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Sample records for activates human myometrium

  1. 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 mRNA...

  2. Ghrelin in the human myometrium

    LENUS (Irish Health Repository)

    O'Brien, Margaret

    2010-05-28

    Abstract Background Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1\\/3 (PC1\\/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. Methods mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of β-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. Results We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1\\/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1\\/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1\\/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while β-Estradiol treatment increased GHS-R1 expression. Conclusions Ghrelin processing occurred in the human

  3. Ghrelin in the human myometrium.

    LENUS (Irish Health Repository)

    O'Brien, Margaret

    2010-01-01

    BACKGROUND: Ghrelin is a 28-amino acid octanolyated peptide, synthesised primarily in the stomach. It stimulates growth hormone release, food intake and exhibits many other diverse effects. Our group have previously determined that ghrelin inhibited human contractility in vitro. The aim of this study therefore, was to investigate the expression of ghrelin, its receptor, the growth hormone secretagogue receptor type 1 (GHS-R1), ghrelin O-acyltransferase (GOAT) which catalyses ghrelin octanoylation, prohormone convertase 1\\/3 (PC1\\/3) responsible for pro-ghrelin processing, in human myometrium, during pregnancy prior to labour, during labour and in the non-pregnant state. Modulation of ghrelin and ghrelin receptor expression in cultured myometrial cells was also investigated. METHODS: mRNA and protein were isolated from human myometrium and the myometrial smooth muscle cell line hTERT-HM; and real-time fluorescence RT-PCR, western blotting and fluorescence microscopy performed. The effects of beta-Estradiol and bacterial lipopolysaccharide (LPS) on hTERT-HM gene expression were evaluated by western blotting. RESULTS: We have reported for the first time the expression and processing of ghrelin, GHS-R1, GOAT and PC1\\/3 expression in human myometrium, and also the down-regulation of ghrelin mRNA and protein expression during labour. Furthermore, GHS-R1 protein expression significantly decreased at labour. Myometrial GOAT expression significantly increased during term non-labouring pregnancy in comparison to both non-pregnant and labouring myometrium. Mature PC1\\/3 protein expression was significantly decreased at term pregnancy and labour in comparison to non-pregnant myometrium. Ghrelin, GHS-R1, GOAT and PC1\\/3 mRNA and protein expression was also detected in the hTERT-HM cells. Ghrelin protein expression decreased upon LPS treatment in these cells while beta-Estradiol treatment increased GHS-R1 expression. CONCLUSIONS: Ghrelin processing occurred in the human

  4. Expression of stretch-activated two-pore potassium channels in human myometrium in pregnancy and labor.

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    Iain L O Buxton

    Full Text Available BACKGROUND: We tested the hypothesis that the stretch-activated, four-transmembrane domain, two pore potassium channels (K2P, TREK-1 and TRAAK are gestationally-regulated in human myometrium and contribute to uterine relaxation during pregnancy until labor. METHODOLOGY: We determined the gene and protein expression of K2P channels in non-pregnant, pregnant term and preterm laboring myometrium. We employed both molecular biological and functional studies of K2P channels in myometrial samples taken from women undergoing cesarean delivery of a fetus. PRINCIPAL FINDINGS: TREK-1, but not TREK-2, channels are expressed in human myometrium and significantly up-regulated during pregnancy. Down-regulation of TREK-1 message was seen by Q-PCR in laboring tissues consistent with a role for TREK-1 in maintaining uterine quiescence prior to labor. The TRAAK channel was unregulated in the same women. Blockade of stretch-activated channels with a channel non-specific tarantula toxin (GsMTx-4 or the more specific TREK-1 antagonist L-methionine ethyl ester altered contractile frequency in a dose-dependent manner in pregnant myometrium. Arachidonic acid treatment lowered contractile tension an effect blocked by fluphenazine. Functional studies are consistent with a role for TREK-1 in uterine quiescence. CONCLUSIONS: We provide evidence supporting a role for TREK-1 in contributing to uterine quiescence during gestation and hypothesize that dysregulation of this mechanism may underlie certain cases of spontaneous pre-term birth.

  5. Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

    LENUS (Irish Health Repository)

    Fanning, Rebecca A

    2013-01-05

    The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

  6. Effect of isoproterenol on uptake of calcium-45 by pregnant human and rat myometrium.

    Science.gov (United States)

    Hodgson, B J

    1976-05-01

    Rat and human myometria contract is response to substitution of external Na+ with Li+. This contraction was accompanied by elevation of 45Ca uptake in rat but not human uterus. The lanthanum technique failed to demonstrate elevation of cellular 45Ca in human myometrium by Li+ substitution. It also failed to demonstrate reduction of Li-elevated 45Ca uptake by isoproterenol or drugs considered to inhibit calcium influx, in rat myometrium although these drugs prevented Li-induced contraction. In human myometrium, isoproterenol increased 45Ca uptake. This probably represents increased extracellular calcium binding. Isoproterenol relaxed depolarized human myometrium provided that the external calcium had been removed for 15 minutes.

  7. Stereology of human myometrium in pregnancy: influence of maternal body mass index and age.

    LENUS (Irish Health Repository)

    Sweeney, Eva M

    2013-04-01

    Knowledge of the stereology of human myometrium in pregnancy is limited. Uterine contractile performance may be altered in association with maternal obesity and advanced maternal age. The aim of this study was to investigate the stereology of human myometrium in pregnancy, and to evaluate a potential influence of maternal body mass index (BMI) and age.

  8. Correlation between selective inhibition of the cyclic nucleotide phosphodiesterases and the contractile activity in human pregnant myometrium near term.

    Science.gov (United States)

    Leroy, M J; Cedrin, I; Breuiller, M; Giovagrandi, Y; Ferre, F

    1989-01-01

    The present study was carried out to determine the ability of various pharmacological agents to selectively inhibit each cytosolic form of phosphodiesterase isolated from the longitudinal layer of human myometria near term. Among the drugs tested, zaprinast specifically inhibits the first form of PDE which hydrolyses both substrates (cAMP and cGMP) and is stimulated by the Ca2+-calmodulin complex. A second form of PDE specific for cAMP hydrolysis and Ca2+-calmodulin insensitive is only present during pregnancy. Rolipram is the most potent and selective inhibitor of this second form. It is also the most efficient compound to inhibit in vitro the spontaneous contractions of near term myometria. The double effect of rolipram suggests an important role of the second form of PDE in the mechanisms of contractility during the pregnancy. In addition rolipram or other derivatives might be of a therapeutic interest in the prevention of prematurity in so far as they are devoid of undesirable maternal and fetal side effects.

  9. Phasic phosphorylation of caldesmon and ERK 1/2 during contractions in human myometrium.

    Science.gov (United States)

    Paul, Jonathan; Maiti, Kaushik; Read, Mark; Hure, Alexis; Smith, Julia; Chan, Eng-Cheng; Smith, Roger

    2011-01-01

    Human myometrium develops phasic contractions during labor. Phosphorylation of caldesmon (h-CaD) and extracellular signal-regulated kinase 1/2 (ERK 1/2) has been implicated in development of these contractions, however the phospho-regulation of these proteins is yet to be examined during periods of both contraction and relaxation. We hypothesized that protein phosphorylation events are implicated in the phasic nature of myometrial contractions, and aimed to examine h-CaD and ERK 1/2 phosphorylation in myometrium snap frozen at specific stages, including; (1) prior to onset of contractions, (2) at peak contraction and (3) during relaxation. We aimed to compare h-CaD and ERK 1/2 phosphorylation in vitro against results from in vivo studies that compared not-in-labor (NIL) and laboring (L) myometrium. Comparison of NIL (n = 8) and L (n = 8) myometrium revealed a 2-fold increase in h-CaD phosphorylation (ser-789; P = 0.012) during onset of labor in vivo, and was associated with significantly up-regulated ERK2 expression (P = 0.022), however no change in ERK2 phosphorylation was observed (P = 0.475). During in vitro studies (n = 5), transition from non-contracting tissue to tissue at peak contraction was associated with increased phosphorylation of both h-CaD and ERK 1/2. Furthermore, tissue preserved at relaxation phase exhibited diminished levels of h-CaD and ERK 1/2 phosphorylation compared to tissue preserved at peak contraction, thereby producing a phasic phosphorylation profile for h-CaD and ERK 1/2. h-CaD and ERK 1/2 are phosphorylated during myometrial contractions, however their phospho-regulation is dynamic, in that h-CaD and ERK 1/2 are phosphorylated and dephosphorylated in phase with contraction and relaxation respectively. Comparisons of NIL and L tissue are at risk of failing to detect these changes, as L samples are not necessarily preserved in the midst of an active contraction.

  10. Poor spontaneous and oxytocin-stimulated contractility in human myometrium from postdates pregnancies.

    Directory of Open Access Journals (Sweden)

    Sarah Arrowsmith

    Full Text Available Prolongation of pregnancy i.e. going more than 10 days over the estimated due date, complicates up to 10% of all pregnancies and is associated with increased risk to both mother and fetus. Despite the obvious need for contractions of the uterus to end pregnancy, there have been no studies directly examining the role of uterine smooth muscle, myometrium, in the aetiology of prolonged pregnancy. This study tested the hypothesis that the intrinsic contractile characteristics of myometrium taken from women with prolonged pregnancy (>41 weeks and 3 days was reduced compared to those delivering at term (39-41 weeks. We recruited women undergoing Caesarean Section (CS delivery either pre-labour (n = 27 or in labour (n = 66 at term or postdates. The contractile ability of the postdates myometrium, whether spontaneous or elicited by oxytocin or high-K solution, was significantly reduced compared to term myometrium. These differences remained when adjusted for parity and other maternal characteristics. The findings remained significant when expressed per cross sectional area. Histological examination revealed no differences between the two groups. The contractile differences were however related to intracellular Ca transients suggesting an effect of [Ca] on reduced force production in the postdates group. In summary, myometrium from prolonged pregnancies contracts poorly in vitro even when stimulated with oxytocin and in active labour. Responses to high K(+ and measurements of Ca suggest that alterations in excitation contraction coupling, rather than any histological changes of the myometrium, may underlie the differences between term and postdates myometrium. We show that postdates pregnancy is associated with poor myometrial activity and suggest that this may contribute to increased myometrial quiescence and hence, prolonged gestation.

  11. Analysis of Maxi-K alpha subunit splice variants in human myometrium

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    Morrison John J

    2004-09-01

    Full Text Available Abstract Background Large-conductance, calcium-activated potassium (Maxi-K channels are implicated in the modulation of human uterine contractions and myometrial Ca2+ homeostasis. However, the regulatory mechanism(s governing the expression of Maxi-K channels with decreased calcium sensitivity at parturition are unclear. The objectives of this study were to investigate mRNA expression of the Maxi-K alpha subunit, and that of its splice variants, in human non-pregnant and pregnant myometrium, prior to and after labour onset, to determine whether altered expression of these splice variants is associated with decreased calcium sensitivity observed at labour onset. Methods Myometrial biopsies were obtained at hysterectomy (non-pregnant, NP, and at Caesarean section, at elective (pregnant not-in-labour, PNL and intrapartum (pregnant in-labour, PL procedures. RNA was extracted from all biopsies and quantitative real-time RT-PCR was used to investigate for possible differential expression of the Maxi-K alpha subunit, and that of its splice variants, between these functionally-distinct myometrial tissue sets. Results RT-PCR analysis identified the presence of a 132 bp and an 87 bp spliced exon of the Maxi-K alpha subunit in all three myometrial tissue sets. Quantitative real-time PCR indicated a decrease in the expression of the Maxi-K alpha subunit with labour onset. While there was no change in the proportion of Maxi-K alpha subunits expressing the 87 bp spliced exon, the proportion of alpha subunits expressing the 132 bp spliced exon was significantly increased with labour onset, compared to both non-pregnant and pregnant not-in-labour tissues. An increased proportion of 132 bp exon-containing alpha subunit variants with labour onset is of interest, as channels expressing this spliced exon have decreased calcium and voltage sensitivities. Conclusions Our findings suggest that decreased Maxi-K alpha subunit mRNA expression in human myometrium at

  12. Differential Expression of MicroRNA Species in Human Uterine Leiomyoma versus Normal Myometrium

    Science.gov (United States)

    Marsh, Erica E.; Lin, Zhihong; Yin, Ping; Milad, Magdy; Chakravarti, Debabrata; Bulun, Serdar E.

    2009-01-01

    Objective To determine whether microRNAs are differentially expressed in human leiomyoma versus matched myometrial tissue. Design Microarray with real-time PCR validation. Setting Academic medical center Patients Premenopausal subjects (n=13), who were undergoing hysterectomies for leiomyoma-related symptoms. Interventions none Main Outcome Measure Statistically differential expression of microRNAs in leiomyoma versus myometrium. Results Forty-six miRNA species were differentially expressed in leiomyoma versus normal myometrium with p-values <0.01. Of these, 19 were overexpressed whereas 27 were downregulated in leiomyomas. The fold changes ranged from 1.2 to 11.8. These findings were confirmed using real time RT-PCR for selected miRNAs (miRNAs 21, 34a, 125b, 139 and 323). Conclusions Our findings indicate that miRNAs are differentially expressed between human leiomyoma and matched myometrium. Given this differential expression, miRNAs may play a role in the pathogenesis of uterine leiomyoma and may serve as future therapeutic targets for the treatment of these tumors. PMID:17765232

  13. Prostaglandin E and F2 alpha receptors in human myometrium during the menstrual cycle and in pregnancy and labor

    Energy Technology Data Exchange (ETDEWEB)

    Giannopoulos, G.; Jackson, K.; Kredentser, J.; Tulchinsky, D.

    1985-12-15

    The binding of prostaglandins E1 and F2 alpha has been studied in the human myometrium and cervix during the menstrual cycle and in the myometrium of pregnant patients at term before and during labor. Tritium-labeled prostaglandin E1 and F2 alpha binding was saturable and reversible. Scatchard analysis of tritium-labeled prostaglandin E1 binding was linear, which suggests a single class of high-affinity binding sites with an estimated apparent equilibrium dissociation constant of 2.5 to 5.4 nmol/L and inhibitor affinities of 0.9, 273, 273, and 217 nmol/L for prostaglandins E2, A1, B1, and F2 alpha, respectively. Scatchard analysis of tritium-labeled prostaglandin F2 alpha, binding was also linear, but the affinity of these binding sites was much lower, with an average dissociation constant of 50 nmol/L and inhibitor affinities of 1.6, 2.2, and 11.2 nmol/L for prostaglandins E1, E2, and A1, respectively. In nonpregnant patients, the concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were similar in the myometrium during the proliferative and secretory phases of the menstrual cycle, but the concentration of these sites was much lower in the cervix. The concentration of the tritium-labeled prostaglandin E1 binding sites was significantly lower in the myometrium of pregnant patients at term than in the myometrium of nonpregnant patients. The concentrations and affinities of tritium-labeled prostaglandin E1 binding sites were not significantly different in the upper and lower myometrium of pregnant patients at term or in the myometrium of such patients before and during labor. The concentrations of the tritium-labeled prostaglandin F2 alpha binding sites during the menstrual cycle and in pregnancy at term were similar to those of tritium-labeled prostaglandin E1 binding sites.

  14. STIM and Orai isoform expression in pregnant human myometrium: a potential role in calcium signaling during pregnancy.

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    Evonne eChin-Smith

    2014-05-01

    Full Text Available Store-operated calcium (Ca2+ entry (SOCE can be mediated by two novel proteins, STIM/Orai. We have previously demonstrated that members of the TRPC family, putative basal and store operated calcium entry channels, are present in human myometrium and regulated by labor associated stimuli IL-1β and mechanical stretch. Although STIM and Orai isoforms (1-3 have been reported in other smooth muscle cell types, there is little known about the expression or gestational regulation of STIM and Orai expression in human myometrium. Total RNA was isolated from lower segment human myometrial biopsies obtained at caesarean section from women at the time of preterm no labor (PTNL, preterm labor (PTL, term non-labor (TNL and term with labor (TL; primary cultured human uterine smooth muscle cells, and a human myometrial cell line (hTERT-HM. STIM1-2, and Orai1-3 mRNA expression was assessed by quantitative real-time PCR. All five genes were expressed in myometrial tissue and cultured cells. Orai2 was the most abundant Orai isoform in human myometrium. Expression of STIM1-2/Orai1-3 did not alter with the onset of labor. Orai1 mRNA expression in cultured cells was enhanced by IL-1β treatment. This novel report of STIM1-2 and Orai1-3 mRNA expression in pregnant human myometrium and Orai1 regulation by IL-1β indicates a potential role for these proteins in calcium signaling in human myometrium during pregnancy.

  15. EFFECTS OF NOVEL PHOSPHODIESTERASE 4 INHIBITORS,ARIFLO AND SB242126A, ON ENDOTHELIN-1-INDUCED CONTRACTILITY OF ISOLATED HUMAN MYOMETRIUM

    Institute of Scientific and Technical Information of China (English)

    QI Hong(祁红); ZHANG Yong(张勇); CHEN Hong-zhuan(陈红专); Marie Jo LEROY; Charles ADVENIER

    2005-01-01

    Objective To investigate the effects of novel selective phosphodiesterase4 ( PDE4) inhibitors,Ariflo and SB242126A, on the endothelin-1 ( ET-1 ) - induced contractility occurring in nonpregnant human myometrium specimens. Methods Contractile responses to Ariflo and SB242126A were recorded cumulatively on isolated human longitudinal myometrium specimens obtained through surgical operations. Results Ariflo and SB242126A could inhibit both the frequency and amplitude of spontaneous contractions of myometrium (pD2 =8.6and 7. 6,n =4) and ET-1-induced contractions in a concentration-dependent manner (pD2 =7. 7 and 8. 1 ,n =5),with a potency similar to that of Rolipram. Conclusion Ariflo and SB242126A have an obvious inhibitory effect on endothelin-1-induced contractility of isolated human myometrium. The finding suggested that PDE4 inhibitors might have clinical potential in treating preterm labour and dysmenorrhoea.

  16. α-Galactosylceramide-activated murine NK1.1(+) invariant-NKT cells in the myometrium induce miscarriages in mice.

    Science.gov (United States)

    Ichikawa, Tomoko; Negishi, Yasuyuki; Shimizu, Masumi; Takeshita, Toshiyuki; Takahashi, Hidemi

    2016-08-01

    Innate immunity, which is unable to discriminate self from allo-antigens, is thought to be important players in the induction of miscarriages. Here, we show that the administration of IL-12 to syngeneic-mated C57BL/6 mice on gestation day 7.5 (Gd 7.5), drives significant miscarriages in pregnant females. Furthermore, the administration on Gd 7.5 of α-galactosylceramide (α-GalCer), which is known to activate invariant natural killer T (iNKT) cells, induced miscarriages in both syngeneic-mated C57BL/6 mice and allogeneic-mated mice (C57BL/6 (♀) × BALB/c (♂)). Surprisingly, the percentages of both DEC-205(+) DCs and CD1d-restricted NK1.1(+) iNKT cells were higher in the myometrium of pregnant mice treated i.p. with α-GalCer than in the decidua. IL-12 secreted from α-GalCer-activated DEC-205(+) DCs stimulated the secretion of cytokines, including IL-2, IL-4, IFN-γ, TNF-α, perforin, and granzyme B, from the NK1.1(+) iNKT cells in the myometrium, leading to fetal loss in pregnant mice. Finally, the i.p. administration of IL-12 and/or α-GalCer in iNKT-deficient Jα18(-/-) (Jα18 KO) mice did not induce miscarriages. This study provides a new perspective on the importance of the myometrium, rather than the decidua, in regulating pregnancy and a mechanism of miscarriage mediated by activated DEC-205(+) DCs and NK1.1(+) iNKT cells in the myometrium of pregnant mice. PMID:27198610

  17. Expression of Cyclooxygenase-2 mRNA and Identification of Its Splice Variant in Human Myometrium Obtained from Women in Labor

    Institute of Scientific and Technical Information of China (English)

    HUANG Yinping; WAN Jingyuan; YE Duyun; WU Ping; HUANG Yanjun; ZHANG Li; ZHOU Xiaoyan; HUANG Yunfeng; YUAN Ping; ZHANG Daijuan

    2005-01-01

    In order to investigate the expression of cyclooxygenase-2 (COX-2) in human lower segments of myometrium obtained from women in labor and those not in labor and identify the splicing variant of COX-2, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to detect the expression of COX-2. The primers were designed and synthesized according to the sequence of rat COX-2 splice variant which was discovered firstly by us. Then the splicing variant of COX-2 in human myometrium from woman in labor was identified, cloned into vector and sequenced. The results showed that the expression of COX-2 mRNA was lower in human myometrium obtained from women who were not in labor than that in labor women and a new band of COX-2 was obtained in myometrium from labor woman. The fragment included an unspliced intron, which pitched between exons 7 and 8. It was suggested that COX-2 gene was not only expressed highly in human myometrium from woman in labor, but also produced splicing variant by alternative splicing.

  18. Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.

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    Xing-Ji You

    Full Text Available BACKGROUND: Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2S has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2S produced locally in the control of uterine contractility during labour is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-γ-lyase (CSE and cystathionine-β-synthetase (CBS, the principle enzymes responsible for H(2S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H(2S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10(-7-10(-2 mol/L, a precursor of H(2S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10(-3 mol/L increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips. CONCLUSION/SIGNIFICANCE: H(2S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H(2S synthetic enzymes is down-regulated during labour, suggesting that H(2S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.

  19. Binding of epidermal growth factor and insulin-like growth factor I in human myometrium and leiomyomata

    International Nuclear Information System (INIS)

    Samples of uterine myometrium and leiomyoma from 11 women were analyzed for the presence of epidermal growth factor receptors and insulin-like growth factor I receptors. In addition, the content of soluble insulin-like growth factor binding protein (IGF-BP/PP12) was measured in the tissue cytosols. Cell membrane preparations of myoma tissue bound significantly more insulin-like growth factor I than did those of adjacent normal myometrium, whereas myoma tissue bound less epidermal growth factor than did the normal myometrium. The differences in both insulin-like growth factor I and epidermal growth factor binding were due to changes in receptor concentration rather than to alterations in receptor affinity. Neither myoma nor myometrial tissue contained detectable levels of insulin-like growth factor binding protein. The changes in epidermal growth factor and insulin-like growth factor I binding to the myometrium may play a role in the pathogenesis of uterine leiomyomata

  20. Expression of gastrin-releasing peptide is increased by prolonged stretch of human myometrium, and antagonists of its receptor inhibit contractility.

    Science.gov (United States)

    Tattersall, Mark; Cordeaux, Yolande; Charnock-Jones, D Stephen; Smith, Gordon C S

    2012-05-01

    Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. The aim of this study was to identify factors that mediate the effect of stretch on human myometrium.Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or a 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Tissue held at tonic stretch with the 2.4 g mass for either 24 or 65 h showed increased potassium chloride (KCl)-induced and oxytocin-induced contractility compared with that held with the 0.6 g mass. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP mRNA by stretch was confirmed in a separate series of 10 samples using quantitative RT-PCR (qRT-PCR) (2.8-fold, P =0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 2 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of a further 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h, respectively) significantly reduced KCl- and oxytocin-induced contractility.Tonic stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium with GRP receptor antagonists attenuates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy.

  1. Slit2 is decreased after spontaneous labour in myometrium and regulates pro-labour mediators.

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    Lim, Ratana; Liong, Stella; Barker, Gillian; Lappas, Martha

    2014-12-01

    Preterm birth, a global healthcare problem, is commonly associated with inflammation. As Slit2 plays an emerging role in inflammation, the purpose of this study was to determine the effect of Slit2 on labour mediators in human gestational tissues. Slit2 mRNA and protein expression were assessed using qRT-PCR and immunohistochemistry in foetal membranes and myometrium obtained before and after labour. Slit2 silencing was achieved using siRNA in primary myometrial cells. Pro-inflammatory and pro-labour mediators were evaluated by qRT-PCR, ELISA and gelatin zymography. Slit2 mRNA and protein expression were found to be significantly lower in myometrium after labour onset. There was no effect of term or preterm labour on Slit2 expression in foetal membranes. Slit2 mRNA expression was decreased in myometrium treated with LPS and IL-1β. Slit2 siRNA in myometrial cells increased IL-1β-induced pro-inflammatory cytokine gene expression and release (IL-6 and IL-8), COX-2 expression and prostaglandin PGE2 and PGF2α release, and MMP-9 gene expression and pro MMP-9 release. There was no effect of Slit2 siRNA on IL-1β-induced NF-κB transcriptional activity. Our results demonstrate that Slit2 is decreased in human myometrium after labour and our knock-down studies describe an anti-inflammatory effect of Slit2 in myometrial cells.

