene (hPLP1). Much more is known about the processes that regulate Plp1 gene expression in rodents. From studies with Plp1-lacZ transgenic mice, it was determined that the first intron of mouse Plp1 (mPlp1) is required to attain high levels of expression in brain, concurrent with the active myelination period. Other studies have suggested that within mPlp1 intron 1 (>8 kb) lie several regions with enhancer-like activity. To test whether these sequences (and possibly others) in hPLP1 intron 1 are functional, deletion-transfection analysis was performed with hPLP1-lacZ constructs that contain various portions of the intron, or lack it altogether. Results presented here demonstrate the importance of hPLP1 intron 1 in achieving maximal levels of expression in the immortalized oligodendroglial cell line, Oli-neu. Deletion analysis indicates that the intron contains multiple positive regulatory elements which are active in Oli-neu cells. Some of these elements appear to be functionally conserved between human and mouse, while others are not. Furthermore, our studies demonstrate that multiple splice variants can be formed due to inclusion of extra (supplementary) exons from what is classically thought of as hPLP1 intron 1. Thus, splicing of these novel exons (which are not recognized as such in mPlp1 due to lack of conserved splice sites) must utilize factors common to both human and mouse since Oli-neu cells are of mouse origin. PMID:25694552

  16. Dynamic finite element simulation of the gunshot injury to the human forehead protected by polyvinyl alcohol sponge.

    PubMed

    Karimi, Alireza; Razaghi, Reza; Navidbakhsh, Mahdi; Sera, Toshihiro; Kudo, Susumu

    2016-04-01

    Although there are some traditional models of the gunshot wounds, there is still a need for more modeling analyses due to the difficulties related to the gunshot wounds to the forehead region of the human skull. In this study, the degree of damage as a consequence of penetrating head injuries due to gunshot wounds was determined using a preliminary finite element (FE) model of the human skull. In addition, the role of polyvinyl alcohol (PVA) sponge, which can be used as an alternative to reinforce the kinetic energy absorption capacity of bulletproof vest and helmet materials, to minimize the amount of skull injury due to penetrating processes was investigated through the FE model. Digital computed tomography along with magnetic resonance imaging data of the human head were employed to launch a three-dimensional (3D) FE model of the skull. Two geometrical shapes of projectiles (steel ball and bullet) were simulated for penetrating with an initial impact velocity of 734 m/s using nonlinear dynamic modeling code, namely LS-DYNA. The role of the damaged/distorted elements were removed during computation when the stress or strain reached their thresholds. The stress distributions in various parts of the forehead and sponge after injury were also computed. The results revealed the same amount of stress for both the steel ball and bullet after hitting the skull. The modeling results also indicated the time that steel ball takes to penetrate into the skull is lower than that of the bullet. In addition, more than 21% of the steel ball's kinetic energy was absorbed by the PVA sponge and, subsequently, injury sternness of the forehead was considerably minimized. The findings advise the application of the PVA sponge as a substitute strengthening material to be able to diminish the energy of impact as well as the load transmitted to the object. PMID:26886822

  17. The Human Postsynaptic Density Shares Conserved Elements with Proteomes of Unicellular Eukaryotes and Prokaryotes

    PubMed Central

    Emes, Richard David; Grant, Seth G. N.

    2011-01-01

    The animal nervous system processes information from the environment and mediates learning and memory using molecular signaling pathways in the postsynaptic terminal of synapses. Postsynaptic neurotransmitter receptors assemble to form multiprotein complexes that drive signal transduction pathways to downstream cell biological processes. Studies of mouse and Drosophila postsynaptic proteins have identified key roles in synaptic physiology and behavior for a wide range of proteins including receptors, scaffolds, enzymes, structural, translational, and transcriptional regulators. Comparative proteomic and genomic studies identified components of the postsynaptic proteome conserved in eukaryotes and early metazoans. We extend these studies, and examine the conservation of genes and domains found in the human postsynaptic density with those across the three superkingdoms, archaeal, bacteria, and eukaryota. A conserved set of proteins essential for basic cellular functions were conserved across the three superkingdoms, whereas synaptic structural and many signaling molecules were specific to the eukaryote lineage. Genes involved with metabolism and environmental signaling in Escherichia coli including the chemotactic and ArcAB Two-Component signal transduction systems shared homologous genes in the mammalian postsynaptic proteome. These data suggest conservation between prokaryotes and mammalian synapses of signaling mechanisms from receptors to transcriptional responses, a process essential to learning and memory in vertebrates. A number of human postsynaptic proteins with homologs in prokaryotes are mutated in human genetic diseases with nervous system pathology. These data also indicate that structural and signaling proteins characteristic of postsynaptic complexes arose in the eukaryotic lineage and rapidly expanded following the emergence of the metazoa, and provide an insight into the early evolution of synaptic mechanisms and conserved mechanisms of learning and

  18. Reconstructing past seawater Mg/Ca and Sr/Ca from mid-ocean ridge flank calcium carbonate veins.

    PubMed

    Coggon, Rosalind M; Teagle, Damon A H; Smith-Duque, Christopher E; Alt, Jeffrey C; Cooper, Matthew J

    2010-02-26

    Proxies for past seawater chemistry, such as Mg/Ca and Sr/Ca ratios, provide a record of the dynamic exchanges of elements between the solid Earth, the atmosphere, and the hydrosphere and the evolving influence of life. We estimated past oceanic Mg/Ca and Sr/Ca ratios from suites of 1.6- to 170-million-year-old calcium carbonate veins that had precipitated from seawater-derived fluids in ocean ridge flank basalts. Our data indicate that before the Neogene, oceanic Mg/Ca and Sr/Ca ratios were lower than in the modern ocean. Decreased ocean spreading since the Cretaceous and the resulting slow reduction in ocean crustal hydrothermal exchange throughout the early Tertiary may explain the recent rise in these ratios. PMID:20133522

  19. Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

    SciTech Connect

    Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

    2011-09-27

    A sequence around the start codon of the mRNA of human thymidylate synthase (TS) folds into a secondary-structure motif in which the initiation site is sequestered in a metastable hairpin. Binding of the protein to its own mRNA at the hairpin prevents the production of TS through a translation-repression feedback mechanism. Stabilization of the mRNA hairpin by other ligands has been proposed as a strategy to reduce TS levels in anticancer therapy. Rapidly proliferating cells require high TS activity to maintain the production of thymidine as a building block for DNA synthesis. The crystal structure of a model oligonucleotide (TS1) that represents the TS-binding site of the mRNA has been determined. While fluorescence studies showed that the TS1 RNA preferentially adopts a hairpin structure in solution, even at high RNA concentrations, an asymmetric dimer of two hybridized TS1 strands was obtained in the crystal. The TS1 dimer contains an unusual S-turn motif that also occurs in the 'off' state of the human ribosomal decoding site RNA.

  20. An Objective Evaluation of Mass Scaling Techniques Utilizing Computational Human Body Finite Element Models.

    PubMed

    Davis, Matthew L; Scott Gayzik, F

    2016-10-01

    Biofidelity response corridors developed from post-mortem human subjects are commonly used in the design and validation of anthropomorphic test devices and computational human body models (HBMs). Typically, corridors are derived from a diverse pool of biomechanical data and later normalized to a target body habitus. The objective of this study was to use morphed computational HBMs to compare the ability of various scaling techniques to scale response data from a reference to a target anthropometry. HBMs are ideally suited for this type of study since they uphold the assumptions of equal density and modulus that are implicit in scaling method development. In total, six scaling procedures were evaluated, four from the literature (equal-stress equal-velocity, ESEV, and three variations of impulse momentum) and two which are introduced in the paper (ESEV using a ratio of effective masses, ESEV-EffMass, and a kinetic energy approach). In total, 24 simulations were performed, representing both pendulum and full body impacts for three representative HBMs. These simulations were quantitatively compared using the International Organization for Standardization (ISO) ISO-TS18571 standard. Based on these results, ESEV-EffMass achieved the highest overall similarity score (indicating that it is most proficient at scaling a reference response to a target). Additionally, ESEV was found to perform poorly for two degree-of-freedom (DOF) systems. However, the results also indicated that no single technique was clearly the most appropriate for all scenarios. PMID:27457051

  1. Antigen Specificity of γδ T Cells Depends Primarily on the Flanking Sequences of CDR3δ*

    PubMed Central

    Xi, Xueyan; Guo, Yang; Chen, Hui; Xu, Chunping; Zhang, Huiyuan; Hu, Hongbo; Cui, Lianxian; Ba, Denian; He, Wei

    2009-01-01

    The structural basis that determines the specificity of γδ T cell receptor (TCR) recognition remains undefined. Our previous data show that the complementary determining region of human TCRδ (CDR3δ) is critical to ligand binding. Here we used linear and configurational approaches to examine the roles of V, N-D-N, or J regions in CDR3δ-mediated antigen recognition. Surprisingly, we found that the binding activities of CDR3δ from different γδ TCRs to their target tissues and ligands depend on the conserved flanking sequences (V and J) but not as much on the D region of CDR3δ fragment. We further defined the key residues in the V and J regions of CDR3δ fragments, including the cysteine residue in the V fragment and the leucine residue in the J fragment that determine their ligand binding specificity. Our results demonstrate that TCRδ primarily uses conserved flanking regions to bind ligands. This finding may provide an explanation for the limited number of γδ TCR ligands that have as yet been identified. PMID:19666468

  2. The role of an inverted CCAAT element in transcriptional activation of the human DNA topoisomerase IIalpha gene by heat shock.

    PubMed

    Furukawa, M; Uchiumi, T; Nomoto, M; Takano, H; Morimoto, R I; Naito, S; Kuwano, M; Kohno, K

    1998-04-24

    Expression of the DNA topoisomerase IIalpha (topoIIalpha) gene is highly sensitive to various environmental stimuli including heat shock. The amount of topoIIalpha mRNA was increased 1.5-3-fold 6-24 h after exposure of T24 human urinary bladder cancer cells to heat shock stress at 43 degreesC for 1 h. The effect of heat shock on the transcriptional activity of the human topoIIalpha gene promoter was investigated by transient transfection of T24 cells with luciferase reporter plasmids containing various lengths of the promoter sequence. The transcriptional activity of the full-length promoter (nucleotides (nt) -295 to +85) and of three deletion constructs (nt -197 to +85, -154 to +85, and -74 to +85) was increased approximately 3-fold 24 h after heat shock stress. In contrast, the transcriptional activity of the minimal promoter (nt -20 to +85), which lacks the first inverted CCAAT element (ICE1), the GC box, and the heat shock element located between nt -74 and -21, was not increased by heat shock. Furthermore, the transcriptional activity of promoter constructs containing mutations in the GC box or heat shock element, but not that of a construct containing mutations in ICE1, was significantly increased by heat shock. Electrophoretic mobility shift assays revealed reduced binding of a nuclear factor to an oligonucleotide containing ICE1 when nuclear extracts were derived from cells cultured for 3-24 h after heat shock. No such change in factor binding was apparent with an oligonucleotide containing the heat shock element of the topoIIalpha gene promoter. Finally, in vivo footprint analysis of the topoIIalpha gene promoter revealed that two G residues of ICE1 that were protected in control cells became sensitive to dimethyl sulfate modification after heat shock. These results suggest that transcriptional activation of the topoIIalpha gene by heat shock requires the release of a negative regulatory factor from ICE1. PMID:9553115

  3. The loop 5 element structurally and kinetically coordinates dimers of the human kinesin-5, Eg5.

    PubMed

    Waitzman, Joshua S; Larson, Adam G; Cochran, Jared C; Naber, Nariman; Cooke, Roger; Jon Kull, F; Pate, Edward; Rice, Sarah E

    2011-12-01

    Eg5 is a homotetrameric kinesin-5 motor protein that generates outward force on the overlapping, antiparallel microtubules (MTs) of the mitotic spindle. Upon binding an MT, an Eg5 dimer releases one ADP molecule, undergoes a slow (∼0.5 s(-1)) isomerization, and finally releases a second ADP, adopting a tightly MT-bound, nucleotide-free (APO) conformation. This conformation precedes ATP binding and stepping. Here, we use mutagenesis, steady-state and pre-steady-state kinetics, motility assays, and electron paramagnetic resonance spectroscopy to examine Eg5 monomers and dimers as they bind MTs and initiate stepping. We demonstrate that a critical element of Eg5, loop 5 (L5), accelerates ADP release during the initial MT-binding event. Furthermore, our electron paramagnetic resonance data show that L5 mediates the slow isomerization by preventing Eg5 dimer heads from binding the MT until they release ADP. Finally, we find that Eg5 having a seven-residue deletion within L5 can still hydrolyze ATP and move along MTs, suggesting that L5 is not required to accelerate subsequent steps of the motor along the MT. Taken together, these properties of L5 explain the kinetic effects of L5-directed inhibition on Eg5 activity and may direct further interventions targeting Eg5 activity. PMID:22261065

  4. The Loop 5 Element Structurally and Kinetically Coordinates Dimers of the Human Kinesin-5, Eg5

    PubMed Central

    Waitzman, Joshua S.; Larson, Adam G.; Cochran, Jared C.; Naber, Nariman; Cooke, Roger; Kull, F. Jon; Pate, Edward; Rice, Sarah E.

    2011-01-01

    Eg5 is a homotetrameric kinesin-5 motor protein that generates outward force on the overlapping, antiparallel microtubules (MTs) of the mitotic spindle. Upon binding an MT, an Eg5 dimer releases one ADP molecule, undergoes a slow (∼0.5 s−1) isomerization, and finally releases a second ADP, adopting a tightly MT-bound, nucleotide-free (APO) conformation. This conformation precedes ATP binding and stepping. Here, we use mutagenesis, steady-state and pre-steady-state kinetics, motility assays, and electron paramagnetic resonance spectroscopy to examine Eg5 monomers and dimers as they bind MTs and initiate stepping. We demonstrate that a critical element of Eg5, loop 5 (L5), accelerates ADP release during the initial MT-binding event. Furthermore, our electron paramagnetic resonance data show that L5 mediates the slow isomerization by preventing Eg5 dimer heads from binding the MT until they release ADP. Finally, we find that Eg5 having a seven-residue deletion within L5 can still hydrolyze ATP and move along MTs, suggesting that L5 is not required to accelerate subsequent steps of the motor along the MT. Taken together, these properties of L5 explain the kinetic effects of L5-directed inhibition on Eg5 activity and may direct further interventions targeting Eg5 activity. PMID:22261065

  5. Elemental composition of human semen is associated with motility and genomic sperm defects among older men

    PubMed Central

    Schmid, Thomas E.; Grant, Patrick G.; Marchetti, Francesco; Weldon, Rosana H.; Eskenazi, Brenda; Wyrobek, Andrew J.

    2013-01-01

    BACKGROUND Older men tend to have poorer semen quality and are generally at higher risks for infertility and abnormal reproductive outcomes. METHODS We employed proton-induced X-ray emission (PIXE, 3 MeV proton beam) to investigate the concentrations of zinc, copper, calcium, sulfur, chlorine, potassium, titanium, iron and nickel in washed sperm and seminal plasma from non-smoking groups of 10 older men (65–80 years old) and 10 younger men (22–28 years old) who were concurrently assayed for sperm function and genomicly defective sperm. RESULTS The older group showed elevated zinc, copper and calcium in sperm and elevated sulfur in seminal plasma compared with the younger men. The older group also showed reduced motility as well as increased sperm DNA fragmentation, achondroplasia mutations, DNA strand breaks and chromosomal aberrations. Sperm calcium and copper were positively associated with sperm DNA fragmentation (P < 0.03). Seminal sulfur was positively associated with sperm DNA fragmentation and chromosomal aberrations (P < 0.04), and negatively associated with sperm motility (P < 0.05). Sperm calcium was negatively associated with sperm motility, independent of male age (P = 0.01). CONCLUSIONS We identified major differences in elemental concentrations between sperm and seminal plasma and that higher sperm copper, sulfur and calcium are quantitatively associated with poorer semen quality and increased frequencies of genomic sperm defects. PMID:23042799

  6. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    NASA Astrophysics Data System (ADS)

    Ascenzi, Maria-Grazia; Kawas, Neal P.; Lutz, Andre; Kardas, Dieter; Nackenhorst, Udo; Keyak, Joyce H.

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual's (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method's development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications - varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient's femur, that strains computed at the multi-scale model's micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  7. Sedimentological and geochemical characterization of the Cretaceous strata of Calabar Flank, southeastern Nigeria

    NASA Astrophysics Data System (ADS)

    Boboye, O. A.; Okon, E. E.

    2014-11-01

    An integrated sedimentological and geochemical evaluation has been carried out on the Cretaceous sediments of the Calabar Flank. This study is to characterize the provenance, depositional environments and hydrocarbon potentials. The techniques involved field descriptions, textural parameters, petrographic analysis and biostratigraphic studies using standard sedimentological methods. The geochemical studies involved the determination of major oxides and trace elements using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS); Total Organic Carbon (TOC) and Rock Eval Pyrolysis. Results show that sandstone from Awi Formation have elongation ratio ranging from 0.4b to 0.9, oblate-prolate index and maximum sphericity index range from 9.6 to 9.7 and 0.5 to 0.9 respectively. The sandstone units are arkosic and mineralogically immature (MI = 3); ZTR indexes range from 54.6% to 82.5%, with tourmaline, zircon, staurolite, garnet, apatite, augite and rutile grains being angular-sub-angular. This suggests nearness to source, and that Awi Formation was deposited in a fluvial environment. The limestone deposit of Mfamosing Formation is predominantly bioclastic consisting of algal stromatolites, oolitic and pelloidal grainstones/packstones with high carbonate content. The dark grey fissile shales of Nkporo and Ekenkpon Formations indicate deposition in quiet oxic and/or anoxic conditions. Average TOC suggests good source rocks. Predominance of Type III kerogen, Tmax and hydrocarbon source potential of Mfamosing, Ekenkpon, New Netim Marl and Nkporo Formations suggest marginal mature to mature source rocks deposited in shallow continental to open marine setting that some gas may have been generated. The sediments are derived from passive continental margin in plutonic humid palaeoclimatic setting of continental block province.

