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Sample records for elements flanking human

  1. Novel variants of human SCaMC-3, an isoform of the ATP-Mg/P(i) mitochondrial carrier, generated by alternative splicing from 3'-flanking transposable elements.

    PubMed

    Del Arco, Araceli

    2005-08-01

    CaMCs (calcium-dependent mitochondrial carriers) represent a novel subfamily of metabolite carriers of mitochondria. The ATP-Mg/P(i) co-transporter, functionally characterized more than 20 years ago, has been identified to be a CaMC member. There are three isoforms of the ATP-Mg/P(i) carrier in mammals, SCaMC-1 (short CaMC-1), -2 and -3 (or APC-1, -3 and -2 respectively), corresponding to the genes SLC25A24, SLC25A25 and SLC25A23 respectively, as well as six N-terminal variants generated by alternative splicing for SCaMC-1 and -2 isoforms. In the present study, we describe four new variants of human SCaMC-3 generated by alternative splicing. The new mRNAs use the exon 9 3'-donor site and distinct 5'-acceptor sites from repetitive elements, in regions downstream of exon 10, the last exon in all SCaMCs. Transcripts lacking exon 10 (SCaMC-3b, -3b', -3c and -3d) code for shortened proteins lacking the last transmembrane domain of 422, 456 and 435 amino acids, and were found in human tissues and HEK-293T cells. Mitochondrial targeting of overexpressed SCaMC-3 variants is incomplete. Surprisingly, the import impairment is overcome by removing the N-terminal extension of these proteins, suggesting that the hydrophilic N-terminal domain also participates in the mitochondrial import process, as shown for the CaMC members aralar and citrin [Roesch, Hynds, Varga, Tranebjaerg and Koehler (2004) Hum. Mol. Genet. 13, 2101-2111].

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

    PubMed

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

    1995-11-24

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

  3. 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.

  4. Biogeochemical Fluxes Across the Juan de Fuca Ridge-Flank: Minor and Trace Element Systematics

    NASA Astrophysics Data System (ADS)

    Hulme, S. M.; Wheat, C. G.; Jannasch, H. W.

    2006-12-01

    Crustal ridge-flank hydrothermal convection of seawater profoundly affects; global geochemical fluxes and cycles, plate tectonics through crustal cooling, and the deep biosphere. Comprehensive assessment of chemical fluxes from this type of hydrothermal circulation has been obscured by sampling artifacts during sample retrieval and extraction from drilling and the lack of uncontaminated in situ samples. With the development of sealed borehole observatories (CORKs) it is now possible to obtainable uncontaminated crustal formation fluids. The Endeavor Segment of the Juan de Fuca Ridge presented an ideal region for addressing the effects of ridge flank hydrothermal circulation on global processes because of direct access to basement fluids through six CORKs and the known composition of nearby spring fluids. We present data from fluids collected via osmotically-pumped continuous fluid samplers (OsmoSamplers) from within sealed boreholes. Methods using high-resolution ICP-MS were developed to allow analysis of trace elements (V, Cr, Co, Ni, Cu, Zn, Rb, Y, Mo, Cd, Cs, Ba, and U) and the entire suite of rare-earth elements in 5ml of sample. Fluids from OsmoSamplers deployed at 3 drill sites (1024, 1026, and 1027) were analyzed along with borehole fluids collected at two additional sites (1025 and 1026). Pore fluids from multiple drilling legs were also compared for sampling artifacts associated with differing sediment core collection techniques. The results of this study determined which trace elements can be accurately determined from ocean drilling and pore water extraction from sediments and borehole sampling by comparison with the time-integrated samples obtained from within the sealed boreholes. Once the accurate composition of basement fluids was determined, it was possible to examine regional trends of the hydrothermal aquifer system both along and across strike of the ridge axis. These data of crustal fluids can then be compared to pore fluids collected during

  5. 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

  6. Specialized chromatin structure domain boundary elements flanking a Drosophila heat shock gene locus are under torsional strain in vivo.

    PubMed

    Jupe, E R; Sinden, R R; Cartwright, I L

    1995-02-28

    An in vivo assay employing psoralen cross-linking was used to investigate the presence of unrestrained supercoiling in DNA sequences located in nontranscribed regions flanking the 3' ends of the pair of divergent heat shock protein 70 (hsp70) genes at locus 87A7 of Drosophila. Two of the regions examined contain sequences comprising the previously defined specialized chromatin structure elements (scs and scs'). Both of these putative chromosomal domain boundaries exhibited very similar levels of unrestrained negative supercoiling that remained high regardless of the transcriptional status of the hsp70 genes. The steric accessibility of the scs region before heat shock was 3-fold higher than either flanking region (consistent with its previously documented DNase I hypersensitivity); this increased an additional 2-fold following hsp70 gene activation without a concomitant rise in the accessibility of flanking regions. Most notably, a sequence which lies outside the presumed 87A7 domain, as defined by the centromere-proximal scs element, exhibited no detectable torsional tension regardless of gene activity in the domain. A sequence located just inside the scs region displayed a low level of tension that was also essentially unaffected by transcription, consistent with data obtained previously for a similarly situated fragment at the centromere-distal scs' location. The existence of a highly localized region of supercoiling within the scs and scs' sequences might be related to their activity in vivo as insulators of chromosomal position effects in Drosophila. PMID:7873544

  7. [Analysis of conserved flanking elements associated with antibiotic resistance genes dissemination].

    PubMed

    Liu, Jian; Mao, Da-Qing; Ren, Jun; Luo, Yi; Cao, Wen-Qing

    2012-01-01

    The overuse of antibiotics in medicine, animal husbandry, and aquiculture industry increases the emergence of antibiotic resistant bacteria and antibiotic resistance genes (ARGs), and also, accelerates the dissemination of ARGs within environmental bacteria. In this study, the total DNA was directly extracted from environmental samples, and the upstream and downstream of antibiotic resistance genes were directly amplified by thermal asymmetric interlaced PCR (Tail-PCR) technique. By optimizing the Tail-PCR program, the multiple flanking sequences of tetW, including 6 upstream sequences and 9 downstream sequences, were simultaneously acquired. Through the bioinformatics analysis, the upstream of tetW presented a perfect inverted repeat (IR), a known tetW regulator peptide, and an insertional sequence (IS), whereas the downstream of tetW presented a most conservative fragment and a common open reading frame (ORF) coding methyltransferase. This study not only revealed several conserved flanking tetW gene modules, but also supplied a highly-efficient and convenient methodology for the research of tetW's dissemination within bacteria, i. e., several flanking sequences could be concisely obtained from one sample by using Tail-PCR program.

  8. 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 ...

  9. 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.

  10. Analysis of the role of 5' and 3' flanking sequence elements upon in vivo expression of the plant tRNATrp genes.

    PubMed Central

    Ulmasov, B; Folk, W

    1995-01-01

    We have isolated the majority (seven) of the tRNA(Trp) genes of Arabidopsis and have studied the 5' and 3' flanking sequence requirements for their efficient expression in vivo by using an assay requiring translational suppression of the luciferase reporter gene. The expressed tRNA(Trp) genes contain no highly conserved 5' flanking sequences; however, these sequences are distinctly AT rich, contain several possible TATA elements, and are bound in vitro by recombinant plant TATA binding protein. Replacement of the natural 5' flanking sequences with three different sequences lacking TATA elements reduced expression in vivo up to 10-fold; the same effect was observed when the TATA elements of the natural 5' sequences were inactivated by point mutations. Introduction of a single TATA element from the adenovirus major late promoter into an artificial 5' flanking region of the tRNA(Trp) gene enhanced expression in vivo when the TATA element was placed at position -32 relative to the first nucleotide of the mature tRNA sequence, but not when it was placed at position -24. Primer extension analyses of in vitro transcripts revealed that the position of the TATA element helps dictate the start site of transcription. Efficient expression of the tRNA genes in vivo also required 3' flanking sequences capable of terminating transcription. PMID:7580260

  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. A large duplication associated with dominant white color in pigs originated by homologous recombination between LINE elements flanking KIT.

    PubMed

    Giuffra, Elisabetta; Törnsten, Anna; Marklund, Stefan; Bongcam-Rudloff, Erik; Chardon, Patrick; Kijas, James M H; Anderson, Susan I; Archibald, Alan L; Andersson, Leif

    2002-10-01

    The Dominant White (I/KIT) locus is one of the major coat color loci in the pig. Previous studies showed that the Dominant White (I) and Patch (IP) alleles are both associated with a duplication including the entire KIT coding sequence. We have now constructed a BAC contig spanning the three closely linked tyrosine kinase receptor genes PDGFRA-KIT-KDR. The size of the duplication was estimated at about 450 kb and includes KIT, but not PDGFRA and KDR. Sequence analysis revealed that the duplication arose by unequal homologous recombination between two LINE elements flanking KIT. The same unique duplication breakpoint was identified in animals carrying the I and IP alleles across breeds, implying that Dominant White and Patch alleles are descendants of a single duplication event. An unexpected finding was that Piétrain pigs carry the KIT duplication, since this breed was previously assumed to be wild type at this locus. Comparative sequence analysis indicated that the distinct phenotypic effect of the duplication occurs because the duplicated copy lacks some regulatory elements located more than 150 kb upstream of KIT exon 1 and necessary for normal KIT expression.

  13. Evolution of a behavior-linked microsatellite-containing element in the 5' flanking region of the primate AVPR1A gene

    PubMed Central

    2008-01-01

    Background The arginine vasopressin V1a receptor (V1aR) modulates social cognition and behavior in a wide variety of species. Variation in a repetitive microsatellite element in the 5' flanking region of the V1aR gene (AVPR1A) in rodents has been associated with variation in brain V1aR expression and in social behavior. In humans, the 5' flanking region of AVPR1A contains a tandem duplication of two ~350 bp, microsatellite-containing elements located approximately 3.5 kb upstream of the transcription start site. The first block, referred to as DupA, contains a polymorphic (GT)25 microsatellite; the second block, DupB, has a complex (CT)4-(TT)-(CT)8-(GT)24 polymorphic motif, known as RS3. Polymorphisms in RS3 have been associated with variation in sociobehavioral traits in humans, including autism spectrum disorders. Thus, evolution of these regions may have contributed to variation in social behavior in primates. We examined the structure of these regions in six ape, six monkey, and one prosimian species. Results Both tandem repeat blocks are present upstream of the AVPR1A coding region in five of the ape species we investigated, while monkeys have only one copy of this region. As in humans, the microsatellites within DupA and DupB are polymorphic in many primate species. Furthermore, both single (lacking DupB) and duplicated alleles (containing both DupA and DupB) are present in chimpanzee (Pan troglodytes) populations with allele frequencies of 0.795 and 0.205 for the single and duplicated alleles, respectively, based on the analysis of 47 wild-caught individuals. Finally, a phylogenetic reconstruction suggests two alternate evolutionary histories for this locus. Conclusion There is no obvious relationship between the presence of the RS3 duplication and social organization in primates. However, polymorphisms identified in some species may be useful in future genetic association studies. In particular, the presence of both single and duplicated alleles in

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed

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

    2005-01-01

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

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

    SciTech Connect

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

    1987-11-01

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

  17. Regulated expression of chimaeric genes containing the 5'-flanking regions of human growth hormone-related genes in transiently transfected rat anterior pituitary tumor cells.

    PubMed Central

    Cattini, P A; Eberhardt, N L

    1987-01-01

    The expression and hormonal regulation of chimaeric genes containing the 5'-flanking regions of the normal human growth hormone (hGH-1), the variant hGH (hGH-2) and chorionic somatomammotropin (hCS-1) genes fused to the chloramphenicol acetyl transferase (CAT) gene has been examined after transient transfection into cultured rat pituitary (GC), and non-pituitary (HeLa and Rat 2) tumor cells. As assessed by levels of CAT activity, the hGH-1 and hCS-1 gene hybrids were expressed at 5- to 25-fold higher levels in GC cells than in HeLa or Rat 2 cells. The hGH-2 gene hybrid was expressed at very low levels in all 3 cell types. Triiodothyronine treatment of transiently transfected GC cells had little effect on CAT activity from the hGH-1 gene hybrid but increased CAT activity from the hCS-1 gene hybrid. A slight but significant increase in CAT expression was detected with both genes after dexamethasone treatment. The data indicate that elements present on the hGH-1 and hCS-1 genes' 5'-flanking DNA are required for the efficient expression of these genes in GC cells. Images PMID:3644237

  18. Neuropeptide Y and its flanking peptide in human endocrine tumors and plasma.

    PubMed

    Allen, J M; Yeats, J C; Causon, R; Brown, M J; Bloom, S R

    1987-06-01

    Neuropeptide Y (NPY) and its flanking peptide (CPON) were measured in extracts of pheochromocytomas (n = 26), ganglioneuroblastomas (n = 8), and other tumors (n = 95) and plasma (n = 38). NPY was present in high concentrations in the majority of the pheochromocytomas, but was absent in 3 tumors. Similar concentrations of NPY were measured using N- and C-terminal-directed antisera, and there was a good correlation between the concentrations of NPY immunoreactivity and CPON immunoreactivity in the same extracts. Gel permeation chromatography revealed that the separate peptides NPY and CPON were the major products. No significant amounts of a large mol wt precursor containing both immunoreactivities was found. Among the other tumors, 6 of 22 carcinoid tumors, 2 of 2 somatostatinomas, and 3 of 18 insulinomas contained detectable amounts of NPY. Plasma NPY concentrations were very low in normal subjects, and extraction and a 10-fold concentration step were necessary to establish the normal range (0.35-1.25 pmol/L). Plasma NPY concentrations were detectable in unextracted plasma (10 pmol/L) in 50% of patients with pheochromocytomas, but no correlation was found between plasma NPY concentrations and either plasma norepinephrine or epinephrine concentrations. These results indicate that 1) NPY and CPON are present in most, but not all, pheochromocytomas and ganglioneuroblastomas; 2) secretion of NPY immunoreactivity may be independent of that of catecholamines; 3) CPON immunoreactivity is present in plasma of patients with pheochromocytoma; 4) the majority of NPY and CPON immunoreactivities appears to be in the form of the separate free peptide, and there is very little precursor containing both immunoreactivities expressed in these tumors; and 5) NPY immunoreactivity is present in a variety of other endocrine tumors.

  19. The 3' flanking region of the human ABO histo-blood group gene is involved in negative regulation of gene expression.

    PubMed

    Sano, Rie; Nakajima, Tamiko; Takahashi, Keiko; Kubo, Rieko; Yazawa, Shin; Kominato, Yoshihiko

    2011-01-01

    Gene expression is driven by promoters, enhancers, silencers, and other cis-regulatory elements upstream and downstream of the gene. Previous studies of the regulation of human ABO gene transcription have focused mainly on the 5' region, including the core promoter and the region proximal to it. However, as the involvement of the 3' flanking region in transcriptional regulation has not yet been examined, we focused on this issue. The 3' region approximately 2.2kb downstream of the ABO gene was PCR-amplified and inserted into a cloning vector, followed by sequence determination and preparation of luciferase reporter vectors. Transient transfections into KATOIII and K562 cells were performed using various reporter plasmids containing the 3' region. The 3' region of the ABO gene, which was characterized by a high degree of sequence repetition, was effectively cloned by a single-copy cloning method. Transfections in KATOIII and K562 cells showed that negative elements were demonstrable within the 3' region. These observations suggest that negative regulatory elements seem to be present in the 3' region of ABO in both epithelial and erythroid lineages. As we had observed a negative region just upstream of the ABO promoter, transcription from ABO could be negatively regulated by repressive regions just upstream of the promoter and downstream of the gene. Further studies of the enhancer will be required for elucidating the molecular basis of ABO gene expression. PMID:21144789

  20. The human genes for hemophilia A and hemophilia B flank the X chromosome fragile site at Xq27.3.

    PubMed Central

    Purrello, M; Alhadeff, B; Esposito, D; Szabo, P; Rocchi, M; Truett, M; Masiarz, F; Siniscalco, M

    1985-01-01

    Two DNA recombinant clones, shown by separate studies to contain DNA sequences homologous to the genes coding for the human blood coagulation Factors VIII and IX, were hybridized in situ to metaphases or prometaphases derived from patients with the fragile-X syndrome and from a normal control. The results of these experiments indicate that (i) both genes are located in the subtelomeric region of the long arm of the human X chromosome flanking the fragile site at Xq27.3, (ii) the resolution of this localization is approximately 0.5% the length of the human haploid genome, i.e., 1.8 X 10(7) bp, (iii) the linear order of loci within the above region is Factor IX-fragile site-Factor VIII-Xqter. Both the localization and the linear order of these loci have been confirmed by Southern blotting studies using the same molecular probes and a panel of rodent-human somatic cell hybrids known to have retained different segments of the human X chromosome. The findings described herein and the knowledge that Factor IX deficiency recombines freely with at least two loci of the G6PD cluster support our hypothesis that the chromosomal region which includes the fragile-X site is normally a region of high meiotic recombination. Images Fig. 2. Fig. 3. PMID:3924593

  1. HNRNPA1 interacts with a 5′ flanking distal element of interleukin 6 and up-regulates its basal transcription

    PubMed Central

    Zheng, Dongling; Worthington, Jenny; Timms, John F.; Woo, Patricia

    2013-01-01

    Interleukin-6 (IL-6) is an important pro-inflammatory cytokine involved in many autoimmune and inflammatory diseases. We have shown previously that a region from −5307 to −5202 bp upstream of the IL-6 transcriptional start site is responsible for basal IL-6 gene expression and that there were DNA binding proteins involved from EMSA and transient expression experiments. Here we have combined surface plasmon resonance technology with mass spectrometry analysis and identified nuclear proteins bound to this region. HNRNPA1 and HNRNPA2B1 were found consistently. EMSA supershift and chromatin immunoprecipitation assays confirmed the involvement of HNRNPA1, but not HNRNPA2B1. Knocking down HNRNPA1 expression by siRNA resulted in reduced IL-6 transcriptional activity as assessed from transfection experiments using reporter constructs, mRNA and protein measurements. Overexpression of HNRNPA1 cDNA increased IL-6 mRNA expression. This regulation was dependent on the presence of the sequence from −5307 to −5202 bp of the IL-6 gene. Thus, HNRNPA1 is a novel transcriptional regulator of IL-6 expression, acting via the 5′ flanking sequence of the gene. PMID:23985572

  2. Elements in the distal 5'-flanking sequence and the first intron function cooperatively to regulate glutamine synthetase transcription during adipocyte differentiation.

    PubMed Central

    Hadden, T J; Ryou, C; Miller, R E

    1997-01-01

    Glutamine synthetase (GS) expression increases dramatically during adipocyte differentiation of confluent 3T3-L1 cells. To identify differentiation-responsive cis-acting elements in the GS gene, several GSfusion genes were prepared and analyzed in stably transfected 3T3-L1 cells under conditions that trigger adipocyte differentiation. We find that the GS proximal 5'-flanking sequence lacks the regulatory elements required for differentiation-responsive expression. In contrast, a 2 kb intron 1 restriction fragment fused upstream of a heterologous promoter does drive reporter gene expression during hormone-triggered differentiation. The enhancer activity was localized to a 310 bp sequence near the middle of intron 1. Expression of fusion genes that include this 310 bp sequence does not temporally coincide with native gene expression. However, a composite gene that includes a far upstream GS sequence and the 2 kb intron 1 sequence yields a qualitatively different pattern of expression that closely resembles that of the native GS gene. The far upstream sequence alone exhibits no enhancer activity. Electrophoretic mobility shift analyses indicate that a 32 bp sequence within the 310 bp functional enhancer specifically binds differentiation-associated nuclear proteins. Although a C/EBP consensus sequence occurs in the 32 bp fragment, supershift analyses exclude C/EBP isoforms as the binding factor. In contrast, mutational analysis of the putative enhancer suggests that an HNF-3 isoform is involved. Thus our data indicate that elements in the distal 5'-flanking sequence and the first intron function cooperatively to regulate GS transcription and that HNF-3 may participate in that regulation. PMID:9380519

  3. 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.

  4. Characterization of the 5'-flanking region and regulation of transcription of human BAFF-R gene.

    PubMed

    Yuan, Hongxiang; Wang, Yueguo; Wu, Xinhua; Wang, Huiming; Pu, Jiang; Ding, Weifeng; Wang, Mei; Shen, Xianjuan; Cong, Hui; Zhang, Lurong; Zhang, Mei; Ju, Shaoqing

    2010-03-01

    B-cell activating factor (BAFF) is critical for maintaining the development and homeostasis of B cells. Overexpression of BAFF is associated with autoimmune diseases and malignant B lymphoma. BAFF receptor (BAFF-R) was found to be a specific receptor of BAFF. It not only plays a significant role in splenic B-cell maturation but also works as a major mediator in BAFF-dependent costimulatory response in peripheral B and T cells. Previous studies have demonstrated that BAFF-R is related to several diseases; however, the molecular mechanism of BAFF-R genic transcription has not been clearly defined. The aim of this study was to investigate the transcriptional regulation of the BAFF-R gene. This study was designed to clone and characterize the 5'-regulatory region of the human BAFF-R gene and determine the mechanisms involved in its transcriptional regulation. In addition, the effects of interferon (IFN)-gamma and BAY11-7082 (inhibitor of nuclear factor [NF]-kappaB) on the expression and promoter activity of BAFF-R were examined. The results showed that the sequence between -1420 and +261 could be a core promoter region, and -1562 and -1420 bp harbored a transcriptive silencer. IFN-gamma promoted BAFF-R promoter activity and upregulated BAFF-R mRNA expression. BAY11-7082 (inhibitor of NF-kappaB) exhibited an inhibitory effect on BAFF-R promoter activity and downregulated BAFF-R mRNA expression. Our data provided novel evidence to clarify the mechanism of transcriptional regulation of BAFF-R and illustrated that IFN-gamma and NF-kappaB pathway were involved in regulating BAFF-R expression. Thus some BAFF-R-related diseases might be cured by blocking transcriptional regulation of BAFF-R and reducing its expression.

  5. 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.

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

    PubMed Central

    Bratke, J; Kietzmann, T; Jungermann, K

    1999-01-01

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

  7. 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.

  8. Structure and cell-specific expression of a cloned human retinol binding protein gene: the 5'-flanking region contains hepatoma specific transcriptional signals.

    PubMed

    D'Onofrio, C; Colantuoni, V; Cortese, R

    1985-08-01

    Human plasma retinol binding protein (RBP) is coded by a single gene and is specifically synthesized in the liver. We have characterized a lambda clone, from a human DNA library, carrying the gene coding for plasma RBP. Southern blot analysis and DNA sequencing show that the gene is composed of six exons and five introns. Primer elongation and S1 mapping experiments allowed the definition of the initiation of transcription and the identification of the putative promoter. The 5'-flanking region of the RBP gene was fused upstream to the coding sequence of the bacterial enzyme chloramphenicol acetyl transferase (CAT): the chimeric gene was introduced, by calcium phosphate precipitation, into the human hepatoma cell line Hep G2 and into HeLa cells. Efficient expression of CAT was obtained only in Hep G2. Primer elongation analysis of the RNA extracted from transfected Hep G2 showed that initiation of transcription of the transfected chimeric gene occurs at a position identical to that of the natural gene. Transcriptional analysis of Bal31 deletions from the 3' end of the RBP 5'-flanking DNA allowed the identification of the RBP gene promoter.

  9. 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.

  10. Many LINE1 elements contribute to the transcriptome of human somatic cells

    PubMed Central

    Rangwala, Sanjida H; Zhang, Lili; Kazazian, Haig H

    2009-01-01

    Background While LINE1 (L1) retroelements comprise nearly 20% of the human genome, the majority are thought to have been rendered transcriptionally inactive, due to either mutation or epigenetic suppression. How many L1 elements 'escape' these forms of repression and contribute to the transcriptome of human somatic cells? We have cloned out expressed sequence tags corresponding to the 5' and 3' flanks of L1 elements in order to characterize the population of elements that are being actively transcribed. We also examined expression of a select number of elements in different individuals. Results We isolated expressed sequence tags from human lymphoblastoid cell lines corresponding to 692 distinct L1 element sites, including 410 full-length elements. Four of the expression tagged sites corresponding to full-length elements from the human specific L1Hs subfamily were examined in European-American individuals and found to be differentially expressed in different family members. Conclusions A large number of different L1 element sites are expressed in human somatic tissues, and this expression varies among different individuals. Paradoxically, few elements were tagged at high frequency, indicating that the majority of expressed L1s are transcribed at low levels. Based on our preliminary expression studies of a limited number of elements in a single family, we predict a significant degree of inter-individual transcript-level polymorphism in this class of sequence. PMID:19772661

  11. 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.

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

    PubMed

    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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    1996-11-01

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

  1. Human and mouse ABCA1 comparative sequencing and transgenesis studies identify regulatory elements

    SciTech Connect

    Qiu, Yang; Cavelier, L.; Chiu, Sally; Rubin, Edward; Cheng, Jan-Fang

    2000-08-01

    The expression of ABCA1, a major participant in apolipoprotein mediated cholesterol efflux is highly regulated by a variety of factors including intracellular cholesterol concentration. To analyze its genomic organization and identify those sequences involved in its regulation we sequenced and compared approximately 200 Kb of orthologous DNA from mice and humans containing the ABCA1 gene and significant flanking DNA. The comparison revealed a variety of mouse human conserved sequences including 50 conserved ABCA1 exons over 147Kb of human and 124Kb of mouse genomic DNA as well as multiple mouse human conserved noncoding sequences. Using as a criteria for identifying putative regulatory elements in non-coding sequence, human and mouse sequences that were &62;75% identical for over 120 bp were screened for resulting in the identification of 34 elements. The two most highly conserved human mouse noncoding elements (CNS1: 88% identity over 498 bp, CNS2: 81% identity over 214 bp)! were also highly conserved in the ABCA1 genes of rats, dogs, cows, rabbits and pigs. Two independent studies have demonstrated that the DNA segments containing CNS2 function in vitro as a sterol response promoter. Support for the inclusion of major ABCA1 regulatory elements in the human genomic sequence examined was the demonstration that mice containing a human BAC transgene containing sequences exclusively from the analyzed interval, expressed human ABCA1 in a tissue distribution mimicking expression of endogenous mouse ABC1. These studies using a comparative genomic approach has characterized the structure of the human and mouse ABCA1 genes and has helped identify sequences participating in its expression.

  2. 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.

  3. Isolation of tetranucleotide repeat polymorphisms flanking the BRCA1 gene

    SciTech Connect

    Bennett-Baker, P.E.; Kiousis, S.; King, S.E.

    1996-02-15

    This article reports on the isolation of tetranucleotide repeat polymorphisms which flank the BRCA1 gene on human chromosome 17. BRCA1 has been linked to both hereditary breast and ovarian cancer. Fifteen new short tandem repeat polymorphisms (STRPs) flanking the BRCA1 locus are reported. 18 refs., 2 figs., 1 tab.

  4. 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

  5. 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.

  6. 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.

  7. The 5' flanking region of the gene for the Epstein-Barr virus-encoded nuclear antigen 2 contains a cell type specific cis-acting regulatory element that activates transcription in transfected B-cells.

    PubMed Central

    Ricksten, A; Olsson, A; Andersson, T; Rymo, L

    1988-01-01

    We have recently identified the promoter that positions the initiation (cap) site for RNA encoding the Epstein-Barr virus (EBV) determined nuclear antigen 2 (EBNA2) in transfected COS-1 cells. The cells were transfected with recombinant vectors that contained the BamHI WYH region of the EBV genome. In order to delineate regulatory DNA sequences required for the expression of EBNA2 the 5' flanking region of the gene was linked to reporter genes in expression vectors and transfected into EBV genome-negative lymphoid DG75 cells. We demonstrate that several cis-acting elements contribute to a transcriptional enhancer activity found in the region between nucleotides-553 and -86 relative to the cap site. The enhancer was active in lymphoid DG75 cells but not in HeLa cells and stimulated transcription also from the heterologous thymidine kinase (TK) and beta-globin promoters. Nuclear extracts of lymphoid cells contained protein factors that bound to the enhancer. The in vitro introduction of a mutation in the enhancer sequence that substantially reduced the transcription stimulatory activity concurrently blocked the binding of one of the factors. Images PMID:2843816

  8. 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

  9. Seasonal flank alopecia in affenpinschers.

    PubMed

    Waldman, L

    1995-06-01

    Two intact, distantly related, female affenpinschers, belonging to a breeder, were referred in March 1993 for the investigation of bilateral, symmetrical flank alopecia in one bitch and bilateral, symmetrical flank, dorsum and tail alopecia in the other; the alopecia occurred from November to May and January to May, respectively. During that period the bitches were kept in a conservatory without artificial heating or lighting. The owner reported that the mother of one bitch had had bilateral, symmetrical flank alopecia during one winter when kept in the conservatory, but was normal the following winter when kept in the house. Three other females and a male exhibited the same clinical signs when kept in the conservatory during the winter. Seasonal flank alopecia has not previously been reported in affenpinschers.

  10. Isolation of sequences flanking Ac insertion sites by Ac casting.

    PubMed

    Wang, Dafang; Peterson, Thomas

    2013-01-01

    Localizing Ac insertions is a fundamental task in studying Ac-induced mutation and chromosomal rearrangements involving Ac elements. Researchers may sometimes be faced with the situation in which the sequence flanking one side of an Ac/Ds element is known, but the other flank is unknown. Or, a researcher may have a small sequence surrounding the Ac/Ds insertion site and needs to obtain additional flanking genomic sequences. One way to rapidly clone unknown Ac/Ds flanking sequences is via a PCR-based method termed Ac casting. This approach utilizes the somatic transposition activity of Ac during plant development, and provides an efficient means for short-range genome walking. Here we describe the principle of Ac casting, and show how it can be applied to isolate Ac macrotransposon insertion sites.

  11. Essential and toxic trace elements in human health and disease

    SciTech Connect

    Prasad, A.S.

    1988-01-01

    This book examines the various aspects of trace elements essential for humans, including zinc, copper, iron, chromium, selenium, and manganese. In addition, the clinical importance of elements toxic to humans such as lead, cadmium, mercury, and aluminum are described in detail.

  12. Volcano Flank Terraces on Mars

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

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

  13. 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.

  14. Survey of trace elements in human nails: 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.

    1988-11-01

    Evaluation of trace metals in human tissues such as hair and nails has proven useful in the studies pertaining to chronic body exposure. These have also been suggested as indexes to evaluate environmental exposure by toxic trace metals. Though hair have been more extensively studied than finger nails, yet it remains that the latter tissue is equally promising in the characterization of certain diseases and abnormalities. These studies reveal continued interest in trace elements in the devitalized human tissues. The authors conducted earlier a survey of trace elements in human hair and in continuation of this study the present communication reports the data on trace elements in human nails in populations of diverse regions. Over 500 specimens drawn from Japan, India, Poland, Canada and U.S.A. were analyzed for 21 trace elements. An attempt has also been made to differentiate trace elements distributed according to age, sex and living habits of the donors.

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

    PubMed

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

    2015-12-10

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

  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. The Human Element in the Virtual Library.

    ERIC Educational Resources Information Center

    Saunders, Laverna M.

    1999-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

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

    PubMed Central

    McNamara, Anne V.; Adamson, Antony D.; Dunham, Lee S. S.; Semprini, Sabrina; Spiller, David G.; McNeilly, Alan S.; Mullins, John J.

    2016-01-01

    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. PMID:26691151

  4. Exonization of the LTR transposable elements in human genome

    PubMed Central

    Piriyapongsa, Jittima; Polavarapu, Nalini; Borodovsky, Mark; McDonald, John

    2007-01-01

    Background Retrotransposons have been shown to contribute to evolution of both structure and regulation of protein coding genes. It has been postulated that the primary mechanism by which retrotransposons contribute to structural gene evolution is through insertion into an intron or a gene flanking region, and subsequent incorporation into an exon. Results We found that Long Terminal Repeat (LTR) retrotransposons are associated with 1,057 human genes (5.8%). In 256 cases LTR retrotransposons were observed in protein-coding regions, while 50 distinct protein coding exons in 45 genes were comprised exclusively of LTR RetroTransposon Sequence (LRTS). We go on to reconstruct the evolutionary history of an alternatively spliced exon of the Interleukin 22 receptor, alpha 2 gene (IL22RA2) derived from a sequence of retrotransposon of the Mammalian apparent LTR retrotransposons (MaLR) family. Sequencing and analysis of the homologous regions of genomes of several primates indicate that the LTR retrotransposon was inserted into the IL22RA2 gene at least prior to the divergence of Apes and Old World monkeys from a common ancestor (~25 MYA). We hypothesize that the recruitment of the part of LTR as a novel exon in great ape species occurred prior to the divergence of orangutans and humans from a common ancestor (~14 MYA) as a result of a single mutation in the proto-splice site. Conclusion Our analysis of LRTS exonization events has shown that the patterns of LRTS distribution in human exons support the hypothesis that LRTS played a significant role in human gene evolution by providing cis-regulatory sequences; direct incorporation of LTR sequences into protein coding regions was observed less frequently. Combination of computational and experimental approaches used for tracing the history of the LTR exonization process of IL22RA2 gene presents a promising strategy that could facilitate further studies of transposon initiated gene evolution. PMID:17725822

  5. 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)

  6. 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.

  7. Identification of hepatic nuclear factor 1 binding sites in the 5′ flanking region of the human phenylalanine hydroxylase gene: Implication of a dual function of phenylalanine hydroxylase stimulator in the phenylalanine hydroxylation system

    PubMed Central

    Lei, Xiang-Dong; Kaufman, Seymour

    1998-01-01

    Phenylalanine hydroxylase stimulator (PHS) is a component of the phenylalanine hydroxylation system that is involved in the regeneration of the cofactor tetrahydrobiopterin. It is also identical to the dimerization cofactor of hepatocyte nuclear factor 1 (HNF1) (DCoH) that is able to enhance the transcriptional activity of HNF1. Moreover, it has the structural potential for binding macromolecules such as proteins and nucleic acids, consistent with its involvement in gene expression. We investigated whether PHS/DCoH could enhance the expression of phenylalanine hydroxylase (PAH). Cotransfection assays showed that DCoH itself could not transactivate the 9-kb human PAH 5′ flanking fragment. However, this 9-kb fragment was transactivated by HNF1 in a dose-dependent manner with a maximum of nearly 8-fold activation; DCoH potentiated this transactivation by another 1.6-fold. The HNF1 binding sites were located at −3.5 kb in a region that is 77.5% identical to the mouse liver-specific hormone-inducible PAH gene enhancer. This study suggests a possible dual function of PHS in vivo in the human phenylalanine hydroxylation system: it is involved in the regeneration of the cofactor tetrahydrobiopterin and can also enhance the expression of the human PAH gene. PMID:9465044

  8. 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

  9. Acid precipitation--effects on trace elements and human health.

    PubMed

    Gerhardsson, L; Oskarsson, A; Skerfving, S

    1994-08-22

    Environmental pollution by acid precipitation increases the solubilization and mobilization of toxic metals. Through the food chain, this may alter the intake of toxic and essential elements in man. Potential adverse health effects could follow after increased human exposure. For the general population, the exposure pattern and health effects caused by aluminium, cadmium, lead and mercury are of particular concern. Although there are several indications that the exposure to toxic elements (e.g. aluminium, cadmium, lead and methylmercury), as well as the intake of essential elements (e.g. selenium), may be affected by acid precipitation, there is presently no firm evidence of adverse health effects in man. However, the present data clearly indicate that the safety margins are small. Thus, the ongoing acidification in many areas must be stopped before such effects become evident. The effects on trace element status and human health by acid precipitation were discussed at the ISTERH (International Society for Trace Element Research in Humans) Conference in Stockholm, May, 1992. The main findings are briefly summarized here.

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

    PubMed

    2012-09-01

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

  11. 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

  12. 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…

  13. 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

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

    PubMed Central

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

    2002-01-01

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

  15. Human performance: An essential element in materials control and accountability

    SciTech Connect

    Haber, S.B.; Allentuck, J.

    1996-10-01

    The importance of the role of human performance in the successful and effective operation of many activities throughout many industries has been well documented. Most closely related to the materials control and accountability area is the work in human factors that has been ongoing in the U.S. nuclear industry since the Three Mile Island Nuclear Power Plant accident in 1979. Research related to the role of human reliability, human-system interface, and organization and management influences has been and is still being conducted to identify ways to enhance the safe and effective operation of nuclear facilities. This paper will discuss these human performance areas and how they relate to the materials control and accountability area. Particular attention will be focussed on the notion of {open_quotes}safety culture{close_quotes} and how it can be defined and measured for understanding the values and attitudes held by individuals working in the materials control area. It is widely believed that the culture of an organization, which reflects the expectations and values of the management of an organization, is a key element to the operation of that organization. The human performance element is one which has not received a great deal of consideration in the materials control and accountability area and yet it will be demonstrated that it is an essential component to ensure the success of safeguards activities.