  2. Oxytocin and vasopressin: distinct receptors in myometrium

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    Guillon, G.; Balestre, M.N.; Roberts, J.M.; Bottari, S.P.

    1987-06-01

    The binding characteristics of (/sup 3/H)oxytocin (( /sup 3/H)OT) and (/sup 3/H)lysine vasopressin (( /sup 3/H)LVP) to nonpregnant human myometrium were investigated. Binding of both radioligands was saturable, time dependent, and reversible. Whereas (/sup 3/H)OT was found to bind to a single class of sites with high affinity (Kd, 1.5 +/- 0.4 (+/- SEM) nM) and low capacity (maximum binding (Bmax), 34 +/- 6 fmol/mg protein), (/sup 3/H)LVP bound to two classes of sites, one with high affinity (Kd, 2.2 +/- 0.1 nM) and low capacity (Bmax, 198 +/- 7 fmol/mg protein) and another with low affinity (Kd, 655 +/- 209 nM) and high capacity (Bmax, 5794 +/- 1616 fmol/mg protein). The binding of the labeled peptides also displayed a marked difference in sensitivity to Mg2+ and guanine nucleotides. These differences in binding characteristics as well as the differences in potency of analogs in competing for (/sup 3/H)OT and (/sup 3/H)LVP binding indicate the presence of distinct receptors for OT and vasopressin in human myometrium. Pharmacological characterization of the high affinity binding sites for (/sup 3/H)LVP indicated that these are of the V1 subtype. Although, as suggested by others, vasopressin and OT can bind to the same sites, the presence of distinct receptors for both peptides provides an explanation for the previously reported difference in myometrial responsiveness to OT and vasopressin.

  3. Induction of expression and phosphorylation of heat shock protein B5 (CRYAB) in rat myometrium during pregnancy and labour.

    Science.gov (United States)

    Nicoletti, J G; White, B G; Miskiewicz, E I; MacPhee, D J

    2016-07-01

    During pregnancy the myometrium undergoes a programme of differentiation induced by endocrine, cellular, and biophysical inputs. Small heat shock proteins (HSPs) are a family of ten (B1-B10) small-molecular-weight proteins that not only act as chaperones, but also assist in processes such as cytoskeleton rearrangements and immune system activation. Thus, it was hypothesized that HSPB5 (CRYAB) would be highly expressed in the rat myometrium during the contractile and labour phases of myometrial differentiation when such processes are prominent. Immunoblot analysis revealed that myometrial CRYAB protein expression significantly increased from day (D) 15 to D23 (labour; P<0.05). In correlation with these findings, serine 59-phosphorylated (pSer59) CRYAB protein expression significantly increased from D15 to D23, and was also elevated 1-day post-partum (P<0.05). pSer59-CRYAB was detected in the cytoplasm of myocytes within both uterine muscle layers mid- to late-pregnancy. In unilaterally pregnant rats, pSer59-CRYAB protein expression was significantly elevated in the gravid uterine horns at both D19 and D23 of gestation compared with non-gravid horns. Co-immunolocalization experiments using the hTERT-human myometrial cell line and confocal microscopy demonstrated that pSer59-CRYAB co-localized with the focal adhesion protein FERMT2 at the ends of actin filaments as well as with the exosomal marker CD63. Overall, pSer59-CRYAB is highly expressed in myometrium during late pregnancy and labour and its expression appears to be regulated by uterine distension. CRYAB may be involved in the regulation of actin filament dynamics at focal adhesions and could be secreted by exosomes as a prelude to involvement in immune activation in the myometrium. PMID:27107034

  4. Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones.

    Science.gov (United States)

    Yin, Zongzhi; Sada, Alaa A; Reslan, Ossama M; Narula, Neha; Khalil, Raouf A

    2012-07-01

    Normal pregnancy is associated with uterine relaxation to accommodate the stretch imposed by the growing fetus; however, the mechanisms underlying the relationship between pregnancy-associated uterine stretch and uterine relaxation are unclear. We hypothesized that increased uterine stretch during pregnancy is associated with upregulation of matrix metalloproteinases (MMPs), which in turn cause inhibition of myometrium contraction and promote uterine relaxation. Uteri from virgin, midpregnant (day 12), and late-pregnant rats (day 19) were isolated, and myometrium strips were prepared for measurement of isometric contraction and MMP expression and activity using RT-PCR, Western blot analysis, and gelatin zymography. Oxytocin caused concentration-dependent contraction of myometrium strips that was reduced in mid- and late-pregnant rats compared with virgin rats. Pretreatment with the MMP inhibitors SB-3CT (MMP-2/MMP-9 Inhibitor IV), BB-94 (batimastat), or Ro-28-2653 (cipemastat) enhanced contraction in myometrium of pregnant rats. RT-PCR, Western blot analysis, and gelatin zymography demonstrated increased mRNA expression, protein amount, and activity of MMP-2 and MMP-9 in myometrium of late-pregnant>midpregnant>virgin rats. Prolonged stretch of myometrium strips of virgin rats under 8 g basal tension for 18 h was associated with reduced contraction and enhanced expression and activity of MMP-2 and MMP-9, which were reversed by MMP inhibitors. Concomitant treatment of stretched myometrium of virgin rats with 17β-estradiol (E2), progesterone (P4), or E2+P4 was associated with further reduction in contraction and increased MMP expression and activity. MMP-2 and MMP-9 caused significant reduction of oxytocin-induced contraction of myometrium of virgin rat. Thus, normal pregnancy is associated with reduced myometrium contraction and increased MMPs expression and activity. The results are consistent with the possibility that myometrium stretch and concomitant increase in

  5. A comparison of the contractile properties of myometrium from singleton and twin pregnancies.

    Directory of Open Access Journals (Sweden)

    Peter Turton

    Full Text Available OBJECTIVE: Over half of twin pregnancies in US and UK deliver prematurely but the reasons for this are unclear. The contractility of myometrium from twin pregnancies has not been directly investigated. The objective of this research was to determine if there are differences in the contractile activity and response to oxytocin, between myometrium from singleton and twin pregnancies, across a range of gestational ages. Furthermore, we wished to determine if contractile activity correlates with increasing level of stretch, using neonatal birth weights as a marker of uterine stretch. METHODS: This was an in vitro, laboratory based study of myometrial contractility in women pregnant with one or two babies, using biopsies obtained from non-labouring women undergoing Caesarean section. Spontaneous, oxytocin-stimulated and depolarization induced contractile activity was compared. RESULTS: Direct measurements of myometrial contractility under controlled conditions show that the frequency of contractions and responses to oxytocin are significantly increased in twins compared to singletons. The duration of contraction however was significantly reduced. We find that contractile activity correlates with increasing levels of stretch, using neonatal birth weights as a surrogate for uterine stretch, with response to oxytocin being significantly positively correlated with birth weight. CONCLUSIONS: We have found significant differences in contractile properties between myometrium from singleton and twin pregnancies and that increasing uterine stretch can alter the contractile properties of myometrium. We discuss the implication of these findings to preterm delivery and future studies.

  6. Effects of levobupivacaine and bupivacaine on rat myometrium

    Institute of Scientific and Technical Information of China (English)

    LI Zi-gang; ZHOU Liang; TANG Hui-fang

    2006-01-01

    Objective: To study the effect of levobupivacaine and bupivacaine on the contractility of isolated uterine muscle strips from pregnant and non-pregnant female rats. Methods: Full-thick myometrial strips were prepared from 18- to 21-day pregnant (n=g) and non-pregnant rats (n=7). After contractions became regular, strips were exposed to cumulative concentrations of the two drugs from 10-8 to 10-4 mol/L, amplitude and frequency of the uterine contraction was recorded. Results: Two local anesthetics caused a concentration dependent inhibition on contractility of myometrial strips from pregnant and non-pregnant rats. In the myometrium from non-pregnant rats, -logIC50 of levobupivacaine and bupivacaine were 4.85 and 4.25 respectively. In the myometrium from pregnant rats, similar concentrations of levobupivacaine and bupivacaine were observed, -logIC50 were 2.7 and 2.9respectively. Levobupivacaine produced an increase in amplitude of contractions, while bupivacaine showed an increased trend in frequency. Conclusion: These results demonstrate that levobupivacaine and bupivacaine may inhibit myometrium contractility.The inhibitory effect of levobupivacaine or bupivacaine is not enhanced by gestation in rat. Levobupivacaine may have more positive influence than bupivacaine in pregnant myometrium.

  7. Application of electron spin resonance for evaluation of the level of free radicals in the myometrium in full-term pregnancy with normal labour and uterine inertia

    Indian Academy of Sciences (India)

    V V Zyrianov; A Ye Sumovskaya; A A Shostak

    2003-02-01

    In order to identify and quantify free radicals in the tissues of patients with normal physiological and pathological states of births, we developed a method to evaluate the amount of free radicals in myometrium of subplacental area and from body of uterus, using electron spin resonance spectroscopy. Analysis of the concentration of free radicals in the myometrium in full-term pregnancy with normal labour and during uterine inertia was studied. The activities of Ca2+-ATPase, cytochrome oxidase and succinate dehydrogenase in samples of these tissues were tested too. Low free radical concentrations in these tissues were associated with disturbances in contractile activity of myometrium along with reduction of Ca2+-ATPase, cytochrome oxidase and succinate dehydrogenase activity. There proved to be an association between the level of free radicals in the tissues and alteration in the physiological processes.

  8. 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.

  9. The contribution of Kv7 channels to pregnant mouse and human myometrial contractility.

    Science.gov (United States)

    McCallum, Laura A; Pierce, Stephanie L; England, Sarah K; Greenwood, Iain A; Tribe, Rachel M

    2011-03-01

    Premature birth accounts for approximately 75% of neonatal mortality and morbidity in the developed world. Despite this, methods for identifying and treating women at risk of preterm labour are limited and many women still present in preterm labour requiring tocolytic therapy to suppress uterine contractility. The aim of this study was to assess the utility of Kv7 channel activators as potential uterine smooth muscle (myometrium) relaxants in tissues from pregnant mice and women. Myometrium was obtained from early and late pregnant mice and from lipopolysaccharide (LPS)-injected mice (day 15 of gestation; model of infection in pregnancy). Human myometrium was obtained at the time of Caesarean section from women at term (38-41 weeks). RT-PCR/qRT-PCR detected KCNQ and KCNE expression in mouse and human myometrium. In mice, there was a global suppression of all KCNQ isoforms, except KCNQ3, in early pregnancy (n= 6, P flupirtine (20 μM, Kv7 channel activators) caused profound myometrial relaxation (P < 0.05). In summary, Kv7 activators suppressed myometrial contraction and KCNQ gene expression was sustained throughout gestation, particularly at term. Consequently, activation of the encoded channels represents a novel mechanism for treatment of preterm labour. PMID:20132415

  10. Mechanical stretch regulates hypertrophic phenotype of the myometrium during pregnancy.

    Science.gov (United States)

    Shynlova, Oksana; Kwong, Ruth; Lye, Stephen J

    2010-01-01

    The adaptive growth of the uterus is a critical event that involves changes in cellular phenotypes throughout pregnancy. In early pregnancy, uterine growth is due to hyperplasia of uterine smooth muscle cells (SMCs) within the myometrium; however, the major component of myometrial growth occurs after mid-gestation. This study sought to test the hypothesis that increase in myometrial growth seen during late pregnancy is due to SMC hypertrophy caused by mechanical stretch of uterine tissue by a growing fetus(es) by providing direct measurements of individual SMC size. We employed a stereological approach to calculate the average cell volumes of uterine myocytes through diameter measurements using the Stereoinvestigator statistical software. Uterine tissues were collected from nonpregnant Wistar rats, as well as from gravid and nongravid horns of unilaterally pregnant animals on gestational days (d) 8 (early gestation), 14 (mid-gestation), 19 (late gestation), 22 (term), and 4 days post partum. Anti-caveolin-1 immunostaining was used to clearly delineate SMC boundaries. The stereological analysis revealed that the dramatic increase in myometrial growth seen during late gestation (d19-22) is due to a threefold increase in the size of uterine myocytes. A significant increase in SMC volumes was detected in the gravid uterine horn as compared with the corresponding empty horn of unilateral term pregnant animals (day 22, mean cell volume 1114 vs 361 microm(3), P<0.05), indicating the effect of uterine occupancy. The restriction of the hypertrophy to cells within the gravid horn suggests that it may be a response to the biological mechanical stretch of uterine walls by the growing fetus(es) and placenta(s).

  11. Consolidated Human Activities Database (CHAD)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Consolidated Human Activity Database (CHAD) contains data obtained from human activity studies that were collected at city, state, and national levels. CHAD is...

  12. 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. .

  13. A Giant Gartner Duct Cyst Originating from the Uterine Cervix and Adjacent Myometrium: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Hui; Hwang, Seong Su; Park, Soo Youn [Catholic University, Seoul (Korea, Republic of)

    2008-11-15

    Gartner duct cysts are relatively common congenital cysts in the anterolateral wall of the vagina. Most are small (less than 2 cm) and asymptomatic, but larger cysts may cause problems. We report a rare case of a giant Gartner duct cyst (7 cm) originating from the right lateral portion of the uterine cervix and adjacent myometrium. It appeared as an exophytic multiseptated cystic mass containing different density fluids on CT

  14. Phasic oscillations of extracellular potassium (K(o in pregnant rat myometrium.

    Directory of Open Access Journals (Sweden)

    Roger C Young

    Full Text Available K-sensitive microelectrodes were used to measure K(+ within the extracellular space (K(o of pregnant rat myometrium. Contractile activity was monitored by measuring either force or bioelectrical signals. Single and double-barreled electrodes were used. Double-barreled electrodes allowed monitoring of electrical activity 15 microns from the site of K(o measurement. From double-barreled electrode experiments, the bioelectrical burst started first, and then K(o began to rise 0.6 ± 0.1 seconds later. This delay indicates that K(+ leaves the cells in response to local electrical activity rather than vice versa. Four control experiments were performed to assess the influence of electrical artifacts caused by tissue motion on K(o values. When observed, artifacts were negative and transient, and hence would result in an underestimation of K(o rises. Artifacts were minimized when tissue motion was minimized by fixing the tissue at both ends. At 37°C, 7 single barreled experiments and 45 contractions were analyzed. Resting K(o was within 1 mM of bath K(+ (5 mM at the beginning and end of the experiments. K(o rose during the contraction, fell after the completion of the contraction, and normalized before the next contraction began. Peak K(o values observed during force production were 18.8 ± 5.9 mM, a value high enough to modulate tissue-level electrical activity. K(o required 15.7 ± 2.8 seconds to normalize halfway (t50. Six experiments expressing 38 contractions were performed at 24°C. The contraction period was longer at 24°C. Values for peak K(o (26.2 ± 9.9 mM and t50 (29.8±16.2 sec were both larger than at 37°C (p<0.0003 for both. The direct relationships between peak K(o, t50 and the contraction period, suggest elevations in K(o may modulate contraction frequency. The myometrial interstitial space appears to be functionally important, and K(o metabolism may participate in cell-cell interactions.

  15. Methanol extracts of Hamelia patens containing oxindole alkaloids relax KCl-induced contraction in rat myometrium.

    Science.gov (United States)

    Reyes-Chilpa, Ricardo; Rivera, Jesús; Oropeza, Martha; Mendoza, Pilar; Amekraz, Badia; Jankowski, Christopher; Campos, Maria

    2004-10-01

    Hamelia patens JAQC. (Rubiaceae) is a medicinal bush widely distributed in tropical areas of the American continent. It is used in Mexican Traditional Medicine for the treatment of menstrual disorders, therefore suggesting that its chemical constituents may have some effect on myometrium contractility. Physiological effects might differ due to quantitative variations in the content of alkaloids arising from its wide geographical distribution. To test this hypothesis, the content of oxindole alkaloids in methanol extracts of five different samples collected in Mexico was quantified by GC-MS. Each extract was assayed on contractility of estrogen-primed rat myometrium. Variations in the content of alkaloids were observed among the different samples. All samples relaxed in a concentration-dependent manner the high KCl-induced contraction in rat myometrium. Those which lack rumberine and/or maruquine displayed a higher relaxant effect than samples containing them, suggesting that these alkaloids might counteract the effects of isopteropodine. However, in contrast with verapamil, Hamelia patens metanol extracts are poor relaxants.

  16. Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women.

    Directory of Open Access Journals (Sweden)

    Gemma C Sharp

    Full Text Available An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes and apparent lower expression at 801 probes (789 genes (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP <0.05. Although half of the women in the labouring group had received pharmaceutical treatment to induce or augment labour, sensitivity analysis suggested that this did not confound our results. In agreement with previous studies, functional analysis suggested that labour was characterised by an increase in the expression of inflammatory genes and network analysis suggested a strong neutrophil signature. Our analysis also suggested that labour is characterised by a decrease in the expression of muscle-specific processes, which has not been explicitly discussed previously. We validated these findings through the first formal meta-analysis of raw data from previous experiments and we hypothesise that this represents a change in the

  17. Human telomerase activity regulation

    OpenAIRE

    Wojtyla, Aneta; Gladych, Marta; Rubis, Blazej

    2010-01-01

    Telomerase has been recognized as a relevant factor distinguishing cancer cells from normal cells. Thus, it has become a very promising target for anticancer therapy. The cell proliferative potential can be limited by replication end problem, due to telomeres shortening, which is overcome in cancer cells by telomerase activity or by alternative telomeres lengthening (ALT) mechanism. However, this multisubunit enzymatic complex can be regulated at various levels, including expression control b...

  18. Retracted: Differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids.

    Science.gov (United States)

    2015-10-01

    The above article, published online on 20 December 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Professor L Popescu and John Wiley and Sons Ltd. The retraction has been requested by the University of Florida, Office of Research, in response to their investigation which concluded fabrication of data in Figures 2, 3 and 4. Reference Pan Q, Luo X, Chegini N. Retracted: differential expression of microRNAs in myometrium and leiomyomas and regulation by ovarian steroids. J Cell Mol Med 12: 227-240. Doi: 10.1111/j.1582-4934.2007.00207.x.

  19. Amylase activity in human bile.

    Science.gov (United States)

    Donaldson, L A; Joffe, S N; McIntosh, W; Brodie, M J

    1979-03-01

    The mean amylase level in 42 human bile samples was 154 IU/l and there was no significant difference in the amylase activity of 32 paired serum and bile samples. Estimation of the amylase thermolability of bile showed it to be similar to that of serum. This suggests that the amylase activity in bile may have filtered through the liver from the hepatic circulation rather than refluxed from the pancreatic duct. The presence of amylase in human bile provides further evidence that the liver might have a role in the regulation of serum amylase.

  20. Intrinsic Patterns of Human Activity

    Science.gov (United States)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  1. Dynamic contrast-enhanced MR imaging of endometrial cancer. Optimizing the imaging delay for tumour-myometrium contrast

    International Nuclear Information System (INIS)

    To investigate the optimal imaging delay time of dynamic contrast-enhanced magnetic resonance (MR) imaging in women with endometrial cancer. This prospective single-institution study was approved by the institutional review board, and informed consent was obtained from the participants. Thirty-five women (mean age, 54 years; age range, 29-66 years) underwent dynamic contrast-enhanced MR imaging with a temporal resolution of 25-40 seconds. The signal intensity difference ratios between the myometrium and endometrial cancer were analyzed to investigate the optimal imaging delay time using single change-point analysis. The optimal imaging delay time for appropriate tumour-myometrium contrast ranged from 31.7 to 268.1 seconds. The median optimal imaging delay time was 91.3 seconds, with an interquartile range of 46.2 to 119.5 seconds. The median signal intensity difference ratios between the myometrium and endometrial cancer were 0.03, with an interquartile range of -0.01 to 0.06, on the pre-contrast MR imaging and 0.20, with an interquartile range of 0.15 to 0.25, on the post-contrast MR imaging. An imaging delay of approximately 90 seconds after initiating contrast material injection may be optimal for obtaining appropriate tumour-myometrium contrast in women with endometrial cancer. (orig.)

  2. 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.

  3. Surfactant Protein-A as an Anti-Inflammatory Component in the Amnion: Implications for Human Pregnancy1

    OpenAIRE

    Lee, Deug-Chan; Romero, Roberto; Kim, Chong Jai; Chaiworapongsa, Tinnakorn; Tarca, Adi L.; Lee, JoonHo; Suh, Yeon-Lim; Mazaki-Tovi, Shali; Vaisbuch, Edi; Mittal, Pooja; Draghici, Sorin; Erez, Offer; Kusanovic, Juan Pedro; Hassan, Sonia S; Kim, Jung-Sun

    2010-01-01

    The mechanism of mouse parturition is thought to involve myometrial infiltration by amniotic fluid (AF) macrophages, activated by surfactant protein-A (SP-A). In humans, the concentration of AF SP-A decreases during labor, and no fetal macrophages are found in the myometrium after labor. Therefore, it appears that the mechanisms of labor in mice and humans are different. We investigated a potential role for SP-A in human pregnancy and parturition by examining SP-A expression patterns in AF an...

  4. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

    The overall goal of this collaborative project was to investigate the role in malignant cells of both chromosome telomeres, and telomerase, the enzyme that replicates telomeres. Telomeres are highly conserved nucleoprotein complexes located at the ends of eucaryotic chromosomes. Telomere length in somatic cells is reduced by 40--50 nucleotide pairs with every cell division due to incomplete replication of terminal DNA sequences and the absence of telomerase, the ribonucleoprotein that adds telomere DNA to chromosome ends. Although telomerase is active in cells with extended proliferative capacities, including more than 85% of tumors, work performed under this contract demonstrated that the telomeres of human cancer cells are shorter than those of paired normal cells, and that the length of the telomeres is characteristic of particular types of cancers. The extent of telomere shortening ostensibly is related to the number of cell divisions the tumor has undergone. It is believed that ongoing cell proliferation leads to the accumulation and fixation of new mutations in tumor cell lineages.Therefore, it is not unreasonable to assume that the degree of phenotypic variability is related to the proliferative history of the tumor, and therefore to telomere length, implying a correlation with prognosis. In some human tumors, short telomeres are also correlated with genomic instabilities, including interstitial chromosome translocation, loss of heterozygosity, and aneuoploidy. Moreover, unprotected chromosome ends are highly recombinogenic and telomere shortening in cultured human cells correlates with the formation of dicentric chromosomes, suggesting that critically short telomeres not only identify, but also predispose, cells to genomic instability, again implying a correlation with prognosis. Therefore, telomere length or content could be an important predictor of metastatic potential or responsiveness to various therapeutic modalities.

  5. Complement activation in experimental human malaria infection.

    NARCIS (Netherlands)

    Roestenberg, M.; McCall, M.B.B.; Mollnes, T.E.; Deuren, M. van; Sprong, T.; Klasen, I.S.; Hermsen, C.C.; Sauerwein, R.W.; Ven, A.J.A.M. van der

    2007-01-01

    The objective of this study was to investigate complement activation in uncomplicated, early phases of human malaria. Fifteen healthy volunteers were experimentally infected with Plasmodium falciparum malaria. Parasitemia and complement activation products were assessed. During blood stage parasitem

  6. Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro.

    Science.gov (United States)

    Tamarozzi, F; Wright, H L; Johnston, K L; Edwards, S W; Turner, J D; Taylor, M J

    2014-10-01

    The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll-like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane-associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N-terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan-associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose-dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism. PMID:24909063

  7. Regulation of IGF-I production and proliferation of human leiomyomal smooth muscle cells by Scutellaria barbata D. Don in vitro: isolation of flavonoids of apigenin and luteolin as acting compounds

    International Nuclear Information System (INIS)

    Scutellaria barbata D. Don (Lamiaceae) (SB) is a perennial herb, which is natively distributed throughout Korea and southern China. This herb is known in traditional Chinese Medicine as Ban-Zhi-Lian and traditional Korean medicine as Banjiryun, respectively. SB has been used as an anti-inflammatory and antitumor agent. We aimed to determine the expression of growth factor molecules for growth inhibition after treatment of SB in two different human myometrial smooth muscle cell (SMC)s and leiomyomal SMCs. Water-soluble ingredients of SB, myometrial SMCs, and the leiomyomal cell lines were used in vitro. SB significantly reduced cell numbers in culture and arrested cell proliferation, and also induced apoptosis, indicating that the presence of an intact apoptotic pathway was demonstrated in these cells by SB. Uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium. The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and leiomyomal cells with and without treatment with a water extract of SB for 3 days. IGF-I mRNA expression was significantly higher in leiomyomal cells than in myometrium cells. The IGF-I protein was more abundant in leiomyomal cells than in myometrium. When SB was treated to the cells, the IGF-I protein concentrations in myometrial and leiomyomal cells from the SB-treated cells were similar. The results indicated that IGF-I expression is probably associated with a proliferation of leiomyomal cells than myometrium. However, SB down-regulated the IGF-I expression where IGF-I contributes to the selective growth of the leiomyoma. Therefore, growth modulation of LMs by SB occurs via mechanisms dependent of apoptosis. The raw materials were extracted and subjected to functional isolation for the active molecules in the present assay systems. The five flavonoids were isolated and the chemical structures of resveratrol, baicalin, berberine, apigenin, and luteolin were

  8. Human activities affecting trace gases and climate

    International Nuclear Information System (INIS)

    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

  9. Tumor-like cystic endosalpingiosis in the myometrium: a case report and a review of the literature.

    Science.gov (United States)

    Yığıt, Seyran; Dere, Yelda; Yetımalar, Hakan; Etıt, Demet

    2014-01-01

    Endosalpingiosis is a disorder of the Mullerian system characterized by benign glands lined with tubal type epithelium and involves the peritoneum, subperitoneal tissues and retroperitoneal lymph nodes. Myometrial endosalpingiosis is very rare. A 44-year-old female presented to the hospital complaining of menorrhagia. Gynecological and radiologic examination revealed a pelvic mass 7.5 cm in diameter, suggestive of a leiomyoma with secondary cystic changes. The gross examination showed an intramural large cyst within the right fundic wall of the uterus. Microscopically, the cyst consisted of multiple micro-macro cysts lined with benign tubal epithelium. With these findings, the diagnosis was cystic endosalpingiosis. In this report, the clinicopathologic features of a cystic endosalpingiosis case located in the myometrium was presented with a review of the literature.

