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Sample records for active human sialyltransferase

  1. A new assay for determining ganglioside sialyltransferase activities lactosylceramide-2,3-sialyltransferase (SAT I and monosialylganglioside-2,3-sialyltransferase (SAT IV.

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    Cynthia Q Sun

    Full Text Available A new assay for the determination of lactosylceramide-2,3-sialyltransferase (SAT I, EC 2.4.99.9 and monosialoganglioside sialyltransferase (SAT IV, EC 2.4.99.2 is described. The assay utilised the commercially available fluorophore labelled sphingolipids, boron dipyrromethene difluoride (BODIPY lactosylceramide (LacCer, and BODIPY-monosialotetrahexosylganglioside (GM1 as the acceptor substrates, for SAT I and SAT IV, respectively. HPLC coupled with fluorescence detection was used to analyse product formation. The analysis was performed in a quick and automated fashion. The assay showed good linearity for both BODIPY sphingolipids with a quantitative detection limit of 0.05 pmol. The high sensitivity enabled the detection of SAT I and SAT IV activities as low as 0.001 μU, at least 200 fold lower than that of most radiometric assays. This new assay was applied to the screening of SAT I and SAT IV activities in ovine and bovine organs (liver, heart, kidney, and spleen. The results provided evidence that young animals, such as calves, start to produce ganglioside sialyltransferases as early as 7 days after parturition and that levels change during maturation. Among the organs tested from a bovine source, spleen had the highest specific ganglioside sialyltransferase activity. Due to the organ size, the greatest total ganglioside sialyltransferase activities (SAT I and SAT IV were detected in the liver of both bovine and ovine origin.

  2. The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach.

    Science.gov (United States)

    Harduin-Lepers, Anne; Mollicone, Rosella; Delannoy, Philippe; Oriol, Rafael

    2005-08-01

    The animal sialyltransferases are Golgi type II transmembrane glycosyltransferases. Twenty distinct sialyltransferases have been identified in both human and murine genomes. These enzymes catalyze transfer of sialic acid from CMP-Neu5Ac to the glycan moiety of glycoconjugates. Despite low overall identities, they share four conserved peptide motifs [L (large), S (small), motif III, and motif VS (very small)] that are hallmarks for sialyltransferase identification. We have identified 155 new putative genes in 25 animal species, and we have exploited two lines of evidence: (1) sequence comparisons and (2) exon-intron organization of the genes. An ortholog to the ancestor present before the split of ST6Gal I and II subfamilies was detected in arthropods. An ortholog to the ancestor present before the split of ST6GalNAc III, IV, V, and VI subfamilies was detected in sea urchin. An ortholog to the ancestor present before the split of ST3Gal I and II subfamilies was detected in ciona, and an ortholog to the ancestor of all the ST8Sia was detected in amphioxus. Therefore, single examples of the four families (ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia) have appeared in invertebrates, earlier than previously thought, whereas the four families were all detected in bony fishes, amphibians, birds, and mammals. As previously hypothesized, sequence similarities among sialyltransferases suggest a common genetic origin, by successive duplications of an ancestral gene, followed by divergent evolution. Finally, we propose predictions on these invertebrates sialyltransferase-related activities that have not previously been demonstrated and that will ultimately need to be substantiated by protein expression and enzymatic activity assays.

  3. Expression of Functional Human Sialyltransferases ST3Gal1 and ST6Gal1 in Escherichia coli.

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    Maria Elena Ortiz-Soto

    Full Text Available Sialyltransferases (STs are disulfide-containing, type II transmembrane glycoproteins that catalyze the transfer of sialic acid to proteins and lipids and participate in the synthesis of the core structure oligosaccharides of human milk. Sialic acids are found at the outermost position of glycostructures, playing a key role in health and disease. Sialylation is also essential for the production of recombinant therapeutic proteins (RTPs. Despite their importance, availability of sialyltransferases is limited due to the low levels of stable, soluble and active protein produced in bacterial expression systems, which hampers biochemical and structural studies on these enzymes and restricts biotechnological applications. We report the successful expression of active human sialyltransferases ST3Gal1 and ST6Gal1 in commercial Escherichia coli strains designed for production of disulfide-containing proteins. Fusion of hST3Gal1 with different solubility enhancers and substitution of exposed hydrophobic amino acids by negatively charged residues (supercharging-like approach were performed to promote solubility and folding. Co-expression of sialyltransferases with the chaperon/foldases sulfhydryl oxidase, protein disulfide isomerase and disulfide isomerase C was explored to improve the formation of native disulfide bonds. Active sialyltransferases fused with maltose binding protein (MBP were obtained in sufficient amounts for biochemical and structural studies when expressed under oxidative conditions and co-expression of folding factors increased the yields of active and properly folded sialyltransferases by 20%. Mutation of exposed hydrophobic amino acids increased recovery of active enzyme by 2.5-fold, yielding about 7 mg of purified protein per liter culture. Functionality of recombinant enzymes was evaluated in the synthesis of sialosides from the β-d-galactoside substrates lactose, N-acetyllactosamine and benzyl 2-acetamido-2-deoxy-3-O-(β-d-galactopyranosyl-α-d-galactopyranoside.

  4. Sialyltransferase activity probably counteracts that of sialidase as ...

    African Journals Online (AJOL)

    Sialyltransferase activity probably counteracts that of sialidase as one of the possible mechanisms of natural recovery or stabilization of erythrocyte mass in trypanosome-infected animals - A perspective.

  5. Sialylation potentials of the silkworm, Bombyx mori; B. mori possesses an active α2,6-sialyltransferase.

    Science.gov (United States)

    Kajiura, Hiroyuki; Hamaguchi, Yuichi; Mizushima, Hiroki; Misaki, Ryo; Fujiyama, Kazuhito

    2015-12-01

    N-Glycosylation is an important post-translational modification in most secreted and membrane-bound proteins in eukaryotic cells. However, the insect N-glycosylation pathway and the potentials contributing to the N-glycan synthesis are still unclear because most of the studies on these subjects have focused on mammals and plants. Here, we identified Bombyx mori sialyltransferase (BmST), which is a Golgi-localized glycosyltransferase and which can modify N-glycans. BmST was ubiquitously expressed in different organs and in various stages of development and localized at the Golgi. Biochemical analysis using Sf9-expressed BmST revealed that BmST encoded α2,6-sialyltransferase and transferred N-acetylneuraminic acid (NeuAc) to the nonreducing terminus of Galβ1-R, but exhibited the highest activity toward GalNAcβ1,4-GlcNAc-R. Unlike human α2,6-sialyltransferase, BmST required the post-translational modification, especially N-glycosylation, for its full activity. N-Glycoprotein analysis of B. mori fifth instar larvae revealed that high-mannose-type structure was predominant and GlcNAc-linked and fucosylated structures were observed but endogenous galactosyl-, N-acetylgalactosaminyl- and sialyl-N-glycoproteins were undetectable under the standard analytical approach. These results indicate that B. mori genome encodes an α2,6-sialyltransferase, but further investigations of the sialylation potentials are necessary. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Alpha 1,3-Galactosyltransferase Deficiency in Pigs Increases Sialyltransferase Activities That Potentially Raise Non-Gal Xenoantigenicity

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    Jong-Yi Park

    2011-01-01

    Full Text Available We examined whether deficiency of the GGTA1 gene in pigs altered the expression of several glycosyltransferase genes. Real-time RT-PCR and glycosyltransferase activity showed that 2 sialyltransferases [α2,3-sialyltransferase (α2,3ST and α2,6-sialyltransferase (α2,6ST] in the heterozygote GalT KO liver have higher expression levels and activities compared to controls. Enzyme-linked lectin assays indicated that there were also more sialic acid-containing glycoconjugate epitopes in GalT KO livers than in controls. The elevated level of sialic-acid-containing glycoconjugate epitopes was due to the low level of α-Gal in heterozygote GalT KO livers. Furthermore, proteomics analysis showed that heterozygote GalT KO pigs had a higher expression of NAD+-isocitrate dehydrogenase (IDH, which is related to the CMP-N-acetylneuraminic acid hydroxylase (CMAH enzyme reaction. These findings suggest the deficiency of GGTA1 gene in pigs results in increased production of N-glycolylneuraminic acid (Neu5Gc due to an increase of α2,6-sialyltransferase and a CMAH cofactor, NAD+-IDH. This indicates that Neu5Gc may be a critical xenoantigen. The deletion of the CMAH gene in the GalT KO background is expected to further prolong xenograft survival.

  7. Modulating the regioselectivity of a Pasteurella multocida sialyltransferase for biocatalytic production of 3'- and 6'-sialyllactose

    DEFF Research Database (Denmark)

    Guo, Yao; Jers, Carsten; Meyer, Anne S.

    2015-01-01

    Several bacterial sialyltransferases have been reported to be multifunctional also catalysing sialidase and trans-sialidase reactions. In this study, we examined the trans-sialylation efficacy and regioselectivity of mutants of the multifunctional Pasteurella multocida sialyltransferase (Pm...... activity was abolished. Histidine in this position is conserved in α-2,6-sialyltransferases and has been suggested, and recently confirmed, to be the determinant for strict regiospecificity in the sialyltransferase reaction. Our data verified this theorem. In trans-sialidase reactions, the P34H mutant...... displayed a distinct preference for 6'-sialyllactose synthesis but low levels of 3'-sialyllactose were also produced. The sialyllactose yield was however lower than when using PmSTWT under optimal conditions for 6'-sialyllactose formation. The discrepancy in regiospecificity between the two reactions could...

  8. Capsular Sialyltransferase Specificity Mediates Different Phenotypes in Streptococcus suis and Group B Streptococcus

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    David Roy

    2018-04-01

    Full Text Available The capsular polysaccharide (CPS represents a key virulence factor for most encapsulated streptococci. Streptococcus suis and Group B Streptococcus (GBS are both well-encapsulated pathogens of clinical importance in veterinary and/or human medicine and responsible for invasive systemic diseases. S. suis and GBS are the only Gram-positive bacteria which express a sialylated CPS at their surface. An important difference between these two sialylated CPSs is the linkage between the side-chain terminal galactose and sialic acid, being α-2,6 for S. suis but α-2,3 for GBS. It is still unclear how sialic acid may affect CPS production and, consequently, the pathogenesis of the disease caused by these two bacterial pathogens. Here, we investigated the role of sialic acid and the putative effect of sialic acid linkage modification in CPS synthesis using inter-species allelic exchange mutagenesis. To this aim, a new molecular biogenetic approach to express CPS with modified sialic acid linkage was developed. We showed that sialic acid (and its α-2,6 linkage is crucial for S. suis CPS synthesis, whereas for GBS, CPS synthesis may occur in presence of an α-2,6 sialyltransferase or in absence of sialic acid moiety. To evaluate the effect of the CPS composition/structure on sialyltransferase activity, two distinct capsular serotypes within each bacterial species were compared (S. suis serotypes 2 and 14 and GBS serotypes III and V. It was demonstrated that the observed differences in sialyltransferase activity and specificity between S. suis and GBS were serotype unrestricted. This is the first time that a study investigates the interspecies exchange of capsular sialyltransferase genes in Gram-positive bacteria. The obtained mutants represent novel tools that could be used to further investigate the immunomodulatory properties of sialylated CPSs. Finally, in spite of common CPS structural characteristics and similarities in the cps loci, sialic acid exerts

  9. Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism.

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    Hamada, Yojiro; Kanematsu, Yusuke; Tachikawa, Masanori

    2016-10-11

    The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an S N 1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.

  10. Purification, crystallization and preliminary crystallographic characterization of the α2,6-sialyltransferase from Photobacterium sp. JT-ISH-224

    International Nuclear Information System (INIS)

    Okino, Nozomu; Kakuta, Yoshimitsu; Kajiwara, Hitomi; Ichikawa, Masako; Takakura, Yoshimitsu; Ito, Makoto; Yamamoto, Takeshi

    2007-01-01

    Crystallization of the α2,6-sialyltransferase from Photobacterium. Sialyltransferases transfer sialic acid from cytidine-5-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to the nonreducing termini of the oligosaccharyl structures of various glycoproteins and glycolipids. The newly cloned α2,6-sialyltransferase from Photobacterium sp. JT-ISH-224 (from the Vibrionaceae family) is composed of two domains: an unknown N-terminal domain and a catalytic C-terminal domain which shares significant homology with the Pasteurella multocida multifunctional sialyltransferase. The putative mature form of JT-ISH-224 α2,6-sialyltransferase was overproduced in Escherichia coli, purified and crystallized using the hanging-drop vapour-diffusion method at 293 K. The crystal belonged to space group P3 1 21 or P3 2 21, with unit-cell parameters a = b = 90.29, c = 204.33 Å. X-ray diffraction data were collected to 2.5 Å resolution

  11. Development of sandwich enzyme-linked immunosorbent assay systems for plasma β-galactoside α2,6-sialyltransferase, a possible hepatic disease biomarker

    International Nuclear Information System (INIS)

    Futakawa, Satoshi; Kitazume, Shinobu; Oka, Ritsuko; Ogawa, Kazuko; Hagiwara, Yoshiaki; Kinoshita, Akinori; Miyashita, Kazuya; Hashimoto, Yasuhiro

    2009-01-01

    Previous reports, including our work, have shown that plasma β-galactoside α2,6-sialyltransferase (ST6Gal I) activity is significantly increased in particular hepatopathological situations, suggesting that it may represent a sensitive biomarker for diagnosing hepatic diseases. So far, activity of ST6Gal I have been measured by using radioactive tracer method in place of measuring amount of ST6Gal I. However, this method is tangled and cannot exclude other sialyltransferase activities. Thus, simple and specific methods for measuring plasma ST6Gal I had been unavailable. Here, we developed two kinds of sandwich enzyme-linked immunosorbent assay (ELISA) systems that specifically detect the soluble cleaved form of ST6Gal I in plasma. In one sandwich ELISA, we detected rat specific sequence, EFQMPK, which is N-terminus of soluble ST6Gal I. In the other sandwich ELISA, we detected internal common sequence among rat, mouse and human ST6Gal I in plasma (M2 ELISA). Using the M2 ELISA, we observed that elevation of plasma ST6Gal I was much faster than elevation of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a carbon tetrachloride (CCl 4 )-induced mouse liver injury model. Our data suggest that these ELISA systems are very useful tools for measuring plasma ST6Gal I, which represents a potential biomarker for diagnosing hepatic diseases

  12. Development of sandwich enzyme-linked immunosorbent assay systems for plasma {beta}-galactoside {alpha}2,6-sialyltransferase, a possible hepatic disease biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Futakawa, Satoshi [Department of Biochemistry, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295 (Japan); Kitazume, Shinobu [Disease Glycomics Laboratory, Institute of Physical and Chemical Research, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 560-0082 (Japan); Oka, Ritsuko [CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 560-0082 (Japan); Glyco-chain Functions Laboratory, Institute of Physical and Chemical Research, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); Ogawa, Kazuko [Disease Glycomics Laboratory, Institute of Physical and Chemical Research, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 560-0082 (Japan); Hagiwara, Yoshiaki; Kinoshita, Akinori; Miyashita, Kazuya [Department of Biological Sciences, Immuno-Biological Laboratories Co. Ltd., 1091-1 Naka, Fujioka-shi, Gunma 375-0005 (Japan); Hashimoto, Yasuhiro [Department of Biochemistry, School of Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi-shi, Saitama 560-0082 (Japan)], E-mail: yasuc@fmu.ac.jp

    2009-01-05

    Previous reports, including our work, have shown that plasma {beta}-galactoside {alpha}2,6-sialyltransferase (ST6Gal I) activity is significantly increased in particular hepatopathological situations, suggesting that it may represent a sensitive biomarker for diagnosing hepatic diseases. So far, activity of ST6Gal I have been measured by using radioactive tracer method in place of measuring amount of ST6Gal I. However, this method is tangled and cannot exclude other sialyltransferase activities. Thus, simple and specific methods for measuring plasma ST6Gal I had been unavailable. Here, we developed two kinds of sandwich enzyme-linked immunosorbent assay (ELISA) systems that specifically detect the soluble cleaved form of ST6Gal I in plasma. In one sandwich ELISA, we detected rat specific sequence, EFQMPK, which is N-terminus of soluble ST6Gal I. In the other sandwich ELISA, we detected internal common sequence among rat, mouse and human ST6Gal I in plasma (M2 ELISA). Using the M2 ELISA, we observed that elevation of plasma ST6Gal I was much faster than elevation of plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in a carbon tetrachloride (CCl{sub 4})-induced mouse liver injury model. Our data suggest that these ELISA systems are very useful tools for measuring plasma ST6Gal I, which represents a potential biomarker for diagnosing hepatic diseases.

  13. Stable expression of human thyrotropin (hTSH) in mammalian cells (CHO) expressing α2,6 sialyltransferase

    International Nuclear Information System (INIS)

    Damiani, Renata

    2009-01-01

    A CHO cell line, previously genetically modified by the introduction of rat α2,6-sialyltransferase cDNA, generated for the first time a human-like sialylated recombinant hTSH (hlsr-hTSH) more similar to the native hormone, with 61% of α2,3- and 39% of α2,6-linked sialic acid residues. The best clone, when submitted to gene amplification with up to 8 μM methotrexate, presented a secretion level of ∼2 μg hTSH/10 6 cells/day, useful for product purification and characterization. The relative molecular masses (M r ) of the heterodimer and of the α- and β-subunits of purified hlsr-hTSH, determined by MALDI-TOF mass spectrometry, and the relative hydrophobicities, determined by RP-HPLC, were not remarkably different from those presented by two r-hTSH preparations secreted by normal CHO cells. Some differences were observed, though, in N-glycan composition, with more tri- and much more tetra-sialylated structures in hlsr-hTSH. When analyzed via an in vivo bioassay based on hTSH-induced T 4 release in mice, hlsr-hTSH was shown to be equipotent (p > 0.05) with the commercial preparation of r-hTSH (Thyrogen), and 1.5-fold more potent than native hTSH (p < 0.001). (author)

  14. Fold-recognition and comparative modeling of human α2,3-sialyltransferases reveal their sequence and structural similarities to CstII from Campylobacter jejuni

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    Balaji Petety V

    2006-04-01

    Full Text Available Abstract Background The 3-D structure of none of the eukaryotic sialyltransferases (SiaTs has been determined so far. Sequence alignment algorithms such as BLAST and PSI-BLAST could not detect a homolog of these enzymes from the protein databank. SiaTs, thus, belong to the hard/medium target category in the CASP experiments. The objective of the current work is to model the 3-D structures of human SiaTs which transfer the sialic acid in α2,3-linkage viz., ST3Gal I, II, III, IV, V, and VI, using fold-recognition and comparative modeling methods. The pair-wise sequence similarity among these six enzymes ranges from 41 to 63%. Results Unlike the sequence similarity servers, fold-recognition servers identified CstII, a α2,3/8 dual-activity SiaT from Campylobacter jejuni as the homolog of all the six ST3Gals; the level of sequence similarity between CstII and ST3Gals is only 15–20% and the similarity is restricted to well-characterized motif regions of ST3Gals. Deriving template-target sequence alignments for the entire ST3Gal sequence was not straightforward: the fold-recognition servers could not find a template for the region preceding the L-motif and that between the L- and S-motifs. Multiple structural templates were identified to model these regions and template identification-modeling-evaluation had to be performed iteratively to choose the most appropriate templates. The modeled structures have acceptable stereochemical properties and are also able to provide qualitative rationalizations for some of the site-directed mutagenesis results reported in literature. Apart from the predicted models, an unexpected but valuable finding from this study is the sequential and structural relatedness of family GT42 and family GT29 SiaTs. Conclusion The modeled 3-D structures can be used for docking and other modeling studies and for the rational identification of residues to be mutated to impart desired properties such as altered stability, substrate

  15. Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia) gene family: tandem duplications in early deuterostomes explain most of the diversity found in the vertebrate ST8Sia genes.

    Science.gov (United States)

    Harduin-Lepers, Anne; Petit, Daniel; Mollicone, Rosella; Delannoy, Philippe; Petit, Jean-Michel; Oriol, Rafael

    2008-09-23

    The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS) that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of alpha2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-alpha2,8-sialylation. We identified in the genome of invertebrate deuterostomes, orthologs to the common ancestor for each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia EX, not found in vertebrates. All these ST8Sia sequences share a new conserved family-motif, named "C-term" that is involved in protein folding, via an intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma floridae orthologous to the common ancestor of polysialyltransferases possess a polysialyltransferase domain (PSTD) and those orthologous to the common ancestor of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we describe the expression profile of ST8Sia genes in Danio rerio. Polysialylation appeared early in the deuterostome lineage. The recent release of several deuterostome genome databases and paralogons combined with synteny analysis allowed us to obtain insight into events at the gene level that led to the diversification of the ST8Sia genes, with their corresponding enzymatic activities, in both invertebrates and vertebrates. The

  16. Evolutionary history of the alpha2,8-sialyltransferase (ST8Sia gene family: Tandem duplications in early deuterostomes explain most of the diversity found in the vertebrate ST8Sia genes

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    Petit Jean-Michel

    2008-09-01

    Full Text Available Abstract Background The animal sialyltransferases, which catalyze the transfer of sialic acid to the glycan moiety of glycoconjugates, are subdivided into four families: ST3Gal, ST6Gal, ST6GalNAc and ST8Sia, based on acceptor sugar specificity and glycosidic linkage formed. Despite low overall sequence identity between each sialyltransferase family, all sialyltransferases share four conserved peptide motifs (L, S, III and VS that serve as hallmarks for the identification of the sialyltransferases. Currently, twenty subfamilies have been described in mammals and birds. Examples of the four sialyltransferase families have also been found in invertebrates. Focusing on the ST8Sia family, we investigated the origin of the three groups of α2,8-sialyltransferases demonstrated in vertebrates to carry out poly-, oligo- and mono-α2,8-sialylation. Results We identified in the genome of invertebrate deuterostomes, orthologs to the common ancestor for each of the three vertebrate ST8Sia groups and a set of novel genes named ST8Sia EX, not found in vertebrates. All these ST8Sia sequences share a new conserved family-motif, named "C-term" that is involved in protein folding, via an intramolecular disulfide bridge. Interestingly, sequences from Branchiostoma floridae orthologous to the common ancestor of polysialyltransferases possess a polysialyltransferase domain (PSTD and those orthologous to the common ancestor of oligosialyltransferases possess a new ST8Sia III-specific motif similar to the PSTD. In osteichthyans, we have identified two new subfamilies. In addition, we describe the expression profile of ST8Sia genes in Danio rerio. Conclusion Polysialylation appeared early in the deuterostome lineage. The recent release of several deuterostome genome databases and paralogons combined with synteny analysis allowed us to obtain insight into events at the gene level that led to the diversification of the ST8Sia genes, with their corresponding enzymatic

  17. Sialylation of lipooligosaccharides is dispensable for the virulence of Haemophilus ducreyi in humans.

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    Spinola, Stanley M; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Zwickl, Beth; Katz, Barry P; Munson, Robert S

    2012-02-01

    Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.

  18. Enhanced Bacterial α(2,6-Sialyltransferase Reaction through an Inhibition of Its Inherent Sialidase Activity by Dephosphorylation of Cytidine-5'-Monophosphate.

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    Ji-Yeon Kang

    Full Text Available Bacterial α(2,6-sialyltransferases (STs from Photobacterium damsela, Photobacterium sp. JT-ISH-224, and P. leiognathi JT-SHIZ-145 were recombinantly expressed in Escherichia coli and their ST activities were compared directly using a galactosylated bi-antennary N-glycan as an acceptor substrate. In all ST reactions, there was an increase of sialylated glycans at shorter reaction times and later a decrease in prolonged reactions, which is related with the inherent sialidase activities of bacterial STs. These sialidase activities are greatly increased by free cytidine monophosphate (CMP generated from a donor substrate CMP-N-acetylneuraminic acid (CMP-Neu5Ac during the ST reactions. The decrease of sialylated glycans in prolonged ST reaction was prevented through an inhibition of sialidase activity by simple treatment of alkaline phosphatase (AP, which dephosphorylates CMP to cytidine. Through supplemental additions of AP and CMP-Neu5Ac to the reaction using the recombinant α(2,6-ST from P. leiognathi JT-SHIZ-145 (P145-ST, the content of bi-sialylated N-glycan increased up to ~98% without any decrease in prolonged reactions. This optimized P145-ST reaction was applied successfully for α(2,6-sialylation of asialofetuin, and this resulted in a large increase in the populations of multi-sialylated N-glycans compared with the reaction without addition of AP and CMP-Neu5Ac. These results suggest that the optimized reaction using the recombinant P145-ST readily expressed from E. coli has a promise for economic glycan synthesis and glyco-conjugate remodeling.

  19. Immobilized sialyltransferase fused to a fungal biotin-binding protein: Production, properties, and applications.

    Science.gov (United States)

    Kajiwara, Hitomi; Tsunashima, Masako; Mine, Toshiki; Takakura, Yoshimitsu; Yamamoto, Takeshi

    2016-04-01

    A β-galactoside α2,6-sialyltransferase (ST) from the marine bacterium Photobacterium sp. JT-ISH-224 with a broad acceptor substrate specificity was fused to a fungal biotin-binding protein tamavidin 2 (TM2) to produce immobilized enzyme. Specifically, a gene for the fusion protein, in which ST from Photobacterium sp. JT-ISH-224 and TM2 were connected via a peptide linker (ST-L-TM2) was constructed and expressed in Escherichia coli. The ST-L-TM2 was produced in the soluble form with a yield of approximately 15,000 unit/300 ml of the E. coli culture. The ST-L-TM2 was partially purified and part of it was immobilized onto biotin-bearing magnetic microbeads. The immobilized ST-L-TM2 onto microbeads could be used at least seven consecutive reaction cycles with no observed decrease in enzymatic activity. In addition, the optimum pH and temperature of the immobilized enzyme were changed compared to those of a free form of the ST. Considering these results, it was strongly expected that the immobilized ST-L-TM2 was a promising tool for the production of various kind of sialoligosaccharides. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  20. Targeting Selectins and Their Ligands in Cancer

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    Alessandro eNatoni

    2016-04-01

    Full Text Available Aberrant glycosylation is a hallmark of cancer cells with increased evidence pointing to a role in tumor progression. In particular, aberrant sialylation of glycoproteins and glycolipids have been linked to increased immune cell evasion, drug evasion, drug resistance, tumor invasiveness, and vascular dissemination leading to metastases. Hypersialylation of cancer cells is largely the result of overexpression of sialyltransferases. Humans differentially express twenty different sialyltransferases in a tissue-specific manner, each of which catalyze the attachment of sialic acids via different glycosidic linkages (2-3; 2-6 or 2-8 to the underlying glycan chain. One important mechanism whereby overexpression of sialyltransferases contributes to an enhanced metastatic phenotype is via the generation of selectin ligands. Selectin ligand function requires the expression of sialyl-Lewis X and its structural-isomer sialyl-Lewis A, which are synthesized by the combined action of alpha 1-3-fucosyltransferases, 2-3-sialyltransferases, 1-4-galactosyltranferases, and N-acetyl--glucosaminyltransferases. The α2-3-sialyltransferases ST3Gal4 and ST3Gal6 are critical to the generation of functional E- and P-selectin ligands and overexpression of these sialyltransferases have been linked to increased risk of metastatic disease in solid tumors and poor outcome in multiple myeloma. Thus, targeting selectins and their ligands as well as the enzymes involved in their generation, in particular sialyltransferases, could be beneficial to many cancer patients. Potential strategies include sialyltransferase inhibition and the use of selectin antagonists, such as glycomimetic drugs and antibodies. Here, we review ongoing efforts to optimize the potency and selectivity of sialyltransferase inhibitors, including the potential for targeted delivery approaches, as well as evaluate the potential utility of selectin inhibitors, which are now in early clinical

  1. Combinatorial chemoenzymatic synthesis and high-throughput screening of sialosides.

    Science.gov (United States)

    Chokhawala, Harshal A; Huang, Shengshu; Lau, Kam; Yu, Hai; Cheng, Jiansong; Thon, Vireak; Hurtado-Ziola, Nancy; Guerrero, Juan A; Varki, Ajit; Chen, Xi

    2008-09-19

    Although the vital roles of structures containing sialic acid in biomolecular recognition are well documented, limited information is available on how sialic acid structural modifications, sialyl linkages, and the underlying glycan structures affect the binding or the activity of sialic acid-recognizing proteins and related downstream biological processes. A novel combinatorial chemoenzymatic method has been developed for the highly efficient synthesis of biotinylated sialosides containing different sialic acid structures and different underlying glycans in 96-well plates from biotinylated sialyltransferase acceptors and sialic acid precursors. By transferring the reaction mixtures to NeutrAvidin-coated plates and assaying for the yields of enzymatic reactions using lectins recognizing sialyltransferase acceptors but not the sialylated products, the biotinylated sialoside products can be directly used, without purification, for high-throughput screening to quickly identify the ligand specificity of sialic acid-binding proteins. For a proof-of-principle experiment, 72 biotinylated alpha2,6-linked sialosides were synthesized in 96-well plates from 4 biotinylated sialyltransferase acceptors and 18 sialic acid precursors using a one-pot three-enzyme system. High-throughput screening assays performed in NeutrAvidin-coated microtiter plates show that whereas Sambucus nigra Lectin binds to alpha2,6-linked sialosides with high promiscuity, human Siglec-2 (CD22) is highly selective for a number of sialic acid structures and the underlying glycans in its sialoside ligands.

  2. Structure-function analysis of the human sialyltransferase ST3Gal I - Role of N-glycosylation and a novel conserved sialylmotif

    DEFF Research Database (Denmark)

    Jeanneau, C.; Chazalet, V.; Auge, C.

    2004-01-01

    of these residues and of the conserved residues of motif VS (HX4E) was assessed using as a template the human ST3Gal I. Mutational analysis showed that residues His(299) and Tyr(300) of the new motif, and His(316) of the VS motif, are essential for activity since their substitution by alanine yielded inactive...... showed that none of the mutants tested had any significant effect in nucleotide donor binding. Instead the mutant proteins were affected in their binding to the acceptor and/or demonstrated lower catalytic efficiency. Although the human ST3Gal I has four N-glycan attachment sites in its catalytic domain...... that are potentially glycosylated, none of them was shown to be necessary for enzyme activity. However, N-glycosylation appears to contribute to the proper folding and trafficking of the enzyme....

  3. Alpha2,3-sialyltransferase III knockdown sensitized ovarian cancer cells to cisplatin-induced apoptosis.

    Science.gov (United States)

    Wang, Xiaoyu; Zhang, Yiting; Lin, Haiyingjie; Liu, Yan; Tan, Yi; Lin, Jie; Gao, Fenze; Lin, Shaoqiang

    2017-01-22

    Emerging evidence indicates that β-galactoside-α2,3-sialyltransferase III (ST3Gal3) involves in development, inflammation, neoplastic transformation, and metastasis. However, the role of ST3Gal3 in regulating cancer chemoresistance remains elusive. Herein, we investigated the functional effects of ST3Gal3 in cisplatin-resistant ovarian cancer cells. We found that the levels of ST3Gal3 mRNA differed significantly among ovarian cancer cell lines. HO8910PM cells that have high invasive and metastatic capacity express elevated ST3Gal3 mRNA and are resistant to cisplatin, comparing to SKOV3 cells that have a lower level of ST3Gal3 expression and are more chemosensitive to cisplatin. We found that the expression of ST3Gal3 has reverse correlation with the dosage of cisplatin used in both SKOV3 and HO8910PM cells, and high dose of cisplatin could down-regulate ST3Gal3 expression. We then examined the functional effects of ST3Gal3 knockdown in cancer cell lines using FACS analysis. The number of apoptotic cells was much higher in cells if ST3Gal3 expression was knocked down by siRNA and/or by treating cells with higher dosage of cisplatin in comparison to control cells. Interestingly, in HO8910PM cells with ST3Gal3 knockdown, the levels of caspase 8 and caspase 3 proteins increased, which was more obvious in cells treated with both ST3Gal3 knockdown and cisplatin, suggesting that ST3Gal3 knockdown synergistically enhanced cisplatin-induced apoptosis in ovarian cancer cells. Taken together, these results uncover an alternative mechanism of cisplatin-resistance through ST3Gal3 and open a window for effective prevention of chemoresistance and relapse of ovarian cancer by targeting ST3Gal3. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression.

    Directory of Open Access Journals (Sweden)

    Bérengère Boutard

    Full Text Available Myxoma virus (MYXV induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an α2,3-sialyltransferase through its M138L gene. In this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the M138L deficient strains are highly attenuated in vivo. Indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one rabbit inoculated with the M138L deficient strains survived the infection. In primary lesions, this resistance to the infection was associated with an increased ability of innate immune cells, mostly neutrophils, to migrate to the site of virus replication at 4 days post-infection. This was followed by the development of a better specific immune response against MYXV. Indeed, at day 9 post-infection, we observed an important proliferation of lymphocytes and an intense congestion of blood vessels in lymph nodes after M138L knockouts infection. Accordingly, in these rabbits, we observed an intense mononuclear cell infiltration throughout the dermis in primary lesions and higher titers of neutralizing antibodies. Finally, this adaptive immune response provided protection to these surviving rabbits against a challenge with the MYXV WT strain. Altogether, these results show that expression of the M138L gene contributes directly or indirectly to immune evasion by MYXV. In the future, these results could help us to better understand the pathogenesis of myxomatosis but also the importance of glycans in regulation of immune responses.

  5. The α2,3-sialyltransferase encoded by myxoma virus is a virulence factor that contributes to immunosuppression.

    Science.gov (United States)

    Boutard, Bérengère; Vankerckhove, Sophie; Markine-Goriaynoff, Nicolas; Sarlet, Mickaël; Desmecht, Daniel; McFadden, Grant; Vanderplasschen, Alain; Gillet, Laurent

    2015-01-01

    Myxoma virus (MYXV) induces a lethal disease called Myxomatosis in European rabbits. MYXV is one of the rare viruses that encodes an α2,3-sialyltransferase through its M138L gene. In this study, we showed that although the absence of the enzyme was not associated with any in vitro deficit, the M138L deficient strains are highly attenuated in vivo. Indeed, while all rabbits infected with the parental and the revertant strains died within 9 days post-infection from severe myxomatosis, all but one rabbit inoculated with the M138L deficient strains survived the infection. In primary lesions, this resistance to the infection was associated with an increased ability of innate immune cells, mostly neutrophils, to migrate to the site of virus replication at 4 days post-infection. This was followed by the development of a better specific immune response against MYXV. Indeed, at day 9 post-infection, we observed an important proliferation of lymphocytes and an intense congestion of blood vessels in lymph nodes after M138L knockouts infection. Accordingly, in these rabbits, we observed an intense mononuclear cell infiltration throughout the dermis in primary lesions and higher titers of neutralizing antibodies. Finally, this adaptive immune response provided protection to these surviving rabbits against a challenge with the MYXV WT strain. Altogether, these results show that expression of the M138L gene contributes directly or indirectly to immune evasion by MYXV. In the future, these results could help us to better understand the pathogenesis of myxomatosis but also the importance of glycans in regulation of immune responses.

  6. Identification of sialyltransferase 8B as a generalized susceptibility gene for psychotic and mood disorders on chromosome 15q25-26.

    Directory of Open Access Journals (Sweden)

    Erica Z McAuley

    Full Text Available We previously identified a significant bipolar spectrum disorder linkage peak on 15q25-26 using 35 extended families with a broad clinical phenotype, including bipolar disorder (types I and II, recurrent unipolar depression and schizoaffective disorder. However, the specific gene(s contributing to this signal had not been identified. By a fine mapping association study in an Australian case-control cohort (n = 385, we find that the sialyltransferase 8B (ST8SIA2 gene, coding for an enzyme that glycosylates proteins involved in neuronal plasticity which has previously shown association to both schizophrenia and autism, is associated with increased risk to bipolar spectrum disorder. Nominal single point association was observed with SNPs in ST8SIA2 (rs4586379, P = 0.0043; rs2168351, P = 0.0045, and a specific risk haplotype was identified (frequency: bipolar vs controls = 0.41 vs 0.31; χ(2 = 6.46, P = 0.011, OR = 1.47. Over-representation of the specific risk haplotype was also observed in an Australian schizophrenia case-control cohort (n = 256 (χ(2 = 8.41, P = 0.004, OR = 1.82. Using GWAS data from the NIMH bipolar disorder (n = 2055 and NIMH schizophrenia (n = 2550 cohorts, the equivalent haplotype was significantly over-represented in bipolar disorder (χ(2 = 5.91, P = 0.015, OR = 1.29, with the same direction of effect in schizophrenia, albeit non-significant (χ(2 = 2.3, P = 0.129, OR = 1.09. We demonstrate marked down-regulation of ST8SIA2 gene expression across human brain development and show a significant haplotype×diagnosis effect on ST8SIA2 mRNA levels in adult cortex (ANOVA: F(1,87 = 6.031, P = 0.016. These findings suggest that variation the ST8SIA2 gene is associated with increased risk to mental illness, acting to restrict neuronal plasticity and disrupt early neuronal network formation, rendering the developing and adult brain more vulnerable to

  7. Defense Human Resources Activity > PERSEREC

    Science.gov (United States)

    Skip to main content (Press Enter). Toggle navigation Defense Human Resources Activity Search Search Defense Human Resources Activity: Search Search Defense Human Resources Activity: Search Defense Human Resources Activity U.S. Department of Defense Defense Human Resources Activity Overview

  8. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  9. Sialyltransferase activity probably counteracts that of sialidase as ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-12-29

    Dec 29, 2008 ... protection to and adaptation to life, but they have been found to be utilized ... The anti-recognition effect of SAs is exerted by their negative charge .... red cell precursors in the bone marrow (Wikipedia, 2006). The concept that ..... nutrition on milk production and some biochemical parameters in. West African ...

  10. Enzymatic production of human milk oligosaccharides

    DEFF Research Database (Denmark)

    Guo, Yao

    . A recombinant Pasteurella multocida sialyltransferase (EC 2.4.99.-), namely PmST, exhibiting promiscuous trans-sialidase activities was examined. The enzyme catalysed α-2,3- and α-2,6- sialylation of lactose using either 2- O -(p-nitrophenyl)-α- D - N -acetylneuraminic acid or casein glycomacropeptide...... galactooligosaccharides with use of galactooligosaccharides as acceptors. Secondly, we examined the regioselectivity of five designed mutants of PmST catalysing synthesis of 3'- and 6'-sialyllactoses using casein glycomacropeptide and lactose as substrates. The mutants PmST E271F , PmST R313Y and PmST E271F/R313Y...... was almost abolished. The k cat / K m value for PmST P34H catalysing 6'-sialyllactose synthesis using 3'-sialyllactose as donor was 31.2 M -1 s -1 . Moreover, both the wild type enzyme and PmST P34H were capable of catalysing the hydrolysis and transfer of α-2,6 bound sialic acid....

  11. A Review of Human Activity Recognition Methods

    Directory of Open Access Journals (Sweden)

    Michalis eVrigkas

    2015-11-01

    Full Text Available Recognizing human activities from video sequences or still images is a challenging task due to problems such as background clutter, partial occlusion, changes in scale, viewpoint, lighting, and appearance. Many applications, including video surveillance systems, human-computer interaction, and robotics for human behavior characterization, require a multiple activity recognition system. In this work, we provide a detailed review of recent and state-of-the-art research advances in the field of human activity classification. We propose a categorization of human activity methodologies and discuss their advantages and limitations. In particular, we divide human activity classification methods into two large categories according to whether they use data from different modalities or not. Then, each of these categories is further analyzed into sub-categories, which reflect how they model human activities and what type of activities they are interested in. Moreover, we provide a comprehensive analysis of the existing, publicly available human activity classification datasets and examine the requirements for an ideal human activity recognition dataset. Finally, we report the characteristics of future research directions and present some open issues on human activity recognition.

  12. Production of human milk oligosaccharides by enzymatic and whole-cell microbial biotransformations.

    Science.gov (United States)

    Sprenger, Georg A; Baumgärtner, Florian; Albermann, Christoph

    2017-09-20

    Human milk oligosaccharides (HMO) are almost unique constituents of breast milk and are not found in appreciable amounts in cow milk. Due to several positive aspects of HMO for the development, health, and wellbeing of infants, production of HMO would be desirable. As a result, scientists from different disciplines have developed methods for the preparation of single HMO compounds. Here, we review approaches to HMO preparation by (chemo-)enzymatic syntheses or by whole-cell biotransformation with recombinant bacterial cells. With lactose as acceptor (in vitro or in vivo), fucosyltransferases can be used for the production of 2'-fucosyllactose, 3-fucosyllactose, or more complex fucosylated core structures. Sialylated HMO can be produced by sialyltransferases and trans-sialidases. Core structures as lacto-N-tetraose can be obtained by glycosyltransferases from chemical donor compounds or by multi-enzyme cascades; recent publications also show production of lacto-N-tetraose by recombinant Escherichia coli bacteria and approaches to obtain fucosylated core structures. In view of an industrial production of HMOs, the whole cell biotransformation is at this stage the most promising option to provide human milk oligosaccharides as food additive. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Glycomic analysis of gastric carcinoma cells discloses glycans as modulators of RON receptor tyrosine kinase activation in cancer

    DEFF Research Database (Denmark)

    Mereiter, Stefan; Magalhães, Ana; Adamczyk, Barbara

    2016-01-01

    gastric carcinoma cells transfected with the sialyltransferase ST3GAL4 were established as a model overexpressing sialylated terminal glycans. We have evaluated at the structural level the glycome and the sialoproteome of this gastric cancer cell line applying liquid chromatography and mass spectrometry...... known to be key players in malignancy. Further analysis of RON confirmed its modification with SLe(X) and the concomitant activation. SLe(X) and RON co-expression was validated in gastric tumors. CONCLUSION: The overexpression of ST3GAL4 interferes with the overall glycophenotype of cancer cells...... affecting a multitude of key proteins involved in malignancy. Aberrant glycosylation of the RON receptor was shown as an alternative mechanism of oncogenic activation. GENERAL SIGNIFICANCE: This study provides novel targets and points to an integrative tumor glycomic/proteomic-profiling for gastric cancer...

  14. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

    Directory of Open Access Journals (Sweden)

    Youngsoo Sohn

    2013-03-01

    Full Text Available Human α-galactosidase A (GLA has been used in enzymereplacement therapy for patients with Fabry disease. Weexpressed recombinant GLA from Chinese hamster ovary cellswith very high productivity. When compared to an approvedGLA (agalsidase beta, its size and charge were found to besmaller and more neutral. These differences resulted from thelack of terminal sialic acids playing essential roles in the serumhalf-life and proper tissue targeting. Because a simplesialylation reaction was not enough to increase the sialic acidcontent, a combined reaction using galactosyltransferase,sialyltransferase, and their sugar substrates at the same timewas developed and optimized to reduce the incubation time.The product generated by this reaction had nearly the samesize, isoelectric points, and sialic acid content as agalsidasebeta. Furthermore, it had better in vivo efficacy to degrade theaccumulated globotriaosylceramide in target organs of Fabrymice compared to an unmodified version. [BMB Reports 2013;46(3: 157-162

  15. Characterization of P1 promoter activity of the β-galactoside α2,6 ...

    Indian Academy of Sciences (India)

    2012-04-05

    Apr 5, 2012 ... The level of β-galactoside α2,6-sialyltransferase I (ST6Gal I) mRNA, encoded by the gene siat1, is increased in malignant tissues. Expression is regulated by different promoters – P1, P2 and P3 – generating three mRNA isoforms. H, X and YZ. In cervical cancer tissue the mRNA isoform H, which results ...

  16. Human Activity in the Web

    OpenAIRE

    Radicchi, Filippo

    2009-01-01

    The recent information technology revolution has enabled the analysis and processing of large-scale datasets describing human activities. The main source of data is represented by the Web, where humans generally use to spend a relevant part of their day. Here we study three large datasets containing the information about Web human activities in different contexts. We study in details inter-event and waiting time statistics. In both cases, the number of subsequent operations which differ by ta...

  17. Brain Activity and Human Unilateral Chewing

    Science.gov (United States)

    Quintero, A.; Ichesco, E.; Myers, C.; Schutt, R.; Gerstner, G.E.

    2012-01-01

    Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

  18. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    KAUST Repository

    Heilbron, Fabian Caba

    2015-06-02

    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  19. ActivityNet: A Large-Scale Video Benchmark for Human Activity Understanding

    KAUST Repository

    Heilbron, Fabian Caba; Castillo, Victor; Ghanem, Bernard; Niebles, Juan Carlos

    2015-01-01

    In spite of many dataset efforts for human action recognition, current computer vision algorithms are still severely limited in terms of the variability and complexity of the actions that they can recognize. This is in part due to the simplicity of current benchmarks, which mostly focus on simple actions and movements occurring on manually trimmed videos. In this paper we introduce ActivityNet, a new largescale video benchmark for human activity understanding. Our benchmark aims at covering a wide range of complex human activities that are of interest to people in their daily living. In its current version, ActivityNet provides samples from 203 activity classes with an average of 137 untrimmed videos per class and 1.41 activity instances per video, for a total of 849 video hours. We illustrate three scenarios in which ActivityNet can be used to compare algorithms for human activity understanding: untrimmed video classification, trimmed activity classification and activity detection.

  20. HUMAN ACTIVITY MONITORING USING SMARTPHONE

    OpenAIRE

    TOKALA, SAI SUJIT; ROKALA, RANADEEP

    2014-01-01

    The main aim of the project is to develop an algorithm which will classify the activity performed by a human who is carrying a smart phone. The day to day life made humans very busy at work and during daily activities, mostly elderly people who are at home have an important need to monitor their activity by others when they are alone, if they are inactive for a long time without movement, or in some situations like if they have fallen down, became unconscious for sometime or seized with a car...

  1. Anti-complement activities of human breast-milk.

    Science.gov (United States)

    Ogundele, M O

    1999-08-01

    It has long been observed that the human milk possesses significant anti-inflammatory properties, while simultaneously protecting the infant against many intestinal and respiratory pathogens. There is, however, a paucity of information on the degree and extent of this anti-inflammatory activity. In the present study, the inhibitory effects of different fractions of human milk on serum complement activity were analysed. Colostrum and milk samples from healthy voluntary lactating donors at different postpartum ages were obtained and pooled normal human serum was used as source of complement in a modified CH50 assay. Inherent complement activity in human milk was also investigated by measuring the deposition of an activated C3 fragment on a serum-sensitive bacteria, and by haemolytic assays. Most whole- and defatted-milk samples consistently showed a dose-dependent inhibition of the serum complement activity. This inhibition was greater in mature milk compared to transitional milk samples. It was enhanced by inactivation of milk complement, and diminished by centrifugation of milk samples, which partly removed fat and larger protein components including casein micelles. Inherent complement activity in human milk was also demonstrated by haemolysis of sensitised sheep erythrocytes and deposition of C3 fragments on solid-phase bacteria. These activities were highest in the colostrum and gradually decreased as lactation proceeded. Several natural components abundant in the fluid phase of the human breast-milk have been shown to be inhibitors of complement activation in vitro. Their physiological significance probably reside in their ability to prevent inflammatory-induced tissue damage of the delicate immature gastrointestinal tract of the new-born as well as the mammary gland itself, which may arise from ongoing complement activation.

  2. ASSESSMENT OF HUMAN RESOURCES FOR REGIONAL INNOVATION ACTIVITY

    Directory of Open Access Journals (Sweden)

    R. R. Lukyanova

    2010-03-01

    Full Text Available The paper deals with the issues of human resource development regarding an innovation activity. Concepts of labor and human resources have been surveyed. An integral index for assessment of human resources for regional innovation activity has been developed and assessment of the Russian regions has been made on the basis of it. Development tendencies of modern human resources for innovation activity in Russia have been revealed.

  3. Monetary reward activates human prefrontal cortex

    International Nuclear Information System (INIS)

    Thut, G.; Roelcke, U.; Nienhusmeier, M.; Missimer, J.; Maguire, R.P.; Leenders, K.L.; Schultz, W.

    1997-01-01

    We present a rCBF PET activation study, in which we demonstrated that reward processing in humans activates a cortical-subcortical network including dorsolateral prefrontal, orbital frontal, thalamic and midbrain regions. It is suggested that, as found for non-human primates, the basal ganglia-thalamo-cortical system is implicated in reward processing. (author) 1 fig., 3 refs

  4. A Review on Video-Based Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Shian-Ru Ke

    2013-06-01

    Full Text Available This review article surveys extensively the current progresses made toward video-based human activity recognition. Three aspects for human activity recognition are addressed including core technology, human activity recognition systems, and applications from low-level to high-level representation. In the core technology, three critical processing stages are thoroughly discussed mainly: human object segmentation, feature extraction and representation, activity detection and classification algorithms. In the human activity recognition systems, three main types are mentioned, including single person activity recognition, multiple people interaction and crowd behavior, and abnormal activity recognition. Finally the domains of applications are discussed in detail, specifically, on surveillance environments, entertainment environments and healthcare systems. Our survey, which aims to provide a comprehensive state-of-the-art review of the field, also addresses several challenges associated with these systems and applications. Moreover, in this survey, various applications are discussed in great detail, specifically, a survey on the applications in healthcare monitoring systems.

  5. Real-time Human Activity Recognition

    Science.gov (United States)

    Albukhary, N.; Mustafah, Y. M.

    2017-11-01

    The traditional Closed-circuit Television (CCTV) system requires human to monitor the CCTV for 24/7 which is inefficient and costly. Therefore, there’s a need for a system which can recognize human activity effectively in real-time. This paper concentrates on recognizing simple activity such as walking, running, sitting, standing and landing by using image processing techniques. Firstly, object detection is done by using background subtraction to detect moving object. Then, object tracking and object classification are constructed so that different person can be differentiated by using feature detection. Geometrical attributes of tracked object, which are centroid and aspect ratio of identified tracked are manipulated so that simple activity can be detected.

  6. Human body contour data based activity recognition.

    Science.gov (United States)

    Myagmarbayar, Nergui; Yuki, Yoshida; Imamoglu, Nevrez; Gonzalez, Jose; Otake, Mihoko; Yu, Wenwei

    2013-01-01

    This research work is aimed to develop autonomous bio-monitoring mobile robots, which are capable of tracking and measuring patients' motions, recognizing the patients' behavior based on observation data, and providing calling for medical personnel in emergency situations in home environment. The robots to be developed will bring about cost-effective, safe and easier at-home rehabilitation to most motor-function impaired patients (MIPs). In our previous research, a full framework was established towards this research goal. In this research, we aimed at improving the human activity recognition by using contour data of the tracked human subject extracted from the depth images as the signal source, instead of the lower limb joint angle data used in the previous research, which are more likely to be affected by the motion of the robot and human subjects. Several geometric parameters, such as, the ratio of height to weight of the tracked human subject, and distance (pixels) between centroid points of upper and lower parts of human body, were calculated from the contour data, and used as the features for the activity recognition. A Hidden Markov Model (HMM) is employed to classify different human activities from the features. Experimental results showed that the human activity recognition could be achieved with a high correct rate.

  7. Scaling behavior of online human activity

    Science.gov (United States)

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

    2012-11-01

    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  8. Activation of peroxisome proliferator-activated receptor-α enhances fatty acid oxidation in human adipocytes

    International Nuclear Information System (INIS)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki; Kawada, Teruo

    2011-01-01

    Highlights: → PPARα activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. → PPARα activation also increased insulin-dependent glucose uptake in human adipocytes. → PPARα activation did not affect lipid accumulation in human adipocytes. → PPARα activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-α (PPARα) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPARα in adipocytes have been unclarified. We examined the functions of PPARα using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPARα by GW7647, a potent PPARα agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPARγ, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPARα activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPARγ is activated. On the other hand, PPARα activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPARα-dependent manner. Moreover, PPARα activation increased the production of CO 2 and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPARα stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPARα agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected effects of PPARα activation are very valuable for managing diabetic conditions accompanied by obesity, because

  9. Human rights education (HRE) and transnational activism

    NARCIS (Netherlands)

    Mihr, A.; Schmitz, Hans-Peter

    2007-01-01

    Transnational human rights activism occupies today a significant place in the practice and scholarship of current global affairs. This article reviews the past successes and limits of this activism and suggests Human Rights Education (HRE) as a strategic tool currently underutilized by activists and

  10. Analysis of Gait Pattern to Recognize the Human Activities

    Directory of Open Access Journals (Sweden)

    Jay Prakash Gupta

    2014-09-01

    Full Text Available Human activity recognition based on the computer vision is the process of labelling image sequences with action labels. Accurate systems for this problem are applied in areas such as visual surveillance, human computer interaction and video retrieval. The challenges are due to variations in motion, recording settings and gait differences. Here we propose an approach to recognize the human activities through gait. Activity recognition through Gait is the process of identifying an activity by the manner in which they walk. The identification of human activities in a video, such as a person is walking, running, jumping, jogging etc are important activities in video surveillance. We contribute the use of Model based approach for activity recognition with the help of movement of legs only. Experimental results suggest that our method are able to recognize the human activities with a good accuracy rate and robust to shadows present in the videos.

  11. Activation of peroxisome proliferator-activated receptor-{alpha} enhances fatty acid oxidation in human adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Joo-Young; Hashizaki, Hikari; Goto, Tsuyoshi; Sakamoto, Tomoya; Takahashi, Nobuyuki [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan); Kawada, Teruo, E-mail: fat@kais.kyoto-u.ac.jp [Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011 (Japan)

    2011-04-22

    Highlights: {yields} PPAR{alpha} activation increased mRNA expression levels of adipocyte differentiation marker genes and GPDH activity in human adipocytes. {yields} PPAR{alpha} activation also increased insulin-dependent glucose uptake in human adipocytes. {yields} PPAR{alpha} activation did not affect lipid accumulation in human adipocytes. {yields} PPAR{alpha} activation increased fatty acid oxidation through induction of fatty acid oxidation-related genes in human adipocytes. -- Abstract: Peroxisome proliferator-activated receptor-{alpha} (PPAR{alpha}) is a key regulator for maintaining whole-body energy balance. However, the physiological functions of PPAR{alpha} in adipocytes have been unclarified. We examined the functions of PPAR{alpha} using human multipotent adipose tissue-derived stem cells as a human adipocyte model. Activation of PPAR{alpha} by GW7647, a potent PPAR{alpha} agonist, increased the mRNA expression levels of adipocyte differentiation marker genes such as PPAR{gamma}, adipocyte-specific fatty acid-binding protein, and lipoprotein lipase and increased both GPDH activity and insulin-dependent glucose uptake level. The findings indicate that PPAR{alpha} activation stimulates adipocyte differentiation. However, lipid accumulation was not changed, which is usually observed when PPAR{gamma} is activated. On the other hand, PPAR{alpha} activation by GW7647 treatment induced the mRNA expression of fatty acid oxidation-related genes such as CPT-1B and AOX in a PPAR{alpha}-dependent manner. Moreover, PPAR{alpha} activation increased the production of CO{sub 2} and acid soluble metabolites, which are products of fatty acid oxidation, and increased oxygen consumption rate in human adipocytes. The data indicate that activation of PPAR{alpha} stimulates both adipocyte differentiation and fatty acid oxidation in human adipocytes, suggesting that PPAR{alpha} agonists could improve insulin resistance without lipid accumulation in adipocytes. The expected

  12. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    Ponz de Leon, M.; Carubbi, F.; Di Donato, P.; Carulli, N.

    1985-01-01

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14 C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  13. Fire, Climate, and Human Activity: A Combustive Combination

    Science.gov (United States)

    Kehrwald, N. M.; Battistel, D.; Argiriadis, E.; Barbante, C.; Barber, L. B.; Fortner, S. K.; Jasmann, J.; Kirchgeorg, T.; Zennaro, P.

    2017-12-01

    Ice and lake core records demonstrate that fires caused by human activity can dominate regional biomass burning records in the Common Era. These major increases in fires are often associated with extensive land use change such as an expansion in agriculture. Regions with few humans, relatively stable human populations and/or unvarying land use often have fire histories that are dominated by climate parameters such as temperature and precipitation. Here, we examine biomass burning recorded in ice cores from northern Greenland (NEEM, (77°27'N; 51°3.6'W), Alaska (Juneau Icefield, 58° 35' N; 134° 29'W) and East Antarctica (EPICA DOME C; 75°06'S; 123°21'E), along with New Zealand lake cores to investigate interactions between climate, fire and human activity. Biomarkers such as levoglucosan, and its isomers mannosan and galactosan, can only be produced by cellulose combustion and therefore are specific indicators of past fire activity archived in ice and lake cores. These fire histories add another factor to climate proxies from the same core, and provide a comparison to regional fire syntheses from charcoal records and climate models. For example, fire data from the JSBACH-Spitfire model for the past 2000 years demonstrates that a climate-only scenario would not increase biomass burning in high northern latitudes for the past 2000 years, while NEEM ice core and regional pollen records demonstrate both increased fire activity and land use change that may be ascribed to human activity. Additional biomarkers such as fecal sterols in lake sediments can determine when people were in an area, and can help establish if an increased human presence in an area corresponds with intensified fire activity. This combination of specific biomarkers, other proxy data, and model output can help determine the relative impact of humans versus climate factors on regional fire activity.

  14. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    Science.gov (United States)

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  15. Human Activity Recognition in AAL Environments Using Random Projections

    Directory of Open Access Journals (Sweden)

    Robertas Damaševičius

    2016-01-01

    Full Text Available Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject’s body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL, for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD data are presented.

  16. Human Activity Recognition in AAL Environments Using Random Projections.

    Science.gov (United States)

    Damaševičius, Robertas; Vasiljevas, Mindaugas; Šalkevičius, Justas; Woźniak, Marcin

    2016-01-01

    Automatic human activity recognition systems aim to capture the state of the user and its environment by exploiting heterogeneous sensors attached to the subject's body and permit continuous monitoring of numerous physiological signals reflecting the state of human actions. Successful identification of human activities can be immensely useful in healthcare applications for Ambient Assisted Living (AAL), for automatic and intelligent activity monitoring systems developed for elderly and disabled people. In this paper, we propose the method for activity recognition and subject identification based on random projections from high-dimensional feature space to low-dimensional projection space, where the classes are separated using the Jaccard distance between probability density functions of projected data. Two HAR domain tasks are considered: activity identification and subject identification. The experimental results using the proposed method with Human Activity Dataset (HAD) data are presented.

  17. Smartphone-based human activity recognition

    OpenAIRE

    Reyes Ortiz, Jorge Luis

    2014-01-01

    Cotutela Universitat Politècnica de Catalunya i Università degli Studi di Genova Human Activity Recognition (HAR) is a multidisciplinary research field that aims to gather data regarding people's behavior and their interaction with the environment in order to deliver valuable context-aware information. It has nowadays contributed to develop human-centered areas of study such as Ambient Intelligence and Ambient Assisted Living, which concentrate on the improvement of people's Quality of Lif...

  18. Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

    Science.gov (United States)

    Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

    2013-07-01

    The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

  19. Similarity of hydrolyzing activity of human and rat small intestinal disaccharidases

    Directory of Open Access Journals (Sweden)

    Oku T

    2011-06-01

    Full Text Available Tsuneyuki Oku¹, Kenichi Tanabe¹, Shigeharu Ogawa², Naoki Sadamori¹, Sadako Nakamura¹¹Graduate School of Human Health Science, University of Nagasaki, Siebold, Nagayo, Japan; ²Juzenkai Hospital, Kagomachi, Nagasaki, JapanBackground: The purpose of this study was to clarify whether it is possible to extrapolate results from studies of the hydrolyzing activity of disaccharidases from rats to humans.Materials and methods: We measured disaccharidase activity in humans and rats using identical preparation and assay methods, and investigated the similarity in hydrolyzing activity. Small intestinal samples without malignancy were donated by five patients who had undergone bladder tumor surgery, and homogenates were prepared to measure disaccharidase activity. Adult rat homogenates were prepared using small intestine.Results: Maltase activity was the highest among the five disaccharidases, followed by sucrase and then palatinase in humans and rats. Trehalase activity was slightly lower than that of palatinase in humans and was similar to that of sucrase in rats. Lactase activity was the lowest in humans, but was similar to that of palatinase in rats. Thus, the hydrolyzing activity of five disaccharidases was generally similar in humans and rats. The relative activity of sucrose and palatinase versus maltase was generally similar between humans and rats. The ratio of rat to human hydrolyzing activity of maltase, sucrase, and palatinase was 1.9–3.1, but this was not a significant difference. Leaf extract from Morus alba strongly inhibited the activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and the degree of inhibition was similar in humans and rats. L-arabinose mildly inhibited sucrase activity, but hardly inhibited the activity of maltase, palatinase, trehalase and lactase in humans and rats. The digestibility of 1-kestose, galactosylsucrose, and panose by small intestinal enzymes was very similar between humans and

  20. Human activities affecting trace gases and climate

    International Nuclear Information System (INIS)

    Braatz, B.; Ebert, C.

    1990-01-01

    The Earth's climate has been in a constant state of change throughout geologic time due to natural perturbations in the global geobiosphere. However, various human activities have the potential to cause future global warming over a relatively short amount of time. These activities, which affect the Earth's climate by altering the concentrations of trace gases in the atmosphere, include energy consumption, particularly fossil-fuel consumption; industrial processes (production and use of chlorofluorocarbons, halons, and chlorocarbons, landfilling of wastes, and cement manufacture); changes in land use patterns, particularly deforestation and biomass burning; and agricultural practices (waste burning, fertilizer usage, rice production, and animal husbandry). Population growth is an important underlying factor affecting the level of growth in each activity. This paper describes how the human activities listed above contribute to atmospheric change, the current pattern of each activity, and how levels of each activity have changed since the early part of this century

  1. Decision Support System Development for Human Extravehicular Activity

    Data.gov (United States)

    National Aeronautics and Space Administration — The extension of human presence into deep space will depend on how successfully human planetary extravehicular activities (EVAs) are conducted without real-time...

  2. Modeling and Visualization of Human Activities for Multicamera Networks

    Directory of Open Access Journals (Sweden)

    Aswin C. Sankaranarayanan

    2009-01-01

    Full Text Available Multicamera networks are becoming complex involving larger sensing areas in order to capture activities and behavior that evolve over long spatial and temporal windows. This necessitates novel methods to process the information sensed by the network and visualize it for an end user. In this paper, we describe a system for modeling and on-demand visualization of activities of groups of humans. Using the prior knowledge of the 3D structure of the scene as well as camera calibration, the system localizes humans as they navigate the scene. Activities of interest are detected by matching models of these activities learnt a priori against the multiview observations. The trajectories and the activity index for each individual summarize the dynamic content of the scene. These are used to render the scene with virtual 3D human models that mimic the observed activities of real humans. In particular, the rendering framework is designed to handle large displays with a cluster of GPUs as well as reduce the cognitive dissonance by rendering realistic weather effects and illumination. We envision use of this system for immersive visualization as well as summarization of videos that capture group behavior.

  3. A human activity approach to User Interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    1989-01-01

    the work situations in which computer-based artifacts are used: The framework deals with the role of the user interface in purposeful human work. Human activity theory is used in this analysis. The purpose of this article is to make the reader curious and hopefully open his or her eyes to a somewhat...

  4. Human activities threatening the biodiversity of the Uzungwa Scarp ...

    African Journals Online (AJOL)

    Studies of human activities in the Uzungwa Scarp Forest Reserve, Udzungwa Mountains, were conducted in March-April and September 1997, in the western and southern parts of the forest. Different human activities, such as timber and pole cutting and withies harvesting, as well as the collection of non-timber forest ...