  8. Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution

    SciTech Connect

    Kass, D.H.; Batzer, M.A.; Deininger, P.L. |

    1995-01-01

    The Alu repetitive family of short interspersed elements (SINEs) in primates can be subdivided into distinct subfamilies by specific diagnostic nucleotide changes. The older subfamilies are generally very abundant, while the younger subfamilies have fewer copies. Some of the youngest Alu elements are absent in the orthologous loci of nonhuman primates, indicative of recent retroposition events, the primary mode of SINE evolutions. PCR analysis of one young Alu subfamily (Sb2) member found in the low-density lipoprotein receptor gene apparently revealed the presence of this element in the green monkey, orangutan, gorilla, and chimpanzee genomes, as well as the human genome. However, sequence analysis of these genomes revealed a highly mutated, older, primate-specific Alu element was present at this position in the nonhuman primates. Comparison of the flanking DNA sequences upstream of this Alu insertion corresponded to evolution expected for standard primate phylogeny, but comparison of the Alu repeat sequences revealed that the human element departed from this phylogeny. The change in the human sequence apparently occurred by a gene conversion event only within the Alu element itself, converting it from one of the oldest to one of the youngest Alu subfamilies. Although gene conversions of Alu elements are clearly very rare, this finding shows that such events can occur and contribute to specific cases of SINE subfamily evolution.

  9. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    SciTech Connect

    Ascenzi, Maria-Grazia; Kardas, Dieter; Nackenhorst, Udo; Keyak, Joyce H.

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual’s (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method’s development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications – varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient’s femur, that strains computed at the multi-scale model’s micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  10. HUMAN SCALP HAIR: AN ENVIRONMENTAL EXPOSURE INDEX FOR TRACE ELEMENTS. I. FIFTEEN TRACE ELEMENTS IN NEW YORK, N.Y. (1971-72)

    EPA Science Inventory

    Previous studies have revealed that hair trace element concentrations can reflect exposure in cases of frank poisoning and deficiency. Correlations have been found also in some populations living in regions where metallurgic processes are conducted. This study reports significant...

  11. Multiple human papillomavirus type 16 glucocorticoid response elements functional for transformation, transient expression, and DNA-protein interactions.

    PubMed Central

    Mittal, R; Pater, A; Pater, M M

    1993-01-01

    We have previously shown that human papillomavirus type 16 (HPV-16) can efficiently transform primary baby rat kidney cells in the presence of the steroid hormones progesterone and the glucocorticoid dexamethasone. To study this effect of hormone, different combinations of the previously identified glucocorticoid response element (GRE) at nucleotide 7640 of HPV-16 and the other two GREs that we have recently identified, at nucleotides 7385 and 7474, were mutated. The previously described GRE and the other two GREs were shown to be functional for the induction of transformation by dexamethasone. In addition, transient assays in cervical HeLa cells demonstrated the functional importance of the three individual GREs. Assays for in vitro interaction demonstrated the specific binding of a 97-kDa protein, the glucocorticoid receptor, to both recently identified HPV-16 GREs. Images PMID:8394465

  12. Development of a Finite Element Model of the Human Shoulder to Investigate the Mechanical Responses and Injuries in Side Impact

    NASA Astrophysics Data System (ADS)

    Iwamoto, Masami; Miki, Kazuo; Yang, King H.

    Previous studies in both fields of automotive safety and orthopedic surgery have hypothesized that immobilization of the shoulder caused by the shoulder injury could be related to multiple rib fractures, which are frequently life threatening. Therefore, for more effective occupant protection, it is important to understand the relationship between shoulder injury and multiple rib fractures in side impact. The purpose of this study is to develop a finite element model of the human shoulder in order to understand this relationship. The shoulder model included three bones (the humerus, scapula and clavicle) and major ligaments and muscles around the shoulder. The model also included approaches to represent bone fractures and joint dislocations. The relationships between shoulder injury and immobilization of the shoulder are discussed using model responses for lateral shoulder impact. It is also discussed how the injury can be related to multiple rib fractures.

  13. An application of boundary element method calculations to hearing aid systems: The influence of the human head

    NASA Astrophysics Data System (ADS)

    Rasmussen, Karsten B.; Juhl, Peter

    2001-05-01

    Boundary element method (BEM) calculations are used for the purpose of predicting the acoustic influence of the human head in two cases. In the first case the sound source is the mouth and in the second case the sound is plane waves arriving from different directions in the horizontal plane. In both cases the sound field is studied in relation to two positions above the right ear being representative of hearing aid microphone positions. Both cases are relevant for hearing aid development. The calculations are based upon a direct BEM implementation in Matlab. The meshing is based on the original geometrical data files describing the B&K Head and Torso Simulator 4128 combined with a 3D scan of the pinna.

  14. The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures.

    PubMed Central

    McBride, M S; Panganiban, A T

    1996-01-01

    We analyzed the leader region of human immunodeficiency virus type 1 (HIV-1) RNA to decipher the nature of the cis-acting E/psi element required for encapsidation of viral RNA into virus particles. Our data indicate that, for RNA encapsidation, there are at least two functional subregions in the leader region. One subregion is located at a position immediately proximal to the major splice donor, and the second is located between the splice donor and the beginning of the gag gene. This suggests that at least two discrete cis-acting elements are recognition signals for encapsidation. To determine whether specific putative RNA secondary structures serve as the signal(s) for encapsidation, we constructed primary base substitution mutations that would be expected to destabilize these potential structures and second-site compensatory mutations that would restore secondary structure. Analysis of these mutants allowed the identification of two discrete hairpins that facilitate RNA encapsidation in vivo. Thus, the HIV-1 E/psi region is a multipartite element composed of specific and functional RNA secondary structures. Compensation of the primary mutations by the second-site mutations could not be attained in trans. This indicates that interstrand base pairing between these two stem regions within the hairpins does not appear to be the basis for HIV-1 RNA dimer formation. Comparison of the hypothetical RNA secondary structures from 10 replication-competent HIV-1 strains suggests that a subset of the hydrogen-bonded base pairs within the stems of the hairpins is likely to be required for function in cis. PMID:8627772

  15. Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

    PubMed

    Wen, Xin-Xin; Xu, Chao; Zong, Chun-Lin; Feng, Ya-Fei; Ma, Xiang-Yu; Wang, Fa-Qi; Yan, Ya-Bo; Lei, Wei

    2016-07-01

    Micro-finite element (μFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from μFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate μFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from μFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E. PMID:26999702

  16. Regulatory elements in the introns of the human HPRT gene are necessary for its expression in embryonic stem cells.

    PubMed Central

    Reid, L H; Gregg, R G; Smithies, O; Koller, B H

    1990-01-01

    We have examined the expression of transfected human hypoxanthine phosphoribosyltransferase minigenes (HPRT) in mouse embryonic stem (ES) cells. cDNA constructs of this gene that have been successfully used in somatic cell lines failed to confer hypoxanthine/aminopterin/thymidine (HAT) resistance in ES cells. In contrast, constructs containing introns 1 and 2 from the HPRT gene produced a high frequency of HAT-resistant colonies. This observation allowed us to identify two sequences in these introns that influence expression of the HPRT gene in ES cells. One element, located in intron 2, is required for effective HPRT expression in these cells; the other element, located in intron 1, acts as an enhancer of HPRT expression. Using this information, we have constructed an HPRT minigene that can be used for either positive or negative selection in ES cell experiments. This dual capability allows the design of "in-out" procedures to create subtle changes in target genes by homologous recombination with the aid of this selectable minigene. PMID:2349238

  17. Determination of the elemental status of ancient human bones from Bockenheim/Rheinland-Pfalz by PIGE and PIXE

    NASA Astrophysics Data System (ADS)

    Jankuhn, St.; Vogt, J.; Butz, T.

    2000-03-01

    Continuing the investigations on ancient human bones of the Merowingian period (6-8th century AD) [St. Jankuhn, T. Butz, R.-H. Flagmeyer, T. Reinert, J. Vogt, J. Hammerl, R. Protsch von Zieten, M. Wolf, H. Baumann, K. Bethge, I. Symietz, in: J.L. Duggan, I.L. Morgan (Eds.), CP392, Appl. of Accelerators in Res. and Ind., AIP, Woodbury, NY, 1997, p. 575], we have prepared a series of 57 samples of bone from the so-called Ward's triangle. This region is an inner part of the femoral neck and one of the areas of high fracture risk in the case of osteoporosis. The bones were excavated from a former cemetery near Bockenheim/Rheinland-Pfalz, Germany. Firstly, the sample preparation method will be described. Secondly, the experimental setup will be outlined for the ion beam methods proton backscattering (PBS), proton induced γ-ray emission (PIGE), and proton induced X-ray emission (PIXE) which are implemented simultaneously at the 2 MV Van de Graaff accelerator of the Universität Leipzig. Thirdly, the concentrations of the main and trace elements will be presented in the form of a correlation matrix for the elements detected by PIGE and PIXE. From this, a correlation coefficient matrix is derived whose values will be discussed in detail.

  18. The Effect of Varying Jaw-elevator Muscle Forces on a Finite Element Model of a Human Cranium.

    PubMed

    Toro-Ibacache, Viviana; O'Higgins, Paul

    2016-07-01

    Finite element analyses simulating masticatory system loading are increasingly undertaken in primates, hominin fossils and modern humans. Simplifications of models and loadcases are often required given the limits of data and technology. One such area of uncertainty concerns the forces applied to cranial models and their sensitivity to variations in these forces. We assessed the effect of varying force magnitudes among jaw-elevator muscles applied to a finite element model of a human cranium. The model was loaded to simulate incisor and molar bites using different combinations of muscle forces. Symmetric, asymmetric, homogeneous, and heterogeneous muscle activations were simulated by scaling maximal forces. The effects were compared with respect to strain distribution (i.e., modes of deformation) and magnitudes; bite forces and temporomandibular joint (TMJ) reaction forces. Predicted modes of deformation, strain magnitudes and bite forces were directly proportional to total applied muscle force and relatively insensitive to the degree of heterogeneity of muscle activation. However, TMJ reaction forces and mandibular fossa strains decrease and increase on the balancing and working sides according to the degree of asymmetry of loading. These results indicate that when modes, rather than magnitudes, of facial deformation are of interest, errors in applied muscle forces have limited effects. However the degree of asymmetric loading does impact on TMJ reaction forces and mandibular fossa strains. These findings are of particular interest in relation to studies of skeletal and fossil material, where muscle data are not available and estimation of muscle forces from skeletal proxies is prone to error. Anat Rec, 299:828-839, 2016. © 2016 Wiley Periodicals, Inc. PMID:27111484

  19. Elemental maps in human allantochorial placental vessels cells: 1. High K + and acetylcholine effects

    NASA Astrophysics Data System (ADS)

    Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.

    2003-09-01

    Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

  20. Nicotine and the Developing Human: A Neglected Element in the Electronic Cigarette Debate.

    PubMed

    England, Lucinda J; Bunnell, Rebecca E; Pechacek, Terry F; Tong, Van T; McAfee, Tim A

    2015-08-01

    The elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths. It has been suggested that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes or other electronic nicotine delivery systems, will accelerate progress toward ending combustible cigarette use. However, careful consideration of the potential adverse health effects from nicotine itself is often absent from public health debates. Human and animal data support that nicotine exposure during periods of developmental vulnerability (fetal through adolescent stages) has multiple adverse health consequences, including impaired fetal brain and lung development, and altered development of cerebral cortex and hippocampus in adolescents. Measures to protect the health of pregnant women and children are needed and could include (1) strong prohibitions on marketing that increase youth uptake; (2) youth access laws similar to those in effect for other tobacco products; (3) appropriate health warnings for vulnerable populations; (4) packaging to prevent accidental poisonings; (5) protection of non-users from exposure to secondhand electronic cigarette aerosol; (6) pricing that helps minimize youth initiation and use; (7) regulations to reduce product addiction potential and appeal for youth; and (8) the age of legal sale. PMID:25794473

  1. [Natural toxins in inter- and intraspecies interaction of human being (elements of ethnotoxinology)].

    PubMed

    Gelashvili, D B

    2002-01-01

    The author considers the application of natural toxins as arrow poison by Homo sapiens from ancient time till today for hunting and ethnic wars on the example of natives of Asia, Africa, South America and Oceania. Geographic isolation was important determining the spectrum of natural toxin sources and the methods of their application. Cellular and molecular mechanisms of arrow poisons effects are considered in biogeographical context: aconitin and strychnin in Asia, diamphotoxin in Africa, indole alcaloids of plants and steroid alcaloids of amphibian in Central and South America, palytoxin in Oceania islands. High efficiency and selective effect of natural toxins allow to use them as molecular markers in current studies of functional membrane architecture and cellular structures. Great differences in pace of civilization development leads to the co-existence at the beginning of the XXI century ethnic groups that use natural toxins as arrow poison and human beings that use the same toxins in fundamental and applied investigations within international scientific society. PMID:12070945

  2. Expression of human LINE-1 elements in enhanced by isochromosome 12p; evidence from testicular germ cell tumors and the Pallister-Killian syndrome

    SciTech Connect

    Swergold, D.

    1994-09-01

    Expression of the human LINE-1 (L1Hs) transposable element is restricted to a narrow range of cell types. Specific expression of either endogenous elements or transfected recombinant elements has been reported primarily in tumors and cell lines of germ cell origin, including the NTera2D1, 2102EP, and JEG3 cell lines. These tumors and cell lines often contain one or more copies of isochromosome 12p, or translocations of 12p. Another human condition, the Pallister-Killian syndrome, is also characterized by the mosaic presence of an isochromosome 12p in patient`s cells. M28, a previously described somatic hybrid cell line, contains a human isochromosone 12p derived from fibroblasts of a patient with Pallister-Killian syndrome in a mouse LMTK-background. I asked whether the M28 cell line would exhibit enhanced expression of endogenous or transfected L1Hs elements. Expression of transfected recombinant L1Hs elements was 10-20 fold higher in M28 than in LMTK-cells. Expression of L1Hs elements was not increased in the GM10868A somatic cell hybrid line which contains a complete human chromosome 12 in a Chinese Hamster Ovary background. Somatic cell hybrid lines containing various human chromosomes in a LMTK-background also exhibited no enhanced L1Hs expression. P40, the protein encoded by the L1Hs first open reading frame, was detected in NTera2D1 but not in non-transfected M28 cells. Preliminary promoter deletion experiments indicate that similar, but non-identical regions of the L1Hs 5{prime} UTR, contribute to high level expression in the NTera2D1 and the M28 cell lines. These data suggest that the enhanced expression of human LINE-1 elements in tumors of germ cell origin is due in part to the presence of the isochromosome 12p.

  3. Structural style of east flank of Bighorn Mountains, Johnson and Sheridan Counties, Wyoming

    SciTech Connect

    Furner, R.B. )

    1989-09-01

    The 70 mi-long portion of the east flank of the Bighorn Mountains, between Sheridan and Mayoworth, Wyoming, is structurally divisible into three distinct segments - northern, central, and southern - each distinguished by a dominant sense of vergence and structural style. The northern segment displays southwest-verging reverse faults and associated folds, indicating tectonic transport out of the Powder River basin and onto the mountain flank. The central segment displays northeast and east-northeast-verging reverse faults and associated folds, indicating tectonic transport of the mountain flank over the Powder River basin. Seismic and drill-hole data indicate most of these reverse faults dip to the southwest and west-southwest at angles of 35{degree} or less. The southern segment displays west-southwest-verging reverse faults and associated folds, again indicating tectonic transport out of the Powder River basin and onto the mountain flank. All major structures identified within the area of investigation are basement involved, and the geometry of the rocks supports the concept that the mountain flank deformed under the influence of northeast-southwest-directed horizontal compression rather than vertically oriented block uplift.

  4. Alternative promoters and repetitive DNA elements define the species-dependent tissue-specific expression of the FMO1 genes of human and mouse

    PubMed Central

    Shephard, Elizabeth A.; Chandan, Pritpal; Stevanovic-Walker, Milena; Edwards, Mina; Phillips, Ian R.