  10. Deep Human Parsing with Active Template Regression.

    Science.gov (United States)

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28]. PMID:26539846

  11. Deep Human Parsing with Active Template Regression.

    Science.gov (United States)

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28].

  12. Integrated Extravehicular Activity Human Research Plan: 2016

    Science.gov (United States)

    Abercromby, Andrew F. J.; Ross, Amy J.; Cupples, J. Scott; Rajulu, Sudhakar; Norcross, Jason R.; Chappell, Steven P.

    2016-01-01

    Multiple organizations within NASA and outside of NASA fund and participate in research related to extravehicular activity (EVA). In October 2015, representatives of the EVA Office, the Crew and Thermal Systems Division (CTSD), and the Human Research Program (HRP) at NASA Johnson Space Center agreed on a formal framework to improve multi-year coordination and collaboration in EVA research. At the core of the framework is an Integrated EVA Human Research Plan and a process by which it will be annually reviewed and updated. The over-arching objective of the collaborative framework is to conduct multi-disciplinary cost-effective research that will enable humans to perform EVAs safely, effectively, comfortably, and efficiently, as needed to enable and enhance human space exploration missions. Research activities must be defined, prioritized, planned and executed to comprehensively address the right questions, avoid duplication, leverage other complementary activities where possible, and ultimately provide actionable evidence-based results in time to inform subsequent tests, developments and/or research activities. Representation of all appropriate stakeholders in the definition, prioritization, planning and execution of research activities is essential to accomplishing the over-arching objective. A formal review of the Integrated EVA Human Research Plan will be conducted annually. External peer review of all HRP EVA research activities including compilation and review of published literature in the EVA Evidence Report is will also continue at a frequency determined by HRP management. Coordination with stakeholders outside of the EVA Office, CTSD, and HRP is already in effect on a study-by-study basis; closer coordination on multi-year planning with other EVA stakeholders including academia is being actively pursued. Details of the current Integrated EVA Human Research Plan are presented including description of ongoing and planned research activities in the areas of

  13. A human activity approach to User Interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    1989-01-01

    different way of thinking about the user interface. The article applies examples of real-life interfaces to support this process, but it does not include a systematic presentation of empirical results. I focus on the role of the computer application in use. Thus, it is necessary to consider human......-computer interaction and other related work conditions. I deal with human experience and competence as being rooted in the practice of the group that conducts the specific work activity. The main conclusions are: The user interface cannot be seen independently of the use activity (i.e., the professional, socially...

  14. Human telomerase: biogenesis, trafficking, recruitment, and activation.

    Science.gov (United States)

    Schmidt, Jens C; Cech, Thomas R

    2015-06-01

    Telomerase is the ribonucleoprotein enzyme that catalyzes the extension of telomeric DNA in eukaryotes. Recent work has begun to reveal key aspects of the assembly of the human telomerase complex, its intracellular trafficking involving Cajal bodies, and its recruitment to telomeres. Once telomerase has been recruited to the telomere, it appears to undergo a separate activation step, which may include an increase in its repeat addition processivity. This review covers human telomerase biogenesis, trafficking, and activation, comparing key aspects with the analogous events in other species.

  15. Clouds caused by human activities: the anthropoclouds

    Science.gov (United States)

    Mazon, Jordi; Costa, Marcel; Pino, David; Lorente, Jeroni

    2013-04-01

    The classification of clouds is based on the pioneering classification carried out by Howard (1804). In this classification, and also in the successive editions of the International Classification of Clouds published by the World Meteorological Organization (WMO, 1975, 1987) 10 basic cloud genera are included and described. In all cases, the cause that leads to the formation of clouds remains as a secondary issue. It is assumed that all of them are exclusively produced by natural mechanisms without any human intervention. However, aerosol and water vapour emissions produced by human activity may increase cloud formation having an increasing importance in the atmospheric energy budget and consequently in the earth's climate. Effectively, since the end of the Nineteenth century, human activity has been injecting large amounts of water vapour into the atmosphere, cloud condensation nuclei and hot air mainly generated in the combustion processes that under certain spatial and temporal conditions can enhance cloud formation. These anthropogenic aerosols are linked to the climate and the water cycle (Kaufman et al, 2002). The aim of this communication is to point out the anthropic origin of some clouds in the cloud classification. Several cases of the 7 basic genera cloud caused by human activities will be shown to discuss the importance of differentiating the origin of clouds in weather observations. This differentiation would improve the understanding the contribution of these clouds to climate change. To differentiate the clouds formed by human activity, we propose to use the prefix anthropo- before the scientific name (and a- before the abbreviation) in some of the 10 basic clouds defined by the International Classification of Clouds, those which could have an anthropic origin, and thus begin new data of cloud observations that could help future research to improve the effect of human activity in the troposphere.

  16. 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.

  17. 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…

  18. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    Science.gov (United States)

    To assess the potential for using saliva in pesticide biomonitoring, the consistency of cholinesterase activity in human saliva collected over time was examined. In this pilot study, saliva was collected from 20 healthy adults once per week for 5 consecutive weeks using 2 differe...

  19. Aldehyde oxidase activity in fresh human skin.

    Science.gov (United States)

    Manevski, Nenad; Balavenkatraman, Kamal Kumar; Bertschi, Barbara; Swart, Piet; Walles, Markus; Camenisch, Gian; Schiller, Hilmar; Kretz, Olivier; Ling, Barbara; Wettstein, Reto; Schaefer, Dirk J; Pognan, Francois; Wolf, Armin; Litherland, Karine

    2014-12-01

    Human aldehyde oxidase (AO) is a molybdoflavoenzyme that commonly oxidizes azaheterocycles in therapeutic drugs. Although high metabolic clearance by AO resulted in several drug failures, existing in vitro-in vivo correlations are often poor and the extrahepatic role of AO practically unknown. This study investigated enzymatic activity of AO in fresh human skin, the largest organ of the body, frequently exposed to therapeutic drugs and xenobiotics. Fresh, full-thickness human skin was obtained from 13 individual donors and assayed with two specific AO substrates: carbazeran and zoniporide. Human skin explants from all donors metabolized carbazeran to 4-hydroxycarbazeran and zoniporide to 2-oxo-zoniporide. Average rates of carbazeran and zoniporide hydroxylations were 1.301 and 0.164 pmol⋅mg skin(-1)⋅h(-1), resulting in 13 and 2% substrate turnover, respectively, after 24 hours of incubation with 10 μM substrate. Hydroxylation activities for the two substrates were significantly correlated (r(2) = 0.769), with interindividual variability ranging from 3-fold (zoniporide) to 6-fold (carbazeran). Inclusion of hydralazine, an irreversible inhibitor of AO, resulted in concentration-dependent decrease of hydroxylation activities, exceeding 90% inhibition of carbazeran 4-hydroxylation at 100 μM inhibitor. Reaction rates were linear up to 4 hours and well described by Michaelis-Menten enzyme kinetics. Comparison of carbazeran and zoniporide hydroxylation with rates of triclosan glucuronidation and sulfation and p-toluidine N-acetylation showed that cutaneous AO activity is comparable to tested phase II metabolic reactions, indicating a significant role of AO in cutaneous drug metabolism. To our best knowledge, this is the first report of AO enzymatic activity in human skin. PMID:25249692

  20. Human Activity Detection from RGBD Images

    CERN Document Server

    Sung, Jaeyong; Selman, Bart; Saxena, Ashutosh

    2011-01-01

    Being able to detect and recognize human activities is important for making personal assistant robots useful in performing assistive tasks. The challenge is to develop a system that is low-cost, reliable in unstructured home settings, and also straightforward to use. In this paper, we use a RGBD sensor (Microsoft Kinect) as the input sensor, and present learning algorithms to infer the activities. Our algorithm is based on a hierarchical maximum entropy Markov model (MEMM). It considers a person's activity as composed of a set of sub-activities, and infers the two-layered graph structure using a dynamic programming approach. We test our algorithm on detecting and recognizing twelve different activities performed by four people in different environments, such as a kitchen, a living room, an office, etc., and achieve an average performance of 84.3% when the person was seen before in the training set (and 64.2% when the person was not seen before).

  1. Scaling behavior of online human activity

    CERN Document Server

    Zhao, Zhi-Dan; Huang, Junming; Fu, Yan; Zhou, Tao; 10.1209/0295-5075/100/48004

    2013-01-01

    The rapid development of Internet technology enables human 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 dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, book, and movie rating, are comprehensively investigated by using detrended fluctuation analysis technique and multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three type medias show the similar scaling property 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 their activities (i.e., rating per unit time), we find that the scaling exponents of interevent time series in three groups are different. Hence, these results suggest the stronger long-rang...

  2. Does human activity widen the tropics?

    CERN Document Server

    Georgieva, Katya

    2008-01-01

    The progress article - Widening of the tropical belt in a changing climate - by Seidel et al. (2008) published in the first issue of Nature Geosciences, summarizes the results of several methods to determine the width of the tropical zone. All they show evidence that the tropics have been expanding over the past few decades. We confirm this widening based on one more indicator - the position of the subtropical centers of high pressure. However, we question the implication of the authors that the tropics widen in response to human activity, and suggest as a more probable cause the increasing solar activity. Consequently, we question their conclusion that this widening may continue into the future in association with anthropogenic climate change, and suggest that whether the tropics will continue widening will depend on the future evolution of solar activity rather than on anthropogenic activity.

  3. 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.

  4. 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. PMID:27480376

  5. 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.

  6. 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. PMID:25707281

  7. Transcription analysis of the myometrium of labouring and non-labouring women

    OpenAIRE

    Sharp, Gemma C.; Hutchinson, James L.; Nanette, Hibbert; Freeman, Thomas; Saunders, Philippa; Norman, Jane

    2016-01-01

    An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial...

  8. Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women

    OpenAIRE

    Sharp, Gemma C.; Hutchinson, Lawrence; Hibbert, Nannette; Freeman, Tom; Saunders, Philippa; Norman, Jane

    2016-01-01

    An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial...

  9. Physiological increases in lactate inhibit intracellular calcium transients, acidify myocytes and decrease force in term pregnant rat myometrium.

    Science.gov (United States)

    Hanley, Jacqui-Ann; Weeks, Andrew; Wray, Susan

    2015-10-15

    Lactate is increased in myometrial capillary blood from women in slow or non-progressive labour (dystocia), suggesting that it is detrimental to uterine contractions. There are, however, no studies of the effect of lactate on the myometrium. We therefore investigated its effects and mechanism of action on myometrial strips from term pregnant rats. The effects on spontaneous and oxytocin-induced contractility in response to sodium lactate and other weak acids (1-20 mM) were studied. In some experiments, simultaneous force and intracellular Ca(2+) or pH (pH(i)) were measured with Indo-1 or Carboxy-SNARF, respectively. Statistical differences were tested using non-parametric tests. Lactate significantly decreased spontaneous contractility with an EC50 of 3.9 mM. Propionate, butyrate and pyruvate also reduced contractions with similar potency. The effects of lactate were reduced in the presence of oxytocin but remained significant. Lactate decreased pH(i) and nulling the decrease in pH(i) abolished its effects. We also show that lactate inhibited Ca(2+) transients, with these changes mirroring those produced on force. If Ca(2+) entry was enhanced by depolarization (high KCl) or applying the Ca(2+) channel agonist, Bay K 4644, the effects of lactate were abolished. Taken together, these data show that lactate in the physiological range potently decreases myometrial contractility as a result of its inhibition of Ca(2+) transients, which can be attributed to the induced acidification. The present study suggests that the accumulation of extracellular lactate will reduce myometrial contractions and could therefore contribute to labour dystocia. PMID:26223765

  10. Universal activity pattern in human interactive dynamics

    CERN Document Server

    Formentin, Marco; Maritan, Amos; Zanzotto, Giovanni

    2014-01-01

    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new universal pattern for how the reactive dynamics of individuals is distributed across the set of each agent's contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We show this universal behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one's environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns constrain future models of com...

  11. 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.

  12. Towards a computational reconstruction of the electrodynamics of premature and full term human labour.

    Science.gov (United States)

    Aslanidi, O; Atia, J; Benson, A P; van den Berg, H A; Blanks, A M; Choi, C; Gilbert, S H; Goryanin, I; Hayes-Gill, B R; Holden, A V; Li, P; Norman, J E; Shmygol, A; Simpson, N A B; Taggart, M J; Tong, W C; Zhang, H

    2011-10-01

    We apply virtual tissue engineering to the full term human uterus with a view to reconstruction of the spatiotemporal patterns of electrical activity of the myometrium that control mechanical activity via intracellular calcium. The three-dimensional geometry of the gravid uterus has been reconstructed from segmented in vivo magnetic resonance imaging as well as ex vivo diffusion tensor magnetic resonance imaging to resolve fine scale tissue architecture. A late-pregnancy uterine smooth muscle cell model is constructed and bursting analysed using continuation algorithms. These cell models are incorporated into partial differential equation models for tissue synchronisation and propagation. The ultimate objective is to develop a quantitative and predictive understanding of the mechanisms that initiate and regulate labour.

  13. Loss of the repressor REST in uterine fibroids promotes aberrant G protein-coupled receptor 10 expression and activates mammalian target of rapamycin pathway

    Science.gov (United States)

    Varghese, Binny V.; Koohestani, Faezeh; McWilliams, Michelle; Colvin, Arlene; Gunewardena, Sumedha; Kinsey, William H.; Nowak, Romana A.; Nothnick, Warren B.; Chennathukuzhi, Vargheese M.

    2013-01-01

    Uterine fibroids (leiomyomas) are the most common tumors of the female reproductive tract, occurring in up to 77% of reproductive-aged women, yet molecular pathogenesis remains poorly understood. A role for atypically activated mammalian target of rapamycin (mTOR) pathway in the pathogenesis of uterine fibroids has been suggested in several studies. We identified that G protein-coupled receptor 10 [GPR10, a putative signaling protein upstream of the phosphoinositide 3-kinase–protein kinase B/AKT–mammalian target of rapamycin (PI3K/AKT–mTOR) pathway] is aberrantly expressed in uterine fibroids. The activation of GPR10 by its cognate ligand, prolactin releasing peptide, promotes PI3K–AKT–mTOR pathways and cell proliferation specifically in cultured primary leiomyoma cells. Additionally, we report that RE1 suppressing transcription factor/neuron-restrictive silencing factor (REST/NRSF), a known tumor suppressor, transcriptionally represses GPR10 in the normal myometrium, and that the loss of REST in fibroids permits GPR10 expression. Importantly, mice overexpressing human GPR10 in the myometrium develop myometrial hyperplasia with excessive extracellular matrix deposition, a hallmark of uterine fibroids. We demonstrate previously unrecognized roles for GPR10 and its upstream regulator REST in the pathogenesis of uterine fibroids. Importantly, we report a unique genetically modified mouse model for a gene that is misexpressed in uterine fibroids. PMID:23284171

  14. Transcription Analysis of the Myometrium of Labouring and Non-Labouring Women.

    Science.gov (United States)

    Sharp, Gemma C; Hutchinson, James L; Hibbert, Nanette; Freeman, Tom C; Saunders, Philippa T K; Norman, Jane E

    2016-01-01

    An incomplete understanding of the molecular mechanisms that initiate normal human labour at term seriously hampers the development of effective ways to predict, prevent and treat disorders such as preterm labour. Appropriate analysis of large microarray experiments that compare gene expression in non-labouring and labouring gestational tissues is necessary to help bridge these gaps in our knowledge. In this work, gene expression in 48 (22 labouring, 26 non-labouring) lower-segment myometrial samples collected at Caesarean section were analysed using Illumina HT-12 v4.0 BeadChips. Normalised data were compared between labouring and non-labouring groups using traditional statistical methods and a novel network graph approach. We sought technical validation with quantitative real-time PCR, and biological replication through inverse variance-weighted meta-analysis with published microarray data. We have extended the list of genes suggested to be associated with labour: Compared to non-labouring samples, labouring samples showed apparent higher expression at 960 probes (949 genes) and apparent lower expression at 801 probes (789 genes) (absolute fold change ≥1.2, rank product percentage of false positive value (RP-PFP) MTAB-3136) to facilitate progression of this work. PMID:27176052

  15. The climatic change induced by human activities

    International Nuclear Information System (INIS)

    The climate of the Earth is a changing climate. Along their history many natural climate changes have existed in all time scales. At the present time we use the term climate changes have existed in all time scales. At the present time we use the term climate change in a restricted way, understanding that we have referring to a singular change that has their origin in the modification of the natural composition of the atmosphere. The increase of greenhouse gases from the second half the XVIII century, is due to the human activities of fossil fuels burning to obtain energy and to industrial and agricultural activities needing for the development of a world which population has been duplicated between 1960 and 2000, until overcoming the 6,000 million inhabitants. In particular, the concentrations of carbon dioxide-CO2 have increased in a 34%. The more recent emission scenarios proposed by the IPCC (SRES, 2000) are based on hypothesis about the population evolution, the energy consumption and the word patterns of development, which are grouped in four families dominated as A1, A2, B1 and B2. The answer for these scenarios from a range of climate models results in an increase of the world average surface atmospheric temperature between 1,4 degree centigrade and 5,8 degree centigrade and a corresponding sea level rise understood between 9 cm and 88 cm. The changes in the precipitation patterns show us that could be above to the current one in high and media latitudes and below in subtropical latitudes, with exceptions highly depending of the model used. (Author)

  16. New activity pattern in human interactive dynamics

    Science.gov (United States)

    Formentin, Marco; Lovison, Alberto; Maritan, Amos; Zanzotto, Giovanni

    2015-09-01

    We investigate the response function of human agents as demonstrated by written correspondence, uncovering a new pattern for how the reactive dynamics of individuals is distributed across the set of each agent’s contacts. In long-term empirical data on email, we find that the set of response times considered separately for the messages to each different correspondent of a given writer, generate a family of heavy-tailed distributions, which have largely the same features for all agents, and whose characteristic times grow exponentially with the rank of each correspondent. We furthermore show that this new behavioral pattern emerges robustly by considering weighted moving averages of the priority-conditioned response-time probabilities generated by a basic prioritization model. Our findings clarify how the range of priorities in the inputs from one’s environment underpin and shape the dynamics of agents embedded in a net of reactive relations. These newly revealed activity patterns might be universal, being present in other general interactive environments, and constrain future models of communication and interaction networks, affecting their architecture and evolution.

  17. Reshaping Human Antibodies: Grafting an Antilysozyme Activity

    Science.gov (United States)

    Verhoeyen, Martine; Milstein, Cesar; Winter, Greg

    1988-03-01

    The production of therapeutic human monoclonal antibodies by hybridoma technology has proved difficult, and this has prompted the ``humanizing'' of mouse monoclonal antibodies by recombinant DNA techniques. It was shown previously that the binding site for a small hapten could be grafted from the heavy-chain variable domain of a mouse antibody to that of a human myeloma protein by transplanting the hypervariable loops. It is now shown that a large binding site for a protein antigen (lysozyme) can also be transplanted from mouse to human heavy chain. The success of such constructions may be facilitated by an induced-fit mechanism.

  18. 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...... and in established cell lines was reduced to about the same basic level after treatment with heparin, a highly specific inhibitor of CKII activity. The activity of the cAMP-dependent protein kinase was virtually the same in fibroblasts and various human tumour cell lines investigated....

  19. Recombinant human interleukin 5 is a selective activator of human eosinophil function

    OpenAIRE

    1988-01-01

    Human rIL-5 was found to selectively stimulate morphological changes and the function of human eosinophils. This molecule is thus a prime candidate for the selective eosinophilia and eosinophil activation seen in disease.

  20. Expression and significance of transforming growth factor β-activated kinase 1 in uterine myoma tissue

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Chen; Li Zhao

    2016-01-01

    Objective:To compare the expression of TAK1 in normal myometrium and uterine leiomyoma tissue, and explore the relationship between these molecules and pathogenesis of uterine leiomyoma. Methods:Formaldehyde-fixed, paraffin-embedded specimen from 76 patients with uterine leiomyoma and normal myometrium adjacent were obtained from our hospital. The expression of TAK1 was detected by immunohistochemical staining and PCR analysis. Results:The expression of protein and mRNA levels TAK1 in uterine leiomyoma tissues were significantly increased when compared with normal myometrium, but not related to the number of leiomyoma. Furthermore, TAK1 expression was associated with the size of uterine leiomyoma. Conclusion:The present results suggest that the abundant expression of TAK1 protein may have a molecular basis characteristic of leiomyomas in the human uterus, and TAK1 may be a therapeutic target for the treatment of uterine leiomyoma.

  1. Activities of Human Gene Nomenclature Committee

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2002-07-16

    The objective of this project, shared between NIH and DOE, has been and remains to enable the medical genetics communities to use common names for genes that are discovered by different gene hunting groups, in different species. This effort provides consistent gene nomenclature and approved gene symbols to the community at large. This contributes to a uniform and consistent understanding of genomes, particularly the human as well as functional genomics based on comparisons between homologous genes in related species (human and mice).

  2. Immunohistochemical evaluation of leiomyoma tissue and normal myometrium in patients with uter-ine leiomyoma during hypo- and hyperestrogenic conditions caused by of use of gonadotropin-releasing hormone ana-logues

    Directory of Open Access Journals (Sweden)

    Medvedev M.V.

    2012-01-01

    Full Text Available In study immunohistochemical an alysis of markers of proliferation, apoptosis, extracellular ma trix degradation, angiogenesis and steroid hormone receptors in myomatous tissue and myometrium was conducted in 62 patients with uterine leiomyomas during long-term and short-term correction of hormonal status by gosere line acetate. Studies have shown that pseudocapsule of fibroids at immunohistochemical level is unchanged myometrium. For le iomyoma tissue compared to myometrium were characteristic greater expression of steroid hormone receptors and aromatase, inhibition of apoptosis, greater expression of angiogenic factors compared to unchanged myometrium. Under the action of GnRH-a direct and medi-ated by reduction of estradiol occurred molecular changes, which cover almost all parts of th e pathogenesis of fibroids and include inhibition of expression of estrogen receptor and aromat ase synthesis, enhancing of e xpression of progesterone recep-tors, inhibition of proliferation and angi ogenesis, accelerated degradation of ECM. Under the influence of hyperestrogeny caused by flare-up effect of GnRH-a and direct peripheral effect of GnRH analogs progression of uterine leiomyoma pro-vides increased sensitivity of uterine myocyt es to ischemia. Despite the obvious role of antiapoptotic factor bcl-2 in the pathogenesis of uterine fibroids, short- and long-term hormonal treatment with GnRH-a does not lead to significant changes in its expression.

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Task-dependent differences in relative activity between "functional" subdivisions within human muscles are well documented. Contrary, independent voluntary control of anatomical subdivisions, termed neuromuscular compartments is not observed in human muscles. Therefore, the main aim of this study...... was to investigate whether subdivisions within the human trapezius can be independently activated by voluntary command using biofeedback guidance. Bipolar electromyographical electrodes were situated on four subdivisions of the trapezius muscle. The threshold for "active" and "rest" for each subdivision was set...... to >12% and subdivisions, 11 of 15 subjects learned selective activation of at least one of the four anatomical subdivisions of the trapezius...

  4. Uterine stretch regulates temporal and spatial expression of fibronectin protein and its alpha 5 integrin receptor in myometrium of unilaterally pregnant rats.