  5. Detection of cardiac activity changes from human speech

    Science.gov (United States)

    Tovarek, Jaromir; Partila, Pavol; Voznak, Miroslav; Mikulec, Martin; Mehic, Miralem

    2015-05-01

    Impact of changes in blood pressure and pulse from human speech is disclosed in this article. The symptoms of increased physical activity are pulse, systolic and diastolic pressure. There are many methods of measuring and indicating these parameters. The measurements must be carried out using devices which are not used in everyday life. In most cases, the measurement of blood pressure and pulse following health problems or other adverse feelings. Nowadays, research teams are trying to design and implement modern methods in ordinary human activities. The main objective of the proposal is to reduce the delay between detecting the adverse pressure and to the mentioned warning signs and feelings. Common and frequent activity of man is speaking, while it is known that the function of the vocal tract can be affected by the change in heart activity. Therefore, it can be a useful parameter for detecting physiological changes. A method for detecting human physiological changes by speech processing and artificial neural network classification is described in this article. The pulse and blood pressure changes was induced by physical exercises in this experiment. The set of measured subjects was formed by ten healthy volunteers of both sexes. None of the subjects was a professional athlete. The process of the experiment was divided into phases before, during and after physical training. Pulse, systolic, diastolic pressure was measured and voice activity was recorded after each of them. The results of this experiment describe a method for detecting increased cardiac activity from human speech using artificial neural network.

  6. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...

  7. Human activity understanding for robot-assisted living

    NARCIS (Netherlands)

    Hu, N.

    2016-01-01

    This thesis investigated the problem of understanding human activities, at different levels of granularity and taking into account both the variability in activities and annotator disagreement. To be able to capture the large variations within each of the action classes, we propose a model that uses

  8. Human Activity Recognition as Time-Series Analysis

    Directory of Open Access Journals (Sweden)

    Hyesuk Kim

    2015-01-01

    Full Text Available We propose a system that can recognize daily human activities with a Kinect-style depth camera. Our system utilizes a set of view-invariant features and the hidden state conditional random field (HCRF model to recognize human activities from the 3D body pose stream provided by MS Kinect API or OpenNI. Many high-level daily activities can be regarded as having a hierarchical structure where multiple subactivities are performed sequentially or iteratively. In order to model effectively these high-level daily activities, we utilized a multiclass HCRF model, which is a kind of probabilistic graphical models. In addition, in order to get view-invariant, but more informative features, we extract joint angles from the subject’s skeleton model and then perform the feature transformation to obtain three different types of features regarding motion, structure, and hand positions. Through various experiments using two different datasets, KAD-30 and CAD-60, the high performance of our system is verified.

  9. Synthesis of sialoglycopolypeptide for potentially blocking influenza virus infection using a rat α2,6-sialyltransferase expressed in BmNPV bacmid-injected silkworm larvae

    Directory of Open Access Journals (Sweden)

    Ogata Makoto

    2009-06-01

    Full Text Available Abstract Background Sialic acid is a deoxy uronic acid with a skeleton of nine carbons which is mostly found on cell surface in animals. This sialic acid on cell surface performs various biological functions by acting as a receptor for microorganisms, viruses, toxins, and hormones; by masking receptors; and by regulating the immune system. In order to synthesize an artificial sialoglycoprotein, we developed a large-scale production of rat α2,6-sialyltransferase (ST6Gal1. The ST6Gal1 was expressed in fifth instar silkworm larval hemolymph using recombinant both cysteine protease- and chitinase-deficient Bombyx mori nucleopolyhedrovirus (BmNPV-CP--Chi- bacmid. The expressed ST6Gal1 was purified, characterized and used for sialylation of asialoglycopolypeptide. We tested the inhibitory effect of the synthesized α2,6-sialoglycopolypeptide on hemagglutination by Sambucus nigra (SNA lectin. Results FLAG-tagged recombinant ST6Gal1 was expressed efficiently and purified by precipitation with ammonium sulphate followed by affinity chromatography on an anti-FLAG M2 column, generating 2.2 mg purified fusion protein from only 11 silkworm larvae, with a recovery yield of 64%. The purified ST6Gal1 was characterized and its N-glycan patterns were found to be approximately paucimannosidic type by HPLC mapping method. Fluorescently-labelled N-acetyllactosamine (LacNAc glycoside containing dansyl group was synthesized chemo-enzymatically as high-sensitivity acceptor substrate for ST6Gal1. The acceptor substrate specificity of the enzyme was similar to that of rat liver ST6Gal1. The fluorescent glycoside is useful as a substrate for a highly sensitive picomole assay of ST6Gal1. Asialoglycopolypeptide was regioselectively and quantitatively sialylated by catalytic reaction at the terminal Gal residue to obtain α2,6-sialoglycopolypeptide using ST6Gal1. The α2,6-sialoglycopolypeptide selectively inhibited hemagglutination induced by Sambucus nigra (SNA lectin

  10. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    Directory of Open Access Journals (Sweden)

    Kandhasamy Sowndhararajan

    2016-11-01

    Full Text Available The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG. The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz, theta (4–8 Hz, alpha (8–13 Hz, beta (13–30 Hz and gamma (30–50 Hz, and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  11. Influence of Fragrances on Human Psychophysiological Activity: With Special Reference to Human Electroencephalographic Response

    Science.gov (United States)

    Sowndhararajan, Kandhasamy; Kim, Songmun

    2016-01-01

    The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (13–30 Hz) and gamma (30–50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the

  12. The significance of human factors in nuclear activities

    International Nuclear Information System (INIS)

    Weil, L.; Berg, H.P.

    1999-01-01

    Human factors is an aspect increasingly investigated in the last few years in efforts and programmes for enhancing the operational safety of nuclear systems. Methodology has been elaborated for analysis and evaluation of human reliability, or development of instruments supporting the decisions to be taken by the operators at the man-control room interface of nuclear installations, as well as initial approaches to introduce organisational factors which may influence the man-machine function allocation, and thus are an element of the safety culture concept. The significance of human factors in nuclear activities, as well as activities at the national and international level for optimisation of the man-machine interface and the man-organisation interface are discussed. (orig./CB) [de

  13. Towards discrete wavelet transform-based human activity recognition

    Science.gov (United States)

    Khare, Manish; Jeon, Moongu

    2017-06-01

    Providing accurate recognition of human activities is a challenging problem for visual surveillance applications. In this paper, we present a simple and efficient algorithm for human activity recognition based on a wavelet transform. We adopt discrete wavelet transform (DWT) coefficients as a feature of human objects to obtain advantages of its multiresolution approach. The proposed method is tested on multiple levels of DWT. Experiments are carried out on different standard action datasets including KTH and i3D Post. The proposed method is compared with other state-of-the-art methods in terms of different quantitative performance measures. The proposed method is found to have better recognition accuracy in comparison to the state-of-the-art methods.

  14. Predicting human activities in sequences of actions in RGB-D videos

    Science.gov (United States)

    Jardim, David; Nunes, Luís.; Dias, Miguel

    2017-03-01

    In our daily activities we perform prediction or anticipation when interacting with other humans or with objects. Prediction of human activity made by computers has several potential applications: surveillance systems, human computer interfaces, sports video analysis, human-robot-collaboration, games and health-care. We propose a system capable of recognizing and predicting human actions using supervised classifiers trained with automatically labeled data evaluated in our human activity RGB-D dataset (recorded with a Kinect sensor) and using only the position of the main skeleton joints to extract features. Using conditional random fields (CRFs) to model the sequential nature of actions in a sequence has been used before, but where other approaches try to predict an outcome or anticipate ahead in time (seconds), we try to predict what will be the next action of a subject. Our results show an activity prediction accuracy of 89.9% using an automatically labeled dataset.

  15. The influence of human activity in the Arctic on climate and climate impacts

    Energy Technology Data Exchange (ETDEWEB)

    Huntington, H.P. [23834 The Clearing Dr., Eagle River, AK 99577 (United States); Boyle, M. [Institute for Resources, Environment and Sustainability, University of British Columbia, 2202 Main Mall, Vancouver, BC, V6S 1K4 (Canada); Flowers, G.E. [Department of Earth Sciences, Simon Fraser University, 8888 University Drive, Burnaby, BC, V5A 1S6 (Canada); Weatherly, J.W. [Snow and Ice Division, Cold Regions Research and Engineering Laboratory, 72 Lyme Road, Hanover, NH 03755 (United States); Hamilton, L.C. [Department of Sociology, University of New Hampshire, 20 College Road, Durham, NH 03824 (United States); Hinzman, L. [Water and Environment Research Center, University of Alaska Fairbanks, P.O. Box 755860, Fairbanks, AK 99775 (United States); Gerlach, C. [Department of Anthropology, University of Alaska Fairbanks, P.O. Box 757720, Fairbanks, AK 99775 (United States); Zulueta, R. [Department of Biology, Global Change Research Group, San Diego State University, 5500 Campanile Drive, PS-240, San Diego, CA 92182 (United States); Nicolson, C. [Department of Natural Resources Conservation, University of Massachusetts, 160 Holdsworth Way, Amherst, MA , 01003 (United States); Overpeck, J. [Institute for the Study of Planet Earth, University of Arizona, 715 North Park Avenue, 2nd Floor, Tucson, AZ, 85721 (United States)

    2007-05-15

    Human activities in the Arctic are often mentioned as recipients of climate-change impacts. In this paper we consider the more complicated but more likely possibility that human activities themselves can interact with climate or environmental change in ways that either mitigate or exacerbate the human impacts. Although human activities in the Arctic are generally assumed to be modest, our analysis suggests that those activities may have larger influences on the arctic system than previously thought. Moreover, human influences could increase substantially in the near future. First, we illustrate how past human activities in the Arctic have combined with climatic variations to alter biophysical systems upon which fisheries and livestock depend. Second, we describe how current and future human activities could precipitate or affect the timing of major transitions in the arctic system. Past and future analyses both point to ways in which human activities in the Arctic can substantially influence the trajectory of arctic system change.

  16. Exploring Human Activity Patterns Using Taxicab Static Points

    Directory of Open Access Journals (Sweden)

    Bin Jiang

    2012-06-01

    Full Text Available This paper explores the patterns of human activities within a geographical space by adopting the taxicab static points which refer to the locations with zero speed along the tracking trajectory. We report the findings from both aggregated and individual aspects. Results from the aggregated level indicate the following: (1 Human activities exhibit an obvious regularity in time, for example, there is a burst of activity during weekend nights and a lull during the week. (2 They show a remarkable spatial drifting pattern, which strengthens our understanding of the activities in any given place. (3 Activities are heterogeneous in space irrespective of their drifting with time. These aggregated results not only help in city planning, but also facilitate traffic control and management. On the other hand, investigations on an individual level suggest that (4 activities witnessed by one taxicab will have different temporal regularity to another, and (5 each regularity implies a high level of prediction with low entropy by applying the Lempel-Ziv algorithm.

  17. A Pattern Mining Approach to Sensor-based Human Activity Recognition

    DEFF Research Database (Denmark)

    Gu, Tao; Wang, Liang; Wu, Zhanqing

    2011-01-01

    Recognizing human activities from sensor readings has recently attracted much research interest in pervasive computing due to its potential in many applications such as assistive living and healthcare. This task is particularly challenging because human activities are often performed in not only...

  18. Humpback Dolphin (Genus Sousa) Behavioural Responses to Human Activities.

    Science.gov (United States)

    Piwetz, Sarah; Lundquist, David; Würsig, Bernd

    2015-01-01

    Humpback dolphins (genus Sousa) use shallow, near-shore waters throughout their range. This coastal distribution makes them vulnerable to recreational and commercial disturbances, especially near heavily populated and industrialized areas. Most research focusing on Sousa and human activities has emphasized direct impacts and threats, involving injury and death, with relatively little focus on indirect effects on dolphins, such as changes in behaviour that may lead to deleterious effects. Understanding behaviour is important in resolving human-wildlife conflict and is an important component of conservation. This chapter gives an overview of animal behavioural responses to human activity with examples from diverse taxa; reviews the scientific literature on behavioural responses of humpback dolphins to human activity throughout their range, including marine vessel traffic, dolphin tourism, cetacean-fishery interactions, noise pollution, and habitat alteration; and highlights information and data gaps for future humpback dolphin research to better inform behaviour-based management decisions that contribute to conservation efforts. © 2015 Elsevier Ltd All rights reserved.

  19. Human Activity Differentially Redistributes Large Mammals in the Canadian Rockies National Parks

    Directory of Open Access Journals (Sweden)

    James Kimo. Rogala

    2011-09-01

    Full Text Available National parks are important for conservation of species such as wolves (Canis lupus and elk (Cervus canadensis. However, topography, vegetation conditions, and anthropogenic infrastructure within parks may limit available habitat. Human activity on trails and roads may lead to indirect habitat loss, further limiting available habitat. Predators and prey may respond differentially to human activity, potentially disrupting ecological processes. However, research on such impacts to wildlife is incomplete, especially at fine spatial and temporal scales. Our research investigated the relationship between wolf and elk distribution and human activity using fine-scale Global Positioning System (GPS wildlife telemetry locations and hourly human activity measures on trails and roads in Banff, Kootenay, and Yoho National Parks, Canada. We observed a complex interaction between the distance animals were located from trails and human activity level resulting in species adopting both mutual avoidance and differential response behaviors. In areas < 50 m from trails human activity led to a mutual avoidance response by both wolves and elk. In areas 50 - 400 m from trails low levels of human activity led to differential responses; wolves avoided these areas, whereas elk appeared to use these areas as a predation refugia. These differential impacts on elk and wolves may have important implications for trophic dynamics. As human activity increased above two people/hour, areas 50 - 400 m from trails were mutually avoided by both species, resulting in the indirect loss of important montane habitat. If park managers are concerned with human impacts on wolves and elk, or on these species' trophic interactions with other species, they can monitor locations near trails and roads and consider hourly changes of human activity levels in areas important to wildlife.

  20. Human Activity Recognition from Body Sensor Data using Deep Learning.

    Science.gov (United States)

    Hassan, Mohammad Mehedi; Huda, Shamsul; Uddin, Md Zia; Almogren, Ahmad; Alrubaian, Majed

    2018-04-16

    In recent years, human activity recognition from body sensor data or wearable sensor data has become a considerable research attention from academia and health industry. This research can be useful for various e-health applications such as monitoring elderly and physical impaired people at Smart home to improve their rehabilitation processes. However, it is not easy to accurately and automatically recognize physical human activity through wearable sensors due to the complexity and variety of body activities. In this paper, we address the human activity recognition problem as a classification problem using wearable body sensor data. In particular, we propose to utilize a Deep Belief Network (DBN) model for successful human activity recognition. First, we extract the important initial features from the raw body sensor data. Then, a kernel principal component analysis (KPCA) and linear discriminant analysis (LDA) are performed to further process the features and make them more robust to be useful for fast activity recognition. Finally, the DBN is trained by these features. Various experiments were performed on a real-world wearable sensor dataset to verify the effectiveness of the deep learning algorithm. The results show that the proposed DBN outperformed other algorithms and achieves satisfactory activity recognition performance.

  1. Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells

    International Nuclear Information System (INIS)

    Perkel, V.S.; Mohan, S.; Herring, S.J.; Baylink, D.J.; Linkhart, T.A.

    1990-01-01

    Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis. In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation ([3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens

  2. RNA-Guided Activation of Pluripotency Genes in Human Fibroblasts

    DEFF Research Database (Denmark)

    Xiong, Kai; Zhou, Yan; Blichfeld, Kristian Aabo

    2017-01-01

    -associated protein 9 (dCas9)-VP64 (CRISPRa) alone, or a combination of dCas9-VP64 and MS2-P65-HSF1 [synergistic activation mediator (SAM) system] mediated activation of five pluripotency genes: KLF4 (K), LIN28 (L), MYC (M), OCT4 (O), and SOX2 (S) in human cells (HEK293T, HeLa, HepG2, and primary fibroblasts...... could be obtained from these SAM fibroblasts. In conclusion, our study showed that CRISPR/Cas9-based ATFs are potent to activate and maintain transcription of endogenous human pluripotent genes. However, future improvements of the system are still required to improve activation efficiency and cellular...

  3. Magnetogastrographic detection of gastric electrical response activity in humans

    International Nuclear Information System (INIS)

    Irimia, Andrei; Richards, William O; Bradshaw, L Alan

    2006-01-01

    The detection and characterization of gastric electrical activity has important clinical applications, including the early diagnosis of gastric diseases in humans. In mammals, this phenomenon has two important features: an electrical control activity (ECA) that manifests itself as an electric slow wave (with a frequency of 3 cycles per minute in humans) and an electrical response activity (ERA) that is characterized by spiking potentials during the plateau phase of the ECA. Whereas the ECA has been recorded in humans both invasively and non-invasively (magnetogastrography-MGG), the ERA has never been detected non-invasively in humans before. In this paper, we report on our progress towards the non-invasive detection of ERA from the human stomach using a procedure that involves the application of principal component analysis to MGG recordings, which were acquired in our case from ten normal human patients using a Superconducting QUantum Interference Device (SQUID) magnetometer. Both pre- and post-prandial recordings were acquired for each patient and 20 min of recordings (10 min of pre-prandial and 10 min of post-prandial data) were analysed for each patient. The mean percentage of ECA slow waves that were found to exhibit spikes of suspected ERA origin was 41% and 61% for pre- and post-prandial recordings, respectively, implying a 47% ERA increase post-prandially (P < 0.0001 at a 95% confidence level). The detection of ERA in humans is highly encouraging and points to the possible use of non-invasive ERA recordings as a valuable tool for the study of human gastric disorders

  4. Impact of the human activities on the climate

    International Nuclear Information System (INIS)

    Deque, M.

    2007-01-01

    In the framework of the A2 scenario of the GIEC, the possible impacts on the french climate, of the human activities are examined. It seems that the human activities imposed and will be able to impose a faster change of the climate than the natural changes. For the hundred coming years the main characteristics could be: an increase of the temperature, an increase of the rains in winter and a decrease in summer, a decrease of the water in soils expected in freezing areas and an increase of the drought periods. (A.L.B.)

  5. Elevation of telomerase activity in chronic radiation ulcer of human skin

    International Nuclear Information System (INIS)

    Li Xiaoying; Zhao Po; Wang Dewen; Yang Zhixiang

    1997-01-01

    Objective: To investigate the levels of telomerase activity in chronic radiation ulcers of human skin and the possible relationship between the enzyme and cancer transformation. Method: Using nonisotopic telomere repeat amplification protocol (TRAP), detections were performed in 20 cases of chronic radiation ulcers of human skin, 5 cases of normal skin tissues and 5 cases of carcinoma. Results: The positive rates for telomerase activity were 30.0%(6/20), 0(0/5) and 100%(5/5) in chronic radiation ulcers of human skin, normal skin and carcinoma, respectively. The telomerase activity in radiation ulcer was weaker than in carcinoma. Conclusion: The telomerase activity assay might be used as a marker for predicting the prognosis and the effect of treatment in chronic radiation ulcer of human skin

  6. Human Reliability Assessment and Human Performance Evaluation: Research and Analysis Activities at the U.S. NRC

    International Nuclear Information System (INIS)

    Ramey-Smith, A.M.

    1998-01-01

    The author indicates the themes of the six programs identified by the US NRC mission on human performance and human reliability activities. They aim at developing the technical basis to support human performance, at developing and updating a model of human performance and human reliability, at fostering national and international dialogue and cooperation efforts on human performance evaluation, at conducting operating events analysis and database development, and at providing support to human performance and human reliability inspection

  7. The Activation Pathway of Human Rhodopsin in Comparison to Bovine Rhodopsin*

    Science.gov (United States)

    Kazmin, Roman; Rose, Alexander; Szczepek, Michal; Elgeti, Matthias; Ritter, Eglof; Piechnick, Ronny; Hofmann, Klaus Peter; Scheerer, Patrick; Hildebrand, Peter W.; Bartl, Franz J.

    2015-01-01

    Rhodopsin, the photoreceptor of rod cells, absorbs light to mediate the first step of vision by activating the G protein transducin (Gt). Several human diseases, such as retinitis pigmentosa or congenital night blindness, are linked to rhodopsin malfunctions. Most of the corresponding in vivo studies and structure-function analyses (e.g. based on protein x-ray crystallography or spectroscopy) have been carried out on murine or bovine rhodopsin. Because these rhodopsins differ at several amino acid positions from human rhodopsin, we conducted a comprehensive spectroscopic characterization of human rhodopsin in combination with molecular dynamics simulations. We show by FTIR and UV-visible difference spectroscopy that the light-induced transformations of the early photointermediates are very similar. Significant differences between the pigments appear with formation of the still inactive Meta I state and the transition to active Meta II. However, the conformation of Meta II and its activity toward the G protein are essentially the same, presumably reflecting the evolutionary pressure under which the active state has developed. Altogether, our results show that although the basic activation pathways of human and bovine rhodopsin are similar, structural deviations exist in the inactive conformation and during receptor activation, even between closely related rhodopsins. These differences between the well studied bovine or murine rhodopsins and human rhodopsin have to be taken into account when the influence of point mutations on the activation pathway of human rhodopsin are investigated using the bovine or murine rhodopsin template sequences. PMID:26105054

  8. Combination of Accumulated Motion and Color Segmentation for Human Activity Analysis

    Directory of Open Access Journals (Sweden)

    Briassouli Alexia

    2008-01-01

    Full Text Available Abstract The automated analysis of activity in digital multimedia, and especially video, is gaining more and more importance due to the evolution of higher-level video processing systems and the development of relevant applications such as surveillance and sports. This paper presents a novel algorithm for the recognition and classification of human activities, which employs motion and color characteristics in a complementary manner, so as to extract the most information from both sources, and overcome their individual limitations. The proposed method accumulates the flow estimates in a video, and extracts "regions of activity" by processing their higher-order statistics. The shape of these activity areas can be used for the classification of the human activities and events taking place in a video and the subsequent extraction of higher-level semantics. Color segmentation of the active and static areas of each video frame is performed to complement this information. The color layers in the activity and background areas are compared using the earth mover's distance, in order to achieve accurate object segmentation. Thus, unlike much existing work on human activity analysis, the proposed approach is based on general color and motion processing methods, and not on specific models of the human body and its kinematics. The combined use of color and motion information increases the method robustness to illumination variations and measurement noise. Consequently, the proposed approach can lead to higher-level information about human activities, but its applicability is not limited to specific human actions. We present experiments with various real video sequences, from sports and surveillance domains, to demonstrate the effectiveness of our approach.

  9. Combination of Accumulated Motion and Color Segmentation for Human Activity Analysis

    Directory of Open Access Journals (Sweden)

    Ioannis Kompatsiaris

    2008-03-01

    Full Text Available The automated analysis of activity in digital multimedia, and especially video, is gaining more and more importance due to the evolution of higher-level video processing systems and the development of relevant applications such as surveillance and sports. This paper presents a novel algorithm for the recognition and classification of human activities, which employs motion and color characteristics in a complementary manner, so as to extract the most information from both sources, and overcome their individual limitations. The proposed method accumulates the flow estimates in a video, and extracts “regions of activity” by processing their higher-order statistics. The shape of these activity areas can be used for the classification of the human activities and events taking place in a video and the subsequent extraction of higher-level semantics. Color segmentation of the active and static areas of each video frame is performed to complement this information. The color layers in the activity and background areas are compared using the earth mover's distance, in order to achieve accurate object segmentation. Thus, unlike much existing work on human activity analysis, the proposed approach is based on general color and motion processing methods, and not on specific models of the human body and its kinematics. The combined use of color and motion information increases the method robustness to illumination variations and measurement noise. Consequently, the proposed approach can lead to higher-level information about human activities, but its applicability is not limited to specific human actions. We present experiments with various real video sequences, from sports and surveillance domains, to demonstrate the effectiveness of our approach.

  10. Antiproliferative activity of recombinant human interferon-λ2 ...

    African Journals Online (AJOL)

    Antiproliferative activity of recombinant human interferon-λ2 expressed in stably ... The representing 26 kDa protein band of IFN-λ2 was detected by SDS-PAGE and ... The antiproliferative activity of hIFN-λ2 was determined by MTT assay.

  11. Human activity and climate variability project: annual report 2001

    International Nuclear Information System (INIS)

    Harle, K.J.; Heijnis, H.; Henderson-Sellers, A.; Sharmeen, S.; Zahorowski, W.

    2002-01-01

    Knowledge of the state of the Australian environment, including natural climate variability, prior to colonial settlement is vital if we are to define and understand the impact of over two hundred years of post-industrial human activity on our landscape. ANSTO, in conjunction with university partners, is leading a major research effort to provide natural archives of human activity and climate variability over the last 500 years in Australia, utilising a variety of techniques, including lead-210 and radiocarbon dating and analyses of proxy indicators (such as microfossils) as well as direct evidence (such as trace elements) of human activity and climate variability. The other major project objectives were to contribute to the understanding of the impact of human induced and natural aerosols in the East Asian region on climate through analysis and sourcing of fine particles and characterisation of air samples using radon concentrations and to contribute to the improvement of land surface parameterisation schemes and investigate the potential to use stable isotopes to improve global climate models and thus improve our understanding of future climate

  12. Food & Fitness. Directory. Human Nutrition Activities.

    Science.gov (United States)

    Department of Agriculture, Washington, DC.

    Activities of the following regulatory and food service agencies of the Department of Agriculture are described: (1) Agricultural Research Service; (2) Cooperative State Research Service; (3) Economic Research Service; (4) Human Nutrition Information Service; (5) Office of Grants and Program Systems; (6) Office of International Cooperation and…

  13. A Multiscale Survival Process for Modeling Human Activity Patterns.

    Science.gov (United States)

    Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

    2016-01-01

    Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

  14. BACTERICIDAL ACTIVITY OF HUMAN SERA AGAINST ...

    African Journals Online (AJOL)

    hi-tech

    East African Medical Journal Vol. 77 No. 12 December 2000. BACTERICIDAL ACTIVITY OF HUMAN SERA AGAINST SALMONELLA TYPHI AND SALMONELLA PARATYPHI A, B, C. E.O. Igumbor, BSc, MSc, PhD, Department of Medical Microbiology, School of Medicine, University of Zimbabwe P.O. Box Al78, Avondale, ...

  15. Stretch activates human myometrium via ERK, caldesmon and focal adhesion signaling.

    Directory of Open Access Journals (Sweden)

    Yunping Li

    2009-10-01

    Full Text Available An incomplete understanding of the molecular mechanisms responsible for myometrial activation from the quiescent pregnant state to the active contractile state during labor has hindered the development of effective therapies for preterm labor. Myometrial stretch has been implicated clinically in the initiation of labor and the etiology of preterm labor, but the molecular mechanisms involved in the human have not been determined. We investigated the mechanisms by which gestation-dependent stretch contributes to myometrial activation, by using human uterine samples from gynecologic hysterectomies and Cesarean sections. Here we demonstrate that the Ca requirement for activation of the contractile filaments in human myometrium increases with caldesmon protein content during gestation and that an increase in caldesmon phosphorylation can reverse this inhibitory effect during labor. By using phosphotyrosine screening and mass spectrometry of stretched human myometrial samples, we identify 3 stretch-activated focal adhesion proteins, FAK, p130Cas, and alpha actinin. FAK-Y397, which signals integrin engagement, is constitutively phosphorylated in term human myometrium whereas FAK-Y925, which signals downstream ERK activation, is phosphorylated during stretch. We have recently identified smooth muscle Archvillin (SmAV as an ERK regulator. A newly produced SmAV-specific antibody demonstrates gestation-specific increases in SmAV protein levels and stretch-specific increases in SmAV association with focal adhesion proteins. Thus, whereas increases in caldesmon levels suppress human myometrium contractility during pregnancy, stretch-dependent focal adhesion signaling, facilitated by the ERK activator SmAV, can contribute to myometrial activation. These results suggest that focal adhesion proteins may present new targets for drug discovery programs aimed at regulation of uterine contractility.

  16. A Novel Wearable Sensor-Based Human Activity Recognition Approach Using Artificial Hydrocarbon Networks.

    Science.gov (United States)

    Ponce, Hiram; Martínez-Villaseñor, María de Lourdes; Miralles-Pechuán, Luis

    2016-07-05

    Human activity recognition has gained more interest in several research communities given that understanding user activities and behavior helps to deliver proactive and personalized services. There are many examples of health systems improved by human activity recognition. Nevertheless, the human activity recognition classification process is not an easy task. Different types of noise in wearable sensors data frequently hamper the human activity recognition classification process. In order to develop a successful activity recognition system, it is necessary to use stable and robust machine learning techniques capable of dealing with noisy data. In this paper, we presented the artificial hydrocarbon networks (AHN) technique to the human activity recognition community. Our artificial hydrocarbon networks novel approach is suitable for physical activity recognition, noise tolerance of corrupted data sensors and robust in terms of different issues on data sensors. We proved that the AHN classifier is very competitive for physical activity recognition and is very robust in comparison with other well-known machine learning methods.

  17. Human activity and the spread of Phytophthora ramorum

    Science.gov (United States)

    Hall J. Cushman; Michelle Cooper; Ross K. Meentemeyer; Shelly Benson

    2008-01-01

    Increasing numbers of studies are finding that humans can facilitate the spread of exotic plant species in protected wildlands. Hiking trails commonly serve as conduits for invaders and the number of exotic plant species occurring in protected areas is often correlated positively with visitation rates. Despite such evidence linking human activity to the spread of...

  18. Influence of vestibular activation on respiration in humans

    Science.gov (United States)

    Monahan, Kevin D.; Sharpe, Melissa K.; Drury, Daniel; Ertl, Andrew C.; Ray, Chester A.

    2002-01-01

    The purpose of this study was to determine the effects of the semicircular canals and otolith organs on respiration in humans. On the basis of animal studies, we hypothesized that vestibular activation would elicit a vestibulorespiratory reflex. To test this hypothesis, respiratory measures, arterial blood pressure, and heart rate were measured during engagement of semicircular canals and/or otolith organs. Dynamic upright pitch and roll (15 cycles/min), which activate the otolith organs and semicircular canals, increased respiratory rate (Delta2 +/- 1 and Delta3 +/- 1 breaths/min, respectively; P < 0.05). Dynamic yaw and lateral pitch (15 cycles/min), which activate the semicircular canals, increased respiration similarly (Delta3 +/- 1 and Delta2 +/- 1, respectively; P < 0.05). Dynamic chair rotation (15 cycles/min), which mimics dynamic yaw but eliminates neck muscle afferent, increased respiration (Delta3 +/- 1; P < 0.05) comparable to dynamic yaw (15 cycles/min). Increases in respiratory rate were graded as greater responses occurred during upright (Delta5 +/- 2 breaths/min) and lateral pitch (Delta4 +/- 1) and roll (Delta5 +/- 1) performed at 30 cycles/min. Increases in breathing frequency resulted in increases in minute ventilation during most interventions. Static head-down rotation, which activates otolith organs, did not alter respiratory rate (Delta1 +/- 1 breaths/min). Collectively, these data indicate that semicircular canals, but not otolith organs or neck muscle afferents, mediate increased ventilation in humans and support the concept that vestibular activation alters respiration in humans.

  19. a Three-Step Spatial-Temporal Clustering Method for Human Activity Pattern Analysis

    Science.gov (United States)

    Huang, W.; Li, S.; Xu, S.

    2016-06-01

    How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time) to four dimensions (space, time and semantics). More specifically, not only a location and time that people stay and spend are collected, but also what people "say" for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The results show that the

  20. Affinity purification of recombinant human plasminogen activator ...

    African Journals Online (AJOL)

    Affinity purification of recombinant human plasminogen activator from ... Screening antibody was performed using rhPA milk in an ELISA-elution assay. ... useful for purifying other tPA mutants or other novel recombinant milkderived proteins.

  1. Robust Indoor Human Activity Recognition Using Wireless Signals.

    Science.gov (United States)

    Wang, Yi; Jiang, Xinli; Cao, Rongyu; Wang, Xiyang

    2015-07-15

    Wireless signals-based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI) of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP) and access points (AP). First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions' CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO) signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM) based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

  2. Robust Indoor Human Activity Recognition Using Wireless Signals

    Directory of Open Access Journals (Sweden)

    Yi Wang

    2015-07-01

    Full Text Available Wireless signals–based activity detection and recognition technology may be complementary to the existing vision-based methods, especially under the circumstance of occlusions, viewpoint change, complex background, lighting condition change, and so on. This paper explores the properties of the channel state information (CSI of Wi-Fi signals, and presents a robust indoor daily human activity recognition framework with only one pair of transmission points (TP and access points (AP. First of all, some indoor human actions are selected as primitive actions forming a training set. Then, an online filtering method is designed to make actions’ CSI curves smooth and allow them to contain enough pattern information. Each primitive action pattern can be segmented from the outliers of its multi-input multi-output (MIMO signals by a proposed segmentation method. Lastly, in online activities recognition, by selecting proper features and Support Vector Machine (SVM based multi-classification, activities constituted by primitive actions can be recognized insensitive to the locations, orientations, and speeds.

  3. Biologic activities of recombinant human-beta-defensin-4 toward cultured human cancer cells.

    Science.gov (United States)

    Gerashchenko, O L; Zhuravel, E V; Skachkova, O V; Khranovska, N N; Filonenko, V V; Pogrebnoy, P V; Soldatkina, M A

    2013-06-01

    The aim of the study was in vitro analysis of biological activity of recombinant human beta-defensin-4 (rec-hBD-4). hBD-4 cDNA was cloned into pGEX-2T vector, and recombinant plasmid was transformed into E. coli BL21(DE3) cells. To purify soluble fusion GST-hBD-4 protein, affinity chromatography was applied. Rec-hBD-4 was cleaved from the fusion protein with thrombin, and purified by reverse phase chromatography on Sep-Pack C18. Effects of rec-hBD-4 on proliferation, viability, cell cycle distribution, substrate-independent growth, and mobility of cultured human cancer cells of A431, A549, and TPC-1 lines were analyzed by direct cell counting technique, MTT assay, flow cytofluorometry, colony forming assay in semi-soft medium, and wound healing assay. Rec-hBD-4 was expressed in bacterial cells as GST-hBD-4 fusion protein, and purified by routine 3-step procedure (affine chromatography on glutathione-agarose, cleavage of fusion protein by thrombin, and reverse phase chromatography). Analysis of in vitro activity of rec-hBD-4 toward three human cancer cell lines has demonstrated that the defensin is capable to affect cell behaviour in concentration-dependent manner. In 1-100 nM concentrations rec-hBD-4 significantly stimulates cancer cell proliferation and viability, and promotes cell cycle progression through G2/M checkpoint, greatly enhances colony-forming activity and mobility of the cells. Treatment of the cells with 500 nM of rec-hBD-4 resulted in opposite effects: significant suppression of cell proliferation and viability, blockage of cell cycle in G1/S checkpoint, significant inhibition of cell migration and colony forming activity. Recombinant human beta-defensin-4 is biologically active peptide capable to cause oppositely directed effects toward biologic features of cancer cells in vitro dependent on its concentration.

  4. Physical activity and human health

    Directory of Open Access Journals (Sweden)

    Paulina Wojciechowska

    2015-01-01

    Full Text Available Introduction: The dynamic development of the automotive industry, transport, and the media means that human life has become much easier. At the same time, the comfortable living conditions have decreased physical activity. Biologically conditioned, the need of activity has been minimised by the ever-increasing pace of life. As a result, it may lead to the loss of physical and mental health. Active recreation is not only an excellent source of activity, but also a source of satisfaction. Youths and adults should therefore spend their free time primarily on various forms of physical activity. Aim of the research : To evaluate the physical fitness of students who regularly practice physical exercise, those who occasionally practice, and those not practicing any form of physical activity. Material and methods : In the research we used a questionnaire of the Ruffier test and an orthostatic test. The study involved a group of 15 people aged 20–25 years. Participation in the study was entirely voluntary and anonymous. The study group consisted only of women. Results obtained from the questionnaire survey were fully reflected during exercise tests performed. Results and conclusions: Only regularly practiced physical activity has an effect on our body. Regular exercise increases our body’s physical capacity. Activity is the best means of prevention of lifestyle diseases. Youths and adults should spend their free time mainly doing various forms of physical activity.

  5. Exploring Techniques for Vision Based Human Activity Recognition: Methods, Systems, and Evaluation

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2013-01-01

    Full Text Available With the wide applications of vision based intelligent systems, image and video analysis technologies have attracted the attention of researchers in the computer vision field. In image and video analysis, human activity recognition is an important research direction. By interpreting and understanding human activity, we can recognize and predict the occurrence of crimes and help the police or other agencies react immediately. In the past, a large number of papers have been published on human activity recognition in video and image sequences. In this paper, we provide a comprehensive survey of the recent development of the techniques, including methods, systems, and quantitative evaluation towards the performance of human activity recognition.

  6. Combining users' activity survey and simulators to evaluate human activity recognition systems.

    Science.gov (United States)

    Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

    2015-04-08

    Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

  7. Combining Users’ Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

    Directory of Open Access Journals (Sweden)

    Gorka Azkune

    2015-04-01

    Full Text Available Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant.

  8. Combining Users' Activity Survey and Simulators to Evaluate Human Activity Recognition Systems

    Science.gov (United States)

    Azkune, Gorka; Almeida, Aitor; López-de-Ipiña, Diego; Chen, Liming

    2015-01-01

    Evaluating human activity recognition systems usually implies following expensive and time-consuming methodologies, where experiments with humans are run with the consequent ethical and legal issues. We propose a novel evaluation methodology to overcome the enumerated problems, which is based on surveys for users and a synthetic dataset generator tool. Surveys allow capturing how different users perform activities of daily living, while the synthetic dataset generator is used to create properly labelled activity datasets modelled with the information extracted from surveys. Important aspects, such as sensor noise, varying time lapses and user erratic behaviour, can also be simulated using the tool. The proposed methodology is shown to have very important advantages that allow researchers to carry out their work more efficiently. To evaluate the approach, a synthetic dataset generated following the proposed methodology is compared to a real dataset computing the similarity between sensor occurrence frequencies. It is concluded that the similarity between both datasets is more than significant. PMID:25856329

  9. Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Rosen, Mitchell B.; Das, Kaberi P.; Wood, Carmen R.; Wolf, Cynthia J.; Abbott, Barbara D.; Lau, Christopher

    2013-01-01

    While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48 h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited

  10. Water quality degradation effects on freshwater availability: Impacts to human activities

    Science.gov (United States)

    Peters, N.E.; Meybeck, Michel

    2000-01-01

    The quality of freshwater at any point on the landscape reflects the combined effects of many processes along water pathways. Human activities on all spatial scales affect both water quality and quantity. Alteration of the landscape and associated vegetation has not only changed the water balance, but typically has altered processes that control water quality. Effects of human activities on a small scale are relevant to an entire drainage basin. Furthermore, local, regional, and global differences in climate and water flow are considerable, causing varying effects of human activities on land and water quality and quantity, depending on location within a watershed, geology, biology, physiographic characteristics, and climate. These natural characteristics also greatly control human activities, which will, in turn, modify (or affect) the natural composition of water. One of the most important issues for effective resource management is recognition of cyclical and cascading effects of human activities on the water quality and quantity along hydrologic pathways. The degradation of water quality in one part of a watershed can have negative effects on users downstream. Everyone lives downstream of the effects of some human activity. An extremely important factor is that substances added to the atmosphere, land, and water generally have relatively long time scales for removal or clean up. The nature of the substance, including its affinity for adhering to soil and its ability to be transformed, affects the mobility and the time scale for removal of the substance. Policy alone will not solve many of the degradation issues, but a combination of policy, education, scientific knowledge, planning, and enforcement of applicable laws can provide mechanisms for slowing the rate of degradation and provide human and environmental protection. Such an integrated approach is needed to effectively manage land and water resources.

  11. Regulation of calcium homeostasis in activated human neutrophils ...

    African Journals Online (AJOL)

    Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

  12. Scaling down the size and increasing the throughput of glycosyltransferase assays: activity changes on stem cell differentiation.

    Science.gov (United States)

    Patil, Shilpa A; Chandrasekaran, E V; Matta, Khushi L; Parikh, Abhirath; Tzanakakis, Emmanuel S; Neelamegham, Sriram

    2012-06-15

    Glycosyltransferases (glycoTs) catalyze the transfer of monosaccharides from nucleotide-sugars to carbohydrate-, lipid-, and protein-based acceptors. We examined strategies to scale down and increase the throughput of glycoT enzymatic assays because traditional methods require large reaction volumes and complex chromatography. Approaches tested used (i) microarray pin printing, an appropriate method when glycoT activity was high; (ii) microwells and microcentrifuge tubes, a suitable method for studies with cell lysates when enzyme activity was moderate; and (iii) C(18) pipette tips and solvent extraction, a method that enriched reaction product when the extent of reaction was low. In all cases, reverse-phase thin layer chromatography (RP-TLC) coupled with phosphorimaging quantified the reaction rate. Studies with mouse embryonic stem cells (mESCs) demonstrated an increase in overall β(1,3)galactosyltransferase and α(2,3)sialyltransferase activity and a decrease in α(1,3)fucosyltransferases when these cells differentiate toward cardiomyocytes. Enzymatic and lectin binding data suggest a transition from Lewis(x)-type structures in mESCs to sialylated Galβ1,3GalNAc-type glycans on differentiation, with more prominent changes in enzyme activity occurring at later stages when embryoid bodies differentiated toward cardiomyocytes. Overall, simple, rapid, quantitative, and scalable glycoT activity analysis methods are presented. These use a range of natural and synthetic acceptors for the analysis of complex biological specimens that have limited availability. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. HuAc: Human Activity Recognition Using Crowdsourced WiFi Signals and Skeleton Data

    Directory of Open Access Journals (Sweden)

    Linlin Guo

    2018-01-01

    Full Text Available The joint of WiFi-based and vision-based human activity recognition has attracted increasing attention in the human-computer interaction, smart home, and security monitoring fields. We propose HuAc, the combination of WiFi-based and Kinect-based activity recognition system, to sense human activity in an indoor environment with occlusion, weak light, and different perspectives. We first construct a WiFi-based activity recognition dataset named WiAR to provide a benchmark for WiFi-based activity recognition. Then, we design a mechanism of subcarrier selection according to the sensitivity of subcarriers to human activities. Moreover, we optimize the spatial relationship of adjacent skeleton joints and draw out a corresponding relationship between CSI and skeleton-based activity recognition. Finally, we explore the fusion information of CSI and crowdsourced skeleton joints to achieve the robustness of human activity recognition. We implemented HuAc using commercial WiFi devices and evaluated it in three kinds of scenarios. Our results show that HuAc achieves an average accuracy of greater than 93% using WiAR dataset.

  14. TECHNOLOGY AND INNOVATION IN HUMAN ACTIVITY OF THE INFORMATION AGE: HUMAN AND ICT

    Directory of Open Access Journals (Sweden)

    Oleksandr Yu. Burov

    2016-01-01

    Full Text Available In the article a brief overview of projects initiated by the U.S. National Science Foundation that related to new knowledge on integration and mutual development of social systems is proposed. The projects have a potential for transformation of science and researches, improvement of life quality and economy prosperity, as well as they should ensure outrunning development of information and communication technologies for all spheres of human activity: anthropocentric computerization, integration of information and informatics, robust intelligence, cyber-human systems, as well as two cross-technical areas - human and/or robots interaction, security and information protection.

  15. Functional assessment of human enhancer activities using whole-genome STARR-sequencing.

    Science.gov (United States)

    Liu, Yuwen; Yu, Shan; Dhiman, Vineet K; Brunetti, Tonya; Eckart, Heather; White, Kevin P

    2017-11-20

    Genome-wide quantification of enhancer activity in the human genome has proven to be a challenging problem. Recent efforts have led to the development of powerful tools for enhancer quantification. However, because of genome size and complexity, these tools have yet to be applied to the whole human genome.  In the current study, we use a human prostate cancer cell line, LNCaP as a model to perform whole human genome STARR-seq (WHG-STARR-seq) to reliably obtain an assessment of enhancer activity. This approach builds upon previously developed STARR-seq in the fly genome and CapSTARR-seq techniques in targeted human genomic regions. With an improved library preparation strategy, our approach greatly increases the library complexity per unit of starting material, which makes it feasible and cost-effective to explore the landscape of regulatory activity in the much larger human genome. In addition to our ability to identify active, accessible enhancers located in open chromatin regions, we can also detect sequences with the potential for enhancer activity that are located in inaccessible, closed chromatin regions. When treated with the histone deacetylase inhibitor, Trichostatin A, genes nearby this latter class of enhancers are up-regulated, demonstrating the potential for endogenous functionality of these regulatory elements. WHG-STARR-seq provides an improved approach to current pipelines for analysis of high complexity genomes to gain a better understanding of the intricacies of transcriptional regulation.

  16. Human Activity-Understanding: A Multilayer Approach Combining Body Movements and Contextual Descriptors Analysis

    Directory of Open Access Journals (Sweden)

    Consuelo Granata

    2015-07-01

    Full Text Available A deep understanding of human activity is key to successful human-robot interaction (HRI. The translation of sensed human behavioural signals/cues and context descriptors into an encoded human activity remains a challenge because of the complex nature of human actions. In this paper, we propose a multilayer framework for the understanding of human activity to be implemented in a mobile robot. It consists of a perception layer which exploits a D-RGB-based skeleton tracking output used to simulate a physical model of virtual human dynamics in order to compensate for the inaccuracy and inconsistency of the raw data. A multi-support vector machine (MSVM model trained with features describing the human motor coordination through temporal segments in combination with environment descriptors (object affordance is used to recognize each sub-activity (classification layer. The interpretation of sequences of classified elementary actions is based on discrete hidden Markov models (DHMMs (interpretation layer. The framework assessment was performed on the Cornell Activity Dataset (CAD-120 [1]. The performances of our method are comparable with those presented in [2] and clearly show the relevance of this model-based approach.

  17. Ensemble Manifold Rank Preserving for Acceleration-Based Human Activity Recognition.

    Science.gov (United States)

    Tao, Dapeng; Jin, Lianwen; Yuan, Yuan; Xue, Yang

    2016-06-01

    With the rapid development of mobile devices and pervasive computing technologies, acceleration-based human activity recognition, a difficult yet essential problem in mobile apps, has received intensive attention recently. Different acceleration signals for representing different activities or even a same activity have different attributes, which causes troubles in normalizing the signals. We thus cannot directly compare these signals with each other, because they are embedded in a nonmetric space. Therefore, we present a nonmetric scheme that retains discriminative and robust frequency domain information by developing a novel ensemble manifold rank preserving (EMRP) algorithm. EMRP simultaneously considers three aspects: 1) it encodes the local geometry using the ranking order information of intraclass samples distributed on local patches; 2) it keeps the discriminative information by maximizing the margin between samples of different classes; and 3) it finds the optimal linear combination of the alignment matrices to approximate the intrinsic manifold lied in the data. Experiments are conducted on the South China University of Technology naturalistic 3-D acceleration-based activity dataset and the naturalistic mobile-devices based human activity dataset to demonstrate the robustness and effectiveness of the new nonmetric scheme for acceleration-based human activity recognition.

  18. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

    Directory of Open Access Journals (Sweden)

    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  19. Human Activity Recognition by Combining a Small Number of Classifiers.

    Science.gov (United States)

    Nazabal, Alfredo; Garcia-Moreno, Pablo; Artes-Rodriguez, Antonio; Ghahramani, Zoubin

    2016-09-01

    We consider the problem of daily human activity recognition (HAR) using multiple wireless inertial sensors, and specifically, HAR systems with a very low number of sensors, each one providing an estimation of the performed activities. We propose new Bayesian models to combine the output of the sensors. The models are based on a soft outputs combination of individual classifiers to deal with the small number of sensors. We also incorporate the dynamic nature of human activities as a first-order homogeneous Markov chain. We develop both inductive and transductive inference methods for each model to be employed in supervised and semisupervised situations, respectively. Using different real HAR databases, we compare our classifiers combination models against a single classifier that employs all the signals from the sensors. Our models exhibit consistently a reduction of the error rate and an increase of robustness against sensor failures. Our models also outperform other classifiers combination models that do not consider soft outputs and an Markovian structure of the human activities.

  20. A Flexible Approach for Human Activity Recognition Using Artificial Hydrocarbon Networks.

    Science.gov (United States)

    Ponce, Hiram; Miralles-Pechuán, Luis; Martínez-Villaseñor, María de Lourdes

    2016-10-25

    Physical activity recognition based on sensors is a growing area of interest given the great advances in wearable sensors. Applications in various domains are taking advantage of the ease of obtaining data to monitor personal activities and behavior in order to deliver proactive and personalized services. Although many activity recognition systems have been developed for more than two decades, there are still open issues to be tackled with new techniques. We address in this paper one of the main challenges of human activity recognition: Flexibility. Our goal in this work is to present artificial hydrocarbon networks as a novel flexible approach in a human activity recognition system. In order to evaluate the performance of artificial hydrocarbon networks based classifier, experimentation was designed for user-independent, and also for user-dependent case scenarios. Our results demonstrate that artificial hydrocarbon networks classifier is flexible enough to be used when building a human activity recognition system with either user-dependent or user-independent approaches.

  1. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies.

    Science.gov (United States)

    Correa, Néstor; Covarrubias, Cristian; Rodas, Paula I; Hermosilla, Germán; Olate, Verónica R; Valdés, Cristián; Meyer, Wieland; Magne, Fabien; Tapia, Cecilia V

    2017-01-01

    Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an important virulence factor. To evaluate if cryptococcal and human melanins have antifungal activity against Cryptococcus species they both were assayed for their antifungal properties and physico-chemical characters. Melanin extracts from human hair and different strains of C. neoformans ( n = 4) and C. gattii ( n = 4) were investigated. The following minimum inhibitory concentrations were found for different melanins against C. neoformans and C. gattii were (average/range): 13.7/(7.8-15.6) and 19.5/(15.6-31.2) μg/mL, respectively, for human melanin; 273.4/(125->500) and 367.2/(125.5->500) μg/mL for C. neoformans melanin and 125/(62.5-250) and 156.2/(62-250) μg/mL for C. gattii melanin. Using Scanning Electron Microscopy we observed that human melanin showed a compact conformation and cryptococcal melanins exposed an amorphous conformation. Infrared spectroscopy (FTIR) showed some differences in the signals related to C-C bonds of the aromatic ring of the melanin monomers. High Performance Liquid Chromatography established differences in the chromatograms of fungal melanins extracts in comparison with human and synthetic melanin, particularly in the retention time of the main compound of fungal melanin extracts and also in the presence of minor unknown compounds. On the other hand, MALDI-TOF-MS analysis showed slight differences in the spectra, specifically the presence of a minor intensity ion in synthetic and human melanin, as well as in some fungal melanin extracts. We

  2. Profiling gene expression induced by protease-activated receptor 2 (PAR2 activation in human kidney cells.

    Directory of Open Access Journals (Sweden)

    Jacky Y Suen

    Full Text Available Protease-Activated Receptor-2 (PAR2 has been implicated through genetic knockout mice with cytokine regulation and arthritis development. Many studies have associated PAR2 with inflammatory conditions (arthritis, airways inflammation, IBD and key events in tumor progression (angiogenesis, metastasis, but they have relied heavily on the use of single agonists to identify physiological roles for PAR2. However such probes are now known not to be highly selective for PAR2, and thus precisely what PAR2 does and what mechanisms of downstream regulation are truly affected remain obscure. Effects of PAR2 activation on gene expression in Human Embryonic Kidney cells (HEK293, a commonly studied cell line in PAR2 research, were investigated here by comparing 19,000 human genes for intersecting up- or down-regulation by both trypsin (an endogenous protease that activates PAR2 and a PAR2 activating hexapeptide (2f-LIGRLO-NH(2. Among 2,500 human genes regulated similarly by both agonists, there were clear associations between PAR2 activation and cellular metabolism (1,000 genes, the cell cycle, the MAPK pathway, HDAC and sirtuin enzymes, inflammatory cytokines, and anti-complement function. PAR-2 activation up-regulated four genes more than 5 fold (DUSP6, WWOX, AREG, SERPINB2 and down-regulated another six genes more than 3 fold (TXNIP, RARG, ITGB4, CTSD, MSC and TM4SF15. Both PAR2 and PAR1 activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1, SDC4 known to be important in cancer. This is the first widespread profiling of specific activation of PAR2 and provides a valuable platform for better understanding key mechanistic roles of PAR2 in human physiology. Results clearly support the development of both antagonists and agonists of human PAR2 as potential disease modifying therapeutic agents.

  3. Effect of losartan on human platelet activation.

    Science.gov (United States)

    Guerra-Cuesta, J I; Montón, M; Rodríguez-Feo, J A; Jiménez, A M; González-Fernández, F; Rico, L A; García, R; Gómez, J; Farré, J; Casado, S; López-Farré, A

    1999-03-01

    Previous studies have demonstrated that losartan can block the thromboxane A2 receptor on the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men, aged 26-40 years. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by the thromboxane A2 analog U46619 (5 x 10(-6) mol/l) or ADP (10(-5) mol/l). U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-dependent manner. Only a high dose of EXP 3174 (5 x 10(-5) mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I converting inhibitor, failed to modify U46619-induced platelet aggregation. Furthermore, the binding of [3H]-U46619 to platelets was competitively inhibited by losartan, whereas only a high dose of EXP 3174 reduced the binding of [3H]-U46619. Captopril failed to modify the binding of [3H]-U46619 to platelets. Losartan also reduced the platelet activation induced by ADP (10(-5) mol/l), a platelet agonist partially dependent on thromboxane A2. In addition, when thromboxane A2 generation was blocked by aspirin, ADP-induced platelet aggregation was inhibited to a similar degree to the inhibition induced by losartan. Exogenous angiotensin II did not elicit any modification of either U46619- or ADP-stimulated platelet aggregation. Losartan decreased platelet aggregation by a thromboxane A2-dependent mechanism. EXP 3174 was less potent than losartan in reducing thromboxane A2-dependent platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced thromboxane A2-dependent platelet activation independently of its effect on angiotensin II.

  4. Metabolic activity and collagen turnover in human tendon in response to physical activity

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, H; Miller, B F

    2005-01-01

    Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene...... of overuse tendon injuries occurring during sport, work or leisure-related activities....

  5. Differential effects of human activity on Hawaiian spinner dolphins in their resting bays

    Directory of Open Access Journals (Sweden)

    Heather L. Heenehan

    2017-04-01

    Full Text Available Hawaiian spinner dolphins display predictable daily behavior, using shallow bays to rest during the daytime, bays that are also frequented by humans. All previous research on the potential response of Hawaiian spinner dolphins to human activity has been conducted visually, at the surface. In this study we take a different approach by using passive acoustic monitoring to analyze dolphin behavior and assess whether human activity affects the behavior of the animals. We used days (n=99 and hours (n=641 when dolphins were confirmed present in visual surveys between January 9, 2011 and August 15, 2012 and metrics generated from concomitant 30-second sound recordings (n=9615. Previous research found that the dolphins were predictably silent during rest and that acoustic activity matched general activity of the dolphins with higher acoustic activity before and after rest, and silence during rest. The daily pattern of dolphin whistle activity in Bay 2 and 4 (Kealakekua and Kauhako matched what would be expected from this earlier work. However, in Bay 1 and 3 (Makako and Honaunau there was no drop in dolphin whistle activity during rest. After assessing the relationship between time of day and dolphin acoustic activity, data on human presence were used to determine how variability in the dolphins’ acoustic activity might be explained by human activity (i.e. the number of vessels, kayaks and swimmer snorkelers present. Bay 2, the bay with the most human activity, showed no relationship between dolphin whistle activity and human presence (either vessels, kayaks, or swimmer/snorkelers. Although the relationships were weak, Bay 1 displayed a positive relationship between dolphin whistle activity and the number of vessels and swimmer/snorkelers present in the bay. Bay 4 also showed a positive relationship between dolphin whistle activity and the number of swimmer snorkelers. We also documented less sound being added to the soundscape with each additional

  6. Tactile interactions activate mirror system regions in the human brain.

    Science.gov (United States)

    McKyton, Ayelet

    2011-12-07

    Communicating with others is essential for the development of a society. Although types of communications, such as language and visual gestures, were thoroughly investigated in the past, little research has been done to investigate interactions through touch. To study this we used functional magnetic resonance imaging. Twelve participants were scanned with their eyes covered while stroking four kinds of items, representing different somatosensory stimuli: a human hand, a realistic rubber hand, an object, and a simple texture. Although the human and the rubber hands had the same overall shape, in three regions there was significantly more blood oxygen level dependent activation when touching the real hand: the anterior medial prefrontal cortex, the ventral premotor cortex, and the posterior superior temporal cortex. The last two regions are part of the mirror network and are known to be activated through visual interactions such as gestures. Interestingly, in this study, these areas were activated through a somatosensory interaction. A control experiment was performed to eliminate confounds of temperature, texture, and imagery, suggesting that the activation in these areas was correlated with the touch of a human hand. These results reveal the neuronal network working behind human tactile interactions, and highlight the participation of the mirror system in such functions.

  7. Human activity spaces and plague risks in three contrasting ...

    African Journals Online (AJOL)

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto ...

  8. Cytotoxic activities of Coriolus versicolor (Yunzhi) extracts on human ...

    African Journals Online (AJOL)

    SERVER

    2007-08-06

    Aug 6, 2007 ... four human liver cancer (7703, HepG2, 7721, PLC) and four human breast cancer (Bcap37, ZR75-30,. MCF-7, T-47D) cell lines ... Key words: Coriolus versicolor, fruit body, polysaccharide, anti-tumor. INTRODUCTION. Coriolus ... somewhat in structure, composition, and physiological activity. The present ...

  9. Selective activation of neuromuscular compartments within the human trapezius muscle

    DEFF Research Database (Denmark)

    Holtermann, A; Roeleveld, K; Mork, P J

    2009-01-01

    of the human trapezius muscle can be independently activated by voluntary command, indicating neuromuscular compartmentalization of the trapezius muscle. The independent activation of the upper and lower subdivisions of the trapezius is in accordance with the selective innervation by the fine cranial and main...... branch of the accessory nerve to the upper and lower subdivisions. These findings provide new insight into motor control characteristics, learning possibilities, and function of the clinically relevant human trapezius muscle....

  10. Ex-vivo α-galactosylceramide activation of NKT cells in humans and macaques.

    Science.gov (United States)

    Fernandez, Caroline S; Cameron, Garth; Godfrey, Dale I; Kent, Stephen J

    2012-08-31

    NKT cells are key mediators of antiviral and anticancer immunity. Experiments in mice have demonstrated that activation of NKT cells in vivo induces the expression of multiple effector molecules critical to successful immunity. Human clinical trials have shown similar responses, although in vivo activation of NKT cells in humans or primate models are far more limited in number and scope. Measuring ex vivo activation of NKT cells by the CD1d-restricted glycolipid ligand α-Galactosylceramide (α-GalCer) through cytokine expression profiles is a useful marker of NKT cell function, but for reasons that are unclear, this approach does not appear to work as well in humans and non-human primate macaque models in comparison to mice. We performed a series of experiments on human and macaque (Macaca nemestrina) fresh whole blood samples to define optimal conditions to detect NKT cell cytokine (TNF, IFNγ, IL-2) and degranulation marker (CD107a) expression by flow cytometry. We found that conditions previously described for mouse splenocyte NKT cell activation were suboptimal on human or macaque blood NKT cells. In contrast, a 6h incubation with brefeldin A added for the last 4h, in a 96-well plate based assay, and using an α-GalCer concentration of 1 μg/ml were optimal methods to stimulate NKT cells in fresh blood from both humans and macaques. Unexpectedly, we noted that blood NKT cells from macaques infected with SIV were more readily activated by α-GalCer than NKT cells from uninfected macaques, suggesting that SIV infection may have primed the NKT cells. In conclusion, we describe optimized methods for the ex vivo antigen-specific activation of human and macaque blood NKT cells. These assays should be useful in monitoring NKT cells in disease and in immunotherapy studies. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Understanding Usability Work as a Human Activity

    DEFF Research Database (Denmark)

    Nørgaard, Mie

    Three core themes are explored in eight papers: Usability work as a human activity, usability practice and methods, and persuasiveness of evaluation results and feedback. We explore how usability work is much more than methods and work procedures, and argue that maturing our understanding...

  12. A THREE-STEP SPATIAL-TEMPORAL-SEMANTIC CLUSTERING METHOD FOR HUMAN ACTIVITY PATTERN ANALYSIS

    Directory of Open Access Journals (Sweden)

    W. Huang

    2016-06-01

    Full Text Available How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time to four dimensions (space, time and semantics. More specifically, not only a location and time that people stay and spend are collected, but also what people “say” for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The

  13. Nuclear factor-kappaB activation correlates with better prognosis and Akt activation in human gastric cancer.

    Science.gov (United States)

    Lee, Byung Lan; Lee, Hye Seung; Jung, Jieun; Cho, Sung Jin; Chung, Hee-Yong; Kim, Woo Ho; Jin, Young-Woo; Kim, Chong Soon; Nam, Seon Young

    2005-04-01

    Because the biological significance of constitutive nuclear factor-kappaB (NF-kappaB) activation in human gastric cancer is unclear, we undertook this study to clarify the regulatory mechanism of NF-kappaB activation and its clinical significance. Immunohistochemistry for NF-kappaB/RelA was done on 290 human gastric carcinoma specimens placed on tissue array slides. The correlations between NF-kappaB activation and clinicopathologic features, prognosis, Akt activation, tumor suppressor gene expression, or Bcl-2 expression were analyzed. We also did luciferase reporter assay, Western blot analysis, and reverse transcription-PCR using the SNU-216 human gastric cancer cell line transduced with retroviral vectors containing constitutively active Akt or the NF-kappaB repressor mutant of IkappaBalpha. Nuclear expression of RelA was found in 18% of the gastric carcinomas and was higher in early-stage pathologic tumor-node-metastasis (P = 0.019). A negative correlation was observed between NF-kappaB activation and lymphatic invasion (P = 0.034) and a positive correlation between NF-kappaB activation and overall survival rate of gastric cancer patients (P = 0.0228). In addition, NF-kappaB activation was positively correlated with pAkt (P = 0.047), p16 (P = 0.004), adenomatous polyposis coli (P Smad4 (P = 0.002), and kangai 1 (P Akt. NF-kappaB activation was frequently observed in early-stage gastric carcinoma and was significantly correlated with better prognosis and Akt activation. These findings suggest that NF-kappaB activation is a valuable prognostic variable in gastric carcinoma.

  14. Monitoring Human Activity through Portable Devices

    Directory of Open Access Journals (Sweden)

    G. Sebestyen

    2012-06-01

    Full Text Available Monitoring human activity may be useful for medical supervision and for prophylactic purposes. Mobile devices like intelligent phones or watches have multiple sensors and wireless communication capabilities which can be used for this purpose. This paper presents some integrated solutions for determining and continuous monitoring of a person’s state. Aspects taken into consideration are: activity detection and recognition based on acceleration sensors, wireless communication protocols for data acquisition, web monitoring, alerts generation and statistical processing of multiple sensorial data. As practical implementations two case studies are presented, one using an intelligent phone and another using a mixed signal processor integrated in a watch.

