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Sample records for elements flanking human

  1. Sequences flanking the repeat arrays of human minisatellites: association with tandem and dispersed repeat elements.

    PubMed Central

    Armour, J A; Wong, Z; Wilson, V; Royle, N J; Jeffreys, A J

    1989-01-01

    We present DNA sequences flanking cloned hypervariable human minisatellites. In addition to providing confirmatory evidence that minisatellites cluster with other tandem repeats, these flanking sequences contain a high frequency of interspersed repetitive elements. These elements include a retroviral LTR-like sequence, from which one of the minisatellites appears to have expanded, and a recently described short interspersed repeat. We present our own findings concerning this element, in particular that those examples studied do not show significant evolutionary conservation, despite suggestions that the element may have a cis-acting function. Images PMID:2762114

  2. Constitutive androstane receptor transcriptionally activates human CYP1A1 and CYP1A2 genes through a common regulatory element in the 5'-flanking region.

    PubMed

    Yoshinari, Kouichi; Yoda, Noriaki; Toriyabe, Takayoshi; Yamazoe, Yasushi

    2010-01-15

    Phenobarbital has long been known to increase cellular levels of CYP1A1 and CYP1A2 possibly through a pathway(s) independent of aryl hydrocarbon receptor. We have investigated the role of constitutive androstane receptor (CAR), a xenobiotic-responsive nuclear receptor, in the transactivation of human CYP1A1 and CYP1A2. These genes are located in a head-to-head orientation, sharing a 5'-flanking region. Reporter assays were thus performed with dual-reporter constructs, containing the whole or partially deleted human CYP1A promoter between two different reporter genes. In this system, human CAR (hCAR) enhanced the transcription of both genes through common promoter regions from -461 to -554 and from -18089 to -21975 of CYP1A1. With reporter assays using additional deleted and mutated constructs, electrophoresis mobility shift assays and chromatin immunoprecipitation assays, an ER8 motif (everted repeat separated by eight nucleotides), located at around -520 of CYP1A1, was identified as an hCAR-responsive element and a binding motif of hCAR/human retinoid X receptor alpha heterodimer. hCAR enhanced the transcription of both genes also in the presence of an aryl hydrocarbon receptor ligand. Finally, hCAR activation increased CYP1A1 and CYP1A2 mRNA levels in cultured human hepatocytes. Our results indicate that CAR transactivates human CYP1A1 and CYP1A2 in human hepatocytes through the common cis-element ER8. Interestingly, the ER8 motif is highly conserved in the CYP1A1 proximal promoter sequences of various species, suggesting a fundamental role of CAR in the xenobiotic-induced expression of CYP1A1 and CYP1A2 independent of aryl hydrocarbon receptor.

  3. Isolation and characterization of the 5'-flanking sequence of the human ocular lens MIP gene.

    PubMed

    Wang, X Y; Ohtaka-Maruyama, C; Pisano, M M; Jaworski, C J; Chepelinsky, A B

    1995-12-29

    The MIP (major intrinsic protein) gene, a member of an ancient family of membrane channel genes, encodes the predominant fiber cell membrane protein of the ocular lens. Its specific expression in the lens fibers is temporally and spatially regulated during development. To study the regulation of expression of MIP and delineate the regulatory elements underlying its tissue specificity and ontogenic profile, we have cloned 2840 bp of the human MIP 5'-flanking sequence. The human MIP 5'-flanking sequence contains three complete Alu repetitive elements in tandem at position between nt -1699 and -2684 (nt -1699/-2684). These Alu elements appear to have had a complex evolutionary history with insertions at different times. We have fused DNA fragments containing MIP 5'-flanking sequences to the bacterial cat reporter gene encoding chloramphenicol acetyltransferase and assayed them in primary cultures of chicken lens cells. We have mapped two negative regulatory regions in the human MIP 5'-flanking sequences -1564/-1696 and -948/-1000. We demonstrated that the human MIP 5'-flanking sequence -253/+42 contains a functional promoter in lens cells but is inactive in kidney epithelial cells or mouse fibroblasts, suggesting that this sequence contains regulatory elements responsible for the lens-specific expression of MIP.

  4. 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.

  5. 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

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

    PubMed

    Chen, Zhuo; Xu, Shixia; Zhou, Kaiya; Yang, Guang

    2011-10-27

    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. 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. 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 relationships in the future.

  7. 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

  8. Thermodynamic stability and folding kinetics of the major G-quadruplex and its loop-isomers formed in the Nuclease Hypersensitive Element in the human c-Myc promoter-Effect of loops and flanking segments on the stability of parallel-stranded intramolecular G-quadruplexes

    PubMed Central

    Hatzakis, Emmanuel; Okamoto, Keika; Yang, Danzhou

    2010-01-01

    Overexpression of the c-Myc proto-oncogene is associated with a broad spectrum of human cancers. The nuclease hypersensitivity element III1 (NHE III1) of the c-Myc promoter can form transcriptionally active and silenced forms and the formation of DNA G-quadruplex structures has been shown to be critical for c-Myc transcriptional silencing. The major G-quadruplex formed in the c-Myc NHE III1 is a mixture of four loop-isomers, which have all been shown to be biologically relevant to c-Myc transcriptional control. In this study we performed a thorough thermodynamic and kinetic study of the four c-Myc loop-isomers in K+ solution. The four loop-isomers all form parallel-stranded G-quadruplexes with short loop lengths. While the parallel-stranded G-quadruplex has been known to favor short loop lengths, our results show that the difference in thermodynamic and kinetic properties of the four loop-isomers, and hence between the parallel G-quadruplexes with similar loop lengths, is more significant than previously recognized. At 20 mM K+, the average difference of the Tm values between the most stable loop-isomer 14/23 and the least stable loop-isomer 11/20 is greater than 10 degrees. In addition, the capping structures formed by the extended flanking segments are shown to contribute to a stabilization of 2–3°C in Tm for the c-Myc promoter G-quadruplex. Understanding the intrinsic thermodynamic stability and kinetic properties of the c-Myc G-quadruplex loop-isomers can help understand their biological roles and drug targeting. PMID:20849082

  9. 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 ...

  10. Splicing of intron 3 of human BACE requires the flanking introns 2 and 4.

    PubMed

    Annies, Maik; Stefani, Muriel; Hueber, Andreas; Fischer, Frauke; Paganetti, Paolo

    2009-10-16

    Regulation of proteolytic cleavage of the amyloid precursor protein by the aspartic protease BACE may occur by alternative splicing and the generation of enzymatically inactive forms. In fact, the presence of exonic donor and acceptor sites for intron 3 generates the two deficient variants BACE457 and BACE476. In HEK293 cells, when introns are inserted separately in the BACE cDNA, we found that whilst introns 2 and 4 are efficiently spliced out, intron 3 is not removed. On the other hand, splicing to wild-type BACE is restored when intron 3 is flanked by the two other introns. The presence of all three introns also leads to alternative splicing of intron 3 and the generation of BACE476. In contrast, BACE457 expression takes place only after mutating the donor splice site of intron 3, indicating that additional regulatory elements are necessary for the use of the splicing site within exon 4. Overall, our data demonstrate that a complex splicing of intron 3 regulates the maturation of the BACE mRNA. This appears orchestrated by domains present in the exons and introns flanking intron 3. Excessive BACE activity is a risk factor for Alzheimer's disease, therefore this complex regulation might guarantee low neuronal BACE activity and disease prevention.

  11. Retroposed elements and their flanking regions resolve the evolutionary history of xenarthran mammals (armadillos, anteaters, and sloths).

    PubMed

    Möller-Krull, Maren; Delsuc, Frédéric; Churakov, Gennady; Marker, Claudia; Superina, Mariella; Brosius, Jürgen; Douzery, Emmanuel J P; Schmitz, Jürgen

    2007-11-01

    Armadillos, anteaters, and sloths (Order Xenarthra) comprise 1 of the 4 major clades of placental mammals. Isolated in South America from the other continental landmasses, xenarthrans diverged over a period of about 65 Myr, leaving more than 200 extinct genera and only 31 living species. The presence of both ancestral and highly derived anatomical features has made morphoanatomical analyses of the xenarthran evolutionary history difficult, and previous molecular analyses failed to resolve the relationships within armadillo subfamilies. We investigated the presence/absence patterns of retroposons from approximately 7,400 genomic loci, identifying 35 phylogenetically informative elements and an additional 39 informative rare genomic changes (RGCs). DAS-short interspersed elements (SINEs), previously described only in the Dasypus novemcinctus genome, were found in all living armadillo genera, including the previously unsampled Chlamyphorus, but were noticeably absent in sloths. The presence/absence patterns of the phylogenetically informative retroposed elements and other RGCs were then compared with data from the DNA sequences of the more than 12-kb flanking regions of these retroposons. Together, these data provide the first fully resolved genus tree of xenarthrans. Interestingly, multiple evidence supports the grouping of Chaetophractus and Zaedyus as a sister group to Euphractus within Euphractinae, an association that was not previously demonstrated. Also, flanking sequence analyses favor a close phylogenetic relationship between Cabassous and Tolypeutes within Tolypeutinae. Finally, the phylogenetic position of the subfamily Chlamyphorinae is resolved by the noncoding sequence data set as the sister group of Tolypeutinae. The data provide a stable phylogenetic framework for further evolutionary investigations of xenarthrans and important information for defining conservation priorities to save the diversity of one of the most curious groups of mammals.

  12. 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

  13. Early demethylation of non-CpG, CpC-rich, elements in the myogenin 5′-flanking region

    PubMed Central

    Fuso, Andrea; Ferraguti, Giampiero; Grandoni, Francesco; Ruggeri, Raffaella; Scarpa, Sigfrido; Strom, Roberto

    2010-01-01

    The dynamic changes and structural patterns of DNA methylation of genes without CpG islands are poorly characterized. The relevance of CpG to the non-CpG methylation equilibrium in transcriptional repression is unknown. In this work, we analyzed the DNA methylation pattern of the 5′-flanking of the myogenin gene, a positive regulator of muscle differentiation with no CpG island and low CpG density, in both C2C12 muscle satellite cells and embryonic muscle. Embryonic brain was studied as a non-expressing tissue. High levels of both CpG and non-CpG methylation were observed in non-expressing experimental conditions. Both CpG and non-CpG methylation rapidly dropped during muscle differentiation and myogenin transcriptional activation with active demethylation dynamics. Non-CpG demethylation occurred more rapidly than CpG demethylation. Demethylation spread from initially highly methylated short CpC-rich elements to a virtually unmethylated status. These short elements have a high CpC content and density, share some motifs and largely coincide with putative recognition sequences of some differentiation-related transcription factors. Our findings point to a dynamically controlled equilibrium between CpG and non-CpG active demethylation in the transcriptional control of tissue-specific genes. The short CpC-rich elements are new structural features of the methylation machinery, whose functions may include priming the complete demethylation of a transcriptionally crucial DNA region. PMID:20935518

  14. Finite Element Analysis Of Influence Of Flank Wear Evolution On Forces In Orthogonal Cutting Of 42CrMo4 Steel

    NASA Astrophysics Data System (ADS)

    Madajewski, Marek; Nowakowski, Zbigniew

    2017-01-01

    This paper presents analysis of flank wear influence on forces in orthogonal turning of 42CrMo4 steel and evaluates capacity of finite element model to provide such force values. Data about magnitude of feed and cutting force were obtained from measurements with force tensiometer in experimental test as well as from finite element analysis of chip formation process in ABAQUS/Explicit software. For studies an insert with complex rake face was selected and flank wear was simulated by grinding operation on its flank face. The aim of grinding inset surface was to obtain even flat wear along cutting edge, which after the measurement could be modeled with CAD program and applied in FE analysis for selected range of wear width. By comparing both sets of force values as function of flank wear in given cutting conditions FEA model was validated and it was established that it can be applied to analyze other physical aspects of machining. Force analysis found that progression of wear causes increase in cutting force magnitude and steep boost to feed force magnitude. Analysis of Fc/Ff force ratio revealed that flank wear has significant impact on resultant force in orthogonal cutting and magnitude of this force components in cutting and feed direction. Surge in force values can result in transfer of substantial loads to machine-tool interface.

  15. Sequence analysis of a group of low molecular-weight plasmids carrying multiple IS903 elements flanking a kanamycin resistance aph gene in Salmonella enterica serovars

    USDA-ARS?s Scientific Manuscript database

    A group of low molecular-weight ColE1-like plasmids carrying the aph sequence type aph(ii), from three different Salmonella serovars were sequenced. These plasmids carry 2 or more copies of IS903 elements, with up to 21 bp sequence differences to one another, two of which flank the aph gene. This g...

  16. Finding the start site: redefining the human initiator element

    PubMed Central

    Kugel, Jennifer F.; Goodrich, James A.

    2017-01-01

    Transcription by RNA polymerase II (Pol II) is dictated in part by core promoter elements, which are DNA sequences flanking the transcription start site (TSS) that help direct the proper initiation of transcription. Taking advantage of recent advances in genome-wide sequencing approaches, Vo ngoc and colleagues (pp. 6–11) identified transcripts with focused sites of initiation and found that many were transcribed from promoters containing a new consensus sequence for the human initiator (Inr) core promoter element. PMID:28130343

  17. Functions of milk protein gene 5' flanking regions on human growth hormone gene.

    PubMed

    Ninomiya, T; Hirabayashi, M; Sagara, J; Yuki, A

    1994-03-01

    Fragments containing 5' flanking regions of four bovine milk protein genes--alpha lactalbumin (b alpha LA), alpha S1 casein (b alpha S1CN), beta casein (b beta CN), kappa casein (b kappa CN)--and mouse whey acidic protein (mWAP) gene were prepared by PCR and ligated to human growth hormone (hGH) gene. These recombinant DNAs were microinjected into rat embryos to produce transgenic rats, and the functions of the 5' regions to direct secretion of hGH in the milk were tested. Although milk was obtained only in 5 of 19 mWAP/hGH rat lines, more than two-thirds of the rats carrying the other four DNAs produced milk. More than 80% of the lactated rats carrying b alpha LA/, b beta CN/, and mWAP/hGH, and 33% of the lactated b alpha S1CN/hGH rats secreted detectable amounts of hGH (> 0.05 microgram/ml) in the milk. In some rats, the hGH concentrations in the milk were comparable to or more than that of the corresponding milk protein in bovine milk. The ranges of hGH concentrations in the milk of b alpha LA/, b beta CN/, b alpha S1CN/, and mWAP/hGH rats were 1.13-4,360 micrograms/ml, 0.11-10,900 micrograms/ml, 86.8-6,480 micrograms/ml, and 6.87-151 micrograms/ml, respectively. HGH was also detected in the sera of these rats, and some abnormalities of growth and reproduction were observed. All but one virgin mWAP/hGH rat secreted up to 0.0722 microgram/ml of hGH in the serum, and more than half of them showed abnormal fat accumulations at their abdomen.(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Multiple 5'-flanking regions of the human alpha-skeletal actin gene synergistically modulate muscle-specific expression.

    PubMed

    Muscat, G E; Kedes, L

    1987-11-01

    Transfection into myogenic and nonmyogenic cell lines was used to investigate the transcriptional regulation of the human alpha-skeletal actin gene. We demonstrated that 1,300 base pairs of the 5'-flanking region directed high-level transient expression of the bacterial chloramphenicol acetyltransferase gene in differentiated mouse C2C12 and rat L8 myotubes but not in mouse nonmuscle L.TK- and HuT-12 cells. Unidirectional 5' deletion analysis and heterologous promoter stimulation experiments demonstrated that at least three transcription-regulating subdomains lie in this 1,300-base-pair region. A proximal cis-acting transcriptional element located between positions -153 and -87 relative to the start of transcription at +1 was both sufficient and necessary for muscle-specific expression and developmental regulation during myogenesis in the two myogenic cell systems. The region 3' of position -87 interacted with factors present in both myogenic and fibroblastic cells and appeared to define, or to be a major component of, the basal promoter. In C2C12 myotubes, but not in L8 myotubes, a distal sequence domain between positions -1300 and -626 and the proximal sequence domain between positions -153 and -87 each induced transcription about 10-fold and synergistically increased CAT expression 100-fold over levels achieved by the sequences 3' of position -87. Furthermore, these cis-acting elements independently and synergistically modulated an enhancerless, heterologous simian virus 40 promoter in a tissue-specific manner. DNA fragments which included the proximal domain displayed classical enhancerlike properties. The central region between positions -626 and -153, although required in neither cell line, had a positive, two- to threefold, additive role in augmenting expression in L8 cells but not in C2C12 cells. This suggests that certain elements between positions -1300 and -153 appear to be differentially utilized for maximal expression in different myogenic cells and

  19. 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. Copyright © 2015 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

  20. Genomic Sequence Analysis of Fugu rubripes CFTR and Flanking Genes in a 60 kb Region Conserving Synteny with 800 kb of Human Chromosome 7

    PubMed Central

    Davidson, Heather; Taylor, Martin S.; Doherty, Ann; Boyd, A. Christopher; Porteous, David J.

    2000-01-01

    To define control elements that regulate tissue-specific expression of the cystic fibrosis transmembrane regulator (CFTR), we have sequenced 60 kb of genomic DNA from the puffer fish Fugu rubripes (Fugu) that includes the CFTR gene. This region of the Fugu genome shows conservation of synteny with 800-kb sequence of the human genome encompassing the WNT2, CFTR, Z43555, and CBP90 genes. Additionally, the genomic structure of each gene is conserved. In a multiple sequence alignment of human, mouse, and Fugu, the putative WNT2 promoter sequence is shown to contain highly conserved elements that may be transcription factor or other regulatory binding sites. We have found two putative ankyrin repeat-containing genes that flank the CFTR gene. Overall sequence analysis suggests conservation of intron/exon boundaries between Fugu and human CFTR and revealed extensive homology between functional protein domains. However, the immediate 5′ regions of human and Fugu CFTR are highly divergent with few conserved sequences apart from those resembling diminished cAMP response elements (CRE) and CAAT box elements. Interestingly, the polymorphic polyT tract located upstream of exon 9 is present in human and Fugu but absent in mouse. Similarly, an intron 1 and intron 9 element common to human and Fugu is absent in mouse. The euryhaline killifish CFTR coding sequence is highly homologous to the Fugu sequence, suggesting that upregulation of CFTR in that species in response to salinity may be regulated transcriptionally. [The sequence data described in this paper have been submitted to the GenBank data library under accession no. AJ271361, for the combined cosmids 159C9, 146H13, 6M15, and 145M20.] PMID:10958637

  1. 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

  2. Human U1 small nuclear RNA genes: extensive conservation of flanking sequences suggests cycles of gene amplification and transposition.

    PubMed Central

    Bernstein, L B; Manser, T; Weiner, A M

    1985-01-01

    The DNA immediately flanking the 164-base-pair U1 RNA coding region is highly conserved among the approximately 30 human U1 genes. The U1 multigene family also contains many U1 pseudogenes (designated class I) with striking although imperfect flanking homology to the true U1 genes. Using cosmid vectors, we now have cloned, characterized, and partially sequenced three 35-kilobase (kb) regions of the human genome spanning U1 homologies. Two clones contain one true U1 gene each, and the third bears two class I pseudogenes 9 kb apart in the opposite orientation. We show by genomic blotting and by direct DNA sequence determination that the conserved sequences surrounding U1 genes are much more extensive than previously estimated: nearly perfect sequence homology between many true U1 genes extends for at least 24 kb upstream and at least 20 kb downstream from the U1 coding region. In addition, the sequences of the two new pseudogenes provide evidence that class I U1 pseudogenes are more closely related to each other than to true genes. Finally, it is demonstrated elsewhere (Lindgren et al., Mol. Cell. Biol. 5:2190-2196, 1985) that both true U1 genes and class I U1 pseudogenes map to chromosome 1, but in separate clusters located far apart on opposite sides of the centromere. Taken together, these results suggest a model for the evolution of the U1 multigene family. We speculate that the contemporary family of true U1 genes was derived from a more ancient family of U1 genes (now class I U1 pseudogenes) by gene amplification and transposition. Gene amplification provides the simplest explanation for the clustering of both U1 genes and class I pseudogenes and for the conservation of at least 44 kb of DNA flanking the U1 coding region in a large fraction of the 30 true U1 genes. Images PMID:3837185

  3. Finding the start site: redefining the human initiator element.

    PubMed

    Kugel, Jennifer F; Goodrich, James A

    2017-01-01

    Transcription by RNA polymerase II (Pol II) is dictated in part by core promoter elements, which are DNA sequences flanking the transcription start site (TSS) that help direct the proper initiation of transcription. Taking advantage of recent advances in genome-wide sequencing approaches, Vo ngoc and colleagues (pp. 6-11) identified transcripts with focused sites of initiation and found that many were transcribed from promoters containing a new consensus sequence for the human initiator (Inr) core promoter element. © 2017 Kugel and Goodrich; Published by Cold Spring Harbor Laboratory Press.

  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. Insertions of IS256-like element flanking the chromosomal beta-lactamase gene of Enterococcus faecalis CX19.

    PubMed Central

    Rice, L B; Marshall, S H

    1994-01-01

    We have previously identified an inverted repeat characteristic of staphylococcal beta-lactamase transposons adjacent to the chromosomal beta-lactamase genes of Enterococcus faecalis CH19 and its beta-lactamase-producing transconjugant CX19. Nucleotide sequence analysis of the CH19 beta-lactamase structural gene (blaZ) reveals it to be identical to the blaZ gene from E. faecalis HH22 and to the blaZ gene from the staphylococcal beta-lactamase transposon Tn552. We also report the presence of nucleotide sequence identical to a 317-bp region of the staphylococcal insertion sequence IS256 upstream of the blaZ gene in both CH19 and CX19. The identical segment of IS256 is present downstream of the blaZ gene of CX19, suggesting a second insertion of the element (in the inverted orientation) accompanying transfer to the recipient strain. Restriction analysis of the areas beyond the ClaI sites used to clone these regions suggests that full copies of the IS256-like element (designated IS256E) are present in all positions but that these elements were not directly involved in the transfer of the beta-lactamase gene to the recipient strain. We have also identified a region downstream of the second IS256E insertion site which exhibits substantial homology to ISSIW, an iso-ISSI insertion originally identified in Lactococcus lactis subsp. cremoris. These data suggest that the two enterococcal blaZ genes sequenced to date evolved from a common ancestor and may at one time have been incorporated into a transposon similar to Tn552. They also suggest that IS256-like elements are mobile in E. faecalis and capable of inserting in a manner consistent with the formation of novel composite transposons. Finally, they provide the first confirmation of the presence of an ISSI-like element in enterococci, raising the possibility that these elements play a role in the exchange of chromosomal antimicrobial resistance determinants. Images PMID:8031032

  6. 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.

  7. Variation in the sequence and modification state of the human insulin gene flanking regions.

    PubMed

    Ullrich, A; Dull, T J; Gray, A; Philips, J A; Peter, S

    1982-04-10

    The nucleotide sequence of a highly repetitive sequence region upstream from the human insulin gene is reported. The length of this region varies between alleles in the population, and appears to be stably transmitted to the next generation in a Mendelian fashion. There is no significant correlation between the length of this sequence and two types of diabetes mellitus. We observe variation in the cleavability of a BglI recognition site downstream from the human insulin gene, which is probably due to variable nucleotide modification. This presumed modification state appears not to be inherited, and varies between tissues within an individual and between individuals for a given tissue. Both alleles in a given tissue DNA sample are modified to the same extent.

  8. Functional characterization of the 5' flanking region of human ubiquitin fusion degradation 1 like gene (UFD1L).

    PubMed

    Amati, Francesca; Conti, Emanuela; Botta, Annalisa; Amicucci, Paola; Dallapiccola, Bruno; Novelli, Giuseppe

    2002-06-01

    UFD1L (Ubiquitin Fusion Degradation 1 Like) gene encodes for a component of a multi-complex involved in the degradation of ubiquitin fusion proteins. The gene maps on chromosome 22q11, in a region commonly deleted in severe congenital disorders such as DiGeorge (DGS) and velo-cardio-facial (VCFS) syndromes. UFD1L is a single copy gene ubiquitously expressed in high levels in the pharyngeal pouches and fourth branchial arch artery during development. To understand the regulation of UFD1L expression we performed a functional analysis of its 5' regulatory region. 5'-RACE and primer extension analyses revealed the presence of different transcription start sites in adult and fetal tissues. UFD1L 5' flanking region contains a TATA-box motif and is also very GC-rich with a CpG island encompassing exon 1. Transcriptional activity of this region was examined by transfection experiments of promoter-GFP reporter gene constructs in a human epithelial cell line. These experiments revealed the importance of the region between -17 and -463 nt which contains the TATA-box. EMSA assay resulted in the detection of five functional consensus sequences respectively for the transcription complex TFIID and for the transcription factors AP-1 (one site), AP-2 (one) and Sp1 (two).

  9. Short tandem repeat polymorphism in the flanking region of the human phosphoglycerate kinase gene in a Japanese population.

    PubMed

    Tie, Jian; Serizawa, Yuka; Oshida, Shigemi; Usami, Ron; Yoshida, Yasuhiko

    2006-04-01

    The human phosphoglycerate kinase (PGK1) gene is located within Xqll-Xql3 and is closely linked to the androgen receptor gene within a region implicated in a number of X-chromosome-linked urologic disorders. A polymorphism of a TATC short tandem repeat (STR) is present downstream from the PGK1 3' nuclease-sensitive site. We present the PGK1 flanking STR sequence and population genetic data for 190 Japanese males and 83 Japanese females. Ten STR alleles and 29 genotypes were identified in the population. Five alleles--*10, *11, *12, *13, and *14--were common in the Japanese with frequencies greater than 10%. No significant deviations from Hardy-Weinberg equilibrium were established. The power of discrimination was 0.993 for females and 0.819 for males; heterozygosity was 0.759 for females; and the polymorphic information content was 0.936. These data indicate that this STR locus shows a high degree of polymorphism in this Japanese population and may prove to be a useful genetic marker in forensic medicine, in determining the clonality of neoplasms, and potentially in studying predisposition to prostate cancer and other urologic diseases.

  10. 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.

  11. XIST-induced silencing of flanking genes is achieved by additive action of repeat a monomers in human somatic cells.

    PubMed

    Minks, Jakub; Baldry, Sarah El; Yang, Christine; Cotton, Allison M; Brown, Carolyn J

    2013-08-01

    The establishment of facultative heterochromatin by X-chromosome inactivation requires the long non-coding RNA XIST/Xist. However, the molecular mechanism by which the RNA achieves chromosome-wide gene silencing remains unknown. Mouse Xist has been shown to have redundant domains for cis-localization, and requires a series of well-conserved tandem 'A' repeats for silencing. We previously described a human inducible XIST transgene that is capable of cis-localization and suppressing a downstream reporter gene in somatic cells, and have now leveraged these cells to dissect the sequences critical for XIST-dependent gene silencing in humans. We demonstrated that expression of the inducible full-length XIST cDNA was able to suppress expression of two nearby reporter genes as well as endogenous genes up to 3 MB from the integration site. An inducible construct containing the repeat A region of XIST alone could silence the flanking reporter genes but not the more distal endogenous genes. Reporter gene silencing could also be accomplished by a synthetic construct consisting of nine copies of a consensus repeat A sequence, consistent with previous studies in mice. Progressively shorter constructs showed a linear relationship between the repeat number and the silencing capacity of the RNA. Constructs containing only two repeat A units were still able to partially silence the reporter genes and could thus be used for site-directed mutagenesis to demonstrate that sequences within the two palindromic cores of the repeat are essential for silencing, and that it is likely the first palindrome sequence folds to form a hairpin, consistent with compensatory mutations observed in eutherian sequences. Silencing of adjacent reporter genes can be effected by as little as 94 bp of XIST, including two 'monomers' of the A repeat. This region includes a pair of essential palindromic sequences that are evolutionarily well-conserved and the first of these is likely to form an intra

  12. 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.

  13. 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.

  14. Protein binding elements in the human beta-polymerase promoter.

    PubMed Central

    Englander, E W; Wilson, S H

    1990-01-01

    The core promoter for human DNA polymerase beta contains discrete binding sites for mammalian nuclear proteins, as revealed by DNasel footprinting and gel mobility shift assays. Two sites correspond to sequences identical with the Sp1 factor binding element, and a third site includes an eight residue palindromic sequence, TGACGTCA, known as the CRE element of several cAMP responsive promoters; the 5 to 10 residues flanking this palindrome on each side have no apparent sequence homology with known elements in other promoters. Nuclear extract from a variety of tissues and cells were examined; these included rat liver and testes and cultured cells of human and hamster origin. The DNasel footprint is strong over and around the palindromic element for each of the extracts and is equivalent in size (approximately 22 residues); footprinting over the Sp1 binding sites is seen also. Two potential tissue-specific binding sites, present in liver but not in testes, were found corresponding to residues -13 to -10 and +33 to +48, respectively. Protein binding to the palindromic element was confirmed by an electrophoretic mobility shift assay with the core promoter as probe. Binding specificity of the 22 residue palindromic element, as revealed by oligonucleotide competition, is different from that of AP-1 binding element. Controlled proteolysis with trypsin was used to study structural properties of proteins forming the mobility shift bands. Following digestion with trypsin, most of the palindrome binding activity of each extract corresponded to a sharp, faster migrating band, potentially representing a DNA binding domain of the palindrome binding protein. Images PMID:2315044

  15. Sequence-specific flexibility organization of splicing flanking sequence and prediction of splice sites in the human genome.

    PubMed

    Zuo, Yongchun; Zhang, Pengfei; Liu, Li; Li, Tao; Peng, Yong; Li, Guangpeng; Li, Qianzhong

    2014-09-01

    More and more reported results of nucleosome positioning and histone modifications showed that DNA structure play a well-established role in splicing. In this study, a set of DNA geometric flexibility parameters originated from molecular dynamics (MD) simulations were introduced to discuss the structure organization around splice sites at the DNA level. The obtained profiles of specific flexibility/stiffness around splice sites indicated that the DNA physical-geometry deformation could be used as an alternative way to describe the splicing junction region. In combination with structural flexibility as discriminatory parameter, we developed a hybrid computational model for predicting potential splicing sites. And the better prediction performance was achieved when the benchmark dataset evaluated. Our results showed that the mechanical deformability character of a splice junction is closely correlated with both the splice site strength and structural information in its flanking sequences.

  16. Characterization of the 5'-flanking region of the human TP53 gene and its response to the natural compound, Resveratrol.

    PubMed

    Uchiumi, Fumiaki; Shoji, Koichiro; Sasaki, Yuki; Sasaki, Moe; Sasaki, Yamato; Oyama, Takahiro; Sugisawa, Kyoko; Tanuma, Sei-ichi

    2016-04-01

    Tumour suppressor p53, which is encoded by theTP53gene, is widely known to play an important role in response to DNA damage and various stresses. It has recently been reported that p53 regulates glucose metabolism and that an increase in p53 protein level is induced after serum deprivation or treatments with a natural compound,trans-Resveratrol (Rsv). In this study, we constructed a Luciferase expression vector, pGL4-TP53-551, containing 551 bp of the 5'-upstream region of the humanTP53gene, which was then transfected into HeLa S3 cells. A Luciferase assay showed that Rsv treatment increased the promoter activity of theTP53gene in comparison to that ofPIF1 Detailed deletion and mutation analyses revealed that Nkx-2.5 and E2F-binding elements are required in addition to duplicated GGAA (TTCC), for the regulation ofTP53promoter activity. In this study, it is suggested that the transient induction ofTP53gene expression by Rsv treatment might be partly involved in its anti-aging effect through maintenance of chromosomal DNAs. © The Authors 2015. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  17. Inversely repeating integrated hepatitis B virus DNA and cellular flanking sequences in the human hepatoma-derived cell line huSP.

    PubMed Central

    Mizusawa, H; Taira, M; Yaginuma, K; Kobayashi, M; Yoshida, E; Koike, K

    1985-01-01

    Among recombinant phages carrying integrated hepatitis B virus (HBV) DNA sequences cloned from the human hepatoma-derived cell line huSP, one clone, lambda hu-489, revealed some unusual features. The 2.25-kilobase Eco D fragment from the insert of this clone hybridized to the HBV DNA probe only and its nucleotide sequence was determined. The viral sequence, as well as a cellular flanking sequence, showed extensive rearrangement accompanied by inverted repetition. The Eco D fragment contained HBV DNA from the 5'-end region of gene S to the middle of gene X, followed by a long cellular flanking sequence. Moreover, a part of gene X was found inversely repeated at the head of the same gene S in a head-to-head configuration truncated by the same cellular sequence. Therefore, the same junction sequence of viral DNA and the cellular sequence was found at two different sites in the Eco D fragment in opposite polarities. Images PMID:2982143

  18. Flank solar wind interaction

    NASA Technical Reports Server (NTRS)

    Moses, Stewart L.; Greenstadt, Eugene W.

    1992-01-01

    This report summarizes the results of the first 12 months of our program to study the interaction of the Earth's magnetosphere with the solar wind on the far flanks of the bow shock. This study employs data from the ISEE-3 spacecraft during its traversals of the Earth's magnetotail and correlative data from spacecraft monitoring the solar wind upstream. Our main effort to date has involved assembling data sets and developing new plotting programs. Two talks were given at the Spring Meeting of the American Geophysical Union describing our initial results from analyzing data from the far flank foreshock and magnetosheath. The following sections summarize our results.

  19. The 5'-flanking region of the human dopamine beta-hydroxylase gene promotes neuron subtype-specific gene expression in the central nervous system of transgenic mice.

    PubMed

    Morita, S; Kobayashi, K; Mizuguchi, T; Yamada, K; Nagatsu, I; Titani, K; Fujita, K; Hidaka, H; Nagatsu, T

    1993-03-01

    Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) catalyzes the conversion of dopamine to norepinephrine, the third step of catecholamine biosynthesis. We have previously created transgenic mice harboring a chimeric gene consisting of the 4-kb DNA fragment of the human DBH gene promoter and the human phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) cDNA, to express PNMT in norepinephrine- and epinephrine-producing cells in the brain, sympathetic ganglia, and adrenal medullary chromaffin cells (Kobayashi et al., Proc. Natl. Acad. Sci. U.S.A., 89 (1992) 1631-1635). In this paper, we produced for the first time the antibody that specifically detects human PNMT, but not mouse PNMT, with the synthetic oligopeptide characteristic of the human PNMT sequence, and used this antibody to investigate the cells expressing human PNMT in transgenic mice. Immunohistochemical analysis of transgenic mice showed typical expression of human PNMT immunoreactivity in norepinephrinergic and epinephrinergic neurons in brain, as well as norepinephrine- and epinephrine-producing cells in the adrenal gland, indicating that the 4-kb 5'-flanking region is essential for the tissue-specific expression of the DBH gene. We also detected the ectopic expression in some DBH-immunonegative cells in the olfactory bulb of transgenic mice.

  20. Glucocorticoid regulation of a phenobarbital-inducible cytochrome P-450 gene: the presence of a functional glucocorticoid response element in the 5'-flanking region of the CYP2B2 gene.

    PubMed Central

    Jaiswal, A K; Haaparanta, T; Luc, P V; Schembri, J; Adesnik, M

    1990-01-01

    The rat cytochrome P450 CYP2B2 gene encodes one of the two major phenobarbital-inducible forms of hepatic microsomal cytochrome P-450. The sequence of a 1.4 Kb DNA segment from the 5' flanking region of this region [Jaiswal, A., Rivkin, E. and Adesnik, M. Nucl. Acids. Res. 15: 6755 (1987)] reveals the presence of a pentadecameric oligonucleotide sequence, located approximately 1.3 Kb upstream of the transcription initiation site, which is highly similar to the sequences of glucocorticoid response elements (GREs) that mediate the hormone-dependent transcriptional activation of many other genes. The putative GRE in the CYP2B2 gene 5' flanking region is shown to be functional by demonstrating that segments of DNA that contain it, including one that is only 25bp long, are capable of conferring dexamethasone inducibility on a chloramphenicol acetyltransfer-ase gene whose transcription is driven by the Herpes virus thymidine kinase gene promoter. Moreover, binding of a protein contained in a rat liver nuclear extract to a 25 bp synthetic DNA segment that contains the putative GRE was demonstrated in a gel mobility shift assay. This binding was specifically competed away by a DNA segment that contains the murine mammary tumor virus long terminal repeat which encompasses several well characterized GRE elements. The implications of these findings for the in vivo regulation of the P450IIB2 gene by glucocorticoids are discussed. Images PMID:2377462

  1. 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.

  2. p53 responsive elements in human retrotransposons

    PubMed Central

    Harris, CR; DeWan, A; Zupnick, A; Normart, R; Gabriel, A; Prives, C; Levine, AJ; Hoh, J

    2011-01-01

    Long interspersed nuclear elements-1 (L1s) are highly repetitive DNA elements that are capable of altering the human genome through retrotransposition. To protect against L1 retroposition, the cell downregulates the expression of L1 proteins by various mechanisms, including high-density cytosine methylation of L1 promoters and DICER-dependent destruction of L1 mRNAs. In this report, a large number of p53 responsive elements, or p53 DNA binding sites, were detected in L1 elements within the human genome. At least some of these p53 responsive elements are functional and can act to increase the levels of L1 mRNA expression. The p53 protein can directly bind to a short 15-nucleotide sequence within the L1 promoter. This p53 responsive element within L1 is a recent addition to evolution, appearing ~20 million years ago. This suggests an interplay between L1 elements, which have a rich history of causing changes in the genome, and the p53 protein, the function of which is to protect against genomic changes. To understand these observations, a model is proposed in which the increased expression of L1 mRNAs by p53 actually increases, rather than decreases, the genomic stability through amplification of p53-dependent processes for genomic protection. PMID:19718052

  3. p53 responsive elements in human retrotransposons.

    PubMed

    Harris, C R; Dewan, A; Zupnick, A; Normart, R; Gabriel, A; Prives, C; Levine, A J; Hoh, J

    2009-11-05

    Long interspersed nuclear elements-1 (L1s) are highly repetitive DNA elements that are capable of altering the human genome through retrotransposition. To protect against L1 retroposition, the cell downregulates the expression of L1 proteins by various mechanisms, including high-density cytosine methylation of L1 promoters and DICER-dependent destruction of L1 mRNAs. In this report, a large number of p53 responsive elements, or p53 DNA binding sites, were detected in L1 elements within the human genome. At least some of these p53 responsive elements are functional and can act to increase the levels of L1 mRNA expression. The p53 protein can directly bind to a short 15-nucleotide sequence within the L1 promoter. This p53 responsive element within L1 is a recent addition to evolution, appearing approximately 20 million years ago. This suggests an interplay between L1 elements, which have a rich history of causing changes in the genome, and the p53 protein, the function of which is to protect against genomic changes. To understand these observations, a model is proposed in which the increased expression of L1 mRNAs by p53 actually increases, rather than decreases, the genomic stability through amplification of p53-dependent processes for genomic protection.

  4. 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.

  5. 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.

  6. The Evolutionary Origin of Man Can Be Traced in the Layers of Defunct Ancestral Alpha Satellites Flanking the Active Centromeres of Human Chromosomes

    PubMed Central

    Shepelev, Valery A.; Alexandrov, Alexander A.; Yurov, Yuri B.; Alexandrov, Ivan A.

    2009-01-01

    Alpha satellite domains that currently function as centromeres of human chromosomes are flanked by layers of older alpha satellite, thought to contain dead centromeres of primate progenitors, which lost their function and the ability to homogenize satellite repeats, upon appearance of a new centromere. Using cladistic analysis of alpha satellite monomers, we elucidated complete layer patterns on chromosomes 8, 17, and X and related them to each other and to primate alpha satellites. We show that discrete and chronologically ordered alpha satellite layers are partially symmetrical around an active centromere and their succession is partially shared in non-homologous chromosomes. The layer structure forms a visual representation of the human evolutionary lineage with layers corresponding to ancestors of living primates and to entirely fossil taxa. Surprisingly, phylogenetic comparisons suggest that alpha satellite arrays went through periods of unusual hypermutability after they became “dead” centromeres. The layer structure supports a model of centromere evolution where new variants of a satellite repeat expanded periodically in the genome by rounds of inter-chromosomal transfer/amplification. Each wave of expansion covered all or many chromosomes and corresponded to a new primate taxon. Complete elucidation of the alpha satellite phylogenetic record would give a unique opportunity to number and locate the positions of major extinct taxa in relation to human ancestors shared with extant primates. If applicable to other satellites in non-primate taxa, analysis of centromeric layers could become an invaluable tool for phylogenetic studies. PMID:19749981

  7. The evolutionary origin of man can be traced in the layers of defunct ancestral alpha satellites flanking the active centromeres of human chromosomes.

    PubMed

    Shepelev, Valery A; Alexandrov, Alexander A; Yurov, Yuri B; Alexandrov, Ivan A

    2009-09-01

    Alpha satellite domains that currently function as centromeres of human chromosomes are flanked by layers of older alpha satellite, thought to contain dead centromeres of primate progenitors, which lost their function and the ability to homogenize satellite repeats, upon appearance of a new centromere. Using cladistic analysis of alpha satellite monomers, we elucidated complete layer patterns on chromosomes 8, 17, and X and related them to each other and to primate alpha satellites. We show that discrete and chronologically ordered alpha satellite layers are partially symmetrical around an active centromere and their succession is partially shared in non-homologous chromosomes. The layer structure forms a visual representation of the human evolutionary lineage with layers corresponding to ancestors of living primates and to entirely fossil taxa. Surprisingly, phylogenetic comparisons suggest that alpha satellite arrays went through periods of unusual hypermutability after they became "dead" centromeres. The layer structure supports a model of centromere evolution where new variants of a satellite repeat expanded periodically in the genome by rounds of inter-chromosomal transfer/amplification. Each wave of expansion covered all or many chromosomes and corresponded to a new primate taxon. Complete elucidation of the alpha satellite phylogenetic record would give a unique opportunity to number and locate the positions of major extinct taxa in relation to human ancestors shared with extant primates. If applicable to other satellites in non-primate taxa, analysis of centromeric layers could become an invaluable tool for phylogenetic studies.