    Science.gov (United States)

    Shynlova, Oksana; Williams, S Joy; Draper, Haley; White, Bryan G; MacPhee, Daniel J; Lye, Stephen J

    2007-11-01

    The adaptive growth of the uterus during pregnancy is a critical event that involves increased synthesis of extracellular matrix (ECM) proteins and dynamic remodeling of smooth muscle cell (SMC)-ECM interactions. We have previously found a dramatic increase in the expression of the mRNAs that encode fibronectin (FN) and its alpha5-integrin receptor (ITGA5) in pregnant rat myometrium near to term. Since the myometrium at term is exposed to considerable mechanical stretching of the uterine wall by the growing fetus(es), the objective of the present study was to examine its role in the regulation of FN and ITGA5 expression at late gestation and during labor. Using myometrial tissues from unilaterally pregnant rats, we investigated the temporal changes in Itga5 gene expression in gravid and empty uterine horns by Northern blotting and real-time PCR, in combination with immunoblotting and immunofluorescence analyses of the temporal/spatial distributions of the FN and ITGA5 proteins. In addition, we studied the effects of early progesterone (P4) withdrawal on Itga5 mRNA levels and ITGA5 protein detection. At all time-points examined, the Itga5 mRNA levels were increased in the gravid uterine horn, compared to the empty horn (P < 0.05). Immunoblot analysis confirmed higher ITGA5 and FN protein levels in the myometrium, associated with gravidity (P < 0.05). Immunodetection of ITGA5 was consistently high in the longitudinal muscle layer, increased with gestational age in the circular muscle layer of the gravid horn, and remained low in the empty horn. ITGA5 and FN immunostaining in the gravid horn exhibited a continuous layer of variable thickness associated directly with the surfaces of individual SMCs. In contrast to the effects of stretch, P4 does not appear to regulate ITGA5 expression. We speculate that the reinforcement of the FN-ITGA5 interaction: 1) contributes to myometrial hypertrophy and remodeling during late pregnancy; and 2) facilitates force transduction

  5. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    Energy Technology Data Exchange (ETDEWEB)

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  6. 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.

  7. Human task-specific somatosensory activation.

    Science.gov (United States)

    Ginsberg, M D; Yoshii, F; Vibulsresth, S; Chang, J Y; Duara, R; Barker, W W; Boothe, T E

    1987-08-01

    We used positron emission tomography to study normal patterns of local cortical metabolic activation induced by somatosensory stimuli. Palpation and sorting of mah-jongg tiles by textured design increased local glucose metabolic rate (lCMRgl), by 18% on average, in contralateral somatosensory cortex. A graphesthesia task gave a similar result. In contrast, vigorous vibrotactile stimulation of fingers, face, or knee did not produce a consistent focus of activation. Our results indicate that lCMRgl activation is best achieved by somatosensory tasks requiring an active perceptual effort.

  8. Window Size Impact in Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Oresti Banos

    2014-04-01

    Full Text Available Signal segmentation is a crucial stage in the activity recognition process; however, this has been rarely and vaguely characterized so far. Windowing approaches are normally used for segmentation, but no clear consensus exists on which window size should be preferably employed. In fact, most designs normally rely on figures used in previous works, but with no strict studies that support them. Intuitively, decreasing the window size allows for a faster activity detection, as well as reduced resources and energy needs. On the contrary, large data windows are normally considered for the recognition of complex activities. In this work, we present an extensive study to fairly characterize the windowing procedure, to determine its impact within the activity recognition process and to help clarify some of the habitual assumptions made during the recognition system design. To that end, some of the most widely used activity recognition procedures are evaluated for a wide range of window sizes and activities. From the evaluation, the interval 1–2 s proves to provide the best trade-off between recognition speed and accuracy. The study, specifically intended for on-body activity recognition systems, further provides designers with a set of guidelines devised to facilitate the system definition and configuration according to the particular application requirements and target activities.

  9. 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.

  10. Characterization of ATPase Activity of Recombinant Human Pif1

    Institute of Scientific and Technical Information of China (English)

    Yu HUANG; Deng-Hong ZHANG; Jin-Qiu ZHOU

    2006-01-01

    Saccharomyces cerevisiae Pif1p helicase is the founding member of the Pif1 subfamily that is conserved from yeast to human. The potential human homolog of the yeast PIF1 gene has been cloned from the cDNA library of the Hek293 cell line. Here, we described a purification procedure of glutathione Stransferase (GST)-fused N terminal truncated human Pif1 protein (hPif1△N) from yeast and characterized the enzymatic kinetics of its ATP hydrolysis activity. The ATPase activity of human Pif1 is dependent on divalent cation, such as Mg2+, Ca2+ and single-stranded DNA. Km for ATP for the ATPase activity is approximately 200 μM. As the ATPase activity is essential for hPif1's helicase activity, these results will facilitate the further investigation on hPif1.

  11. Mapping human brain activity in vivo.

    OpenAIRE

    Mazziotta, J.C.

    1994-01-01

    A wide range of structural and functional techniques now exists to map the human brain in health and disease. These approaches span the gamut from external tomographic imaging devices (positron-emission tomography, single photon-emission computed tomography, magnetic resonance imaging, computed tomography), to surface detectors (electroencephalography, magnetoencephalography, transcranial magnetic stimulation), to measurements made directly on the brain's surface or beneath it (intrinsic sign...

  12. Determination of the functional size of oxytocin receptors in plasma membranes from mammary gland and uterine myometrium of the rat by radiation inactivation

    Energy Technology Data Exchange (ETDEWEB)

    Soloff, M.S.; Beauregard, G.; Potier, M.

    1988-05-01

    Gel filtration of detergent-solubilized oxytocin (OT) receptors in plasma membrane fractions from both regressed mammary gland and labor myometrium of the rat, showed that specific (/sup 3/H)OT binding was associated with a heterogeneously sized population of macromolecules. As radiation inactivation is the only method available to measure the apparent molecular weights of membrane proteins in situ, we used this approach to define the functional sizes of OT receptors. The results indicate that both mammary and myometrial receptors are uniform in size and of similar molecular mass. Mammary and myometrial receptors were estimated to be 57.5 +/- 3.8 (SD) and 58.8 +/- 1.6 kilodaltons, respectively. Knowledge of the functional size of OT receptors will be useful in studies involving the purification and characterization of the receptor and associated membrane components.

  13. Human immunodeficiency syndromes affecting human natural killer cell cytolytic activity

    Directory of Open Access Journals (Sweden)

    Daniel Denis Billadeau

    2014-01-01

    Full Text Available NK cells are lymphocytes of the innate immune system that secrete cytokines upon activation and mediate the killing of tumor cells and virus-infected cells, especially those that escape the adaptive T-cell response caused by the down regulation of MHC-I. The induction of cytotoxicity requires that NK cells contact target cells through adhesion receptors, and initiate activation signaling leading to increased adhesion and accumulation of F-actin at the NK cell cytotoxic synapse. Concurrently, lytic granules undergo minus-end directed movement and accumulate at the microtubule-organizing center (MTOC through the interaction with microtubule motor proteins, followed by polarization of the lethal cargo toward the target cell. Ultimately, myosin-dependent movement of the lytic granules toward the NK cell plasma membrane through F-actin channels, along with SNARE-dependent fusion promotes lytic granule release into the cleft between the NK cell and target cell resulting in target cell killing. Herein, we will discuss several disease-causing mutations in primary immunodeficiency syndromes and how they impact NK cell-mediated killing by disrupting distinct steps of this tightly regulated process.

  14. 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.

  15. Type IV collagen-degrading enzyme activity in human serum.

    Directory of Open Access Journals (Sweden)

    Hashimoto,Noriaki

    1988-02-01

    Full Text Available Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful for estimating the degradation of type IV collagen.

  16. Type IV collagen-degrading enzyme activity in human serum.

    OpenAIRE

    Hashimoto, Noriaki; Kobayashi,Michio; Watanabe,Akiharu; Higashi,Toshiro; Tsuji, Takao

    1988-01-01

    Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful...

  17. POTENT INVITRO ANTI-HUMAN IMMUNODEFICIENCY VIRUS-1 ACTIVITY OF MODIFIED HUMAN SERUM ALBUMINS

    NARCIS (Netherlands)

    JANSEN, RW; MOLEMA, G; PAUWELS, R; SCHOLS, D; DECLERCQ, E; MEIJER, DKF

    1991-01-01

    A series of neoglycoproteins was synthesized by coupling of thiophosgene-activated p-aminophenyl derivatives [Biol. Cell. 47:95-110 (1983); J. Histochem. Cytochem. 32:1091-1094 (1984)] of various sugars to human serum albumin. The compounds were evaluated for their in vitro activity against human im

  18. Human activities change marine ecosystems by altering predation risk.

    Science.gov (United States)

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. PMID:26448058

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

    OpenAIRE

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

    1995-01-01

    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 line...

  20. Impact of the spatial context on human communication activity

    OpenAIRE

    Dashdorj, Zolzaya; Sobolevsky, Stanislav

    2015-01-01

    Technology development produces terabytes of data generated by hu- man activity in space and time. This enormous amount of data often called big data becomes crucial for delivering new insights to decision makers. It contains behavioral information on different types of human activity influenced by many external factors such as geographic infor- mation and weather forecast. Early recognition and prediction of those human behaviors are of great importance in many societal applications like hea...

  1. Understanding Usability Work as a Human Activity

    DEFF Research Database (Denmark)

    Nørgaard, Mie

    of usability work to include a human perspective, is crucial to downstream utility—how usability work impacts the on-going development process. Our work shows that cross-professional collaboration is subject to challenges that arise from stakeholders having conflicting priorities, procedures and personalities....... Such challenges include evaluation results lacking relevance, poor timing of evaluation results, little respect for other disciplines, and difficulties sharing important information about a design. The studies of practical usability work suggest that user researchers working with computer games and task oriented...... systems struggle with making methods meet practical realities and demands, and that the concept of usability in games is not satisfactorily covered by for example the ISO 9241-11. With this in mind we call for future work that broadens the concept of usability to include concepts more relevant to games...

  2. Dietary methanol regulates human gene activity.

    Directory of Open Access Journals (Sweden)

    Anastasia V Shindyapina

    Full Text Available Methanol (MeOH is considered to be a poison in humans because of the alcohol dehydrogenase (ADH-mediated conversion of MeOH to formaldehyde (FA, which is toxic. Our recent genome-wide analysis of the mouse brain demonstrated that an increase in endogenous MeOH after ADH inhibition led to a significant increase in the plasma MeOH concentration and a modification of mRNA synthesis. These findings suggest endogenous MeOH involvement in homeostasis regulation by controlling mRNA levels. Here, we demonstrate directly that study volunteers displayed increasing concentrations of MeOH and FA in their blood plasma when consuming citrus pectin, ethanol and red wine. A microarray analysis of white blood cells (WBC from volunteers after pectin intake showed various responses for 30 significantly differentially regulated mRNAs, most of which were somehow involved in the pathogenesis of Alzheimer's disease (AD. There was also a decreased synthesis of hemoglobin mRNA, HBA and HBB, the presence of which in WBC RNA was not a result of red blood cells contamination because erythrocyte-specific marker genes were not significantly expressed. A qRT-PCR analysis of volunteer WBCs after pectin and red wine intake confirmed the complicated relationship between the plasma MeOH content and the mRNA accumulation of both genes that were previously identified, namely, GAPDH and SNX27, and genes revealed in this study, including MME, SORL1, DDIT4, HBA and HBB. We hypothesized that human plasma MeOH has an impact on the WBC mRNA levels of genes involved in cell signaling.

  3. Supporting Human Activities - Exploring Activity-Centered Computing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Bardram, Jakob

    2002-01-01

    In this paper we explore an activity-centered computing paradigm that is aimed at supporting work processes that are radically different from the ones known from office work. Our main inspiration is healthcare work that is characterized by an extreme degree of mobility, many interruptions, ad......-hoc collaboration based on shared material, and organized in terms of well-defined, recurring, work activities. We propose that this kind of work can be supported by a pervasive computing infrastructure together with domain-specific services, both designed from a perspective where work activities are first class...... objects. We also present an exploratory prototype design and first implementation and present some initial results from evaluations in a healthcare environment....

  4. Telomerase Activity in Human Ovarian Carcinoma

    Science.gov (United States)

    Counter, Christopher M.; Hirte, Hal W.; Bacchetti, Silvia; Harley, Calvin B.

    1994-04-01

    Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.

  5. COMMUNICATIVE INTERACTION ACTIVITIES USING HUMAN INTEREST STORIES

    Institute of Scientific and Technical Information of China (English)

    Song Shunling

    1983-01-01

    @@ As an EFL teacher actively engaged in promoting communicative approach in teaching post-intermediate students I have been all the time aware of the risks involved in classroom discussion and debate in the target language. Despite elaborate preparations on thepart of both teacher and students and numerous encouraging cues from the teacher to induce an adequate interaction during the session, the end product is anything but satisfactory: few more able students may hog the show for a few minutes while the rest clamp up, then stony silence dominates and the teacher has recourse to monologue.

  6. Anticipating Human Activities Using Object Affordances for Reactive Robotic Response.

    Science.gov (United States)

    Koppula, Hema S; Saxena, Ashutosh

    2016-01-01

    An important aspect of human perception is anticipation, which we use extensively in our day-to-day activities when interacting with other humans as well as with our surroundings. Anticipating which activities will a human do next (and how) can enable an assistive robot to plan ahead for reactive responses. Furthermore, anticipation can even improve the detection accuracy of past activities. The challenge, however, is two-fold: We need to capture the rich context for modeling the activities and object affordances, and we need to anticipate the distribution over a large space of future human activities. In this work, we represent each possible future using an anticipatory temporal conditional random field (ATCRF) that models the rich spatial-temporal relations through object affordances. We then consider each ATCRF as a particle and represent the distribution over the potential futures using a set of particles. In extensive evaluation on CAD-120 human activity RGB-D dataset, we first show that anticipation improves the state-of-the-art detection results. We then show that for new subjects (not seen in the training set), we obtain an activity anticipation accuracy (defined as whether one of top three predictions actually happened) of 84.1, 74.4 and 62.2 percent for an anticipation time of 1, 3 and 10 seconds respectively. Finally, we also show a robot using our algorithm for performing a few reactive responses.

  7. Broad-spectrum antimicrobial activity of human intestinal defensin 5.

    OpenAIRE

    Porter, E M; van Dam, E; Valore, E V; Ganz, T

    1997-01-01

    Defensins are antibiotic peptides expressed in human and animal myeloid and epithelial cells. Due to the limited availability of natural peptides, the properties of human epithelial defensins have not been studied. We assayed the microbicidal activity of recombinant human intestinal defensin 5 (rHD-5) in the presence of salt (O to 150 mM NaCl) with varied pH (pH 5.5 to pH 8.5) and trypsin (25 and 250 microg/ml). rHD-5 exhibits microbicidal activity against Listeria monocytogenes, Escherichia ...

  8. Structure activity relationships of human galactokinase inhibitors.

    Science.gov (United States)

    Liu, Li; Tang, Manshu; Walsh, Martin J; Brimacombe, Kyle R; Pragani, Rajan; Tanega, Cordelle; Rohde, Jason M; Baker, Heather L; Fernandez, Elizabeth; Blackman, Burchelle; Bougie, James M; Leister, William H; Auld, Douglas S; Shen, Min; Lai, Kent; Boxer, Matthew B

    2015-02-01

    Classic Galactosemia is a rare inborn error of metabolism that is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), an enzyme within the Leloir pathway that is responsible for the conversion of galactose-1-phosphate (gal-1-p) and UDP-glucose to glucose-1-phosphate and UDP-galactose. This deficiency results in elevated intracellular concentrations of its substrate, gal-1-p, and this increased concentration is believed to be the major pathogenic mechanism in Classic Galactosemia. Galactokinase (GALK) is an upstream enzyme of GALT in the Leloir pathway and is responsible for conversion of galactose and ATP to gal-1-p and ADP. Therefore, it was hypothesized that the identification of a small-molecule inhibitor of human GALK would act to prevent the accumulation of gal-1-p and offer a novel entry therapy for this disorder. Herein we describe a quantitative high-throughput screening campaign that identified a single chemotype that was optimized and validated as a GALK inhibitor. PMID:25553891

  9. Neutron activation analysis of human hair

    International Nuclear Information System (INIS)

    As a part of IAEA research project, ''Activation analysis of hair as an indicator of contamination of man by environmental trace element pollutants'', a survey was carried out to elucidate the levels of various trace element concentration in hair of local population in the Tokyo Metropolitan areas, by applying instrumental neutron activation analysis. A total of 202 scalp hair samples were collected from the inhabitants classified by sex and five age classes. Irradiation was made in the Rikkyo University 100 kW TRIGA MARK-II reactor. Using several combinations of irradiation time, cooling time and counting time, forty elements were determined. The relationship between several trace element contents in hair and such factors as sex, age class, hair treatment, smoking habit and dental treatment, was analyzed by using the method of multiple regression. It was shown that (1) Hair treatment had a predominant effect on the contents of bromine, magnesium and calcium in hair, (2) Aging and amoking contributed increasing mercury content in hair, and hair treatment acted reversely. (author)

  10. Natural radiation exposure modified by human activities

    International Nuclear Information System (INIS)

    We are now living in the radiation environment modified by our technology. It is usually called 'Technologically Enhanced Natural Radiation' and have been discussed in the UNSCEAR Reports as an important source of exposure. The terrestrial radionuclide concentrations as well as the intensity of cosmic rays are considered to have been constant after our ancestors came down from trees and started walking on their two feet. However, we have been changing our environment to be more comfortable for our life and consequently ambient radiation levels are nomore what used to be. In this paper exposures due to natural radiation modified by our following activities are discussed: housing, balneology, cave excursion, mountain climbing, skiing, swimming, smoking and usage of mineral water, well water, coal, natural gas, phosphate rocks and minerals. In the ICRP Publication No. 39, it is clearly mentioned that even natural radiation should be controlled as far as it is controllable. We have to pay more attention to our activities not to enhance the exposure due to unnecessary, avoidable radiation. (author)

  11. Estrogen biosynthesis in human uterine adenomyosis

    Energy Technology Data Exchange (ETDEWEB)

    Urabe, Mamoru; Yamamoto, Takara; Kitawaki, Jo; Honjo, Hideo; Okada, Hiroji (Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto (Japan))

    1989-01-01

    Estrogen biosynthesis (aromatiase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrical cancer tissues. Homogenates were incubated with (1,2,6,7-{sup 3}H)androstenedione and NADPH at 37 deg. C for 1 h. After stopping the enzymatic reaction with ethyl acetate, (4-{sup 14}C)estrone and (4-{sup 14}C)estradiol-17{beta} were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the {sup 3}H/{sup 14}C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol{sup .}h{sup -1.}g{sup -1} wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progresterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease. (author).

  12. 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.

  13. 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. PMID:26555621

  14. Human activity understanding for robot-assisted living

    NARCIS (Netherlands)

    N. Hu

    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

  15. ACTIVATION OF HUMAN BLOOD MONONUCLEARS BY LIPOPOLYSACCHARIDE OF DIFFERENT COMPOSITION

    Directory of Open Access Journals (Sweden)

    S. V. Zubova

    2010-01-01

    Full Text Available Influence of lipopolysaccharide (LPS composition upon activation of human blood mononuclears was investigated, by measuring levels of pro-inflammatory TNFα and IL-6 cytokines released by the cells. It is shown that LPS from Rhodobacter capsulatus PG, in contrast to E. coli LPS, did not activate the target cells for synthesis of the cytokines.

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

    International Nuclear Information System (INIS)

    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 CO2 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 PPAR

  17. 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. PMID:26966964

  18. Dual-induced multifractality of human online activity

    CERN Document Server

    Qin, Yuhao; Cai, Shimin; Gao, Liang

    2014-01-01

    Recent discoveries of human activity reveal the existence of long-term correlation and its relation with the fat-tailed distribution of inter-event times, which imply that there exists the fractality of human activity. However, works further analyzing the type of fractality and its origin still lack. Herein, DFA and MFDFA methods are applied in the analysis of time series of online reviewing activity from Movielens and Netflix. Results show the long-term correlation at individual and whole community level, while the strength of such correlation at individual level is restricted to activity level. Such long-term correlation reveals the fractality of online reviewing activity. In our further investigation of this fractality, we \\emph{first} demonstrate it is multifractality, which results from the dual effect of broad probability density function and long-term correlation of time series in online reviewing activity. This result is also verified by three synthesized series. Therefore, we conclude that the combin...

  19. A Competitive Approach for Human Activity Recognition on Smartphones

    OpenAIRE

    Reiss, Attila; Hendeby, Gustaf; Stricker, Didier

    2013-01-01

    This paper describes a competitive approach developed for an activity recognition challenge. The competition was defined on a new and publicly available dataset of human activities, recorded with smartphone sensors. This work investigates different feature sets for the activity recognition task of the competition. Moreover, the focus is also on the introduction of a new, confidence-based boosting algorithm called ConfAda- Boost.M1. Results show that the new classification method outperforms c...

  20. Human activity recognition from object interaction in domestic scenarios

    OpenAIRE

    Flores Vázquez, Carlos

    2014-01-01

    This work describes the recognition of human activity based on the interaction between people and objects in domestic settings, specifically in a kitchen. In order to achieve the aim of recognizing activity it is necessary to establish a procedure and essential equipment. Regarding the procedure, in a simplified manner, it is based on capturing local images where the activity takes place using a colour camera (RGB), and processing the above mentioned images to recognize the present objects an...

  1. 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.

  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. Activity of antiretroviral drugs in human infections by opportunistic agents

    OpenAIRE

    Izabel Galhardo Demarchi; Daniela Maira Cardozo; Sandra Mara Alessi Aristides; Ricardo Alberto Moliterno; Thaís Gomes Verzignassi Silveira; Rosilene Fressatti Cardoso; Dennis Armando Bertolini; Terezinha Inez Estivalet Svidzinski; Jorge Juarez Vieira Teixeira; Maria Valdrinez Campana Lonardoni

    2012-01-01

    Highly active antiretroviral therapy (HAART) is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV), human ...

  4. Multiple biological activities of human recombinant interleukin 1.

    OpenAIRE

    Dinarello, C A; Cannon, J. G.; Mier, J W; Bernheim, H. A.; LoPreste, G; Lynn, D L; Love, R N; Webb, A C; Auron, P. E.; Reuben, R C

    1986-01-01

    Complementary DNA coding for human monocyte interleukin 1 (IL-1), pI 7 form, was expressed in Escherichia coli. During purification, IL-1 activity on murine T cells was associated with the recombinant protein. Homogeneous human recombinant IL-1 (hrIL-1) was tested in several assays to demonstrate the immunological and inflammatory properties attributed to this molecule. hrIL-1 induced proliferative responses in a cloned murine T cell in the presence of suboptimal concentrations of mitogen, wh...

  5. Autoproteolytic Cleavage and Activation of Human Acid Ceramidase*

    OpenAIRE

    Shtraizent, Nataly; Eliyahu, Efrat; Park, Jae-Ho; He, Xingxuan; Shalgi, Ruth; Schuchman, Edward H.

    2008-01-01

    Herein we report the mechanism of human acid ceramidase (AC; N-acylsphingosine deacylase) cleavage and activation. A highly purified, recombinant human AC precursor underwent self-cleavage into α and β subunits, similar to other members of the N-terminal nucleophile hydrolase superfamily. This reaction proceeded with first order kinetics, characteristic of self-cleavage. AC self-cleavage occurred most rapidly at acidic pH, but also at neutral pH. Site-directed mutagene...