  16. Conserved sequences in both coding and 5' flanking regions of mammalian opal suppressor tRNA genes.

    PubMed Central

    Pratt, K; Eden, F C; You, K H; O'Neill, V A; Hatfield, D

    1985-01-01

    The rabbit genome encodes an opal suppressor tRNA gene. The coding region is strictly conserved between the rabbit gene and the corresponding gene in the human genome. The rabbit opal suppressor gene contains the consensus sequence in the 3' internal control region but like the human and chicken genes, the rabbit 5' internal control region contains two additional nucleotides. The 5' flanking sequences of the rabbit and the human opal suppressor genes contain extensive regions of homology. A subset of these homologies is also present 5' to the chicken opal suppressor gene. Both the rabbit and the human genomes also encode a pseudogene. That of the rabbit lacks the 3' half of the coding region. Neither pseudogene has homologous regions to the 5' flanking regions of the genes. The presence of 5' homologies flanking only the transcribed genes and not the pseudogenes suggests that these regions may be regulatory control elements specifically involved in the expression of the eukaryotic opal suppressor gene. Moreover the strict conservation of coding sequences indicates functional importance for the opal suppressor tRNA genes. Images PMID:4022772

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

  19. 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.

  20. 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

  1. A knowledgebase of the human Alu repetitive elements.

    PubMed

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

    2016-04-01

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

  2. A knowledgebase of the human Alu repetitive elements.

    PubMed

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

    2016-04-01

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

  3. 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.

  4. NASA Human Research Program Space Radiation Program Element

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  5. 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.

  6. Transposable elements have contributed to thousands of human proteins.

    PubMed

    Britten, Roy

    2006-02-01

    This is a report of many distant but significant protein sequence relationships between human proteins and transposable elements (TEs). The libraries of human repeated sequences contain the DNA sequences of many TEs. These were translated in all reading frames, ignoring stop codons, and were used as amino acid sequence probes to search with BLASTP for similar sequences in a library of 25,193 human proteins. The probes show regions of significant amino acid sequence similarity to 1,950 different human genes, with an expectation of <10(-3). In comparison with previous REPEATMASKER (Institute for Systems Biology, Seattle) studies, these probes detect many more TE sequences in more human coding sequences with greater length than previous work using DNA sequences. If the criterion is opened, very many matches are found occurring on 4,653 different genes after correction for the number seen with random amino acid sequence probes. The processes that led to these extensive sets of sequence relationships between TEs and coding sequences of human genes have been a major source of variation and novel genes during evolution. This paper lists the number of sequence similarities seen by amino acid sequence comparison, which is surely an underestimate of the actual number of significant relationships. It appears that many of these are the result of past events of duplication of genes or gene regions, rather than a direct result of TE insertion. This report of observable relationships leaves to the future the functional implications as well as the detection of the events of TE insertion. PMID:16443682

  7. Expression of the human Hand1 gene in trophoblastic cells is transcriptionally regulated by activating and repressing specificity protein (Sp)-elements.

    PubMed

    Vasicek, Richard; Meinhardt, Gudrun; Haidweger, Eva; Rotheneder, Hans; Husslein, Peter; Knöfler, Martin

    2003-01-01

    The tissue-specific basic helix-loop-helix protein Hand1 is essential for the formation of trophoblast giant cells of the murine placenta. In humans, Hand1 is detectable in trophoblastic tumour cells suggesting an equivalent role in trophoblast differentiation. To understand its mode of expression we have cloned and characterized the human Hand1 gene promoter. Primer extension analyses suggest that transcription initiates 19 nucleotides downstream of the TATA element of the proximal 5' flanking region. Expression of luciferase reporter constructs harboring deletions of the 9.5 kb Hand1 5' flanking sequence defines a promoter region within 274 bp upstream of the transcriptional start site. Compared to a reporter bearing only the TATA box, the proximal promoter activates transcription up to 30-fold. However, transcriptional activity of the region was observed in both Hand1-expressing and non-expressing cell lines. Sequencing, DNAseI footprint analyses and electrophoretic mobility shift assays reveal the presence of four GC-rich sequences, which show different affinities to the endogenous specificity proteins (Sp), and a CCAAT box. In vitro, the Sp-elements mainly interact with Sp1 and Sp3 while the CCAAT element is recognized by the alpha CAAT binding factor protein. Mutant luciferase reporters bearing single active or inactive recognition sites demonstrate that two of the four Sp-binding sites (I and IV) contribute little to the overall transcription rate. The two other Sp-cognate sequences, II and III, downregulate and activate reporter expression 2.3- and 2.6-fold, respectively. Co-transfections of Sp1/Sp3 expression vectors and mutated reporter constructs in Sp-deficient SL2 cells indicate that the Sp-binding site II and III indeed function as repressing and activating enhancer sequences. In summary, the data suggest that constitutive expression of the Hand1 gene in cultured cells is regulated by a complex interplay of Sp-proteins interacting with activator and

  8. Characterization of the rat glutathione S-transferase Yc2 subunit gene, GSTA5: identification of a putative antioxidant-responsive element in the 5'-flanking region of rat GSTA5 that may mediate chemoprotection against aflatoxin B1.

    PubMed

    Pulford, D J; Hayes, J D

    1996-08-15

    We have isolated and characterized genomic DNA encoding the rat glutathione S-transferase Yc2 subunit. This protein is now referred to as rGSTA5 and is noteworthy because of its high activity towards aflatoxin B1-8,9-epoxide, its marked inducibility by chemoprotectors, its sex-specific regulation, and its over-expression in hepatoma and preneoplastic nodules. The rGSTA5 gene, which was isolated on two overlapping bacteriophage lambda clones, is approx. 12 kb in length and, unlike other class Alpha genes described to date, it comprises six exons. The transcription start site has been identified 228 bp upstream from the ATG translational initiation codon, and is situated 51 bp downstream from a consensus TATA-box. Deletion analysis, using luciferase reporter constructs, has shown that the region between -177 bp and +65 bp from the transcriptional start site contains a functional promoter. Computer-assisted analysis of the upstream sequence has indicated the presence of an antioxidant-responsive element (ARE), and several elements thought to be required for tissue-specific expression of the enzyme. In addition, several putative oestrogen-responsive half sites were observed in both upstream and intronic sequences. PMID:8761455

  9. 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.

  10. Colored neon flanks and line gap enhancement.

    PubMed

    Redies, C; Spillmann, L; Kunz, K

    1984-01-01

    When a colored line connects two black (or differently colored) lines across a gap, colored neon flanks are seen on either side of it. These flanks extend over gap sizes of 50 min arc foveally and are not explained by Bezold-type assimilation. They may be elicited by black lines as short as 6 min arc adjoining the colored line at each end. To maximize these flanks, the black and colored lines must appear linearly continuous. Nonaligned junctions weaken the effect and an angular tilt of more than 40 dog destroys it. In this and other respects, (local) neon flanks are similar to van Tuijl's (global) neon color spreading (1975). Both phenomena have analogs in brightness perception. We propose that neon spreading is a lateral extension of neon flanks across the empty space between them, and discuss similarities of these effects with other brightness illusions (Schumann, Prandtl, Ehrenstein). For this group of illusions the term "line gap enhancement" is introduced to imply perceptual enhancement of changes in brightness and/or color along lines. Correspondences between the psychophysical properties and structural prerequisites for line gap enhancement on one hand and neuronal response properties of end-zone inhibited (hypercomplex) cortical cells on the other are discussed.

  11. 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

  12. 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.

  13. 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

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

    PubMed

    Tapiero, Haim; Tew, Kenneth D

    2003-11-01

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

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

    PubMed

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

    2002-01-01

    Kappa-casein plays an essential role in the formation, stabilisation and aggregation of milk micelles. Control of kappa-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 kappa-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 kappa-casein sequences. This study identified conserved candidate transcriptional regulatory elements within the kappa-casein gene promoter.

  16. Volcano Flank Structures on Earth and Mars

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

  17. 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. PMID:19827322

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Chromatin Insulator Elements Block Transgene Silencing in Engineered Human Embryonic Stem Cell Lines at a Defined Chromosome 13 Locus

    PubMed Central

    MacArthur, Chad C.; Xue, Haipeng; Van Hoof, Dennis; Lieu, Pauline T.; Dudas, Miroslav; Fontes, Andrew; Swistowski, Andrzej; Touboul, Thomas; Seerke, Rina; Laurent, Louise C.; Loring, Jeanne F.; German, Michael S.; Zeng, Xianmin; Rao, Mahendra S.; Lakshmipathy, Uma; Chesnut, Jonathan D.

    2012-01-01

    Lineage reporters of human embryonic stem cell (hESC) lines are useful for differentiation studies and drug screening. Previously, we created reporter lines driven by an elongation factor 1 alpha (EF1α) promoter at a chromosome 13q32.3 locus in the hESC line WA09 and an abnormal hESC line BG01V in a site-specific manner. Expression of reporters in these lines was maintained in long-term culture at undifferentiated state. However, when these cells were differentiated into specific lineages, reduction in reporter expression was observed, indicating transgene silencing. To develop an efficient and reliable genetic engineering strategy in hESCs, we used chromatin insulator elements to flank single-copy transgenes and integrated the combined expression constructs via PhiC31/R4 integrase-mediated recombination technology to the chromosome 13 locus precisely. Two copies of cHS4 double-insulator sequences were placed adjacent to both 5′ and 3′ of the promoter reporter constructs. The green fluorescent protein (GFP) gene was driven by EF1α or CMV early enhancer/chicken β actin (CAG) promoter. In the engineered hESC lines, for both insulated CAG-GFP and EF1α-GFP, constitutive expression at the chromosome 13 locus was maintained during prolonged culture and in directed differentiation assays toward diverse types of neurons, pancreatic endoderm, and mesodermal progeny. In particular, described here is the first normal hESC fluorescent reporter line that robustly expresses GFP in both the undifferentiated state and throughout dopaminergic lineage differentiation. The dual strategy of utilizing insulator sequences and integration at the constitutive chromosome 13 locus ensures appropriate transgene expression. This is a valuable tool for lineage development study, gain- and loss-of-function experiments, and human disease modeling using hESCs. PMID:21699412

  3. 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.

  4. 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.

  5. 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.

  6. West Flank Coso, CA FORGE Seismic Reflection

    DOE Data Explorer

    Doug Blankenship

    2016-05-16

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

  7. Cloning, sequencing, and functional analysis of the 5'-flanking region of the rat 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase gene.

    PubMed

    Lin, H K; Penning, T M

    1995-09-15

    Rat liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (3 alpha-HSD/DD) is a member of the aldo-keto reductase gene superfamily. It displays high constitutive expression and inactivates circulating steroid hormones and suppresses the formation of polycyclic aromatic hydrocarbon anti- and syn-diol-epoxides (ultimate carcinogens). To elucidate mechanisms responsible for constitutive expression of the 3 alpha-HSD/DD gene a rat genomic library obtained from adult Sprague-Dawley female liver (HaeIII partial digest) was screened, using a probe corresponding to the 5'-end of the cDNA (-15 to +250), and a 15.8-kb genomic clone was isolated. Sequencing revealed that 6.3 kb contained exon 1 (+16 to +138 bp) plus additional introns and exons. The transcription start site (+1) was located by primer extension analysis, and the initiation codon, ATG, was located at +55 bp. The remaining 9.5 kb represented the 5'-flanking region of the rat 3 alpha-HSD/DD gene. A 1.6-kb fragment of this region was sequenced. A TATTTAA sequence (TATA box) was found at 33 bp upstream from the major transcription start site. cis-acting elements responsible for the constitutive expression of the rat 3 alpha-HSD/DD gene were located on the 5'-flanking region by transient transfection of reporter-gene (chloramphenicol acetyl transferase, CAT) constructs into human hepatoma cells (HepG2). CAT assays identified the basal promoter between (-199 and +55 bp), the presence of a proximal enhancer (-498 to -199 bp) which stimulated CAT activity 6-fold, the existence of a powerful silencer (-755 to -498 bp), and a strong distal enhancer (-4.0 to -2.0 kb) which increased CAT activity by 20-40-fold. A computer search of available consensus sequences for trans-acting factors revealed that a cluster of Oct-sites were uniquely located in the silencer region. Using the negative response element (-797 to -498 bp) as a probe and nuclear extracts from HepG2 cells, three bands were identified by gel mobility shift

  8. Overlapping protein-binding sites within a negative regulatory element modulate the brain-preferential expression of the human HPRT gene

    SciTech Connect

    Rincon-Limas, D.E.; Amaya-Manzanares, E.; Nino-Rosales, M.L.

    1994-09-01

    The hypoxanthine phosphoribosyltransferase (HPRT) gene, whose deficiency in humans causes the Lesch-Nyhan syndrome, is constitutively expressed at low levels in all tissues but at higher levels in the brain, the significance and mechanism of which is unknown. Towards dissecting this molecular mechanism, we have previously identified a 182 bp element (hHPRT-NE) within the 5{prime}-flanking region of the human HPRT gene which is involved not only in conferring neuronal specificity but also in repressing gene expression in non-neuronal tissues. Here we report that this element interacts with different nuclear proteins, some of which are present specifically in neuronal cells (complex I) and others of which are present in cells showing constitutive expression of the gene (complex II). In addition, we found that complex I factors are expressed in human NT2/D1 cells following induction of neuronal differentiation by retinoic acid. This finding correlates with an increase of HPRT gene transcription following neuronal differentiation, as demonstrated by RT-PCR and RNAase protection assays. We also mapped the binding sites for both complexes to a 60 bp region which, when tested by transient transfections in cultured fibroblasts, functioned as a repressor element. Methylation interference footprinting revealed a minimal unique DNA motif as the binding site for nuclear proteins from both neuronal and non-neuronal sources. Moreover, UV-crosslinking experiments showed that both complexes are formed by the association of several distinct proteins. Strikingly, site-directed mutagenesis of the footprinted region indicated that different nucleotides are essential for the association of these two complexes. These data suggest that differential formation of DNA-protein complexes at this regulatory domain could be a major determinant in the brain-preferential expression of the human HPRT gene.

  9. 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.

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

    PubMed

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

    1984-08-25

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

  11. 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.

  12. 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.

  13. 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.

  14. Stable reconnection at the dusk flank magnetopause

    NASA Astrophysics Data System (ADS)

    Gomez, R. G.; Vines, S. K.; Fuselier, S. A.; Cassak, P. A.; Strangeway, R. J.; Petrinec, S. M.; Burch, J. L.; Trattner, K. J.; Russell, C. T.; Torbert, R. B.; Pollock, C.; Young, D. T.; Lewis, W. S.; Mukherjee, J.

    2016-09-01

    The dusk flank magnetopause was surveyed with instruments on board the Magnetospheric Multiscale (MMS) spacecraft on 28 August 2015 between 13:55 UT and 14:15 UT during a period of persistent southward interplanetary magnetic field (IMF) with varying dawn-dusk component. Plasma measurements (500 eV electrons, > 2 keV ions) revealed the existence of at least one active reconnection region that persisted throughout the interval. The reconnection region convected equatorward despite the poleward and tailward magnetosheath flow, which ranged from slightly sub-Alfvénic to slightly super-Alfvénic throughout the interval. These results suggest that magnetic reconnection moved in response to changes in the IMF clock angle rather than the magnetosheath flow, which is corroborated using predictions of the maximum magnetic shear model.

  15. Identification of altered cis-regulatory elements in human disease.

    PubMed

    Mathelier, Anthony; Shi, Wenqiang; Wasserman, Wyeth W

    2015-02-01

    It has long been appreciated that variations in regulatory regions of genes can impact gene expression. With the advent of whole-genome sequencing (WGS), it has become possible to begin cataloging these noncoding variants. Evidence continues to accumulate linking clinical cases with cis-regulatory element disruption in a wide range of diseases. Identifying variants is becoming routine, but assessing their impact on regulation remains challenging. Bioinformatics approaches that identify variations functionally altering transcription factor (TF) binding are increasingly important for meeting this challenge. We present the current state of computational tools and resources for identifying the genomic regulatory components (cis-regulatory regions and TF binding sites, TFBSs) controlling gene transcriptional regulation. We review how such approaches can be used to interpret the potential disease causality of point mutations and small insertions or deletions. We hope this will motivate further the development of methods enabling the identification of etiological cis-regulatory variations.

  16. Comparative Analysis of Transposable Element Vector Systems in Human Cells

    PubMed Central

    Grabundzija, Ivana; Irgang, Markus; Mátés, Lajos; Belay, Eyayu; Matrai, Janka; Gogol-Döring, Andreas; Kawakami, Koichi; Chen, Wei; Ruiz, Patricia; Chuah, Marinee K. L.; VandenDriessche, Thierry; Izsvák, Zsuzsanna; Ivics, Zoltán

    2010-01-01

    Transposon-based gene vectors have become indispensable tools in vertebrate genetics for applications ranging from insertional mutagenesis and transgenesis in model species to gene therapy in humans. The transposon toolkit is expanding, but a careful, side-by-side characterization of the diverse transposon systems has been lacking. Here we compared the Sleeping Beauty (SB), piggyBac (PB), and Tol2 transposons with respect to overall activity, overproduction inhibition (OPI), target site selection, transgene copy number as well as long-term expression in human cells. SB was the most efficient system under conditions where the availability of the transposon DNA is limiting the transposition reaction including hard-to-transfect hematopoietic stem/progenitor cells (HSCs), and the most sensitive to OPI, underpinning the need for careful optimization of the transposon components. SB and PB were about equally active, and both more efficient than Tol2, under nonrestrictive conditions. All three systems provided long-term transgene expression in human cells with minimal signs of silencing. Indeed, mapping of Tol2 insertion sites revealed significant underrepresentation within chromosomal regions with H3K27me3 histone marks typically associated with transcriptionally repressed heterochromatin. SB, Tol2, and PB constitute complementary research tools for gene transfer in mammalian cells with important implications for fundamental and translational research. PMID:20372108

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2010-05-01

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

  19. 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.

  20. 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.

  1. Effects of controlled element dynamics on human feedforward behavior in ramp-tracking tasks.

    PubMed

    Laurense, Vincent A; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus René M; Mulder, Max

    2015-02-01

    In real-life manual control tasks, human controllers are often required to follow a visible and predictable reference signal, enabling them to use feedforward control actions in conjunction with feedback actions that compensate for errors. Little is known about human control behavior in these situations. This paper investigates how humans adapt their feedforward control dynamics to the controlled element dynamics in a combined ramp-tracking and disturbance-rejection task. A human-in-the-loop experiment is performed with a pursuit display and vehicle-like controlled elements, ranging from a single integrator through second-order systems with a break frequency at either 3, 2, or 1 rad/s, to a double integrator. Because the potential benefits of feedforward control increase with steeper ramp segments in the target signal, three steepness levels are tested to investigate their possible effect on feedforward control with the various controlled elements. Analyses with four novel models of the operator, fitted to time-domain data, reveal feedforward control for all tested controlled elements and both (nonzero) tested levels of ramp steepness. For the range of controlled element dynamics investigated, it is found that humans adapt to these dynamics in their feedforward response, with a close to perfect inversion of the controlled element dynamics. No significant effects of ramp steepness on the feedforward model parameters are found.

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

    PubMed

    Skeie, Jessica M; Mahajan, Vinit B

    2011-01-01

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

  3. Somatic expression of LINE-1 elements in human tissues.

    PubMed

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

    2010-07-01

    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 beta-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.

  4. Repeat-element driven activation of proto-oncogenes in human malignancies.

    PubMed

    Lamprecht, Björn; Bonifer, Constanze; Mathas, Stephan

    2010-11-01

    Recent data demonstrated that the aberrant activity of endogenous repetitive elements of the DNA in humans can drive the expression of proto-oncogenes. This article summarizes these results and gives an outlook on the impact of these findings on the pathogenesis and therapy of human cancer.

  5. 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.

  6. A novel regulatory element between the human FGA and FGG genes.

    PubMed

    Fish, Richard J; Neerman-Arbez, Marguerite

    2012-09-01

    High circulating fibrinogen levels correlate with cardiovascular disease (CVD) risk. Fibrinogen levels vary between people and also change in response to physiological and environmental stimuli. A modest proportion of the variation in fibrinogen levels can be explained by genotype, inferring that variation in genomic sequences that regulate the fibrinogen genes ( FGA , FGB and FGG ) may affect hepatic fibrinogen production and perhaps CVD risk. We previously identified a conserved liver enhancer in the fibrinogen gene cluster (CNC12), between FGB and FGA . Genome-wide Chromatin immunoprecipitation-sequencing (ChIP-seq) demonstrated that transcription factors which bind fibrinogen gene promoters also interact with CNC12, as well as two potential fibrinogen enhancers (PFE), between FGA and FGG . Here we show that one of the PFE sequences has potent hepatocyte enhancer activity. Using a luciferase reporter gene system, we found that PFE2 enhances minimal promoter- and FGA promoter-driven gene expression in hepatoma cells, regardless of its orientation with respect to the promoters. A region within PFE2 bears a short series of conserved nucleotides which maintain enhancer activity without flanking sequence. We also demonstrate that PFE2 is a liver enhancer in vivo, driving enhanced green fluorescent protein expression in transgenic zebrafish larval livers. Our study shows that combining public domain ChIP-seq data with in vitro and in vivo functional tests can identify novel fibrinogen gene cluster regulatory sequences. Variation in such elements could affect fibrinogen production and influence CVD risk.

  7. Dissecting a locus control region: facilitation of enhancer function by extended enhancer-flanking sequences.

    PubMed Central

    Aronow, B J; Ebert, C A; Valerius, M T; Potter, S S; Wiginton, D A; Witte, D P; Hutton, J J

    1995-01-01

    Using transgenic mice, we have defined novel gene regulatory elements, termed "facilitators." These elements bilaterally flank, by up to 1 kb, a 200-bp T-cell-specific enhancer domain in the human adenosine deaminase (ADA) gene. Facilitators were essential for gene copy-proportional and integration site-independent reporter expression in transgenic thymocytes, but they had no effect on the enhancer in transfected T cells. Both segments were required. Individual segments had no activity. A lack of facilitator function caused positional susceptibility and prevented DNase I-hypersensitive site formation at the enhancer. The segments were required to be at opposed ends of the enhancer, and they could not be grouped together. Reversing the orientation of a facilitator segment caused a partial loss of function, suggesting involvement of a stereospecific chromatin structure. trans-acting factor access to enhancer elements was modeled by exposing nuclei to a restriction endonuclease. The enhancer domain was accessible to the 4-cutter DpnII in a tissue- and cell-type-specific fashion. However, unlike DNase I hypersensitivity and gene expression, accessibility to the endonuclease could occur without the facilitator segments, suggesting that an accessible chromatin domain is an intermediate state in the activational pathway. These results suggest that facilitators (i) are distinct from yet positionally constrained to the enhancer, (ii) participate in a chromatin structure transition that is necessary for the DNase I hypersensitivity and the transcriptional activating function of the enhancer, and (iii) act after cell-type-specific accessibility to the enhancer sequences is established by factors that do not require the facilitators to be present. PMID:7823928

  8. Eukaryote-specific insertion elements control human ARGONAUTE slicer activity.

    PubMed

    Nakanishi, Kotaro; Ascano, Manuel; Gogakos, Tasos; Ishibe-Murakami, Satoko; Serganov, Artem A; Briskin, Daniel; Morozov, Pavel; Tuschl, Thomas; Patel, Dinshaw J

    2013-06-27

    We have solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify changes that evolutionarily rendered hAGO1 inactive, we compared our structure with guide-RNA-containing and cleavage-active hAGO2. Aside from mutation of a catalytic tetrad residue, proline residues at positions 670 and 675 in hAGO1 introduce a kink in the cS7 loop, forming a convex surface within the hAGO1 nucleic-acid-binding channel near the inactive catalytic site. We predicted that even upon restoration of the catalytic tetrad, hAGO1-cS7 sterically hinders the placement of a fully paired guide-target RNA duplex into the endonuclease active site. Consistent with this hypothesis, reconstitution of the catalytic tetrad with R805H led to low-level hAGO1 cleavage activity, whereas combining R805H with cS7 substitutions P670S and P675Q substantially augmented hAGO1 activity. Evolutionary amino acid changes to hAGO1 were readily reversible, suggesting that loading of guide RNA and pairing of seed-based miRNA and target RNA constrain its sequence drift.

  9. 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

  10. Trace element inputs into soils by anthropogenic activities and implications for human health.

    PubMed

    Senesi, G S; Baldassarre, G; Senesi, N; Radina, B

    1999-07-01

    Trace element definition and functions, and inputs into soils from the most important anthropogenic sources, related and not related to agricultural practices, of general and local or incidental concern, are discussed in the first part of this review. Trace element inputs include those from commercial fertilizers, liming materials and agrochemicals, sewage sludges and other wastes used as soil amendments, irrigation waters, and atmospheric depositions from urban, industrial, and other sources. In the second part of the review, the most important ascertained effects of soil trace elements on human health are presented. The possible relations found between some specific soil trace elements, such as Cd, Se, As and others, and cancer incidence and mortality, and diffusion of other important human diseases are reviewed. Brief conclusions and recommendations conclude this review.

  11. 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.

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

    NASA Technical Reports Server (NTRS)

    Glowacki, Julie; Gregor, Robert

    2009-01-01

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

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

    PubMed

    Dror, Itiel E

    2015-08-01

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

  14. 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

  15. West Flank Coso, CA FORGE ArcGIS data 2

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

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

  16. 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.

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

    PubMed

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

    2005-02-01

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

  18. 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

  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. 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.

  1. 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.

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

    PubMed

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

    2016-04-19

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

  3. 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

  4. 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.

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

    PubMed

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

    2013-11-01

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

  6. 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.

  7. 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…

  8. 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…

  9. A finite element model of the human buttocks for prediction of seat pressure distributions.

    PubMed

    Verver, M M; van Hoof, J; Oomens, C W J; Wismans, J S H M; Baaijens, F P T

    2004-08-01

    Seating comfort is becoming increasingly important for the automotive industry. Car manufacturers use seating comfort to distinguish their products from those of competitors. However, the development and design of a new, more comfortable seat is time consuming and costly. The introduction of computer models of human and seat will accelerate this process. The contact interaction between human and seat is an important factor in the comfort sensation of subjects. This paper presents a finite element (FE) model of the human buttocks, able to predict the pressure distribution between human and seating surface by its detailed and realistic geometric description. A validation study based on volunteer experiments shows reasonable correlation in pressure distributions between the buttocks model and the volunteers. Both for simulations on a rigid and a soft cushion, the model predicts realistic seat pressure distributions. A parameter study shows that a pressure distribution at the interface between human and seat strongly depends on variations in human flesh and seat cushion properties.

  10. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2012-05-01

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

  12. 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.

  13. Transformation of the human ovarian surface epithelium with genetically defined elements.

    PubMed

    Shan, Weiwei; Liu, Jinsong

    2013-01-01

    Success in in vitro transformation of primary cells from the human ovarian surface epithelium (OSE) has provided significant insight to the study of human ovarian cancer. Here, we describe the method used to immortalize and transform OSE by serial introduction of viral and nonviral genetic elements as well as to test the tumorigenicity of hence established cell lines in appropriate animal models. Successful transformation of OSE cells in the laboratory is of critical significance to the study of ovarian cancer. It not only allows for testing the roles of numerous potential oncogenes in initiating and promoting human ovarian cancer but provides a convenient tool to comprehensively dissect ovarian tumorigenesis in the laboratory.

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

    PubMed

    Östh, Jonas; Brolin, Karin; Happee, Riender

    2012-01-01

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

  15. 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.

  16. 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.

  17. 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

  18. 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.

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

    PubMed

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

    2016-09-01

    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.

  20. 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.

  1. Coding sequences of functioning human genes derived entirely from mobile element sequences.

    PubMed

    Britten, Roy J

    2004-11-30

    Among all of the many examples of mobile elements or "parasitic sequences" that affect the function of the human genome, this paper describes several examples of functioning genes whose sequences have been almost completely derived from mobile elements. There are many examples where the synthetic coding sequences of observed mRNA sequences are made up of mobile element sequences, to an extent of 80% or more of the length of the coding sequences. In the examples described here, the genes have named functions, and some of these functions have been studied. It appears that each of the functioning genes was originally formed from mobile elements and that in some process of molecular evolution a coding sequence was derived that could be translated into a protein that is of some importance to human biology. In one case (AD7C), the coding sequence is 99% made up of a cluster of Alu sequences. In another example, the gene BNIP3 coding sequence is 97% made up of sequences from an apparent human endogenous retrovirus. The Syncytin gene coding sequence appears to be made from an endogenous retrovirus envelope gene. PMID:15546984

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Detail view of fireplace and mantel, and flanking columns, in ...

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

    Detail view of fireplace and mantel, and flanking columns, in first floor main room, looking from the southwest - National Park Seminary, Swiss Chalet, 2802 Woodstock Avenue, Silver Spring, Montgomery County, MD

  7. 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

  8. 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

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

    PubMed

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

    2016-01-01

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

  10. 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.

  11. 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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2016-06-09

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

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

    PubMed

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

    2016-01-01

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

  16. 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.

  17. PIXE analysis of human serum - A preliminary study of the correlation between trace elements in human serum and the ``Deficiency Syndrome Complex'' theory of traditional Chinese medicine

    NASA Astrophysics Data System (ADS)

    Ming-chien, Li; Ming-guang, Tan; Jun-fa, Chin; Kang-long, Shen; Zhi-xiang, Chen; Jia-hua, Chang; Wen, Zhu; Wei-yi, Li; Zong-qin, Xia; An-kun, Kuang

    1981-03-01

    To be able to study the correlation between trace elements and the "Deficiency Syndrome Complex" theory of traditional Chinese medicine, we have used a completely automated PIXE analysis system to determine the trace element concentrations in human serum. The experimental results show a marked correlation between the concentrations of trace elements in serum and the two types of patients with the "Deficiency Syndrome Complex".

  18. Human health risk associated with exposure to toxic elements in mainstream and sidestream cigarette smoke.

    PubMed

    Behera, Sailesh N; Xian, Huang; Balasubramanian, Rajasekhar

    2014-02-15

    Toxic particulate elements present in cigarette smoke pose health threats to the life of smokers due to direct inhalation and at the same time increase health risks to non-smokers present in the vicinity of smokers because of their exposure. This study conducted a series of experiments using a controlled experimental chamber, equipped with simulated smoking conditions for characterization of particulate trace elements in mainstream and sidestream cigarette smoke. Four popular commercial cigarette brands available in Singapore market were used in this study. The target elements for extraction and analysis were Al, As, B, Ba, Be, Bi, Ca, Cd, Co, Cr, Cs, Cu, Fe, Ga, Hg, K, Li, Mg, Mn, Na, Ni, Pb, Rb, Se, Sn, Sr, Te, Tl and Zn of both water-soluble and total constituents. The human health risk assessment results showed that the sidestream smoke had higher concentrations of toxic elements than those in the mainstream smoke. However, risk assessment analysis revealed that the sidestream smoke resulted in less human health risks compared to the mainstream smoke due to the influence of dilution of particulate emissions in sidestream smoke prior to inhalation exposure experienced by non-smokers. The cumulative non-cancer and cancer risks of toxic elements varied from 2.0 to 3.1 and from 398.4×10(-6) to 626.1×10(-6) due to inhalation of cigarette smoke by an active smoker. In the case of non-smokers, the risks were estimated under three possible cases of exposure. The cumulative cancer risks under three different cases were greater than the permissible limits. Therefore, it could be concluded that the toxic particulate elements present in cigarette smoke have significant carcinogenic and non-carcinogenic health effects due to inhalation exposure in the environment.

  19. 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.

  20. Proton NMR assignment and secondary structural elements of human transforming growth factor. alpha

    SciTech Connect

    Brown, S.C.; Mueller, L.; Jeffs, P.W. )

    1989-01-24

    The {sup 1}H NMR spectrum of human transforming growth factor {alpha} (hTGF-{alpha}) has been completely assigned, and secondary structural elements have been identified as a preliminary step in determining the structure of this protein by distance geometry methods. Many of these structural elements closely correspond to those previously found in a truncated human EGF and murine EGF. These include the presence of an antiparallel {beta}-sheet between residues G19 and C34 with a type I {beta}-turn at V25-D28, a type II {beta}-turn at H35-Y38, and another short {beta}-sheet between residues Y38-V39 and H45-A46.

  1. [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.

  2. [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. PMID:27356355

  3. 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.

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

    PubMed

    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

  5. 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

  6. Analysis of functional elements in the human Egr-1 gene promoter.

    PubMed

    Aicher, W K; Sakamoto, K M; Hack, A; Eibel, H

    1999-01-01

    The early growth response (Egr)-1 gene encoding a zinc-finger transcription factor is transiently induced in many different cell types upon various differentiation signals. However, in synovial fibroblasts of rheumatoid arthritis patients, Egr-1 is constitutively expressed at high levels, and several genes with Egr-1 binding sites in their promoter regions have been associated with disease progression of RA. We analyzed the control of Egr-1 transcription by characterizing those regulatory elements in the Egr-1 promoter that induce Egr-1 expression in fibroblasts. Using reporter gene assays and deletion mutants of the Egr-1 promoter we could demonstrate that Egr-1 transcription is mainly activated by a single serum response element, whereas other transcription factor binding sites, including binding sites for AP-1 or Egr-1, were found to play a minor role. Furthermore, we identified a novel regulatory element in the human Egr-1 promoter similar to a NF kappa-B binding site. Deletion of this element enhanced Egr-1 promoter activity in 3T3 but not in L929 fibroblasts. Stimulation by phorbolester induced only transient Egr-1 expression in 3T3 fibroblasts but a extended expression of Egr-1 in L929 cells. These data suggest that in fibroblasts the most proximal serum response element in the Egr-1 promoter represents the major activation site, whereas binding of the NFkB-like factor may serve as negative regulatory signal for Egr-1 transcription in fibroblasts.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Functional redundancy of promoter elements ensures efficient transcription of the human 7SK gene in vivo.

    PubMed

    Boyd, D C; Turner, P C; Watkins, N J; Gerster, T; Murphy, S

    1995-11-10

    Deletion and mutation studies of the human 7SK gene transfected into HeLa cells have identified three functional regions of the promoter corresponding to the TATA box at -25, the proximal sequence element (PSE) between -49 and -65 and the distal sequence element (DSE) between -243 and -210. These elements show sequence homology to equivalent regions in other snRNA genes and are functionally analogous. Unlike the DSEs of many snRNA genes however, the 7SK DSE does not contain a consensus binding site for the transcription factor Oct-1 but rather, contains two non-consensus Oct-1 binding sites that can function independently of one another to enhance transcription. Unusually, the 7SK PSE can retain function even after extensive mutation and removal of the conserved TGACC of the PSE has little effect in the context of the whole promoter. However, the same mutation abolishes transcription in the absence of the DSE suggesting that protein/protein interactions between DSE and PSE binding factors can compensate for a mutant PSE. Mutation of the 7SK TATA box allows snRNA type transcription by RNA polymerase II to occur and this is enhanced by the DSE, indicating that both the DSE and the PSE can also function with pol II. In addition, mutation of the TATA box does not abolish pol III dependent transcription, suggesting that other sequence elements may also play a role in the determination of polymerase specificity. Although the human 7SK gene is transcribed efficiently in Xenopus oocytes, analysis of the 7SK wild-type gene and mutants in Xenopus oocytes gives significantly different results from the analysis in HeLa cells indicating that the recognition of functional elements is not the same in the two systems.

  12. 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.

  13. Human GLI-2 Is a Tat Activation Response Element-Independent Tat Cofactor

    PubMed Central

    Browning, Catherine M.; Smith, Michael J.; Clark, Nina M.; Lane, Brian R.; Parada, Camilo; Montano, Monty; KewalRamani, Vineet N.; Littman, Dan R.; Essex, Max; Roeder, Robert G.; Markovitz, David M.

    2001-01-01

    Zinc finger-containing GLI proteins are involved in the development of Caenorhabditis elegans, Xenopus, Drosophila, zebrafish, mice, and humans. In this study, we show that an isoform of human GLI-2 strongly synergizes with the Tat transactivating proteins of human immunodeficiency virus types 1 and 2 (HIV-1 and -2) and markedly stimulates viral replication. GLI-2 also synergizes with the previously described Tat cofactor cyclin T1 to stimulate Tat function. Surprisingly, GLI-2/Tat synergy is not dependent on either a typical GLI DNA binding site or an intact Tat activation response element but does require an intact TATA box. Thus, GLI-2/Tat synergy results from a mechanism of action which is novel both for a GLI protein and for a Tat cofactor. These findings link the GLI family of transcriptional and developmental regulatory proteins to Tat function and HIV replication. PMID:11160734

  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. Toxicological importance of human biomonitoring of metallic and metalloid elements in different biological samples.

    PubMed

    Gil, F; Hernández, A F

    2015-06-01

    Human biomonitoring has become an important tool for the assessment of internal doses of metallic and metalloid elements. These elements are of great significance because of their toxic properties and wide distribution in environmental compartments. Although blood and urine are the most used and accepted matrices for human biomonitoring, other non-conventional samples (saliva, placenta, meconium, hair, nails, teeth, breast milk) may have practical advantages and would provide additional information on health risk. Nevertheless, the analysis of these compounds in biological matrices other than blood and urine has not yet been accepted as a useful tool for biomonitoring. The validation of analytical procedures is absolutely necessary for a proper implementation of non-conventional samples in biomonitoring programs. However, the lack of reliable and useful analytical methodologies to assess exposure to metallic elements, and the potential interference of external contamination and variation in biological features of non-conventional samples are important limitations for setting health-based reference values. The influence of potential confounding factors on metallic concentration should always be considered. More research is needed to ascertain whether or not non-conventional matrices offer definitive advantages over the traditional samples and to broaden the available database for establishing worldwide accepted reference values in non-exposed populations.