  8. 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

  9. Regulatory xenobiotic responsive elements in the distal 5'-flanking region of the mouse Cyp1a2 gene required for transcriptional activation by 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Kawasaki, Yuki; Sakuma, Tsutomu; Goto, Yuma; Nemoto, Nobuo

    2010-10-01

    We examined the xenobiotic responsive element (XRE) responsible for induction of the mouse Cyp1a2 gene by 3-methylcholanthrene (3MC) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) using a reporter gene assay in mouse hepatocytes in primary culture. Although, the 5'-flanking region up to -9.5 kilobase pairs did not show a significant increase in transcriptional activity after treatment with 3MC or TCDD, a further distal 5'-flanking region from -13,958 to -12,520 containing 12 putative XREs (5'-GCGTG-3') demonstrated distinctive transcriptional activity after treatment with 3MC or TCDD. When a mutation was introduced into XRE14 at -12,972, the activation was decreased, and concurrent mutations in XRE14, XRE13, and XRE15 completely abolished it. However, mutations in XRE13, XRE15, XRE16, or XRE17 did not affect the inducible transcriptional activation of the mouse Cyp1a2 gene. These results suggest that XRE14 is important and that XRE13 at -12,897 and/or XRE15 at -13,061 are cooperative to the inducible transcriptional activation of the mouse Cyp1a2 gene by ligands of the aryl hydrocarbon receptor.

  10. Human mirtrons can express functional microRNAs simultaneously from both arms in a flanking exon-independent manner

    PubMed Central

    Schamberger, Anita; Sarkadi, Balázs; Orbán, Tamás I.

    2012-01-01

    Mirtrons are short intronic microRNA (miRNA) precursors representing an alternative, Drosha/DGCR8-independent miRNA biogenesis pathway. In this study we characterized three predicted human mirtrons. Their expression was proven to be context-independent, since functional mirtrons could be derived either from their endogenous or from a heterologous coding environment. Systematic testing revealed that both 5′- and 3′-arms of mir-877 are capable of producing functional miRNA simultaneously in the various cell types examined. On the other hand, experimental validations revealed that the predicted mir-1233 is not a bona fide mirtron. For functional mirtrons, we were able to detect mature mirtron-derived miRNAs for the first time by qRT-PCR or northern blot analysis, when silencing activity was proven by functional assays. Our results emphasize the need for functional testing of both arms of miRNAs and the importance of experimentally validating human mirtrons since, in spite of being localized in a short intron, predicted species could mature via other miRNA processing pathways. PMID:23018783

  11. Physical map of human 6p21.2-6p21.3: region flanking the centromeric end of the major histocompatibility complex.

    PubMed

    Tripodis, N; Mason, R; Humphray, S J; Davies, A F; Herberg, J A; Trowsdale, J; Nizetic, D; Senger, G; Ragoussis, J

    1998-06-01

    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.

  12. Direct selection of expressed sequences within a 1-Mb region flanking BRCA1 on human chromosome 17q21

    SciTech Connect

    Osborne-Lawrence, S.; Welcsh, P.L.; Spillman, M.

    1995-01-01

    Direct selection of genes within the interval of chromosome 17q21 containing BRCA1 was performed. YAC and cosmid contigs spanning the BRCA1 region were used to select cDNA clones from pools of cDNAs derived from human placenta, HeLa cells, activated T cells, and fetal head. A minimum set of 48 fragments of nonoverlapping cDNAs that unequivocally mapped within a 1-Mb region was identified, although it is not yet known how many of these are derived from the same transcript. DNA sequence analyses revealed that 4 of these cDNAs were derived from known genes (EDH17B2, glucose-6-phosphatase, IAI.3B, and E1AF), 1 is a member of a previously described gene family (EMG-17), and 7 share substantial identity with previously described genes from human or other species. The remainder showed no significant homology to known genes. Limited PCR-based expression profiles of a set of 13 of the genes were performed, and all gave positive results with at least some cDNA sources supporting the contention that they truly represent transcribed sequences. A comparison between genes obtained from this region by direct selection with those obtained by direct screening or exon trapping revealed that over 90% of the genes identified by exon trapping were represented in the selected material and that at least two additional genes that appear to represent low abundance transcripts with restricted expression profiles were identified by selection but not by other means. 39 refs., 3 figs., 2 tabs.

  13. Ultraconserved elements in the human genome.

    PubMed

    Bejerano, Gill; Pheasant, Michael; Makunin, Igor; Stephen, Stuart; Kent, W James; Mattick, John S; Haussler, David

    2004-05-28

    There are 481 segments longer than 200 base pairs (bp) that are absolutely conserved (100% identity with no insertions or deletions) between orthologous regions of the human, rat, and mouse genomes. Nearly all of these segments are also conserved in the chicken and dog genomes, with an average of 95 and 99% identity, respectively. Many are also significantly conserved in fish. These ultraconserved elements of the human genome are most often located either overlapping exons in genes involved in RNA processing or in introns or nearby genes involved in the regulation of transcription and development. Along with more than 5000 sequences of over 100 bp that are absolutely conserved among the three sequenced mammals, these represent a class of genetic elements whose functions and evolutionary origins are yet to be determined, but which are more highly conserved between these species than are proteins and appear to be essential for the ontogeny of mammals and other vertebrates.

  14. Cis-regulatory Elements and Human Evolution

    PubMed Central

    Siepel, Adam

    2014-01-01

    Modification of gene regulation has long been considered an important force in human evolution, particularly through changes to cis-regulatory elements (CREs) that function in transcriptional regulation. For decades, however, the study of cis-regulatory evolution was severely limited by the available data. New data sets describing the locations of CREs and genetic variation within and between species have now made it possible to study CRE evolution much more directly on a genome-wide scale. Here, we review recent research on the evolution of CREs in humans based on large-scale genomic data sets. We consider inferences based on primate divergence, human polymorphism, and combinations of divergence and polymorphism. We then consider “new frontiers” in this field stemming from recent research on transcriptional regulation. PMID:25218861

  15. Neuraminidase-mediated haemagglutination of recent human influenza A(H3N2) viruses is determined by arginine 150 flanking the neuraminidase catalytic site.

    PubMed

    Mögling, Ramona; Richard, Mathilde J; Vliet, Stefan van der; Beek, Ruud van; Schrauwen, Eefje J A; Spronken, Monique I; Rimmelzwaan, Guus F; Fouchier, Ron A M

    2017-06-01

    Over the last decade, an increasing proportion of circulating human influenza A(H3N2) viruses exhibited haemagglutination activity that was sensitive to neuraminidase inhibitors. This change in haemagglutination as compared to older circulating A(H3N2) viruses prompted an investigation of the underlying molecular basis. Recent human influenza A(H3N2) viruses were found to agglutinate turkey erythrocytes in a manner that could be blocked with either oseltamivir or neuraminidase-specific antisera, indicating that agglutination was driven by neuraminidase, with a low or negligible contribution of haemagglutinin. Using representative virus recombinants it was shown that the haemagglutinin of a recent A(H3N2) virus indeed had decreased activity to agglutinate turkey erythrocytes, while its neuraminidase displayed increased haemagglutinating activity. Viruses with chimeric and mutant neuraminidases were used to identify the amino acid substitution histidine to arginine at position 150 flanking the neuraminidase catalytic site as the determinant of this neuraminidase-mediated haemagglutination. An analysis of publicly available neuraminidase gene sequences showed that viruses with histidine at position 150 were rapidly replaced by viruses with arginine at this position between 2005 and 2008, in agreement with the phenotypic data. As a consequence of neuraminidase-mediated haemagglutination of recent A(H3N2) viruses and poor haemagglutination via haemagglutinin, haemagglutination inhibition assays with A(H3N2) antisera are no longer useful to characterize the antigenic properties of the haemagglutinin of these viruses for vaccine strain selection purposes. Continuous monitoring of the evolution of these viruses and potential consequences for vaccine strain selection remains important.

  16. Heat Shield Flank Close Up

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This image from NASA's Mars Exploration Rover Opportunity features an up-close view of the flank piece of the rover's broken heat shield.

    The rover spent 36 sols investigating how the severe heating during entry through the atmosphere affected the heat shield. The most obvious is the fact that the heat shield inverted upon impact. Overall, engineers were interested in evaluating the performance of the heat shield's thermal protection system.

    This is the the panormamic camera team's best current attempt at generating a 'true color' view of what this scene would look like if viewed by a human on Mars. It was generated from a mathematical combination of six calibrated, left-eye panoramic camera images acquired around 3:07 p.m. local solar time on Opportunity's sol 331 (Dec. 28, 2004) using filters ranging in wavelengths from 430 to 750 nanometers.

  17. Human histamine N-methyltransferase pharmacogenetics: gene resequencing, promoter characterization, and functional studies of a common 5'-flanking region single nucleotide polymorphism (SNP).

    PubMed

    Wang, Liewei; Thomae, Bianca; Eckloff, Bruce; Wieben, Eric; Weinshilboum, Richard

    2002-08-15

    Histamine N-methyltransferase (HNMT) catalyzes one of two major metabolic pathways for histamine. The levels of HNMT activity and immunoreactive protein in human tissues are regulated primarily by inheritance. Previous studies of HNMT identified two common single nucleotide polymorphisms (SNPs), including a functionally significant nonsynonymous coding SNP (cSNP), (C314T, Thr105Ile), but that polymorphism did not explain all of the phenotypic variation. In the present study, a genotype-to-phenotype strategy was used to search for additional genetic factors that might contribute to the regulation of human HNMT activity. Specifically, we began by resequencing the human HNMT gene using 90 ethnically anonymous DNA samples from the Coriell Cell Repository and identified a total of eight SNPs, including the two that had been reported previously. No new nonsynonymous cSNPs were observed, but three of the six novel SNPs were located in the 5'-flanking region (5'-FR) of the gene-including a third common polymorphism with a frequency of 0.367 (36.7%). That observation directed our attention to possible genetic effects on HNMT transcription. As a first step in testing that possibility, we created and studied a series of reporter gene constructs for the initial 1kb of the HNMT 5'-FR. The core promoter and possible regulatory regions were identified and verified by electrophoresis mobility shift assays. We then studied the possible functional implications of the new common HNMT 5'-FR SNP. However, on the basis of reporter gene studies, that SNP appeared to have little effect on transcription. Phenotype-genotype correlation analysis performed with 112 human kidney biopsy samples that had been phenotyped for their level of HNMT activity confirmed that the common 5'-FR SNP was not associated with the level of HNMT activity in vivo. In summary, this series of experiments resulted in the identification of several novel HNMT polymorphisms, identification of the HNMT core promoter

  18. 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.

  19. 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

  20. 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.

  1. Vitamin D3 supports osteoclastogenesis via functional vitamin D response element of human RANKL gene promoter.

    PubMed

    Kitazawa, Sohei; Kajimoto, Kazuyoshi; Kondo, Takeshi; Kitazawa, Riko

    2003-07-01

    Receptor activator of NF-kappaB ligand (RANKL) has been identified as requisite for osteoclastogenesis. To elucidate the molecular mechanism that conducts its catabolic action on bone, the effect of 1alpha,25 dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) on osteoclastogenesis and RANKL mRNA expression was examined by coculture, RT-PCR and nuclear run-on studies. By accelerating the transcription rate of the RANKL gene in SaOS2 osteoblastic cells, 1alpha,25(OH)(2)D(3) enhanced in vitro osteoclast formation from peripheral monocytes. Cloning and characterization of the 5'-flanking region of the human RANKL gene revealed that the basic promoter comprises inverted TATA- and CAAT-boxes flanked by RUNX2 binding sites. Both electrophoresis mobility shift assay (EMSA) and transfection studies demonstrated that 1alpha,25(OH)(2)D(3) activated human RANKL promoter through vitamin D responsive elements (VDRE) located at -1584/-1570 by binding VDR and RXRalpha heterodimers in a ligand-dependent manner. The results provide direct evidence that 1alpha,25(OH)(2)D(3) augments osteoclastogenesis by transactivating the human RANKL gene in osteoblastic cells through VDRE.

  2. The human tartrate-resistant acid phosphatase (TRAP): involvement of the hemin responsive elements (HRE) in transcriptional regulation.

    PubMed

    Fleckenstein, E C; Dirks, W G; Drexler, H G

    2000-02-01

    The biochemical properties and protein structure of the tartrate-resistant acid phosphatase (TRAP), an iron-containing lysosomal glycoprotein in cells of the mononuclear phagocyte system, are well known. In contrast, little is known about the physiology and genic structure of this unique enzyme. In some diseases, like hairy cell leukemia, Gaucher's disease and osteoclastoma, cytochemically detected TRAP expression is used as a disease-associated marker. In order to begin to elucidate the regulation of this gene we generated different deletion constructs of the TRAP 5'-flanking region, placed them upstream of the luciferase reporter gene and assayed them for their ability to direct luciferase expression in human 293 cells. Treatment of these cells with the iron-modulating reagents transferrin and hemin causes opposite effects on the TRAP promoter activity. Two regulatory GAGGC tandem repeat sequences (the hemin responsive elements, HRE) within the 5'-flanking region of the human TRAP gene were identified. Studies with specific HRE-deletion constructs of the human TRAP 5'-flanking region upstream of the luciferase reporter gene document the functionality of these HRE-sequences which are apparently responsible for mediating transcriptional inhibition upon exposure to hemin. In addition to the previously published functional characterization of the murine TRAP HRE motifs, these results provide the first description of a new iron/hemin-responsive transcriptional regulation in the human TRAP gene.

  3. 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.

  4. Whole-genome expression analysis of mammalian-wide interspersed repeat elements in human cell lines

    PubMed Central

    Carnevali, Davide; Conti, Anastasia; Pellegrini, Matteo

    2017-01-01

    Abstract With more than 500,000 copies, mammalian-wide interspersed repeats (MIRs), a sub-group of SINEs, represent ∼2.5% of the human genome and one of the most numerous family of potential targets for the RNA polymerase (Pol) III transcription machinery. Since MIR elements ceased to amplify ∼130 myr ago, previous studies primarily focused on their genomic impact, while the issue of their expression has not been extensively addressed. We applied a dedicated bioinformatic pipeline to ENCODE RNA-Seq datasets of seven human cell lines and, for the first time, we were able to define the Pol III-driven MIR transcriptome at single-locus resolution. While the majority of Pol III-transcribed MIR elements are cell-specific, we discovered a small set of ubiquitously transcribed MIRs mapping within Pol II-transcribed genes in antisense orientation that could influence the expression of the overlapping gene. We also identified novel Pol III-transcribed ncRNAs, deriving from transcription of annotated MIR fragments flanked by unique MIR-unrelated sequences, and confirmed the role of Pol III-specific internal promoter elements in MIR transcription. Besides demonstrating widespread transcription at these retrotranspositionally inactive elements in human cells, the ability to profile MIR expression at single-locus resolution will facilitate their study in different cell types and states including pathological alterations. PMID:28028040

  5. Tipping elements in the human intestinal ecosystem.

    PubMed

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

    2014-07-08

    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.

  6. 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

  7. Identification of the functional elements in the promoter region of human DNA topoisomerase IIIbeta gene.

    PubMed

    Cho, Young Hoon; Park, Jee Young; Han, Sang Youp; Chung, In Kwon

    2004-09-17

    In this study, we have isolated and characterized the promoter region of the human DNA topoisomerase IIIbeta (hTOP3beta) gene. The 5' RACE assay showed a short exon 1 encoding only the 35-bp untranslated region and suggested the presence of multiple transcription initiation sites. The hTOP3beta gene promoter lacks a canonical TATA box or initiation element and is moderately high in GC content. Transient expression of a luciferase reporter gene under the control of serially deleted 5'-flanking sequence identified an activator element between -141 and -119 upstream of the transcription initiation site and a second regulatory element between -91 and -71. On the basis of scanning mutations of triple nucleotides, we demonstrated that a 5'GGAACC3' element between -117 and -112 plays a critical role in the up-regulation of the basal transcription activity. Changing the 5'GGAACC3' sequence leads to markedly reduced promoter activity. Gel mobility shift assays revealed that the 5'GGAACC3' element is required for DNA binding by the transcription factor complex. These observations lead to the conclusion that the positive regulatory region including the 5'GGAACC3' core element is essential for efficient expression of the hTOP3beta gene as well as for the binding of as yet unidentified regulatory factor(s).

  8. Recycling of trace elements required for humans in CELSS.

    PubMed

    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 possibility that living things absorb some trace elements from atmosphere. Management and recycling of trace elements in CELSS is discussed.

  9. Identification of an SAS (Sp1c adjacent site)-like element in the distal 5'-flanking region of the rat lutropin receptor gene essential for cyclic adenosine 3',5'-monophosphate responsiveness.

    PubMed

    Chen, S; Liu, X; Segaloff, D L

    2001-05-01

    One of the hallmarks of the differentiation of granulosa cells is the estradiol and FSH/cAMP-dependent induction of the LH receptor (LHR). Previous studies using granulosa cells isolated from diethylstilbestrol-pretreated immature rats identified a novel cAMP-responsive element termed the SAS site (Sp1c adjacent site) in the promoter region of the rat (r) LHR gene. The studies presented herein show that there is an additional distal site located at nucleotide (nt) -933/-924 that appears to interact with the same transcription factor that binds to the promoter SAS site. Similar to the SAS site, the complex formed between granulosa cell nuclear extracts and this distal site is enhanced by cAMP treatment of the granulosa cells. The core sequence required for the formation of the DNA/protein complex at this distal rLHR site was determined to be AGTGG(A)GGGG. With the exception of adenine at -928, substitution of any residue within this sequence prevented formation of this complex. The core sequence of this distal site differs from that of the proximal SAS site, which is GGGGG, and hence the distal site has been termed a SAS-like site. Reporter gene assays using constructs containing the -2,109/-1 region of the rLHR demonstrate that mutation of the distal SAS-like site abolishes the cAMP-induced transcription of the rLHR gene in rat granulosa cells, underscoring the functional significance of this site. Given the lack of sequences in the 5'-flanking region of the rLHR gene consistent with known cAMP-responsive elements, the identification of the novel SAS and SAS-like sites in the rLHR gene provides important clues toward understanding the mechanisms by which the rLHR gene is induced by FSH/cAMP.

  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. Structural Variation of Alu Element and Human Disease.

    PubMed

    Kim, Songmi; Cho, Chun-Sung; Han, Kyudong; Lee, Jungnam

    2016-09-01

    Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders.

  12. Structural Variation of Alu Element and Human Disease

    PubMed Central

    Kim, Songmi; Cho, Chun-Sung; Han, Kyudong

    2016-01-01

    Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders. PMID:27729835

  13. Three transposed elements in the intron of a human VK immunoglobulin gene.

    PubMed

    Straubinger, B; Osterholzer, E; Zachau, H G

    1987-11-25

    Two gene segments coding for the variable region of human immunoglobulin light chains of the kappa type (VK genes, ref. 2) were found to have unusual structures. The two genes which are called A6 and A22 are located in duplicated gene clusters. Their restriction maps are very similar. About 4 kb of the A22 gene region were sequenced. It turned out that the intron contains an insert with the characteristics of a transposed element. The inserted DNA of 1.2 kb length contains imperfect direct and inverted repeats at its ends; at the insertion site a duplication of five nucleotides was found. Within the inserted DNA one copy each of an Alu element and of the simple sequence motif (T-G)17 were identified. Also these two repetitive sequences are themselves flanked by short direct repeats. The major inserted DNA has no significant homology to published human nucleic acid sequences. The whole structure is interpreted best by assuming a sequential insertion of the three elements. The coding region of the VK gene itself has several mutations which by themselves would render it a pseudogene; we assume that the insertion event(s) occurred prior to the mutations. According to mapping and hybridization data A6 is very similar to A22.

  14. Characterization of the human beta-secretase 2 (BACE2) 5'-flanking region: identification of a 268-bp region as the basal BACE2 promoter.

    PubMed

    Maloney, Bryan; Ge, Yuan-Wen; Greig, Nigel H; Lahiri, Debomoy K

    2006-01-01

    The main characteristic of Alzheimer's disease (AD) is brain deposition of the beta-amyloid (Abeta) peptide, generated endoproteolytically from Abeta precursor protein (APP) by beta- and gamma-secretases. A transmembrane aspartyl protease, beta-APP-cleaving enzyme (BACE1), was identified as beta-secretase. Although BACE1 cleaves APP at the beta-secretase site, the role of its homolog, beta-secretase 2 (BACE2) is poorly understood. We report the mRNA expression profile, DNA sequence, and molecular characterization of the BACE2 gene, located on chromosome 21q22.3. The BACE2 gene expresses more strongly in peripheral tissues, although BACE2 mRNA is found in the majority of brain regions, including the postcentral gyrus and temporal lobe. Characterization of 2932 bp of the BACE2 5'-flanking region (GC content of 55%), reveals the absence of canonical CCAAT and TATA boxes within 1 kb of the transcription start site (TSS). The sequence lacks significant internal repeats and has a housekeeping gene structure. Two active regions of the BACE2 promoter determine its basal expression and cell-type specificity. The proximal region (-31/+238) likely determines general basal expression, and the distal region (-2618/-1513), cell-type specificity. Several putative transcription factor sites, particularly SP1, Oct-1, and HES-1, are predicted to be within 1 kb of the TSS. On either side of the proximal promoter region, two negative regulatory domains might reduce BACE2 expression under an induced condition. The BACE2 5'-flanking region is likely to be highly regulated and expressed in a tissue type-specific manner.

  15. Discovery and Characterization of Human Exonic Transcriptional Regulatory Elements

    PubMed Central

    Khan, Arshad H.; Lin, Andy; Smith, Desmond J.

    2012-01-01

    We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome. PMID:23029400

  16. 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.

  17. 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.

  18. 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.

  19. Safety in shipping: the human element.

    PubMed

    Hetherington, Catherine; Flin, Rhona; Mearns, Kathryn

    2006-01-01

    There are numerous diverse papers that have addressed issues within maritime safety; to date there has been no comprehensive review of this literature to aggregate the causal factors within accidents in shipping and surmise current knowledge. This paper reviewed the literature on safety in three key areas: common themes of accidents, the influence of human error, and interventions to make shipping safer. The review included 20 studies of seafaring across the following areas: fatigue, stress, health, situation awareness, teamwork, decision-making, communication, automation, and safety culture. The review identifies the relative contributions of individual and organizational factors in shipping accidents, and also presents the methodological issues with previous research. The paper concludes that monitoring and modifying the human factors issues presented in this paper could contribute to maritime safety performance. This review illustrates which human factors issues are prevalent in incidents therefore this gives shipping practitioners a focus for interventions.

  20. 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…

  1. 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…

  2. 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.

  3. 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.

  4. PIXE measurement applied to trace elemental analysis of human tissues

    NASA Astrophysics Data System (ADS)

    Tanaka, M.; Matsugi, E.; Miyasaki, K.; Yamagata, T.; Inoue, M.; Ogata, H.; Shimoura, S.

    1987-03-01

    PIXE measurement was applied for trace elemental analyses of 40 autoptic human kidneys. To investigate the reproducibility of the PIXE data, 9 targets obtained from one human liver were examined. The targets were prepared by wet-digestion using nitric and sulfuric acid. Yttrium was used as an internal standard. The extracted elemental concentrations for K, Fe, Cu, Zn, and Cd were in reasonable agreement with those obtained by atomic absorption spectrometry (AAS) and flame photometry (FP). Various correlations among the elements K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Rb, and Cd were examined individually for the renal cortex and renal medulla.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. Latent Regulatory Potential of Human-Specific Repetitive Elements

    PubMed Central

    Ward, Michelle C.; Wilson, Michael D.; Barbosa-Morais, Nuno L.; Schmidt, Dominic; Stark, Rory; Pan, Qun; Schwalie, Petra C.; Menon, Suraj; Lukk, Margus; Watt, Stephen; Thybert, David; Kutter, Claudia; Kirschner, Kristina; Flicek, Paul; Blencowe, Benjamin J.; Odom, Duncan T.

    2013-01-01

    Summary At least half of the human genome is derived from repetitive elements, which are often lineage specific and silenced by a variety of genetic and epigenetic mechanisms. Using a transchromosomic mouse strain that transmits an almost complete single copy of human chromosome 21 via the female germline, we show that a heterologous regulatory environment can transcriptionally activate transposon-derived human regulatory regions. In the mouse nucleus, hundreds of locations on human chromosome 21 newly associate with activating histone modifications in both somatic and germline tissues, and influence the gene expression of nearby transcripts. These regions are enriched with primate and human lineage-specific transposable elements, and their activation corresponds to changes in DNA methylation at CpG dinucleotides. This study reveals the latent regulatory potential of the repetitive human genome and illustrates the species specificity of mechanisms that control it. PMID:23246434

  11. Role of Estrogen Response Element in the Human Prolactin Gene: Transcriptional Response and Timing.

    PubMed

    McNamara, Anne V; Adamson, Antony D; Dunham, Lee S S; Semprini, Sabrina; Spiller, David G; McNeilly, Alan S; Mullins, John J; Davis, Julian R E; White, Michael R H

    2016-02-01

    The use of bacterial artificial chromosome (BAC) reporter constructs in molecular physiology enables the inclusion of large sections of flanking DNA, likely to contain regulatory elements and enhancers regions that contribute to the transcriptional output of a gene. Using BAC recombineering, we have manipulated a 160-kb human prolactin luciferase (hPRL-Luc) BAC construct and mutated the previously defined proximal estrogen response element (ERE) located -1189 bp relative to the transcription start site, to assess its involvement in the estrogen responsiveness of the entire hPRL locus. We found that GH3 cell lines stably expressing Luc under control of the ERE-mutated hPRL promoter (ERE-Mut) displayed a dramatically reduced transcriptional response to 17β-estradiol (E2) treatment compared with cells expressing Luc from the wild-type (WT) ERE hPRL-Luc promoter (ERE-WT). The -1189 ERE controls not only the response to E2 treatment but also the acute transcriptional response to TNFα, which was abolished in ERE-Mut cells. ERE-WT cells displayed a biphasic transcriptional response after TNFα treatment, the acute phase of which was blocked after treatment with the estrogen receptor antagonist 4-hydroxy-tamoxifen. Unexpectedly, we show the oscillatory characteristics of hPRL promoter activity in individual living cells were unaffected by disruption of this crucial response element, real-time bioluminescence imaging showed that transcription cycles were maintained, with similar cycle lengths, in ERE-WT and ERE-Mut cells. These data suggest the -1189 ERE is the dominant response element involved in the hPRL transcriptional response to both E2 and TNFα and, crucially, that cycles of hPRL promoter activity are independent of estrogen receptor binding.

  12. "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. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. [The role of macro-elements in the human body].

    PubMed

    Lakatos, Béla; Balla, József; Vinkler, Péter; Szentmihályi, Klára

    2006-05-21

    The authors summarize the role of essential macro metal elements (Na, K, Ca, Mg) in human body: their homeostasis, absorption, transport, storage and excretion. Metabolism of macro-elements, daily requirements, cause of metal deficiencies and diseases caused by deficiencies are also discussed. Messenger and prooxidant effect of Ca2+-ions, indirect antioxidant effect of Mg2+-ions and the adjuvant application of magnesium are also reviewed.

  15. LINE dancing in the human genome: transposable elements and disease

    PubMed Central

    2009-01-01

    Transposable elements (TEs) have been consistently underestimated in their contribution to genetic instability and human disease. TEs can cause human disease by creating insertional mutations in genes, and also contributing to genetic instability through non-allelic homologous recombination and introduction of sequences that evolve into various cis-acting signals that alter gene expression. Other outcomes of TE activity, such as their potential to cause DNA double-strand breaks or to modulate the epigenetic state of chromosomes, are less fully characterized. The currently active human transposable elements are members of the non-LTR retroelement families, LINE-1, Alu (SINE), and SVA. The impact of germline insertional mutagenesis by TEs is well established, whereas the rate of post-insertional TE-mediated germline mutations and all forms of somatic mutations remain less well quantified. The number of human diseases discovered to be associated with non-allelic homologous recombination between TEs, and particularly between Alu elements, is growing at an unprecedented rate. Improvement in the technology for detection of such events, as well as the mounting interest in the research and medical communities in resolving the underlying causes of the human diseases with unknown etiology, explain this increase. Here, we focus on the most recent advances in understanding of the impact of the active human TEs on the stability of the human genome and its relevance to human disease. PMID:19863772

  16. Reference values of elements in human hair: a systematic review.

    PubMed

    Mikulewicz, Marcin; Chojnacka, Katarzyna; Gedrange, Thomas; Górecki, Henryk

    2013-11-01

    The lack of systematic review on reference values of elements in human hair with the consideration of methodological approach. The absence of worldwide accepted and implemented universal reference ranges causes that hair mineral analysis has not become yet a reliable and useful method of assessment of nutritional status and exposure of individuals. Systematic review of reference values of elements in human hair. PubMed, ISI Web of Knowledge, Scopus. Humans, hair mineral analysis, elements or minerals, reference values, original studies. The number of studies screened and assessed for eligibility was 52. Eventually, included in the review were 5 papers. The studies report reference ranges for the content of elements in hair: macroelements, microelements, toxic elements and other elements. Reference ranges were elaborated for different populations in the years 2000-2012. The analytical methodology differed, in particular sample preparation, digestion and analysis (ICP-AES, ICP-MS). Consequently, the levels of hair minerals reported as reference values varied. It is necessary to elaborate the standard procedures and furtherly validate hair mineral analysis and deliver detailed methodology. Only then it would be possible to provide meaningful reference ranges and take advantage of the potential that lies in Hair Mineral Analysis as a medical diagnostic technique. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. A review of radiologically important trace elements in human bones.

    PubMed

    Tandon, L; Iyengar, G V; Parr, R M

    1998-08-01

    The authors recently compiled and reviewed the literature for minor and trace elements in human bones and teeth as a part of an International Atomic Energy Agency (IAEA) study. Various aspects of elemental composition, analytical methodologies, quality assurance and quality control methods for hard tissue analysis were evaluated. Important data on selected radiologically important elements (Cs, Pu, Ra, Sr, Th, and U) in calcified tissue from various countries are discussed. The results of this compilation study suggest a need for new reference materials with matrix properties similar to bones including one with separated cortical and trabecular segments.

  18. 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)

  19. 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.

  20. 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

  1. Transposable Elements in Human Cancer: Causes and Consequences of Deregulation

    PubMed Central

    Anwar, Sumadi Lukman; Wulaningsih, Wahyu; Lehmann, Ulrich

    2017-01-01

    Transposable elements (TEs) comprise nearly half of the human genome and play an essential role in the maintenance of genomic stability, chromosomal architecture, and transcriptional regulation. TEs are repetitive sequences consisting of RNA transposons, DNA transposons, and endogenous retroviruses that can invade the human genome with a substantial contribution in human evolution and genomic diversity. TEs are therefore firmly regulated from early embryonic development and during the entire course of human life by epigenetic mechanisms, in particular DNA methylation and histone modifications. The deregulation of TEs has been reported in some developmental diseases, as well as for different types of human cancers. To date, the role of TEs, the mechanisms underlying TE reactivation, and the interplay with DNA methylation in human cancers remain largely unexplained. We reviewed the loss of epigenetic regulation and subsequent genomic instability, chromosomal aberrations, transcriptional deregulation, oncogenic activation, and aberrations of non-coding RNAs as the potential mechanisms underlying TE deregulation in human cancers. PMID:28471386

  2. 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.

  3. 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

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

    PubMed

    2012-09-06

    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.

  5. Trace elements in human milk, selenium a case study.

    PubMed

    Roekens, E; Deelstra, H; Robberecht, H

    1985-03-15

    Longitudinal changes of the trace element (Fe, Cu, Zn, Mn, Mo, Cr, Co, As, Se) composition of human milk are discussed. The mean daily intake of breast fed infants is compared with the intake of infants fed cow's milk and with recommended dietary allowances. Parameters which can be used to check the selenium status are discussed. Clinical consequences of selenium deficiency are discussed.

  6. 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…

  7. Human exposure and health effects of inorganic and elemental mercury.

    PubMed

    Park, Jung-Duck; Zheng, Wei

    2012-11-01

    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.

  8. 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

  9. DNA Double-Strand Breaks Coupled with PARP1 and HNRNPA2B1 Binding Sites Flank Coordinately Expressed Domains in Human Chromosomes

    PubMed Central

    Fedoseeva, Daria M.; Sosin, Dmitri V.; Grachev, Sergei A.; Serebraykova, Marina V.; Romanenko, Svetlana A.; Vorobieva, Nadezhda V.; Kravatsky, Yuri V.

    2013-01-01

    Genome instability plays a key role in multiple biological processes and diseases, including cancer. Genome-wide mapping of DNA double-strand breaks (DSBs) is important for understanding both chromosomal architecture and specific chromosomal regions at DSBs. We developed a method for precise genome-wide mapping of blunt-ended DSBs in human chromosomes, and observed non-random fragmentation and DSB hot spots. These hot spots are scattered along chromosomes and delimit protected 50–250 kb DNA domains. We found that about 30% of the domains (denoted forum domains) possess coordinately expressed genes and that PARP1 and HNRNPA2B1 specifically bind DNA sequences at the forum domain termini. Thus, our data suggest a novel type of gene regulation: a coordinated transcription or silencing of gene clusters delimited by DSB hot spots as well as PARP1 and HNRNPa2B1 binding sites. PMID:23593027

  10. Transposable element insertions have strongly affected human evolution.

    PubMed

    Britten, Roy J

    2010-11-16

    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.

  11. Distributions of sulphur and other elements in human hair follicles

    NASA Astrophysics Data System (ADS)

    Ollerhead, R. W.; Legge, G. J. F.; Jones, L. N.

    1989-04-01

    Distributions of sulphur and other elements have been measured in several different specimens of human hair follicles. Whole specimens, longitudinal bisections, and 10 μm thick longitudinal sections have been analyzed by PIXE using the Melbourne scanning proton microprobe. Elemental maps consistently showed that sulphur contents of the presumptive hair shaft (PHS) were uniformly low from 0 to 400 μm (bulb end), increased continuously from about 400 to 800 μm, and reached a plateau. Sulphur levels were uniformly low in the inner root sheath. These observations are consistent with previous protein analysis of PHS sections, indicating sequential synthesis of the major classes of keratin proteins. Maps of other elements indicated that Si, Ca, and Fe tended to be concentrated randomly, whereas, P, Cl, K, and Zn were more uniformly distributed. Average relative concentrations of Si, P, Cl, K, Ca, Fe, Cu, and Zn were estimated from total X-ray spectra.

  12. Use of human MAR elements to improve retroviral vector production.

    PubMed

    Buceta, M; Galbete, J L; Kostic, C; Arsenijevic, Y; Mermod, N

    2011-01-01

    Retroviral vectors have many favorable properties for gene therapies, but their use remains limited by safety concerns and/or by relatively lower titers for some of the safer self-inactivating (SIN) derivatives. In this study, we evaluated whether increased production of SIN retroviral vectors can be achieved from the use of matrix attachment region (MAR) epigenetic regulators. Two MAR elements of human origin were found to increase and to stabilize the expression of the green fluorescent protein transgene in stably transfected HEK-293 packaging cells. Introduction of one of these MAR elements in retroviral vector-producing plasmids yielded higher expression of the viral vector RNA. Consistently, viral titers obtained from transient transfection of MAR-containing plasmids were increased up to sixfold as compared with the parental construct, when evaluated in different packaging cell systems and transfection conditions. Thus, use of MAR elements opens new perspectives for the efficient generation of gene therapy vectors.

  13. Trace elements in human body fluids and tissues.

    PubMed

    Versieck, J

    1985-01-01

    Published figures for trace element concentrations in body fluids and tissues of apparently healthy subjects are widely divergent. For a considerable time, the apparent disparities were readily ascribed to biological sources of variation such as age, sex, dietary habits, physiological conditions, environmental exposure, geographical circumstances, or similar influences. Growing evidence, however, suggests that this interpretation may be seriously questioned in numerous instances. First, values obtained in reference materials leave no doubt that some previous studies must have been subject to gross analytical inaccuracies. Second, it has now been thoroughly documented that inadequate sample collection and manipulation may drastically distort the intrinsic trace element content of biological matrices. This review scrutinizes data reported by a number of investigators. In an effort to settle the currently flourishing confusion, critically selected reference values are set forth for trace element levels in human blood plasma or serum, packed blood cells, urine, lung, liver, kidney, and skeletal muscle tissue.

  14. Transposable elements in cancer and other human diseases.

    PubMed

    Chenais, Benoit

    2015-01-01

    Transposable elements (TEs) are mobile DNA sequences representing a substantial fraction of most genomes. Through the creation of new genes and functions, TEs are important elements of genome plasticity and evolution. However TE insertion in human genomes may be the cause of genetic dysfunction and alteration of gene expression contributing to cancer and other human diseases. Besides the chromosome rearrangements induced by TE repeats, this mini-review shows how gene expression may be altered following TE insertion, for example by the creation of new polyadenylation sites, by the creation of new exons (exonization), by exon skipping and by other modification of alternative splicing, and also by the alteration of regulatory sequences. Through the correlation between TE mobility and the methylation status of DNA, the importance of chromatin regulation is evident in several diseases. Finally this overview ends with a brief presentation of the use of TEs as biotechnology tools for insertional mutagenesis screening and gene therapy with DNA transposons.

  15. Trace element analysis of human hair by PIXE

    NASA Astrophysics Data System (ADS)

    Jian-xin, Chen; Yuan-zhuang, Guo; Hong-kou, Li; Chi-gang, Ren; Guo-hun, Tang; Xi-de, Wang; Fu-chia, Yang; Hui-ying, Yao

    1981-03-01

    PIXE was used to analyze trace elements in human hair. Using an external beam, hair from workers exposed to GaAs was examined. The results are in fairly good agreement with those obtained by atomic absorption spectroscopy. Using the PIXE technique in vacuum hair from mentally defective children was analyzed and compared with the hair of normal children. In a similar way, hair from a 3200 year old preserved mummy was studied.

  16. The prediction of flanking sound transmission below the critical frequency.

    PubMed

    Davy, John L; Mahn, Jeffrey P; Guigou-Carter, Catherine; Villot, Michel

    2012-10-01

    Although reliable methods exist to predict the apparent sound reduction index of heavy, homogeneous isotopic building constructions, these methods are not appropriate for use with lightweight building constructions which typically have critical frequencies in or above the frequency range of interest. Three main methods have been proposed for extending the prediction of flanking sound transmission to frequencies below the critical frequency. The first method is the direct prediction which draws on a database of measurements of the flanking transmission of individual flanking paths. The second method would be a modification of the method in existing standards. This method requires the calculation of the resonant sound transmission factors. However, most of the approaches proposed to calculate the resonant sound transmission factor work only for the case of single leaf homogeneous isotropic building elements and therefore are not readily applicable to complex building elements. The third method is the measurement or prediction of the resonant radiation efficiency and the airborne diffuse field excited radiation efficiency which includes both the resonant and the non-resonant radiation efficiencies. The third method can currently deal with complex building elements if the radiation efficiencies can be measured or predicted. This paper examines these prediction methods.

  17. Muscle-driven finite element simulation of human foot movements.

    PubMed

    Spyrou, L A; Aravas, N

    2012-01-01

    This paper describes a finite element scheme for realistic muscle-driven simulation of human foot movements. The scheme is used to simulate human ankle plantar flexion. A three-dimensional anatomically detailed finite element model of human foot and lower leg is developed and the idea of generating natural foot movement based entirely on the contraction of the plantar flexor muscles is used. The bones, ligaments, articular cartilage, muscles, tendons, as well as the rest soft tissues of human foot and lower leg are included in the model. A realistic three-dimensional continuum constitutive model that describes the biomechanical behaviour of muscles and tendons is used. Both the active and passive properties of muscle tissue are accounted for. The materials for bones and ligaments are considered as homogeneous, isotropic and linearly elastic, whereas the articular cartilage and the rest soft tissues (mainly fat) are defined as hyperelastic materials. The model is used to estimate muscle tissue deformations as well as stresses and strains that develop in the lower leg muscles during plantar flexion of the ankle. Stresses and strains that develop in Achilles tendon during such a movement are also investigated.

  18. A comprehensive map of mobile element insertion polymorphisms in humans.

    PubMed

    Stewart, Chip; Kural, Deniz; Strömberg, Michael P; Walker, Jerilyn A; Konkel, Miriam K; Stütz, Adrian M; Urban, Alexander E; Grubert, Fabian; Lam, Hugo Y K; Lee, Wan-Ping; Busby, Michele; Indap, Amit R; Garrison, Erik; Huff, Chad; Xing, Jinchuan; Snyder, Michael P; Jorde, Lynn B; Batzer, Mark A; Korbel, Jan O; Marth, Gabor T

    2011-08-01

    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations.

  19. A Comprehensive Map of Mobile Element Insertion Polymorphisms in Humans

    PubMed Central

    Walker, Jerilyn A.; Konkel, Miriam K.; Stütz, Adrian M.; Urban, Alexander E.; Grubert, Fabian; Lam, Hugo Y. K.; Lee, Wan-Ping; Busby, Michele; Indap, Amit R.; Garrison, Erik; Huff, Chad; Xing, Jinchuan; Snyder, Michael P.; Jorde, Lynn B.; Batzer, Mark A.; Korbel, Jan O.; Marth, Gabor T.

    2011-01-01

    As a consequence of the accumulation of insertion events over evolutionary time, mobile elements now comprise nearly half of the human genome. The Alu, L1, and SVA mobile element families are still duplicating, generating variation between individual genomes. Mobile element insertions (MEI) have been identified as causes for genetic diseases, including hemophilia, neurofibromatosis, and various cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the 1000 Genomes Project whole-genome sequencing data of 185 samples in three major populations detected with two detection methods. This catalog enables us to systematically study mutation rates, population segregation, genomic distribution, and functional properties of MEI polymorphisms and to compare MEI to SNP variation from the same individuals. Population allele frequencies of MEI and SNPs are described, broadly, by the same neutral ancestral processes despite vastly different mutation mechanisms and rates, except in coding regions where MEI are virtually absent, presumably due to strong negative selection. A direct comparison of MEI and SNP diversity levels suggests a differential mobile element insertion rate among populations. PMID:21876680

  20. New insight into transcription of human endogenous retroviral elements.

    PubMed

    Pačes, Jan; Huang, Yao-Ting; Pačes, Václav; Rídl, Jakub; Chang, Chung-Ming

    2013-03-25

    It is generally assumed that human endogenous retroviral elements (HERVs) belong to the class of genomic repetitive nucleotide sequences often called 'junk DNA'. These elements were categorized to families, and members of some of these families (e.g. HERV-H, HERV-W and HERV-K) were shown to be transcribed. These transcriptions were associated with several severe diseases such as mental disorders, AIDS, autoimmune diseases and cancer. In this review we discuss several bioinformatics strategies for genome-wide scan of HERVs transcription using high-throughput RNA sequencing on several platforms. We show that many more HERVs than previously described are transcribed to various levels and we discuss possible implications of these transcriptions.