  6. Human receptor activation by aroclor 1260, a polychlorinated biphenyl mixture.

    Science.gov (United States)

    Wahlang, Banrida; Falkner, K Cameron; Clair, Heather B; Al-Eryani, Laila; Prough, Russell A; States, J Christopher; Coslo, Denise M; Omiecinski, Curtis J; Cave, Matthew C

    2014-08-01

    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of U.S. adults and dose-dependently associated with obesity and non-alcoholic fatty liver disease (NAFLD). PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), liver-X-receptor (LXRα), and farnesoid-X-receptor (FXR). This study evaluates Aroclor 1260, a PCB mixture with congener composition mimicking that of human adipose tissue, and selected congeners, as potential ligands for these receptors utilizing human hepatoma-derived (HepG2) and primate-derived (COS-1) cell lines, and primary human hepatocytes. Aroclor 1260 (20 μg/ml) activated AhR, and PCB 126, a minor component, was a potent inducer. Aroclor 1260 activated PXR in a simple concentration-dependent manner at concentrations ≥10 μg/ml. Among the congeners tested, PCBs 138, 149, 151, 174, 183, 187, and 196 activated PXR. Aroclor 1260 activated CAR2 and CAR3 variants at lower concentrations and antagonize CAR2 activation by the CAR agonist, CITCO, at higher concentrations (≥20 μg/ml). Additionally, Aroclor 1260 induced CYP2B6 in primary hepatocytes. At subtoxic doses, Aroclor 1260 did not activate LXR or FXR and had no effect on LXR- or FXR-dependent induction by the agonists T0901317 or GW4064, respectively. Aroclor 1260 (20 μg/ml) suppressed PPARα activation by the agonist nafenopin, although none of the congeners tested demonstrated significant inhibition. The results suggest that Aroclor 1260 is a human AhR, PXR and CAR3 agonist, a mixed agonist/antagonist for CAR2, and an antagonist for human PPARα. PMID:24812009

  7. CRISPR RNA-guided activation of endogenous human genes

    OpenAIRE

    Maeder, Morgan L.; Linder, Samantha J; Cascio, Vincent M.; Fu, Yanfang; Ho, Quan H; Joung, J Keith

    2013-01-01

    Catalytically inactive CRISPR-associated 9 nuclease (dCas9) can be directed by short guide RNAs (gRNAs) to repress endogenous genes in bacteria and human cells. Here we show that a dCas9-VP64 transcriptional activation domain fusion protein can be directed by single or multiple gRNAs to increase expression of specific endogenous human genes. These results provide an important proof-of-principle that CRISPR-Cas systems can be used to target heterologous effector domains in human cells.

  8. Protein composition of catalytically active human telomerase from immortal cells

    DEFF Research Database (Denmark)

    Cohen, Scott B; Graham, Mark E; Lovrecz, George O;

    2007-01-01

    Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on the...... enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules...... each of telomerase reverse transcriptase, telomerase RNA, and dyskerin....

  9. Dipeptides Increase Functional Activity of Human Skin Fibroblasts.

    Science.gov (United States)

    Malinin, V V; Durnova, A O; Polyakova, V O; Kvetnoi, I M

    2015-05-01

    We analyzed the effect of dipeptide Glu-Trp and isovaleroyl-Glu-Trp in concentrations of 0.2, 2 and 20 μg/ml and Actovegin preparation on functional activity of human skin fibroblasts. Dipeptides, especially Glu-Trp, produce a stimulating effect on human skin fibroblasts and their effect is equivalent to that of Actovegin. Dipeptides stimulate cell renewal processes by activating synthesis of Ki-67 and reducing expression of caspase-9 and enhance antioxidant function of the cells by stimulating the expression of Hsp-90 and inducible NO-synthase. These findings suggest that dipeptides are promising candidates for preparations stimulating reparative processes.

  10. The impacts of local human activities on the Antarctic environment

    Science.gov (United States)

    Tin, T.; Fleming, Z. L.; Hughes, K. A.; Ainley, D. G.; Convey, P.; Moreno, C. A.; Pfeiffer, S.; Scott, J.; Snape, I.

    2009-04-01

    An overview of a recently published review of the scientific literature from the past decade on the impacts of human activities on the Antarctic environment is presented. An assessment of the cumulative effects of scientists and accompanying base construction, tourists and fishery activities in Antarctica is timely given a decade since the Protocol on Environmental Protection to the Antarctic Treaty came into force in 1998 and the increasing attention given to and human presence in Antarctica during this 2007-2009 IPY. A range of impacts has been identified at a variety of spatial and temporal scales. Chemical contamination and sewage disposal on the continent have been found to be long-lived, with contemporary sewage management practices at many coastal stations insufficient to prevent local contamination. Human activities, particularly construction and transport, have affected Antarctic flora and fauna and a small number of non-indigenous plant and animal species has become established on some of the Antarctic Peninsula and sub Antarctic islands. There is little indication of recovery of overexploited fish stocks, and ramifications of fishing activity on bycatch species and the ecosystem could also be far-reaching. The Antarctic Treaty System and its instruments, in particular the Convention for the Conservation of Antarctic Marine Living Resources (CCAMLR) and the Environmental Protocol, provide a framework within which management of human activities take place. In order to ensure comprehensive protection of the Antarctic environment, including its intrinsic, wilderness and scientific values in the face of the continuing expansion of human activities in Antarctica, a more effective implementation of a wide range of measures is essential. These include effective environmental impact assessments, long-term monitoring, mitigation measures for non-indigenous species, ecosystem-based management of living resources, and increased regulation of National Antarctic

  11. Implications of Special Regions to Conducting Human Activities on Mars

    Science.gov (United States)

    Rummel, J. D.; Barlow, N. G.; Beaty, D. W.; Jones, M. A.; Hipkin, V.

    2014-12-01

    A MEPAG Science Analysis Group (SAG) has undertaken an analysis of Special Regions (SR) on Mars—regions where indigenous martian life could exist or where Earth microbes, if introduced, could survive and reproduce. The SR-SAG has considered the impact of SR on future human activities on the martian surface. Human exploration requires access to in-situ resources, some of which may be found in SR. Water and oxygen for ISRU are found in the atmosphere, surface/near-surface ice, hydrated minerals, and perchlorates. Water ice is most abundant at latitudes poleward of ~60 degrees, but polar darkness, cold temperatures, and CO2 degassing present hazards to human operations in these regions. Accessible water is more limited toward the equator, though temperature and solar energy conditions become more favorable. The possible presence of liquid water in Recurring Slope Lineae and active gullies leads to their treatment as SR. Fuel for surface operations and propellants for crew ascent could be manufactured from the martian atmosphere and surface materials, but dust in the atmosphere may clog ISRU equipment and perchlorate is toxic to humans. Power may be produced from solar or nuclear energy. Reliance on solar energy limits operations to the equatorial zone where easily accessible ice resources are limited. Nuclear power allows surface operations at a range of latitudes, but waste heat could convert some non-SR into SR. Radiation shielding is necessary for long-term human operations on Mars and could be obtained by deposition of regolith or by water storage in tanks or as ice around habitats, or the use of underground habitats. SR-SAG recognizes that it will be impossible for all human-associated processes and operations to be conducted within entirely closed systems. Protocols need to be established so (1) human missions to Mars will not contaminate SR nor be contaminated by materials from them, and (2) human activities on Mars will avoid converting areas into SR.

  12. Human ECG signal parameters estimation during controlled physical activity

    Science.gov (United States)

    Maciejewski, Marcin; Surtel, Wojciech; Dzida, Grzegorz

    2015-09-01

    ECG signal parameters are commonly used indicators of human health condition. In most cases the patient should remain stationary during the examination to decrease the influence of muscle artifacts. During physical activity, the noise level increases significantly. The ECG signals were acquired during controlled physical activity on a stationary bicycle and during rest. Afterwards, the signals were processed using a method based on Pan-Tompkins algorithms to estimate their parameters and to test the method.

  13. Recognition of Human Activities Using Continuous Autoencoders with Wearable Sensors

    OpenAIRE

    Lukun Wang

    2016-01-01

    This paper provides an approach for recognizing human activities with wearable sensors. The continuous autoencoder (CAE) as a novel stochastic neural network model is proposed which improves the ability of model continuous data. CAE adds Gaussian random units into the improved sigmoid activation function to extract the features of nonlinear data. In order to shorten the training time, we propose a new fast stochastic gradient descent (FSGD) algorithm to update the gradients of CAE. The recons...

  14. Characterization of acid sphingomyelinase activity in human cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    Christiane Mühle

    Full Text Available BACKGROUND: As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. METHODS: An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. RESULTS: We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme's properties. The enzyme resembles plasmatic ASM including protein stability and Zn(2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. CONCLUSIONS: Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.

  15. Accelerometry-Based Classification of Human Activities Using Markov Modeling

    Directory of Open Access Journals (Sweden)

    Andrea Mannini

    2011-01-01

    Full Text Available Accelerometers are a popular choice as body-motion sensors: the reason is partly in their capability of extracting information that is useful for automatically inferring the physical activity in which the human subject is involved, beside their role in feeding biomechanical parameters estimators. Automatic classification of human physical activities is highly attractive for pervasive computing systems, whereas contextual awareness may ease the human-machine interaction, and in biomedicine, whereas wearable sensor systems are proposed for long-term monitoring. This paper is concerned with the machine learning algorithms needed to perform the classification task. Hidden Markov Model (HMM classifiers are studied by contrasting them with Gaussian Mixture Model (GMM classifiers. HMMs incorporate the statistical information available on movement dynamics into the classification process, without discarding the time history of previous outcomes as GMMs do. An example of the benefits of the obtained statistical leverage is illustrated and discussed by analyzing two datasets of accelerometer time series.

  16. Differences in transcriptional activity of cutaneous human papillomaviruses

    DEFF Research Database (Denmark)

    Vasiljevic, Natasa; Nielsen, Lone; Doherty, Geoff;

    2008-01-01

    The interaction between UV-B irradiation and cutaneous human papillomaviruses (HPV) has been suggested to be of relevance for the development of non-melanoma skin cancers. We investigated the activity within the upstream regulatory region (URR) of the HPV types 8, 38, 92, 93 and 96, as well as th...

  17. The interaction between ICT and human activity-travel behavior

    NARCIS (Netherlands)

    Kwan, M.P.; Dijst, M.J.; Schwanen, T.

    2007-01-01

    The interaction between information and communication technologies (ICT) and human activity-travel behavior has been an important theme in transportation research in recent years. Researchers have recognized that an increase in the use of ICT may lead to changes in the location, timing and duration

  18. 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 hum

  19. Activation of the human brain by monetary reward

    NARCIS (Netherlands)

    Thut, G; Schultz, W; Roelcke, U; Nienhusmeier, M; Missimer, J; Maguire, RP; Leenders, KL

    1997-01-01

    WITH the purpose of studying neural activation associated with reward processing in humans, we measured regional cerebral blood flow in 10 right-handed healthy subjects performing a delayed go-no go task in two different reinforcement conditions. Correct responses were either rewarded by money or a

  20. 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...

  1. 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

  2. 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. PMID:26353344

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

    International Nuclear Information System (INIS)

    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

  4. Muscular activity and its relationship to biomechanics and human performance

    Science.gov (United States)

    Ariel, Gideon

    1994-01-01

    The purpose of this manuscript is to address the issue of muscular activity, human motion, fitness, and exercise. Human activity is reviewed from the historical perspective as well as from the basics of muscular contraction, nervous system controls, mechanics, and biomechanical considerations. In addition, attention has been given to some of the principles involved in developing muscular adaptations through strength development. Brief descriptions and findings from a few studies are included. These experiments were conducted in order to investigate muscular adaptation to various exercise regimens. Different theories of strength development were studied and correlated to daily human movements. All measurement tools used represent state of the art exercise equipment and movement analysis. The information presented here is only a small attempt to understand the effects of exercise and conditioning on Earth with the objective of leading to greater knowledge concerning human responses during spaceflight. What makes life from nonliving objects is movement which is generated and controlled by biochemical substances. In mammals. the controlled activators are skeletal muscles and this muscular action is an integral process composed of mechanical, chemical, and neurological processes resulting in voluntary and involuntary motions. The scope of this discussion is limited to voluntary motion.

  5. Random mitotic activities across human embryonic stem cell colonies.

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Q.; Duggan, R.; Dasa, S.; Li, F.; Chen, L. (Biosciences Division)

    2010-08-01

    A systemic and quantitative study was performed to examine whether different levels of mitotic activities, assessed by the percentage of S-phase cells at any given time point, existed at different physical regions of human embryonic stem (hES) cell colonies at 2, 4, 6 days after cell passaging. Mitotically active cells were identified by the positive incorporation of 5-bromo-2-deoxyuridine (BrdU) within their newly synthesized DNA. Our data indicated that mitotically active cells were often distributed as clusters randomly across the colonies within the examined growth period, presumably resulting from local deposition of newly divided cells. This latter notion was further demonstrated by the confined growth of enhanced green florescence protein (EGFP) expressing cells amongst non-GFP expressing cells. Furthermore, the overall percentage of mitotically active cells remained constantly at about 50% throughout the 6-day culture period, indicating mitotic activities of hES cell cultures were time-independent under current growth conditions.

  6. Human ADAM 12 (meltrin alpha) is an active metalloprotease

    DEFF Research Database (Denmark)

    Loechel, F; Gilpin, B J; Engvall, E;

    1998-01-01

    The ADAMs (a disintegrin and metalloprotease) are a family of multidomain proteins with structural homology to snake venom metalloproteases. We recently described the cloning and sequencing of human ADAM 12 (meltrin alpha). In this report we provide evidence that the metalloprotease domain of ADAM...... 12 is catalytically active. We used the trapping mechanism of alpha2-macroglobulin to assay for protease activity of wild-type and mutant ADAM 12 proteins produced in a COS cell transfection system. We found that ADAM 12 is synthesized as a zymogen, with the prodomain maintaining the metalloprotease...... in a latent form, probably by means of a cysteine switch. The zymogen could be activated chemically by alkylation with N-ethylmaleimide. Cleavage of the prodomain at a site for a furin-like endopeptidase resulted in an ADAM 12 protein with proteolytic activity. The protease activity was sensitive...

  7. Pharmacological activity in growth inhibition and apoptosis of cultured human leiomyomal cells of tropical plant Scutellaria barbata D. Don (Lamiaceae).

    Science.gov (United States)

    Lee, Tae-Kyun; Lee, Yun-Jeong; Kim, Dong-Il; Kim, Hyung-Min; Chang, Young-Chae; Kim, Cheorl-Ho

    2006-01-01

    Scutellaria barbata D. Don (Lamiaceae) (SB), which is known in traditional Korean medicine, has been used as an anti-inflammatory and antitumor agent. Since uterine leiomyoma is the most common benign smooth muscle cell tumor of the myometrium, we aimed to determine the growth inhibition and the induction of apoptotic cell death brought about by the herb SB in two different leiomyomal cells, named LM-1 and LM-2, and to clarify the mechanism of this apoptosis. Water-soluble ingredients of SB, and the leiomyomal cell lines of LM-1 and LM-2, were used in vitro. Growth inhibition, induction of cell death, morphological features, the presence of DNA ladders, increases in Caspase 3-like activity, the effects of a Caspase 3 inhibitor on apoptotic cell death, and the release of Cytochrome C by SB were analyzed. SB inhibited the growth and decreased the viability of the leiomyomal cells. The viability of normal myomatrial smooth muscle cells (SMC) in the presence of low concentrations of SB was higher than those of leiomyomal cells. Apoptotic bodies and DNA ladders were observed to be induced in leiomyomal cells of LM-1 and LM-2 by SB. The synthetic tetrapeptide Caspase 3 inhibitor, N-acetyl-Asp-Glu-Val-Asp-aldehyde (Ac-DEVD-CHO), inhibited the apoptotic cell death of leiomyomal cells induced by SB. The Caspase 3-like activity in leiomyomal cells LM-1 and LM-2 increased after the addition of SB. Cytochrome C was released from mitochondria into the cytosol 8h after the addition of SB, and reached a peak at 16h. The peak of Cytochrome C release was earlier than that of Caspase 3-like activity. We concluded that SB inhibited the growth of the leiomyomal cells and induced apoptosis. The apoptosis of leiomyomal cells induced by SB was associated with the release of Cytochrome C from the mitochondria, followed by an increase in Caspase 3-like activity.

  8. Human monoamine oxidase A gene determines levels of enzyme activity.

    OpenAIRE

    Hotamisligil, G S; Breakefield, X O

    1991-01-01

    Monoamine oxidase (MAO) is a critical enzyme in the degradative deamination of biogenic amines throughout the body. Two biochemically distinct forms of the enzyme, A and B, are encoded in separate genes on the human X chromosome. In these studies we investigated the role of the structural gene for MAO-A in determining levels of activity in humans, as measured in cultured skin fibroblasts. The coding sequence of the mRNA for MAO-A was determined by first-strand cDNA synthesis, PCR amplificatio...

  9. Mechanotransduction mechanisms for coordinating uterine contractions in human labor.

    Science.gov (United States)

    Young, Roger C

    2016-08-01

    This review presents evolving concepts of how the human uterus contracts in pregnancy, with emphasis on the mechanisms of long-distance signaling. Action potential propagation has historically been assumed to be the sole mechanism for signaling and tissue recruitment over both short and long distances. However, data in animals and humans indicate that a single action potential does not travel distances greater than a few centimeters. To address this enigma, a long-distance signaling mechanism based on hydraulic signaling and mechanotransduction is developed. By combining this mechanism for long-distance signaling with the action potential propagation mechanism for signaling over short distances, a comprehensive dual mechanism model (or 'dual model') of uterine function is formulated. Mechanotransduction is an accepted phenomenon of myometrium, but the dual model identifies mechanotransduction as relevant to normal labor. For hydraulic signaling, a local contraction slightly increases intrauterine pressure, which globally increases wall tension. Increased wall tension then mechanically induces additional local contractions that further raise pressure. This leads to robust, positive feedback recruitment that explains the emergence of consistently strong contractions of human labor. Three key components of the dual model - rapid long-distance signaling, mechanical triggering, and electrical activity - converge with the concept of mechanically sensitive electrogenic pacemakers distributed throughout the wall. The dual model retains excitation-contraction coupling and action potential propagation for signaling over short distances (<10cm) and hence is an extension of the action potential model rather than a replacement. PMID:27165050

  10. The DNA methylation profile of activated human natural killer cells.

    Science.gov (United States)

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-01

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308

  11. Expression of immunoreactive urocortin in human tissue

    Institute of Scientific and Technical Information of China (English)

    GU Qing; Vicki L Clifton; CUI Ying; HUI Ning; ZHOU Xiao-ning; HE Qian; HAN Qing-feng; SHA Jin-yan; Roger Smith

    2001-01-01

    To localize where urocortin is expressed in human tissue in an attempt to study its physiological functions. Methods: Expression of immunoreactive urocortin in different human tissue was examined using a specific urocortin antibody and the immunoperoxidase staining method. Results: Immunoreactive urocortin was observed in the anterior pituitary cells, decidual stromal cells, syncytiotrophoblasts, amnion epithelium, the vascular smooth muscles of myometrium, fallopian tube and small intestine. Conclusion: The study indicates that urocortin is expressed in some specific areas of human tissue. The data are consistent with the hypothesis that urocortin is produced locally as an endocrine factor, which may act as a neural regulator and a regulator of local blood flow.

  12. Activities of human RRP6 and structure of the human RRP6 catalytic domain

    Energy Technology Data Exchange (ETDEWEB)

    Januszyk, Kurt; Liu, Quansheng; Lima, Christopher D. (SKI)

    2011-08-29

    The eukaryotic RNA exosome is a highly conserved multi-subunit complex that catalyzes degradation and processing of coding and noncoding RNA. A noncatalytic nine-subunit exosome core interacts with Rrp44 and Rrp6, two subunits that possess processive and distributive 3'-to-5' exoribonuclease activity, respectively. While both Rrp6 and Rrp44 are responsible for RNA processing in budding yeast, Rrp6 may play a more prominent role in processing, as it has been demonstrated to be inhibited by stable RNA secondary structure in vitro and because the null allele in budding yeast leads to the buildup of specific structured RNA substrates. Human RRP6, otherwise known as PM/SCL-100 or EXOSC10, shares sequence similarity to budding yeast Rrp6 and is proposed to catalyze 3'-to-5' exoribonuclease activity on a variety of nuclear transcripts including ribosomal RNA subunits, RNA that has been poly-adenylated by TRAMP, as well as other nuclear RNA transcripts destined for processing and/or destruction. To characterize human RRP6, we expressed the full-length enzyme as well as truncation mutants that retain catalytic activity, compared their activities to analogous constructs for Saccharomyces cerevisiae Rrp6, and determined the X-ray structure of a human construct containing the exoribonuclease and HRDC domains that retains catalytic activity. Structural data show that the human active site is more exposed when compared to the yeast structure, and biochemical data suggest that this feature may play a role in the ability of human RRP6 to productively engage and degrade structured RNA substrates more effectively than the analogous budding yeast enzyme.

  13. Human hair identification by instrumental neutron activation analysis

    International Nuclear Information System (INIS)

    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 104-106 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)

  14. Human mediator subunit MED15 promotes transcriptional activation.

    Science.gov (United States)

    Nakatsubo, Takuya; Nishitani, Saori; Kikuchi, Yuko; Iida, Satoshi; Yamada, Kana; Tanaka, Aki; Ohkuma, Yoshiaki

    2014-10-01

    In eukaryotes, the Mediator complex is an essential transcriptional cofactor of RNA polymerase II (Pol II). In humans, it contains up to 30 subunits and consists of four modules: head, middle, tail, and CDK/Cyclin. One of the subunits, MED15, is located in the tail module, and was initially identified as Gal11 in budding yeast, where it plays an essential role in the transcriptional regulation of galactose metabolism with the potent transcriptional activator Gal4. For this reason, we investigated the function of the human MED15 subunit (hMED15) in transcriptional activation. First, we measured the effect of hMED15 knockdown on cell growth in HeLa cells. The growth rate was greatly reduced. By immunostaining, we observed the colocalization of hMED15 with the general transcription factors TFIIE and TFIIH in the nucleus. We measured the effects of siRNA-mediated knockdown of hMED15 on transcriptional activation using two different transcriptional activators, VP16 and SREBP1a. Treatment with siRNAs reduced transcriptional activation, and this reduction could be rescued by overexpression of HA/Flag-tagged, wild-type hMED15. To investigate hMED15 localization, we treated human MCF-7 cells with the MDM2 inhibitor Nutlin-3, thus inducing p21 transcription. We found that hMED15 localized to both the p53 binding site and the p21 promoter region, along with TFIIE and TFIIH. These results indicate that hMED15 promotes transcriptional activation.

  15. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

    Science.gov (United States)

    Oniga, Stefan; József, Sütő

    2015-12-01

    The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  16. Ontology-based improvement to human activity recognition

    Science.gov (United States)

    Tahmoush, David; Bonial, Claire

    2016-05-01

    Human activity recognition has often prioritized low-level features extracted from imagery or video over higher-level class attributes and ontologies because they have traditionally been more effective on small datasets. However, by including knowledge-driven associations between actions and attributes while recognizing the lower-level attributes with their temporal relationships, we can attempt a hybrid approach that is more easily extensible to much larger datasets. We demonstrate a combination of hard and soft features with a comparison factor that prioritizes one approach over the other with a relative weight. We then exhaustively search over the comparison factor to evaluate the performance of a hybrid human activity recognition approach in comparison to the base hard approach at 84% accuracy and the current state-of-the-art.

  17. Optimal Recognition Method of Human Activities Using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Oniga Stefan

    2015-12-01

    Full Text Available The aim of this research is an exhaustive analysis of the various factors that may influence the recognition rate of the human activity using wearable sensors data. We made a total of 1674 simulations on a publically released human activity database by a group of researcher from the University of California at Berkeley. In a previous research, we analyzed the influence of the number of sensors and their placement. In the present research we have examined the influence of the number of sensor nodes, the type of sensor node, preprocessing algorithms, type of classifier and its parameters. The final purpose is to find the optimal setup for best recognition rates with lowest hardware and software costs.

  18. A voltage-activated proton current in human cardiac fibroblasts

    International Nuclear Information System (INIS)

    A voltage-activated proton current in human cardiac fibroblasts, measured using the whole-cell recording configuration of the patch-clamp technique, is reported. Increasing the pH of the bathing solution shifted the current activation threshold to more negative potentials and increased both the current amplitude and its rate of activation. Changing the pH gradient by one unit caused a 51 mV shift in the reversal potential of the current, demonstrating a high selectivity for protons of the channel carrying the current. Extracellularly applied Zn2+ reversibly inhibited the current. Activation of the current contributes to the resting membrane conductance under conditions of intracellular acidosis. It is proposed that this current in cardiac fibroblasts is involved in the regulation of the intracellular pH and the membrane potential under physiological conditions as well as in response to pathological conditions such as ischemia

  19. 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

  20. 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

  1. Human psychophysiological activity monitoring methods using fiber optic sensors

    Science.gov (United States)

    Zyczkowski, M.; Uzieblo-Zyczkowska, B.

    2010-10-01

    The paper presents the concept of fiber optic sensor system for human psycho-physical activity detection. A fiber optic sensor that utilizes optical phase interferometry or intensity in modalmetric to monitor a patient's vital signs such as respiration cardiac activity, blood pressure and body's physical movements. The sensor, which is non-invasive, comprises an optical fiber interferometer that includes an optical fiber proximately situated to the patient so that time varying acusto-mechanical signals from the patient are coupled into the optical fiber. The system can be implemented in embodiments ranging form a low cost in-home to a high end product for in hospital use.