  15. Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

    Science.gov (United States)

    Ito, Yuki; Nakamura, Toshiki; Yanagiba, Yukie; Ramdhan, Doni Hikmat; Yamagishi, Nozomi; Naito, Hisao; Kamijima, Michihiro; Gonzalez, Frank J.; Nakajima, Tamie

    2012-01-01

    Dibutylphthalate (DBP), di(2-ethylhexyl)phthalate (DEHP), and di(2-ethylhexyl)adipate (DEHA) are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR) α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα) and humanized PPARα (hPPARα) mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control), 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg), DEHP (977, 1953 mg/kg), and DEHA (926, 1853 mg/kg), respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR) more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR. PMID:22792086

  16. Plasticizers May Activate Human Hepatic Peroxisome Proliferator-Activated Receptor α Less Than That of a Mouse but May Activate Constitutive Androstane Receptor in Liver

    Directory of Open Access Journals (Sweden)

    Yuki Ito

    2012-01-01

    Full Text Available Dibutylphthalate (DBP, di(2-ethylhexylphthalate (DEHP, and di(2-ethylhexyladipate (DEHA are used as plasticizers. Their metabolites activate peroxisome proliferator-activated receptor (PPAR α, which may be related to their toxicities. However, species differences in the receptor functions between rodents and human make it difficult to precisely extrapolate their toxicity from animal studies to human. In this paper, we compared the species differences in the activation of mouse and human hepatic PPARα by these plasticizers using wild-type (mPPARα and humanized PPARα (hPPARα mice. At 12 weeks old, each genotyped male mouse was classified into three groups, and fed daily for 2 weeks per os with corn oil (vehicle control, 2.5 or 5.0 mmol/kg DBP (696, 1392 mg/kg, DEHP (977, 1953 mg/kg, and DEHA (926, 1853 mg/kg, respectively. Generally, hepatic PPARα of mPPARα mice was more strongly activated than that of hPPARα mice when several target genes involving β-oxidation of fatty acids were evaluated. Interestingly, all plasticizers also activated hepatic constitutive androstane receptor (CAR more in hPPARα mice than in mPPARα mice. Taken together, these plasticizers activated mouse and human hepatic PPARα as well as CAR. The activation of PPARα was stronger in mPPARα mice than in hPPARα mice, while the opposite was true of CAR.

  17. Aloe vera extract activity on human corneal cells.

    Science.gov (United States)

    Woźniak, Anna; Paduch, Roman

    2012-02-01

    Ocular diseases are currently an important problem in modern societies. Patients suffer from various ophthalmologic ailments namely, conjunctivitis, dry eye, dacryocystitis or degenerative diseases. Therefore, there is a need to introduce new treatment methods, including medicinal plants usage. Aloe vera [Aloe barbadensis Miller (Liliaceae)] possesses wound-healing properties and shows immunomodulatory, anti-inflammatory or antioxidant activities. NR uptake, MTT, DPPH• reduction, Griess reaction, ELISA and rhodamine-phalloidin staining were used to test toxicity, antiproliferative activity, reactive oxygen species (ROS) reduction, nitric oxide (NO) and cytokine level, and distribution of F-actin in cells, respectively. The present study analyzes the effect of Aloe vera extracts obtained with different solvents on in vitro culture of human 10.014 pRSV-T corneal cells. We found no toxicity of ethanol, ethyl acetate and heptane extracts of Aloe vera on human corneal cells. No ROS reducing activity by heptane extract and trace action by ethanol (only at high concentration 125 µg/ml) extract of Aloe vera was observed. Only ethyl acetate extract expressed distinct free radical scavenging effect. Plant extracts decreased NO production by human corneal cells as compared to untreated controls. The cytokine (IL-1β, IL-6, TNF-α and IL-10) production decreased after the addition of Aloe vera extracts to the culture media. Aloe vera contains multiple pharmacologically active substances which are capable of modulating cellular phenotypes and functions. Aloe vera ethanol and ethyl acetate extracts may be used in eye drops to treat inflammations and other ailments of external parts of the eye such as the cornea.

  18. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

    Directory of Open Access Journals (Sweden)

    Néstor Correa

    2017-07-01

    Full Text Available Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an important virulence factor. To evaluate if cryptococcal and human melanins have antifungal activity against Cryptococcus species they both were assayed for their antifungal properties and physico-chemical characters. Melanin extracts from human hair and different strains of C. neoformans (n = 4 and C. gattii (n = 4 were investigated. The following minimum inhibitory concentrations were found for different melanins against C. neoformans and C. gattii were (average/range: 13.7/(7.8–15.6 and 19.5/(15.6–31.2 μg/mL, respectively, for human melanin; 273.4/(125–>500 and 367.2/(125.5–>500 μg/mL for C. neoformans melanin and 125/(62.5–250 and 156.2/(62–250 μg/mL for C. gattii melanin. Using Scanning Electron Microscopy we observed that human melanin showed a compact conformation and cryptococcal melanins exposed an amorphous conformation. Infrared spectroscopy (FTIR showed some differences in the signals related to C-C bonds of the aromatic ring of the melanin monomers. High Performance Liquid Chromatography established differences in the chromatograms of fungal melanins extracts in comparison with human and synthetic melanin, particularly in the retention time of the main compound of fungal melanin extracts and also in the presence of minor unknown compounds. On the other hand, MALDI-TOF-MS analysis showed slight differences in the spectra, specifically the presence of a minor intensity ion in synthetic and human melanin, as well as in some fungal

  19. Setting the scene: Human activities, environmental impacts and governance arrangements in Antarctica

    NARCIS (Netherlands)

    Tin, T.; Lamers, M.A.J.; Liggett, D.; Maher, P.T.; Hughes, K.A.

    2014-01-01

    The scope and intensity of human activity in the Antarctic region has changed considerably over the past 100 years, resulting in significant modifications to the Antarctic environment and its ecosystems, and to the institutional arrangements governing human activities. Since the nineteenth century,

  20. Context-dependent spatially periodic activity in the human entorhinal cortex.

    Science.gov (United States)

    Nadasdy, Zoltan; Nguyen, T Peter; Török, Ágoston; Shen, Jason Y; Briggs, Deborah E; Modur, Pradeep N; Buchanan, Robert J

    2017-04-25

    The spatially periodic activity of grid cells in the entorhinal cortex (EC) of the rodent, primate, and human provides a coordinate system that, together with the hippocampus, informs an individual of its location relative to the environment and encodes the memory of that location. Among the most defining features of grid-cell activity are the 60° rotational symmetry of grids and preservation of grid scale across environments. Grid cells, however, do display a limited degree of adaptation to environments. It remains unclear if this level of environment invariance generalizes to human grid-cell analogs, where the relative contribution of visual input to the multimodal sensory input of the EC is significantly larger than in rodents. Patients diagnosed with nontractable epilepsy who were implanted with entorhinal cortical electrodes performing virtual navigation tasks to memorized locations enabled us to investigate associations between grid-like patterns and environment. Here, we report that the activity of human entorhinal cortical neurons exhibits adaptive scaling in grid period, grid orientation, and rotational symmetry in close association with changes in environment size, shape, and visual cues, suggesting scale invariance of the frequency, rather than the wavelength, of spatially periodic activity. Our results demonstrate that neurons in the human EC represent space with an enhanced flexibility relative to neurons in rodents because they are endowed with adaptive scalability and context dependency.

  1. Elevated personal exposure to particulate matter from human activities in a residence.

    Science.gov (United States)

    Ferro, Andrea R; Kopperud, Royal J; Hildemann, Lynn M

    2004-01-01

    Continuous laser particle counters collocated with time-integrated filter samplers were used to measure personal, indoor, and outdoor particulate matter (PM) concentrations for a variety of prescribed human activities during a 5-day experimental period in a home in Redwood City, CA, USA. The mean daytime personal exposures to PM(2.5) and PM(5) during prescribed activities were 6 and 17 times, respectively, as high as the pre-activity indoor background concentration. Activities that resulted in the highest exposures of PM(2.5), PM(5), and PM(10) were those that disturbed dust reservoirs on furniture and textiles, such as dry dusting, folding clothes and blankets, and making a bed. The vigor of activity and type of flooring were also important factors for dust resuspension. Personal exposures to PM(2.5) and PM(5) were 1.4 and 1.6 times, respectively, as high as the indoor concentration as measured by a stationary monitor. The ratio of personal exposure to the indoor concentration was a function of both particle size and the distance of the human activity from the stationary indoor monitor. The results demonstrate that a wide variety of indoor human resuspension activities increase human exposure to PM and contribute to the "personal cloud" effect.

  2. Incorporating twitter-based human activity information in spatial analysis of crashes in urban areas.

    Science.gov (United States)

    Bao, Jie; Liu, Pan; Yu, Hao; Xu, Chengcheng

    2017-09-01

    The primary objective of this study was to investigate how to incorporate human activity information in spatial analysis of crashes in urban areas using Twitter check-in data. This study used the data collected from the City of Los Angeles in the United States to illustrate the procedure. The following five types of data were collected: crash data, human activity data, traditional traffic exposure variables, road network attributes and social-demographic data. A web crawler by Python was developed to collect the venue type information from the Twitter check-in data automatically. The human activities were classified into seven categories by the obtained venue types. The collected data were aggregated into 896 Traffic Analysis Zones (TAZ). Geographically weighted regression (GWR) models were developed to establish a relationship between the crash counts reported in a TAZ and various contributing factors. Comparative analyses were conducted to compare the performance of GWR models which considered traditional traffic exposure variables only, Twitter-based human activity variables only, and both traditional traffic exposure and Twitter-based human activity variables. The model specification results suggested that human activity variables significantly affected the crash counts in a TAZ. The results of comparative analyses suggested that the models which considered both traditional traffic exposure and human activity variables had the best goodness-of-fit in terms of the highest R 2 and lowest AICc values. The finding seems to confirm the benefits of incorporating human activity information in spatial analysis of crashes using Twitter check-in data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The anti-papillomavirus activity of human and bovine lactoferricin.

    Science.gov (United States)

    Mistry, Nitesh; Drobni, Peter; Näslund, Jonas; Sunkari, Vivekananda Gupta; Jenssen, Håvard; Evander, Magnus

    2007-09-01

    Human papillomavirus (HPV) cause common warts, laryngeal papilloma and genital condylomata and is necessary for the development of cervical cancer. We have previously found that lactoferrin has antiviral activity against HPV-16 and others have demonstrated that lactoferricin, an N-terminal fragment of lactoferrin, has inhibitory activities against several viruses. Two cell lines and two virus types, HPV-5 and HPV-16, were used to study if lactoferrin and lactoferricin could inhibit HPV pseudovirus (PsV) infection. We demonstrated that bovine lactoferrin (bLf) and human lactoferrin (hLf) were both potent inhibitors of HPV-5 and -16 PsV infections. Among the four lactoferricin derivatives we analyzed, a 15 amino acid peptide from bovine lactoferricin (bLfcin) 17-31 was the most potent inhibitor of both HPV-5 and HPV-16 PsV infection. Among the other derivatives, the human lactoferricin (hLfcin) 1-49 showed some antiviral activity against HPV PsV infection while bLfcin 17-42 inhibited only HPV-5 PsV infection in one of the cell lines. When we studied initial attachment of HPV-16, only bLfcin 17-42 and hLfcin 1-49 had an antiviral effect. This is the first time that lactoferricin was demonstrated to have an inhibitory effect on HPV infection and the antiviral activity differed depending on size, charge and structures of the lactoferricin.

  4. Social touch modulates endogenous μ-opioid system activity in humans.

    Science.gov (United States)

    Nummenmaa, Lauri; Tuominen, Lauri; Dunbar, Robin; Hirvonen, Jussi; Manninen, Sandra; Arponen, Eveliina; Machin, Anna; Hari, Riitta; Jääskeläinen, Iiro P; Sams, Mikko

    2016-09-01

    In non-human primates, opioid-receptor blockade increases social grooming, and the endogenous opioid system has therefore been hypothesized to support maintenance of long-term relationships in humans as well. Here we tested whether social touch modulates opioidergic activation in humans using in vivo positron emission tomography (PET). Eighteen male participants underwent two PET scans with [11C]carfentanil, a ligand specific to μ-opioid receptors (MOR). During the social touch scan, the participants lay in the scanner while their partners caressed their bodies in a non-sexual fashion. In the baseline scan, participants lay alone in the scanner. Social touch triggered pleasurable sensations and increased MOR availability in the thalamus, striatum, and frontal, cingulate, and insular cortices. Modulation of activity of the opioid system by social touching might provide a neurochemical mechanism reinforcing social bonds between humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Prediction of Human Activity by Discovering Temporal Sequence Patterns.

    Science.gov (United States)

    Li, Kang; Fu, Yun

    2014-08-01

    Early prediction of ongoing human activity has become more valuable in a large variety of time-critical applications. To build an effective representation for prediction, human activities can be characterized by a complex temporal composition of constituent simple actions and interacting objects. Different from early detection on short-duration simple actions, we propose a novel framework for long -duration complex activity prediction by discovering three key aspects of activity: Causality, Context-cue, and Predictability. The major contributions of our work include: (1) a general framework is proposed to systematically address the problem of complex activity prediction by mining temporal sequence patterns; (2) probabilistic suffix tree (PST) is introduced to model causal relationships between constituent actions, where both large and small order Markov dependencies between action units are captured; (3) the context-cue, especially interactive objects information, is modeled through sequential pattern mining (SPM), where a series of action and object co-occurrence are encoded as a complex symbolic sequence; (4) we also present a predictive accumulative function (PAF) to depict the predictability of each kind of activity. The effectiveness of our approach is evaluated on two experimental scenarios with two data sets for each: action-only prediction and context-aware prediction. Our method achieves superior performance for predicting global activity classes and local action units.

  6. Elastolytic activity of human blood monocytes characterized by a new monoclonal antibody against human leucocyte elastase. Relationship to rheumatoid arthritis

    DEFF Research Database (Denmark)

    Jensen, H S; Christensen, L D

    1990-01-01

    The leucocyte elastase of human blood monocytes was investigated by applying a new monoclonal antibody which did not block the enzyme activity against elastin. In a fixed population of mononuclear cells (MNC) and using fluorescence activated cell sorting (FACS), the human leucocyte elastase (HLE...

  7. Robust, synergistic regulation of human gene expression using TALE activators.

    Science.gov (United States)

    Maeder, Morgan L; Linder, Samantha J; Reyon, Deepak; Angstman, James F; Fu, Yanfang; Sander, Jeffry D; Joung, J Keith

    2013-03-01

    Artificial activators designed using transcription activator-like effector (TALE) technology have broad utility, but previous studies suggest that these monomeric proteins often exhibit low activities. Here we demonstrate that TALE activators can robustly function individually or in synergistic combinations to increase expression of endogenous human genes over wide dynamic ranges. These findings will encourage applications of TALE activators for research and therapy, and guide design of monomeric TALE-based fusion proteins.

  8. 3D Data Acquisition Platform for Human Activity Understanding

    Science.gov (United States)

    2016-03-02

    SECURITY CLASSIFICATION OF: In this project, we incorporated motion capture devices, 3D vision sensors, and EMG sensors to cross validate...multimodality data acquisition, and address fundamental research problems of representation and invariant description of 3D data, human motion modeling and...applications of human activity analysis, and computational optimization of large-scale 3D data. The support for the acquisition of such research

  9. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposi-tion of human activity and inactivity that may lead to a profound understanding of the essence, causes and existen-tial aspects of human activity and inactivity. The implementation of the objective assumes the solution of the follow-ing tasks: analysis of philosophical interpretation of fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inac-tivity through the opposition of fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of hu-man activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authen-tic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific nov-elty. For the first time the analysis of the fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the fundamental existential character of the fear and courage opposition and its es-sential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being. If classical philosophy placed emphasis on courage and associated fear with human mind and conscious decision, non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental mean

  10. COURAGE AND FEAR IN THE CONTEXT OF OPPOSITION OF HUMAN ACTIVITY AND INACTIVITY: EXISTENTIAL ASPECT

    Directory of Open Access Journals (Sweden)

    Dmytro Yu. Snitko

    2013-12-01

    Full Text Available The purpose of the article is to analyse fear and courage in the history of philosophy in the context of opposition of human activity and inactivity that may lead to a profound understanding of the essence, causes and existential aspects of human activity and inactivity. The implementation of the objective assumes the solution of the following tasks: analysis of philosophical interpretation of  fear and courage; investigation of the relationship of fear and courage with active and passive forms of human being; revelation of existential dialectic of human activity and inactivity through the opposition of  fear and courage. Methodology. The application of phenomenological approach and other methods of existential philosophy enabled to discover the importance of fear and courage for human existence. Significant contribution to the importance of the investigation of the fear-courage opposition in the context of human activity and inactivity was made by M. Heidegger who pointed to the main modes of human being - «authentic» and «inauthentic» in the context of human activity and passivity. The application of hermeneutic method made possible the reconstruction of the reflection of fear-courage opposition in the history of philosophy. Scientific novelty. For the first time the analysis of the  fear-courage opposition in the context of human activity and inactivity was carried out. Due to the analysis the  fundamental existential character of the fear and courage opposition and its essential relationship with active and passive forms of human being were justified. Conclusions. In the course of this research it was found out that fear is closely connected with passive modes of human being.  If classical philosophy placed emphasis on courage and associated fear with  human mind and conscious decision,  non-classical philosophy of the XIX century and existentialism focused on existential and ontological character of fear, its fundamental meaning

  11. SRS-A leukotrienes decrease the activity of human respiratory cilia

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, M

    1987-01-01

    We have studied the effects of the slow reacting substance of anaphylaxis (SRS-A) constituents leukotrienes (LT) C4 and D4 on the ciliary activity of human respiratory cells. The ciliary beat frequency on human nasal cells harvested by cell scraping from the inferior turbinate was measured...

  12. Human Activity Recognition Using Hierarchically-Mined Feature Constellations

    NARCIS (Netherlands)

    Oikonomopoulos, A.; Pantic, Maja

    In this paper we address the problem of human activity modelling and recognition by means of a hierarchical representation of mined dense spatiotemporal features. At each level of the hierarchy, the proposed method selects feature constellations that are increasingly discriminative and

  13. Dioxin-like activity of environmental compounds in human blood and environmental samples

    DEFF Research Database (Denmark)

    Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

  14. Dioxin-like activity in environmental and human samples from Greenland and Denmark

    DEFF Research Database (Denmark)

    Long, Manhai; Bonefeld-Jørgensen, Eva Cecilie

    2012-01-01

    and humans. We found that some pesticides, plasticizers and phytoestrogens can activate the AhR, and the combined effect of compounds with no or weak AhR potency cannot be ignored. The significant DL-activity in the wastewater effluent indicates the treatment is not sufficient to prevent contamination...... of surface waters with dioxins. Our results from human studies suggest that the serum DL-activity reflect the complex mixture of persistent organic pollutants (POPs). Greenlandic Inuit had lower serum DL-activity level compared to Europeans, probably due to long distance from the dioxin sources and UV...

  15. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity.

    Science.gov (United States)

    Dolinska, Monika B; Kovaleva, Elena; Backlund, Peter; Wingfield, Paul T; Brooks, Brian P; Sergeev, Yuri V

    2014-01-01

    Tyrosinase (TYR) catalyzes the rate-limiting, first step in melanin production and its gene (TYR) is mutated in many cases of oculocutaneous albinism (OCA1), an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1.

  16. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Monika B Dolinska

    Full Text Available Tyrosinase (TYR catalyzes the rate-limiting, first step in melanin production and its gene (TYR is mutated in many cases of oculocutaneous albinism (OCA1, an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes.The intra-melanosomal domain of human tyrosinase (residues 19-469 and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure.The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1.

  17. Immediate-early gene region of human cytomegalovirus trans-activates the promoter of human immunodeficiency virus

    International Nuclear Information System (INIS)

    Davis, M.G.; Kenney, S.C.; Kamine, J.; Pagano, J.S.; Huang, E.S.

    1987-01-01

    Almost all homosexual patients with acquired immunodeficiency syndrome are also actively infected with human cytomegalovirus (HCMV). The authors have hypothesized that an interaction between HCMV and human immunodeficiency virus (HIV), the agent that causes acquired immunodeficiency syndrome, may exist at a molecular level and contribute to the manifestations of HIV infection. In this report, they demonstrate that the immediate-early gene region of HCMV, in particular immediate-early region 2, trans-activates the expression of the bacterial gene chloramphenicol acetyltransferase that is fused to the HIV long terminal repeat and carried by plasmid pHIV-CAT. The HCMV immediate-early trans-activator increases the level of mRNA from the plamid pHIV-CAT. The sequences of HIV that are responsive to trans-activation by the HDMV immediate-early region are distinct from HIV sequences that are required for response to the HIV tat. The stimulation of HIV gene expression by HDMV gene functions could enhance the consequences of HIV infection in persons with previous or concurrent HCMV infection

  18. Report: EPA Prepared to Implement Strategic Human Capital Management Activities But Challenges Remain

    Science.gov (United States)

    Report #2004-P-00024, September 20, 2004. EPA’s headquarters and regional offices are prepared to implement strategic human capital management activities, but an alignment of office-level activities to the Agency’s Strategy for Human Capital is lacking.

  19. Application of activity theory to analysis of human-related accidents: Method and case studies

    International Nuclear Information System (INIS)

    Yoon, Young Sik; Ham, Dong-Han; Yoon, Wan Chul

    2016-01-01

    This study proposes a new approach to human-related accident analysis based on activity theory. Most of the existing methods seem to be insufficient for comprehensive analysis of human activity-related contextual aspects of accidents when investigating the causes of human errors. Additionally, they identify causal factors and their interrelationships with a weak theoretical basis. We argue that activity theory offers useful concepts and insights to supplement existing methods. The proposed approach gives holistic contextual backgrounds for understanding and diagnosing human-related accidents. It also helps identify and organise causal factors in a consistent, systematic way. Two case studies in Korean nuclear power plants are presented to demonstrate the applicability of the proposed method. Human Factors Analysis and Classification System (HFACS) was also applied to the case studies. The results of using HFACS were then compared with those of using the proposed method. These case studies showed that the proposed approach could produce a meaningful set of human activity-related contextual factors, which cannot easily be obtained by using existing methods. It can be especially effective when analysts think it is important to diagnose accident situations with human activity-related contextual factors derived from a theoretically sound model and to identify accident-related contextual factors systematically. - Highlights: • This study proposes a new method for analysing human-related accidents. • The method was developed based on activity theory. • The concept of activity system model and contradiction was used in the method. • Two case studies in nuclear power plants are presented. • The method is helpful to consider causal factors systematically and comprehensively.

  20. Immunosuppressive activity of human cord-blood lipoproteins

    International Nuclear Information System (INIS)

    Forte, T.M.; Davis, P.A.; Curtiss, L.K.

    1985-01-01

    It is now known that the role of plasma lipoproteins is multifunctional. More recently it has been shown that lipoproteins may regulate immune responses as well. Low-density lipoproteins carrying apolipoprotein B (apoB) are known to suppress phytohemagglutinin (PHA) activated lymphocytes by inhibiting DNA synthesis. More recently, an immunoregulatory role has been described for another apolipoprotein, apoE, which is found in low quantities in normal plasma. In these studies with human umbilical-cord blood the authors were intrigued by two factors: the low level of LDL and hence apoB, and the elevated quantity of apoE. This study examines the hypothesis that apoE may regulate lymphocyte function in the human fetus

  1. Human temporal cortical single neuron activity during working memory maintenance.

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-06-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  2. Human Temporal Cortical Single Neuron Activity During Working Memory Maintenance

    Science.gov (United States)

    Zamora, Leona; Corina, David; Ojemann, George

    2016-01-01

    The Working Memory model of human memory, first introduced by Baddeley and Hitch (1974), has been one of the most influential psychological constructs in cognitive psychology and human neuroscience. However the neuronal correlates of core components of this model have yet to be fully elucidated. Here we present data from two studies where human temporal cortical single neuron activity was recorded during tasks differentially affecting the maintenance component of verbal working memory. In Study One we vary the presence or absence of distracting items for the entire period of memory storage. In Study Two we vary the duration of storage so that distractors filled all, or only one-third of the time the memory was stored. Extracellular single neuron recordings were obtained from 36 subjects undergoing awake temporal lobe resections for epilepsy, 25 in Study one, 11 in Study two. Recordings were obtained from a total of 166 lateral temporal cortex neurons during performance of one of these two tasks, 86 study one, 80 study two. Significant changes in activity with distractor manipulation were present in 74 of these neurons (45%), 38 Study one, 36 Study two. In 48 (65%) of those there was increased activity during the period when distracting items were absent, 26 Study One, 22 Study Two. The magnitude of this increase was greater for Study One, 47.6%, than Study Two, 8.1%, paralleling the reduction in memory errors in the absence of distracters, for Study One of 70.3%, Study Two 26.3% These findings establish that human lateral temporal cortex is part of the neural system for working memory, with activity during maintenance of that memory that parallels performance, suggesting it represents active rehearsal. In 31 of these neurons (65%) this activity was an extension of that during working memory encoding that differed significantly from the neural processes recorded during overt and silent language tasks without a recent memory component, 17 Study one, 14 Study two

  3. Telomere elongation in immortal human cells without detectable telomerase activity.

    Science.gov (United States)

    Bryan, T M; Englezou, A; Gupta, J; Bacchetti, S; Reddel, R R

    1995-09-01

    Immortalization of human cells is often associated with reactivation of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening. We examined whether telomerase activation is necessary for immortalization. All normal human fibroblasts tested were negative for telomerase activity. Thirteen out of 13 DNA tumor virus-transformed cell cultures were also negative in the pre-crisis (i.e. non-immortalized) stage. Of 35 immortalized cell lines, 20 had telomerase activity as expected, but 15 had no detectable telomerase. The 15 telomerase-negative immortalized cell lines all had very long and heterogeneous telomeres of up to 50 kb. Hybrids between telomerase-negative and telomerase-positive cells senesced. Two senescent hybrids demonstrated telomerase activity, indicating that activation of telomerase is not sufficient for immortalization. Some hybrid clones subsequently recommenced proliferation and became immortalized either with or without telomerase activity. Those without telomerase activity also had very long and heterogeneous telomeres. Taken together, these data suggest that the presence of lengthened or stabilized telomeres is necessary for immortalization, and that this may be achieved either by the reactivation of telomerase or by a novel and as yet unidentified mechanism.

  4. Chloride transport in human fibroblasts is activated by hypotonic shock

    Energy Technology Data Exchange (ETDEWEB)

    Rugolo, M.; Mastocola, T.; Flamigni, A.; Lenaz, G. (Universita' di Bologna (Italy))

    1989-05-15

    Incubation of human skin fibroblasts in hypotonic media induced the activation of {sup 36}Cl- efflux which was roughly proportional to the decrease in the osmolality of the media. The efflux of {sup 36}Cl- was insensitive to DIDS plus furosemide and inhibited by addition of a Cl- channel blocker such as 5-nitro-2-(3-phenyl propylamino) benzoic acid (NPPB). We propose that a conductive pathway for Cl- transport, almost silent in isotonic conditions, is activated by exposing human fibroblasts to hypotonic shock, this conclusion being supported by evidence that also {sup 36}Cl- influx was enhanced by hypotonic medium.

  5. Activation of ERK mitogen-activated protein kinase in human cells by the mycotoxin patulin

    International Nuclear Information System (INIS)

    Wu, T.-S.; Yu, F.-Y.; Su, C.-C.; Kan, J.-C.; Chung, C.-P.; Liu, B.-H.

    2005-01-01

    Patulin (PAT), a mycotoxin produced by certain species of Penicillium and Aspergillus, is often detectable in moldy fruits and their derivative products. PAT led to a concentration-dependent and time-dependent increase in phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) in human embryonic kidney (HEK293) cells, human peripheral blood mononuclear cells (PBMCs), and Madin-Darby canine kidney (MDCK) cells. Exposure of HEK293 cells to concentrations above 5 μM PAT for 30 min induced ERK1/2 phosphorylation; activation of ERK1/2 was also observed after 24 h incubation with 0.05 μM of PAT. Treatment of human PBMCs for 30 min with 30 μM PAT dramatically increased the phosphorylated ERK1/2 levels. Both MEK1/2 inhibitors, U0126 and PD98059, suppressed ERK1/2 activation in either HEK293 or MDCK cells. In HEK293 cells, U0126-mediated inhibition of PAT-induced ERK1/2 phosphorylation resulted in a significant decrease in levels of DNA damage, expressed as tail moment values, in the single cell gel electrophoresis assay. Conversely, U0126 did not affect cell viability, lactate dehydrogenase release, and the DNA synthesis rate in PAT-treated cultures. Exposure of HEK293 cells for 90 min to 15 μM PAT elevated the levels of early growth response gene-1 (egr-1) mRNA, but not of c-fos, fosB, and junB mRNAs. These results indicate that in human cells, PAT causes a rapid and persistent activation of ERK1/2 and this signaling pathway plays an important role in mediating PAT-induced DNA damage and egr-1 gene expression

  6. A Hierarchical Representation for Human Activity Recognition with Noisy Labels

    NARCIS (Netherlands)

    Hu, N.; Englebienne, G.; Lou, Z.; Kröse, B.

    2015-01-01

    Human activity recognition is an essential task for robots to effectively and efficiently interact with the end users. Many machine learning approaches for activity recognition systems have been proposed recently. Most of these methods are built upon a strong assumption that the labels in the

  7. Does solar activity affect human happiness?

    Science.gov (United States)

    Kristoufek, Ladislav

    2018-03-01

    We investigate the direct influence of solar activity (represented by sunspot numbers) on human happiness (represented by the Twitter-based Happiness Index). We construct four models controlling for various statistical and dynamic effects of the analyzed series. The final model gives promising results. First, there is a statistically significant negative influence of solar activity on happiness which holds even after controlling for the other factors. Second, the final model, which is still rather simple, explains around 75% of variance of the Happiness Index. Third, our control variables contribute significantly as well: happiness is higher in no sunspots days, happiness is strongly persistent, there are strong intra-week cycles and happiness peaks during holidays. Our results strongly contribute to the topical literature and they provide evidence of unique utility of the online data.

  8. Guinea pig complement potently measures vibriocidal activity of human antibodies in response to cholera vaccines.

    Science.gov (United States)

    Kim, Kyoung Whun; Jeong, Soyoung; Ahn, Ki Bum; Yang, Jae Seung; Yun, Cheol-Heui; Han, Seung Hyun

    2017-12-01

    The vibriocidal assay using guinea pig complement is widely used for the evaluation of immune responses to cholera vaccines in human clinical trials. However, it is unclear why guinea pig complement has been used over human complement in the measurement of vibriocidal activity of human sera and there have not been comparison studies for the use of guinea pig complement over those from other species. Therefore, we comparatively investigated the effects of complements derived from human, guinea pig, rabbit, and sheep on vibriocidal activity. Complements from guinea pig, rabbit, and human showed concentration-dependent vibriocidal activity in the presence of quality control serum antibodies. Of these complements, guinea pig complement was the most sensitive and effective over a wide concentration range. When the vibriocidal activity of complements was measured in the absence of serum antibodies, human, sheep, and guinea pig complements showed vibriocidal activity up to 40-fold, 20-fold, and 1-fold dilution, respectively. For human pre- and post-vaccination sera, the most potent vibriocidal activity was observed when guinea pig complement was used. In addition, the highest fold-increases between pre- and post- vaccinated sera were obtained with guinea pig complement. Furthermore, human complement contained a higher amount of V. cholerae- and its lipopolysaccharide-specific antibodies than guinea pig complement. Collectively, these results suggest that guinea pig complements are suitable for vibriocidal assays due to their high sensitivity and effectiveness to human sera.

  9. Assessment of physical activity of the human body considering the thermodynamic system.

    Science.gov (United States)

    Hochstein, Stefan; Rauschenberger, Philipp; Weigand, Bernhard; Siebert, Tobias; Schmitt, Syn; Schlicht, Wolfgang; Převorovská, Světlana; Maršík, František

    2016-01-01

    Correctly dosed physical activity is the basis of a vital and healthy life, but the measurement of physical activity is certainly rather empirical resulting in limited individual and custom activity recommendations. Certainly, very accurate three-dimensional models of the cardiovascular system exist, however, requiring the numeric solution of the Navier-Stokes equations of the flow in blood vessels. These models are suitable for the research of cardiac diseases, but computationally very expensive. Direct measurements are expensive and often not applicable outside laboratories. This paper offers a new approach to assess physical activity using thermodynamical systems and its leading quantity of entropy production which is a compromise between computation time and precise prediction of pressure, volume, and flow variables in blood vessels. Based on a simplified (one-dimensional) model of the cardiovascular system of the human body, we develop and evaluate a setup calculating entropy production of the heart to determine the intensity of human physical activity in a more precise way than previous parameters, e.g. frequently used energy considerations. The knowledge resulting from the precise real-time physical activity provides the basis for an intelligent human-technology interaction allowing to steadily adjust the degree of physical activity according to the actual individual performance level and thus to improve training and activity recommendations.

  10. Screening vaccine formulations for biological activity using fresh human whole blood.

    Science.gov (United States)

    Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression.

  11. Statistics and risk philosophy in human activities

    International Nuclear Information System (INIS)

    Failla, L.

    1983-01-01

    Two leading interpretations of the use of statistics exist, the first one considering statistics as a physical law regulating the phenomena studied, and the other considering statistics as a method allowing to achieve exhaustive knowledge of the phenomena. The Author chooses the second theory, applies this concept of statistics to the risk involved in human activities and discusses the different kinds of risk in this field. The Author distinguishes between the risk that can be eliminated or at least reduced, and the risk inherent in the activity itself, that can never be completely eliminated -unless the activity is suppressed-; yet, also this kind of risk can be kept under control. Furthermore, she distinguishes between risks that can or cannot be foreseen. The Author supports the theory according to which the risk foreseen must be prevented through up-to-date techniques: this should be done coherently with the aim of the activity but independently of the economic cost. The theory considering risk probability as a physical law is mainly based on events happened in the past: it uses the occurrence probability as a law. This theory accepts the statistical risk and estimates its costs, including the ''human cost''. The Author examines the different statistical possibilities to study this specific phenomenon: so, the possibility to avoid the risks may arise along with -last but not least- the opportunity to eliminate or reduce the damage connected. On the contrary, statistics used as a physical law implies the acceptable of a given amount of risk compared with the cost of improving the technical conditions required to eliminate damages. In the end, a practical example of this theory is described

  12. Activation of human herpesvirus replication by apoptosis.

    Science.gov (United States)

    Prasad, Alka; Remick, Jill; Zeichner, Steven L

    2013-10-01

    A central feature of herpesvirus biology is the ability of herpesviruses to remain latent within host cells. Classically, exposure to inducing agents, like activating cytokines or phorbol esters that stimulate host cell signal transduction events, and epigenetic agents (e.g., butyrate) was thought to end latency. We recently showed that Kaposi's sarcoma-associated herpesvirus (KSHV, or human herpesvirus-8 [HHV-8]) has another, alternative emergency escape replication pathway that is triggered when KSHV's host cell undergoes apoptosis, characterized by the lack of a requirement for the replication and transcription activator (RTA) protein, accelerated late gene kinetics, and production of virus with decreased infectivity. Caspase-3 is necessary and sufficient to initiate the alternative replication program. HSV-1 was also recently shown to initiate replication in response to host cell apoptosis. These observations suggested that an alternative apoptosis-triggered replication program might be a general feature of herpesvirus biology and that apoptosis-initiated herpesvirus replication may have clinical implications, particularly for herpesviruses that almost universally infect humans. To explore whether an alternative apoptosis-initiated replication program is a common feature of herpesvirus biology, we studied cell lines latently infected with Epstein-Barr virus/HHV-4, HHV-6A, HHV-6B, HHV-7, and KSHV. We found that apoptosis triggers replication for each HHV studied, with caspase-3 being necessary and sufficient for HHV replication. An alternative apoptosis-initiated replication program appears to be a common feature of HHV biology. We also found that commonly used cytotoxic chemotherapeutic agents activate HHV replication, which suggests that treatments that promote apoptosis may lead to activation of latent herpesviruses, with potential clinical significance.

  13. Transposable element activity, genome regulation and human health.

    Science.gov (United States)

    Wang, Lu; Jordan, I King

    2018-03-02

    A convergence of novel genome analysis technologies is enabling population genomic studies of human transposable elements (TEs). Population surveys of human genome sequences have uncovered thousands of individual TE insertions that segregate as common genetic variants, i.e. TE polymorphisms. These recent TE insertions provide an important source of naturally occurring human genetic variation. Investigators are beginning to leverage population genomic data sets to execute genome-scale association studies for assessing the phenotypic impact of human TE polymorphisms. For example, the expression quantitative trait loci (eQTL) analytical paradigm has recently been used to uncover hundreds of associations between human TE insertion variants and gene expression levels. These include population-specific gene regulatory effects as well as coordinated changes to gene regulatory networks. In addition, analyses of linkage disequilibrium patterns with previously characterized genome-wide association study (GWAS) trait variants have uncovered TE insertion polymorphisms that are likely causal variants for a variety of common complex diseases. Gene regulatory mechanisms that underlie specific disease phenotypes have been proposed for a number of these trait associated TE polymorphisms. These new population genomic approaches hold great promise for understanding how ongoing TE activity contributes to functionally relevant genetic variation within and between human populations. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. The expression of essential components for human influenza virus internalisation in Vero and MDCK cells.

    Science.gov (United States)

    Ugiyadi, Maharani; Tan, Marselina I; Giri-Rachman, Ernawati A; Zuhairi, Fawzi R; Sumarsono, Sony H

    2014-05-01

    MDCK and Vero cell lines have been used as substrates for influenza virus replication. However, Vero cells produced lower influenza virus titer yield compared to MDCK. Influenza virus needs molecules for internalisation of the virus into the host cell, such as influenza virus receptor and clathrin. Human influenza receptor is usually a membrane protein containing Sia(α2,6) Gal, which is added into the protein in the golgi apparatus by α2,6 sialyltransferase (SIAT1). Light clathrin A (LCA), light clathrin B (LCB) and heavy clathrin (HC) are the main components needed for virus endocytosis. Therefore, it is necessary to compare the expression of SIAT1 and clathrin in Vero and MDCK cells. This study is reporting the expression of SIAT1 and clathrin observed in both cells with respect to the levels of (1) RNA by using RT-PCR, (2) protein by using dot blot analysis and confocal microscope. The results showed that Vero and MDCK cells expressed both SIAT1 and clathrin proteins, and the expression of SIAT1 in MDCK was higher compared to Vero cells. On the other hand, the expressions of LCA, LCB and HC protein in MDCK cells were not significantly different to Vero cells. This result showed that the inability of Vero cells to internalize H1N1 influenza virus was possibly due to the lack of transmembrane protein receptor which contained Sia(α2,6) Gal.

  15. First forensic records of termite activity on non-fossilized human bones in Brazil

    Directory of Open Access Journals (Sweden)

    R. A. Queiroz

    Full Text Available Abstract The aim of this study was to describe the first records of termite activity on non-fossilized human bones in Brazil. The cases reported in this study resulted from forensic analysis of six human skeletons found in northeastern Brazil between 2012 and 2014. Traces of tunnels and nests commonly produced by termites were found on several human bone surfaces as well as the specimens and characteristic signs of osteophagic activity. In four cases, the species were identified: Amitermes amifer Silvestri, 1901, Nasutitermes corniger (Motschulsky, 1855 (on two skeletons, and Microcerotermes indistinctus Mathews, 1977. In two other cases, the activity of termites on bone surfaces was evidenced by remains of nests and tunnels produced by these insects. At least in the samples of human remains available for this report, the number of termites collected was greater on bones found during autumn, the rainy season in the Northeast of Brazil. The human bones examined showed termites like insects with lots of strength at bone degradation, capable of continuing the process of decomposition of human remains even in completely skeletonized bodies.

  16. Activities of IAEA related to human interface in man-machine system

    International Nuclear Information System (INIS)

    Nishiwaki, Yasushi

    1988-01-01

    The present paper outlines some activities of IAEA related to human interface in man-machine systems. It has been recognized for quite some time that in large and complex man-machine interactive systems human errors can contribute substantially to failures of these systems, and that the improvement in the human interface in man-machine systems is essential for the safety of the plant. Many important surveys have been made in some member countries. These studies and operational experience have shown that it is possible to substantially reduce this adverse impact of human errors in nuclear power plant operations by the application of human factors technology. This technology. This technology includes: (1) selection of people with the requisite skills and knowledge and providing them with job-relevant training, (2) maintenance of the necessary job qualifications for each person in the plant, (3) design of man-machine interfaces which are fully compatible with the capabilities and limitations of the people in the system, and (4) design of job operations, including written materials, to facilitate required quality of human performance. A review is made of education/training, operator support systems, human error data collection, analysis of safety significant events and future activities. (Nogami, K.)

  17. A Review on Human Activity Recognition Using Vision-Based Method.

    Science.gov (United States)

    Zhang, Shugang; Wei, Zhiqiang; Nie, Jie; Huang, Lei; Wang, Shuang; Li, Zhen

    2017-01-01

    Human activity recognition (HAR) aims to recognize activities from a series of observations on the actions of subjects and the environmental conditions. The vision-based HAR research is the basis of many applications including video surveillance, health care, and human-computer interaction (HCI). This review highlights the advances of state-of-the-art activity recognition approaches, especially for the activity representation and classification methods. For the representation methods, we sort out a chronological research trajectory from global representations to local representations, and recent depth-based representations. For the classification methods, we conform to the categorization of template-based methods, discriminative models, and generative models and review several prevalent methods. Next, representative and available datasets are introduced. Aiming to provide an overview of those methods and a convenient way of comparing them, we classify existing literatures with a detailed taxonomy including representation and classification methods, as well as the datasets they used. Finally, we investigate the directions for future research.

  18. Convolutional Neural Networks for Human Activity Recognition Using Body-Worn Sensors

    Directory of Open Access Journals (Sweden)

    Fernando Moya Rueda

    2018-05-01

    Full Text Available Human activity recognition (HAR is a classification task for recognizing human movements. Methods of HAR are of great interest as they have become tools for measuring occurrences and durations of human actions, which are the basis of smart assistive technologies and manual processes analysis. Recently, deep neural networks have been deployed for HAR in the context of activities of daily living using multichannel time-series. These time-series are acquired from body-worn devices, which are composed of different types of sensors. The deep architectures process these measurements for finding basic and complex features in human corporal movements, and for classifying them into a set of human actions. As the devices are worn at different parts of the human body, we propose a novel deep neural network for HAR. This network handles sequence measurements from different body-worn devices separately. An evaluation of the architecture is performed on three datasets, the Oportunity, Pamap2, and an industrial dataset, outperforming the state-of-the-art. In addition, different network configurations will also be evaluated. We find that applying convolutions per sensor channel and per body-worn device improves the capabilities of convolutional neural network (CNNs.

  19. Physical Human Activity Recognition Using Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Ferhat Attal

    2015-12-01

    Full Text Available This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle. Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN, Support Vector Machines (SVM, Gaussian Mixture Models (GMM, and Random Forest (RF as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM and Hidden Markov Model (HMM, are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  20. Physical Human Activity Recognition Using Wearable Sensors.

    Science.gov (United States)

    Attal, Ferhat; Mohammed, Samer; Dedabrishvili, Mariam; Chamroukhi, Faicel; Oukhellou, Latifa; Amirat, Yacine

    2015-12-11

    This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors' placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject.

  1. Training Classifiers with Shadow Features for Sensor-Based Human Activity Recognition.

    Science.gov (United States)

    Fong, Simon; Song, Wei; Cho, Kyungeun; Wong, Raymond; Wong, Kelvin K L

    2017-02-27

    In this paper, a novel training/testing process for building/using a classification model based on human activity recognition (HAR) is proposed. Traditionally, HAR has been accomplished by a classifier that learns the activities of a person by training with skeletal data obtained from a motion sensor, such as Microsoft Kinect. These skeletal data are the spatial coordinates (x, y, z) of different parts of the human body. The numeric information forms time series, temporal records of movement sequences that can be used for training a classifier. In addition to the spatial features that describe current positions in the skeletal data, new features called 'shadow features' are used to improve the supervised learning efficacy of the classifier. Shadow features are inferred from the dynamics of body movements, and thereby modelling the underlying momentum of the performed activities. They provide extra dimensions of information for characterising activities in the classification process, and thereby significantly improve the classification accuracy. Two cases of HAR are tested using a classification model trained with shadow features: one is by using wearable sensor and the other is by a Kinect-based remote sensor. Our experiments can demonstrate the advantages of the new method, which will have an impact on human activity detection research.

  2. High Accuracy Human Activity Recognition Based on Sparse Locality Preserving Projections.

    Science.gov (United States)

    Zhu, Xiangbin; Qiu, Huiling

    2016-01-01

    Human activity recognition(HAR) from the temporal streams of sensory data has been applied to many fields, such as healthcare services, intelligent environments and cyber security. However, the classification accuracy of most existed methods is not enough in some applications, especially for healthcare services. In order to improving accuracy, it is necessary to develop a novel method which will take full account of the intrinsic sequential characteristics for time-series sensory data. Moreover, each human activity may has correlated feature relationship at different levels. Therefore, in this paper, we propose a three-stage continuous hidden Markov model (TSCHMM) approach to recognize human activities. The proposed method contains coarse, fine and accurate classification. The feature reduction is an important step in classification processing. In this paper, sparse locality preserving projections (SpLPP) is exploited to determine the optimal feature subsets for accurate classification of the stationary-activity data. It can extract more discriminative activities features from the sensor data compared with locality preserving projections. Furthermore, all of the gyro-based features are used for accurate classification of the moving data. Compared with other methods, our method uses significantly less number of features, and the over-all accuracy has been obviously improved.

  3. Training Classifiers with Shadow Features for Sensor-Based Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Simon Fong

    2017-02-01

    Full Text Available In this paper, a novel training/testing process for building/using a classification model based on human activity recognition (HAR is proposed. Traditionally, HAR has been accomplished by a classifier that learns the activities of a person by training with skeletal data obtained from a motion sensor, such as Microsoft Kinect. These skeletal data are the spatial coordinates (x, y, z of different parts of the human body. The numeric information forms time series, temporal records of movement sequences that can be used for training a classifier. In addition to the spatial features that describe current positions in the skeletal data, new features called ‘shadow features’ are used to improve the supervised learning efficacy of the classifier. Shadow features are inferred from the dynamics of body movements, and thereby modelling the underlying momentum of the performed activities. They provide extra dimensions of information for characterising activities in the classification process, and thereby significantly improve the classification accuracy. Two cases of HAR are tested using a classification model trained with shadow features: one is by using wearable sensor and the other is by a Kinect-based remote sensor. Our experiments can demonstrate the advantages of the new method, which will have an impact on human activity detection research.

  4. High Accuracy Human Activity Recognition Based on Sparse Locality Preserving Projections.

    Directory of Open Access Journals (Sweden)

    Xiangbin Zhu

    Full Text Available Human activity recognition(HAR from the temporal streams of sensory data has been applied to many fields, such as healthcare services, intelligent environments and cyber security. However, the classification accuracy of most existed methods is not enough in some applications, especially for healthcare services. In order to improving accuracy, it is necessary to develop a novel method which will take full account of the intrinsic sequential characteristics for time-series sensory data. Moreover, each human activity may has correlated feature relationship at different levels. Therefore, in this paper, we propose a three-stage continuous hidden Markov model (TSCHMM approach to recognize human activities. The proposed method contains coarse, fine and accurate classification. The feature reduction is an important step in classification processing. In this paper, sparse locality preserving projections (SpLPP is exploited to determine the optimal feature subsets for accurate classification of the stationary-activity data. It can extract more discriminative activities features from the sensor data compared with locality preserving projections. Furthermore, all of the gyro-based features are used for accurate classification of the moving data. Compared with other methods, our method uses significantly less number of features, and the over-all accuracy has been obviously improved.

  5. Cleavage of ST6Gal I by Radiation-Induced BACE1 Inhibits Golgi-Anchored ST6Gal I-Mediated Sialylation of Integrin β1 and Migration in Colon Cancer Cells

    International Nuclear Information System (INIS)

    Lee, Minyoung; Park, Jung-Jin; Ko, Young-Gyu; Lee, Yun-Sil

    2012-01-01

    Previously, we found that β-galactoside α2,6-sialyltransferase (ST6Gal I), an enzyme that adds sialic acids to N-linked oligosaccharides of glycoproteins and is frequently overexpressed in cancer cells, is up-regulated by ionizing radiation (IR) and cleaved to a form possessing catalytic activity comparable to that of the Golgi-localized enzyme. Moreover, this soluble form is secreted into the culture media. Induction of ST6Gal I significantly increased the migration of colon cancer cells via sialylation of integrin β1. Here, we further investigated the mechanisms underlying ST6Gal I cleavage, solubilization and release from cells, and addressed its functions, focusing primarily on cancer cell migration. We performed immunoblotting and lectin affinity assay to analyze the expression of ST6 Gal I and level of sialylated integrin β1. After ionizing radiation, migration of cells was measured by in vitro migration assay. α2, 6 sialylation level of cell surface was analyzed by flow cytometry. Cell culture media were concentrated and then analyzed for soluble ST6Gal I levels using an α2, 6 sialyltransferase sandwich ELISA. We found that ST6Gal I was cleaved by BACE1 (β-site amyloid precursor protein-cleaving enzyme), which was specifically overexpressed in response to IR. The soluble form of ST6Gal I, which also has sialyltransferase enzymatic activity, was cleaved from the Golgi membrane and then released into the culture media. Both non-cleaved and cleaved forms of ST6Gal I significantly increased colon cancer cell migration in a sialylation-dependent manner. The pro-migratory effect of the non-cleaved form of ST6Gal I was dependent on integrin β1 sialylation, whereas that of the cleaved form of ST6Gal I was not, suggesting that other intracellular sialylated molecules apart from cell surface molecules such as integrin β1 might be involved in mediating the pro-migratory effects of the soluble form of ST6Gal I. Moreover, production of soluble form ST6Gal I by

  6. Application of the Human Activity Assistive Technology model for occupational therapy research.

    Science.gov (United States)

    Giesbrecht, Ed

    2013-08-01

    Theoretical models provide a framework for describing practice and integrating evidence into systematic research. There are few models that relate specifically to the provision of assistive technology in occupational therapy practice. The Human Activity Assistive Technology model is an enduring example that has continued to develop by integrating a social model of disability, concepts from occupational therapy theory and principles of assistive technology adoption and abandonment. This study first describes the core concepts of the Human Activity Assistive Technology model and reviews its development over three successive published versions. A review of the research literature reflects application of the model to clinical practice, study design, outcome measure selection and interpretation of results, particularly among occupational therapists. An evaluative framework is used to critique the adequacy of the Human Activity Assistive Technology model for practice and research, exploring attributes of clarity, simplicity, generality, accessibility and importance. Finally, recommendations are proposed for continued development of the model and research applications. Most of the existing research literature employs the Human Activity Assistive Technology model for background and study design; there is emerging evidence to support the core concepts as predictive factors. Although the concepts are generally simple, clear and applicable to occupational therapy practice and research, evolving terminology and outcomes become more complex with the conflation of integrated theories. The development of the Human Activity Assistive Technology model offers enhanced access and application for occupational therapists, but poses challenges to clarity among concepts. Suggestions are made for further development and applications of the model. © 2013 Occupational Therapy Australia.

  7. Neutrophil activation during acetaminophen hepatotoxicity and repair in mice and humans

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. David; Bajt, Mary Lynn [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Sharpe, Matthew R. [Department of Internal Medicine, University of Kansas Hospital, Kansas City, KS (United States); McGill, Mitchell R. [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2014-03-01

    Following acetaminophen (APAP) overdose there is an inflammatory response triggered by the release of cellular contents from necrotic hepatocytes into the systemic circulation which initiates the recruitment of neutrophils into the liver. It has been demonstrated that neutrophils do not contribute to APAP-induced liver injury, but their role and the role of NADPH oxidase in injury resolution are controversial. C57BL/6 mice were subjected to APAP overdose and neutrophil activation status was determined during liver injury and liver regeneration. Additionally, human APAP overdose patients (ALT: > 800 U/L) had serial blood draws during the injury and recovery phases for the determination of neutrophil activation. Neutrophils in the peripheral blood of mice showed an increasing activation status (CD11b expression and ROS priming) during and after the peak of injury but returned to baseline levels prior to complete injury resolution. Hepatic sequestered neutrophils showed an increased and sustained CD11b expression, but no ROS priming was observed. Confirming that NADPH oxidase is not critical to injury resolution, gp91{sup phox}−/− mice following APAP overdose displayed no alteration in injury resolution. Peripheral blood from APAP overdose patients also showed increased neutrophil activation status after the peak of liver injury and remained elevated until discharge from the hospital. In mice and humans, markers of activation, like ROS priming, were increased and sustained well after active liver injury had subsided. The similar findings between surviving patients and mice indicate that neutrophil activation may be a critical event for host defense or injury resolution following APAP overdose, but not a contributing factor to APAP-induced injury. - Highlights: • Neutrophil (PMN) function increases during liver repair after acetaminophen overdose. • Liver repair after acetaminophen (APAP)-overdose is not dependent on NADPH oxidase. • Human PMNs do not appear

  8. Acute activation, desensitization and smoldering activation of human acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Barbara G Campling

    Full Text Available The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β22β2 and (α4β22α4. The (α4β22β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β22α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

  9. The impact of human activities in the Wulan Delta Estuary, Indonesia

    Science.gov (United States)

    Fadlillah, L. N.; Sunarto; Widyastuti, M.; Marfai, M. A.

    2018-04-01

    The increasing of human population in the watershed and the coastal area and the need of life exert pressure in the delta that provides various resources. Wulan Delta is one of active Delta in Central Java, Indonesia. It has been experienced multiple pressures because of natural factors and human factors. In order to provide the scientific solution and to analyze the impact of human intervention in delta, we collected several pieces of evidence based on secondary data and primary data. The secondary data is water quality data on sites 6 and 7, meanwhile the secondary data is the water quality data in site 1 to 5. This paper present a review and problems identification in Wulan Delta, based on hydrological condition, land use, and human activities in the delta. Meanwhile, the human intervention in the land which is land use exchange leads to several problems such as the land use changes, high sediment load, and water degradation. Almost 80% of Delta has been transformed into the fish pond by local communities.

  10. Mapping Cumulative Impacts of Human Activities on Marine Ecosystems

    OpenAIRE

    , Seaplan

    2018-01-01

    Given the diversity of human uses and natural resources that converge in coastal waters, the potential independent and cumulative impacts of those uses on marine ecosystems are important to consider during ocean planning. This study was designed to support the development and implementation of the 2009 Massachusetts Ocean Management Plan. Its goal was to estimate and visualize the cumulative impacts of human activities on coastal and marine ecosystems in the state and federal waters off of Ma...

  11. Alternative pathways of thromboplastin-dependent activation of human factor X in plasma

    International Nuclear Information System (INIS)

    Marlar, R.A.; Griffin, J.H.

    1981-01-01

    To determine the interrelationships of the major coagulation pathways, the activation of 3H-labeled factor X in normal and various deficient human plasmas was evaluated when clotting was triggered by dilute rabbit or human thromboplastin. Various dilutions of thromboplastin and calcium were added to plasma samples containing 3H-factor X, and the time course of factor X activation was determined. At a 1/250 dilution of rabbit brain thromboplastin, the rate of factor X activation in plasmas deficient in factor VIII or factor IX was 10% of the activation rate of normal plasma or of factor XI deficient plasma. Reconstitution of the deficient plasmas with factors VIII or IX, respectively, reconstituted normal factor X activation. Similar results were obtained when various dilutions of human thromboplastin replaced the rabbit thromboplastin. From these plasma experiments, it is inferred that the dilute thromboplastin-dependent activation of factor X requires factors VII, IX, and VIII. An alternative extrinsic pathway that involves factors IX and VIII may be the physiologic extrinsic pathway and hence help to explain the consistent clinical observations of bleeding diatheses in patients deficient in factors IX or VIII

  12. Timing of nurses activities: human resources management

    Directory of Open Access Journals (Sweden)

    Hamid Hosein Poor

    2016-11-01

    Full Text Available Costs of human resources include a high percentage of hospital’s costs; therefore, determination of number of real and optimal employees needed for organizations is very important. In the meantime, the optimal organization of nurses, as the biggest human resource in health care organizations, is of great importance. The present study aimed to assess the distribution of nurses’ activities in shifts and the results of productivity in human resources management in Imam Khomeini hospital in Shirvan. The present cross-sectional study was conducted in 2016. All nurses, working in three shifts of morning, afternoon, and evening in emergency unit and general units of Imam Khomeini hospital, Shirvan, were enrolled into the study through census methods. The instrument, used in this study, was the checklist of timing activities and patients’ satisfaction from nurses. The statistical software SPSS was used for analysis. Mean age of employees in these two units/wards was 31 years and mean duration of work experience was 5.24 years, The difference was significant between the two wards. necessity of the work, especially in emergency unit, are issues that need more assessment and need to be adjusted. Given the high volume of non-care matters of nursing staff, including writing services, including completing paper records and work with HIS (Hospital Information System, which has been emphasized in several studies, new definition of service and use of artificial intelligence with high efficacy is proposed. The status of the available equipment, availability, and efficiency of digital equipment and hoteling state of wards and hospitals also play an important factor in the distribution of time of nursing care activities. Employment of nurses to perform non-nursing duties, because of the shortage of other classes or lack of their permanent presence and based on Although there were differences in standard time of direct and indirect care in emergency unit and

  13. Inflammatory aetiology of human myometrial activation tested using directed graphs.

    Directory of Open Access Journals (Sweden)

    2005-07-01

    Full Text Available THERE ARE THREE MAIN HYPOTHESES FOR THE ACTIVATION OF THE HUMAN UTERUS AT LABOUR: functional progesterone withdrawal, inflammatory stimulation, and oxytocin receptor activation. To test these alternatives we have taken information and data from the literature to develop causal pathway models for the activation of human myometrium. The data provided quantitative RT-PCR results on key genes from samples taken before and during labour. Principal component analysis showed that pre-labour samples form a homogenous group compared to those during labour. We therefore modelled the alternative causal pathways in non-labouring samples using directed graphs and statistically compared the likelihood of the different models using structural equations and D-separation approaches. Using the computer program LISREL, inflammatory activation as a primary event was highly consistent with the data (p = 0.925, progesterone withdrawal, as a primary event, is plausible (p = 0.499, yet comparatively unlikely, oxytocin receptor mediated initiation is less compatible with the data (p = 0.091. DGraph, a software program that creates directed graphs, produced similar results (p= 0.684, p= 0.280, and p = 0.04, respectively. This outcome supports an inflammatory aetiology for human labour. Our results demonstrate the value of directed graphs in determining the likelihood of causal relationships in biology in situations where experiments are not possible.

  14. A Low Power, Parallel Wearable Multi-Sensor System for Human Activity Evaluation.

    Science.gov (United States)

    Li, Yuecheng; Jia, Wenyan; Yu, Tianjian; Luan, Bo; Mao, Zhi-Hong; Zhang, Hong; Sun, Mingui

    2015-04-01

    In this paper, the design of a low power heterogeneous wearable multi-sensor system, built with Zynq System-on-Chip (SoC), for human activity evaluation is presented. The powerful data processing capability and flexibility of this SoC represent significant improvements over our previous ARM based system designs. The new system captures and compresses multiple color images and sensor data simultaneously. Several strategies are adopted to minimize power consumption. Our wearable system provides a new tool for the evaluation of human activity, including diet, physical activity and lifestyle.

  15. Human activities threaten coral reefs

    International Nuclear Information System (INIS)

    Tveitdal, Svein; Bjoerke, Aake

    2002-01-01

    Research indicates that 58 per cent of the coral reefs of the world are threatened by human activities. Pollution and global heating represent some of the threats. Coral reefs just beneath the surface of the sea are very sensitive to temperature changes. Since 1979, mass death of coral reefs has been reported increasingly often. More than 1000 marine species live in the coral reefs, among these are one fourth of all marine species of fish. It is imperative that the coral reefs be preserved, as coastal communities all over the world depend on them as sources of food and as they are the raw materials for important medicines. The article discusses the threats to the coral reefs in general and does not single out any particular energy-related activity as the principal threat. For instance, the El-Nino phenomenon of the Pacific Ocean is probably involved in mass death of coral reefs and in the North Sea large parts of deep-water reefs have been crushed by heavy beam trawlers fishing for bottom fish

  16. Gemfibrozil, a lipid lowering drug, inhibits the activation of primary human microglia via peroxisome proliferator-activated receptor β.

    Science.gov (United States)

    Jana, Malabendu; Pahan, Kalipada

    2012-08-01

    Microglial activation participates in the pathogenesis of various neuroinflammatory and neurodegenerative diseases. However, mechanisms by which microglial activation could be controlled are poorly understood. Peroxisome proliferator-activated receptors (PPAR) are transcription factors belonging to the nuclear receptor super family with diverse effect. This study underlines the importance of PPARβ/δ in mediating the anti-inflammatory effect of gemfibrozil, an FDA-approved lipid-lowering drug, in primary human microglia. Bacterial lipopolysachharides (LPS) induced the expression of various proinflammatory molecules and upregulated the expression of microglial surface marker CD11b in human microglia. However, gemfibrozil markedly suppressed proinflammatory molecules and CD11b in LPS-stimulated microglia. Human microglia expressed PPAR-β and -γ, but not PPAR-α. Interestingly, either antisense knockdown of PPAR-β or antagonism of PPAR-β by a specific chemical antagonist abrogated gemfibrozil-mediated inhibition of microglial activation. On the other hand, blocking of PPAR-α and -γ had no effect on gemfibrozil-mediated anti-inflammatory effect in microglia. These results highlight the fact that gemfibrozil regulates microglial activation by inhibiting inflammatory gene expression in a PPAR-β dependent pathway and further reinforce its therapeutic application in several neuroinflammatory and neurodegenerative diseases.

  17. Active Site Mapping of Human Cathepsin F with Dipeptide Nitrile Inhibitors.

    Science.gov (United States)

    Schmitz, Janina; Furtmann, Norbert; Ponert, Moritz; Frizler, Maxim; Löser, Reik; Bartz, Ulrike; Bajorath, Jürgen; Gütschow, Michael

    2015-08-01

    Cleavage of the invariant chain is the key event in the trafficking pathway of major histocompatibility complex class II. Cathepsin S is the major processing enzyme of the invariant chain, but cathepsin F acts in macrophages as its functional synergist which is as potent as cathepsin S in invariant chain cleavage. Dedicated low-molecular-weight inhibitors for cathepsin F have not yet been developed. An active site mapping with 52 dipeptide nitriles, reacting as covalent-reversible inhibitors, was performed to draw structure-activity relationships for the non-primed binding region of human cathepsin F. In a stepwise process, new compounds with optimized fragment combinations were designed and synthesized. These dipeptide nitriles were evaluated on human cysteine cathepsins F, B, L, K and S. Compounds 10 (N-(4-phenylbenzoyl)-leucylglycine nitrile) and 12 (N-(4-phenylbenzoyl)leucylmethionine nitrile) were found to be potent inhibitors of human cathepsin F, with Ki values nitriles from our study, a 3D activity landscape was generated to visualize structure-activity relationships for this series of cathepsin F inhibitors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Human hair identification by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Cho, S.Y.; Jang, S.G.; Chung, Y.S.