  16. Effects of rare earth elements on telomerase activity and apoptosis of human peripheral blood mononuclear cells.

    PubMed

    Yu, Li; Dai, Yucheng; Yuan, Zhaokang; Li, Jie

    2007-04-01

    To study the effects of rare earth exposure on human telomerase and apoptosis of mononuclear cells from human peripheral blood (PBMNCs). The blood contents of 15 rare earth elements, including La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, and Y, were measured by inductively coupled plasma-mass spectrometry. Telomeric repeat amplification protocol assay and flow cytometer analysis were carried out to analyze the telomerase activity and apoptosis of PBMNCs, respectively. The total content of rare earth elements in the blood showed significant differences between the exposed group and the control group. The rare earth exposure increased the telomerase activity and the percentages of cells in the S-phase and the G2/M phase in PBMNCs, but it had no effect on the apoptotic rate of PBMNCs. Under the exposure to lower concentrations of rare earth elements, the telomerase activity of PBMNCs in the exposed group was higher than that of the control group, and there was no effect on the apoptotic rate of PBMNCs, but promoted the diploid DNA replication and increased the percentages of G2/M- and S-phase cells.

  17. 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

  18. Cis-acting RNA elements in human and animal plus-strand RNA viruses

    PubMed Central

    Liu, Ying; Wimmer, Eckard; Paul, Aniko V.

    2009-01-01

    The RNA genomes of plus-strand RNA viruses have the ability to form secondary and higher-order structures that contribute to their stability and to their participation in inter- and intramolecular interactions. Those structures that are functionally important are called cis-acting RNA elements because their functions cannot be complemented in trans. They can be involved not only in RNA/RNA interactions but also in binding of viral and cellular proteins during the complex processes of translation, RNA replication and encapsidation. Most viral cis-acting RNA elements are located in the highly structured 5′- and 3′-nontranslated regions of the genomes but sometimes they also extend into the adjacent coding sequences. In addition, some cis-acting RNA elements are embedded within the coding sequences far away from the genomic ends. Although the functional importance of many of these structures have been confirmed by genetic and biochemical analyses their precise roles are not yet fully understood. In this review we have summarized what is known about cis-acting RNA elements in nine families of human and animal plus-strand RNA viruses with an emphasis on the most thoroughly characterized virus families, the Picornaviridae and Flaviviridae. PMID:19781674

  19. 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.

  20. 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

  1. Trace elements in animal-based food from Shanghai markets and associated human daily intake and uptake estimation considering bioaccessibility.

    PubMed

    Lei, Bingli; Chen, Liang; Hao, Ying; Cao, Tiehua; Zhang, Xinyu; Yu, Yingxin; Fu, Jiamo

    2013-10-01

    The concentrations of four human essential trace elements [iron (Fe), manganese (Mn), zinc (Zn), chromium (Cr)] and non-essential elements [cadmium (Cd), lead (Pb), arsenic (As), and mercury (Hg)] in eighteen animal-based foods including meat, fish, and shellfish collected from markets in Shanghai, China, were analyzed, and the associated human daily intake and uptake considering bioaccessibility were estimated. The mean concentration ranges for eight trace elements measured in the foods were 3.98-131µgg(-1) for Fe, 0.437-18.5µgg(-1) for Mn, 5.47-53.8µgg(-1) for Zn, none detected-0.101µgg(-1) for Cr, 2.88×10(-4)-2.48×10(-2)µgg(-1) for Cd, 1.18×10(-3)-0.747µgg(-1) for Pb, none detected-0.498µgg(-1) for As, and 8.98×10(-4)-6.52×10(-2)µgg(-1) for Hg. The highest mean concentrations of four human essential elements were all found in shellfish. For all the trace elements, the observed mean concentrations are mostly in agreement with the reported values around the world. The total daily intake of trace elements via ingestion of animal-based food via an average Shanghai resident was estimated as 7371µgd(-1) for the human essential elements and 13.0µgd(-1) for the human non-essential elements, but the uptake decreased to 4826µgd(-1) and 6.90µgd(-1), respectively, after trace element bioaccessibility was considered. Livestock and fish for human essential and non-essential elements, respectively, were the main contributor, no matter whether the bioaccessibility was considered or not. Risk estimations showed that the intake and uptake of a signal trace element for an average Shanghai resident via ingestion animal-based foods from Shanghai markets do not exceed the recommended dietary allowance values; consequently, a health risk situation is not indicated.

  2. 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.

  3. West Flank Coso FORGE Magnetotelluric 3D Data

    DOE Data Explorer

    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.

  4. 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.

  5. 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

  6. 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.

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

    PubMed

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

    2016-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Wheat, C. Geoffrey; Mottl, Michael J.

    2000-02-01

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

  9. 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.

  10. 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

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

    NASA Astrophysics Data System (ADS)

    Ponce L., Ernesto; Ponce S., Daniel

    2008-11-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

  13. 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

  14. West Flank Coso, CA FORGE Natural Fracture data

    DOE Data Explorer

    Doug Blankenship

    2016-05-16

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

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

    PubMed Central

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

    2013-01-01

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

  16. 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

  17. 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).

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

    Levy, Asaf; Schwartz, Schraga; Ast, Gil

    2010-01-01

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

  20. 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.

  1. 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…

  2. 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

  3. Accumulation of potentially toxic elements in plants and their transfer to human food chain.

    PubMed

    Dudka, S; Miller, W P

    1999-07-01

    Contaminated soils can be a source for crop plants of such elements like As, Cd, Cr, Cu, Ni, Pb, and Zn. The excessive transfer of As, Cu, Ni, and Zn to the food chain is controlled by a "soil-plant barrier"; however, for some elements, including Cd, the soil-plant barrier fails. The level of Cd ingested by average person in USA is about 12 micrograms/day, which is relatively low comparing to Risk Reference Dose (70 micrograms Cd/day) established by USEPA. Food of plant origin is a main source of Cd intake by modern society. Fish and shellfish may be a dominant dietary sources of Hg for some human populations. About half of human Pb intake is through food, of which more than half originates from plants. Dietary intake of Cd and Pb may be increased by application of sludges on cropland with already high levels of these metals. Soils amended with sludges in the USA will be permitted (by USEPA-503 regulations) to accumulate Cr, Cd, Cu, Pb, Hg, Ni, and Se, and Zn to levels from 10 to 100 times the present baseline concentrations. These levels are very permissive by international standards. Because of the limited supply of toxicity data obtained from metals applied in sewage sludge, predictions as to the new regulations will protect crop plants from metal toxicities, and food chain from contamination, are difficult to make.

  4. Novel PRD-like homeodomain transcription factors and retrotransposon elements in early human development

    PubMed Central

    Töhönen, Virpi; Katayama, Shintaro; Vesterlund, Liselotte; Jouhilahti, Eeva-Mari; Sheikhi, Mona; Madissoon, Elo; Filippini-Cattaneo, Giuditta; Jaconi, Marisa; Johnsson, Anna; Bürglin, Thomas R.; Linnarsson, Sten; Hovatta, Outi; Kere, Juha

    2015-01-01

    Transcriptional program that drives human preimplantation development is largely unknown. Here, by using single-cell RNA sequencing of 348 oocytes, zygotes and single blastomeres from 2- to 3-day-old embryos, we provide a detailed analysis of the human preimplantation transcriptome. By quantifying transcript far 5′-ends (TFEs), we include in our analysis transcripts that derive from alternative promoters. We show that 32 and 129 genes are transcribed during the transition from oocyte to four-cell stage and from four- to eight-cell stage, respectively. A number of identified transcripts originates from previously unannotated genes that include the PRD-like homeobox genes ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB and LEUTX. Employing de novo promoter motif extraction on sequences surrounding TFEs, we identify significantly enriched gene regulatory motifs that often overlap with Alu elements. Our high-resolution analysis of the human transcriptome during preimplantation development may have important implications on future studies of human pluripotent stem cells and cell reprograming. PMID:26360614

  5. Long interspersed element-1 protein expression is a hallmark of many human cancers.

    PubMed

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

    2014-05-01

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

  6. 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

  7. 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.

  8. Differences in elements between intact and disrupted human ligamenta capitum femorum.

    PubMed

    Shinohara, Yasushi; Kumai, Tsukasa; Higashiyama, Ichiro; Tanaka, Yasuhito; Takakura, Yoshinori; Nishi, Mayumi; Azuma, Cho; Minami, Takeshi; Tohno, Yoshiyuki

    2014-08-01

    To compare the element compositions between intact (i.e., intact throughout its length) and disrupted (i.e., ligament no longer attached to the attachment) ligaments, the contents of elements in the human ligamenta capitum femorum (LCF) were analyzed by inductively coupled plasma-atomic emission spectrometry. Histological and immunohistological assessments were also performed in both groups. The subjects were 8 men and 32 women. Trace element analyses showed that the sulfur and iron contents were significantly greater in the intact group than in the disrupted group, while the phosphorus and magnesium contents were significantly smaller in the intact group than in the disrupted group. The calcium and zinc contents were smaller in the intact group than in the disrupted group, with no significant differences. Histologically, there were fibrocartilage cells and extracellular matrix metachromasia in ligaments of the intact group. In contrast, fibrocartilage cells disappeared, and fat cells appeared instead of collagen fibrils in ligaments of the disrupted group. The LCFs of the intact group were immunohistologically positive for all components examined including collagens, glycosaminoglycans, and proteoglycans. The increase in sulfur suggested the presence of high glycosaminoglycan levels associated with fibrocartilaginous metaplasia in the ligament by compressive force. The reduction in iron may show a decreased number of blood vessels in the synovium after ligament disruption. The increases in phosphorus, magnesium, and calcium are indicative of degenerative changes including calcification and ossification. We conclude that differences in the contents of elements between intact and disrupted LCFs indicate degenerative alterations to the ligament structure after disruption. PMID:24930779

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

    PubMed

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

    2011-09-01

    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.

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

    SciTech Connect

    Erickson, L.M.; Maeda, N.

    1995-06-10

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

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

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. Fluid-sediment Interaction and Formation of Mn oxi-hydroxide related to a Ridge Flank Hydrothermal System

    NASA Astrophysics Data System (ADS)

    Buatier, M. D.; Bodei, S.; Steinmann, M.; Manceau, A.; Karpoff, A.; Guillaume, D.; Wheat, C. G.

    2005-12-01

    Fluid-sediment interaction at ridge flank permits the formation of metalliferous deposits that play a role in the scavenging of Fe, Mn and other trace elements. Several sites of active hydrothermal flow have been found on the eastern flank of Juan de Fuca Ridge (Retroflux) and along the Costa Rica margin (Ticoflux). These sites are typically located along edges of basaltic outcrops and seamounts where the sediment layers are thin. Mn and Fe oxides can be formed at such interfaces. These oxides form soft micro-concretions or slightly indurated black crusts. Detailed investigations combining geochemical (major, trace elements and REEY) and mineralogical (SEM, TEM, EELS EXAFS) analyses of these Mn and Fe-oxides allow formation mechanisms to be proposed. On the eastern flank of the Juan de Fuca Ridge above the 3.5 Ma-old seafloor, amorphous and poorly crystallized Mn-oxides are dispersed in altered sediments whereas pure birnessite is observed as crust layers. Hydrothermal birnessite and well-crystallized todorokite are found in sediments from the Costa Rica margin, on an 18-24 Ma seafloor. Our data suggest that the formation of hydrothermal Mn concretions occurs in several steps. The initial step is the adsorption or precipitation of Mn, Si and Fe around siliceous remains of fossils and around cell wall of bacteria and extracellular polymers. These poorly crystallized phyllomanganates give rise to the formation of better crystallized birnessite and todorokite, which progressively increase in size and crystallinity. This study shows that biogenic and amorphous components of sediments provide reactive sites for precipitation of metallic elements and the formation of hydrothermal oxi-hydroxides in ridge flank environments. These minerals, which are good scavengers of metallic elements, must be taken into account when considering the water-rocks reactions controlling oceanic chemical budgets.

  14. 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.

  15. The human endogenous retrovirus K Rev response element coincides with a predicted RNA folding region.

    PubMed Central

    Yang, J; Bogerd, H; Le, S Y; Cullen, B R

    2000-01-01

    Human endogenous retrovirus K (HERV-K) is the name given to an approximately 30-million-year-old family of endogenous retroviruses present at >50 copies per haploid human genome. Previously, the HERV-K were shown to encode a nuclear RNA export factor, termed K-Rev, that is the functional equivalent of the H-Rev protein encoded by human immunodeficiency virus type 1. HERV-K was also shown to contain a cis-acting target element, the HERV-K Rev response element (K-RRE), that allowed the nuclear export of linked RNA transcripts in the presence of either K-Rev or H-Rev. Here, we demonstrate that the functionally defined K-RRE coincides with a statistically highly significant unusual RNA folding region and present a potential RNA secondary structure for the approximately 416-nt K-RRE. Both in vitro and in vivo assays of sequence specific RNA binding were used to map two primary binding sites for K-Rev, and one primary binding site for H-Rev, within the K-RRE. Of note, all three binding sites map to discrete predicted RNA stem-loop subdomains within the larger K-RRE structure. Although almost the entire 416-nt K-RRE was required for the activation of nuclear RNA export in cells expressing K-Rev, mutational inactivation of the binding sites for K-Rev resulted in the selective loss of the K-RRE response to K-Rev but not to H-Rev. Together, these data strongly suggest that the K-RRE, like the H-RRE, coincides with an extensive RNA secondary structure and identify specific sites within the K-RRE that can recruit either K-Rev or H-Rev to HERV-K RNA transcripts. PMID:11105755

  16. Dynamic simulation and finite element analysis of the human mandible injury protected by polyvinyl alcohol sponge.

    PubMed

    Karimi, Alireza; Navidbakhsh, Mahdi; Razaghi, Reza

    2014-09-01

    There have been intensive efforts to find a suitable kinetic energy absorbing material for helmet and bulletproof vest design. Polyvinyl alcohol (PVA) sponge is currently in extensive use as scaffolding material for tissue engineering applications. PVA can also be employed instead of commonly use kinetic energy absorbing materials to increase the kinetic energy absorption capacity of current helmet and bulletproof vest materials owing to its excellent mechanical properties. In this study, a combined hexahedral finite element (FE) model is established to determine the potential protection ability of PVA sponge in controlling the level of injury for gunshot wounds to the human mandible. Digital computed tomography data for the human mandible are used to establish a three-dimensional FE model of the human mandible. The mechanism by which a gunshot injures the protected mandible by PVA sponge is dynamically simulated using the LS-DYNA code under two different shot angles. The stress distributions in different parts of the mandible and sponge after injury are also simulated. The modeling results regardless of shot angle reveal that the substantial amount of kinetic energy of the steel ball (67%) is absorbed by the PVA sponge and, consequently, injury severity of the mandible is significantly decreased. The highest energy loss (170 J) is observed for the impact at entry angle of 70°. The results suggest the application of the PVA sponge as an alternative reinforcement material in helmet and bulletproof vest design to absorb most of the impact energy and reduce the transmitted load.

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

    PubMed

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

    2016-04-01

    Genome engineering of human cells plays an important role in biotechnology and molecular medicine. In particular, insertions of functional multi-transgene cassettes into suitable endogenous sequences will lead to novel applications. Although several tools have been exploited in this context, safety issues such as cytotoxicity, insertional mutagenesis and off-target cleavage together with limitations in cargo size/expression often compromise utility. Phage λ integrase (Int) is a transgenesis tool that mediates conservative site-specific integration of 48 kb DNA into a safe harbor site of the bacterial genome. Here, we show that an Int variant precisely recombines large episomes into a sequence, 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.

  18. 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

  19. A finite element study relating to the rapid filling phase of the human ventricles.

    PubMed

    Bettendorff-Bakman, D-E; Schmid, P; Lunkenheimer, P P; Niederer, P

    2006-01-21

    During the rapid diastolic filling phase at rest, the ventricles of the human heart double approximately in volume. In order to investigate whether the ventricular filling pressures measured under physiological conditions can give rise to such an extensive augmentation in ventricular volumes, a finite element model of the human right and left ventricles has been developed, taking into account the nonlinear mechanical behavior and effective compressibility of the myocardial tissue. The results were compared with the filling phase of the human left ventricle as extrapolated from measurements documented in the literature. We arrived at the conclusion that the ventricular pressures measured during the rapid filling phase cannot be the sole cause of the rise of the observed ventricular volumes. We rather advocate the assumption that further dilating mechanisms might be part of ventricular activity thus heralding a multiple function of the ventricular muscle body. A further result indicates that under normal conditions the influence of the viscoelasticity of the tissue should not be disregarded in ventricular mechanics.

  20. 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.

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

    NASA Astrophysics Data System (ADS)

    Goenaga Infante, Heidi

    2016-01-01

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

  2. Flank collapses and tsunami hazard in the Antilles Arc

    NASA Astrophysics Data System (ADS)

    Teeuw, R.; Rust, D.; Solana, C.; Dewdney, C.; Robertson, R.

    2009-04-01

    We highlight potentially tsunamigenic volcanic flank instability on the north coast of Dominica in the Lesser Antilles arc. 3-D views from Google Earth were key to the initial recognition of this hazardous terrain. Seismic, bathymetric and geomorphological data suggest that this coast is bounded by an active fault structure, with the relatively up-thrown flank displaying evidence of both shallow translational and deep-seated rotational slope instability. A probable landslide block of ~1 M tonnes on the seaward margin of the instability complex has large tension cracks on its upslope margin, clearly visible on Quickbird satellite imagery and X-band SRTM digital elevation models . Failure of this block could destabilise a larger adjacent upslope block (~ 3 M tonnes). Preliminary calculations indicate that landslides at these scales could trigger tsunami waves, locally reaching up to 4 m in height, with the greatest hazard along the southern coast of Guadeloupe, 30-40 km to the north of Dominica.

  3. Changes in quantitative norepinephrine levels in delayed pig flank flaps.

    PubMed

    Cutting, C; Bumsted, R; Bardach, J; Mooney, M; Johnson, S

    1982-04-01

    A quantitative norepinephrine assay was used to follow tissue norepinephrine concentrations serially in bipedicle delayed pig flank flaps. In contrast to a previous study by Palmer, norepinephrine concentration decreased significantly after 24 hr, but then gradually returned to normal at 10 days. This suggests that the pig flank flap maintains much of its adrenergic innervation following bipedicle delay. It appears unlikely that adrenergic denervation explains the delay phenomenon in this model. The combined results of this study and others suggest that the degree of adrenergic denervation of a flap is determined by the anatomic layout of the flap with respect to the underlying cutaneous adrenergic neural anatomy. This experiment suggests that the effectiveness of adrenergic blocking agents in improving flap survival is dependent on the degree of adrenergic denervation of the flap.

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

    PubMed

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

    2015-01-01

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

  5. 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.

  6. The highlights, and the lows, of aviation medicine in the 1940's: the human element.

    PubMed

    Cheetham, R W

    1989-07-01

    This article describes the experience and knowledge gained by the author during an extensive study tour of the majority of aviation medicine centres in the United Kingdom, Canada, and the United States in 1942. The emphasis is upon the human element rather than the technical, and the contribution of thousands of scientists from medical, psychological, and allied disciplines whose dedication was vital to air supremacy. This required a symbiosis between them and aircraft engineers and, inter alia, courageous participation in operational missions or dangerous experiments. The price was, on occasion, tragedy. Individual instances are described, as are visits to operational air force squadrons. The tour concluded with a return to South Africa and the establishment of the first South African Aviation Medical Laboratory. In spite of the implementation of the knowledge gained during the tour, the laboratory was closed after the war.

  7. 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.

  8. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2007-12-01

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

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

    PubMed

    Türke, Andreas; Nakamura, Kentaro; Bach, Wolfgang

    2015-10-01

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

  11. 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

  12. 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.

  13. 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

  14. Genome-wide discovery of drug-dependent human liver regulatory elements.

    PubMed

    Smith, Robin P; Eckalbar, Walter L; Morrissey, Kari M; Luizon, Marcelo R; Hoffmann, Thomas J; Sun, Xuefeng; Jones, Stacy L; Force Aldred, Shelley; Ramamoorthy, Anuradha; Desta, Zeruesenay; Liu, Yunlong; Skaar, Todd C; Trinklein, Nathan D; Giacomini, Kathleen M; Ahituv, Nadav

    2014-10-01

    Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR) and three active regulatory marks (p300, H3K4me1, H3K27ac) on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4%) that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements.

  15. Genome-Wide Discovery of Drug-Dependent Human Liver Regulatory Elements

    PubMed Central

    Morrissey, Kari M.; Luizon, Marcelo R.; Hoffmann, Thomas J.; Sun, Xuefeng; Jones, Stacy L.; Force Aldred, Shelley; Ramamoorthy, Anuradha; Desta, Zeruesenay; Liu, Yunlong; Skaar, Todd C.; Trinklein, Nathan D.; Giacomini, Kathleen M.; Ahituv, Nadav

    2014-01-01

    Inter-individual variation in gene regulatory elements is hypothesized to play a causative role in adverse drug reactions and reduced drug activity. However, relatively little is known about the location and function of drug-dependent elements. To uncover drug-associated elements in a genome-wide manner, we performed RNA-seq and ChIP-seq using antibodies against the pregnane X receptor (PXR) and three active regulatory marks (p300, H3K4me1, H3K27ac) on primary human hepatocytes treated with rifampin or vehicle control. Rifampin and PXR were chosen since they are part of the CYP3A4 pathway, which is known to account for the metabolism of more than 50% of all prescribed drugs. We selected 227 proximal promoters for genes with rifampin-dependent expression or nearby PXR/p300 occupancy sites and assayed their ability to induce luciferase in rifampin-treated HepG2 cells, finding only 10 (4.4%) that exhibited drug-dependent activity. As this result suggested a role for distal enhancer modules, we searched more broadly to identify 1,297 genomic regions bearing a conditional PXR occupancy as well as all three active regulatory marks. These regions are enriched near genes that function in the metabolism of xenobiotics, specifically members of the cytochrome P450 family. We performed enhancer assays in rifampin-treated HepG2 cells for 42 of these sequences as well as 7 sequences that overlap linkage-disequilibrium blocks defined by lead SNPs from pharmacogenomic GWAS studies, revealing 15/42 and 4/7 to be functional enhancers, respectively. A common African haplotype in one of these enhancers in the GSTA locus was found to exhibit potential rifampin hypersensitivity. Combined, our results further suggest that enhancers are the predominant targets of rifampin-induced PXR activation, provide a genome-wide catalog of PXR targets and serve as a model for the identification of drug-responsive regulatory elements. PMID:25275310

  16. Analogue modelling of flank dynamics at Mount Etna, Italy

    NASA Astrophysics Data System (ADS)

    Norini, Gianluca; Acocella, Valerio

    2010-05-01

    Mount Etna, Italy, is characterized by the instability of its East and South flanks. Factors governing this flank instability are still matter of debate. We investigate the role of different possible factors on flank instability, using analogue models. The apparatus consists of a cone and base made of granular material, simulating the volcanic edifice and its basement, respectively. The granular material we use is a mixture of low cohesion silica sand and high cohesion crushed silica powder. Alternated layers with different cohesion are used to account for differences in the crustal structure of the basement, in terms of cohesion and permeability. The geometry of the experiments is designated to simulate the topographic and bathymetric gradients at the base of the volcano. Injections of high viscosity silicone putty and low viscosity vegetable oil are used to model the inflation of reservoirs below the volcano and the emplacement of dikes, respectively. Some experiments are conducted on a sheared basal layer, to simulate regional extensional tectonics. Finally, injection of compressed air at the base of the model allows to simulate the effect of pore pressure and the behavior of low friction - low shear strength materials. Several sets of experiments are run to account for the role of each factor or combination of factors on the flank dynamics of the volcano. We use a high resolution laser scanner and control points on the surface of the models to trace surface deformation as a function of the imposed physical conditions. The experiments show that the asymmetric topography systematically enhances the deformation on the side with the highest topographic gradient (i.e. seaside), under inflating reservoirs and dike emplacements (up to 3-4 times), regional tectonics (up to 15%), crustal layering (up to 25%) and the effect of pore pressures. These results, compared with the known rates in nature, allow us to define the relative importance of the different factors on

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

    PubMed

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

    2016-10-01

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

  18. 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.

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

    PubMed

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

    2013-03-01

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

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

    PubMed

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

    2015-07-01

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

  1. 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

  2. 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.

  3. [Importance of the flank line in the radiologic semiotics of abdominal pathology].

    PubMed

    Minutoli, A; Gaeta, M; Mantineo, G; Bosurgi, G

    1986-04-01

    The authors have analysed the flank stripe in 70 normal subjects and in patients with abdominal disease. The flank stripe has a wide variability and is very useful to detect and locate abdominal pathologic conditions.

  4. 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

  5. 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

  6. DNase I hypersensitive sites flank the mouse class II major histocompatibility complex during B cell development.

    PubMed Central

    Carson, S

    1991-01-01

    The mouse class II major histocompatibility complex (MHC) encodes a polymorphic, multigene family important in the immune response, and is expressed mainly on mature B cells, on certain types of dendritic cells and is also inducible by gamma-interferon on antigen presenting cells. To study the regulatory elements which control this expression pattern, we have examined the chromatin structure flanking the class II MHC region, in particular during B cell differentiation. Using a panel of well-characterised mouse cell lines specific for different stages of B cell development (pre-B, B, plasma cell) as well as non-B cell lines, we have mapped the DNase I hypersensitive (DHS) sites adjacent to the mouse MHC class II region. The results presented show, for the first time that there are specific hypersensitive sites flanking the class II MHC locus during pre B cell, B cell and plasma cell stages of B cell differentiation, irrespective of the status of class II MHC expression. These hypersensitive sites are not found in T cell, fibroblast or uninduced myelomonocytic cell lines. This suggests that these DHS sites define a developmentally stable, chromatin structure, which can be used as a marker of B cell lineage commitment and may indicate that a combination of these hypersensitive sites reflect regulatory proteins involved in the immediate expression of a particular class II MHC gene or possibly control of the entire locus. Images PMID:1923768

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

    PubMed

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

    2016-01-01

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

  8. 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.

  9. Sequence and characteristics of IS900, an insertion element identified in a human Crohn's disease isolate of Mycobacterium paratuberculosis.

    PubMed Central

    Green, E P; Tizard, M L; Moss, M T; Thompson, J; Winterbourne, D J; McFadden, J J; Hermon-Taylor, J

    1989-01-01

    The complete sequence of an insertion element IS900 in Mycobacterium paratuberculosis is reported. This is the first characterised example of a mycobacterial insertion element. IS900 consists of 1451bp of which 66% is G + C. It lacks terminal inverted and direct repeats, characteristic of Escherichia coli insertion elements but shows a degree of target sequence specificity. A single open reading frame (ORF 1197) coding for 399 amino acids is predicted. This amino acid sequence, and to a lesser extent the nucleotide sequence, show significant homologies to IS110, an insertion element of Streptomyces coelicolor A3(2). It is proposed that IS900, IS110, and similar insertion elements recently identified in disease isolates of Mycobacterium avium are members of a phylogenetically related family. IS900 will provide highly specific markers for the precise identification of Mycobacterium paratuberculosis, useful in defining its relationship to animal and human diseases. PMID:2555783

  10. 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

  11. An element in the 3' untranslated region of human LINE-1 retrotransposon mRNA binds NXF1(TAP) and can function as a nuclear export element.

    PubMed Central

    Lindtner, Susan; Felber, Barbara K; Kjems, Jørgen

    2002-01-01

    Export of unspliced mRNA to the cytoplasm is required for the replication of all retroviruses. In simian type D retroviruses, the RNA export is mediated by the constitutive transport element (CTE) that binds the cellular nuclear export factor 1, NXF1(TAP). To search for potential cellular RNA substrates for NXF1, we have set up an in vitro selection procedure, using an RNA library expressed from total human genomic DNA. A sequence that was isolated most frequently as independent clones exhibits extensive homology to the 3' untranslated region of expressed LINE1 (L1) retrotransposons. This region, termed L1-NXF1 binding element (L1-NBE) bears no structural resemblance to the viral CTE, but binds NXF1 as strongly as CTE, based on gel mobility shift competition assays. A deletion analysis of the NXF1 protein reveals that CTE and L1-NBE have different, but overlapping, binding domains on NXF1. Placed in an intron, L1-NBE is capable of mediating nuclear export of lariat RNA species in Xenopus laevis oocytes and of an unspliced HIV-1 derived RNA in human 293 cells, suggesting that it may function as a nuclear export element for the intronless L1 mRNA. PMID:12003494

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

    PubMed Central

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

    1990-01-01

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

  13. 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. PMID:15697230

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

    DOE Data Explorer

    Doug Blankenship

    2016-03-01

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

  15. Tsunami deposits related to Fogo flank failure (Cape Verde Islands)

    NASA Astrophysics Data System (ADS)

    Paris, Raphael; Chevalier, Joel; Lavigne, Franck

    2010-05-01

    Oceanic shield volcanoes are prone to massive flank failures involving dozens to hundreds of km³. Fogo active volcano (Cape Verde Islands) is nested in a large horseshoe shaped caldera opened to the east. This volcano-tectonic structure could be the result of past failures of the edifice (Day et al., 1999). Debris avalanche deposits were identified offshore (Masson et al., 2008). The volume of the last collapse (> 62 ka) ranges between 130 and 160 km³, making the hypothesis for a past giant tsunami highly probable. Santiago island is located 50 km east of Fogo island. The west coast of Santiago may have been severely affected by the tsunami. A field survey was carried out in March 2009. Surprisingly, tsunami deposits were found only in Tarrafal, where a large bay may have amplified the wave and provided sediments. Elsewhere, no evidences of tsunami were found. The tsunami deposits appear as marine conglomerate in discontinuity above a reddish to yellowish paleo-soil. Nice cross-sections were found along the coast, in the northern part of the Tarrafal Bay. The thickness apparently increases landward (up to 4 m). The deposits consist in stacked units of pebbles or boulders, with numerous marine bioclasts (shells, corals, coralline algae). The basal contact with the paleo-soil displays scour-and-fill features. These tsunami deposits are similar to those previously described by Pérez-Torrado et al. (2006) in the Canary Islands. References Day, S.J., Heleno da Silva, S.I.N., Fonseca, J.F.B.D., 1999. A past giant lateral collapse and present-day flank instability of Fogo, Cape Verde Islands. Journal of Volcanology and Geothermal Research 99, 191-218. Masson, D.G., Le Bas, T.P., Grevemeyer, I., Weinrebe, W., 2008. Flank collapse and large-scale landsliding in the Cape Verde Islands, off West Africa. Geochemistry, Geophysics, Geosystems 9 (7). Pérez Torrado, F.J., Paris, R., Cabrera, M.C., Schneider, J.L., Wassmer, P., Carracedo, J.C., Rodriguez Santana, A., Santana, F

  16. 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

  17. 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.

  18. 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.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-10-01

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

  1. 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.

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

    PubMed

    Nigenda, Gustavo; Muños, José Alberto

    2015-01-01

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

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

    PubMed

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

    2013-03-01

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

  4. 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.

  5. 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.

  6. 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.

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

    PubMed Central

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

    2015-01-01

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

  8. 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.

  9. [Origin and elimination of fibrous elements seen in CRL antirabies vaccine for human use].

    PubMed

    Amasino, C F; Lezcano, L I; Lucena, A R

    1986-01-01

    The present work describes the discovery of an organoleptic alteration in some batchs of suckling mouse brain rabies vaccine for human use, produced in the Central Laboratory of Public Health of the Province of Buenos Aires. This alteration consists in the appearance of fibrous particles, light-white, slightly perceptible, suspended in the diluent. The production procedure is that of Fuenzalida and Palacios (4), with the modifications proposed by the Panamerican Zoonoses Center (Larghi and col.) (6), which include a refrigerated centrifugation of the viral suspension to 17,000 g during 10 minutes. This alteration caused 20% or more of dosis loss and a decrease in vaccine potency (2). In order to determine the origin of this alteration, we controlled the homogenization systems, the elements employed, the production of experimental batchs with diversity of isotonizators (dextrose-sucrose) and preservatives, the utilization of glass filters in the treatment of water, all drugs employed, variation of pH of diluent solutions, double centrifugation, the glass employed (ampoules, flasks), pumps of dispensation and wash systems (3) (5). We conclude that the alterations are produced by partial freezing of the infected brain suspension to 10% in water, during the last part of the centrifugation. Particles are formed by irreversible precipitation of a proteic nature (1) (7). It is recommended that during the production of this vaccine the temperature be maintained between 3 to 5 degrees C carefully avoiding freezing the brain suspension in distilled water.

  10. 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

  11. 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.

  12. 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

  13. 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…

  14. 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.

  15. 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.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  18. 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. PMID:11046136

  19. Co-localization of neuropeptide tyrosine (NPY) and its C-terminal flanking peptide (C-PON).

    PubMed

    Gulbenkian, S; Wharton, J; Hacker, G W; Varndell, I M; Bloom, S R; Polak, J M

    1985-01-01

    Neuropeptide tyrosine (NPY) is one of the most abundant and widespread peptides in the mammalian nervous system. Recent isolation and sequencing of the DNA encoding NPY has predicted the existence of a 97 amino acid precursor peptide. Proteolytic processing of this precursor could yield three separate peptide products, an N-terminal signal peptide, neuropeptide tyrosine and a 30 amino acid C-terminal flanking peptide (C-PON). Here, we present evidence that the predicted C-flanking peptide of NPY is widely distributed in both the central and peripheral nervous systems of several mammalian species including man, and has an identical distribution to NPY. It was also demonstrated, using correlative light microscopic immunostaining on serial sections and double electron microscopic immunocytochemistry, that C-PON and NPY immunoreactivities are co-localized in neuronal cell bodies of the brain cortex, sympathetic ganglion cells, norepinephrine-containing granules of the adrenal medulla and in human pheochromocytoma tumor cells.

  20. 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

  1. 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.

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

    PubMed

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

    2015-08-01

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

  3. The human beta fibrinogen promoter contains a hepatocyte nuclear factor 1-dependent interleukin-6-responsive element.

    PubMed Central

    Dalmon, J; Laurent, M; Courtois, G

    1993-01-01

    Acute-phase reactants are liver proteins whose synthesis is positively or negatively regulated during inflammation. The main mediators of this phenomenon are glucocorticoids and interleukin-6 (IL-6), a pleiotropic cytokine that also controls hematopoiesis. Functional analysis of several acute-phase reactant promoter regions has identified two major DNA motifs used by IL-6-regulated genes. The first one corresponds to a CTGG(G/A)AA sequence, and the other is a binding site for members of the C/EBP family of nuclear proteins. We have previously shown that the human beta fibrinogen (beta Fg) promoter contains an IL-6-responsive region, located between bp -150 and -67 (P. Huber, M. Laurent, and J. Dalmon, J. Biol. Chem. 265:5695-5701, 1990). In this study, using DNase I footprinting, mobility shift assays, and mutagenesis, we demonstrate that at least three subdomains of this region are necessary to observe a full response to IL-6. The most distal contains a CTGGGAA motif, and its mutation inhibits IL-6 stimulation. Another, which is able to interact with several distinct nuclear proteins, among them members of the C/EBP family, is dispensable for IL-6 induction but plays an important role in the constitutive expression of beta Fg. Finally, a proximal hepatocyte nuclear factor 1 binding site, already described as the major determinant of beta Fg tissue-specific expression, is also required for IL-6 stimulation. These results indicate a complex interplay between nuclear proteins within the beta Fg IL-6-responsive region and suggest a tight functional coupling between the tissue-specific and inducible elements. Images PMID:8423785

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

    NASA Astrophysics Data System (ADS)

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

    2009-02-01

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

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

    PubMed

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

    2016-08-01

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

  6. Analysis of strength and failure pattern of human proximal femur using quantitative computed tomography (QCT)-based finite element method.

    PubMed

    Mirzaei, Majid; Keshavarzian, Maziyar; Naeini, Vahid

    2014-07-01

    This paper presents a novel method for fast and reliable prediction of the failure strength of human proximal femur, using the quantitative computed tomography (QCT)-based linear finite element analysis (FEA). Ten fresh frozen human femora (age: 34±16) were QCT-scanned and the pertinent 3D voxel-based finite element models were constructed. A specially-designed holding frame was used to define and maintain a unique geometrical reference system for both FEA and in-vitro mechanical testing. The analyses and tests were carried out at 8 different loading orientations. A new scheme was developed for assortment of the element risk factor (defined as the ratio of the strain energy density to the yield strain energy for each element) and implemented for the prediction of the failure strength. The predicted and observed failure patterns were in correspondence, and the FEA predictions of the failure loads were in very good agreement with the experimental results (R2=0.86, slope=0.96, p<0.01). The average computational time was 5 min (on a regular desktop personal computer) for an average element number of 197,000. Noting that the run-time for a similar nonlinear model is about 8h, it was concluded that the proposed linear scheme is overwhelmingly efficient in terms of computational costs. Thus, it can efficiently be used to predict the femoral failure strength with the same accuracy of similar nonlinear models. PMID:24735974

  7. The Behaviour of Uranium in a Ridge Flank Setting

    NASA Astrophysics Data System (ADS)

    Dunk, R. M.; Mills, R. A.; Jenkins, W. J.; Mottl, M. J.; Wheat, G.; Devey, C. W.