    2007-01-01

    In humans, expression of the FMO1 (flavin-containing mono-oxygenase 1) gene is silenced postnatally in liver, but not kidney. In adult mouse, however, the gene is active in both tissues. We investigated the basis of this species-dependent tissue-specific transcription of FMO1. Our results indicate the use of three alternative promoters. Transcription of the gene in fetal human and adult mouse liver is exclusively from the P0 promoter, whereas in extra-hepatic tissues of both species, P1 and P2 are active. Reporter gene assays showed that the proximal P0 promoters of human (hFMO1) and mouse (mFmo1) genes are equally effective. However, sequences upstream (−2955 to −506) of the proximal P0 of mFmo1 increased reporter gene activity 3-fold, whereas hFMO1 upstream sequences (−3027 to −541) decreased reporter gene activity by 75%. Replacement of the upstream sequence of human P0 with the upstream sequence of mouse P0 increased activity of the human proximal P0 8-fold. Species-specific repetitive elements are present immediately upstream of the proximal P0 promoters. The human gene contains five LINE (long-interspersed nuclear element)-1-like elements, whereas the mouse gene contains a poly A region, an 80-bp direct repeat, an LTR (long terminal repeat), a SINE (short-interspersed nuclear element) and a poly T tract. The rat and rabbit FMO1 genes, which are expressed in adult liver, lack some (rat) or all (rabbit) of the elements upstream of mouse P0. Thus silencing of FMO1 in adult human liver is due apparently to the presence upstream of the proximal P0 of L1 (LINE-1) elements rather than the absence of retrotransposons similar to those found in the mouse gene. PMID:17547558

  5. CCAAT displacement protein (CDP/cut) binds a negative regulatory element in the human tryptophan hydroxylase gene.

    PubMed

    Teerawatanasuk, N; Skalnik, D G; Carr, L G

    1999-01-01

    Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of serotonin, a neurotransmitter that has been implicated in many psychiatric illnesses. The mechanism of transcriptional regulation of the human TPH gene is largely unknown. We have identified a negative regulatory element located between nucleotides -310 and -220 in the human TPH (hTPH) gene. Electromobility shift analyses performed with the -310/-220 hTPH probe and nuclear extract from P815-HTR (a TPH-expressing cell line) revealed two slow migrating protein-DNA complexes, designated I and II. CCAAT displacement protein (CDP/Cut) is involved in complex I formation as shown in electromobility shift analysis, using consensus oligonucleotide competitor and antibody. Mutations in the CDP/Cut binding site not only disrupted the CDP-DNA complex but also disrupted the second complex, suggesting that the core binding sequences of the two proteins are overlapping. The functional importance of these protein-DNA interactions was assessed by transiently transfecting wild-type and mutant pTPH/luciferase reporter constructs into P815-HTR cells. Mutations in the core CDP/Cut site resulted in an approximately fourfold increase in relative luciferase activities. Because CDP/Cut has been shown to repress transcription of many target genes, we speculate that disruption of the CDP/Cut binding was responsible, at least in part, for the activation of hTPH gene. PMID:9886051

  6. An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle.

    PubMed

    Hassaballah, Abdallah I; Hassan, Mohsen A; Mardi, Azizi N; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium's tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle. PMID:24367544

  7. An Inverse Finite Element Method for Determining the Tissue Compressibility of Human Left Ventricular Wall during the Cardiac Cycle

    PubMed Central

    Hassaballah, Abdallah I.; Hassan, Mohsen A.; Mardi, Azizi N.; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium’s tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle. PMID:24367544

  8. Ectopic T Cell Receptor-α Locus Control Region Activity in B Cells Is Suppressed by Direct Linkage to Two Flanking Genes at Once

    PubMed Central

    Andino, Blanca E.; Harrow, Faith; Erhard, Karl F.; Kovalovsky, Damian; Sant'Angelo, Derek B.; Ortiz, Benjamin D.

    2010-01-01

    The molecular mechanisms regulating the activity of the TCRα gene are required for the production of the circulating T cell repertoire. Elements of the mouse TCRα locus control region (LCR) play a role in these processes. We previously reported that TCRα LCR DNA supports a gene expression pattern that mimics proper thymus-stage, TCRα gene-like developmental regulation. It also produces transcription of linked reporter genes in peripheral T cells. However, TCRα LCR-driven transgenes display ectopic transcription in B cells in multiple reporter gene systems. The reasons for this important deviation from the normal TCRα gene regulation pattern are unclear. In its natural locus, two genes flank the TCRα LCR, TCRα (upstream) and Dad1 (downstream). We investigated the significance of this gene arrangement to TCRα LCR activity by examining transgenic mice bearing a construct where the LCR was flanked by two separate reporter genes. Surprisingly, the presence of a second, distinct, reporter gene downstream of the LCR virtually eliminated the ectopic B cell expression of the upstream reporter observed in earlier studies. Downstream reporter gene activity was unaffected by the presence of a second gene upstream of the LCR. Our findings indicate that a gene arrangement in which the TCRα LCR is flanked by two distinct transcription units helps to restrict its activity, selectively, on its 5′-flanking gene, the natural TCRα gene position with respect to the LCR. Consistent with these findings, a TCRα/Dad1 locus bacterial artificial chromosome dual-reporter construct did not display the ectopic upstream (TCRα) reporter expression in B cells previously reported for single TCRα transgenes. PMID:21124935

  9. The modeling of the whole human body and the simulations of the waveguide intra-body communication by using the finite-element method

    NASA Astrophysics Data System (ADS)

    Song, Yong; Chu, Yingfang; Zhang, Kai; Kang, Bangzhi; Hao, Qun

    2010-11-01

    The simulation based on the finite-element (FE) method plays an important role in the investigation of the intra-body communication (IBC). In this paper, the method for modeling the whole human body based on the finite-element method is proposed, while a finite-element model of the whole human body used for the simulations of the waveguide intra-body communication has been developed. Finally, the simulations of the waveguide IBC with different signal transmission paths have been achieved by using the developed finite-element model. Moreover, both the potential distributions and the signal attenuations of the simulation results are discussed in detail, which indicate that the proposed method and model offer the significant advantages in the theoretical analysis and the system design of the waveguide intra-body communication.

  10. THE ASSOCIATION BETWEEN SEROTONIN TRANSPORTER GENE PROMOTOR POLYMORPHISM (5-HTTLPR) AND ELEMENTAL MERCURY EXPOSURE ON MOOD AND BEHAVIOR IN HUMANS

    PubMed Central

    Echeverria, Diana; Woods, James S.; Heyer, Nicholas J.; Martin, Michael D.; Rohlman, Dianne S.; Farin, Federico M.; Li, Tingting

    2010-01-01

    A functional polymorphism in the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) is reported to affect mood and behavior in humans. In this study, the effects of 5-HTTLPR polymorphism on neurobehavioral and mood domains that are known to be affected by elemental mercury (Hg°) exposure in human subjects were examined. The Behavioral Evaluation for Epidemiologic Studies (BEES) test battery was administered concurrently with urine and buccal-cell collections for 164 male dentists (DD) and 101 female dental assistants (DA) with occupational exposure to Hg° for an average of 19 and 10 yr, respectively. Geometric mean urinary mercury (Hg) levels in DD and DA were 2.52 (2.22) µg/L and 1.98 (1.98) µg/L, respectively. Corresponding indices of chronic occupational Hg° exposure, weighted for historical exposure, were 1212 (1877) and 316 (429). 5-HTTLPR status was 40% and 20% wild type, 40% and 56% single allelic substitution, and 20% and 24% double allelic substitution for the two genders. DD and DA were evaluated separately. Regression analyses controlled for age, premorbid intelligence, frequency of alcohol per week, and education. 5-HTTLPR polymorphism was associated with 5 behavioral measures in DD and with 12 behavioral measures in DA. Mood scores were more consistently associated with the variant in both groups. The strongest evidence for an additive effect for urinary Hg and 5-HTTLPR polymorphism in both groups was for tests of Finger TapAlternate and Hand SteadinessFactor1. Other significant additive effects that were less consistent across groups were also observed. These results add to the growing evidence of genetic determinants of mood and behavior that potentially increase susceptibility to Hg toxicity in humans. PMID:20526950

  11. A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

    PubMed

    Cázares-Ordoñez, V; González-Duarte, R J; Díaz, L; Ishizawa, M; Uno, S; Ortíz, V; Ordoñez-Sánchez, M L; Makishima, M; Larrea, F; Avila, E

    2015-02-01

    The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression. PMID:25495694

  12. Magmatism on rift flanks: Insights from ambient noise phase velocity in Afar region

    NASA Astrophysics Data System (ADS)

    Korostelev, Félicie; Weemstra, Cornelis; Leroy, Sylvie; Boschi, Lapo; Keir, Derek; Ren, Yong; Molinari, Irene; Ahmed, Abdulhakim; Stuart, Graham W.; Rolandone, Frédérique; Khanbari, Khaled; Hammond, James O. S.; Kendall, J. M.; Doubre, Cécile; Ganad, Ismail Al; Goitom, Berhe; Ayele, Atalay

    2015-04-01

    During the breakup of continents in magmatic settings, the extension of the rift valley is commonly assumed to initially occur by border faulting and progressively migrate in space and time toward the spreading axis. Magmatic processes near the rift flanks are commonly ignored. We present phase velocity maps of the crust and uppermost mantle of the conjugate margins of the southern Red Sea (Afar and Yemen) using ambient noise tomography to constrain crustal modification during breakup. Our images show that the low seismic velocities characterize not only the upper crust beneath the axial volcanic systems but also both upper and lower crust beneath the rift flanks where ongoing volcanism and hydrothermal activity occur at the surface. Magmatic modification of the crust beneath rift flanks likely occurs for a protracted period of time during the breakup process and may persist through to early seafloor spreading.

  13. Physical properties of lava flows on the southwest flank of Tyrrhena Patera, Mars

    NASA Technical Reports Server (NTRS)

    Crown, David A.; Porter, Tracy K.; Greeley, Ronald

    1991-01-01

    Tyrrhena Patera (TP) (22 degrees S, 253.5 degrees W), a large, low-relief volcano located in the ancient southern highlands of Mars, is one of four highland paterae thought to be structurally associated with the Hellas basin. The highland paterae are Hesperian in age and among the oldest central vent volcanoes on Mars. The morphology and distribution of units in the eroded shield of TP are consistent with the emplacement of pyroclastic flows. A large flank unit extending from TP to the SW contains well-defined lava flow lobes and leveed channels. This flank unit is the first definitive evidence of effusive volcanic activity associated with the highland paterae and may include the best preserved lava flows observed in the Southern Hemisphere of Mars. Flank flow unit averages, channelized flow, flow thickness, and yield strength estimates are discussed. Analysis suggests the temporal evolution of Martian magmas.

  14. Preliminary Study to Test the Feasibility of Sex Identification of Human (Homo sapiens) Bones Based on Differences in Elemental Profiles Determined by Handheld X-ray Fluorescence.

    PubMed

    Nganvongpanit, Korakot; Buddhachat, Kittisak; Brown, Janine L; Klinhom, Sarisa; Pitakarnnop, Tanita; Mahakkanukrauh, Pasuk

    2016-09-01

    Sex assignment of human remains is a crucial step in forensic anthropological studies. The aim of this study was to examine elemental differences between male and female bones using X-ray fluorescence (XRF) and determine if elemental profiling could be used for sex discrimination. Cranium, humerus, and os coxae of 60 skeletons (30 male, 30 female) from the Chiang Mai University Skeletal Collection were scanned by XRF and differences in elemental profiles between male and female bones determined using discriminant analysis. In the cranium, three elements (S, Ca, Pb) were significantly higher in males and five elements (Si, Mn, Fe, Zn, Ag) plus light elements (atomic number lower than 12) were higher in females. In humerus and os coxae, nine elements were significantly higher in male and one element was higher in female samples. The accuracy rate for sex estimation was 60, 63, and 61 % for cranium, humerus, and os coxae, respectively, and 67 % when data for all three bones were combined. We conclude that there are sex differences in bone elemental profiles; however, the accuracy of XRF analyses for discriminating between male and female samples was low compared to standard morphometric and molecular methods. XRF could be used on small samples that cannot be sexed by traditional morphological methods, but more work is needed to increase the power of this technique for gender assignment. PMID:26821354

  15. Stabilization of volcanic flanks by dike intrusion: An example from Kilauea

    USGS Publications Warehouse

    Delaney, P.T.; Denlinger, R.P.

    1999-01-01

    Dike propagation and dilation increases the compression of adjacent rocks. On volcanoes, especially oceanic shields, dikes are accordingly thought to be structurally destabilizing. As compression is incremented, volcanic flanks are driven outward or downslope and thus increase their susceptibility to destructive earthquakes and giant landslides. We show, however, that the 2-m-thick dike emplaced along the east rift zone of Kilauea in 1983 actually stabilized that volcano's flank. Specifically, production of flank earthquakes dropped more than twofold after 1983 as maximum downslope motion slowed to 6 cm ?? year-1 from approximately 40 cm ?? year-1 during 1980-1982. As much as 65 cm of deflationary subsidence above Kilauea's summit and upper rift zones accompanied the dike intrusion. According to recent estimates, this deflation corresponds to a reduction in magma-reservoir pressure of approximately 4 MPa, probably about as much as the driving pressure of the 1983 dike. The volume of the dike, approximately 0.10-0.15 km3, is orders of magnitude less than the estimated 200- to 250-km3 volume of Kilauea's reservoir of magma and nearby hot, mushy rock. Thus, deflation of that reservoir reduces the compressional load on the flank over a much larger area than intrusion of the dike adds to it, particularly at the dominant depth of seismicity, 8-9 km. A Coulomb block model for flank motion during intervals between major earthquakes requires the low-angle fault beneath Kilauea's flank to exhibit slip weakening, conducive to earthquake instability. Accordingly, the triggering mechanism of destructive earthquakes, several of which have struck Hawaii during the past 150 years, need not require stresses accumulated by dike intrusions.

  16. Effects of heavy elements in the sludge conveyed by the 2011 tsunami on human health and the recovery of the marine ecosystem

    NASA Astrophysics Data System (ADS)

    Sera, K.; Goto, S.; Takahashi, C.; Saitoh, Y.; Yamauchi, K.

    2014-01-01

    The 2011 tsunami not only caused significant damage, but also drew a large amount of sludge from the bottom of the sea. This may have exerted negative effects on human health. In order to evaluate changes in elemental concentrations in the body before and after the tsunami, we collected long hairs from victims of the disaster. Furthermore, sludge and plant samples were collected from three prefectures. The sludge samples on land were found to be still contaminated with heavy elements. The concentrations of heavy elements in the soils and plants gathered from the same tidelands decreased after one year. In hair analyses, no clear changes have been observed in heavy element concentrations measured before and after the tsunami. However, the concentration of some essential elements, such as Cu, Ca and Mg, showed a decreasing tendency after the tsunami.

  17. A short, highly repetitive element in intron -1 of the human c-Ha-ras gene acts as a block to transcriptional readthrough by a viral promoter.

    PubMed Central

    Lowndes, N F; Bushel, P; Mendelsohn, L; Wu, J; Yen, M Y; Allan, M

    1990-01-01

    We have identified a short, highly repetitive element within intron -1 of the human c-Ha-ras gene. This element was found to be transcribed in both orientations and to be homologous to heterogeneous nonpolyadenylated transcripts. The repetitive element blocked transcriptional readthrough from a strong upstream viral promoter but allowed unimpaired readthrough from the c-Has-ras promoter. We suggest that it may serve to prevent excessive transcription into the coding region of the gene under such circumstances as viral insertion. Images PMID:2201911

  18. Comparison of flank modification on Ascraeus and Arsia Montes volcanoes, Mars

    NASA Technical Reports Server (NTRS)

    Zimbelman, James R.

    1993-01-01

    Geologic mapping of the Tharsis Montes on Mars is in progress as part of the Mars Geologic Mapping Program of NASA. Mapping of the southern flanks of Ascraeus Mons at 1:500,000 scale was undertaken first followed by detailed mapping of Arsia Mons; mapping of Pavonis Mons will begin later this year. Results indicate that each of the Tharsis volcanoes displays unique variations on the general 'theme' of a martian shield volcano. Here we concentrate on the flank characteristics on Ascraeus Mons and Arsia Mons, the northernmost and southernmost of the Tharsis Montes, as illustrative of the most prominent trends.

  19. Flank pain and acute renal failure after binge drinking: a growing concern?

    PubMed

    Calviño, Jesús; Bravo, Juan; Millán, Beatriz; Gonzalez-Tabares, Lourdes

    2013-01-01

    We describe two cases of acute renal failure (ARF) after heavy alcohol intake. Remarkable features included a few days latency period after binge drinking, acute flank pain resembling pyelonephritis, lack of rhabdomyolysis or liver injury, and concomitant intake of non-steroidal anti-inflammatory drugs (NSAIDs). Renal function improved with conservative treatment, and despite NSAIDs use, hyperkalemia was not clinically significant. Since binge drinking is common in the Western population, early recognition of this syndrome may be helpful when examining a patient with flank pain and ARF of unclear etiology. PMID:23477481

  20. Upwelling of hydrothermal solutions through ridge flank sediments shown by pore water profiles

    SciTech Connect

    Maris, C.R.P.; Bender, M.L.

    1982-05-07

    High calcium ion and low magnesium ion concentrations in sediment pore waters in cores from the Galapagos Mounds Hydrothermal Field on the flank of the Galapagos Spreading Center are believed to be due to a calcium-magnesium exchange reaction between circulating seawater and basement basalt. The nonlinearity of the calcium ions and magnesium ion gradients indicates that these discharging hydrothermal solutions on the ridge flank are upwelling at the rate of about 1 centimeter per year through the pelagic sediments of the Mounds Field and at about 20 centimeters per year through the hydrothermal mounds themselves.

  1. Mobilized retrotransposon Tos17 of rice by alien DNA introgression transposes into genes and causes structural and methylation alterations of a flanking genomic region.