  1. [Is chromium an essential trace element in human nutrition?].

    PubMed

    Yoshida, Munehiro

    2012-01-01

    It has been recognized that chromium is an essential trace element associated with carbohydrate metabolism, and chromium deficiency causes an impaired glucose tolerance. Recently, however, Vincent et al. have reported that chromium is not an essential trace element. In the present report, the author evaluated the nutritional essentiality of chromium by reviewing several previous reports. In almost all previous reports, the chromium concentration in the animal feed used was higher than 0.1 μg/g, and it is difficult to consider that the experimental animals were in a low-chromium state. In addition, the amount of chromium administered to the animals for the improvement of glucose tolerance was at a pharmacological level, and corresponded to a level that far exceeded the human daily chromium intake (20 to 80 μg/day). On the other hand, recent research has clearly shown that feeding with a severely low-chromium diet (0.016 μg/g) does not impair glucose tolerance. The amount of chromium absorbed in humans estimated from chromium intake (20 to 80 μg/day), chromium absorption rate (1%), and urinary chromium excretion (<1 μg/day) is less than 1 μg/day, which is much lower than those of other essential trace elements. In addition, because there is an inconsistency between the chromium concentration in food and chromium intake, chromium intake seems to be dependent on chromium contamination during food processing and cooking. It is concluded that there is a high possibility that chromium is not an essential trace element.

  2. Diagnosis of susceptibility to malignant hyperthermia with flanking DNA markers.

    PubMed Central

    Healy, S J; Heffron, J J; Lehane, M; Bradley, D G; Johnson, K; McCarthy, T V

    1991-01-01

    OBJECTIVE--To define the region on human chromosome 19 carrying the gene for malignant hyperthermia susceptibility and to evaluate the use of flanking DNA markers in diagnosing susceptibility. DESIGN--Prospective molecular genetic linkage studies in a large malignant hyperthermia pedigree. SETTING--Irish malignant hyperthermia testing centre. SUBJECTS--A large Irish malignant hyperthermia pedigree. MAIN OUTCOME MEASURES--Routine diagnosis of susceptibility to malignant hyperthermia with in vitro contracture test on muscle biopsy specimens and genetic linkage between susceptibility and polymorphic DNA markers in a malignant hyperthermia family. RESULTS--Genetic typing of polymorphic DNA markers in a large Irish malignant hyperthermia pedigree generated a lod score of greater than 3 for the marker D19S9 and showed that the gene for susceptibility is flanked by the markers D19S9 and D19S16. These tightly linked flanking markers allowed non-invasive presymptomatic diagnosis of susceptibility in five untested subjects in the large pedigree with an accuracy of greater than 99.7%. CONCLUSIONS--DNA markers flanking the gene for susceptibility to malignant hyperthermia can be used with high accuracy to diagnose susceptibility in subjects in large known malignant hyperthermia pedigrees and may replace the previous in vitro contracture test for diagnosing this inherited disorder in large families with malignant hyperthermia. PMID:1684123

  3. Defining functional DNA elements in the human genome.

    PubMed

    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

    2014-04-29

    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.

  4. 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

  5. Characterization of 5' end of human thromboxane receptor gene. Organizational analysis and mapping of protein kinase C--responsive elements regulating expression in platelets.

    PubMed

    D'Angelo, D D; Davis, M G; Houser, W A; Eubank, J J; Ritchie, M E; Dorn, G W

    1995-09-01

    Platelet thromboxane receptors are acutely and reversibly upregulated after acute myocardial infarction. To determine if platelet thromboxane receptors are under transcriptional control, we isolated and characterized human genomic DNA clones containing the 5' flanking region of the thromboxane receptor gene. The exon-intron structure of the 5' portion of the thromboxane receptor gene was determined initially by comparing the nucleotide sequence of the 5' flanking genomic clone with that of a novel human uterine thromboxane receptor cDNA that extended the mRNA 141 bp further upstream than the previously identified human placental cDNA. A major transcription initiation site was located in three human tissues approximately 560 bp upstream from the translation initiation codon and 380 bp upstream from any previously identified transcription initiation site. The thromboxane receptor gene has neither a TATA nor a CAAT consensus site. Promoter function of the 5' flanking region of the thromboxane receptor gene was evaluated by transfection of thromboxane receptor gene promoter/chloramphenicol acetyltransferase (CAT) chimera plasmids into platelet-like K562 cells. Thromboxane receptor promoter activity, as assessed by CAT expression, was relatively weak but was significantly enhanced by phorbol ester treatment. Functional analysis of 5' deletion constructs in transfected K562 cells and gel mobility shift localized the major phorbol ester-responsive motifs in the thromboxane receptor gene promoter to a cluster of activator protein-2 (AP-2) binding consensus sites located approximately 1.8 kb 5' from the transcription initiation site. These studies are the first to determine the structure and organization of the 5' end of the thromboxane receptor gene and demonstrate that thromboxane receptor gene expression can be regulated by activation of protein kinase C via induction of an AP-2-like nuclear factor binding to upstream promoter elements. These findings strongly suggest

  6. 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; hide

    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.

  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.

  8. Genomic landscape of CpG rich elements in human.

    PubMed

    Babenko, Vladimir N; Chadaeva, Irina V; Orlov, Yuriy L

    2017-02-07

    The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location. Recent emergence of high resolution 3D map of human genome allowed segregating the genome into the large scale chromatin domains of naturally observable nuclear subcompartments, or Topologically Associated Domains (TADs), designated by spatial chromatin distribution. We utilized the chromatin map to elucidate relations between large scale chromatin state and CpG rich elements landscape. In the course of analysis it was confirmed that genes, Alu and CGI clusters maintain obvious, albeit different in strength, preference for open chromatin. For the first time it was clearly shown that the clusters density of the Alu and CGIs monotonically depend on the chromatin accessibility rate. In particular, the highest density of these elements is found in A1 euchromatin regions characterized by a high density of small length genes replicating in the early S-phase. It implies that these elements mediate (CGIs) or are a side element (Alus) of chromatin accessibility. We elucidated that both methylated and non-methylated CGIs display the affinity to chromatin accessibility. As a part of comparative genomics section, we elucidated that the dog's genome non-canonical structure, outstanding in mammals for its high CGIs abundance compared to gene number, is explained by the presence of dense tandem CGI extended hotspots

  9. 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.

  10. The Unusual 23S rRNA Gene of Coxiella burnetii: Two Self-Splicing Group I Introns Flank a 34-Base-Pair Exon, and One Element Lacks the Canonical ΩG▿

    PubMed Central

    Raghavan, Rahul; Miller, Scott R.; Hicks, Linda D.; Minnick, Michael F.

    2007-01-01

    We describe the presence and characteristics of two self-splicing group I introns in the sole 23S rRNA gene of Coxiella burnetii. The two group I introns, Cbu.L1917 and Cbu.L1951, are inserted at sites 1917 and 1951 (Escherichia coli numbering), respectively, in the 23S rRNA gene of C. burnetii. Both introns were found to be self-splicing in vivo and in vitro even though the terminal nucleotide of Cbu.L1917 is adenine and not the canonical conserved guanine, termed ΩG, found in Cbu.L1951 and all other group I introns described to date. Predicted secondary structures for both introns were constructed and revealed that Cbu.L1917 and Cbu.L1951 were group IB2 and group IA3 introns, respectively. We analyzed strains belonging to eight genomic groups of C. burnetii to determine sequence variation and the presence or absence of the elements and found both introns to be highly conserved (≥99%) among them. Although phylogenetic analysis did not identify the specific identities of donors, it indicates that the introns were likely acquired independently; Cbu.L1917 was acquired from other bacteria like Thermotoga subterranea and Cbu.L1951 from lower eukaryotes like Acanthamoeba castellanii. We also confirmed the fragmented nature of mature 23S rRNA in C. burnetii due to the presence of an intervening sequence. The presence of three selfish elements in C. burnetii's 23S rRNA gene is very unusual for an obligate intracellular bacterium and suggests a recent shift to its current lifestyle from a previous niche with greater opportunities for lateral gene transfer. PMID:17644584

  11. Lentivirus vectors using human and simian immunodeficiency virus elements.

    PubMed

    White, S M; Renda, M; Nam, N Y; Klimatcheva, E; Zhu, Y; Fisk, J; Halterman, M; Rimel, B J; Federoff, H; Pandya, S; Rosenblatt, J D; Planelles, V

    1999-04-01

    Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34(+) cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans.

  12. Lentivirus Vectors Using Human and Simian Immunodeficiency Virus Elements

    PubMed Central

    White, Sarah M.; Renda, Matthew; Nam, Na-Yon; Klimatcheva, Ekaterina; Zhu, Yonghong; Fisk, Jennifer; Halterman, Mark; Rimel, Bobbie J.; Federoff, Howard; Pandya, Snehal; Rosenblatt, Joseph D.; Planelles, Vicente

    1999-01-01

    Lentivirus vectors based on human immunodeficiency virus (HIV) type 1 (HIV-1) constitute a recent development in the field of gene therapy. A key property of HIV-1-derived vectors is their ability to infect nondividing cells. Although high-titer HIV-1-derived vectors have been produced, concerns regarding safety still exist. Safety concerns arise mainly from the possibility of recombination between transfer and packaging vectors, which may give rise to replication-competent viruses with pathogenic potential. We describe a novel lentivirus vector which is based on HIV, simian immunodeficiency virus (SIV), and vesicular stomatitis virus (VSV) and which we refer to as HIV/SIVpack/G. In this system, an HIV-1-derived genome is encapsidated by SIVmac core particles. These core particles are pseudotyped with VSV glycoprotein G. Because the nucleotide homology between HIV-1 and SIVmac is low, the likelihood of recombination between vector elements should be reduced. In addition, the packaging construct (SIVpack) for this lentivirus system was derived from SIVmac1A11, a nonvirulent SIV strain. Thus, the potential for pathogenicity with this vector system is minimal. The transduction ability of HIV/SIVpack/G was demonstrated with immortalized human lymphocytes, human primary macrophages, human bone marrow-derived CD34+ cells, and primary mouse neurons. To our knowledge, these experiments constitute the first demonstration that the HIV-1-derived genome can be packaged by an SIVmac capsid. We demonstrate that the lentivirus vector described here recapitulates the biological properties of HIV-1-derived vectors, although with increased potential for safety in humans. PMID:10074131

  13. Neglecting human ecology: The common element of global health failures.

    PubMed

    Hanley, Matthew

    2016-02-01

    Attempts to control malaria, AIDS, and maternal mortality in Africa have been woefully inadequate. This has involved adopting an almost exclusively technical preventive approach in the context of AIDS even though emphasizing human behavior holds the most promise. But on the other hand, it has also involved abandoning highly effective technical measures, as in the case of malaria. This suggests that the failure, at root, is anthropological in nature. The common element, it is argued here, is the failure to place the human ecology resolutely above destructive ideologies. Sound public-health approaches have been spurned in favor of predetermined preventive approaches in the service of ideological aims rather than of man and the common good. This article examines the ideological forces that have ultimately driven global health policy, and proposes that a more humane anthropology would be beneficial. Lay Summary: The scourges of malaria, AIDS, and maternal mortality have persisted in Africa, even though sensible and available means of addressing these epidemics, when stressed, have met with success. The reluctance to consistently emphasize the soundest public-health approaches-whether technical or behavioral in nature-indicate that global health policy has to a large extent been improperly concerned with advancing ideological agendas. The challenge we face today is not primarily technical but philosophical; the healing professions would perform a service by cultivating a higher view of man and an appreciation for objective moral truths that protect him.

  14. Neglecting human ecology: The common element of global health failures

    PubMed Central

    Hanley, Matthew

    2016-01-01

    Attempts to control malaria, AIDS, and maternal mortality in Africa have been woefully inadequate. This has involved adopting an almost exclusively technical preventive approach in the context of AIDS even though emphasizing human behavior holds the most promise. But on the other hand, it has also involved abandoning highly effective technical measures, as in the case of malaria. This suggests that the failure, at root, is anthropological in nature. The common element, it is argued here, is the failure to place the human ecology resolutely above destructive ideologies. Sound public-health approaches have been spurned in favor of predetermined preventive approaches in the service of ideological aims rather than of man and the common good. This article examines the ideological forces that have ultimately driven global health policy, and proposes that a more humane anthropology would be beneficial. Lay Summary: The scourges of malaria, AIDS, and maternal mortality have persisted in Africa, even though sensible and available means of addressing these epidemics, when stressed, have met with success. The reluctance to consistently emphasize the soundest public-health approaches—whether technical or behavioral in nature—indicate that global health policy has to a large extent been improperly concerned with advancing ideological agendas. The challenge we face today is not primarily technical but philosophical; the healing professions would perform a service by cultivating a higher view of man and an appreciation for objective moral truths that protect him. PMID:27833184

  15. [Molecular variability in the commom shrew Sorex araneus L. from European Russia and Siberia inferred from the length polymorphism of DNA regions flanked by short interspersed elements (Inter-SINE PCR) and the relationships between the Moscow and Seliger chromosome races].

    PubMed

    Bannikova, A A; Bulatova, N Sh; Kramerov, D A

    2006-06-01

    Genetic exchange among chromosomal races of the common shrew Sorex araneus and the problem of reproductive barriers have been extensively studied by means of such molecular markers as mtDNA, microsatellites, and allozymes. In the present study, the interpopulation and interracial polymorphism in the common shrew was derived, using fingerprints generated by amplified DNA regions flanked by short interspersed repeats (SINEs)-interSINE PCR (IS-PCR). We used primers, complementary to consensus sequences of two short retroposons: mammalian element MIR and the SOR element from the genome of Sorex araneus. Genetic differentiation among eleven populations of the common shrew from eight chromosome races was estimated. The NP and MJ analyses, as well as multidimensional scaling showed that all samples examined grouped into two main clusters, corresponding to European Russia and Siberia. The bootstrap support of the European Russia cluster in the NJ and MP analyses was respectively 76 and 61%. The bootstrap index for the Siberian cluster was 100% in both analyses; the Tomsk race, included into this cluster, was separated with the bootstrap support of NJ/MP 92/95%.

  16. 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.

  17. The elements of a commercial human spaceflight safety reporting system

    NASA Astrophysics Data System (ADS)

    Christensen, Ian

    2017-10-01

    In its report on the SpaceShipTwo accident the National Transportation Safety Board (NTSB) included in its recommendations that the Federal Aviation Administration (FAA) ;in collaboration with the commercial spaceflight industry, continue work to implement a database of lessons learned from commercial space mishap investigations and encourage commercial space industry members to voluntarily submit lessons learned.; In its official response to the NTSB the FAA supported this recommendation and indicated it has initiated an iterative process to put into place a framework for a cooperative safety data sharing process including the sharing of lessons learned, and trends analysis. Such a framework is an important element of an overall commercial human spaceflight safety system.

  18. Distributions of elements in the human retinal pigment epithelium.

    PubMed

    Ulshafer, R J; Allen, C B; Rubin, M L

    1990-01-01

    Distributions of elements above the atomic number of sodium were mapped in the retinal pigment epithelia of eight human eyes. X-ray energy spectra and maps were collected from cryofixed, freeze-dried, and epoxy-embedded tissues using energy-dispersive x-ray microanalysis. All eyes had high concentrations of phosphorus in the nuclei of retinal pigment epithelial cells. Melanosomes were rich in sulfur, zinc, calcium, and iron. Lipofuscin and cytoplasm contained only phosphorus and sulfur in detectable amounts. Drusen, when present, contained phosphorus and calcium. Six eyes had a prominent aluminum peak recorded from melanosomes, nuclei, and Bruch's membrane. In one pair of 90-year-old eyes, small, electron-dense deposits surrounded many melanosomes and contained mercury and selenium. Retinal pigment epithelial melanosomes may bind and accumulate metals and other potentially toxic ions over time, preventing them from reaching the neural retina.

  19. The effect of giant flank collapses on magma pathways and location of volcanic vents

    NASA Astrophysics Data System (ADS)

    Maccaferri, Francesco; Richter, Nicole; Walter, Thomas

    2017-04-01

    Flank collapses have been identified at tall volcanoes and ocean islands worldwide. They are recurrent processes, significantly contributing to the morphological and structural evolution of volcanic edifices, and they often occur in interaction with magmatic activity. Moreover, it has been observed that the intrusion pathways and eruption's sites often differ before and after flank collapses. While it is understood that dyke intrusions might destabilise a volcano flank, and a moving flank might create the space needed for further intrusions, the effect of collapses on the magma pathways has been rarely addressed. Here we use a boundary element model for dyke propagation to study the effect of the stress redistribution due to a flank collapse on the location of eruptive vents. We use our model to simulate the path of magmatic intrusion after the collapse of the eastern flank of Fogo Volcano, Cabe Verde. We find that the competition between loading stress due to the volcanic edifice and unloading due to the collapse of a flank favours magmatic activity to cluster within the collapse scar, displaced with respect to the pre-collapse volcanic centre. Our results are compared with geomorphological observations at Fogo Island and are discussed in the general context of the long-term evolution intraplate volcanic ocean islands worldwide.

  20. Transposable element dynamics of the hAT element Herves in the human malaria vector Anopheles gambiae s.s.

    PubMed

    Subramanian, Ramanand A; Arensburger, Peter; Atkinson, Peter W; O'Brochta, David A

    2007-08-01

    Transposable elements are being considered as genetic drive agents for introducing phenotype-altering genes into populations of vectors of human disease. The dynamics of endogenous elements will assist in predicting the behavior of introduced elements. Transposable element display was used to estimate the site-occupancy frequency distribution of Herves in six populations of Anopheles gambiae s.s. The site-occupancy distribution data suggest that the element has been recently active within the sampled populations. All 218 individuals sampled contained at least one copy of Herves with a mean of 3.6 elements per diploid genome. No significant differences in copy number were observed among populations. Nucleotide polymorphism within the element was high (pi = 0.0079 in noncoding sequences and 0.0046 in coding sequences) relative to that observed in some of the more well-studied elements in Drosophila melanogaster. In total, 33 distinct forms of Herves were found on the basis of the sequence of the first 528 bp of the transposase open reading frame. Only two forms were found in all six study populations. Although Herves elements in An. gambiae are quite diverse, 85% of the individuals examined had evidence of complete forms of the element. Evidence was found for the lateral transfer of Herves from an unknown source into the An. gambiae lineage prior to the diversification of the An. gambiae species complex. The characteristics of Herves in An. gambiae are somewhat unlike those of P elements in D. melanogaster.

  1. 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

  2. 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.

  3. Comparative analysis on the structural features of the 5' flanking region of κ-casein genes from six different species

    PubMed Central

    Gerencsér, Ákos; Barta, Endre; Boa, Simon; Kastanis, Petros; Bösze, Zsuzsanna; Whitelaw, C Bruce A

    2002-01-01

    κ-casein plays an essential role in the formation, stabilisation and aggregation of milk micelles. Control of κ-casein expression reflects this essential role, although an understanding of the mechanisms involved lags behind that of the other milk protein genes. We determined the 5'-flanking sequences for the murine, rabbit and human κ-casein genes and compared them to the published ruminant sequences. The most conserved region was not the proximal promoter region but an approximately 400 bp long region centred 800 bp upstream of the TATA box. This region contained two highly conserved MGF/STAT5 sites with common spacing relative to each other. In this region, six conserved short stretches of similarity were also found which did not correspond to known transcription factor consensus sites. On the contrary to ruminant and human 5' regulatory sequences, the rabbit and murine 5'-flanking regions did not harbour any kind of repetitive elements. We generated a phylogenetic tree of the six species based on multiple alignment of the κ-casein sequences. This study identified conserved candidate transcriptional regulatory elements within the κ-casein gene promoter. PMID:11929628

  4. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293

    PubMed Central

    Kanhayuwa, Lakkhana; Coutts, Robert H. A.

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4–14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140–493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3’-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50–65% and 60–75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259–343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity. PMID:27736869

  5. Short Interspersed Nuclear Element (SINE) Sequences in the Genome of the Human Pathogenic Fungus Aspergillus fumigatus Af293.

    PubMed

    Kanhayuwa, Lakkhana; Coutts, Robert H A

    2016-01-01

    Novel families of short interspersed nuclear element (SINE) sequences in the human pathogenic fungus Aspergillus fumigatus, clinical isolate Af293, were identified and categorised into tRNA-related and 5S rRNA-related SINEs. Eight predicted tRNA-related SINE families originating from different tRNAs, and nominated as AfuSINE2 sequences, contained target site duplications of short direct repeat sequences (4-14 bp) flanking the elements, an extended tRNA-unrelated region and typical features of RNA polymerase III promoter sequences. The elements ranged in size from 140-493 bp and were present in low copy number in the genome and five out of eight were actively transcribed. One putative tRNAArg-derived sequence, AfuSINE2-1a possessed a unique feature of repeated trinucleotide ACT residues at its 3'-terminus. This element was similar in sequence to the I-4_AO element found in A. oryzae and an I-1_AF long nuclear interspersed element-like sequence identified in A. fumigatus Af293. Families of 5S rRNA-related SINE sequences, nominated as AfuSINE3, were also identified and their 5'-5S rRNA-related regions show 50-65% and 60-75% similarity to respectively A. fumigatus 5S rRNAs and SINE3-1_AO found in A. oryzae. A. fumigatus Af293 contains five copies of AfuSINE3 sequences ranging in size from 259-343 bp and two out of five AfuSINE3 sequences were actively transcribed. Investigations on AfuSINE distribution in the fungal genome revealed that the elements are enriched in pericentromeric and subtelomeric regions and inserted within gene-rich regions. We also demonstrated that some, but not all, AfuSINE sequences are targeted by host RNA silencing mechanisms. Finally, we demonstrated that infection of the fungus with mycoviruses had no apparent effects on SINE activity.

  6. 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.

  7. Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein.

    PubMed Central

    Iwai, S; Pritchard, C; Mann, D A; Karn, J; Gait, M J

    1992-01-01

    The Human Immunodeficiency Virus type-1 rev protein binds with high affinity to a bubble structure located within the rev-response element (RRE) RNA in stemloop II. After this initial interaction, additional rev molecules bind to the RRE RNA in an ordered assembly process which requires a functional bubble structure, since mutations in the bubble sequence that reduce rev affinity block multiple complex formation. We have used synthetic chemistry to characterize the interaction between rev protein and its high affinity binding site. A minimal synthetic duplex RNA (RBC6) carrying the bubble and 12 flanking base pairs is able to bind rev with 1 to 1 stoichiometry and with high affinity. When the bubble structure is inserted into synthetic RNA molecules carrying longer stretches of flanking double-stranded RNA, rev forms additional complexes resembling the multimers observed with the RRE RNA. The ability of rev to bind to RBC6 analogues containing functional group modifications on base and sugar moieties of nucleoside residues was also examined. The results provide strong evidence that the bubble structure contains specific configurations of non-Watson--Crick G:G and G:A base pairs and suggest that high affinity recognition of RRE RNA by rev requires hydrogen bonding to functional groups in the major groove of a distorted RNA structure. Images PMID:1282702

  8. The Submarine Flanks of Anatahan Volcano

    NASA Astrophysics Data System (ADS)

    Chadwick, W. W.; Embley, R. W.; Johnson, P. D.; Merle, S. G.; Ristau, S.

    2003-12-01

    The submarine flanks of Anatahan volcano were surveyed with EM300 multibeam sonar and the MR1 sidescan sonar from the R/V Thomas G. Thompson in February 2003. This was part of a larger survey of over 50 submarine volcanoes within the Marianas volcanic arc between 13° 10'N and 23° 10'N (see Embley et al. and Baker et al. abstracts, this meeting). This work was part of a multi-year study of seafloor volcanism in diverse tectonic settings, funded by NOAA's Office of Ocean Exploration. (see: http://oceanexplorer.noaa.gov/explorations/03fire/). The island of Anatahan has a maximum elevation of 798 m, but its submarine flanks descend to depths of 2000-2600 m, so most of the volcano lies below sea level. The submarine part of the volcano is elongated in the east-west direction, like the island. Conspicuous in the bathymetry are numerous small parasitic cones and hummocky ridges on the southwest and east submarine flanks of the island that radiate outward (downslope) from the island. These features appear as areas of high reflectivity in the MR1 sidescan sonar and some have distinctly lobate outlines, suggesting that they are areas of relatively young lava flows. Some of these lava flows extend up to 15 km from the coastline of the island and to depths below 2000 m. The upslope sources of these lavas are often ambiguous, but we interpret that they were erupted underwater (as opposed to erupted on land and then flowing into the ocean) because they are associated with cones and ridges that may be vent areas. The other flanks of the island appear to be draped in volcaniclastic material that has been transported downslope from the shoreline, in some cases as distinct flows that radiate outward in braided channels that have slightly higher reflectivity than surrounding areas in the sidescan imagery. These fragmental flows also extend to depths below 2000 m, especially on the west and south flanks of the island. The most prominent feature in the bathymetry around Anatahan is a

  9. Variation in elemental composition of human teeth and its application for feasible species identification.

    PubMed

    Nganvongpanit, Korakot; Buddhachat, Kittisak; Piboon, Promporn; Euppayo, Thippaporn; Mahakkanukrauh, Pasuk

    2017-02-01

    Identifying human remains is a primary task in forensic science. In this study, we propose a possible new technique, handheld X-ray fluorescence (HHXRF), for determining whether a suspected tooth is an authentic human tooth. A total of 444 teeth obtained from 111 human skulls (male=62, female=49) aged between 30-67 years (51.81±8.37 years) were used as subjects. The teeth were scanned by HHXRF to acquire their elemental profile. Differences in elemental composition were analyzed for different tooth positions (numbers 1-32), between crown and root, and between sexes (male and female); also, the proportion of elements in relation to different human ages was examined. Teeth from 20 different animal species, serving as non-human teeth samples, were used to distinguish between human and non-human teeth through a stepwise discriminant analysis. Our results revealed that different tooth positions, different regions (crown and root) of a tooth, and different sexes demonstrated disparities in the proportion of several elements. The accuracy rate of predicting sex based on the elemental profile of human teeth was 65.5%. Likewise, a dissimilar distribution of elements between human and non-human teeth was observed, leading to a high degree of correctness of 83.2% for distinguishing them. In conclusion, elemental analysis by HHXRF could serve as a promising candidate tool for identifying human teeth in forensic science, but is ineffective for sex determination. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Microbial life in ridge flank crustal fluids.

    PubMed

    Huber, Julie A; Johnson, H Paul; Butterfield, David A; Baross, John A

    2006-01-01

    To determine the microbial community diversity within old oceanic crust, a novel sampling strategy was used to collect crustal fluids at Baby Bare Seamount, a 3.5 Ma old outcrop located in the north-east Pacific Ocean on the eastern flank of the Juan de Fuca Ridge. Stainless steel probes were driven directly into the igneous ocean crust to obtain samples of ridge flank crustal fluids. Genetic signatures and enrichment cultures of microorganisms demonstrate that these crustal fluids host a microbial community composed of species indigenous to the subseafloor, including anaerobic thermophiles, and species from other deep-sea habitats, such as seawater and sediments. Evidence using molecular techniques indicates the presence of a relatively small but active microbial population, dominated by bacteria. The microbial community diversity found in the crustal fluids may indicate habitat variability in old oceanic crust, with inputs of nutrients from seawater, sediment pore-water fluids and possibly hydrothermal sources. This report further supports the presence of an indigenous microbial community in ridge flank crustal fluids and advances our understanding of the potential physiological and phylogenetic diversity of this community.

  11. Characteristics of the flank magnetopause: Cluster observations

    NASA Astrophysics Data System (ADS)

    Haaland, S.; Reistad, J.; Tenfjord, P.; Gjerloev, J.; Maes, L.; DeKeyser, J.; Maggiolo, R.; Anekallu, C.; Dorville, N.

    2014-11-01

    The magnetopause is a current sheet forming the boundary between the geomagnetic field on one side and the shocked solar wind on the other side. This paper discusses properties of the low-latitude dawn and dusk flanks of the magnetopause. The reported results are based on a large number of measurements obtained by the Cluster satellites during magnetopause traversals. Using a combination of single-spacecraft and multispacecraft techniques, we calculated macroscopic features such as thickness, location, and motion of the magnetopause. The results show that the typical flank magnetopause is significantly thicker than the dayside magnetopause and also possesses a pronounced and persistent dawn-dusk asymmetry. Thicknesses vary from 150 to 5000 km, with an median thickness of around 1400 km at dawn and around 1150 km at dusk. Current densities are on average higher on dusk, suggesting that the total current at dawn and dusk are similar. Solar wind conditions and the interplanetary magnetic field cannot fully explain the observed dawn-dusk asymmetry. For a number of crossings we were also able to derive detailed current density profiles. The profiles show that the magnetopause often consists of two or more adjacent current sheets, each current sheet typically several ion gyroradii thick and often with different current direction. This demonstrates that the flank magnetopause has a structure that is more complex than the thin, one-dimensional current sheet described by a Chapman-Ferraro layer.

  12. Transposable elements and circular DNAs

    PubMed Central

    2016-01-01

    ABSTRACT Circular DNAs are extra-chromosomal fragments that become circularized by genomic recombination events. We have recently shown that yeast LTR elements generate circular DNAs through recombination events between their flanking long terminal repeats (LTRs). Similarly, circular DNAs can be generated by recombination between LTRs residing at different genomic loci, in which case the circular DNA will contain the intervening sequence. In yeast, this can result in gene copy number variations when circles contain genes and origins of replication. Here, I speculate on the potential and implications of circular DNAs generated through recombination between human transposable elements. PMID:28090380

  13. Biorecognition Element Design and Characterization for Human Performance Biomarkers Sensing

    DTIC Science & Technology

    2015-07-16

    chemistry needed to immobilize biorecognition elements (BRE) on gold nanoparticles (AuNPs) to create selective nanoprobes for integration in micro...July 1, 2014-July 1, 2015 Abstract: The chemistry needed to perform biorecognition elements (BREs) immobilization on gold nanoparticles

  14. A comparison of human elements and nonhuman elements in private health care settings: customers' perceptions and expectations.

    PubMed

    Mohd Suki, Norazah; Chwee Lian, Jennifer Chiam; Suki, Norbayah Mohd

    2009-01-01

    In today's highly competitive health care environment, many private health care settings are now looking into customer service indicators to learn customers' perceptions and determine whether they are meeting customers' expectations in order to ensure that their customers are satisfied with the services. This research paper aims to investigate whether the human elements were more important than the nonhuman elements in private health care settings. We used the internationally renowned SERVQUAL five-dimension model plus three additional dimensions-courtesy, communication, and understanding of customers of the human element-when evaluating health care services. A total of 191 respondents from three private health care settings in the Klang Valley region of Malaysia were investigated. Descriptive statistics were calculated by the Statistical Package for Social Sciences (SPSS) computer program, version 15. Interestingly, the results suggested that customers nowadays have very high expectations especially when it comes to the treatment they are receiving. Overall, the research indicated that the human elements were more important than the nonhuman element in private health care settings. Hospital management should look further to improve on areas that have been highlighted. Implications for management practice and directions for future research are discussed.

  15. 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

  16. Finite element dependence of stress evaluation for human trabecular bone.

    PubMed

    Depalle, B; Chapurlat, R; Walter-Le-Berre, H; Bou-Saïd, B; Follet, H

    2013-02-01

    Numerical simulation using finite element models (FEM) has become more and more suitable to estimate the mechanical properties of trabecular bone. The size and kind of elements involved in the models, however, may influence the results. The purpose of this study is to analyze the influence of hexahedral elements formulation on the evaluation of mechanical stress applied to trabeculae bone during a compression test simulation. Trabecular bone cores were extracted from 18 L2 vertebrae (12 women and 6 men, mean age: 76 ± 11, BV/TV=7.5 ± 1.9%). Samples were micro-CT scanned at 20 μm isotropic voxel size. Micro-CT images have been sub-sampled (20, 40 and 80 μm) to create 5.6 mm cubic FEM. For each sample, a compression test FEM has been created, using either 8-nodes linear hexahedral elements with full or reduced integration or 20-nodes quadratic hexahedral elements fully integrated, resulting in nine models per samples. Bone mechanical properties have been assumed isotropic, homogenous and to follow a linear elastic behavior law (Young modulus: 8 GPa, Poisson ratio: 0.3). Despite micro-architecture modifications (loss of connectivity, trabeculae thickening) due to voxel size increase, apparent mechanical properties calculated with low resolution models are significantly correlated with high resolution results, no matter the element formulation. However, stress distributions are more sensitive to both resolution and element formulation modifications. With linear elements, increasing voxel size leads to an alteration of stress concentration areas due to stiffening errors. On the opposite, the use of reduced integration induces severe smoothing and underestimation of stress fields resulting in stress raisers loss. Notwithstanding their high computational cost, quadratic elements are most appropriate for stress prediction in low resolution trabecular bone FEM. These observations are dependent on trabecular bone micro-architecture, and are more significant for low

  17. A modal-spectral model for flanking transmissions

    NASA Astrophysics Data System (ADS)

    Poblet-Puig, Jordi

    2016-11-01

    A model for the prediction of direct and indirect (flanking) sound transmissions is presented. It can be applied to geometries with extrusion symmetry. The structures are modelled with spectral finite elements. The acoustic domains are described by means of a modal expansion of the pressure field and must be cuboid-shaped. These reasonable simplifications in the geometry allow the use of more efficient numerical methods. Consequently the coupled vibroacoustic problem in structures such as junctions is efficiently solved. The vibration reduction index of T-junctions with acoustic excitation and with point force excitation is compared. The differences due to the excitation type obey quite general trends that could be taken into account by prediction formulas. However, they are smaller than other uncertainties not considered in practice. The model is also used to check if the sound transmissions of a fully vibroacoustic problem involving several flanking paths can be reproduced by superposition of independent paths. There exist some differences caused by the interaction between paths, which are more important at low frequencies.

  18. Nucleotide sequence of murine PCNA: interspecies comparison of the cDNA and the 5' flanking region of the gene.

    PubMed

    Shipman-Appasamy, P M; Cohen, K S; Prystowsky, M B

    1991-01-01

    Proliferating cell nuclear antigen (PCNA) RNA levels are regulated by transcription as well as changes in stability, in growing cells. We have cloned the murine PCNA cDNA and a fragment of the murine PCNA gene flanking the transcription initiation site. Comparison of the murine deduced amino acid sequence with the PCNA sequence from rat, human, Drosophila, Saccharomyces cerevisiae, and higher plants, reveals extensive homology between species. The homology is likely to be related to the fundamental role of PCNA as an auxiliary protein for DNA replication. Consensus sequences for transcriptional regulatory factors identified within 520 bp 5' of the cap site of the murine PCNA gene include: an inverted CCAAT site, an enhancer core element (EBP-1), three cAMP-response elements (CRE-BP), one AP-2 site, three Sp1 sites, and two octamer sequences. The first 20 bp of the transcriptional unit are homologous to an initiator element, which may direct transcription from RNA polymerase II in the absence of a TATAA box. The consensus elements in the murine PCNA gene are similar in sequence and/or location to elements identified in the genes for human, Drosophilia, and yeast PCNA.

  19. West Flank Coso, CA FORGE Seismic Reflection

    SciTech Connect

    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).

  20. Genome-wide target site triplication of Alu elements in the human genome.

    PubMed

    Lee, Wooseok; Mun, Seyoung; Kang, Keunsoo; Hennighausen, Lothar; Han, Kyudong

    2015-05-01

    Alu elements are the most successful short interspersed elements in primate genomes and their retrotransposition is a major source of genomic expansion. Alu elements integrate into genomic regions through target-site primed reverse transcription, which generates target site duplications (TSDs). Unexpectedly, we have identified target site triplications (TSTs) at some loci, where two Alu elements in tandem share one direct repeat. Thus, the three copies of the repeat are present. We located 212 TST loci in the human genome and examined 25 putative human-specific TST loci using PCR validation. As a result, 12 human-specific TST loci were identified. These findings suggest that unequal homologous recombination between TSDs can lead to TST. Through this mechanism, the copy number of Alu elements could have increased in primate genomes without new Alu retrotransposition events. This study provides new insight into the augmentation of Alu elements in the primate genome.

  1. Microsatellite flanking region similarities among different loci within insect species.

    PubMed

    Meglécz, E; Anderson, S J; Bourguet, D; Butcher, R; Caldas, A; Cassel-Lundhagen, A; d'Acier, A C; Dawson, D A; Faure, N; Fauvelot, C; Franck, P; Harper, G; Keyghobadi, N; Kluetsch, C; Muthulakshmi, M; Nagaraju, J; Patt, A; Péténian, F; Silvain, J-F; Wilcock, H R

    2007-04-01

    Although microsatellites are ubiquitous in eukaryota, the number of available markers varies strongly among taxa. This meta-analysis was conducted on 32 insect species. Sequences were obtained from two assembled whole genomes, whole genome shotgun (WGS) sequences from 10 species and screening partial genomic libraries for microsatellites from 23 species. We have demonstrated: (1) strong differences in the abundance of microsatellites among species; (2) that microsatellites within species are often grouped into families based on similarities in their flanking sequences; (3) that the proportion of microsatellites grouped into families varies strongly among taxa; and (4) that microsatellite families were significantly more often associated with transposable elements - or their remnants - than unique microsatellite sequences.

  2. 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.

  3. 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.

  4. 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.

  5. Electron microprobe analysis of elemental distribution in excavated human femurs

    SciTech Connect

    Lambert, J.B.; Simpson, S.V.; Buikstra, J.E.; Hanson, D.

    1983-12-01

    Elemental distributions have been determined for femur cross sections of eight individuals from the Gibson and Ledders Woodland sites. The analyses were obtained by x-ray fluorescence with a scanning electron microscope. Movement of an element from soil to bone should give rise to inhomogeneous distributions within the bone. We found that the distributions of zinc, strontium, and lead are homogeneous throughout the femur. In contrast, iron, aluminum, potassium, and manganese show clear buildup along the outer surface of the femur and sometimes along the inner (endosteal) surface, as the result of postmortem enrichment. The buildup penetrates 10-400 micron into the femur. The major elements calcium and sodium show homogeneous distributions, but considerable material could be lost by leaching (10-15%) without causing a palpable effect on the electron maps. Magnesium shows buildup on the outer edge of some samples. These results suggest that diagenetic contamination may exclude Fe, Al, K, Mn, and probably Mg from use as indicators of ancient data. The homogeneous distributions of Zn, Sr, and Pb suggest that these elements are not altered appreciably and may serve as useful dietary indicators.

  6. Composition measurements in the dusk flank magnetosphere

    NASA Astrophysics Data System (ADS)

    Fuselier, S. A.; Elphic, R. C.; Gosling, J. T.

    1999-03-01

    The dusk flank magnetosphere exhibits significant structure. Several regions have been identified, including the plasma sheet, mantle, and low latitude boundary layer. Transitions from one region to the next, for example from the mantle to the plasma sheet, can be abrupt or indistinct. In addition, the density within the flank mantle can range over several orders of magnitude. Although there is significant structure in this region of the magnetosphere, individual regions often can be distinguished by their energy spectra and ion composition. ISEE Fast Plasma Experiment and Plasma Composition Experiment data are used to examine the composition of the mantle and to study a set of transitions from the mantle to the plasma sheet where plasmas with mantle-like and plasma sheet-like energies mix. This study indicates that the variability of the mantle density is largely due to variability in the solar wind component (H+ and He2+); the ionospheric plasma (O+) density is roughly constant. Similarly, the plasma with mantle-like energy found in the mixed region is largely of solar wind origin.

  7. Flank suspended supine position for percutaneous nephrolithotomy.

    PubMed

    Pan, Tie-jun; Li, Gong-cheng; Ye, Zhang-qun; Wen, Han-dong; Shen, Guo-qiu; Zhang, Jia-qiao

    2012-01-01

    Prone and supine positions for percutaneous nephrolithotomy are widely used but have their drawbacks. We report a new positioning method called "flank suspended supine position" (FSSP) for PCNL and describe our experience with PCNL in this position to evaluate its safety and efficacy. Retrospective study of 150 cases of renal stone patients treated with PCNL in a new position called flank suspended supine position (FSSP) from June 2009 to July 2010. All patients were treated with PCNL in FSSP under epidural anesthesia. Operation time, bleeding rate, stone free rate, and complications were recorded. All patients tolerated FSSP. Mean operation time was 78.29±26.13 min. Initial stone-free rate was 83%. For those with residual stones (26 cases), 18 were stone-free after a second PCNL, 8 after extracorporeal shock wave lithotripsy (ESWL). Mean hospital stay was 7.63±2.39 days. No penetrating injury of the pleural cavity or injury to visceral organs was reported. FSSP is an effective and safe position for PCNL in our hands and its effectiveness relative to traditional prone position needs to be determined in future randomized studies.

  8. 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.

  9. Boundary element modeling of the external human auditory system

    NASA Astrophysics Data System (ADS)

    Walsh, Timothy; Demkowicz, Leszek; Charles, Richard

    2004-03-01

    In this paper the response of the external auditory system to acoustical waves of varying frequencies and angles of incidence is computed using a boundary element method. The resonance patterns of both the ear canal and the concha are computed and compared with experimental data. Specialized numerical algorithms are developed that allow for the efficient computation of the eardrum pressures. In contrast to previous results in the literature that consider only the ``blocked meatus'' configuration, in this work the simulations are conducted on a boundary element mesh that includes both the external head/ear geometry, as well as the ear canal and eardrum. The simulation technology developed in this work is intended to demonstrate the utility of numerical analysis in studying physical phenomena related to the external auditory system. Later work could extend this towards simulating in situ hearing aids, and possibly using the simulations as a tool for optimizing hearing aid technologies for particular individuals.