    1998-01-01

    Nondestructive neutron activation technique was used to analyze 17 elements (Al, As, Au, Ba, Br, Cl, Cu, Hg, I, K, Mg, Mn, Na, Sb, Sr, V and Zn) in 75 human hair samples in 5 different locations, respectively, from 15 glassware workers. The analytical results were treated further statistically to find the elemental distribution among different human hairs and to identify the individual's hair. The identifying probability of one's hair by the comparison of elemental concentrations is found to be 10 4 -10 6 times higher from the same person's than from any other person's. The standard deviation of the elemental concentrations of samples taken from 5 different locations of one person is about 5 time smaller than the standard deviation for individual's hair. These data support the possibility of using NAA of hair for human hair identification. (author)

  19. Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth

    NARCIS (Netherlands)

    Bull, C.; Boltje, T.J.; Wassink, M.; Graaf, A.M.A. de; Delft, F.L. van; Brok, M.H.M.G.M. den; Adema, G.J.

    2013-01-01

    Cancer cells decorate their surface with a dense layer of sialylated glycans by upregulating the expression of sialyltransferases and other glycogenes. Although sialic acids play a vital role in many biologic processes, hypersialylation in particular has been shown to contribute to cancer cell

  20. Linguistic Human Rights Discourse in Deaf Community Activism

    Science.gov (United States)

    Murray, Joseph J.

    2015-01-01

    The past three decades of activism for linguistic human rights (Skutnabb-Kangas 2000) have witnessed examples of language planning by various national and supranational actors in national and international spaces, with an exchange of ideas and strategies employed by national, regional, and worldwide organizations. In many countries a key goal of…

  1. Activation of human T lymphocytes by Leishmania lipophosphoglycan

    DEFF Research Database (Denmark)

    Kemp, M; Theander, T G; Handman, E

    1991-01-01

    This study describes Leishmania antigen-induced activation of lymphocytes isolated from Kenyan donors, previously treated for visceral leishmaniasis, and from Danish and Kenyan controls. Peripheral blood mononuclear cells (PBMC) from cured Kala-Azar patients proliferated and produced Interferon......, the results suggest that human T lymphocytes can respond to glycolipid antigens....

  2. Development and oversight of ethical health promotion quality assurance and evaluation activities involving human participants.

    Science.gov (United States)

    Sainsbury, Peter

    2015-12-01

    This paper considers the role of ethics and ethics review processes in the development of health promotion quality assurance and evaluation activities involving human participants. The Australian National Health and Medical Research Council (NHMRC) National Statement on Ethical Conduct in Human Research and associated documents provide the framework for the ethical conduct and independent review of research (including quality assurance and evaluation) involving humans in Australia. Identifying the level of risk to which participants may be exposed by participation in quality assurance and evaluation activities is essential for health promotion workers undertaking such activities. Organisations can establish processes other than review by a Human Research Ethics Committee for negligible and low risk research activities. Health promotion quality assurance and evaluation activities often involve negligible and low risk to participants. Seven triggers that indicate the need for ethics review of quality assurance and evaluation activities and a procedural checklist for developing ethical quality assurance and evaluation activities are provided. Health promotion workers should be familiar with the NHMRC's National Statement on Ethical Conduct in Human Research. When ethical considerations underpin the planning and conduct of all quality assurance and evaluation from the very beginning, the activity is the better for it, independent 'ethics approval' can mostly be secured without much trouble and workers' frustration levels are reduced. So what? Health promotion quality assurance and evaluation activities must be ethically justified. Health promotion workers should be familiar with the NHMRC's National Statement on Ethical Conduct in Human Research and should use it when developing health promotion quality assurance and evaluation activities.

  3. Effects of Age, Season, Gender and Urban-Rural Status on Time-Activity: Canadian Human Activity Pattern Survey 2 (CHAPS 2)

    OpenAIRE

    Matz, Carlyn J.; Stieb, David M.; Davis, Karelyn; Egyed, Marika; Rose, Andreas; Chou, Benedito; Brion, Orly

    2014-01-01

    Estimation of population exposure is a main component of human health risk assessment for environmental contaminants. Population-level exposure assessments require time-activity pattern distributions in relation to microenvironments where people spend their time. Societal trends may have influenced time-activity patterns since previous Canadian data were collected 15 years ago. The Canadian Human Activity Pattern Survey 2 (CHAPS 2) was a national survey conducted in 2010–2011 to collect time-...

  4. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Directory of Open Access Journals (Sweden)

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

  5. Effects of Butyltins (BTs) on Mitogen-Activated-Protein Kinase Kinase Kinase (MAP3K) and Ras Activity in Human Natural Killer Cells

    Science.gov (United States)

    Celada, Lindsay J.; Whalen, Margaret M.

    2013-01-01

    Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT), diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally-infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to the activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 minutes of TBT exposure and the MAP3K, ASK1, after one hour exposures to TBT. In addition, our results suggest that both TBT and DBT are impacting the regulation of c-Raf. PMID:24038145

  6. Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

    Science.gov (United States)

    Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

    2018-01-01

    Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.

  7. Characterization of STAT3 activation and expression in canine and human osteosarcoma

    Directory of Open Access Journals (Sweden)

    Li Pui-Kai

    2009-03-01

    Full Text Available Abstract Background Dysregulation of signal transducer and activator of transcription 3 (STAT3 has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. Methods To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656 or STAT3 (LLL3 inhibitors and cell proliferation (CyQUANT, caspase 3/7 activity (ELISA, apoptosis (Western blotting for PARP cleavage and/or viability (Wst-1 were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Results Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known

  8. Characterization of STAT3 activation and expression in canine and human osteosarcoma

    International Nuclear Information System (INIS)

    Fossey, Stacey L; Liao, Albert T; McCleese, Jennifer K; Bear, Misty D; Lin, Jiayuh; Li, Pui-Kai; Kisseberth, William C; London, Cheryl A

    2009-01-01

    Dysregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a key participant in tumor cell survival, proliferation, and metastasis and is often correlated with a more malignant tumor phenotype. STAT3 phosphorylation has been demonstrated in a subset of human osteosarcoma (OSA) tissues and cell lines. OSA in the canine population is known to exhibit a similar clinical behavior and molecular biology when compared to its human counterpart, and is often used as a model for preclinical testing of novel therapeutics. The purpose of this study was to investigate the potential role of STAT3 in canine and human OSA, and to evaluate the biologic activity of a novel small molecule STAT3 inhibitor. To examine STAT3 and Src expression in OSA, we performed Western blotting and RT-PCR. OSA cells were treated with either STAT3 siRNA or small molecule Src (SU6656) or STAT3 (LLL3) inhibitors and cell proliferation (CyQUANT), caspase 3/7 activity (ELISA), apoptosis (Western blotting for PARP cleavage) and/or viability (Wst-1) were determined. Additionally, STAT3 DNA binding after treatment was determined using EMSA. Expression of STAT3 targets after treatment was demonstrated with Western blotting, RT-PCR, or gel zymography. Our data demonstrate that constitutive activation of STAT3 is present in a subset of canine OSA tumors and human and canine cell lines, but not normal canine osteoblasts. In both canine and human OSA cell lines, downregulation of STAT3 activity through inhibition of upstream Src family kinases using SU6656, inhibition of STAT3 DNA binding and transcriptional activities using LLL3, or modulation of STAT3 expression using siRNA, all resulted in decreased cell proliferation and viability, ultimately inducing caspase-3/7 mediated apoptosis in treated cells. Furthermore, inhibition of either Src or STAT3 activity downregulated the expression of survivin, VEGF, and MMP2, all known transcriptional targets of STAT3. These data

  9. Sympathetic activation during early pregnancy in humans

    Science.gov (United States)

    Jarvis, Sara S; Shibata, Shigeki; Bivens, Tiffany B; Okada, Yoshiyuki; Casey, Brian M; Levine, Benjamin D; Fu, Qi

    2012-01-01

    Sympathetic activity has been reported to increase in normotensive pregnant women, and to be even greater in women with gestational hypertension and preeclampsia at term. Whether sympathetic overactivity develops early during pregnancy, remaining high throughout gestation, or whether it only occurs at term providing the substrate for hypertensive disorders is unknown. We tested the hypothesis that sympathetic activation occurs early during pregnancy in humans. Eleven healthy women (29 ± 3 (SD) years) without prior hypertensive pregnancies were tested during the mid-luteal phase (PRE) and early pregnancy (EARLY; 6.2 ± 1.2 weeks of gestation). Muscle sympathetic nerve activity (MSNA) and haemodynamics were measured supine, at 30 deg and 60 deg upright tilt for 5 min each. Blood samples were drawn for catecholamines, direct renin, and aldosterone. MSNA was significantly greater during EARLY than PRE (supine: 25 ± 8 vs. 14 ± 8 bursts min−1, 60 deg tilt: 49 ± 14 vs. 40 ± 10 bursts min−1; main effect, P < 0.05). Resting diastolic pressure trended lower (P = 0.09), heart rate was similar, total peripheral resistance decreased (2172 ± 364 vs. 2543 ± 352 dyne s cm−5; P < 0.05), sympathetic vascular transduction was blunted (0.10 ± 0.05 vs. 0.36 ± 0.47 units a.u.−1 min−1; P < 0.01), and both renin (supine: 27.9 ± 6.2 vs. 14.2 ± 8.7 pg ml−1, P < 0.01) and aldosterone (supine: 16.7 ± 14.1 vs. 7.7 ± 6.8 ng ml−1, P = 0.05) were higher during EARLY than PRE. These results suggest that sympathetic activation is a common characteristic of early pregnancy in humans despite reduced diastolic pressure and total peripheral resistance. These observations challenge conventional thinking about blood pressure regulation during pregnancy, showing marked sympathetic activation occurring within the first few weeks of conception, and may provide the substrate for pregnancy induced cardiovascular complications. PMID:22687610

  10. Human Error Probability Assessment During Maintenance Activities of Marine Systems

    Directory of Open Access Journals (Sweden)

    Rabiul Islam

    2018-03-01

    Full Text Available Background: Maintenance operations on-board ships are highly demanding. Maintenance operations are intensive activities requiring high man–machine interactions in challenging and evolving conditions. The evolving conditions are weather conditions, workplace temperature, ship motion, noise and vibration, and workload and stress. For example, extreme weather condition affects seafarers' performance, increasing the chances of error, and, consequently, can cause injuries or fatalities to personnel. An effective human error probability model is required to better manage maintenance on-board ships. The developed model would assist in developing and maintaining effective risk management protocols. Thus, the objective of this study is to develop a human error probability model considering various internal and external factors affecting seafarers' performance. Methods: The human error probability model is developed using probability theory applied to Bayesian network. The model is tested using the data received through the developed questionnaire survey of >200 experienced seafarers with >5 years of experience. The model developed in this study is used to find out the reliability of human performance on particular maintenance activities. Results: The developed methodology is tested on the maintenance of marine engine's cooling water pump for engine department and anchor windlass for deck department. In the considered case studies, human error probabilities are estimated in various scenarios and the results are compared between the scenarios and the different seafarer categories. The results of the case studies for both departments are also compared. Conclusion: The developed model is effective in assessing human error probabilities. These probabilities would get dynamically updated as and when new information is available on changes in either internal (i.e., training, experience, and fatigue or external (i.e., environmental and operational conditions

  11. Effect of ligand activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in human lung cancer cell lines

    International Nuclear Information System (INIS)

    He Pengfei; Borland, Michael G.; Zhu Bokai; Sharma, Arun K.; Amin, Shantu; El-Bayoumy, Karam; Gonzalez, Frank J.; Peters, Jeffrey M.

    2008-01-01

    There is compelling evidence that peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) mediates terminal differentiation and is associated with inhibition of cell growth. However, it was recently suggested that growth of two human lung cancer cell lines is enhanced by PPARβ/δ. The goal of the present study was to provide insight in resolving this controversy. Therefore, the effect of ligand activation of PPARβ/δ in A549 and H1838 human lung cancer cell lines was examined using two high affinity PPARβ/δ ligands. Ligand activation of PPARβ/δ caused up-regulation of a known PPARβ/δ target gene, angiopoietin-like 4 (Angptl4) but did not influence expression of phosphatase and tensin homolog (PTEN) or phosphorylation of protein kinase B (Akt), and did not affect cell growth. Results from this study demonstrate that two human lung cancer cell lines respond to ligand activation of PPARβ/δ by modulation of target gene expression (Angptl4), but fail to exhibit significant modulation of cell proliferation

  12. Human Research Program Science Management: Overview of Research and Development Activities

    Science.gov (United States)

    Charles, John B.

    2007-01-01

    An overview of research and development activities of NASA's Human Research Science Management Program is presented. The topics include: 1) Human Research Program Goals; 2) Elements and Projects within HRP; 3) Development and Maintenance of Priorities; 4) Acquisition and Evaluation of Research and Technology Proposals; and 5) Annual Reviews

  13. Human innate responses and adjuvant activity of TLR ligands in vivo in mice reconstituted with a human immune system.

    Science.gov (United States)

    Cheng, Liang; Zhang, Zheng; Li, Guangming; Li, Feng; Wang, Li; Zhang, Liguo; Zurawski, Sandra M; Zurawski, Gerard; Levy, Yves; Su, Lishan

    2017-10-27

    TLR ligands (TLR-Ls) represent a class of novel vaccine adjuvants. However, their immunologic effects in humans remain poorly defined in vivo. Using a humanized mouse model with a functional human immune system, we investigated how different TLR-Ls stimulated human innate immune response in vivo and their applications as vaccine adjuvants for enhancing human cellular immune response. We found that splenocytes from humanized mice showed identical responses to various TLR-Ls as human PBMCs in vitro. To our surprise, various TLR-Ls stimulated human cytokines and chemokines differently in vivo compared to that in vitro. For example, CpG-A was most efficient to induce IFN-α production in vitro. In contrast, CpG-B, R848 and Poly I:C stimulated much more IFN-α than CpG-A in vivo. Importantly, the human innate immune response to specific TLR-Ls in humanized mice was different from that reported in C57BL/6 mice, but similar to that reported in nonhuman primates. Furthermore, we found that different TLR-Ls distinctively activated and mobilized human plasmacytoid dendritic cells (pDCs), myeloid DCs (mDCs) and monocytes in different organs. Finally, we showed that, as adjuvants, CpG-B, R848 and Poly I:C can all enhance antigen specific CD4 + T cell response, while only R848 and Poly I:C induced CD8 + cytotoxic T cells response to a CD40-targeting HIV vaccine in humanized mice, correlated with their ability to activate human mDCs but not pDCs. We conclude that humanized mice serve as a highly relevant model to evaluate and rank the human immunologic effects of novel adjuvants in vivo prior to testing in humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. EUROPEAN COURT OF HUMAN RIGHTS AS THE GUARANTOR OF LEGAL PROTECTION OF A HUMAN IN THE FIELD OF AVIATION ACTIVITIES OF UKRAINE

    Directory of Open Access Journals (Sweden)

    Yuriy Pyvovar

    2017-11-01

    Full Text Available Purpose: The effectiveness of human rights protection in the Council of Europe largely depends on activities of the European Court, which demonstrates high standards of justice, particularly in matters of human rights protection in the field of aviation activities. The article offers a critical assessment of Ukrainian national legislation in terms of its internal legal consistency and compliance with international legal acts. Methods: The methods of legal analysis are used to study court decisions in the aviation field; methods of comparative legal analysis, forecasting and dialectical - in the study of problems in the further improvement of Ukrainian legislation. Also in article applied the theory of legal comparative, approaches to applying the analogy of legal and law in process of making decisions on similar court cases. Results: The article deals with the analysis of the European Court of Human Rights jurisdiction on cases of protection of human rights in the field of aviation activities. Two groups of cases in which Ukraine is a defendant are identified: a cases of international concern (in particular the Malaysia Airlines’ Boeing 777-200ER crash; b cases of national character (citizens of Ukraine against the State of Ukraine. The author's position on deciding the cases in the field of aviation activities is based on the principles of respect for the European Convention on Human Rights, 1950. Discussion: The conclusion about the necessity of amending some national laws, taking into account the legal positions of the European Court (in particular, regarding the right of airlines workers to strike is made, and the fact that the issues of States and airlines activities to respect human and civil rights in the field of aviation activities are covered by jurisdiction of the European Court of Human Rights and occupy an important place in its practice is indicated.

  15. Endothelin receptors and activity differ in human, dog, and rabbit lung.

    Science.gov (United States)

    McKay, K O; Armour, C L; Black, J L

    1996-01-01

    In this study, we have examined dog and rabbit airways as potential models for human airways in regard to the activity of endothelin. The receptors involved in the response to endothelin-1 (ET-1) in airway tissue from human, rabbit, and dog lung were investigated, as was the mechanism responsible for the contraction to ET-1 in tissue from the three species. By using specific endothelin receptor agonists and antagonists, we have demonstrated that ETB receptors predominate in rabbit and human airways and ETA receptors in dog airways. The contraction to ET-1 is not dependent on cyclooxygenase products of arachidonic acid, as indomethacin had no effect on the response to ET-1. Extracellular calcium influx via voltage-dependent channels is necessary for contraction to ET-1 in rabbit and dog airways. These results are in contrast to our previously reported results in human airways, in which neither removal of extracellular calcium nor verapamil affected the ET-1 response. The sustained phase of the contraction to ET-1 in all three species may be mediated in part by activation of protein kinase C (PKC), as the inhibitor staurosporine significantly altered the time course of the response to endothelin. We therefore conclude that in rabbit airways ET-1 activates ETB receptors, triggers the influx of extracellular calcium through voltage-dependent channels, and induces a contractile response that is, in part, dependent upon stimulation of PKC. The same mechanism is triggered in dog bronchus; however, the receptors involved in this species are of the ETA type. Finally, in human airways, the contractile response to ET-1, while independent of extracellular calcium influx, is dependent upon PKC activation after binding of the peptide to ETB receptors.

  16. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro

    NARCIS (Netherlands)

    Bardy, C.; Hurk, M. van den; Eames, T.; Marchand, C.; Hernandez, R.V.; Kellogg, M.; Gorris, M.A.J.; Galet, B.; Palomares, V.; Brown, J.; Bang, A.G.; Mertens, J.; Bohnke, L.; Boyer, L.; Simon, S.; Gage, F.H.

    2015-01-01

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely

  17. IgE-dependent activation of human mast cells and fMLP-mediated activation of human eosinophils is controlled by the circadian clock.

    Science.gov (United States)

    Baumann, Anja; Feilhauer, Katharina; Bischoff, Stephan C; Froy, Oren; Lorentz, Axel

    2015-03-01

    Symptoms of allergic attacks frequently exhibit diurnal variations. Accordingly, we could recently demonstrate that mast cells and eosinophils - known as major effector cells of allergic diseases - showed an intact circadian clock. Here, we analyzed the role of the circadian clock in the functionality of mast cells and eosinophils. Human intestinal mast cells (hiMC) were isolated from intestinal mucosa; human eosinophils were isolated from peripheral blood. HiMC and eosinophils were synchronized by dexamethasone before stimulation every 4h around the circadian cycle by FcɛRI crosslinking or fMLP, respectively. Signaling molecule activation was examined using Western blot, mRNA expression by real-time RT-PCR, and mediator release by multiplex analysis. CXCL8 and CCL2 were expressed and released in a circadian manner by both hiMC and eosinophils in response to activation. Moreover, phosphorylation of ERK1/2, known to be involved in activation of hiMC and eosinophils, showed circadian rhythms in both cell types. Interestingly, all clock genes hPer1, hPer2, hCry1, hBmal1, and hClock were expressed in a similar circadian pattern in activated and unstimulated cells indicating that the local clock controls hiMC and eosinophils and subsequently allergic reactions but not vice versa. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells.

    Science.gov (United States)

    Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

    2015-01-01

    Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). RESULTS/METHODOLOGY: We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease.

  19. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    International Nuclear Information System (INIS)

    Tachibana, Keisuke; Takeuchi, Kentaro; Inada, Hirohiko; Yamasaki, Daisuke; Ishimoto, Kenji; Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Doi, Takefumi

    2009-01-01

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial β-oxidation. The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor that plays an important role in the regulation of β-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPARα and found that PPARα induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPARα regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  20. Structure of human milk bile salt activated lipase

    International Nuclear Information System (INIS)

    Baba, T.; Downs, D.; Jackson, K.W.; Tang, J.; Wang, Chi-Sun

    1991-01-01

    The structure and some functional sites of human milk bile salt activated lipase (BAL) were studied by cDNA cloning and chemical analysis of the enzyme. Eighteen cDNA clones of human BAL were identified from lactating human breast cDNA libraries in λgt11 and λgt10 with antibody and synthetic oligonucleotides as probes. The sequence of four clones was sufficient to construct a 3018-bp BAL cDNA structure. This sequence codes for an open reading frame of 742 amino acid residues. There is a putative signal sequence of 20 residues which is followed by the amino-terminal sequence of BAL, and the mature BAL contains 722 amino acid residues. The cDNA sequence also contains a 678-base 5'-untranslated sequence, a 97-base 3'-untranslated region, and a 14-base poly(A) tail. The sequence of a 1.8-kbp insert of clone G10-4A differs from that of the other cDNA in that it contains a deletion of 198 bases (1966-2163) corresponding to 66 amino acid residues. By use of BAL cDAN as probe, it was found that the major molecular species of BAL mRNA in human mammary gland HBL-100 cells had a size of 2.9 kb and two minor species had sizes of 3.8 and 5.1 kb by Northern blot analyses. These chemical studies established that the active site of human milk BAL is located at serine-194, the N-glycosylation site is present at asparagine-187, the O-glycosylation region is in the 16 repeating units near the C-terminus, and the heparin binding domain is in the N-terminal region. The authors have also determined the location of disulfide bridges as Cys64-Cys80 and Cys246-Cys257. The cyanogen bromide cleavage and the partial sequencing of CNBr peptides also confirmed the location of methionines in the polypeptide chain as well as the deduced cDNA sequence of BAL

  1. Human activity recognition based on feature selection in smart home using back-propagation algorithm.

    Science.gov (United States)

    Fang, Hongqing; He, Lei; Si, Hao; Liu, Peng; Xie, Xiaolei

    2014-09-01

    In this paper, Back-propagation(BP) algorithm has been used to train the feed forward neural network for human activity recognition in smart home environments, and inter-class distance method for feature selection of observed motion sensor events is discussed and tested. And then, the human activity recognition performances of neural network using BP algorithm have been evaluated and compared with other probabilistic algorithms: Naïve Bayes(NB) classifier and Hidden Markov Model(HMM). The results show that different feature datasets yield different activity recognition accuracy. The selection of unsuitable feature datasets increases the computational complexity and degrades the activity recognition accuracy. Furthermore, neural network using BP algorithm has relatively better human activity recognition performances than NB classifier and HMM. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  2. Enabling Collaborative Human-Machine (H-M) Decision Making in Time-critical Activities

    Data.gov (United States)

    National Aeronautics and Space Administration — Self-adjusting autonomous systems (SAS) are spreading from well-defined control activities, such as manufacturing, to complex activities with multi-faceted human...

  3. Association of Single Nucleotide Polymorphisms in the ST3GAL4 Gene with VWF Antigen and Factor VIII Activity.

    Science.gov (United States)

    Song, Jaewoo; Xue, Cheng; Preisser, John S; Cramer, Drake W; Houck, Katie L; Liu, Guo; Folsom, Aaron R; Couper, David; Yu, Fuli; Dong, Jing-Fei

    2016-01-01

    VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC) study for the association of single nucleotide polymorphisms (SNPs) in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects. We also analyzed ST3GAL4 SNPs found in 2,535 subjects of 26 ethnicities from the 1000 Genomes (1000G) project for ethnic diversity, SNP imputation, and ST3GAL4 haplotypes. We identified 14 and 1,714 ST3GAL4 variants in the ARIC GWAS and 1000G databases respectively, with 46% being ethnically diverse in their allele frequencies. Among the 14 ST3GAL4 SNPs found in ARIC GWAS, the intronic rs2186717, rs7928391, and rs11220465 were associated with VWF levels and with FVIII activity after adjustment for age, BMI, hypertension, diabetes, ever-smoking status, and ABO. This study illustrates the power of next-generation sequencing in the discovery of new genetic variants and a significant ethnic diversity in the ST3GAL4 gene. We discuss potential mechanisms through which these intronic SNPs regulate ST3GAL4 biosynthesis and the activity that affects VWF and FVIII.

  4. Sitting is the new smoking : online complex human activity recognition with smartphones and wearables

    NARCIS (Netherlands)

    Shoaib, Muhammad

    2017-01-01

    Human activity recognition plays an important role in fitness tracking, health monitoring, context-aware feedback and self-management of smartphones and wearable devices. These devices are equipped with different sensors which can be used to recognize various human activities. A significant amount of

  5. Active site of tripeptidyl peptidase II from human erythrocytes is of the subtilisin type

    Energy Technology Data Exchange (ETDEWEB)

    Tomkinson, B.; Wernstedt, C.; Hellman, U.; Zetterqvist, Oe.

    1987-11-01

    The present report presents evidence that the amino acid sequence around the serine of the active site of human tripeptidyl peptidase II is of the subtilisin type. The enzyme from human erythrocytes was covalently labeled at its active site with (/sup 3/H)diisopropyl fluorophosphate, and the protein was subsequently reduced, alkylated, and digested with trypsin. The labeled tryptic peptides were purified by gel filtration and repeated reversed-phase HPLC, and their amino-terminal sequences were determined. Residue 9 contained the radioactive label and was, therefore, considered to be the active serine residue. The primary structure of the part of the active site (residues 1-10) containing this residue was concluded to be Xaa-Thr-Gln-Leu-Met-Asx-Gly-Thr-Ser-Met. This amino acid sequence is homologous to the sequence surrounding the active serine of the microbial peptidases subtilisin and thermitase. These data demonstrate that human tripeptidyl peptidase II represents a potentially distinct class of human peptidases and raise the question of an evolutionary relationship between the active site of a mammalian peptidase and that of the subtilisin family of serine peptidases.

  6. Neuronal medium that supports basic synaptic functions and activity of human neurons in vitro.

    Science.gov (United States)

    Bardy, Cedric; van den Hurk, Mark; Eames, Tameji; Marchand, Cynthia; Hernandez, Ruben V; Kellogg, Mariko; Gorris, Mark; Galet, Ben; Palomares, Vanessa; Brown, Joshua; Bang, Anne G; Mertens, Jerome; Böhnke, Lena; Boyer, Leah; Simon, Suzanne; Gage, Fred H

    2015-05-19

    Human cell reprogramming technologies offer access to live human neurons from patients and provide a new alternative for modeling neurological disorders in vitro. Neural electrical activity is the essence of nervous system function in vivo. Therefore, we examined neuronal activity in media widely used to culture neurons. We found that classic basal media, as well as serum, impair action potential generation and synaptic communication. To overcome this problem, we designed a new neuronal medium (BrainPhys basal + serum-free supplements) in which we adjusted the concentrations of inorganic salts, neuroactive amino acids, and energetic substrates. We then tested that this medium adequately supports neuronal activity and survival of human neurons in culture. Long-term exposure to this physiological medium also improved the proportion of neurons that were synaptically active. The medium was designed to culture human neurons but also proved adequate for rodent neurons. The improvement in BrainPhys basal medium to support neurophysiological activity is an important step toward reducing the gap between brain physiological conditions in vivo and neuronal models in vitro.

  7. A novel framework for intelligent surveillance system based on abnormal human activity detection in academic environments.

    Science.gov (United States)

    Al-Nawashi, Malek; Al-Hazaimeh, Obaida M; Saraee, Mohamad

    2017-01-01

    Abnormal activity detection plays a crucial role in surveillance applications, and a surveillance system that can perform robustly in an academic environment has become an urgent need. In this paper, we propose a novel framework for an automatic real-time video-based surveillance system which can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment. To develop our system, we have divided the work into three phases: preprocessing phase, abnormal human activity detection phase, and content-based image retrieval phase. For motion object detection, we used the temporal-differencing algorithm and then located the motions region using the Gaussian function. Furthermore, the shape model based on OMEGA equation was used as a filter for the detected objects (i.e., human and non-human). For object activities analysis, we evaluated and analyzed the human activities of the detected objects. We classified the human activities into two groups: normal activities and abnormal activities based on the support vector machine. The machine then provides an automatic warning in case of abnormal human activities. It also embeds a method to retrieve the detected object from the database for object recognition and identification using content-based image retrieval. Finally, a software-based simulation using MATLAB was performed and the results of the conducted experiments showed an excellent surveillance system that can simultaneously perform the tracking, semantic scene learning, and abnormality detection in an academic environment with no human intervention.

  8. Legal regime of human activities in outer space law

    Science.gov (United States)

    Golda, Carlo

    1994-01-01

    Current developments in space activities increasingly involve the presence of humans on board spacecraft and, in the near future, on the Moon, on Mars, on board Space Stations, etc. With respect to these challenges, the political and legal issues connected to the status of astronauts are largely unclear and require a new doctrinal attention. In the same way, many legal and political questions remain open in the structure of future space crews: the need for international standards in the definition and training of astronauts, etc.; but, first of all, an international uniform legal definition of astronauts. Moreover, the legal structure for human life and operations in outer space can be a new and relevant paradigm for the definition of similar rules in all the situations and environments in which humans are involved in extreme frontiers. The present article starts from an overview on the existing legal and political definitions of 'astronauts', moving to the search of a more useful definition. This is followed by an analysis of the concrete problems created by human space activities, and the legal and political responses to them (the need for a code of conduct; the structure of the crew and the existing rules in the US and ex-USSR; the new legal theories on the argument; the definition and structure of a code of conduct; the next legal problems in fields such as privacy law, communications law, business law, criminal law, etc.).

  9. Characterization of a plasminogen activator from human melanoma cells cultured in vitro

    International Nuclear Information System (INIS)

    Heussen, C.

    1982-08-01

    This thesis describes the work that have been done on the isolation and characterization of a plasminogen activator, Mel-PA, that is released by human melanoma cells cultured in vitro. This enzyme was compared to the urinary plasminogen activator, urokinase. The human melanoma cell line released large amounts of Mel-PA into the surrounding medium when cultured under serum-free conditions. These cells released only one type of plasminogen activator. A technique was developed in which plasminogen activators were seperated electrophoretically and detected in polyacrylamide gel slabs. Mel-PA was concentrated and partially purified by affinity chromatography on benzamidine-sepharose. A study of the distribution of plasminogen activators in tissues and body fluids showed that all mammals examined had two immunochemically distinct plasminogen activators that corresponded, in their distribution, to the urokinase-like and Mel-PA like enzymes of man. A comparitive study of the kinetic behaviour of Mel-PA and urokinase showed numerous differences between the catalytic activities of these two enzymes

  10. Impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased.

    Science.gov (United States)

    Chen, Ming; Qin, Xiaosheng; Zeng, Guangming; Li, Jian

    2016-06-01

    Groundwater quality deterioration has attracted world-wide concerns due to its importance for human water supply. Although more and more studies have shown that human activities and climate are changing the groundwater status, an investigation on how different groundwater heavy metals respond to human activity modes (e.g. mining, waste disposal, agriculture, sewage effluent and complex activity) in a varying climate has been lacking. Here, for each of six heavy metals (i.e. Fe, Zn, Mn, Pb, Cd and Cu) in groundwater, we use >330 data points together with mixed-effect models to indicate that (i) human activity modes significantly influence the Cu and Mn but not Zn, Fe, Pb and Cd levels, and (ii) annual mean temperature (AMT) only significantly influences Cu and Pb levels, while annual precipitation (AP) only significantly affects Fe, Cu and Mn levels. Given these differences, we suggest that the impacts of human activity modes and climate on heavy metal "spread" in groundwater are biased. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Enhanced bag of words using multilevel k-means for human activity recognition

    Directory of Open Access Journals (Sweden)

    Motasem Elshourbagy

    2016-07-01

    Full Text Available This paper aims to enhance the bag of features in order to improve the accuracy of human activity recognition. In this paper, human activity recognition process consists of four stages: local space time features detection, feature description, bag of features representation, and SVMs classification. The k-means step in the bag of features is enhanced by applying three levels of clustering: clustering per video, clustering per action class, and clustering for the final code book. The experimental results show that the proposed method of enhancement reduces the time and memory requirements, and enables the use of all training data in the k-means clustering algorithm. The evaluation of accuracy of action classification on two popular datasets (KTH and Weizmann has been performed. In addition, the proposed method improves the human activity recognition accuracy by 5.57% on the KTH dataset using the same detector, descriptor, and classifier.

  12. EVALUATION OF HUMAN RELIABILITY IN SELECTED ACTIVITIES IN THE RAILWAY INDUSTRY

    Directory of Open Access Journals (Sweden)

    Erika SUJOVÁ

    2016-07-01

    Full Text Available The article focuses on evaluation of human reliability in the human – machine system in the railway industry. Based on a survey of a train dispatcher and of selected activities, we have identified risk factors affecting the dispatcher‘s work and the evaluated risk level of their influence on the reliability and safety of preformed activities. The research took place at the authors‘ work place between 2012-2013. A survey method was used. With its help, authors were able to identify selected work activities of train dispatcher’s risk factors that affect his/her work and the evaluated seriousness of its in-fluence on the reliability and safety of performed activities. Amongst the most important finding fall expressions of un-clear and complicated internal regulations and work processes, a feeling of being overworked, fear for one’s safety at small, insufficiently protected stations.

  13. The influence of periodic increases of human activity on crepuscular and nocturnal mammals: Testing the weekend effect.

    Science.gov (United States)

    Nix, Joshua H; Howell, Ryan G; Hall, Lucas K; McMillan, Brock R

    2018-01-01

    Human recreation can negatively affect wildlife, particularly on weekends when human activity is highest (i.e., the weekend effect). Much of what we understand about the weekend effect is based on research conducted on diurnal species, which have greater temporal overlap with humans. Because nocturnal species generally avoid times when humans are active, they are likely less affected by anthropogenic activity on weekends. Our objective was to test the weekend effect in relation to the degree of nocturnality of mammals in a recreational area. We predicted that as nocturnality increased, the effect of human activity would decrease. To address our objective, we placed 50 remote cameras along the Diamond Fork River in Utah from January to June 2015. We found that three out of the four focal species supported our predictions. Mule deer (crepuscular) reduced activity throughout our entire study area during weekends and avoided campgrounds. Beavers and mountain lions (both nocturnal) did not negatively respond to increased human activity. Raccoons (nocturnal) reduced activity during weekends, but only within campground areas. Our findings indicate that as the temporal overlap increases between wildlife and humans, so does the influence that humans have on wildlife. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Activity of upper limb muscles during human walking.

    Science.gov (United States)

    Kuhtz-Buschbeck, Johann P; Jing, Bo

    2012-04-01

    The EMG activity of upper limb muscles during human gait has rarely been studied previously. It was examined in 20 normal volunteers in four conditions: walking on a treadmill (1) with unrestrained natural arm swing (Normal), (2) while volitionally holding the arms still (Held), (3) with the arms immobilized (Bound), and (4) with the arms swinging in phase with the ipsilateral legs, i.e. opposite-to-normal phasing (Anti-Normal). Normal arm swing involved weak rhythmical lengthening and shortening contractions of arm and shoulder muscles. Phasic muscle activity was needed to keep the unrestricted arms still during walking (Held), indicating a passive component of arm swing. An active component, possibly programmed centrally, existed as well, because some EMG signals persisted when the arms were immobilized during walking (Bound). Anti-Normal gait involved stronger EMG activity than Normal walking and was uneconomical. The present results indicate that normal arm swing has both passive and active components. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Relating Eye Activity Measures to Human Controller Remnant Characteristics

    NARCIS (Netherlands)

    Popovici, A; Zaal, P.M.T.; Pool, D.M.; Mulder, M.; Sawaragi, T

    2016-01-01

    This study attempts to partially explain the characteristics of the human perceptual remnant, following Levison’s representation of the remnant as an equivalent observation noise. Eye activity parameters are recorded using an eye tracker in two compensatory tracking tasks in which the visual

  16. Immunocapture and microplate-based activity and quantity measurement of pyruvate dehydrogenase in human peripheral blood mononuclear cells

    Science.gov (United States)

    Liu, Xiaowen; Pervez, Hira; Andersen, Lars W; Uber, Amy; Montissol, Sophia; Patel, Parth; Donnino, Michael W

    2015-01-01

    Background Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). Results/Methodology We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects. Conclusion Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease. PMID:25826140

  17. Current status and issues of nuclear human resource development/General activities of Japan nuclear human resource development network

    International Nuclear Information System (INIS)

    Murakami, Hiroyuki; Hino, Sadami; Tsuru, Hisanori

    2013-01-01

    The Japan Nuclear Human Resource Development Network (JN-HRD Net) was established in November 2010 with the aim of developing a framework for mutual cooperation and information sharing among nuclear-related organizations. Although the tasks and goals of developing human resources in the nuclear field have been shifted since the accident at the Tokyo Electric Power Company (TEPCO) Fukushima Daiichi Nuclear Power Plant, the necessity of fostering capable personnel in this field stays unchanged and the importance of our network activities has further emphasized. The meeting of JN-HRD Net was held on the 5th of February 2013, where its activities by each field were reported and views and opinions were actively exchanged between more than 90 participants. This paper briefly describes current status and issues of JN-HRD Net and its general activities conducted by the JN-HRD Net secretariat. (J.P.N.)

  18. Human Protein C produces anticoagulation and increased fibrinolytic activity in the cat

    International Nuclear Information System (INIS)

    Burdick, M.D.; Schaub, R.G.

    1986-01-01

    The effect of activated human Protein C (PCa) infusion on the coagulation and fibrinolytic systems of the Nembutal anesthetized cat was assessed. Human Protein C was activated by incubation with thrombin or by passage over a column of thrombin immobilized on CNBr Sepharose 4B. Cats were given bolus i.v. injections of either vehicle or PCa in a dose range of 3-16 μg/mL of calculated whole body volume. Citrated blood samples (9:1) were taken from a femoral vein prior to and at 5, 10, 20, 30, 60, 120, and 180 min. after PCa. Activated partial thromboplastin time (APTT), thrombin time (TT) euglobulin clot lysis (ECLT) and I-125 fibrin release (FR) was measured. Vehicle treated cats had no change in any parameter. PCa produced a dose and time dependent prolongation of APTT while TT was unchanged. Anticoagulation was evident immediately after PCa infusion and began to normalize within 20 min. Fibrinolytic activity measured by ECLT and FR was also stimulated by PCa but was not evident until 40-60 minutes after PCa injection. The results show that human PCa induces anticoagulation effects in the cat similar to other species. However, stimulation of fibrinolysis requires a longer period of time before expression. This delay of fibrinolytic stimulation should be considered when assessing the effects of human Protein C in other species

  19. Characterizing human activity induced impulse and slip-pulse excitations through structural vibration

    Science.gov (United States)

    Pan, Shijia; Mirshekari, Mostafa; Fagert, Jonathon; Ramirez, Ceferino Gabriel; Chung, Albert Jin; Hu, Chih Chi; Shen, John Paul; Zhang, Pei; Noh, Hae Young

    2018-02-01

    Many human activities induce excitations on ambient structures with various objects, causing the structures to vibrate. Accurate vibration excitation source detection and characterization enable human activity information inference, hence allowing human activity monitoring for various smart building applications. By utilizing structural vibrations, we can achieve sparse and non-intrusive sensing, unlike pressure- and vision-based methods. Many approaches have been presented on vibration-based source characterization, and they often either focus on one excitation type or have limited performance due to the dispersion and attenuation effects of the structures. In this paper, we present our method to characterize two main types of excitations induced by human activities (impulse and slip-pulse) on multiple structures. By understanding the physical properties of waves and their propagation, the system can achieve accurate excitation tracking on different structures without large-scale labeled training data. Specifically, our algorithm takes properties of surface waves generated by impulse and of body waves generated by slip-pulse into account to handle the dispersion and attenuation effects when different types of excitations happen on various structures. We then evaluate the algorithm through multiple scenarios. Our method achieves up to a six times improvement in impulse localization accuracy and a three times improvement in slip-pulse trajectory length estimation compared to existing methods that do not take wave properties into account.

  20. An implicit spatiotemporal shape model for human activity localization and recognition

    NARCIS (Netherlands)

    Oikonomopoulos, A.; Patras, I.; Pantic, Maja

    2009-01-01

    In this paper we address the problem of localisation and recognition of human activities in unsegmented image sequences. The main contribution of the proposed method is the use of an implicit representation of the spatiotemporal shape of the activity which relies on the spatiotemporal localization

  1. Down-regulation of telomerase activity in DLD-1 human colorectal adenocarcinoma cells by tocotrienol

    International Nuclear Information System (INIS)

    Eitsuka, Takahiro; Nakagawa, Kiyotaka; Miyazawa, Teruo

    2006-01-01

    As high telomerase activity is detected in most cancer cells, inhibition of telomerase by drug or dietary food components is a new strategy for cancer prevention. Here, we investigated the inhibitory effect of vitamin E, with particular emphasis on tocotrienol (unsaturated vitamin E), on human telomerase in cell-culture study. As results, tocotrienol inhibited telomerase activity of DLD-1 human colorectal adenocarcinoma cells in time- and dose-dependent manner, interestingly, with δ-tocotrienol exhibiting the highest inhibitory activity. Tocotrienol inhibited protein kinase C activity, resulting in down-regulation of c-myc and human telomerase reverse transcriptase (hTERT) expression, thereby reducing telomerase activity. In contrast to tocotrienol, tocopherol showed very weak telomerase inhibition. These results provide novel evidence for First time indicating that tocotrienol acts as a potent candidate regulator of telomerase and supporting the anti-proliferative function of tocotrienol

  2. The Evolution of Lineage-Specific Regulatory Activities in the Human Embryonic Limb

    OpenAIRE

    Cotney, Justin; Leng, Jing; Yin, Jun; Reilly, Steven K.; DeMare, Laura E.; Emera, Deena; Ayoub, Albert E.; Rakic, Pasko; Noonan, James P.

    2013-01-01

    The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find...

  3. Use of human tissue to assess the oncogenic activity of melanoma-associated mutations.

    Science.gov (United States)

    Chudnovsky, Yakov; Adams, Amy E; Robbins, Paul B; Lin, Qun; Khavari, Paul A

    2005-07-01

    Multiple genetic alterations occur in melanoma, a lethal skin malignancy of increasing incidence. These include mutations that activate Ras and two of its effector cascades, Raf and phosphoinositide 3-kinase (PI3K). Induction of Ras and Raf can be caused by active N-Ras and B-Raf mutants as well as by gene amplification. Activation of PI3K pathway components occurs by PTEN loss and by AKT3 amplification. Melanomas also commonly show impairment of the p16(INK4A)-CDK4-Rb and ARF-HDM2-p53 tumor suppressor pathways. CDKN2A mutations can produce p16(INK4A) and ARF protein loss. Rb bypass can also occur through activating CDK4 mutations as well as by CDK4 amplification. In addition to ARF deletion, p53 pathway disruption can result from dominant negative TP53 mutations. TERT amplification also occurs in melanoma. The extent to which these mutations can induce human melanocytic neoplasia is unknown. Here we characterize pathways sufficient to generate human melanocytic neoplasia and show that genetically altered human tissue facilitates functional analysis of mutations observed in human tumors.

  4. An Alternative to the Human Hemoglobin Test in the Investigation of Bloodstains Treated with Active Oxygen: The Human Glycophorin A Test

    Directory of Open Access Journals (Sweden)

    Ana Castelló

    2011-01-01

    Full Text Available In criminal investigations, there are three stages involved when studying bloodstains: search and orientation, confirmation, and individualization. Confirmatory tests have two aims: to show that the stain contains a human biological fluid and to confirm the type of biological fluid. The need to determine the nature of the evidence is reflected in the latest bibliography, where the possibility of employing mRNA and miRNA markers for this purpose is proposed. While these new proposals are being investigated, the kits for determining human hemoglobin currently provide a simple solution for resolving this issue. With these kits, the possibility of obtaining false positives and false negatives is well known. However, recently, a new problem has been detected. This involves the interference caused by new cleaning products that contain sodium percarbonate (or active oxygen when determining human hemoglobin. With the aim to resolve this problem, this work studied the ability of the human glycophorin A test to determine human blood in samples that have been treated with active oxygen. Our results show that the human glycophorin A test has a greater resistance to the destructive effect of the new detergents containing active oxygen; consequently, it provides an alternative to be taken into consideration in the confirmatory diagnoses of bloodstains.

  5. Protein S binding to human endothelial cells is required for expression of cofactor activity for activated protein C

    NARCIS (Netherlands)

    Hackeng, T. M.; Hessing, M.; van 't Veer, C.; Meijer-Huizinga, F.; Meijers, J. C.; de Groot, P. G.; van Mourik, J. A.; Bouma, B. N.

    1993-01-01

    An important feedback mechanism in blood coagulation is supplied by the protein C/protein S anticoagulant pathway. In this study we demonstrate that the binding of human protein S to cultured human umbilical vein endothelial cells (HUVECs) is required for the expression of cofactor activity of

  6. Regulation of the human SLC25A20 expression by peroxisome proliferator-activated receptor alpha in human hepatoblastoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Tachibana, Keisuke, E-mail: nya@phs.osaka-u.ac.jp [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Takeuchi, Kentaro; Inada, Hirohiko [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Yamasaki, Daisuke [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Ishimoto, Kenji [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Toshiya; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko [Laboratory for System Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8904 (Japan); Doi, Takefumi [Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); The Center for Advanced Medical Engineering and Informatics, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)

    2009-11-20

    Solute carrier family 25, member 20 (SLC25A20) is a key molecule that transfers acylcarnitine esters in exchange for free carnitine across the mitochondrial membrane in the mitochondrial {beta}-oxidation. The peroxisome proliferator-activated receptor alpha (PPAR{alpha}) is a ligand-activated transcription factor that plays an important role in the regulation of {beta}-oxidation. We previously established tetracycline-regulated human cell line that can be induced to express PPAR{alpha} and found that PPAR{alpha} induces the SLC25A20 expression. In this study, we analyzed the promoter region of the human slc25a20 gene and showed that PPAR{alpha} regulates the expression of human SLC25A20 via the peroxisome proliferator responsive element.

  7. Human dignity and the future of the voluntary active euthanasia debate in South Africa.

    Science.gov (United States)

    Jordaan, Donrich W

    2017-04-25

    The issue of voluntary active euthanasia was thrust into the public policy arena by the Stransham-Ford lawsuit. The High Court legalised voluntary active euthanasia - however, ostensibly only in the specific case of Mr Stransham-Ford. The Supreme Court of Appeal overturned the High Court judgment on technical grounds, not on the merits. This means that in future the courts can be approached again to consider the legalisation of voluntary active euthanasia. As such, Stransham-Ford presents a learning opportunity for both sides of the legalisation divide. In particular, conceptual errors pertaining to human dignity were made in Stransham-Ford, and can be avoided in future. In this article, I identify these errors and propose the following three corrective principles to inform future debate on the subject: (i) human dignity is violable; (ii) human suffering violates human dignity; and (iii) the 'natural' causes of suffering due to terminal illness do not exclude the application of human dignity.

  8. Human dignity and the future of the voluntary active euthanasia debate in South Africa

    Directory of Open Access Journals (Sweden)

    Donrich W Jordaan

    2017-05-01

    Full Text Available The issue of voluntary active euthanasia was thrust into the public policy arena by the Stransham-Ford lawsuit. The High Court legalised voluntary active euthanasia – however, ostensibly only in the specific case of Mr Stransham-Ford. The Supreme Court of Appeal overturned the High Court judgment on technical grounds, not on the merits. This means that in future the courts can be approached again to consider the legalisation of voluntary active euthanasia. As such, Stransham-Ford presents a learning opportunity for both sides of the legalisation divide. In particular, conceptual errors pertaining to human dignity were made in Stransham-Ford, and can be avoided in future. In this article, I identify these errors and propose the following three corrective principles to inform future debate on the subject: (i human dignity is violable; (ii human suffering violates human dignity; and (iii the ‘natural’ causes of suffering due to terminal illness do not exclude the application of human dignity.

  9. Contributions of climate change and human activities to runoff change in seven typical catchments across China.

    Science.gov (United States)

    Zhai, Ran; Tao, Fulu

    2017-12-15

    Climate change and human activities are two major factors affecting water resource change. It is important to understand the roles of the major factors in affecting runoff change in different basins for watershed management. Here, we investigated the trends in climate and runoff in seven typical catchments in seven basins across China from 1961 to 2014. Then we attributed the runoff change to climate change and human activities in each catchment and in three time periods (1980s, 1990s and 2000s), using the VIC model and long-term runoff observation data. During 1961-2014, temperature increased significantly, while the trends in precipitation were insignificant in most of the catchments and inconsistent among the catchments. The runoff in most of the catchments showed a decreasing trend except the Yingluoxia catchment in the northwestern China. The contributions of climate change and human activities to runoff change varied in different catchments and time periods. In the 1980s, climate change contributed more to runoff change than human activities, which was 84%, 59%, -66%, -50%, 59%, 94%, and -59% in the Nianzishan, Yingluoxia, Xiahui, Yangjiaping, Sanjiangkou, Xixian, and Changle catchment, respectively. After that, human activities had played a more essential role in runoff change. In the 1990s and 2000s, human activities contributed more to runoff change than in the 1980s. The contribution by human activities accounted for 84%, -68%, and 67% in the Yingluoxia, Xiahui, and Sanjiangkou catchment, respectively, in the 1990s; and -96%, -67%, -94%, and -142% in the Nianzishan, Yangjiaping, Xixian, and Changle catchment, respectively, in the 2000s. It is also noted that after 2000 human activities caused decrease in runoff in all catchments except the Yingluoxia. Our findings highlight that the effects of human activities, such as increase in water withdrawal, land use/cover change, operation of dams and reservoirs, should be well managed. Copyright © 2017 Elsevier

  10. Inhibition by nucleosides of glucose-transport activity in human erythrocytes.

    OpenAIRE

    Jarvis, S M

    1988-01-01

    The interaction of nucleosides with the glucose carrier of human erythrocytes was examined by studying the effect of nucleosides on reversible cytochalasin B-binding activity and glucose transport. Adenosine, inosine and thymidine were more potent inhibitors of cytochalasin B binding to human erythrocyte membranes than was D-glucose [IC50 (concentration causing 50% inhibition) values of 10, 24, 28 and 38 mM respectively]. Moreover, low concentrations of thymidine and adenosine inhibited D-glu...

  11. Metabolites of alectinib in human: their identification and pharmacological activity

    Directory of Open Access Journals (Sweden)

    Mika Sato-Nakai

    2017-07-01

    Full Text Available Two metabolites (M4 and M1b in plasma and four metabolites (M4, M6, M1a and M1b in faeces were detected through the human ADME study following a single oral administration of [14C]alectinib, a small-molecule anaplastic lymphoma kinase inhibitor, to healthy subjects. In the present study, M1a and M1b, which chemical structures had not been identified prior to the human ADME study, were identified as isomers of a carboxylate metabolite oxidatively cleaved at the morpholine ring. In faeces, M4 and M1b were the main metabolites, which shows that the biotransformation to M4 and M1b represents two main metabolic pathways for alectinib. In plasma, M4 was a major metabolite and M1b was a minor metabolite. The contribution to in vivo pharmacological activity of these circulating metabolites was assessed from their in vitro pharmacological activity and plasma protein binding. M4 had a similar cancer cell growth inhibitory activity and plasma protein binding to that of alectinib, suggesting its contribution to the antitumor activity of alectinib, whereas the pharmacological activity of M1b was insignificant.

  12. Complex Human Activity Recognition Using Smartphone and Wrist-Worn Motion Sensors

    NARCIS (Netherlands)

    Shoaib, M.; Bosch, S.; Durmaz, O.; Scholten, Johan; Havinga, Paul J.M.

    2016-01-01

    The position of on-body motion sensors plays an important role in human activity recognition. Most often, mobile phone sensors at the trouser pocket or an equivalent position are used for this purpose. However, this position is not suitable for recognizing activities that involve hand gestures, such

  13. Isothiocyanates: An Overview of Their Antimicrobial Activity against Human Infections

    Directory of Open Access Journals (Sweden)

    Letizia Romeo

    2018-03-01

    Full Text Available The use of plant-derived products as antimicrobial agents has been investigated in depth. Isothiocyanates (ITCs are bioactive products resulting from enzymatic hydrolysis of glucosinolates (GLs, the most abundant secondary metabolites in the botanical order Brassicales. Although the antimicrobial activity of ITCs against foodborne and plant pathogens has been well documented, little is known about their antimicrobial properties against human pathogens. This review collects studies that focus on this topic. Particular focus will be put on ITCs’ antimicrobial properties and their mechanism of action against human pathogens for which the current therapeutic solutions are deficient and therefore of prime importance for public health. Our purpose was the evaluation of the potential use of ITCs to replace or support the common antibiotics. Even though ITCs appear to be effective against the most important human pathogens, including bacteria with resistant phenotypes, the majority of the studies did not show comparable results and thus it is very difficult to compare the antimicrobial activity of the different ITCs. For this reason, a standard method should be used and further studies are needed.

  14. Anthocyanin contents in the seed coat of black soya bean and their anti-human tyrosinase activity and antioxidative activity.

    Science.gov (United States)

    Jhan, J-K; Chung, Y-C; Chen, G-H; Chang, C-H; Lu, Y-C; Hsu, C-K

    2016-06-01

    The seed coat of black soya bean (SCBS) contains high amount of anthocyanins and shows antioxidant and anti-mushroom tyrosinase activities. The objectives of this study were to analyse the anthocyanins in SCBS with different solvents and to find the relationship between anthocyanin profile with anti-human and anti-mushroom tyrosinase activities. SCBS was extracted with hot water, 50 and 80% ethanol, 50 and 80% acetone and 50 and 80% acidified acetone. Total phenol and total flavonoid contents in the extracts were determined. Anthocyanins in the extracts were analysed using HPLC and LC/MS/MS. A genetically engineered human tyrosinase was used to evaluate the anti-tyrosinase potential of the extracts from SCBS. 80% acetone extract from SCBS obtained the highest total phenol, total flavonoid and cyanidin-3-O-glucoside (C3G) contents among all the extracts, whereas the hot water extract showed the lowest antioxidant contents. Three anthocyanin compounds were found in all the extracts from SCBS, and the analysis of HPLC and LC/MS/MS indicated that they were C3G, delphinidin-3-O-glucoside (D3G) and peonidin-3-O-glucoside (P3G). The ratios of C3G (2.84 mg g(-1) ), D3G (0.34 mg g(-1) ) and P3G (0.35 mg g(-1) ) in 80% acidified acetone extract were 76.6, 9.1 and 9.3%, respectively. All the extracts from SCBS possessed anti-human tyrosinase activity. Moreover, a good correlation was found between the anti-human tyrosinase activities and C3G contents in the extracts. Antioxidants in SCBS also possess anti-human and anti-mushroom tyrosinase activities. © 2015 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

  15. Quantitation of fibroblast activation protein (FAP-specific protease activity in mouse, baboon and human fluids and organs

    Directory of Open Access Journals (Sweden)

    Fiona M. Keane

    2014-01-01

    Full Text Available The protease fibroblast activation protein (FAP is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

  16. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    NARCIS (Netherlands)

    Self, Matthew W.; Peters, Judith C.; Possel, Jessy K.; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C.; Roelfsema, Pieter R.

    2016-01-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive

  17. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex

    NARCIS (Netherlands)

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive

  18. Wearable-Based Human Activity Recognition Using an IoT Approach

    Directory of Open Access Journals (Sweden)

    Diego Castro

    2017-11-01

    Full Text Available This paper presents a novel system based on the Internet of Things (IoT to Human Activity Recognition (HAR by monitoring vital signs remotely. We use machine learning algorithms to determine the activity done within four pre-established categories (lie, sit, walk and jog. Meanwhile, it is able to give feedback during and after the activity is performed, using a remote monitoring component with remote visualization and programmable alarms. This system was successfully implemented with a 95.83% success ratio.

  19. Active glass-type human augmented cognition system considering attention and intention

    Science.gov (United States)

    Kim, Bumhwi; Ojha, Amitash; Lee, Minho

    2015-10-01

    Human cognition is the result of an interaction of several complex cognitive processes with limited capabilities. Therefore, the primary objective of human cognitive augmentation is to assist and expand these limited human cognitive capabilities independently or together. In this study, we propose a glass-type human augmented cognition system, which attempts to actively assist human memory functions by providing relevant, necessary and intended information by constantly assessing intention of the user. To achieve this, we exploit selective attention and intention processes. Although the system can be used in various real-life scenarios, we test the performance of the system in a person identity scenario. To detect the intended face, the system analyses the gaze points and change in pupil size to determine the intention of the user. An assessment of the gaze points and change in pupil size together indicates that the user intends to know the identity and information about the person in question. Then, the system retrieves several clues through speech recognition system and retrieves relevant information about the face, which is finally displayed through head-mounted display. We present the performance of several components of the system. Our results show that the active and relevant assistance based on users' intention significantly helps the enhancement of memory functions.

  20. A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks

    Directory of Open Access Journals (Sweden)

    Alejandra García-Hernández

    2017-11-01

    Full Text Available Human Activity Recognition (HAR is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location.

  1. Actively learning human gaze shifting paths for semantics-aware photo cropping.

    Science.gov (United States)

    Zhang, Luming; Gao, Yue; Ji, Rongrong; Xia, Yingjie; Dai, Qionghai; Li, Xuelong

    2014-05-01

    Photo cropping is a widely used tool in printing industry, photography, and cinematography. Conventional cropping models suffer from the following three challenges. First, the deemphasized role of semantic contents that are many times more important than low-level features in photo aesthetics. Second, the absence of a sequential ordering in the existing models. In contrast, humans look at semantically important regions sequentially when viewing a photo. Third, the difficulty of leveraging inputs from multiple users. Experience from multiple users is particularly critical in cropping as photo assessment is quite a subjective task. To address these challenges, this paper proposes semantics-aware photo cropping, which crops a photo by simulating the process of humans sequentially perceiving semantically important regions of a photo. We first project the local features (graphlets in this paper) onto the semantic space, which is constructed based on the category information of the training photos. An efficient learning algorithm is then derived to sequentially select semantically representative graphlets of a photo, and the selecting process can be interpreted by a path, which simulates humans actively perceiving semantics in a photo. Furthermore, we learn a prior distribution of such active graphlet paths from training photos that are marked as aesthetically pleasing by multiple users. The learned priors enforce the corresponding active graphlet path of a test photo to be maximally similar to those from the training photos. Experimental results show that: 1) the active graphlet path accurately predicts human gaze shifting, and thus is more indicative for photo aesthetics than conventional saliency maps and 2) the cropped photos produced by our approach outperform its competitors in both qualitative and quantitative comparisons.

  2. Correlation between proliferative activity and cellular thickness of human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Katsube, Yoshihiro; Hirose, Motohiro; Nakamura, Chikashi; Ohgushi, Hajime

    2008-01-01

    A cell's shape is known to be related to its proliferative activity. In particular, large and flat mammalian adult stem cells seem to show slow proliferation, however using quantitative analysis to prove the phenomenon is difficult. We measured the proliferation and cellular thickness of human mesenchymal stem cells (MSCs) by atomic force microscopy and found that MSCs with high proliferative activity were thick while those with low proliferative activity were thin, even though these MSCs were early passage cells. Further, low proliferative MSCs contained many senescence-associated β-galactosidase positive cells together with high senescence-associated gene expression. These findings suggest that the measurement of cellular thickness is useful for estimating the proliferative activity of human MSCs and is expected to be a practical tool for MSC applications in regenerative medicine

  3. Environmental Health in Relation to Urban Planning and Human Physical Activity

    International Nuclear Information System (INIS)

    Oliver, L.H.L.; Siti Nur Afiqah Mohamed Musthafa; Dasimah Omar

    2015-01-01

    The world is changing everyday in a fast pace that makes majority of the urbanized areas becoming more congested and polluted by the development. The planning of the urban world has brought about a great impact towards the environment and health. With the large number of human population, urban areas will have various kinds of activities that contributed to the higher rate of pollutants compared to areas with less development. In a car oriented urban development pattern, majority of the population will choose automobiles as their transportation modes rather than walking or cycling. Due to that, the air emission in urban areas will increase rapidly, and reduce the physical activity. Air pollutants contribute to various health problems, especially respiratory infection. Besides, lacking of physical activities also increase the health risk. However, there is limited study on the relationship between urban land use setting and health in developing country. Thus, a study had been carried out to establish the relationship between urban setting and human health. It involved air quality data collection, observation on land use setting, and questionnaire survey on human health and the lifestyle. Findings from the relationship analysis had been discussed with suitable recommendation and conclusion. (author)

  4. N-glycan sialylation in a silkworm-baculovirus expression system.

    Science.gov (United States)

    Suganuma, Masatoshi; Nomura, Tsuyoshi; Higa, Yukiko; Kataoka, Yukiko; Funaguma, Shunsuke; Okazaki, Hironobu; Suzuki, Takeo; Fujiyama, Kazuhito; Sezutsu, Hideki; Tatematsu, Ken-Ichiro; Tamura, Toshiki

    2018-02-09

    A silkworm-baculovirus system is particularly effective for producing recombinant proteins, including glycoproteins. However, N-glycan structures in silkworm differ from those in mammals. Glycoproteins in silkworm are secreted as pauci-mannose type N-glycans without sialic acid or galactose residues. Sialic acid on N-glycans plays important roles in protein functions. Therefore, we developed pathways for galactosylation and sialylation in silkworm. Sialylated N-glycans on proteins were successfully produced in silkworm by co-expressing galactosyltransferase and sialyltransferase and providing an external supply of a sialylation-related substrate. α2,3/α2,6 Sialylation to N-glycans was controlled by changing the type of sialyltransferase expressed in silkworm. Furthermore, the co-expression of N-acetylglucosaminyltransferase II facilitated the formation of additional di-sialylated N-glycan structures. Our results provide new information on the control of N-glycosylation in silkworm. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  5. Focus-of-attention for human activity recognition from UAVs

    NARCIS (Netherlands)

    Burghouts, G.J.; Eekeren, A.W.M. van; Dijk, J.

    2014-01-01

    This paper presents a system to extract metadata about human activities from full-motion video recorded from a UAV. The pipeline consists of these components: tracking, motion features, representation of the tracks in terms of their motion features, and classification of each track as one of the

  6. Downregulation of telomerase activity in human promyelocytic cell line using RNA interference.

    Science.gov (United States)

    Miri-Moghaddam, E; Deezagi, A; Soheili, Z S

    2009-12-01

    Telomerase is a ribonucleoprotein complex. It consists of two main components, human telomerase reverse transcriptase (hTERT) and human telomerase RNA. High telomerase activity is present in most malignant cells, but it is barely detectable in majority of somatic cells. The direct correlation between telomerase reactivation and carcinogens has made hTERT a key target for anticancer therapeutic studies. In this study, for the first time, we evaluated the ability of the new generation of short interfering RNA (siRNA) to regulate telomerase activity in the human promyelocytic leukemia cell line (HL-60). Transient transfection cell line by hTERT siRNAs resulted in statistically significant suppression of hTERT messenger RNAs which were detected by quantitative real-time polymerase chain reaction, while the expressed hTERT protein levels were measured by flow cytometry. The results of telomeric repeat amplification protocol showed that telomerase activity was significantly reduced upon transfection of the HL-60 cell line with hTERT siRNAs. The results of this study showed that telomerase activity and cell proliferation were efficiently inhibited in the hTERT siRNA-treated leukemic cell line.