    2002-12-01

    The magnitude and locus of hydrothermal circulation remains one of the largest uncertainties in global geochemical budgets. In particular, a large and poorly constrained chemical flux may be associated with low temperature fluid flow through the mid-ocean ridge flanks. Uranium is potentially a valuable tracer of this low temperature hydrothermal exchange as removal of U during high temperature on-axis hydrothermal circulation is quantitative and appears to be virtually complete in warm spring fluids of 62-64°C. The exchange of U across a young thinly sedimented ridge flank has been examined along a transect across the eastern flank of the East Pacific Rise at 14°S. Sediment cores were collected and pore fluids extracted during the EXCOII cruise from locations overlying oceanic crust with estimated ages of 0.3, 1.5 and 4.0 Ma. Upwelling of basement fluids was observed in some cores collected from each site. A number of these cores reached basement, providing a good measure of sediment thickness and allowing the composition of basement fluids to be inferred. The maximum ΔT in the EXCO study area was ~2°C, thus these samples represent very low temperature hydrothermal fluids. Two distinct basement fluids were identified from pore fluid measurements. A reducing fluid with U concentrations indicating removal of ~60% seawater U, and a less altered fluid suggesting removal of ~10-20% seawater U. A large diagenetic signal, with significant release of U at ~150 cm depth, was observed in regions of no flow at the 0.3 Ma site. The systematic deviations of pore fluid U concentration from the background diagenetic profile have been used to estimate basement fluid upwelling velocities at this site in the range of a few mm to cm per year through the application of a simple advection-diffusion model. Incorporating these new data into a simple fluid flow model based on geophysical and geochemical budget constraints suggests that the hydrothermal U sink is on the order of ~10

  8. 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

  9. 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.

  10. A human cytomegalovirus early promoter with upstream negative and positive cis-acting elements: IE2 negates the effect of the negative element, and NF-Y binds to the positive element.

    PubMed Central

    Huang, L; Malone, C L; Stinski, M F

    1994-01-01

    The human cytomegalovirus early promoter for the UL4 gene, which codes for an early viral envelope glycoprotein designated gpUL4, requires immediate-early viral protein two (IE2) synthesis to be activated (C.-P. Chang, C. L. Malone, and M. F. Stinski, J. Virol. 63:281, 1989). We investigated the cis-acting and trans-acting factors that regulate transcription from this UL4 promoter. In transient transfection assays, the viral IE2 protein negated the effect of an upstream cis-acting negative element and enhanced downstream gene expression. A cis-acting positive element contributed to the activity of the viral promoter when an upstream cis-acting negative element was deleted or when the viral IE2 protein was present. The cellular protein(s) that binds to the cis-acting negative element requires further investigation. The cellular protein that binds to the cis-acting positive element was characterized. Two DNA sequence-specific protein complexes were detected with DNA probes spanning the region containing the cis-acting positive element and human cytomegalovirus-infected human fibroblast cell nuclear extracts. The more slowly migrating complex was labeled complex A, and the faster was labeled complex B. Only complex B was detected with mock-infected cell nuclear extracts. Competition experiments confirmed the specificity of the A and B complexes. The protein bound to the DNA in both the complexes contacts a CCAAT box imperfect dyad symmetry (5'CCAATCACTGG3'). Either CCAAT box within the dyad symmetry could compete for binding the nuclear factor. Mutation of the CCAAT box dyad symmetry resulted in a decrease of the transcriptional activity from the UL4 promoter. A cellular transcription factor, antigenically related to nuclear factor-Y (NF-Y), was found in both complexes A and B. Events associated with viral infection caused phosphorylation of protein complex A. Dephosphorylation of the DNA-binding protein converts complex A to complex B. The effect of phosphorylation

  11. 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.

  12. 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.

  13. 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).

  14. 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.

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

    PubMed Central

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

    2015-01-01

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

  16. 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.

  17. 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

  18. 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

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

    SciTech Connect

    Lonsdale, P. )

    1989-01-10

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

  20. Comparison between elemental composition of human fingernails of healthy and opium-addicted subjects by laser-induced breakdown spectroscopy.

    PubMed

    Shadman, S; Bahreini, M; Tavassoli, S H

    2012-04-20

    The objective of the present work is to identify differences in elemental fingernail composition between opium-addicted and healthy adult human subjects using laser-induced breakdown spectroscopy. Thirty nails from normal, healthy male subjects and 30 nails from opium-addicted male individuals were analyzed. Measurements on 60 nail samples were carried out, identifying 13 key species including 11 neutral elements and 2 ions. Discriminant Function Analysis (DFA) was used to classify the samples between the two groups. Spectral line intensities of elements including Fe, C, Ti, Mg, Si, Al, Ca, H, K, O, and Na were considered variables in DFA. This analysis demonstrates the efficient discrimination between the two groups. However, the number of samples in this work is not sufficient for a decisive conclusion and further research is needed to generalize this idea.

  1. Validation of finite element predictions of cartilage contact pressure in the human hip joint.

    PubMed

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

    2008-10-01

    Methods to predict contact stresses in the hip can provide an improved understanding of load distribution in the normal and pathologic joint. The objectives of this study were to develop and validate a three-dimensional finite element (FE) model for predicting cartilage contact stresses in the human hip using subject-specific geometry from computed tomography image data, and to assess the sensitivity of model predictions to boundary conditions, cartilage geometry, and cartilage material properties. Loads based on in vivo data were applied to a cadaveric hip joint to simulate walking, descending stairs, and stair-climbing. Contact pressures and areas were measured using pressure sensitive film. CT image data were segmented and discretized into FE meshes of bone and cartilage. FE boundary and loading conditions mimicked the experimental testing. Fair to good qualitative correspondence was obtained between FE predictions and experimental measurements for simulated walking and descending stairs, while excellent agreement was obtained for stair-climbing. Experimental peak pressures, average pressures, and contact areas were 10.0 MPa (limit of film detection), 4.4-5.0 MPa, and 321.9-425.1 mm(2), respectively, while FE-predicted peak pressures, average pressures, and contact areas were 10.8-12.7 MPa, 5.1-6.2 MPa, and 304.2-366.1 mm(2), respectively. Misalignment errors, determined as the difference in root mean squared error before and after alignment of FE results, were less than 10%. Magnitude errors, determined as the residual error following alignment, were approximately 30% but decreased to 10-15% when the regions of highest pressure were compared. Alterations to the cartilage shear modulus, bulk modulus, or thickness resulted in +/-25% change in peak pressures, while changes in average pressures and contact areas were minor (+/-10%). When the pelvis and proximal femur were represented as rigid, there were large changes, but the effect depended on the particular

  2. Parametric comparisons of intracranial mechanical responses from three validated finite element models of the human head.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2010-01-01

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

  5. Activation of human long interspersed nuclear element 1 retrotransposition by benzo(a)pyrene, an ubiquitous environmental carcinogen.

    PubMed

    Stribinskis, Vilius; Ramos, Kenneth S

    2006-03-01

    Long interspersed nuclear elements [LINE-1 (L1)] are abundant retrotransposons in mammalian genomes that remain silent under most conditions. Cellular stress signals activate L1, but the molecular mechanisms controlling L1 activation remain unclear. Evidence is presented here that benzo(a)pyrene (BaP), an environmental hydrocarbon metabolized by mammalian cytochrome P450s to reactive carcinogenic intermediates, increases L1 retrotransposition in HeLa cells. Increased retrotransposition is mediated by up-regulation of L1 RNA levels, increased L1 cDNA synthesis, and stable genomic integration. Activation of L1 is dependent on the ability of BaP to cause DNA damage because it is absent in HeLa cells challenged with nongenotoxic hydrocarbon carcinogens. Thus, the mutations and genomic instability observed in human populations exposed to genotoxic environmental hydrocarbons may involve epigenetic activation of mobile elements dispersed throughout the human genome.

  6. Quantitative analysis of toxic and essential elements in human hair. Clinical validity of results.

    PubMed

    Kosanovic, Melita; Jokanovic, Milan

    2011-03-01

    Over the last three decades, there has been an increasing awareness of environmental and occupational exposures to toxic or potentially toxic trace elements. The evolution of biological monitoring includes knowledge of kinetics of toxic and/or essential elements and adverse health effects related to their exposure. The debate whether a hair is a valid sample for biomonitoring or not is still attracting the attention of analysts, health care professionals, and environmentalists. Although researchers have found many correlations of essential elements to diseases, metabolic disorders, environmental exposures, and nutritional status, opponents of the concept of hair analysis object that hair samples are unreliable due to the influence of external factors. This review discusses validity of hair as a sample for biomonitoring of essential and toxic elements, with emphasis on pre-analytical, analytical, and post-analytical factors influencing results.

  7. International project on human daily dietary intake of minor and trace elements

    SciTech Connect

    Iyengar, V.

    1986-01-01

    A coordinate research program on dietary intake of nutrient and other elements initiated by the International Atomic Energy Agency (IAEA) is currently under way. The purpose of the core program of this project is to obtain reliable data on the average daily intakes of several important minor and trace elements in diets consumed in a number of developed and developing countries such as Brazil, Canada, China, Iran, Italy, Spain, Sudan, Sweden, Thailand, and Turkey. In the core program which will be collected for determination of the nutrient elements such as calcium, magnesium, copper, iron, iodine, selenium, and zinc, among others. The project also provides for the measurement of aluminum, arsenic, cadmium, mercury, and lead in view of the biological significance of these elements as toxicants in the diet and includes estimation of the energy, phytate, and fiber components of the diet.

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

    PubMed

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

    2015-12-01

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

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

    PubMed

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

    2015-12-01

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

  10. Incorporation of Trace Elements in Ancient and Modern Human Bone: An X-Ray Absorption Spectroscopy Study

    NASA Astrophysics Data System (ADS)

    Pingitore, N. E.; Cruz-Jimenez, G.; Price, T. D.

    2001-12-01

    X-ray absorption spectroscopy (XAS) affords the opportunity to probe the atomic environment of trace elements in human bone. We are using XAS to investigate the mode(s) of incorporation of Sr, Zn, Pb, and Ba in both modern and ancient (and thus possibly altered) human and animal bone. Because burial and diagenesis may add trace elements to bone, we performed XAS analysis on samples of pristine contemporary and ancient, buried human and animal bone. We assume that deposition of these elements during burial occurs by processes distinct from those in vivo, and this will be reflected in their atomic environments. Archaeologists measure strontium in human and animal bone as a guide to diet. Carnivores show lower Sr/Ca ratios than their herbivore prey due to discrimination against Sr relative to Ca up the food chain. In an initial sample suite no difference was observed between modern and buried bone. Analysis of additional buried samples, using a more sensitive detector, revealed significant differences in the distance to the second and third neighbors of the Sr in some of the buried samples. Distances to the first neighbor, oxygen, were similar in all samples. Zinc is also used in paleo-diet studies. Initial x-ray absorption spectroscopy of a limited suite of bones did not reveal any differences between modern and buried samples. This may reflect the limited number of samples examined or the low levels of Zn in typical aqueous solutions in soils. Signals from barium and lead were too low to record useful XAS spectra. Additional samples will be studied for Zn, Ba, and Pb. We conducted our XAS experiments on beam lines 4-1 and 4-3 at the Stanford Synchrotron Radiation Laboratory. Data were collected in the fluorescence mode, using a Lytle detector and appropriate filter, and a solid state, 13-element Ge-detector.

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

    NASA Astrophysics Data System (ADS)

    Marov, Mikhail Ya.; Duke, Michael B.

    1993-10-01

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

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

    NASA Technical Reports Server (NTRS)

    Marov, Mikhail YA.; Duke, Michael B.

    1993-01-01

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

  13. The MYC 3' Wnt-Responsive Element Drives Oncogenic MYC Expression in Human Colorectal Cancer Cells.

    PubMed

    Rennoll, Sherri A; Eshelman, Melanie A; Raup-Konsavage, Wesley M; Kawasawa, Yuka Imamura; Yochum, Gregory S

    2016-01-01

    Mutations in components of the Wnt/β-catenin signaling pathway drive colorectal cancer (CRC) by deregulating expression of downstream target genes including the c-MYC proto-oncogene (MYC). The critical regulatory DNA enhancer elements that control oncogenic MYC expression in CRC have yet to be fully elucidated. In previous reports, we correlated T-cell factor (TCF) and β-catenin binding to the MYC 3' Wnt responsive DNA element (MYC 3' WRE) with MYC expression in HCT116 cells. Here we used CRISPR/Cas9 to determine whether this element is a critical driver of MYC. We isolated a clonal population of cells that contained a deletion of a single TCF binding element (TBE) within the MYC 3' WRE. This deletion reduced TCF/β-catenin binding to this regulatory element and decreased MYC expression. Using RNA-Seq analysis, we found altered expression of genes that regulate metabolic processes, many of which are known MYC target genes. We found that 3' WRE-Mut cells displayed a reduced proliferative capacity, diminished clonogenic growth, and a decreased potential to form tumors in vivo. These findings indicate that the MYC 3' WRE is a critical driver of oncogenic MYC expression and suggest that this element may serve as a therapeutic target for CRC. PMID:27223305

  14. 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.

  15. Human contribution to trace elements in urban areas as measured in holm oak (Quercus ilex L.) bark.

    PubMed

    Minganti, Vincenzo; Drava, Giuliana; Giordani, Paolo; Malaspina, Paola; Modenesi, Paolo

    2016-06-01

    The effect of human activities on the presence of trace elements in the atmosphere was evaluated by analyzing samples of holm oak bark, collected in Italy in a large city, in a small town, and in a reference area, scarcely inhabited. In all cases, point sources of pollution were excluded (e.g., industries and incinerators). The concentrations of As, Cd, Co, Cu, Fe, Mn, Ni, Pb, V, and Zn were measured using inductively coupled plasma optical emission spectrometry (ICP-OES). The element concentrations in the small town are not different from the reference area, except for Pb and Cu, while the samples collected in the large city show higher concentrations of Co, Cu, Fe, Ni, Pb, V, and Zn with respect to the rural area. In particular, the Pb levels in the large city are approximately 16 times higher than in the reference site, and five times higher than in the small town. Most element concentrations are correlated in the large city, while in the reference site, only a few significant correlations between elements were found. Even in the absence of specific sources of pollution, populations living in big cities are exposed to higher concentrations of trace elements than those living in rural environments or in small urban centers. PMID:27000118

  16. Human prion protein sequence elements impede cross-species chronic wasting disease transmission.

    PubMed

    Kurt, Timothy D; Jiang, Lin; Fernández-Borges, Natalia; Bett, Cyrus; Liu, Jun; Yang, Tom; Spraker, Terry R; Castilla, Joaquín; Eisenberg, David; Kong, Qingzhong; Sigurdson, Christina J

    2015-04-01

    Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165-175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165-175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission. PMID:25705888

  17. Human prion protein sequence elements impede cross-species chronic wasting disease transmission

    PubMed Central

    Kurt, Timothy D.; Jiang, Lin; Fernández-Borges, Natalia; Bett, Cyrus; Liu, Jun; Yang, Tom; Spraker, Terry R.; Castilla, Joaquín; Eisenberg, David; Kong, Qingzhong; Sigurdson, Christina J.

    2015-01-01

    Chronic wasting disease (CWD) is a fatal prion disease of North American deer and elk and poses an unclear risk for transmission to humans. Human exposure to CWD occurs through hunting activities and consumption of venison from prion-infected animals. Although the amino acid residues of the prion protein (PrP) that prevent or permit human CWD infection are unknown, NMR-based structural studies suggest that the β2-α2 loop (residues 165–175) may impact species barriers. Here we sought to define PrP sequence determinants that affect CWD transmission to humans. We engineered transgenic mice that express human PrP with four amino acid substitutions that result in expression of PrP with a β2-α2 loop (residues 165–175) that exactly matches that of elk PrP. Compared with transgenic mice expressing unaltered human PrP, mice expressing the human-elk chimeric PrP were highly susceptible to elk and deer CWD prions but were concurrently less susceptible to human Creutzfeldt-Jakob disease prions. A systematic in vitro survey of amino acid differences between humans and cervids identified two additional residues that impacted CWD conversion of human PrP. This work identifies amino acids that constitute a substantial structural barrier for CWD transmission to humans and helps illuminate the molecular requirements for cross-species prion transmission. PMID:25705888

  18. Identification of a conserved sequence in the non-coding regions of many human genes.

    PubMed Central

    Donehower, L A; Slagle, B L; Wilde, M; Darlington, G; Butel, J S

    1989-01-01

    We have analyzed a sequence of approximately 70 base pairs (bp) that shows a high degree of similarity to sequences present in the non-coding regions of a number of human and other mammalian genes. The sequence was discovered in a fragment of human genomic DNA adjacent to an integrated hepatitis B virus genome in cells derived from human hepatocellular carcinoma tissue. When one of the viral flanking sequences was compared to nucleotide sequences in GenBank, more than thirty human genes were identified that contained a similar sequence in their non-coding regions. The sequence element was usually found once or twice in a gene, either in an intron or in the 5' or 3' flanking regions. It did not share any similarities with known short interspersed nucleotide elements (SINEs) or presently known gene regulatory elements. This element was highly conserved at the same position within the corresponding human and mouse genes for myoglobin and N-myc, indicating evolutionary conservation and possible functional importance. Preliminary DNase I footprinting data suggested that the element or its adjacent sequences may bind nuclear factors to generate specific DNase I hypersensitive sites. The size, structure, and evolutionary conservation of this sequence indicates that it is distinct from other types of short interspersed repetitive elements. It is possible that the element may have a cis-acting functional role in the genome. Images PMID:2536922

  19. Functional genetic screens for enhancer elements in the human genome using CRISPR-Cas9.

    PubMed

    Korkmaz, Gozde; Lopes, Rui; Ugalde, Alejandro P; Nevedomskaya, Ekaterina; Han, Ruiqi; Myacheva, Ksenia; Zwart, Wilbert; Elkon, Ran; Agami, Reuven

    2016-02-01

    Systematic identification of noncoding regulatory elements has, to date, mainly relied on large-scale reporter assays that do not reproduce endogenous conditions. We present two distinct CRISPR-Cas9 genetic screens to identify and characterize functional enhancers in their native context. Our strategy is to target Cas9 to transcription factor binding sites in enhancer regions. We identified several functional enhancer elements and characterized the role of two of them in mediating p53 (TP53) and ERα (ESR1) gene regulation. Moreover, we show that a genomic CRISPR-Cas9 tiling screen can precisely map functional domains within enhancer elements. Our approach expands the utility of CRISPR-Cas9 to elucidate the functions of the noncoding genome.

  20. Human placenta processed for encapsulation contains modest concentrations of 14 trace minerals and elements.

    PubMed

    Young, Sharon M; Gryder, Laura K; David, Winnie B; Teng, Yuanxin; Gerstenberger, Shawn; Benyshek, Daniel C

    2016-08-01

    Maternal placentophagy has recently emerged as a rare but increasingly popular practice among women in industrialized countries who often ingest the placenta as a processed, encapsulated supplement, seeking its many purported postpartum health benefits. Little scientific research, however, has evaluated these claims, and concentrations of trace micronutrients/elements in encapsulated placenta have never been examined. Because the placenta retains beneficial micronutrients and potentially harmful toxic elements at parturition, we hypothesized that dehydrated placenta would contain detectable concentrations of these elements. To address this hypothesis, we analyzed 28 placenta samples processed for encapsulation to evaluate the concentration of 14 trace minerals/elements using inductively coupled plasma mass spectrometry. Analysis revealed detectable concentrations of arsenic, cadmium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, rubidium, selenium, strontium, uranium, and zinc. Based on one recommended daily intake of placenta capsules (3300 mg/d), a daily dose of placenta supplements contains approximately 0.018 ± 0.004 mg copper, 2.19 ± 0.533 mg iron, 0.005 ± 0.000 mg selenium, and 0.180 ± 0.018 mg zinc. Based on the recommended dietary allowance (RDA) for lactating women, the recommended daily intake of placenta capsules would provide, on average, 24% RDA for iron, 7.1% RDA for selenium, 1.5% RDA for zinc, and 1.4% RDA for copper. The mean concentrations of potentially harmful elements (arsenic, cadmium, lead, mercury, uranium) were well below established toxicity thresholds. These results indicate that the recommended daily intake of encapsulated placenta may provide only a modest source of some trace micronutrients and a minimal source of toxic elements.

  1. Human placenta processed for encapsulation contains modest concentrations of 14 trace minerals and elements.

    PubMed

    Young, Sharon M; Gryder, Laura K; David, Winnie B; Teng, Yuanxin; Gerstenberger, Shawn; Benyshek, Daniel C

    2016-08-01

    Maternal placentophagy has recently emerged as a rare but increasingly popular practice among women in industrialized countries who often ingest the placenta as a processed, encapsulated supplement, seeking its many purported postpartum health benefits. Little scientific research, however, has evaluated these claims, and concentrations of trace micronutrients/elements in encapsulated placenta have never been examined. Because the placenta retains beneficial micronutrients and potentially harmful toxic elements at parturition, we hypothesized that dehydrated placenta would contain detectable concentrations of these elements. To address this hypothesis, we analyzed 28 placenta samples processed for encapsulation to evaluate the concentration of 14 trace minerals/elements using inductively coupled plasma mass spectrometry. Analysis revealed detectable concentrations of arsenic, cadmium, cobalt, copper, iron, lead, manganese, mercury, molybdenum, rubidium, selenium, strontium, uranium, and zinc. Based on one recommended daily intake of placenta capsules (3300 mg/d), a daily dose of placenta supplements contains approximately 0.018 ± 0.004 mg copper, 2.19 ± 0.533 mg iron, 0.005 ± 0.000 mg selenium, and 0.180 ± 0.018 mg zinc. Based on the recommended dietary allowance (RDA) for lactating women, the recommended daily intake of placenta capsules would provide, on average, 24% RDA for iron, 7.1% RDA for selenium, 1.5% RDA for zinc, and 1.4% RDA for copper. The mean concentrations of potentially harmful elements (arsenic, cadmium, lead, mercury, uranium) were well below established toxicity thresholds. These results indicate that the recommended daily intake of encapsulated placenta may provide only a modest source of some trace micronutrients and a minimal source of toxic elements. PMID:27440542

  2. A Clinically Oriented Introduction and Review on Finite Element Models of the Human Cochlea

    PubMed Central

    Kikidis, Dimitrios; Bibas, Athanasios

    2014-01-01

    Due to the inaccessibility of the inner ear, direct in vivo information on cochlear mechanics is difficult to obtain. Mathematical modelling is a promising way to provide insight into the physiology and pathology of the cochlea. Finite element method (FEM) is one of the most popular discrete mathematical modelling techniques, mainly used in engineering that has been increasingly used to model the cochlea and its elements. The aim of this overview is to provide a brief introduction to the use of FEM in modelling and predicting the behavior of the cochlea in normal and pathological conditions. It will focus on methodological issues, modelling assumptions, simulation of clinical scenarios, and pathologies. PMID:25530973

  3. The study of double flank micro gear roll testing

    NASA Astrophysics Data System (ADS)

    Liu, Yen-Chih; An, Nai-Chun; Yang, Shu-Han; Yan, Sheng-Zhan; Chen, Shih-Lu

    2011-12-01

    The recent fast development of multifunctional portable electronic devices results in the obvious requirement of micro mechanical components. Due to the popular application of the micro actuators and the micro gearboxes, micro gears become the frequently used micro mechanical component in a small device such as small intelligent robots or dental surgical devices. Metal Industries Research & Development Centre (MIRDC) has successfully developed a small speed reducer that comprises several micro planetary gear trains. The module of this micro planetary gear train is 0.12mm. Since all gears are small, no commercial instrument is available for inspection. How to evaluate the manufacturing quality of micro gears becomes an important issue. This study focuses on the double flank gear rolling test and a specialized apparatus is built referring to the testing requirements in the international standards. The center distance variation during the rolling test is recorded and two indices, the total radial composite deviation and the maximum tooth-to-tooth radial composite deviation, are calculated to evaluate the accuracy grade of the micro gears. Experimental results show that the accuracy of the micro gear made by the cold forging process conforms to grade 7 defined in the ISO 1328-2 while grade 2 is achieved if the JGMA 116-02 is specified.

  4. Asymmetric nucleosomes flank promoters in the budding yeast genome.

    PubMed

    Ramachandran, Srinivas; Zentner, Gabriel E; Henikoff, Steven

    2015-03-01

    Nucleosomes in active chromatin are dynamic, but whether they have distinct structural conformations is unknown. To identify nucleosomes with alternative structures genome-wide, we used H4S47C-anchored cleavage mapping, which revealed that 5% of budding yeast (Saccharomyces cerevisiae) nucleosome positions have asymmetric histone-DNA interactions. These asymmetric interactions are enriched at nucleosome positions that flank promoters. Micrococcal nuclease (MNase) sequence-based profiles of asymmetric nucleosome positions revealed a corresponding asymmetry in MNase protection near the dyad axis, suggesting that the loss of DNA contacts around H4S47 is accompanied by protection of the DNA from MNase. Chromatin immunoprecipitation mapping of selected nucleosome remodelers indicated that asymmetric nucleosomes are bound by the RSC chromatin remodeling complex, which is required for maintaining nucleosomes at asymmetric positions. These results imply that the asymmetric nucleosome-RSC complex is a metastable intermediate representing partial unwrapping and protection of nucleosomal DNA on one side of the dyad axis during chromatin remodeling.

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

    PubMed Central

    Mano, Roy

    2014-01-01

    Secondary to the widespread use of the modern imaging techniques of computed tomography, magnetic resonance imaging, and ultrasound, 70% of renal tumors today are detected incidentally with a median tumor size of less than 4 cm. Twenty years ago, all renal tumors, regardless of size were treated with radical nephrectomy (RN). Elective partial nephrectomy (PN) has emerged as the treatment of choice for small renal tumors. The basis of this paradigm shift is three major factors: (1) cancer specific survival is equivalent for T1 tumors (7 cm or less) whether treated by PN or RN; (2) approximately 45% of renal tumors have indolent or benign pathology; and (3) PN prevents or delays the onset of chronic kidney disease, a condition associated with increased cardiovascular morbidity and mortality. Although PN can be technically demanding and associated with potential complications of bleeding, infection, and urinary fistula, the patient derived benefits of this operation far outweigh the risks. We have developed a "mini-flank" open surgical approach that is highly effective and, coupled with rapid recovery postoperative care pathways associated with a 2-day length of hospital stay. PMID:25237456

  6. TM6, a novel nuclear matrix attachment region, enhances its flanking gene expression through influencing their chromatin structure.

    PubMed

    Ji, Lusha; Xu, Rui; Lu, Longtao; Zhang, Jiedao; Yang, Guodong; Huang, Jinguang; Wu, Changai; Zheng, Chengchao

    2013-08-01

    Nuclear matrix attachment regions (MARs) regulate the higher-order organization of chromatin and affect the expression of their flanking genes. In this study, a tobacco MAR, TM6, was isolated and demonstrated to remarkably increase the expression of four different promoters that drive gusA gene and adjacent nptII gene. In turn, this expression enhanced the transformation frequency of transgenic tobacco. Deletion analysis of topoisomerase II-binding site, AT-rich element, and MAR recognition signature (MRS) showed that MRS has the highest contribution (61.7%) to the TM6 sequence-mediated transcription activation. Micrococcal nuclease (MNase) accessibility assay showed that 35S and NOS promoter regions with TM6 are more sensitive than those without TM6. The analysis also revealed that TM6 reduces promoter DNA methylation which can affect the gusA expression. In addition, two tobacco chromatin-associated proteins, NtMBP1 and NtHMGB, isolated using a yeast one-hybrid system, specifically bound to the TM6II-1 region (761 bp to 870 bp) and to the MRS element in the TM6II-2 (934 bp to 1,021 bp) region, respectively. We thus suggested that TM6 mediated its chromatin opening and chromatin accessibility of its flanking promoters with consequent enhancement of transcription.

  7. TM6, a novel nuclear matrix attachment region, enhances its flanking gene expression through influencing their chromatin structure.

    PubMed

    Ji, Lusha; Xu, Rui; Lu, Longtao; Zhang, Jiedao; Yang, Guodong; Huang, Jinguang; Wu, Changai; Zheng, Chengchao

    2013-08-01

    Nuclear matrix attachment regions (MARs) regulate the higher-order organization of chromatin and affect the expression of their flanking genes. In this study, a tobacco MAR, TM6, was isolated and demonstrated to remarkably increase the expression of four different promoters that drive gusA gene and adjacent nptII gene. In turn, this expression enhanced the transformation frequency of transgenic tobacco. Deletion analysis of topoisomerase II-binding site, AT-rich element, and MAR recognition signature (MRS) showed that MRS has the highest contribution (61.7%) to the TM6 sequence-mediated transcription activation. Micrococcal nuclease (MNase) accessibility assay showed that 35S and NOS promoter regions with TM6 are more sensitive than those without TM6. The analysis also revealed that TM6 reduces promoter DNA methylation which can affect the gusA expression. In addition, two tobacco chromatin-associated proteins, NtMBP1 and NtHMGB, isolated using a yeast one-hybrid system, specifically bound to the TM6II-1 region (761 bp to 870 bp) and to the MRS element in the TM6II-2 (934 bp to 1,021 bp) region, respectively. We thus suggested that TM6 mediated its chromatin opening and chromatin accessibility of its flanking promoters with consequent enhancement of transcription. PMID:23852133

  8. [Effects of discharges of the aluminium works on the elemental contents of human biosubstrates].

    PubMed

    Zhuk, L I; Khadzhibaeva, G S; Kist, A A; Kovaleva, V A; Mikhol'skaia, I N; Danilova, E A

    1991-10-01

    Data of the chemical elements content in blood, placenta, breast milk, hairs of Sariasy region in Surhandarya area inhabitants are given. This region is situated under aluminium work discharge. High content of fluorine and very low levels of selenium, chromium, manganese, iron, cobalt, copper in hairs were noted.

  9. Investigation of elemental distribution in human femoral head by PIXE and SRXRF microprobe

    NASA Astrophysics Data System (ADS)

    Zhang, Y. X.; Wang, Y. S.; Zhang, Y. P.; Zhang, G. L.; Huang, Y. Y.; He, W.

    2007-07-01

    In order to study the distribution and possible degenerative processes inducing the loss of inorganic substances in bone and to provide a scientific basis for the prevention and therapy of osteoporosis, proton induced X-ray emission (PIXE) method is used for the determination of elemental concentrations in femoral heads from five autopsies and seven patients with femoral neck fractures. Synchrotron radiation X-ray fluorescence (SRXRF) microprobe analysis technique is used to scan a slice of the femoral head from its periphery to its center, via cartilage, compact and spongy zones. The specimen preparation and experiment procedure are described in detail. The results show that the concentrations of P, Ca, Fe, Cu, Sr in the control group are higher than those in the patient group, but the concentrations of S, K, Zn, Mn are not significantly different. The quantitative results of elemental distribution, such as Ca, P, K, Fe, Zn, Sr and Pb in bone slice tissue including cartilage, substantial compact and substantial spongy, are investigated. The data obtained show that the concentrations of Ca, P, K, (the major elements of bone composition), are obviously low in both spongy and cartilage zones in the patient group, but there are no remarkable differences in the compact zone. Combined with the correlations between P, K, Zn, Sr and Ca, the loss mechanism of minerals and the physiological functions of some metal elements in bone are also discussed.

  10. DNA sequences of Alu elements indicate a recent replacement of the human autosomal genetic complement

    SciTech Connect

    Knight, A.; Deininger, P.L.; Batzer, M.A.

    1996-04-30

    DNA sequences of neutral nuclear autosomal loci, compared across diverse human populations, provide a previously untapped perspective into the mode and tempo of the emergence of modern humans and a critical comparison with published clonally inherited mitochondrial DNA and Y chromosome measurements of human diversity. We obtained over 55 kilobases of sequence from three autosomal loci encompassing Alu repeats for representatives of diverse human populations as well as orthologous sequences for other hominoid species at one of these loci. Nucleotide diversity was exceedingly low. Most individuals and populations were identical. Only a single nucleotide difference distinguished presumed ancestral alleles from descendants. These results differ from those expected if alleles from divergent archaic populations were maintained through multiregional continuity. The observed virtual lack of sequence polymorphism is the signature of a recent single origin for modern humans, with general replacement of archaic populations. 47 refs., 2 figs., 1 tab.

  11. Composition and distribution of elements and ultrastructural topography of a human cardiac calculus.

    PubMed

    Cheng, Ching-Li; Chang, Hsiao-Huang; Huang, Pei-Jung; Chu, Yu-Ting; Lin, Shan-Yang

    2013-04-01

    Trace elements (TEs) may contribute to the formation of calculi or stones or be involved in the aetiopathogenesis of stone diseases. The compositions and spatial distribution of elements from the inner nucleus to outer crust of the cardiac calculus were investigated by energy-dispersive X-ray fluorescence (EDXRF) spectrometer. The surface topograph, distribution map of elements, elemental and chemical compositions were also determined by environmental scanning electron microscope (ESEM)-energy-dispersive X-ray (EDX) analysis. Twenty-five elements were identifiable from 18 positions on the cardiac calculus by EDXRF spectrometer, in which the highest concentrations of toxic TEs (Ni, Pt, Hg, Sn, Pb, W, Au, Al, Si) and higher levels of essential TEs (Ca, Sr, Cr, P) were detected. A moderate positive Pearson's correlation between TEs concentrations of Mg, Ca or P and location differences from centre to periphery in the cardiac calculus was observed. A positive correlation was also found for Ca/Zn and Ca/Cu, indicating the gradual increase of calcium concentration from inner nucleus to outer crust of cardiac calculus. The drop-like nodules/crystals on the surface of petrous part of cardiac calculus were observed from ESEM analysis. ESEM-EDX analysis determined the calculus to be predominantly composed of calcium hydroxyapatite and cholesterol, as indicated by the petrous surface and drop-like nodules/crystals, respectively. This composition was confirmed using a portable Raman analyser. The spatial distribution analysis indicated a gradual increase in Mg, P and Ca concentrations from the inner nucleus to the outer crust of the cardiac calculus. The major chemical compositions of calcium hydroxyapatite and cholesterol were detected on this cardiac calculus. PMID:23404458

  12. Automatic measurement of spur gear dimensions using laser light, part 2: measurement of flank profile

    NASA Astrophysics Data System (ADS)

    Younes, M. A.; Khalil, Abdallah M.; Damir, Mohamed

    2005-10-01

    In part I of this study a laser-based system for automatic measurement of spur gears' tooth thickness and pitch was introduced. The developed system provides an inaccuracy value on the order of 5 µm, and the measurement time, for all gear teeth, was just about 1 min. In this part the experimental work is further extended to measure the tooth flank profile of spur gears. Flank profile is one of the most important factors that affect gear performance. In gear meshing, motion is transferred through contact along gear flanks. Deviations in flank profile due to errors in manufacturing or nonuniform wear result in variations in gear movement. Measurement of the flank profile can help in adjusting the gear manufacturing process, control the quality of manufactured gears, and monitor the wear of gears during action. The proposed flank profile measurement system is based on the principle of optical triangulation. The flank profile measurement setup is integrated with that of the tooth thickness and pitch, and hence tooth thickness, pitch, and profile measurements are performed simultaneously, and the measurement time for the three parameters for all gear teeth remains less than 1 min. Software is developed to graph the actual tooth profile and evaluate its deviation from nominal shape. The flank profiles measured using the developed system are in good agreement with those obtained from a well-established measurement method.

  13. Multiple single-stranded cis elements are associated with activated chromatin of the human c-myc gene in vivo.

    PubMed Central

    Michelotti, G A; Michelotti, E F; Pullner, A; Duncan, R C; Eick, D; Levens, D

    1996-01-01

    Transcription activation and repression of eukaryotic genes are associated with conformational and topological changes of the DNA and chromatin, altering the spectrum of proteins associated with an active gene. Segments of the human c-myc gene possessing non-B structure in vivo located with enzymatic and chemical probes. Sites hypertensive to cleavage with single-strand-specific S1 nuclease or the single-strand-selective agent potassium permanganate included the major promoters P1 and P2 as well as the far upstream sequence element (FUSE) and CT elements, which bind, respectively, the single-strand-specific factors FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K in vitro. Active and inactive c-myc genes yielded different patterns of S1 nuclease and permanganate sensitivity, indicating alternative chromatin configurations of active and silent genes. The melting of specific cis elements of active c-myc genes in vivo suggested that transcriptionally associated torsional strain might assist strand separation and facilitate factor binding. Therefore, the interaction of FUSE-binding protein and heterogeneous nuclear ribonucleoprotein K with supercoiled DNA was studied. Remarkably, both proteins recognize their respective elements torsionally strained but not as liner duplexes. Single-strand- or supercoil-dependent gene regulatory proteins may directly link alterations in DNA conformation and topology with changes in gene expression. PMID:8649373

  14. A finite element study of age-based size and shape variation of the human rib cage.

    PubMed

    Gayzik, F Scott; Loftis, Kathryn L; Slice, Dennis E; Stitzel, Joel D

    2006-01-01

    To fully understand the effects of aging on the integrity of the normal skeleton, detailed geometric models are needed to complement material property data. The purpose of this research is to develop a predictive model for age-related changes in rib-cage geometry using the generalized Procrustes approach, an advanced method of shape analysis. This predictive model is coupled with the finite element method to isolate the effects age-related size and shape change have on the structural response of the rib cage. Using a relatively small sample set (n = 12), trends in the age-related size and shape change of the human thorax consistent with clinical observations are identified. Finite element models constructed from landmark datasets generated via the generalized Procrustes approach demonstrate a decrease with age in the energy absorbing capacity of the thorax during a blunt impact.