    PubMed

    Han, F P; Liu, Z L; Tan, M; Hao, S; Fedak, G; Liu, B

    2004-01-01

    Tos17 is a copia-like endogenous retrotransposon of rice, which can be activated by various stresses such as tissue culture and alien DNA introgression. To confirm element mobilization by introgression and to study possible structural and epigenetic effects of Tos17 insertion on its target sequences, we isolated all flanking regions of Tos17 in an introgressed rice line (Tong35) that contains minute amount of genomic DNA from wild rice (Zizania latifolia). It was found that there has been apparent but limited mobilization of Tos17 in this introgression line, as being reflected by increased but stable copy number of the element in progeny of the line. Three of the five activated copies of the element have transposed into genes. Based on sequence analysis and Southern blot hybridization with several double-enzyme digests, no structural change in Tos17 could be inferred in the introgression line. Cytosine methylation status at all seven CCGG sites within Tos17 was also identical between the introgression line and its rice parent (Matsumae)-all sites being heavily methylated. In contrast, changes in structure and cytosine methylation patterns were detected in one of the three low-copy genomic regions that flank newly transposed Tos17, and all changes are stably inherited through selfed generations. PMID:15703040

  2. Mercury, elemental

    Integrated Risk Information System (IRIS)

    Mercury , elemental ; CASRN 7439 - 97 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  3. Molecular Dissection of the Human Ubiquitin C Promoter Reveals Heat Shock Element Architectures with Activating and Repressive Functions.

    PubMed

    Crinelli, Rita; Bianchi, Marzia; Radici, Lucia; Carloni, Elisa; Giacomini, Elisa; Magnani, Mauro

    2015-01-01

    The promoter of the polyubiquitin C gene (UBC) contains putative heat shock elements (HSEs) which are thought to mediate UBC induction upon stress. However, the mapping and the functional characterization of the cis-acting determinants for its up-regulation have not yet been addressed. In this study, the sequence encompassing 916 nucleotides upstream of the transcription start site of the human UBC gene has been dissected by in silico, in vitro and in vivo approaches. The information derived from this analysis was used to study the functional role and the interplay of the identified HSEs in mediating the transcriptional activation of the UBC gene under conditions of proteotoxic stress, induced by the proteasome inhibitor MG132. Here we demonstrate that at least three HSEs, with different configurations, exist in the UBC promoter: two distal, residing within nucleotides -841/-817 and -715/-691, and one proximal to the transcription start site (nt -100/-65). All of them are bound by transcription factors belonging to the heat shock factor (HSF) family, as determined by bandshift, supershift and ChIP analyses. Site-directed mutagenesis of reporter constructs demonstrated that while the distal elements are involved in the up-regulation of UBC in response to proteasome inhibition, the proximal one appears rather to function as negative regulator of the stress-induced transcriptional activity. This is the first evidence that an HSE may exert a negative role on the transcription driven by other HSE motifs on the same gene promoter, highlighting a new level of complexity in the regulation of HSFs and in the control of ubiquitin levels. PMID:26317694

  4. a Modal Analysis of Whole-Body Vertical Vibration, Using a Finite Element Model of the Human Body

    NASA Astrophysics Data System (ADS)

    Kitazaki, S.; Griffin, M. J.

    1997-02-01

    A two-dimensional model of human biomechanical responses to whole-body vibration has been developed, by using the finite element method. Beam, spring and mass elements were used to model the spine, viscera, head, pelvis and buttocks tissue in the mid-sagittal plane. The model was developed by comparison of the vibration mode shapes with those previously measured in the laboratory. At frequencies below 10 Hz, the model produced seven modes which coincided well with the measurements. The principal resonance of the driving point response at about 5 Hz consisted of an entire body mode, in which the head, spinal column and the pelvis move almost rigidly, with axial and shear deformation of tissue beneath the pelvis occurring in phase with a vertical visceral mode. The second principal resonance at about 8 Hz corresponded to a rotational mode of the pelvis, with a possible contribution from a second visceral mode. A shift of the principal resonance of the driving point response, when changing posture, was achieved only by changing the axial stiffness of the buttocks tissue. It is suggested that an increase in contact area between the buttocks and the thighs and the seat surface, when changing posture from erect to slouched, may decrease the axial stiffness beneath the pelvis, with a non-linear force-deflection relationship of tissue resulting in decreases in the natural frequencies. A change in posture from erect to slouched also increased shear deformation of tissue beneath the pelvis in the entire body mode, and the natural frequency was decreased as a result of the much lower shear stiffness of tissue compared to the axial stiffness.

  5. Effect of clenching on biomechanical response of human mandible and temporomandibular joint to traumatic force analyzed by finite element method

    PubMed Central

    Yamamoto, Kazuhiko; Sugiura, Tsutomu; Kawakami, Masayoshi; Kang, Yu B.; Tsutsumi, Sadami; Kirita, Tadaaki

    2013-01-01

    Purpose: The purpose of the present study was to analyze the effect of clenching on the biomechanical response of human mandible and temporomandibular joint (TMJ) to traumatic force by the finite element (FE) method. Material and Methods: FE models of the mandible and the TMJ in resting and clenching positions were prepared. Distribution and magnitude of von Mises stress were analyzed by applying force as a point load in the symphyseal, canine, body and angle regions of the mandible. In addition, strain energy density (SED) at the articular disc and in posterior connective tissue of TMJ was analyzed. Results: In the resting position, von Mises stress was mainly concentrated at the condylar neck and in the retromolar region of the mandible. In the clenching position, the stress at the condylar neck decreased in all loadings. The stress in the retromolar region similary decreased in the symphyseal, canine and body loading, respectively; however, higher stress was observed in the retromolar region on the loading side in the angle loading. High SED was generated at the articular disc and in posterior connective tissues of TMJ in the resting position. The SED in these tissues decreased in all loadings in the clenching position. Conclusions: Clenching generally reduces stress at the condylar neck and in the retromolar region of the mandible, and strain energy at the articular disc and in posterior connective tissue of TMJ by traumatic forces on the mandible; however, clenching induces greater stress in the retromolar region on the loading side by traumatic force to the angle region. Key words:Mandibular, temporomandibular joint, traumatic force, clenching, finite element analysis. PMID:23524422

  6. The Role of Heterologous Chloroplast Sequence Elements in Transgene Integration and Expression1[W][OA

    PubMed Central

    Ruhlman, Tracey; Verma, Dheeraj; Samson, Nalapalli; Daniell, Henry

    2010-01-01

    Heterologous regulatory elements and flanking sequences have been used in chloroplast transformation of several crop species, but their roles and mechanisms have not yet been investigated. Nucleotide sequence identity in the photosystem II protein D1 (psbA) upstream region is 59% across all taxa; similar variation was consistent across all genes and taxa examined. Secondary structure and predicted Gibbs free energy values of the psbA 5′ untranslated region (UTR) among different families reflected this variation. Therefore, chloroplast transformation vectors were made for tobacco (Nicotiana tabacum) and lettuce (Lactuca sativa), with endogenous (Nt-Nt, Ls-Ls) or heterologous (Nt-Ls, Ls-Nt) psbA promoter, 5′ UTR and 3′ UTR, regulating expression of the anthrax protective antigen (PA) or human proinsulin (Pins) fused with the cholera toxin B-subunit (CTB). Unique lettuce flanking sequences were completely eliminated during homologous recombination in the transplastomic tobacco genomes but not unique tobacco sequences. Nt-Ls or Ls-Nt transplastomic lines showed reduction of 80% PA and 97% CTB-Pins expression when compared with endogenous psbA regulatory elements, which accumulated up to 29.6% total soluble protein PA and 72.0% total leaf protein CTB-Pins, 2-fold higher than Rubisco. Transgene transcripts were reduced by 84% in Ls-Nt-CTB-Pins and by 72% in Nt-Ls-PA lines. Transcripts containing endogenous 5′ UTR were stabilized in nonpolysomal fractions. Stromal RNA-binding proteins were preferentially associated with endogenous psbA 5′ UTR. A rapid and reproducible regeneration system was developed for lettuce commercial cultivars by optimizing plant growth regulators. These findings underscore the need for sequencing complete crop chloroplast genomes, utilization of endogenous regulatory elements and flanking sequences, as well as optimization of plant growth regulators for efficient chloroplast transformation. PMID:20130101

  7. Identification and characterization of methylation-dependent/independent DNA regulatory elements in the human SLC9B1 gene

    PubMed Central

    Kumar, Priya L.; James, Paul F.

    2015-01-01

    The human NHEDC1 (hNHEDC1) protein is thought to be essential for sperm motility and fertility however the mechanisms regulating its gene expression are largely unknown. In this study we have identified multiple DNA regulatory elements in the 5′ end of the gene encoding hNHEDC1 (SLC9B1) and have explored the role that DNA methylation at these elements plays in the regulation of its expression. We first show that the full-length hNHEDC1 protein is testis-specific for the tissues that we tested and that it localizes to the cells of the seminiferous tubules. In silico analysis of the SLC9B1 gene locus identified two putative promoters (P1 and P2) and two CpG islands - CpGI (overlapping with P1) and CpGII (intragenic) - at the 5′ end of the gene. By deletion analysis of P1, we show that the region from −23bp to +200bp relative to the transcription start site (TSS) is sufficient for optimal promoter activity in a germ cell line. Additionally, in vitro methylation of the P1 (the −500bp to +200bp region relative to the TSS) abolishes its activity in germ cells and somatic cells strongly suggesting that DNA methylation at this promoter could regulate SLC9B1 expression. Furthermore, bisulfite-sequencing analysis of the P1/CpGI uncovered reduced methylation in the testis vs. lung whereas CpGII displayed no differences in methylation between these two tissues. Additionally, treatment of HEK 293 cells with 5-Aza2-Deoxycytidine led to upregulation of NHEDC1 transcript and reduced methylation in the promoter CpGI. Finally, we have uncovered both enhancer and silencer functions of the intragenic SLC9B1 CpGII. In all, our data suggests that SLC9B1 gene expression could be regulated via a concerted action of DNA methylation-dependent and independent mechanisms mediated by these multiple DNA regulatory elements. PMID:25701605

  8. Brain Response to Primary Blast Wave Using Validated Finite Element Models of Human Head and Advanced Combat Helmet

    PubMed Central

    Zhang, Liying; Makwana, Rahul; Sharma, Sumit

    2013-01-01

    Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen

  9. Brain response to primary blast wave using validated finite element models of human head and advanced combat helmet.

    PubMed

    Zhang, Liying; Makwana, Rahul; Sharma, Sumit

    2013-01-01

    Blast-induced traumatic brain injury has emerged as a "signature injury" in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27-0.66 MPa) from the Bowen's lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen's cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10-35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence "iso-damage" curves for brain injury are likely different than the Bowen curves for lung

  10. Modification of the carboxy-terminal flanking region of a universal influenza epitope alters CD4+ T-cell repertoire selection

    PubMed Central

    Cole, David K.; Gallagher, Kathleen; Lemercier, Brigitte; Holland, Christopher J.; Junaid, Sayed; Hindley, James P.; Wynn, Katherine K.; Gostick, Emma; Sewell, Andrew K.; Gallimore, Awen M.; Ladell, Kristin; Price, David A.; Gougeon, Marie-Lise; Godkin, Andrew

    2012-01-01

    Human CD4+ αβ T cells are activated via T-cell receptor recognition of peptide epitopes presented by major histocompatibility complex (MHC) class II (MHC-II). The open ends of the MHC-II binding groove allow peptide epitopes to extend beyond a central nonamer core region at both the amino- and carboxy-terminus. We have previously found that these non-bound C-terminal residues can alter T cell activation in an MHC allele-transcending fashion, although the mechanism for this effect remained unclear. Here we show that modification of the C-terminal peptide-flanking region of an influenza hemagglutinin (HA305−320) epitope can alter T-cell receptor binding affinity, T-cell activation and repertoire selection of influenza-specific CD4+ T cells expanded from peripheral blood. These data provide the first demonstration that changes in the C-terminus of the peptide-flanking region can substantially alter T-cell receptor binding affinity, and indicate a mechanism through which peptide flanking residues could influence repertoire selection. PMID:22314361

  11. The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region.

    PubMed Central

    Tan, W; Schwartz, S

    1995-01-01

    We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element. PMID:7707519

  12. Effects of human-induced alteration of groundwater flow on concentrations of naturally-occurring trace elements at water-supply wells

    USGS Publications Warehouse

    Ayotte, J.D.; Szabo, Z.; Focazio, M.J.; Eberts, S.M.

    2011-01-01

    The effects of human-induced alteration of groundwater flow patterns on concentrations of naturally-occurring trace elements were examined in five hydrologically distinct aquifer systems in the USA. Although naturally occurring, these trace elements can exceed concentrations that are considered harmful to human health. The results show that pumping-induced hydraulic gradient changes and artificial connection of aquifers by well screens can mix chemically distinct groundwater. Chemical reactions between these mixed groundwaters and solid aquifer materials can result in the mobilization of trace elements such as U, As and Ra, with subsequent transport to water-supply wells. For example, in the High Plains aquifer near York, Nebraska, mixing of shallow, oxygenated, lower-pH water from an unconfined aquifer with deeper, confined, anoxic, higher-pH water is facilitated by wells screened across both aquifers. The resulting higher-O2, lower-pH mixed groundwater facilitated the mobilization of U from solid aquifer materials, and dissolved U concentrations were observed to increase significantly in nearby supply wells. Similar instances of trace element mobilization due to human-induced mixing of groundwaters were documented in: (1) the Floridan aquifer system near Tampa, Florida (As and U), (2) Paleozoic sedimentary aquifers in eastern Wisconsin (As), (3) the basin-fill aquifer underlying the California Central Valley near Modesto (U), and (4) Coastal Plain aquifers of New Jersey (Ra). Adverse water-quality impacts attributed to human activities are commonly assumed to be related solely to the release of the various anthropogenic contaminants to the environment. The results show that human activities including various land uses, well drilling, and pumping rates and volumes can adversely impact the quality of water in supply wells, when associated with naturally-occurring trace elements in aquifer materials. This occurs by causing subtle but significant changes in

  13. Influence of far upstream element binding protein 1 gene on chemotherapy sensitivity in human U251 glioblastoma cells

    PubMed Central

    Hong, Yang; Shi, Yu; Shang, Chao; Xue, Yixue

    2016-01-01

    Introduction The aim of this study was to determine the influence of the far upstream element binding protein 1 gene (FUBP1) on chemotherapy sensitivity in human U251 glioblastoma cells. Material and methods Real-time polymerase chain reaction (PCR) was used to determine the expression of the FUBP1 gene in 43 cases of human brain gliomas. Western blot analysis was used to determine the inhibitory effect of RNA interference on FUBP1 gene expression. Methyl thiazolyl tetrazolium assay (MTT) and flow cytometry methods were used to determine the growth inhibitory rate and apoptosis rate of the U251 cells with FUBP1 silencing. The growth inhibitory rate and apoptosis rate were further determined after treatment of those U251 cells with cisplatin (DDP). Results The expression of FUBP1 mRNA was up-regulated significantly in gliomas, 177.65% as much as in peri-cancerous tissues (p < 0.05). The expression of FUBP1 protein was inhibited significantly with siRNA-FUBP1 (p < 0.05). In FUBP1-silenced cells, the growth inhibitory rate increased from 1.4% to 29.5%, and the apoptosis rate increased from 2.68% to 5.84% (p < 0.05 for both). After treating with DDP at various concentrations (1, 3, 5 µg/ml), the growth inhibitory rate of FUBP1-silenced cells increased from 14.42%, 17.46% and 23.55% to 21.69%, 27.51% and 37.57%; the apoptosis rate increased from 8.85%, 14.37% and 18.21% to 13.25%, 18.46% and 26.52%. Conclusions The up-regulation of FUBP1 relates to the carcinogenesis of gliomas. FUBP1 silencing increases the growth inhibitory rate and apoptosis rate of the U251 cells, and enhances the chemotherapy sensitivity of U251 cells to DDP. PMID:26925132

  14. Two initiator-like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4.

    PubMed

    Pastier, Daniele; Lacorte, Jean-Marc; Chambaz, Jean; Cardot, Philippe; Ribeiro, Agnes

    2002-04-26

    Human apoC-III (-890/+24) promoter activity is strongly activated by hepatic nuclear factor (HNF)-4 through its binding to the proximal (-87/-72) element B. This site overlaps the binding site for an activity that we identified as the ubiquitously expressed upstream stimulatory factor (USF) (Ribeiro, A., Pastier, D., Kardassis, D., Chambaz, J., and Cardot, P. (1999) J. Biol. Chem. 274, 1216-1225). In the present study, we characterized the relationship between USF and HNF-4 in the activation of human apoC-III transcription. Although USF and HNF-4 binding to element B is mutually exclusive, co-transfection experiments in HepG2 cells surprisingly showed a combined effect of USF and HNF-4 in the transactivation of the (-890/+24) apoC-III promoter. This effect only requires the proximal region (-99/+24) of the apoC-III promoter and depends neither on USF binding to its cognate site in element B nor on a USF-dependent facilitation of HNF-4 binding to its site. By contrast, we found by electrophoretic mobility shift assay and footprinting analysis two USF low affinity binding sites, located within the proximal promoter at positions -58/-31 (element II) and -19/-4 (element I), which are homologous to initiator-like element sequence. Co-transfection experiments in HepG2 cells show that a mutation in element II reduces 2-fold the USF transactivation effect on the proximal promoter of apoC-III and that a mutation in element I inhibits the combined effect of USF and HNF-4. In conclusion, these initiator-like elements are directly involved in the transactivation of the apoC-III promoter by USF and are necessary to the combined effect between USF and HNF-4 for the apoC-III transcription. PMID:11839757

  15. Cloning and Characterization of 5′ Flanking Regulatory Sequences of AhLEC1B Gene from Arachis Hypogaea L.

    PubMed Central

    Tang, Guiying; Xu, Pingli; Liu, Wei; Liu, Zhanji; Shan, Lei

    2015-01-01

    LEAFY COTYLEDON1 (LEC1) is a B subunit of Nuclear Factor Y (NF-YB) transcription factor that mainly accumulates during embryo development. We cloned the 5′ flanking regulatory sequence of AhLEC1B gene, a homolog of Arabidopsis LEC1, and analyzed its regulatory elements using online software. To identify the crucial regulatory region, we generated a series of GUS expression frameworks driven by different length promoters with 5′ terminal and/or 3′ terminal deletion. We further characterized the GUS expression patterns in the transgenic Arabidopsis lines. Our results show that both the 65bp proximal promoter region and the 52bp 5′ UTR of AhLEC1B contain the key motifs required for the essential promoting activity. Moreover, AhLEC1B is preferentially expressed in the embryo and is co-regulated by binding of its upstream genes with both positive and negative corresponding cis-regulatory elements. PMID:26426444

  16. An Anthropometric-Based Subject-Specific Finite Element Model of the Human Breast for Predicting Large Deformations.

    PubMed

    Pianigiani, Silvia; Ruggiero, Leonardo; Innocenti, Bernardo

    2015-01-01

    The large deformation of the human breast threatens proper nodules tracking when the subject mammograms are used as pre-planning data for biopsy. However, techniques capable of accurately supporting the surgeons during biopsy are missing. Finite element (FE) models are at the basis of currently investigated methodologies to track nodules displacement. Nonetheless, the impact of breast material modeling on the mechanical response of its tissues (e.g., tumors) is not clear. This study proposes a subject-specific FE model of the breast, obtained by anthropometric measurements, to predict breast large deformation. A healthy breast subject-specific FE parametric model was developed and validated by Cranio-caudal (CC) and Medio-Lateral Oblique (MLO) mammograms. The model was successively modified, including nodules, and utilized to investigate the effect of nodules size, typology, and material modeling on nodules shift under the effect of CC, MLO, and gravity loads. Results show that a Mooney-Rivlin material model can estimate healthy breast large deformation. For a pathological breast, under CC compression, the nodules displacement is very close to zero when a linear elastic material model is used. Finally, when nodules are modeled, including tumor material properties, under CC, or MLO or gravity loads, nodules shift shows ~15% average relative difference. PMID:26734604

  17. Validation of Shoulder Response of Human Body Finite-Element Model (GHBMC) Under Whole Body Lateral Impact Condition.