  7. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Directory of Open Access Journals (Sweden)

    Dario Moreira-Arce

    Full Text Available Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in

  8. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    Science.gov (United States)

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  9. Elemental analysis of human serum and serum protein fractions by thermal neutron activation

    International Nuclear Information System (INIS)

    Woittiez, J.R.W.

    1984-01-01

    Some applications of thermal neutron activation for the determination of elemental contents in human serum and human serum protein fractions are presented. Firstly total serum is dealt with, secondly serum protein fractions obtained by gel filtration are described. A brief review on the role of (trace) elements in human health and disease and a compilation of literature data for elemental contents in human serum, as obtained by neutron activation techniques, are given. The most important sources of statistical and systematic errors are evaluated. Results for the contents of sodium, potassium, magnesium, bromine, iron, copper, zinc, selenium, rubidium, cesium and antimony in serum are given, with emphasis on control of accuracy and precision. The possible relation between selenium in blood and cancer occurrence in humans is discussed. The results of elemental analyses from cancer patients and from a patient receiving a cytostatic treatment are presented. A survey of literature results for the determination of protein-bound elemental contents in serum is presented. Subsequently, results from a study on the behaviour of elements during gel filtration are discussed. Gel-element and protein-element interactions are studied. Finally the protein-bound occurrence of trace elements in human serum is determined by gel filtration and neutron activation analysis. Results for both desalting and fractionation are given, for the elements bromine, copper, manganese, vanadium, selenium, zinc, rubidium, iron and iodine. (Auth.)

  10. Antagonistic activity of antibiotic producing Streptomyces sp. against fish and human pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Nazmul Hossain

    2014-04-01

    Full Text Available In this study, attempts were made to isolate Streptomyces sp. from soil samples of two different regions of Bangladesh and evaluate their antagonistic activity against fish and human pathogenic bacteria. A total of 10 isolates were identified as Streptomyces sp. based on several morphological, physiological and biochemical tests. Cross streak method was used to observe the antagonistic activity of the Streptomyces sp. isolates against different fish pathogens belonging to the genus Aeromonas, Pseudomonas and Edwardsiella and human clinical isolates belonging to the genus Klebsiella, Salmonella and Streptococcus. Seven Streptomyces sp. isolates showed antagonism against both fish and human pathogenic bacteria. Four isolates viz., N24, N26, N28 and N47 showed broad spectrum of antagonistic activity (80-100% against all genera of fish and human pathogenic bacteria. The isolate N49 exhibited highest spectrum of antagonism against all fish pathogens (90-100% but comparatively lower degree of antagonism against human pathogens (50-60%. Rest of the two isolates (N21 and N23 showed variability in their antagonism. Results showed that broad spectrum antibiotic(s could be developed from the isolates N24, N26, N28 and N47against several human and fish pathogens. The isolate N49 could be a potential source of antibiotic, especially for fish pathogenic bacteria.

  11. Toshiba's activity concerning technology succession and human resource development

    International Nuclear Information System (INIS)

    Ogura, Kenji; Hoshide, Akehiko

    2008-01-01

    Recently, from the viewpoint of the reduction of carbon-dioxide emission that cause global warming and the energy security, the importance of nuclear power generation is recognized again as an effective approach for solving the problems, and many nuclear power plants are planed to be constructed worldwide. On the other hand, the experienced engineers will face the time of the retirement in the near future and technology succession and human resource development has become important problems. In this paper, Toshiba's Nuclear Energy Systems and Services Division's activity concerning technology succession and human resource development will be introduced. (author)

  12. AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

    Science.gov (United States)

    2013-01-01

    Chemokine (C-C motif) ligand 3 (CCL3), also known as macrophage inflammatory protein-1α, is a cytokine involved in inflammation and activation of polymorphonuclear leukocytes. CCL3 has been detected in infiltrating cells and tumor cells. Chondrosarcoma is a highly malignant tumor that causes distant metastasis. However, the effect of CCL3 on human chondrosarcoma metastasis is still unknown. Here, we found that CCL3 increased cellular migration and expression of matrix metalloproteinase (MMP)-2 in human chondrosarcoma cells. Pre-treatment of cells with the MMP-2 inhibitor or transfection with MMP-2 specific siRNA abolished CCL3-induced cell migration. CCL3 has been reported to exert its effects through activation of its specific receptor, CC chemokine receptor 5 (CCR5). The CCR5 and AMP-activated protein kinase (AMPK) inhibitor or siRNA also attenuated CCL3-upregulated cell motility and MMP-2 expression. CCL3-induced expression of MMP-2 and migration were also inhibited by specific inhibitors, and inactive mutants of AMPK, p38 mitogen activated protein kinase (p38 or p38-MAPK), and nuclear factor κB (NF-κB) cascades. On the other hand, CCL3 treatment demonstrably activated AMPK, p38, and NF-κB signaling pathways. Furthermore, the expression levels of CCL3, CCR5, and MMP-2 were correlated in human chondrosarcoma specimens. Taken together, our results indicate that CCL3 enhances the migratory ability of human chondrosarcoma cells by increasing MMP-2 expression via the CCR5, AMPK, p38, and NF-κB pathways. PMID:24047437

  13. Human-robot interaction: kinematics and muscle activity inside a powered compliant knee exoskeleton.

    Science.gov (United States)

    Knaepen, Kristel; Beyl, Pieter; Duerinck, Saartje; Hagman, Friso; Lefeber, Dirk; Meeusen, Romain

    2014-11-01

    Until today it is not entirely clear how humans interact with automated gait rehabilitation devices and how we can, based on that interaction, maximize the effectiveness of these exoskeletons. The goal of this study was to gain knowledge on the human-robot interaction, in terms of kinematics and muscle activity, between a healthy human motor system and a powered knee exoskeleton (i.e., KNEXO). Therefore, temporal and spatial gait parameters, human joint kinematics, exoskeleton kinetics and muscle activity during four different walking trials in 10 healthy male subjects were studied. Healthy subjects can walk with KNEXO in patient-in-charge mode with some slight constraints in kinematics and muscle activity primarily due to inertia of the device. Yet, during robot-in-charge walking the muscular constraints are reversed by adding positive power to the leg swing, compensating in part this inertia. Next to that, KNEXO accurately records and replays the right knee kinematics meaning that subject-specific trajectories can be implemented as a target trajectory during assisted walking. No significant differences in the human response to the interaction with KNEXO in low and high compliant assistance could be pointed out. This is in contradiction with our hypothesis that muscle activity would decrease with increasing assistance. It seems that the differences between the parameter settings of low and high compliant control might not be sufficient to observe clear effects in healthy subjects. Moreover, we should take into account that KNEXO is a unilateral, 1 degree-of-freedom device.

  14. Activation of the lectin complement pathway on human renal ...

    African Journals Online (AJOL)

    This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro. Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface ...

  15. Human factors in remote control engineering development activities

    International Nuclear Information System (INIS)

    Clarke, M.M.; Hamel, W.R.; Draper, J.V.

    1983-01-01

    Human factors engineering, which is an integral part of the advanced remote control development activities at the Oak Ridge National Laboratory, is described. First, work at the Remote Systems Development Facility (RSDF) has shown that operators can perform a wide variety of tasks, some of which were not specifically designed for remote systems, with a dextrous electronic force-reflecting servomanipulator and good television remote viewing capabilities. Second, the data collected during mock-up remote maintenance experiments at the RSDF have been analyzed to provide guidelines for the design of human interfaces with an integrated advanced remote maintenance system currently under development. Guidelines have been provided for task allocation between operators, remote viewing systems, and operator controls. 6 references, 5 figures, 2 tables

  16. Human Spaceflight. Activities for the Primary Student. Aerospace Education Services Project.

    Science.gov (United States)

    Hartsfield, John W.; Hartsfield, Kendra J.

    Since its beginning, the space program has caught the attention of young people. This space science activity booklet was designed to provide information and learning activities for students in elementary grades. It contains chapters on: (1) primitive beliefs about flight; (2) early fantasies of flight; (3) the United States human spaceflight…

  17. Interaction of Human Enterochromaffin Cells with Human Enteric Adenovirus 41 Leads to Serotonin Release and Subsequent Activation of Enteric Glia Cells.

    Science.gov (United States)

    Westerberg, Sonja; Hagbom, Marie; Rajan, Anandi; Loitto, Vesa; Persson, B David; Allard, Annika; Nordgren, Johan; Sharma, Sumit; Magnusson, Karl-Eric; Arnberg, Niklas; Svensson, Lennart

    2018-04-01

    Human adenovirus 41 (HAdV-41) causes acute gastroenteritis in young children. The main characteristics of HAdV-41 infection are diarrhea and vomiting. Nevertheless, the precise mechanism of HAdV-41-induced diarrhea is unknown, as a suitable small-animal model has not been described. In this study, we used the human midgut carcinoid cell line GOT1 to investigate the effect of HAdV-41 infection and the individual HAdV-41 capsid proteins on serotonin release by enterochromaffin cells and on enteric glia cell (EGC) activation. We first determined that HAdV-41 could infect the enterochromaffin cells. Immunofluorescence staining revealed that the cells expressed HAdV-41-specific coxsackievirus and adenovirus receptor (CAR); flow cytometry analysis supported these findings. HAdV-41 infection of the enterochromaffin cells induced serotonin secretion dose dependently. In contrast, control infection with HAdV-5 did not induce serotonin secretion in the cells. Confocal microscopy studies of enterochromaffin cells infected with HAdV-41 revealed decreased serotonin immunofluorescence compared to that in uninfected cells. Incubation of the enterochromaffin cells with purified HAdV-41 short fiber knob and hexon proteins increased the serotonin levels in the harvested cell supernatant significantly. HAdV-41 infection could also activate EGCs, as shown in the significantly altered expression of glia fibrillary acidic protein (GFAP) in EGCs incubated with HAdV-41. The EGCs were also activated by serotonin alone, as shown in the significantly increased GFAP staining intensity. Likewise, EGCs were activated by the cell supernatant of HAdV-41-infected enterochromaffin cells. IMPORTANCE The nonenveloped human adenovirus 41 causes diarrhea, vomiting, dehydration, and low-grade fever mainly in children under 2 years of age. Even though acute gastroenteritis is well described, how human adenovirus 41 causes diarrhea is unknown. In our study, we analyzed the effect of human adenovirus 41

  18. Disturbances of electrodynamic activity affect abortion in human

    Science.gov (United States)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  19. Disturbances of electrodynamic activity affect abortion in human

    International Nuclear Information System (INIS)

    Jandová, A; Cifra, M; Pokorný, J; Nedbalová, M; Dohnalová, A; Kobilková, J; Cocek, A

    2011-01-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich; he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  20. Semi-synthetic salinomycin analogs exert cytotoxic activity against human colorectal cancer stem cells.

    Science.gov (United States)

    Klose, Johannes; Kattner, Sarah; Borgström, Björn; Volz, Claudia; Schmidt, Thomas; Schneider, Martin; Oredsson, Stina; Strand, Daniel; Ulrich, Alexis

    2018-01-01

    Salinomycin, a polyether antibiotic, is a well-known inhibitor of human cancer stem cells. Chemical modification of the allylic C20 hydroxyl of salinomycin has enabled access to synthetic analogs that display increased cytotoxic activity compared to the native structure. The aim of this study was to investigate the activity of a cohort of C20-O-acyl analogs of salinomycin on human colorectal cancer cell lines in vitro. Two human colorectal cancer cell lines (SW480 and SW620) were exposed to three C20-O-acylated analogs and salinomycin. The impact of salinomycin and its analogs on tumor cell number, migration, cell death, and cancer stem cell specifity was analyzed. Exposure of human colorectal cancer cells to the C20-O-acylated analogs of salinomycin resulted in reduced tumor cell number and impaired tumor cell migration at lower concentrations than salinomycin. When used at higher (micromolar) concentrations, these effects were accompanied by induction of apoptotic cell death. Salinomycin analogs further expose improved activity against cancer stem cells compared to salinomycin. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Ionizing Radiation Activates AMP-Activated Kinase (AMPK): A Target for Radiosensitization of Human Cancer Cells

    International Nuclear Information System (INIS)

    Sanli, Toran; Rashid, Ayesha; Liu Caiqiong

    2010-01-01

    Purpose: Adenosine monophosphate (AMP)-activated kinase (AMPK) is a molecular energy sensor regulated by the tumor suppressor LKB1. Starvation and growth factors activate AMPK through the DNA damage sensor ataxia-telangiectasia mutated (ATM). We explored the regulation of AMPK by ionizing radiation (IR) and its role as a target for radiosensitization of human cancer cells. Methods and Materials: Lung, prostate, and breast cancer cells were treated with IR (2-8 Gy) after incubation with either ATM or AMPK inhibitors or the AMPK activator metformin. Then, cells were subjected to either lysis and immunoblotting, immunofluorescence microscopy, clonogenic survival assays, or cell cycle analysis. Results: IR induced a robust phosphorylation and activation of AMPK in all tumor cells, independent of LKB1. IR activated AMPK first in the nucleus, and this extended later into cytoplasm. The ATM inhibitor KU-55933 blocked IR activation of AMPK. AMPK inhibition with Compound C or anti-AMPK α subunit small interfering RNA (siRNA) blocked IR induction of the cell cycle regulators p53 and p21 waf/cip as well as the IR-induced G2/M arrest. Compound C caused resistance to IR, increasing the surviving fraction after 2 Gy, but the anti-diabetic drug metformin enhanced IR activation of AMPK and lowered the surviving fraction after 2 Gy further. Conclusions: We provide evidence that IR activates AMPK in human cancer cells in an LKB1-independent manner, leading to induction of p21 waf/cip and regulation of the cell cycle and survival. AMPK appears to (1) participate in an ATM-AMPK-p21 waf/cip pathway, (2) be involved in regulation of the IR-induced G2/M checkpoint, and (3) may be targeted by metformin to enhance IR responses.

  2. Human movement activity classification approaches that use wearable sensors and mobile devices

    Science.gov (United States)

    Kaghyan, Sahak; Sarukhanyan, Hakob; Akopian, David

    2013-03-01

    Cell phones and other mobile devices become part of human culture and change activity and lifestyle patterns. Mobile phone technology continuously evolves and incorporates more and more sensors for enabling advanced applications. Latest generations of smart phones incorporate GPS and WLAN location finding modules, vision cameras, microphones, accelerometers, temperature sensors etc. The availability of these sensors in mass-market communication devices creates exciting new opportunities for data mining applications. Particularly healthcare applications exploiting build-in sensors are very promising. This paper reviews different approaches of human activity recognition.

  3. The spatial structure of transnational human activity.

    Science.gov (United States)

    Deutschmann, Emanuel

    2016-09-01

    Starting from conflictive predictions of hitherto disconnected debates in the natural and social sciences, this article examines the spatial structure of transnational human activity (THA) worldwide (a) across eight types of mobility and communication and (b) in its development over time. It is shown that the spatial structure of THA is similar to that of animal displacements and local-scale human motion in that it can be approximated by Lévy flights with heavy tails that obey power laws. Scaling exponent and power-law fit differ by type of THA, being highest in refuge-seeking and tourism and lowest in student exchange. Variance in the availability of resources and opportunities for satisfying associated needs appears to explain these differences. Over time (1960-2010), the Lévy-flight pattern remains intact and remarkably stable, contradicting the popular notion that socio-technological trends lead to a "death of distance." Humans have not become more "global" over time, they rather became more mobile in general, i.e. they move and communicate more at all distances. Hence, it would be more adequate to speak of "mobilization" than of "globalization." Longitudinal change occurs only in some types of THA and predominantly at short distances, indicating regional rather than global shifts. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  5. A survey on using domain and contextual knowledge for human activity recognition in video streams

    NARCIS (Netherlands)

    Onofri, L.; Soda, P.; Pechenizkiy, M.; Iannello, G.

    2016-01-01

    Human activity recognition has gained an increasing relevance in computer vision and it can be tackled with either non-hierarchical or hierarchical approaches. The former, also known as single-layered approaches, are those that represent and recognize human activities directly from the extracted

  6. The stability of complement-mediated bactericidal activity in human serum against Salmonella.

    Directory of Open Access Journals (Sweden)

    Colette M O'Shaughnessy

    Full Text Available The complement cascade includes heat-labile proteins and care is required when handling serum in order to preserve its functional integrity. We have previously used a whole human serum bactericidal assay to show that antibody and an intact complement system are required in blood for killing of invasive isolates of Salmonella. The aim of the present study was to evaluate the conditions under which human serum can be stored and manipulated while maintaining complement integrity. Serum bactericidal activity against Salmonella was maintained for a minimum of 35 days when stored at 4°C, eight days at 22°C and 54 hours at 37°C. Up to three freeze-thaw cycles had no effect on the persistence of bactericidal activity and hemolytic complement assays confirmed no effect on complement function. Delay in the separation of serum for up to four days from clotted blood stored at 22°C did not affect bactericidal activity. Dilution of serum resulted in an increased rate of loss of bactericidal activity and so serum should be stored undiluted. These findings indicate that the current guidelines concerning manipulation and storage of human serum to preserve complement integrity and function leave a large margin for safety with regards to bactericidal activity against Salmonella. The study provides a scheme for determining the requirements for serum handling in relation to functional activity of complement in other systems.

  7. Using human brain activity to guide machine learning.

    Science.gov (United States)

    Fong, Ruth C; Scheirer, Walter J; Cox, David D

    2018-03-29

    Machine learning is a field of computer science that builds algorithms that learn. In many cases, machine learning algorithms are used to recreate a human ability like adding a caption to a photo, driving a car, or playing a game. While the human brain has long served as a source of inspiration for machine learning, little effort has been made to directly use data collected from working brains as a guide for machine learning algorithms. Here we demonstrate a new paradigm of "neurally-weighted" machine learning, which takes fMRI measurements of human brain activity from subjects viewing images, and infuses these data into the training process of an object recognition learning algorithm to make it more consistent with the human brain. After training, these neurally-weighted classifiers are able to classify images without requiring any additional neural data. We show that our neural-weighting approach can lead to large performance gains when used with traditional machine vision features, as well as to significant improvements with already high-performing convolutional neural network features. The effectiveness of this approach points to a path forward for a new class of hybrid machine learning algorithms which take both inspiration and direct constraints from neuronal data.

  8. Role of sialic acid for platelet life span: exposure of beta-galactose results in the rapid clearance of platelets from the circulation by asialoglycoprotein receptor-expressing liver macrophages and hepatocytes

    DEFF Research Database (Denmark)

    Sørensen, Anne Louise; Rumjantseva, Viktoria; Nayeb-Hashemi, Sara

    2009-01-01

    Although surface sialic acid is considered a key determinant for the survival of circulating blood cells and glycoproteins, its role in platelet circulation lifetime is not fully clarified. We show that thrombocytopenia in mice deficient in the St3gal4 sialyltransferase gene (St3Gal-IV(-/-) mice...

  9. Structure-activity relationships of diverse xanthones against multidrug resistant human tumor cells.

    Science.gov (United States)

    Wang, Qiwen; Ma, Chenyao; Ma, Yun; Li, Xiang; Chen, Yong; Chen, Jianwei

    2017-02-01

    Thirteen xanthones were isolated naturally from the stem of Securidaca inappendiculata Hassk, and structure-activity relationships (SARs) of these compounds were comparatively predicted for their cytotoxic activity against three human multidrug resistant (MDR) cell lines MCF-7/ADR, SMMC-7721/Taxol, and A549/Taxol cells. The results showed that the selected xanthones exhibited different potent cytotoxic activity against the growth of different human tumor cell lines, and most of the xanthones exhibited selective cytotoxicity against SMMC-7721/Taxol cells. Furthermore, some tested xanthones showed stronger cytotoxicity than Cisplatin, which has been used in clinical application extensively. The SARs analysis revealed that the cytotoxic activities of diverse xanthones were affected mostly by the number and position of methoxyl and hydroxyl groups. Xanthones with more free hydroxyl and methoxyl groups increased the cytotoxic activity significantly, especially for those with the presence of C-3 hydroxyl and C-4 methoxyl groups. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Super Normal Vector for Human Activity Recognition with Depth Cameras.

    Science.gov (United States)

    Yang, Xiaodong; Tian, YingLi

    2017-05-01

    The advent of cost-effectiveness and easy-operation depth cameras has facilitated a variety of visual recognition tasks including human activity recognition. This paper presents a novel framework for recognizing human activities from video sequences captured by depth cameras. We extend the surface normal to polynormal by assembling local neighboring hypersurface normals from a depth sequence to jointly characterize local motion and shape information. We then propose a general scheme of super normal vector (SNV) to aggregate the low-level polynormals into a discriminative representation, which can be viewed as a simplified version of the Fisher kernel representation. In order to globally capture the spatial layout and temporal order, an adaptive spatio-temporal pyramid is introduced to subdivide a depth video into a set of space-time cells. In the extensive experiments, the proposed approach achieves superior performance to the state-of-the-art methods on the four public benchmark datasets, i.e., MSRAction3D, MSRDailyActivity3D, MSRGesture3D, and MSRActionPairs3D.

  11. Workshop on Human Activity at Scale in Earth System Models

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Melissa R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Aziz, H. M. Abdul [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Coletti, Mark A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Kennedy, Joseph H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nair, Sujithkumar S. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Omitaomu, Olufemi A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2017-01-26

    Changing human activity within a geographical location may have significant influence on the global climate, but that activity must be parameterized in such a way as to allow these high-resolution sub-grid processes to affect global climate within that modeling framework. Additionally, we must have tools that provide decision support and inform local and regional policies regarding mitigation of and adaptation to climate change. The development of next-generation earth system models, that can produce actionable results with minimum uncertainties, depends on understanding global climate change and human activity interactions at policy implementation scales. Unfortunately, at best we currently have only limited schemes for relating high-resolution sectoral emissions to real-time weather, ultimately to become part of larger regions and well-mixed atmosphere. Moreover, even our understanding of meteorological processes at these scales is imperfect. This workshop addresses these shortcomings by providing a forum for discussion of what we know about these processes, what we can model, where we have gaps in these areas and how we can rise to the challenge to fill these gaps.

  12. THE HUMAN ACTIVITY AS AFFECTIVE-COGNITIVE UNIT: A HISTORIC-CULTURAL APPROACH

    Directory of Open Access Journals (Sweden)

    Lígia Márcia Martins

    2017-01-01

    Full Text Available This article puts in question the affectional-cognitive unit which sustains the human activity, with the purpose to light incorrectness of approaches which dichotomize reason and emotion. It asserts that such dissociations are founded in theorical-methodological principles which set bounds for explanations about the human psychism, so that the overcoming of referred dualisms puts on as a method matter. For making explicit that assertion, it resorted to Historic-Cultural Psychology, based on that it explains about the psychism as subjective image of objective reality, of Vygotskyan criticisms to Cartesian dualism and the need of a historic-cultural approach on emotion studies, intend to analyzing the human activity as a affective-cognitive unit and the imbricated relations that are waged, within it, among affections, emotions, feelings and thoughts. Once presented the interrelations between emotions and cognitions this exhibition argues that the concepts are necessary as a minimum unit of analysis both of thought and feelings.

  13. Multiplexed activity-based protein profiling of the human pathogen Aspergillus fumigatus reveals large functional changes upon exposure to human serum.

    Science.gov (United States)

    Wiedner, Susan D; Burnum, Kristin E; Pederson, LeeAnna M; Anderson, Lindsey N; Fortuin, Suereta; Chauvigné-Hines, Lacie M; Shukla, Anil K; Ansong, Charles; Panisko, Ellen A; Smith, Richard D; Wright, Aaron T

    2012-09-28

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli.

  14. Multiplexed Activity-based Protein Profiling of the Human Pathogen Aspergillus fumigatus Reveals Large Functional Changes upon Exposure to Human Serum*

    Science.gov (United States)

    Wiedner, Susan D.; Burnum, Kristin E.; Pederson, LeeAnna M.; Anderson, Lindsey N.; Fortuin, Suereta; Chauvigné-Hines, Lacie M.; Shukla, Anil K.; Ansong, Charles; Panisko, Ellen A.; Smith, Richard D.; Wright, Aaron T.

    2012-01-01

    Environmental adaptability is critical for survival of the fungal human pathogen Aspergillus fumigatus in the immunocompromised host lung. We hypothesized that exposure of the fungal pathogen to human serum would lead to significant alterations to the organism's physiology, including metabolic activity and stress response. Shifts in functional pathway and corresponding enzyme reactivity of A. fumigatus upon exposure to the human host may represent much needed prognostic indicators of fungal infection. To address this, we employed a multiplexed activity-based protein profiling (ABPP) approach coupled to quantitative mass spectrometry-based proteomics to measure broad enzyme reactivity of the fungus cultured with and without human serum. ABPP showed a shift from aerobic respiration to ethanol fermentation and utilization over time in the presence of human serum, which was not observed in serum-free culture. Our approach provides direct insight into this pathogen's ability to survive, adapt, and proliferate. Additionally, our multiplexed ABPP approach captured a broad swath of enzyme reactivity and functional pathways and provides a method for rapid assessment of the A. fumigatus response to external stimuli. PMID:22865858

  15. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Singaravelu, Ragunath [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Lyn, Rodney K. [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Srinivasan, Prashanth [National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Delcorde, Julie [Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada); Steenbergen, Rineke H.; Tyrrell, D. Lorne [Department of Medical Microbiology and Immunology, University of Alberta (Canada); Li Ka Shing Institute of Virology, Katz Centre for Pharmacy and Health Research, Edmonton, Alberta T6G 2S2 (Canada); Pezacki, John P., E-mail: John.Pezacki@nrc-cnrc.gc.ca [Department of Chemistry, University of Ottawa, Ottawa, Ontario K1N 6N5 (Canada); National Research Council of Canada, Ottawa, Ontario K1A 0R6 (Canada)

    2013-11-15

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway.

  16. Human serum activates CIDEB-mediated lipid droplet enlargement in hepatoma cells

    International Nuclear Information System (INIS)

    Singaravelu, Ragunath; Lyn, Rodney K.; Srinivasan, Prashanth; Delcorde, Julie; Steenbergen, Rineke H.; Tyrrell, D. Lorne; Pezacki, John P.

    2013-01-01

    Highlights: •Human serum induced differentiation of hepatoma cells increases cellular lipid droplet (LD) size. •The observed increase in LD size correlates with increased PGC-1α and CIDEB expression. •Induction of CIDEB expression correlates with rescue of VLDL secretion and loss of ADRP. •siRNA knockdown of CIDEB impairs the human serum mediated increase in LD size. •This system represents a cost-efficient model to study CIDEB’s role in lipid biology. -- Abstract: Human hepatocytes constitutively express the lipid droplet (LD) associated protein cell death-inducing DFFA-like effector B (CIDEB). CIDEB mediates LD fusion, as well as very-low-density lipoprotein (VLDL) maturation. However, there are limited cell culture models readily available to study CIDEB’s role in these biological processes, as hepatoma cell lines express negligible levels of CIDEB. Recent work has highlighted the ability of human serum to differentiate hepatoma cells. Herein, we demonstrate that culturing Huh7.5 cells in media supplemented with human serum activates CIDEB expression. This activation occurs through the induced expression of PGC-1α, a positive transcriptional regulator of CIDEB. Coherent anti-Stokes Raman scattering (CARS) microscopy revealed a correlation between CIDEB levels and LD size in human serum treated Huh7.5 cells. Human serum treatment also resulted in a rapid decrease in the levels of adipose differentiation-related protein (ADRP). Furthermore, individual overexpression of CIDEB was sufficient to down-regulate ADRP protein levels. siRNA knockdown of CIDEB revealed that the human serum mediated increase in LD size was CIDEB-dependent. Overall, our work highlights CIDEB’s role in LD fusion, and presents a new model system to study the PGC-1α/CIDEB pathway’s role in LD dynamics and the VLDL pathway

  17. Bacterial expression of human kynurenine 3-monooxygenase: Solubility, activity, purification☆

    Science.gov (United States)

    Wilson, K.; Mole, D.J.; Binnie, M.; Homer, N.Z.M.; Zheng, X.; Yard, B.A.; Iredale, J.P.; Auer, M.; Webster, S.P.

    2014-01-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington’s disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. PMID:24316190

  18. DMEM enhances tyrosinase activity in B16 mouse melanoma cells and human melanocytes

    Directory of Open Access Journals (Sweden)

    Panpen Diawpanich

    2008-07-01

    Full Text Available Media components may affect the activities of cultured cells. In this study, tyrosinase activity was evaluated by using B16-F10 mouse melanoma cell lines (B16-F10 and primary human melanocytes cultured in different media. An optical density measurement and a L-dopa reaction assay were used as the determination of the tyrosinase activity. The study of B16-F10 found the optical density to be 2010, 2246 and 2961 in cells cultured in RPMI Medium 1640 (RPMI1640,Minimum Essential Medium (MEM and Dulbecco’s Modified Eagle Medium (DMEM, respectively. Moreover, compared to RPMI 1640 and MEM, DMEM showed the darkest color of melanin formation in culture media and in cells after the L-dopa reaction assay. Addition of kojic acid showed a significant inhibitory effect on tyrosinase activity in all media.Whereas MCDB153 showed no significant effect on human melanocytes, DMEM caused a dramatic increase in tyrosinase activity after 4 days of cultivation. Addition of kojic acid showed a significant tyrosinase inhibitory effect in DMEM only. Furthermore, an active ingredient in green tea, epigallocathechin gallate (EGCG could inhibit tyrosinase activity in both B16-F10 and human melanocytes cultured in DMEM. In summary, these results suggest that DMEM is a suitable medium that provides high detection sensitivity in a tyrosinase inhibition assay.

  19. Xanthine oxidase activity regulates human embryonic brain cells growth

    Directory of Open Access Journals (Sweden)

    Kevorkian G. A.

    2011-10-01

    Full Text Available Aim. Involvement of Xanthine Oxidase (XO; EC1.1.3.22 in cellular proliferation and differentiation has been suggested by the numerous investigations. We have proposed that XO might have undoubtedly important role during the development, maturation as well as the death of human embryos brain cells. Methods. Human abortion material was utilized for the cultivation of brain cells (E90. XO activity was measured by the formation of uric acid in tissue. Cell death was detected by the utility of Trypan Blue dye. Results. Allopurinol suppressed the XO activity in the brain tissue (0.12 ± 0.02; 0.20 ± 0.03 resp., p < 0.05. On day 12th the number of cells in the culture treated with the Allopurinol at the early stage of development was higher in comparison with the Control (2350.1 ± 199.0 vs 2123 ± 96 and higher in comparison with the late period of treatment (1479.6 ± 103.8, p < < 0.05. In all groups, the number of the dead cells was less than in Control, indicating the protective nature of Allopurinol as an inhibitor of XO. Conclusions. Allopurinol initiates cells proliferation in case of the early treatment of the human brain derived cell culture whereas at the late stages it has an opposite effect.

  20. Energy-Efficient Real-Time Human Activity Recognition on Smart Mobile Devices

    Directory of Open Access Journals (Sweden)

    Jin Lee

    2016-01-01

    Full Text Available Nowadays, human activity recognition (HAR plays an important role in wellness-care and context-aware systems. Human activities can be recognized in real-time by using sensory data collected from various sensors built in smart mobile devices. Recent studies have focused on HAR that is solely based on triaxial accelerometers, which is the most energy-efficient approach. However, such HAR approaches are still energy-inefficient because the accelerometer is required to run without stopping so that the physical activity of a user can be recognized in real-time. In this paper, we propose a novel approach for HAR process that controls the activity recognition duration for energy-efficient HAR. We investigated the impact of varying the acceleration-sampling frequency and window size for HAR by using the variable activity recognition duration (VARD strategy. We implemented our approach by using an Android platform and evaluated its performance in terms of energy efficiency and accuracy. The experimental results showed that our approach reduced energy consumption by a minimum of about 44.23% and maximum of about 78.85% compared to conventional HAR without sacrificing accuracy.

  1. Understanding the Functionality of Human Activity Hotspots from Their Scaling Pattern Using Trajectory Data

    Directory of Open Access Journals (Sweden)

    Tao Jia

    2017-11-01

    Full Text Available Human activity hotspots are the clusters of activity locations in space and time, and a better understanding of their functionality would be useful for urban land use planning and transportation. In this article, using trajectory data, we aim to infer the functionality of human activity hotspots from their scaling pattern in a reliable way. Specifically, a large number of stopping locations are extracted from trajectory data, which are then aggregated into activity hotspots. Activity hotspots are found to display scaling patterns in terms of the sublinear scaling relationships between the number of stopping locations and the number of points of interest (POIs, which indicates economies of scale of human interactions with urban land use. Importantly, this scaling pattern remains stable over time. This finding inspires us to devise an allometric ruler to identify the activity hotspots, whose functionality could be reliably estimated using the stopping locations. Thereafter, a novel Bayesian inference model is proposed to infer their urban functionality, which examines the spatial and temporal information of stopping locations covering 75 days. Experimental results suggest that the functionality of identified activity hotspots are reliably inferred by stopping locations, such as the railway station.

  2. Action Search: Learning to Search for Human Activities in Untrimmed Videos

    KAUST Repository

    Alwassel, Humam

    2017-06-13

    Traditional approaches for action detection use trimmed data to learn sophisticated action detector models. Although these methods have achieved great success at detecting human actions, we argue that huge information is discarded when ignoring the process, through which this trimmed data is obtained. In this paper, we propose Action Search, a novel approach that mimics the way people annotate activities in video sequences. Using a Recurrent Neural Network, Action Search can efficiently explore a video and determine the time boundaries during which an action occurs. Experiments on the THUMOS14 dataset reveal that our model is not only able to explore the video efficiently but also accurately find human activities, outperforming state-of-the-art methods.

  3. Opinion formation in a social network: The role of human activity

    Science.gov (United States)

    Grabowski, Andrzej

    2009-03-01

    The model of opinion formation in human population based on social impact theory is investigated numerically. On the basis of a database received from the on-line game server, we examine the structure of social network and human dynamics. We calculate the activity of individuals, i.e. the relative time devoted daily to interactions with others in the artificial society. We study the influence of correlation between the activity of an individual and its connectivity on the process of opinion formation. We find that such correlations have a significant influence on the temperature of the phase transition and the effect of the mass media, modeled as an external stimulation acting on the social network.

  4. Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at Mucosal Surface.

    Science.gov (United States)

    Michaelsen, T E; Emilsen, S; Sandin, R H; Granerud, B K; Bratlie, D; Ihle, O; Sandlie, I

    2017-01-01

    IgM molecules circulate in serum as large polymers, mainly pentamers, which can be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have non-covalently attached secretory component (SC), which is the extracellular part of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies do not contain SC and have previously been shown to make a conformational change from 'a star' to a 'staple' conformation upon reaction with antigens on a cell surface, enabling them to activate complement. However, it is not clear whether SIgM similarly can induce complement activation. To clarify this issue, we constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5-iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM formed after immunization with a meningococcal group B vaccine. The monoclonal and polyclonal IgM molecules were purified by affinity chromatography on a column containing human SC in order to isolate joining-chain (J-chain) containing IgM, followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+). These SIgM preparations were tested for complement activation ability and shown to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer protection against pathogens at mucosal surface by complement-mediated cell lysis or by phagocytosis mediated by complement receptors present on effector cells on mucosa. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  5. Fish invasions in the world's river systems: when natural processes are blurred by human activities.

    Directory of Open Access Journals (Sweden)

    Fabien Leprieur

    2008-02-01

    Full Text Available Because species invasions are a principal driver of the human-induced biodiversity crisis, the identification of the major determinants of global invasions is a prerequisite for adopting sound conservation policies. Three major hypotheses, which are not necessarily mutually exclusive, have been proposed to explain the establishment of non-native species: the "human activity" hypothesis, which argues that human activities facilitate the establishment of non-native species by disturbing natural landscapes and by increasing propagule pressure; the "biotic resistance" hypothesis, predicting that species-rich communities will readily impede the establishment of non-native species; and the "biotic acceptance" hypothesis, predicting that environmentally suitable habitats for native species are also suitable for non-native species. We tested these hypotheses and report here a global map of fish invasions (i.e., the number of non-native fish species established per river basin using an original worldwide dataset of freshwater fish occurrences, environmental variables, and human activity indicators for 1,055 river basins covering more than 80% of Earth's surface. First, we identified six major invasion hotspots where non-native species represent more than a quarter of the total number of species. According to the World Conservation Union, these areas are also characterised by the highest proportion of threatened fish species. Second, we show that the human activity indicators account for most of the global variation in non-native species richness, which is highly consistent with the "human activity" hypothesis. In contrast, our results do not provide support for either the "biotic acceptance" or the "biotic resistance" hypothesis. We show that the biogeography of fish invasions matches the geography of human impact at the global scale, which means that natural processes are blurred by human activities in driving fish invasions in the world's river systems

  6. Geo-spatial Cognition on Human's Social Activity Space Based on Multi-scale Grids

    Directory of Open Access Journals (Sweden)

    ZHAI Weixin

    2016-12-01

    Full Text Available Widely applied location aware devices, including mobile phones and GPS receivers, have provided great convenience for collecting large volume individuals' geographical information. The researches on the human's society behavior space has attracts an increasingly number of researchers. In our research, based on location-based Flickr data From 2004 to May, 2014 in China, we choose five levels of spatial grids to form the multi-scale frame for investigate the correlation between the scale and the geo-spatial cognition on human's social activity space. The HT-index is selected as the fractal inspired by Alexander to estimate the maturity of the society activity on different scales. The results indicate that that the scale characteristics are related to the spatial cognition to a certain extent. It is favorable to use the spatial grid as a tool to control scales for geo-spatial cognition on human's social activity space.

  7. Development of organophosphate hydrolase activity in a bacterial homolog of human cholinesterase

    Science.gov (United States)

    Legler, Patricia; Boisvert, Susanne; Compton, Jaimee; Millard, Charles

    2014-07-01

    We applied a combination of rational design and directed evolution (DE) to Bacillus subtilis p-nitrobenzyl esterase (pNBE) with the goal of enhancing organophosphorus acid anhydride hydrolase (OPAAH) activity. DE started with a designed variant, pNBE A107H, carrying a histidine homologous with human butyrylcholinesterase G117H to find complementary mutations that further enhance its OPAAH activity. Five sites were selected (G105, G106, A107, A190, and A400) within a 6.7 Å radius of the nucleophilic serine O?. All 95 variants were screened for esterase activity with a set of five substrates: pNP-acetate, pNP-butyrate, acetylthiocholine, butyrylthiocholine, or benzoylthiocholine. A microscale assay for OPAAH activity was developed for screening DE libraries. Reductions in esterase activity were generally concomitant with enhancements in OPAAH activity. One variant, A107K, showed an unexpected 7-fold increase in its kcat/Km for benzoylthiocholine, demonstrating that it is also possible to enhance the cholinesterase activity of pNBE. Moreover, DE resulted in at least three variants with modestly enhanced OPAAH activity compared to wild type pNBE. A107H/A190C showed a 50-fold increase in paraoxonase activity and underwent a slow time- and temperature-dependent change affecting the hydrolysis of OPAA and ester substrates. Structural analysis suggests that pNBE may represent a precursor leading to human cholinesterase and carboxylesterase 1 through extension of two vestigial specificity loops; a preliminary attempt to transfer the Ω-loop of BChE into pNBE is described. pNBE was tested as a surrogate scaffold for mammalian esterases. Unlike butyrylcholinesterase and pNBE, introducing a G143H mutation (equivalent to G117H) did not confer detectable OP hydrolase activity on human carboxylesterase 1. We discuss the importance of the oxyanion-hole residues for enhancing the OPAAH activity of selected serine hydrolases.

  8. In-vitro archaeacidal activity of biocides against human-associated archaea.

    Directory of Open Access Journals (Sweden)

    Saber Khelaifia

    Full Text Available BACKGROUND: Several methanogenic archaea have been detected in the human intestinal microbiota. These intestinal archaea may contaminate medical devices such as colonoscopes. However, no biocide activity has been reported among these human-associated archaea. METHODOLOGY: The minimal archaeacidal concentration (MAC of peracetic acid, chlorhexidine, squalamine and twelve parent synthetic derivatives reported in this study was determined against five human-associated methanogenic archaea including Methanobrevibacter smithii, Methanobrevibacter oralis, Methanobrevibacter arboriphilicus, Methanosphaera stadtmanae, Methanomassiliicoccus luminyensis and two environmental methanogens Methanobacterium beijingense and Methanosaeta concilii by using a serial dilution technique in Hungates tubes. PRINCIPAL FINDINGS: MAC of squalamine derivative S1 was 0.05 mg/L against M. smithii strains, M. oralis, M. arboriphilicus, M. concilii and M. beijingense whereas MAC of squalamine and derivatives S2-S12 varied from 0.5 to 5 mg/L. For M. stadtmanae and M. luminyensis, MAC of derivative S1 was 0.1 mg/L and varied from 1 to ≥ 10 mg/L for squalamine and its parent derivatives S2-S12. Under the same experimental conditions, chlorhexidine and peracetic acid lead to a MAC of 0.2 and 1.5 mg/L, respectively against all tested archaea. CONCLUSIONS/SIGNIFICANCE: Squalamine derivative S1 exhibited a 10-200 higher archaeacidal activity than other tested squalamine derivatives, on the majority of human-associated archaea. As previously reported and due to their week corrosivity and their wide spectrum of antibacterial and antifungal properties, squalamine and more precisely derivative S1 appear as promising compounds to be further tested for the decontamination of medical devices contaminated by human-associated archaea.

  9. Activation of the insular cortex during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Williamson, James; Nobrega, A C; McColl, R

    1997-01-01

    role as a site for regulation of autonomic activity. 2. Eight subjects were studied during voluntary active cycling and passively induced cycling. Additionally, four of the subjects underwent passive movement combined with electrical stimulation of the legs. 3. Increases in regional cerebral blood flow...... during active, but not passive cycling. There were no significant changes in rCBF for the right insula. Also, the magnitude of rCBF increase for leg primary motor areas was significantly greater for both active cycling and passive cycling combined with electrical stimulation compared with passive cycling...... alone. 5. These findings provide the first evidence of insular activation during dynamic exercise in humans, suggesting that the left insular cortex may serve as a site for cortical regulation of cardiac autonomic (parasympathetic) activity. Additionally, findings during passive cycling with electrical...

  10. Human activated protein C variants in a rat model of arterial thrombosis

    Directory of Open Access Journals (Sweden)

    Dahlbäck Björn

    2008-10-01

    Full Text Available Abstract Background Activated protein C (APC inhibits coagulation by degrading activated factor V (FVa and factor VIII (FVIIIa, protein S (PS functioning as a cofactor to APC. Methods By mutagenesis of the vitamin K-dependent Gla domain of APC, we have recently created an APC variant having enhanced anticoagulant activity due to increased affinity for negatively charged phospholipid membranes. In the present study, the potential antithrombotic effects of this APC variant, and of a variant APC that is additionally mutated in the serine protease domain, have been evaluated in a blind randomized study in a rat model of arterial thrombosis. In this model, we have previously found the combination of bovine APC and PS to be highly antithrombotic. Four treatment groups each containing 10 rats were, in a blind random fashion, given intravenous bolus injections of wild-type or mutant variants of APC (0.8 mg/kg together with human PS (0.6 mg/kg or human PS (0.6 mg/kg alone. A control group with 20 animals where given vehicle only. Results A trend to increased patency rates was noted in a group receiving one of the APC variants, but it did not reach statistical significance. Conclusion In conclusion, administration of human APC variants having enhanced anticoagulant efficacy together with human PS in a rat model of arterial thrombosis did not give an efficient antithrombotic effect. The lack of effect may be due to species-specific differences between the human protein C system and the rat hemostatic system.

  11. Alterations in calcium metabolism during human monocyte activation

    International Nuclear Information System (INIS)

    Scully, S.P.

    1984-01-01

    Human peripheral blood monocytes have been prepared from plateletpheresis residues by counterflow centrifugal elutriation in sufficient quantities to enable quantitative studies of cell calcium. Kinetic analysis of 45 Ca exchange data in resting monocytes was compatible with a model of cellular calcium containing three exchangeable calcium pools. These pools are thought to represent a putative ectocellular pool, a putative cytoplasmic chelated pool, and a putative organelle sequestered pool. Exposure of monocytes to the plant lectin Con A at a concentration that maximally simulated superoxide production caused an increase in the size and a doubling in the exchange rate of the putative cytoplasmic pool without a change in the other cellular pools. The cytoplasmic ionized calcium, [Ca]/sub i/, measured with the fluorescent probe, Quin 2 rose from a resting level of 83 nM to 165 mN within 30 sec of exposure to Con A. This increase in cytoplasmic calcium preceded the release of superoxide radicals. Calcium transport and calcium ATPase activities were identified and characterized in plasma membrane vesicles prepared from monocytes. Both activities were strictly dependent on ATP and Mg, had a Km/sub Ca/ in the submicromolar range and were stimulated by calmodulin. Thus, it seems that monocyte calcium is in a dynamic steady state that is a balance between efflux and influx rates, and that the activation of these cells results in the transition to a new steady state. The alteration in [Ca]/sub i/ that accompany the new steady state are essential for superoxide production by human monocytes

  12. HMM Adaptation for Improving a Human Activity Recognition System

    Directory of Open Access Journals (Sweden)

    Rubén San-Segundo

    2016-09-01

    Full Text Available When developing a fully automatic system for evaluating motor activities performed by a person, it is necessary to segment and recognize the different activities in order to focus the analysis. This process must be carried out by a Human Activity Recognition (HAR system. This paper proposes a user adaptation technique for improving a HAR system based on Hidden Markov Models (HMMs. This system segments and recognizes six different physical activities (walking, walking upstairs, walking downstairs, sitting, standing and lying down using inertial signals from a smartphone. The system is composed of a feature extractor for obtaining the most relevant characteristics from the inertial signals, a module for training the six HMMs (one per activity, and the last module for segmenting new activity sequences using these models. The user adaptation technique consists of a Maximum A Posteriori (MAP approach that adapts the activity HMMs to the user, using some activity examples from this specific user. The main results on a public dataset have reported a significant relative error rate reduction of more than 30%. In conclusion, adapting a HAR system to the user who is performing the physical activities provides significant improvement in the system’s performance.

  13. Deep Recurrent Neural Networks for Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Abdulmajid Murad

    2017-11-01

    Full Text Available Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM and k-nearest neighbors (KNN. Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs and CNNs.

  14. Human PrimPol activity is enhanced by RPA.

    Science.gov (United States)

    Martínez-Jiménez, María I; Lahera, Antonio; Blanco, Luis

    2017-04-10

    Human PrimPol is a primase belonging to the AEP superfamily with the unique ability to synthesize DNA primers de novo, and a non-processive DNA polymerase able to bypass certain DNA lesions. PrimPol facilitates both mitochondrial and nuclear replication fork progression either acting as a conventional TLS polymerase, or repriming downstream of blocking lesions. In vivo assays have shown that PrimPol is rapidly recruited to sites of DNA damage by interaction with the human replication protein A (RPA). In agreement with previous findings, we show here that the higher affinity of RPA for ssDNA inhibits PrimPol activities in short ssDNA templates. In contrast, once the amount of ssDNA increases up to a length in which both proteins can simultaneously bind ssDNA, as expected during replicative stress conditions, PrimPol and RPA functionally interact, and their binding capacities are mutually enhanced. When using M13 ssDNA as template, RPA stimulated both the primase and polymerase activities of PrimPol, either alone or in synergy with Polε. These new findings supports the existence of a functional PrimPol/RPA association that allows repriming at the exposed ssDNA regions formed in the leading strand upon replicase stalling.

  15. Deep Recurrent Neural Networks for Human Activity Recognition.

    Science.gov (United States)

    Murad, Abdulmajid; Pyun, Jae-Young

    2017-11-06

    Adopting deep learning methods for human activity recognition has been effective in extracting discriminative features from raw input sequences acquired from body-worn sensors. Although human movements are encoded in a sequence of successive samples in time, typical machine learning methods perform recognition tasks without exploiting the temporal correlations between input data samples. Convolutional neural networks (CNNs) address this issue by using convolutions across a one-dimensional temporal sequence to capture dependencies among input data. However, the size of convolutional kernels restricts the captured range of dependencies between data samples. As a result, typical models are unadaptable to a wide range of activity-recognition configurations and require fixed-length input windows. In this paper, we propose the use of deep recurrent neural networks (DRNNs) for building recognition models that are capable of capturing long-range dependencies in variable-length input sequences. We present unidirectional, bidirectional, and cascaded architectures based on long short-term memory (LSTM) DRNNs and evaluate their effectiveness on miscellaneous benchmark datasets. Experimental results show that our proposed models outperform methods employing conventional machine learning, such as support vector machine (SVM) and k-nearest neighbors (KNN). Additionally, the proposed models yield better performance than other deep learning techniques, such as deep believe networks (DBNs) and CNNs.

  16. Assessment of Nicotine Exposure From Active Human Cigarette Smoking Time

    Directory of Open Access Journals (Sweden)

    Cahours Xavier

    2017-09-01

    Full Text Available The burning of a cigarette is a series of consecutive sequences of both passive and active burnings when a smoking cycle is applied to the cigarette. A previous study, using a smoking machine, showed that cigarette nicotine yields are dependent linearly on the difference between the time of smouldering (passive burning and the time of smoking (active burning. It is predicted that the smoker’s nicotine yield increases when the intensity of smoking increases, i.e., when the time to smoke a cigarette (smoking time decreases. Note that observations made on machines might not be comparable to human behaviours. The aim of this study was to determine whether nicotine mouth-level exposure could be predicted through measurement of human smoking time. A smoking behaviour study was conducted to compare human smoking nicotine yields obtained from both filter tip analysis and the cigarette burning time model. Results showed that smokers’ exposure to the smoke depends essentially on the speed at which the cigarette is smoked. An increase in human smoking intensity, resulting in a decrease in smoking time, generates an increase in smoke exposure, whatever the puff number, puff duration, puff volume and filter ventilation (open or blocked. The association of a machine smoking yield with a corresponding smoking time, and the time taken by a consumer to smoke the cigarette would provide information on the exposure to smoke constituents in a simple and effective manner.

  17. [-25]A Similarity Analysis of Audio Signal to Develop a Human Activity Recognition Using Similarity Networks.

    Science.gov (United States)

    García-Hernández, Alejandra; Galván-Tejada, Carlos E; Galván-Tejada, Jorge I; Celaya-Padilla, José M; Gamboa-Rosales, Hamurabi; Velasco-Elizondo, Perla; Cárdenas-Vargas, Rogelio

    2017-11-21

    Human Activity Recognition (HAR) is one of the main subjects of study in the areas of computer vision and machine learning due to the great benefits that can be achieved. Examples of the study areas are: health prevention, security and surveillance, automotive research, and many others. The proposed approaches are carried out using machine learning techniques and present good results. However, it is difficult to observe how the descriptors of human activities are grouped. In order to obtain a better understanding of the the behavior of descriptors, it is important to improve the abilities to recognize the human activities. This paper proposes a novel approach for the HAR based on acoustic data and similarity networks. In this approach, we were able to characterize the sound of the activities and identify those activities looking for similarity in the sound pattern. We evaluated the similarity of the sounds considering mainly two features: the sound location and the materials that were used. As a result, the materials are a good reference classifying the human activities compared with the location.

  18. Correlation between the dielectric properties and biological activities of human ex vivo hepatic tissue

    International Nuclear Information System (INIS)

    Wang, Hang; You, Fusheng; Fu, Feng; Dong, Xiuzhen; Shi, Xuetao; He, Yong; Yang, Min; Yan, Qingguo

    2015-01-01

    Dielectric properties are vital biophysical features of biological tissues, and biological activity is an index to ascertain the active state of tissues. This study investigated the potential correlation between the dielectric properties and biological activities of human hepatic tissue with prolonged ex vivo time through correlation and regression analyses. The dielectric properties of 26 cases of normal human hepatic tissue at 10 Hz to 100 MHz were measured from 15 min after isolation to 24 h at 37 °C with 90% humidity. Cell morphologies, including nucleus area (NA) and alteration rate of intercellular area (ICAR), were analyzed as indicators of biological activities. Conductivity, complex resistivity, and NA exhibited opposing changes 1 h after isolation. Relative permittivity and ex vivo time were not closely correlated (p > 0.05). The dielectric properties measured at low frequencies (i.e. <1 MHz) were more sensitive than those measured at high frequencies in reflecting the biological activity of ex vivo tissue. Highly significant correlations were found between conductivity, resistivity and the ex vivo time (p < 0.05) as well as conductivity and the cell morphology (p < 0.05). The findings indicated that establishing the correlation between the dielectric properties and biological activities of human hepatic tissue is of great significance for promoting the role of dielectric properties in biological science, particularly in human biology. (paper)

  19. Bacterial expression of human kynurenine 3-monooxygenase: solubility, activity, purification.

    Science.gov (United States)

    Wilson, K; Mole, D J; Binnie, M; Homer, N Z M; Zheng, X; Yard, B A; Iredale, J P; Auer, M; Webster, S P

    2014-03-01

    Kynurenine 3-monooxygenase (KMO) is an enzyme central to the kynurenine pathway of tryptophan metabolism. KMO has been implicated as a therapeutic target in several disease states, including Huntington's disease. Recombinant human KMO protein production is challenging due to the presence of transmembrane domains, which localise KMO to the outer mitochondrial membrane and render KMO insoluble in many in vitro expression systems. Efficient bacterial expression of human KMO would accelerate drug development of KMO inhibitors but until now this has not been achieved. Here we report the first successful bacterial (Escherichia coli) expression of active FLAG™-tagged human KMO enzyme expressed in the soluble fraction and progress towards its purification. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Through-wall bio-radio location and characterization of human activities

    International Nuclear Information System (INIS)

    Fu, Lei; Gui, Yong-Sheng; Hu, Can-Ming

    2016-01-01

    In this paper, a through-the-wall life detection system has been developed by using a broadband microwave technique. This system can not only determine and characterize human movement behind an obstacle but also determine the person’s position by employing the Fourier transform technique. The effectiveness of this system is shown by the experimental results where the presence of stationary and moving person behind an obstacle can be identified upto a distance of 17 and 30 m respectively. Since the movement of a human body is continuous, an averaged background subtraction technique has been developed which allows real time detection of human activities without requiring any prior knowledge of the environment, thus making the system suitable for practical applications. (paper)

  1. Application of cultured human mast cells (CHMC) for the design and structure-activity relationship of IgE-mediated mast cell activation inhibitors.

    Science.gov (United States)

    Argade, Ankush; Bhamidipati, Somasekhar; Li, Hui; Carroll, David; Clough, Jeffrey; Keim, Holger; Sylvain, Catherine; Rossi, Alexander B; Coquilla, Christina; Issakani, Sarkiz D; Masuda, Esteban S; Payan, Donald G; Singh, Rajinder

    2015-01-01

    Here we report the optimization of small molecule inhibitors of human mast cell degranulation via anti-IgE-mediated tryptase release following cross-linking and activation of IgE-loaded FcεR1 receptors. The compounds are selective upstream inhibitors of FcεR1-dependent human mast cell degranulation and proved to be devoid of activity in downstream ionomycin mediated degranulation. Structure-activity relationship (SAR) leading to compound 26 is outlined. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Novel Class of Small Molecule Agonists with Preference for Human over Mouse TLR4 Activation.

    Directory of Open Access Journals (Sweden)

    Jason D Marshall

    Full Text Available The best-characterized Toll-like receptor 4 (TLR4 ligands are lipopolysaccharide (LPS and its chemically modified and detoxified variant, monophosphoryl lipid A (MPL. Although both molecules are active for human TLR4, they demonstrate a potency preference for mouse TLR4 based on data from transfected cell lines and primary cells of both species. After a high throughput screening process of small molecule libraries, we have discovered a new class of TLR4 agonist with a species preference profile differing from MPL. Products of the 4-component Ugi synthesis reaction were demonstrated to potently trigger human TLR4-transfected HEK cells but not mouse TLR4, although inclusion of the human MD2 with mTLR4 was able to partially recover activity. Co-expression of CD14 was not required for optimal activity of Ugi compounds on transfected cells, as it is for LPS. The species preference profile for the panel of Ugi compounds was found to be strongly active for human and cynomolgus monkey primary cells, with reduced but still substantial activity for most Ugi compounds on guinea pig cells. Mouse, rat, rabbit, ferret, and cotton rat cells displayed little or no activity when exposed to Ugi compounds. However, engineering the human versions of TLR4 and MD2 to be expressed in mTLR4/MD2 deficient mice allowed for robust activity by Ugi compounds both in vitro and in vivo. These findings extend the range of compounds available for development as agonists of TLR4 and identify novel molecules which reverse the TLR4 triggering preference of MPL for mouse TLR4 over human TLR4. Such compounds may be amenable to formulation as more potent human-specific TLR4L-based adjuvants than typical MPL-based adjuvants.

  3. Radiochemical neutron activation analysis for trace elements evaluation of human milk

    International Nuclear Information System (INIS)

    Gill, K.P.; Zaidi, J.H.; Ahmad, S.

    2003-01-01

    The principal objective pursued in this study is to establish the base-line data on the status of elemental composition in human milk from Pakistani subjects of Rawalpindi/Islamabad area. Radiochemical neutron activation analysis (RNAA) methodology was developed and successfully employed to determine the concentration of 18 minor and trace elements (essential, toxic and nonessential) in human milk. This methodology has significantly improved the detection limits of most of these elements due to suppression of Compton background. The data provide the base-line values of these elements in human milk of low- and medium-income group subjects of the region. The results obtained show good compatibility with the data reported by the WHO on elemental composition of human milk from different geological regions. (orig.)

  4. Definitive characterization of human thymine glycol N-glycosylase activity

    International Nuclear Information System (INIS)

    Higgins, S.A.; Frenkel, K.; Cummings, A.; Teebor, G.W.

    1987-01-01

    An N-glycosylase activity that released cis-[ 3 H]-5,6-dihydroxy-5,6-dihydrothymine (thymine glycol, TG) from chemically oxidized poly(dA-[ 3 H]dT) was unambiguously characterized both in extracts of HeLa cells and in purified Escherichia coli endonuclease III. This was accomplished by use of a microderivatization procedure that quantitatively converted cis-TG to 5-hydroxy-5-methylhydantoin (HMH). The reaction products were analyzed by high-pressure liquid chromatography before and after derivation by using cis-[ 14 C]TG and [ 14 C]HMH, which had been independently synthesized, as reference compounds. This technique facilitated construction of a v/[E]/sub t/ plot for the enzyme activity in HeLa cells, permitting estimation of its specific activity. The results obtained prove the existence of both human and bacterial N-glycosylase activities that effect removal of TG from DNA

  5. Activity of the hypoxia-activated prodrug, TH-302, in preclinical human acute myeloid leukemia models.

    Science.gov (United States)

    Portwood, Scott; Lal, Deepika; Hsu, Yung-Chun; Vargas, Rodrigo; Johnson, Megan K; Wetzler, Meir; Hart, Charles P; Wang, Eunice S

    2013-12-01

    Acute myeloid leukemia (AML) is an aggressive hematologic neoplasm. Recent evidence has shown the bone marrow microenvironment in patients with AML to be intrinsically hypoxic. Adaptive cellular responses by leukemia cells to survive under low oxygenation also confer chemoresistance. We therefore asked whether therapeutic exploitation of marrow hypoxia via the hypoxia-activated nitrogen mustard prodrug, TH-302, could effectively inhibit AML growth. We assessed the effects of hypoxia and TH-302 on human AML cells, primary samples, and systemic xenograft models. We observed that human AML cells and primary AML colonies cultured under chronic hypoxia (1% O2, 72 hours) exhibited reduced sensitivity to cytarabine-induced apoptosis as compared with normoxic controls. TH-302 treatment resulted in dose- and hypoxia-dependent apoptosis and cell death in diverse AML cells. TH-302 preferentially decreased proliferation, reduced HIF-1α expression, induced cell-cycle arrest, and enhanced double-stranded DNA breaks in hypoxic AML cells. Hypoxia-induced reactive oxygen species by AML cells were also diminished. In systemic human AML xenografts (HEL, HL60), TH-302 [50 mg/kg intraperitoneally (i.p.) 5 times per week] inhibited disease progression and prolonged overall survival. TH-302 treatment reduced the number of hypoxic cells within leukemic bone marrows and was not associated with hematologic toxicities in nonleukemic or leukemic mice. Later initiation of TH-302 treatment in advanced AML disease was as effective as earlier TH-302 treatment in xenograft models. Our results establish the preclinical activity of TH-302 in AML and provide the rationale for further clinical studies of this and other hypoxia-activated agents for leukemia therapy. ©2013 AACR.

  6. Early development of synchrony in cortical activations in the human.

    Science.gov (United States)

    Koolen, N; Dereymaeker, A; Räsänen, O; Jansen, K; Vervisch, J; Matic, V; Naulaers, G; De Vos, M; Van Huffel, S; Vanhatalo, S

    2016-05-13

    Early intermittent cortical activity is thought to play a crucial role in the growth of neuronal network development, and large scale brain networks are known to provide the basis for higher brain functions. Yet, the early development of the large scale synchrony in cortical activations is unknown. Here, we tested the hypothesis that the early intermittent cortical activations seen in the human scalp EEG show a clear developmental course during the last trimester of pregnancy, the period of intensive growth of cortico-cortical connections. We recorded scalp EEG from altogether 22 premature infants at post-menstrual age between 30 and 44 weeks, and the early cortical synchrony was quantified using recently introduced activation synchrony index (ASI). The developmental correlations of ASI were computed for individual EEG signals as well as anatomically and mathematically defined spatial subgroups. We report two main findings. First, we observed a robust and statistically significant increase in ASI in all cortical areas. Second, there were significant spatial gradients in the synchrony in fronto-occipital and left-to-right directions. These findings provide evidence that early cortical activity is increasingly synchronized across the neocortex. The ASI-based metrics introduced in our work allow direct translational comparison to in vivo animal models, as well as hold promise for implementation as a functional developmental biomarker in future research on human neonates. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Amplification of a transcriptionally active DNA sequence in the human brain

    International Nuclear Information System (INIS)

    Yakovlev, A.G.; Sazonov, A.E.; Spunde, A.Ya.; Gindilis, V.M.