  15. Cribra orbitalia and trace element content in human teeth from Neolithic and Early Bronze Age graves in southern Poland.

    PubMed

    Gleń-Haduch, E; Szostek, K; Głab, H

    1997-06-01

    Determination of element levels in bones and teeth can complement knowledge of the diagnostics and etiology of various diseases in prehistoric populations. Calcium (Ca), cadmium (Cd), copper (Cu), iron (Fe), and lead (Pb) content were analyzed in teeth from human skeletons dated to 3,000-1,400 BC from Malopolska Upland loess. Levels of iron and calcium were determined using atomic absorption spectroscopy (AAS), and lead, cadmium, and copper levels were measured using anodic stripping voltametry (ASV). Molar teeth from specimens with cribra orbitalia were selected for analyses, and teeth from specimens with no pathological changes were used as a control. No significant correlations between the content of particular elements and the tooth class, specimen age, or depth of burial pit were observed. The Fe content in specimens with cribra orbitalia is not the best measure for this disease's etiology. Thus, interelement correlations and proportions might give a better picture of the biological condition of the specimen and of the investigated groups.

  16. [Distant interactions between enhancers and promoters in Drosophila melanogaster are mediated by transgene-flanking Su(Hw) insulators].

    PubMed

    Davydova, A I; Erokhin, M M; Georgiev, P G; Chetverina, D A

    2011-08-01

    Insulators are DNA elements modulating gene activation by enhancers. Interaction between insulators can result in either isolation, or activation of promoter by the enhancer. In the present study, it is demonstrated that in transgenic lines, the yellow enhancers are unable to activate promoter of the tagged gene through the mini-white gene. The mini-white promoter, which functions as an insulator, can block the enhancer activity. In case that the genes and regulatory elements in the construct are flanked by Su(Hw) insulators from retroposon MDG4, interaction between enhancers and the yellow promoter is restored. The data obtained are congruent with the model suggesting that promoters can function as insulators, and that interaction between the insulators facilitates the interaction between enhancers and promoters within transcriptional domain.

  17. Investigating the potential for volcano flank instability triggered by recent dike intrusions at Fogo volcano, Cape Verde

    NASA Astrophysics Data System (ADS)

    Bagnardi, Marco; González, Pablo; Hooper, Andrew; Wright, Tim

    2015-04-01

    Gravitational flank-collapses at volcanoes are rare but catastrophic events that have rarely been witnessed by humans (e.g., Mount St. Helens in 1980). It has been proposed that gravitationally unstable volcanic flanks can be classified in two different types based on the flanks slope: volcanoes characterized by gentle slopes (Hawaiian-like) and that have very dynamic flanks exhibiting high rates of deformation and, conversely, steep-sided volcanoes (Macaronesian-like) showing minimal ground deformation. The two types of volcanoes could therefore reach the stable-state through different mechanisms and experience different mass-wasting processes. Numerous giant debris-avalanche deposits have been identified offshore the volcanoes of the Canary Islands and Cape Verde. Given the steep slopes of these volcanoes, the mass-wasting events may have occurred suddenly and with minimal precursory signals. Several mechanisms have been proposed as potential triggers and among these the intrusion of shallow dikes feeding fissure eruptions is one of the best candidates. In this work, we investigate this hypothesis in the light of new and revised results derived from the analysis of geodetic observations at Fogo volcano (Cape Verde). Fogo has erupted twice in the last 20 years (1995 and 2014-2015) and in both occasions the volcano erupted along fissures that seem to be fed by dykes intruding the shallow crust and the volcanic edifice. We re-process radar data from the ERS satellite to obtain state-of-the-art deformation maps spanning the 1995 eruption and revisit previously proposed models of the magmatic system. Our results indicate that both eruptions were fed by sub-vertical dikes, steeply dipping to the SE, and radiating from the Pico do Fogo volcanic cone to the SW. We also study the effect of such magmatic intrusions in terms of the stress regime that they generate and analyze whether the 1995 and 2014 intrusions could potentially destabilize the structures along which a

  18. Toxic elements in groundwater of Lagos and Ogun States, Southwest, Nigeria and their human health risk assessment.

    PubMed

    Ayedun, H; Gbadebo, A M; Idowu, O A; Arowolo, T A

    2015-06-01

    A good quality drinking water is essential for human survival. However, a large percentage of the populations in most developing countries (Nigeria inclusive) do not have access to potable water. This study was therefore conducted to assess the extent of risk arising from consumption of toxic elements in groundwater samples collected from Lagos and Ogun States, Southwest, Nigeria. Twelve toxic elements concentrations (As, Mn, Cd, Cr, Pb, Ni, Al, Ti, V, Hg, Li, and Sn) were determined from 170 groundwater samples using inductively coupled plasma-mass spectrometry, and the physicochemical parameters were determined using standard methods. The pH results revealed that most of the water samples were slightly acidic. Of the twelve toxic elements, only Mn, Cd, Pb, Ni, and Al have concentrations higher than the WHO recommended limit in drinking water. The average dose of Mn and Al consumed daily from groundwater by an adult in Lagos state is 3.4 and 23.2 (μg/kg body weight), respectively. Similarly, an adult in Ogun State consumed an average daily dose of 6.09 and 25 (μg/kg body weight) Mn and Al, respectively. A greater threat was posed to children and infants. The order for risk of cancer in groundwater from Lagos State was Pb > Cr > As > Cd while the order in Ogun State groundwater was Cr > Cd > As > Pb. The relative high concentrations of Mn, Al, and Pb obtained in this study can be attributed to industrial and anthropogenic activities in the study area. Treatment of groundwater before consumption is recommended to avoid possible adverse cumulative effect. Improved waste disposal methods and regular monitoring of toxic elements in groundwater of the study area should be adopted to safeguard human health. PMID:25971518

  19. Toxic elements in groundwater of Lagos and Ogun States, Southwest, Nigeria and their human health risk assessment.

    PubMed

    Ayedun, H; Gbadebo, A M; Idowu, O A; Arowolo, T A

    2015-06-01

    A good quality drinking water is essential for human survival. However, a large percentage of the populations in most developing countries (Nigeria inclusive) do not have access to potable water. This study was therefore conducted to assess the extent of risk arising from consumption of toxic elements in groundwater samples collected from Lagos and Ogun States, Southwest, Nigeria. Twelve toxic elements concentrations (As, Mn, Cd, Cr, Pb, Ni, Al, Ti, V, Hg, Li, and Sn) were determined from 170 groundwater samples using inductively coupled plasma-mass spectrometry, and the physicochemical parameters were determined using standard methods. The pH results revealed that most of the water samples were slightly acidic. Of the twelve toxic elements, only Mn, Cd, Pb, Ni, and Al have concentrations higher than the WHO recommended limit in drinking water. The average dose of Mn and Al consumed daily from groundwater by an adult in Lagos state is 3.4 and 23.2 (μg/kg body weight), respectively. Similarly, an adult in Ogun State consumed an average daily dose of 6.09 and 25 (μg/kg body weight) Mn and Al, respectively. A greater threat was posed to children and infants. The order for risk of cancer in groundwater from Lagos State was Pb > Cr > As > Cd while the order in Ogun State groundwater was Cr > Cd > As > Pb. The relative high concentrations of Mn, Al, and Pb obtained in this study can be attributed to industrial and anthropogenic activities in the study area. Treatment of groundwater before consumption is recommended to avoid possible adverse cumulative effect. Improved waste disposal methods and regular monitoring of toxic elements in groundwater of the study area should be adopted to safeguard human health.

  20. Scattering of the field of a multi-element phased array by human ribs

    NASA Astrophysics Data System (ADS)

    Gélat, P.; ter Haar, G.; Saffari, N.

    2012-03-01

    The efficacy of high intensity focused ultrasound (HIFU) for the non-invasive treatment of cancer has been demonstrated for a range of different cancers including those of the liver, kidney, prostate and breast. As a non-invasive focused therapy, HIFU offers considerable advantages over other techniques such as chemotherapy and surgical resection, in terms of invasiveness and risk of harmful side effects. Despite its advantages, however, there are a number of significant challenges currently hindering its widespread clinical application. One of these challenges is the need to transmit sufficient energy through the ribcage to induce tissue necrosis at the required foci whilst minimising the formation of side lobes. Multielement random arrays are currently showing great promise in overcoming the limitations of single-element transducers. Nevertheless, successfully treating a patient for liver tumours requires a thorough understanding of the way in which the ultrasonic pressure field from a HIFU array is scattered by the ribcage. A mesh of quadratic pressure patches was generated using CT scan data for ribs nine to twelve on the right side. A boundary element approach based on a Generalised Minimal Residual (GMRES) implementation of the Burton-Miller formulation was used, in conjunction with phase conjugation techniques to focus the field of a 256-element random HIFU array past the ribs at both intercostal and transcostal treatment locations. This method has the advantage of accounting for full effects of scattering and diffraction in three dimensions under continuous wave excitation.

  1. Does intake of trace elements through urban gardening in Copenhagen pose a risk to human health?

    PubMed

    Warming, Marlies; Hansen, Mette G; Holm, Peter E; Magid, Jakob; Hansen, Thomas H; Trapp, Stefan

    2015-07-01

    This study investigates the potential health risk from urban gardening. The concentrations of the trace elements arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn) in five common garden crops from three garden sites in Copenhagen were measured. Concentrations (mg/kg dw) of As were 0.002-0.21, Cd 0.03-0.25, Cr < 0.09-0.38, Cu 1.8-8.7, Ni < 0.23-0.62, Pb 0.05-1.56, and Zn 10-86. Generally, elemental concentrations in the crops do not reflect soil concentrations, nor exceed legal standards for Cd and Pb in food. Hazard quotients (HQs) were calculated from soil ingestion, vegetable consumption, measured trace element concentrations and tolerable intake levels. The HQs for As, Cd, Cr, Cu, Ni, and Zn do not indicate a health risk through urban gardening in Copenhagen. Exposure to Pb contaminated sites may lead to unacceptable risk not caused by vegetable consumption but by unintentional soil ingestion. PMID:25796073

  2. Trace elements in the environment and in human organs. I. Methods and results

    SciTech Connect

    Takacs, S.; Tatar, A.

    1987-04-01

    The authors have determined by spectrophotometry the copper, zinc, lead, and cadmium content of the kidney, liver, lung, and adrenal derived from 1072 autopsies. The metallic content of food and drink was examined and the daily quantity consumed was stated by measuring and calculation. According to the results in Hungary the daily ingestion of these four microelements is small, as reflected by the metal content of the organs. An average 75% of the kidney's whole cadmium content is present in the cortex of the kidney. Lead in the medulla and zinc in the cortex are found in larger quantities. Analyzing the distribution according to sexes it was found that lead in the liver and kidney and cadmium in the kidney and lung of women is significantly lower than in the male. However, the element content in the adrenal is significantly higher for zinc and cadmium in women. The cadmium distribution in the kidney is similar to the essential elements. The correlation of the element pairs is better in the kidney and lung (Zn-Cu is 0.55 in the kidney and 0.51 in the lung).

  3. Does intake of trace elements through urban gardening in Copenhagen pose a risk to human health?

    PubMed

    Warming, Marlies; Hansen, Mette G; Holm, Peter E; Magid, Jakob; Hansen, Thomas H; Trapp, Stefan

    2015-07-01

    This study investigates the potential health risk from urban gardening. The concentrations of the trace elements arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu), lead (Pb), nickel (Ni), and zinc (Zn) in five common garden crops from three garden sites in Copenhagen were measured. Concentrations (mg/kg dw) of As were 0.002-0.21, Cd 0.03-0.25, Cr < 0.09-0.38, Cu 1.8-8.7, Ni < 0.23-0.62, Pb 0.05-1.56, and Zn 10-86. Generally, elemental concentrations in the crops do not reflect soil concentrations, nor exceed legal standards for Cd and Pb in food. Hazard quotients (HQs) were calculated from soil ingestion, vegetable consumption, measured trace element concentrations and tolerable intake levels. The HQs for As, Cd, Cr, Cu, Ni, and Zn do not indicate a health risk through urban gardening in Copenhagen. Exposure to Pb contaminated sites may lead to unacceptable risk not caused by vegetable consumption but by unintentional soil ingestion.

  4. Organization of the human myoglobin gene.

    PubMed Central

    Weller, P; Jeffreys, A J; Wilson, V; Blanchetot, A

    1984-01-01

    Cross-hybridization of the grey seal myoglobin gene to human DNA detected a single human myoglobin gene plus an extensive family of sequences apparently related to the central exon of this gene. The functional human gene is 10.4 kb long and has a haemoglobin-like three exon/two intron structure with long non-coding regions similar to its seal homologue. At least 300 bp of 5'-flanking region are closely homologous between the two genes, with the exception of a divergent purine-rich region 68-114 bp upstream of the cap site. A diverged tandem repetitive sequence based on (GGAT)165 is located 1100-1750 bp upstream from the gene; internal homology units within this sequence suggest sequence homogenization by gene microconversions. A second 33-bp tandem repeat element in the first intron is flanked by a 9-bp direct repeat, shares homology with other tandem repetitive elements in the human genome and may represent a novel form of transposable element. Images Fig. 2. PMID:6571704

  5. Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells

    PubMed Central

    Coufal, Nicole G.; Garcia-Perez, Josè Luis; Peng, Grace E.; Marchetto, Maria C. N.; Muotri, Alysson R.; Mu, Yangling; Carson, Christian T.; Macia, Angela; Moran, John V.; Gage, Fred H.

    2011-01-01

    Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition. PMID:22159035

  6. Ataxia telangiectasia mutated (ATM) modulates long interspersed element-1 (L1) retrotransposition in human neural stem cells.

    PubMed

    Coufal, Nicole G; Garcia-Perez, Josè Luis; Peng, Grace E; Marchetto, Maria C N; Muotri, Alysson R; Mu, Yangling; Carson, Christian T; Macia, Angela; Moran, John V; Gage, Fred H

    2011-12-20

    Long interspersed element-1 (L1) retrotransposons compose ∼20% of the mammalian genome, and ongoing L1 retrotransposition events can impact genetic diversity by various mechanisms. Previous studies have demonstrated that endogenous L1 retrotransposition can occur in the germ line and during early embryonic development. In addition, recent data indicate that engineered human L1s can undergo somatic retrotransposition in human neural progenitor cells and that an increase in human-specific L1 DNA content can be detected in the brains of normal controls, as well as in Rett syndrome patients. Here, we demonstrate an increase in the retrotransposition efficiency of engineered human L1s in cells that lack or contain severely reduced levels of ataxia telangiectasia mutated, a serine/threonine kinase involved in DNA damage signaling and neurodegenerative disease. We demonstrate that the increase in L1 retrotransposition in ataxia telangiectasia mutated-deficient cells most likely occurs by conventional target-site primed reverse transcription and generate either longer, or perhaps more, L1 retrotransposition events per cell. Finally, we provide evidence suggesting an increase in human-specific L1 DNA copy number in postmortem brain tissue derived from ataxia telangiectasia patients compared with healthy controls. Together, these data suggest that cellular proteins involved in the DNA damage response may modulate L1 retrotransposition.

  7. Human Endogenous Retrovirus K (HML-2) Elements in the Plasma of People with Lymphoma and Breast Cancer ▿ †

    PubMed Central

    Contreras-Galindo, Rafael; Kaplan, Mark H.; Leissner, Philippe; Verjat, Thibault; Ferlenghi, Ilaria; Bagnoli, Fabio; Giusti, Fabiola; Dosik, Michael H.; Hayes, Daniel F.; Gitlin, Scott D.; Markovitz, David M.

    2008-01-01

    Actively replicating endogenous retroviruses entered the human genome millions of years ago and became a stable part of the inherited genetic material. They subsequently acquired multiple mutations, leading to the assumption that these viruses no longer replicate. However, certain human tumor cell lines have been shown to release endogenous retroviral particles. Here we show that RNA from human endogenous retrovirus K (HERV-K) (HML-2), a relatively recent entrant into the human genome, can be found in very high titers in the plasma of patients with lymphomas and breast cancer as measured by either reverse transcriptase PCR or nucleic acid sequence-based amplification. Further, these titers drop dramatically with cancer treatment. We also demonstrate the presence of reverse transcriptase and viral RNA in plasma fractions that contain both immature and correctly processed HERV-K (HML-2) Gag and envelope proteins. Finally, using immunoelectron microscopy, we show the presence of HERV-K (HML-2) virus-like particles in the plasma of lymphoma patients. Taken together, these findings demonstrate that elements of the endogenous retrovirus HERV-K (HML-2) can be found in the blood of modern-day humans with certain cancers. PMID:18632860

  8. Determining comparative elemental profile using handheld X-ray fluorescence in humans, elephants, dogs, and dolphins: Preliminary study for species identification.

    PubMed

    Nganvongpanit, Korakot; Buddhachat, Kittisak; Klinhom, Sarisa; Kaewmong, Patcharaporn; Thitaram, Chatchote; Mahakkanukrauh, Pasuk

    2016-06-01

    Species identification is a crucial step in forensic anthropological studies. The aim of this study was to determine elemental profiles in bones from four mammal species, to be used for species discrimination. Human, elephant, dog, and dolphin bones were scanned by X-ray fluorescence (XRF); the differences in elemental profiles between species were determined using discriminant analysis. Dogs had the greatest number of elements (23), followed by humans (22) and elephants (20). Dolphins had the lowest number of elements (16). The accuracy rate of species identification in humans, elephants, dogs, and dolphins was 98.7%, 100%, 94.9%, and 92.3%, respectively. We conclude that element profiles of bones based on XRF analyses can serve as a tool for determining species. PMID:27093230

  9. The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained.

  10. The 5'-flanking regions of three pea legumin genes: comparison of the DNA sequences.

    PubMed Central

    Lycett, G W; Croy, R R; Shirsat, A H; Richards, D M; Boulter, D

    1985-01-01

    Approximately 1200 nucleotides of sequence data from the promoter and 5'-flanking regions of each of three pea (Pisum sativum L.) legumin genes (legA, legB and legC) are presented. The promoter regions of all three genes were found to be identical including the "TATA box", and "CAAT box', and sequences showing homology to the SV40 enhancers. The legA sequence begins to diverge from the others about 300bp from the start codon, whereas the other two genes remain identical for another 550bp. The regions of partial homology exhibit deletions or insertions and some short, comparatively well conserved sequences. The significance of these features is discussed in terms of evolutionary mechanisms and their possible functional roles. The legC gene contains a region that may potentially form either of two mutually exclusive stem-loop structures, one of which has a stem 42bp long, which suggests that it could be fairly stable. We suggest that a mechanism of switching between such alternative structures may play some role in gene control or may represent the insertion of a transposable element. PMID:2997721

  11. Ensemble modeling coupled with six element concentrations in human blood for cancer diagnosis.

    PubMed

    Chen, Hui; Tan, Chao; Wu, Tong

    2011-10-01

    Six important metal contents (i.e., zinc, barium, magnesium, calcium, copper, and selenium) in blood samples coupled with an ensemble classification algorithm have been used for the classification of normal people and cancer patients. A dataset containing 42 healthy samples and 32 cancer samples was used for experiment. The prediction results from this method outperformed those from the newly developed support vector machine, i.e., a sensitivity of 100%, a specificity of 95.2%, and an overall accuracy of 98.6%. It seems that ELDA coupled with blood element analysis can serve as a valuable tool for diagnosing cancer in clinical practice.

  12. Numerical study of human vocal folds vibration using Immersed Finite Element Method

    NASA Astrophysics Data System (ADS)

    Wang, Xingshi; Zhang, Lucy; Krane, Michael

    2011-11-01

    The voice production procedure is a self-oscillating, fluid-structure interaction problem. In this study, the vocal folds vibration during phonation will be simulated by self-oscillated layered-structure vocal folds model, using Immersed Finite Element Method. With the numerical results, we will find out the vocal folds vibration pattern, and also show how the lung pressure, stiffness and geometry of vocal folds will affect the vocal folds vibration. With further analysis, we shall get better understanding of the dynamics of voice production. National Institute on Deafness and Other Communication Disorders.

  13. Human polyomavirus JCV late leader peptide region contains important regulatory elements

    SciTech Connect

    Akan, Ilhan; Sariyer, Ilker Kudret; Biffi, Renato; Palermo, Victoria; Woolridge, Stefanie; White, Martyn K.; Amini, Shohreh |; Khalili, Kamel; Safak, Mahmut . E-mail: msafak@temple.edu

    2006-05-25

    Transcription is a complex process that relies on the cooperative interaction between sequence-specific factors and the basal transcription machinery. The strength of a promoter depends on upstream or downstream cis-acting DNA elements, which bind transcription factors. In this study, we investigated whether DNA elements located downstream of the JCV late promoter, encompassing the late leader peptide region, which encodes agnoprotein, play regulatory roles in the JCV lytic cycle. For this purpose, the entire coding region of the leader peptide was deleted and the functional consequences of this deletion were analyzed. We found that viral gene expression and replication were drastically reduced. Gene expression also decreased from a leader peptide point mutant but to a lesser extent. This suggested that the leader peptide region of JCV might contain critical cis-acting DNA elements to which transcription factors bind and regulate viral gene expression and replication. We analyzed the entire coding region of the late leader peptide by a footprinting assay and identified three major regions (region I, II and III) that were protected by nuclear proteins. Further investigation of the first two protected regions by band shift assays revealed a new band that appeared in new infection cycles, suggesting that viral infection induces new factors that interact with the late leader peptide region of JCV. Analysis of the effect of the leader peptide region on the promoter activity of JCV by transfection assays demonstrated that this region has a positive and negative effect on the large T antigen (LT-Ag)-mediated activation of the viral early and late promoters, respectively. Furthermore, a partial deletion analysis of the leader peptide region encompassing the protected regions I and II demonstrated a significant down-regulation of viral gene expression and replication. More importantly, these results were similar to that obtained from a complete deletion of the late leader

  14. Long interspersed element-1 (LINE-1): passenger or driver in human neoplasms?

    PubMed

    Rodić, Nemanja; Burns, Kathleen H

    2013-03-01

    LINE-1 (L1) retrotransposons make up a significant portion of human genomes, with an estimated 500,000 copies per genome. Like other retrotransposons, L1 retrotransposons propagate through RNA sequences that are reverse transcribed into DNA sequences, which are integrated into new genomic loci. L1 somatic insertions have the potential to disrupt the transcriptome by inserting into or nearby genes. By mutating genes and playing a role in epigenetic dysregulation, L1 transposons may contribute to tumorigenesis. Studies of the "mobilome" have lagged behind other tumor characterizations at the sequence, transcript, and epigenetic levels. Here, we consider evidence that L1 retrotransposons may sometimes drive human tumorigenesis.

  15. Simulation of bone-conducted sound transmission in a three-dimensional finite-element model of a human skull

    NASA Astrophysics Data System (ADS)

    Chang, You; Kim, Namkeun; Stenfelt, Stefan

    2015-12-01

    Bone conduction (BC) is the transmission of sound to the inner ear through the bones of the skull. This type of transmission is used in humans fitted with BC hearing aids as well as to classify between conductive and sensorineural hearing losses. The objective of the present study is to develop a finite-element (FE) model of the human skull based on cryosectional images of a female cadaver head in order to gain better understanding of the sound transmission. Further, the BC behavior was validated in terms of sound transmission against experimental data published in the literature. Results showed the responses of the simulated skull FE model were consistent with the experimentally reported data.

  16. An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Goodman, Allen; Hooley, Becky L.

    2003-01-01

    An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

  17. An AP-2 element acts synergistically with the cyclic AMP- and Phorbol ester-inducible enhancer of the human proenkephalin gene

    SciTech Connect

    Hyman, S.E.; Comb, M.; Pearlberg, J.; Goodman, H.M.

    1989-01-01

    An enhancer with two DNA elements, one containing the sequence CGTCA, is required for cyclic AMP-and phorbol ester-inducible transcription of the human proenkephalin gene. The authors report that an AP-2 element located adjacent to the enhancer acts synergistically with it to confer maximal response to cyclic AMP and phorbol esters.

  18. Multi-Element Behaviour Support as a Model for the Delivery of a Human Rights Based Approach for Working with People with Intellectual Disabilities and Behaviours that Challenge

    ERIC Educational Resources Information Center

    Doody, Christina

    2009-01-01

    This paper demonstrates the effectiveness of the multi-element behaviour support (MEBS) model in meeting the rights of persons with intellectual disabilities and behaviours that challenge. It does this through explicitly linking the multi-element model to the guiding principles of a human rights based approach (HRBA) using a vignette to…

  19. Edible flowers--a new promising source of mineral elements in human nutrition.

    PubMed

    Rop, Otakar; Mlcek, Jiri; Jurikova, Tunde; Neugebauerova, Jarmila; Vabkova, Jindriska

    2012-05-31

    On a global scale, people are demanding more attractive and tasty food. Both the quality of foodstuffs and aesthetic aspects contribute to the appearance of consumed meals. The attraction and appeal of individual dishes could be enhanced by edible flowers. New information concerning the composition and nutritional value of edible flowers is also important and represents a sufficient reason for their consumption. The aim of this study is to contribute to the popularization of some selected edible flowers of ornamental plants involving altogether 12 species. The flowers were used to determine their antioxidant capacity, which fluctuated between 4.21 and 6.96 g of ascorbic acid equivalents (AAE)/kg of fresh mass (FM). Correlation coefficients between antioxidant capacity and the contents of total phenolics and flavonoids were r² = 0.9705 and r² = 0.7861, respectively. Moreover, the results were supplemented with new data about the mineral composition of edible flowers (mostly, not found in the available literature). The highest levels of mineral elements were observed in the flowers of species Chrysanthemum, Dianthus or Viola. The most abundant element was potassium, the content of which ranged from 1,842.61 to 3,964.84 mg/kg of FM.

  20. Trace elements and electrolytes in human resting mixed saliva after exercise

    PubMed Central

    Chicharro, J. L.; Serrano, V.; Urena, R.; Gutierrez, A. M.; Carvajal, A.; Fernandez-, H; Lucia, A.

    1999-01-01

    OBJECTIVES: Exercise is known to cause changes in the concentration of salivary components such as amylase, Na, and Cl. The aim of this investigation was to evaluate the effect of physical exercise on the levels of trace elements and electrolytes in whole (mixed) saliva. METHODS: Forty subjects performed a maximal exercise test on a cycle ergometer. Samples of saliva were obtained before and immediately after the exercise test. Sample concentrations of Fe, Mg, Sc, Cr, Mn, Co, Cu, Zn, Se, Sr, Ag, Sb, Cs, and Hg were determined by inductively coupled plasma mass spectrometry and concentrations of Ca and Na by atomic absorption spectrometry. RESULTS: After exercise, Mg and Na levels showed a significant increase (p < 0.05) while Mn levels fell (p < 0.05). Zn/Cu molar ratios were unaffected by exercise. CONCLUSIONS: Intense physical exercise induced changes in the concentrations of only three (Na, Mg, and Mn) of the 16 elements analysed in the saliva samples. Further research is needed to assess the clinical implications of these findings. 


 PMID:10378074

  1. Finite element modeling of 129Xe diffusive gas exchange NMR in the human alveoli

    NASA Astrophysics Data System (ADS)

    Stewart, Neil J.; Parra-Robles, Juan; Wild, Jim M.

    2016-10-01

    Existing models of 129Xe diffusive exchange for lung microstructural modeling with time-resolved MR spectroscopy data have considered analytical solutions to one-dimensional, homogeneous models of the lungs with specific assumptions about the alveolar geometry. In order to establish a model system for simulating the effects of physiologically-realistic changes in physical and microstructural parameters on 129Xe exchange NMR, we have developed a 3D alveolar capillary model for finite element analysis. To account for the heterogeneity of the alveolar geometry across the lungs, we have derived realistic geometries for finite element analysis based on 2D histological samples and 3D micro-CT image volumes obtained from ex vivo biopsies of lung tissue from normal subjects and patients with interstitial lung disease. The 3D alveolar capillary model permits investigation of the impact of alveolar geometrical parameters and diffusion and perfusion coefficients on the in vivo measured 129Xe CSSR signal response. The heterogeneity of alveolar microstructure that is accounted for in image-based models resulted in considerable alterations to the shape of the 129Xe diffusive uptake curve when compared to 1D models. Our findings have important implications for the future design and optimization of 129Xe MR experiments and in the interpretation of lung microstructural changes from this data.

  2. Finite element modeling of (129)Xe diffusive gas exchange NMR in the human alveoli.

    PubMed

    Stewart, Neil J; Parra-Robles, Juan; Wild, Jim M

    2016-10-01

    Existing models of (129)Xe diffusive exchange for lung microstructural modeling with time-resolved MR spectroscopy data have considered analytical solutions to one-dimensional, homogeneous models of the lungs with specific assumptions about the alveolar geometry. In order to establish a model system for simulating the effects of physiologically-realistic changes in physical and microstructural parameters on (129)Xe exchange NMR, we have developed a 3D alveolar capillary model for finite element analysis. To account for the heterogeneity of the alveolar geometry across the lungs, we have derived realistic geometries for finite element analysis based on 2D histological samples and 3D micro-CT image volumes obtained from ex vivo biopsies of lung tissue from normal subjects and patients with interstitial lung disease. The 3D alveolar capillary model permits investigation of the impact of alveolar geometrical parameters and diffusion and perfusion coefficients on the in vivo measured (129)Xe CSSR signal response. The heterogeneity of alveolar microstructure that is accounted for in image-based models resulted in considerable alterations to the shape of the (129)Xe diffusive uptake curve when compared to 1D models. Our findings have important implications for the future design and optimization of (129)Xe MR experiments and in the interpretation of lung microstructural changes from this data.

  3. Finite element modeling of (129)Xe diffusive gas exchange NMR in the human alveoli.

    PubMed

    Stewart, Neil J; Parra-Robles, Juan; Wild, Jim M

    2016-10-01

    Existing models of (129)Xe diffusive exchange for lung microstructural modeling with time-resolved MR spectroscopy data have considered analytical solutions to one-dimensional, homogeneous models of the lungs with specific assumptions about the alveolar geometry. In order to establish a model system for simulating the effects of physiologically-realistic changes in physical and microstructural parameters on (129)Xe exchange NMR, we have developed a 3D alveolar capillary model for finite element analysis. To account for the heterogeneity of the alveolar geometry across the lungs, we have derived realistic geometries for finite element analysis based on 2D histological samples and 3D micro-CT image volumes obtained from ex vivo biopsies of lung tissue from normal subjects and patients with interstitial lung disease. The 3D alveolar capillary model permits investigation of the impact of alveolar geometrical parameters and diffusion and perfusion coefficients on the in vivo measured (129)Xe CSSR signal response. The heterogeneity of alveolar microstructure that is accounted for in image-based models resulted in considerable alterations to the shape of the (129)Xe diffusive uptake curve when compared to 1D models. Our findings have important implications for the future design and optimization of (129)Xe MR experiments and in the interpretation of lung microstructural changes from this data. PMID:27526397

  4. The elements of human well-being with an emphasis on the contribution of ecosystem services

    EPA Science Inventory

    Natural ecosystems perform fundamental life-support services upon which human civilization depends. However, many people believe that Nature provides these services for free and therefore, they are of little or no value. While we do not pay for them, we pay significantly for th...

  5. Simultaneous and Sequential Feature Negative Discriminations: Elemental Learning and Occasion Setting in Human Pavlovian Conditioning

    ERIC Educational Resources Information Center

    Baeyens, Frank; Vervliet, Bram; Vansteenwegen, Debora; Beckers, Tom; Hermans, Dirk; Eelen, Paul

    2004-01-01

    Using a conditioned suppression task, we investigated simultaneous (XA-/A+) vs. sequential (X [right arrow] A-/A+) Feature Negative (FN) discrimination learning in humans. We expected the simultaneous discrimination to result in X (or alternatively the XA configuration) becoming an inhibitor acting directly on the US, and the sequential…

  6. Humanism, Feminism, and Multiculturalism: Essential Elements of Social Justice in Counseling, Education, and Advocacy

    ERIC Educational Resources Information Center

    Brady-Amoon, Peggy

    2011-01-01

    This article explores the association between and among humanism, feminism, multiculturalism, and social justice in counseling, education, and advocacy. In so doing, it shows how these theoretical forces, individually and collectively, are essential to professional counseling, client welfare, education, and the promotion of social justice. The…

  7. Exploring the Human Element of Computer-Assisted Language Learning: An Iranian Context

    ERIC Educational Resources Information Center

    Fatemi Jahromi, Seyed Abolghasseminits; Salimi, Farimah

    2013-01-01

    Based on various theories of human agency (Ajzen, I. (2005). "Attitudes, personality and behavior" (2nd ed.). London: Open University Press; Davis, F.D. (1989). Perceived usefulness, perceived ease of use, and user acceptance of information technology. "MIS Quarterly", 13, 319-340; Rogers, E.M. (1983). "Diffusion of innovations" (3rd ed.). New…

  8. Imitation, pretend play, and childhood: essential elements in the evolution of human culture?

    PubMed

    Nielsen, Mark

    2012-05-01

    There is much controversy over what is needed for culture to flourish and what has led human culture to be different from "cultural" characteristics of other animals. Here I argue that the emergence of childhood as a step in the life cycle was critical to the evolution of the human cultural mind. My line of reasoning is built around two complementary features of childhood: imitation and play. When children imitate adults they routinely copy unnecessary and arbitrary actions. They will persistently replicate how an object is used, even when doing so interferes with their ability to produce the very outcome those actions are intended to bring about. Though seemingly maladaptive, this behavior provides for the faithful transmission of cultural ideas across generations. When children play together they commonly construct rules and meanings that exist purely because the players agree they "exist." Play thus provides the building blocks with which children rehearse the kinds of institutional realities that typify cultural practices. I argue that these forms of imitation and play represent a foundation upon which human culture flourished and that neither are prevalent in nonhuman animals. In light of these arguments evidence will be assessed suggesting that childhood emerged relatively late in human evolution. PMID:21859186

  9. Element content analysis by WDXRF in pistachios grown under organic and conventional farming regimes for human nutrition and health.

    PubMed

    Akbaba, Ugur; Sahin, Yusuf; Türkez, Hasan

    2012-10-01

    In this investigation, the elemental composition of various Antep pistachios (Pistacia vera L.) samples was determined using a sensitive method called wavelength dispersive x-ray fluorescence (WDXRF). A total of 27 elements, such as Al, As, Bi, Ca, Cd, Cu, Fe, Mn, Ni, P, S, Sr, Zn, Cl, Pb, K, Mg, Na, Ba, Rb, Si, Br, Sn, Au, La, Ti and Zr, were determined in pistachios samples (n = 10) grown under organic and conventional farming regimes. The obtained results from each group were analyzed statistically using SPSS statistic program. It was observed that the concentration and peak intensity values of Ca, Fe, Mn, P, Mg, Cl, Na and K elements were higher in the pistachios samples grown under organic farming regime. Similarly, Al was found in higher level in the samples grown under conventional farming regime. As, Bi, Cd, Pb, Ti, La, Sn and Zr contents were measured. Their contents were below the detection limits. Our findings clearly revealed that organic pistachios are likely to have higher nutritional mineral content. The pistachios samples grown under conventional farming regime could contain harmful metals like Al that might damage various systems and/or organs of humans and animals.

  10. Discovery of cell-type specific regulatory elements in the human genome using differential chromatin modification analysis

    PubMed Central

    Chen, Chen; Zhang, Shihua; Zhang, Xiang-Sun

    2013-01-01

    Chromatin modifications have been comprehensively illustrated to play important roles in gene regulation and cell diversity in recent years. Given the rapid accumulation of genome-wide chromatin modification maps across multiple cell types, there is an urgent need for computational methods to analyze multiple maps to reveal combinatorial modification patterns and define functional DNA elements, especially those are specific to cell types or tissues. In this current study, we developed a computational method using differential chromatin modification analysis (dCMA) to identify cell-type-specific genomic regions with distinctive chromatin modifications. We then apply this method to a public data set with modification profiles of nine marks for nine cell types to evaluate its effectiveness. We found cell-type-specific elements unique to each cell type investigated. These unique features show significant cell-type-specific biological relevance and tend to be located within functional regulatory elements. These results demonstrate the power of a differential comparative epigenomic strategy in deciphering the human genome and characterizing cell specificity. PMID:23945931

  11. 5'-flanking sequences of zebrafish fast myosin heavy chain genes regulate unique expression in the anterior, medial subsection and posterior tail somites of the skeletal muscle.