    PubMed

    Park, Gwansik; Kim, Taewung; Panzer, Matthew B; Crandall, Jeff R

    2016-08-01

    In previous shoulder impact studies, the 50th-percentile male GHBMC human body finite-element model was shown to have good biofidelity regarding impact force, but under-predicted shoulder deflection by 80% compared to those observed in the experiment. The goal of this study was to validate the response of the GHBMC M50 model by focusing on three-dimensional shoulder kinematics under a whole-body lateral impact condition. Five modifications, focused on material properties and modeling techniques, were introduced into the model and a supplementary sensitivity analysis was done to determine the influence of each modification to the biomechanical response of the body. The modified model predicted substantially improved shoulder response and peak shoulder deflection within 10% of the observed experimental data, and showed good correlation in the scapula kinematics on sagittal and transverse planes. The improvement in the biofidelity of the shoulder region was mainly due to the modifications of material properties of muscle, the acromioclavicular joint, and the attachment region between the pectoralis major and ribs. Predictions of rib fracture and chest deflection were also improved because of these modifications. PMID:26753830

  18. Environmental distribution and associated human health risk due to trace elements and organic compounds in soil in Jiangxi province, China.

    PubMed

    Teng, Yanguo; Li, Jiao; Wu, Jin; Lu, Sijin; Wang, Yeyao; Chen, Haiyang

    2015-12-01

    The government of China launched its first national soil quality and pollution survey (NSQPS) during April 2006 to December 2013. Data gathered in several earlier soil surveys were rarely used to understand the status of pollution. In this study, the dataset collected at the provincial level was analyzed for the first time. Concentrations, distribution, diversity, and human health risks of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, V and Zn) and organic pollutants (benzene hexachloride (BHCs), dichlorodiphenyltrichloroethanes (DDTs), phthalic acid esters (PAEs), polycyclic aromatic hydrocarbon (PAHs), polychlorinated biphenyls (PCBs), and petroleum hydrocarbons (PHCs)) in surface soil samples collected across Jiangxi province,China were presented. The results showed that, the proportion of contaminants with concentrations higher than their corresponding regulatory reference value ranged from 0.12% to 17%. It is worth note that, the local residents are exposed to moderate non-carcinogenic and carcinogenic risks at some sites. The comprehensive analysis of soil pollutants provide baseline information for establishing a long-term soil environmental monitoring program in Jiangxi province, China. PMID:26363984

  19. Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid

    PubMed Central

    Derse, David; Hill, Shawn A.; Princler, Gerald; Lloyd, Patricia; Heidecker, Gisela

    2007-01-01

    Human T cell leukemia virus type 1 (HTLV-1) has evolved a remarkable strategy to thwart the antiviral effects of the cellular cytidine deaminase APOBEC3G (hA3G). HTLV-1 infects T lymphocytes in vivo, where, like HIV-1, it is likely to encounter hA3G. HIV-1 counteracts the innate antiviral activity of hA3G by producing an accessory protein, Vif, which hastens the degradation of hA3G. In contrast, HTLV-1 does not encode a Vif homologue; instead, HTLV-1 has evolved a cis-acting mechanism to prevent hA3G restriction. We demonstrate here that a peptide motif in the C terminus of the HTLV-1 nucleocapsid (NC) domain inhibits hA3G packaging into nascent virions. Mutation of amino acids within this region resulted in increased levels of hA3G incorporation into virions and increased susceptibility to hA3G restriction. Elements within the C-terminal extension of the NC domain are highly conserved among the primate T cell leukemia viruses, but this extension is absent in all other retroviral NC proteins. PMID:17299050

  20. An Anthropometric-Based Subject-Specific Finite Element Model of the Human Breast for Predicting Large Deformations

    PubMed Central

    Pianigiani, Silvia; Ruggiero, Leonardo; Innocenti, Bernardo

    2015-01-01

    The large deformation of the human breast threatens proper nodules tracking when the subject mammograms are used as pre-planning data for biopsy. However, techniques capable of accurately supporting the surgeons during biopsy are missing. Finite element (FE) models are at the basis of currently investigated methodologies to track nodules displacement. Nonetheless, the impact of breast material modeling on the mechanical response of its tissues (e.g., tumors) is not clear. This study proposes a subject-specific FE model of the breast, obtained by anthropometric measurements, to predict breast large deformation. A healthy breast subject-specific FE parametric model was developed and validated by Cranio-caudal (CC) and Medio-Lateral Oblique (MLO) mammograms. The model was successively modified, including nodules, and utilized to investigate the effect of nodules size, typology, and material modeling on nodules shift under the effect of CC, MLO, and gravity loads. Results show that a Mooney–Rivlin material model can estimate healthy breast large deformation. For a pathological breast, under CC compression, the nodules displacement is very close to zero when a linear elastic material model is used. Finally, when nodules are modeled, including tumor material properties, under CC, or MLO or gravity loads, nodules shift shows ~15% average relative difference. PMID:26734604

  1. A sequence homologous to kappa-deleting element is located 5 prime to the human J sub K locus

    SciTech Connect

    Kennedy, M.A.; Morris, C.M.; Fitzgerald, P.H. )

    1989-01-25

    The human kappa deleting element (Kde) mediates loss of CK and JK genes in B cells. A probe for Kde detects two genomic sequences on Southern blots. The Kde is located 24kb 3{prime} to CK, but the position of the homologous sequence is unknown. The authors in situ hybridized m141-2 to metaphase cells of JC11, a B-cell line bearing a t(2;14)(p11;q32) in which the chromosome 2 breakpoint is within JK or the VK-JK intron. Three peaks of labelled sites were obtained. Southern analysis of BamH1 digested DNA showed that Kde (14kb) and the homologous sequence (3kb) were both intact. Kde accounts for hybridization to 14q+ and the 2p- signal presumably derives from the related sequence. This locates the sequence homologous to Kde upstream from JK, possibly within the VK cluster, and may reflect transposition or some other duplicative event as proposed for the evolution of other regions of the kappa locus.

  2. Simulation of temperature and thermally induced stress of human tooth under CO2 pulsed laser beams using finite element method.

    PubMed

    Sabaeian, Mohammad; Shahzadeh, Mohammadreza

    2015-02-01

    The authors report the simulation of temperature distribution and thermally induced stresses of human tooth under CO2 pulsed laser beam. A detailed tooth structure comprising enamel, dentin, and pulp with realistic shapes and thicknesses were considered, and a numerical method of finite element was adopted to solve time-dependent bio-heat and stress equations. The realistic boundary conditions of constant temperature for those parts embedded in the gingiva and heat flux condition for those parts out of the gingiva were applied. The results which were achieved as a function of energy density (J/cm(2)) showed when laser beam is irradiated downward (from the top of the tooth), the temperature and thermal stresses decrease quickly as a function of depth that is a result of strong absorption of CO2 beams by enamel. This effect is so influential that one can use CO2 beams to remove micrometer layers while underlying tissues, especially the pulp, are safe from thermal effects. PMID:23868367

  3. 7. INTERIOR LIVING ROOM SHOWING 6LIGHT FRONT DOOR FLANKED BY ...

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

    7. INTERIOR LIVING ROOM SHOWING 6-LIGHT FRONT DOOR FLANKED BY ONE OF TWO 6-LIGHT OVER 1-LIGHT SASH WINDOWS AT PHOTO RIGHT, AND OPEN DOORWAY TO BEDROOM NUMBER ONE (AND BEDROOM NUMBER TWO IN BACKGROUND) AT PHOTO LEFT. VIEW TO NORTH. - Rush Creek Hydroelectric System, Worker Cottage, Rush Creek, June Lake, Mono County, CA

  4. Hazard potential of volcanic flank collapses raised by new megatsunami evidence.

    PubMed

    Ramalho, Ricardo S; Winckler, Gisela; Madeira, José; Helffrich, George R; Hipólito, Ana; Quartau, Rui; Adena, Katherine; Schaefer, Joerg M

    2015-10-01

    Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet, evidence for the generation and impact of collapse-triggered megatsunamis and their high run-ups remains scarce or is highly controversial. Therefore, doubts remain on whether island flank failures truly generate enough volume flux to trigger giant tsunamis, leading to diverging opinions concerning the real hazard potential of such collapses. We show that one of the most prominent oceanic volcanoes on Earth-Fogo, in the Cape Verde Islands-catastrophically collapsed and triggered a megatsunami with devastating effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic (3)He dating of tsunamigenic deposits found on nearby Santiago Island, which attest to the impact of this giant tsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo's flank failure involved at least one fast and voluminous event that led to a giant tsunami, in contrast to what has been suggested before. Our observations therefore further demonstrate that flank collapses may indeed catastrophically happen and are capable of triggering tsunamis of enormous height and energy, adding to their hazard potential. PMID:26601287

  5. Hazard potential of volcanic flank collapses raised by new megatsunami evidence

    PubMed Central

    Ramalho, Ricardo S.; Winckler, Gisela; Madeira, José; Helffrich, George R.; Hipólito, Ana; Quartau, Rui; Adena, Katherine; Schaefer, Joerg M.

    2015-01-01

    Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet, evidence for the generation and impact of collapse-triggered megatsunamis and their high run-ups remains scarce or is highly controversial. Therefore, doubts remain on whether island flank failures truly generate enough volume flux to trigger giant tsunamis, leading to diverging opinions concerning the real hazard potential of such collapses. We show that one of the most prominent oceanic volcanoes on Earth—Fogo, in the Cape Verde Islands—catastrophically collapsed and triggered a megatsunami with devastating effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic 3He dating of tsunamigenic deposits found on nearby Santiago Island, which attest to the impact of this giant tsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo’s flank failure involved at least one fast and voluminous event that led to a giant tsunami, in contrast to what has been suggested before. Our observations therefore further demonstrate that flank collapses may indeed catastrophically happen and are capable of triggering tsunamis of enormous height and energy, adding to their hazard potential. PMID:26601287

  6. Window type: 4x4 multipaned steel window flanked by 1x4 multipaned ...

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

    Window type: 4x4 multipaned steel window flanked by 1x4 multipaned steel, casements. Concrete stoop, entry overhang and pipe rail detail also illustrated. Building 36, facing northwest - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  7. Window type: paired 2x4 multipaned steel windows flanked by 1x4 ...

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

    Window type: paired 2x4 multipaned steel windows flanked by 1x4 multipaned steel casements, breaking building corner. Raised panel door front entry also illustrated. Ground floor detail Building 19, facing north - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  8. Window type: paired 3x2 multipaned steel window flanked by 1x3 ...

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

    Window type: paired 3x2 multipaned steel window flanked by 1x3 multipaned steel casements, breaking building corner. Broad overhanging eave also illustrated. Second story detail. Building 13, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  9. Magmatism on rift flanks: insights from Ambient-Noise Phase-velocity in Afar region

    NASA Astrophysics Data System (ADS)

    Korostelev, Félicie; Weemstra, Cornelis; Leroy, Sylvie; Boschi, Lapo; Ren, Yong; Ahmed, Abdulhakim; Keir, Derek; Stuart, Graham W.; Rolandone, Frédérique; Khanbari, Khaled; Hammond, James O. S.; Kendall, J. Michael; Doubre, Cécile; Ganad, Ismail Al

    2015-04-01

    During the breakup of continent in the presence of magma, strain is commonly assumed to initially occur by border faulting, and progressively migrate in space and time towards axial magma intrusion. Magmatic processes near the rift flanks are commonly ignored. We present phase-velocity maps of the crust and uppermost mantle of the conjugate margins of the southern Red Sea (Afar and Yemen) using ambient noise tomography to constrain crustal modification during breakup. Our images show that the low seismic velocities characterize not only upper crust beneath the axial volcanic systems, but also both upper and lower crust beneath rift flanks where ongoing volcanism and hydrothermal activity occurs at the surface. The results show that magmatic modification of the crust beneath rift flanks likely occurs for a protracted period of time during the breakup process, and may persist through to early seafloor spreading. Since ongoing flank magmatism during breakup impacts the thermal evolution of the lithosphere, it has implications for the subsidence history of the rift.

  10. Sudden aseismic fault slip on the south flank of Kilauea volcano.

    PubMed

    Cervelli, Peter; Segall, Paul; Johnson, Kaj; Lisowski, Michael; Miklius, Asta

    2002-02-28

    One of the greatest hazards associated with oceanic volcanoes is not volcanic in nature, but lies with the potential for catastrophic flank failure. Such flank failure can result in devastating tsunamis and threaten not only the immediate vicinity, but coastal cities along the entire rim of an ocean basin. Kilauea volcano on the island of Hawaii, USA, is a potential source of such flank failures and has therefore been monitored by a network of continuously recording geodetic instruments, including global positioning system (GPS) receivers, tilt meters and strain meters. Here we report that, in early November 2000, this network recorded transient southeastward displacements, which we interpret as an episode of aseismic fault slip. The duration of the event was about 36 hours, it had an equivalent moment magnitude of 5.7 and a maximum slip velocity of about 6[?]cm per day. Inversion of the GPS data reveals a shallow-dipping thrust fault at a depth of 4.5[?]km that we interpret as the down-dip extension of the Hilina Pali--Holei Pali normal fault system. This demonstrates that continuously recording geodetic networks can detect accelerating slip, potentially leading to warnings of volcanic flank collapse. PMID:11875566

  11. Tsunami deposits at high altitudes on the flanks of volcanic islands

    NASA Astrophysics Data System (ADS)

    Paris, Raphael

    2016-04-01

    It is actually difficult to infer the mechanisms and dynamics of giant mass failures of oceanic shield volcanoes and to evaluate related tsunami hazards. Marine conglomerates and gravels found at unusually high elevations in Hawaii, Cape Verde, Mauritius and Canary Islands are often interpreted as being the result of tsunami waves generated by such massive flank failures. In the first part of this contribution, we document tsunami deposits (marine gravels with pumices) attached to the northwestern slopes of Tenerife, Canary Islands, at altitudes up to 132 m asl. Stratigraphy of the deposits and composition of the pumices allows identifying sources of the successive tsunamis and proposing a new scenario for the Icod flank failure and El Abrigo caldera-forming eruption ca. 170 ka. Then we propose a litterature review of tsunami deposits at high altitudes on the flanks of volcanic islands, and especially oceanic shield volcanoes. These deposits are discussed in terms of texture, structure, composition and particularly the juvenile volcanic material, and implications for better understanding the mechanisms controlling massive flank failures.

  12. Carboniferous tectonic history of the eastern flank of the Ozark dome

    SciTech Connect

    Nelson, W.J. )

    1993-03-01

    Detailed geologic mapping in southwestern Illinois and southeastern Missouri indicates that the eastern flank of the Ozark dome was a low positive area throughout Carboniferous (Mississippian and Pennsylvanian) time. Rock units of this age consistently thin onto the flank of the dome, and are punctuated by numerous disconformities. Effects of shoaling are prominent in Chesterian strata, which change from dominantly subtidal in the proto-Illinois basin to shallow subtidal, intertidal and supratidal on the flank of the dome. Although the dome probably was exposed subaerially for much of Carboniferous time, it contributed little sediment eastward. The exposed rocks were largely carbonates, which weathered by solution. Several long-lived basement structures on the east flank of the Ozarks were active during the Carboniferous. Chief among them were the Lincoln and Waterloo-Dupo anticlines, the Du Quoin monocline, and the Ste. Genevieve fault zone. All are high-angle reverse faults that strike north to northwest, and are overlain by sharp folds in sedimentary cover. Major displacements took place in late Valmeyeran to Atokan time, and addition deformation occurred in Desmoinesian through post-Pennsylvanian time. The compressional deformation probably is a product of the Ouachita orogeny.