    1986-01-01

    The authors present their findings of tissue-specific amplification of a DNA fragment actively transcribed in the human brain. This genome fragment was found in the library complement of cDNA of the human brain and evidently belongs to a new class of moderate repetitions of DNA with an unstable copying capacity in the human genome. The authors isolated total cell RNA from various human tissues (brain, placenta), and rat tissues (brain, liver), by the method of hot phenol extraction with guanidine thiocynate. The poly(A + ) RNA fraction was isolated by chromatography. Synthesis of cDNA was done on a matrix of poly(A + ) RNA of human brain. The cDNA obtained was cloned in plasmid pBR322 for the PstI site using (dC/dG) sequences synthesized on the 3' ends of the vector molecule and cDNA respectively. In cloning 75 ng cDNA, the authors obtained approximately 10 5 recombinant. This library was analyzed by the hybridization method on columns with two radioactive ( 32 P) probes: the total cDNA preparation and the total nuclear DNA from the human brain. The number of copies of the cloned DNA fragment in the genome was determined by dot hybridization. Restricting fragments of human and rat DNA genomes homologous to the cloned cDNA were identified on radio-autographs. In each case, 10 micrograms of EcoRI DNA hydrolyzate was fractionated in 1% agarose gel. The probe was also readied with RNA samples fractionated in agarose gel with formaldehyde and transferred to a nitrocellulose filter under weak vacuum. The filter was hybridized with 0.1 micrograms DNA pAG 02, labeled with ( 32 P) to a specific activity of 0.5-1 x 10 9 counts/min x microgram. The autograph was exposed with amplifying screens at -70 0 C for 2 days

  8. Association of Single Nucleotide Polymorphisms in the ST3GAL4 Gene with VWF Antigen and Factor VIII Activity.

    Directory of Open Access Journals (Sweden)

    Jaewoo Song

    Full Text Available VWF is extensively glycosylated with biantennary core fucosylated glycans. Most N-linked and O-linked glycans on VWF are sialylated. FVIII is also glycosylated, with a glycan structure similar to that of VWF. ST3GAL sialyltransferases catalyze the transfer of sialic acids in the α2,3 linkage to termini of N- and O-glycans. This sialic acid modification is critical for VWF synthesis and activity. We analyzed genetic and phenotypic data from the Atherosclerosis Risk in Communities (ARIC study for the association of single nucleotide polymorphisms (SNPs in the ST3GAL4 gene with plasma VWF levels and FVIII activity in 12,117 subjects. We also analyzed ST3GAL4 SNPs found in 2,535 subjects of 26 ethnicities from the 1000 Genomes (1000G project for ethnic diversity, SNP imputation, and ST3GAL4 haplotypes. We identified 14 and 1,714 ST3GAL4 variants in the ARIC GWAS and 1000G databases respectively, with 46% being ethnically diverse in their allele frequencies. Among the 14 ST3GAL4 SNPs found in ARIC GWAS, the intronic rs2186717, rs7928391, and rs11220465 were associated with VWF levels and with FVIII activity after adjustment for age, BMI, hypertension, diabetes, ever-smoking status, and ABO. This study illustrates the power of next-generation sequencing in the discovery of new genetic variants and a significant ethnic diversity in the ST3GAL4 gene. We discuss potential mechanisms through which these intronic SNPs regulate ST3GAL4 biosynthesis and the activity that affects VWF and FVIII.

  9. Active numerical model of human body for reconstruction of falls from height.

    Science.gov (United States)

    Milanowicz, Marcin; Kędzior, Krzysztof

    2017-01-01

    Falls from height constitute the largest group of incidents out of approximately 90,000 occupational accidents occurring each year in Poland. Reconstruction of the exact course of a fall from height is generally difficult due to lack of sufficient information from the accident scene. This usually results in several contradictory versions of an incident and impedes, for example, determination of the liability in a judicial process. In similar situations, in many areas of human activity, researchers apply numerical simulation. They use it to model physical phenomena to reconstruct their real course over time; e.g. numerical human body models are frequently used for investigation and reconstruction of road accidents. However, they are validated in terms of specific road traffic accidents and are considerably limited when applied to the reconstruction of other types of accidents. The objective of the study was to develop an active numerical human body model to be used for reconstruction of accidents associated with falling from height. Development of the model involved extension and adaptation of the existing Pedestrian human body model (available in the MADYMO package database) for the purposes of reconstruction of falls from height by taking into account the human reaction to the loss of balance. The model was developed by using the results of experimental tests of the initial phase of the fall from height. The active numerical human body model covering 28 sets of initial conditions related to various human reactions to the loss of balance was developed. The application of the model was illustrated by using it to reconstruct a real fall from height. From among the 28 sets of initial conditions, those whose application made it possible to reconstruct the most probable version of the incident was selected. The selection was based on comparison of the results of the reconstruction with information contained in the accident report. Results in the form of estimated

  10. Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

    Science.gov (United States)

    Hou, Jin-Jun; Shen, Yao; Yang, Zhou; Fang, Lin; Cai, Lu-Ying; Yao, Shuai; Long, Hua-Li; Wu, Wan-Ying; Guo, De-An

    2017-10-01

    Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC 50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  11. Human activities and climate and environment changes: an inevitable relation

    International Nuclear Information System (INIS)

    Sanchez, Aretha

    2009-01-01

    The human interference in the environment and the consequent climate change is today a consensus. The climate change can be local, regional and global. The global climate change is mainly caused by the greenhouse gases, and consequently the climate change intervenes in the environment. The interference cycle emerges in several forms and results in several consequences. However, the Global Warming has certainly the most import global impact. The main cause of the increase in the temperature (Greenhouse Effect) is the intensive use of the fossil fuels. Thus, to minimize the climatic changes actions are necessary to reduce, to substitute and to use with more efficient the fossil fuels. Looking at the past, the old agriculturists may have released greenhouse gases since thousand years ago, thus, modifying slowly but in significant form the earth climate much before the Industrial Age. If this theory is confirmed, its consequences would be decisive for the man history in the planet. For example, in parts of the North America and Europe the current temperatures could be even four Celsius degrees smaller. This change in temperature is enough to hinder agricultural used of these regions and consequently to diminish the human development. The main focus of this work is to perform a retrospective in some of civilizations who collapse due to environmental problems and make a historical description of the human activities (agriculture and livestock) since the primordium of the man up to the Industrial Age, aiming at the man interference on the natural dynamics of the global climate and the environment. This work will show through data comparisons and inferences that the gases emissions from these activities had a significant magnitude comparatively by the emissions after the Industrial Age. It is also demonstrated that the climate and environment interference was inevitable because the human evolution was caused by these activities. Another important point of this work is to

  12. A triboelectric motion sensor in wearable body sensor network for human activity recognition.

    Science.gov (United States)

    Hui Huang; Xian Li; Ye Sun

    2016-08-01

    The goal of this study is to design a novel triboelectric motion sensor in wearable body sensor network for human activity recognition. Physical activity recognition is widely used in well-being management, medical diagnosis and rehabilitation. Other than traditional accelerometers, we design a novel wearable sensor system based on triboelectrification. The triboelectric motion sensor can be easily attached to human body and collect motion signals caused by physical activities. The experiments are conducted to collect five common activity data: sitting and standing, walking, climbing upstairs, downstairs, and running. The k-Nearest Neighbor (kNN) clustering algorithm is adopted to recognize these activities and validate the feasibility of this new approach. The results show that our system can perform physical activity recognition with a successful rate over 80% for walking, sitting and standing. The triboelectric structure can also be used as an energy harvester for motion harvesting due to its high output voltage in random low-frequency motion.

  13. Active role of a human genomic insert in replication of a yeast artificial chromosome.

    Science.gov (United States)

    van Brabant, A J; Fangman, W L; Brewer, B J

    1999-06-01

    Yeast artificial chromosomes (YACs) are a common tool for cloning eukaryotic DNA. The manner by which large pieces of foreign DNA are assimilated by yeast cells into a functional chromosome is poorly understood, as is the reason why some of them are stably maintained and some are not. We examined the replication of a stable YAC containing a 240-kb insert of DNA from the human T-cell receptor beta locus. The human insert contains multiple sites that serve as origins of replication. The activity of these origins appears to require the yeast ARS consensus sequence and, as with yeast origins, additional flanking sequences. In addition, the origins in the human insert exhibit a spacing, a range of activation efficiencies, and a variation in times of activation during S phase similar to those found for normal yeast chromosomes. We propose that an appropriate combination of replication origin density, activation times, and initiation efficiencies is necessary for the successful maintenance of YAC inserts.

  14. Human activities on the deep seafloor in the North East Atlantic: an assessment of spatial extent.

    Directory of Open Access Journals (Sweden)

    Angela R Benn

    Full Text Available BACKGROUND: Environmental impacts of human activities on the deep seafloor are of increasing concern. While activities within waters shallower than 200 m have been the focus of previous assessments of anthropogenic impacts, no study has quantified the extent of individual activities or determined the relative severity of each type of impact in the deep sea. METHODOLOGY: The OSPAR maritime area of the North East Atlantic was chosen for the study because it is considered to be one of the most heavily impacted by human activities. In addition, it was assumed data would be accessible and comprehensive. Using the available data we map and estimate the spatial extent of five major human activities in the North East Atlantic that impact the deep seafloor: submarine communication cables, marine scientific research, oil and gas industry, bottom trawling and the historical dumping of radioactive waste, munitions and chemical weapons. It was not possible to map military activities. The extent of each activity has been quantified for a single year, 2005. PRINCIPAL FINDINGS: Human activities on the deep seafloor of the OSPAR area of the North Atlantic are significant but their footprints vary. Some activities have an immediate impact after which seafloor communities could re-establish, while others can continue to make an impact for many years and the impact could extend far beyond the physical disturbance. The spatial extent of waste disposal, telecommunication cables, the hydrocarbon industry and marine research activities is relatively small. The extent of bottom trawling is very significant and, even on the lowest possible estimates, is an order of magnitude greater than the total extent of all the other activities. CONCLUSIONS/SIGNIFICANCE: To meet future ecosystem-based management and governance objectives for the deep sea significant improvements are required in data collection and availability as well as a greater awareness of the relative impact of

  15. Tracking a Subset of Skeleton Joints: An Effective Approach towards Complex Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Muhammad Latif Anjum

    2017-01-01

    Full Text Available We present a robust algorithm for complex human activity recognition for natural human-robot interaction. The algorithm is based on tracking the position of selected joints in human skeleton. For any given activity, only a few skeleton joints are involved in performing the activity, so a subset of joints contributing the most towards the activity is selected. Our approach of tracking a subset of skeleton joints (instead of tracking the whole skeleton is computationally efficient and provides better recognition accuracy. We have developed both manual and automatic approaches for the selection of these joints. The position of the selected joints is tracked for the duration of the activity and is used to construct feature vectors for each activity. Once the feature vectors have been constructed, we use a Support Vector Machines (SVM multiclass classifier for training and testing the algorithm. The algorithm has been tested on a purposely built dataset of depth videos recorded using Kinect camera. The dataset consists of 250 videos of 10 different activities being performed by different users. Experimental results show classification accuracy of 83% when tracking all skeleton joints, 95% when using manual selection of subset joints, and 89% when using automatic selection of subset joints.

  16. The impact of the human DNA topoisomerase II C-terminal domain on activity.

    Directory of Open Access Journals (Sweden)

    Emma L Meczes

    2008-03-01

    Full Text Available Type II DNA topoisomerases (topos are essential enzymes needed for the resolution of topological problems that occur during DNA metabolic processes. Topos carry out an ATP-dependent strand passage reaction whereby one double helix is passed through a transient break in another. Humans have two topoII isoforms, alpha and beta, which while enzymatically similar are differentially expressed and regulated, and are thought to have different cellular roles. The C-terminal domain (CTD of the enzyme has the most diversity, and has been implicated in regulation. We sought to investigate the impact of the CTD domain on activity.We have investigated the role of the human topoII C-terminal domain by creating constructs encoding C-terminally truncated recombinant topoIIalpha and beta and topoIIalpha+beta-tail and topoIIbeta+alpha-tail chimeric proteins. We then investigated function in vivo in a yeast system, and in vitro in activity assays. We find that the C-terminal domain of human topoII isoforms is needed for in vivo function of the enzyme, but not needed for cleavage activity. C-terminally truncated enzymes had similar strand passage activity to full length enzymes, but the presence of the opposite C-terminal domain had a large effect, with the topoIIalpha-CTD increasing activity, and the topoIIbeta-CTD decreasing activity.In vivo complementation data show that the topoIIalpha C-terminal domain is needed for growth, but the topoIIbeta isoform is able to support low levels of growth without a C-terminal domain. This may indicate that topoIIbeta has an additional localisation signal. In vitro data suggest that, while the lack of any C-terminal domain has little effect on activity, the presence of either the topoIIalpha or beta C-terminal domain can affect strand passage activity. Data indicates that the topoIIbeta-CTD may be a negative regulator. This is the first report of in vitro data with chimeric human topoIIs.

  17. Depth-based human activity recognition: A comparative perspective study on feature extraction

    Directory of Open Access Journals (Sweden)

    Heba Hamdy Ali

    2018-06-01

    Full Text Available Depth Maps-based Human Activity Recognition is the process of categorizing depth sequences with a particular activity. In this problem, some applications represent robust solutions in domains such as surveillance system, computer vision applications, and video retrieval systems. The task is challenging due to variations inside one class and distinguishes between activities of various classes and video recording settings. In this study, we introduce a detailed study of current advances in the depth maps-based image representations and feature extraction process. Moreover, we discuss the state of art datasets and subsequent classification procedure. Also, a comparative study of some of the more popular depth-map approaches has provided in greater detail. The proposed methods are evaluated on three depth-based datasets “MSR Action 3D”, “MSR Hand Gesture”, and “MSR Daily Activity 3D”. Experimental results achieved 100%, 95.83%, and 96.55% respectively. While combining depth and color features on “RGBD-HuDaAct” Dataset, achieved 89.1%. Keywords: Activity recognition, Depth, Feature extraction, Video, Human body detection, Hand gesture

  18. Molecular analysis of human papillomavirus virus-like particle activated Langerhans cells in vitro.

    Science.gov (United States)

    Woodham, Andrew W; Raff, Adam B; Da Silva, Diane M; Kast, W Martin

    2015-01-01

    Langerhans cells (LC) are the resident antigen-presenting cells in human epithelium, and are therefore responsible for initiating immune responses against human papillomaviruses (HPV) entering the epithelial and mucosal layers in vivo. Upon proper pathogenic stimulation, LC become activated causing an internal signaling cascade that results in the up-regulation of co-stimulatory molecules and the release of inflammatory cytokines. Activated LC then migrate to lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response. However, HPV manipulates LC in a suppressive manner that alters these normal maturation responses. Here, in vitro LC activation assays for the detection of phosphorylated signaling intermediates, the up-regulation of activation-associated surface markers, and the release of inflammatory cytokines in response to HPV particles are described.

  19. Enhanced stimulus-induced gamma activity in humans during propofol-induced sedation.

    Directory of Open Access Journals (Sweden)

    Neeraj Saxena

    Full Text Available Stimulus-induced gamma oscillations in the 30-80 Hz range have been implicated in a wide number of functions including visual processing, memory and attention. While occipital gamma-band oscillations can be pharmacologically modified in animal preparations, pharmacological modulation of stimulus-induced visual gamma oscillations has yet to be demonstrated in non-invasive human recordings. Here, in fifteen healthy humans volunteers, we probed the effects of the GABAA agonist and sedative propofol on stimulus-related gamma activity recorded with magnetoencephalography, using a simple visual grating stimulus designed to elicit gamma oscillations in the primary visual cortex. During propofol sedation as compared to the normal awake state, a significant 60% increase in stimulus-induced gamma amplitude was seen together with a 94% enhancement of stimulus-induced alpha suppression and a simultaneous reduction in the amplitude of the pattern-onset evoked response. These data demonstrate, that propofol-induced sedation is accompanied by increased stimulus-induced gamma activity providing a potential window into mechanisms of gamma-oscillation generation in humans.

  20. Physical activity is associated with retained muscle metabolism in human myotubes challenged with palmitate

    DEFF Research Database (Denmark)

    Green, C J; Bunprajun, T; Pedersen, B K

    2013-01-01

    in satellite cells challenged with palmitate. Although the benefits of physical activity on whole body physiology have been well investigated, this paper presents novel findings that both diet and exercise impact satellite cells directly. Given the fact that satellite cells are important for muscle maintenance......  The aim of this study was to investigate whether physical activity is associated with preserved muscle metabolism in human myotubes challenged with saturated fatty acids. Human muscle satellite cells were isolated from sedentary or active individuals and differentiated into myocytes in culture...... and correlated positively to JNK phosphorylation. In conclusion, muscle satellite cells retain metabolic differences associated with physical activity. Physical activity partially protects myocytes from fatty acid-induced insulin resistance and inactivity is associated with dysregulation of metabolism...

  1. Effects of PVA-coated nanoparticles on human T helper cell activity.

    Science.gov (United States)

    Strehl, Cindy; Schellmann, Saskia; Maurizi, Lionel; Hofmann-Amtenbrink, Margarethe; Häupl, Thomas; Hofmann, Heinrich; Buttgereit, Frank; Gaber, Timo

    2016-03-14

    Superparamagnetic iron oxide nanoparticles (SPION) are used as high-sensitive enhancer for magnetic resonance imaging, where they represent a promising tool for early diagnosis of destructive diseases such as rheumatoid arthritis (RA). Since we could demonstrate that professional phagocytes are activated by amino-polyvinyl-alcohol-coated-SPION (a-PVA-SPION), the study here focuses on the influence of a-PVA-SPION on human T cells activity. Therefore, primary human CD4+ T cells from RA patients and healthy subjects were treated with varying doses of a-PVA-SPION for 20h or 72h. T cells were then analyzed for apoptosis, cellular energy, expression of the activation marker CD25 and cell proliferation. Although, we observed that T cells from RA patients are more susceptible to low-dose a-PVA-SPION-induced apoptosis than T cells from healthy subjects, in both groups a-PVA-SPION do not activate CD4+ T cells per se and do not influence mitogen-mediated T cells activation with regard to CD25 expression and cell proliferation. Nevertheless, our results demonstrate that CD4+ T cells from RA patients and healthy subjects differ in their response to mitogen stimulation and oxygen availability. We conclude from our data, that a-PVA-SPION do neither activate nor significantly influence mitogen-stimulated CD4+ T cells activation and have negligible influence on T cells apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Science.gov (United States)

    Kato, Kazuki; Ishii, Ryohei; Goto, Eiji; Ishitani, Ryuichiro; Tokunaga, Fuminori; Nureki, Osamu

    2013-01-01

    The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  3. Structural and functional analyses of DNA-sensing and immune activation by human cGAS.

    Directory of Open Access Journals (Sweden)

    Kazuki Kato

    Full Text Available The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING, resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-κB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.

  4. Human activity and damaging landslides and floods on Madeira Island

    Science.gov (United States)

    Baioni, D.

    2011-11-01

    Over the last few decades, the island of Madeira has become an important offshore tourism and business center, with rapid economic and demographic development that has caused changes to the landscape due to human activity. In Madeira's recent history, there has been an increase over time in the frequency of occurrence of damaging landslide and flood events. As a result, the costs of restoration work due to damage caused by landslide and flood events have become a larger and larger component of Madeira's annual budget. Landslides and floods in Madeira deserve particular attention because they represent the most serious hazard to human life, to property, and to the natural environment and its important heritage value. The work reported on in this paper involved the analysis of historical data regarding damaging landslide and flood events on Madeira (in particular from 1941 to 1991) together with data on geological characteristics, topographic features, and climate, and from field observations. This analysis showed that the main factor triggering the occurrence of damaging landslide and flood events is rainfall, but that the increase in the number of damaging events recorded on Madeira Island, especially in recent times, seems to be related mostly to human activity, specifically to economic development and population growth, rather than to natural factors.

  5. Expression of GARP selectively identifies activated human FOXP3+ regulatory T cells.

    Science.gov (United States)

    Wang, Rui; Kozhaya, Lina; Mercer, Frances; Khaitan, Alka; Fujii, Hodaka; Unutmaz, Derya

    2009-08-11

    The molecules that define human regulatory T cells (Tregs) phenotypically and functionally remain to be fully characterized. We recently showed that activated human Tregs express mRNA for a transmembrane protein called glycoprotein A repetitions predominant (GARP, or LRRC32). Here, using a GARP-specific mAb, we demonstrate that expression of GARP on activated Tregs correlates with their suppressive capacity. However, GARP was not induced on T cells activated in the presence of TGFbeta, which expressed high levels of FOXP3 and lacked suppressive function. Ectopic expression of FOXP3 in conventional T cells was also insufficient for induction of GARP expression in most donors. Functionally, silencing GARP in Tregs only moderately attenuated their suppressive activity. CD25+ T cells sorted for high GARP expression displayed more potent suppressive activity compared with CD25+GARP- cells. Remarkably, CD25+GARP- T cells expanded in culture contained 3-5 fold higher IL-17-secreting cells compared with either CD25+GARP+ or CD25-GARP- cells, suggesting that high GARP expression can potentially discriminate Tregs from those that have switched to Th17 lineage. We also determined whether GARP expression correlates with FOXP3-expressing T cells in human immunodeficiency virus (HIV) -infected subjects. A subset of HIV+ individuals with high percentages of FOXP3+ T cells did not show proportionate increase in GARP+ T cells. This finding suggests that higher FOXP3 levels observed in these HIV+ individuals is possibly due to immune activation rather than to an increase in Tregs. Our findings highlight the significance of GARP both in dissecting duality of Treg/Th17 cell differentiation and as a marker to identify bona fide Tregs during diseases with chronic immune activation.

  6. Some human activities to decrease public radiation dose

    International Nuclear Information System (INIS)

    Pan Ziqiang; Guo Minqiang

    1994-01-01

    The necessity of studying the variations in radiation levels from the balance viewpoint is discussed. Some human activities may increase, while others may decrease, radiation dose to population. In 1988, China's investigation showed that travel by air caused a raise of population collective dose by 3.6 x 10 1 man·Sv, while travel by ship, train and vehicle lead to a drop of 5.36 x 10 2 man·Sv, and that dwellings of coal cinder brick decreased collective dose by 3.5 x 10 3 man·Sv, while buildings of reinforced concrete structure increased collective dose by 3.7 x 10 3 man·Sv. It is inadequate to only study those activities which may increase radiation levels

  7. Human health and ecological risks from environmental restoration and waste management activities

    International Nuclear Information System (INIS)

    Pehlman, P.A.; Wollert, D.A.; Phillippi, R.H.

    1994-01-01

    This paper summarizes the methodologies for estimating human health and ecological risks resulting from Environmental Restoration and Waste Management activities across the Department of Energy (DOE) complex. DOE is currently assessing these activities as part of the Environmental Restoration and Waste Management Programmatic Environmental Impact Statement (EM-PEIS)

  8. Wearable strain sensors based on thin graphite films for human activity monitoring

    Science.gov (United States)

    Saito, Takanari; Kihara, Yusuke; Shirakashi, Jun-ichi

    2017-12-01

    Wearable health-monitoring devices have attracted increasing attention in disease diagnosis and health assessment. In many cases, such devices have been prepared by complicated multistep procedures which result in the waste of materials and require expensive facilities. In this study, we focused on pyrolytic graphite sheet (PGS), which is a low-cost, simple, and flexible material, used as wearable devices for monitoring human activity. We investigated wearable devices based on PGSs for the observation of elbow and finger motions. The thin graphite films were fabricated by cutting small films from PGSs. The wearable devices were then made from the thin graphite films assembled on a commercially available rubber glove. The human motions could be observed using the wearable devices. Therefore, these results suggested that the wearable devices based on thin graphite films may broaden their application in cost-effective wearable electronics for the observation of human activity.

  9. Assessment of activity incorporated in human body by means of a HPGe-detector

    Energy Technology Data Exchange (ETDEWEB)

    Boshkova, T; Minev, L [Sofia Univ. (Bulgaria). Fizicheski Fakultet; Konstantinov, V [Kombinat Atomna Energetika, Kozloduj (Bulgaria)

    1996-12-31

    Human body models (phantoms) have been used to study relations between efficiency in measurement of radionuclide activity and measurement conditions. A comparison is made between the activity measurement with and without a motion. When the phantom is moved under the detector, an absolute efficiency increase of 30-40% in homogeneously distributed activity and 2-3 times increase in activity concentrated in the lungs are found. Incorrect calibration is found to introduce an error of 30-40% in the measurement with motion while without motion the error can reach 150-300%. The effects of object weight, size and shield are studied. A procedure for accurate measurement has been developed. The incorporated activity in a human body has been measured using this procedure. Two Kozloduy-2 staff members have been subject to measurement. Cs-137 activity was homogeneously distributed with values 175 Bq in person X and 1050 Bq in person Y. Co-60 activity was concentrated in the lungs with values of 110 Bq and 470 Bq respectively. 14 refs., 5 tabs.

  10. Telomerase activation by the E6 gene product of human papillomavirus type 16.

    Science.gov (United States)

    Klingelhutz, A J; Foster, S A; McDougall, J K

    1996-03-07

    Activation of telomerase, a ribonucleoprotein complex that synthesizes telomere repeat sequences, is linked to cell immortalization and is characteristic of most cell lines and tumours. Here we show that expression of the human papillomavirus type 16 (HPV-16) E6 protein activates telomerase in early-passage human keratinocytes and mammary epithelial cells. This activation was observed in cells pre-crisis, that is, before they became immortal, and occurred within one passage of retroviral infection with vectors expressing HPV-16 E6. Studies using HPV-16 E6 mutants showed that there was no correlation between the ability of the mutants to activate telomerase and their ability to target p53 for degradation, suggesting that telomerase activation by HPV-16 E6 is p53 independent. Keratinocytes expressing wild-type HPV-16 E6 have an extended lifespan, but do not become immortal, indicating that telomerase activation and E6-mediate degradation of p53 are insufficient for their immortalization. These results show that telomerase activation is an intrinsic, but insufficient, component of transformation by HPV.

  11. Analyzing the distribution of human activity space from mobile phone usage - An individual and urban-oriented study

    OpenAIRE

    Yuan Y.; Raubal M.

    2016-01-01

    Travel activities are embodied as people’s needs to be physically present at certain locations. The development of Information and Communication Technologies (ICTs such as mobile phones) has introduced new data sources for modeling human activities. Based on the scattered spatiotemporal points provided in mobile phone datasets it is feasible to study the patterns (e.g. the scale shape and regularity) of human activities. In this paper we propose methods for analyzing the distribution of human...

  12. Immunolocalization and expression of small-conductance calcium-activated potassium channels in human myometrium

    DEFF Research Database (Denmark)

    Rosenbaum, Sofia T; Svalø, Julie; Nielsen, Karsten

    2012-01-01

    Small-conductance calcium-activated potassium (SK3) channels have been detected in human myometrium and we have previously shown a functional role of SK channels in human myometrium in vitro. The aims of this study were to identify the precise localization of SK3 channels and to quantify SK3 m....... This is the first report to provide evidence for a possible role of SK3 channels in human uterine telocytes....

  13. New method in the criminalistics: neutron-activation analysis of the human hair

    International Nuclear Information System (INIS)

    Gabor, I.; Simonits, A.

    1979-01-01

    The application of the neutron activation analysis for the examination of human hair for criminological purposes is discussed. Earlier Nal scintillation detector and 256-channels analyzer were used and only form trace elements could be detected in the hair. Recently using Ge/Li detector and a 1024-channels analyzer 11 trace elements were detected in the human hair. (H.E.)

  14. Classifying Human Activity Patterns from Smartphone Collected GPS data: a Fuzzy Classification and Aggregation Approach.

    Science.gov (United States)

    Wan, Neng; Lin, Ge

    2016-12-01

    Smartphones have emerged as a promising type of equipment for monitoring human activities in environmental health studies. However, degraded location accuracy and inconsistency of smartphone-measured GPS data have limited its effectiveness for classifying human activity patterns. This study proposes a fuzzy classification scheme for differentiating human activity patterns from smartphone-collected GPS data. Specifically, a fuzzy logic reasoning was adopted to overcome the influence of location uncertainty by estimating the probability of different activity types for single GPS points. Based on that approach, a segment aggregation method was developed to infer activity patterns, while adjusting for uncertainties of point attributes. Validations of the proposed methods were carried out based on a convenient sample of three subjects with different types of smartphones. The results indicate desirable accuracy (e.g., up to 96% in activity identification) with use of this method. Two examples were provided in the appendix to illustrate how the proposed methods could be applied in environmental health studies. Researchers could tailor this scheme to fit a variety of research topics.

  15. Pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

    Science.gov (United States)

    Watanabe, Takahiro; Kawamura, Tatsuyoshi; Jacob, Sharon E; Aquilino, Elisabeth A; Orenstein, Jan M; Black, Jodi B; Blauvelt, Andrew

    2002-10-01

    Pityriasis rosea is a common skin disease that has been suspected to have a viral etiology. We performed nested polymerase chain reaction to detect human herpesvirus-7, human herpesvirus-6, and cytomegalovirus DNA in lesional skin, nonlesional skin, peripheral blood mononuclear cells, serum, and saliva samples isolated from 14 pityriasis rosea patients. Viral mRNA expression and virion visualization within lesional skin were studied by in situ hybridization and transmission electron microscopy, respectively. By nested polymerase chain reaction, human herpesvirus-7 DNA was present in lesional skin (93%), nonlesional skin (86%), saliva (100%), peripheral blood mononuclear cells (83%), and serum (100%) samples, whereas human herpesvirus-6 DNA was detected in lesional skin (86%), nonlesional skin (79%), saliva (80%), peripheral blood mononuclear cells (83%), and serum (88%) samples. By contrast, cytomegalovirus DNA was not detected in these tissues. Control samples from 12 healthy volunteers and 10 psoriasis patients demonstrated rare positivity for either human herpesvirus-7 or human herpesvirus-6 DNA in skin or serum. By in situ hybridization, infiltrating mononuclear cells expressing human herpesvirus-7 and human herpesvirus-6 mRNA were identified in perivascular and periappendageal areas in 100% and 75% pityriasis rosea skin lesions, respectively, compared to herpesviral mRNA positivity in only 13% normal skin and psoriasis skin controls. Transmission electron microscopy failed to reveal herpesviral virions in pityriasis rosea lesional skin. Nested polymerase chain reaction and in situ hybridization enabled detection of human herpesvirus-7 and human herpesvirus-6 in skin and other tissues isolated from patients with pityriasis rosea. These results suggest that pityriasis rosea is associated with systemic active infection with both human herpesvirus-7 and human herpesvirus-6.

  16. The Effect of Bad Human Activities on Marine Life as Portrayed in Sammy's Adventure: the Secret Passage

    OpenAIRE

    LATHIFAH, ISNA NUR

    2015-01-01

    Keywords: ecocriticism, bad humans activities, marine life, Sammy's Adventure: the Secret Passage movie. The balance of marine life is often damaged by irresponsible humans who do not care about their environment. This problem has inspired some works to criticize humans' reckless behavior toward environment, especially ocean. Sammy's Adventure: the Secret Passage is one of the examples that have been created to criticize the bad human activities in the ocean. This research applies ecocritici...

  17. Human Brain Activity Patterns beyond the Isoelectric Line of Extreme Deep Coma

    Science.gov (United States)

    Kroeger, Daniel; Florea, Bogdan; Amzica, Florin

    2013-01-01

    The electroencephalogram (EEG) reflects brain electrical activity. A flat (isoelectric) EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human) or by application of high doses of anesthesia (isoflurane in animals) leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes). Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region) we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma. PMID:24058669

  18. Influence of human activity patterns on epidemiology of plague in Western Usambara Mountains, Tanzania.

    Science.gov (United States)

    Hubeau, Marianne; Gulinck, Hubert; Kimaro, Didas N; Hieronimo, Proches; Meliyo, Joel

    2014-07-01

    Human plague has been a recurring public health threat in some villages in the Western Usambara Mountains, Tanzania, in the period between 1980 and 2004. Despite intensive past biological and medical research, the reasons for the plague outbreaks in the same set of villages remain unknown. Plague research needs to broaden its scope and formulate new hypotheses. This study was carried out to establish relationships between the nature and the spatial extent of selected human activities on one hand, and the reported plague cases on the other hand. Three outdoor activities namely, fetching water, collecting firewood and going to the market, were selected. Through enquiries the activity patterns related to these activities were mapped in 14 villages. Standard deviation ellipses represent the extent of action spaces. Over 130 activity types were identified and listed. Of these, fetching water, collecting firewood and going to the market were used for further analysis. The results indicate a significant correlation between the plague frequency and the size of these action spaces. Different characteristics of land use and related human activities were correlated with the plague frequency at village and hamlet levels. Significant relationships were found between plague frequency and specific sources of firewood and water, and specific market places.

  19. Quantifying multi-dimensional attributes of human activities at various geographic scales based on smartphone tracking.

    Science.gov (United States)

    Zhou, Xiaolu; Li, Dongying

    2018-05-09

    Advancement in location-aware technologies, and information and communication technology in the past decades has furthered our knowledge of the interaction between human activities and the built environment. An increasing number of studies have collected data regarding individual activities to better understand how the environment shapes human behavior. Despite this growing interest, some challenges exist in collecting and processing individual's activity data, e.g., capturing people's precise environmental contexts and analyzing data at multiple spatial scales. In this study, we propose and implement an innovative system that integrates smartphone-based step tracking with an app and the sequential tile scan techniques to collect and process activity data. We apply the OpenStreetMap tile system to aggregate positioning points at various scales. We also propose duration, step and probability surfaces to quantify the multi-dimensional attributes of activities. Results show that, by running the app in the background, smartphones can measure multi-dimensional attributes of human activities, including space, duration, step, and location uncertainty at various spatial scales. By coordinating Global Positioning System (GPS) sensor with accelerometer sensor, this app can save battery which otherwise would be drained by GPS sensor quickly. Based on a test dataset, we were able to detect the recreational center and sports center as the space where the user was most active, among other places visited. The methods provide techniques to address key issues in analyzing human activity data. The system can support future studies on behavioral and health consequences related to individual's environmental exposure.

  20. Anti-human rhinoviral activity of polybromocatechol compounds isolated from the rhodophyta, Neorhodomela aculeata.

    Science.gov (United States)

    Park, Soon-Hye; Song, Jae-Hyoung; Kim, Taejung; Shin, Woon-Seob; Park, Gab Man; Lee, Seokjoon; Kim, Young-Joo; Choi, Pilju; Kim, Heejin; Kim, Hui-Seong; Kwon, Dur-Han; Choi, Hwa Jung; Ham, Jungyeob

    2012-10-01

    An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1) and five polybromocatechols (2-6) by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC₅₀) of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC₅₀ of 7.11 μg/mL, and anti-HRV3 activity, with an IC₅₀ of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

  1. Orthogonal use of a human tRNA synthetase active site to achieve multifunctionality.

    Science.gov (United States)

    Zhou, Quansheng; Kapoor, Mili; Guo, Min; Belani, Rajesh; Xu, Xiaoling; Kiosses, William B; Hanan, Melanie; Park, Chulho; Armour, Eva; Do, Minh-Ha; Nangle, Leslie A; Schimmel, Paul; Yang, Xiang-Lei

    2010-01-01

    Protein multifunctionality is an emerging explanation for the complexity of higher organisms. In this regard, aminoacyl tRNA synthetases catalyze amino acid activation for protein synthesis, but some also act in pathways for inflammation, angiogenesis and apoptosis. It is unclear how these multiple functions evolved and how they relate to the active site. Here structural modeling analysis, mutagenesis and cell-based functional studies show that the potent angiostatic, natural fragment of human tryptophanyl-tRNA synthetase (TrpRS) associates via tryptophan side chains that protrude from its cognate cellular receptor vascular endothelial cadherin (VE-cadherin). VE-cadherin's tryptophan side chains fit into the tryptophan-specific active site of the synthetase. Thus, specific side chains of the receptor mimic amino acid substrates and expand the functionality of the active site of the synthetase. We propose that orthogonal use of the same active site may be a general way to develop multifunctionality of human tRNA synthetases and other proteins.

  2. Human activity and rest in situ.

    Science.gov (United States)

    Roenneberg, Till; Keller, Lena K; Fischer, Dorothee; Matera, Joana L; Vetter, Céline; Winnebeck, Eva C

    2015-01-01

    Our lives are structured by the daily alternation of activity and rest, of wake and sleep. Despite significant advances in circadian and sleep research, we still lack answers to many of the most fundamental questions about this conspicuous behavioral pattern. We strongly believe that investigating this pattern in entrained conditions, real-life and daily contexts-in situ-will help the field to elucidate some of these central questions. Here, we present two common approaches for in situ investigation of human activity and rest: the Munich ChronoType Questionnaire (MCTQ) and actimetry. In the first half of this chapter, we provide detailed instructions on how to use and interpret the MCTQ. In addition, we give an overview of the main insights gained with this instrument over the past 10 years, including some new findings on the interaction of light and age on sleep timing. In the second half of this chapter, we introduce the reader to the method of actimetry and share our experience in basic analysis techniques, including visualization, smoothing, and cosine model fitting of in situ recorded data. Additionally, we describe our new approach to automatically detect sleep from activity recordings. Our vision is that the broad use of such easy techniques in real-life settings combined with automated analyses will lead to the creation of large databases. The resulting power of big numbers will promote our understanding of such fundamental biological phenomena as sleep. © 2015 Elsevier Inc. All rights reserved.

  3. Apoptosis may determine the release of skeletal alkaline phosphatase activity from human osteoblast-line cells.

    Science.gov (United States)

    Farley, J R; Stilt-Coffing, B

    2001-01-01

    Although quantitative measurement of skeletal alkaline phosphatase (sALP) activity in serum can provide an index of the rate of bone formation, the metabolic process that determines the release of sALP - from the surface of osteoblasts, into circulation-is unknown. The current studies were intended to examine the hypothesis that the release of sALP from human osteoblasts is a consequence of apoptotic cell death. We measured the release of sALP activity from human osteosarcoma (SaOS-2) cells and normal human bone cells, under basal conditions and in response to agents that increased apoptosis (TNF-a, okadiac acid) and agents that inhibit apoptosis (IGF-I, calpain, and caspase inhibitors). Apoptosis was determined by the presence of nucleosomes (histone-associated DNA) in the cytoplasm of the cells by using a commercial kit. The results of these studies showed that TNF-a and okadiac acid caused dose- and time-dependent increases in apoptosis in the SaOS-2 cells (r = 0.78 for doses of TNF-a and r = 0.93 for doses of okadiac acid, P sALP activity (e.g., r = 0.89 for TNF-a and r = 0.75 for okadiac acid, P sALP activity (P sALP activity (P sALP release. The associations between apoptosis and sALP release were not unique to osteosarcoma (i.e., SaOS-2) cells, but also seen with osteoblast-line cells derived from normal human bone. Together, these data demonstrate that the release of sALP activity from human osteoblast-line cells in vitro is associated with, and may be a consequence of, apoptotic cell death. These findings are consistent with the general hypothesis that the appearance of sALP activity in serum may reflect the turnover of osteoblast-line cells.

  4. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  5. Inorganic arsenic represses interleukin-17A expression in human activated Th17 lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Morzadec, Claudie; Macoch, Mélinda; Robineau, Marc; Sparfel, Lydie [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Fardel, Olivier [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France); Pôle Biologie, Centre Hospitalier Universitaire (CHU) Rennes, 2 rue Henri Le Guilloux, 35033 Rennes (France); Vernhet, Laurent, E-mail: laurent.vernhet@univ-rennes1.fr [UMR INSERM U1085, Institut de Recherche sur la Santé, l' Environnement et le Travail (IRSET), Université de Rennes 1, 2 avenue du Professeur Léon Bernard, 35043 Rennes (France)

    2012-08-01

    Trivalent inorganic arsenic [As(III)] is an efficient anticancer agent used to treat patients suffering from acute promyelocytic leukemia. Recently, experimental studies have clearly demonstrated that this metalloid can also cure lymphoproliferative and/or pro-inflammatory syndromes in different murine models of chronic immune-mediated diseases. T helper (Th) 1 and Th17 lymphocytes play a central role in development of these diseases, in mice and humans, especially by secreting the potent pro-inflammatory cytokine interferon-γ and IL-17A, respectively. As(III) impairs basic functions of human T cells but its ability to modulate secretion of pro-inflammatory cytokines by differentiated Th lymphocytes is unknown. In the present study, we demonstrate that As(III), used at concentrations clinically achievable in plasma of patients, has no effect on the secretion of interferon-γ from Th1 cells but almost totally blocks the expression and the release of IL-17A from human Th17 lymphocytes co-stimulated for five days with anti-CD3 and anti-CD28 antibodies, in the presence of differentiating cytokines. In addition, As(III) specifically reduces mRNA levels of the retinoic-related orphan receptor (ROR)C gene which encodes RORγt, a key transcription factor controlling optimal IL-17 expression in fully differentiated Th17 cells. The metalloid also blocks initial expression of IL-17 gene induced by the co-stimulation, probably in part by impairing activation of the JNK/c-Jun pathway. In conclusion, our results demonstrate that As(III) represses expression of the major pro-inflammatory cytokine IL-17A produced by human Th17 lymphocytes, thus strengthening the idea that As(III) may be useful to treat inflammatory immune-mediated diseases in humans. -- Highlights: ► Arsenic inhibits secretion of IL-17A from human naïve and memory Th17 lymphocytes. ► Arsenic represses early expression of IL-17A gene in human activated T lymphocytes. ► Arsenic interferes with activation of

  6. Learning dictionaries of sparse codes of 3D movements of body joints for real-time human activity understanding.

    Science.gov (United States)

    Qi, Jin; Yang, Zhiyong

    2014-01-01

    Real-time human activity recognition is essential for human-robot interactions for assisted healthy independent living. Most previous work in this area is performed on traditional two-dimensional (2D) videos and both global and local methods have been used. Since 2D videos are sensitive to changes of lighting condition, view angle, and scale, researchers begun to explore applications of 3D information in human activity understanding in recently years. Unfortunately, features that work well on 2D videos usually don't perform well on 3D videos and there is no consensus on what 3D features should be used. Here we propose a model of human activity recognition based on 3D movements of body joints. Our method has three steps, learning dictionaries of sparse codes of 3D movements of joints, sparse coding, and classification. In the first step, space-time volumes of 3D movements of body joints are obtained via dense sampling and independent component analysis is then performed to construct a dictionary of sparse codes for each activity. In the second step, the space-time volumes are projected to the dictionaries and a set of sparse histograms of the projection coefficients are constructed as feature representations of the activities. Finally, the sparse histograms are used as inputs to a support vector machine to recognize human activities. We tested this model on three databases of human activities and found that it outperforms the state-of-the-art algorithms. Thus, this model can be used for real-time human activity recognition in many applications.

  7. Learning dictionaries of sparse codes of 3D movements of body joints for real-time human activity understanding.

    Directory of Open Access Journals (Sweden)

    Jin Qi

    Full Text Available Real-time human activity recognition is essential for human-robot interactions for assisted healthy independent living. Most previous work in this area is performed on traditional two-dimensional (2D videos and both global and local methods have been used. Since 2D videos are sensitive to changes of lighting condition, view angle, and scale, researchers begun to explore applications of 3D information in human activity understanding in recently years. Unfortunately, features that work well on 2D videos usually don't perform well on 3D videos and there is no consensus on what 3D features should be used. Here we propose a model of human activity recognition based on 3D movements of body joints. Our method has three steps, learning dictionaries of sparse codes of 3D movements of joints, sparse coding, and classification. In the first step, space-time volumes of 3D movements of body joints are obtained via dense sampling and independent component analysis is then performed to construct a dictionary of sparse codes for each activity. In the second step, the space-time volumes are projected to the dictionaries and a set of sparse histograms of the projection coefficients are constructed as feature representations of the activities. Finally, the sparse histograms are used as inputs to a support vector machine to recognize human activities. We tested this model on three databases of human activities and found that it outperforms the state-of-the-art algorithms. Thus, this model can be used for real-time human activity recognition in many applications.

  8. Probiotic Activity of Saccharomyces cerevisiae var. boulardii Against Human Pathogens

    Directory of Open Access Journals (Sweden)

    Katarzyna Rajkowska

    2012-01-01

    Full Text Available Infectious diarrhoea is associated with a modification of the intestinal microflora and colonization of pathogenic bacteria. Tests were performed for seven probiotic yeast strains of Saccharomyces cerevisiae var. boulardii, designated for the prevention and treatment of diarrhoea. To check their possible effectiveness against diarrhoea of different etiologies, the activity against a variety of human pathogenic or opportunistic bacteria was investigated in vitro. In mixed cultures with S. cerevisiae var. boulardii, a statistically significant reduction was observed in the number of cells of Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus, by even 55.9 % in the case of L. monocytogenes compared with bacterial monocultures. The influence of yeasts was mostly associated with the shortening of the bacterial lag phase duration, more rapid achievement of the maximum growth rates, and a decrease by 4.4–57.1 % (L. monocytogenes, P. aeruginosa, or an increase by 1.4–70.6 % (Escherichia coli, Enterococcus faecalis, Salmonella Typhimurium in the exponential growth rates. Another issue included in the research was the ability of S. cerevisiae var. boulardii to bind pathogenic bacteria to its cell surface. Yeasts have shown binding capacity of E. coli, S. Typhimurium and additionally of S. aureus, Campylobacter jejuni and E. faecalis. However, no adhesion of L. monocytogenes and P. aeruginosa to the yeast cell wall was noted. The probiotic activity of S. cerevisiae var. boulardii against human pathogens is related to a decrease in the number of viable and active cells of bacteria and the binding capacity of yeasts. These processes may limit bacterial invasiveness and prevent bacterial adherence and translocation in the human intestines.

  9. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Sandra C. [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States); Chau, Mary D.L.; Yang, Qing [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Gauthier, Marie-Soleil [Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02140 (United States); Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper [Cardiovascular and Metabolism Disease Area, Novartis Institutes for Biomedical Research, Inc., 100 Technology Square, Cambridge, MA 02139 (United States); Dole, William P., E-mail: bill.dole@novartis.com [Translational Sciences - Translational Medicine, Novartis Institutes for Biomedical Research, Inc., 220 Massachusetts Avenue, Cambridge, MA 02139 (United States)

    2011-07-08

    Highlights: {yields} Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). {yields} ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. {yields} ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. {yields} Exposure of human adipocytes to fatty acids and (TNF{alpha}) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and

  10. Atrial natriuretic peptide regulates lipid mobilization and oxygen consumption in human adipocytes by activating AMPK

    International Nuclear Information System (INIS)

    Souza, Sandra C.; Chau, Mary D.L.; Yang, Qing; Gauthier, Marie-Soleil; Clairmont, Kevin B.; Wu, Zhidan; Gromada, Jesper; Dole, William P.

    2011-01-01

    Highlights: → Treatment of differentiated human adipocytes with atrial natriuretic peptide (ANP) increased lipolysis and oxygen consumption by activating AMP-activated protein kinase (AMPK). → ANP stimulated lipid mobilization by selective activation of the alpha2 subunit of AMPK and increased energy utilization through activation of both the alpha1 and alpha2 subunits of AMPK. → ANP enhanced adipocyte mitochondrial oxidative capacity as evidenced by induction of oxidative mitochondrial genes and increase in oxygen consumption. → Exposure of human adipocytes to fatty acids and (TNFα) induced insulin resistance and decreased expression of mitochondrial genes which was restored to normal by ANP. -- Abstract: Atrial natriuretic peptide (ANP) has been shown to regulate lipid and carbohydrate metabolism providing a possible link between cardiovascular function and metabolism by mediating the switch from carbohydrate to lipid mobilization and oxidation. ANP exerts a potent lipolytic effect via cGMP-dependent protein kinase (cGK)-I mediated-stimulation of AMP-activated protein kinase (AMPK). Activation of the ANP/cGK signaling cascade also promotes muscle mitochondrial biogenesis and fat oxidation. Here we demonstrate that ANP regulates lipid metabolism and oxygen utilization in differentiated human adipocytes by activating the alpha2 subunit of AMPK. ANP treatment increased lipolysis by seven fold and oxygen consumption by two fold, both of which were attenuated by inhibition of AMPK activity. ANP-induced lipolysis was shown to be mediated by the alpha2 subunit of AMPK as introduction of dominant-negative alpha2 subunit of AMPK attenuated ANP effects on lipolysis. ANP-induced activation of AMPK enhanced mitochondrial oxidative capacity as evidenced by a two fold increase in oxygen consumption and induction of mitochondrial genes, including carnitine palmitoyltransferase 1A (CPT1a) by 1.4-fold, cytochrome C (CytC) by 1.3-fold, and peroxisome proliferator-activated

  11. Human medial frontal cortex activity predicts learning from errors.

    Science.gov (United States)

    Hester, Robert; Barre, Natalie; Murphy, Kevin; Silk, Tim J; Mattingley, Jason B

    2008-08-01

    Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippocampus also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected."

  12. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  13. Bifenthrin activates homotypic aggregation in human T-cell lines.

    Science.gov (United States)

    Hoffman, Nataly; Tran, Van; Daniyan, Anthony; Ojugbele, Olutosin; Pryor, Stephen C; Bonventre, Josephine A; Flynn, Katherine; Weeks, Benjamin S

    2006-03-01

    Here, we addressed the concern that, despite the lack of overt toxicity, exposure to low levels of the common household pyrethroid pesticide, bifenthrin, could cause harm to the immune system. To do this, we measure the effect of bifenthrin on phytohemagglutinin (PHA) activation of homotypic aggregation in human T-cell lines. The human CD4+ H9, and Jurkat cell lines and the human promonocyte U937 cell line, were exposed to varying concentrations of bifenthrin. Cell viability was determined using the AlmarBlue Toxicity Assay. Concentrations of bifenthrin which did not reduce cell viability were determined and these concentrations were tested for the effect of bifenthrin on PHA-mediated homotypic aggregation. Blocking antibodies to ICAM and LFA-1 were used to disrupt aggregation and a nonspecific IgG was used as a control. Bifenthrin was found to be nontoxic at concentrations ranging from 10(-4) to 10(-13) M. Bifenthrin did not inhibit PHA induced cell aggregation in all cell lines tested. However, at 10(-4) M, bifenthrin to form aggregates stimulated homotypic aggregation in the H9 and Jurkat T-cell lines. The bifenthrin-induced aggregate formation, like that seen with PHA, was blocked by treating the cells with antibodies to either LFA-1 or ICAM. The results here show that bifenthrin activates T-cell function by stimulating ICAM/LFA-1 mediated homotypic aggregation. This data suggests that exposure to bifenthrin, even at "acceptable" limits, can increase the risk for and frequency of inflammatory responses and diseases such as asthma.

  14. The human ARF tumor suppressor senses blastema activity and suppresses epimorphic tissue regeneration

    Science.gov (United States)

    Hesse, Robert G; Kouklis, Gayle K; Ahituv, Nadav; Pomerantz, Jason H

    2015-01-01

    The control of proliferation and differentiation by tumor suppressor genes suggests that evolution of divergent tumor suppressor repertoires could influence species’ regenerative capacity. To directly test that premise, we humanized the zebrafish p53 pathway by introducing regulatory and coding sequences of the human tumor suppressor ARF into the zebrafish genome. ARF was dormant during development, in uninjured adult fins, and during wound healing, but was highly expressed in the blastema during epimorphic fin regeneration after amputation. Regenerative, but not developmental signals resulted in binding of zebrafish E2f to the human ARF promoter and activated conserved ARF-dependent Tp53 functions. The context-dependent activation of ARF did not affect growth and development but inhibited regeneration, an unexpected distinct tumor suppressor response to regenerative versus developmental environments. The antagonistic pleiotropic characteristics of ARF as both tumor and regeneration suppressor imply that inducing epimorphic regeneration clinically would require modulation of ARF –p53 axis activation. DOI: http://dx.doi.org/10.7554/eLife.07702.001 PMID:26575287

  15. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration

    DEFF Research Database (Denmark)

    Saclier, Marielle; Yacoub-Youssef, Houda; Mackey, Abigail

    2013-01-01

    , we explored both in vitro and in vivo, in human, the interactions of differentially activated MPs with myogenic precursor cells (MPCs) during adult myogenesis and skeletal muscle regeneration. We showed in vitro that through the differential secretion of cytokines and growth factors, proinflammatory...... anti-inflammatory markers. These data demonstrate for the first time in human that MPs sequentially orchestrate adult myogenesis during regeneration of damaged skeletal muscle. These results support the emerging concept that inflammation, through MP activation, controls stem cell fate and coordinates......Macrophages (MPs) exert either beneficial or deleterious effects on tissue repair, depending on their activation/polarization state. They are crucial for adult skeletal muscle repair, notably by acting on myogenic precursor cells. However, these interactions have not been fully characterized. Here...

  16. Biomaterials trigger endothelial cell activation when co-incubated with human whole blood.

    Science.gov (United States)

    Herklotz, Manuela; Hanke, Jasmin; Hänsel, Stefanie; Drichel, Juliane; Marx, Monique; Maitz, Manfred F; Werner, Carsten

    2016-10-01

    Endothelial cell activation resulting from biomaterial contact or biomaterial-induced blood activation may in turn also affect hemostasis and inflammatory processes in the blood. Current in vitro hemocompatibility assays typically ignore these modulating effects of the endothelium. This study describes a co-incubation system of human whole blood, biomaterial and endothelial cells (ECs) that was developed to overcome this limitation. First, human endothelial cells were characterized in terms of their expression of coagulation- and inflammation-relevant markers in response to various activators. Subsequently, their capacity to regulate hemostasis as well as complement and granulocyte activation was monitored in a hemocompatibility assay. After blood contact, quiescent ECs exhibited anticoagulant and anti-inflammatory properties. When they were co-incubated with surfaces exhibiting pro-coagulant or pro-inflammatory characteristics, the ECs down-regulated coagulation but not complement or leukocyte activation. Analysis of intracellular levels of the endothelial activation markers E-selectin and tissue factor showed that co-incubation with model surfaces and blood significantly increased the activation state of ECs. Finally, the coagulation- and inflammation-modulating properties of the ECs were tested after blood/biomaterial exposure. Pre-activation of ECs by biomaterials in the blood induced a pro-coagulant and pro-inflammatory state of the ECs, wherein the pro-coagulant response was higher for biomaterial/blood pre-activated ECs than for TNF-α-pre-activated cells. This work provides evidence that biomaterials, even without directly contacting the endothelium, affect the endothelial activation state with and have consequences for plasmatic and cellular reactions in the blood. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    International Nuclear Information System (INIS)

    Lee, Kiwon; Liu, Yin; Mo, Jun Qin; Zhang, Jinsong; Dong, Zhongyun; Lu, Shan

    2008-01-01

    Our previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor, and stimulates growth in prostate cancer cells. The current study is to determine a potential role of Vav3 oncogene in human breast cancer and impact on estrogen receptor a (ERα)-mediated signaling axis. Immunohistochemistry analysis was performed in 43 breast cancer specimens and western blot analysis was used for human breast cancer cell lines to determine the expression level of Vav3 protein. The impact of Vav3 on breast cancer cell growth was determined by siRNA knockdown of Vav3 expression. The role of Vav3 in ERα activation was examined in luciferase reporter assays. Deletion mutation analysis of Vav3 protein was performed to localize the functional domain involved in ERα activation. Finally, the interaction of Vav3 and ERα was assessed by GST pull-down analysis. We found that Vav3 was overexpressed in 81% of human breast cancer specimens, particularly in poorly differentiated lesions. Vav3 activated ERα partially via PI3K-Akt signaling and stimulated growth of breast cancer cells. Vav3 also potentiated EGF activity for cell growth and ERα activation in breast cancer cells. More interestingly, we found that Vav3 complexed with ERα. Consistent with its function for AR, the DH domain of Vav3 was essential for ERα activation. Vav3 oncogene is overexpressed in human breast cancer. Vav3 complexes with ERα and enhances ERα activity. These findings suggest that Vav3 overexpression may aberrantly enhance ERα-mediated signaling axis and play a role in breast cancer development and/or progression

  18. Endogenous acute phase serum amyloid A lacks pro-inflammatory activity, contrasting the two recombinant variants that activate human neutrophils through different receptors

    Directory of Open Access Journals (Sweden)

    Karin eChristenson

    2013-04-01

    Full Text Available Most notable among the acute phase proteins is serum amyloid A (SAA, levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2 that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1 both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2. We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein.

  19. Screening vaccine formulations for biological activity using fresh human whole blood.

    OpenAIRE

    Brookes, RH; Hakimi, J; Ha, Y; Aboutorabian, S; Ausar, SF; Hasija, M; Smith, SG; Todryk, SM; Dockrell, HM; Rahman, N

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it rem...

  20. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

    OpenAIRE

    Néstor Correa; Néstor Correa; Néstor Correa; Cristian Covarrubias; Paula I. Rodas; Germán Hermosilla; Verónica R. Olate; Verónica R. Olate; Cristián Valdés; Wieland Meyer; Fabien Magne; Cecilia V. Tapia; Cecilia V. Tapia

    2017-01-01

    Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an...

  1. The effect of human activity noise on the acoustic quality in open plan office

    DEFF Research Database (Denmark)

    Dehlbæk, Tania Stenholt; Jeong, Cheol-Ho; Brunskog, Jonas

    2016-01-01

    A disadvantage of open plan offices is the noise annoyance. Noise problems in open plan offices have been dealt with in several studies, and standards have been set up. Still, what has not been taken into account is the effect of human activity noise on acoustic conditions. In this study......, measurements of the general office noise levels and the room acoustic conditions according to ISO 3382-3 have been carried out in five open plan offices. Probability density functions of the sound pressure level have been obtained, and the human activity noise has been identified. Results showed a decrease...... in STI-values including the human activity noise compared to STI-values including only technical background noise as the standard recommends. Furthermore, at 500 Hz a regression analysis showed that the density of people in an room, absorption area, reverberation time as well as the ISO 3382-3 parameter...

  2. A Novel Energy-Efficient Approach for Human Activity Recognition.

    Science.gov (United States)

    Zheng, Lingxiang; Wu, Dihong; Ruan, Xiaoyang; Weng, Shaolin; Peng, Ao; Tang, Biyu; Lu, Hai; Shi, Haibin; Zheng, Huiru

    2017-09-08

    In this paper, we propose a novel energy-efficient approach for mobile activity recognition system (ARS) to detect human activities. The proposed energy-efficient ARS, using low sampling rates, can achieve high recognition accuracy and low energy consumption. A novel classifier that integrates hierarchical support vector machine and context-based classification (HSVMCC) is presented to achieve a high accuracy of activity recognition when the sampling rate is less than the activity frequency, i.e., the Nyquist sampling theorem is not satisfied. We tested the proposed energy-efficient approach with the data collected from 20 volunteers (14 males and six females) and the average recognition accuracy of around 96.0% was achieved. Results show that using a low sampling rate of 1Hz can save 17.3% and 59.6% of energy compared with the sampling rates of 5 Hz and 50 Hz. The proposed low sampling rate approach can greatly reduce the power consumption while maintaining high activity recognition accuracy. The composition of power consumption in online ARS is also investigated in this paper.

  3. Extracellular microvesicle production by human eosinophils activated by “inflammatory” stimuli

    Directory of Open Access Journals (Sweden)

    Praveen Akuthota

    2016-10-01

    Full Text Available A key function of human eosinophils is to secrete cytokines, chemokines and cationic proteins, trafficking and releasing these mediators for roles in inflammation and other immune responses. Eosinophil activation leads to secretion of pre-synthesized granule-stored mediators through different mechanisms, but the ability of eosinophils to secrete extracellular vesicles (EVs, very small vesicles with preserved membrane topology, is still poorly understood. In the present work, we sought to identify and characterize EVs released from human eosinophils during different conditions: after a culturing period or after isolation and stimulation with inflammatory stimuli, which are known to induce eosinophil activation and secretion: CCL11 (eotaxin-1 and tumor necrosis factor alpha (TNF-α. EV production was investigated by nanoscale flow cytometry, conventional transmission electron microscopy (TEM and pre-embedding immunonanogold EM. The tetraspanins CD63 and CD9 were used as EV biomarkers for both flow cytometry and ultrastructural immunolabeling. Nanoscale flow cytometry showed that human eosinophils produce EVs in culture and that a population of EVs expressed detectable CD9, while CD63 was not consistently detected. When eosinophils were stimulated immediately after isolation and analyzed by TEM, EVs were clearly identified as microvesicles (MVsoutwardly budding off the plasma membrane. Both CCL11 and TNF-α induced significant increases of MVs compared to unstimulated cells.TNF-α induced amplified release of MVs more than CCL11. Eosinophil MV diameters varied from 20-1000 nm. Immunonanogold EM revealed clear immunolabeling for CD63 and CD9 on eosinophil MVs, although not all MVs were labeled. Altogether, we identified, for the first time, that human eosinophils secrete MVs and that this production increases in response to inflammatory stimuli. This is important to understand the complex secretory activities of eosinophils underlying immune

  4. Long-term constraints on human activity

    Energy Technology Data Exchange (ETDEWEB)

    Lovins, A. B.

    1976-04-01

    Biophysical and other ''outer limits'' of food, land, water, climatic change, stratospheric chemistry, energy, hazardous substances, non-fuel minerals, human stress, and social and ecological stability raise fundamental questions about present trends in management methods and in global organization. The diverse outer limits reflect complex, poorly perceived, and often unsuspected, interconnections between numerous biological and geophysical processes, many of which are obscure or still unknown. Our lack of predictive power, let alone of quantitative understanding, implies a need to treat essential life-support systems with great caution and forbearance, lest we erode safety margins whose importance we do not yet appreciate. Even those outer limits which now seem remote are relevant to present policy, as their timely avoidance may require us to discard otherwise attractive short-term policies in favor of others that offer less immediate advantage but that retain options which may be needed later. Such alternative policies may have to rely more on social than on technical innovation in order to address underlying disequilibria rather than merely palliating their symptoms. Moreover, some outer limits are sufficiently imminent, or require such long lead-times to avoid, that fundamental changes in policy, in institutions, and in the degree of global interdependence, seem necessary if we are to live to enjoy some of the later and more interesting limits to human activity.

  5. FINITE MARKOV CHAINS IN THE MODEL REPRESENTATION OF THE HUMAN OPERATOR ACTIVITY IN QUASI-FUNCTIONAL ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    M. V. Serzhantova

    2016-05-01

    Full Text Available Subject of Research. We analyze the problems of finite Markov chains apparatus application for simulating a human operator activity in the quasi-static functional environment. It is shown that the functional environment stochastic nature is generated by a factor of interval character of human operator properties. Method. The problem is solved in the class of regular (recurrent finite Markov chains with three states of the human operator: with a favorable, median and unfavorable combination of the values of mathematical model parameters of the human operator in a quasi-static functional environment. The finite Markov chain is designed taking into account the factors of human operator tiredness and interval character of parameters of the model representation of his properties. The device is based on the usage of mathematical approximation of the standard curve of the human operator activity performance during work shift. The standard curve of the human operator activity performance is based on the extensive research experience of functional activity of the human operator with the help of photos of the day, his action timing and ergonomic generalizations. Main Results. The apparatus of regular finite Markov chains gave the possibility to evaluate correctly the human operator activity performance in a quasi-static functional environment with the use of the main information component of these chains as a vector of final probabilities. In addition, we managed to build an algorithmic basis for estimating the stationary time (time study for transit of human operator from arbitrary initial functional state into a state corresponding to a vector of final probabilities for a used chain after it reaches the final state based on the analysis of the eigenvalues spectrum of the matrix of transition probabilities for a regular (recurrent finite Markov chain. Practical Relevance. Obtained theoretical results are confirmed by illustrative examples, which

  6. Tetraspanin CD9 modulates human lymphoma cellular proliferation via histone deacetylase activity

    Energy Technology Data Exchange (ETDEWEB)

    Herr, Michael J. [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Longhurst, Celia M.; Baker, Benjamin [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Homayouni, Ramin [Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States); Speich, Henry E.; Kotha, Jayaprakash [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Jennings, Lisa K., E-mail: ljennings@uthsc.edu [Vascular Biology Center of Excellence, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Medicine, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Molecular Sciences, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Surgery, The University of Tennessee Health Science Center, Memphis, TN 38163 (United States); Department of Biology, Bioinformatics Program, University of Memphis, Memphis, TN 38152 (United States)

    2014-05-16

    Highlights: • CD9 is differentially expressed in human Burkitt’s lymphoma cells. • We found that CD9 expression promotes these cells proliferation. • CD9 expression also increases HDAC activity. • HDAC inhibition decreased both cell proliferation and importantly CD9 expression. • CD9 may dictate HDAC efficacy and play a role in HDAC regulation. - Abstract: Non-Hodgkin Lymphoma (NHL) is a type of hematological malignancy that affects two percent of the overall population in the United States. Tetraspanin CD9 is a cell surface protein that has been thoroughly demonstrated to be a molecular facilitator of cellular phenotype. CD9 expression varies in two human lymphoma cell lines, Raji and BJAB. In this report, we investigated the functional relationship between CD9 and cell proliferation regulated by histone deacetylase (HDAC) activity in these two cell lines. Introduction of CD9 expression in Raji cells resulted in significantly increased cell proliferation and HDAC activity compared to Mock transfected Raji cells. The increase in CD9–Raji cell proliferation was significantly inhibited by HDAC inhibitor (HDACi) treatment. Pretreatment of BJAB cells with HDAC inhibitors resulted in a significant decrease in endogenous CD9 mRNA and cell surface expression. BJAB cells also displayed decreased cell proliferation after HDACi treatment. These results suggest a significant relationship between CD9 expression and cell proliferation in human lymphoma cells that may be modulated by HDAC activity.