  2. Human hair neutron activation analysis: analysis on population level, mapping

    International Nuclear Information System (INIS)

    Neutron activation analysis is an outstanding analytical method having very wide applications in various fields. Analysis of human hair within last decades mostly based on neutron activation analysis is a very attractive illustration of the application of nuclear analytical techniques. Very interesting question is how the elemental composition differs in different areas or cities. In this connection the present paper gives average data and maps of various localities in the vicinity of drying-out Aral Sea and of various industrial cities in Central Asia. (author)

  3. Through the Interface - a human activity approach to user interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    In providing a theoretical framework for understanding human- computer interaction as well as design of user interfaces, this book combines elements of anthropology, psychology, cognitive science, software engineering, and computer science. The framework examines the everyday work practices...... of users when analyzing and designing computer applications. The text advocates the unique theory that computer application design is fundamentally a collective activity in which the various practices of the participants meet in a process of mutual learning....

  4. Concurrent activities and instructed human fixed-interval performance.

    OpenAIRE

    Barnes, D; Keenan, M

    1993-01-01

    Two experiments explored the effects of two types of concurrent activity on human fixed-interval performance. Eight adult subjects were given access to either reading material or a working television set across three fixed-interval values (60 s, 300 s, and 600 s). During Experiment 1, 2 subjects produced "scalloped" patterns and reported no verbal regulation (e.g., counting) in the presence of the reading material, but shifted to low-rate patterns and reported verbal regulation when the readi...

  5. 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.

    2016-01-01

    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. PMID:26876605

  6. Interactions between cardiac, respiratory, and brain activity in humans

    Science.gov (United States)

    Musizza, Bojan; Stefanovska, Aneta

    2005-05-01

    The electrical activity of the heart (ECG), respiratory function and electric activity of the brain (EEG) were simultaneously recorded in conscious, healthy humans. Instantaneous frequencies of the heart beat, respiration and α-waves were then determined from 30-minutes recordings. The instantaneous cardiac frequency was defined as the inverse value of the time interval between two consecutive R-peaks. The instantaneous respiratory frequency was obtained from recordings of the excursions of thorax by application of the Hilbert transform. To obtain the instantaneous frequency of α-waves, the EEG signal recorded from the forehead was first analysed using the wavelet transform. Then the frequency band corresponding to α-waves was extracted and the Hilbert transform applied. Synchronization analysis was performed and the direction of coupling was ascertained, using pairs of instantaneous frequencies in each case. It is shown that the systems are weakly bidirectionally coupled. It was confirmed that, in conscious healthy humans, respiration drives cardiac activity. We also demonstrate from these analyses that α-activity drives both respiration and cardiac activity.

  7. Antiviral activity of purified human breast milk mucin.

    Science.gov (United States)

    Habte, Habtom H; Kotwal, Girish J; Lotz, Zoë E; Tyler, Marilyn G; Abrahams, Melissa; Rodriques, Jerry; Kahn, Delawir; Mall, Anwar S

    2007-01-01

    Human breast milk is known to contain numerous biologically active components which protect breast fed infants against microbes, viruses, and toxins. The purpose of this study was to purify and characterize the breast milk mucin and determine its anti-poxvirus activity. In this study human milk mucin, free of contaminant protein and of sufficient quantity for further analysis, was isolated and purified by Sepharose CL-4B gel filtration and cesiumchloride density-gradient centrifugation. Based on the criteria of size and appearance of the bands and their electrophoretic mobility on sodium dodecyl sulfate polyacrylamide-gel electrophoresis, Western blotting together with the amino acid analysis, it is very likely that the human breast milk mucin is MUC1. It was shown that this breast milk mucin inhibits poxvirus activity by 100% using an inhibition assay with a viral concentration of 2.4 million plaque-forming units/ml. As the milk mucin seems to aggregate poxviruses prior to their entry into host cells, it is possible that this mucin may also inhibit other enveloped viruses such as HIV from entry into host cells. PMID:17361093

  8. Activity of protease-activated receptors in primary cultured human myenteric neurons

    Directory of Open Access Journals (Sweden)

    Eva Maria Kugler

    2012-09-01

    Full Text Available Activity of the four known protease-activated receptors (PARs has been well studied in rodent enteric nervous system and results in animal models established an important role for neuronal PAR2. We recently demonstrated that, unlike in rodents, PAR1 is the dominant neuronal protease receptor in the human submucous plexus. With this study we investigated whether this also applies to the human myenteric plexus. We used voltage sensitive dye recordings to detect action potential discharge in primary cultures of human myenteric neurons in response to PAR activating peptides (AP. Application of the PAR1-AP (TFLLR or PAR4-AP (GYPGQV evoked spike discharge in 79% or 23% of myenteric neurons, respectively. The PAR1-AP response was mimicked by the endogenous PAR1 activator thrombin and blocked by the PAR1 antagonists SCH79797. Human myenteric neurons did not respond to PAR2-AP. This was not due to culture conditions because all three PAR-APs evoked action potentials in cultured guinea pig myenteric neurons. Consecutive application of PAR-APs revealed coexpression (relative to the population responding to PAR-APs of PAR1/PAR2 in 51%, PAR1/PAR4 in 43% and of PAR2/PAR4 in 29% of guinea pig myenteric neurons. Our study provided further evidence for the prominent role of neuronal PAR1 in the human enteric nervous system.

  9. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.

    Science.gov (United States)

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin; Henriques-Normark, Birgitta; Olliver, Marie

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  10. Human temporal lobe activation by speech and nonspeech sounds.

    Science.gov (United States)

    Binder, J R; Frost, J A; Hammeke, T A; Bellgowan, P S; Springer, J A; Kaufman, J N; Possing, E T

    2000-05-01

    Functional organization of the lateral temporal cortex in humans is not well understood. We recorded blood oxygenation signals from the temporal lobes of normal volunteers using functional magnetic resonance imaging during stimulation with unstructured noise, frequency-modulated (FM) tones, reversed speech, pseudowords and words. For all conditions, subjects performed a material-nonspecific detection response when a train of stimuli began or ceased. Dorsal areas surrounding Heschl's gyrus bilaterally, particularly the planum temporale and dorsolateral superior temporal gyrus, were more strongly activated by FM tones than by noise, suggesting a role in processing simple temporally encoded auditory information. Distinct from these dorsolateral areas, regions centered in the superior temporal sulcus bilaterally were more activated by speech stimuli than by FM tones. Identical results were obtained in this region using words, pseudowords and reversed speech, suggesting that the speech-tones activation difference is due to acoustic rather than linguistic factors. In contrast, previous comparisons between word and nonword speech sounds showed left-lateralized activation differences in more ventral temporal and temporoparietal regions that are likely involved in processing lexical-semantic or syntactic information associated with words. The results indicate functional subdivision of the human lateral temporal cortex and provide a preliminary framework for understanding the cortical processing of speech sounds.

  11. 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.

  12. Induction of human complement activation without cytolysis by mouse monoclonal antibodies to human leukocyte antigens.

    Science.gov (United States)

    Sugita, K; Majdic, O; Stockinger, H; Holter, W; Burger, R; Knapp, W

    1987-04-01

    Ten monoclonal antibodies to human leukocyte subsets that had previously been shown to lyse their respective target cells in the presence of rabbit serum as complement source were evaluated for their cytolytic capacity with human complement. Four of the ten were lytic with human complement. All were of IgM type. Antibodies were also evaluated for their capacity to induce C3 binding to target cells. With this method we could demonstrate that, indeed, 3 of the 6 noncytolytic antibodies had the capacity to initiate the human complement activation process and to induce C3 binding. Two of these 3 antibodies were of IgM class (VIT3 and VIM13), one of IgG3 (562). From the practical point of view the most interesting of these 3 antibodies is the nonmitogenic anti-CD3 pan-T cell antibody VIT3. Therefore, this antibody was analyzed in more detail. VIT3 antibody concentrations needed to induce detectable C3 binding to human T cells are very low (down to 1 ng VIT3/ml). Human serum as complement source can also be considerably (100X) diluted before C3 binding becomes undetectable. Activation of C3 is a prerequesite for VIT3-induced C3 binding, and bound C3 seems to lack the C3a fragment. Bound C3, in contrast to the quickly occuring antigenic modulation of the CD3 complex and the simultaneous disappearance of the antibody coat, remains expressed also after prolonged incubation at 37 degrees C. C3 fragments bound to T cells after activation with VIT3 are also recognized by cells bearing C3 receptors of types CR1 and CR2. PMID:3576673

  13. Human ZCCHC12 activates AP-1 and CREB signaling as a transcriptional co-activator

    Institute of Scientific and Technical Information of China (English)

    Hong Li; Qian Liu; Xiang Hu; Du Feng; Shuanglin Xiang; Zhicheng He; Xingwang Hu; Jianlin Zhou; Xiaofeng Ding; Chang Zhou; Jian Zhang

    2009-01-01

    Mouse zinc finger CCHC domain containing 12 gene (ZCCHC12) has been identified as a transcriptional co-activator of bone morphogenetic protein (BMP) sig-naling,and human ZCCHC12 was reported to be related to non-syndromic X-linked mental retardation (NS-XLMR).However,the details of how human ZCCHCI2 involve in the NS-XLMR still remain unclear.In this study,we identified a novel nuclear localization signal (NLS) in the middle of human ZCCHC12 protein which is responsible for the nuclear localization.Multiple-tissue northern blot analysis indi-cated that ZCCHC12 is highly expressed in human brain.Furthermore,in situ hybridization showed that ZCCHC12 is specifically expressed in neuroepithelium of forebrain,midbrain,and diencephalon regions of mouse E10.5 embryos.Luciferase reporter assays demonstrated that ZCCHC12 enhanced the transcrip-tional activities of activator protein 1 (AP-1) and cAMP response element binding protein (CREB) as a co-activator.In conclusion,we identified a new NLS in ZCCHC12 and figured out that ZCCHC12 functions as a transcriptional co-activator of AP-1 and CREB.

  14. Reconstituted high-density lipoprotein modulates activation of human leukocytes.

    Directory of Open Access Journals (Sweden)

    Rolf Spirig

    Full Text Available An anti-inflammatory effect of reconstituted High Density Lipoprotein (rHDL has been demonstrated in atherosclerosis and in sepsis models. An increase of adhesion molecules as well as tissue factor expression on endothelial cells in response to inflammatory or danger signals are attenuated by the treatment with rHDL. Here we show the inhibitory effect of rHDL on the activation of human leukocytes in a whole blood assay as well as on monocyte-derived human dendritic cells (DC. Multiplex analysis of human whole blood showed that phytohaemagglutinin (PHA-induced secretion of the cytokines IL-1β, IL-1RA, IL-2R, IL-6, IL-7, IL-12(p40, IL-15 and IFN-α was inhibited. Furthermore, an inhibitory effect on the production of the chemokines CCL-2, CCL-4, CCL-5, CXCL-9 and CXCL-10 was observed. Activation of granulocytes and CD14+ monocytes by PHA is inhibited dose-dependently by rHDL shown as decreased up-regulation of ICAM-1 surface expression. In addition, we found a strong inhibitory effect of rHDL on toll-like receptor 2 (TLR2- and TLR4-mediated maturation of DC. Treatment of DC with rHDL prevented the up-regulation of cell surface molecules CD80, CD83 and CD86 and it inhibited the TLR-driven activation of inflammatory transcription factor NF-κB. These findings suggest that rHDL prevents activation of crucial cellular players of cellular immunity and could therefore be a useful reagent to impede inflammation as well as the link between innate and adaptive immunity.

  15. Nonpathogenic, environmental fungi induce activation and degranulation of human eosinophils.

    Science.gov (United States)

    Inoue, Yoshinari; Matsuwaki, Yoshinori; Shin, Seung-Heon; Ponikau, Jens U; Kita, Hirohito

    2005-10-15

    Eosinophils and their products are probably important in the pathophysiology of allergic diseases, such as bronchial asthma, and in host immunity to certain organisms. An association between environmental fungal exposure and asthma has been long recognized clinically. Although products of microorganisms (e.g., lipopolysaccharides) directly activate certain inflammatory cells (e.g., macrophages), the mechanism(s) that triggers eosinophil degranulation is unknown. In this study we investigated whether human eosinophils have an innate immune response to certain fungal organisms. We incubated human eosinophils with extracts from seven environmental airborne fungi (Alternaria alternata, Aspergillus versicolor, Bipolaris sorokiniana, Candida albicans, Cladosporium herbarum, Curvularia spicifera, and Penicillium notatum). Alternaria and Penicillium induced calcium-dependent exocytosis (e.g., eosinophil-derived neurotoxin release) in eosinophils from normal individuals. Alternaria also strongly induced other activation events in eosinophils, including increases in intracellular calcium concentration, cell surface expression of CD63 and CD11b, and production of IL-8. Other fungi did not induce eosinophil degranulation, and Alternaria did not induce neutrophil activation, suggesting specificity for fungal species and cell type. The Alternaria-induced eosinophil degranulation was pertussis toxin sensitive and desensitized by preincubating cells with G protein-coupled receptor agonists, platelet-activating factor, or FMLP. The eosinophil-stimulating activity in Alternaria extract was highly heat labile and had an M(r) of approximately 60 kDa. Thus, eosinophils, but not neutrophils, possess G protein-dependent cellular activation machinery that directly responds to an Alternaria protein product(s). This innate response by eosinophils to certain environmental fungi may be important in host defense and in the exacerbation of inflammation in asthma and allergic diseases.

  16. Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

    Directory of Open Access Journals (Sweden)

    Padberg Jan-Sören

    2012-12-01

    Full Text Available Abstract Background Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so far. We thus aimed to study changes in blood pressure in parallel with tryptophan and kynurenine levels during experimental endotoxemia in humans. Findings Six healthy male volunteers were given E. coli lipopolysaccharide (LPS; 4 ng/kg as a 1-min intravenous infusion. They had levels of soluble E-Selectin and soluble vascular cell adhesion molecule-1 as well as IDO activity assessed as the kynurenine-to-tryptophan plasma ratio by liquid chromatography-tandem mass spectrometry at various time points during a 24 h time course. During endotoxemia, IDO activity significantly increased, reaching peak levels at 8 h after LPS infusion (44.0 ± 15.2 vs. 29.4 ± 6.8 at baseline, P Conclusions LPS is a triggering factor for the induction of IDO in men. Our findings strongly support the concept that the induction of IDO in the vascular endothelium contributes to hypotension in human sepsis.

  17. 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.

  18. Natural image classification driven by human brain activity

    Science.gov (United States)

    Zhang, Dai; Peng, Hanyang; Wang, Jinqiao; Tang, Ming; Xue, Rong; Zuo, Zhentao

    2016-03-01

    Natural image classification has been a hot topic in computer vision and pattern recognition research field. Since the performance of an image classification system can be improved by feature selection, many image feature selection methods have been developed. However, the existing supervised feature selection methods are typically driven by the class label information that are identical for different samples from the same class, ignoring with-in class image variability and therefore degrading the feature selection performance. In this study, we propose a novel feature selection method, driven by human brain activity signals collected using fMRI technique when human subjects were viewing natural images of different categories. The fMRI signals associated with subjects viewing different images encode the human perception of natural images, and therefore may capture image variability within- and cross- categories. We then select image features with the guidance of fMRI signals from brain regions with active response to image viewing. Particularly, bag of words features based on GIST descriptor are extracted from natural images for classification, and a sparse regression base feature selection method is adapted to select image features that can best predict fMRI signals. Finally, a classification model is built on the select image features to classify images without fMRI signals. The validation experiments for classifying images from 4 categories of two subjects have demonstrated that our method could achieve much better classification performance than the classifiers built on image feature selected by traditional feature selection methods.

  19. Multi-dimensional dynamics of human electromagnetic brain activity

    Directory of Open Access Journals (Sweden)

    Tetsuo eKida

    2016-01-01

    Full Text Available Magnetoencephalography (MEG and electroencephalography (EEG are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency, which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain.

  20. 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.

  1. 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.

  2. ras activation in human tumors and in animal model systems

    Energy Technology Data Exchange (ETDEWEB)

    Corominas, M.; Sloan, S.R.; Leon, J.; Kamino, Hideko; Newcomb, E.W.; Pellicer, A. (New York Univ. Medical Center, New York (United States))

    1991-06-01

    Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. The authors have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbenzanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. They found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation.

  3. Relationship between acrosin activity of human spermatozoa and oxidative stress

    Institute of Scientific and Technical Information of China (English)

    AdelA.Zalata; AshrafH.Ahmed; ShyamS.R.Allamaneni; H.Comhaire; AshokAgarwal

    2004-01-01

    Aim: To study the association between seminal oxidative stress and human sperm acrosin activity.Methods: It is a prospective study consisting of 30 infertile men and 12 fertile normozoospermic volunteers. A full history, clinical examination and scrotal ultrasound were done to exclude other related factors such as smoking and varicocele. Presence of white blood cells (WBCs) in semen samples was evaluated by peroxidase staining. Lipid peroxidation in spermatozoa was induced after incubating with ferrous sulphate (4mmol/L) and sodium ascorbate (20 mmol/L). Induced peroxidation of spermatozoa was assessed by determining the production of thiobarbituric acid reactive substances (TBARS). Acrosin activity was measured using the gelatinolysis technique. The halo diameters around the sperm heads and the percentages of spermatozoa showing halo formation were evaluated. An acrosin activity index was calculated by multiplying the halo diameter by the halo formation rate. Results: A significant difference was observed in acrosin activity parameters and TBARS levels between samples with WBCs (>1×106/mL of ejaculate) and those without. This difference was also noted between the normozoospermic and the oligoasthenoteratozoospermic semen samples. The TBARS production by spermatozoa had a significant negativecorrelation with the acrosin activity index (r=-0.89, P<0.001). Conclusion: The presence of oxidative stress in an individual with leukocytospermia and/or abnormal semen parameters is associated with impaired sperm function as measured by its acrosin activity. (Asian J Androl 2004 Dec; 6:313-318)

  4. Acetaminophen induces human neuroblastoma cell death through NFKB activation.

    Directory of Open Access Journals (Sweden)

    Inmaculada Posadas

    Full Text Available Neuroblastoma resistance to apoptosis may contribute to the aggressive behavior of this tumor. Therefore, it would be relevant to activate endogenous cellular death mechanisms as a way to improve neuroblastoma therapy. We used the neuroblastoma SH-SY5Y cell line as a model to study the mechanisms involved in acetaminophen (AAP-mediated toxicity by measuring CYP2E1 enzymatic activity, NFkB p65 subunit activation and translocation to the nucleus, Bax accumulation into the mitochondria, cytochrome c release and caspase activation. AAP activates the intrinsic death pathway in the SH-SY5Y human neuroblastoma cell line. AAP metabolism is partially responsible for this activation, because blockade of the cytochrome CYP2E1 significantly reduced but did not totally prevent, AAP-induced SH-SY5Y cell death. AAP also induced NFkB p65 activation by phosphorylation and its translocation to the nucleus, where NFkB p65 increased IL-1β production. This increase contributed to neuroblastoma cell death through a mechanism involving Bax accumulation into the mitochondria, cytochrome c release and caspase3 activation. Blockade of NFkB translocation to the nucleus by the peptide SN50 prevented AAP-mediated cell death and IL-1β production. Moreover, overexpression of the antiapoptotic protein Bcl-x(L did not decrease AAP-mediated IL-1β production, but prevented both AAP and IL-1β-mediated cell death. We also confirmed the AAP toxic actions on SK-N-MC neuroepithelioma and U87MG glioblastoma cell lines. The results presented here suggest that AAP activates the intrinsic death pathway in neuroblastoma cells through a mechanism involving NFkB and IL-1β.

  5. Activation-induced force enhancement in human adductor pollicis.

    Science.gov (United States)

    Oskouei, Ali E; Herzog, Walter

    2009-10-01

    It has been known for a long time that the steady-state isometric force after muscle stretch is bigger than the corresponding force obtained in a purely isometric contraction for electrically stimulated and maximal voluntary contractions (MVC). Recent studies using sub-maximal voluntary contractions showed that force enhancement only occurred in a sub-group of subjects suggesting that force enhancement for sub-maximal voluntary contractions has properties different from those of electrically-induced and maximal voluntary contractions. Specifically, force enhancement for sub-maximal voluntary contractions may contain an activation-dependent component that is independent of muscle stretching. To address this hypothesis, we tested for force enhancement using (i) sub-maximal electrically-induced contractions and stretch and (ii) using various activation levels preceding an isometric reference contraction at 30% of MVC (no stretch). All tests were performed on human adductor pollicis muscles. Force enhancement following stretching was found for all subjects (n=10) and all activation levels (10%, 30%, and 60% of MVC) for electrically-induced contractions. In contrast, force enhancement at 30% of MVC, preceded by 6s of 10%, 60%, and 100% of MVC was only found in a sub-set of the subjects and only for the 60% and 100% conditions. This result suggests that there is an activation-dependent force enhancement for some subjects for sub-maximal voluntary contractions. This activation-dependent force enhancement was always smaller than the stretch-induced force enhancement obtained at the corresponding activation levels. Active muscle stretching increased the force enhancement in all subjects, independent whether they showed activation dependence or not. It appears that post-activation potentiation, and the associated phosphorylation of the myosin light chains, might account for the stretch-independent force enhancement observed here.

  6. Relationship Between Myometrium Closure Methods and the Incidence of Cesarean Scar Defect in Cesarean Section%剖宫产子宫切口缝合术式与子宫切口假腔的关系

    Institute of Scientific and Technical Information of China (English)

    游一平; 阳笑; 唐雅兵; 靳晓丹

    2013-01-01

    [目的]探讨剖宫产子宫切口缝合术式与子宫切口假腔(cesarean scar defect)发生的关系.[方法]应用阴道四维B超观察改良新式剖宫产中“连续套锁缝合(continuous lock catch suture)”及“连续单层缝合(Continuous single-layer closure)”在子宫切口缝合后患者子宫切口假腔发生的情况(阴道B超追踪术后4d、42 d、1年、2年子宫切口情况).计算切口假腔的发生率.[结果]行“连续单层缝合”子宫切口的患者,子宫切口假腔发生率显著低于行“连续套锁缝合”子宫切口的患者(2.74% vs 6.76%,P<0.05).[结论]子宫切口假腔的发生与子宫切口缝合术式相关,“连续单层缝合”子宫切口的缝合术式可有效降低子宫切口假腔的发生.%[Objective] To explore the relationship between myometrium closure methods and the incidence of cesarean scar defect. [Methods] Transvaginal B-ultrasound scan was used to observe the incidence of cesarean scar defect after continuous lock catch suture or continuous single-layer closure in modified new cesarean section. Uterine incision condition at 4d, 42d, 1 year and 2 years after the operation was followed up by using transvaginal B-ultrasound scan. The incidence of cesarean scar defect was calculated. [Results] The incidence of cesarean scar defect in patients undergoing continuous single-layer closure of myometrium was significantly lower than that in patients undergoing continuous lock catch closure of myometrium. [Conclusion] The incidence of cesarean scar defect is related with myometrium closure methods. Continuous single-layer closure can effectively decrease the incidence of cesarean scar defect.

  7. High Accuracy Human Activity Monitoring using Neural network

    CERN Document Server

    Sharma, Annapurna; Chung, Wan-Young

    2011-01-01

    This paper presents the designing of a neural network for the classification of Human activity. A Triaxial accelerometer sensor, housed in a chest worn sensor unit, has been used for capturing the acceleration of the movements associated. All the three axis acceleration data were collected at a base station PC via a CC2420 2.4GHz ISM band radio (zigbee wireless compliant), processed and classified using MATLAB. A neural network approach for classification was used with an eye on theoretical and empirical facts. The work shows a detailed description of the designing steps for the classification of human body acceleration data. A 4-layer back propagation neural network, with Levenberg-marquardt algorithm for training, showed best performance among the other neural network training algorithms.

  8. Efficient expression and purification of biologically active human cystatin proteins.

    Science.gov (United States)

    Chauhan, Sakshi; Tomar, Raghuvir S

    2016-02-01

    Cystatins are reversible cysteine protease inhibitor proteins. They are known to play important roles in controlling cathepsins, neurodegenerative disease, and in immune system regulation. Production of recombinant cystatin proteins is important for biochemical and function characterization. In this study, we cloned and expressed human stefin A, stefin B and cystatin C in Escherichia coli. Human stefin A, stefin B and cystatin C were purified from soluble fraction. For cystatin C, we used various chaperone plasmids to make cystatin C soluble, as it is reported to localize in inclusion bodies. Trigger factor, GroES-GroEL, DnaK-DnaJ-GrpE chaperones lead to the presence of cystatin C in the soluble fraction. Immobilized metal affinity chromatography, glutathione sepharose and anion exchange chromatography techniques were employed for efficient purification of these proteins. Their biological activities were tested by inhibition assays against cathepsin L and H3 protease.