  10. Inversion of coeval shear and normal stress of Piton de la Fournaise flank displacement

    NASA Astrophysics Data System (ADS)

    Tridon, Marine; Cayol, Valérie; Froger, Jean-Luc; Augier, Aurélien; Bachèlery, Patrick

    2016-11-01

    The April 2007 eruption of Piton de la Fournaise was the biggest volcano eruptive crisis of the 20th and 21st centuries. Interferometric synthetic aperture radar (InSAR) captured a large coeruptive seaward displacement on the volcano's eastern flank, which continued for more than a year at a decreasing rate. Coeruptive uplift and posteruptive subsidence were also observed. While it is generally agreed that flank displacement is induced by fault slip, we suggest that this flank displacement might have been induced by a sheared sill, based on observations of sheared sills at Piton des Neiges. To test this hypothesis, we develop a new method to invert a quadrangular curved source submitted to simultaneous pressure and shear stress changes. This method, based on boundary elements, is applied to data acquired along six Envisat orbits covering a 14 month period subsequent to the April 2007 eruption. Posteruptive displacement is well explained by closure and slip of a large (5 km by 8 km) and shallow (500 m) trapezoidal fracture parallel to the flank and probably coincident with a lithological discontinuity. We investigate whether thermal contraction or degassing of a coeruptive sill can explain the displacement. Such a sill would have to be 10 times thicker than inferred from the coeruptive uplift and solidification time 10 times shorter ( 20 days) than the duration of the posteruptive subsidence (24 to 33 months). Instead, we propose that the posteruptive eastern flank displacement is due to the compaction and ongoing slow slip on a shallow detachment fault.

  11. [Determination of trace elements in ancient Cheshi human costa by ICP-AES].

    PubMed

    Jin, Hai-yan; Zhang, Quan-chao; Zhu, Hong

    2004-02-01

    In recent years, the study on palaeodiet is an important research in the international archaeological field. Trace elements in human bones can supply a lot of valuable information to reconstruct ancient diet. In this study, The trace elements in Bronze age Cheshi human costa from Chubeixi cemetery in shanshan, Xinjiang were determined by ICP-AES. The sample was dissolved by HNO3 and HCl. Under the optimum conditions, eight elements can be determined simultaneously. The recoveries of the method are in the range of 87.4%-106.6%, and RSDs are in the range of 0.5%-3.3%. The method is simple, rapid, precise and convenient to operate. The results would be helpful for research in archaeology. This analysis established Xinjiang' s consult system of trace elements analysis for ancient human bones. The effects of various concentrations of acid solution on analysis results, the interference of coexistent elements, standard addition recovery, and precision of the method were investigated.

  12. Development of a finite element model of the human cervical spine.

    PubMed

    Zafarparandeh, Iman; Erbulut, Deniz U; Lazoglu, Ismail; Ozer, Ali Fahir

    2014-01-01

    The finite element model has been used as an effective tool in human spine biomechanics. Biomechanical finite element models have provided basic insights into the workings of the cervical spine system. Advancements in numerical methods during the last decade have enabled researchers to propose more accurate models of the cervical spine. The new finite element model of the cervical spine considers the accurate representation of each tissue regarding the geometry and material. The aim of this paper is to address the new advancements in the finite element model of the human cervical spine. The procedures for creating a finite element model are introduced, including geometric construction, material-property assignment, boundary conditions and validation. The most recent and published finite element models of the cervical spine are reviewed.

  13. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. 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.

  15. Elemental composition of some essential cations in human ocular tissue

    SciTech Connect

    Panessa-Warren, B.J.; Kraner, H.W.; Warren, J.B.

    1983-01-01

    To obtain data on the baseline elemental content in normal adult sensory retina, RPE and iris, normal non-diabetic eyes were analyzed and these results were used for comparison to similarly prepared samples from diabetic donor eyes. To determine if the concentrations of the cations, Ca, Ba and Zn were altered by the age, alimentation and exposure to light of the donor, tissue from children (from 25 weeks gestation to 8-1/2 years old) was also analyzed by x-ray fluorescence spectroscopy, proton induced x-ray emission spectroscopy, and light and electron (scanning and transmission) microscopy.

  16. Regional differences in elements of human peroneus longus tendons.

    PubMed

    Matsumoto, Norikazu; Kumai, Tsukasa; Isomoto, Shinji; Shinohara, Yasushi; Tanaka, Yasuhito; Azuma, Cho; Minami, Takeshi; Tohno, Yoshiyuki

    2013-08-01

    Many studies have been performed on the structure, molecular composition, and biochemical properties of tendons. However, comparatively little research has been conducted on the content of various trace elements within tendons. Six elements were analyzed in four regions of the peroneus longus tendon: the tensional part of the tendon immediately proximal to the lateral malleolus (region A), the compressive region of the tendon in contact with the lateral malleolus (region B), the compressive region of the tendon in contact with the deep surface of the cuboid (region C), and the tensional part of the tendon between the cuboid and first metatarsal, to which the tendon is attached (region D). Regions B and C are wraparound regions. The calcium content was higher in region C (2.10 ± 0.93 mg/g) than in both regions A (1.25 ± 0.51 mg/g) and D (1.43 ± 0.41 mg/g) (p < 0.05), indicating that it is likely related to regional differences in cartilage degeneration. The phosphorus content was also higher in region C, possibly because of low alkaline phosphatase activity in this region. The sulfur content was higher in the wraparound regions (region B: 0.98 ± 0.09 mg/g, region C: 1.24 ± 0.19 mg/g) than in both regions A (0.83 ± 0.11 mg/g) and D (0.83 ± 0.1 mg/g) (p < 0.01); sulfur content is thought to be influenced by tendon-bone compression. Finally, the magnesium content in the wraparound regions was also higher, which is probably related to a higher level of fibrocartilage. No significant relationships were found with regard to zinc or iron. Overall, the findings of the present study indicate that element contents are related to function and anatomical differences in tendons, and that they may even vary within the same tendon.

  17. Trace elements in human physiology and pathology. Copper.

    PubMed

    Tapiero, H; Townsend, D M; Tew, K D

    2003-11-01

    Copper is a trace element, important for the function of many cellular enzymes. Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I), allowing the metal to play a pivotal role in cell physiology as a catalytic cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron absorption, free radical scavenging and elastin cross-linking. If present in excess, free copper ions can cause damage to cellular components and a delicate balance between the uptake and efflux of copper ions determines the amount of cellular copper. In biological systems, copper homeostasis has been characterized at the molecular level. It is coordinated by several proteins such as glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson proteins and by cytoplasmic transport proteins called copper chaperones to ensure that it is delivered to specific subcellular compartments and thereby to copper-requiring proteins.

  18. Revised genomic consensus for the hypermethylated CpG island region of the human L1 transposon and integration sites of full length L1 elements from recombinant clones made using methylation-tolerant host strains.

    PubMed Central

    Crowther, P J; Doherty, J P; Linsenmeyer, M E; Williamson, M R; Woodcock, D M

    1991-01-01

    Efficient recovery of clones from the 5' end of the human L1 dispersed repetitive elements necessitates the use of deletion mcr- host strains since this region contains a CpG island which is hypermethylated in vivo. Clones recovered with conventional mcr+ hosts seem to have been derived preferentially from L1 members which have accumulated mutations that have removed sites of methylation. We present a revised consensus from the 5' presumptive control region of these elements. This revised consensus contains a consensus RNA polymerase III promoter which would permit the synthesis of transcripts from the 5' end of full length L1 elements. Such potential transcripts are likely to exhibit a high degree of secondary structure. In addition, we have determined the flanking sequences for 6 full length L1 elements. The majority of full length L1 clones show no convincing evidence for target site duplication in the insertion site as commonly observed with truncated L1 elements. These data would be consistent with two mechanisms of integration of transposing L1 elements with different mechanisms predominating for full length and truncated elements. PMID:1710354

  19. Coverage intervals for trace elements in human scalp hair are site specific.

    PubMed

    Tamburo, E; Varrica, D; Dongarrà, G

    2015-01-01

    Coverage intervals for trace elements in human scalp hair commonly provide the basis for interpreting laboratory results and also in comparative decision-making processes regarding exposure risk assessment. This short communication documents, by some examples, that those computed for human hair are to be considered site specific, as they reflect local environmental conditions; also each geographic area has a typical profile of hair elemental composition of its inhabitants. Therefore, the levels of trace elements in hair are not strictly comparable between different areas of the world. This issue is particularly relevant when identification of anomalous environmental exposures are requested or even in detecting physiological disorders.

  20. Characterization of various promoter regions of the human DNA helicase-encoding genes and identification of duplicated ets (GGAA) motifs as an essential transcription regulatory element.

    PubMed

    Uchiumi, Fumiaki; Watanabe, Takeshi; Tanuma, Sei-ichi

    2010-05-15

    DNA helicases are important in the regulation of DNA transaction and thereby various cellular functions. In this study, we developed a cost-effective multiple DNA transfection assay with DEAE-dextran reagent and analyzed the promoter activities of the human DNA helicases. The 5'-flanking regions of the human DNA helicase-encoding genes were isolated and subcloned into luciferase (Luc) expression plasmids. They were coated onto 96-well plate and used for co-transfection with a renilla-Luc expression vector into various cells, and dual-Luc assays were performed. The profiles of promoter activities were dependent on cell lines used. Among these human DNA helicase genes, XPB, RecQL5, and RTEL promoters were activated during TPA-induced HL-60 cell differentiation. Interestingly, duplicated ets (GGAA) elements are commonly located around the transcription start sites of these genes. The duplicated GGAA motifs are also found in the promoters of DNA replication/repair synthesis factor genes including PARG, ATR, TERC, and Rb1. Mutation analyses suggested that the duplicated GGAA-motifs are necessary for the basal promoter activity in various cells and some of them positively respond to TPA in HL-60 cells. TPA-induced response of 44-bp in the RTEL promoter was attenuated by co-transfection of the PU.1 expression vector. These findings suggest that the duplicated ets motifs regulate DNA-repair associated gene expressions during macrophage-like differentiation of HL-60 cells.

  1. 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.

  2. 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

  3. A brief review on the Human Encyclopedia of DNA Elements (ENCODE) project.

    PubMed

    Qu, Hongzhu; Fang, Xiangdong

    2013-06-01

    The ENCyclopedia Of DNA Elements (ENCODE) project is an international research consortium that aims to identify all functional elements in the human genome sequence. The second phase of the project comprised 1640 datasets from 147 different cell types, yielding a set of 30 publications across several journals. These data revealed that 80.4% of the human genome displays some functionality in at least one cell type. Many of these regulatory elements are physically associated with one another and further form a network or three-dimensional conformation to affect gene expression. These elements are also related to sequence variants associated with diseases or traits. All these findings provide us new insights into the organization and regulation of genes and genome, and serve as an expansive resource for understanding human health and disease. Copyright © 2013. Production and hosting by Elsevier Ltd.

  4. Rapid deformation of the South flank of kilauea volcano, hawaii.

    PubMed

    Owen, S; Segall, P; Freymueller, J; Mikijus, A; Denlinger, R; Arnadóttir, T; Sako, M; Bürgmann, R

    1995-03-03

    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.

  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. Finite element analysis of the human mastication cycle.

    PubMed

    Commisso, Maria S; Martínez-Reina, Javier; Ojeda, Joaquín; Mayo, Juana

    2015-01-01

    The aim of this paper is to propose a biomechanical model that could serve as a tool to overcome some difficulties encountered in experimental studies of the mandible. One of these difficulties is the inaccessibility of the temporomandibular joint (TMJ) and the lateral pterygoid muscle. The focus of this model is to study the stresses in the joint and the influence of the lateral pterygoid muscle on the mandible movement. A finite element model of the mandible, including the TMJ, was built to simulate the process of unilateral mastication. Different activation patterns of the left and right pterygoid muscles were tried. The maximum stresses in the articular disc and in the whole mandible during a complete mastication cycle were reached during the instant of centric occlusion. The simulations show a great influence of the coordination of the right and left lateral pterygoid muscles on the movement of the jaw during mastication. An asynchronous activation of the lateral pterygoid muscles is needed to achieve a normal movement of the jaw during mastication.

  7. Inversion of Coeval Shear and Normal Stress of Piton de la Fournaise Flank Displacement

    NASA Astrophysics Data System (ADS)

    Cayol, V.; Tridon, M.; Froger, J. L.; Augier, A.; Bachelery, P.

    2016-12-01

    The April 2007 eruption of Piton de la Fournaise was the biggest volcano eruptive crisis of the 20th and 21st centuries. InSAR captured a large (1.4 m) co-eruptive seaward slip of the volcano's eastern flank, which continued for more than a year at a decreasing rate. Co-eruptive uplift and post-eruptive subsidence were also observed. While it is generally agreed that flank displacement is induced by fault slip, we investigate wether this flank displacement might have been induced by a sheared sill, as suggested by observations of sheared sills at Piton des Neiges. To test this hypothesis, we develop a new method to invert a quadrangular curved source submitted to co-eval pressure and shear stress changes. This method, based on boundary elements, is applied to co-eruptive and post-eruptive InSAR data. We find that co-eruptive displacement is explained by a 2 km by 2 km detachment fault, parallel to the flank and probably coincident with a lithological discontinuity. The fracture is shallow enough to induce the co-eval uplift characteristic of a detachment fold. We determine the co-eruptive overpressure is zero, which indicates that the fracture is not a sheared sill. This finding confirms a previous determination obtained using a decision tree based on ratios of maximum displacements. The determined shear stress change of 2 MPa is conistent with the eastern flank loaded by previously intruded rift dikes. Post-eruptive displacement is well explained by slip and closure of the same fracture but over a larger (5 km by 8 km). This displacements is consistent with relaxation and the co-eruptive flank displacement and causal link between both displacement is investigated.

  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. Somatic expression of LINE-1 elements in human tissues

    PubMed Central

    Belancio, Victoria P.; Roy-Engel, Astrid M.; Pochampally, Radhika R.; Deininger, Prescott

    2010-01-01

    LINE-1 expression damages host DNA via insertions and endonuclease-dependent DNA double-strand breaks (DSBs) that are highly toxic and mutagenic. The predominant tissue of LINE-1 expression has been considered to be the germ line. We show that both full-length and processed L1 transcripts are widespread in human somatic tissues and transformed cells, with significant variation in both L1 expression and L1 mRNA processing. This is the first demonstration that RNA processing is a major regulator of L1 activity. Many tissues also produce translatable spliced transcript (SpORF2). An Alu retrotransposition assay, COMET assays and 53BP1 foci staining show that the SpORF2 product can support functional ORF2 protein expression and can induce DNA damage in normal cells. Tests of the senescence-associated β-galactosidase expression suggest that expression of exogenous full-length L1, or the SpORF2 mRNA alone in human fibroblasts and adult stem cells triggers a senescence-like phenotype, which is one of the reported responses to DNA damage. In contrast to previous assumptions that L1 expression is germ line specific, the increased spectrum of tissues exposed to L1-associated damage suggests a role for L1 as an endogenous mutagen in somatic tissues. These findings have potential consequences for the whole organism in the form of cancer and mammalian aging. PMID:20215437

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

    PubMed

    Skeie, Jessica M; Mahajan, Vinit B

    2011-01-23

    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.

  11. The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements.

    PubMed

    Copeland, Claudia S; Mann, Victoria H; Morales, Maria E; Kalinna, Bernd H; Brindley, Paul J

    2005-02-23

    Of the major families of long terminal repeat (LTR) retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs representing transcripts of Sinbad in numerous

  12. The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements

    PubMed Central

    Copeland, Claudia S; Mann, Victoria H; Morales, Maria E; Kalinna, Bernd H; Brindley, Paul J

    2005-01-01

    Background Of the major families of long terminal repeat (LTR) retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. Results A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT), RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs representing transcripts of Sinbad

  13. 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.

  14. [Comparison of 51 element contents in normal human lung tissue over twenty years].

    PubMed

    Zeng, Jing; Ouyang, Li; Wang, Xiao-Yan; Liu, Ya-Qiong; Xie, Qing; Chu, Hong-Da; Wu, Quan; Fan, Ti-Qiang; Wang, Jing-Yu

    2008-05-01

    Changes in content and distribution of elements in human tissues may reflect changes in environmental backgrounds, and are closely related to human health. To investigate the change in element background in normal lung tissue in different stage, we used ICP-MS, ICP-AES and GFAAS to determine 51 element contents in normal human lung samples of 1982-83 year (n = 7) and compare with those of 2004-05 year (n = 16). Samples were from healthy male adults who died suddenly, and were treated with microwave digestion and wet digestion method. The results show that the contents of 23 elements (Na, Mg, P, K, As, Mo, Ag, Ba, Bi, Y, La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho, Er, Tm, Yb and Lu) are significantly higher, and 6 elements (Zn, Ga, Ge, Se, Au and Zr) are significantly lower in the 2004-05 samples than those in the 1982-83 samples. This difference would be related to the changes in environmental backgrounds and people's living habit during twenty years. The distinctive decrease in contents of the 2004-05 samples for most measured rare earth elements (REEs) may be due to more rational usage of REEs in present, while were the soil and corps were largely abused in 1980s in China. The significant increase in contents of some useful micro-elements (Zn and Se ) in the present samples maybe because of the increased intake of these elements as people own more health consciousness. Besides, the increased contents of heavy metal Pb, Cd, Cr and Ni in the present samples may be related to the deterioration of air quality as industrialization course. More than half of measured elements have been significantly changed over twenty years, indicating that some normal value ranges of element contents should be adjusted according to the difference.

  15. A chemist's view of the analysis of human hair for trace elements.

    PubMed

    Chittleborough, G

    1980-01-01

    With the comparatively recent development of analytical techniques of great power and sensitivity, the significance of the levels of trace elements in human hair has attracted the attention of many disciplines including the environmental sciences. This paper presents the view that an agreed basis for the chemical analysis of trace elements in hair has not been established by the many workers in the field; a chemical basis is proposed here. Levels of 37 trace elements found in human hair are tabulated. Endogenous and exogenous sources of such trace elements are described and discussed. An extended review of the many pre-analysis treatments of hair (for the removal of exogenous elements) is presented. Twenty-four representative treatments are tabulated. Some of these treatments clearly removed significant fractions of endogenous elements along with exogenous elements. It is clear that method of cleaning have frequently been chosen without knowing enough about the basic chemistry and behaviour of the hair shaft. The significance of the results obtained cannot therefore be reliably assessed. A collation of recent literature reports leads to the tentative conclusion that disulphide bonds in the cuticular proteins of hair are major sites both for the deposition of metals during formation of hair and for interaction with exogenous elements. The feasibility of a holistic, no-wash policy for hair analysis is outlined and supported.

  16. Characterization and distribution of repetitive elements in association with genes in the human genome.

    PubMed

    Liang, Kai-Chiang; Tseng, Joseph T; Tsai, Shaw-Jenq; Sun, H Sunny

    2015-08-01

    Repetitive elements constitute more than 50% of the human genome. Recent studies implied that the complexity of living organisms is not just a direct outcome of a number of coding sequences; the repetitive elements, which do not encode proteins, may also play a significant role. Though scattered studies showed that repetitive elements in the regulatory regions of a gene control gene expression, no systematic survey has been done to report the characterization and distribution of various types of these repetitive elements in the human genome. Sequences from 5' and 3' untranslated regions and upstream and downstream of a gene were downloaded from the Ensembl database. The repetitive elements in the neighboring of each gene were identified and classified using cross-matching implemented in the RepeatMasker. The annotation and distribution of distinct classes of repetitive elements associated with individual gene were collected to characterize genes in association with different types of repetitive elements using systems biology program. We identified a total of 1,068,400 repetitive elements which belong to 37-class families and 1235 subclasses that are associated with 33,761 genes and 57,365 transcripts. In addition, we found that the tandem repeats preferentially locate proximal to the transcription start site (TSS) of genes and the major function of these genes are involved in developmental processes. On the other hand, interspersed repetitive elements showed a tendency to be accumulated at distal region from the TSS and the function of interspersed repeat-containing genes took part in the catabolic/metabolic processes. Results from the distribution analysis were collected and used to construct a gene-based repetitive element database (GBRED; http://www.binfo.ncku.edu.tw/GBRED/index.html). A user-friendly web interface was designed to provide the information of repetitive elements associated with any particular gene(s). This is the first study focusing on the gene

  17. “Reverse Genomics” Predicts Function of Human Conserved Noncoding Elements

    PubMed Central

    Marcovitz, Amir; Jia, Robin; Bejerano, Gill

    2016-01-01

    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

  18. West Flank Coso, CA FORGE ArcGIS data 2

    SciTech Connect

    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

  19. Effect of Flanking Sounds on the Auditory Continuity Illusion

    PubMed Central

    Kobayashi, Maori; Kashino, Makio

    2012-01-01

    Background The auditory continuity illusion or the perceptual restoration of a target sound briefly interrupted by an extraneous sound has been shown to depend on masking. However, little is known about factors other than masking. Methodology/Principal Findings We examined whether a sequence of flanking transient sounds affects the apparent continuity of a target tone alternated with a bandpass noise at regular intervals. The flanking sounds significantly increased the limit of perceiving apparent continuity in terms of the maximum target level at a fixed noise level, irrespective of the frequency separation between the target and flanking sounds: the flanking sounds enhanced the continuity illusion. This effect was dependent on the temporal relationship between the flanking sounds and noise bursts. Conclusions/Significance The spectrotemporal characteristics of the enhancement effect suggest that a mechanism to compensate for exogenous attentional distraction may contribute to the continuity illusion. PMID:23251666

  20. A 3,387 bp 5'-flanking sequence of the goat alpha-S1-casein gene provides correct tissue-specific expression of human granulocyte colony-stimulating factor (hG-CSF) in the mammary gland of transgenic mice.

    PubMed

    Serova, Irina A; Dvoryanchikov, Gennady A; Andreeva, Ludmila E; Burkov, Ivan A; Dias, Luciene P B; Battulin, Nariman R; Smirnov, Alexander V; Serov, Oleg L

    2012-06-01

    A new expression vector containing the 1,944 bp 5'-flanking regulatory region together with exon 1 and intron 1 of the goat alpha-S1-casein gene (CSN1S1), the full-sized human granulocyte colony-stimulating factor gene (hGCSF) and the 3'-flanking sequence of the bovine CSN1S1, was created. The vector DNA was used for generation of four mouse transgenic lines. The transgene was integrated into chromosomes 8 and 12 of two founders as 2 and 5 copies, respectively. Tissue-specific secretion of hG-CSF into the milk of transgenic mice was in the range of 19-40 μg/ml. RT-PCR analysis of various tissues of the transgenic mice demonstrated that expression of hGCSF was detected in only the mammary gland in the progeny of all founders. Moreover, cells were shown to be positive for hG-CSF by immunofluorescent analysis in the mammary glands but not in any other tissues. There were no signs of mosaic expression in the mammary gland. Trace amounts of hG-CSF were detected in the serum of females of two transgenic lines during lactation only. However, no transgenic mice showed any changes in hematopoiesis based on the number of granulocytes in blood. Immunoblotting of hG-CSF in the milk of transgenic mice revealed two forms, presumably the glycosylated and non-glycosylated forms. The hematopoietic activity of hG-CSF in the milk of transgenic females is comparable to that of recombinant G-CSF. In general, the data obtained in this study show that the new expression vector is able to provide correct tissue-specific expression of hG-CSF with high biological activity in transgenic mice.

  1. Glucocorticoid regulation of mouse and human dual specificity phosphatase 1 (DUSP1) genes: unusual cis-acting elements and unexpected evolutionary divergence.

    PubMed

    Tchen, Carmen R; Martins, Joana R S; Paktiawal, Nasren; Perelli, Roberta; Saklatvala, Jeremy; Clark, Andrew R

    2010-01-22

    Anti-inflammatory effects of glucocorticoids (GCs) are partly mediated by up-regulation of DUSP1 (dual specificity phosphatase 1), which dephosphorylates and inactivates mitogen-activated protein kinases. We identified putative GC-responsive regions containing GC receptor (GR) binding site consensus sequences that are well conserved between human and mouse DUSP1 loci in position, orientation, and sequence (at least 11 of 15 positions identical) and lie within regions of extended sequence conservation (minimum 65% identity over at least 100 bp). These were located approximately 29, 28, 24, 4.6, and 1.3 kb upstream of the DUSP1 transcription start site. The homology-based approach successfully identified four cis-acting regions that mediated transcriptional responses to dexamethasone. However, there was surprising interspecies divergence in site usage. This could not be explained by variations of the GR binding sites themselves. Instead, variations in flanking sequences appear to have driven the evolutionary divergence in mechanisms of regulation of mouse and human DUSP1 genes. There was a good correlation between the ability of cis-acting elements to respond to GC in transiently transfected reporter constructs and their ability to recruit GR in the context of intact chromatin. We propose that divergence of gene regulation has involved the loss or gain of binding sites for accessory transcription factors that assist in GR recruitment. Finally, a novel GC-responsive region of the human DUSP1 gene contains a highly unusual element, in which three closely spaced GR half-sites are required for potent transcriptional activation by GC.

  2. 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

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

    PubMed

    Dror, Itiel E

    2015-08-05

    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.

  4. Trace elements during primordial plexiform network formation in human cerebral organoids

    PubMed Central

    Sartore, Rafaela C.; Cardoso, Simone C.; Lages, Yury V.M.; Paraguassu, Julia M.; Stelling, Mariana P.; Madeiro da Costa, Rodrigo F.; Guimaraes, Marilia Z.; Pérez, Carlos A.

    2017-01-01

    Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development in vitro. In the present work, we analyzed cerebral organoids derived from human pluripotent stem cells by synchrotron radiation X-ray fluorescence in order to measure biologically valuable micronutrients incorporated and distributed into the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves P, S, K, Ca, Fe and Zn. Occurrence of different concentration gradients also suggests active regulation of elemental transmembrane transport. Finally, the analysis of pairs of elements shows interesting elemental interaction patterns that change from 30 to 45 days of development, suggesting short- or long-term associations, such as storage in similar compartments or relevance for time-dependent biological processes. These findings shed light on which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood. PMID:28194309

  5. Concentration of trace elements in human semen and relation to spermatozoa quality.

    PubMed

    Slivkova, Jana; Popelkova, Miroslava; Massanyi, Peter; Toporcerova, Silvia; Stawarz, Robert; Formicki, Grzegorz; Lukac, Norbert; Putała, Aldona; Guzik, Marek

    2009-03-01

    In this study the concentrations of trace elements such as lead, cadmium, iron, nickel, copper and zinc in the human semen (n = 47), occurrence of pathological spermatozoa, and correlations of these elements to pathological forms were investigated. For each sample of human spermatozoa at least 500 spermatozoa were evaluated. Metal contents were determined by the voltametric method and flame absorption spectrophotometry method. The concentrations of trace elements in human semen were: lead 1.49 +/- 0.40 mg x kg(- 1), cadmium 0.13 +/- 0.15 mg x kg(- 1), iron 2.59 +/- 0.21 mg x kg(- 1), nickel 0.40 +/- 0.07 mg x kg(- 1), copper 0.28 +/- 0.06 mg x kg(- 1), and zinc 153.93 +/- 67.08 mg x kg(- 1), respectively. The total percentage of pathological spermatozoa was 41.61 +/- 9.80% with predominancy of broken flagellum, flagellum torso and separated flagellum. In relation to trace elements the analysis showed correlation between copper and lead (r = -0.47), nickel and iron (r = 0.36), lead and flagellum ball (r = -0.39), cadmium and large heads (r = 0.37) and between iron and other forms of pathological spermatozoa (r = -0.32). Results of this study describe possible effects of trace elements on the spermatozoa quality in normal human sperm.

  6. 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

  7. 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.

  8. 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

  9. Investigation of the content and of the distribution of chemical elements in human nails by SRXRF.

    PubMed

    Trunova, V A; Brenner, N V; Zvereva, V V

    2009-01-01

    The purpose of this investigation is to analyze 20 nails in individuals (and several persons) for the definition of how chemical elements distribute from nail to nail. The aim was to determine whether it will be rightful to take only one nail for the elemental analysis for the diagnostic of human state in future or not? Another purpose of the research is to analyze the elemental content of nails in temporal dynamic (in several persons). Analytical determinations of 20 nails of nine donors (healthy persons), nails of both hands and both feet were carried out. The analysis was performed by SRXRF. Symmetry of the elemental distribution in nails of right and left hands and right and left feet was found. The analysis of the distribution of chemical elements on the total area of a nail (55 points) was performed. The nail cutaway reflects adequately the distribution of several chemical elements over the nail plate area. In this study the elemental concentrations in nails of three donors in a 6-month period was determined. This study found the content of the chemical elements in donors' nails changes with time, individually.

  10. Are sheath folds late stage flanking structures?

    NASA Astrophysics Data System (ADS)

    Reber, Jacqueline E.; Dabrowski, Marcin; Schmid, Daniel W.

    2010-05-01

    Sheath folds can be described as highly non-cylindrical folds or as cone shaped with a rounded apex. A cross section of a sheath fold perpendicular to its elongation direction shows usually an elliptical shape. Sheath folds can be observed in nature within a wide range of materials and across many orders of size magnitude. A classification scheme has been developed by Alsop and Holdsworth (Journal of Structural Geology, 2006) which divides sheath folds into different categories depending on the ratio of the aspect ratio of the innermost and outermost "ring". Different initial conditions such as rigid objects and precursor folds formed through buckling were suggested as a trigger for the development of sheath folds. However, in nature sheath folds can also be observed where no rigid objects or precursor folds can be seen. In such cases we propose weak objects or zones as possible activators. According to this approach sheath folds represent a late stage of flanking structures. To simulate the weak zone we use an infinitely weak elliptical inclusion embedded in a homogeneous matrix. Planar markers such as bedding or foliation make the sheath geometry visible. To test the impact of the initial shape of the weak zone on the formation of the sheath folds the aspect ratio of the slip ellipse is changed systematically. As the geometry of sheath folds is truly three dimensional we use a 3D analytical model to investigate their formation. The model is based on an adapted internal and external Eshelby solution (Eshelby, Proceedings of the Royal Society of London series a-Mathematical and Physical Sciences, 1957 and 1959) for viscous rheologies and elliptical inclusions described in Exner and Dabrowski (Journal of Structural Geology, 2010 (submitted)). The ellipse as well as the matrix has linear viscous, isotropic, incompressible material properties. To analyze the cross-section the calculated folds are cut perpendicular to the simple shear stretching direction while the

  11. Regulatory elements controlling pituitary-specific expression of the human prolactin gene.

    PubMed Central

    Peers, B; Voz, M L; Monget, P; Mathy-Hartert, M; Berwaer, M; Belayew, A; Martial, J A

    1990-01-01

    We have performed transfection and DNase I footprinting experiments to investigate pituitary-specific expression of the human prolactin (hPRL) gene. When fused to the chloramphenicol acetyltransferase (CAT) reporter gene, 5,000 base pairs of the 5'-flanking sequences of the hPRL gene were able to drive high cat gene expression in prolactin-expressing GH3B6 cells specifically. Deletion analysis indicated that this pituitary-specific expression was controlled by three main positive regulatory regions. The first was located just upstream from the TATA box between coordinates -40 and -250 (proximal region). We have previously shown that three motifs of this region bind the pituitary-specific Pit-1 factor. The second positive region was located in the vicinity of coordinates -1300 to -1750 (distal region). DNase I footprinting assays revealed that eight DNA motifs of this distal region bound protein Pit-1 and that two other motifs were recognized by ubiquitous factors, one of which seems to belong to the AP-1 (jun) family. The third positive region was located further upstream, between -3500 and -5000 (superdistal region). This region appears to enhance transcription only in the presence of the distal region. Images PMID:2388622

  12. Regulatory elements controlling pituitary-specific expression of the human prolactin gene.

    PubMed

    Peers, B; Voz, M L; Monget, P; Mathy-Hartert, M; Berwaer, M; Belayew, A; Martial, J A

    1990-09-01

    We have performed transfection and DNase I footprinting experiments to investigate pituitary-specific expression of the human prolactin (hPRL) gene. When fused to the chloramphenicol acetyltransferase (CAT) reporter gene, 5,000 base pairs of the 5'-flanking sequences of the hPRL gene were able to drive high cat gene expression in prolactin-expressing GH3B6 cells specifically. Deletion analysis indicated that this pituitary-specific expression was controlled by three main positive regulatory regions. The first was located just upstream from the TATA box between coordinates -40 and -250 (proximal region). We have previously shown that three motifs of this region bind the pituitary-specific Pit-1 factor. The second positive region was located in the vicinity of coordinates -1300 to -1750 (distal region). DNase I footprinting assays revealed that eight DNA motifs of this distal region bound protein Pit-1 and that two other motifs were recognized by ubiquitous factors, one of which seems to belong to the AP-1 (jun) family. The third positive region was located further upstream, between -3500 and -5000 (superdistal region). This region appears to enhance transcription only in the presence of the distal region.

  13. Comparative structure, proximal promoter elements, and chromosome location of the human eosinophil major basic protein genes.

    PubMed

    Plager, D A; Weiler, D A; Loegering, D A; Johnson, W B; Haley, L; Eddy, R L; Shows, T B; Gleich, G J

    2001-02-01

    Human eosinophil major basic protein (MBP) is strongly implicated as a mediator of disease, especially bronchial asthma. We recently isolated a highly divergent human homologue of MBP (MBPH). Given human MBP's importance in disease and the restricted expression of it and human MBPH, we isolated the 4.6-kb human MBPH gene (HGMW-approved symbol PRG3). Comparisons among the human MBP (PRG2), human MBPH, and murine MBP-1 (mMBP-1; Prg2) genes suggest that the human MBP and mMBP-1 genes are more closely related than either is to the human MBPH gene. Proximal promoters of these three genes show conservation of potential binding sites for IK2 and STAT and of a known GATA site. However, a known C/EBP site is altered in the human MBPH gene's proximal promoter. The human MBP and MBPH genes localized to chromosome 11 in the centromere to 11q12 region. Thus, the human MBP and MBPH genes have diverged considerably, probably following a gene duplication event. Furthermore, the identified conserved and distinct proximal promoter elements likely contribute to the eosinophil-restricted and relatively reduced transcription of the human MBPH gene. Copyright 2001 Academic Press.

  14. 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

  15. 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.

  16. A study of frictional property of the human fingertip using three-dimensional finite element analysis.

    PubMed

    Yoshida, Hiroaki; Tada, Mitsunori; Mochimaru, Masaaki

    2011-03-01

    Since the tactile perception detects skin deformation due to the contact of an object, it is important to understand contact mechanics, especially, frictional behavior of the human fingertip. The coefficient of friction is recently modeled as a function of the applied normal load in which case the traditional Coulomb's law does not provide a description for the skin surface. When a surface is a rubber-like material, the frictional behavior follows the frictional law of the rubber-like material. Therefore, we developed a three-dimensional Finite Element model of the fingertip and analyzed frictional behavior based on the frictional law of rubber-like material. We proposed a combined technique using both experimental and Finite Element analyses in order to investigate the frictional property of the fingertip. A three-dimensional Finite Element model of the fingertip was developed using MRI images. We hypothesized a frictional equation of the critical shear stress. Squared differences between equivalent coefficient of friction of the FE analysis and the coefficient of kinetic friction of the experiment while sliding was decreased and the Finite Element analysis iterated until the error was minimized, and thus the frictional equation was determined. We obtained the equation of the critical shear stress and simulated kinetic friction of the fingertip while sliding under arbitrary normal loading condition by using the Finite Element analysis. We think this study is an appropriate method for understanding the frictional property of the human fingertip using the Finite Element analysis.

  17. Repetitive elements may comprise over two-thirds of the human genome.

    PubMed

    de Koning, A P Jason; Gu, Wanjun; Castoe, Todd A; Batzer, Mark A; Pollock, David D

    2011-12-01

    Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo "clouds"). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%-69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed "element-specific" P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed.

  18. Repetitive Elements May Comprise Over Two-Thirds of the Human Genome

    PubMed Central

    de Koning, A. P. Jason; Gu, Wanjun; Castoe, Todd A.; Batzer, Mark A.; Pollock, David D.

    2011-01-01

    Transposable elements (TEs) are conventionally identified in eukaryotic genomes by alignment to consensus element sequences. Using this approach, about half of the human genome has been previously identified as TEs and low-complexity repeats. We recently developed a highly sensitive alternative de novo strategy, P-clouds, that instead searches for clusters of high-abundance oligonucleotides that are related in sequence space (oligo “clouds”). We show here that P-clouds predicts >840 Mbp of additional repetitive sequences in the human genome, thus suggesting that 66%–69% of the human genome is repetitive or repeat-derived. To investigate this remarkable difference, we conducted detailed analyses of the ability of both P-clouds and a commonly used conventional approach, RepeatMasker (RM), to detect different sized fragments of the highly abundant human Alu and MIR SINEs. RM can have surprisingly low sensitivity for even moderately long fragments, in contrast to P-clouds, which has good sensitivity down to small fragment sizes (∼25 bp). Although short fragments have a high intrinsic probability of being false positives, we performed a probabilistic annotation that reflects this fact. We further developed “element-specific” P-clouds (ESPs) to identify novel Alu and MIR SINE elements, and using it we identified ∼100 Mb of previously unannotated human elements. ESP estimates of new MIR sequences are in good agreement with RM-based predictions of the amount that RM missed. These results highlight the need for combined, probabilistic genome annotation approaches and suggest that the human genome consists of substantially more repetitive sequence than previously believed. PMID:22144907

  19. HUMAN EYE OPTICS: Determination of positions of optical elements of the human eye

    NASA Astrophysics Data System (ADS)

    Galetskii, S. O.; Cherezova, T. Yu

    2009-02-01

    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.

  20. Development of an Anatomically Accurate Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies

    DTIC Science & Technology

    2017-02-01

    ARL-TR-7945 ● FEB 2017 US Army Research Laboratory Development of an Anatomically Accurate Finite Element Human Ocular Globe...ARL-TR-7945 ● FEB 2017 US Army Research Laboratory Development of an Anatomically Accurate Finite Element Human Ocular Globe Model...Finite Element Human Ocular Globe Model for Blast-Related Fluid-Structure Interaction Studies 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  1. 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…

  2. 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…

  3. 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.

  4. 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…

  5. 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

  6. Microsatellite Tandem Repeats Are Abundant in Human Promoters and Are Associated with Regulatory Elements

    PubMed Central

    Sawaya, Sterling; Bagshaw, Andrew; Buschiazzo, Emmanuel; Kumar, Pankaj; Chowdhury, Shantanu; Black, Michael A.; Gemmell, Neil

    2013-01-01

    Tandem repeats are genomic elements that are prone to changes in repeat number and are thus often polymorphic. These sequences are found at a high density at the start of human genes, in the gene’s promoter. Increasing empirical evidence suggests that length variation in these tandem repeats can affect gene regulation. One class of tandem repeats, known as microsatellites, rapidly alter in repeat number. Some of the genetic variation induced by microsatellites is known to result in phenotypic variation. Recently, our group developed a novel method for measuring the evolutionary conservation of microsatellites, and with it we discovered that human microsatellites near transcription start sites are often highly conserved. In this study, we examined the properties of microsatellites found in promoters. We found a high density of microsatellites at the start of genes. We showed that microsatellites are statistically associated with promoters using a wavelet analysis, which allowed us to test for associations on multiple scales and to control for other promoter related elements. Because promoter microsatellites tend to be G/C rich, we hypothesized that G/C rich regulatory elements may drive the association between microsatellites and promoters. Our results indicate that CpG islands, G-quadruplexes (G4) and untranslated regulatory regions have highly significant associations with microsatellites, but controlling for these elements in the analysis does not remove the association between microsatellites and promoters. Due to their intrinsic lability and their overlap with predicted functional elements, these results suggest that many promoter microsatellites have the potential to affect human phenotypes by generating mutations in regulatory elements, which may ultimately result in disease. We discuss the potential functions of human promoter microsatellites in this context. PMID:23405090

  7. Microsatellite tandem repeats are abundant in human promoters and are associated with regulatory elements.

    PubMed

    Sawaya, Sterling; Bagshaw, Andrew; Buschiazzo, Emmanuel; Kumar, Pankaj; Chowdhury, Shantanu; Black, Michael A; Gemmell, Neil

    2013-01-01

    Tandem repeats are genomic elements that are prone to changes in repeat number and are thus often polymorphic. These sequences are found at a high density at the start of human genes, in the gene's promoter. Increasing empirical evidence suggests that length variation in these tandem repeats can affect gene regulation. One class of tandem repeats, known as microsatellites, rapidly alter in repeat number. Some of the genetic variation induced by microsatellites is known to result in phenotypic variation. Recently, our group developed a novel method for measuring the evolutionary conservation of microsatellites, and with it we discovered that human microsatellites near transcription start sites are often highly conserved. In this study, we examined the properties of microsatellites found in promoters. We found a high density of microsatellites at the start of genes. We showed that microsatellites are statistically associated with promoters using a wavelet analysis, which allowed us to test for associations on multiple scales and to control for other promoter related elements. Because promoter microsatellites tend to be G/C rich, we hypothesized that G/C rich regulatory elements may drive the association between microsatellites and promoters. Our results indicate that CpG islands, G-quadruplexes (G4) and untranslated regulatory regions have highly significant associations with microsatellites, but controlling for these elements in the analysis does not remove the association between microsatellites and promoters. Due to their intrinsic lability and their overlap with predicted functional elements, these results suggest that many promoter microsatellites have the potential to affect human phenotypes by generating mutations in regulatory elements, which may ultimately result in disease. We discuss the potential functions of human promoter microsatellites in this context.

  8. 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.

  9. 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.

  10. Population and clinical genetics of human transposable elements in the (post) genomic era

    PubMed Central

    Rishishwar, Lavanya; Wang, Lu; Clayton, Evan A.; Mariño-Ramírez, Leonardo; McDonald, John F.; Jordan, I. King

    2017-01-01

    ABSTRACT Recent technological developments—in genomics, bioinformatics and high-throughput experimental techniques—are providing opportunities to study ongoing human transposable element (TE) activity at an unprecedented level of detail. It is now possible to characterize genome-wide collections of TE insertion sites for multiple human individuals, within and between populations, and for a variety of tissue types. Comparison of TE insertion site profiles between individuals captures the germline activity of TEs and reveals insertion site variants that segregate as polymorphisms among human populations, whereas comparison among tissue types ascertains somatic TE activity that generates cellular heterogeneity. In this review, we provide an overview of these new technologies and explore their implications for population and clinical genetic studies of human TEs. We cover both recent published results on human TE insertion activity as well as the prospects for future TE studies related to human evolution and health. PMID:28228978

  11. 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.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 9. NORTH FLANK AND (WEST) REAR WITH REAR OF ADMINISTRATION ...