    PubMed

    Asaduzzaman, M; Shakur Ahammad, A K; Asakawa, S; Kinoshita, S; Watabe, S

    2016-01-01

    In zebrafish, fast muscle-specific myosin heavy chain genes have their unique expression patterns in a well-defined and restricted region of the skeletal muscle. However, the transcriptional regulatory mechanisms involved have remained unclear. Here, we examined the regulation of spatio-temporal expression patterns of myhz1 (myhz1.1, myhz1.2 and myhz1.3) and myhz2 during their development by using transient gene and stable transgenic techniques. Embryos microinjected with different length 5'-flanking sequences of myhz1 conjugated with the enhanced green fluorescent protein (EGFP) gene showed EGFP expression in the anterior and medial subsections of somites, but not in the tail somite region. In contrast, embryos microinjected with different length 5'-flanking sequences of myhz2 showed EGFP expression exclusively at the posterior tail somite domain. Promoter deletion analyses demonstrated that reduced EGFP fluorescence typically is correlated with smaller 5'-flanking sequences. The immunohistochemical observation revealed that zebrafish larvae provided with the transient gene and those from stable transgenic lines consistently expressed EGFP in the fast muscle fibers. r-VISTA plot identified one common conserved region of about 140°bp among myhz1.1, myhz1.2 and myhz1.3. Deletion of this conserved region from the 5'-flanking sequence of each myhz1 markedly reduced EGFP expression in its unique spatial somite region. Deletion mutation analysis demonstrated that myhz2 expression in the tail somite region might be mediated by Tbx (family of transcription factors having a common DNA-binding sequence known as T-box) binding elements. In summary, 5'-flanking sequences of myhz1 and myhz2 regulate their unique expression patterns in a well-defined and restricted somite region of the skeletal muscle in zebrafish.

  12. High precision locations of microseismicity on south-eastern flank of Mt. Etna: reconstruction of fault planes geometry and related dynamic

    NASA Astrophysics Data System (ADS)

    Salvatore, A.; Savatore, G.; Vincenza, M.

    2006-12-01

    Since the beginning of 2001 Mt. Etna seismic activity revealed a change in the dynamic conditions acting on the volcano revealed by moderate-high levels of seismicity mainly restricted to the eastern flank of the edifice. The 2001-2006 period has been characterized by the 2001, 2002-2003 and 2004-2005 eruptive episodes and by a marked eastward displacement of the eastern flank. Hypocenters of eastern flank seismicity have been relocated applying two different techniques: the double- difference approach of Waldhauser and Ellsworth (2000) and a multiplets technique that use a cross-spectrum method based on that discussed by Fremont and Malone (1987). For the last technique we also investigated the presence of possible multiplet events measuring the waveform similarity with a cross-correlation function. The two approach give as very similar results furnishing high-precision locations of ca. 90 earthquakes distributed along some structure oriented ca. NE-SW and NW-SE; these alignments are in agreement with fault plane solutions (FPSs) calculated for all the events. This approach has allowed us to define: a) geometry of some depth structures of the eastern flank that have no surface evidences. b) the complex dynamic of these structure that may give new elements to the scientific debate about the causes of the large deformative effects measured on the eastern flank of the edifice. Frèmont, M.J., Malone, S.D., 1987. High precision relative locations of earthquake at Mount St. Helens, Washington. J. Geophy. Res., 92, 10223-10236. Waldhauser F. and W.L. Ellsworth, 2000 A double-difference earthquake location algorithm: Method and application to the northern Hayward fault, Bull. Seism. Soc. Am., 90, 1353-1368.

  13. Investigating Late Amazonian Volcanotectonic Activity on Olympus Mons, Mars using Flank Vents and Arcuate Graben

    NASA Astrophysics Data System (ADS)

    Peters, S.; Christensen, P. R.

    2015-12-01

    Volcanism, a fundamental process in shaping the Martian surface, is crucial to understanding its evolution. Olympus Mons, the largest volcano on Mars, is one of several large shield volcanoes. Previous studies were technologically limited to large features associated with these constructs. With the advent of high resolution datasets, we are now able to investigate smaller features, such as flank vents and arcuate graben. Flank vents, common on polygenetic volcanoes, indicate that magma has propagated away from the main conduit and/or magma chamber. Vent morphology allows for the characterization of magma properties and eruption rates. Graben indicate extensional deformation. The distribution of graben provides information on stresses that acted on the volcano. In lieu of geophysical, spectral and in-situ data, morphology, morphometry and spatial relationships are powerful tools. We utilized high resolution image data (CTX, HiRISE and THEMIS IR) and topographic data (HRSC DTM, MOLA) to identify and characterize flank vents and graben. We observed 60 flank vents and 84 arcuate graben on Olympus Mons. Flank vents display varying morphologies and morphometries, suggesting different eruption styles and variable magma volatility. Vents occur primarily on the lower flank. This suggests magma has propagated substantial distances from the magma chamber. Observed clustering of vents may also indicate shallow magma sources. Similarly, graben are observed on the lower flank crosscutting young lava flows that have mantled portions of the escarpment. This indicates either gravitational spreading of Olympus Mons or flexure of the lithosphere in response to the load of the edifice. Collectively, the distribution of flank vents and arcuate graben suggests a similar development to that proposed for Ascraeus Mons. Based on superposition relationships and dates from previous studies, the flank vents and graben formed in the Late Amazonian (≤500 Ma).

  14. A three-dimensional finite-element model of a human dry skull for bone-conduction hearing.

    PubMed

    Kim, Namkeun; Chang, You; Stenfelt, Stefan

    2014-01-01

    A three-dimensional finite-element (FE) model of a human dry skull was devised for simulation of human bone-conduction (BC) hearing. Although a dry skull is a simplification of the real complex human skull, such model is valuable for understanding basic BC hearing processes. For validation of the model, the mechanical point impedance of the skull as well as the acceleration of the ipsilateral and contralateral cochlear bone was computed and compared to experimental results. Simulation results showed reasonable consistency between the mechanical point impedance and the experimental measurements when Young's modulus for skull and polyurethane was set to be 7.3 GPa and 1 MPa with 0.01 and 0.1 loss factors at 1 kHz, respectively. Moreover, the acceleration in the medial-lateral direction showed the best correspondence with the published experimental data, whereas the acceleration in the inferior-superior direction showed the largest discrepancy. However, the results were reasonable considering that different geometries were used for the 3D FE skull and the skull used in the published experimental study. The dry skull model is a first step for understanding BC hearing mechanism in a human head and simulation results can be used to predict vibration pattern of the bone surrounding the middle and inner ear during BC stimulation.

  15. Retinoic acid response element in the human alcohol dehydrogenase gene ADH3: implications for regulation of retinoic acid synthesis.

    PubMed Central

    Duester, G; Shean, M L; McBride, M S; Stewart, M J

    1991-01-01

    Retinoic acid regulation of one member of the human class I alcohol dehydrogenase (ADH) gene family was demonstrated, suggesting that the retinol dehydrogenase function of ADH may play a regulatory role in the biosynthetic pathway for retinoic acid. Promoter activity of human ADH3, but not ADH1 or ADH2, was shown to be activated by retinoic acid in transient transfection assays of Hep3B human hepatoma cells. Deletion mapping experiments identified a region in the ADH3 promoter located between -328 and -272 bp which confers retinoic acid activation. This region was also demonstrated to confer retinoic acid responsiveness on the ADH1 and ADH2 genes in heterologous promoter fusions. Within a 34-bp stretch, the ADH3 retinoic acid response element (RARE) contains two TGACC motifs and one TGAAC motif, both of which exist in RAREs controlling other genes. A block mutation of the TGACC sequence located at -289 to -285 bp eliminated the retinoic acid response. As assayed by gel shift DNA binding studies, the RARE region (-328 to -272 bp) of ADH3 bound the human retinoic acid receptor beta (RAR beta) and was competed for by DNA containing a RARE present in the gene encoding RAR beta. Since ADH catalyzes the conversion of retinol to retinal, which can be further converted to retinoic acid by aldehyde dehydrogenase, these results suggest that retinoic acid activation of ADH3 constitutes a positive feedback loop regulating retinoic acid synthesis. Images PMID:1996113

  16. A Three-Dimensional Finite-Element Model of a Human Dry Skull for Bone-Conduction Hearing

    PubMed Central

    2014-01-01

    A three-dimensional finite-element (FE) model of a human dry skull was devised for simulation of human bone-conduction (BC) hearing. Although a dry skull is a simplification of the real complex human skull, such model is valuable for understanding basic BC hearing processes. For validation of the model, the mechanical point impedance of the skull as well as the acceleration of the ipsilateral and contralateral cochlear bone was computed and compared to experimental results. Simulation results showed reasonable consistency between the mechanical point impedance and the experimental measurements when Young's modulus for skull and polyurethane was set to be 7.3 GPa and 1 MPa with 0.01 and 0.1 loss factors at 1 kHz, respectively. Moreover, the acceleration in the medial-lateral direction showed the best correspondence with the published experimental data, whereas the acceleration in the inferior-superior direction showed the largest discrepancy. However, the results were reasonable considering that different geometries were used for the 3D FE skull and the skull used in the published experimental study. The dry skull model is a first step for understanding BC hearing mechanism in a human head and simulation results can be used to predict vibration pattern of the bone surrounding the middle and inner ear during BC stimulation. PMID:25243148

  17. Melt inclusion constraints on the magma source of Eyjafjallajökull 2010 flank eruption

    NASA Astrophysics Data System (ADS)

    Moune, S.; Sigmarsson, O.; Schiano, P.; Thordarson, T.; Keiding, J. K.

    2012-09-01

    The 2010 eruptive activity at the Eyjafjallajökull volcanic system began 20 March with a basaltic flank eruption on a 300 m long fissure on the Fimmvörðuháls Pass, in between Eyjafjallajökull and Mýrdalsjökull volcanoes. The magma expelled from the fissure is olivine- and plagioclase-bearing mildly alkali basalt that exhibits uniform and rather primitive whole-rock composition. This event provides a rare opportunity to assess deep magmatic processes in Iceland. Melt inclusions (MIs) hosted in olivine phenocrysts were analyzed for their major, trace and volatile element concentrations to enable identification of magmatic source(s) for Eyjafjallajökull volcano and to better constrain processes occurring at depth. The MIs, in particular those in Mg-rich olivines, record primary magma composition before homogenisation and differentiation during magma ascent. The olivine phenocrysts hosting the MIs have a large compositional range, extending from Fo73 to Fo87, reflecting changes in the magma characteristics from the source to the surface. The MI compositions exhibit significant variations with MgO ranging from 5.2 to 7.2 wt%. This compositional range was caused by a binary mixing of two basaltic end-members followed by fractional crystallization process. The sources of these end-members are identical to those of Katla and Surtsey basalts, with a dominant role of the Katla source. Trace element characteristics of the Fimmvörðuháls MIs suggest important proportions of recycled oceanic crust in their mantle sources.

  18. Tables for the metric evaluation of pair-matching of human skeletal elements.

    PubMed

    Thomas, Richard M; Ubelaker, Douglas H; Byrd, John E

    2013-07-01

    A common task in forensic anthropology involves pair-matching of left and right skeletal elements. This can be achieved through visual pair-matching by evaluating similarities in morphology, and through osteometric sorting, a quantitative technique. To simplify the process of osteometric sorting, this article explains the use of a statistic (M), which captures the amount of size variation found between homologous bones from single individuals. A database of skeletal measurements for all major paired postcranial bones is used to calculate values of M from a variety of sources. The maximum value and the 90th and 95th percentiles of M are provided in tabular format, and values of M from forensic cases can be compared to these tables as an objective means for determining whether homologous bones could have originated from the same individual. This simple technique can be combined with visual pair-matching to be particularly effective in cases involving commingling of skeletons. PMID:23682771

  19. Ovariectomy by left flank approach in prepubertal Nelore (Bos indicus) heifers

    PubMed Central

    Peiró, Juliana R.; Nogueira, Geison M.; Nogueira, Guilherme P.; Perri, Silvia H.V.; Cardoso, Daniel

    2009-01-01

    The main objective of this study was to evaluate a recumbent left flank approach to bilateral ovariectomy in prepubertal heifers and to develop an optimal surgical technique for this procedure. Both ovaries were removed from 6 Nelore heifers by left flank approach without any complications, except in 1 heifer, which was believed to have had only 1 ovary based on ultrasound and exploration during surgery, but was later found to have a remaining functional ovary. Ovariectomy via left flank approach in recumbent prepubertal heifers is feasible and technically easy. This procedure does not involve special instrumentation and, despite the invasive approach, it allows optimal visualization of the ovaries and uterus. PMID:19794897

  20. A method for amplification of unknown flanking sequences based on touchdown PCR and suppression-PCR.

    PubMed

    Gao, Song; He, Dan; Li, Guangquan; Zhang, Yanhua; Lv, Huiying; Wang, Li

    2016-09-15

    Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample. PMID:27393656

  1. A method for amplification of unknown flanking sequences based on touchdown PCR and suppression-PCR.

    PubMed

    Gao, Song; He, Dan; Li, Guangquan; Zhang, Yanhua; Lv, Huiying; Wang, Li

    2016-09-15

    Thermal asymmetric staggered PCR is the most widely used technique to obtain the flanking sequences. However, it has some limitations, including a low rate of positivity, and complex operation. In this study, a improved method of it was made based on suppression-PCR and touchdown PCR. The PCR fragment obtained by the amplification was used directly for sequencing after gel purification. Using this improved method, the positive rate of amplified flanking sequences of the ATMT mutants reached 99%. In addition, the time from DNA extraction to flanking sequence analysis was shortened to 2 days with about 6 dollars each sample.

  2. Applying aviation factors to oral and maxillofacial surgery--the human element.

    PubMed

    Seager, Leonie; Smith, Dave W; Patel, Anish; Brunt, Howard; Brennan, Peter A

    2013-01-01

    There are many similarities between flying commercial aircraft and surgery, particularly in relation to minimising risk, and managing potentially fatal or catastrophic complications, or both. Since 1979, the development of Crew Resource Management (CRM) has improved air safety significantly by reducing human factors that are responsible for error. Similar developments in the operating theatre have, to a certain extent, lagged behind aviation, and it is well recognised that we can learn much from the industry. An increasing number of publications on aviation factors relate to surgery but to our knowledge there is a lack of research in our own specialty. We discuss how aviation principles related to human factors can be translated to the operating theatre to improve teamwork and safety for patients. Clinical research is clearly needed to develop this fascinating area more fully.

  3. A three-dimensional finite element analysis of the osseointegration progression in the human mandible

    NASA Astrophysics Data System (ADS)

    Esmail, Enas; Hassan, Noha; Kadah, Yasser

    2010-02-01

    In this study, three-dimensional (3D) finite element analysis was used to model the effect of the peri-implant bone geometry and thickness on the biomechanical behavior of a dental implant/supporting bone system. The 3D finite element model of the jaw bone, cancellous and cortical, was developed based on computerized tomography (CT) scan technology while the dental implant model was created based on a commercially available implant design. Two models, cylindrical and threaded, representing the peri-implant bone region were simulated. In addition, various thicknesses (0.1 mm, 0.3 mm, 0.5 mm) of the peri-implant bone region were modeled to account for the misalingnment during the drilling process. Different biomechanical properties of the peri-implant bone region were used to simulate the progression of the osseointegration process with time. Four stages of osseointegration were modeled to mimic different phases of tissue healing of the peri- implant region starting with soft connective tissue and ending with complete bone maturation. For the realistic threaded model of the peri-implant bone region, the maximum von Mises stress and displacement in the dental implant and jaw bone were higher than those computed for the simple cylindrical peri-implant bone region model. The average von Mises stress and displacement in the dental implant and the jaw bone decreased as the oseeointegration progressed with time for all thicknesses of the peri-implant bone region. On the other hand, the maximum absolute vertical displacement of the dental implant increased as the drilled thickness of the peri-implant bone region increased.

  4. Identification of human TERT elements necessary for telomerase recruitment to telomeres

    PubMed Central

    Schmidt, Jens C; Dalby, Andrew B; Cech, Thomas R

    2014-01-01

    Human chromosomes terminate in telomeres, repetitive DNA sequences bound by the shelterin complex. Shelterin protects chromosome ends, prevents recognition by the DNA damage machinery, and recruits telomerase. A patch of amino acids, termed the TEL-patch, on the OB-fold domain of the shelterin component TPP1 is essential to recruit telomerase to telomeres. In contrast, the site on telomerase that interacts with the TPP1 OB-fold is not well defined. In this study, we identify separation-of-function mutations in the TEN-domain of human telomerase reverse transcriptase (hTERT) that disrupt the interaction of telomerase with TPP1 in vivo and in vitro but have very little effect on the catalytic activity of telomerase. Suppression of a TEN-domain mutation with a compensatory charge-swap mutation in the TEL-patch indicates that their association is direct. Our findings define the interaction interface required for telomerase recruitment to telomeres, an important step towards developing modulators of this interaction as therapeutics for human disease. DOI: http://dx.doi.org/10.7554/eLife.03563.001 PMID:25271372

  5. Proximal promoter elements of the human zeta-globin gene confer embryonic-specific expression on a linked reporter gene in transgenic mice.

    PubMed

    Pondel, M D; Sharpe, J A; Clark, S; Pearson, L; Wood, W G; Proudfoot, N J

    1996-11-01

    We have investigated the transcriptional regulation of the human embryonic zeta-globin gene promoter. First, we examined the effect that deletion of sequences 5' to zeta-globin's CCAAT box have on zeta-promoter activity in erythroid cell lines. Deletions of sequences between -116 and -556 (cap = 0) had little effect while further deletion to -84 reduced zeta-promoter activity by only 2-3-fold in both transiently and stably transfected erythroid cells. Constructs containing 67, 84 and 556 bp of zeta-globin 5' flanking region linked to a beta-galactosidase reporter gene (lacZ) and hypersensitive site -40 (HS-40) of the human alpha-globin gene cluster were then employed for the generation of transgenic mice. LacZ expression from all constructs, including a 67 bp zeta-globin promoter, was erythroid-specific and most active between 8.5 and 10.5 days post-fertilisation. By 16.5 days gestation, lacZ expression dropped 40-100-fold. These results suggest that embryonic-specific activation of the human zeta-globin promoter is conferred by a 67 bp zeta-promoter fragment containing only a CCAAT and TATA box. PMID:8932366

  6. Amino acids flanking the central core of Cu,Zn superoxide dismutase are important in retaining enzyme activity after autoclaving.

    PubMed

    Kumar, Arun; Randhawa, Vinay; Acharya, Vishal; Singh, Kashmir; Kumar, Sanjay

    2016-01-01

    Enzymes are known to be denatured upon boiling, although Cu,Zn superoxide dismutase of Potentilla atrosanguinea (Pot-SOD) retains significant catalytic activity even after autoclaving (heating at 121 °C at a pressure of 1.1 kg per square cm for 20 min). The polypeptide backbone of Pot-SOD consists of 152 amino acids with a central core spanning His45 to Cys145 that is involved in coordination of Cu(2+) and Zn(2+) ions. While the central core is essential for imparting catalytic activity and structural stability to the enzyme, the role of sequences flanking the central core was not understood. Experiments with deletion mutants showed that the amino acid sequences flanking the central core were important in retaining activity of Pot-SOD after autoclaving. Molecular dynamics simulations demonstrated the unfavorable structure of mutants due to increased size of binding pocket and enhanced negative charge on the electrostatic surface, resulting in unavailability of the substrate superoxide radical ([Formula: see text]) to the catalytic pocket. Deletion caused destabilization of structural elements and reduced solvent accessibility that further produced unfavorable structural geometry of the protein. PMID:25990646

  7. Leakage of active crater lake brine through the north flank at Rincon de la Vieja volcano, northwest Costa Rica, and implications for crater collapse

    USGS Publications Warehouse

    Kempter, K.A.; Rowe, G.L.

    2000-01-01

    de la Vieja. The distribution of thermal water types at Rincon de la Vieja strongly indicates that formation of the north-flank ACS waters is not due to mixing of shallow, steam-heated AS water with deep-seated NC water. More likely, hyper-acidic brines formed in the Active Crater area are migrating through permeable zones in the volcanic strata that make up the Active Crater's north flank. Dissolution and shallow subsurface alteration of north-flank volcanoclastic material by interaction with acidic lake brine, particularly in the more permeable tephra units, could weaken the already oversteepened north flank of the Active Crater. Sector collapse of the Active Crater, with or without a volcanic eruption, represents a potential threat to human lives, property, and ecosystems at Rincon de la Vieja volcano.

  8. Leakage of Active Crater lake brine through the north flank at Rincón de la Vieja volcano, northwest Costa Rica, and implications for crater collapse

    NASA Astrophysics Data System (ADS)

    Kempter, K. A.; Rowe, G. L.

    2000-04-01

    Rincón de la Vieja. The distribution of thermal water types at Rincón de la Vieja strongly indicates that formation of the north-flank ACS waters is not due to mixing of shallow, steam-heated AS water with deep-seated NC water. More likely, hyper-acidic brines formed in the Active Crater area are migrating through permeable zones in the volcanic strata that make up the Active Crater's north flank. Dissolution and shallow subsurface alteration of north-flank volcanoclastic material by interaction with acidic lake brine, particularly in the more permeable tephra units, could weaken the already oversteepened north flank of the Active Crater. Sector collapse of the Active Crater, with or without a volcanic eruption, represents a potential threat to human lives, property, and ecosystems at Rincón de la Vieja volcano.

  9. Natural Selection and Functional Potentials of Human Noncoding Elements Revealed by Analysis of Next Generation Sequencing Data.

    PubMed

    Jha, Pankaj; Lu, Dongsheng; Xu, Shuhua

    2015-01-01

    Noncoding DNA sequences (NCS) have attracted much attention recently due to their functional potentials. Here we attempted to reveal the functional roles of noncoding sequences from the point of view of natural selection that typically indicates the functional potentials of certain genomic elements. We analyzed nearly 37 million single nucleotide polymorphisms (SNPs) of Phase I data of the 1000 Genomes Project. We estimated a series of key parameters of population genetics and molecular evolution to characterize sequence variations of the noncoding genome within and between populations, and identified the natural selection footprints in NCS in worldwide human populations. Our results showed that purifying selection is prevalent and there is substantial constraint of variations in NCS, while positive selectionis more likely to be specific to some particular genomic regions and regional populations. Intriguingly, we observed larger fraction of non-conserved NCS variants with lower derived allele frequency in the genome, indicating possible functional gain of non-conserved NCS. Notably, NCS elements are enriched for potentially functional markers such as eQTLs, TF motif, and DNase I footprints in the genome. More interestingly, some NCS variants associated with diseases such as Alzheimer's disease, Type 1 diabetes, and immune-related bowel disorder (IBD) showed signatures of positive selection, although the majority of NCS variants, reported as risk alleles by genome-wide association studies, showed signatures of negative selection. Our analyses provided compelling evidence of natural selection forces on noncoding sequences in the human genome and advanced our understanding of their functional potentials that play important roles in disease etiology and human evolution.

  10. Human exposure to lead and other potentially harmful elements associated with galena mining at New Zurak, central Nigeria

    NASA Astrophysics Data System (ADS)

    Lar, U. A.; Ngozi-Chika, C. S.; Ashano, E. C.

    2013-08-01

    Galena mining in New Zurak, central Nigeria is currently increasing in intensity, with widespread artisanal mining taking place alongside mechanised mining. These activities are causing immeasurable damage to the environment. The prolonged human exposure and ingestion of Pb and other potentially harmful elements (PHEs) such as U, Cd, Se, Zn and As that are released from ores during these (mining) activities is a cause of great concern to populations that live in the vicinity of these mine fields. Many of the communities make their living from subsistence farming, growing food from the surroundings, and obtaining drinking water from nearby surface and sub-surface water resources. An overall assessment of the degree of contamination or toxicity of Pb and other PHEs was carried out using the indices of geoaccumulation (Igeo) and contamination factors (CFs), in the different media sampled - farmland soils, uncultivated lands, mine tailings/dumps, natural waters and vegetables. Results reveal that the mine tailings and dumps are highly contaminated with Pb and other PHEs followed in decreasing degree of contamination by the uncultivated lands, farmlands and natural waters. These findings suggest that release of Pb and other PHEs from the galena mining activity has contributed significantly to the enrichment of these elements in the surrounding environment, including the natural water bodies, and are disposed to subsequent entry into the human body through the food chain. As such these PHE accumulations pose significant risks to the environment and human health, especially of children and pregnant women who are the most vulnerable groups in the area. In order to forestall a reoccurrence of the Zamfara Pb poisoning episode in northwestern Nigeria in 2010, where more than 400 children died, the authorities concerned should ensure that mining in New Zurak is done in a more environmentally friendly manner, ensuring the maintenance of an environmental quality adequate for

  11. Dynamic finite element simulation of the gunshot injury to the human forehead protected by polyvinyl alcohol sponge.

    PubMed

    Karimi, Alireza; Razaghi, Reza; Navidbakhsh, Mahdi; Sera, Toshihiro; Kudo, Susumu

    2016-04-01

    Although there are some traditional models of the gunshot wounds, there is still a need for more modeling analyses due to the difficulties related to the gunshot wounds to the forehead region of the human skull. In this study, the degree of damage as a consequence of penetrating head injuries due to gunshot wounds was determined using a preliminary finite element (FE) model of the human skull. In addition, the role of polyvinyl alcohol (PVA) sponge, which can be used as an alternative to reinforce the kinetic energy absorption capacity of bulletproof vest and helmet materials, to minimize the amount of skull injury due to penetrating processes was investigated through the FE model. Digital computed tomography along with magnetic resonance imaging data of the human head were employed to launch a three-dimensional (3D) FE model of the skull. Two geometrical shapes of projectiles (steel ball and bullet) were simulated for penetrating with an initial impact velocity of 734 m/s using nonlinear dynamic modeling code, namely LS-DYNA. The role of the damaged/distorted elements were removed during computation when the stress or strain reached their thresholds. The stress distributions in various parts of the forehead and sponge after injury were also computed. The results revealed the same amount of stress for both the steel ball and bullet after hitting the skull. The modeling results also indicated the time that steel ball takes to penetrate into the skull is lower than that of the bullet. In addition, more than 21% of the steel ball's kinetic energy was absorbed by the PVA sponge and, subsequently, injury sternness of the forehead was considerably minimized. The findings advise the application of the PVA sponge as a substitute strengthening material to be able to diminish the energy of impact as well as the load transmitted to the object. PMID:26886822

  12. Elevation of transgene expression level by flanking matrix attachment regions (MAR) is promoter dependent: a study of the interactions of six promoters with the RB7 3' MAR.

    PubMed

    Mankin, S Luke; Allen, George C; Phelan, Thomas; Spiker, Steven; Thompson, William F

    2003-02-01

    We have analyzed effects of a matrix attachment region (MAR) from the tobacco RB7 gene on transgene expression from six different promoters in stably transformed tobacco cell cultures. The presence of MARs flanking the transgene increased expression of constructs based on the constitutive CaMV 35S, NOS, and OCS promoters. Expression from an induced heat shock promoter was also increased and MARs did not cause expression in the absence of heat shock. There was also no effect of MARs on the pea ferredoxin promoter, which is not normally expressed in this cell line. Importantly, most transgenes flanked by RB7 MAR elements showed a large reduction in the number of low expressing GUS transformants relative to control constructs without MARs. PMID:12650520

  13. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    NASA Astrophysics Data System (ADS)

    Ascenzi, Maria-Grazia; Kawas, Neal P.; Lutz, Andre; Kardas, Dieter; Nackenhorst, Udo; Keyak, Joyce H.

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual's (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method's development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications - varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient's femur, that strains computed at the multi-scale model's micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  14. Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

    PubMed Central

    Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

    2011-01-01

    A sequence around the start codon of the mRNA of human thymidylate synthase (TS) folds into a secondary-structure motif in which the initiation site is sequestered in a metastable hairpin. Binding of the protein to its own mRNA at the hairpin prevents the production of TS through a translation-repression feedback mechanism. Stabilization of the mRNA hairpin by other ligands has been proposed as a strategy to reduce TS levels in anticancer therapy. Rapidly proliferating cells require high TS activity to maintain the production of thymidine as a building block for DNA synthesis. The crystal structure of a model oligonucleotide (TS1) that represents the TS-binding site of the mRNA has been determined. While fluorescence studies showed that the TS1 RNA preferentially adopts a hairpin structure in solution, even at high RNA concentrations, an asymmetric dimer of two hybridized TS1 strands was obtained in the crystal. The TS1 dimer contains an unusual S-­turn motif that also occurs in the ‘off’ state of the human ribosomal decoding site RNA. PMID:21245530

  15. CT-based geometry analysis and finite element models of the human and ovine bronchial tree.

    PubMed

    Tawhai, Merryn H; Hunter, Peter; Tschirren, Juerg; Reinhardt, Joseph; McLennan, Geoffrey; Hoffman, Eric A

    2004-12-01

    The interpretation of experimental results from functional medical imaging is complicated by intersubject and interspecies differences in airway geometry. The application of computational models in understanding the significance of these differences requires methods for generation of subject-specific geometric models of the bronchial airway tree. In the current study, curvilinear airway centerline and diameter models have been fitted to human and ovine bronchial trees using detailed data segmented from multidetector row X-ray-computed tomography scans. The trees have been extended to model the entire conducting airway system by using a volume-filling algorithm to generate airway centerline locations within detailed volume descriptions of the lungs or lobes. Analysis of the geometry of the scan-based and model-based airways has verified their consistency with measures from previous anatomic studies and has provided new anatomic data for the ovine bronchial tree. With the use of an identical parameter set, the volume-filling algorithm has produced airway trees with branching asymmetry appropriate for the human and ovine lung, demonstrating the dependence of the method on the shape of the lung or lobe volume. The modeling approach that has been developed can be applied to any level of detail of the airway tree and into any volume shape for the lung; hence it can be used directly for different individuals or animals and for any number of scan-based airways. The resulting models are subject-specific computational meshes with anatomically consistent geometry, suitable for application in simulation studies.

  16. A recent evolutionary change affects a regulatory element in the human FOXP2 gene.

    PubMed

    Maricic, Tomislav; Günther, Viola; Georgiev, Oleg; Gehre, Sabine; Curlin, Marija; Schreiweis, Christiane; Naumann, Ronald; Burbano, Hernán A; Meyer, Matthias; Lalueza-Fox, Carles; de la Rasilla, Marco; Rosas, Antonio; Gajovic, Srecko; Kelso, Janet; Enard, Wolfgang; Schaffner, Walter; Pääbo, Svante

    2013-04-01

    The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.

  17. Structure of an RNA dimer of a regulatory element from human thymidylate synthase mRNA

    SciTech Connect

    Dibrov, Sergey; McLean, Jaime; Hermann, Thomas

    2011-09-27

    A sequence around the start codon of the mRNA of human thymidylate synthase (TS) folds into a secondary-structure motif in which the initiation site is sequestered in a metastable hairpin. Binding of the protein to its own mRNA at the hairpin prevents the production of TS through a translation-repression feedback mechanism. Stabilization of the mRNA hairpin by other ligands has been proposed as a strategy to reduce TS levels in anticancer therapy. Rapidly proliferating cells require high TS activity to maintain the production of thymidine as a building block for DNA synthesis. The crystal structure of a model oligonucleotide (TS1) that represents the TS-binding site of the mRNA has been determined. While fluorescence studies showed that the TS1 RNA preferentially adopts a hairpin structure in solution, even at high RNA concentrations, an asymmetric dimer of two hybridized TS1 strands was obtained in the crystal. The TS1 dimer contains an unusual S-turn motif that also occurs in the 'off' state of the human ribosomal decoding site RNA.

  18. An Objective Evaluation of Mass Scaling Techniques Utilizing Computational Human Body Finite Element Models.

    PubMed

    Davis, Matthew L; Scott Gayzik, F

    2016-10-01

    Biofidelity response corridors developed from post-mortem human subjects are commonly used in the design and validation of anthropomorphic test devices and computational human body models (HBMs). Typically, corridors are derived from a diverse pool of biomechanical data and later normalized to a target body habitus. The objective of this study was to use morphed computational HBMs to compare the ability of various scaling techniques to scale response data from a reference to a target anthropometry. HBMs are ideally suited for this type of study since they uphold the assumptions of equal density and modulus that are implicit in scaling method development. In total, six scaling procedures were evaluated, four from the literature (equal-stress equal-velocity, ESEV, and three variations of impulse momentum) and two which are introduced in the paper (ESEV using a ratio of effective masses, ESEV-EffMass, and a kinetic energy approach). In total, 24 simulations were performed, representing both pendulum and full body impacts for three representative HBMs. These simulations were quantitatively compared using the International Organization for Standardization (ISO) ISO-TS18571 standard. Based on these results, ESEV-EffMass achieved the highest overall similarity score (indicating that it is most proficient at scaling a reference response to a target). Additionally, ESEV was found to perform poorly for two degree-of-freedom (DOF) systems. However, the results also indicated that no single technique was clearly the most appropriate for all scenarios.

  19. An Objective Evaluation of Mass Scaling Techniques Utilizing Computational Human Body Finite Element Models.

    PubMed

    Davis, Matthew L; Scott Gayzik, F

    2016-10-01

    Biofidelity response corridors developed from post-mortem human subjects are commonly used in the design and validation of anthropomorphic test devices and computational human body models (HBMs). Typically, corridors are derived from a diverse pool of biomechanical data and later normalized to a target body habitus. The objective of this study was to use morphed computational HBMs to compare the ability of various scaling techniques to scale response data from a reference to a target anthropometry. HBMs are ideally suited for this type of study since they uphold the assumptions of equal density and modulus that are implicit in scaling method development. In total, six scaling procedures were evaluated, four from the literature (equal-stress equal-velocity, ESEV, and three variations of impulse momentum) and two which are introduced in the paper (ESEV using a ratio of effective masses, ESEV-EffMass, and a kinetic energy approach). In total, 24 simulations were performed, representing both pendulum and full body impacts for three representative HBMs. These simulations were quantitatively compared using the International Organization for Standardization (ISO) ISO-TS18571 standard. Based on these results, ESEV-EffMass achieved the highest overall similarity score (indicating that it is most proficient at scaling a reference response to a target). Additionally, ESEV was found to perform poorly for two degree-of-freedom (DOF) systems. However, the results also indicated that no single technique was clearly the most appropriate for all scenarios. PMID:27457051

  20. 8. DETAIL OF ENTRANCE WITH FLANKING ROUND TOWERS TO A.O.H. ...

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

    8. DETAIL OF ENTRANCE WITH FLANKING ROUND TOWERS TO A.O.H. HALL, EAST SIDE - Anaconda Historic District, Ancient Order of Hibernians Hall, 321-323 East Commercial Street, Anaconda, Deer Lodge County, MT

  1. Window type: 2x3 fixed multipaned steel window flanked by 1x3 ...

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

    Window type: 2x3 fixed multipaned steel window flanked by 1x3 multipaned steel casements. Concrete sill and spandrel also illustrated. Building 43, facing east - Harbor Hills Housing Project, 26607 Western Avenue, Lomita, Los Angeles County, CA

  2. Flank mass and pain in a 72-year-old man.

    PubMed

    Brady, M B; Ewing, R H; Robinson, A E; Dowling, E A

    1986-05-01

    This patient had retroperitoneal multiseptated masses, which extensively invaded the right flank and thigh musculature. The radiologic, pathologic, and clinical findings were consistent with a retroperitoneal pseudomyxoma from an appendiceal mucocele.

  3. Genome-Wide Computational Analysis of Dioxin Response Element Location and Distribution in the Human, Mouse and Rat Genomes

    PubMed Central

    Dere, Edward; Forgacs, Agnes L; Zacharewski, Timothy R; Burgoon, Lyle D

    2014-01-01

    The aryl hydrocarbon receptor (AhR) mediates responses elicited by 2,3,7,8-tetrachlorodibenzo-p-dioxin by binding to dioxin response elements (DRE) containing the core consensus sequence 5′-GCGTG-3′. The human, mouse and rat genomes were computationally searched for all DRE cores. Each core was then extended by 7bp upstream and downstream, and matrix similarity (MS) scores for the resulting 19bp DRE sequences were calculated using a revised position weight matrix constructed from bona fide functional DREs. In total, 72,318 human, 70,720 mouse and 88,651 rat high-scoring (MS ≥ 0.8437) putative DREs were identified. Gene encoding intragenic DNA regions had ~1.6-times more putative DREs than the non-coding intergenic DNA regions. Furthermore, the promoter region spanning ±1.5kb of a TSS had the highest density of putative DREs within the genome. Chromosomal analysis found that the putative DRE densities of chromosomes X and Y were significantly lower than the mean chromosomal density. Interestingly, the 10kb upstream promoter region on chromosome X of the genomes were significantly less dense than the chromosomal mean, while the same region in chromosome Y was the most dense. In addition to providing a detailed genomic map of all DRE cores in the human, mouse and rat genomes, these data will further aid the elucidation of AhR-mediated signal transduction. PMID:21370876

  4. Repair of naturally occurring mismatches can induce mutations in flanking DNA

    PubMed Central

    Chen, Jia; Miller, Brendan F; Furano, Anthony V

    2014-01-01

    ‘Normal’ genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the ‘mutator phenotype’ of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change. DOI: http://dx.doi.org/10.7554/eLife.02001.001 PMID:24843013

  5. Repair of naturally occurring mismatches can induce mutations in flanking DNA.

    PubMed

    Chen, Jia; Miller, Brendan F; Furano, Anthony V

    2014-01-01

    'Normal' genomic DNA contains hundreds of mismatches that are generated daily by the spontaneous deamination of C (U/G) and methyl-C (T/G). Thus, a mutagenic effect of their repair could constitute a serious genetic burden. We show here that while mismatches introduced into human cells on an SV40-based episome were invariably repaired, this process induced mutations in flanking DNA at a significantly higher rate than no mismatch controls. Most mutations involved the C of TpC, the substrate of some single strand-specific APOBEC cytidine deaminases, similar to the mutations that can typify the 'mutator phenotype' of numerous tumors. siRNA knockdowns and chromatin immunoprecipitation showed that TpC preferring APOBECs mediate the mutagenesis, and siRNA knockdowns showed that both the base excision and mismatch repair pathways are involved. That naturally occurring mispairs can be converted to mutators, represents an heretofore unsuspected source of genetic changes that could underlie disease, aging, and evolutionary change.DOI: http://dx.doi.org/10.7554/eLife.02001.001. PMID:24843013

  6. An INDEL polymorphism at the X-STR GATA172D05 flanking region.

    PubMed

    Rodrigues, Elzemar Martins Ribeiro; dos Santos, Ney Pereira Carneiro; dos Santos, Andrea Kely Campos Ribeiro; Marinho, Anderson Nonato; Zago, Marco Antonio; Gomes, Iva; Amorim, António; Gusmão, Leonor; dos Santos, Sidney Emanuel Batista

    2009-01-01

    A new polymorphic INDEL was detected at the X-STR GATA172D05 flanking region, which corresponds to an 18-bp deletion, 141 bp upstream the TAGA repeat motif. This INDEL was found to be polymorphic in different population samples from Native Americans, Africans, and Europeans as well as in an admixed population from the Amazonia (Belém). Gene diversities varied between 37.5% in Native Americans and 49.9% in Africans. Comparison between human and chimpanzee sequences showed that the ancestral state corresponds to the presence of two copies of 18 bp, detected in both species; and the mutated allele has lost one of these two copies. The simultaneous analysis of the short tandem repeat (STR) and INDEL variation showed an association between the INDEL ancestral allele with the shorter STR alleles. High diversities were found in all population groups when combining the information provided by the INDEL and STR variation. Gene diversities varied between 76.7% in Native Americans and 80.6% in both Portugal and Belém.