  9. Circadian pattern and burstiness in human communication activity

    CERN Document Server

    Jo, Hang-Hyun; Kertész, János; Kaski, Kimmo

    2011-01-01

    The temporal pattern of human communication is inhomogeneous and bursty, as reflected by the heavy tail distribution of the inter-event times. For the origin of this behavior two main mechanisms have been suggested: a) Externally driven inhomogeneities due to the circadian and weekly activity patterns and b) intrinsic correlation based inhomogeneity rooted deeply in the task handling strategies of humans. Here we address this question by providing systematic de-seasoning methods to remove the circadian and weekly patterns from the time series of communication events. We find that the heavy tails of the inter-event time distributions are robust with respect to this procedure indicating that burstiness is mostly caused by the latter mechanism b). Moreover, we find that our de-seasoning procedure improves the scaling behavior of the distribution.

  10. 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 pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders. PMID:23960123

  11. Disturbances of electrodynamic activity affect abortion in human

    International Nuclear Information System (INIS)

    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.

  12. [The effects of PEMF on the activation of human monocytes].

    Science.gov (United States)

    Chen, Xiaoying; Han, Xiaoyu; Wang, Qian; Wu, Wenchao; Liu, Xiaojing

    2012-08-01

    The aim of the present study is to investigate the effect of pulsed electromagnetic field (PEMF) on the activation of human monocytes (THP-1). Cultured THP-1 cells were exposed to PEMF stimulation with radiation of 32Hz or 64Hz respectively, using sinusoidal wave, and 1mT, twice a day, 30 minutes each time, with an interval of 8 hours, for 3 days. Those with 0Hz stimulation served as the controls. Monocytes activation was monitored by measuring both the release of monocyte chemoattractant protein-1 (MCP-1) from monocytes and their adhesion to monolayers of human umbilical vein endothelial cells (HUVECs). The adhesion of THP-1 cells to HUVECs was evaluated by cell counting method. The secretion of MCP-1 from THP-1 cells was detected by ELISA and MCP-1 mRNA expression was assessed by real time quantitative RT-PCR. The data showed that exposure to PEMF with above parameters could significantly inhibit the adhesion of THP-1 cells to HUVECs and decrease the MCP-1 mRNA and protein expression. The results demonstrated that exposure to PEMF of 1mT, 32Hz or 64Hz for 3 days could significantly inhibit the activation of THP-1 cells. PMID:23016400

  13. 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 pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  14. Recognition of Human Activities Using Continuous Autoencoders with Wearable Sensors.

    Science.gov (United States)

    Wang, Lukun

    2016-01-01

    This paper provides an approach for recognizing human activities with wearable sensors. The continuous autoencoder (CAE) as a novel stochastic neural network model is proposed which improves the ability of model continuous data. CAE adds Gaussian random units into the improved sigmoid activation function to extract the features of nonlinear data. In order to shorten the training time, we propose a new fast stochastic gradient descent (FSGD) algorithm to update the gradients of CAE. The reconstruction of a swiss-roll dataset experiment demonstrates that the CAE can fit continuous data better than the basic autoencoder, and the training time can be reduced by an FSGD algorithm. In the experiment of human activities' recognition, time and frequency domain feature extract (TFFE) method is raised to extract features from the original sensors' data. Then, the principal component analysis (PCA) method is applied to feature reduction. It can be noticed that the dimension of each data segment is reduced from 5625 to 42. The feature vectors extracted from original signals are used for the input of deep belief network (DBN), which is composed of multiple CAEs. The training results show that the correct differentiation rate of 99.3% has been achieved. Some contrast experiments like different sensors combinations, sensor units at different positions, and training time with different epochs are designed to validate our approach. PMID:26861319

  15. 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.

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

    International Nuclear Information System (INIS)

    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

  17. Co-activation based parcellation of the human frontal pole.

    Science.gov (United States)

    Ray, K L; Zald, D H; Bludau, S; Riedel, M C; Bzdok, D; Yanes, J; Falcone, K E; Amunts, K; Fox, P T; Eickhoff, S B; Laird, A R

    2015-12-01

    Historically, the human frontal pole (FP) has been considered as a single architectonic area. Brodmann's area 10 is located in the frontal lobe with known contributions in the execution of various higher order cognitive processes. However, recent cytoarchitectural studies of the FP in humans have shown that this portion of cortex contains two distinct cytoarchitectonic regions. Since architectonic differences are accompanied by differential connectivity and functions, the frontal pole qualifies as a candidate region for exploratory parcellation into functionally discrete sub-regions. We investigated whether this functional heterogeneity is reflected in distinct segregations within cytoarchitectonically defined FP-areas using meta-analytic co-activation based parcellation (CBP). The CBP method examined the co-activation patterns of all voxels within the FP as reported in functional neuroimaging studies archived in the BrainMap database. Voxels within the FP were subsequently clustered into sub-regions based on the similarity of their respective meta-analytically derived co-activation maps. Performing this CBP analysis on the FP via k-means clustering produced a distinct 3-cluster parcellation for each hemisphere corresponding to previously identified cytoarchitectural differences. Post-hoc functional characterization of clusters via BrainMap metadata revealed that lateral regions of the FP mapped to memory and emotion domains, while the dorso- and ventromedial clusters were associated broadly with emotion and social cognition processes. Furthermore, the dorsomedial regions contain an emphasis on theory of mind and affective related paradigms whereas ventromedial regions couple with reward tasks. Results from this study support previous segregations of the FP and provide meta-analytic contributions to the ongoing discussion of elucidating functional architecture within human FP. PMID:26254112

  18. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    徐进平; 叶林柏

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  19. Human Erythropoietin Dimers with Markedly Enhanced in vivo Activity

    Science.gov (United States)

    Sytkowski, Arthur J.; Dotimas Lunn, Elizabeth; Davis, Kerry Lynn; Feldman, Laurie; Siekman, Suvia

    1998-02-01

    Human erythropoietin, a widely used and important therapeutic glycoprotein, has a relatively short plasma half-life due to clearance by glomerular filtration as well as by other mechanisms. We hypothesized that an erythropoietin species with a larger molecular size would exhibit an increased plasma half-life and, potentially, an enhanced biological activity. We now report the production of biologically active erythropoietin dimers and trimers by chemical crosslinking of the conventional monomeric form. We imparted free sulfhydryl residues to a pool of erythropoietin monomer by chemical modification. A second pool was reacted with another modifying reagent to yield monomer with male-imido groups. Upon mixing these two pools, covalently linked dimers and trimers were formed that were biologically active in vitro. The plasma half-life of erythropoietin dimers in rabbits was >24 h compared with 4 h for the monomers. Importantly, erythropoietin dimers were biologically active in vivo as shown by their ability to increase the hematocrits of mice when injected subcutaneously. In addition, the dimers exhibited >26-fold higher activity in vivo than did the monomers and were very effective after only one dose. Dimeric and other oligomeric forms of Epo may have an important role in therapy.

  20. Spontaneous neural activity during human slow wave sleep

    OpenAIRE

    Dang-Vu, Thien Thanh; Schabus, Manuel; Desseilles, Martin; Albouy, Geneviève; Boly, Mélanie; Darsaud, Annabelle; Gais, Steffen; Rauchs, Géraldine; Sterpenich, Virginie; Vandewalle, Gilles; Carrier, Julie; Moonen, Gustave; Balteau, Evelyne; Degueldre, Christian; Luxen, André

    2008-01-01

    Slow wave sleep (SWS) is associated with spontaneous brain oscillations that are thought to participate in sleep homeostasis and to support the processing of information related to the experiences of the previous awake period. At the cellular level, during SWS, a slow oscillation (140 μV) and delta waves (75–140 μV) during SWS in 14 non-sleep-deprived normal human volunteers. Significant increases in activity were associated with these waves in several cortical areas, including the inferior f...

  1. Automated conductimetric assay of human serum cholinesterase activity.

    Science.gov (United States)

    Duffy, P; Wallach, J M

    1989-01-01

    Serum cholinesterase activity was determined by conductimetry using samples in the microliter range. Butyrylcholine iodide was demonstrated to be a convenient substrate for the conductimetric assay. Validation of the microassay was made by using either purified enzyme or control serum. In the range of 0-60 U/l, a linear relationship was demonstrated. Correlation with a reference spectrophotometric method was obtained with a slope of 1.18. An explanation of this value is proposed, as different hydrolysis rates were obtained with human sera, depending on the substrate used (butyrylthio- or butyryl-choline ester).

  2. 77 FR 33774 - Agency Information Collection Activities: Comment Request; Education and Human Resources Project...

    Science.gov (United States)

    2012-06-07

    ... Agency Information Collection Activities: Comment Request; Education and Human Resources Project... of Collection: Education and Human Resources Project Monitoring Clearance. OMB Approval Number: 3145... States and internationally. The Directorate for Education and Human Resources (EHR), a unit within...

  3. 2000 years of human activity in Tuchola Pinewoods (northern Poland)

    Science.gov (United States)

    Obremska, Milena; Ott, Florian; Słowiński, Michał; Lutyńska, Monika; Błaszkiewicz, Mirosław; Brauer, Achim

    2014-05-01

    During the last two millennia human activity and their settlements together with varying climate conditions strongly influenced landscape scale changes. Especially within palaeoecological records these environmental responses are well expressed. However, a robust age control is needed for the evaluation and interpretation of biotic proxies.We present a record from the annually laminated (varved) sediments of Lake Czechowskie, located in northern Poland. The investigated record covers the past 2000 years and demonstrates the continuous vegetation history and human activity in the Northern part of the Tuchola Pinewoods. The chronology was established by varve counting and confirmed by AMS 14C dating, 137Cs activity measurement and a tephra layer (Askja 1875). We used high-resolution biotic (pollen, green algae and diatom analysis) sedimentological (varve and sublayer thickness variations) and geochemical (µ-XRF data) proxies to reconstruct the environmental changes within a time of increasing human activity and fluctuating climatic conditions. Based on different spatial sampling and measuring increments the temporal resolution varies between subseasonal (µ-XRF), annual (varves) up to five-varveresolution (biotic proxies) making it possible to trace even short lasting local and regional changes. Our results display visible human pressure in this area between 50- 350 yr. AD (Roman Period) exerted by tribes related to the Wielbark Culture. The development of persisting settlements and agriculture took place at expense of surrounding hornbeam forests. An intensification of lake productivity (expressed as an increase of varve thickness) started after 250 AD. If this lake ecosystem response relates to an intensified agriculture (and a possible transport of nutrients from neighboring rural lands) or to a climate shift will be further discussed. The rapid decline of human indicators about 350 years AD at the transition to the migration period might be related to cooler

  4. Radioimmunological activity of 22K variant of human growth hormone

    International Nuclear Information System (INIS)

    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 < 0,01). It was checked using the F test between the slope of the two curves. The parallelism shown the immunochemical identity of the two preparation and indicates that the separation process developed does not produce alterations in the immunological properties of the variant. (Author)

  5. 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.

  6. Activity clocks: spreading dynamics on temporal networks of human contact

    CERN Document Server

    Gauvin, Laetitia; Cattuto, Ciro; Barrat, Alain

    2013-01-01

    Dynamical processes on time-varying complex networks are key to un- derstanding and modeling a broad variety of processes in socio-technical systems. Here we focus on empirical temporal networks of human proxim- ity and we aim at understanding the factors that, in simulation, shape the arrival time distribution of simple spreading processes. Abandoning the notion of wall-clock time in favour of node-specific clocks based on activ- ity exposes robust statistical patterns in the arrival times across different social contexts. Using randomization strategies and generative models constrained by data, we show that these patterns can be understood in terms of heterogeneous inter-event time distributions coupled with hetero- geneous numbers of events per edge. We also show, both empirically and by using a synthetic dataset, that significant deviations from the above behavior can be caused by the presence of edge classes with strong activity correlations.

  7. Modelling large scale human activity in San Francisco

    Science.gov (United States)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  8. 3D active workspace of human hand anatomical model

    Directory of Open Access Journals (Sweden)

    Ungureanu Loredana

    2007-05-01

    Full Text Available Abstract Background If the model of the human hand is created with accuracy by respecting the type of motion provided by each articulation and the dimensions of articulated bones, it can function as the real organ providing the same motions. Unfortunately, the human hand is hard to model due to its kinematical chains submitted to motion constraints. On the other hand, if an application does not impose a fine manipulation it is not necessary to create a model as complex as the human hand is. But always the hand model has to perform a certain space of motions in imposed workspace architecture no matter what the practical application does. Methods Based on Denavit-Hartenberg convention, we conceived the kinematical model of the human hand, having in mind the structure and the behavior of the natural model. We obtained the kinematical equations describing the motion of every fingertip with respect to the general coordinate system, placed on the wrist. For every joint variable, a range of motion was established. Dividing these joint variables to an appropriate number of intervals and connecting them, the complex surface bordering the active hand model workspace was obtained. Results Using MATLAB 7.0, the complex surface described by fingertips, when hand articulations are all simultaneously moving, was obtained. It can be seen that any point on surface has its own coordinates smaller than the maximum length of the middle finger in static position. Therefore, a sphere having the centre in the origin of the general coordinate system and the radius which equals this length covers the represented complex surface. Conclusion We propose a human hand model that represents a new solution compared to the existing ones. This model is capable to make special movements like power grip and dexterous manipulations. During them, the fingertips do not exceed the active workspace encapsulated by determined surfaces. The proposed kinematical model can help to choose

  9. Human Endogenous Retrovirus W Activity in Cartilage of Osteoarthritis Patients

    Directory of Open Access Journals (Sweden)

    Signy Bendiksen

    2014-01-01

    Full Text Available The etiology of viruses in osteoarthritis remains controversial because the prevalence of viral nucleic acid sequences in peripheral blood or synovial fluid from osteoarthritis patients and that in healthy control subjects are similar. Until now the presence of virus has not been analyzed in cartilage. We screened cartilage and chondrocytes from advanced and non-/early osteoarthritis patients for parvovirus B19, herpes simplex virus-1, Epstein Barr virus, cytomegalovirus, human herpes virus-6, hepatitis C virus, and human endogenous retroviruses transcripts. Endogenous retroviruses transcripts, but none of the other viruses, were detected in 15 out the 17 patients. Sequencing identified the virus as HERV-WE1 and E2. HERV-W activity was confirmed by high expression levels of syncytin, dsRNA, virus budding, and the presence of virus-like particles in all advanced osteoarthritis cartilages examined. Low levels of HERV-WE1, but not E2 envelope RNA, were observed in 3 out of 8 non-/early osteoarthritis patients, while only 3 out of 7 chondrocytes cultures displayed low levels of syncytin, and just one was positive for virus-like particles. This study demonstrates for the first time activation of HERV-W in cartilage of osteoarthritis patients; however, a causative role for HERV-W in development or deterioration of the disease remains to be proven.

  10. Recognition of Human Activities Using Continuous Autoencoders with Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Lukun Wang

    2016-02-01

    Full Text Available This paper provides an approach for recognizing human activities with wearable sensors. The continuous autoencoder (CAE as a novel stochastic neural network model is proposed which improves the ability of model continuous data. CAE adds Gaussian random units into the improved sigmoid activation function to extract the features of nonlinear data. In order to shorten the training time, we propose a new fast stochastic gradient descent (FSGD algorithm to update the gradients of CAE. The reconstruction of a swiss-roll dataset experiment demonstrates that the CAE can fit continuous data better than the basic autoencoder, and the training time can be reduced by an FSGD algorithm. In the experiment of human activities’ recognition, time and frequency domain feature extract (TFFE method is raised to extract features from the original sensors’ data. Then, the principal component analysis (PCA method is applied to feature reduction. It can be noticed that the dimension of each data segment is reduced from 5625 to 42. The feature vectors extracted from original signals are used for the input of deep belief network (DBN, which is composed of multiple CAEs. The training results show that the correct differentiation rate of 99.3% has been achieved. Some contrast experiments like different sensors combinations, sensor units at different positions, and training time with different epochs are designed to validate our approach.

  11. Antimicrobial activity of Uncaria tomentosa against oral human pathogens.

    Science.gov (United States)

    Ccahuana-Vasquez, Renzo Alberto; Santos, Silvana Soléo Ferreira dos; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso

    2007-01-01

    Uncaria tomentosa is considered a medicinal plant used over centuries by the peruvian population as an alternative treatment for several diseases. Many microorganisms usually inhabit the human oral cavity and under certain conditions can become etiologic agents of diseases. The aim of the present study was to evaluate the antimicrobial activity of different concentrations of Uncaria tomentosa on different strains of microorganisms isolated from the human oral cavity. Micropulverized Uncaria tomentosa was tested in vitro to determine the minimum inhibitory concentration (MIC) on selected microbial strains. The tested strains were oral clinical isolates of Streptococcus mutans, Staphylococcus spp., Candida albicans, Enterobacteriaceae and Pseudomonas aeruginosa. The tested concentrations of Uncaria tomentosa ranged from 0.25-5% in Müeller-Hinton agar. Three percent Uncaria tomentosa inhibited 8% of Enterobacteriaceae isolates, 52% of S. mutans and 96% of Staphylococcus spp. The tested concentrations did not present inhibitory effect on P. aeruginosa and C. albicans. It could be concluded that micropulverized Uncaria tomentosa presented antimicrobial activity on Enterobacteriaceae, S. mutans and Staphylococcus spp. isolates.

  12. Anticancer activity of glucomoringin isothiocyanate in human malignant astrocytoma cells.

    Science.gov (United States)

    Rajan, Thangavelu Soundara; De Nicola, Gina Rosalinda; Iori, Renato; Rollin, Patrick; Bramanti, Placido; Mazzon, Emanuela

    2016-04-01

    Isothiocyanates (ITCs) released from their glucosinolate precursors have been shown to inhibit tumorigenesis and they have received significant attention as potential chemotherapeutic agents against cancer. Astrocytoma grade IV is the most frequent and most malignant primary brain tumor in adults without any curative treatment. New therapeutic drugs are therefore urgently required. In the present study, we investigated the in vitro antitumor activity of the glycosylated isothiocyanate moringin [4-(α-l-rhamnopyranosyloxy)benzyl isothiocyanate] produced from quantitative myrosinase-induced hydrolysis of glucomoringin (GMG) under neutral pH value. We have evaluated the potency of moringin on apoptosis induction and cell death in human astrocytoma grade IV CCF-STTG1 cells. Moringin showed to be effective in inducing apoptosis through p53 and Bax activation and Bcl-2 inhibition. In addition, oxidative stress related Nrf2 transcription factor and its upstream regulator CK2 alpha expressions were modulated at higher doses, which indicated the involvement of oxidative stress-mediated apoptosis induced by moringin. Moreover, significant reduction in 5S rRNA was noticed with moringin treatment. Our in vitro results demonstrated the antitumor efficacy of moringin derived from myrosinase-hydrolysis of GMG in human malignant astrocytoma cells. PMID:26882972

  13. A near atomic structure of the active human apoptosome

    Science.gov (United States)

    Cheng, Tat Cheung; Hong, Chuan; Akey, Ildikó V; Yuan, Shujun; Akey, Christopher W

    2016-01-01

    In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease. DOI: http://dx.doi.org/10.7554/eLife.17755.001

  14. Human transcriptional coactivator PC4 stimulates DNA end joining and activates DSB repair activity.

    Science.gov (United States)

    Batta, Kiran; Yokokawa, Masatoshi; Takeyasu, Kunio; Kundu, Tapas K

    2009-01-23

    Human transcriptional coactivator PC4 is a highly abundant nuclear protein that is involved in diverse cellular processes ranging from transcription to chromatin organization. Earlier, we have shown that PC4, a positive activator of p53, overexpresses upon genotoxic insult in a p53-dependent manner. In the present study, we show that PC4 stimulates ligase-mediated DNA end joining irrespective of the source of DNA ligase. Pull-down assays reveal that PC4 helps in the association of DNA ends through its C-terminal domain. In vitro nonhomologous end-joining assays with cell-free extracts show that PC4 enhances the joining of noncomplementary DNA ends. Interestingly, we found that PC4 activates double-strand break (DSB) repair activity through stimulation of DSB rejoining in vivo. Together, these findings demonstrate PC4 as an activator of nonhomologous end joining and DSB repair activity.

  15. Quantitative morphological assessment of microvascular network of leiomyoma tissue and the layers of myometrium in patients with uterine leiomyoma with hypo- and hyperestrogenic conditions induced by different schemes of gonadotroping relising hormone agonists therapy

    Directory of Open Access Journals (Sweden)

    Medvedev M.V.

    2011-01-01

    Full Text Available Microvascular components of myomatous tissue and the layers of myometrium were evaluated using mорmorphometric analysis in 35 patients with uterine leiomyoma with long-term and short-term preoperative hormonal correction with Gosereline Acetate. Our results show that the microvessels density depends on morphological type of the fibroid, which in case of the cellular leiomyoma is 2.9 times greater compared to the regular one. The tissue is characterized by decreased vascularization of simple leiomyoma as compared to surrounding myometrium. In conditions of a drug-induced 3-month menopause density of microvessels was significantly decreased. In conditions of elevated levels of sex steroids amount of microvessels in fibrois tissue increases, with expanding of the lumen of arterioles and metarterioles and thickening of their walls. Hipoestrogenic condition contributes significantly to reduction of the average diameter of arterioles in the tissue of cellular and simple leiomyoma, which in some cases leads to complete obliteration of the vessels. Short-time hypere-strogenemia leads to a statistically significant increase in wall thickness of arterioles in fibroid tissue samples. Similar changes observed in vessels of pseudocapsula of women with cellular leiomyoma.

  16. 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.

  17. Is Peroxiredoxin II's peroxidase activity strongly inhibited in human erythrocytes?

    Science.gov (United States)

    Benfeitas, Rui; Selvaggio, Gianluca; Antunes, Fernando; Coelho, Pedro; Salvador, Armindo

    2014-10-01

    H2O2 elimination in human erythrocytes is mainly carried out by catalase (Cat), glutathione peroxidase (GPx1) and the more recently discovered peroxiredoxin 2 (Prx2). However, the contribution of Prx2 to H2O2 consumption is still unclear. Prx2's high reactivity with H2O2 (kPrx2=10×10(7) M(-1)s(-1), kCat =7×10(7) M(-1)s(-1), kGPx1 =4×10(7) M(-1)s(-1)) and high abundance ([Prx2]= 570µM, [Cat]= 32µM, [GPx1]= 1µM) suggest that under low H2O2 supply rates it should consume >99% of the H2O2. However, extensive evidence indicates that in intact erythrocytes Prx2 contributes no more than Cat to H2O2 consumption. In order for this to be attained, Prx2's effective rate constant with H2O2would have to be just ~10(5) M(-1)s(-1), much lower than that determined in multiple experiments with the purified proteins. Nevertheless, nearly all Prx2 is oxidized within 1min of exposing erythrocytes to a H2O2 bolus, which is inconsistent with an irreversible inhibition. A mathematical model of the H2O2 metabolism in human erythrocytes [Benfeitas et al. (2014) Free Radic. Biol. Med.] where Prx2 either has a low kPrx2 or is subject to a strong (>99%) but readily reversible inhibition achieves quantitative agreement with detailed experimental observations of the responses of the redox status of Prx2 in human erythrocytes and suggests functional advantages of this design (see companion abstract). By contrast, a variant where Prx2 is fully active with kPrx2=10(8) M(-1)s(-1) shows important qualitative discrepancies. Altogether, these results suggest that Prx2's peroxidase activity is strongly inhibited in human erythrocytes. We acknowledge fellowship SFRH/BD/51199/2010, grants PEst-C/SAU/LA0001/2013-2014, PEst-OE/QUI/UI0612/2013, PEst-OE/QUI/UI0313/2014, and FCOMP-01-0124-FEDER-020978 (PTDC/QUI-BIQ/119657/2010) co-financed by FEDER through the COMPETE program and by FCT. PMID:26461310

  18. Endothelin 1 activates and sensitizes human C-nociceptors.

    Science.gov (United States)

    Namer, Barbara; Hilliges, Marita; Orstavik, Kristin; Schmidt, Roland; Weidner, Christian; Torebjörk, Erik; Handwerker, Hermann; Schmelz, Martin

    2008-07-01

    Microneurography was used to record action potentials from afferent C-fibers in cutaneous fascicles of the peroneal nerve in healthy volunteers. Afferent fibers were classified according to their mechanical responsiveness to von Frey stimulation (75g) into mechano-responsive and mechano-insensitive nociceptors. Various concentrations of Endothelin1 (ET1) and Histamine were injected into the receptive fields of C-fibers. Activation and heat sensitization were monitored. Axon reflex flare and psychophysical ratings were assessed after injection of ET1 and codeine into the forearms after pre-treatment with an H1 blocker or sodium chloride. 65% of mechanosensitive nociceptors were activated by ET1. One-third showed long lasting responses (>15min). In contrast, none of thirteen mechano-insensitive fibers were activated. Sensitization to heat was observed in 62% of mechanosensitive and in 46% of mechano-insensitive fibers. Injection of ET1 produced a widespread axon reflex flare, which was suppressed by pre-treatment with an H1 receptor blocker. In addition, pain sensations were induced more often than itching by ET1 in contrast to codeine. No wheal was observed after injection of ET1. Both itching and pain were decreased after H1 blocker treatment. In summary: (1) In humans ET1 activates mechanosensitive, but not mechano-insensitive, nociceptors. (2) Histamine released from mast cells is not responsible for all effects of ET1 on C-nociceptors. (3) ET1 could have a differential role in pain compared to other chemical algogens which activate additionally or even predominantly mechano-insensitive fibers. PMID:17884295

  19. Purification of human plasma platelet-activating factor acetylhydrolase

    International Nuclear Information System (INIS)

    Platelet-activating factor (PAF;1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine is synthesized by a variety of cells. It induces hypotension, and activates platelets, neutrophils, and macrophages at nanomolar concentrations. Removal of the acetate abolishes biological activity, and is catalyzed by a specific PAF acetylhydrolase present in plasma and tissues. The authors developed a rapid assay, based on separation of [3H]acetate from [3H-acetyl]PAF by reversed-phase chromatography. In human plasma the enzyme exhibits an apparent Km of 5.7μM, with a Vmax of 0.027μmol/h/mg. Ultracentrifugation in density gradients showed that 30% of the activity is associated with high density lipoproteins (HDL) and 70% with low density lipoproteins (LDL). The enzyme was purified from LDL by precipitation with Na phosphotungstate and MgCl2, solubilization with Tween 20, column chromatography and electrophoresis. This procedure resulted in a preparation that was 21,000-fold purified from plasma (spec. act. 575μmol/h/mg) with a recovery of 10%. The purified enzyme has a molecular weight of about 43,000, a broad pH optimum (peak 7.5-8.0), and a pl of 4.6. It has greater activity when PAF is in a micellar, as compared to monomeric, and exhibits surface dilution kinetics, which may be important in vivo. The purification and characterization of this enzyme will allow detailed studies of its role in PAF metabolism

  20. Exosomes: novel effectors of human platelet lysate activity

    Directory of Open Access Journals (Sweden)

    E Torreggiani

    2014-09-01

    Full Text Available Despite the popularity of platelet-rich plasma (PRP and platelet lysate (PL in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF, vascular endothelial growth factor (VEGF, platelet-derived growth factor (PDGF-BB and transforming growth factor beta 1 (TGF-β1 as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies.