  13. Flanking Magnitudes: Dissociation between Numerosity and Numerical Value in a Selective Attention Task

    ERIC Educational Resources Information Center

    Naparstek, Sharon; Safadi, Ziad; Lichtenstein-Vidne, Limor; Henik, Avishai

    2015-01-01

    The current research examined whether peripherally presented numerical information can affect the speed of number processing. In 2 experiments, participants were presented with a target matrix flanked by a distractor matrix and were asked to perform a comparative judgment (i.e., decide whether the target was larger or smaller than the reference…

  14. Autoradiographic localization of tritiated dihydrotestosterone in the flank organ of the albino hamster

    SciTech Connect

    Lucky, A.W.; Eisenfeld, A.J.; Visintin, I.

    1985-02-01

    In the hamster flank organ, the growth of hair and growth of sebaceous glands are androgen-dependent functions. Although dihydrotestosterone (DHT) is known to be a potent stimulator of flank organ growth, there is no information about localization of DHT receptor sites in this organ. The purpose of this study was to use steroid autoradiography to localize DHT receptors in the hamster flank organ. Because steroid hormones are functional when translocated to nuclear receptors, nuclear localization by autoradiography defines receptor sites. In order to be able to visualize autoradiographic grains from radiolabeled androgens around hair follicles, albino hamsters were studied to avoid confusion between the grains and pigment granules which are abundant in the more common Golden Syrian hamster. Mature male hamsters castrated 24 hours earlier were given tritium-labeled dihydrotestosterone ( (/sup 3/H)DHT). Using the technique of thaw-mount steroid autoradiography, 4-micron unfixed frozen sections were mounted in the dark onto emulsion-coated glass slides and allowed to develop for 4-6 months. (/sup 3/H)DHT was found to be concentrated over sebocyte nuclei. The label was present peripherally as well as in differentiating sebocytes. There was no nuclear localization of (/sup 3/H)DHT in animals pretreated with excessive quantities of unlabeled DHT. Steroid metabolites of (/sup 3/H) DHT were assessed by thin-layer chromatography in paired tissue samples. Most of the label remained with DHT. Uptake was inhibited in the flank organ of hamsters pretreated with unlabeled DHT.

  15. Rift flank segmentation, basin initiation and propagation: a neotectonic example from Lake Baikal

    USGS Publications Warehouse

    Agar, S.M.; Klitgord, Kim D.

    1995-01-01

    New surficial data (field, Landsat TM and topography) define morpho-tectonic domains and rift flank segmentation in the Ol'khon region of the Central Baikal rift. Deformation, drainage and depositional patterns indicate a change in the locus of active extension that may relate to a recent (flank graben has propagated southwards along the rift flank and is still actively fragmenting. These surficial data are used to constrain a model for the time-dependent topographic variations during progressive subsidence along a rift flank, involving the transfer of footwall units to hanging-wall domains. Rapid changes in border fault footwall relief in this model are associated with change in the active border fault location with widespread mass-wasting. The model shows that time-dependent histories need to be integrated with flexural uplift models for active normal faults. The active, syn-rift depositional systems of the Ol'khon region provide a valuable analogue for the early evolution of continental margins and the structural controls on syn-rift hydrocarbon sources and reservoirs.

  16. Evidence for hydrothermal Archaea within the basaltic flanks of the East Pacific Rise.

    PubMed

    Ehrhardt, Christopher J; Haymon, Rachel M; Lamontagne, Michael G; Holden, Patricia A

    2007-04-01

    Little is known about the fluids or the microbial communities present within potentially vast hydrothermal reservoirs contained in still-hot volcanic ocean crust beneath the flanks of the mid-ocean ridge. During Alvin dives in 2002, organic material attached to basalt was collected at low, near-ambient temperatures from an abyssal hill fault scarp in 0.5 Ma lithosphere on the western ridge flank of the East Pacific Rise. Mineral analysis by X-ray diffractometry and scanning electron microscopy revealed high-temperature (> 110 degrees C) phases chalcopyrite (Cu(5)FeS(4)) and 1C pyrrhotite (Fe(1-x)S) within the fault scarp materials. A molecular survey of archaeal genes encoding 16S rRNA identified a diverse hyperthermophilic community, including groups within Crenarchaeota, Euryarchaeota, and Korarchaeota. We propose that the sulfide, metals and archaeal communities originated within a basalt-hosted subseafloor hydrothermal habitat beneath the East Pacific Rise ridge flank and were transported to the seafloor during a recent episode of hydrothermal venting from the abyssal hill fault. Additionally, inferred metabolisms from the fault scarp community suggest that an ecologically unique high-temperature archaeal biosphere may thrive beneath the young East Pacific Rise ridge flank and that abyssal hill fault scarps may present new opportunities for sampling for this largely unexplored microbial habitat. PMID:17359262

  17. Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs.

    PubMed Central

    Scheper, W; Meinsma, D; Holthuizen, P E; Sussenbach, J S

    1995-01-01

    Human insulin-like growth factor II (IGF-II) mRNAs are subject to site-specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the first and rate-limiting step in degradation of IGF-II mRNAs. Two sequence elements within the 3' untranslated region are required for cleavage: element I, located approximately 2 kb upstream of the cleavage site, and element II, encompassing the cleavage site itself. We have identified a stable double-stranded RNA stem structure (delta G = -100 kcal/mol [418.4 kJ/mol]) that can be formed between element I and a region downstream of the cleavage site in element II. This structure is conserved among human, rat, and mouse mRNAs. Detailed analysis of the requirements for cleavage shows that the relative position of the elements is not essential for cleavage. Furthermore, the distance between the coding region and the cleavage site does not affect the cleavage reaction. Mutational analysis of the long-range RNA-RNA interaction shows that not only the double-stranded character but also the sequence of the stable RNA stem is important for cleavage. PMID:7799930

  18. Size and sequence polymorphism in the isocitrate dehydrogenase kinase/phosphatase gene (aceK) and flanking regions in Salmonella enterica and Escherichia coli.

    PubMed

    Nelson, K; Wang, F S; Boyd, E F; Selander, R K

    1997-12-01

    The sequence of aceK, which codes for the regulatory catalytic enzyme isocitrate dehydrogenase kinase/phosphatase (IDH K/P), and sequences of the 5' flanking region and part or all of the 3' flanking region were determined for 32 strains of Salmonella enterica and Escherichia coli. In E. coli, the aceK gene was 1734 bp long in 13 strains, but in three strains it was 12 bp shorter and the stop codon was TAA rather than TGA. Strains with the shorter aceK lacked an open reading frame (f728) downstream between aceK and iclR that was present, in variable length, in the other strains. Among the 72 ECOR strains, the truncated aceK gene was present in all isolates of the B2 group and half of those of the D group. Other variant conditions included the presence of IS1 elements in two strains and large deletions in two strains. The aceK-aceA intergenic region varied in length from 48 to 280 bp in E. coli, depending largely on the number of repetitive extragenic palindromic (REP) sequences present. Among the ECOR strains, the number of REP elements showed a high degree of phylogenetic association, and sequencing of the region in the ECOR strains permitted partial reconstruction of its evolutionary history. In S. entica, the normal length of aceK was 1752 bp, but three other length variants, ranging from 1746 to 1785 bp, were represented in five of the 16 strains examined. The flanking intergenic regions showed relatively minor variation in length and sequence. The occurrence of several nonrandom patterns of distribution of polymorphic synonymous nucleotide sites indicated that intragenic recombination of horizontally exchanged DNA has contributed to the generation of allelic diversity at the aceK locus in both species. PMID:9409817

  19. Mapping of a gene for familial juvenile nephronophthisis: Refining the map and defining flanking markers on chromosome 2

    SciTech Connect

    Hildebrandt, F.; Singh-Sawhney, I.; Schnieders, B.; Centofante, L.; Omran, H.; Pohlmann, A.; Schmaltz, C.; Wedekind, H.; Schubotz, D.; Brandis, M. ); Antignac, C. ); Weber, J.L. )

    1993-12-01

    Familial juvenile nephronophthisis (NPH) is an autosomal recessive kidney disease that leads to end-stage renal failure in adolescence and is associated with the formation of cysts at the cortico-medullary junction of the kidneys. NPH is responsible for about 15% of end-stage renal disease in children, as shown by Kleinknecht and Habib. NPH in combination with autosomal recessive retinitis pigmentosa is known as the Senior-Loken syndrome (SLS) and exhibits renal pathology that is identical to NPH. The authors had excluded 40% of the human genome from linkage with a disease locus for NH or SLS when Antignac et al. first demonstrated linkage for an NPH locus on chromosome 2. The authors present confirmation of linkage of an NPH locus to microsatellite markers on chromosome 2 in nine families with NPH. By linkage analysis with marker AFM262xb5 at locus D2S176, a maximum lod score of 5.05 at a [theta][sub max] = .03 was obtained. In a large NPH family that yielded at D2S176 a maximum lod score of 2.66 at [theta][sub max] = .0, markers AFM172xc3 and AFM016yc5, representing loci D2S135 and D2S110, respectively, were identified as flanking markers, thereby defining the interval for an NPH locus to a region of approximately 15 cM. Furthermore, the cytogenetic assignment of the NPH region was specified to 2p12-(2q13 or adjacent bands) by calculation of linkage between these flanking markers and markers with known unique cytogenic assignment. The refined map may serve as a genetic framework for additional genetic and physical mapping of the region. 26 refs., 3 figs., 1 tab.

  20. Concurrent Preoperative Presence of Hydronephrosis and Flank Pain Independently Predicts Worse Outcome of Upper Tract Urothelial Carcinoma

    PubMed Central

    Yeh, Hsin-Chih; Jan, Hau-Chern; Wu, Wen-Jeng; Li, Ching-Chia; Li, Wei-Ming; Ke, Hung-Lung; Huang, Shu-Pin; Liu, Chia-Chu; Lee, Yung-Chin; Yang, Sheau-Fang; Liang, Peir-In; Huang, Chun-Nung

    2015-01-01

    Objectives To investigate the impact of preoperative hydronephrosis and flank pain on prognosis of patients with upper tract urothelial carcinoma. Methods In total, 472 patients with upper tract urothelial carcinoma managed by radical nephroureterectomy were included from Kaohsiung Medical University Hospital Healthcare System. Clinicopathological data were collected retrospectively for analysis. The significance of hydronephrosis, especially when combined with flank pain, and other relevant factors on overall and cancer-specific survival were evaluated. Results Of the 472 patients, 292 (62%) had preoperative hydronephrosis and 121 (26%) presented with flank pain. Preoperative hydronephrosis was significantly associated with age, hematuria, flank pain, tumor location, and pathological tumor stage. Concurrent presence of hydronephrosis and flank pain was a significant predictor of non-organ-confined disease (multivariate-adjusted hazard ratio = 2.10, P = 0.025). Kaplan-Meier analysis showed significantly poorer overall and cancer-specific survival in patients with preoperative hydronephrosis (P = 0.005 and P = 0.026, respectively) and in patients with flank pain (P < 0.001 and P = 0.001, respectively) than those without. However, only simultaneous hydronephrosis and flank pain independently predicted adverse outcome (hazard ratio = 1.98, P = 0.016 for overall survival and hazard ratio = 1.87, P = 0.036 for and cancer-specific survival, respectively) in multivariate Cox proportional hazards models. In addition, concurrent presence of hydronephrosis and flank pain was also significantly predictive of worse survival in patient with high grade or muscle-invasive disease. Notably, there was no difference in survival between patients with hydronephrosis but devoid of flank pain and those without hydronephrosis. Conclusion Concurrent preoperative presence of hydronephrosis and flank pain predicted non-organ-confined status of upper tract urothelial carcinoma. When

  1. Identification and characterization of a HeLa nuclear protein that specifically binds to the trans-activation-response (TAR) element of human immunodeficiency virus.

    PubMed Central

    Marciniak, R A; Garcia-Blanco, M A; Sharp, P A

    1990-01-01

    Human immunodeficiency virus type 1 RNAs contain a sequence, trans-activation-response (TAR) element, which is required for tat protein-mediated trans-activation of viral gene expression. We have identified a nuclear protein from extracts of HeLa cells that binds to the TAR element RNA in a sequence-specific manner. The binding of this 68-kDa polypeptide was detected by UV cross-linking proteins to TAR element RNA transcribed in vitro. Competition experiments were performed by using a partially purified preparation of the protein to quantify the relative binding affinities of TAR element RNA mutants. The binding affinity of the TAR mutants paralleled the reported ability of those mutants to support tat trans-activation in vivo. We propose that this cellular protein moderates TAR activity in vivo. Images PMID:2333305

  2. Trace Elements and Health

    ERIC Educational Resources Information Center

    Pettyjohn, Wayne A.

    1972-01-01

    Summarizes the effects of arsenic, lead, zinc, mercury, and cadmium on human health, indicates the sources of the elements in water, and considers the possibility of students in high schools analyzing water for trace amounts of the elements. (AL)

  3. Validity and sensitivity of a human cranial finite element model: implications for comparative studies of biting performance.

    PubMed

    Toro-Ibacache, Viviana; Fitton, Laura C; Fagan, Michael J; O'Higgins, Paul

    2016-01-01

    Finite element analysis (FEA) is a modelling technique increasingly used in anatomical studies investigating skeletal form and function. In the case of the cranium this approach has been applied to both living and fossil taxa to (for example) investigate how form relates to function or infer diet or behaviour. However, FE models of complex musculoskeletal structures always rely on simplified representations because it is impossible completely to image and represent every detail of skeletal morphology, variations in material properties and the complexities of loading at all spatial and temporal scales. The effects of necessary simplifications merit investigation. To this end, this study focuses on one aspect, model geometry, which is particularly pertinent to fossil material where taphonomic processes often destroy the finer details of anatomy or in models built from clinical CTs where the resolution is limited and anatomical details are lost. We manipulated the details of a finite element (FE) model of an adult human male cranium and examined the impact on model performance. First, using digital speckle interferometry, we directly measured strains from the infraorbital region and frontal process of the maxilla of the physical cranium under simplified loading conditions, simulating incisor biting. These measured strains were then compared with predicted values from FE models with simplified geometries that included modifications to model resolution, and how cancellous bone and the thin bones of the circum-nasal and maxillary regions were represented. Distributions of regions of relatively high and low principal strains and principal strain vector magnitudes and directions, predicted by the most detailed FE model, are generally similar to those achieved in vitro. Representing cancellous bone as solid cortical bone lowers strain magnitudes substantially but the mode of deformation of the FE model is relatively constant. In contrast, omitting thin plates of bone in

  4. Flank pain

    MedlinePlus

    ... FF, ed. Ferri's Clinical Advisor 2015. Philadelphia: PA: Elsevier Mosby; 2015:1205-1207. Landry DW, Bazari H. ... eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 114. McQuaid K. Approach to ...

  5. Aquifers in melt-water channels along the southwest flank of the Des Moines Lobe, Lyon County, Minnesota

    USGS Publications Warehouse

    Schneider, Robert; Rodis, Harry G.

    1961-01-01

    The melt-water channels in Lyon County trend southeastward because the flank of the ice sheet was confined by a landmass that sloped to the northeast. Similar buried channels may be present elsewhere along the southwest flank of the Des Moines lobe. If so, they probably can be located by the methods described.

  6. Adhesive and Migratory Effects of Phosphophoryn Are Modulated by Flanking Peptides of the Integrin Binding Motif

    PubMed Central

    Suzuki, Shigeki; Kobuke, Seiji; Haruyama, Naoto; Hoshino, Hiroaki; Kulkarni, Ashok B.; Nishimura, Fusanori

    2014-01-01

    Phosphophoryn (PP) is generated from the proteolytic cleavage of dentin sialophosphoprotein (DSPP). Gene duplications in the ancestor dentin matrix protein-1 (DMP-1) genomic sequence created the DSPP gene in toothed animals. PP and DMP-1 are phosphorylated extracellular matrix proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs). Many SIBLING members have been shown to evoke various cell responses through the integrin-binding Arg-Gly-Asp (RGD) domain; however, the RGD-dependent function of PP is not yet fully understood. We demonstrated that recombinant PP did not exhibit any obvious cell adhesion ability, whereas the simultaneously purified recombinant DMP-1 did. A cell adhesion inhibitory analysis was performed by pre-incubating human osteosarcoma MG63 cells with various PP peptides before seeding onto vitronectin. The results obtained revealed that the incorporation of more than one amino acid on both sides of the PP-RGD domain was unable to inhibit the adhesion of MG63 cells onto vitronectin. Furthermore, the inhibitory activity of a peptide containing the PP-RGD domain with an open carboxyl-terminal side (H-463SDESDTNSESANESGSRGDA482-OH) was more potent than that of a peptide containing the RGD domain with an open amino-terminal side (H-478SRGDASYTSDESSDDDNDSDSH499-OH). This phenomenon was supported by the potent cell adhesion and migration abilities of the recombinant truncated PP, which terminated with Ala482. Furthermore, various point mutations in Ala482 and/or Ser483 converted recombinant PP into cell-adhesive proteins. Therefore, we concluded that the Ala482-Ser483 flanking sequence, which was detected in primates and mice, was the key peptide bond that allowed the PP-RGD domain to be sequestered. The differential abilities of PP and DMP-1 to act on integrin imply that DSPP was duplicated from DMP-1 to serve as a crucial extracellular protein for tooth development rather than as an integrin

  7. Assessment of the effect of reduced compositional heterogeneity on fracture resistance of human cortical bone using finite element modeling.