  7. Individual density-elasticity relationships improve accuracy of subject-specific finite element models of human femurs.

    PubMed

    Eberle, Sebastian; Göttlinger, Michael; Augat, Peter

    2013-09-01

    In a previous study on subject-specific finite-element-models, we found that appropriate density-elasticity relationships to compute the mechanical behavior of femurs seem to be subject-specific. The purpose of this study was to test the hypothesis that the predictive error of a cohort of subject-specific finite element-models is lower with subject-specific density-elasticity relationships than with a cohort-specific density-elasticity relationship. Finite-element-analysis and inverse optimization based on response surface methodology were employed to test the hypothesis. Subject-specific FE-models of 17 human femurs and corresponding experimental data from biomechanical tests were taken from a previous study. A power function for the relation between radiological bone density and elastic modulus was set up with the optimization variables a and b: E(MPa)=aρqCT(b)(gK2HPO4/cm(3)). The goal of the optimization was to minimize the root-mean-square error in percent (RMSE%) between computational and experimental results. A Wilcoxon test (p=0.05) was performed on all absolute relative errors between the two groups (subject-specific functions vs. cohort-specific function). The subject-specific functions resulted in a 6% lower overall prediction error and a 6% lower RMSE% than the cohort-specific function (p<0.001). The determined subject-specific relations were mostly linear, with variable a ranging from 9307 to 15673 and variable b ranging from 0.68 to 1.40. For the cohort-specific relation, the following power law was obtained: E(MPa)=12486ρqCT(1.16)(gK2HPO4/cm(3)). We conclude that individual density-elasticity relationships improve the accuracy of subject-specific finite element models. Future subject-specific finite-element-analyses of bones should include the individuality of the elastic properties by a stochastic density-elasticity relationship with mean and standard deviation of a and b.

  8. Flank bulge following supracostal percutaneous nephrolithotomy: A report of 2 cases

    PubMed Central

    Lantz, Andrea G.; Pace, Kenneth T.; Honey, R. John D’A.

    2013-01-01

    Damage to intercostal nerves during surgical procedures has been associated with a postoperative flank bulge, due to denervation of the anterolateral abdominal wall musculature. This complication has not been reported following percutaneous nephrolithotomy (PCNL). We are aware of 3 cases, but have details on 2 cases of postoperative flank bulge following supracostal PCNL which are reported here. We also suggest how this complication could potentially be minimized. PMID:24032069

  9. Ultrasound Detection of a Renal Mass in a Patient with Flank Pain and Hematuria

    PubMed Central

    Marzec, Karl; Mailhot, Thomas; Perera, Phillips

    2013-01-01

    Flank pain with hematuria is a common chief complaint in the emergency department (ED). Patients are often diagnosed with renal calculi or pyelonephritis and discharged with analgesics or antibiotics and follow-up. This case study describes a patient who presented to the ED with a 1 week history of flank pain and hematuria and was subsequently found to have a large renal mass on bedside ultrasound. PMID:23599845

  10. Chronic exposure to aluminum, nickel, thallium and uranium and their relationship with essential elements in human whole blood and blood serum.

    PubMed

    Zeneli, Lulzim; Sekovanić, Ankica; Daci, Nexhat

    2015-01-01

    This study aimed to evaluate the influence of exposure to aluminum, nickel, thallium and uranium on the metabolism of essential elements in humans, as well as the relationship between uranium, thallium, nickel, and aluminum and essential elements (Ca, Mg, Zn, Se, Mn, Co, Cr, and Mo) in the whole blood and blood serum of healthy men who were occupationally exposed. This study included 97 healthy men, 31-64 years age, including 70 workers in a thermo power plant and 27 control subjects. The results showed that chronic, moderate exposure of trace elements (Al, Ni, Tl, and U) lead to decreased serum chromium (SCr) and blood molybdenum levels (BMo), whereas by the results achieved in terms of correlations between non-essential and essential elements, non-essential elements such as uranium, thallium, nickel, and aluminum, despite their concentration within the reference values, are strongly competitive with essential elements in biochemical processes.

  11. Gene conversion as a secondary mechanism of short interspersed element (SINE) evolution

    SciTech Connect

    Kass, D.H.; Batzer, M.A.; Deininger, P.L. |

    1995-01-01

    The Alu repetitive family of short interspersed elements (SINEs) in primates can be subdivided into distinct subfamilies by specific diagnostic nucleotide changes. The older subfamilies are generally very abundant, while the younger subfamilies have fewer copies. Some of the youngest Alu elements are absent in the orthologous loci of nonhuman primates, indicative of recent retroposition events, the primary mode of SINE evolutions. PCR analysis of one young Alu subfamily (Sb2) member found in the low-density lipoprotein receptor gene apparently revealed the presence of this element in the green monkey, orangutan, gorilla, and chimpanzee genomes, as well as the human genome. However, sequence analysis of these genomes revealed a highly mutated, older, primate-specific Alu element was present at this position in the nonhuman primates. Comparison of the flanking DNA sequences upstream of this Alu insertion corresponded to evolution expected for standard primate phylogeny, but comparison of the Alu repeat sequences revealed that the human element departed from this phylogeny. The change in the human sequence apparently occurred by a gene conversion event only within the Alu element itself, converting it from one of the oldest to one of the youngest Alu subfamilies. Although gene conversions of Alu elements are clearly very rare, this finding shows that such events can occur and contribute to specific cases of SINE subfamily evolution.

  12. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    SciTech Connect

    Ascenzi, Maria-Grazia; Kardas, Dieter; Nackenhorst, Udo; Keyak, Joyce H.

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual’s (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method’s development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications – varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient’s femur, that strains computed at the multi-scale model’s micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  13. Effect of flanking bases on quadruplex stability and Watson-Crick duplex competition.

    PubMed

    Arora, Amit; Nair, Divya R; Maiti, Souvik

    2009-07-01

    Guanine-rich DNA sequences have the ability to fold into four-stranded structures called G-quadruplexes, and are considered as promising anticancer targets. Although the G-quadruplex structure is composed of quartets and interspersed loops, in the genome it is also flanked on each side by numerous bases. The effect of loop length and composition on quadruplex conformation and stability has been well investigated in the past, but the effect of flanking bases on quadruplex stability and Watson-Crick duplex competition has not been addressed. We have studied in detail the effect of flanking bases on quadruplex stability and on duplex formation by the G-quadruplex in the presence of complementary strands using the quadruplex-forming sequence located in the promoter region of the c-kit oncogene. The results obtained from CD, thermal difference spectrum and UV melting demonstrated the effect of flanking bases on quadruplex structure and stability. With the increase in flank length, the increase in the more favorable DeltaH(vH) is accompanied by a striking increase in the unfavorable DeltaS(vH), which resulted in a decrease in the overall DeltaG(vH) of quadruplex formation. Furthermore, CD, fluorescence and isothermal titration calorimetry studies demonstrated that the propensity to attain quadruplex structure decreases with increasing flank length.

  14. 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 Central

    Hopkins, William D.; Donaldson, Zoe R.; Young, Larry J.

    2012-01-01

    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 due to 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. PMID:22520444

  15. Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

    PubMed

    Wen, Xin-Xin; Xu, Chao; Zong, Chun-Lin; Feng, Ya-Fei; Ma, Xiang-Yu; Wang, Fa-Qi; Yan, Ya-Bo; Lei, Wei

    2016-07-01

    Micro-finite element (μFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from μFE model. 5 Human lumbar vertebral bodies (L1-L5) were scanned by micro-CT. Cubic concentric samples of different lengths were constructed as the experimental groups and the largest possible volumes of interest (VOI) were constructed as the control group. A direct voxel-to-element approach was used to generate μFE models and steel layers were added to the superior and inferior surface to mimic axial compression tests. A 1% axial strain was prescribed to the top surface of the model to obtain the E values. ANOVA tests were performed to compare the E values from the different VOIs against that of the control group. Nonlinear function curve fitting was performed to study the relationship between volumes and E values. The larger cubic VOI included more nodes and elements, and more CPU times were needed for calculations. E values showed a descending tendency as the length of cubic VOI decreased. When the volume of VOI was smaller than (7.34mm(3)), E values were significantly different from the control group. The fit function showed that E values approached an asymptotic values with increasing length of VOI. Our study demonstrated that apparent elastic modulus calculated from μFE models were affected by the sample volumes. There was a descending tendency of E values as the length of cubic VOI decreased. Sample volume which was not smaller than (7.34mm(3)) was efficient enough and timesaving for the calculation of E.

  16. The human immunodeficiency virus type 1 encapsidation site is a multipartite RNA element composed of functional hairpin structures.

    PubMed Central

    McBride, M S; Panganiban, A T

    1996-01-01

    We analyzed the leader region of human immunodeficiency virus type 1 (HIV-1) RNA to decipher the nature of the cis-acting E/psi element required for encapsidation of viral RNA into virus particles. Our data indicate that, for RNA encapsidation, there are at least two functional subregions in the leader region. One subregion is located at a position immediately proximal to the major splice donor, and the second is located between the splice donor and the beginning of the gag gene. This suggests that at least two discrete cis-acting elements are recognition signals for encapsidation. To determine whether specific putative RNA secondary structures serve as the signal(s) for encapsidation, we constructed primary base substitution mutations that would be expected to destabilize these potential structures and second-site compensatory mutations that would restore secondary structure. Analysis of these mutants allowed the identification of two discrete hairpins that facilitate RNA encapsidation in vivo. Thus, the HIV-1 E/psi region is a multipartite element composed of specific and functional RNA secondary structures. Compensation of the primary mutations by the second-site mutations could not be attained in trans. This indicates that interstrand base pairing between these two stem regions within the hairpins does not appear to be the basis for HIV-1 RNA dimer formation. Comparison of the hypothetical RNA secondary structures from 10 replication-competent HIV-1 strains suggests that a subset of the hydrogen-bonded base pairs within the stems of the hairpins is likely to be required for function in cis. PMID:8627772

  17. Sensing of human plasma fibrinogen on polished, chemically etched and carbon treated titanium surfaces by diffractive optical element based sensor.

    PubMed

    Silvennoinen, Raimo; Vetterl, Vladimir; Hason, Stanislav; Tuononen, Heikki; Silvennoinen, Martti; Myller, Kari; Cvrcek, Ladislav; Vanek, Jiri; Prachar, Patrik

    2008-07-01

    Adsorption of human plasma fibrinogen (HPF) on 6 differently treated titanium samples (polished, polished and etched, and 4 titanium carbide coatings samples produced by using plasma-enhanced chemical vapour deposition (PECVD) method) is investigated by using diffractive optical element (DOE) sensor. Permittivity (susceptibility) change and fluctuation in optical roughness (R(opt)) of treated titanium surface in the presence of background electrolyte without and with HPF molecules are sensed by using DOE sensor and optical ellipsometry. Correlation between transmitted light and thickness of molecule layer was found. The findings allow to sense temporal organization and severity of adsorption of nano-scale HPF molecules on polished, on polished and etched, and on titanium carbide surface.

  18. Development of a Finite Element Model of the Human Shoulder to Investigate the Mechanical Responses and Injuries in Side Impact

    NASA Astrophysics Data System (ADS)

    Iwamoto, Masami; Miki, Kazuo; Yang, King H.

    Previous studies in both fields of automotive safety and orthopedic surgery have hypothesized that immobilization of the shoulder caused by the shoulder injury could be related to multiple rib fractures, which are frequently life threatening. Therefore, for more effective occupant protection, it is important to understand the relationship between shoulder injury and multiple rib fractures in side impact. The purpose of this study is to develop a finite element model of the human shoulder in order to understand this relationship. The shoulder model included three bones (the humerus, scapula and clavicle) and major ligaments and muscles around the shoulder. The model also included approaches to represent bone fractures and joint dislocations. The relationships between shoulder injury and immobilization of the shoulder are discussed using model responses for lateral shoulder impact. It is also discussed how the injury can be related to multiple rib fractures.

  19. A Drosophila protein homologous to the human p70 Ku autoimmune antigen interacts with the P transposable element inverted repeats.

    PubMed Central

    Beall, E L; Admon, A; Rio, D C

    1994-01-01

    P transposable elements in Drosophila are mobilized via a cut-and-paste mechanism. This mode of transposition requires repair of both a double-strand break at the donor DNA site and gapped DNA at the target site. Biochemical studies have identified a cellular non-P element-encoded DNA binding protein, termed the inverted repeat binding protein (IRBP), that specifically interacts with the outer half of the 31-bp terminal inverted repeats. Protein sequence information was used to isolate cDNA clones encoding IRBP. Sequence analysis shows that IRBP is related to the 70-kDa subunit of the human Ku autoimmune antigen. The mammalian Ku antigen binds free DNA termini and has been implicated in immunoglobulin VDJ recombination, DNA repair, and transcription. In addition, Ku is the DNA binding subunit of the double-strand DNA-dependent protein kinase. Cytogenetic mapping indicates that the IRBP gene maps to chromosomal position 86E on the right arm of the third chromosome. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7809101

  20. Cloning and characterization of the 5' flanking region of the sialomucin complex/rat Muc4 gene: promoter activity in cultured cells.

    PubMed Central

    Price-Schiavi, S A; Perez, A; Barco, R; Carraway, K L

    2000-01-01

    Sialomucin complex (SMC/Muc4) is a heterodimeric glycoprotein complex consisting of a mucin subunit ascites sialoglycoprotein-1 (ASGP-1) and a transmembrane subunit (ASGP-2), which is aberrantly expressed on the surfaces of a variety of tumour cells. SMC is transcribed from a single gene, translated into a large polypeptide precursor, and further processed to yield the mature ASGP-1/ASGP-2 complex. SMC has complex spatial and temporal expression patterns in the normal rat, suggesting that it has complex regulatory mechanisms. A crude exon/intron map of the 5' regions of the SMC/Muc4 gene generated from clones isolated from a normal rat liver genomic DNA library reveals that this gene has a small first exon comprising the 5' untranslated region and signal peptide, followed by a large intron. The second exon appears to be large, comprising the 5' unique region and a large part (probably all) of the tandem repeat domain. This structure is strikingly similar to that reported for the human MUC4 gene. Using PCR-based DNA walking, 2.4 kb of the 5'-flanking region of the SMC/Muc4 gene was cloned and characterized. Promoter-pattern searches yielded multiple motifs commonly found in tissue-specific promoters. Reporter constructs generated from this 2.4 kb fragment demonstrate promoter activity in primary rat mammary epithelial cells (MEC), the human colon tumour cell line HCT-116, and the human lung carcinoma cell line NCI-H292, but not in COS-7 cells, suggesting epithelial cell specificity. Deletion constructs of this sequence transfected into rat MEC or HCT-116 cells demonstrate greatly varying levels of activity, suggesting that there are positive and negative, as well as tissue-specific, regulatory elements in this sequence. Taken together, these data suggest that the rat SMC/Muc4 promoter has been identified, that it is tissue- (epithelial cell-) specific, and that there are both positive and negative, as well as tissue-specific, regulatory elements in the sequence

  1. Efficient recovery of centric heterochromatin P-element insertions in Drosophila melanogaster.

    PubMed Central

    Yan, Christopher M; Dobie, Kenneth W; Le, Hiep D; Konev, Alexander Y; Karpen, Gary H

    2002-01-01

    Approximately one-third of the human and Drosophila melanogaster genomes are heterochromatic, yet we know very little about the structure and function of this enigmatic component of eukaryotic genomes. To facilitate molecular and cytological analysis of heterochromatin we introduced a yellow(+) (y(+))-marked P element into centric heterochromatin by screening for variegated phenotypes, that is, mosaic gene inactivation. We recovered >110 P insertions with variegated yellow expression from approximately 3500 total mobilization events. FISH analysis of 71 of these insertions showed that 69 (97%) were in the centric heterochromatin, rather than telomeres or euchromatin. High-resolution banding analysis showed a wide but nonuniform distribution of insertions within centric heterochromatin; variegated insertions were predominantly recovered near regions of satellite DNA. We successfully used inverse PCR to clone and sequence the flanking DNA for approximately 63% of the insertions. BLAST analysis of the flanks demonstrated that either most of the variegated insertions could not be placed on the genomic scaffold, and thus may be inserted within novel DNA sequence, or that the flanking DNA hit multiple sites on the scaffold, due to insertions within different transposons. Taken together these data suggest that screening for yellow variegation is a very efficient method for recovering centric insertions and that a large-scale screen for variegated yellow P insertions will provide important tools for detailed analysis of centric heterochromatin structure and function. PMID:12019236

  2. Two distinct structural elements of 5S rRNA are needed for its import into human mitochondria.

    PubMed

    Smirnov, Alexandre; Tarassov, Ivan; Mager-Heckel, Anne-Marie; Letzelter, Michel; Martin, Robert P; Krasheninnikov, Igor A; Entelis, Nina

    2008-04-01

    RNA import into mitochondria is a widespread phenomenon. Studied in details for yeast, protists, and plants, it still awaits thorough investigation for human cells, in which the nuclear DNA-encoded 5S rRNA is imported. Only the general requirements for this pathway have been described, whereas specific protein factors needed for 5S rRNA delivery into mitochondria and its structural determinants of import remain unknown. In this study, a systematic analysis of the possible role of human 5S rRNA structural elements in import was performed. Our experiments in vitro and in vivo show that two distinct regions of the human 5S rRNA molecule are needed for its mitochondrial targeting. One of them is located in the proximal part of the helix I and contains a conserved uncompensated G:U pair. The second and most important one is associated with the loop E-helix IV region with several noncanonical structural features. Destruction or even destabilization of these sites leads to a significant decrease of the 5S rRNA import efficiency. On the contrary, the beta-domain of the 5S rRNA was proven to be dispensable for import, and thus it can be deleted or substituted without affecting the 5S rRNA importability. This finding was used to demonstrate that the 5S rRNA can function as a vector for delivering heterologous RNA sequences into human mitochondria. 5S rRNA-based vectors containing a substitution of a part of the beta-domain by a foreign RNA sequence were shown to be much more efficiently imported in vivo than the wild-type 5S rRNA.

  3. Combining RT-PCR-seq and RNA-seq to catalog all genic elements encoded in the human genome.

    PubMed

    Howald, Cédric; Tanzer, Andrea; Chrast, Jacqueline; Kokocinski, Felix; Derrien, Thomas; Walters, Nathalie; Gonzalez, Jose M; Frankish, Adam; Aken, Bronwen L; Hourlier, Thibaut; Vogel, Jan-Hinnerk; White, Simon; Searle, Stephen; Harrow, Jennifer; Hubbard, Tim J; Guigó, Roderic; Reymond, Alexandre

    2012-09-01

    Within the ENCODE Consortium, GENCODE aimed to accurately annotate all protein-coding genes, pseudogenes, and noncoding transcribed loci in the human genome through manual curation and computational methods. Annotated transcript structures were assessed, and less well-supported loci were systematically, experimentally validated. Predicted exon-exon junctions were evaluated by RT-PCR amplification followed by highly multiplexed sequencing readout, a method we called RT-PCR-seq. Seventy-nine percent of all assessed junctions are confirmed by this evaluation procedure, demonstrating the high quality of the GENCODE gene set. RT-PCR-seq was also efficient to screen gene models predicted using the Human Body Map (HBM) RNA-seq data. We validated 73% of these predictions, thus confirming 1168 novel genes, mostly noncoding, which will further complement the GENCODE annotation. Our novel experimental validation pipeline is extremely sensitive, far more than unbiased transcriptome profiling through RNA sequencing, which is becoming the norm. For example, exon-exon junctions unique to GENCODE annotated transcripts are five times more likely to be corroborated with our targeted approach than with extensive large human transcriptome profiling. Data sets such as the HBM and ENCODE RNA-seq data fail sampling of low-expressed transcripts. Our RT-PCR-seq targeted approach also has the advantage of identifying novel exons of known genes, as we discovered unannotated exons in ~11% of assessed introns. We thus estimate that at least 18% of known loci have yet-unannotated exons. Our work demonstrates that the cataloging of all of the genic elements encoded in the human genome will necessitate a coordinated effort between unbiased and targeted approaches, like RNA-seq and RT-PCR-seq.

  4. EEG beta suppression and low gamma modulation are different elements of human upright walking.

    PubMed

    Seeber, Martin; Scherer, Reinhold; Wagner, Johanna; Solis-Escalante, Teodoro; Müller-Putz, Gernot R

    2014-01-01

    Cortical involvement during upright walking is not well-studied in humans. We analyzed non-invasive electroencephalographic (EEG) recordings from able-bodied volunteers who participated in a robot-assisted gait-training experiment. To enable functional neuroimaging during walking, we applied source modeling to high-density (120 channels) EEG recordings using individual anatomy reconstructed from structural magnetic resonance imaging scans. First, we analyzed amplitude differences between the conditions, walking and upright standing. Second, we investigated amplitude modulations related to the gait phase. During active walking upper μ (10-12 Hz) and β (18-30 Hz) oscillations were suppressed [event-related desynchronization (ERD)] compared to upright standing. Significant β ERD activity was located focally in central sensorimotor areas for 9/10 subjects. Additionally, we found that low γ (24-40 Hz) amplitudes were modulated related to the gait phase. Because there is a certain frequency band overlap between sustained β ERD and gait phase related modulations in the low γ range, these two phenomena are superimposed. Thus, we observe gait phase related amplitude modulations at a certain ERD level. We conclude that sustained μ and β ERD reflect a movement related state change of cortical excitability while gait phase related modulations in the low γ represent the motion sequence timing during gait. Interestingly, the center frequencies of sustained β ERD and gait phase modulated amplitudes were identified to be different. They may therefore be caused by different neuronal rhythms, which should be taken under consideration in future studies.

  5. Elemental maps in human allantochorial placental vessels cells: 1. High K + and acetylcholine effects

    NASA Astrophysics Data System (ADS)

    Michelet-Habchi, C.; Barberet, Ph.; Dutta, R. K.; Guiet-Bara, A.; Bara, M.; Moretto, Ph.

    2003-09-01

    Regulation of vascular tone in the fetal extracorporeal circulation most likely depends on circulating hormones, local paracrine mechanisms and changes in membrane potential of vascular smooth muscle cells (VSMCs) and of vascular endothelial cells (VECs). The membrane potential is a function of the physiological activities of ionic channels (particularly, K + and Ca 2+ channels in these cells). These channels regulate the ionic distribution into these cells. Micro-particle induced X-ray emission (PIXE) analysis was applied to determine the ionic composition of VSMC and of VEC in the placental human allantochorial vessels in a physiological survival medium (Hanks' solution) modified by the addition of acetylcholine (ACh: which opens the calcium-sensitive K + channels, K Ca) and of high concentration of K + (which blocks the voltage-sensitive K + channels, K df). In VSMC (media layer), the addition of ACh induced no modification of the Na, K, Cl, P, S, Mg and Ca concentrations and high K + medium increased significantly the Cl and K concentrations, the other ion concentrations remaining constant. In endothelium (VEC), ACh addition implicated a significant increase of Na and K concentration, and high K + medium, a significant increase in Cl and K concentration. These results indicated the importance of K df, K Ca and K ATP channels in the regulation of K + intracellular distribution in VSMC and VEC and the possible intervention of a Na-K-2Cl cotransport and corroborated the previous electrophysiological data.

  6. Nicotine and the Developing Human: A Neglected Element in the Electronic Cigarette Debate.

    PubMed

    England, Lucinda J; Bunnell, Rebecca E; Pechacek, Terry F; Tong, Van T; McAfee, Tim A

    2015-08-01

    The elimination of cigarettes and other combusted tobacco products in the U.S. would prevent tens of millions of tobacco-related deaths. It has been suggested that the introduction of less harmful nicotine delivery devices, such as electronic cigarettes or other electronic nicotine delivery systems, will accelerate progress toward ending combustible cigarette use. However, careful consideration of the potential adverse health effects from nicotine itself is often absent from public health debates. Human and animal data support that nicotine exposure during periods of developmental vulnerability (fetal through adolescent stages) has multiple adverse health consequences, including impaired fetal brain and lung development, and altered development of cerebral cortex and hippocampus in adolescents. Measures to protect the health of pregnant women and children are needed and could include (1) strong prohibitions on marketing that increase youth uptake; (2) youth access laws similar to those in effect for other tobacco products; (3) appropriate health warnings for vulnerable populations; (4) packaging to prevent accidental poisonings; (5) protection of non-users from exposure to secondhand electronic cigarette aerosol; (6) pricing that helps minimize youth initiation and use; (7) regulations to reduce product addiction potential and appeal for youth; and (8) the age of legal sale.

  7. [Natural toxins in inter- and intraspecies interaction of human being (elements of ethnotoxinology)].

    PubMed

    Gelashvili, D B

    2002-01-01

    The author considers the application of natural toxins as arrow poison by Homo sapiens from ancient time till today for hunting and ethnic wars on the example of natives of Asia, Africa, South America and Oceania. Geographic isolation was important determining the spectrum of natural toxin sources and the methods of their application. Cellular and molecular mechanisms of arrow poisons effects are considered in biogeographical context: aconitin and strychnin in Asia, diamphotoxin in Africa, indole alcaloids of plants and steroid alcaloids of amphibian in Central and South America, palytoxin in Oceania islands. High efficiency and selective effect of natural toxins allow to use them as molecular markers in current studies of functional membrane architecture and cellular structures. Great differences in pace of civilization development leads to the co-existence at the beginning of the XXI century ethnic groups that use natural toxins as arrow poison and human beings that use the same toxins in fundamental and applied investigations within international scientific society. PMID:12070945

  8. Binding of cellular repressor protein or the IE2 protein to a cis-acting negative regulatory element upstream of a human cytomegalovirus early promoter.

    PubMed Central

    Huang, L; Stinski, M F

    1995-01-01

    We have previously shown that the human cytomegalovirus early UL4 promoter has upstream negative and positive cis-acting regulatory elements. In the absence of the upstream negative regulatory region, the positive element confers strong transcriptional activity. The positive element contains a CCAAT box dyad symmetry and binds the cellular transcription factor NF-Y. The effect of the negative regulatory element is negated by the viral IE2 protein (L. Huang, C.L. Malone, and M.F. Stinski, J. Virol. 68:2108, 1994). We investigated the binding of cellular or viral IE2 protein to the negative regulatory region. The major cis-acting negative regulatory element was located between -168 and -134 bp relative to the transcription start site. This element could be transferred to a heterologous promoter, and it functioned in either orientation. Mutational analysis demonstrated that a core DNA sequence in the cis-acting negative regulatory element, 5'-GTTTGGAATCGTT-3', was required for the binding of either a cellular repressor protein(s) or the viral IE2 protein. The cellular DNA binding activity was present in both nonpermissive HeLa and permissive human fibroblast cells but more abundant in HeLa cells. Binding of the cellular repressor protein to the upstream cis-acting negative regulatory element correlates with repression of transcription from the early UL4 promoter. Binding of the viral IE2 protein correlates with negation of the repressive effect. PMID:7494269

  9. A human chromosome 12-associated 83-kilodalton cellular protein specifically binds to the loop region of human immunodeficiency virus type 1 trans-activation response element RNA.

    PubMed Central

    Hart, C E; Saltrelli, M J; Galphin, J C; Schochetman, G

    1995-01-01

    trans activation of human immunodeficiency virus type 1 (HIV-1) involves the viral trans-activator protein (Tat) and a cellular factor(s) encoded on human chromosome 12 (HuChr12) that targets the trans-activation response element (TAR) in the viral long terminal repeat. Because nascent TAR RNA is predicted to form a secondary structure that specifically binds cellular proteins, we investigated the composition of the TAR RNA-protein complex for HuChr12-specific proteins. UV cross-linking of TAR RNA-nuclear protein complexes formed in vitro identified an 83-kDa protein in human cells and in a human-hamster hybrid cell containing only HuChr12. The 83-kDa TAR RNA-binding protein was absent in the parental hamster cells. TAR RNA mutations that inhibited binding of the 83-kDa protein in vitro also inhibited HuChr12-dependent Tat trans activation. These TAR mutations changed the native sequence or secondary structure of the TAR loop. The TAR RNA binding activity of the 83-kDa protein also correlated with a HuChr12-dependent increase in steady-state HIV-1 RNA expression during Tat trans activation. Our results suggest that either a species-specific 83-kDa TAR RNA loop-binding protein is directly encoded on HuChr12 or a HuChr12 protein(s) induces the expression of an 83-kDa TAR-binding protein in nonprimate cells. PMID:7666565

  10. Characterization of Human Endogenous Retroviral Elements in the Blood of HIV-1-Infected Individuals

    PubMed Central

    Contreras-Galindo, Rafael; Kaplan, Mark H.; Contreras-Galindo, Angie C.; Gonzalez-Hernandez, Marta J.; Ferlenghi, Ilaria; Giusti, Fabiola; Lorenzo, Eric; Gitlin, Scott D.; Dosik, Michael H.; Yamamura, Yasuhiro

    2012-01-01

    We previously reported finding the RNA of a type K human endogenous retrovirus, HERV-K (HML-2), at high titers in the plasma of HIV-1-infected and cancer patients (R. Contreras-Galindo et al., J. Virol. 82:9329–9236, 2008.). The extent to which the HERV-K (HML-2) proviruses become activated and the nature of their activated viral RNAs remain important questions. Therefore, we amplified and sequenced the full-length RNA of the env gene of the type 1 and 2 HERV-K (HML-2) viruses collected from the plasma of seven HIV-1-infected patients over a period of 1 to 3 years and from five breast cancer patients in order to reconstruct the genetic evolution of these viruses. HERV-K (HML-2) RNA was found in plasma fractions of HIV-1 patients at a density of ∼1.16 g/ml that contained both immature and correctly processed HERV-K (HML-2) proteins and virus-like particles that were recognized by anti-HERV-K (HML-2) antibodies. RNA sequences from novel HERV-K (HML-2) proviruses were discovered, including K111, which is specifically active during HIV-1 infection. Viral RNA arose from complete proviruses and proviruses devoid of a 5′ long terminal repeat, suggesting that the expression of HERV-K (HML-2) RNA in these patients may involve sense and antisense transcription. In HIV-1-infected individuals, the HERV-K (HML-2) viral RNA showed evidence of frequent recombination, accumulation of synonymous rather than nonsynonymous mutations, and conserved N-glycosylation sites, suggesting that some of the HERV-K (HML-2) viral RNAs have undergone reverse transcription and are under purifying selection. In contrast, HERV-K (HML-2) RNA sequences found in the blood of breast cancer patients showed no evidence of recombination and exhibited only sporadic viral mutations. This study suggests that HERV-K (HML-2) is active in HIV-1-infected patients, and the resulting RNA message reveals previously undiscovered HERV-K (HML-2) genomic sequences. PMID:22031938

  11. Numerical model (switchable/dual model) of the human head for rigid body and finite elements applications.

    PubMed

    Tabacu, Stefan

    2015-01-01

    In this paper, a methodology for the development and validation of a numerical model of the human head using generic procedures is presented. All steps required, starting with the model generation, model validation and applications will be discussed. The proposed model may be considered as a dual one due to its capabilities to switch from deformable to a rigid body according to the application's requirements. The first step is to generate the numerical model of the human head using geometry files or medical images. The required stiffness and damping for the elastic connection used for the rigid body model are identified by performing a natural frequency analysis. The presented applications for model validation are related to impact analysis. The first case is related to Nahum's (Nahum and Smith 1970) experiments pressure data being evaluated and a pressure map generated using the results from discrete elements. For the second case, the relative displacement between the brain and the skull is evaluated according to Hardy's (Hardy WH, Foster CD, Mason, MJ, Yang KH, King A, Tashman S. 2001.Investigation of head injury mechanisms using neutral density technology and high-speed biplanar X-ray. Stapp Car Crash J. 45:337-368, SAE Paper 2001-22-0016) experiments. The main objective is to validate the rigid model as a quick and versatile tool for acquiring the input data for specific brain analyses. PMID:24156633

  12. An Inverse Finite Element Method for Determining the Tissue Compressibility of Human Left Ventricular Wall during the Cardiac Cycle

    PubMed Central

    Hassaballah, Abdallah I.; Hassan, Mohsen A.; Mardi, Azizi N.; Hamdi, Mohd

    2013-01-01

    The determination of the myocardium’s tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle. PMID:24367544

  13. Numerical model (switchable/dual model) of the human head for rigid body and finite elements applications.

    PubMed

    Tabacu, Stefan

    2015-01-01

    In this paper, a methodology for the development and validation of a numerical model of the human head using generic procedures is presented. All steps required, starting with the model generation, model validation and applications will be discussed. The proposed model may be considered as a dual one due to its capabilities to switch from deformable to a rigid body according to the application's requirements. The first step is to generate the numerical model of the human head using geometry files or medical images. The required stiffness and damping for the elastic connection used for the rigid body model are identified by performing a natural frequency analysis. The presented applications for model validation are related to impact analysis. The first case is related to Nahum's (Nahum and Smith 1970) experiments pressure data being evaluated and a pressure map generated using the results from discrete elements. For the second case, the relative displacement between the brain and the skull is evaluated according to Hardy's (Hardy WH, Foster CD, Mason, MJ, Yang KH, King A, Tashman S. 2001.Investigation of head injury mechanisms using neutral density technology and high-speed biplanar X-ray. Stapp Car Crash J. 45:337-368, SAE Paper 2001-22-0016) experiments. The main objective is to validate the rigid model as a quick and versatile tool for acquiring the input data for specific brain analyses.

  14. The modeling of the whole human body and the simulations of the waveguide intra-body communication by using the finite-element method

    NASA Astrophysics Data System (ADS)

    Song, Yong; Chu, Yingfang; Zhang, Kai; Kang, Bangzhi; Hao, Qun

    2010-11-01

    The simulation based on the finite-element (FE) method plays an important role in the investigation of the intra-body communication (IBC). In this paper, the method for modeling the whole human body based on the finite-element method is proposed, while a finite-element model of the whole human body used for the simulations of the waveguide intra-body communication has been developed. Finally, the simulations of the waveguide IBC with different signal transmission paths have been achieved by using the developed finite-element model. Moreover, both the potential distributions and the signal attenuations of the simulation results are discussed in detail, which indicate that the proposed method and model offer the significant advantages in the theoretical analysis and the system design of the waveguide intra-body communication.

  15. Mercury, elemental

    Integrated Risk Information System (IRIS)

    Mercury , elemental ; CASRN 7439 - 97 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinoge

  16. Dissecting the influence of the collinear and flanking bars in White's effect.

    PubMed

    Blakeslee, Barbara; Padmanabhan, Ganesh; McCourt, Mark E

    2016-10-01

    In White's effect equiluminant test patches placed on the black and white bars of a square-wave grating appear different in brightness. The illusion has generated intense interest because the direction of the brightness effect does not correlate with the amount of black or white border in contact with the test patch, or in its general vicinity. Therefore, unlike brightness induction effects such as simultaneous contrast, White's effect is not consistent with explanations based on contrast or assimilation that depend solely on the relative amounts of black and white surrounding the test patches. We independently manipulated the luminance of the collinear and flanking bars to investigate their influence on test patch matching luminance (brightness). The inducing grating was a 0.5c/d square-wave and test patches measured 1.0° in width and either 0.5° or 3.0° in height. Test patches measuring 0.5° in height had more extensive contact with the collinear bars and test patches measuring 3.0° in height had more extensive contact with the flanking bars. The luminance of the collinear (or flanking) bars assumed twenty values from 3.2 to 124.8cd/m(2), while the luminance of the flanking (or collinear) bars remained white (124.8cd/m(2)) or black (3.2cd/m(2)). Under these conditions the influence of the collinear and flanking bars was found to be purely in the direction of contrast. The effect was dominated by contrast from the collinear bars (which results in White's effect), however, the influence of the flanking bars was also in the contrast direction. The data elucidate the luminance relationships between the collinear and flanking bars which produce the behavior associated with White's effect as well as that associated with "the inverted White effect" which is akin to simultaneous contrast.