  7. Virulent Type A Francisella tularensis actively suppresses cytokine responses in human monocytes

    Science.gov (United States)

    Gillette, Devyn D.; Curry, Heather M.; Cremer, Thomas; Ravneberg, David; Fatehchand, Kavin; Shah, Prexy A.; Wewers, Mark D.; Schlesinger, Larry S.; Butchar, Jonathan P.; Tridandapani, Susheela; Gavrilin, Mikhail A.

    2014-01-01

    Background: Human monocyte inflammatory responses differ between virulent and attenuated Francisella infection. Results: A mixed infection model showed that the virulent F. tularensis Schu S4 can attenuate inflammatory cytokine responses to the less virulent F. novicida in human monocytes. Conclusion: F. tularensis dampens inflammatory response by an active process. Significance: This suppression may contribute to enhanced pathogenicity of F. tularensis. Francisella tularensis is a Gram-negative facultative bacterium that can cause the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. Previous work has shown that monocytes infected with highly virulent F. tularensis subsp. tularensis strain Schu S4 responded with a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes and cytokine production in comparison to those infected with the less virulent related F. novicida. However, it has been unclear whether the virulent Schu S4 was merely evading or actively suppressing monocyte responses. By using mixed infection assays with F. tularensis and F. novicida, we show that F. tularensis actively suppresses monocyte pro-inflammatory responses. Additional experiments show that this suppression occurs in a dose-dependent manner and is dependent upon the viability of F. tularensis. Importantly, F. tularensis was able to suppress pro-inflammatory responses to earlier infections with F. novicida. These results lend support that F. tularensis actively dampens human monocyte responses and this likely contributes to its enhanced pathogenicity. PMID:24783062

  8. Evaluation of Hemagglutination Activity of Chitosan Nanoparticles Using Human Erythrocytes

    Directory of Open Access Journals (Sweden)

    Jefferson Muniz de Lima

    2015-01-01

    Full Text Available Chitosan is a polysaccharide composed of randomly distributed chains of β-(1-4 D-glucosamine and N-acetyl-D-glucosamine. This compound is obtained by partial or total deacetylation of chitin in acidic solution. The chitosan-based hemostatic agents have been gaining much attention in the management of bleeding. The aim of this study was to evaluate in vitro hemagglutination activity of chitosan nanoparticles using human erythrocytes. The preparation of nanoparticles was achieved by ionotropic gelification technique followed by neutralization with NaOH 1 mol/L−1. The hemagglutination activity was performed on a solution of 2% erythrocytes (pH 7.4 on PBS collected from five healthy volunteers. The hemolysis determination was made by spectrophotometric analysis. Chitosan nanoparticle solutions without NaOH addition changed the reddish colour of the wells into brown, suggesting an oxidative reaction of hemoglobin and possible cell lysis. All neutralized solutions of chitosan nanoparticles presented positive haemagglutination, without any change in reaction color. Chitosan nanoparticles presented hemolytic activity ranging from 186.20 to 223.12%, while neutralized solutions ranged from 2.56 to 72.54%, comparing to distilled water. Results highlight the need for development of new routes of synthesis of chitosan nanoparticles within human physiologic pH.

  9. Measurement of human tissue-type plasminogen activator by a two-site immunoradiometric assay

    International Nuclear Information System (INIS)

    Rijken, D.C.; Juhan-Vague, I.; De Cock, F.; Collen, D.

    1983-01-01

    A two-site immunoradiometric assay for human extrinsic (tissue-type) plasminogen activator was developed by using rabbit antibodies raised against plasminogen activator purified from human melanoma cell culture fluid. Samples of 100 μl containing 1 to 100 ng/ml plasminogen activator were incubated in the wells of polyvinyl chloride microtiter plates coated with antibody. The amount of bound extrinsic plasminogen activator was quantitated by the subsequent binding of 125 I-labeled affinospecific antibody. The mean level of plasma samples taken at rest was 6.6 +/- 2.9 ng/ml (n = 54). This level increased approximately threefold by exhaustive physical exercise, venous occlusion, or infusion of DDAVP. Extrinsic plasminogen activator in plasma is composed of a fibrin-adsorbable and active component (1.9 +/- 1.1 ng/ml, n = 54, in resting conditions) and an inactive component that does not bind to a fibrin clot (probably extrinsic plasminogen activator-proteinase inhibitor complexes). The fibrin-adsorbable fraction increased approximately fivefold to eightfold after physical exercise, venous occlusion, or DDAVP injections. Potential applications of the immunoradiometric assay are illustrated by the measurement of extrinsic plasminogen activator in different tissue extracts, body fluids, and cell culture fluids and in oocyte translation products after injection with mRNA for plasminogen activator

  10. Cortical GABAergic excitation contributes to epileptic activities around human glioma

    Science.gov (United States)

    Pallud, Johan; Varlet, Pascale; Cresto, Noemie; Baulac, Michel; Duyckaerts, Charles; Kourdougli, Nazim; Chazal, Geneviève; Devaux, Bertrand; Rivera, Claudio; Miles, Richard; Capelle, Laurent; Huberfeld, Gilles

    2015-01-01

    Rationale Diffuse brain gliomas induce seizures in a majority of patients. As in most epileptic disorders, excitatory glutamatergic mechanisms are involved in the generation of epileptic activities in the neocortex surrounding gliomas. However, chloride homeostasis is known to be perturbed in glial tumor cells. Thus the contribution of GABAergic mechanisms which depend on intracellular chloride and which are defective or pro-epileptic in other structural epilepsies merits closer study. Objective We studied in neocortical slices from the peritumoral security margin resected around human brain gliomas, the occurrence, networks, cells and signaling basis of epileptic activities. Results Postoperative glioma tissue from 69% of patients spontaneously generated interictal-like discharges. These events were synchronized, with a high frequency oscillation signature, in superficial layers of neocortex around glioma areas with tumor infiltration. Interictal-like events depended on both glutamatergic transmission and on depolarizing GABAergic signaling. About 65% of pyramidal cells were depolarized by GABA released by interneurons. This effect was related to perturbations in Chloride homeostasis, due to changes in expression of chloride co-transporters: KCC2 was reduced and expression of NKCC1 increased. Ictal-like activities were initiated by convulsant stimuli exclusively in these epileptogenic areas. Conclusions Epileptic activities are sustained by excitatory effects of GABA in the peritumoral human neocortex, as in temporal lobe epilepsies. Glutamate and GABA signaling are involved in oncogenesis and chloride homeostasis is perturbed. These same factors, induce an imbalance between synaptic excitatory and inhibition underly epileptic discharges in tumor patients. PMID:25009229

  11. Human activity and damaging landslides and floods on Madeira Island

    Directory of Open Access Journals (Sweden)

    D. Baioni

    2011-11-01

    Full Text Available Over the last few decades, the island of Madeira has become an important offshore tourism and business center, with rapid economic and demographic development that has caused changes to the landscape due to human activity. In Madeira's recent history, there has been an increase over time in the frequency of occurrence of damaging landslide and flood events. As a result, the costs of restoration work due to damage caused by landslide and flood events have become a larger and larger component of Madeira's annual budget. Landslides and floods in Madeira deserve particular attention because they represent the most serious hazard to human life, to property, and to the natural environment and its important heritage value.

    The work reported on in this paper involved the analysis of historical data regarding damaging landslide and flood events on Madeira (in particular from 1941 to 1991 together with data on geological characteristics, topographic features, and climate, and from field observations. This analysis showed that the main factor triggering the occurrence of damaging landslide and flood events is rainfall, but that the increase in the number of damaging events recorded on Madeira Island, especially in recent times, seems to be related mostly to human activity, specifically to economic development and population growth, rather than to natural factors.

  12. Human presence diminishes the importance of climate in driving fire activity across the United States

    Science.gov (United States)

    Syphard, Alexandra D.; Keeley, Jon E.; Pfaff, Anne Hopkins; Ferschweiler, Ken

    2017-01-01

    Growing human and ecological costs due to increasing wildfire are an urgent concern in policy and management, particularly given projections of worsening fire conditions under climate change. Thus, understanding the relationship between climatic variation and fire activity is a critically important scientific question. Different factors limit fire behavior in different places and times, but most fire-climate analyses are conducted across broad spatial extents that mask geographical variation. This could result in overly broad or inappropriate management and policy decisions that neglect to account for regionally specific or other important factors driving fire activity. We developed statistical models relating seasonal temperature and precipitation variables to historical annual fire activity for 37 different regions across the continental United States and asked whether and how fire-climate relationships vary geographically, and why climate is more important in some regions than in others. Climatic variation played a significant role in explaining annual fire activity in some regions, but the relative importance of seasonal temperature or precipitation, in addition to the overall importance of climate, varied substantially depending on geographical context. Human presence was the primary reason that climate explained less fire activity in some regions than in others. That is, where human presence was more prominent, climate was less important. This means that humans may not only influence fire regimes but their presence can actually override, or swamp out, the effect of climate. Thus, geographical context as well as human influence should be considered alongside climate in national wildfire policy and management.

  13. Source strengths for indoor human activities that resuspend particulate matter.

    Science.gov (United States)

    Ferro, Andrea R; Kopperud, Royal J; Hildemann, Lynn M

    2004-03-15

    A mathematical model was applied to continuous indoor and outdoor particulate matter (PM) measurements to estimate source strengths for a variety of prescribed human activities that resuspend house dust in the home. Activities included folding blankets, folding clothes, dry dusting, making a bed, dancing on a rug, dancing on a wood floor, vacuuming, and walking around and sitting on upholstered furniture. Although most of the resuspended particle mass from these activities was larger than 5 microm in diameter, the resuspension of PM2.5 and PM5 was substantial, with source strengths ranging from 0.03 to 0.5 mg min(-1) for PM2.5 and from 0.1 to 1.4 mg min(-1) for PM5. Source strengths for PM > 5 microm could not be quantified due to instrument limitations. The source strengths were found to be a function of the number of persons performing the activity, the vigor of the activity, the type of activity, and the type of flooring.

  14. Comparison of rhythmic masticatory muscle activity during non-rapid eye movement sleep in guinea pigs and humans.

    Science.gov (United States)

    Kato, Takafumi; Toyota, Risa; Haraki, Shingo; Yano, Hiroyuki; Higashiyama, Makoto; Ueno, Yoshio; Yano, Hiroshi; Sato, Fumihiko; Yatani, Hirofumi; Yoshida, Atsushi

    2017-09-27

    Rhythmic masticatory muscle activity can be a normal variant of oromotor activity, which can be exaggerated in patients with sleep bruxism. However, few studies have tested the possibility in naturally sleeping animals to study the neurophysiological mechanisms of rhythmic masticatory muscle activity. This study aimed to investigate the similarity of cortical, cardiac and electromyographic manifestations of rhythmic masticatory muscle activity occurring during non-rapid eye movement sleep between guinea pigs and human subjects. Polysomnographic recordings were made in 30 freely moving guinea pigs and in eight healthy human subjects. Burst cycle length, duration and activity of rhythmic masticatory muscle activity were compared with those for chewing. The time between R-waves in the electrocardiogram (RR interval) and electroencephalogram power spectrum were calculated to assess time-course changes in cardiac and cortical activities in relation to rhythmic masticatory muscle activity. In animals, in comparison with chewing, rhythmic masticatory muscle activity had a lower burst activity, longer burst duration and longer cycle length (P motor activation in comparison to human subjects. © 2017 European Sleep Research Society.

  15. Roles of calpain-calpastatin system (CCS) in human T cell activation.

    Science.gov (United States)

    Mikosik, Anna; Jasiulewicz, Aleksandra; Daca, Agnieszka; Henc, Izabella; Frąckowiak, Joanna E; Ruckemann-Dziurdzińska, Katarzyna; Foerster, Jerzy; Le Page, Aurelie; Bryl, Ewa; Fulop, Tamas; Witkowski, Jacek M

    2016-11-22

    The immune response is determined by the speed of the T cell reaction to antigens assured by a state of readiness for proliferation and cytokine secretion. Proliferation, apoptosis and motion of many cell types are controlled by cytoplasmic proteases - µ- and m-calpain - and their inhibitor calpastatin, together forming the "calpain-calpastatin system" (CCS), assumed to modify their targets only upon activation-dependent cytoplasmic Ca2+ increase. Contrastingly to this notion, using quantitative real time PCR and semiquantitative flow cytometry respectively, we show here that the CCS genes are constitutively expressed, and that both calpains are constitutively active in resting, circulating human CD4+ and CD8+ lymphocytes. Furthermore, we demonstrate that calpain inhibition in the resting T cells prevents them from proliferation in vitro and greatly reduces secretion of multiple cytokines. The mechanistic reason for these effects of calpain inhibition on T cell functions might be the demonstrated significant reduction of the expression of active (phosphorylated) upstream signalling molecules, including the phospholipase C gamma, p56Lck and NFκB, in the inhibitor-treated cells. Thus, we propose that the constitutive, self-regulatory calpain-calpastatin system activity in resting human T cells is a necessary, controlling element of their readiness for complex and effective response to antigenic challenge.

  16. The 2001 activities and the 3rd workshop of the human resources development project in FNCA

    International Nuclear Information System (INIS)

    2002-07-01

    In 1999, the Project for Human Resources Development (HRD) was initiated as defined in the framework of the Forum for Nuclear Cooperation in Asia (FNCA), organized by the Atomic Energy Commission of Japan. The objective of the HRD Project is to solidify the foundation of technologies for nuclear development and utilization in Asia by promoting human resources development in Asian countries. In the Project are two kinds of activity; In-workshop activity and Outside-of-workshop activity. The 3rd Workshop on Human Resources Development in the Nuclear Field was held on October 29 to November 1, at the Nuclear Training Center of KAERI. Participating countries were China, Indonesia, Republic of Korea, Japan, Malaysia, the Philippines, Thailand, and Vietnam. The secretariat for the Human Resources Development Project is provided by the Nuclear Training Center of the Korea Atomic Energy Research Institute and the Nuclear Technology and Education Center of the Japan Atomic Energy Research Institute. This report consists of presentation papers and materials at the Workshop as In-Workshop Activity, a document of project review on Human Resources Development for the fourth Coordinators Meeting of FNCA at Tokyo on March, 2002, a letter of proposal from the Project Leader of Japan to the project leaders of the participating countries, and training materials of participating countries as Outside-Workshop Activity. (author)

  17. The Consolidated Human Activity Database — Master Version (CHAD-Master) Technical Memorandum

    Science.gov (United States)

    This technical memorandum contains information about the Consolidated Human Activity Database -- Master version, including CHAD contents, inventory of variables: Questionnaire files and Event files, CHAD codes, and references.

  18. Transgenic chickens expressing human urokinase-type plasminogen activator.

    Science.gov (United States)

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P huPA protein in eggs increased from 7.82 IU/egg in the G0 generation to 17.02 IU/egg in the G1 generation. However, huPA-expressing embryos had reduced survival and hatchability at d 18 and 21 of incubation, respectively, and the blood clotting time was significantly higher in transgenic chickens than their nontransgenic counterparts (P huPA transgenic chickens could be successfully produced by the retroviral vector system. Transgenic chickens, expressing the huPA under the control of a ubiquitous promoter, may not only be used as a bioreactor for pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  19. Environmental contaminants activate human and polar bear (Ursus maritimus) pregnane X receptors (PXR, NR1I2) differently

    Energy Technology Data Exchange (ETDEWEB)

    Lille-Langøy, Roger, E-mail: Roger.lille-langoy@bio.uib.no [University of Bergen, Department of Biology, P.O. Box 7803, N-5020 Bergen (Norway); Goldstone, Jared V. [Woods Hole Oceanographic Institution, 266 Woods Hole Road, 02543-1050 Woods Hole, MA (United States); Rusten, Marte [University of Bergen, Department of Molecular Biology, P.O. Box 7803, N-5020 Bergen (Norway); Milnes, Matthew R. [Mars Hill University, 100 Athletic Street, Box 6671, Mars Hill, 28754 NC (United States); Male, Rune [University of Bergen, Department of Molecular Biology, P.O. Box 7803, N-5020 Bergen (Norway); Stegeman, John J. [Woods Hole Oceanographic Institution, 266 Woods Hole Road, 02543-1050 Woods Hole, MA (United States); Blumberg, Bruce [University of California, Irvine, 92697 CA (United States); Goksøyr, Anders [University of Bergen, Department of Biology, P.O. Box 7803, N-5020 Bergen (Norway)

    2015-04-01

    Background: Many persistent organic pollutants (POPs) accumulate readily in polar bears because of their position as apex predators in Arctic food webs. The pregnane X receptor (PXR, formally NR1I2, here proposed to be named promiscuous xenobiotic receptor) is a xenobiotic sensor that is directly involved in metabolizing pathways of a wide range of environmental contaminants. Objectives: In the present study, we comparably assess the ability of 51 selected pharmaceuticals, pesticides and emerging contaminants to activate PXRs from polar bears and humans using an in vitro luciferase reporter gene assay. Results: We found that polar bear PXR is activated by a wide range of our test compounds (68%) but has a slightly more narrow ligand specificity than human PXR that was activated by 86% of the 51 test compounds. The majority of the agonists identified (70%) produces a stronger induction of the reporter gene via human PXR than via polar bear PXR, however with some notable and environmentally relevant exceptions. Conclusions: Due to the observed differences in activation of polar bear and human PXRs, exposure of each species to environmental agents is likely to induce biotransformation differently in the two species. Bioinformatics analyses and structural modeling studies suggest that amino acids that are not part of the ligand-binding domain and do not interact with the ligand can modulate receptor activation. - Highlights: • Comparative study of ligand activation of human and polar bear PXRs. • Polar bear PXR is a promiscuous ligand-activated nuclear receptor but less so than human PXR. • Environmental contaminants activate human and polar bear PXRs differently. • Expression and ligand promiscuity indicate that PXR is a xenosensor in polar bears.

  20. Environmental contaminants activate human and polar bear (Ursus maritimus) pregnane X receptors (PXR, NR1I2) differently

    International Nuclear Information System (INIS)

    Lille-Langøy, Roger; Goldstone, Jared V.; Rusten, Marte; Milnes, Matthew R.; Male, Rune; Stegeman, John J.; Blumberg, Bruce; Goksøyr, Anders

    2015-01-01

    Background: Many persistent organic pollutants (POPs) accumulate readily in polar bears because of their position as apex predators in Arctic food webs. The pregnane X receptor (PXR, formally NR1I2, here proposed to be named promiscuous xenobiotic receptor) is a xenobiotic sensor that is directly involved in metabolizing pathways of a wide range of environmental contaminants. Objectives: In the present study, we comparably assess the ability of 51 selected pharmaceuticals, pesticides and emerging contaminants to activate PXRs from polar bears and humans using an in vitro luciferase reporter gene assay. Results: We found that polar bear PXR is activated by a wide range of our test compounds (68%) but has a slightly more narrow ligand specificity than human PXR that was activated by 86% of the 51 test compounds. The majority of the agonists identified (70%) produces a stronger induction of the reporter gene via human PXR than via polar bear PXR, however with some notable and environmentally relevant exceptions. Conclusions: Due to the observed differences in activation of polar bear and human PXRs, exposure of each species to environmental agents is likely to induce biotransformation differently in the two species. Bioinformatics analyses and structural modeling studies suggest that amino acids that are not part of the ligand-binding domain and do not interact with the ligand can modulate receptor activation. - Highlights: • Comparative study of ligand activation of human and polar bear PXRs. • Polar bear PXR is a promiscuous ligand-activated nuclear receptor but less so than human PXR. • Environmental contaminants activate human and polar bear PXRs differently. • Expression and ligand promiscuity indicate that PXR is a xenosensor in polar bears

  1. Activation of protein kinase A and exchange protein directly activated by cAMP promotes adipocyte differentiation of human mesenchymal stem cells

    DEFF Research Database (Denmark)

    Jia, Bingbing; Madsen, Lise; Petersen, Rasmus Koefoed

    2012-01-01

    ) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence......Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA...... results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells....

  2. Radioimmunological activity of 22K variant of human growth hormone

    International Nuclear Information System (INIS)

    Camillo, M.A.P.; Ribela, M.T.C.P.; Rogero, J.R.

    1986-01-01

    From a preparation of human growth hormone its integral variant (hGH-22K) was isolated by isoelectric focusing, having a pI of 5,20 and relative mobility (Rm) of 0,621 in the polyacrylamide gel electrophoresis. Several experiments for the characterization of the isolated variant were carried out. The immunological properties was tested by radioimmunoassay (RIE), in which the activity of the isolated variant and the activity of the total preparation were compared. The dose response-curves obtained by RIE were found to be considered parallels (p [pt

  3. Listening to humans walking together activates the social brain circuitry.

    Science.gov (United States)

    Saarela, Miiamaaria V; Hari, Riitta

    2008-01-01

    Human footsteps carry a vast amount of social information, which is often unconsciously noted. Using functional magnetic resonance imaging, we analyzed brain networks activated by footstep sounds of one or two persons walking. Listening to two persons walking together activated brain areas previously associated with affective states and social interaction, such as the subcallosal gyrus bilaterally, the right temporal pole, and the right amygdala. These areas seem to be involved in the analysis of persons' identity and complex social stimuli on the basis of auditory cues. Single footsteps activated only the biological motion area in the posterior STS region. Thus, hearing two persons walking together involved a more widespread brain network than did hearing footsteps from a single person.

  4. Impact Of Human Activities On Ecosystem In Rivers State, Nigeria ...

    African Journals Online (AJOL)

    This study was to assess the percent sample population size of people involved in selected human economic activities and the impact on ecosystem in Rivers State. The data for this study was obtained from a sample size of 1000 respondents who were purposively selected from the study area. Purposive sample was used ...

  5. Antitumor activity of vorinostat-incorporated nanoparticles against human cholangiocarcinoma cells

    OpenAIRE

    Kwak, Tae Won; Kim, Do Hyung; Jeong, Young-Il; Kang, Dae Hwan

    2015-01-01

    Background The aim of this study is to evaluate the anticancer activity of vorinostat-incorporated nanoparticles (vorinostat-NPs) against HuCC-T1 human cholangiocarcinoma cells. Vorinostat-NPs were fabricated by a nanoprecipitation method using poly(dl-lactide-co-glycolide)/poly(ethylene glycol) copolymer. Results Vorinostat-NPs exhibited spherical shapes with sizes

  6. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    Science.gov (United States)

    Self, Matthew W; Peters, Judith C; Possel, Jessy K; Reithler, Joel; Goebel, Rainer; Ris, Peterjan; Jeurissen, Danique; Reddy, Leila; Claus, Steven; Baayen, Johannes C; Roelfsema, Pieter R

    2016-03-01

    Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

  7. The Effects of Context and Attention on Spiking Activity in Human Early Visual Cortex.

    Directory of Open Access Journals (Sweden)

    Matthew W Self

    2016-03-01

    Full Text Available Here we report the first quantitative analysis of spiking activity in human early visual cortex. We recorded multi-unit activity from two electrodes in area V2/V3 of a human patient implanted with depth electrodes as part of her treatment for epilepsy. We observed well-localized multi-unit receptive fields with tunings for contrast, orientation, spatial frequency, and size, similar to those reported in the macaque. We also observed pronounced gamma oscillations in the local-field potential that could be used to estimate the underlying spiking response properties. Spiking responses were modulated by visual context and attention. We observed orientation-tuned surround suppression: responses were suppressed by image regions with a uniform orientation and enhanced by orientation contrast. Additionally, responses were enhanced on regions that perceptually segregated from the background, indicating that neurons in the human visual cortex are sensitive to figure-ground structure. Spiking responses were also modulated by object-based attention. When the patient mentally traced a curve through the neurons' receptive fields, the accompanying shift of attention enhanced neuronal activity. These results demonstrate that the tuning properties of cells in the human early visual cortex are similar to those in the macaque and that responses can be modulated by both contextual factors and behavioral relevance. Our results, therefore, imply that the macaque visual system is an excellent model for the human visual cortex.

  8. Gamma-glutamylcyclotransferase promotes the growth of human glioma cells by activating Notch-Akt signaling

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Shang-Hang; Yu, Ning; Liu, Xi-Yao; Tan, Guo-Wei; Wang, Zhan-Xiang, E-mail: md_wzx7189@163.com

    2016-03-18

    Glioma as an aggressive type tumor is rapidly growing and has become one of the leading cause of cancer-related death worldwide. γ-Glutamylcyclotransferase (GGCT) has been shown as a diagnostic marker in various cancers. To reveal whether there is a correlation between GGCT and human glioma, GGCT expression in human glioma tissues and cell lines was first determined. We found that GGCT expression was up-regulated in human glioma tissues and cell lines. Further, we demonstrate that GGCT knockdown inhibits glioma cell T98G and U251 proliferation and colony formation, whereas GGCT overexpression leads to oppose effects. GGCT overexpression promotes the expression of Notch receptors and activates Akt signaling in glioma cells, and Notch-Akt signaling is activated in glioma tissues with high expression of GGCT. Finally, we show that inhibition of Notch-Akt signaling with Notch inhibitor MK-0752 blocks the effects of GGCT on glioma proliferation and colony formation. In conclusion, GGCT plays a critical role in glioma cell proliferation and may be a potential cancer therapeutic target. - Highlights: • GGCT expression is up-regulated in human glioma tissues and cell lines. • GGCT promotes glioma cell growth and colony formation. • GGCT promotes the activation of Notch-Akt signaling in glioma cells and tissues. • Notch inhibition blocks the role of GGCT in human glioma cells.

  9. Human factors activities in teleoperator development at the Oak Ridge National Laboratory

    International Nuclear Information System (INIS)

    Draper, J.V.; Herndon, J.N.

    1986-01-01

    The Consolidated Fuel Reprocessing Program (CFRP) at the Oak Ridge National Laboratory is developing advanced teleoperator systems for maintenance of future nuclear reprocessing facilities. Remote maintenance systems developed by the CFRP emphasize man-in-the-loop teleoperation. Consequently, human factors issues which affect teleoperator performance must be addressed. This papers surveys research and development activities carried out by the human factors group within the Remote Control Engineering Task of the CFRP

  10. Basic Characteristics of Human Erroneous Actions during Test and Maintenance Activities Leading to Unplanned Reactor Trips

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun

    2010-01-01

    Test and maintenance (T and M) activities of nuclear power plants are essential for sustaining the safety of a power plant and maintaining the reliability of plant systems and components. However, the potential of human errors during T and M activities has also the potential to induce unplanned reactor trips or power derate or making safety-related systems unavailable. According to the major incident/accident reports of nuclear power plants in Korea, contribution of human errors takes up about 20% of the total events. The previous study presents that most of human-related unplanned reactor trip events during normal power operation are associated with T and M activities (63%), which are comprised of plant maintenance activities such as a 'periodic preventive maintenance (PPM)', a 'planned maintenance (PM)' and a 'corrective maintenance (CM)'. This means that T and M activities should be a major subject for reducing the frequency of human-related unplanned reactor trips. This paper aims to introduce basic characteristics of human erroneous actions involved in the test and maintenance-induced unplanned reactor trip events that have occurred between 1986 and 2006 in Korean nuclear power plants. The basic characteristics are described by dividing human erroneous actions into planning-based errors and execution-based errors. For the events associated with planning failures, they are, firstly, classified according to existence of the work procedure and then described for what aspects of the procedure or work plan have deficiency or problem. On the other hand, for the events associated with execution failures, they are described from the aspect of external error modes

  11. Anticancer activities of bovine and human lactoferricin-derived peptides.

    Science.gov (United States)

    Arias, Mauricio; Hilchie, Ashley L; Haney, Evan F; Bolscher, Jan G M; Hyndman, M Eric; Hancock, Robert E W; Vogel, Hans J

    2017-02-01

    Lactoferrin (LF) is a mammalian host defense glycoprotein with diverse biological activities. Peptides derived from the cationic region of LF possess cytotoxic activity against cancer cells in vitro and in vivo. Bovine lactoferricin (LFcinB), a peptide derived from bovine LF (bLF), exhibits broad-spectrum anticancer activity, while a similar peptide derived from human LF (hLF) is not as active. In this work, several peptides derived from the N-terminal regions of bLF and hLF were studied for their anticancer activities against leukemia and breast-cancer cells, as well as normal peripheral blood mononuclear cells. The cyclized LFcinB-CLICK peptide, which possesses a stable triazole linkage, showed improved anticancer activity, while short peptides hLF11 and bLF10 were not cytotoxic to cancer cells. Interestingly, hLF11 can act as a cell-penetrating peptide; when combined with the antimicrobial core sequence of LFcinB (RRWQWR) through either a Pro or Gly-Gly linker, toxicity to Jurkat cells increased. Together, our work extends the library of LF-derived peptides tested for anticancer activity, and identified new chimeric peptides with high cytotoxicity towards cancerous cells. Additionally, these results support the notion that short cell-penetrating peptides and antimicrobial peptides can be combined to create new adducts with increased potency.

  12. Cytidine triphosphate synthase activity and mRNA expression in normal human blood cells

    NARCIS (Netherlands)

    Verschuur, A. C.; van Gennip, A. H.; Muller, E. J.; Voûte, P. A.; Vreken, P.; van Kuilenburg, A. B.

    1999-01-01

    Cytidine triphosphate (CTP) synthase is one of the key enzymes in pyrimidine nucleotide anabolic pathways. The activity of this enzyme is elevated in various malignancies including acute lymphocytic leukemia (ALL). In this study we investigated the activity of CTP synthase in various human blood

  13. NDVI-Based analysis on the influence of human activities on vegetation variation on Hainan Island

    Science.gov (United States)

    Luo, Hongxia; Dai, Shengpei; Xie, Zhenghui; Fang, Jihua

    2018-02-01

    Using the Moderate Resolution Imaging Spectroradiometer-normalized difference vegetation index (NDVI) dataset, we analyzed the predicted NDVI values variation and the influence of human activities on vegetation on Hainan Island during 2001-2015. We investigated the roles of human activities in vegetation variation, particularly from 2002 when implemented the Grain-for-Greenprogram on Hainan Island. The trend analysis, linear regression model and residual analysis were used to analyze the data. The results of the study showed that (1) The predicted vegetation on Hainan Island showed an general upward trend with a linear growth rate of 0.0025/10y (phuman activities. (3) In general, human activities had played a positive role in the vegetation increase on Hainan Island, and the residual NDVI trend of this region showed positive outcomes for vegetation variation after implementing ecological engineering projects. However, it indicated a growing risk of vegetation degradation in the coastal region of Hainan Island as a result of rapid urbanization, land reclamation.

  14. Large-scale production and properties of human plasma-derived activated Factor VII concentrate.

    Science.gov (United States)

    Tomokiyo, K; Yano, H; Imamura, M; Nakano, Y; Nakagaki, T; Ogata, Y; Terano, T; Miyamoto, S; Funatsu, A

    2003-01-01

    An activated Factor VII (FVIIa) concentrate, prepared from human plasma on a large scale, has to date not been available for clinical use for haemophiliacs with antibodies against FVIII and FIX. In the present study, we attempted to establish a large-scale manufacturing process to obtain plasma-derived FVIIa concentrate with high recovery and safety, and to characterize its biochemical and biological properties. FVII was purified from human cryoprecipitate-poor plasma, by a combination of anion exchange and immunoaffinity chromatography, using Ca2+-dependent anti-FVII monoclonal antibody. To activate FVII, a FVII preparation that was nanofiltered using a Bemberg Microporous Membrane-15 nm was partially converted to FVIIa by autoactivation on an anion-exchange resin. The residual FVII in the FVII and FVIIa mixture was completely activated by further incubating the mixture in the presence of Ca2+ for 18 h at 10 degrees C, without any additional activators. For preparation of the FVIIa concentrate, after dialysis of FVIIa against 20 mm citrate, pH 6.9, containing 13 mm glycine and 240 mm NaCl, the FVIIa preparation was supplemented with 2.5% human albumin (which was first pasteurized at 60 degrees C for 10 h) and lyophilized in vials. To inactivate viruses contaminating the FVIIa concentrate, the lyophilized product was further heated at 65 degrees C for 96 h in a water bath. Total recovery of FVII from 15 000 l of plasma was approximately 40%, and the FVII preparation was fully converted to FVIIa with trace amounts of degraded products (FVIIabeta and FVIIagamma). The specific activity of the FVIIa was approximately 40 U/ micro g. Furthermore, virus-spiking tests demonstrated that immunoaffinity chromatography, nanofiltration and dry-heating effectively removed and inactivated the spiked viruses in the FVIIa. These results indicated that the FVIIa concentrate had both high specific activity and safety. We established a large-scale manufacturing process of human plasma

  15. Visual image reconstruction from human brain activity: A modular decoding approach

    International Nuclear Information System (INIS)

    Miyawaki, Yoichi; Uchida, Hajime; Yamashita, Okito; Sato, Masa-aki; Kamitani, Yukiyasu; Morito, Yusuke; Tanabe, Hiroki C; Sadato, Norihiro

    2009-01-01

    Brain activity represents our perceptual experience. But the potential for reading out perceptual contents from human brain activity has not been fully explored. In this study, we demonstrate constraint-free reconstruction of visual images perceived by a subject, from the brain activity pattern. We reconstructed visual images by combining local image bases with multiple scales, whose contrasts were independently decoded from fMRI activity by automatically selecting relevant voxels and exploiting their correlated patterns. Binary-contrast, 10 x 10-patch images (2 100 possible states), were accurately reconstructed without any image prior by measuring brain activity only for several hundred random images. The results suggest that our approach provides an effective means to read out complex perceptual states from brain activity while discovering information representation in multi-voxel patterns.

  16. Combined roles of human IgG subclass, alternative complement pathway activation, and epitope density in the bactericidal activity of antibodies to meningococcal factor h binding protein.

    Science.gov (United States)

    Giuntini, Serena; Reason, Donald C; Granoff, Dan M

    2012-01-01

    Meningococcal vaccines containing factor H binding protein (fHbp) are in clinical development. fHbp binds human fH, which enables the meningococcus to resist complement-mediated bacteriolysis. Previously, we found that chimeric human IgG1 mouse anti-fHbp monoclonal antibodies (MAbs) had human complement-mediated bactericidal activity only if the MAb inhibited fH binding. Since IgG subclasses differ in their ability to activate complement, we investigated the role of human IgG subclasses on antibody functional activity. We constructed chimeric MAbs in which three different murine fHbp-specific binding domains were each paired with human IgG1, IgG2, or IgG3. Against a wild-type group B isolate, all three IgG3 MAbs, irrespective of their ability to inhibit fH binding, had bactericidal activity that was >5-fold higher than the respective IgG1 MAbs, while the IgG2 MAbs had the least activity. Against a mutant with increased fHbp expression, the anti-fHbp MAbs elicited greater C4b deposition (classical pathway) and greater bactericidal activity than against the wild-type strain, and the IgG1 MAbs had similar or greater activity than the respective IgG3 MAbs. The bactericidal activity against both wild-type and mutant strains also was dependent, in part, on activation of the alternative complement pathway. Thus, at lower epitope density in the wild-type strain, the IgG3 anti-fHbp MAbs had the greatest bactericidal activity. At a higher epitope density in the mutant, the IgG1 MAbs had similar or greater bactericidal activity than the IgG3 MAbs, and the activity was less dependent on the inhibition of fH binding than at a lower epitope density.

  17. Biological Activity Alterations of Human Amniotic Membrane Pre and Post Irradiation Tissue Banking.

    Science.gov (United States)

    Nemr, Waleed; Bashandy, A S; Araby, Eman; Khamiss, O

    Innate immunity of Human Amniotic Membrane (HAM) and its highly active secretome that rich with various types of growth factors and anti-inflammatory substances proposed it as a promising material for many medical studies and applications. This study evaluate the biological activity of cultivated HAM pre and post tissue banking process in which freeze-dried HAM was sterilized by 25 KGray (kGy) dose of γ radiation. The HAM's antimicrobial activity, viability, growth of isolated human amniotic epithelial cells (HAECs), hematopoietic stimulation of co-cultivated murine bone marrow cells (mammalian model), scaffold efficiency for fish brain building up (non-mammalian model) and self re-epithelialization after trypsin denuding treatment were examined as supposed biological activity features. Native HAM revealed viability indications and was active to kill all tested microorganisms; 6 bacterial species (3 Gram-positive and 3 Gram-negative) and Candida albicans as a pathogenic fungus. Also, HAM activity promoted colony formation of murine hematopoietic cells, Tilapia nilotica brain fragment building-up and self re-epithelialization after trypsin treatment. In contrary, radiation-based tissue banking of HAM caused HAM cellular death and consequently lacked almost all of examined biological activity features. Viable HAM was featured with biological activity than fixed HAM prepared by irradiation tissue banking.

  18. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated disruption of the CD40 ligand-induced activation of primary human B cells

    International Nuclear Information System (INIS)

    Lu Haitian; Crawford, Robert B.; Kaplan, Barbara L.F.; Kaminski, Norbert E.

    2011-01-01

    Suppression of the primary antibody response is particularly sensitive to suppression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice; however, surprisingly little is known concerning the effects of TCDD on humoral immunity or B cell function in humans. Results from a limited number of previous studies, primarily employing in vitro activation models, suggested that human B cell effector function is suppressed by TCDD. The present study sought to extend these findings by investigating, in primary human B cells, the effects of TCDD on several critical stages leading to antibody secretion including activation and plasmacytic differentiation using an in vitro CD40 ligand activation model. These studies revealed important differences in the response of human and mouse B cells to TCDD, the most striking being altered expression of plasmacytic differentiation regulators, B lymphocyte-induced maturation protein 1 and paired box protein 5, in mouse but not human B cells. The activation of human B cells was profoundly impaired by TCDD, as evidenced by decreased expression of activation markers CD80, CD86, and CD69. The impaired activation correlated with decreased cell viability, which prevented the progression of human B cells toward plasmacytic differentiation. TCDD treatment also attenuated the early activation of mitogen-activated protein kinases (MAPK) and Akt signaling in human B cells. Collectively, the present study provided experimental evidence for novel mechanisms by which TCDD impairs the effector function of primary human B cells. - Highlights: → In this study primary human and mouse B cell toxicity to TCDD was compared. → TCDD altered the expression of Blimp-1 and Pax5 in mouse but not human B cells. → TCDD markedly suppressed human B cell activation as characterized by CD80, CD86 and CD69 expression. → TCDD inhibited ERK, p38, and Akt phosphorylation in human B cells.

  19. Resonance of about-weekly human heart rate rhythm with solar activity change.

    Science.gov (United States)

    Cornelissen, G; Halberg, F; Wendt, H W; Bingham, C; Sothern, R B; Haus, E; Kleitman, E; Kleitman, N; Revilla, M A; Revilla, M; Breus, T K; Pimenov, K; Grigoriev, A E; Mitish, M D; Yatsyk, G V; Syutkina, E V

    1996-12-01

    In several human adults, certain solar activity rhythms may influence an about 7-day rhythm in heart rate. When no about-weekly feature was found in the rate of change in sunspot area, a measure of solar activity, the double amplitude of a circadian heart rate rhythm, approximated by the fit of a 7-day cosine curve, was lower, as was heart rate corresponds to about-weekly features in solar activity and/or relates to a sunspot cycle.

  20. [Effect of losartan on human platelet activation by thromboxane A2].

    Science.gov (United States)

    Guerra, J I; Montón, M; Rodríguez-Feo, J A; Farré, J; Jiménez, A M; Núñez, A; Gómez, J; Rico, L; Marcos, P; Castilla, C; Sánchez De Miguel, L; Casado, S; López-Farré, A

    2000-04-01

    Previous studies have demonstrated that losartan, an AT-1 receptor antagonist of angiotensin II (Ang II) could block the receptor of thromboxane A2 (TXA2) in the vascular wall. The aim of the present study was to assess the effect of losartan on human platelet activation. Platelets were obtained from 15 healthy men between the age 26 and 40. Platelet activation was measured by changes in the light transmission of platelet-rich plasma stimulated by a synthetic TXA2 analogue, U46619 (5 x 10(-6) mol/l). The U46619-stimulated platelet aggregation was significantly inhibited by losartan in a dose-response manner. Only a high dose of EXP 3174 (5 10-5 mol/l), the in vivo active metabolite of losartan, was able to attenuate U46619-induced platelet activation. Captopril, an angiotensin I-converting inhibitor failed to modify U46619-induced platelet aggregation. Despite the platelets expressing AT-1 type receptors, of Ang II exogenous Ang II did not modify platelet aggregation induced by U46619. The binding of U46619 to platelets was competitively inhibited by losartan in dose-dependent manner. However, only a high dose of EXP 3174 reduced the binding of U46619. Captopril failed to modify the binding of U46619 to platelets. Losartan decreased platelet aggregation by a TXA2-dependent mechanism. EXP 3174 showed a lesser potency than losartan to reduce TXA2-platelet activation. Captopril and exogenous angiotensin II had no effect on human platelet activation. These results suggest that losartan reduced TXA2-dependent platelet activation independently of the blockade of AT-1 receptors.

  1. Mechanism of anti-HIV activity of succinylated human serum albumin

    NARCIS (Netherlands)

    Kuipers, ME; Berg, HVD; Swart, PJ; Laman, Jon; Meijer, DKF; Kopelman, MHGM; Huisman, H

    1999-01-01

    In the present study, we described the interaction of succinylated human serum albumin (Suc-HSA), a negatively charged anti-HIV-1 active protein, with HIV-1 gp120 and in detail with the third variable domain of gp120 (V3 loop). To this end, different assay formats were tested in which gp120- and

  2. Anti-Human Rhinoviral Activity of Polybromocatechol Compounds Isolated from the Rhodophyta, Neorhodomela aculeata

    Directory of Open Access Journals (Sweden)

    Hui-Seong Kim

    2012-10-01

    Full Text Available An extract of the red alga, Neorhodomela aculeata, exhibited antiviral activity against human rhinoviruses. Bioassay-guided purification was performed to yield six compounds, which were subsequently identified as lanosol (1 and five polybromocatechols (2–6 by spectroscopic methods, including 1D and 2D NMR and mass spectrometric analyses. Structurally, all of these compounds, except compound 5, contain one or two 2,3-dibromo-4,5-dihydroxyphenyl moieties. In a biological activity assay, compound 1 was found to possess antiviral activity with a 50% inhibitory concentration (IC50 of 2.50 μg/mL against HRV2. Compound 3 showed anti-HRV2 activity, with an IC50 of 7.11 μg/mL, and anti-HRV3 activity, with an IC50 of 4.69 μg/mL, without demonstrable cytotoxicity at a concentration of 20 μg/mL. Collectively, the results suggest that compounds 1 and 3 are candidates for novel therapeutics against two different groups of human rhinovirus.

  3. Measurement of gross alpha and gross beta activity concentrations in human tooth

    International Nuclear Information System (INIS)

    Soeguet, Omer; Aydin, Mehmet Fatih; Kuecuekoender, Erdal; Zorer, Ozlem Selcuk; Dogru, Mahmut

    2010-01-01

    The gross alpha and gross beta activity concentrations were measured in human tooth taken from 3 to 6 age-groups to 40 and over ones. Accumulated teeth samples are investigated in two groups as under and above 18 years. The gross alpha and beta radioactivity of human tooth samples was measured by using a gas-flow proportional counter (PIC-MPC 9604-α/β counter). In tooth samples, for female age-groups, the obtained results show that the mean gross alpha and gross beta activity concentrations varied between 0.534-0.203 and 0.010-0.453 Bq g -1 and the same concentrations for male age-groups varied between 0.009-1.168 and 0.071-0.204 Bq g -1 , respectively.

  4. Modelling of the Human Knee Joint Supported by Active Orthosis

    Science.gov (United States)

    Musalimov, V.; Monahov, Y.; Tamre, M.; Rõbak, D.; Sivitski, A.; Aryassov, G.; Penkov, I.

    2018-02-01

    The article discusses motion of a healthy knee joint in the sagittal plane and motion of an injured knee joint supported by an active orthosis. A kinematic scheme of a mechanism for the simulation of a knee joint motion is developed and motion of healthy and injured knee joints are modelled in Matlab. Angles between links, which simulate the femur and tibia are controlled by Simulink block of Model predictive control (MPC). The results of simulation have been compared with several samples of real motion of the human knee joint obtained from motion capture systems. On the basis of these analyses and also of the analysis of the forces in human lower limbs created at motion, an active smart orthosis is developed. The orthosis design was optimized to achieve an energy saving system with sufficient anatomy, necessary reliability, easy exploitation and low cost. With the orthosis it is possible to unload the knee joint, and also partially or fully compensate muscle forces required for the bending of the lower limb.

  5. Modelling of the Human Knee Joint Supported by Active Orthosis

    Directory of Open Access Journals (Sweden)

    Musalimov V.

    2018-02-01

    Full Text Available The article discusses motion of a healthy knee joint in the sagittal plane and motion of an injured knee joint supported by an active orthosis. A kinematic scheme of a mechanism for the simulation of a knee joint motion is developed and motion of healthy and injured knee joints are modelled in Matlab. Angles between links, which simulate the femur and tibia are controlled by Simulink block of Model predictive control (MPC. The results of simulation have been compared with several samples of real motion of the human knee joint obtained from motion capture systems. On the basis of these analyses and also of the analysis of the forces in human lower limbs created at motion, an active smart orthosis is developed. The orthosis design was optimized to achieve an energy saving system with sufficient anatomy, necessary reliability, easy exploitation and low cost. With the orthosis it is possible to unload the knee joint, and also partially or fully compensate muscle forces required for the bending of the lower limb.

  6. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

    Science.gov (United States)

    Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

    2016-05-23

    The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  7. Aqueous extract of Arbutus unedo inhibits STAT1 activation in human breast cancer cell line MDA-MB-231 and human fibroblasts through SHP2 activation.

    Science.gov (United States)

    Mariotto, S; Ciampa, A R; de Prati, A Carcereri; Darra, E; Vincenzi, S; Sega, M; Cavalieri, E; Shoji, K; Suzuki, H

    2008-05-01

    Arbutus unedo L. has been for a long time employed in traditional and popular medicine as an astringent, diuretic, urinary anti-septic, and more recently, in the therapy of hypertension and diabetes. Signal transducer and activator of transcription 1 (STAT1) is a fascinating and complex protein with multiple yet contrasting transcriptional functions. Although activation of this nuclear factor is finely regulated in order to control the entire inflammatory process, its hyper-activation or time-spatially erroneous activation may lead to exacerbation of inflammation. The modulation of this nuclear factor, therefore, has recently been considered as a new strategy in the treatment of inflammatory diseases. In this study, we present data showing that the aqueous extract of Arbutus unedo's leaves exerts inhibitory action on interferon-gamma (IFN-gamma) elicited activation of STAT1, both in human breast cancer cell line MDA-MB-231 and in human fibroblasts. This down-regulation of STAT1 is shown to result from a reduced tyrosine phosphorylation of STAT1 protein. Evidence is also presented indicating that the inhibitory effect of this extract may be mediated through enhancement of tyrosine phosphorylation of SHP2 tyrosine phosphatase. The modulation of this nuclear factor turns out into the regulation of the expression of a number of genes involved in the inflammatory response such as inducible nitric oxide synthase (iNOS) and intercellular adhesion molecule-1 (ICAM-1). Taken together, our results suggest that the employment of the Arbutus unedo aqueous extract is promising, at least, as an auxiliary anti-inflammatory treatment of diseases in which STAT1 plays a critical role.

  8. Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

    International Nuclear Information System (INIS)

    Samoszuk, Michael; Tan, Jenny; Chorn, Guillaume

    2005-01-01

    Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

  9. Analysing the influence of human activity on runoff in the Weihe River basin

    Directory of Open Access Journals (Sweden)

    C. Shen

    2015-05-01

    Full Text Available Changing runoff patterns can have profound effects on the economic development of river basins. To assess the impact of human activity on runoff in the Weihe River basin, principal component analysis (PCA was applied to a set of 17 widely used indicators of economic development to construct general combined indicators reflecting different types of human activity. Grey relational analysis suggested that the combined indicator associated with agricultural activity was most likely to have influenced the changes in runoff observed within the river basin during 1994–2011. Curve fitting was then performed to characterize the relationship between the general agricultural indicator and the measured runoff, revealing a reasonably high correlation (R2 = 0.393 and an exponential relationship. Finally, a sensitivity analysis was performed to assess the influence of the 17 individual indicators on the measured runoff, confirming that indicators associated with agricultural activity had profound effects whereas those associated with urbanization had relatively little impact.

  10. Human duodenal motor activity in response to acid and different nutrients

    NARCIS (Netherlands)

    Schwartz, M. P.; Samsom, M.; Smout, A. J.

    2001-01-01

    Duodenal motor activity in response to intraduodenal infusion of small volumes of acid and nutrients of different chemical composition was studied in 10 healthy humans, using a water-perfused catheter incorporating 20 antropyloroduodenal sideholes. Saline and dextrose did not affect motility. Acid

  11. Enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity: selective radioassay, properties, and regional distribution in human brain

    International Nuclear Information System (INIS)

    Llorens, C.; Malfroy, B.; Schwartz, J.C.; Gacel, G.; Roques, B.P.; Roy, J.; Morgat, J.L.; Javoy-Agid, F.; Agid, Y.

    1982-01-01

    The compound [ 3 H-Tyr 1 ,D-Ala 2 ,Leu-OH 5 ]enkephalin has been synthesised as a potentially selective substrate for enkephalin dipeptidyl carboxypeptidase (enkephalinase) activity in brain. Incubations in the presence of homogenates and particulate fractions from rodent and human brain result in the formation of [ 3 H]Tyr-D-Ala-Gly, which can be conveniently isolated by polystyrene bead column chromatography. The enzyme activity responsible for the hydrolysis of the Gly 3 -Phe 4 amide bond of this substrate displays close resemblance to that hydrolysing the natural enkephalins at the same level. In addition, enkephalinase activity characterised in postmortem human brain is closely similar to that in rodent brain, with regard to optimal pH and apparent affinities of various substrates and inhibitors, including the potent compound thiorphan. Enkephalinase activity is distributed in a highly heterogeneous fashion among regions of human brain, the highest levels being found in globus pallidus and pars reticulata of the substantia nigra. This distribution is poorly correlated with that of opiate receptor binding sites but displays some resemblance to that of reported Met 5 -enkephalin levels. (author)

  12. Human CD141+ Dendritic Cell and CD1c+ Dendritic Cell Undergo Concordant Early Genetic Programming after Activation in Humanized Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Yoshihito Minoda

    2017-10-01

    Full Text Available Human immune cell subsets develop in immunodeficient mice following reconstitution with human CD34+ hematopoietic stem cells. These “humanized” mice are useful models to study human immunology and human-tropic infections, autoimmunity, and cancer. However, some human immune cell subsets are unable to fully develop or acquire full functional capacity due to a lack of cross-reactivity of many growth factors and cytokines between species. Conventional dendritic cells (cDCs in mice are categorized into cDC1, which mediate T helper (Th1 and CD8+ T cell responses, and cDC2, which mediate Th2 and Th17 responses. The likely human equivalents are CD141+ DC and CD1c+ DC subsets for mouse cDC1 and cDC2, respectively, but the extent of any interspecies differences is poorly characterized. Here, we exploit the fact that human CD141+ DC and CD1c+ DC develop in humanized mice, to further explore their equivalency in vivo. Global transcriptome analysis of CD141+ DC and CD1c+ DC isolated from humanized mice demonstrated that they closely resemble those in human blood. Activation of DC subsets in vivo, with the TLR3 ligand poly I:C, and the TLR7/8 ligand R848 revealed that a core panel of genes consistent with DC maturation status were upregulated by both subsets. R848 specifically upregulated genes associated with Th17 responses by CD1c+ DC, while poly I:C upregulated IFN-λ genes specifically by CD141+ DC. MYCL expression, known to be essential for CD8+ T cell priming by mouse DC, was specifically induced in CD141+ DC after activation. Concomitantly, CD141+ DC were superior to CD1c+ DC in their ability to prime naïve antigen-specific CD8+ T cells. Thus, CD141+ DC and CD1c+ DC share a similar activation profiles in vivo but also have induce unique signatures that support specialized roles in CD8+ T cell priming and Th17 responses, respectively. In combination, these data demonstrate that humanized mice provide an attractive and tractable model to study

  13. Stress hormone levels in a freshwater turtle from sites differing in human activity.

    Science.gov (United States)

    Polich, Rebecca L

    2016-01-01

    Glucocorticoids, such as corticosterone (CORT), commonly serve as a measure of stress levels in vertebrate populations. These hormones have been implicated in regulation of feeding behaviour, locomotor activity, body mass, lipid metabolism and other crucial behaviours and physiological processes. Thus, understanding how glucocorticoids fluctuate seasonally and in response to specific stressors can yield insight into organismal health and the overall health of populations. I compared circulating CORT concentrations between two similar populations of painted turtle, Chrysemys picta, which differed primarily in the level of exposure to human recreational activities. I measured basal CORT concentrations as well as the CORT stress response and did not find any substantive difference between the two populations. This similarity may indicate that painted turtles are not stressed by the presence of humans during the nesting season. The results of this study contribute to our understanding of CORT concentrations in freshwater reptiles, a group that is historically under-represented in studies of circulating hormone concentrations; specifically, studies that seek to use circulating concentrations of stress hormones, such as CORT, as a measure of the effect of human activities on wild populations. They also give insight into how these species as a whole may respond to human recreational activities during crucial life-history stages, such as the nesting season. Although there was no discernable difference between circulating CORT concentrations between the urban and rural populations studied, I did find a significant difference in circulating CORT concentrations between male and female C. picta. This important finding provides better understanding of the sex differences between male and female painted turtles and adds to our understanding of this species and other species of freshwater turtle.

  14. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    2010-09-01

    Full Text Available Blood function defines bleeding and clotting risks and dictates approaches for clinical intervention. Independent of adding exogenous tissue factor (TF, human blood treated in vitro with corn trypsin inhibitor (CTI, to block Factor XIIa will generate thrombin after an initiation time (T(i of 1 to 2 hours (depending on donor, while activation of platelets with the GPVI-activator convulxin reduces T(i to ∼20 minutes. Since current kinetic models fail to generate thrombin in the absence of added TF, we implemented a Platelet-Plasma ODE model accounting for: the Hockin-Mann protease reaction network, thrombin-dependent display of platelet phosphatidylserine, VIIa function on activated platelets, XIIa and XIa generation and function, competitive thrombin substrates (fluorogenic detector and fibrinogen, and thrombin consumption during fibrin polymerization. The kinetic model consisting of 76 ordinary differential equations (76 species, 57 reactions, 105 kinetic parameters predicted the clotting of resting and convulxin-activated human blood as well as predicted T(i of human blood under 50 different initial conditions that titrated increasing levels of TF, Xa, Va, XIa, IXa, and VIIa. Experiments with combined anti-XI and anti-XII antibodies prevented thrombin production, demonstrating that a leak of XIIa past saturating amounts of CTI (and not "blood-borne TF" alone was responsible for in vitro initiation without added TF. Clotting was not blocked by antibodies used individually against TF, VII/VIIa, P-selectin, GPIb, protein disulfide isomerase, cathepsin G, nor blocked by the ribosome inhibitor puromycin, the Clk1 kinase inhibitor Tg003, or inhibited VIIa (VIIai. This is the first model to predict the observed behavior of CTI-treated human blood, either resting or stimulated with platelet activators. CTI-treated human blood will clot in vitro due to the combined activity of XIIa and XIa, a process enhanced by platelet activators and which proceeds

  15. Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes

    International Nuclear Information System (INIS)

    Bjork, J.A.; Butenhoff, J.L.; Wallace, K.B.

    2011-01-01

    Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are surface active fluorochemicals that, due to their exceptional stability to degradation, are persistent in the environment. Both PFOA and PFOS are eliminated slowly in humans, with geometric mean serum elimination half-lives estimated at 3.5 and 4.8 years, respectively. The biological activity of PFOA and PFOS in rodents is attributed primarily to transactivation of the nuclear receptor peroxisome proliferator activated receptor alpha (PPARA), which is an important regulator of lipid and carbohydrate metabolism. However, there are significant species-specific differences in the response to PFOA and PFOS exposure; non-rodent species, including humans, are refractory to several but not all of these effects. Many of the metabolic effects have been attributed to the activation of PPARA; however, recent studies using PPARα knockout mice demonstrate residual PPARA-independent effects, some of which may involve the activation of alternate nuclear receptors, including NR1I2 (PXR), NR1I3 (CAR), NR1H3 (LXRA), and NR1H4 (FXR). The objective of this investigation was to characterize the activation of multiple nuclear receptors and modulation of metabolic pathways associated with exposure to PFOA and PFOS, and to compare and contrast the effects between rat and human primary liver cells using quantitative reverse transcription PCR (RT-qPCR). Our results demonstrate that multiple nuclear receptors participate in the metabolic response to PFOA and PFOS exposure resulting in a substantial shift from carbohydrate metabolism to fatty acid oxidation and hepatic triglyceride accumulation in rat liver cells. This shift in intermediary metabolism was more pronounced for PFOA than PFOS. Furthermore, while there is some similarity in the activation of metabolic pathways between rat and humans, particularly in PPARA regulated responses; the changes in primary human cells were more subtle and possibly reflect an adaptive

  16. Structure–activity relationships of the human prothrombin kringle-2 peptide derivative NSA9: anti-proliferative activity and cellular internalization

    OpenAIRE

    Hwang, Hyun Sook; Kim, Dong Won; Kim, Soung Soo

    2006-01-01

    The human prothrombin kringle-2 protein inhibits angiogenesis and LLC (Lewis lung carcinoma) growth and metastasis in mice. Additionally, the NSA9 peptide (NSAVQLVEN) derived from human prothrombin kringle-2 has been reported to inhibit the proliferation of BCE (bovine capillary endothelial) cells and CAM (chorioallantoic membrane) angiogenesis. In the present study, we examined the structure–activity relationships of the NSA9 peptide in inhibiting the proliferation of endothelial cells lines...

  17. Effects of Climate Change and Human Activities on Surface Runoff in the Luan River Basin

    Directory of Open Access Journals (Sweden)

    Sidong Zeng

    2015-01-01

    Full Text Available Quantifying the effects of climate change and human activities on runoff changes is the focus of climate change and hydrological research. This paper presents an integrated method employing the Budyko-based Fu model, hydrological modeling, and climate elasticity approaches to separate the effects of the two driving factors on surface runoff in the Luan River basin, China. The Budyko-based Fu model and the double mass curve method are used to analyze runoff changes during the period 1958~2009. Then two types of hydrological models (the distributed Soil and Water Assessment Tool model and the lumped SIMHYD model and seven climate elasticity methods (including a nonparametric method and six Budyko-based methods are applied to estimate the contributions of climate change and human activities to runoff change. The results show that all quantification methods are effective, and the results obtained by the nine methods are generally consistent. During the study period, the effects of climate change on runoff change accounted for 28.3~46.8% while those of human activities contributed with 53.2~71.7%, indicating that both factors have significant effects on the runoff decline in the basin, and that the effects of human activities are relatively stronger than those of climate change.

  18. Ubiquitin-Like Protein from Human Placental Extract Exhibits Collagenase Activity

    Science.gov (United States)

    De, Debashree; Datta Chakraborty, Piyali; Mitra, Jyotirmoy; Sharma, Kanika; Mandal, Somnath; Das, Aneesha; Chakrabarti, Saikat; Bhattacharyya, Debasish

    2013-01-01

    An aqueous extract of human placenta exhibits strong gelatinase/collagenase activity in zymography. 2-D gel electrophoresis of the extract with gelatin zymography in the second dimension displayed a single spot, identified as ubiquitin-like component upon MALDI/TOF MS/MS analysis. Immunoblot indicated presence of ubiquitin and absence of collagenase in the extract. Collagenase activity of the ubiquitin-like component was confirmed from the change in solubility of collagen in aqueous buffer, degradation of collagen by size-exclusion HPLC and atomic force microscopy. Quantification with DQ-gelatin showed that the extract contains 0.04 U/ml of collagenase activity that was inhibited up to 95% by ubiquitin antibody. Ubiquitin from bovine erythrocytes demonstrated mild collagenase activity. Bioinformatics studies suggest that placental ubiquitin and collagenase follow structurally divergent evolution. This thermostable intrinsic collagenase activity of placental extract might have wide physiological relevance in degrading and remodeling collagen as it is used as a drug for wound healing and pelvic inflammatory diseases. PMID:23555718

  19. Human-like PB2 627K influenza virus polymerase activity is regulated by importin-α1 and -α7.

    Directory of Open Access Journals (Sweden)

    Ben Hudjetz

    2012-01-01

    Full Text Available Influenza A viruses may cross species barriers and transmit to humans with the potential to cause pandemics. Interplay of human- (PB2 627K and avian-like (PB2 627E influenza polymerase complexes with unknown host factors have been postulated to play a key role in interspecies transmission. Here, we have identified human importin-α isoforms (α1 and α7 as positive regulators of human- but not avian-like polymerase activity. Human-like polymerase activity correlated with efficient recruitment of α1 and α7 to viral ribonucleoprotein complexes (vRNPs without affecting subcellular localization. We also observed that human-like influenza virus growth was impaired in α1 and α7 downregulated human lung cells. Mice lacking α7 were less susceptible to human- but not avian-like influenza virus infection. Thus, α1 and α7 are positive regulators of human-like polymerase activity and pathogenicity beyond their role in nuclear transport.