    PubMed

    Demirtas, Ahmet; Curran, Erin; Ural, Ani

    2016-10-01

    The recent reports of atypical femoral fracture (AFF) and its possible association with prolonged bisphosphonate (BP) use highlighted the importance of a thorough understanding of mechanical modifications in bone due to bisphosphonate treatment. The reduced compositional heterogeneity is one of the modifications in bone due to extensive suppression of bone turnover. Although experimental evaluations suggested that compositional changes lead to a reduction in the heterogeneity of elastic properties, there is limited information on the extent of influence of reduced heterogeneity on fracture resistance of cortical bone. As a result, the goal of the current study is to evaluate the influence of varying the number of unique elastic and fracture properties for osteons, interstitial bone, and cement lines on fracture resistance across seven different human cortical bone specimens using finite element modeling. Fracture resistance of seven human cortical bone samples under homogeneous and three different heterogeneous material levels was evaluated using a compact tension test setup. The simulation results predicted that the crack volume was the highest for the models with homogeneous material properties. Increasing heterogeneity resulted in a lower amount of crack volume indicating an increase in fracture resistance of cortical bone. This reduction was observed up to a certain level of heterogeneity after which further beneficial effects of heterogeneity diminished suggesting a possible optimum level of heterogeneity for the bone tissue. The homogeneous models demonstrated limited areas of damage with extensive crack formation. On the other hand, the heterogeneity in the material properties led to increased damage volume and a more variable distribution of damage compared to the homogeneous models. This resulted in uncracked regions which tended to have less damage accumulation preventing extensive crack propagation. The results also showed that the percent osteonal area

  8. Evidence for Pulsed Hydrothermal Venting from Young Abyssal Hills on the EPR Flank Suggests Frequent Seismic Pumping of Ridge Flank Fluid Flow

    NASA Astrophysics Data System (ADS)

    Haymon, R. M.; MacDonald, K. C.; Benjamin, S. B.; Ehrhardt, C. J.

    2004-12-01

    Although measured heat flow suggests that 40-50% of oceanic hydrothermal heat and fluid flux is from young (0.1-5 Ma) abyssal hill terrain on MOR flanks, hydrothermal vents in this setting rarely have been found. On the EPR flanks, seafloor evidence of venting from abyssal hills has been discovered recently at two sites: on ˜0.1 Ma seafloor at 10° 20'N, 103° 33.2'W ("Tevnia Site") and on ˜0.5 Ma seafloor at 9° 27'N, 104° 32.3'W ("Macrobes Site"). Manifestations of venting at these sites include: fault scarp hydrothermal mineralization and macrofauna; fault scarp flocculations containing hyperthermophilic microbes; and hilltop sediment mounds and craters possibly created by fluid "blow-outs." Hydrothermal deposits recovered at the ˜0.1 Ma "Tevnia Site" are fault breccias that record many episodes of brecciation followed by hydrothermal cementation (Benjamin et al., this session). Tubeworm casings, live crabs, and "dandelions" observed at this site indicate that the most recent episode of venting was active during, or shortly before, this site was visited with Alvin in 1994. To create the 200 m-high axis-facing fault scarp at Tevnia Site in 100,000 years, an average uplift rate of at least 2 cm/y is required. Since off-axis earthquakes located on abyssal hill fault scarps typically are

  9. Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) contains hypoxia response elements: relevance to lytic induction by hypoxia.

    PubMed

    Haque, Muzammel; Davis, David A; Wang, Victoria; Widmer, Isabelle; Yarchoan, Robert

    2003-06-01

    Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as human herpesvirus 8, is an etiologic agent of KS, primary effusion lymphoma (PEL), and multicentric Castleman's disease. We recently demonstrated that hypoxia can induce lytic replication of KSHV in PEL cell lines. Hypoxia induces the accumulation of hypoxia-inducible factors (HIF), and we hypothesized that the KSHV genome may respond to hypoxia through functional hypoxia response elements (HREs). Here, we demonstrate the presence of at least two promoters within the KSHV genome that are activated by hypoxia or hypoxia mimics. One is in the promoter region of the gene for Rta, the main lytic switch gene, and the other is within the promoter region of ORF34, a lytic gene of unknown function. The ORF34 promoter contains three putative consensus HREs oriented in the direction of the gene. Dissection and site-directed mutagenesis studies confirmed that one of the HREs of the ORF34 promoter is functional. Under conditions of hypoxia, the ORF34 promoter was strongly upregulated by HIF-1 alpha and HIF-2 alpha. By contrast, the promoter of the gene for Rta appeared to be preferentially upregulated by HIF-2 alpha. Reverse transcription-PCR analysis revealed that specific messages for ORF34 and ORF50 are upregulated in BCBL-1 cells exposed to hypoxia. An HIF-1 binding and competition assay demonstrated that the HRE sequence from the ORF34 promoter can compete for HIF-1 alpha binding to an erythropoietin HRE oligonucleotide while a mutant sequence cannot. Thus, we demonstrated that a viral gene can be activated by hypoxia through activation of a functional viral HRE. To our knowledge, this is the first example of a functional HRE in a viral promoter. PMID:12767996

  10. Validation of density-elasticity relationships for finite element modeling of human pelvic bone by modal analysis.

    PubMed

    Scholz, Roger; Hoffmann, Falk; von Sachsen, Sandra; Drossel, Welf-Guntram; Klöhn, Carsten; Voigt, Christian

    2013-10-18

    In total hip arthroplasty and particularly in revision surgery, computer assisted pre-operative prediction of the best possible anchorage strategy for implant fixation would be a great help to the surgeon. Computer simulation relies on validated numerical models. In the current study, three density-elasticity relationships (No. 1-3) from the literature for inhomogeneous material parameter assignment from CT data in automated finite element (FE) modeling of long bones were evaluated for their suitability for FE modeling of human pelvic bone. Numerical modal analysis was conducted on 10 FE models of hemipelvic bone specimens and compared to the gold standard provided by experimental modal analysis results from a previous in-vitro study on the same specimens. Overall, calculated resonance frequencies came out lower than measured values. Magnitude of mean relative deviation of numerical resonance frequencies with regard to measured values is lowest for the density-elasticity relationship No. 3 (-15.9%) and considerably higher for both density-elasticity relationships No. 1 (-41.1%) and No. 2 (-45.0%). Mean MAC values over all specimens amount to 77.8% (No. 1), 78.5% (No. 2), and 83.0% (No. 3). MAC results show, that mode shapes are only slightly influenced by material distribution. Calculated resonance frequencies are generally lower than measured values, which indicates, that numerical models lack stiffness. Even when using the best suited (No. 3) out of three investigated density-elasticity relationships, in FE modeling of pelvic bone a considerable underestimation of model stiffness has to be taken into account. PMID:24001928

  11. Stretch-dependent changes in surface profiles of the human crystalline lens during accommodation: A finite element study

    PubMed Central

    Pour, Hooman Mohammad; Kanapathipillai, Sangarapillai; Zarrabi, Khosrow; Manns, Fabrice; Ho, Arthur

    2015-01-01

    Background A nonlinear isotropic finite element (FE) model of a 29 year old human crystalline lens was constructed to study the effects of various geometrical parameters on lens accommodation. Methods The model simulates dis-accommodation by stretching of the lens and predicts the change in the lens capsule, cortex and nucleus surface profiles at select states of stretching/accommodation. Multiple regression analysis (MRA) is used to develop a stretch-dependent mathematical model relating the lens sagittal height to the radial position of the lens surface as a function of dis-accommodative stretch. A load analysis is performed to compare the FE results to empirical results from lens stretcher studies. Using the predicted geometrical changes, the optical response of the whole eye during accommodation was analysed by ray-tracing. Results Aspects of lens shape change relative to stretch were evaluated including change in diameter (d), central thickness (T) and accommodation (A). Maximum accommodation achieved was 10.29 D. From the MRA, the stretch-dependent mathematical model of the lens shape related lens curvatures as a function of lens ciliary stretch well (maximum mean-square residual error 2.5×10−3 µm, p<0.001). The results are compared with those from in vitro studies. Conclusions The FE and ray-tracing predictions are consistent with EVAS studies in terms of load and power change versus change in thickness. The mathematical stretch-dependent model of accommodation presented may have utility in investigating lens behaviour at states other than the relaxed or fully-accommodated states. PMID:25727940

  12. Serum response element-like sequences of the human low density lipoprotein receptor promoter: possible regulation sites for sterol-independent transcriptional activation.

    PubMed

    Pak, Y K

    1996-02-01

    Serum factors stimulate low density lipoprotein receptor (LDLR) gene expression in HepG2 cells through sterol-independent pathways. Promoter element other than sterol regulatory element-1 (SRE-1) seems to be necessary. Protein binding activity of the human LDLR promoter fragment (550bp) beyond the SRE-1 was determined by DNase I footprint assay. Five different promoter regions were protected from DNase I digestion; -226 to -258, -291 to -304, -324 to -336, -360 to -373, and -521 to -528. The regions of -324 to -336 and -521 to -528 showed serum response element (SRE)-like consensus sequence of CC(A/T)6GG. Serum incubation affected the protection degree of the SRE-like elements, but 25-hydroxycholesterol did not. It is proposed, therefore, that the promoter region of -324 to -336 and/or -521 to -528 showed serum response elements, but 25-hydroxycholesterol did not. It is proposed, therefore, that the promoter region of -324 to -336 and/or -521 to -528 in human LDLR gene may be responsible for the rapid activation of the gene transcription by serum factor in a sterol-independent manner. PMID:8932516

  13. Nuclear and related analytical techniques in ecology: Impact of geoecological factors on the balance of trace elements in the human organism

    NASA Astrophysics Data System (ADS)

    Gorbunov, A. V.; Lyapunov, S. M.; Okina, O. I.; Frontasyeva, M. V.; Pavlov, S. S.

    2012-11-01

    Current capabilities of the nuclear and related analytical techniques: neutron activation analysis, X-ray fluorescent analysis, and atomic adsorption spectrometry—are used to carry out multielement analysis of a wide range of foodstuffs and drinking water in various regions of Russia. The results of a more than 20-year-long collaboration of the Geological Institute, Russian Academy of Sciences, and the Neutron Activation Analysis and Applied Research Sector, Frank Laboratory of Neutron Physics, Joint Institute for Nuclear Research, in this field are presented. It is shown that the trace element content of agricultural products depends on the ecological and geochemical conditions in a particular region. A possibility of lettuce and spinach variety determination with respect to Cd and Pb contamination of the soil is demonstrated in the experiment with artificially produced soil contamination. Principles that may underlie accumulation of heavy metals and toxic elements by basidiomycetes are determined. Out of a great deal of human diets in use, the six most typical ones are selected and the intake of macro- and micronutrients from these diets by a human is evaluated. The effect produced on the human organism by the basic elements intake with the food and possible risks are discussed. Dependence of the trace element content of the drinking water on the ecological and geochemical conditions is investigated in three regions of Russia. It is shown that the quality of drinking water critically depends on the condition of the water supply system.

  14. The 5’ flanking region of miR-378 is hypomethylated in acute myeloid leukemia

    PubMed Central

    Zhu, Xiao-Wen; Wen, Xiang-Mei; Zhang, Ying-Ying; Yang, Lei; Guo, Hong; Yang, Jing; Zhang, Ming; Yin, Jia-Yu; Ma, Ji-Chun; Lin, Jiang; Deng, Zhao-Qun; Qian, Jun

    2015-01-01

    Background: Aberrant expression of miR-378 has been observed in various malignancies including acute myeloid leukemia (AML). However, the mechanism regulating of miR-378 expression remains unknown. This study was aimed to investigate miR-378 methylation and to explore its clinical significance in AML. Methods: Methylation status of miR-378 5’-flanking region was investigated by real-time quantitative methylation-specific PCR (RQ-MSP) and bisulfite-sequencing PCR (BSP). The expression of miR-378 was evaluated by real-time quantitative PCR (RQ-PCR). The correlation between expression of miR-378 and 5’-flanking region methylation was analyzed using 5-aza-2’-deoxycytidine (5-aza-dC) treatment. Results: miR-378 5’-flanking region was significantly hypomethylated in AML patients compared to controls (median 0.109 vs. 0.058) (P=0.048). miR-378 expression was correlated with miR-378 5’-flanking region in leukemic cell line treated with 5-aza-dC, but not in AML patients. The level of miR-378 hypomethylation significantly increased in M2 subtype compared to other subtypes. Moreover, patients with t(8;21) harbored the highest level of miR-378 hypomethylation. However, there was no significant difference in overall survival between patients with high and low miR-378 hypomethylation. The association of miR-378 expression with methylation was not observed in AML patients, but miR-378 expression in THP-1 line was increased while methylation status of miR-378 5-flanking region was decreased after 5-aza-dC treatment. Conclusions: Our findings suggest that miR-378 is reactivated by demethylation after 5-aza-dC treatment. 5’-flanking region of miR-378 is hypomethylated in AML especially in those with t(8;21). PMID:26191124

  15. Sequences flanking the pentanucleotide T-antigen binding sites in the polyomavirus core origin help determine selectivity of DNA replication.

    PubMed Central

    Li, L; Li, B L; Hock, M; Wang, E; Folk, W R

    1995-01-01

    Replication of the genomes of the polyomaviruses requires two virus-specified elements, the cis-acting origin of DNA replication, with its auxiliary DNA elements, and the trans-acting viral large tumor antigen (T antigen). Appropriate interactions between them initiate the assembly of a replication complex which, together with cellular proteins, is responsible for primer synthesis and DNA chain elongation. The organization of cis-acting elements within the origins of the polyomaviruses which replicate in mammalian cells is conserved; however, these origins are sufficiently distinct that the T antigen of one virus may function inefficiently or not at all to initiate replication at the origin of another virus. We have studied the basis for such replication selectivity between the murine polyomavirus T antigen and the primate lymphotropic polyomavirus origin. The murine polyomavirus T antigen is capable of carrying out the early steps of the assembly of an initiation complex at the lymphotropic papovavirus origin, including binding to and deformation of origin sequences in vitro. However, the T antigen inefficiently unwinds the origin, and unwinding is influenced by sequences flanking the T antigen pentanucleotide binding sites on the late side of the viral core origin. These same sequences contribute to the replication selectivity observed in vivo and in vitro, suggesting that the inefficient unwinding is the cause of the replication defect. These observations suggest a mechanism by which origins of DNA replication can evolve replication selectivity and by which the function of diverse cellular origins might be temporally activated during the S phase of the eukaryotic cell cycle. PMID:7494263

  16. Fluid and chemical fluxes along a buried-basement ridge in the eastern Juan de Fuca Ridge flank

    NASA Astrophysics Data System (ADS)

    Hulme, S.; Wheat, C. G.

    2010-12-01

    Hydrothermal fluid circulation within oceanic crust at low temperatures affects global biogeochemical cycles, with the volume of fluid circulation rivaling that of the world’s water flux to the oceans from rivers. Our work focuses on the best studied low temperature hydrothermal system on the eastern flank of the Juan de Fuca Ridge where a buried basement ridge 100 km from the active spreading axis has been sampled with a variety of mediums. We use data from deep sea drilling, gravity coring, and submersible operations from five sites along-strike of the buried ridge to better constrain the chemical and fluid fluxes along this transect. A transport (advection-diffusion) model is applied to the data, constraining the volumetric fluid flux per unit length within the oceanic crust from 0.05 and 0.2 m3 y-1 cm-1 and identifying conservative elements within this system. Using an average fluid flux, reactive fluxes are determined for non-conservative elements within basaltic crust for twenty-four chemical species. Conservative species include K, Cl, SO4, Ba, Sr, Cs, Mo, and Y. Only Ca and the rare earth elements Ce and Gd are produced by basaltic basement. The remaining chemical species Mg, Na, ammonium, Li, Rb, Mn, Fe, Co, Zn, Cd, U, La and Yb are all consumed within upper basaltic basement. Fluxes of potentially-bioavailable redox species ammonium, Fe, and Mn into the upper basaltic basement are 3 to 20 nmol y-1cm-2. Possible mechanisms of removal are suggested, placing constraints on microbial metabolic activity and biomineralization.

  17. A reconnaissance for signs of a Mississippi Valley-type lead-zinc mineralizing system on the eastern flank of the Rutbah Uplift, Anbar Province, Iraq

    USGS Publications Warehouse

    Hayes, Timothy S.; Mustafa, Mazin; Bennet, Thair

    2014-01-01

    Reconnaissance field visits and rock sampling were conducted at eight geologically selected locations within Mesozoic rocks on the eastern flank of the Rutbah Uplift, Anbar Province, western Iraq, in an attempt to determine if these rocks have been affected by a Mississippi Valley-Type (MVT) lead-zinc mineralizing system. Samples subsequently were studied by carbonate mineral staining, transmitted and reflected light petrology, and scanning electron microscopy with semi-quantitative energy dispersive elemental analyses. Single samples were studied by each, inductively coupled plasma mass spectrometry analyses of trace elements and fluid inclusion microthermometry. Permissive evidence indicates that there has been a MVT system present, but none of the evidence is considered definitive.

  18. Genomic Loci of the Porphyromonas gingivalis Insertion Element IS1126

    PubMed Central

    Dong, Hong; Chen, Tsute; Dewhirst, Floyd E.; Fleischmann, Robert D.; Fraser, Claire M.; Duncan, Margaret J.