  17. [The determination of the natural content of chemical elements in human biological objects (liver, kidney, stomach) by mass spectrometry with inductively coupled plasma].

    PubMed

    Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V

    2014-01-01

    The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.

  18. Effects of heavy elements in the sludge conveyed by the 2011 tsunami on human health and the recovery of the marine ecosystem

    NASA Astrophysics Data System (ADS)

    Sera, K.; Goto, S.; Takahashi, C.; Saitoh, Y.; Yamauchi, K.

    2014-01-01

    The 2011 tsunami not only caused significant damage, but also drew a large amount of sludge from the bottom of the sea. This may have exerted negative effects on human health. In order to evaluate changes in elemental concentrations in the body before and after the tsunami, we collected long hairs from victims of the disaster. Furthermore, sludge and plant samples were collected from three prefectures. The sludge samples on land were found to be still contaminated with heavy elements. The concentrations of heavy elements in the soils and plants gathered from the same tidelands decreased after one year. In hair analyses, no clear changes have been observed in heavy element concentrations measured before and after the tsunami. However, the concentration of some essential elements, such as Cu, Ca and Mg, showed a decreasing tendency after the tsunami.

  19. Length distribution of long interspersed nucleotide elements (LINEs) and processed pseudogenes of human endogenous retroviruses: implications for retrotransposition and pseudogene detection.

    PubMed

    Pavlícek, Adam; Paces, Jan; Zíka, Radek; Hejnar, Jirí

    2002-10-30

    Deciphering the human genome includes reliable identification and structural characterization of individual retrotransposon elements. The most active group of autonomous transposable elements, the long interspersed nuclear elements (LINE), transpose themselves as well as other RNAs, including those of human endogenous retroviruses (HERV). During this transposition, however, the LINE-encoded reverse transcriptase (RT) often abortively dissociates from the RNA template, leaving a prematurely terminated, 5' truncated copy. We have analyzed the length distributions of LINEs and of processed pseudogenes derived from HERV-W. As expected, we have found that the majority of 5' truncated LINEs and HERV-W processed pseudogenes show a prevalence of very short elements terminated close to the 3' end. On the other hand, the number of complete elements is far above the expectation. The characteristic distribution in both cases indicates two important conclusions: (i) dissociation of LINE RT from the template cannot be fully explained by low processivity of RT modelled as a stochastic, Poisson-type process. (ii) Currently cited numbers of pseudogenes within the human genome are underestimated, since a large percentage of pseudogenes are terminated in the 3' untranslated region and remain undetectable in translated homology searches of protein databases against the human genome.

  20. 5' flanking sequence and genomic structure of Egr-1, a murine mitogen inducible zinc finger encoding gene.

    PubMed

    Tsai-Morris, C H; Cao, X M; Sukhatme, V P

    1988-09-26

    Egr-1 is a murine zinc finger encoding cDNA whose expression is modulated by a variety of ligand-receptor interactions and is often coregulated with c-fos (1). This study reports the isolation of a mouse Egr-1 genomic clone, its intron-exon structure, and 935 bp of 5' flanking sequence. The gene spans about 3.8 kb and consists of 2 exons and one 700 bp intron. S1 nuclease protection and primer extension analysis were used to define the transcription initiation site. "TATA" and "CCAAT" sequences were located at nucleotides -26 and -337 respectively. In addition, there exist five elements whose sequence is nearly identical to the inner core 10 nucleotide region (CCATATTAGG) of the c-fos serum response element, four Sp1 consensus sequences, two AP1 target sequence analogs, and two potential cAMP response elements. These results will ultimately lead to a detailed definition of the intracellular events regulating Egr-1 expression.

  1. a Modal Analysis of Whole-Body Vertical Vibration, Using a Finite Element Model of the Human Body

    NASA Astrophysics Data System (ADS)

    Kitazaki, S.; Griffin, M. J.

    1997-02-01

    A two-dimensional model of human biomechanical responses to whole-body vibration has been developed, by using the finite element method. Beam, spring and mass elements were used to model the spine, viscera, head, pelvis and buttocks tissue in the mid-sagittal plane. The model was developed by comparison of the vibration mode shapes with those previously measured in the laboratory. At frequencies below 10 Hz, the model produced seven modes which coincided well with the measurements. The principal resonance of the driving point response at about 5 Hz consisted of an entire body mode, in which the head, spinal column and the pelvis move almost rigidly, with axial and shear deformation of tissue beneath the pelvis occurring in phase with a vertical visceral mode. The second principal resonance at about 8 Hz corresponded to a rotational mode of the pelvis, with a possible contribution from a second visceral mode. A shift of the principal resonance of the driving point response, when changing posture, was achieved only by changing the axial stiffness of the buttocks tissue. It is suggested that an increase in contact area between the buttocks and the thighs and the seat surface, when changing posture from erect to slouched, may decrease the axial stiffness beneath the pelvis, with a non-linear force-deflection relationship of tissue resulting in decreases in the natural frequencies. A change in posture from erect to slouched also increased shear deformation of tissue beneath the pelvis in the entire body mode, and the natural frequency was decreased as a result of the much lower shear stiffness of tissue compared to the axial stiffness.

  2. 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage

    PubMed Central

    Rands, Chris M.; Meader, Stephen; Ponting, Chris P.; Lunter, Gerton

    2014-01-01

    Ten years on from the finishing of the human reference genome sequence, it remains unclear what fraction of the human genome confers function, where this sequence resides, and how much is shared with other mammalian species. When addressing these questions, functional sequence has often been equated with pan-mammalian conserved sequence. However, functional elements that are short-lived, including those contributing to species-specific biology, will not leave a footprint of long-lasting negative selection. Here, we address these issues by identifying and characterising sequence that has been constrained with respect to insertions and deletions for pairs of eutherian genomes over a range of divergences. Within noncoding sequence, we find increasing amounts of mutually constrained sequence as species pairs become more closely related, indicating that noncoding constrained sequence turns over rapidly. We estimate that half of present-day noncoding constrained sequence has been gained or lost in approximately the last 130 million years (half-life in units of divergence time, d1/2 = 0.25–0.31). While enriched with ENCODE biochemical annotations, much of the short-lived constrained sequences we identify are not detected by models optimized for wider pan-mammalian conservation. Constrained DNase 1 hypersensitivity sites, promoters and untranslated regions have been more evolutionarily stable than long noncoding RNA loci which have turned over especially rapidly. By contrast, protein coding sequence has been highly stable, with an estimated half-life of over a billion years (d1/2 = 2.1–5.0). From extrapolations we estimate that 8.2% (7.1–9.2%) of the human genome is presently subject to negative selection and thus is likely to be functional, while only 2.2% has maintained constraint in both human and mouse since these species diverged. These results reveal that the evolutionary history of the human genome has been highly dynamic, particularly for its

  3. Implementing reverse genetics in Rosaceae: analysis of T-DNA flanking sequences of insertional mutant lines in the diploid strawberry, Fragaria vesca.

    PubMed

    Oosumi, Teruko; Ruiz-Rojas, Juan Jairo; Veilleux, Richard E; Dickerman, Allan; Shulaev, Vladimir

    2010-09-01

    Reverse genetics is used for functional genomics research in model plants. To establish a model system for the systematic reverse genetics research in the Rosaceae family, we analyzed genomic DNA flanking the T-DNA insertions in 191 transgenic plants of the diploid strawberry, Fragaria vesca. One hundred and seventy-six T-DNA flanking sequences were amplified from the right border (RB) and 37 from the left border (LB) by thermal asymmetric interlaced PCR. Analysis of the T-DNA nick positions revealed that T-DNA was most frequently nicked at the cleavage sites. Analysis of 11 T-DNA integration sites indicated that T-DNA was integrated into the F. vesca genome by illegitimate recombination, as reported in other model plants: Arabidopsis, rice and tobacco. First, deletion of DNA was found at T-DNA integration target sites in all transgenic plants tested. Second, microsimilarities of a few base pairs between the left and/or right ends of the T-DNA and genomic sites were found in all transgenic plants tested. Finally, filler DNA was identified in four break-points. Out of 191 transgenic plants, T-DNA flanking sequences of 79 plants (41%) showed significant similarity to genes, elements or proteins of other plant species and 67 (35%) of the sequences are still unknown strawberry gene fragments. T-DNA flanking sequences of 126 plants (66%) showed homology to plant ESTs. This is the first report of T-DNA integration in a sizeable population of a rosaceous species. We have shown in this paper that T-DNA integration in strawberry is not random but directed by sequence microsimilarities in the host genome.

  4. Brain Response to Primary Blast Wave Using Validated Finite Element Models of Human Head and Advanced Combat Helmet

    PubMed Central

    Zhang, Liying; Makwana, Rahul; Sharma, Sumit

    2013-01-01

    Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen

  5. Effects of human-induced alteration of groundwater flow on concentrations of naturally-occurring trace elements at water-supply wells

    USGS Publications Warehouse

    Ayotte, J.D.; Szabo, Z.; Focazio, M.J.; Eberts, S.M.

    2011-01-01

    The effects of human-induced alteration of groundwater flow patterns on concentrations of naturally-occurring trace elements were examined in five hydrologically distinct aquifer systems in the USA. Although naturally occurring, these trace elements can exceed concentrations that are considered harmful to human health. The results show that pumping-induced hydraulic gradient changes and artificial connection of aquifers by well screens can mix chemically distinct groundwater. Chemical reactions between these mixed groundwaters and solid aquifer materials can result in the mobilization of trace elements such as U, As and Ra, with subsequent transport to water-supply wells. For example, in the High Plains aquifer near York, Nebraska, mixing of shallow, oxygenated, lower-pH water from an unconfined aquifer with deeper, confined, anoxic, higher-pH water is facilitated by wells screened across both aquifers. The resulting higher-O2, lower-pH mixed groundwater facilitated the mobilization of U from solid aquifer materials, and dissolved U concentrations were observed to increase significantly in nearby supply wells. Similar instances of trace element mobilization due to human-induced mixing of groundwaters were documented in: (1) the Floridan aquifer system near Tampa, Florida (As and U), (2) Paleozoic sedimentary aquifers in eastern Wisconsin (As), (3) the basin-fill aquifer underlying the California Central Valley near Modesto (U), and (4) Coastal Plain aquifers of New Jersey (Ra). Adverse water-quality impacts attributed to human activities are commonly assumed to be related solely to the release of the various anthropogenic contaminants to the environment. The results show that human activities including various land uses, well drilling, and pumping rates and volumes can adversely impact the quality of water in supply wells, when associated with naturally-occurring trace elements in aquifer materials. This occurs by causing subtle but significant changes in

  6. Sequence of the cDNA and 5'-flanking region for human acid alpha-glucosidase, detection of an intron in the 5' untranslated leader sequence, definition of 18-bp polymorphisms, and differences with previous cDNA and amino acid sequences.

    PubMed

    Martiniuk, F; Mehler, M; Tzall, S; Meredith, G; Hirschhorn, R

    1990-03-01

    Acid maltase or acid alpha-glucosidase (GAA) is a lysosomal enzyme that hydrolyzes glycogen to glucose and is deficient in glycogen storage disease type II. Previously, we isolated a partial cDNA (1.9 kb) for human GAA; we have now used this cDNA to isolate and determine sequence in longer cDNAs from four additional independent cDNA libraries. Primer extension studies indicated that the mRNA extended approximately 200 bp 5' of the cDNA sequence obtained. Therefore, we isolated a genomic fragment containing 5' cDNA sequences that overlapped the previous cDNA sequence and extended an additional 24 bp to an initiation codon within a Kozak consensus sequence. The sequence of the genomic clone revealed an intron-exon junction 32 bp 5' to the ATG, indicating that the 5' leader sequence was interrupted by an intron. The remaining 186 bp of 5' untranslated sequence was identified approximately 3 kb upstream. The promoter region upstream from the start site of transcription was GC rich and contained areas of homology to Sp1 binding sites but no identifiable CAAT or TATA box. The combined data gave a nucleotide sequence of 2,856 bp for the coding region from the ATG to a stop codon, predicting a protein of 952 amino acids. The 3' untranslated region contained 555 bp with a polyadenylation signal at 3,385 bp followed by 16 bp prior to a poly(A) tail. This sequence of the GAA coding region differs from that reported by Hoefsloot et al. (1988) in three areas that change a total of 42 amino acids. Direct determination of the amino acid sequence in one of these areas confirmed the nucleotide sequence reported here but also disagreed with the directly determined amino acid sequence reported by Hoefsloot et al. (1988). At two other areas, changes in base pairs predicted new restriction sites that were identified in cDNAs from several independent libraries. The amino acid changes in all three ares increased the homology to rabbit-human isomaltase. Therefore, we believe that our

  7. Magmatism on rift flanks: Insights from ambient noise phase velocity in Afar region

    NASA Astrophysics Data System (ADS)

    Korostelev, Félicie; Weemstra, Cornelis; Leroy, Sylvie; Boschi, Lapo; Keir, Derek; Ren, Yong; Molinari, Irene; Ahmed, Abdulhakim; Stuart, Graham W.; Rolandone, Frédérique; Khanbari, Khaled; Hammond, James O. S.; Kendall, J. M.; Doubre, Cécile; Ganad, Ismail Al; Goitom, Berhe; Ayele, Atalay

    2015-04-01

    During the breakup of continents in magmatic settings, the extension of the rift valley is commonly assumed to initially occur by border faulting and progressively migrate in space and time toward the spreading axis. Magmatic processes near the rift flanks are commonly ignored. We present phase velocity maps of the crust and uppermost mantle of the conjugate margins of the southern Red Sea (Afar and Yemen) using ambient noise tomography to constrain crustal modification during breakup. Our images show that the low seismic velocities characterize not only the upper crust beneath the axial volcanic systems but also both upper and lower crust beneath the rift flanks where ongoing volcanism and hydrothermal activity occur at the surface. Magmatic modification of the crust beneath rift flanks likely occurs for a protracted period of time during the breakup process and may persist through to early seafloor spreading.

  8. Physical properties of lava flows on the southwest flank of Tyrrhena Patera, Mars

    NASA Technical Reports Server (NTRS)

    Crown, David A.; Porter, Tracy K.; Greeley, Ronald

    1991-01-01

    Tyrrhena Patera (TP) (22 degrees S, 253.5 degrees W), a large, low-relief volcano located in the ancient southern highlands of Mars, is one of four highland paterae thought to be structurally associated with the Hellas basin. The highland paterae are Hesperian in age and among the oldest central vent volcanoes on Mars. The morphology and distribution of units in the eroded shield of TP are consistent with the emplacement of pyroclastic flows. A large flank unit extending from TP to the SW contains well-defined lava flow lobes and leveed channels. This flank unit is the first definitive evidence of effusive volcanic activity associated with the highland paterae and may include the best preserved lava flows observed in the Southern Hemisphere of Mars. Flank flow unit averages, channelized flow, flow thickness, and yield strength estimates are discussed. Analysis suggests the temporal evolution of Martian magmas.

  9. The Rev protein of human immunodeficiency virus type 1 counteracts the effect of an AU-rich negative element in the human papillomavirus type 1 late 3' untranslated region.

    PubMed Central

    Tan, W; Schwartz, S

    1995-01-01

    We have identified a sequence in the late 3' untranslated region of human papillomavirus type 1 mRNAs that acts posttranscriptionally to repress gene expression. Deletion analysis localized the inhibitory element to an AU-rich sequence between nucleotides 6958 and 6984 on the human papillomavirus type 1 genome. This sequence inhibits gene expression in an orientation-dependent manner. Upon transfection of eucaryotic cells with plasmids containing this sequence, approximately 4-fold-lower cytoplasmic mRNA levels and 64- to 128-fold-lower protein levels were produced compared with those produced by plasmids lacking the inhibitory sequence. Interestingly, providing the constitutive transport element of simian retrovirus type 1 in sense orientation counteracted inhibition exerted by the human papillomavirus type 1 sequence. Inhibition could also be overcome by the presence of human immunodeficiency virus type 1 Rev protein in trans and its target sequence, the Rev-responsive element, in cis. Rev is a nuclear protein and acts by promoting nuclear export of human immunodeficiency virus type 1 mRNAs encoding structural proteins. Our results are consistent with a model for human papillomavirus type 1 late-gene expression in which mRNAs containing human papillomavirus type 1 inhibitory sequences enter a nonproductive route in the nucleus, resulting in inefficient mRNA utilization. Rev directs mRNA containing inhibitory sequences to a productive route by interacting with the Rev-responsive element. PMID:7707519

  10. Mobilized retrotransposon Tos17 of rice by alien DNA introgression transposes into genes and causes structural and methylation alterations of a flanking genomic region.

    PubMed

    Han, F P; Liu, Z L; Tan, M; Hao, S; Fedak, G; Liu, B

    2004-01-01

    Tos17 is a copia-like endogenous retrotransposon of rice, which can be activated by various stresses such as tissue culture and alien DNA introgression. To confirm element mobilization by introgression and to study possible structural and epigenetic effects of Tos17 insertion on its target sequences, we isolated all flanking regions of Tos17 in an introgressed rice line (Tong35) that contains minute amount of genomic DNA from wild rice (Zizania latifolia). It was found that there has been apparent but limited mobilization of Tos17 in this introgression line, as being reflected by increased but stable copy number of the element in progeny of the line. Three of the five activated copies of the element have transposed into genes. Based on sequence analysis and Southern blot hybridization with several double-enzyme digests, no structural change in Tos17 could be inferred in the introgression line. Cytosine methylation status at all seven CCGG sites within Tos17 was also identical between the introgression line and its rice parent (Matsumae)-all sites being heavily methylated. In contrast, changes in structure and cytosine methylation patterns were detected in one of the three low-copy genomic regions that flank newly transposed Tos17, and all changes are stably inherited through selfed generations. PMID:15703040

  11. An Anthropometric-Based Subject-Specific Finite Element Model of the Human Breast for Predicting Large Deformations

    PubMed Central

    Pianigiani, Silvia; Ruggiero, Leonardo; Innocenti, Bernardo

    2015-01-01

    The large deformation of the human breast threatens proper nodules tracking when the subject mammograms are used as pre-planning data for biopsy. However, techniques capable of accurately supporting the surgeons during biopsy are missing. Finite element (FE) models are at the basis of currently investigated methodologies to track nodules displacement. Nonetheless, the impact of breast material modeling on the mechanical response of its tissues (e.g., tumors) is not clear. This study proposes a subject-specific FE model of the breast, obtained by anthropometric measurements, to predict breast large deformation. A healthy breast subject-specific FE parametric model was developed and validated by Cranio-caudal (CC) and Medio-Lateral Oblique (MLO) mammograms. The model was successively modified, including nodules, and utilized to investigate the effect of nodules size, typology, and material modeling on nodules shift under the effect of CC, MLO, and gravity loads. Results show that a Mooney–Rivlin material model can estimate healthy breast large deformation. For a pathological breast, under CC compression, the nodules displacement is very close to zero when a linear elastic material model is used. Finally, when nodules are modeled, including tumor material properties, under CC, or MLO or gravity loads, nodules shift shows ~15% average relative difference. PMID:26734604

  12. Validation of Shoulder Response of Human Body Finite-Element Model (GHBMC) Under Whole Body Lateral Impact Condition.

    PubMed

    Park, Gwansik; Kim, Taewung; Panzer, Matthew B; Crandall, Jeff R

    2016-08-01

    In previous shoulder impact studies, the 50th-percentile male GHBMC human body finite-element model was shown to have good biofidelity regarding impact force, but under-predicted shoulder deflection by 80% compared to those observed in the experiment. The goal of this study was to validate the response of the GHBMC M50 model by focusing on three-dimensional shoulder kinematics under a whole-body lateral impact condition. Five modifications, focused on material properties and modeling techniques, were introduced into the model and a supplementary sensitivity analysis was done to determine the influence of each modification to the biomechanical response of the body. The modified model predicted substantially improved shoulder response and peak shoulder deflection within 10% of the observed experimental data, and showed good correlation in the scapula kinematics on sagittal and transverse planes. The improvement in the biofidelity of the shoulder region was mainly due to the modifications of material properties of muscle, the acromioclavicular joint, and the attachment region between the pectoralis major and ribs. Predictions of rib fracture and chest deflection were also improved because of these modifications.

  13. Solution structures and characterization of human immunodeficiency virus Rev responsive element IIB RNA targeting zinc finger proteins.

    PubMed

    Mishra, Subrata H; Shelley, Christopher M; Barrow, Doyle J; Darby, Martyn K; Germann, Markus W

    2006-11-01

    The Rev responsive element (RRE), a part of unspliced human immunodeficiency virus (HIV) RNA, serves a crucial role in the production of infectious HIV virions. The viral protein Rev binds to RRE and facilitates transport of mRNA to the cytoplasm. Inhibition of the Rev-RRE interaction disrupts the viral life cycle. Using a phage display protocol, dual zinc finger proteins (ZNFs) were generated that bind specifically to RREIIB at the high affinity Rev binding site. These proteins were further shortened and simplified, and they still retained their RNA binding affinity. The solution structures of ZNF29 and a mutant, ZNF29G29R, have been determined by nuclear magnetic resonance (NMR) spectroscopy. Both proteins form C(2)H(2)-type zinc fingers with essentially identical structures. RNA protein interactions were evaluated quantitatively by isothermal titration calorimetry, which revealed dissociation constants (K(d)'s) in the nanomolar range. The interaction with the RNA is dependent upon the zinc finger structure; in the presence of EDTA, RNA binding is abolished. For both proteins, RNA binding is mediated by the alpha-helical portion of the zinc fingers and target the bulge region of RREIIB-TR. However, ZNF29G29R exhibits significantly stronger binding to the RNA target than ZNF29; this illustrates that the binding of the zinc finger scaffold is amenable to further improvements.

  14. Environmental distribution and associated human health risk due to trace elements and organic compounds in soil in Jiangxi province, China.

    PubMed

    Teng, Yanguo; Li, Jiao; Wu, Jin; Lu, Sijin; Wang, Yeyao; Chen, Haiyang

    2015-12-01

    The government of China launched its first national soil quality and pollution survey (NSQPS) during April 2006 to December 2013. Data gathered in several earlier soil surveys were rarely used to understand the status of pollution. In this study, the dataset collected at the provincial level was analyzed for the first time. Concentrations, distribution, diversity, and human health risks of trace elements (As, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, V and Zn) and organic pollutants (benzene hexachloride (BHCs), dichlorodiphenyltrichloroethanes (DDTs), phthalic acid esters (PAEs), polycyclic aromatic hydrocarbon (PAHs), polychlorinated biphenyls (PCBs), and petroleum hydrocarbons (PHCs)) in surface soil samples collected across Jiangxi province,China were presented. The results showed that, the proportion of contaminants with concentrations higher than their corresponding regulatory reference value ranged from 0.12% to 17%. It is worth note that, the local residents are exposed to moderate non-carcinogenic and carcinogenic risks at some sites. The comprehensive analysis of soil pollutants provide baseline information for establishing a long-term soil environmental monitoring program in Jiangxi province, China.

  15. Simulation of temperature and thermally induced stress of human tooth under CO2 pulsed laser beams using finite element method.

    PubMed

    Sabaeian, Mohammad; Shahzadeh, Mohammadreza

    2015-02-01

    The authors report the simulation of temperature distribution and thermally induced stresses of human tooth under CO2 pulsed laser beam. A detailed tooth structure comprising enamel, dentin, and pulp with realistic shapes and thicknesses were considered, and a numerical method of finite element was adopted to solve time-dependent bio-heat and stress equations. The realistic boundary conditions of constant temperature for those parts embedded in the gingiva and heat flux condition for those parts out of the gingiva were applied. The results which were achieved as a function of energy density (J/cm(2)) showed when laser beam is irradiated downward (from the top of the tooth), the temperature and thermal stresses decrease quickly as a function of depth that is a result of strong absorption of CO2 beams by enamel. This effect is so influential that one can use CO2 beams to remove micrometer layers while underlying tissues, especially the pulp, are safe from thermal effects.

  16. Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

    PubMed Central

    1993-01-01

    Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells. PMID:8376940

  17. Simulating plastic surgery: from human skin tensile tests, through hyperelastic finite element models to real-time haptics.

    PubMed

    Lapeer, R J; Gasson, P D; Karri, V

    2010-12-01

    In this paper, we provide a summary of a number of experiments we conducted to arrive at a prototype real-time simulator for plastic surgical interventions such as skin flap repair and inguinal herniotomy. We started our research with a series of in-vitro tensile stress tests on human skin, harvested from female patients undergoing plastic reconstructive surgery. We then used the acquired stress-strain data to fit hyperelastic models. Three models were considered: General Polynomial, Reduced Polynomial and Ogden. Only Reduced Polynomial models were found to be stable, hence they progressed to the next stage to be used in an explicit finite element model aimed at real-time performance in conjunction with a haptic feedback device. A total Lagrangian formulation with the half-step central difference method was employed to integrate the dynamic equation of motion of the mesh. The mesh was integrated into two versions of a real-time skin simulator: a single-threaded version running on a computer's main central processing unit and a multi-threaded version running on the computer's graphics card. The latter was achieved by exploiting recent advances in programmable graphics technology.

  18. Trace Elements and Health

    ERIC Educational Resources Information Center

    Pettyjohn, Wayne A.

    1972-01-01

    Summarizes the effects of arsenic, lead, zinc, mercury, and cadmium on human health, indicates the sources of the elements in water, and considers the possibility of students in high schools analyzing water for trace amounts of the elements. (AL)

  19. The distal elements, OCT and SPH, stimulate the formation of preinitiation complexes on a human U6 snRNA gene promoter in vitro.

    PubMed

    Kunkel, G R; Hixson, J D

    1998-03-15

    The distal control region of a human U6 small nuclear RNA (snRNA) gene promoter contains two separable elements, octamer (OCT) and SPH, found in many vertebrate snRNA genes. Complete distal regions generally account for a 4- to 100-fold stimulation of snRNA gene promoters. We examined the mechanism of transcriptional stimulation by each element when linked to the proximal U6 promoter. Multimers of either OCT or SPH did not increase transcriptional levels above that with a single copy, either in transfected human cells or after in vitro transcription in a HeLa S100 extract. The orientation of a single SPH element differentially stimulated transcription in transfected cells, whereas the orientation of an octamer element was not important. Using Sarkosyl to limit transcription to a single-round, we concluded that promoters containing either OCT or SPH elements supported an increased number of preinitiation complexes in vitro. Furthermore, the rate of formation of U6 promoter preinitiation complexes resistant to low (0.015%) concentrations of Sarkosyl was accelerated on templates containing either OCT or SPH. However, neither element had a significant effect on the number of rounds of reinitiation in the S100 extract.

  20. Comparison of flank modification on Ascraeus and Arsia Montes volcanoes, Mars

    NASA Technical Reports Server (NTRS)

    Zimbelman, James R.

    1993-01-01

    Geologic mapping of the Tharsis Montes on Mars is in progress as part of the Mars Geologic Mapping Program of NASA. Mapping of the southern flanks of Ascraeus Mons at 1:500,000 scale was undertaken first followed by detailed mapping of Arsia Mons; mapping of Pavonis Mons will begin later this year. Results indicate that each of the Tharsis volcanoes displays unique variations on the general 'theme' of a martian shield volcano. Here we concentrate on the flank characteristics on Ascraeus Mons and Arsia Mons, the northernmost and southernmost of the Tharsis Montes, as illustrative of the most prominent trends.

  1. Upwelling of hydrothermal solutions through ridge flank sediments shown by pore water profiles

    SciTech Connect

    Maris, C.R.P.; Bender, M.L.

    1982-05-07

    High calcium ion and low magnesium ion concentrations in sediment pore waters in cores from the Galapagos Mounds Hydrothermal Field on the flank of the Galapagos Spreading Center are believed to be due to a calcium-magnesium exchange reaction between circulating seawater and basement basalt. The nonlinearity of the calcium ions and magnesium ion gradients indicates that these discharging hydrothermal solutions on the ridge flank are upwelling at the rate of about 1 centimeter per year through the pelagic sediments of the Mounds Field and at about 20 centimeters per year through the hydrothermal mounds themselves.

  2. Validity and sensitivity of a human cranial finite element model: implications for comparative studies of biting performance.

    PubMed

    Toro-Ibacache, Viviana; Fitton, Laura C; Fagan, Michael J; O'Higgins, Paul

    2016-01-01

    Finite element analysis (FEA) is a modelling technique increasingly used in anatomical studies investigating skeletal form and function. In the case of the cranium this approach has been applied to both living and fossil taxa to (for example) investigate how form relates to function or infer diet or behaviour. However, FE models of complex musculoskeletal structures always rely on simplified representations because it is impossible completely to image and represent every detail of skeletal morphology, variations in material properties and the complexities of loading at all spatial and temporal scales. The effects of necessary simplifications merit investigation. To this end, this study focuses on one aspect, model geometry, which is particularly pertinent to fossil material where taphonomic processes often destroy the finer details of anatomy or in models built from clinical CTs where the resolution is limited and anatomical details are lost. We manipulated the details of a finite element (FE) model of an adult human male cranium and examined the impact on model performance. First, using digital speckle interferometry, we directly measured strains from the infraorbital region and frontal process of the maxilla of the physical cranium under simplified loading conditions, simulating incisor biting. These measured strains were then compared with predicted values from FE models with simplified geometries that included modifications to model resolution, and how cancellous bone and the thin bones of the circum-nasal and maxillary regions were represented. Distributions of regions of relatively high and low principal strains and principal strain vector magnitudes and directions, predicted by the most detailed FE model, are generally similar to those achieved in vitro. Representing cancellous bone as solid cortical bone lowers strain magnitudes substantially but the mode of deformation of the FE model is relatively constant. In contrast, omitting thin plates of bone in

  3. Cloning and Characterization of 5′ Flanking Regulatory Sequences of AhLEC1B Gene from Arachis Hypogaea L.

    PubMed Central

    Tang, Guiying; Xu, Pingli; Liu, Wei; Liu, Zhanji; Shan, Lei

    2015-01-01

    LEAFY COTYLEDON1 (LEC1) is a B subunit of Nuclear Factor Y (NF-YB) transcription factor that mainly accumulates during embryo development. We cloned the 5′ flanking regulatory sequence of AhLEC1B gene, a homolog of Arabidopsis LEC1, and analyzed its regulatory elements using online software. To identify the crucial regulatory region, we generated a series of GUS expression frameworks driven by different length promoters with 5′ terminal and/or 3′ terminal deletion. We further characterized the GUS expression patterns in the transgenic Arabidopsis lines. Our results show that both the 65bp proximal promoter region and the 52bp 5′ UTR of AhLEC1B contain the key motifs required for the essential promoting activity. Moreover, AhLEC1B is preferentially expressed in the embryo and is co-regulated by binding of its upstream genes with both positive and negative corresponding cis-regulatory elements. PMID:26426444

  4. Genomic organization, complete sequence, and chromosomal location of the gene for human eotaxin (SCYA11), an eosinophil-specific CC chemokine

    SciTech Connect

    Garcia-Zepeda, E.A.; Sarafi, M.N.; Luster, A.D. |

    1997-05-01

    Eotaxin is a CC chemokine that is a specific chemoattractant for eosinophils and is implicated in the pathogenesis of eosinophilic inflammatory diseases, such as asthma. We describe the genomic organization, complete sequence, including 1354 bp 5{prime} of the RNA initiation site, and chromosomal localization of the human eotaxin gene. Fluorescence in situ hybridization analysis localized eotaxin to human chromosome 17, in the region q21.1-q21.2, and the human gene name SCYA11 was assigned. We also present the 5{prime} flanking sequence of the mouse eotaxin gene and have identified several regulatory elements that are conserved between the murine and the human promoters. In particular, the presence of elements such as NF-{Kappa}B, interferon-{gamma} response element, and glucocorticoid response element may explain the observed regulation of the eotaxin gene by cytokines and glucocorticoids. 17 refs., 4 figs., 1 tab.

  5. Leptin receptor isoform 219.1: an example of protein evolution by LINE-1-mediated human-specific retrotransposition of a coding SVA element.

    PubMed

    Damert, Annette; Löwer, Johannes; Löwer, Roswitha

    2004-04-01

    Phylogenetically new insertions of repetitive sequences may contribute to genome evolution by altering the function of preexisting proteins. One example is the SVA sequence, which forms the C-terminal coding exon of the human leptin receptor isoform 219.1. Here, we report that the SVA insertion into the LEPR locus has occurred after divergence of humans and chimpanzees. The SVA element was inserted into a Hal-1/LINE element present in all monkeys and apes tested. Structural features point toward an integration event that was mediated by the L1 protein machinery acting in trans. Thus, our findings add evidence to the hypothesis that retrotransposition events are a driving force in genomic evolution and that the presence or absence of specific retroelements are one distinguishing feature that separates humans from chimpanzees.

  6. Evidence for hydrothermal Archaea within the basaltic flanks of the East Pacific Rise.

    PubMed

    Ehrhardt, Christopher J; Haymon, Rachel M; Lamontagne, Michael G; Holden, Patricia A

    2007-04-01

    Little is known about the fluids or the microbial communities present within potentially vast hydrothermal reservoirs contained in still-hot volcanic ocean crust beneath the flanks of the mid-ocean ridge. During Alvin dives in 2002, organic material attached to basalt was collected at low, near-ambient temperatures from an abyssal hill fault scarp in 0.5 Ma lithosphere on the western ridge flank of the East Pacific Rise. Mineral analysis by X-ray diffractometry and scanning electron microscopy revealed high-temperature (> 110 degrees C) phases chalcopyrite (Cu(5)FeS(4)) and 1C pyrrhotite (Fe(1-x)S) within the fault scarp materials. A molecular survey of archaeal genes encoding 16S rRNA identified a diverse hyperthermophilic community, including groups within Crenarchaeota, Euryarchaeota, and Korarchaeota. We propose that the sulfide, metals and archaeal communities originated within a basalt-hosted subseafloor hydrothermal habitat beneath the East Pacific Rise ridge flank and were transported to the seafloor during a recent episode of hydrothermal venting from the abyssal hill fault. Additionally, inferred metabolisms from the fault scarp community suggest that an ecologically unique high-temperature archaeal biosphere may thrive beneath the young East Pacific Rise ridge flank and that abyssal hill fault scarps may present new opportunities for sampling for this largely unexplored microbial habitat.

  7. Hazard potential of volcanic flank collapses raised by new megatsunami evidence.

    PubMed

    Ramalho, Ricardo S; Winckler, Gisela; Madeira, José; Helffrich, George R; Hipólito, Ana; Quartau, Rui; Adena, Katherine; Schaefer, Joerg M

    2015-10-01

    Large-scale gravitational flank collapses of steep volcanic islands are hypothetically capable of triggering megatsunamis with highly catastrophic effects. Yet, evidence for the generation and impact of collapse-triggered megatsunamis and their high run-ups remains scarce or is highly controversial. Therefore, doubts remain on whether island flank failures truly generate enough volume flux to trigger giant tsunamis, leading to diverging opinions concerning the real hazard potential of such collapses. We show that one of the most prominent oceanic volcanoes on Earth-Fogo, in the Cape Verde Islands-catastrophically collapsed and triggered a megatsunami with devastating effects ~73,000 years ago. Our deductions are based on the recent discovery and cosmogenic (3)He dating of tsunamigenic deposits found on nearby Santiago Island, which attest to the impact of this giant tsunami and document wave run-up heights exceeding 270 m. The evidence reported here implies that Fogo's flank failure involved at least one fast and voluminous event that led to a giant tsunami, in contrast to what has been suggested before. Our observations therefore further demonstrate that flank collapses may indeed catastrophically happen and are capable of triggering tsunamis of enormous height and energy, adding to their hazard potential.

  8. Flanking Magnitudes: Dissociation between Numerosity and Numerical Value in a Selective Attention Task

    ERIC Educational Resources Information Center

    Naparstek, Sharon; Safadi, Ziad; Lichtenstein-Vidne, Limor; Henik, Avishai

    2015-01-01

    The current research examined whether peripherally presented numerical information can affect the speed of number processing. In 2 experiments, participants were presented with a target matrix flanked by a distractor matrix and were asked to perform a comparative judgment (i.e., decide whether the target was larger or smaller than the reference…

  9. Sudden aseismic fault slip on the south flank of Kilauea volcano.

    PubMed

    Cervelli, Peter; Segall, Paul; Johnson, Kaj; Lisowski, Michael; Miklius, Asta

    2002-02-28

    One of the greatest hazards associated with oceanic volcanoes is not volcanic in nature, but lies with the potential for catastrophic flank failure. Such flank failure can result in devastating tsunamis and threaten not only the immediate vicinity, but coastal cities along the entire rim of an ocean basin. Kilauea volcano on the island of Hawaii, USA, is a potential source of such flank failures and has therefore been monitored by a network of continuously recording geodetic instruments, including global positioning system (GPS) receivers, tilt meters and strain meters. Here we report that, in early November 2000, this network recorded transient southeastward displacements, which we interpret as an episode of aseismic fault slip. The duration of the event was about 36 hours, it had an equi