  20. Native gel electrophoresis of human telomerase distinguishes active complexes with or without dyskerin

    Science.gov (United States)

    Gardano, Laura; Holland, Linda; Oulton, Rena; Le Bihan, Thierry; Harrington, Lea

    2012-01-01

    Telomeres, the ends of linear chromosomes, safeguard against genome instability. The enzyme responsible for extension of the telomere 3′ terminus is the ribonucleoprotein telomerase. Whereas telomerase activity can be reconstituted in vitro with only the telomerase RNA (hTR) and telomerase reverse transcriptase (TERT), additional components are required in vivo for enzyme assembly, stability and telomere extension activity. One such associated protein, dyskerin, promotes hTR stability in vivo and is the only component to co-purify with active, endogenous human telomerase. We used oligonucleotide-based affinity purification of hTR followed by native gel electrophoresis and in-gel telomerase activity detection to query the composition of telomerase at different purification stringencies. At low salt concentrations (0.1 M NaCl), affinity-purified telomerase was ‘supershifted’ with an anti-dyskerin antibody, however the association with dyskerin was lost after purification at 0.6 M NaCl, despite the retention of telomerase activity and a comparable yield of hTR. The interaction of purified hTR and dyskerin in vitro displayed a similar salt-sensitive interaction. These results demonstrate that endogenous human telomerase, once assembled and active, does not require dyskerin for catalytic activity. Native gel electrophoresis may prove useful in the characterization of telomerase complexes under various physiological conditions. PMID:22187156

  1. Cyclin D3 interacts with human activating transcription factor 5 and potentiates its transcription activity

    International Nuclear Information System (INIS)

    Liu Wenjin; Sun Maoyun; Jiang Jianhai; Shen Xiaoyun; Sun Qing; Liu Weicheng; Shen Hailian; Gu Jianxin

    2004-01-01

    The Cyclin D3 protein is a member of the D-type cyclins. Besides serving as cell cycle regulators, D-type cyclins have been reported to be able to interact with several transcription factors and modulate their transcriptional activations. Here we report that human activating transcription factor 5 (hATF5) is a new interacting partner of Cyclin D3. The interaction was confirmed by in vivo coimmunoprecipitation and in vitro binding analysis. Neither interaction between Cyclin D1 and hATF5 nor interaction between Cyclin D2 and hATF5 was observed. Confocal microscopy analysis showed that Cyclin D3 could colocalize with hATF5 in the nuclear region. Cyclin D3 could potentiate hATF5 transcriptional activity independently of its Cdk4 partner. But Cyclin D1 and Cyclin D2 had no effect on hATF5 transcriptional activity. These data provide a new clue to understand the new role of Cyclin D3 as a transcriptional regulator

  2. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

    Science.gov (United States)

    Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

    2010-10-01

    PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

  3. Activation of lipoprotein lipase by lipoprotein fractions of human serum.

    Science.gov (United States)

    Bier, D M; Havel, R J

    1970-11-01

    Triglycerides in fat emulsions are hydrolyzed by lipoprotein lipase only when they are "activated" by serum lipoproteins. The contribution of different lipoprotein fractions to hydrolysis of triglycerides in soybean oil emulsion was assessed by determining the quantity of lipoprotein fraction required to give half-maximal hydrolysis. Most of the activator property of whole serum from normolipidemic, postabsorptive subjects was in high density lipoproteins. Low density lipoproteins and serum from which all lipoprotein classes were removed had little or no activity. Also, little activator was present in guinea pig serum or in very low density poor serum from an individual with lecithin:cholesterol acyltransferase deficiency, both of which are deficient in high density lipoproteins. Human very low density lipoproteins are potent activators and are much more active than predicted from their content of high density lipoprotein-protein. Per unit weight of protein, very low density lipoproteins had 13 times the activity of high density lipoproteins. These observations suggest that one or more of the major apoproteins of very low density lipoproteins, present as a minor constituent of high density lipoproteins, may be required for the activation process.

  4. Summary of other human activities in the coastal and marine environment

    CSIR Research Space (South Africa)

    Celliers, Louis

    2015-01-01

    Full Text Available The Western Indian Ocean (WIO) offers a wealth of opportunity for the profitable and beneficial use of coastal and marine resources – a prospect for a true ocean economy. These benefits are derived from a range of human activities in the coastal...

  5. Coevolution between human's anticancer activities and functional foods from crop origin center in the world.

    Science.gov (United States)

    Zeng, Ya-Wen; Du, Juan; Pu, Xiao-Ying; Yang, Jia-Zhen; Yang, Tao; Yang, Shu-Ming; Yang, Xiao-Meng

    2015-01-01

    Cancer is the leading cause of death around the world. Anticancer activities from many functional food sources have been reported in years, but correlation between cancer prevalence and types of food with anticancer activities from crop origin center in the world as well as food source with human migration are unclear. Hunger from food shortage is the cause of early human evolution from Africa to Asia and later into Eurasia. The richest functional foods are found in crop origin centers, housing about 70% in the world populations. Crop origin centers have lower cancer incidence and mortality in the world, especially Central Asia, Middle East, Southwest China, India and Ethiopia. Asia and Africa with the richest anticancer crops is not only the most important evolution base of humans and origin center of anticancer functional crop, but also is the lowest mortality and incidence of cancers in the world. Cancer prevention of early human migrations was associated with functional foods from crop origin centers, especially Asia with four centers and one subcenter of crop origin, accounting for 58% of the world population. These results reveal that coevolution between human's anticancer activities associated with functional foods for crop origin centers, especially in Asia and Africa.

  6. Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia

    NARCIS (Netherlands)

    Renckens, Rosemarijn; Weijer, Sebastiaan; de Vos, Alex F.; Pater, Jennie M.; Meijers, Joost C.; Hack, C. Erik; Levi, Marcel; van der Poll, Tom

    2004-01-01

    Objective - Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems. Methods and Results - To

  7. How Do Small Things Make a Big Difference? Activities to Teach about Human-Microbe Interactions.

    Science.gov (United States)

    Jasti, Chandana; Hug, Barbara; Waters, Jillian L; Whitaker, Rachel J

    2014-11-01

    Recent scientific studies are providing increasing evidence for how microbes living in and on us are essential to our good health. However, many students still think of microbes only as germs that harm us. The classroom activities presented here are designed to shift student thinking on this topic. In these guided inquiry activities, students investigate human-microbe interactions as they work together to interpret and analyze authentic data from published articles and develop scientific models. Through the activities, students learn and apply ecological concepts as they come to see the human body as a fascinatingly complex ecosystem.

  8. Blood-group-Ii-active gangliosides of human erythrocyte membranes

    International Nuclear Information System (INIS)

    Feizi, T.; Childs, R.A.; Hakomori, S.-I.; Powell, M.E.

    1978-01-01

    More than ten new types of gangliosides, in addition to haematoside and sialosylparagloboside, were isolated from human erythrocyte membranes. These were separated by successive chromatographies on DAEA-Sephadex, on porous silica-gel columns and on thin-layer silica gel as acetylated compounds. Highly potent blood-group-Ii and moderate blood-group-H activities were demonstrated in some of the ganglioside fractions. The gangliosides incorporated into chlolesterol/phosphatidylcholine liposomes stoicheiometrically inhibited binding of anti-(blood-group-I and i) antibodies to a radioiodinated blood-group-Ii-active glycoprotein. The fraction with the highest blood-group-I activity, I(g) fraction, behaved like sialosyl-deca- to dodeca-glycosylceramides on t.l.c. Certain blood-group-I and most of the i-determinants were in partially or completely cryptic form and could be unmasked by sialidase treatment. Thus the I and i antigens, which are known to occur on internal structures of blood-group-ABH-active glycoproteins in secretions, also occur in the interior of the carbohydrate chains of erythrocyte gangliosides. (author)

  9. Canine and feline parvoviruses preferentially recognize the non-human cell surface sialic acid N-glycolylneuraminic acid

    Energy Technology Data Exchange (ETDEWEB)

    Löfling, Jonas [Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, Center for Academic Research and Training in Anthropogeny, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093 (United States); Michael Lyi, Sangbom; Parrish, Colin R. [Baker Institute for Animal Health, Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 (United States); Varki, Ajit, E-mail: a1varki@ucsd.edu [Departments of Medicine and Cellular and Molecular Medicine, Glycobiology Research and Training Center, Center for Academic Research and Training in Anthropogeny, 9500 Gilman Drive, University of California, San Diego, La Jolla, CA 92093 (United States)

    2013-05-25

    Feline panleukopenia virus (FPV) is a pathogen whose canine-adapted form (canine parvovirus (CPV)) emerged in 1978. These viruses infect by binding host transferrin receptor type-1 (TfR), but also hemagglutinate erythrocytes. We show that hemagglutination involves selective recognition of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) but not N-acetylneuraminic acid (Neu5Ac), which differs by only one oxygen atom from Neu5Gc. Overexpression of α2-6 sialyltransferase did not change binding, indicating that both α2-3 and α2-6 linkages are recognized. However, Neu5Gc expression on target cells did not enhance CPV or FPV infection in vitro. Thus, the conserved Neu5Gc-binding preference of these viruses likely plays a role in the natural history of the virus in vivo. Further studies must clarify relationships between virus infection and host Neu5Gc expression. As a first step, we show that transcripts of CMAH (which generates Neu5Gc from Neu5Ac) are at very low levels in Western dog breed cells. - Highlights: ► Feline and canine parvoviruses recognize Neu5Gc but not Neu5Ac, which differ by one oxygen atom. ► The underlying linkage of these sialic acids does not affect recognition. ► Induced Neu5Gc expression on target cells that normally express Neu5Ac did not enhance infection. ► Thus, the conserved binding preference plays an important yet unknown role in in vivo infections. ► Population and breed variations in Neu5Gc expression occur, likely by regulating the gene CMAH.

  10. Canine and feline parvoviruses preferentially recognize the non-human cell surface sialic acid N-glycolylneuraminic acid

    International Nuclear Information System (INIS)

    Löfling, Jonas; Michael Lyi, Sangbom; Parrish, Colin R.; Varki, Ajit

    2013-01-01

    Feline panleukopenia virus (FPV) is a pathogen whose canine-adapted form (canine parvovirus (CPV)) emerged in 1978. These viruses infect by binding host transferrin receptor type-1 (TfR), but also hemagglutinate erythrocytes. We show that hemagglutination involves selective recognition of the non-human sialic acid N-glycolylneuraminic acid (Neu5Gc) but not N-acetylneuraminic acid (Neu5Ac), which differs by only one oxygen atom from Neu5Gc. Overexpression of α2-6 sialyltransferase did not change binding, indicating that both α2-3 and α2-6 linkages are recognized. However, Neu5Gc expression on target cells did not enhance CPV or FPV infection in vitro. Thus, the conserved Neu5Gc-binding preference of these viruses likely plays a role in the natural history of the virus in vivo. Further studies must clarify relationships between virus infection and host Neu5Gc expression. As a first step, we show that transcripts of CMAH (which generates Neu5Gc from Neu5Ac) are at very low levels in Western dog breed cells. - Highlights: ► Feline and canine parvoviruses recognize Neu5Gc but not Neu5Ac, which differ by one oxygen atom. ► The underlying linkage of these sialic acids does not affect recognition. ► Induced Neu5Gc expression on target cells that normally express Neu5Ac did not enhance infection. ► Thus, the conserved binding preference plays an important yet unknown role in in vivo infections. ► Population and breed variations in Neu5Gc expression occur, likely by regulating the gene CMAH

  11. CP-25 Attenuates the Activation of CD4+ T Cells Stimulated with Immunoglobulin D in Human.

    Science.gov (United States)

    Wu, Yu-Jing; Chen, Heng-Shi; Chen, Wen-Sheng; Dong, Jin; Dong, Xiao-Jie; Dai, Xing; Huang, Qiong; Wei, Wei

    2018-01-01

    Researchers have shown that the level of immunoglobulin D (IgD) is often elevated in patients with autoimmune diseases. The possible roles of IgD on the function of human T cell activation are still unclear. Paeoniflorin-6'- O -benzene sulfonate (code: CP-25), the chemistry structural modifications of paeoniflorin, was a novel drug of anti-inflammation and immunomodulation. The aims of this study were to determine if human CD4 + T cells could be activated by IgD via the IgD receptor (IgDR)-Lck pathway and whether the novel compound CP-25 could affect the activation of T cells by regulating Lck. Human CD4 + T cells were purified from peripheral blood mononuclear cells using microbeads. T cell viability and proliferation were detected by Cell Counting Kit-8 and CFSE Cell Proliferation Kit. Cytokines secreted by T cells were assessed with the Quantibody Human Inflammation Array. The binding affinity and expression of IgDR on T cells were detected by flow cytometry, and protein expression of IgDR, Lck, and P-Lck were analyzed by western blot. IgD was shown to bind to IgDR on CD4 + T cells in a concentration-dependent manner and stimulate the activation and proliferation of these cells by enhancing phosphorylation of the activating tyrosine residue of Lck (Tyr 394 ). CP-25 inhibited the IgD-stimulated activation and proliferation of CD4 + T cells, as well as the production of inflammatory cytokines; it was thus suggested that this process might be related to the downregulation of Lck (Tyr 394 ) phosphorylation. These results demonstrate that IgD amplifies the activation of CD4 + T cells, which could be mediated by Lck phosphorylation. Further, CP-25, via its ability to modulate Lck, is a novel potential therapeutic agent for the treatment of human autoimmune diseases.

  12. Fibulin-4 is a novel Wnt/β-Catenin pathway activator in human osteosarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Li, Renzeng [Department of Othopedics, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450000 Henan (China); Department of Orthopaedics, The No.3 People’s Hospital of Anyang City, Anyang 455000 (China); Wang, Limin, E-mail: gu2keo@163.com [Department of Othopedics, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe Road, Zhengzhou, 450000 Henan (China)

    2016-06-10

    Fibulin-4, an extracellular glycoprotein implicated in connective tissue development and elastic fiber formation, draws increasing focuses in cancer research. However, little is known about the underlying oncogenic roles of Fibulin-4 in human osteosarcoma (OS). In this study, by immunohistochemical analysis, upregulated expression of Fibulin-4 was found in the OS clinical specimens and cell lines compared to their normal counterparts. Fibulin-4 was positively correlated with the T stage of OS patients, and the proliferation index Ki67. Based on informatics analysis and functional verification, microRNA-137 was identified as a potential upstream regulator of Fibulin-4. Knockdown of Fibulin-4 or introduction of microRNA-137 inhibited cell proliferation and promoted cell apoptosis, and adverse effects were observed by overexpression of Fibulin-4. Furthermore, the tumor-suppressive functions of microRNA-137 were markedly abolished by restoration of Fibulin-4 expression in OS cells. Mechanistically, Fibulin-4 activated Wnt/β-Catenin pathway and promoted the expression of its downstream targets, including CCND2, c-Myc and VEGF. Taken together, Fibulin-4 plays critical neoplastic roles in tumor growth of human OS by activating Wnt/β-Catenin signaling and may represent a potential therapeutic target. -- Highlights: •Upregulated Fibulin-4 correlates tumor growth in human OS. •MicroRNA-137 is a critical regulator of Fibulin-4 expression. •Deregulated miR-137/Fibulin-4 axis promotes tumor growth of human OS. •Wnt/β-Catenin pathway is activated by Fibulin-4 stimulation.

  13. Fibulin-4 is a novel Wnt/β-Catenin pathway activator in human osteosarcoma

    International Nuclear Information System (INIS)

    Li, Renzeng; Wang, Limin

    2016-01-01

    Fibulin-4, an extracellular glycoprotein implicated in connective tissue development and elastic fiber formation, draws increasing focuses in cancer research. However, little is known about the underlying oncogenic roles of Fibulin-4 in human osteosarcoma (OS). In this study, by immunohistochemical analysis, upregulated expression of Fibulin-4 was found in the OS clinical specimens and cell lines compared to their normal counterparts. Fibulin-4 was positively correlated with the T stage of OS patients, and the proliferation index Ki67. Based on informatics analysis and functional verification, microRNA-137 was identified as a potential upstream regulator of Fibulin-4. Knockdown of Fibulin-4 or introduction of microRNA-137 inhibited cell proliferation and promoted cell apoptosis, and adverse effects were observed by overexpression of Fibulin-4. Furthermore, the tumor-suppressive functions of microRNA-137 were markedly abolished by restoration of Fibulin-4 expression in OS cells. Mechanistically, Fibulin-4 activated Wnt/β-Catenin pathway and promoted the expression of its downstream targets, including CCND2, c-Myc and VEGF. Taken together, Fibulin-4 plays critical neoplastic roles in tumor growth of human OS by activating Wnt/β-Catenin signaling and may represent a potential therapeutic target. -- Highlights: •Upregulated Fibulin-4 correlates tumor growth in human OS. •MicroRNA-137 is a critical regulator of Fibulin-4 expression. •Deregulated miR-137/Fibulin-4 axis promotes tumor growth of human OS. •Wnt/β-Catenin pathway is activated by Fibulin-4 stimulation.

  14. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  15. TLR4 activates NF-κB in human ovarian granulosa tumor cells

    International Nuclear Information System (INIS)

    Woods, Dori C.; White, Yvonne A.R.; Dau, Caroline; Johnson, A.L.

    2011-01-01

    Highlights: → TLR4 is expressed in human ovarian granulosa tumor cells. → Acting through TLR4, LPS and HSP60 induce a NFκB signaling cascade in human ovarian granulosa tumor cells. → NFκB activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-κB) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to IκB degradation and activation of NF-κB. NF-κB activation was confirmed by nuclear localization of NF-κB p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-κB signaling attenuated LPS-induced TNFα plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-κB signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-κB does not sensitize GCTs to TRAIL or cisplatin.

  16. TLR4 activates NF-{kappa}B in human ovarian granulosa tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Woods, Dori C., E-mail: dwoods2@partners.org [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); White, Yvonne A.R. [Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114 (United States); Dau, Caroline [University of California, San Francisco, School of Dentistry, San Francisco, CA 94143 (United States); Johnson, A.L. [Center for Reproductive Biology and Health, The Pennsylvania State University, University Park, PA 16802 (United States)

    2011-06-17

    Highlights: {yields} TLR4 is expressed in human ovarian granulosa tumor cells. {yields} Acting through TLR4, LPS and HSP60 induce a NF{kappa}B signaling cascade in human ovarian granulosa tumor cells. {yields} NF{kappa}B activation or inhibition did not alter chemosensitivity to TRAIL or cisplatin. -- Abstract: Previous studies have demonstrated expression of Toll-like receptors (TLRs) in the surface epithelium of normal ovaries (OSE) and in epithelial ovarian tumors. Most notably, OSE-derived cancers express TLR4, which activates the nuclear factor-kappa B (NF-{kappa}B) signaling cascade as a mediator of inflammatory response. Currently, there is considerable interest in elucidating the role of TLR-mediated signaling in cancers. Nevertheless, the expression of TLRs in granulosa cell tumors (GCTs) of the ovary, and the extent to which GCT expression of TLRs may influence cell-signaling pathways and/or modulate the efficacy of chemotherapeutics, has yet to be determined. In the present study, human GCT lines (COV434 and KGN) were utilized to evaluate expression of functional TLR4. TLR4 is expressed in GCT cell lines and ligation of TLR4 with bacterial lipopolysaccharide (LPS) led to I{kappa}B degradation and activation of NF-{kappa}B. NF-{kappa}B activation was confirmed by nuclear localization of NF-{kappa}B p65 following treatment with LPS and the naturally occurring ligand, HSP60. Notably, immunoneutralization of TLR4 blocked nuclear localization, and inhibition of NF-{kappa}B signaling attenuated LPS-induced TNF{alpha} plus increased doubling time in both cell lines. Contradictory to reports using human OSE cell lines, inhibition of NF-{kappa}B signaling failed to sensitize GCT lines to TRAIL or cisplatin. In summary, findings herein are the first to demonstrate a functional TLR-signaling pathway specifically in GCTs, and indicate that in contrast to OSE-derived cancers, inhibition of NF-{kappa}B does not sensitize GCTs to TRAIL or cisplatin.

  17. Determination of fluoride in human nails via cyclic instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    Spate, V.L.; Morris, J.S.; Baskett, C.K.; Mason, M.M.; Reams, C.L.

    1994-01-01

    The role of fluorine in human health has become somewhat controversial. It is widely accepted as protective against dental caries, may be protective against osteoporosis, and has been very conservatively implicated with osteosarcoma in male rats. The develepment of a neutron activation analysis method and its application to the analysis of human nails is reported. It has been found that toenails collected in population-based epidemiology studies apparently reflect fluoride intake. (author) 11 refs.; 2 tabs

  18. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Directory of Open Access Journals (Sweden)

    Laura V Cuaya

    Full Text Available Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI. We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  19. Swell activated chloride channel function in human neutrophils

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

    2009-04-17

    Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

  20. Tissue factor-dependent activation of tritium-labeled factor IX and factor X in human plasma

    International Nuclear Information System (INIS)

    Morrison, S.A.; Jesty, J.

    1984-01-01

    A comparism was made of the tissue factor-dependent activation of tritium-labeled factor IX and factor X in a human plasma system and a study was made of the role of proteases known to stimulate factor VII activity. Plasma was defibrinated by heating and depleted of its factors IX and X by passing it through antibody columns. Addition of human brain thromboplastin, Ca2+, and purified 3H-labeled factor X to the plasma resulted, after a short lag, in burst-like activation of the factor X, measured as the release of radiolabeled activation peptide. The progress of activation was slowed by both heparin and a specific inhibitor of factor Xa but factor X activation could not be completely abolished by such inhibitors. In the case of 3H-factor IX activation, the rate also increased for approximately 3 min after addition of thromboplastin, but was not subsequently curtailed. A survey of proteases implicated as activators of factor VII in other settings showed that both factor Xa and factor IXa could accelerate the activation of factor IX. However, factor Xa was unique in obliterating activation when present at concentrations greater than approximately 1 nM. Heparin inhibited the tissue factor-dependent activation of factor IX almost completely, apparently through the effect of antithrombin on the feedback reactions of factors Xa and IXa on factor VII. These results suggest that a very tight, biphasic control of factor VII activity exists in human plasma, which is modulated mainly by factor Xa. At saturation of factor VIIa/tissue factor, factor IX activation was significantly more rapid than was previously found in bovine plasma under similar conditions. The activation of factor X at saturation was slightly more rapid than in bovine plasma, despite the presence of heparin

  1. Unlike PPARγ, PPARα or PPARβ/δ activation does not promote human monocyte differentiation toward alternative macrophages

    International Nuclear Information System (INIS)

    Bouhlel, Mohamed Amine; Brozek, John; Derudas, Bruno; Zawadzki, Christophe; Jude, Brigitte; Staels, Bart; Chinetti-Gbaguidi, Giulia

    2009-01-01

    Macrophages adapt their response to micro-environmental signals. While Th1 cytokines promote pro-inflammatory M1 macrophages, Th2 cytokines promote an 'alternative' anti-inflammatory M2 macrophage phenotype. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors expressed in macrophages where they control the inflammatory response. It has been shown that PPARγ promotes the differentiation of monocytes into anti-inflammatory M2 macrophages in humans and mice, while a role for PPARβ/δ in this process has been reported only in mice and no data are available for PPARα. Here, we show that in contrast to PPARγ, expression of PPARα and PPARβ/δ overall does not correlate with the expression of M2 markers in human atherosclerotic lesions, whereas a positive correlation with genes of lipid metabolism exists. Moreover, unlike PPARγ, PPARα or PPARβ/δ activation does not influence human monocyte differentiation into M2 macrophages in vitro. Thus, PPARα and PPARβ/δ do not appear to modulate the alternative differentiation of human macrophages.

  2. Enavatuzumab, a Humanized Anti-TWEAK Receptor Monoclonal Antibody, Exerts Antitumor Activity through Attracting and Activating Innate Immune Effector Cells

    Directory of Open Access Journals (Sweden)

    Shiming Ye

    2017-01-01

    Full Text Available Enavatuzumab is a humanized IgG1 anti-TWEAK receptor monoclonal antibody that was evaluated in a phase I clinical study for the treatment of solid malignancies. The current study was to determine whether and how myeloid effector cells were involved in postulated mechanisms for its potent antitumor activity in xenograft models. The initial evidence for a role of effector cells was obtained in a subset of tumor xenograft mouse models whose response to enavatuzumab relied on the binding of Fc of the antibody to Fcγ receptor. The involvement of effector cells was further confirmed by immunohistochemistry, which revealed strong infiltration of CD45+ effector cells into tumor xenografts in responding models, but minimal infiltration in nonresponders. Consistent with the xenograft studies, human effector cells preferentially migrated toward in vivo-responsive tumor cells treated by enavatuzumab in vitro, with the majority of migratory cells being monocytes. Conditioned media from enavatuzumab-treated tumor cells contained elevated levels of chemokines, which might be responsible for enavatuzumab-triggered effector cell migration. These preclinical studies demonstrate that enavatuzumab can exert its potent antitumor activity by actively recruiting and activating myeloid effectors to kill tumor cells. Enavatuzumab-induced chemokines warrant further evaluation in clinical studies as potential biomarkers for such activity.

  3. Selective activation of human heat shock gene transcription by nitrosourea antitumor drugs mediated by isocyanate-induced damage and activation of heat shock transcription factor.

    Science.gov (United States)

    Kroes, R A; Abravaya, K; Seidenfeld, J; Morimoto, R I

    1991-01-01

    Treatment of cultured human tumor cells with the chloroethylnitrosourea antitumor drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) selectively induces transcription and protein synthesis of a subset of the human heat shock or stress-induced genes (HSP90 and HSP70) with little effect on other stress genes or on expression of the c-fos, c-myc, or beta-actin genes. The active component of BCNU and related compounds appears to be the isocyanate moiety that causes carbamoylation of proteins and nucleic acids. Transcriptional activation of the human HSP70 gene by BCNU is dependent on the heat shock element and correlates with the level of heat shock transcription factor and its binding to the heat shock element in vivo. Unlike activation by heat or heavy metals, BCNU-mediated activation is strongly dependent upon new protein synthesis. This suggests that BCNU-induced, isocyanate-mediated damage to newly synthesized protein(s) may be responsible for activation of the heat shock transcription factor and increased transcription of the HSP90 and HSP70 genes. Images PMID:2052560

  4. Neural Activity Patterns in the Human Brain Reflect Tactile Stickiness Perception

    Science.gov (United States)

    Kim, Junsuk; Yeon, Jiwon; Ryu, Jaekyun; Park, Jang-Yeon; Chung, Soon-Cheol; Kim, Sung-Phil

    2017-01-01

    Our previous human fMRI study found brain activations correlated with tactile stickiness perception using the uni-variate general linear model (GLM) (Yeon et al., 2017). Here, we conducted an in-depth investigation on neural correlates of sticky sensations by employing a multivoxel pattern analysis (MVPA) on the same dataset. In particular, we statistically compared multi-variate neural activities in response to the three groups of sticky stimuli: A supra-threshold group including a set of sticky stimuli that evoked vivid sticky perception; an infra-threshold group including another set of sticky stimuli that barely evoked sticky perception; and a sham group including acrylic stimuli with no physically sticky property. Searchlight MVPAs were performed to search for local activity patterns carrying neural information of stickiness perception. Similar to the uni-variate GLM results, significant multi-variate neural activity patterns were identified in postcentral gyrus, subcortical (basal ganglia and thalamus), and insula areas (insula and adjacent areas). Moreover, MVPAs revealed that activity patterns in posterior parietal cortex discriminated the perceptual intensities of stickiness, which was not present in the uni-variate analysis. Next, we applied a principal component analysis (PCA) to the voxel response patterns within identified clusters so as to find low-dimensional neural representations of stickiness intensities. Follow-up clustering analyses clearly showed separate neural grouping configurations between the Supra- and Infra-threshold groups. Interestingly, this neural categorization was in line with the perceptual grouping pattern obtained from the psychophysical data. Our findings thus suggest that different stickiness intensities would elicit distinct neural activity patterns in the human brain and may provide a neural basis for the perception and categorization of tactile stickiness. PMID:28936171

  5. Enzymatic characterization of a human acyltransferase activity.

    Directory of Open Access Journals (Sweden)

    Akihiko Ozawa

    Full Text Available Non-histone protein acylation is increasingly recognized as an important posttranslational modification, but little is known as to the biochemical properties of protein serine acylating enzymes.We here report that we have identified a metal-stimulated serine octanoyltransferase activity in microsomes from human erythroleukemic (HEL cells. The HEL acylating enzyme was linear with respect to time and protein, exhibited a neutral pH optimum (stimulated by cobalt and zinc, and inhibited by chelating reagents. Hydroxylamine treatment removed most, but not all, of the attached radioactivity. A salt extract of microsomal membranes contained the major portion of enzyme activity, indicating that this acyltransferase is not an integral membrane protein. Sucrose density fractionation showed that the acyltransferase activity is concentrated in the endoplasmic reticulum. In competition experiments, the acyltransferase was well inhibited by activated forms of fatty acids containing at least eight to fourteen carbons, but not by acetyl CoA. The zinc-stimulated HEL acyltransferase did not octanoylate proenkephalin, proopiomelanocortin, His-tagged proghrelin, or proghrelin lacking the amino-terminal His-tag stub of Gly-Ala-Met. The peptides des-acyl ghrelin and ACTH were also not acylated; however, des-acyl ghrelin containing the N-terminal tripeptide Gly-Ala-Met was acylated. Mutagenesis studies indicated a requirement for serine five residues from the amino terminus, reminiscent of myristoyl transferase, but not of ghrelin acylation. However, recombinant myristoyl transferase could not recapitulate the hydroxylamine sensitivity, zinc-stimulation, nor EDTA inhibition obtained with HEL acyltransferase, properties preserved in the HEL cell enzyme purified through four sequential chromatographic steps.In conclusion, our data demonstrate the presence of a zinc-stimulated acyltransferase activity concentrated in the endoplasmic reticulum in HEL cells which is likely

  6. Protective features of resveratrol on human spermatozoa cryopreservation may be mediated through 5' AMP-activated protein kinase activation.

    Science.gov (United States)

    Shabani Nashtaei, M; Amidi, F; Sedighi Gilani, M A; Aleyasin, A; Bakhshalizadeh, Sh; Naji, M; Nekoonam, S

    2017-03-01

    Biochemical and physical modifications during the freeze-thaw process adversely influence the restoration of energy-dependent sperm functions required for fertilization. Resveratrol, a phytoalexin, has been introduced to activate 5' AMP-activated protein kinase which is a cell energy sensor and a cell metabolism regulator. The cryoprotection of resveratrol on sperm cryoinjury via activation of AMP-activated protein kinase also remains to be elucidated. Our aim, thus, was to investigate: (i) the presence and intracellular localization of AMP-activated protein kinase protein; (ii) whether resveratrol may exert a protective effect on certain functional properties of fresh and post-thaw human spermatozoa through modulation of AMP-activated protein kinase. Spermatozoa from normozoospermic men were incubated with or without different concentrations of Compound C as an AMP-activated protein kinase inhibitor or resveratrol as an AMP-activated protein kinase activator for different lengths of time and were then cryopreserved. AMP-activated protein kinase is expressed essentially in the entire flagellum and the post-equatorial region. Viability of fresh spermatozoa was not significantly affected by the presence of Compound C or resveratrol. However, although Compound C caused a potent inhibition of spermatozoa motility parameters, resveratrol did not induce negative effect, except a significant reduction in motility at 25 μm for 1 h. Furthermore, resveratrol significantly increased AMP-activated protein kinase phosphorylation and mitochondrial membrane potential and decreased reactive oxygen species and apoptosis-like changes in frozen-thawed spermatozoa. Nevertheless, it was not able to compensate decreased sperm viability and motility parameters following cryopreservation. In contrast, Compound C showed opposite effects to resveratrol on AMP-activated protein kinase phosphorylation, reactive oxygen species, apoptosis-like changes, mitochondrial membrane potential, and

  7. Comparative Analysis of Human and Rodent Brain Primary Neuronal Culture Spontaneous Activity Using Micro-Electrode Array Technology.

    Science.gov (United States)

    Napoli, Alessandro; Obeid, Iyad

    2016-03-01

    Electrical activity in embryonic brain tissue has typically been studied using Micro Electrode Array (MEA) technology to make dozens of simultaneous recordings from dissociated neuronal cultures, brain stem cell progenitors, or brain slices from fetal rodents. Although these rodent neuronal primary culture electrical properties are mostly investigated, it has not been yet established to what extent the electrical characteristics of rodent brain neuronal cultures can be generalized to those of humans. A direct comparison of spontaneous spiking activity between rodent and human primary neurons grown under the same in vitro conditions using MEA technology has never been carried out before and will be described in the present study. Human and rodent dissociated fetal brain neuronal cultures were established in-vitro by culturing on a glass grid of 60 planar microelectrodes neurons under identical conditions. Three different cultures of human neurons were produced from tissue sourced from a single aborted fetus (at 16-18 gestational weeks) and these were compared with seven different cultures of embryonic rat neurons (at 18 gestational days) originally isolated from a single rat. The results show that the human and rodent cultures behaved significantly differently. Whereas the rodent cultures demonstrated robust spontaneous activation and network activity after only 10 days, the human cultures required nearly 40 days to achieve a substantially weaker level of electrical function. These results suggest that rat neuron preparations may yield inferences that do not necessarily transfer to humans. © 2015 Wiley Periodicals, Inc.

  8. Wearable Internet of Things - from human activity tracking to clinical integration.

    Science.gov (United States)

    Kumari, Poonam; Lopez-Benitez, Miguel; Gyu Myoung Lee; Tae-Seong Kim; Minhas, Atul S

    2017-07-01

    Wearable devices for human activity tracking have been emerging rapidly. Most of them are capable of sending health statistics to smartphones, smartwatches or smart bands. However, they only provide the data for individual analysis and their data is not integrated into clinical practice. Leveraging on the Internet of Things (IoT), edge and cloud computing technologies, we propose an architecture which is capable of providing cloud based clinical services using human activity data. Such services could supplement the shortage of staff in primary healthcare centers thereby reducing the burden on healthcare service providers. The enormous amount of data created from such services could also be utilized for planning future therapies by studying recovery cycles of existing patients. We provide a prototype based on our architecture and discuss its salient features. We also provide use cases of our system in personalized and home based healthcare services. We propose an International Telecommunication Union based standardization (ITU-T) for our design and discuss future directions in wearable IoT.

  9. Separating the impacts of climate change and human activities on streamflow: A review of methodologies and critical assumptions

    Science.gov (United States)

    Dey, Pankaj; Mishra, Ashok

    2017-05-01

    Climate change and human activity are two major drivers that alter hydrological cycle processes and cause change in spatio-temporal distribution of water availability. Streamflow, the most important component of hydrological cycle undergoes variation which is expected to be influenced by climate change as well as human activities. Since these two affecting conditions are time dependent, having unequal influence, identification of the change point in natural flow regime is of utmost important to separate the individual impact of climate change and human activities on streamflow variability. Subsequently, it is important as well for framing adaptation strategies and policies for regional water resources planning and management. In this paper, a comprehensive review of different approaches used by research community to isolate the impacts of climate change and human activities on streamflow are presented. The important issues pertaining to different approaches, to make rational use of methodology, are discussed so that researcher and policymaker can understand the importance of individual methodology and its use in water resources management. A new approach has also been suggested to select a representative change point under different scenarios of human activities with incorporation of climate variability/change.

  10. Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Tatsuya, E-mail: tatsuya.hasegawa@to.shiseido.co.jp; Nakashima, Masaya; Suzuki, Yoshiharu

    2016-08-26

    Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE{sub 2}. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

  11. Nuclear DNA damage-triggered NLRP3 inflammasome activation promotes UVB-induced inflammatory responses in human keratinocytes

    International Nuclear Information System (INIS)

    Hasegawa, Tatsuya; Nakashima, Masaya; Suzuki, Yoshiharu

    2016-01-01

    Ultraviolet (UV) radiation in sunlight can result in DNA damage and an inflammatory reaction of the skin commonly known as sunburn, which in turn can lead to cutaneous tissue disorders. However, little has been known about how UV-induced DNA damage mediates the release of inflammatory mediators from keratinocytes. Here, we show that UVB radiation intensity-dependently increases NLRP3 gene expression and IL-1β production in human keratinocytes. Knockdown of NLRP3 with siRNA suppresses UVB-induced production of not only IL-1β, but also other inflammatory mediators, including IL-1α, IL-6, TNF-α, and PGE_2. In addition, inhibition of DNA damage repair by knockdown of XPA, which is a major component of the nucleotide excision repair system, causes accumulation of cyclobutane pyrimidine dimer (CPD) and activation of NLRP3 inflammasome. In vivo immunofluorescence analysis confirmed that NLRP3 expression is also elevated in UV-irradiated human epidermis. Overall, our findings indicate that UVB-induced DNA damage initiates NLRP3 inflammasome activation, leading to release of various inflammatory mediators from human keratinocytes. - Highlights: • UVB radiation induces NLRP3 inflammasome activation in human keratinocytes. • NLRP3 knockdown suppresses production of UVB-induced inflammatory mediators. • UVB-induced DNA damage triggers NLRP3 inflammasome activation. • NLRP3 expression in human epidermis is elevated in response to UV radiation.

  12. Human activity spaces and plague risks in three contrasting landscapes in Lushoto District, Tanzania.

    Science.gov (United States)

    Hieronimo, Proches; Gulinck, Hubert; Kimaro, Didas N; Mulungu, Loth S; Kihupi, Nganga I; Msanya, Balthazar M; Leirs, Herwig; Deckers, Jozef A

    2014-07-01

    Since 1980 plague has been a human threat in the Western Usambara Mountains in Tanzania. However, the spatial-temporal pattern of plague occurrence remains poorly understood. The main objective of this study was to gain understanding of human activity patterns in relation to spatial distribution of fleas in Lushoto District. Data were collected in three landscapes differing in plague incidence. Field survey coupled with Geographic Information System (GIS) and physical sample collections were used to collect data in wet (April to June 2012) and dry (August to October 2012) seasons. Data analysis was done using GIS, one-way ANOVA and nonparametric statistical tools. The degree of spatial co-occurrence of potential disease vectors (fleas) and humans in Lushoto focus differs significantly (p ≤ 0.05) among the selected landscapes, and in both seasons. This trend gives a coarse indication of the possible association of the plague outbreaks and the human frequencies of contacting environments with fleas. The study suggests that plague surveillance and control programmes at landscape scale should consider the existence of plague vector contagion risk gradient from high to low incidence landscapes due to human presence and intensity of activities.

  13. Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

    Science.gov (United States)

    Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T.; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R.; Schenk, Mirjam; Sieling, Peter A.; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S.; Bruns, Heiko; Lewinsohn, David M.; Hollis, Bruce W.; Hewison, Martin; Adams, John S.; Steinmeyer, Andreas; Zügel, Ulrich; Cheng, Genhong; Jo, Eun-Kyeong; Bloom, Barry R.; Modlin, Robert L.

    2012-01-01

    Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D–dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D–sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D–deficient serum with 25-hydroxyvitamin D3 restored IFN-γ–induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection. PMID:21998409

  14. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

  15. Application of GPS Trajectory Data for Investigating the Interaction between Human Activity and Landscape Pattern: A Case Study of the Lijiang River Basin, China

    Directory of Open Access Journals (Sweden)

    Jun Li

    2016-06-01

    Full Text Available The interaction between human activity and landscape pattern has been a hot research topic during the last few decades. However, scholars used to measure human activity by social, economic and humanistic indexes. These indexes cannot directly reflect human activity and are not suitable for fine-grained analysis due to the coarse spatial resolution. In view of the above problems, this paper proposes a method that obtains the intensity of human activity from GPS trajectory data, collects landscape information from remote sensing images and further analyzes the interaction between human activity and landscape pattern at a fine-grained scale. The Lijiang River Basin is selected as the study area. Experimental results show that human activity and landscape pattern interact synergistically in this area. Built-up land and water boost human activity, while woodland restrains human activity. The effect of human activity on landscape pattern differs by the land cover category. Overall, human activities make natural land, such as woodland and water, scattered and fragmented, but cause man-built land, such as built-up land and farmland, clustered and regular. Nevertheless, human activities inside and outside urban areas are the opposite. The research findings in this paper are helpful for designing and implementing sustainable management plans.

  16. Interevent time distributions of human multi-level activity in a virtual world

    Science.gov (United States)

    Mryglod, O.; Fuchs, B.; Szell, M.; Holovatch, Yu.; Thurner, S.

    2015-02-01

    Studying human behavior in virtual environments provides extraordinary opportunities for a quantitative analysis of social phenomena with levels of accuracy that approach those of the natural sciences. In this paper we use records of player activities in the massive multiplayer online game Pardus over 1238 consecutive days, and analyze dynamical features of sequences of actions of players. We build on previous work where temporal structures of human actions of the same type were quantified, and provide an empirical understanding of human actions of different types. This study of multi-level human activity can be seen as a dynamic counterpart of static multiplex network analysis. We show that the interevent time distributions of actions in the Pardus universe follow highly non-trivial distribution functions, from which we extract action-type specific characteristic 'decay constants'. We discuss characteristic features of interevent time distributions, including periodic patterns on different time scales, bursty dynamics, and various functional forms on different time scales. We comment on gender differences of players in emotional actions, and find that while males and females act similarly when performing some positive actions, females are slightly faster for negative actions. We also observe effects on the age of players: more experienced players are generally faster in making decisions about engaging in and terminating enmity and friendship, respectively.

  17. Vasodilator-Stimulated Phosphoprotein Activity Is Required for Coxiella burnetii Growth in Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Punsiri M Colonne

    2016-10-01

    Full Text Available Coxiella burnetii is an intracellular bacterial pathogen that causes human Q fever, an acute flu-like illness that can progress to chronic endocarditis and liver and bone infections. Humans are typically infected by aerosol-mediated transmission, and C. burnetii initially targets alveolar macrophages wherein the pathogen replicates in a phagolysosome-like niche known as the parasitophorous vacuole (PV. C. burnetii manipulates host cAMP-dependent protein kinase (PKA signaling to promote PV formation, cell survival, and bacterial replication. In this study, we identified the actin regulatory protein vasodilator-stimulated phosphoprotein (VASP as a PKA substrate that is increasingly phosphorylated at S157 and S239 during C. burnetii infection. Avirulent and virulent C. burnetii triggered increased levels of phosphorylated VASP in macrophage-like THP-1 cells and primary human alveolar macrophages, and this event required the Cα subunit of PKA. VASP phosphorylation also required bacterial protein synthesis and secretion of effector proteins via a type IV secretion system, indicating the pathogen actively triggers prolonged VASP phosphorylation. Optimal PV formation and intracellular bacterial replication required VASP activity, as siRNA-mediated depletion of VASP reduced PV size and bacterial growth. Interestingly, ectopic expression of a phospho-mimetic VASP (S239E mutant protein prevented optimal PV formation, whereas VASP (S157E mutant expression had no effect. VASP (S239E expression also prevented trafficking of bead-containing phagosomes to the PV, indicating proper VASP activity is critical for heterotypic fusion events that control PV expansion in macrophages. Finally, expression of dominant negative VASP (S157A in C. burnetii-infected cells impaired PV formation, confirming importance of the protein for proper infection. This study provides the first evidence of VASP manipulation by an intravacuolar bacterial pathogen via activation of PKA

  18. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hyun Ji Eo

    2016-03-01

    Full Text Available Phlorofucofuroeckol A (PFF-A, one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3 has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB, located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK, glycogen synthase kinase (GSK 3β, and IκB kinase (IKK-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose polymerase (PARP by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

  19. PGC-1α-Dependent Mitochondrial Adaptation Is Necessary to Sustain IL-2-Induced Activities in Human NK Cells.

    Science.gov (United States)

    Miranda, Dante; Jara, Claudia; Ibañez, Jorge; Ahumada, Viviana; Acuña-Castillo, Claudio; Martin, Adrian; Córdova, Alexandra; Montoya, Margarita

    2016-01-01

    Human Natural Killer (NK) cells are a specialized heterogeneous subpopulation of lymphocytes involved in antitumor defense reactions. NK cell effector functions are critically dependent on cytokines and metabolic activity. Among various cytokines modulating NK cell function, interleukin-2 (IL-2) can induce a more potent cytotoxic activity defined as lymphokine activated killer activity (LAK). Our aim was to determine if IL-2 induces changes at the mitochondrial level in NK cells to support the bioenergetic demand for performing this enhanced cytotoxic activity more efficiently. Purified human NK cells were cultured with high IL-2 concentrations to develop LAK activity, which was assessed by the ability of NK cells to lyse NK-resistant Daudi cells. Here we show that, after 72 h of culture of purified human NK cells with enough IL-2 to induce LAK activity, both the mitochondrial mass and the mitochondrial membrane potential increased in a PGC-1α-dependent manner. In addition, oligomycin, an inhibitor of ATP synthase, inhibited IL-2-induced LAK activity at 48 and 72 h of culture. Moreover, the secretion of IFN-γ from NK cells with LAK activity was also partially dependent on PGC-1α expression. These results indicate that PGC-1α plays a crucial role in regulating mitochondrial function involved in the maintenance of LAK activity in human NK cells stimulated with IL-2.

  20. Direct electrical stimulation of human cortex evokes high gamma activity that predicts conscious somatosensory perception

    Science.gov (United States)

    Muller, Leah; Rolston, John D.; Fox, Neal P.; Knowlton, Robert; Rao, Vikram R.; Chang, Edward F.

    2018-04-01

    Objective. Direct electrical stimulation (DES) is a clinical gold standard for human brain mapping and readily evokes conscious percepts, yet the neurophysiological changes underlying these percepts are not well understood. Approach. To determine the neural correlates of DES, we stimulated the somatosensory cortex of ten human participants at frequency-amplitude combinations that both elicited and failed to elicit conscious percepts, meanwhile recording neural activity directly surrounding the stimulation site. We then compared the neural activity of perceived trials to that of non-perceived trials. Main results. We found that stimulation evokes distributed high gamma activity, which correlates with conscious perception better than stimulation parameters themselves. Significance. Our findings suggest that high gamma activity is a reliable biomarker for perception evoked by both natural and electrical stimuli.

  1. Candida albicans orf19.3727 encodes phytase activity and is essential for human tissue damage

    Science.gov (United States)

    Fong, Wing-Ping; Samaranayake, Lakshman Perera

    2017-01-01

    Candida albicans is a clinically important human fungal pathogen. We previously identified the presence of cell-associated phytase activity in C. albicans. Here, we reveal for the first time, that orf19.3727 contributes to phytase activity in C. albicans and ultimately to its virulence potency. Compared with its wild type counterpart, disruption of C. albicans orf19.3727 led to decreased phytase activity, reduced ability to form hyphae, attenuated in vitro adhesion, and reduced ability to penetrate human epithelium, which are the major virulence attributes of this yeast. Thus, orf19.3727 of C. albicans plays a key role in fungal pathogenesis. Further, our data uncover a putative novel strategy for anti-Candidal drug design through inhibition of phytase activity of this common pathogen. PMID:29216308

  2. Motor unit activity after eccentric exercise and muscle damage in humans.

    Science.gov (United States)

    Semmler, J G

    2014-04-01

    It is well known that unaccustomed eccentric exercise leads to muscle damage and soreness, which can produce long-lasting effects on muscle function. How this muscle damage influences muscle activation is poorly understood. The purpose of this brief review is to highlight the effect of eccentric exercise on the activation of muscle by the nervous system, by examining the change in motor unit activity obtained from surface electromyography (EMG) and intramuscular recordings. Previous research shows that eccentric exercise produces unusual changes in the EMG–force relation that influences motor performance during isometric, shortening and lengthening muscle contractions and during fatiguing tasks. When examining the effect of eccentric exercise at the single motor unit level, there are substantial changes in recruitment thresholds, discharge rates, motor unit conduction velocities and synchronization, which can last for up to 1 week after eccentric exercise. Examining the time course of these changes suggests that the increased submaximal EMG after eccentric exercise most likely occurs through a decrease in motor unit conduction velocity and an increase in motor unit activity related to antagonist muscle coactivation and low-frequency fatigue. Furthermore, there is a commonly held view that eccentric exercise produces preferential damage to high-threshold motor units, but the evidence for this in humans is limited. Further research is needed to establish whether there is preferential damage to high-threshold motor units after eccentric exercise in humans, preferably by linking changes in motor unit activity with estimates of motor unit size using selective intramuscular recording techniques.

  3. Protection of Human Podocytes from Shiga Toxin 2-Induced Phosphorylation of Mitogen-Activated Protein Kinases and Apoptosis by Human Serum Amyloid P Component

    Science.gov (United States)

    Dettmar, Anne K.; Binder, Elisabeth; Greiner, Friederike R.; Liebau, Max C.; Kurschat, Christine E.; Jungraithmayr, Therese C.; Saleem, Moin A.; Schmitt, Claus-Peter; Feifel, Elisabeth; Orth-Höller, Dorothea; Kemper, Markus J.; Pepys, Mark; Würzner, Reinhard

    2014-01-01

    Hemolytic uremic syndrome (HUS) is mainly induced by Shiga toxin 2 (Stx2)-producing Escherichia coli. Proteinuria can occur in the early phase of the disease, and its persistence determines the renal prognosis. Stx2 may injure podocytes and induce proteinuria. Human serum amyloid P component (SAP), a member of the pentraxin family, has been shown to protect against Stx2-induced lethality in mice in vivo, presumably by specific binding to the toxin. We therefore tested the hypothesis that SAP can protect against Stx2-induced injury of human podocytes. To elucidate the mechanisms underlying podocyte injury in HUS-associated proteinuria, we assessed Stx2-induced activation of mitogen-activated protein kinases (MAPKs) and apoptosis in immortalized human podocytes and evaluated the impact of SAP on Stx2-induced damage. Human podocytes express Stx2-binding globotriaosylceramide 3. Stx2 applied to cultured podocytes was internalized and then activated p38α MAPK and c-Jun N-terminal kinase (JNK), important signaling steps in cell differentiation and apoptosis. Stx2 also activated caspase 3, resulting in an increased level of apoptosis. Coincubation of podocytes with SAP and Stx2 mitigated the effects of Stx2 and induced upregulation of antiapoptotic Bcl2. These data suggest that podocytes are a target of Stx2 and that SAP protects podocytes against Stx2-induced injury. SAP may therefore be a useful therapeutic option. PMID:24566618

  4. Safety activities and human resource development at NCA

    International Nuclear Information System (INIS)

    Kumanomido, Hironori; Sakurada, Koichi; Yanagisawa, Shigeru; Masuyama, Tadaharu

    2015-01-01

    Toshiba Nuclear Critical Assembly (NCA) has been safely operated since the first criticality in December 1963. The topics covered in this Yayoi Meeting Report are: (1) the outline of NCA, (2) the safety control situation mainly after the Great East Japan Earthquake in 2011, (3) educational training incorporates the lessons learned in this earthquake, and (4) human resource development during 2008-2015. Regarding safety control, facility maintenance has been conducted systematically according to the maintenance plan from the viewpoint of preventive maintenance. Regarding educational training, two disaster handling training based on the safety regulation and one nuclear emergency drill based on the emergency drill plan for licensee of nuclear energy activity based on the Act of Special Measures Concerning Nuclear Emergency Preparedness every year. Regarding human resource development, development training was given to 358 people including students. This year, training that does not require NCA operation was conducted including gamma-ray spectrum measurement of NCA fuel rod and neutron deceleration property measurement using 252 Cf neutron source. (S.K.)

  5. Human glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site

    Directory of Open Access Journals (Sweden)

    Misquitta Stephanie A

    2004-02-01

    Full Text Available Abstract Background Glutaminyl cyclase (QC forms the pyroglutamyl residue at the amino terminus of numerous secretory peptides and proteins. We previously proposed the mammalian QC has some features in common with zinc aminopeptidases. We now have generated a structural model for human QC based on the aminopeptidase fold (pdb code 1AMP and mutated the apparent active site residues to assess their role in QC catalysis. Results The structural model proposed here for human QC, deposited in the protein databank as 1MOI, is supported by a variety of fold prediction programs, by the circular dichroism spectrum, and by the presence of the disulfide. Mutagenesis of the six active site residues present in both 1AMP and QC reveal essential roles for the two histidines (140 and 330, QC numbering and the two glutamates (201 and 202, while the two aspartates (159 and 248 appear to play no catalytic role. ICP-MS analysis shows less than stoichiometric zinc (0.3:1 in the purified enzyme. Conclusions We conclude that human pituitary glutaminyl cyclase and bacterial zinc aminopeptidase share a common fold and active site residues. In contrast to the aminopeptidase, however, QC does not appear to require zinc for enzymatic activity.

  6. Sodium transport and intracellular sodium activity in cultured human nasal epithelium

    DEFF Research Database (Denmark)

    Willumsen, Niels J.; Boucher, Richard C.

    1991-01-01

     human nasal epithelium (HNE). Under control conditions, intracellular Na+ activity (acNa) was 23 +/- 1 mM (n = 44 preparations, 393 impalements).Amiloride (10(-4) M) hyperpolarized the apical membrane and increased the fractional apical membrane resistance but did not affect acNa. Exposure to...

  7. Fisetin, a flavonol, inhibits TH2-type cytokine production by activated human basophils.

    Science.gov (United States)

    Higa, Shinji; Hirano, Toru; Kotani, Mayumi; Matsumoto, Motonobu; Fujita, Akihito; Suemura, Masaki; Kawase, Ichiro; Tanaka, Toshio

    2003-06-01

    Activation of mast cells and basophils through allergen stimulation releases chemical mediators and synthesizes cytokines. Among these cytokines, IL-4, IL-13, and IL-5 have major roles in allergic inflammation. We sought to determine the potency of flavonoids (astragalin, fisetin, kaempferol, myricetin, quercetin, and rutin) for the inhibition of cytokine expression and synthesis by human basophils. The inhibitory effect of flavonoids on cytokine expression by stimulated KU812 cells, a human basophilic cell line, and freshly purified peripheral blood basophils was measured by means of semiquantitative RT-PCR and ELISA assays. The effects of flavonoids on transcriptional activation of the nuclear factor of activated T cells were assessed by means of electrophoretic mobility shift assays. Fisetin suppressed the induction of IL-4, IL-13, and IL-5 mRNA expression by A23187-stimulated KU812 cells and basophils in response to cross-linkage of the IgE receptor. Fisetin reduced IL-4, IL-13, and IL-5 synthesis (inhibitory concentration of 50% [IC(50)] = 19.4, 17.7, and 17.4 micromol/L, respectively) but not IL-6 and IL-8 production by KU812 cells. In addition, fisetin inhibited IL-4 and IL-13 synthesis by anti-IgE antibody-stimulated human basophils (IC(50) = 5.1 and 6.2 micromol/L, respectively) and IL-4 synthesis by allergen-stimulated basophils from allergic patients (IC(50) = 4.8 micromol/L). Among the flavonoids examined, kaempferol and quercetin showed substantial inhibitory activities in cytokine expression but less so than those of fisetin. Fisetin inhibited nuclear localization of nuclear factor of activated T cells c2 by A23187-stimulated KU812 cells. These results provide evidence of a novel activity of the flavonoid fisetin that suppresses the expression of T(H)2-type cytokines (IL-4, IL-13, and IL-5) by basophils.

  8. Solar Energy Education. Humanities: activities and teacher's guide. Field test edition

    Energy Technology Data Exchange (ETDEWEB)

    1982-01-01

    Activities are outlined to introduce students to information on solar energy while performing ordinary classroom work. In this teaching manual solar energy is integrated with the humanities. The activities include such things as stories, newspapers, writing assignments, and art and musical presentations all filled with energy related terms. An energy glossary is provided. (BCS)

  9. TOPOISOMERASE-I AND TOPOISOMERASE-II ACTIVITY IN HUMAN BREAST, CERVIX, LUNG AND COLON-CANCER

    NARCIS (Netherlands)

    MCLEOD, HL; DOUGLAS, F; OATES, M; SYMONDS, RP; PRAKASH, D; VANDERZEE, AGJ; KAYE, SB; BROWN, R; KEITH, WN

    1994-01-01

    The identification of human DNA topoisomerases as cellular targets for active anti-cancer drugs has stimulated further interest in topoisomerase function in tumour biology. Topoisomerase I and II catalytic activity is detectable in many normal and malignant tissues. However, little is known about

  10. Mechanisms of complement activation by dextran-coated superparamagnetic iron oxide (SPIO) nanoworms in mouse versus human serum

    DEFF Research Database (Denmark)

    Banda, Nirmal K; Mehta, Gaurav; Chao, Ying

    2014-01-01

    BACKGROUND: The complement system is a key component of innate immunity implicated in the neutralization and clearance of invading pathogens. Dextran coated superparamagnetic iron oxide (SPIO) nanoparticle is a promising magnetic resonance imaging (MRI) contrast agent. However, dextran SPIO has...... the mechanisms of human complement activation. Mouse data were analyzed by non-paired t-test, human data were analyzed by ANOVA followed by multiple comparisons with Student-Newman-Keuls test. RESULTS: In mouse sera, SPIO NW triggered the complement activation via the LP, whereas the AP contributes via...... the CP, but that did not affect the total level of C3 deposition on the particles. CONCLUSIONS: There were important differences and similarities in the complement activation by SPIO NW in mouse versus human sera. Understanding the mechanisms of immune recognition of nanoparticles in mouse and human...

  11. Cytotoxic activity of water extracts of Trichilia hirta leaves on human tumor cells

    International Nuclear Information System (INIS)

    Hernandez Sosa, Edgar; Mora Gonzalez, Nestor; Morris Quevedo, Humberto J

    2013-01-01

    Trichilia hirta L. (Meliaceae) is traditionally used by patients suffering from cancer as an antitumoral resource. Therefore, the objectives of this study were to evaluate the cytotoxic activity of water extracts of Trichilia hirta leaves on tumour cells and identify through a phytochemical screening the principal families of phytocomponents contained in these extracts. The cytotoxic activity of these extracts was also evaluated on human melanoma cells (SK-mel-3) and human breast carcinoma (T-47D). The African green monkey kidney (AGMK) cells Cercopithecus aethiops (Vero) were used as a non-tumour cells control. The results showed the presence of triterpenes/steroids, saponins, coumarins, reductor sugars, phenols and tannins, flavonoids and carbohydrates/glycosides in the extracts. The water leaf extracts showed cytotoxic activity mainly on tumour cells, which contributes to explain the referred recovery by patients suffering form cancer that traditionally consume these extracts

  12. The effects of extra-low-frequency atmospheric pressure oscillations on human mental activity

    Science.gov (United States)

    Delyukov, A. A.; Didyk, L.

    Slight atmospheric pressure oscillations (APO) in the extra-low-frequency range below 0.1 Hz, which frequently occur naturally, can influence human mental activity. This phenomenon has been observed in experiments with a group of 12 healthy volunteers exposed to experimentally created APO with amplitudes 30-50 Pa in the frequency band 0.011-0.17 Hz. Exposure of the subjects to APO for 15-30 min caused significant changes in attention and short-term memory functions, performance rate, and mental processing flexibility. The character of the response depended on the APO frequency and coherence. Periodic APO promoted purposeful mental activity, accompanied by an increase in breath-holding duration and a slower heart rate. On the other hand, quasi-chaotic APO, similar to the natural perturbations of atmospheric pressure, disrupted mental activity. These observations suggest that APO could be partly responsible for meteorosensitivity in humans.

  13. Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

    International Nuclear Information System (INIS)

    Christman, G.M.; Randolph, J.F. Jr.; Peegel, H.; Menon, K.M.

    1991-01-01

    The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

  14. INPO Perspectives and Activities to Enhance Supplier Human Performance and Safety Culture

    International Nuclear Information System (INIS)

    Duncan, R. J.

    2016-01-01

    Within their own organizations, utilities have made significant improvements in human performance and safety culture, supported by a strong community of practice through INPO and WANO. In recent years, utilities have been making increasing use of suppliers for design, construction, inspection and maintenance services in support of their NPPs. Many of these suppliers do not have the benefit of being members of a community of practice when it comes to human performance and safety culture. To help the supplier community make improvements similar to what the utilities have achieved, INPO has recently expanded its Supplier Participant program to address the issue of human performance and safety culture in the supplier community. The intent of this paper will be to share the INPO’s perspectives and activities in helping suppliers of services and products to NPPs enhance their human performance and safety culture. (author)

  15. Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells

    Directory of Open Access Journals (Sweden)

    Elodie Jouan

    2016-12-01

    Full Text Available Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP, organic anion-transporting polypeptides (OATPs and organic cation transporter 1 (OCT1, and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP. Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2, OCT1 and bile salt export pump or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3 in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR- and nuclear factor erythroid 2-related factor 2 (Nrf2-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation.

  16. Human Activity Recognition in Real-Times Environments using Skeleton Joints

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available In this research work, we proposed a most effective noble approach for Human activity recognition in real-time environments. We recognize several distinct dynamic human activity actions using kinect. A 3D skeleton data is processed from real-time video gesture to sequence of frames and getter skeleton joints (Energy Joints, orientation, rotations of joint angles from selected setof frames. We are using joint angle and orientations, rotations information from Kinect therefore less computation required. However, after extracting the set of frames we implemented several classification techniques Principal Component Analysis (PCA with several distance based classifiers and Artificial Neural Network (ANN respectively with some variants for classify our all different gesture models. However, we conclude that use very less number of frame (10-15% for train our system efficiently from the entire set of gesture frames. Moreover, after successfully completion of our classification methods we clinch an excellent overall accuracy 94%, 96% and 98% respectively. We finally observe that our proposed system is more useful than comparing to other existing system, therefore our model is best suitable for real-time application such as in video games for player action/gesture recognition.

  17. Nanoparticles as Antituberculosis Drugs Carriers: Effect on Activity Against Mycobacterium tuberculosis in Human Monocyte-Derived Macrophages

    International Nuclear Information System (INIS)

    Anisimova, Y.V.; Gelperina, S.I.; Peloquin, C.A.; Heifets, L.B.

    2000-01-01

    This is the first report evaluating the nanoparticle delivery system for three antituberculosis drugs: isoniazid, rifampin, and streptomycin. The typical particle size is 250 nm. We studied accumulation of these drugs in human monocytes as well as their antimicrobial activity against Mycobacterium tuberculosis residing in human monocyte-derived macrophages. Nanoparticle encapsulation increased the intracellular accumulation (cell-association) of all three tested drugs, but it enhanced the antimicrobial activity of isoniazid and streptomycin only. On the other hand, the activity of encapsulated rifampin against intracellular bacteria was not higher than that of the free drug

  18. Ta1, a novel 105 KD human T cell activation antigen defined by a monoclonal antibody.

    Science.gov (United States)

    Fox, D A; Hussey, R E; Fitzgerald, K A; Acuto, O; Poole, C; Palley, L; Daley, J F; Schlossman, S F; Reinherz, E L

    1984-09-01

    By using a murine monoclonal antibody produced against an IL 2-dependent human T cell line, we defined a T lineage-specific molecule, termed Ta1, that is expressed strongly on activated T lymphocytes of both the T4 and T8 subsets, as well as on T cell lines and clones, but only weakly on a fraction of resting T cells. SDS-PAGE analysis of immunoprecipitates from 125I-labeled, activated T cells demonstrates a single major band of apparent m.w. 105 KD under both reducing and nonreducing conditions. Unlike anti-IL 2 receptor antibodies, anti-Ta1 does not inhibit T cell proliferative responses to mitogen, antigen, or IL 2-containing medium. Moreover, anti-Ta1 has no effect on T cell-mediated cytotoxicity. Ta1 appears to be a novel human T cell-specific activation antigen that may serve as a useful marker of T cell activation in human disease.

  19. Nuclear safety regulation on nuclear safety equipment activities in relation to human and organizational factors

    International Nuclear Information System (INIS)

    Li Tianshu

    2013-01-01

    Based on years of knowledge in nuclear safety supervision and experience of investigating and dealing with violation events in repair welding of DFHM, this paper analyzes major faults in manufacturing and maintaining activities of nuclear safety equipment in relation to human and organizational factors. It could be deducted that human and organizational factors has definitely become key features in the development of nuclear energy and technology. Some feasible measures to reinforce supervision on nuclear safety equipment activities have also been proposed. (author)

  20. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...... an endothelial cell cDNA library using the polymerase chain reaction (PCR) and oligonucleotide primers corresponding to the DNA sequence of the receptor cloned from transformed human fibroblasts (Roldan et al, EMBO J 9:467, 1990). The size of the cDNA (approximately 1,054 base pairs, bp) and the presence...