    1999-01-01

    The Porphyromonas gingivalis genome contains multiple copies of insertion element IS1126. When chromosomal DNA digests of different strains were probed with IS1126, between 25 and 35 hybridizing fragments per genome were detected, depending on the strain. Unrelated strains had very different restriction fragment length polymorphism (RFLP) patterns. When different laboratory copies of a specific strain were examined, the IS1126 RFLP patterns were very similar but small differences were observed, indicating that element-associated changes had occurred during laboratory passage. Within the next year, genome sequencing, assembly, and annotation for P. gingivalis W83 will be completed. Because repetitive elements complicate the assembly of randomly sequenced DNA fragments, we isolated and sequenced the flanking regions of IS1126 copies in strain W83. We also isolated and sequenced the flanking regions of IS1126 copies in strain ATCC 33277 in order to compare insertion sites in phylogenetically divergent strains. We identified 37 new sequences flanking IS1126 from strain ATCC 33277 and 30 from strain W83. The insertion element was found between genes except where it transposed into another insertion element. Examination of identifiable flanking genes or open reading frames indicated that the insertion sites were different in the two strains, except that both strains possess an insertion adjacent to the Lys-gingipain gene (J. P. Lewis and F. L. Macrina, Infect. Immun. 66:3035–3042, 1998). Most of the genes or sequences flanking IS1126 in ATCC 33277 were present in W83 but were contiguous and not insertion element associated. Thus, where genes were identified in both strains, their order was maintained, indicating that the two genomes are organized similarly, but the loci of IS1126 are different. In both strains, insertion element-associated duplicated target sites were lost from several copies of IS1126, providing evidence of homologous recombination between elements

  19. Finite element stress analysis of the human left ventricle whose irregular shape is developed from single plane cineangiocardiogram

    NASA Technical Reports Server (NTRS)

    Ghista, D. N.; Hamid, M. S.

    1977-01-01

    The three-dimensional left ventricular chamber geometrical model is developed from single plane cineangiocardiogram. This left ventricular model is loaded by an internal pressure monitored by cardiac catheterization. The resulting stresses in the left ventricular model chamber's wall are determined by computerized finite element procedure. For the discretization of this left ventricular model structure, a 20-node, isoparametric finite element is employed. The analysis and formulation of the computerised procedure is presented in the paper, along with the detailed algorithms and computer programs. The procedure is applied to determine the stresses in a left ventricle at an instant, during systole. Next, a portion (represented by a finite element) of this left ventricular chamber is simulated as being infarcted by making its active-state modulus value equal to its passive-state value; the neighbouring elements are shown to relieve the 'infarcted' element of stress by themselves taking on more stress.

  20. Oceanic phosphorus imbalance: Magnitude of the mid-ocean ridge flank hydrothermal sink

    NASA Astrophysics Data System (ADS)

    Wheat, C. Geoffrey; McManus, James; Mottl, Michael J.; Giambalvo, Emily

    2003-09-01

    We present a new estimate for the crustal phosphorous sink that results from reactions among seawater, basalt, and sediment blanketing low temperature mid-ocean ridge flank hydrothermal systems. New estimates for global hydrothermal power output, sediment thickness, and the dissolved phosphate concentrations in basement formation fluids indicate that fluid flow through ridge flanks removes 2.8 × 1010 mol P yr-1. This value is larger (130%) than the riverine dissolved flux of inorganic phosphate and is as much as 35% of the sedimentary P sink. The concordant seawater flux (2.1 × 1016 kg yr-1) is 65% of the riverine fluid flux and circulates a fluid volume equivalent to the entire ocean in about 70,000 yr. Additional sampling of seafloor springs is required to further constrain the range of calculated phosphate fluxes; nevertheless the modern phosphorus budget is clearly unbalanced with total sinks outpacing sources.

  1. Piggyback tectonics: Long-term growth of Kilauea on the south flank of Mauna Loa

    USGS Publications Warehouse

    Lipman, P.W.; Sisson, T.W.; Coombs, M.L.; Calvert, A.; Kimura, Jun-Ichi

    2006-01-01

    Compositional and age data from offshore pillow lavas and volcaniclastic sediments, along with on-land geologic, seismic, and deformation data, provide broad perspectives on the early growth of Kilauea Volcano and the long-term geometric evolution of its rift zones. Sulfur-rich glass rinds on pillow lavas and volcaniclastic sediments derived from them document early underwater growth of a large compositionally diverse alkalic edifice. The alkalic rocks yield 40Ar/39Ar ages as old as about 275 ka; transitional-composition lavas, which mark beginning of the shield stage while most or all the edifice remained below sea level, probably first erupted after about 150 ka, and tholeiitic lavas of present-day type are probably younger than 100 ka. Breccia clasts from Papau Seamount and along the lower southwest corner of the Hilina bench are derived from subaerial Mauna Loa, requiring that Mauna Loa's flank underlies western parts of Kilauea at shallow depth. The volume of the Kilauea edifice is therefore smaller (???10,000 km3) than previous estimates (15-40,000 km3); lava-thickness accumulation rates appear to have remained nearly constant during edifice growth, as effusion rates increased from ???25 ?? 106 m3/yr at end of the alkalic stage to the present-day tholeiite rate of ???100 ?? 106 m3/yr. Seismic and gravity data show that the deep plumbing system for Kilauea's magma supply extends nearly vertically through the oceanic crust at least to mantle depths of 30-35 km, directly below its present-day caldera. Proximity of Kilauea's caldera to the surface boundary with Mauna Loa and the presence of Mauna Loa rocks at shallow depth beneath the south flank are difficult to reconcile with a submarine origin for early Kilauea alkalic lavas, unless geometric relations between the two volcanoes have changed substantially during growth of the Kilauea shield. Seismic and ground deformation data suggest seaward spreading of the entire south flank of Hawaii Island, independently

  2. Disparity capture by flanking stimuli: a measure for the cooperative mechanism of stereopsis.

    PubMed

    Petrov, Yury

    2002-03-01

    In this work the range and scaling properties of the cooperative (contextual) interaction that was first proposed by Julesz [Foundations of Cyclopean Perception, University of Chicago Press, Chicago, 1971] to address the correspondence problem in stereopsis is measured. To this end the effect that flanking difference of Gaussians (DoG) patches produce on a perception of a target pair of patches is studied. The relative depth configuration of the target pair can switch from the small disparity gradient to a large disparity gradient state as a result of cooperative effects of the flanking stimuli. It is found that the interaction strength falls with distance. Its range varies for different subjects from 2 to 3 DoG patch sizes and scales proportionally to the size of the stimuli. The results suggest that a very localized cooperative interaction is in effect at a broad range of spatial scales. PMID:11927347

  3. The Silent Earthquakes of Kilauea's South Flank and their Ramifications for Catastrophic Failure

    NASA Astrophysics Data System (ADS)

    Cervelli, P. F.

    2004-12-01

    The south flank of Kilauea Volcano is one of the most actively deforming regions on the planet. GPS measurements taken there since the early 1990s show a persistent seaward migration at rates exceeding 5 cm/yr. Large earthquakes occur on Kilauea with alarming frequency. The largest in historical times, a M7.2 event in 1975, caused more than 6 m of seaward displacement in addition to 3.5 m of coastal subsidence. In the last few years, an intermediate form of south flank deformation has been observed. With slip rates of about 10 cm/day, these so-called ``silent earthquake'' are much slower than the nearly instantaneous brittle failure of normal earthquakes, but vastly faster than the creep that carries the south flank relentlessly toward the sea. Kilauea is the latest subaerial volcano in an archipelago of volcanic islands stretching back to the Kamchatka Peninsula. In just the youngest part of this chain, the modern Hawaiian islands, there are more than 70 submarine debris fields, each thought to represent an ancestral flank collapse. If these collapses occurred catastrophically, they almost certainly created tsunami large enough to inundate nearby islands and perhaps long-lived enough to threaten the entire Pacific basin. Evidence for prehistoric inundation on the Hawaiian island consists of anomalously elevated detrital coral deposits, found at several locales and interpreted as the diaspora of passing tsunami. As the youngest and most active of the subaerial Hawaiian volcanoes, it is natural to wonder if Kilauea--in particular the south flank--is the most likely place for future catastrophic collapses. Since the creation of the continuous GPS network on Kilauea in the mid-1990s, as many as four silent earthquakes have been detected. Two of these, occurring in November 2000 and July 2003, have resulted in elastic deformation fields large enough to model. The modeling shows that these events occurred on a shallow ( ˜ 5 km depth) landward dipping fault, possibly

  4. Genomic organization and 5{prime}-flanking DNA sequence of the murine stomatin gene (Epb72)

    SciTech Connect

    Gallagher, P.G.; Turetsky, T.; Mentzer, W.C.

    1996-06-15

    Stomatin is a poorly understood integral membrane protein that is absent from the erythrocyte membranes of many patients with hereditary stomatocytosis. This report describes the cloning of the murine stomatin chromosomal gene, determination of its genomic structure, and characterization of the 5{prime}-flanking genomic DNA sequences. The stomatin gene is encoded by seven exons spread over {approximately}25 kb of genomic DNA. There is no concordance between the exon structure of the stomatin gene and the locations of three domains predicted on the basis of protein structure. Inspection of the 5{prime}-flanking DNA sequences reveals features of a TATA-less housekeeping gene promoter and consensus sequences for a number of potential DNA-binding proteins. 12 refs., 2 figs., 1 tab.

  5. Germ Cell-Specific Excision of loxP-Flanked Transgenes in Rainbow Trout Oncorhynchus mykiss.

    PubMed

    Katayama, Naoto; Kume, Sachi; Hattori-Ihara, Shoko; Sadaie, Sakiko; Hayashi, Makoto; Yoshizaki, Goro

    2016-04-01

    Cre/loxP-mediated DNA excision in germ cell lineages could contribute substantially to the study of germ cell biology in salmonids, which are emerging as a model species in this field. However, a cell type-specific Cre/loxPsystem has not been successfully developed for any salmonid species. Therefore, we examined the feasibility of Cre/loxP-mediated, germ cell-specific gene excision and transgene activation in rainbow trout. Double-transgenic (wTg) progeny were obtained by mating a transgenic male carryingcrewith a transgenic female carrying thehsc-LRLGgene;crewas driven by rainbow troutvasaregulatory regions and thehsc-LRLGgene was made up of the rainbow troutheat-shock-cognate71promoter, theDsRedgene flanked by twoloxPsites, and theEgfpgene. PCR analysis, fluorescence imaging, and histological analysis revealed that excision of theloxP-flanked sequence and activation ofEgfpoccurred only in germ cells of wTg fish. However, progeny tests revealed that the excision efficiency ofloxP-flanked sequence in germ cells was low (≤3.27%). In contrast, the other wTg fish derived from two differentcre-transgenic males frequently excised theloxP-flanked sequence in germ cells (≤89.25%). Thus, we showed for the first time successful germ cell-specific transgene manipulation via the Cre/loxPsystem in rainbow trout. We anticipate that this technology will be suitable for studies of cell function through cell targeting, cell-linage tracing, and generating cell type-specific conditional gene knockouts and separately for developing sterile rainbow trout in aquaculture. PMID:26911430

  6. Evidence of sheared sills related to flank destabilization in a basaltic volcano

    NASA Astrophysics Data System (ADS)

    Berthod, C.; Famin, V.; Bascou, J.; Michon, L.; Ildefonse, B.; Monié, P.

    2016-04-01

    Piton des Neiges basaltic volcano (La Réunion) has been deeply dissected by erosion, exposing large volumes of debris avalanche deposits. To shed light on the factors that led to volcano flank destabilizations, we studied the structure, the crystallographic and magnetic fabrics of the substratum of a debris avalanche unit. This substratum is a complex of > 50 seaward-dipping sills that has been exposed by the avalanche. Structural observations show that the sill plane in contact with the avalanche is one of the latest intrusions in the sill complex. In this uppermost sill, the anisotropy of magnetic susceptibility (AMS) is correlated to the crystallographic preferred orientation of magmatic silicate minerals, allowing us to use AMS as a proxy to infer the magmatic flow. The AMS fabric across the intrusion is strongly asymmetric, which reveals that the contact sill was emplaced with a normal shear displacement of its hanging wall. The shear displacement and the magma flow in the intrusion are both directed toward the NNE, i.e. toward the sea, which is also the direction of the slope and of the debris avalanche runout. Because all the sills in the intrusion complex have a similar dip and dip direction, it is likely that several of them also underwent a cointrusive slip toward the NNE. We conclude that this cointrusive normal slip, repeated over many intrusions of the sill complex, increased the flank instability of the volcano. This incremental instability may have ended up into the observed debris avalanche deposit. At Piton de la Fournaise, the active volcano of La Réunion, sill intrusion and cointrusive flank displacement have been inferred from geophysical studies for the April 2007 eruption. By providing direct evidence of sheared sills, our study substantiates the idea that repeated sill intrusions may eventually trigger flank destabilizations in basaltic volcanoes.

  7. Evidence for a Mega-Tsunami Generated by Giant Flank Collapse of Fogo Volcano, Cape Verde

    NASA Astrophysics Data System (ADS)

    Ramalho, R. S.; Madeira, J.; Helffrich, G. R.; Schaefer, J. M.; Winckler, G.; Quartau, R.; Adena, K.

    2013-12-01

    Mega-tsunamis generated by ocean island flank collapses are expected to be some of the most hazardous forces of nature, yet evidence for their near-source effects and inferred high run-ups so far is scarce or hotly debated. A newly discovered deposit on the northern coast of Santiago Island (Cape Verde), however, documents the magnitude and run-up height associated with this kind of event. Additionally to chaotic conglomerates distributed from sea-level up to 100 m elevation standing on slopes as steep as 20°, the deposit comprises a number of scattered megaclasts of submarine lava flows, limestone and tuff. The megaclasts are presently located over a higher substructural slope built on younger subaerial lava flows and at elevations ranging 160-220 m a.s.l. All megaclasts correspond to lithologies that crop out exclusively in nearby cliff faces. The origin of this deposit is consequently attributed to an exceptional wave that plucked blocks from the cliff face, transported them inland and deposited them over the higher slopes of the volcanic edifice. The distribution of the megaclasts, together with the local geomorphology, is in agreement with a tsunami that approached the island edifice from the west and was refracted along its northern flank, flooding a series of northwest-oriented valleys. This suggests that the well-known flank collapse of Fogo volcano, located 55 km west of Santiago, is the most likely source, a hypothesis being tested with surface exposure dating. The inferred run-up exceeded 200 m and is consistent with numerical simulations by Paris et al. 2011, implying that the present Fogo island morphology probably developed by at least one giant flank collapse with devastating near-source effects.

  8. A 75-year old man complaining of flank pain and obstructive urinary symptoms: a case report.

    PubMed

    Mohseni, Mohammad-Ghasem; Hamidi, Morteza; Salavati, Alborz; Rangzan, Nazir; Kowsari, Farid

    2011-01-01

    Benign renal cystic adenoma with out malignant features is a very rare entity. A 75 year old male with obstructive Lower tract symptoms and vague flank pain was admitted and planned for nephrectomy of non functional kidney -due to long term nephrolithiasis- intra operative finding was a cystic hydronephrotic kidney filled by thick mucous secretions which turned out to be a cyst adenoma of kidney with no malignant features. PMID:21960085

  9. Rejuvenation of the Kuqa foreland basin, northern flank of the Tarim basin, northwest China

    SciTech Connect

    Lu Huafu; Jia Dong; Cai Dongsheng

    1994-12-01

    The Kuqa depression along the northern flank of the Tarim basin is filled with a thick sequence of Neogene and Quaternary coarse elastic continental sediments. This structural depression is part of a large foreland basin that leads south of the Tianshan - an orogenic belt of intracontinental convergence resulting from the northward propagation of stress following the collision of India with the southern margin of Eurasia. 11 refs., 6 figs., 1 tab.

  10. Hazard Potential of Volcanic Flank Collapses Raised by New Megatsunami Evidence

    NASA Astrophysics Data System (ADS)

    Ramalho, R. S.; Winckler, G.; Madeira, J.; Helffrich, G. R.; Hipólito, A.; Quartau, R.; Adena, K.; Schaefer, J. M.

    2015-12-01

    Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet evidence for the existence and impact of collapsed-triggered megatsunamis and their run-up heights remains scarce and/or is highly contentious. Therefore a considerable debate still exists over the potential magnitude of collapse-triggered tsunamis and their inherent hazard. In particular, doubts still remain whether or not large-scale flank failures typically generate enough volume flux to result in megatsunamis, or alternatively operate by slow-moving or multiple smaller episodic failures with much lower tsunamigenic potential. Here we show that one of the tallest and most active oceanic volcanoes on Earth - Fogo, in the Cape Verde Islands - collapsed catastrophically and triggered a megatsunami with devastating near-field effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic 3He dating of tsunamigenic deposits - comprising fields of stranded megaclasts, chaotic conglomerates, and sand sheets - found on the adjacent Santiago Island, which attest to the impact of this megatsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo's flank failure involved at least one sudden and voluminous event that resulted in a megatsunami, in contrast to what has been suggested before. Our work thus provides another line of evidence that large-scale flank failures at steep volcanic islands may indeed happen catastrophically and are capable of triggering tsunamis of enormous height and energy. This new line of evidence therefore reinforces the hazard potential of volcanic island collapses and stands as a warning that such hazard should not be underestimated, particularly in areas where volcanic island edifices are close to other islands or to highly populated continental margins.

  11. Microbial Life in Ridge Flank Crustal Fluids at Baby Bare Seamount, Juan de Fuca Ridge

    NASA Astrophysics Data System (ADS)

    Huber, J. A.; Johnson, H. P.; Butterfield, D. A.; Baross, J. A.

    2005-12-01

    To determine the microbial community diversity within old ocea