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

    9. NORTH FLANK AND (WEST) REAR WITH REAR OF ADMINISTRATION BUILDING, LOOKING SOUTHEAST ACROSS GARDEN FROM TOWER GROVE SOUTH PORCH - Missouri Botanical Garden, Henry Shaw Townhouse, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

  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. Short 5'-flanking regions of the Amy gene of Drosophila kikkawai affect amylase gene expression and respond to food environments.

    PubMed

    Inomata, Nobuyuki; Nakashima, Shuichi

    2008-04-15

    Evolution of the duplicated genes and regulation in gene expression is of great interest, especially in terms of adaptation. Molecular population genetic and evolutionary studies on the duplicated amylase genes of Drosophila species have suggested that their 5'-flanking (cis-regulatory) regions play an important role in evolution of these genes. For better understanding of evolution of the duplicated amylase genes and gene expression, we studied functional significance of the Amy1 gene of Drosophila kikkawai using in vitro deletion mutagenesis followed by P-element-mediated germline transformation. We found that a 1.6-kb of the 5'-flanking region can produce strikingly higher level of larval amylase activity on starch food compared with that on glucose food. We found two cis-regulatory elements, which increase larval amylase activity on starch food. We also found a larval cis-regulatory element, which responds to the food difference. This food-response element is necessary for the function of the element increasing larval activity on starch food. A 5-bp deletion in a putative GRE caused high amylase activity, indicating a cis-regulatory element decreasing amylase activity. These cis-regulatory elements identified in the 5'-flanking region could be the targets of natural selection.

  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. Multi-elemental imaging of paraffin-embedded human samples by laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Moncayo, S.; Trichard, F.; Busser, B.; Sabatier-Vincent, M.; Pelascini, F.; Pinel, N.; Templier, I.; Charles, J.; Sancey, L.; Motto-Ros, V.

    2017-07-01

    Chemical elements play central roles for physiological homeostasis in human cells, and their dysregulation might lead to a certain number of pathologies. Novel imaging techniques that improve the work of pathologists for tissue analysis and diagnostics are continuously sought. We report the use of Laser-Induced Breakdown Spectroscopy (LIBS) to perform multi-elemental images of human paraffin-embedded skin samples on the entire biopsy scale in a complementary and compatible way with microscope histopathological examination. A specific instrumental configuration is proposed in order to detect most of the elements of medical interest (i.e. P, Al, Mg, Na, Zn, Si, Fe, and Cu). As an example of medical application, we selected and analysed skin biopsies, including healthy skin tissue, cutaneous metastasis of melanoma, Merkel-cell carcinoma and squamous cell carcinoma. Clear distinctions in the distribution of chemical elements are observed from the different samples investigated. This study demonstrates the high complementarity of LIBS elemental imaging with conventional histopathology, opening new opportunities for any medical application involving metals.

  3. 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.

  4. The validation and application of a finite element human head model for frontal skull fracture analysis.

    PubMed

    Asgharpour, Z; Baumgartner, D; Willinger, R; Graw, M; Peldschus, S

    2014-05-01

    Traumatic head injuries can result from vehicular accidents, sports, falls or assaults. The current advances in computational methods and the detailed finite element models of the human head provide a significant opportunity for biomechanical study of human head injuries. The biomechanical characteristics of the human head through head impact scenarios can be studied in detail by using the finite element models. Skull fracture is one of the most frequent occurring types of head injuries. The purpose of this study is to analyse the experimental head impacts on cadavers by means of the Strasbourg University Finite Element Head Model (SUFEHM). The results of the numerical model and experimental data are compared for validation purpose. The finite element model has also been applied to predict the skull bone fracture in frontal impacts. The head model includes the scalp, the facial bone, the skull, the cerebral spinal fluid, the meninges, the cerebrum and the cerebellum. The model is used to simulate the experimental frontal head impact tests using a cylindrical padded impactor. Results of the computational simulation shows that the model correlated well with a number of experimental data and a global fracture pattern has been predicted well by the model. Therefore the presented numerical model could be used for reconstruction of head impacts in different impact conditions also the forensic application of the head model would provide a tool for investigation of the causes and mechanism of head injuries.

  5. 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.

  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. 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

  8. Comparing elemental and configural associative theories in human causal learning: a case for attention.

    PubMed

    Lachnit, Harald; Schultheis, Holger; König, Stephan; Ungör, Metin; Melchers, Klaus

    2008-04-01

    In two causal learning experiments with human participants, the authors compared various associative theories that assumed either elemental (unique cue, modified unique cue, replaced elements model, and Harris' model) or configural processing of stimuli (Pearce's theory and a modification of it). The authors used modified patterning problems initially suggested by Redhead and Pearce (1995). Predictions for all theories were generated by computer simulations. Both configural theories and the unique cue approach failed to account for the observations. The replaced elements model was able to account for part of the data, but only if the replacement parameters could vary across discrimination problems. The Harris model and the modified unique cue approach, assuming that the salience of stimuli decreases with an increasing number of stimuli in a compound, successfully accounted for all of our data. This success implies that attentional factors should be explicitly taken into account in associative learning theory.

  9. Experimental measurement of tympanic membrane response for finite element model validation of a human middle ear.

    PubMed

    Ahn, Tae-Soo; Baek, Moo-Jin; Lee, Dooho

    2013-01-01

    The middle ear consists of a tympanic membrane, ligaments, tendons, and three ossicles. An important function of the tympanic membrane is to deliver exterior sound stimulus to the ossicles and inner ear. In this study, the responses of the tympanic membrane in a human ear were measured and compared with those of a finite element model of the middle ear. A laser Doppler vibrometer (LDV) was used to measure the dynamic responses of the tympanic membrane, which had the measurement point on the cone of light of the tympanic membrane. The measured subjects were five Korean male adults and a cadaver. The tympanic membranes were stimulated using pure-tone sine waves at 18 center frequencies of one-third octave band over a frequency range of 200 Hz ~10 kHz with 60 and 80 dB sound pressure levels. The measured responses were converted into the umbo displacement transfer function (UDTF) with a linearity assumption. The measured UDTFs were compared with the calculated UDTFs using a finite element model for the Korean human middle ear. The finite element model of the middle ear consists of three ossicles, a tympanic membrane, ligaments, and tendons. In the finite element model, the umbo displacements were calculated under a unit sound pressure on the tympanic membrane. The UDTF of the finite element model exhibited good agreement with that of the experimental one in low frequency range, whereas in higher frequency band, the two response functions deviated from each other, which demonstrates that the finite element model should be updated with more accurate material properties and/or a frequency dependent material model.

  10. 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

  11. Prediction of Colles' fracture load in human radius using cohesive finite element modeling.

    PubMed

    Ural, Ani

    2009-01-05

    Osteoporotic and age-related fractures are a significant public health problem. One of the most common osteoporotic fracture sites in the aging population is distal radius. There is evidence in the literature that distal radius fractures (Colles' fracture) are an indicative of increased risk of future spine and hip fractures. In this study, a nonlinear fracture mechanics-based finite element method is applied to human radius to assess its fracture load as a function of cortical bone geometry and material properties. Seven three-dimensional finite element models of radius were created and the fracture loads were determined by using cohesive finite element modeling which explicitly represents the crack and the fracture process zone behavior. The fracture loads found in the simulations (731-6793 N) were in the range of experimental values reported in the literature. The fracture loads predicted by the simulations decreased by 4-5% per decade based only on material level changes and by 6-20% per decade when geometrical changes were also included. Cortical polar moment of inertia at 15% distal radius showed the highest correlation to fracture load (r(2)=0.97). These findings demonstrate the strength of fracture mechanics-based finite element modeling and show that combining geometrical and material properties provides a better assessment of fracture risk in human radius.

  12. [THE LEGAL STATUS OF ELEMENTS AND PRODUCTS OF THE HUMAN BODY: OBJECT OR SUBJECT OF LAW?].

    PubMed

    De Lameigné, Anaïs Gayte-Papon

    2015-07-01

    The 2004 Act on bioethics has amended the 1994 Act regarding the donation and the use of elements and products of the human body, medically assisted procreation and prenatal diagnosis. The very purpose of these laws led the legislature not to attempt the summa divisio order distinguishing the object to the person. The analysis of bioethical laws reveals the consecration of the non-commercialization of the human body at the expense of its unavailability. Bioethical laws appear to be catalysts of biological scientific advances releasing the status of the components and the products of the human body while framing it. By limiting scientific opportunities, they prevent human beings from trying to play the sorcerer's apprentice.

  13. Finite-element models of the human head and their applications in forensic practice.

    PubMed

    Raul, Jean-Sébastien; Deck, Caroline; Willinger, Rémy; Ludes, Bertrand

    2008-09-01

    Since the 1960s, predictive human head impact indices have been developed to help the investigation of causation of human head injury. Finite-element models (FEM) can provide interesting tools for the forensic scientists when various human head injury mechanisms need to be evaluated. Human head FEMs are mainly used for car crash evaluations and are not in common use in forensic science. Recent technological progress has resulted in creating more simple tools, which will certainly help to consider the use of FEM in routine forensic practice in the coming years. This paper reviews the main FEMs developed and focuses on the models which can be used as predictive tools. Their possible applications in forensic medicine are discussed.

  14. Effect of transgene concentration, flanking matrix attachment regions, and RecA-coating on the efficiency of mouse transgenesis mediated by intracytoplasmic sperm injection.

    PubMed

    Moreira, Pedro Nuno; Pérez-Crespo, Miriam; Ramírez, Miguel Angel; Pozueta, Julio; Montoliu, Lluís; Gutiérrez-Adán, Alfonso

    2007-02-01

    Intracytoplasmic sperm injection (ICSI) of DNA-loaded sperm cells has been shown to be a valuable tool for the production of transgenic animals, especially when DNA constructs with submegabase magnitude are used. In order to optimize and to understand the mechanism of the ICSI-mediated transgenesis, we have evaluated the impact of transgene DNA concentration, transgene flanking with nuclear matrix attachment regions (MARs), and the use of recombinase A (RecA)-coated DNA on the efficiency of mouse transgenesis production by ICSI. Presented data include assays with three DNA constructs; an enhanced green fluorescent protein (EGFP) plasmid of 5.4 kb, this plasmid flanked with two MAR elements (2.3 Kb of the human beta-interferon domain boundaries), and a yeast artificial chromosome (YAC) construct of approximately 510 kb (the largest transgenic construct introduced by ICSI that we have seen reported). ICSI-mediated transgenesis was done in the B6D2 mouse strain using different concentrations for each construct. Analysis of generated data indicated that ICSI allows the use of higher DNA concentrations than the ones used for pronuclear microinjection, however, when a certain threshold is exceeded, embryo/fetal viability decrease dramatically. In addition, independently of the transgene concentration tested, transgene flanking with MAR sequences did not have a significant impact on the efficiency of this transgenesis method. Finally, we observed that although the overall efficiency of ICSI-mediated transgenesis with fresh spermatozoa and RecA-complexed DNA was similar to the one obtained with the common ICSI-mediated transgenesis approach with frozen-thawed spermatozoa and RecA free DNA, this method was not as efficient in maintaining a low frequency of founder animal mosaicism, suggesting that different mechanisms of transgene integration might result from each procedure.

  15. 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.

  16. Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells.

    PubMed Central

    Moshier, J A; Osborne, D L; Skunca, M; Dosescu, J; Gilbert, J D; Fitzgerald, M C; Polidori, G; Wagner, R L; Friezner Degen, S J; Luk, G D

    1992-01-01

    Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene. Images PMID:1598217

  17. 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.

  18. 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

  19. Sp1 Upregulates cAMP Response Element-Binding Protein Expression During Retinoic Acid-Induced Mucous Differentiation of Normal Human Bronchial Epithelial Cells

    PubMed Central

    Hong, Jeong Soo; Kim, Seung-Wook; Koo, Ja Seok

    2010-01-01

    Cyclic 3′,5′-adenosine monophosphate (cAMP) response-element (CRE) binding protein (CREB) is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA rapidly activates CREB without using retinoic acid (RA) receptors RAR and RXR in normal human tracheobronchial epithelial (NHTBE) cells. However, little is known about RA’s role in the physiologic regulation of CREB expression in the early mucous differentiation of NHTBE cells. Here, we report that RA upregulated CREB gene expression and that using 5′-serial deletion promoter analysis and mutagenesis analyses, two Sp1-binding sites located at nucleotides −217 and −150, which flank the transcription initiation site, were essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nucleotides −119 and −98 contributed to basal promoter activity. Interestingly, RA also upregulated Sp1 in a time- and dose-dependent manner. Knockdown of endogenous Sp1 using small interfering RNA (siRNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA upregulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in upregulating human CREB gene expression. This result implies that cooperation of these two transcription factors play a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells. PMID:17937658

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

    PubMed Central

    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

  1. Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements

    PubMed Central

    Wang, Lu; Mariño-Ramírez, Leonardo

    2017-01-01

    Abstract Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification. PMID:27998931

  2. Human population-specific gene expression and transcriptional network modification with polymorphic transposable elements.

    PubMed

    Wang, Lu; Rishishwar, Lavanya; Mariño-Ramírez, Leonardo; Jordan, I King

    2017-03-17

    Transposable element (TE) derived sequences are known to contribute to the regulation of the human genome. The majority of known TE-derived regulatory sequences correspond to relatively ancient insertions, which are fixed across human populations. The extent to which human genetic variation caused by recent TE activity leads to regulatory polymorphisms among populations has yet to be thoroughly explored. In this study, we searched for associations between polymorphic TE (polyTE) loci and human gene expression levels using an expression quantitative trait loci (eQTL) approach. We compared locus-specific polyTE insertion genotypes to B cell gene expression levels among 445 individuals from 5 human populations. Numerous human polyTE loci correspond to both cis and trans eQTL, and their regulatory effects are directly related to cell type-specific function in the immune system. PolyTE loci are associated with differences in expression between European and African population groups, and a single polyTE loci is indirectly associated with the expression of numerous genes via the regulation of the B cell-specific transcription factor PAX5. The polyTE-gene expression associations we found indicate that human TE genetic variation can have important phenotypic consequences. Our results reveal that TE-eQTL are involved in population-specific gene regulation as well as transcriptional network modification. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Why do humans have chins? Testing the mechanical significance of modern human symphyseal morphology with finite element analysis.

    PubMed

    Gröning, Flora; Liu, Jia; Fagan, Michael J; O'Higgins, Paul

    2011-04-01

    The modern human mandibular symphysis differs from those of all other primates in being vertically orientated and possessing a chin, but the functional significance of this unique morphology is not well understood. Some hypotheses propose that it is an adaptation to specific loads occurring during masticatory function. This study uses finite element analysis to examine these symphyseal loads in a model of a modern human mandible. By modifying the symphyseal cross-sectional form, the mechanical significance of the presence of the chin and symphyseal orientation is tested, and modern human and Neanderthal symphyseal cross-sections are compared with regard to their ability to withstand different loads. The results show that changes in symphyseal form have profound effects on the strains. The presence of a chin leads to lower symphyseal strains overall, whereas a vertical orientation of the symphysis results in higher strains under wishboning, but not under vertical bending in the coronal plane and dorsoventral shear. Compared to Neanderthals, the modern human symphysis shows higher strains during dorsoventral shear and wishboning, but is as effective as the Neanderthal symphysis in resisting vertical bending in the coronal plane and the loads resulting from simulated incision and unilateral molar biting. In general, the results of this study corroborate prior hypotheses about the mechanical effects of the human chin and vertical symphyseal orientation and support the idea that the relative importance of wishboning and vertical bending in the coronal plane might have played a role in the evolution of modern human symphyseal morphology.

  4. Holliday Junctions Are Associated with Transposable Element Sequences in the Human Genome.

    PubMed

    Ladias, Paris; Markopoulos, Georgios; Lazaros, Leandros; Markoula, Sofia; Tzavaras, Theodore; Georgiou, Ioannis

    2016-02-13

    Holliday junctions (HJs) constitute important intermediate structures for many cell functions such as DNA recombination and DNA repair. They derive from a 10-nt degenerate sequence, with a 3-nt core motif. In this study, we explored the human genome whether the HJ degenerate sequence associates with transposable elements (TEs) and mainly with those of the active and inactive ALU, LINE, SVA and HERV families. We identified six different forms of the HJ sequence motif, and we located the genomic coordinates of sequences containing both HJs and TEs. From 2982 total HJs, a significant number of 1319 TE-associated HJs were found, with a median distribution of 1 per 2.4 Mb. The HJs with higher GC content were observed more frequently at the genome. A high percentage of HJs were associated with all main TE families, with specificity for particular active or inactive elements: DNA elements and the retroelements ALUs, LINEs and HERVs up to 41.94%, 72.72%, 42.94% and 84.5%, respectively. Phylogenetic analysis revealed that HJs occur in both active and inactive TEs. Furthermore, the TE-associated HJs were almost exclusively found within a distance less than 1 Mb from human genes, while only 23 were not associated with any genes. This is the first report associating human HJs, with mobile elements. Our data pinpoint that particular HJ forms show preference for specific active retrotransposon families of ALUs and LINEs, suggesting that retrotransposon-incorporated HJs may relocate or replicate in the genome through retrotransposition, contributing to recombination, genome plasticity and DNA repair.

  5. Critical elements for human health risk assessment of less than lifetime exposures.

    PubMed

    Geraets, Liesbeth; Nijkamp, Monique M; Ter Burg, Wouter

    2016-11-01

    Less than lifetime exposure has confronted risk assessors as to how to interpret the risks for human health in case a chronic health-based limit is exceeded. Intermittent, fluctuating and peak exposures do not match with the basis of the chronic limit values possibly leading to conservative outcomes. This paper presents guidance on how to deal with human risk assessment of less than lifetime exposure. Important steps to be considered are characterization of the human exposure situation, evaluation whether the human less than lifetime exposure scenario corresponds to a non-chronic internal exposure: toxicokinetic and toxicodynamic considerations, and, finally, re-evaluation of the risk assessment. Critical elements for these steps are the mode of action, Haber's rule, and toxicokinetics (ADME) amongst others. Previous work for the endpoints non-genotoxic carcinogenicity and developmental toxicity is included in the guidance. The guidance provides a way to consider the critical elements, without setting default factors to correct for the less than lifetime exposure in risk assessment.

  6. Periodic sequence patterns in human exons

    SciTech Connect

    Baldi, P.; Brunak, S.; Engelbrecht, J.; Chauvin, Y.; Krogh, A.

    1995-12-31

    We analyze the sequential structure of human exons and their flanking introns by hidden Markov models. Together, models of donor site regions, acceptor site regions and flanked internal exons, show that exons -- besides the reading frame -- hold a specific periodic pattern. The pattern, which has the consensus: non-T(A/T)G and a minimal periodicity of roughly 10 nucleotides, is not a consequence of the nucleotide statistics in the three codon positions, nor of the well known nucleosome positioning signal. We discuss the relation between the pattern and other known sequence elements responsible for the intrinsic bending or curvature of DNA.

  7. The CYP2B2 5' flank contains a complex glucocorticoid response unit.

    PubMed

    Audet-Walsh, Etienne; Lachaud, Antoine Amaury; Anderson, Alan

    2008-11-15

    Rat CYP2B1 and CYP2B2 and mouse CYP2B10 are dramatically induced by phenobarbital (PB) in liver. PB responsiveness requires the constitutive androstane receptor (CAR). However, dexamethasone treatment can also induce CYP2B genes in both rat and mouse liver. Three regions have been shown to be involved in conferring dexamethasone responsiveness on CYP2B2 reporter constructs. They are the PB response unit, a functional glucocorticoid response element at -1.3kb in the 5' flank and a weak element in the basal promoter. We report here the identification, by deletion analysis of the CYP2B2 5' flank, of new glucocorticoid response elements or accessory factor sites. Moreover, we show that CAR acts as an accessory factor in the dexamethasone response in vivo of CYP2B10 protein in mice, by increasing both the basal and induced levels. We propose a model to explain the dexamethasone responsiveness of the CYP2B2 gene in which induction is mediated by a complex glucocorticoid response unit.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

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

    PubMed

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

    2016-04-07

    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.

  14. Automatic procedure for realistic 3D finite element modelling of human brain for bioelectromagnetic computations

    NASA Astrophysics Data System (ADS)

    Aristovich, K. Y.; Khan, S. H.

    2010-07-01

    Realistic computer modelling of biological objects requires building of very accurate and realistic computer models based on geometric and material data, type, and accuracy of numerical analyses. This paper presents some of the automatic tools and algorithms that were used to build accurate and realistic 3D finite element (FE) model of whole-brain. These models were used to solve the forward problem in magnetic field tomography (MFT) based on Magnetoencephalography (MEG). The forward problem involves modelling and computation of magnetic fields produced by human brain during cognitive processing. The geometric parameters of the model were obtained from accurate Magnetic Resonance Imaging (MRI) data and the material properties - from those obtained from Diffusion Tensor MRI (DTMRI). The 3D FE models of the brain built using this approach has been shown to be very accurate in terms of both geometric and material properties. The model is stored on the computer in Computer-Aided Parametrical Design (CAD) format. This allows the model to be used in a wide a range of methods of analysis, such as finite element method (FEM), Boundary Element Method (BEM), Monte-Carlo Simulations, etc. The generic model building approach presented here could be used for accurate and realistic modelling of human brain and many other biological objects.

  15. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Repressor element-1 silencing transcription factor (REST) is present in human control and Huntington's disease neurones.

    PubMed

    Schiffer, Davide; Caldera, Valentina; Mellai, Marta; Conforti, Paola; Cattaneo, Elena; Zuccato, Chiara

    2014-12-01

    The repressor element-1 silencing transcription factor/neurone-restrictive silencer factor (REST/NRSF) is a master regulator of neuronal gene expression. REST/NRSF functions by recruiting other cofactors to genomic loci that contain the repressor element 1/neurone restrictive silencer element (RE1/NRSE) binding motif. In brain, demonstration of REST protein presence in neurones has remained controversial. However, RE1/NRSE containing neuronal genes are actively modulated and REST dysregulation is implicated in Huntington's disease (HD). We aimed to investigate REST distribution in autopsy brain from control and HD patients. Brain tissues from six controls and six HD cases (Vonsattel grade 3 and 4) were investigated using immunohistochemical analysis. REST was present in neurones and glial cells of the cortex, caudate nucleus, hippocampus and cerebellum. REST labelling was mainly cytoplasmic in neurones while preferential nuclear staining of REST was found in glial cells. We also found that REST and huntingtin (HTT) colocalize in human neurones. Low levels of cytoplasmic REST were detected in neurones of the HD cortex and caudate but no direct relationship between decreased neuronal REST expression and disease grade was observed. These data support the notion of REST presence in human brain neurones and glial cells and indicate the importance of developing compounds able to restore REST-regulated transcription of neuronal genes in HD. © 2014 British Neuropathological Society.

  17. Human Research Program Human Health Countermeasures Element: Evidence Report - Artificial Gravity

    NASA Technical Reports Server (NTRS)

    Clement, Gilles

    2015-01-01

    The most serious risks of long-duration flight involve radiation, behavioral stresses, and physiological deconditioning. Artificial gravity (AG), by substituting for the missing gravitational cues and loading in space, has the potential to mitigate the last of these risks by preventing the adaptive responses from occurring. The rotation of a Mars-bound spacecraft or an embarked human centrifuge offers significant promise as an effective, efficient multi-system countermeasure against the physiological deconditioning associated with prolonged weightlessness. Virtually all of the identified risks associated with bone loss, muscle weakening, cardiovascular deconditioning, and sensorimotor disturbances might be alleviated by the appropriate application of AG. However, experience with AG in space has been limited and a human-rated centrifuge is currently not available on board the ISS. A complete R&D program aimed at determining the requirements for gravity level, gravity gradient, rotation rate, frequency, and duration of AG exposure is warranted before making a decision for implementing AG in a human spacecraft.

  18. Characterization of human passive muscles for impact loads using genetic algorithm and inverse finite element methods.

    PubMed

    Chawla, A; Mukherjee, S; Karthikeyan, B

    2009-02-01

    The objective of this study is to identify the dynamic material properties of human passive muscle tissues for the strain rates relevant to automobile crashes. A novel methodology involving genetic algorithm (GA) and finite element method is implemented to estimate the material parameters by inverse mapping the impact test data. Isolated unconfined impact tests for average strain rates ranging from 136 s(-1) to 262 s(-1) are performed on muscle tissues. Passive muscle tissues are modelled as isotropic, linear and viscoelastic material using three-element Zener model available in PAMCRASH(TM) explicit finite element software. In the GA based identification process, fitness values are calculated by comparing the estimated finite element forces with the measured experimental forces. Linear viscoelastic material parameters (bulk modulus, short term shear modulus and long term shear modulus) are thus identified at strain rates 136 s(-1), 183 s(-1) and 262 s(-1) for modelling muscles. Extracted optimal parameters from this study are comparable with reported parameters in literature. Bulk modulus and short term shear modulus are found to be more influential in predicting the stress-strain response than long term shear modulus for the considered strain rates. Variations within the set of parameters identified at different strain rates indicate the need for new or improved material model, which is capable of capturing the strain rate dependency of passive muscle response with single set of material parameters for wide range of strain rates.

  19. Forward problem of electrocardiography: construction of human torso models and field calculations using finite element method.

    PubMed

    Shahidi, A V; Savard, P

    1994-07-01

    Finite element models of the human torso were constructed using anatomical data measured by serial computerised tomography scans in a subject. A first set of three models with a mesh resolution of 5517 nodes and 29810 elements included an homogeneous conductivity, lungs inhomogeneity, and heart, lungs and spinal region inhomogeneities. A second set comprised similar models with a mesh resolution of 12084 nodes and 67045 elements. A cylindrically shaped volume conductor was also constructed to evaluate the convergency and accuracy of the finite element solutions by comparison with the analytical solution. Forward simulations were performed using different excitation sites on the cardiac surface. The inclusion of conductivity inhomogeneities altered the maximum and minimum values of the body surface potentials, but did not substantially modify the pattern of the potential distributions. The greatest effect was due to the inclusion of the lungs. Increasing the mesh resolution from 5517 to 12084 nodes did not change noticeably the shape or amplitude of the simulated body surface potential maps. These models can readily be used for other bioelectromagnetic problems.

  20. Three-dimensional finite element analysis of the human temporomandibular joint disc.

    PubMed

    Beek, M; Koolstra, J H; van Ruijven, L J; van Eijden, T M

    2000-03-01

    A three-dimensional finite element model of the articular disc of the human temporomandibular joint has been developed. The geometry of the articular cartilage and articular disc surfaces in the joint was measured using a magnetic tracking device. First, polynomial functions were fitted through the coordinates of these scattered measurements. Next, the polynomial description was transformed into a triangulated description to allow application of an automatic mesher. Finally, a finite element mesh of the articular disc was created by filling the geometry with tetrahedral elements. The articulating surfaces of the mandible and skull were modeled by quadrilateral patches. The finite element mesh and the patches were combined to create a three-dimensional model in which unrestricted sliding of the disc between the articulating surfaces was allowed. Simulation of statical joint loading at the closed jaw position predicted that the stress and strain distributions were located primarily in the intermediate zone of the articular disc with the highest values in the lateral part. Furthermore, it was predicted that considerable deformations occurred for relatively small joint loads and that relatively large variations in the direction of joint loading had little influence on the distribution of the deformations.

  1. On the incorporation of trace elements into human hair measured with micro-PIXE

    NASA Astrophysics Data System (ADS)

    Bos, A. J. J.; Van Der Stap, C. C. A. H.; Valković, V.; Vis, R. D.; Verheul, H.

    1984-04-01

    A study has been made on the incorporation of trace elements into human hair by measuring concentration distributions across hair diameters of selected samples using the Amsterdam proton microbeam. Because hair is considered as a recording filament, reflecting metabolic changes over a period of time, a hair of a young mother was plucked 4 months after delivery of her first child. No change in the Zn and Cu concentrations correlated with the period of gestation was observed. A strong increase of Ca in the distal end must be attributed to outside contamination. From a study of a hair root, including the root sheaths, it is found that the method of incorporation of sulfur (minor element) differs strikingly from the behaviour of the trace elements Zn, Cu, Fe and Ca. The Zn and Cu distributions provide evidence of a, not yet reported, transversal transcellular input route, in which the root sheaths play an important role. From the results it is deduced that Zn and Cu seem to be distributed homogeneously by nature, while Fe, present at a high level in the root sheaths, seems to be peaked by nature on the periphery. The results are discussed against the background of the range of values of concentrations of certain elements found in the literature.

  2. 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.

  3. Platinum group element incorporation into human bones resulting from increased anthropogenic utilization

    NASA Astrophysics Data System (ADS)

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

    2009-12-01

    Platinum group elements (including Pt, Pd, Ru, Rh, Os, Ir) are rare precious metals that occur at exceedingly low concentrations in the Earth’s crust (~0.02-0.5 ng/g). Utilization of PGEs in the catalytic converter of automobiles, medical treatments, electronics, and as a catalyst, has rapidly increased since the early 20th century, leading to increased anthropogenic PGE emissions and consequently increasing concentrations in the environment. Recent reports indicate that environmental PGE concentrations are increasing in urban air, roadside soils, and aquatic environments (Rauch and Morrison, 2008). As a result, there is an increased potential for PGE uptake into the biosphere. To evaluate bio-incorporation of PGEs into the human body we use ICP-MS to analyze for PGE concentration in human bones. Human bone minerals serve as a reservoir for the majority of the body’s trace metals and provide a measure of PGE incorporation into the human body from various environmental sources. We compare PGE concentrations in femoral heads of 30 present-day modern humans to those in femurs of 10 humans exhumed from 18th and 19th century burial sites, whose metal exposures predate extensive anthropogenic use of PGEs.

  4. 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

  5. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses.

    PubMed

    Ito, Jumpei; Sugimoto, Ryota; Nakaoka, Hirofumi; Yamada, Shiro; Kimura, Tetsuaki; Hayano, Takahide; Inoue, Ituro

    2017-07-01

    Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified "HERV/LTR-shared regulatory element (HSRE)," defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG), embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2), hematopoietic TFs (e.g., SPI1 (PU1), GATA1/2, and TAL1), and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/). This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into the

  6. Systematic identification and characterization of regulatory elements derived from human endogenous retroviruses

    PubMed Central

    Sugimoto, Ryota; Nakaoka, Hirofumi; Inoue, Ituro

    2017-01-01

    Human endogenous retroviruses (HERVs) and other long terminal repeat (LTR)-type retrotransposons (HERV/LTRs) have regulatory elements that possibly influence the transcription of host genes. We systematically identified and characterized these regulatory elements based on publicly available datasets of ChIP-Seq of 97 transcription factors (TFs) provided by ENCODE and Roadmap Epigenomics projects. We determined transcription factor-binding sites (TFBSs) using the ChIP-Seq datasets and identified TFBSs observed on HERV/LTR sequences (HERV-TFBSs). Overall, 794,972 HERV-TFBSs were identified. Subsequently, we identified “HERV/LTR-shared regulatory element (HSRE),” defined as a TF-binding motif in HERV-TFBSs, shared within a substantial fraction of a HERV/LTR type. HSREs could be an indication that the regulatory elements of HERV/LTRs are present before their insertions. We identified 2,201 HSREs, comprising specific associations of 354 HERV/LTRs and 84 TFs. Clustering analysis showed that HERV/LTRs can be grouped according to the TF binding patterns; HERV/LTR groups bounded to pluripotent TFs (e.g., SOX2, POU5F1, and NANOG), embryonic endoderm/mesendoderm TFs (e.g., GATA4/6, SOX17, and FOXA1/2), hematopoietic TFs (e.g., SPI1 (PU1), GATA1/2, and TAL1), and CTCF were identified. Regulatory elements of HERV/LTRs tended to locate nearby and/or interact three-dimensionally with the genes involved in immune responses, indicating that the regulatory elements play an important role in controlling the immune regulatory network. Further, we demonstrated subgroup-specific TF binding within LTR7, LTR5B, and LTR5_Hs, indicating that gains or losses of the regulatory elements occurred during genomic invasions of the HERV/LTRs. Finally, we constructed dbHERV-REs, an interactive database of HERV/LTR regulatory elements (http://herv-tfbs.com/). This study provides fundamental information in understanding the impact of HERV/LTRs on host transcription, and offers insights into the

  7. 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

  8. Characterization of Promoter Elements Regulating the Expression of the Human Neurotensin/Neuromedin N Gene*

    PubMed Central

    Wang, Xiaofu; Gulhati, Pat; Li, Jing; Dobner, Paul R.; Weiss, Heidi; Townsend, Courtney M.; Evers, B. Mark

    2011-01-01

    Expression of the gene encoding neurotensin/neuromedin N (NT/N) is mostly limited to the brain and specialized enteroendocrine N cells in the distal small intestine. We have identified key regulatory elements in the promoter region that are involved in human NT/N (hNT/N) gene expression in the novel human endocrine cell line, BON, which resembles intestinal N cells in several important aspects including NT/N precursor protein processing, ratios of different NT/N mRNA isoforms, and high levels of constitutive expression of the NT/N gene. In this study, we demonstrated multiple cis-regulatory elements including a proximal region containing a cAMP-responsive element (CRE)/AP-1-like element that binds both the AP-1 and CRE-binding protein (CREB)/ATF proteins (c-Jun, ATF-1, ATF-2, JunD, and CREB). Similar to the rat NT/N gene, this region is critical for constitutive hNT/N gene expression. Moreover, we identified a novel region that binds the orphan hormone receptor, NR2F2. We have demonstrated that the C terminus of NR2F2 strongly represses hNT/N transcription, whereas an N-terminal domain antagonizes this repressive effect. Regulation of NT/N expression by NR2F2 may have important consequences for lipid metabolism. We speculate that a complex interplay between the proximal CRE/AP-1-like motif and NR2F2 binding region exists to regulate hNT/N expression, which is critical for the high level of constitutive expression of NT/N in enteroendocrine cells. Finally, the BON cell line provides a unique model to characterize the factors regulating expression of the hNT/N gene and to better understand the mechanisms responsible for terminal differentiation of the N cell lineage in the gut. PMID:21030593

  9. 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.

  10. 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.

  11. Mobile genetic elements of the human gastrointestinal tract: potential for spread of antibiotic resistance genes.

    PubMed

    Broaders, Eileen; Gahan, Cormac G M; Marchesi, Julian R

    2013-01-01

    The human intestine is an important location for horizontal gene transfer (HGT) due to the presence of a densely populated community of microorganisms which are essential to the health of the human superorganism. HGT in this niche has the potential to influence the evolution of members of this microbial community and to mediate the spread of antibiotic resistance genes from commensal organisms to potential pathogens. Recent culture-independent techniques and metagenomic studies have provided an insight into the distribution of mobile genetic elements (MGEs) and the extent of HGT in the human gastrointestinal tract. In this mini-review, we explore the current knowledge of mobile genetic elements in the gastrointestinal tract, the progress of research into the distribution of antibiotic resistance genes in the gut and the potential role of MGEs in the spread of antibiotic resistance. In the face of reduced treatment options for many clinical infections, understanding environmental and commensal antibiotic resistance and spread is critical to the future development of meaningful and long lasting anti-microbial therapies.

  12. 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.

  13. Concentrations of trace element in human dentin by sex and age.

    PubMed

    Kumagai, Akiko; Fujita, Yuji; Endo, Shigeatsu; Itai, Kazuyoshi

    2012-06-10

    Teeth are recently drawing attention for their potential as biological modeling investigation samples due to their ability to be collected and their slow substance metabolism. There is no active metabolism of elements after the completion of dentin. Dentin is surrounded by enamel and cementum, and is not affected by the oral environment. Therefore, the amount of trace elements in dentin may change with age, and this is considered to be a reliable biological load index. The objectives in this study are to demonstrate concentrations of elements in the dentin of healthy Japanese subjects by sex and age, and to reveal the relationship between element levels and age. 121 healthy teeth samples were extracted due to periodontal disease or orthodontic treatment. Each tooth was sliced from the crown to the root apex into 0.5-1mm thickness, then enamel, cementum, and the pulp were removed; the dentins were used as samples. The concentration of 10 trace elements (B, Mn, Co, Cu, Zn, Rb, Sr, Mo, Cd, and Pb) in the dentin was measured using inductively coupled plasma mass spectrometer (ICP-MS). The differences Co and Pb in the dentin between men and women were significant (p<0.01). Significant positive correlation was observed between B, Co, Cu, Zn, Sr and Pb concentrations in the dentin and age (p<0.001). The results of the present study suggest that human dentin is an appropriate substance for relativity with sex and age at further future research. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. 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

  15. 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

  16. West Flank Coso, CA FORGE Natural Fracture data

    SciTech Connect

    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.

  17. [DNA sequences from mobile genetic elements, a hidden half of the human genome].

    PubMed

    Medina, Julie; Perron, Hervé

    2017-02-01

    Current data estimate that mobile genetic elements represent more than one-half of the human genome. The literature is constantly updating data following the evolution of sequencing techniques and of algorithms for genome analyses. This review aims to provide an overview of the topic showing the complexity given by the various designations and classifications found in scientific papers. A particular focus is made on retrotransposons, including Endogenous RetroViruses (ERV), to introduce a second article focusing on their activation and their involvement in physiological functions and/or pathological mechanisms associated with diseases like multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS). © 2017 médecine/sciences – Inserm.

  18. [Levels of mineral elements composition and heavy metal pollution in human breast milk in Shenzhen City].

    PubMed

    Deng, Bo; Zhang, Huimin; Yan, Chunrong; Zhang, Lishi

    2009-05-01

    To investigate the levels of some mineral elements composition and heavy metal in human breast milk in Shenzhen, and estimate the status of infant with breast feeding. ICP-MS and ICP-AES instruments were used to detect the levels of four macroelements of Ca, K, Na, Mg and four microelements of Zn, Fe, Se, Cu, totally eight minerals as well as three heavy metal of Pb, As and Cd in human breast milk. 60 breast milk samples were collected from the women aged 20-35, lived in Shenzhen over 5 years, postdelivery 3 weeks to 2 months from Jul. to Nov. 2007. Average concentration for four kinds of macroelement of Ca, K, Na, Mg was 280.22, 498.61, 188.65 and 28.31 mg/L respectively, that for four kinds of microelements of Zn, Fe, Se, Cu was 2.29 mg/L, 358.88 microg/L, 8.28 microg/L and 339.16 microg/L respectively in 60 human breast milk samples. Average concentration of Pb was 2.13 microg/L in 60 human breest milk samples, and heavy metal As and Cd were non-detected. The nutrition status of four kinds of macroelement of Ca, K, Na, Mg and three kinds of microelements of Zn, Fe, Cu in 60 human breast milk samples were reasonable, but the lack of microelement Se and the pollution of the heavy metal should been taken into account.

  19. The Role of Transposable Elements in the Origin and Evolution of MicroRNAs in Human

    PubMed Central

    Qin, Sheng; Jin, Ping; Zhou, Xue; Chen, Liming; Ma, Fei

    2015-01-01

    MicroRNAs (miRNAs) are crucial regulators of gene expression at the post-transcriptional level in eukaryotes via targeting gene 3'-untranslated regions. Transposable elements (TEs) are considered as natural origins of some miRNAs. However, what miRNAs are and how these miRNAs originate and evolve from TEs remain unclear. We identified 409 TE-derived miRNAs (386 overlapped with TEs and 23 un-overlapped with TEs) which are derived from TEs in human. This indicates that the TEs play important roles in origin of miRNAs in human. In addition, we found that the proportions of miRNAs derived from TEs (MDTEs) in human are more than other vertebrates especially non-mammal vertebrates. Furthermore, we classified MDTEs into three types and found that TE head or tail sequences along with adjacent genomic sequences contribute to generation of human miRNAs. Our current study will improve the understanding of origin and evolution of human miRNAs. PMID:26115450

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

    PubMed

    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

    2015-08-01

    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.

  1. 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.

  2. 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.

  3. Flexural uplift of rift flanks in central Greece

    NASA Astrophysics Data System (ADS)

    Poulimenos, George; Doutsos, Theodor

    1997-12-01

    Uplifts, with elevations of up to 2000 m and short wavelengths (30-35 km), flank three major grabens in central Greece: the Rio, Sparta, and Atalanti grabens. They are bordered on their landward sides by narrow basins oriented parallel to the graben axes: the Manesi and Trichonis basins at the Rio graben and Copais and Istiea basins at the Atalanti graben. The flexural origin of these uplift profiles is investigated here by using thin, broken plate models. It is demonstrated that the observed topography of the graben flanks is consistent with the upward deflection of elastic and viscoelastic plates in response to upward directed forces applied at the graben flanks. In order to evaluate to applicability of each model, their predictions are checked against the observations. The elastic predictive modeling fits well with the observed flexural wavelengths and the flanking seismicity. However, it fails to predict the graben widths and the inferred elastic layer thickness. In contrast, the viscoelastic model successfully explains the graben widths and the "back" basins as flexural hinterland basins and matches the seismological data and the time constraints of rifting. It is therefore suggested that flexural uplift with viscoelastic relaxation accounts for the building of the graben flanks. The invoked viscoelastic models constrain the effective elastic thickness of the plates at 10 km for the Rio graben and 15 km for the Sparta and Atalanti grabens, suggesting a low-viscosity lower crust. Furthermore, they predict low rates of tectonic uplift of the order of 0.1 mm a-1 for the Atalanti graben, intermediate rates of 0.24-0.37 mm a-1 for the Rio graben, and high rates of 0.7-0.9 mm a-1 for the Sparta graben. The latter are quite possibly overestimated since napping events, capable of producing high local relief, are traced normal to the modeled profiles.

  4. Unilateral flank ovariohysterectomy in guinea pigs (Cavia porcellus).

    PubMed

    Rozanska, D; Rozanski, P; Orzelski, M; Chlebicka, N; Putowska, K

    2016-11-01

    To describe a simple, minimally invasive method of ovariohysterectomy via a unilateral flank approach in guinea pigs, for use in routine desexing of healthy female guinea pigs or treatment of ovarian cysts. The subjects of this retrospective study were 41 client-owned guinea pigs submitted for routine desexing or treatment of ovarian cysts. They included 16 healthy female guinea pigs aged 8-12 months (Group 1), and 15 females aged from 9 months to 3 years (Group 2), and 10 females aged from 3 to 7 years (Group 3) with different-sized ovarian cysts. Prior to surgery, the animals received clinical examination, blood testing (complete blood count and serum biochemistry profile) and examination of the abdomen using ultrasonography, to assess the condition of the reproductive tract and ensure the guinea pigs were fit for surgery. Ovariohysterectomy was performed via a unilateral flank incision made close to the erector spinae muscle starting approximately 1 cm caudal to the last rib. Both ovaries, uterine horns, and the uterine cervix were localised, ligated, and dissected through this unilateral retroperitoneal incision. Ovariohysterectomy was successfully completed via a single flank incision in 38/41 (93%) guinea pigs. Three guinea pigs with ovarian cysts from Group 3, which were >6 years old died during surgery due to circulatory and respiratory failure under anaesthesia. In the remaining 38 cases, surgery proceeded without complications. A further two guinea pigs from Group 3 were reluctant to move or eat for the first 3 days after surgery but recovered after provision of supportive care. All 38 animals fully recovered and wound healing was normal. This is the first report of ovariohysterectomy via a unilateral flank incision in guinea pigs. This approach is a simple, minimally invasive and safe alternative to the midline or bilateral flank approaches currently used for surgery of the reproductive tract in guinea pigs.

  5. 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.

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

    PubMed

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

    2015-09-01

    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.

  7. 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

  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. 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).

  10. Finite element analysis (FEA): applying an engineering method to functional morphology in anthropology and human biology.

    PubMed

    Panagiotopoulou, O

    2009-01-01

    A fundamental research question for morphologists is how morphological variation in the skeleton relates to function. Traditional approaches have advanced our understanding of form-function relationships considerably but have limitations. Strain gauges can only record strains on a surface, and the geometry of the structure can limit where they can be bonded. Theoretical approaches, such as geometric abstractions, work well on problems with simple geometries and material properties but biological structures typically have neither of these. Finite element analysis (FEA) is a method that overcomes these problems by reducing a complex geometry into a finite number of elements with simple geometries. In addition, FEA allows strain to be modelled across the entire surface of the structure and throughout the internal structure. With advances in the processing power of computers, FEA has become more accessible and as such is becoming an increasingly popular tool to address questions about form-function relationships in development and evolution, as well as human biology generally. This paper provides an introduction to FEA including a review of the sequence of steps needed for the generation of biologically accurate finite element models that can be used for the testing of biological and functional morphology hypotheses.

  11. Antioxidant enzyme activities of human peripheral blood mononuclear cells exposed to trace elements.

    PubMed

    Kuppusamy, U R; Dharmani, M; Kanthimathi, M S; Indran, M

    2005-07-01

    The trace elements copper, zinc, and selenium are important immune modulators and essential cofactors of the antioxidant enzymes. In the present study, the proliferative effect of human peripheral mononuclear cells (PBMCs) that have been exposed to copper, zinc, and selenium and the corresponding activities of antioxidant enzymes, namely superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, were determined. Zinc and copper stimulated the PBMC proliferation in a dose-dependent manner within the dose range 25-200 micromol/L. SOD and GPx activities in PBMCs exposed to zinc were inhibited, whereas catalase activity was unaffected. All the three antioxidant enzymes in the cells exposed to copper were inhibited. Selenium exerted more potent inhibition of the cell proliferation while causing stimulation of the antioxidant enzymes at the lowest dose (25 micromol/L) than at the highest dose (200 micromol/L) tested. A significant negative correlation was observed between proliferation and antioxidant enzyme (SOD and GPx) activities in trace-element-exposed PBMC. The present findings substantiate the importance of trace elements as immune modulators and the involvement of enzymatic antioxidant system in the immune cell regulation.

  12. Application of an ETV-ICP system for the determination of elements in human hair*1

    NASA Astrophysics Data System (ADS)

    Plantikow-Voβgätter, F.; Denkhaus, E.

    1996-01-01

    When determining element contents in hair samples without sample digestion it is necessary to analyze large sample volumes in order to minimize problems of inhomogeneity of biological sample materials. Therefore an electrothermal vaporization system (ETV) is used for solid sample introduction into an inductively coupled plasma (ICP) for the determination of matrix and trace elements in hair. This paper concentrates on the instrumental aspects without time consuming sample preparation. The results obtained for optimization tests, ETV operating parameters and ICP operating parameters, are shown and discussed. Standard additions are used for calibration for the determination of Zn, Mg, and Mn in human hair. Studies including reproducibility and detection limits for chosen elements have been carried out on certified reference materials (CRMs). The determination of reproducibility (relative standard deviation (RSD) of n = 10) and detection limits (DLs) of Zn (RSD < 8.5%, DL < 0.8 μ g -1), Mn (RSD < 14.1%, DL < 0.3 μ g -1), and Mg (RSD < 7.4%, DL < 6.6 μ g -1) are satisfactory. The concentration values found show good agreement with the corresponding certified values. Further sample preparation steps, including hair sampling, washing procedure and homogenization for hair, relating to measurements of real hair samples are described.

  13. Accumulation of rare earth elements in human bone within the lifespan.

    PubMed

    Zaichick, Sofia; Zaichick, Vladimir; Karandashev, Vasilii; Nosenko, Sergey

    2011-02-01

    For the first time, the contents of rare earth elements (REEs) in a rib bone of a healthy human were determined. The mean value of the contents of Ce, Dy, Er, Gd, La, Nd, Pr, Sm, Tb, and Yb (10 elements out of 17 total REEs), as well as the upper limit of means for Ho, Lu, Tm, and Y (4 elements) were measured in the rib bone tissue of 38 females and 42 males (15 to 55 years old) using inductively coupled plasma mass spectrometry (ICP-MS). We found age-related accumulation of REEs in the bone tissue of healthy individuals who lived in a non-industrial region. It was calculated that during a lifespan the content of REEs in a skeleton of non-industrial region residents may increase by one to two orders of magnitude. Using our results as indicative normal values and published data we estimated relative Gd accumulation in the bone tissue of patients according to magnetic resonance imaging with contrast agent and La accumulation in the bone tissue of patients receiving hemodialysis after treatment with lanthanum carbonate as a phosphate binder. It was shown that after such procedures contents of Gd and La in the bone tissue of patients are two to three orders of magnitude higher than normal levels. In our opinion, REEs incorporation may affect bone quality and health similar to other potentially toxic trace metals. The impact of elevated REEs content on bone physiology, biochemistry and morphology requires further investigation.

  14. Ionising irradiation alters the dynamics of human long interspersed nuclear elements 1 (LINE1) retrotransposon.

    PubMed

    Tanaka, Atsushi; Nakatani, Youko; Hamada, Nobuyuki; Jinno-Oue, Atsushi; Shimizu, Nobuaki; Wada, Seiichi; Funayama, Tomoo; Mori, Takahisa; Islam, Salequl; Hoque, Sheikh Ariful; Shinagawa, Masahiko; Ohtsuki, Takahiro; Kobayashi, Yasuhiko; Hoshino, Hiroo

    2012-09-01

    It is important to identify the mechanism by which ionising irradiation induces various genomic alterations in the progeny of surviving cells. Ionising irradiation activates mobile elements like retrotransposons, although the mechanism of its phenomena consisting of transcriptions and insertions of the products into new sites of the genome remains unclear. In this study, we analysed the effects of sparsely ionising X-rays and densely ionising carbon-ion beams on the activities of a family of active retrotransposons, long interspersed nuclear elements 1 (L1). We used the L1/reporter knock-in human glioma cell line, NP-2/L1RP-enhanced GFP (EGFP), that harbours full-length L1 tagged with EGFP retrotransposition detection cassette (L1RP-EGFP) in the chromosomal DNA. X-rays and carbon-ion beams similarly increased frequencies the transcription from L1RP-EGFP and its retrotransposition. Short-sized de novo L1RP-EGFP insertions with 5'-truncation were induced by X-rays, while full-length or long-sized insertions (>5 kb, containing ORF1 and ORF2) were found only in cell clones irradiated by the carbon-ion beams. These data suggest that X-rays and carbon-ion beams induce different length of de novo L1 insertions, respectively. Our findings thus highlight the necessity to investigate the mechanisms of mutations caused by transposable elements by ionising irradiation.

  15. 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.

  16. Molecular Diversity and Evolutionary Relationships of Tn1546-Like Elements in Enterococci from Humans and Animals

    PubMed Central

    Willems, Rob J. L.; Top, Janetta; van den Braak, Nicole; van Belkum, Alex; Mevius, Dik J.; Hendriks, Giel; van Santen-Verheuvel, Marga; van Embden, Jan D. A.

    1999-01-01

    We report on a detailed study on the molecular diversity and evolutionary relationships of Tn1546-like elements in vancomycin-resistant enterococci (VRE) from humans and animals. Restriction fragment length polymorphism (RFLP) analysis of the VanA transposon of 97 VRE revealed seven different Tn1546 types. Subsequent sequencing of the complete VanA transposons of 13 VRE isolates representing the seven RFLP types followed by sequencing of the identified polymorphic regions in 84 other VanA transposons resulted in the identification of 22 different Tn1546 derivatives. Differences between the Tn1546 types included point mutations in orf1, vanS, vanA, vanX, and vanY. Moreover, insertions of an IS1216V-IS3-like element in orf1, of IS1251 in the vanS-vanH intergenic region, and of IS1216V in the vanX-vanY intergenic region were found. The presence of insertion sequence elements was often associated with deletions in Tn1546. Identical Tn1546 types were found among isolates from humans and farm animals in The Netherlands, suggesting the sharing of a common vancomycin resistance gene pool. Application of the genetic analysis of Tn1546 to VRE isolates causing infections in hospitals in Oxford, United Kingdom, and Chicago, Ill., suggested the possibility of the horizontal transmission of the vancomycin resistance transposon. The genetic diversity in Tn1546 combined with epidemiological data suggest that the DNA polymorphism among Tn1546 variants can successfully be exploited for the tracing of the routes of transmission of vancomycin resistance genes. PMID:10049255

  17. A dynamic finite element analysis of human foot complex in the sagittal plane during level walking.

    PubMed

    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.

  18. 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

  19. 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

  20. Comparative analysis of dioxin response elements in human, mouse and rat genomic sequences.

    PubMed

    Sun, Y V; Boverhof, D R; Burgoon, L D; Fielden, M R; Zacharewski, T R

    2004-01-01

    Comparative approaches were used to identify human, mouse and rat dioxin response elements (DREs) in genomic sequences unambiguously assigned to a nucleotide RefSeq accession number. A total of 13 bona fide DREs, all including the substitution intolerant core sequence (GCGTG) and adjacent variable sequences, were used to establish a position weight matrix and a matrix similarity (MS) score threshold to rank identified DREs. DREs with MS scores above the threshold were disproportionately distributed in close proximity to the transcription start site in all three species. Gene expression assays in hepatic mouse tissue confirmed the responsiveness of 192 genes possessing a putative DRE. Previously identified functional DREs in well-characterized AhR-regulated genes including Cyp1a1 and Cyp1b1 were corroborated. Putative DREs were identified in 48 out of 2437 human-mouse-rat orthologous genes between -1500 and the transcriptional start site, of which 19 of these genes possessed positionally conserved DREs as determined by multiple sequence alignment. Seven of these nineteen genes exhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated regulation, although there were significant discrepancies between in vivo and in vitro results. Interestingly, of the mouse-rat orthologous genes with a DRE between -1500 and +1500, only 37% had an equivalent human ortholog. These results suggest that AhR-mediated gene expression may not be well conserved across species, which could have significant implications in human risk assessment.

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

    PubMed

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

    2011-09-07

    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.

  2. 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.

  3. Exploring the links between volcano flank collapse and magma evolution: Fogo oceanic shield volcano, Cape Verde

    NASA Astrophysics Data System (ADS)

    Cornu, Melodie-Neige; Paris, Raphael; Doucelance, Regis; Bachelery, Patrick; Guillou, Hervé

    2017-04-01

    Mass wasting of oceanic shield volcanoes is largely documented through the recognition of collapse scars and submarine debris fans. However, it is actually difficult to infer the mechanisms controlling volcano flank failures that potentially imply tens to hundreds of km3. Studies coupling detailed petrological and geochemical analyses of eruptive products hold clues for better understanding the relationships between magma sources, the plumbing system, and flank instability. Our study aims at tracking potential variations of magma source, storage and transport beneath Fogo shield volcano (Cape Verde) before and after its major flank collapse. We also provide a geochronological framework of this magmatic evolution through new radiometric ages (K-Ar and Ar-Ar) of both pre-collapse and post-collapse lavas. The central part of Fogo volcanic edifice is truncated by an 8 km-wide caldera opened to the East, corresponding to the scar of the last flank collapse (Monte Amarelo collapse, Late Pleistocene, 150 km3). Lavas sampled at the base of the scar (the so-called Bordeira) yielded ages between 158 and 136 ka. The age of the collapse is constrained between 68 ka (youngest lava flow cut by the collapse scar) and 59 ka (oldest lava flow overlapping the scar). The collapse walls display a complex structural, intrusive and eruptive history. Undersaturated volcanism (SiO2<43%) is surprisingly dominated by explosive products such as ignimbrites, with 4 major explosive episodes representing half of the volume of the central edifice. This explosive record onshore is correlated with the offshore record of mafic tephra and turbidites (Eisele et al., 2015). Major elements analyses indicate that the pre-collapse lavas are significantly less differentiated than post-collapse lavas, with a peak of alkalis at the collapse. Rare-earth elements concentration decreases with time, with a notable positive anomaly before the collapse. The evolution of the isotopic ratios (Sr, Nd and Pb) through

  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. [Cloning of 5', 3' flanking sequence of ovine BLG and regulating the expression of GFP in mammary gland cell line].

    PubMed

    Liu, Ming-Jun; Li, Wen-Rong; Wu, Jian; Huang, Jun-Cheng; Guo, Zhi-Qin; Qu, Xin-Yong; Paul, Kroon

    2002-01-01

    5' and 3' flanking region of ovine BLG were amplified from sheep genomic DNA according to the published whole sequence of ovine BLG and cloned to pGEM-T vector correspondently. By partially sequencing, the sequences of BLG 5' and 3' flanking were the same as that of publication completely. The recombinant structure used to direct exogenous gene especially to express in mammary gland was constructed by joining 4.2 kb 5' flanking with 2.1 kb 3' flanking. In order to assess the efficiency of BLG regulatory elements, green fluorescent protein (GFP) gene as a reporter was fused with BLG construct and transfected the mammary epithelial cells (TD47). Through observation under UV microscope and detection by fluorometer, it is demonstrated that the GFP has been successfully expressed in TD47 cell line. By virtue of direct observation and quantitative analysis, the BLG-GFP construct can be served as a model for the quick assessment of mammary gland expression construct.

  6. Flanking region variation of ForenSeq™ DNA Signature Prep Kit STR and SNP loci in Yavapai Native Americans.

    PubMed

    Wendt, Frank R; King, Jonathan L; Novroski, Nicole M M; Churchill, Jennifer D; Ng, Jillian; Oldt, Robert F; McCulloh, Kelly L; Weise, Jessica A; Smith, David Glenn; Kanthaswamy, Sreetharan; Budowle, Bruce

    2017-05-01

    Massively parallel sequencing (MPS) offers advantages over current capillary electrophoresis-based analysis of short tandem repeat (STR) loci for human identification testing. In particular STR repeat motif sequence information can be obtained, thereby increasing the discrimination power of some loci. While sequence variation within the repeat region is observed relatively frequently in some of the commonly used STRs, there is an additional degree of variation found in the flanking regions adjacent to the repeat motif. Repeat motif and flanking region sequence variation have been described for major population groups, however, not for more isolated populations. Flanking region sequence variation in STR and single nucleotide polymorphism (SNP) loci in the Yavapai population was analyzed using the ForenSeq™ DNA Signature Prep Kit and STRait Razor v2s. Seven and 14 autosomal STRs and identity-informative single nucleotide polymorphisms (iiSNPs), respectively, had some degree of flanking region variation. Three and four of these identity-informative loci, respectively, showed ≥5% increase in expected heterozygosity. The combined length- and sequence-based random match probabilities (RMPs) for 27 autosomal STRs were 6.11×10(-26) and 2.79×10(-29), respectively. When combined with 94 iiSNPs (a subset of which became microhaplotypes) the combined RMP was 5.49×10(-63). Analysis of length-based and sequence-based autosomal STRs in STRUCTURE indicated that the Yavapai are most similar to the Hispanic population. While producing minimal increase in X- and Y-STR discrimination potential, access to flanking region data enabled identification of one novel X-STR and three Y-STR alleles relative to previous reports. Five ancestry-informative SNPs (aiSNPs) and two phenotype-informative SNPs (piSNPs) exhibited notable flanking region variation. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Evolutionary conservation of an atypical glucocorticoid-responsive element in the human tyrosine hydroxylase gene.

    PubMed

    Sheela Rani, C S; Soto-Pina, Alexandra; Iacovitti, Lorraine; Strong, Randy

    2013-07-01

    The human tyrosine hydroxylase (hTH) gene has a 42 bp evolutionarily conserved region designated (CR) II at -7.24 kb, which bears 93% homology to the region we earlier identified as containing the glucocorticoid response element, a 7 bp activator protein-1 (AP-1)-like motif in the rat TH gene. We cloned this hTH-CRII region upstream of minimal basal hTH promoter in luciferase (Luc) reporter vector, and tested glucocorticoid responsiveness in human cell lines. Dexamethasone (Dex) stimulated Luc activity of hTH-CRII in HeLa cells, while mifepristone, a glucocorticoid receptor (GR) antagonist, prevented Dex stimulation. Deletion of the 7 bp 5'-TGACTAA at -7243 bp completely abolished the Dex-stimulated Luc activity of hTH-CRII construct. The AP-1 agonist, tetradeconoyl-12,13-phorbol acetate (TPA), also stimulated hTH promoter activity, and Dex and TPA together further accentuated this response. Chromatin immunoprecipitation assays revealed the presence of both GR and AP-1 proteins, especially Jun family members, at this hTH promoter site. Dex did not stimulate hTH promoter activity in a catecholaminergic cell line, which had low endogenous GR levels, but did activate the response when GR was expressed exogenously. Thus, our studies have clearly identified a glucocorticoid-responsive element in a 7 bp AP-1-like motif in the promoter region at -7.24 kb of the human TH gene.

  8. A Novel Intron Element Operates Posttranscriptionally To Regulate Human N-myc Expression

    PubMed Central

    Sivak, Louise E.; Pont-Kingdon, Geneviève; Le, Kim; Mayr, Gabriele; Tai, Kuei-Fang; Stevens, Ben T.; Carroll, William L.

    1999-01-01

    Precisely regulated expression of oncogenes and tumor suppressor genes is essential for normal development, and deregulated expression can lead to cancer. The human N-myc gene normally is expressed in only a subset of fetal epithelial tissues, and its expression is extinguished in all adult tissues except transiently in pre-B lymphocytes. The N-myc gene is overexpressed due to genomic amplification in the childhood tumor neuroblastoma. In previous work to investigate mechanisms of regulation of human N-myc gene expression, we observed that N-myc promoter–chloramphemicol acelyltransferase reporter constructs containing sequences 5′ to exon 1 were active in all cell types examined, regardless of whether endogenous N-myc RNA was detected. In contrast, inclusion of the first exon and a portion of the first intron allowed expression only in those cell types with detectable endogenous N-myc transcripts. We investigated further the mechanisms by which this tissue-specific control of N-myc expression is achieved. Using nuclear run-on analyses, we determined that the N-myc gene is actively transcribed in all cell types examined, indicating a posttranscriptional mode of regulation. Using a series of N-myc intron 1 deletion constructs, we localized a 116-bp element (tissue-specific element [TSE]) within the first intron that directs tissue-specific N-myc expression. The TSE can function independently to regulate expression of a heterologous promoter-reporter minigene in a cell-specific pattern that mirrors the expression pattern of the endogenous N-myc gene. Surprisingly, the TSE can function in both sense and antisense orientations to regulate gene expression. Our data indicate that the human N-myc TSE functions through a posttranscriptional mechanism to regulate N-myc expression. PMID:9858540

  9. Transmembrane Helix Association Affinity Can Be Modulated by Flanking and Noninterfacial Residues

    PubMed Central

    Zhang, Jinming; Lazaridis, Themis

    2009-01-01

    The GxxxG sequence motif mediates the association of transmembrane (TM) helices by providing a site of close contact between them. However, it is not sufficient for strong association. For example, both bacteriophage M13 major coat protein (MCP) and human erythrocyte protein glycophorin A (GpA) contain a GxxxG motif in their TM domains and form a homodimer, but the association affinity of MCP, measured by the ToxCAT in vivo assay, is dramatically weaker than that of GpA. Even when all interfacial residues of MCP were substituted for those of GpA (MCP-GpA), association remained significantly weaker than in GpA. Here we provide an explanation for these experimental observations using molecular dynamics simulations in an implicit membrane (IMM1-GC). The association free energies of GpA29 (GpA with 29 residues all from the wild-type sequence), GpA15p11 (GpA with 15 residues from the wild-type sequence plus 11 flanking residues from the ToxCAT construct), MCP, and MCP-GpA TM helices were calculated and compared. MCP and MCP-GpA have the same flanking residues used in the ToxCAT assay as those in GpA15p11, but the position of the flanking residues relative to the GxxxG motif is different. The calculated association free energies follow experimental observations: the association affinity of MCP-GpA falls between those of GpA15p11 and MCP wild-type. MCP exhibits an equally strong interhelical interaction in the TM domain. A major reason for the weaker association of MCP in the calculations was the noninterfacial residue Lys-40, which in the dimer structure is forced to be buried in the membrane interior. To alleviate the desolvation cost, in MCP and MCP-GpA dimers, Lys-40 gets deprotonated. A second factor that modulates association affinity is the flanking residues. Thanks to them, GpA15p11 exhibits a much stronger association affinity than GpA29. The positioning of the flanking residues is also important, as evidenced by the difference in association affinity between

  10. Computational identification of new structured cis-regulatory elements in the 3'-untranslated region of human protein coding genes.

    PubMed

    Chen, Xiaowei Sylvia; Brown, Chris M

    2012-10-01

    Messenger ribonucleic acids (RNAs) contain a large number of cis-regulatory RNA elements that function in many types of post-transcriptional regulation. These cis-regulatory elements are often characterized by conserved structures and/or sequences. Although some classes are well known, given the wide range of RNA-interacting proteins in eukaryotes, it is likely that many new classes of cis-regulatory elements are yet to be discovered. An approach to this is to use computational methods that have the advantage of analysing genomic data, particularly comparative data on a large scale. In this study, a set of structural discovery algorithms was applied followed by support vector machine (SVM) classification. We trained a new classification model (CisRNA-SVM) on a set of known structured cis-regulatory elements from 3'-untranslated regions (UTRs) and successfully distinguished these and groups of cis-regulatory elements not been strained on from control genomic and shuffled sequences. The new method outperformed previous methods in classification of cis-regulatory RNA elements. This model was then used to predict new elements from cross-species conserved regions of human 3'-UTRs. Clustering of these elements identified new classes of potential cis-regulatory elements. The model, training and testing sets and novel human predictions are available at: http://mRNA.otago.ac.nz/CisRNA-SVM.

  11. 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…

  12. 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…

  13. Imaging of flank pain: readdressing state-of-the-art.

    PubMed

    Jha, Priyanka; Bentley, Brian; Behr, Spencer; Yee, Judy; Zagoria, Ronald

    2017-02-01

    Pain resulting from renal and ureteral stones is a common cause for patients presenting in the acute setting. Since the late 1990s, computed tomography (CT) has been the initial imaging method of choice to evaluate patients with suspected ureteral stones; however, concerns regarding both radiation dose and cost-effectiveness have prompted investigations into a different imaging algorithm. Studies utilizing ultrasound have provided evidence indicating that it may be a more appropriate first step, with selective use of CT in selected cases, in the diagnostic work-up. Techniques have evolved with low-dose CT, dual-energy CT, and magnetic resonance urography emerging as useful in imaging of renal colic patients. This manuscript reviews the current literature on state-of-the-art imaging for acute flank pain and proposes a new imaging algorithm in the evaluation of patients with acute flank pain and suspected ureteral stones.

  14. Force Modelling in Orthogonal Cutting Considering Flank Wear Effect

    NASA Astrophysics Data System (ADS)

    Rathod, Kanti Bhikhubhai; Lalwani, Devdas I.

    2017-05-01

    In the present work, an attempt has been made to provide a predictive cutting force model during orthogonal cutting by combining two different force models, that is, a force model for a perfectly sharp tool plus considering the effect of edge radius and a force model for a worn tool. The first force model is for a perfectly sharp tool that is based on Oxley's predictive machining theory for orthogonal cutting as the Oxley's model is for perfectly sharp tool, the effect of cutting edge radius (hone radius) is added and improve model is presented. The second force model is based on worn tool (flank wear) that was proposed by Waldorf. Further, the developed combined force model is also used to predict flank wear width using inverse approach. The performance of the developed combined total force model is compared with the previously published results for AISI 1045 and AISI 4142 materials and found reasonably good agreement.

  15. Comparison of orthologous and paralogous DNA flanking the wheat high molecular weight glutenin genes: sequence conservation and divergence, transposon distribution, and matrix-attachment regions.

    PubMed

    Anderson, O D; Larka, L; Christoffers, M J; McCue, K F; Gustafson, J P

    2002-04-01

    Extended flanking DNA sequences were characterized for five members of the wheat high molecular weight (HMW) glutenin gene family to understand more of the structure, control, and evolution of these genes. Analysis revealed more sequence conservation among orthologous regions than between paralogous regions, with differences mainly owing to transposition events involving putative retrotransposons and several miniature inverted transposable elements (MITEs). Both gyspy-like long terminal repeat (LTR) and non-LTR retrotransposon sequences are represented in the flanking DNAs. One of the MITEs is a novel class, but another MITE is related to the maize Stowaway family and is widely represented in Triticeae express sequence tags (ESTs). Flanking DNA of the longest sequence, a 20 425-bp fragment including and surrounding the HMW-glutenin Bx7 gene, showed additional cereal gene-like sequences both immediately 5' and 3' to the HMW-glutenin coding region. The transcriptional activities of sequences related to these flanking putative genes and the retrotransposon-related regions were indicated by matches to wheat and other Triticeae ESTs. Predictive analysis of matrix-attachment regions (MARs) of the HMW glutenin and several alpha-, gamma-, and omega-gliadin flanking DNAs indicate potential MARs immediately flanking each of the genes. Matrix binding activity in the predicted regions was confirmed for two of the HMW-glutenin genes.

  16. 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

  17. 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.

  18. View of field of boulders on flank of Cone Crater

    NASA Image and Video Library

    1971-02-06

    AS14-64-9103 (6 Feb. 1971) --- Astronaut Alan B. Shepard Jr., commander, photographed this overall view of a field of boulders on the flank of Cone Crater during the second extravehicular activity (EVA) on the lunar surface. Astronaut Edgar D. Mitchell, lunar module pilot, joined Shepard in exploring the moon, while astronaut Stuart A. Roosa, command module pilot, remained with the Command and Service Modules (CSM) in lunar orbit.

  19. Geomorphology of the north flank of the Uinta Mountains

    USGS Publications Warehouse

    Bradley, W.H.

    1936-01-01

    beds now form hogbacks ranked along the sides of the fold. In places large faults, approximating the regional strike, cut these steeply inclined beds. Gently warped Tertiary sediments, mostly of Eocene age, fill the large Green River Basin, which lies north of the range, to a depth of several thousand feet and lap up on the flanks of the mountains, from which they were chiefly derived.

  20. 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

  1. In situ localization of cytoskeletal elements in the human trabecular meshwork and cornea.

    PubMed

    Weinreb, R N; Ryder, M I

    1990-09-01

    The authors compared cytoskeletal elements of the in situ human trabecular-meshwork cell with in situ human corneal cells using indirect immunofluorescence staining for tubulin and intermediate filaments (vimentin, cytokeratin, and desmin) and NBD-phallacidin staining for f-actin using both fixed frozen and unfixed frozen sections from postmortem eyes. Both f-actin and tubulin were found throughout the cell body of trabecular-meshwork cells, keratocytes, corneal endothelium, and corneal epithelium. The f-actin staining pattern was concentrated at the cell periphery of these four cell types. Vimentin stain was intensely localized in focal areas of the trabecular-meshwork cell, keratocytes, and throughout the corneal endothelium. A general anticytokeratin antibody was intensely localized in corneal epithelium and endothelium. However, PKK-1 anticytokeratin antibody was seen only in superficial layers of corneal epithelium and not in corneal endothelium. The 4.62 anticytokeratin antibody was not observed in either corneal epithelium or endothelium. None of these three cytokeratin antibodies were seen in trabecular-meshwork cells or keratocytes. Desmin stain was not noted in any of these cell types. In general, cytoskeletal staining of unfixed frozen sections showed a similar staining pattern for f-actin and tubulin but a more uniform and intense staining pattern for vimentin and cytokeratin compared with fixed frozen material. The authors conclude that these cytoskeletal stains can differentiate human trabecular-meshwork cells from cells of the cornea in situ.

  2. Comparative analysis of dioxin response elements in human, mouse and rat genomic sequences

    PubMed Central

    Sun, Y. V.; Boverhof, D. R.; Burgoon, L. D.; Fielden, M. R.; Zacharewski, T. R.

    2004-01-01

    Comparative approaches were used to identify human, mouse and rat dioxin response elements (DREs) in genomic sequences unambiguously assigned to a nucleotide RefSeq accession number. A total of 13 bona fide DREs, all including the substitution intolerant core sequence (GCGTG) and adjacent variable sequences, were used to establish a position weight matrix and a matrix similarity (MS) score threshold to rank identified DREs. DREs with MS scores above the threshold were disproportionately distributed in close proximity to the transcription start site in all three species. Gene expression assays in hepatic mouse tissue confirmed the responsiveness of 192 genes possessing a putative DRE. Previously identified functional DREs in well-characterized AhR-regulated genes including Cyp1a1 and Cyp1b1 were corroborated. Putative DREs were identified in 48 out of 2437 human–mouse–rat orthologous genes between −1500 and the transcriptional start site, of which 19 of these genes possessed positionally conserved DREs as determined by multiple sequence alignment. Seven of these nineteen genes exhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated regulation, although there were significant discrepancies between in vivo and in vitro results. Interestingly, of the mouse–rat orthologous genes with a DRE between −1500 and +1500, only 37% had an equivalent human ortholog. These results suggest that AhR-mediated gene expression may not be well conserved across species, which could have significant implications in human risk assessment. PMID:15328365

  3. Farnesoid X Receptor Inhibits the Transcriptional Activity of Carbohydrate Response Element Binding Protein in Human Hepatocytes

    PubMed Central

    Caron, Sandrine; Huaman Samanez, Carolina; Dehondt, Hélène; Ploton, Maheul; Briand, Olivier; Lien, Fleur; Dorchies, Emilie; Dumont, Julie; Postic, Catherine; Cariou, Bertrand; Lefebvre, Philippe

    2013-01-01

    The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. The farnesoid X receptor (FXR) is a nuclear bile acid receptor controlling bile acid, lipid, and glucose homeostasis. FXR negatively regulates hepatic glycolysis and lipogenesis in mouse liver. The aim of this study was to determine whether FXR regulates the transcriptional activity of ChREBP in human hepatocytes and to unravel the underlying molecular mechanisms. Agonist-activated FXR inhibits glucose-induced transcription of several glycolytic genes, including the liver-type pyruvate kinase gene (L-PK), in the immortalized human hepatocyte (IHH) and HepaRG cell lines. This inhibition requires the L4L3 region of the L-PK promoter, known to bind the transcription factors ChREBP and hepatocyte nuclear factor 4α (HNF4α). FXR interacts directly with ChREBP and HNF4α proteins. Analysis of the protein complex bound to the L4L3 region reveals the presence of ChREBP, HNF4α, FXR, and the transcriptional coactivators p300 and CBP at high glucose concentrations. FXR activation does not affect either FXR or HNF4α binding to the L4L3 region but does result in the concomitant release of ChREBP, p300, and CBP and in the recruitment of the transcriptional corepressor SMRT. Thus, FXR transrepresses the expression of genes involved in glycolysis in human hepatocytes. PMID:23530060

  4. 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

  5. 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

    2016-04-07

    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, term edattH4X, 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.

  6. Differential regulation of baboon SP-A1 and SP-A2 genes: structural and functional analysis of 5'-flanking DNA.

    PubMed

    Li, J; Gao, E; Seidner, S R; Mendelson, C R

    1998-12-01

    Surfactant protein (SP) A gene transcription is developmentally regulated and stimulated by hormones and factors that increase intracellular cAMP. The baboon (b) genome contains two highly similar SP-A genes, bSP-A1 and bSP-A2. With the use of a ribonuclease protection assay with gene-specific probes, the two bSP-A genes were found to be differentially regulated during baboon fetal lung development in that expression of the bSP-A2 gene appeared to be induced to a high level at a later time in gestation than that of the bSP-A1 gene. Both the bSP-A1 and bSP-A2 genes were found to be highly responsive to the inductive effects of cAMP in baboon fetal lung explants in culture. By DNase I footprinting and electrophoretic mobility shift assays with bacterially expressed thyroid transcription factor-1 (TTF-1) and type II cell nuclear extracts, three TTF-1 binding elements were identified within the 255-bp region flanking the 5'-end of each bSP-A gene; however, these differed in position and spacing for the two bSP-A genes. To functionally define the genomic regions that are required for cAMP regulation of bSP-A gene expression in type II cells, fusion genes composed of various amounts of 5'-flanking DNA from the bSP-A1 and bSP-A2 genes linked to the human growth hormone structural gene as a reporter were transfected into type II cells in primary culture. We found that 255 bp of 5'-flanking DNA, which contain three TTF-1 binding elements, from bSP-A1 and bSP-A2 genes were sufficient to mediate high basal and cAMP-inducible expression in type II cells. We also observed that there were no obvious differences in the magnitude of the responses of these fusion genes to cAMP treatment.

  7. 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

  8. Cohesive finite element modeling of age-related toughness loss in human cortical bone.

    PubMed

    Ural, Ani; Vashishth, Deepak

    2006-01-01

    Although the age-related loss of bone quality has been implicated in bone fragility, a mechanistic understanding of the relationship is necessary for developing diagnostic and treatment modalities in the elderly population at risk of fracture. In this study, a finite element based cohesive zone model is developed and applied to human cortical bone in order to capture the experimentally shown rising crack growth behavior and age-related loss of bone toughness. The cohesive model developed here is based on a traction-crack opening displacement relationship representing the fracture processes in the vicinity of a propagating crack. The traction-displacement curve, defining the cohesive model, is composed of ascending and descending branches that incorporate material softening and nonlinearity. The results obtained indicate that, in contrast to initiation toughness, the finite element simulations of crack growth in compact tension (CT) specimens successfully capture the rising R-curve (propagation toughness) behavior and the age-related loss of bone toughness. In close correspondence with the experimentally observed decrease of 14-15% per decade, the finite element simulation results show a decrease of 13% in the R-curve slope per decade. The success of the simulations is a result of the ability of cohesive models to capture and predict the parameters related to bone fracture by representing the physical processes occurring in the vicinity of a propagating crack. These results illustrate that fracture mechanisms in the process zone control bone toughness and any modification to these would cause age-related toughness loss.

  9. Finite element analysis of mechanical behavior of human dysplastic hip joints: a systematic review.

    PubMed

    Vafaeian, B; Zonoobi, D; Mabee, M; Hareendranathan, A R; El-Rich, M; Adeeb, S; Jaremko, J L

    2017-04-01

    Developmental dysplasia of the hip (DDH) is a common condition predisposing to osteoarthritis (OA). Especially since DDH is best identified and treated in infancy before bones ossify, there is surprisingly a near-complete absence of literature examining mechanical behavior of infant dysplastic hips. We sought to identify current practice in finite element modeling (FEM) of DDH, to inform future modeling of infant dysplastic hips. We performed multi-database systematic review using PRISMA criteria. Abstracts (n = 126) fulfilling inclusion criteria were screened for methodological quality, and results were analyzed and summarized for eligible articles (n = 12). The majority of the studies modeled human adult dysplastic hips. Two studies focused on etiology of DDH through simulating mechanobiological growth of prenatal hips; we found no FEM-based studies in infants or children. Finite element models used either patient-specific geometry or idealized average geometry. Diversities in choice of material properties, boundary conditions, and loading scenarios were found in the finite-element models. FEM of adult dysplastic hips demonstrated generally smaller cartilage contact area in dysplastic hips than in normal joints. Contact pressure (CP) may be higher or lower in dysplastic hips depending on joint geometry and mechanical contribution of labrum (Lb). FEM of mechanobiological growth of prenatal hip joints revealed evidence for effects of the joint mechanical environment on formation of coxa valga, asymmetrically shallow acetabulum and malformed femoral head associated with DDH. Future modeling informed by the results of this review may yield valuable insights into optimal treatment of DDH, and into how and why OA develops early in DDH.

  10. 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.

  11. Prenatal exposure to mixtures of xenoestrogens and repetitive element DNA methylation changes in human placenta

    PubMed Central

    Vilahur, Nadia; Bustamante, Mariona; Byun, Hyang-Min; Fernandez, Mariana F.; Marina, Loreto Santa; Basterrechea, Mikel; Ballester, Ferran; Murcia, Mario; Tardón, Adonina; Fernández-Somoano, Ana; Estivill, Xavier; Olea, Nicolas; Sunyer, Jordi; Baccarelli, Andrea A.

    2014-01-01

    Background Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods The biomarker Total Effective Xenoestrogen Burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retrovirus (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results A significant sex interaction was observed for AluYb8 (p value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p value<0.001), while no significant effects were found in girls (p value= 0.134). Conclusions Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development. PMID:24980756

  12. Three-dimensional finite element models of the human pubic symphysis with viscohyperelastic soft tissues.

    PubMed

    Li, Zuoping; Alonso, Jorge E; Kim, Jong-Eun; Davidson, James S; Etheridge, Brandon S; Eberhardt, Alan W

    2006-09-01

    Three-dimensional finite element (FE) models of human pubic symphyses were constructed from computed tomography image data of one male and one female cadaver pelvis. The pubic bones, interpubic fibrocartilaginous disc and four pubic ligaments were segmented semi-automatically and meshed with hexahedral elements using automatic mesh generation schemes. A two-term viscoelastic Prony series, determined by curve fitting results of compressive creep experiments, was used to model the rate-dependent effects of the interpubic disc and the pubic ligaments. Three-parameter Mooney-Rivlin material coefficients were calculated for the discs using a heuristic FE approach based on average experimental joint compression data. Similarly, a transversely isotropic hyperelastic material model was applied to the ligaments to capture average tensile responses. Linear elastic isotropic properties were assigned to bone. The applicability of the resulting models was tested in bending simulations in four directions and in tensile tests of varying load rates. The model-predicted results correlated reasonably with the joint bending stiffnesses and rate-dependent tensile responses measured in experiments, supporting the validity of the estimated material coefficients and overall modeling approach. This study represents an important and necessary step in the eventual development of biofidelic pelvis models to investigate symphysis response under high-energy impact conditions, such as motor vehicle collisions.

  13. Improving the finite element forward model of the human head by warping using elastic deformation.

    PubMed

    Tizzard, A; Bayford, R H

    2007-07-01

    As the use of realistic geometry in the forward model of electrical impedance tomography (EIT) of brain function appears to improve image reconstruction, the generation of patient-specific finite element meshes has been the subject of much recent work. This paper presents a more rapid method of generating more geometrically accurate finite element meshes of the human head by warping existing meshes such that the surface boundary beneath the electrodes closely matches that of the subject with minimal degradation to the quality of the mesh. Pre-existing meshes of spheres and adult head models incorporating key internal anatomical features are warped, using elastic deformation, to match a phantom latex tank incorporating a real skull. The algorithm is described and tests are carried out to optimize the key parameters to ensure minimal degradation of mesh quality and distortion of internal features. Results show that the algorithm operating with the optimum parameters produces meshes of sound quality and could represent an important step in the timely and productive creation of forward models in clinical applications.

  14. Short interspersed transposable elements (SINEs) are excluded from imprinted regions in the human genome.

    PubMed

    Greally, John M

    2002-01-08

    To test whether regions undergoing genomic imprinting have unique genomic characteristics, imprinted and nonimprinted human loci were compared for nucleotide and retroelement composition. Maternally and paternally expressed subgroups of imprinted genes were found to differ in terms of guanine and cytosine, CpG, and retroelement content, indicating a segregation into distinct genomic compartments. Imprinted regions have been normally permissive to L1 long interspersed transposable element retroposition during mammalian evolution but universally and significantly lack short interspersed transposable elements (SINEs). The primate-specific Alu SINEs, as well as the more ancient mammalian-wide interspersed repeat SINEs, are found at significantly low densities in imprinted regions. The latter paleogenomic signature indicates that the sequence characteristics of currently imprinted regions existed before the mammalian radiation. Transitions from imprinted to nonimprinted genomic regions in cis are characterized by a sharp inflection in SINE content, demonstrating that this genomic characteristic can help predict the presence and extent of regions undergoing imprinting. During primate evolution, SINE accumulation in imprinted regions occurred at a decreased rate compared with control loci. The constraint on SINE accumulation in imprinted regions may be mediated by an active selection process. This selection could be because of SINEs attracting and spreading methylation, as has been found at other loci. Methylation-induced silencing could lead to deleterious consequences at imprinted loci, where inactivation of one allele is already established, and expression is often essential for embryonic growth and survival.

  15. Short interspersed transposable elements (SINEs) are excluded from imprinted regions in the human genome

    PubMed Central

    Greally, John M.

    2002-01-01

    To test whether regions undergoing genomic imprinting have unique genomic characteristics, imprinted and nonimprinted human loci were compared for nucleotide and retroelement composition. Maternally and paternally expressed subgroups of imprinted genes were found to differ in terms of guanine and cytosine, CpG, and retroelement content, indicating a segregation into distinct genomic compartments. Imprinted regions have been normally permissive to L1 long interspersed transposable element retroposition during mammalian evolution but universally and significantly lack short interspersed transposable elements (SINEs). The primate-specific Alu SINEs, as well as the more ancient mammalian-wide interspersed repeat SINEs, are found at significantly low densities in imprinted regions. The latter paleogenomic signature indicates that the sequence characteristics of currently imprinted regions existed before the mammalian radiation. Transitions from imprinted to nonimprinted genomic regions in cis are characterized by a sharp inflection in SINE content, demonstrating that this genomic characteristic can help predict the presence and extent of regions undergoing imprinting. During primate evolution, SINE accumulation in imprinted regions occurred at a decreased rate compared with control loci. The constraint on SINE accumulation in imprinted regions may be mediated by an active selection process. This selection could be because of SINEs attracting and spreading methylation, as has been found at other loci. Methylation-induced silencing could lead to deleterious consequences at imprinted loci, where inactivation of one allele is already established, and expression is often essential for embryonic growth and survival. PMID:11756672

  16. 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.

  17. 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

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

    NASA Astrophysics Data System (ADS)

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

    2013-05-01

    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. The role of viscous magma mush spreading in volcanic flank motion at Kilauea Volcano, Hawai'i

    NASA Astrophysics Data System (ADS)

    Plattner, Christina; Amelung, Falk; Baker, Scott; Govers, Rob; Poland, Mike

    2014-05-01

    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 x 10^17 - 2.5 x 10^19 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 x 10^19 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.

  20. Rare earth elements in human and animal health: State of art and research priorities.

    PubMed

    Pagano, Giovanni; Aliberti, Francesco; Guida, Marco; Oral, Rahime; Siciliano, Antonietta; Trifuoggi, Marco; Tommasi, Franca

    2015-10-01

    A number of applications have been developed using rare earth elements (REE), implying several human exposures and raising unsolved questions as to REE-associated health effects. A MedLine survey was retrieved from early reports (1980s) up to June 2015, focused on human and animal exposures to REE. Literature from animal models was selected focusing on REE-associated health effects. Some REE occupational exposures, in jobs such as glass polishers, photoengravers and movie projectionists showed a few case reports on health effects affecting the respiratory system. No case-control or cohort studies of occupational REE exposures were retrieved. Environmental exposures have been biomonitored in populations residing in REE mining areas, showing REE accumulation. The case for a iatrogenic REE exposure was raised by the use of gadolinium-based contrast agents for nuclear magnetic resonance. Animal toxicity studies have shown REE toxicity, affecting a number of endpoints in liver, lungs and blood. On the other hand, the use of REE as feed additives in livestock is referred as a safe and promising device in zootechnical activities, possibly suggesting a hormetic effect both known for REE and for other xenobiotics. Thus, investigations on long-term exposures and observations are warranted. The state of art provides a limited definition of the health effects in occupationally or environmentally REE-exposed human populations. Research priorities should be addressed to case-control or cohort studies of REE-exposed humans and to life-long animal experiments. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Effects of model definitions and parameter values in finite element modeling of human middle ear mechanics.

    PubMed

    De Greef, Daniel; Pires, Felipe; Dirckx, Joris J J

    2017-02-01

    Despite continuing advances in finite element software, the realistic simulation of middle ear response under acoustic stimulation continues to be challenging. One reason for this is the wide range of possible choices that can be made during the definition of a model. Therefore, an explorative study of the relative influences of some of these choices is potentially very helpful. Three finite element models of the human middle ear were constructed, based on high-resolution micro-computed tomography scans from three different human temporal bones. Interesting variations in modeling definitions and parameter values were selected and their influences on middle ear transmission were evaluated. The models were compared against different experimental validation criteria, both from the literature and from our own measurements. Simulation conditions were restricted to the frequency range 0.1-10 kHz. Modeling the three geometries with the same modeling definitions and parameters produces stapes footplate response curves that exhibit similar shapes, but quantitative differences of 4 dB in the lower frequencies and up to 6 dB around the resonance peaks. The model properties with the largest influences on our model outcomes are the tympanic membrane (TM) damping and stiffness and the cochlear load. Model changes with a small to negligible influence include the isotropy or orthotropy of the TM, the geometry of the connection between the TM and the malleus, the microstructure of the incudostapedial joint, and the length of the tensor tympani tendon. The presented results provide insights into the importance of different features in middle ear finite element modeling. The application of three different individual middle ear geometries in a single study reduces the possibility that the conclusions are strongly affected by geometrical abnormalities. Some modeling variations that were hypothesized to be influential turned out to be of minor importance. Furthermore, it could be

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

    PubMed Central

    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

  3. Finite element study of human pelvis model in side impact for Chinese adult occupants.

    PubMed

    Ma, Zhengwei; Lan, Fengchong; Chen, Jiqing; Liu, Weiguo

    2015-01-01

    The occupant's pelvis is very vulnerable to side collision in road accidents. Finite element (FE) studies on pelvic injury help to design occupant protection devices to improve vehicle safety. This study was aimed to develop a highly biofidelic pelvis model of Chinese adults and assess its sensitivity to variations in pelvis cortical bone thickness, bone material properties, and loading conditions. In this study, 4 different FE models of the pelvis were developed from the computed tomography (CT) data of a volunteer representing the 50th percentile Chinese male. Two of them were meshed using entirely hexahedral elements with variable and constant cortical thickness distribution (the V-Hex and C-Hex models), and the others were modeled with hexahedral elements for cancellous bone and variable or constant thickness shell elements for cortical bone (the V-HS and C-HS models). In model developments, the semi-automatic multiblock meshing approach was employed to maintain the pelvis geometric curvature and generate a high-quality hexahedral mesh. Then, several simulations with postmortem human subjects (PMHS) tests were performed to obtain the most accurate model in predicting pelvic injury. Based on the most accurate model, sensitivity studies were conducted to analyze the effects of the cortex thickness, Young's modulus of the cortical and cancellous bone, impactor velocity, and impactor with or without padding on the biomechanical responses and injuries of pelvis. The results indicate that the models with variable cortical bone thickness can give more accurate predictions than those with constant cortical thickness. Both the V-Hex and V-HS models are favorable for simulating pelvic response and injury, but the simulation results of the V-Hex model agree with the tests better. The sensitivity study shows that pelvic response is more sensitive to alterations in the Young's modulus of cortical bone than cancellous bone. Compared to failure displacement, peak force is

  4. Human liver finite element model validation using compressive and tensile experimental data - biomed 2013.

    PubMed

    Davis, Matthew L; Moreno, Daniel P; Vavalle, Nicholas A; Gayzik, F Scott

    2013-01-01

    Motor vehicle crashes commonly result in blunt abdominal trauma. Approximately 19,000 such injuries occur each year in the United States. While finite element models of the human body are becoming an important tool for injury assessment, their reliability depends on the accuracy of the material models used. Recently, Samur et al. proposed a hyperelastic and viscoelastic material model of the liver. The aim of this study was to compare the results of a computational model using this material law to uniaxial tension and compression data from biomechanical tests on liver samples by Kemper et al. In this study, the liver samples were modeled using the finite element method. Both the tension and compression test specimen geometries were created from descriptions in the literature. Each sample was meshed using four approaches: fine hexahedral, coarse hexahedral, fine tetrahedral, and coarse tetrahedral. The average element edge lengths of the coarse and fine meshes were 5 mm and 2.5 mm respectively. The samples were loaded in both tension and compression at four rates: 0.01 strain/sec, 0.1 strain/sec, 1 strain/sec, and 10 strain/sec. For each mesh type (n=4), strain rate (n=4), and loading condition (n=2), 32 simulations in total, the results were plotted against the published experimental data. The results were quantitatively evaluated for magnitude and phase agreement with the experimental data using an objective comparison software package, CORA. The model predicted the tensile response of the liver sample more accurately than the compressive response with an average CORA size error factor of 0.66 versus 0.19 for the compressive model (1 is a perfect match). The fine tetrahedral, fine hexahedral, and coarse hexahedral meshes predicted a similar response. The worst performing mesh was the coarse tetrahedral mesh, which had an average size error factor of 8.6% higher than the fine tetrahedral simulations. The peak stress in both tension and compression varied as a

  5. Development of a computationally efficient full human body finite element model.

    PubMed

    Schwartz, Doron; Guleyupoglu, Berkan; Koya, Bharath; Stitzel, Joel D; Gayzik, F Scott

    2015-01-01

    A simplified and computationally efficient human body finite element model is presented. The model complements the Global Human Body Models Consortium (GHBMC) detailed 50th percentile occupant (M50-O) by providing kinematic and kinetic data with a significantly reduced run time using the same body habitus. The simplified occupant model (M50-OS) was developed using the same source geometry as the M50-O. Though some meshed components were preserved, the total element count was reduced by remeshing, homogenizing, or in some cases omitting structures that are explicitly contained in the M50-O. Bones are included as rigid bodies, with the exception of the ribs, which are deformable but were remeshed to a coarser element density than the M50-O. Material models for all deformable components were drawn from the biomechanics literature. Kinematic joints were implemented at major articulations (shoulder, elbow, wrist, hip, knee, and ankle) with moment vs. angle relationships from the literature included for the knee and ankle. The brain of the detailed model was inserted within the skull of the simplified model, and kinematics and strain patterns are compared. The M50-OS model has 11 contacts and 354,000 elements; in contrast, the M50-O model has 447 contacts and 2.2 million elements. The model can be repositioned without requiring simulation. Thirteen validation and robustness simulations were completed. This included denuded rib compression at 7 discrete sites, 5 rigid body impacts, and one sled simulation. Denuded tests showed a good match to the experimental data of force vs. deflection slopes. The frontal rigid chest impact simulation produced a peak force and deflection within the corridor of 4.63 kN and 31.2%, respectively. Similar results vs. experimental data (peak forces of 5.19 and 8.71 kN) were found for an abdominal bar impact and lateral sled test, respectively. A lateral plate impact at 12 m/s exhibited a peak of roughly 20 kN (due to stiff foam used around

  6. Modeling "secular" flank motion at Kilauea Volcano (Hawai'i) during 2000-2003

    NASA Astrophysics Data System (ADS)

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

    2011-12-01

    Kilauea's south flank is moving seaward due to flank instabilities. The rate is influenced by magmatic events (dike intrusions) and tectonic events (earthquakes and slow-slip events at the decollement), but the general flank motion signal remains significant at any time, with rates of 6-10 cm/yr during the past decade. The surface displacements were explained by fault slip along the decollement beneath Kilauea combined with deep-rift opening in elastic halfspace dislocation models. While these models explain the kinematics well, the dynamics of the rift opening are not resolved, and the question on contribution from magmatic driving forces versus an entirely gravitationally-driven system remains. InSAR time-series analysis (Small Baseline Algorithm; SBAS) showed linear surface subsidence at Kilauea summit (maximum rate 5.5 cm/yr south of the caldera) during 2000-2003, a time-period during which the influence of distinct deformation events is small in comparison to previous and later time-periods. Here, we investigate if summit subsidence can be explained as a consequence of secular flank motion at Kilauea by ductile creep of a deep magma mush, using a numerical model with time-dependent material deformation properties to constrain velocities rather than displacements. We developed a 2D finite element model that investigates the deformation response of Kilauea to gravitational driving forces only. The model geometry includes a decollement fault beneath the volcano that can have locked and creeping fault segments. We introduce time-dependent material behavior using a viscoelastic model media. The host rock remains stable over geodetic timescales given its high viscosity value, while the deep-seated magma mush beneath Kilauea caldera is assigned a lower viscosity and spreads at significant rates. The deformation signal of the magma mush is transmitted to the surface, causing local subsidence at Kilauea summit, showing that summit subsidence can be explained by flank

  7. 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

  8. Human skeletal muscle behavior in vivo: Finite element implementation, experiment, and passive mechanical characterization.

    PubMed

    Clemen, Christof B; Benderoth, Günther E K; Schmidt, Andreas; Hübner, Frank; Vogl, Thomas J; Silber, Gerhard

    2017-01-01

    In this study, useful methods for active human skeletal muscle material parameter determination are provided. First, a straightforward approach to the implementation of a transversely isotropic hyperelastic continuum mechanical material model in an invariant formulation is presented. This procedure is found to be feasible even if the strain energy is formulated in terms of invariants other than those predetermined by the software's requirements. Next, an appropriate experimental setup for the observation of activation-dependent material behavior, corresponding data acquisition, and evaluation is given. Geometry reconstruction based on magnetic resonance imaging of different deformation states is used to generate realistic, subject-specific finite element models of the upper arm. Using the deterministic SIMPLEX optimization strategy, a convenient quasi-static passive-elastic material characterization is pursued; the results of this approach used to characterize the behavior of human biceps in vivo indicate the feasibility of the illustrated methods to identify active material parameters comprising multiple loading modes. A comparison of a contact simulation incorporating the optimized parameters to a reconstructed deformed geometry of an indented upper arm shows the validity of the obtained results regarding deformation scenarios perpendicular to the effective direction of the nonactivated biceps. However, for a valid, activatable, general-purpose material characterization, the material model needs some modifications as well as a multicriteria optimization of the force-displacement data for different loading modes.

  9. 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.

  10. 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.

  11. 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

  12. A review of Human Biomonitoring studies of trace elements in Pakistan.

    PubMed

    Waseem, Amir; Arshad, Jahanzaib

    2016-11-01

    Human biomonitoring (HBM) measures the concentration levels of substances or their metabolites in human body fluids and tissues. HBM of dose and biochemical effect monitoring is an effective way of measuring human exposure to chemical substances. Many countries have conducted HBM studies to develop a data base for many chemicals including trace metals of health concern for their risk assessment and risk management. However, in Pakistan, HBM program on large scale for general population does not exist at present or in the past has been reported. Various individual HBM studies have been reported on the assessment of trace elements (usually heavy metals) from Pakistan; most of them are epidemiological cross sectional surveys. In this current review we tried to develop a data base of HBM studies of trace elements namely arsenic, cadmium, copper, chromium, iron, lead, manganese, nickel, and zinc in biological fluids (blood, urine) and tissues (hair, nails) in general population of Pakistan. Studies from all available sources have been explored, discussed and presented in the form of tables and figures. The results of these studies were critically compared with large scale HBM programs of other countries, (US & European communities etc). It was observed from the present study that the most of the toxic metals in biological fluids/tissues in general population of Pakistan, have higher background values comparatively. For example the mean values of toxic metals like As, Cd, Cr, Ni, and Pb in blood of general population were found as 2.08 μg/L, 4.24 μg/L, 60.5 μg/L, 1.95 μg/L, 198 μg/L respectively. Similarly, the urine mean values of 67.6 μg/L, 3.2 μg/L, 16.4 μg/L, 6.2 μg/L and 86.5 μg/L were observed for As, Cd, Cr, Ni, and Pb respectively.

  13. 29 Mammalian Genomes Reveal Novel Exaptations of Mobile Elements for Likely Regulatory Functions in the Human Genome

    PubMed Central

    Lowe, Craig B.; Haussler, David

    2012-01-01

    Recent research supports the view that changes in gene regulation, as opposed to changes in the genes themselves, play a significant role in morphological evolution. Gene regulation is largely dependent on transcription factor binding sites. Researchers are now able to use the available 29 mammalian genomes to measure selective constraint at the level of binding sites. This detailed map of constraint suggests that mammalian genomes co-opt fragments of mobile elements to act as gene regulatory sequence on a large scale. In the human genome we detect over 280,000 putative regulatory elements, totaling approximately 7 Mb of sequence, that originated as mobile element insertions. These putative regulatory regions are conserved non-exonic elements (CNEEs), which show considerable cross-species constraint and signatures of continued negative selection in humans, yet do not appear in a known mature transcript. These putative regulatory elements were co-opted from SINE, LINE, LTR and DNA transposon insertions. We demonstrate that at least 11%, and an estimated 20%, of gene regulatory sequence in the human genome showing cross-species conservation was co-opted from mobile elements. The location in the genome of CNEEs co-opted from mobile elements closely resembles that of CNEEs in general, except in the centers of the largest gene deserts where recognizable co-option events are relatively rare. We find that regions of certain mobile element insertions are more likely to be held under purifying selection than others. In particular, we show 6 examples where paralogous instances of an often co-opted mobile element region define a sequence motif that closely matches a transcription factor’s binding profile. PMID:22952639

  14. Pulmonary haptoglobin and CD163 are functional immunoregulatory elements in the human lung.

    PubMed

    Abdullah, M; Kähler, D; Vock, C; Reiling, N; Kugler, C; Drömann, D; Rupp, J; Hauber, H P; Fehrenbach, H; Zabel, P; Vollmer, E; Dalhoff, K; Goldmann, T

    2012-01-01

    The acute-phase protein haptoglobin (Hp) and its receptor CD163 serve as immunomodulators and possess anti-inflammatory besides antioxidant functions. To further understand the role of the recently described pulmonary Hp (pHp) and its receptor CD163 in case of inflammation and infection, pHp and CD163 were investigated on mRNA and protein level to gain insight into the cellular events taking place upon stimulation with the inflammatory mediators LPS, Pam3, cytokine IL-6 and dexamethasone, and upon infection with respiratory pathogens (Haemophilus influenzae, Streptococcuspneumoniae and Chlamydia pneumoniae) by use of a human ex vivo tissue culture model and cell cultures of A549 and alveolar epithelial cells type II. In addition, pHp and CD163 expression in COPD and sarcoidosis was assessed. We conducted experiments using 942 ex vivo cultured lung samples applying immunohistochemistry, immunocytochemistry, in situ hybridization, immunofluorescence, real-time PCR, RT-PCR, slot and Western immunoblot analyses with tissue lysates and culture supernatants as well as ELISA and cytometric bead array analyses. This study describes for the first time the expression, regulation and secretion of pHp and its receptor CD163 in the human lung. The release of soluble mediators from A549 cell line and human monocyte-derived macrophages was observed indicating that Hp differentially activates the release of soluble mediators and major chemoattractants. The findings indicate a native function of pHp and CD163 as functional pulmonary defense elements due to local expression, regulation and secretion during lung infection and as part of the inflammatory immune response of the respiratory system. Copyright © 2011 S. Karger AG, Basel.

  15. A c-Myc regulatory subnetwork from human transposable element sequences†‡

    PubMed Central

    Wang, Jianrong; Bowen, Nathan J.; Mariño-Ramírez, Leonardo

    2010-01-01

    Transposable elements (TEs) can donate regulatory sequences that help to control the expression of human genes. The oncogene c-Myc is a promiscuous transcription factor that is thought to regulate the expression of hundreds of genes. We evaluated the contribution of TEs to the c-Myc regulatory network by searching for c-Myc binding sites derived from TEs and by analyzing the expression and function of target genes with nearby TE-derived c-Myc binding sites. There are thousands of TE sequences in the human genome that are bound by c-Myc. A conservative analysis indicated that 816–4564 of these TEs contain canonical c-Myc binding site motifs. c-Myc binding sites are over-represented among sequences derived from the ancient TE families L2 and MIR, consistent with their preservation by purifying selection. Genes associated with TE-derived c-Myc binding sites are co-expressed with each other and with c-Myc. A number of these putative TE-derived c-Myc target genes are differentially expressed between Burkitt’s lymphoma cells versus normal B cells and encode proteins with cancer-related functions. Despite several lines of evidence pointing to their regulation by c-Myc and relevance to cancer, the set of genes identified as TE-derived c-Myc targets does not significantly overlap with two previously characterized c-Myc target gene sets. These data point to a substantial contribution of TEs to the regulation of human genes by c-Myc. Genes that are regulated by TE-derived c-Myc binding sites appear to form a distinct c-Myc regulatory subnetwork. PMID:19763338

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

    PubMed

    Iijima, Kenta; Okudaira, Noriyuki; Tamura, Masato; Doi, Akihiro; Saito, Yoshikazu; Shimura, Mari; Goto, Motohito; Matsunaga, Akihiro; Kawamura, Yuki I; Otsubo, Takeshi; Dohi, Taeko; Hoshino, Shigeki; Kano, Shigeyuki; Hagiwara, Shotaro; Tanuma, Junko; Gatanaga, Hiroyuki; Baba, Masanori; Iguchi, Taku; Yanagita, Motoko; Oka, Shinichi; Okamura, Tadashi; Ishizaka, Yukihito

    2013-08-05

    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). 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. 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.

  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. 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.

  19. 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.

  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

    2010-05-07

    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.

  1. 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

  2. The effect of precrash velocity reduction on occupant response using a human body finite element model.

    PubMed

    Guleyupoglu, B; Schap, J; Kusano, K D; Gayzik, F S

    2017-07-04

    The objective of this study is to use a validated finite element model of the human body and a certified model of an anthropomorphic test dummy (ATD) to evaluate the effect of simulated precrash braking on driver kinematics, restraint loads, body loads, and computed injury criteria in 4 commonly injured body regions. The Global Human Body Models Consortium (GHBMC) 50th percentile male occupant (M50-O) and the Humanetics Hybrid III 50th percentile models were gravity settled in the driver position of a generic interior equipped with an advanced 3-point belt and driver airbag. Fifteen simulations per model (30 total) were conducted, including 4 scenarios at 3 severity levels: median, severe, and the U.S. New Car Assessment Program (U.S.-NCAP) and 3 extra per model with high-intensity braking. The 4 scenarios were no precollision system (no PCS), forward collision warning (FCW), FCW with prebraking assist (FCW+PBA), and FCW and PBA with autonomous precrash braking (FCW + PBA + PB). The baseline ΔV was 17, 34, and 56.4 kph for median, severe, and U.S.-NCAP scenarios, respectively, and were based on crash reconstructions from NASS/CDS. Pulses were then developed based on the assumed precrash systems equipped. Restraint properties and the generic pulse used were based on literature. In median crash severity cases, little to no risk (<10% risk for Abbreviated injury Scale [AIS] 3+) was found for all injury measures for both models. In the severe set of cases, little to no risk for AIS 3+ injury was also found for all injury measures. In NCAP cases, highest risk was typically found with No PCS and lowest with FCW + PBA + PB. In the higher intensity braking cases (1.0-1.4 g), head injury criterion (HIC), brain injury criterion (BrIC), and chest deflection injury measures increased with increased braking intensity. All other measures for these cases tended to decrease. The ATD also predicted and trended similar to the human body models predictions for both the median

  3. Ice burn: protecting the flank during renal cryotherapy.

    PubMed

    Young, Jennifer L; Sountoulides, Petros; Kolla, Surendra B; Pick, Donald L; Kaufmann, Oskar B; Huynh, Victor B; Kaplan, Adam G; Ortiz, Cervando; Louie, Michael K; Andrade, Lorena A; Osann, Kathryn E; McDougall, Elspeth M; Clayman, Ralph V

    2010-08-01

    Cryoablation is a viable minimally invasive strategy for the treatment of small renal masses. One of the most common postoperative complaints is pain or paresthesia at the cryoprobe insertion site. The use of a 14-gauge angiocatheter to insulate the flank during renal cryotherapy was investigated. Six Yorkshire swine underwent laparoscopy-guided percutaneous cryoablation of the upper and lower poles of both kidneys with a 1.47 mm (17 gauge) cryoneedle. Treatment consisted of a double 10-minute freeze separated by a 5-minute active thaw. Trials were randomized to placement of the cryoneedle directly through the flank or through a 14-gauge angiocatheter as an insulating sheath. Temperatures were recorded adjacent to the cryoneedle at two depths in the flank with a Multi-Point Thermal Sensor. Twelve trials were completed each with a bare and sheathed cryoneedle. The coldest temperature observed was -26 degrees C for the bare cryoneedle and -21 degrees C for the sheathed cryoneedle. At the outer sensor, there was a 4.1 degrees C increase in mean temperature for freeze 1, and 6.2 degrees C increase in mean temperature for freeze 2 with sheath use. At the inner sensor, there was a 3.0 degrees C increase in mean temperature for freeze 1, and 9.4 degrees C increase in mean temperature for freeze 2 with sheath use. There was a trend toward statistical significance of sheath insulation at the outer (p = 0.07) and inner (p = 0.08) temperature sensors. A 14-gauge angiocatheter may provide some insulation and thereby might help protect against "ice burn" during renal cryotherapy.

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

    SciTech Connect

    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.

  5. Flank Terraces of Martian Shield Volcanoes: Architecture and Formation

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

    Flank terraces are topographically subtle bulge-like structures on the sides of numerous Martian shield volcanoes. They have a gentle convex profile in cross section. These structures have an arcuate outline in plan, and are arranged in a distinctive, imbricate "fish scale" pattern about each terraced edifice. Terraces are generally regarded as compressive features, formed by magma chamber inflation or lithospheric flexure. Some workers argue they are extensional in nature however, due to flank relaxation or gravitational slumping. Previously recognised on Olympus Mons and the Tharsis Montes (Ascraeus, Pavonis, and Arsia), we show that this pattern also exists on Elysium Mons, Hecates Tholus, Albor Tholus, and Ceraunius Tholus, and Alba Patera. Terrace distribution differs between volcanoes, but the characteristic pattern remains the same. Terraces must be late-stage/reactivated structures relative to volcano growth, as they remain visible today. The mechanism responsible for terrace formation probably acts throughout the edifices, as terraces occur at all volcano elevations. Differences in distribution may be due to variations in edifice internal structure, geometry, or the interplay between local and regional stresses. That terraces occur across such a range of Martian volcanoes implies they are size-, slope-, and volcano age-independent structures. The presence and number of other tectonic structures, e.g. calderas and gräben, also vary between terraced volcanoes. Like these other structures, flank terraces may be a fundamental feature of Martian volcano development. In light of these observations, existing formation mechanism hypotheses must be revisited. Magma chamber tumescence, which may have occurred to varying extents on these volcanoes, does not produce convex terrace structures. Both flank relaxation and shallow slumps are associated with volcano spreading, yet none of the Martian examples shows evidence of radially oriented gräben or collapse scars. A

  6. Flanking gene and genetic background problems in genetically manipulated mice.

    PubMed

    Crusio, Wim E

    2004-09-15

    Mice carrying engineered genetic modifications have become an indispensable tool in the study of gene functioning. The interpretation of results obtained with targeted mutants is not completely straightforward, however, because of genetic complications due to linkage and epistasis. Effects of closely linked genes flanking the targeted locus might sometimes be responsible for phenotypic changes ascribed to the null mutation. The effects of the latter might also be modified by the general genetic background. This review presents some examples and discusses some simple strategies to deal with these complications.

  7. Concentrations of trace elements in human milk: Comparisons among women in Argentina, Namibia, Poland, and the United States

    PubMed Central

    Breakey, Alicia A.; Scelza, Brooke; Valeggia, Claudia; Jasienska, Grazyna; Hinde, Katie

    2017-01-01

    Human milk contains essential micronutrients for growth and development during early life. Environmental pollutants, such as potentially toxic metals, can also be transferred to the infant through human milk. These elements have been well-studied, but changing diets and environments and advances in laboratory technology require re-examining these elements in a variety of settings. The aim of this study was to characterize the concentrations of essential and toxic metals in human milk from four diverse populations. Human milk samples (n = 70) were collected in Argentina (n = 21), Namibia (n = 6), Poland (n = 23), and the United States (n = 20) using a standardized mid-feed collection procedure. Milk concentrations of calcium, zinc, iron, copper, manganese, lead, arsenic, and cadmium were determined using inductively coupled plasma mass spectrometry (ICP-MS). We used standard multiple linear regression models to evaluate differences among populations, while including infant age, infant sex, and maternal parity status (multiparous or primiparous) as covariates. Concentrations of all elements, except zinc, varied across populations after controlling for infant age, infant sex, and maternal parity. Calcium and magnesium showed more differences across populations than iron or copper. There were no significant differences among population in zinc concentrations. Mean concentrations of lead, but not arsenic, were low compared to recently published values from other populations. The concentrations of trace elements in human milk are variable among populations. Limitations due to small sample sizes and environmental contamination of some samples prevent us from drawing robust conclusions about the causes of these differences. PMID:28817665

  8. Concentrations of trace elements in human milk: Comparisons among women in Argentina, Namibia, Poland, and the United States.

    PubMed

    Klein, Laura D; Breakey, Alicia A; Scelza, Brooke; Valeggia, Claudia; Jasienska, Grazyna; Hinde, Katie

    2017-01-01

    Human milk contains essential micronutrients for growth and development during early life. Environmental pollutants, such as potentially toxic metals, can also be transferred to the infant through human milk. These elements have been well-studied, but changing diets and environments and advances in laboratory technology require re-examining these elements in a variety of settings. The aim of this study was to characterize the concentrations of essential and toxic metals in human milk from four diverse populations. Human milk samples (n = 70) were collected in Argentina (n = 21), Namibia (n = 6), Poland (n = 23), and the United States (n = 20) using a standardized mid-feed collection procedure. Milk concentrations of calcium, zinc, iron, copper, manganese, lead, arsenic, and cadmium were determined using inductively coupled plasma mass spectrometry (ICP-MS). We used standard multiple linear regression models to evaluate differences among populations, while including infant age, infant sex, and maternal parity status (multiparous or primiparous) as covariates. Concentrations of all elements, except zinc, varied across populations after controlling for infant age, infant sex, and maternal parity. Calcium and magnesium showed more differences across populations than iron or copper. There were no significant differences among population in zinc concentrations. Mean concentrations of lead, but not arsenic, were low compared to recently published values from other populations. The concentrations of trace elements in human milk are variable among populations. Limitations due to small sample sizes and environmental contamination of some samples prevent us from drawing robust conclusions about the causes of these differences.

  9. Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization.

    PubMed

    Ambrus, Attila; Chen, Ding; Dai, Jixun; Jones, Roger A; Yang, Danzhou

    2005-02-15

    The nuclease hypersensitivity element III(1) (NHE III(1)) of the c-MYC promoter strongly controls the transcriptional activity of the c-MYC oncogene. The purine-rich strand of the NHE III(1) element has been shown to be a silencer element for c-MYC transcription upon formation of a G-quadruplex structure. We have determined the predominant G-quadruplex structure of this silencer element in potassium solution by NMR. The G-quadruplex structure adopts an intramolecular parallel-stranded quadruplex conformation with three guanine tetrads and three side loops, including two single-nucleotide side loops and one double-nucleotide side loop, that connect the four guanine strands. The three side loops are very stable and well-defined. The 3'-flanking sequence forms a stable fold-back stacking conformation capping the top end of the G-quadruplex structure. The 5'-flanking A and G bases cap the bottom end of the G-quadruplex, with the adenine stacking very well with the bottom tetrad. This paper reports the first solution structure of a G-quadruplex found to form in the promoter region of an oncogene (c-MYC). This G-quadruplex structure is extremely stable, with a similar melting temperature (>85 degrees C) to that of the wild-type 27-mer purine-rich NHE III(1) sequence of the c-MYC promoter. This predominant quadruplex structure has been shown to be biologically relevant, and the structural information revealed in this research provides an important basis for the design of new drug candidates that specifically target the c-MYC G-quadruplex structure and modulate gene expression.

  10. A polymorphic indel containing the RS3 microsatellite in the 5' flanking region of the vasopressin V1a receptor gene is associated with chimpanzee (Pan troglodytes) personality.

    PubMed

    Hopkins, W D; Donaldson, Z R; Young, L J

    2012-07-01

    Vasopressin is a neuropeptide that has been strongly implicated in the development and evolution of complex social relations and cognition in mammals. Recent studies in voles have shown that polymorphic variation in the promoter region of the arginine vasopressin V1a receptor gene (avpr1a) is associated with different dimensions of sociality. In humans, variation in a repetitive sequence element in the 5' flanking region of the AVPR1A, known as RS3, have also been associated with variation in AVPR1a gene expression, brain activity and social behavior. Here, we examined the association of polymorphic variation in this same 5' flanking region of the AVPR1A on subjective ratings of personality in a sample of 83 chimpanzees (Pan troglodytes). Initial analyses indicated that 34 females and 19 males were homozygous for the short allele, which lacks RS3 (DupB(-/-)), while 18 females and 12 males were heterozygous and thus had one copy of the long allele containing RS3 (DupB(+/-)), yielding overall allelic frequencies of 0.82 for the DupB(-) allele and 0.18 for the DupB(+) allele. DupB(+/+) chimpanzees were excluded from the analysis because of the limited number of individuals. Results indicated no significant sex difference in personality between chimpanzees homozygous for the deletion of the RS3-containing DupB region (DupB(-/-)); however, among chimpanzees carrying one allele with the DupB present (DupB(+/-)), males had significantly higher dominance and lower conscientiousness scores than females. These findings are the first evidence showing that the AVPR1A gene plays a role in different aspects of personality in male and female chimpanzees. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  11. An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing

    PubMed Central

    Margulies, Elliott H.; Vinson, Jade P.; Miller, Webb; Jaffe, David B.; Lindblad-Toh, Kerstin; Chang, Jean L.; Green, Eric D.; Lander, Eric S.; Mullikin, James C.; Clamp, Michele

    2005-01-01

    With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful approach for finding such elements by identifying sequences that have been highly conserved during evolution. Here, we propose an initial strategy for detecting such regions by generating low-redundancy sequence from a collection of 16 eutherian mammals, beyond the 7 for which genome sequence data are already available. We show that such sequence can be accurately aligned to the human genome and used to identify most of the highly conserved regions. Although not a long-term substitute for generating high-quality genomic sequences from many mammalian species, this strategy represents a practical initial approach for rapidly annotating the most evolutionarily conserved sequences in the human genome, providing a key resource for the systematic study of human genome function. PMID:15778292

  12. 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

  13. 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.

  14. Southward flow on the western flank of the Florida Current

    NASA Astrophysics Data System (ADS)

    Soloviev, Alexander V.; Hirons, Amy; Maingot, Christopher; Dean, Cayla W.; Dodge, Richard E.; Yankovsky, Alexander E.; Wood, Jon; Weisberg, Robert H.; Luther, Mark E.; McCreary, Julian P.

    2017-07-01

    A suite of long-term in situ measurements in the Straits of Florida, including the ADCP bottom moorings at an 11-m isobath and 244-m isobath (Miami Terrace) and several ADCP ship transects, have revealed a remarkable feature of the ocean circulation - southward flow on the western, coastal flank of the Florida Current. We have observed three forms of the southward flow - a seasonally varying coastal countercurrent, an undercurrent jet attached to the Florida shelf, and an intermittent undercurrent on the Miami Terrace. According to a 13-year monthly climatology obtained from the near-shore mooring, the coastal countercurrent is a persistent feature from October through January. The southward flow in the form of an undercurrent jet attached to the continental slope was observed during five ship transects from April through September but was not observed during three transects in February, March, and November. This undercurrent jet is well mixed due to strong shear at its top associated with the northward direction of the surface flow (Florida Current) and friction at the bottom. At the same time, no statistically significant seasonal cycle has been observed in the undercurrent flow on the Miami Terrace. Theoretical considerations suggest that several processes could drive the southward current, including interaction between the Florida Current and the shelf, as well as forcing that is independent of the Florida Current. The exact nature of the southward flow on the western flank of the Florida Current is, however, unknown.

  15. Flanking fractures and the formation of double ridges on Europa

    NASA Astrophysics Data System (ADS)

    Dombard, Andrew J.; Patterson, G. Wesley; Lederer, Adam P.; Prockter, Louise M.

    2013-03-01

    Europa, a satellite of Jupiter, is one of the most intriguing worlds in the Solar System. Its dearth of impact craters and plethora of surface morphologies point to a dynamic evolution of its icy shell in geologically recent times. Double ridges are a common landform and appear to have formed over a significant fraction of the satellite’s observed geologic history. Thus, understanding their formation is critical to unraveling Europa’s history, and many models have been proposed to explain their creation. A clue to the formation of ridges may lie in evidence for flexure of the lithosphere in response to a load imposed by the ridge itself (marginal troughs and subparallel flanking fractures). When this flexure has been modeled, a simple elastic lithosphere has typically been assumed; however, the generally thin lithospheres suggested by these models require very high heat flows that are inconsistent with Europa’s expected thermal budget (of order 1 W m-2 vs. of order 10 mW m-2). Each of the proposed formational models, however, predicts a thermal anomaly that may facilitate the flexure of Europa’s lithosphere. Here, we simulate this flexure in the presence of these anomalies, as a means to evaluate the different models of ridge formation. We find that nearly all models of double ridge formation are inconsistent with the observation of flexure (specifically the flanking fractures), except for a cryovolcanic model in which the growing ridge is underlain by a cryomagmatic sill that locally heats and thins the lithosphere.

  16. 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.

  17. 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.

  18. 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.

  19. Finite element analysis to investigate variability of MR elastography in the human thigh.

    PubMed

    Hollis, L; Barnhill, E; Perrins, M; Kennedy, P; Conlisk, N; Brown, C; Hoskins, P R; Pankaj, P; Roberts, N

    2017-06-29

    To develop finite element analysis (FEA) of magnetic resonance elastography (MRE) in the human thigh and investigate inter-individual variability of measurement of muscle mechanical properties. Segmentation was performed on MRI datasets of the human thigh from 5 individuals and FEA models consisting of 12 muscles and surrounding tissue created. The same material properties were applied to each tissue type and a previously developed transient FEA method of simulating MRE using Abaqus was performed at 4 frequencies. Synthetic noise was applied to the simulated data at various levels before inversion was performed using the Elastography Software Pipeline. Maps of material properties were created and visually assessed to determine key features. The coefficient of variation (CoV) was used to assess the variability of measurements in each individual muscle and in the groups of muscles across the subjects. Mean measurements for the set of muscles were ranked in size order and compared with the expected ranking. At noise levels of 2% the CoV in measurements of |G(*)| ranged from 5.3 to 21.9% and from 7.1 to 36.1% for measurements of ϕ in the individual muscles. A positive correlation (R(2) value 0.80) was attained when the expected and measured |G(*)| ranking were compared, whilst a negative correlation (R(2) value 0.43) was found for ϕ. Created elastograms demonstrated good definition of muscle structure and were robust to noise. Variability of measurements across the 5 subjects was dramatically lower for |G(*)| than it was for ϕ. This large variability in ϕ measurements was attributed to artefacts. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. An Sp1/Sp3 Site in the Downstream Region of Varicella-Zoster Virus (VZV) oriS Influences Origin-Dependent DNA Replication and Flanking Gene Transcription and Is Important for VZV Replication In Vitro and in Human Skin

    PubMed Central

    Robinson, Makeda; Sommer, Marvin; Arvin, Ann; Hay, John; Ruyechan, William T.

    2012-01-01

    The distribution and orientation of origin-binding protein (OBP) sites are the main architectural contrasts between varicella-zoster virus (VZV) and herpes simplex virus (HSV) origins of DNA replication (oriS). One important difference is the absence of a downstream OBP site in VZV, raising the possibility that an alternative cis element may replace its function. Our previous work established that Sp1, Sp3, and YY1 bind to specific sites within the downstream region of VZV oriS; we hypothesize that one or both of these sites may be the alternative cis element(s). Here, we show that the mutation of the Sp1/Sp3 site decreases DNA replication and transcription from the adjacent ORF62 and ORF63 promoters following superinfection with VZV. In contrast, in the absence of DNA replication or in transfection experiments with ORF62, only ORF63 transcription is affected. YY1 site mutations had no significant effect on either process. Recombinant viruses containing these mutations were then constructed. The Sp1/Sp3 site mutant exhibited a significant decrease in virus growth in MeWo cells and in human skin xenografts, while the YY1 site mutant virus grew as well as the wild type in MeWo cells, even showing a late increase in VZV replication in skin xenografts following infection. These results suggest that the Sp1/Sp3 site plays an important role in both VZV origin-dependent DNA replication and ORF62 and ORF63 transcription and that, in contrast to HSV, these events are linked during virus replication. PMID:22933283

  1. An Sp1/Sp3 site in the downstream region of varicella-zoster virus (VZV) oriS influences origin-dependent DNA replication and flanking gene transcription and is important for VZV replication in vitro and in human skin.

    PubMed

    Khalil, Mohamed I; Robinson, Makeda; Sommer, Marvin; Arvin, Ann; Hay, John; Ruyechan, William T

    2012-12-01

    The distribution and orientation of origin-binding protein (OBP) sites are the main architectural contrasts between varicella-zoster virus (VZV) and herpes simplex virus (HSV) origins of DNA replication (oriS). One important difference is the absence of a downstream OBP site in VZV, raising the possibility that an alternative cis element may replace its function. Our previous work established that Sp1, Sp3, and YY1 bind to specific sites within the downstream region of VZV oriS; we hypothesize that one or both of these sites may be the alternative cis element(s). Here, we show that the mutation of the Sp1/Sp3 site decreases DNA replication and transcription from the adjacent ORF62 and ORF63 promoters following superinfection with VZV. In contrast, in the absence of DNA replication or in transfection experiments with ORF62, only ORF63 transcription is affected. YY1 site mutations had no significant effect on either process. Recombinant viruses containing these mutations were then constructed. The Sp1/Sp3 site mutant exhibited a significant decrease in virus growth in MeWo cells and in human skin xenografts, while the YY1 site mutant virus grew as well as the wild type in MeWo cells, even showing a late increase in VZV replication in skin xenografts following infection. These results suggest that the Sp1/Sp3 site plays an important role in both VZV origin-dependent DNA replication and ORF62 and ORF63 transcription and that, in contrast to HSV, these events are linked during virus replication.

  2. 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.

  3. A three-dimensional finite element model of human atrial anatomy: New methods for cubic Hermite meshes with extraordinary vertices

    PubMed Central

    Gonzales, Matthew J.; Sturgeon, Gregory; Krishnamurthy, Adarsh; Hake, Johan; Jonas, René; Stark, Paul; Rappel, Wouter-Jan; Narayan, Sanjiv M.; Zhang, Yongjie; Segars, W. Paul; McCulloch, Andrew D.

    2013-01-01

    High-order cubic Hermite finite elements have been valuable in modeling cardiac geometry, fiber orientations, biomechanics, and electrophysiology, but their use in solving three-dimensional problems has been limited to ventricular models with simple topologies. Here, we utilized a subdivision surface scheme and derived a generalization of the “local-to-global” derivative mapping scheme of cubic Hermite finite elements to construct bicubic and tricubic Hermite models of the human atria with extraordinary vertices from computed tomography images of a patient with atrial fibrillation. To an accuracy of 0.6 millimeters, we were able to capture the left atrial geometry with only 142 bicubic Hermite finite elements, and the right atrial geometry with only 90. The left and right atrial bicubic Hermite meshes were G1 continuous everywhere except in the one-neighborhood of extraordinary vertices, where the mean dot products of normals at adjacent elements were 0.928 and 0.925. We also constructed two biatrial tricubic Hermite models and defined fiber orientation fields in agreement with diagrammatic data from the literature using only 42 angle parameters. The meshes all have good quality metrics, uniform element sizes, and elements with aspect ratios near unity, and are shared with the public. These new methods will allow for more compact and efficient patient-specific models of human atrial and whole heart physiology. PMID:23602918

  4. A three-dimensional finite element model of human atrial anatomy: new methods for cubic Hermite meshes with extraordinary vertices.

    PubMed

    Gonzales, Matthew J; Sturgeon, Gregory; Krishnamurthy, Adarsh; Hake, Johan; Jonas, René; Stark, Paul; Rappel, Wouter-Jan; Narayan, Sanjiv M; Zhang, Yongjie; Segars, W Paul; McCulloch, Andrew D

    2013-07-01

    High-order cubic Hermite finite elements have been valuable in modeling cardiac geometry, fiber orientations, biomechanics, and electrophysiology, but their use in solving three-dimensional problems has been limited to ventricular models with simple topologies. Here, we utilized a subdivision surface scheme and derived a generalization of the "local-to-global" derivative mapping scheme of cubic Hermite finite elements to construct bicubic and tricubic Hermite models of the human atria with extraordinary vertices from computed tomography images of a patient with atrial fibrillation. To an accuracy of 0.6 mm, we were able to capture the left atrial geometry with only 142 bicubic Hermite finite elements, and the right atrial geometry with only 90. The left and right atrial bicubic Hermite meshes were G1 continuous everywhere except in the one-neighborhood of extraordinary vertices, where the mean dot products of normals at adjacent elements were 0.928 and 0.925. We also constructed two biatrial tricubic Hermite models and defined fiber orientation fields in agreement with diagrammatic data from the literature using only 42 angle parameters. The meshes all have good quality metrics, uniform element sizes, and elements with aspect ratios near unity, and are shared with the public. These new methods will allow for more compact and efficient patient-specific models of human atrial and whole heart physiology. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Characterization of the Nanog 5′-flanking Region in Bovine

    PubMed Central

    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

    2016-01-01

    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

  6. Integrated remodeling-to-fracture finite element model of human proximal femur behavior.

    PubMed

    Hambli, Ridha; Lespessailles, Eric; Benhamou, Claude-Laurent

    2013-01-01

    The purpose of this work was to develop an integrated remodeling-to-fracture finite element model allowing for the combined simulation of (i) simulation of a human proximal femur remodeling under a given boundary conditions, (ii) followed by the simulation of its fracture behavior (force-displacement curve and fracture pattern) under quasi-static load. The combination of remodeling and fracture simulation into one unified model consists in considering that the femur properties resulting from the remodeling simulation correspond to the initial state for the fracture prediction. The remodeling model is based on phenomenological one based on a coupled strain and fatigue damage stimulus. The fracture model is based on continuum damage mechanics in order to predict the progressive fracturing process which allows to predict the fracture pattern and the complete force-displacement curve under quasi-static load. To prevent mesh-dependence that generally affects the damage propagation rate, regularization technique was applied in the current work. To investigate the potential of the proposed unified remodeling-to-fracture model, we performed remodeling simulations on a 3D proximal femur model for a duration of 365 days under five different daily loading conditions followed by a side fall fracture simulation reproducing previously published experimental tests (de Bakker et al. (2009), case C, male, 72 years old). We show here that the implementation of an integrated remodeling-to-fracture model provides more realistic prediction strategy to assess the bone remodeling effects on the fracture risk of bone.

  7. The human kallikrein 10 promoter contains a functional retinoid response element.

    PubMed

    Zeng, Musheng; Zhang, Ying; Bhat, Ishfaq; Wazer, David E; Band, Hamid; Band, Vimla

    2006-06-01

    Human kallikrein 10 (hK10) protein is expressed in normal breast but is significantly downregulated in a majority of invasive breast cancers. Thus, understanding how hK10 expression is regulated is of substantial significance. In this study, we analyzed the promoter region of hK10 using a website software (TRANSFAC 3.0), which predicted three possible retinoic acid response elements (RAREs), RARE1 at -1041 (TGACCTCGTGATCC), RARE2 at -859 (TGACCTCCTATGA) and RARE3 at -765 (TGACCTCCTGTGA), each with a half-site of a canonical sequence (TGACCT; reverse complement AGGTCA). Using electrophoretic mobility shift assays and nucleotide competition analysis, as well as chromatin immunoprecipitation of the native hK10 promoter, we demonstrated specific binding of RXR only to RARE1. The functional importance of RARE in the hK10 promoter was demonstrated by retinoid induction of hk10 promoter-reporters; furthermore, mutation of RARE1 but not of RARE2 or RARE3 abolished the induction of the reporter. Finally, we demonstrated the induction of hK10 mRNA and protein expression upon retinoid treatment of cells. In view of the correlation of the downregulation of hK10 mRNA and protein with breast cancer progression, these findings suggest a potential approach to restore hK10 expression in cancer patients.

  8. Bone Conduction Hearing: Three-Dimensional Finite Element Model of the Human Middle and Inner Ear

    NASA Astrophysics Data System (ADS)

    Kim, Namkeun; Homma, Kenji; Puria, Sunil; Steele, Charles R.

    2011-11-01

    A finite-element (FE) simulation model of a human auditory periphery was developed to gain insight into the fundamental mechanisms of bone conduction (BC) hearing. Three dimensional geometry of middle ear and cochlea including semi-circular canal was obtained by μCT images. The simulation effectively focused on the middle ear and then the cochlea fluid-inertial BC component. The FE model was first tuned and validated against various frequency responses available from the literature. The characteristics of various cochlear response quantities such as the basilar membrane (BM) displacement, window volume velocities, and cochlear fluid pressure were examined for both BC and air conduction (AC) excitations. Especially, the decomposition analysis was applied to window volume velocities and cochlear fluid pressures to separate them into anti-symmetric and symmetric components. The preliminary result shows that the BM vibration is driven by the part of the fluid pressure that is anti-symmetric (i.e. differential slow wave) with respect to the BM, which is generated by the anti-symmetric window volume velocity.

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

    PubMed

    Nigenda, Gustavo; Muños, José Alberto

    2015-09-22

    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.

  10. Rare earth elements in human hair from a mining area of China.

    PubMed

    Wei, Binggan; Li, Yonghua; Li, Hairong; Yu, Jiangping; Ye, Bixiong; Liang, Tao

    2013-10-01

    Rare earth minerals have been mined for more than 50 years in Inner Mongolia of China. In the mining area rare earth elements (REE) may be significantly accumulated in humans. Therefore, the aim of this paper is to characterize the REE concentrations in hair of local residents. REE concentrations in hair of 118 subjects were determined. The results showed that the mean concentrations of the determined REE in the hair of both females and males were usually higher from mining area than from control area. The mean concentrations of all the fifteen REE were much higher in hair of males than in hair of females from mining area. This suggested that males might be more sensitive to REE than females. In addition, the mean contents of the REE in hair of miners, particularly light REE (La, Ce, Pr and Nd), were usually much higher than the values in hair of non-miners from both mining area and control area, indicating that the miners were exposed to higher concentrations of REE in occupational environment. Among age groups, the relationships between REE concentrations and age groups showed that more and more concentrations of light REE accumulated in body of both females and males with age until 60 years, while heavy REE concentrations decreased with age in males who were exposed to low concentrations of heavy REE. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. 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.

  12. Finite element simulation of bone remodelling in human mandible around osseointegrated dental implant

    NASA Astrophysics Data System (ADS)

    Lian, Z. Q.; Guan, H.; Loo, Y. C.; Ivanovski, S.; Johnson, N. W.

    2010-06-01

    Modern dental implant is a biocompatible titanium device surgically placed into a jawbone to support a prosthetic tooth crown in order to replace missing teeth. Implants are superior to conventional prostheses, in both function and long-term predictability. However, placement of an implant changes the normal mechanical environment of jawbone, which causes the bone density to redistribute and adapt to the new environment through a process of remodelling. This study aims to predict the density distribution in human jawbone around osseointegrated dental implant. Based on two popular, yet distinctive theories for bone remodelling, a new remodelling algorithm is proposed. The proposed algorithm is verified by a two-dimensional (2D) plate model. Then, a 2D finite element model of implant and jawbone is studied. The effects of two parameters, viz the reference value of strain energy density (SED) and 'lazy zone' region, on density distribution, are also examined. This study has demonstrated that consideration of the lazy zone, is less important than consideration of the stress and strain (quantified as SED) induced within the bone. Taking into account both 'lazy zone' effect and self-organisational control process, the proposed bone remodelling algorithm has overcome the shortcomings of the two existing theories.

  13. In vivo measurements of human neck skin elasticity using MRI and finite element modeling.

    PubMed

    An, Yunqiang; Ji, Changjin; Li, Yong; Wang, Jianxia; Zhang, Xinyue; Huang, Yaqi

    2017-04-01

    The assessment of mechanical properties of the human skin is very important in investigating the mechanism of obstructive sleep apnea, a common disorder characterized by repetitive collapse and obstruction of the upper airway during sleep. In this study, a unique method, combining magnetic resonance imaging (MRI) and finite element modeling (FEM), was developed to obtain the value of the in vivo elastic modulus of the neck skin. A total of 22 subjects, 16 males and six females, were recruited to participate in the MRI studies. The changes in the airway and the neck size resulting from fluid shift from the lower body to the neck were measured based on the MR images. A two-dimensional plane strain FE model was built to simulate such changes in the neck cross-section for each subject. Solving an inverse problem using FEM by matching the measured data, we obtained the in vivo elastic modulus of the neck skin to be 1.78 ± 1.73 MPa. Results showed that the elastic modulus tended to increase with age and body mass index for these subjects. A sensitivity analysis of the muscle and fat mechanical parameters was also performed to test their effects on the predicted skin elasticity. The unique method developed in this study for measuring the in vivo elastic modulus of the neck skin is quite effective, and the skin elasticity value obtained using this method is credible. © 2017 American Association of Physicists in Medicine.

  14. 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.

  15. 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.

  16. Finite element modelling of human auditory periphery including a feed-forward amplification of the cochlea.

    PubMed

    Wang, Xuelin; Wang, Liling; Zhou, Jianjun; Hu, Yujin

    2014-08-01

    A three-dimensional finite element model is developed for the simulation of the sound transmission through the human auditory periphery consisting of the external ear canal, middle ear and cochlea. The cochlea is modelled as a straight duct divided into two fluid-filled scalae by the basilar membrane (BM) having an orthotropic material property with dimensional variation along its length. In particular, an active feed-forward mechanism is added into the passive cochlear model to represent the activity of the outer hair cells (OHCs). An iterative procedure is proposed for calculating the nonlinear response resulting from the active cochlea in the frequency domain. Results on the middle-ear transfer function, BM steady-state frequency response and intracochlear pressure are derived. A good match of the model predictions with experimental data from the literatures demonstrates the validity of the ear model for simulating sound pressure gain of middle ear, frequency to place map, cochlear sensitivity and compressive output for large intensity input. The current model featuring an active cochlea is able to correlate directly the sound stimulus in the ear canal with the vibration of BM and provides a tool to explore the mechanisms by which sound pressure in the ear canal is converted to a stimulus for the OHCs.

  17. Characterization of the interaction of the human mineralocorticosteroid receptor with hormone response elements.

    PubMed Central

    Lombès, M; Binart, N; Oblin, M E; Joulin, V; Baulieu, E E

    1993-01-01

    Although the mineralocorticosteroid receptor (MR) belongs to the superfamily of hormone-dependent transcription factors, the molecular mechanism by which it regulates gene expression is poorly understood. Binding of the MR to target gene promoters has never been characterized, and specific mineralocorticosteroid response elements (MREs) remain to be identified. The human MR (hMR) was overexpressed in Sf21 insect cells using the baculovirus system. The high degree of similarity between the glucocorticosteroid receptor (GR) and the MR prompted us to examine the DNA-binding properties of the recombinant MR with glucocorticosteroid-regulated genes. Gel shift mobility assays demonstrated that the recombinant receptor interacted with oligonucleotides containing perfect and imperfect palindromic sequences of GRE. A monoclonal anti-hMR antibody (FD4) induced a supershift of protein-DNA complexes and identified the MR in Western blot analysis. In vitro DNAse I protection assays with the hormone-regulated murine mammary tumour virus promoter showed that recombinant hMR generated four footprints whose limits encompassed the GRE motifs. By means of these two complementary approaches, no difference between the interaction of free, agonist- or antagonist-bound MR and DNA was detected. We provide evidence that hMR functions as a sequence-specific DNA-binding protein. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:8389140

  18. Assessing astronaut injury potential from suit connectors using a human body finite element model.

    PubMed

    Danelson, Kerry A; Bolte, John H; Stitzel, Joel D

    2011-02-01

    The new Orion space capsule requires additional consideration of possible injury during landing due to the dynamic nature of the impact. The purpose of this parametric study was to determine changes in the injury response of a human body finite element model with a suit connector (SC). The possibility of thoracic bony injury, thoracic soft tissue injury, and femur injury were assessed in 24 different model configurations. These simulations had two SC placements and two SC types, a 2.27-kg rectangular and a 3.17-kg circular SC. A baseline model was tested with the same acceleration pulses and no SC for comparison. Further simulations were conducted to determine the protective effect of SC location changes and adding small and large rigid chest plates. The possibilities of rib, chest soft tissue, and femur injury were evaluated using sternal deflection, chest deflection, viscous criterion, and strain values. The results indicated a higher likelihood of chest injury than femur injury. The mean first principal strain in the femur was 0.136 +/- 0.007%, which is well below the failure limit for cortical bone. The placement of chest plates had a protective effect and reduced the sternal deflection, chest deflection, and viscous criterion values. If possible, the SC should be placed on the thigh to minimize injury risk metrics. Chest plates appear to offer some protective value; therefore, a large rigid chest plate or similar countermeasure should be considered for chest SC placement.

  19. Identification of an intronic cis-acting element in the human dopamine transporter gene

    PubMed Central

    Zhao, Ying; Zhou, Yanhong; Lin, Zhicheng

    2017-01-01

    The human dopamine transporter gene (hDAT) encodes the dopamine transporter in dopamine (DA) neurons to regulate DA transmission. hDAT expression varies significantly from neuron to neuron, and from individual to individual so that dysregulation of hDAT is related to many neuropsychiatric disorders. It is critical to identify hDAT-specific cis-acting elements that regulate the hDAT expression. Previous studies showed that hDAT Intron 1 displayed inhibitory activity for reporter gene expression. Here we report that the hDAT Intron 1 contains a 121-bp fragment that down-regulated both SV40 and hDAT promoter activities by 80% in vitro. Subfragments of 121-bp still down-regulated the SV40 promoter but not the hDAT promoter, as supported by nuclear protein-binding activities. Collectively, 121-bp is a silencer in vitro that might coordinate with transcriptional activities both inside and outside 121-bp in regulation of hDAT. PMID:22160470

  20. 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.

  1. 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.

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

    PubMed

    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 Ca(2+) 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.

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

    PubMed Central

    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

  4. High similarity between flanking regions of different microsatellites detected within each of two species of Lepidoptera: Parnassius apollo and Euphydryas aurinia.

    PubMed

    Meglecz, Emese; Petenian, Frederic; Danchin, Etienne; D'Acier, Armelle Coeur; Rasplus, Jean-Yves; Faure, Eric

    2004-06-01

    Microsatellite flanking regions have been compared in two butterfly species. Several microsatellite flanking regions showed high similarity to one another among different microsatellites within a same species, but very few similarities were found between species. This can be the consequence of either duplication/multiplication events involving large regions containing microsatellites or of microsatellites imbedded in minisatellite regions. The multiplication of microsatellites might also be linked to mobile elements. Furthermore, crossing over between nonhomologous microsatellites can lead to the exchange of the flanking regions between microsatellites. The same phenomenon was observed in both studied butterfly species but not in Aphis fabae (Hemiptera), which was screened at the same time using the same protocol. These findings might explain, at least partially, why microsatellite isolation in Lepidoptera has been relatively unsuccessful so far.

  5. A finite-element simulation of galvanic coupling intra-body communication based on the whole human body.

    PubMed

    Song, Yong; Zhang, Kai; Hao, Qun; Hu, Lanxin; Wang, Jingwen; Shang, Fuzhou

    2012-10-09

    Simulation based on the finite-element (FE) method plays an important role in the investigation of intra-body communication (IBC). In this paper, a finite-element model of the whole body model used for the IBC simulation is proposed and verified, while the FE simulation of the galvanic coupling IBC with different signal transmission paths has been achieved. Firstly, a novel finite-element method for modeling the whole human body is proposed, and a FE model of the whole human body used for IBC simulation was developed. Secondly, the simulations of the galvanic coupling IBC with the different signal transmission paths were implemented. Finally, the feasibility of the proposed method was verified by using in vivo measurements within the frequency range of 10 kHz-5 MHz, whereby some important conclusions were deduced. Our results indicate that the proposed method will offer significant advantages in the investigation of the galvanic coupling intra-body communication.

  6. A Finite-Element Simulation of Galvanic Coupling Intra-Body Communication Based on the Whole Human Body

    PubMed Central

    Song, Yong; Zhang, Kai; Hao, Qun; Hu, Lanxin; Wang, Jingwen; Shang, Fuzhou

    2012-01-01

    Simulation based on the finite-element (FE) method plays an important role in the investigation of intra-body communication (IBC). In this paper, a finite-element model of the whole body model used for the IBC simulation is proposed and verified, while the FE simulation of the galvanic coupling IBC with different signal transmission paths has been achieved. Firstly, a novel finite-element method for modeling the whole human body is proposed, and a FE model of the whole human body used for IBC simulation was developed. Secondly, the simulations of the galvanic coupling IBC with the different signal transmission paths were implemented. Finally, the feasibility of the proposed method was verified by using in vivo measurements within the frequency range of 10 kHz–5 MHz, whereby some important conclusions were deduced. Our results indicate that the proposed method will offer significant advantages in the investigation of the galvanic coupling intra-body communication. PMID:23202010

  7. 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…

  8. 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…

  9. Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements.

    PubMed

    Wu, Sen; Mariotti, Marco; Santesmasses, Didac; Hill, Kristina E; Baclaocos, Janinah; Aparicio-Prat, Estel; Li, Shuping; Mackrill, John; Wu, Yuanyuan; Howard, Michael T; Capecchi, Mario; Guigó, Roderic; Burk, Raymond F; Atkins, John F

    2016-11-01

    Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3' UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3' of SECIS 2, two further sites were identified with one resulting in 10-25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon. They were fed on either high or selenium-deficient diets. The mutants had very different effects on the proportions of shorter and longer product Sepp1 protein isoforms isolated from plasma, and on viability. Spatially and functionally distinctive effects of the two SECIS elements on UGA decoding were inferred. We also bioinformatically identify two selenoprotein S mRNAs with different 5' sequences predicted to yield products with different N-termini. These results provide insights into SECIS function and mRNA processing in selenoprotein isoform diversity.

  10. Human selenoprotein P and S variant mRNAs with different numbers of SECIS elements and inferences from mutant mice of the roles of multiple SECIS elements

    PubMed Central

    Wu, Sen; Mariotti, Marco; Santesmasses, Didac; Hill, Kristina E.; Baclaocos, Janinah; Aparicio-Prat, Estel; Li, Shuping; Mackrill, John; Wu, Yuanyuan; Howard, Michael T.; Capecchi, Mario; Guigó, Roderic; Burk, Raymond F.

    2016-01-01

    Dynamic redefinition of the 10 UGAs in human and mouse selenoprotein P (Sepp1) mRNAs to specify selenocysteine instead of termination involves two 3′ UTR structural elements (SECIS) and is regulated by selenium availability. In addition to the previously known human Sepp1 mRNA poly(A) addition site just 3′ of SECIS 2, two further sites were identified with one resulting in 10–25% of the mRNA lacking SECIS 2. To address function, mutant mice were generated with either SECIS 1 or SECIS 2 deleted or with the first UGA substituted with a serine codon. They were fed on either high or selenium-deficient diets. The mutants had very different effects on the proportions of shorter and longer product Sepp1 protein isoforms isolated from plasma, and on viability. Spatially and functionally distinctive effects of the two SECIS elements on UGA decoding were inferred. We also bioinformatically identify two selenoprotein S mRNAs with different 5′ sequences predicted to yield products with different N-termini. These results provide insights into SECIS function and mRNA processing in selenoprotein isoform diversity. PMID:27881738

  11. 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

  12. Developmentally regulated excision of a 28-base-pair sequence from the Paramecium genome requires flanking DNA.

    PubMed

    Ku, M; Mayer, K; Forney, J D

    2000-11-01

    The micronuclear DNA of Paramecium tetraurelia is estimated to contain over 50,000 short DNA elements that are precisely removed during the formation of the transcriptionally active macronucleus. Each internal eliminated sequence (IES) is bounded by 5'-TA-3' dinucleotide repeats, a feature common to some classes of DNA transposons. We have developed an in vivo assay to analyze these highly efficient and precise DNA excision events. The microinjection of a cloned IES into mating cells results in accurately spliced products, and the transformed cells maintain the injected DNA as extrachromosomal molecules. A series of deletions flanking one side of a 28-bp IES were constructed and analyzed with the in vivo assay. Whereas 72 bp of DNA flanking the eliminated region is sufficient for excision, lengths of 31 and 18 bp result in reduced excision and removal of all wild-type sequences adjacent to the TA results in complete failure of excision. In contrast, nucleotide mutations within the middle of the 28-bp IES do not prevent excision. The results are consistent with a functional role for perfect inverted repeats flanking the IES.

  13. Developmentally Regulated Excision of a 28-Base-Pair Sequence from the Paramecium Genome Requires Flanking DNA†

    PubMed Central

    Ku, Michael; Mayer, Kimberly; Forney, James D.

    2000-01-01

    The micronuclear DNA of Paramecium tetraurelia is estimated to contain over 50,000 short DNA elements that are precisely removed during the formation of the transcriptionally active macronucleus. Each internal eliminated sequence (IES) is bounded by 5′-TA-3′ dinucleotide repeats, a feature common to some classes of DNA transposons. We have developed an in vivo assay to analyze these highly efficient and precise DNA excision events. The microinjection of a cloned IES into mating cells results in accurately spliced products, and the transformed cells maintain the injected DNA as extrachromosomal molecules. A series of deletions flanking one side of a 28-bp IES were constructed and analyzed with the in vivo assay. Whereas 72 bp of DNA flanking the eliminated region is sufficient for excision, lengths of 31 and 18 bp result in reduced excision and removal of all wild-type sequences adjacent to the TA results in complete failure of excision. In contrast, nucleotide mutations within the middle of the 28-bp IES do not prevent excision. The results are consistent with a functional role for perfect inverted repeats flanking the IES. PMID:11046136

  14. Regulation of rat liver glucose-6-phosphatase gene expression in different nutritional and hormonal states: gene structure and 5'-flanking sequence.

    PubMed

    Argaud, D; Zhang, Q; Pan, W; Maitra, S; Pilkis, S J; Lange, A J

    1996-11-01

    The mRNA level of the catalytic subunit of rat liver glucose-6-phosphatase (Glu-6-Pase) was regulated by hormones commensurate with activity changes in vivo. Insulin exerts a dominant negative effect on the mRNA levels of Glu-6-Pase. Both mRNA levels and activities of the enzyme are low in the fed and refed state where insulin levels are elevated. Insulin administration to diabetic rats also decreases levels of mRNA and Glu-6-Pase activity. Insulin at a concentration of 1 nmol/l completely overcomes the stimulatory effect of glucocorticoids on Glu-6-Pase message levels in FAO hepatoma cells. The stimulatory response to glucocorticoid in FAO cells is biphasic, with maxima seen at 3 and 18 h after hormone addition (respectively 1.6- and 3.3-fold). 8-(4-chlorophenylthio)-cAMP (CPT-cAMP) causes a fourfold increase in Glu-6-Pase mRNA at 3 h in FAO cells. The gene of rat liver Glu-6-Pase is 13 kilobases in length and comprised of 5 exons. The exon-intron structure is completely conserved when compared with the mouse and human genes. A 0.5-kb 3'-untranslated region, which is present in rat and mouse liver Glu-6-Pase cDNA, is absent in the Glu-6-Pase gene reported here, indicating the possible duplication of either the terminal fifth exon or the entire gene. The promoter region contains a consensus core CCAAT element at position -207 and a TATAAA at position -31. Several possible response elements have been identified in the 5'-flanking region (from a HindIII site at position -1641). A consensus glucocorticoid response element is located at base pair -1552, a 9/10 match of the insulin response sequence is located at position -1449, and a 7/8 match of the cAMP response element is located at position -164.

  15. ToF-SIMS analysis of elemental distributions in human hair.

    PubMed

    Kempson, Ivan M; Skinner, William M

    2005-02-15

    Elemental distributions on whole and longitudinal sections of hairs plucked from the scalp were studied with the surface sensitive technique time-of-flight secondary ion mass spectrometry (ToF-SIMS). Endogenous and environmental influences on the distributions of elemental species were identified. The cuticle scales appear to play the major role in the accumulation of exogenous products. The functionality of the outer surfaces and scale edges each preferentially bind different elemental species. The majority of elements considered accumulated longitudinally on the outer surface of the hair above the scalp level. Internally, most elemental signals (especially Al) decreased longitudinally once exposed to the environment with the exception of Si, which showed an increase. Images of elemental distributions within the medulla suggest that regions of different reactivity exist and show a variable ability to accumulate elemental species. The greatest signal intensities were observed in the cuticle and medulla regions rather than the cortex. The cuticle is continually exposed to environmental contamination and the medulla may, or may not, exist in a hair. Therefore, the components of a hair that potentially contribute the most to the elemental concentrations (i.e. the cuticle and medulla) are also the most variable, and as such greatly complicate the interpretation of elemental concentrations in hair. Results also suggest that bleaching hair can enhance the accumulation of contaminants.

  16. 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).

  17. Determination of trace elements and calcium in bone of the human iliac crest by atomic absorption spectrometry.

    PubMed

    Scancar, J; Milacic, R; Benedik, M; Bukovec, P

    2000-03-01

    A rapid and reliable analytical method for the determination of trace elements in human bone by atomic absorption spectrometry is reported. Calcium was determined to estimate the homogeneity of samples. Human bone from the iliac crest was obtained at autopsy of adult subjects. Before analysis samples were decomposed by microwave digestion and acid digestion in a Parr bomb. Zinc, rubidium, strontium, calcium and iron were determined by flame atomic absorption spectrometry (FAAS) and aluminium, copper and lead by electrothermal atomic absorption spectrometry (ETAAS) at optimum measurement conditions. The results for the two digestion procedures agreed for zinc, rubidium and calcium within +/-5%, for copper within +/-7% and for strontium, iron, aluminium and lead within +/-10%. The repeatability of measurement (R.S.D.) for determination of calcium and trace elements after microwave digestion and acid digestion in a Parr bomb was tested in one representative autopsy bone sample by six parallel determinations. It was found to be better than +/-5% either for microwave digested samples or samples digested in a Parr bomb, for all elements determined by FAAS and ETAAS techniques. The accuracy of the applied digestion procedures was checked by analysis of trace elements in NIST SRM 1486 Bone Meal reference material. Good agreement of the results with certified values was obtained for both digestion procedures. The microwave procedure developed for digestion of small amounts of sample was applied in trace elements analysis of bone biopsy samples from dialysis patients.

  18. 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.

  19. 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.

  20. 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

  1. Prehension of a Flanked Target in Individuals With Amblyopia.

    PubMed

    Buckley, John G; Pacey, Ian E; Panesar, Gurvinder K; Scally, Andrew; Barrett, Brendan T

    2015-11-01

    Reduced binocularity is a prominent feature of amblyopia and binocular cues are thought to be important for prehension. We examine prehension in individuals with amblyopia when the target-object was flanked, thus mimicking everyday prehension. Amblyopes (n = 20, 36.4 ± 11.7 years; 6 anisometropic, 3 strabismic, 11 mixed) and visually-healthy controls (n = 20, 27.5 ± 6.3 years) reached forward, grasped, and lifted a cylindrical target-object that was flanked with objects either (lateral) side of the target, or in front and behind it in depth. Only six amblyopes (30%) had measurable stereoacuity. Trials were completed in binocular and monocular viewing, using the better eye in amblyopic participants. Compared with visual normals, amblyopes displayed a longer overall movement time (P = 0.031), lower average reach velocity (P = 0.021), smaller maximum aperture (P = 0.007), and a longer duration between object contact and lift (P = 0.003). Differences between groups were more apparent when the flankers were in front and behind, compared with either side, as evidenced by significant group-by-flanker configuration interactions for reach duration (P < 0.001), size and timing of maximum aperture (P ≤ 0.009), end-of-reach to object-contact (P < 0.001), and object-contact to lift (P = 0.044), suggesting that amblyopic deficits are greatest when binocular cues are richest. Both groups demonstrated a significant binocular advantage, in that in both groups performance was worse for monocular compared with binocular viewing, but interestingly, amblyopic deficits in binocular viewing largely persisted during monocular viewing with the better eye. These results suggest that amblyopes either display considerable residual binocularity or that they have adapted to make good use of their abnormal binocularity.

  2. Pore Pressure Distribution and Flank Instability in Hydrothermally Altered Stratovolcanoes

    NASA Astrophysics Data System (ADS)

    Ball, J. L.; Taron, J.; Hurwitz, S.; Reid, M. E.

    2015-12-01

    Field and geophysical investigations of stratovolcanoes with long-lived hydrothermal systems commonly reveal that initially permeable regions (such as brecciated layers of pyroclastic material) can become both altered and water-bearing. Hydrothermal alteration in these regions, including clay formation, can turn them into low-permeability barriers to fluid flow, which could increase pore fluid pressures resulting in flank slope instability. We examined elevated pore pressure conditions using numerical models of hydrothermal flow in stratovolcanoes, informed by geophysical data about internal structures and deposits. Idealized radially symmetric meshes were developed based on cross-sectional profiles and alteration/permeability structures of Cascade Range stratovolcanoes. We used the OpenGeoSys model to simulate variably saturated conditions in volcanoes heated only by regional heat fluxes, as well as 650°C intrusions at two km depth below the surface. Meteoric recharge was estimated from precipitation rates in the Cascade Range. Preliminary results indicate zones of elevated pore pressures form: 1) where slopes are underlain by continuous low-permeability altered layers, or 2) when the edifice has an altered core with saturated, less permeable limbs. The first scenario might control shallow collapses on the slopes above the altered layers. The second could promote deeper flank collapses that are initially limited to the summit and upper slopes, but could progress to the core of an edifice. In both scenarios, pore pressures can be further elevated by shallow intrusions, or evolve over longer time scales under forcing from regional heat flux. Geometries without confining low-permeability layers do not show these pressure effects. Our initial scenarios use radially symmetric models, but we are also simulating hydrothermal flow under real 3D geometries with asymmetric subsurface structures (Mount Adams). Simulation results will be used to inform 3D slope

  3. Historical landscape elements in preserving steppic species - vegetation responses on micro-topography and human disturbances

    NASA Astrophysics Data System (ADS)

    Deák, Balázs; Valkó, Orsolya; Török, Péter; Tóthmérész, Béla

    2017-04-01

    Land use changes of past centuries resulted in a considerable loss and isolation of grassland habitats worldwide which also led to a serious loss in ecosystem functions. In intensively used agricultural landscapes remnants of natural flora persisted only in small habitat islands embedded in a hostile matrix, which are inadequate for arable farming or construction. In the steppe zone of Eurasia burial mounds, so-called kurgans, have a great potential to preserve the natural flora and habitats and act as local biodiversity hotspots. Their special micro-topography and historical origin makes kurgans characteristic landscape elements of the steppe region. These features also result in a specific soil development and micro-climate, which makes kurgans especially adequate habitats for several steppe specialist plant species. Furthermore, they are proper objects for studying the effects of present and past human disturbances on the vegetation of semi-natural habitats. Exploration of the main factors driving biodiversity in isolated habitat fragments is crucial for understanding the ecological processes shaping their vegetation and for designing effective strategies for their protection. We surveyed the vegetation of 44 isolated kurgans in East-Hungary and studied the effects of habitat area, slope, recent disturbance, past destruction and the level of woody encroachment on the species richness and cover of grassland specialist and weedy species. We used model selection techniques and linear models for testing relevant factors affecting specialist species in grassland fragments. We found that the biodiversity conservation potential of kurgans is supported by their steep slopes, which provide adequate habitat conditions and micro-climate for steppic specialist plant species. By harbouring several grassland specialist species, kurgans have a great potential for preserving the natural species pool of even considerably altered agricultural landscapes, and can mitigate the

  4. The effect of boundary constraints on finite element modelling of the human pelvis.

    PubMed

    Watson, Peter J; Dostanpor, Ali; Fagan, Michael J; Dobson, Catherine A

    2017-05-01

    The use of finite element analysis (FEA) to investigate the biomechanics of anatomical systems critically relies on the specification of physiologically representative boundary conditions. The biomechanics of the pelvis has been the specific focus of a number of FEA studies previously, but it is also a key aspect in other investigations of, for example, the hip joint or new design of hip prostheses. In those studies, the pelvis has been modelled in a number of ways with a variety of boundary conditions, ranging from a model of the whole pelvic girdle including soft tissue attachments to a model of an isolated hemi-pelvis. The current study constructed a series of FEA models of the same human pelvis to investigate the sensitivity of the predicted stress distributions to the type of boundary conditions applied, in particular to represent the sacro-iliac joint and pubic symphysis. Varying the method of modelling the sacro-iliac joint did not produce significant variations in the stress distribution, however changes to the modelling of the pubic symphysis were observed to have a greater effect on the results. Over-constraint of the symphysis prevented the bending of the pelvis about the greater sciatic notch, and underestimated high stresses within the ilium. However, permitting medio-lateral translation to mimic widening of the pelvis addressed this problem. These findings underline the importance of applying the appropriate boundary conditions to FEA models, and provide guidance on suitable methods of constraining the pelvis when, for example, scan data has not captured the full pelvic girdle. The results also suggest a valid method for performing hemi-pelvic modelling of cadaveric or archaeological remains which are either damaged or incomplete.

  5. 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.

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

    PubMed

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

    2011-09-01

    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 (M(1)). The antagonistic crowns M(1) and P(2)-M(1) 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 M(1) and P(2)-M(1) 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 M(1) 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.

  7. 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

  8. Estimating human indoor exposure to elemental mercury from broken compact fluorescent lamps (CFLs).

    PubMed

    Salthammer, T; Uhde, E; Omelan, A; Lüdecke, A; Moriske, H-J

    2012-08-01

    The 2008 EU regulation, which prohibits conventional incandescent light bulbs, is to be implemented in phases, completing in 2012. One of the possible substitutes is the compact fluorescent lamp (CFL), which, however, does contain up to 5 mg of mercury in its elemental or amalgamated form. The question arises as to the possible exposure of individuals to mercury as a result of lamp breakage during operation or when disconnected from the power supply. Therefore, an apparatus was built to shatter CFLs and drop the shards onto glycol-modified polyethylene terephthalate, a carpeted floor, or laminate floor under defined climatic parameters and operating conditions. Six CFLs of different types and mercury content were studied. After the breakage of a common CFL containing liquid mercury, concentrations up to 8000 ng/m(3) were reached in the chamber. Much lower peak values were obtained with amalgam-type lamps (414 ng/m(3)) or with lamps with a shatter-proof coating (60 ng/m(3)). It was found that ventilation can considerably reduce the indoor air concentration within 20 min. Acute health effects would only be expected if the mercury is not removed immediately. Careful collection and disposal of the lamp fragments would also prevent dwellers from the risk of long-term exposure. After accidental breakage of a compact fluorescent lamp (CFL) indoors, dwellers could be exposed to high mercury concentrations. From the results of our studies in test chambers and real rooms using different lamp types and scenarios, it was possible to estimate the possible human uptake of mercury by inhalation. Immediate action is important to reduce indoor mercury concentrations to a minimum level. The first step is to maximize ventilation followed by careful collection of spilled mercury. © 2011 John Wiley & Sons A/S.

  9. Genomic Heat Shock Element Sequences Drive Cooperative Human Heat Shock Factor 1 DNA Binding and Selectivity*

    PubMed Central

    Jaeger, Alex M.; Makley, Leah N.; Gestwicki, Jason E.; Thiele, Dennis J.

    2014-01-01

    The heat shock transcription factor 1 (HSF1) activates expression of a variety of genes involved in cell survival, including protein chaperones, the protein degradation machinery, anti-apoptotic proteins, and transcription factors. Although HSF1 activation has been linked to amelioration of neurodegenerative disease, cancer cells exhibit a dependence on HSF1 for survival. Indeed, HSF1 drives a program of gene expression in cancer cells that is distinct from that activated in response to proteotoxic stress, and HSF1 DNA binding activity is elevated in cycling cells as compared with arrested cells. Active HSF1 homotrimerizes and binds to a DNA sequence consisting of inverted repeats of the pentameric sequence nGAAn, known as heat shock elements (HSEs). Recent comprehensive ChIP-seq experiments demonstrated that the architecture of HSEs is very diverse in the human genome, with deviations from the consensus sequence in the spacing, orientation, and extent of HSE repeats that could influence HSF1 DNA binding efficacy and the kinetics and magnitude of target gene expression. To understand the mechanisms that dictate binding specificity, HSF1 was purified as either a monomer or trimer and used to evaluate DNA-binding site preferences in vitro using fluorescence polarization and thermal denaturation profiling. These results were compared with quantitative chromatin immunoprecipitation assays in vivo. We demonstrate a role for specific orientations of extended HSE sequences in driving preferential HSF1 DNA binding to target loci in vivo. These studies provide a biochemical basis for understanding differential HSF1 target gene recognition and transcription in neurodegenerative disease and in cancer. PMID:25204655

  10. 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

  11. 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.

  12. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2003-01-01

    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 μg 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.

  14. Elemental transfer from Chinese soil via the diet to the whole human body.

    PubMed

    Zhu, Hong-da; Wu, Quan; Fan, Ti-Jiang; Liu, Qingfen; Zhang, We

    2008-12-01

    Based on results from recent studies of elemental dietary intake and organ or tissue content for adult Chinese men, quoted nationwide elemental concentrations in Chinese soil and newly published national average consumption of dietary foods, values of both transfer coefficients and discrimination factor (DF) for transfer from soil via the diet to both critical organs and the whole body have been calculated for important elements in radiation protection, including alkaline earths, alkali metals, rare earths and other related elements. These calculations have used both the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) model and the DF method. In the UNSCEAR model, the basic parameters used to describe the transport of radionuclides are the transfer coefficients P(ij), which describe the relationship of concentrations or other amounts between compartment i and the following compartment j, whereas the DF is the ratio between the transfer coefficients for one element and a chemically similar element. From a comparison of the transfer coefficients of different elements for a particular transport pathway, those for alkaline earths are generally speaking higher than those for halogen elements and alkali metals, whereas those for rare earth elements, U and Th are lower. Relative to Ca, the DFs of transfer from soil to diet and from diet to critical organs or the whole body for the other alkaline earth elements and Pb are all less than 1, the DFs for the other elements decrease with increasing or decreasing atomic number. For alkali metals, the DFs of transfer from diet to critical organs and the whole body seem to increase with increasing atomic number, but those from soil to diet decrease with increasing atomic number.

  15. 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.

  16. Trace elements in human cancerous and healthy tissues: A comparative study by EDXRF, TXRF, synchrotron radiation and PIXE

    NASA Astrophysics Data System (ADS)

    Carvalho, M. L.; Magalhães, T.; Becker, M.; von Bohlen, A.

    2007-09-01

    It is known that trace elements play an important role in a number of biological processes. These include the activation or inhibition of enzymatic reactions, competition between elements and metal proteins for binding positions and modifications in the permeability of cellular membranes. These elements may also influence carcinogenic processes, thus the knowledge of trace element concentrations in healthy and neoplastic tissues might help in diagnostic and in the etiology and development of cancer. This work intends to give an overview of the achieved results in the analysis of several healthy and neoplastic human tissues, using multi-elemental techniques. The described measurements were carried out by means of synchrotron radiation induced X-ray emission (SRIXE), energy dispersive X-ray fluorescence (EDXRF), total-reflection X-ray fluorescence (TXRF), and proton-induced X-ray emission (PIXE). A brief description of each method is given and the analytical results discussed and compared. There is a good agreement between the results obtained with the several techniques for the same tissue. However, the behavior of the elements is not always the same for the several analyzed tissues.

  17. Temperature Estimates for the Slow Slip Region on the Decollement Underlying the South Flank of Kilauea

    NASA Astrophysics Data System (ADS)

    Spinelli, G. A.

    2013-12-01

    Eleven slow slip events on the decollement beneath the south flank of Kilauea volcano have been documented geodetically since 1998 (Brooks et al., 2006; Montgomery-Brown et al., 2009; 2013). Tectonic tremor has not been observed associated with these events, in contrast to most slow slip events in subduction zones (Montgomery-Brown et al., 2013). The slow slip events occur on the decollement at ~8 km depth, and updip of the 'normal' earthquakes on the fault. Constraining temperatures on Kilauea's decollement allows comparisons between its slow slip events and those in subduction zones. Kilauea's slow slip events (~8 km depth) are significantly shallower than most subduction zone slow slip events. I estimate temperatures in a 2-D cross-section through the south flank of Kilauea by combining methods used in subduction zone thermal models (Wang et al., 1995) with elements of intrusion cooling models of volcanoes (e.g., Civetta et al., 2004). Temperatures in the cross-section are controlled by: 1) heat sources from friction on the decollement, radioactive decay, and volcanic activity, and 2) heat transport by conduction, advection of the volcanic pile to the southeast over the underlying oceanic lithosphere, and advective heat transport associated with groundwater flow. I examine the thermal effects of a range of effective friction coefficients on the fault from 0-0.2. I determine the potential effects of groundwater flow in the upper ~1-2 km of the onshore and near-offshore volcanic pile (e.g., Kauahikaua, 1993; Buttner and Huenges, 2003) on decollement temperatures. Finally, I examine how heat input from Kilauea volcano may result in higher decollement temperatures than at the same depth on plate boundary faults in subduction zones.

  18. Linear amplification mediated PCR--localization of genetic elements and characterization of unknown flanking DNA.

    PubMed

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

    2014-06-25

    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.

  19. 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