  1. Exosomes: novel effectors of human platelet lysate activity.

    Science.gov (United States)

    Torreggiani, E; Perut, F; Roncuzzi, L; Zini, N; Baglìo, S R; Baldini, N

    2014-01-01

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one of the effectors of PL activity. Exosomes were isolated from human PL by differential ultracentrifugation, and analysed by electron microscopy and Western blotting. Bone marrow stromal cells (MSC) treated with three different exosome concentrations (0.6 μg, 5 μg and 50 μg) showed a significant, dose-dependent increase in cell proliferation and migration compared to the control. In addition, osteogenic differentiation assays demonstrated that exosome concentration differently affected the ability of MSC to deposit mineralised matrix. Finally, the analysis of exosome protein content revealed a higher amount of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) as compared to PL. In regards to RNA content, an enrichment of small RNAs in exosomes as compared to donor platelets has been found. These results suggest that exosomes consistently contribute to PL activity and could represent an advantageous nanodelivery system for cell-free regeneration therapies. PMID:25241964

  2. Respiratory activity and growth of human skin derma fibroblasts.

    Science.gov (United States)

    Papa, F; Scacco, S; Vergari, R; Bucaria, V; Dioguardi, D; Papa, S

    1998-09-01

    A study has been made on the speed of growth and respiratory activity of fibroblast cultures from control derma, cheloid (hypertrophic) scar and stabilized scar taken from human skin. The speed of growth and the efficiency of plaque formation of fibroblasts from cheloid scar were greater in comparison with those of fibroblasts from stabilized scar and were stimulated by the addition to the culture medium of the exudate from post-traumatic ulcer. Measurement of the contents of cytochromes showed a decrease in the content of cytochromes b562 and c + c1 in the fibroblast culture from both cheloid and stabilized scar as compared to the fibroblast culture from control derma. Cytochrome aa3 content did not show significant difference among the three types of fibroblast cultures. The respiratory activities supported by pyruvate plus malate, succinate or ascorbate plus N,N,N',N'-tetramethyl-p-phenylenediamine did not show, however, significant difference among the three fibroblast cultures. These observations show that the speed of growth of skin fibroblasts does not depend on the overall respiratory capacity. The exudate stimulated the activity of cytochrome c oxidase in fibroblasts from control derma, and cheloid scar. This effect and the accompanying stimulation of fibroblast growth might be correlated with the balance of oxygen free radicals.

  3. Environmental layout complexity affects neural activity during navigation in humans.

    Science.gov (United States)

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.

  4. Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation.

    Science.gov (United States)

    Schwalm, Céline; Jamart, Cécile; Benoit, Nicolas; Naslain, Damien; Prémont, Christophe; Prévet, Jérémy; Van Thienen, Ruud; Deldicque, Louise; Francaux, Marc

    2015-08-01

    In humans, nutrient deprivation and extreme endurance exercise both activate autophagy. We hypothesized that cumulating fasting and cycling exercise would potentiate activation of autophagy in skeletal muscle. Well-trained athletes were divided into control (n = 8), low-intensity (LI, n = 8), and high-intensity (HI, n = 7) exercise groups and submitted to fed and fasting sessions. Muscle biopsy samples were obtained from the vastus lateralis before, at the end, and 1 h after a 2 h LI or HI bout of exercise. Phosphorylation of ULK1(Ser317) was higher after exercise (P diet. PMID:25957282

  5. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    Science.gov (United States)

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  6. Efficiency of Human Activity on Information Spreading on Twitter

    CERN Document Server

    Morales, A J; Losada, J C; Benito, R M

    2014-01-01

    Understanding the collective reaction to individual actions is key to effectively spread information in social media. In this work we define efficiency on Twitter, as the ratio between the emergent spreading process and the activity employed by the user. We characterize this property by means of a quantitative analysis of the structural and dynamical patterns emergent from human interactions, and show it to be universal across several Twitter conversations. We found that some influential users efficiently cause remarkable collective reactions by each message sent, while the majority of users must employ extremely larger efforts to reach similar effects. Next we propose a model that reproduces the retweet cascades occurring on Twitter to explain the emergent distribution of the user efficiency. The model shows that the dynamical patterns of the conversations are strongly conditioned by the topology of the underlying network. We conclude that the appearance of a small fraction of extremely efficient users resul...

  7. Which activation function of cooperation describes human behavior?

    CERN Document Server

    Jarynowski, Andrzej

    2016-01-01

    Properties of cooperation's probability function in Prisoner`s Dilemma have impact on evolution of game. Basic model defines that probability of cooperation depends linearly, both on the player's altruism and the co-player's reputation. I propose modification of activation function to smooth one (hyperbolic tangent with scaling parameter a, which corresponds to its shape) and observe three phases for different range of a. (1) For small a, strategies seem to randomly change in time and situation of mixed choices (one cooperates and second defects) dominate. (2) For medium a, players choose only one strategy for given period of time (the common state can switch to opposite one with some probability). (3) For large a, mixed strategy (once defect, once cooperate) is coexisting with common strategies and no change is allowed. I believe that proposed function characterizes better socio-economical phenomena and especially phase 1 and 2 contain most of human behavior.

  8. Neutron activation analysis of organohalogens in Chinese human hair

    International Nuclear Information System (INIS)

    To effectively extract organohalogens from human hair, two factors, the extracting time and hair length on the extraction efficiency of organohalogens were studied by neutron activation analysis (NAA) and gas chromatograph-electron capture detector (GC-ECD), respectively. Furthermore, the concentrations of extractable organohalogens (EOX) and extractable persistent organohalogens (EPOX) in hair samples from angioma and control babies were also measured by the established method. The results indicated that the optimal Soxhlet-extraction time for EOX and EPOX in hair was from 8 to 11 hours, and the extraction efficiencies for organochlorine pesticides in hair were in the order of powder >2 mm>5 mm. Also, the mean levels of EOCl and EPOCl in hair of the angioma babies were significantly higher than those in the control babies (PEOClEPOCl<0.05), which implied the possible relationship between the environmental pollution and angioma. (author)

  9. Safety activities and human resource development at NCA

    International Nuclear Information System (INIS)

    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 252Cf neutron source. (S.K.)

  10. Sensitivity of the Indian Monsoon to Human Activities

    Institute of Scientific and Technical Information of China (English)

    B. KNOPF; K. ZICKFELD; M. FLECHSIG; V. PETOUKHOV

    2008-01-01

    In this paper the authors perform an extensive sensitivity analysis of the Indian summer monsoon rainfall to changes in parameters and boundary conditions which are influenced by human activities. For this study, the authors use a box model of the Indian monsoon which reproduces key features of the observed monsoon dynamics such as the annual course of precipitation and the transitions between winter and summer regimes. Because of its transparency and computational efficiency, this model is highly suitable for exploring the effects of anthropogenic perturbations such as emissions of greenhouse gases and sulfur dioxide, and land cover changes, on the Indian monsoon. Results of a systematic sensitivity analysis indicate that changes in those parameters which are related to emissions of greenhouse gases lead to an increase in Indian summer rainfall. In contrast, all parameters related to higher atmospheric aerosol concentrations lead to a decrease in Indian rainfall. Similarly, changes in parameters which can be related to forest conversion or desertification, act to decrease the summer precipitation. The results indicate that the sign of precipitation changes over India will be dependent on the direction and relative magnitude of different human perturbations.

  11. Exergy Analysis of Human Respiration Under Physical Activity

    Directory of Open Access Journals (Sweden)

    Jurandir Itizo Yanagihara

    2010-09-01

    Full Text Available

    This paper presents an exergy analysis of the human body under physical activity. A model of the respiratory system and a model of the thermal system were used for this purpose. These models consider heat and mass transfers in lungs, tissues and blood. Each component of these models is represented by a uniform compartment governed by equations for diffusion, convection, O2 consumption, CO2/heat generation and heat and mass transfer with the environment. The models allow the calculation of the exergy destruction in the lung and tissues, and the contribution of each entropy generation mechanism in the total generation. Furthermore, a discussion is proposed regarding the efficiency of the human body under physical exercise.

  12. Neurotrophin receptors expression and JNK pathway activation in human astrocytomas

    International Nuclear Information System (INIS)

    Neurotrophins are growth factors that regulate cell growth, differentiation and apoptosis in the nervous system. Their diverse actions are mediated through two different transmembrane – receptor signaling systems: Trk receptor tyrosine kinases (TrkA, TrkB, TrkC) and p75NTR neurotrophin receptor. Trk receptors promote cell survival and differentiation while p75NTR induces, in most cases, the activity of JNK-p53-Bax apoptosis pathway or suppresses intracellular survival signaling cascades. Robust Trk activation blocks p75NTR -induced apoptosis by suppressing the JNK-p53-Bax pathway. The aim of this exploratory study was to investigate the expression levels of neurotrophin receptors, Trks and p75NTR, and the activation of JNK pathway in human astrocytomas and in adjacent non-neoplastic brain tissue. Formalin-fixed paraffin-embedded serial sections from 33 supratentorial astrocytomas (5 diffuse fibrillary astrocytomas, WHO grade II; 6 anaplastic astrocytomas, WHO grade III; 22 glioblastomas multiforme, WHO grade IV) were immunostained following microwave pretreatment. Polyclonal antibodies against TrkA, TrkB, TrkC and monoclonal antibodies against p75NTR and phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were used. The labeling index (LI), defined as the percentage of positive (labeled) cells out of the total number of tumor cells counted, was determined. Moderate to strong, granular cytoplasmic immunoreactivity for TrkA, TrkB and TrkC receptors was detected in greater than or equal to 10% of tumor cells in the majority of tumors independently of grade; on the contrary, p75NTR receptor expression was found in a small percentage of tumor cells (~1%) in some tumors. The endothelium of tumor capillaries showed conspicuous immunoreactivity for TrkB receptor. Trk immunoreactivity seemed to be localized in some neurons and astrocytes in non-neoplastic tissue. Phosphorylated forms of JNK (pJNK) and c-Jun (pc-Jun) were significantly co-expressed in a tumor grade

  13. 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

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

    International Nuclear Information System (INIS)

    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

  15. Activation of human complement by immunoglobulin G antigranulocyte antibody.

    Science.gov (United States)

    Rustagi, P K; Currie, M S; Logue, G L

    1982-01-01

    The ability of antigranulocyte antibody to fix the third component of complement (C3) to the granulocyte surface was investigated by an assay that quantitates the binding of monoclonal anti-C3 antibody to paraformaldehyde-fixed cells preincubated with Felty's syndrome serum in the presence of human complement. The sera from 7 of 13 patients with Felty's syndrome bound two to three times as much C3 to granulocytes as sera from patients with uncomplicated rheumatoid arthritis. The complement-activating ability of Felty's syndrome serum seemed to reside in the monomeric IgG-containing serum fraction. For those sera capable of activating complement, the amount of C3 fixed to granulocytes was proportional to the amount of granulocyte-binding IgG present in the serum. Thus, complement fixation appeared to be a consequence of the binding of antigranulocyte antibody to the cell surface. These studies suggest a role for complement-mediated injury in the pathophysiology of immune granulocytopenia, as has been demonstrated for immune hemolytic anemia and immune thrombocytopenia. PMID:7174786

  16. Chemotactic Activity on Human Neutrophils to Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tetiana Haniastuti

    2013-07-01

    Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

  17. Active site conformational dynamics in human uridine phosphorylase 1.

    Directory of Open Access Journals (Sweden)

    Tarmo P Roosild

    Full Text Available Uridine phosphorylase (UPP is a central enzyme in the pyrimidine salvage pathway, catalyzing the reversible phosphorolysis of uridine to uracil and ribose-1-phosphate. Human UPP activity has been a focus of cancer research due to its role in activating fluoropyrimidine nucleoside chemotherapeutic agents such as 5-fluorouracil (5-FU and capecitabine. Additionally, specific molecular inhibitors of this enzyme have been found to raise endogenous uridine concentrations, which can produce a cytoprotective effect on normal tissues exposed to these drugs. Here we report the structure of hUPP1 bound to 5-FU at 2.3 A resolution. Analysis of this structure reveals new insights as to the conformational motions the enzyme undergoes in the course of substrate binding and catalysis. The dimeric enzyme is capable of a large hinge motion between its two domains, facilitating ligand exchange and explaining observed cooperativity between the two active sites in binding phosphate-bearing substrates. Further, a loop toward the back end of the uracil binding pocket is shown to flexibly adjust to the varying chemistry of different compounds through an "induced-fit" association mechanism that was not observed in earlier hUPP1 structures. The details surrounding these dynamic aspects of hUPP1 structure and function provide unexplored avenues to develop novel inhibitors of this protein with improved specificity and increased affinity. Given the recent emergence of new roles for uridine as a neuron protective compound in ischemia and degenerative diseases, such as Alzheimer's and Parkinson's, inhibitors of hUPP1 with greater efficacy, which are able to boost cellular uridine levels without adverse side-effects, may have a wide range of therapeutic applications.

  18. Complement alternative pathway activation in human nonalcoholic steatohepatitis.

    Directory of Open Access Journals (Sweden)

    Filip M Segers

    Full Text Available The innate immune system plays a major role in the pathogenesis of nonalcoholic steatohepatitis (NASH. Recently we reported complement activation in human NASH. However, it remained unclear whether the alternative pathway of complement, which amplifies C3 activation and which is frequently associated with pathological complement activation leading to disease, was involved. Here, alternative pathway components were investigated in liver biopsies of obese subjects with healthy livers (n = 10 or with NASH (n = 12 using quantitative PCR, Western blotting, and immunofluorescence staining. Properdin accumulated in areas where neutrophils surrounded steatotic hepatocytes, and colocalized with the C3 activation product C3c. C3 activation status as expressed by the C3c/native C3 ratio was 2.6-fold higher (p<0.01 in subjects with NASH despite reduced native C3 concentrations (0.94±0.12 vs. 0.57±0.09; p<0.01. Hepatic properdin levels positively correlated with levels of C3c (rs = 0.69; p<0.05 and C3c/C3 activation ratio (rs = 0.59; p<0.05. C3c, C3 activation status (C3c/C3 ratio and properdin levels increased with higher lobular inflammation scores as determined according to the Kleiner classification (C3c: p<0.01, C3c/C3 ratio: p<0.05, properdin: p<0.05. Hepatic mRNA expression of factor B and factor D did not differ between subjects with healthy livers and subjects with NASH (factor B: 1.00±0.19 vs. 0.71±0.07, p = 0.26; factor D: 1.00±0.21 vs. 0.66±0.14, p = 0.29;. Hepatic mRNA and protein levels of Decay Accelerating Factor tended to be increased in subjects with NASH (mRNA: 1.00±0.14 vs. 2.37±0.72; p = 0.22; protein: 0.51±0.11 vs. 1.97±0.67; p = 0.28. In contrast, factor H mRNA was downregulated in patients with NASH (1.00±0.09 vs. 0.71±0.06; p<0.05 and a similar trend was observed with hepatic protein levels (1.12±0.16 vs. 0.78±0.07; p = 0.08. Collectively, these data suggest a role for alternative

  19. Polystyrene nanoparticles activate ion transport in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    McCarthy J

    2011-06-01

    Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

  20. Human activity and landscape change at Adjiyska Vodenitsa, central Bulgaria

    Science.gov (United States)

    Chiverrell, R. C.; Archibald, Z.

    2009-04-01

    reflects processes during the late Holocene, with the low level hill slopes flanking the river littered with small agricultural communities. It is easy to envisage the landscape as one made susceptible to erosion by human activity feeding materials through the Momina Klissoura Gorge to the Belovo fan near the settlement at Adjiyska Vodenitsa. Sharp increases in non-arboreal pollen during the period 2880-1620 BP, associated with Greek and Roman times, in the Rila Mountains, have been attributed to seasonal animal husbandry in the higher mountains, with associated permanent settlement in the surrounding lowlands.

  1. Activation of human tonsil and skin mast cells by agonists of proteinase activated receptor-2

    Institute of Scientific and Technical Information of China (English)

    Shao-heng HE; Hua XIE; Yi-ling FU

    2005-01-01

    Aim: To investigate the effects of the agonists of proteinase activated receptor (PAR)-2,and histamine on degranulation of human mast cells. Methods: Human mast cells were enzymatically dispersed from tonsil and skin tissues. The dis persed cells were then cultured with various stimuli, and tryptase and histamine levels in cell supernatants collected from challenge tubes were measured. Results:PAR-2 agonist peptide SLIGKV provoked a dose-dependent release of histamine from skin mast cells. It also induced tryptase release from tonsil mast cells, tcLIGRLO appeared less potent than SLIGKV in induction of release of histamine and tryptase. Trypsin was able to induce a "bell" shape increase in tryptase release from tonsil mast cells. It was also able to induce a dose-dependent release of histamine from both tonsil and skin mast cells. The actions of trypsin on mast cells were inhibited by soy bean trypsin inhibitor (SBTI) or α1-antitrypsin (α1-AT).Time course study revealed that both stimulated tryptase or histamine release initiated within 10 s and reached their peak release between 4 and 6 min. Pretreatment of cells with metabolic inhibitors or pertussis toxin reduced the ability of mast cells to release tryptase or histamine. Conclusion: It was demonstrated that the in vitro tryptase release properties of human tonsil and skin mast cells suggested a novel type of mast cell heterogeneity. The activation of mast cells by PAR-2 agonists indicated a self-amplification mechanism of mast cell degranulation.

  2. The contribution of Kv7 channels to pregnant mouse and human myometrial contractility

    OpenAIRE

    McCallum, Laura A; Pierce, Stephanie L.; ENGLAND, SARAH K.; Greenwood, Iain A.; Tribe, Rachel M.

    2010-01-01

    Abstract Premature birth accounts for approximately 75% of neonatal mortality and morbidity in the developed world. Despite this, methods for identifying and treating women at risk of preterm labour are limited and many women still present in preterm labour requiring tocolytic therapy to suppress uterine contractility. The aim of this study was to assess the utility of Kv7 channel activators as potential uterine smooth muscle (myometrium) relaxants in tissues from pregnant mice and women. Myo...

  3. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  4. Epigenetic signature and enhancer activity of the human APOE gene

    Science.gov (United States)

    Yu, Chang-En; Cudaback, Eiron; Foraker, Jessica; Thomson, Zachary; Leong, Lesley; Lutz, Franziska; Gill, James Anthony; Saxton, Aleen; Kraemer, Brian; Navas, Patrick; Keene, C. Dirk; Montine, Thomas; Bekris, Lynn M.

    2013-01-01

    The human apolipoprotein E (APOE) gene plays an important role in lipid metabolism. It has three common genetic variants, alleles ɛ2/ɛ3/ɛ4, which translate into three protein isoforms of apoE2, E3 and E4. These isoforms can differentially influence total serum cholesterol levels; therefore, APOE has been linked with cardiovascular disease. Additionally, its ɛ4 allele is strongly associated with the risk of Alzheimer's disease (AD), whereas the ɛ2 allele appears to have a modest protective effect for AD. Despite decades of research having illuminated multiple functional differences among the three apoE isoforms, the precise mechanisms through which different APOE alleles modify diseases risk remain incompletely understood. In this study, we examined the genomic structure of APOE in search for properties that may contribute novel biological consequences to the risk of disease. We identify one such element in the ɛ2/ɛ3/ɛ4 allele-carrying 3′-exon of APOE. We show that this exon is imbedded in a well-defined CpG island (CGI) that is highly methylated in the human postmortem brain. We demonstrate that this APOE CGI exhibits transcriptional enhancer/silencer activity. We provide evidence that this APOE CGI differentially modulates expression of genes at the APOE locus in a cell type-, DNA methylation- and ɛ2/ɛ3/ɛ4 allele-specific manner. These findings implicate a novel functional role for a 3′-exon CGI and support a modified mechanism of action for APOE in disease risk, involving not only the protein isoforms but also an epigenetically regulated transcriptional program at the APOE locus driven by the APOE CGI. PMID:23892237

  5. Differences in neural activation for object-directed grasping in chimpanzees and humans.

    Science.gov (United States)

    Hecht, Erin E; Murphy, Lauren E; Gutman, David A; Votaw, John R; Schuster, David M; Preuss, Todd M; Orban, Guy A; Stout, Dietrich; Parr, Lisa A

    2013-08-28

    The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of this system, we performed functional neuroimaging in humans' closest living relatives, chimpanzees. We compare activations during performance of an object-directed manual grasping action, observation of the same action, and observation of a mimed version of the action that consisted of only movements without results. Performance and observation of the same action activated a distributed frontoparietal network similar to that reported in macaques and humans. Like humans and unlike macaques, these regions were also activated by observing movements without results. However, in a direct chimpanzee/human comparison, we also identified unique aspects of human neural responses to observed grasping. Chimpanzee activation showed a prefrontal bias, including significantly more activity in ventrolateral prefrontal cortex, whereas human activation was more evenly distributed across more posterior regions, including significantly more activation in ventral premotor cortex, inferior parietal cortex, and inferotemporal cortex. This indicates a more "bottom-up" representation of observed action in the human brain and suggests that the evolution of tool use, social learning, and cumulative culture may have involved modifications of frontoparietal interactions. PMID:23986247

  6. Myelostimulatory activity of recombinant human interleukin-2 in mice

    International Nuclear Information System (INIS)

    In a series of studies designed to extend our understanding of interleukin-2 (IL-2) and to study the effect of biologic response modifiers on bone marrow, we observed that administering recombinant human (rH) IL-2 to normal mice resulted in an increase in the frequency of colony-forming units-culture (CFU-C) in bone marrow. In addition, rH IL-2 was able to accelerate host recovery from cyclophosphamide (CTX)- or radiation-induced bone marrow depression and peripheral blood leukopenia. Not only can rH IL-2 accelerate, in a dose-dependent manner, the return of bone marrow, peripheral blood cellularity, and CFU-C frequency to normal levels following cytoreduction by CTX or irradiation, but it also significantly increases CFU-C frequency to greater than normal levels. Furthermore, rH IL-2 can significantly prolong survival of animals receiving a lethal dose of irradiation or CTX. Thus, multiple mechanisms are responsible for the synergistic therapeutic activity associated with rH IL-2 and CTX. rH IL-2 does not act only as an immunomodulatory agent in the presence or absence of suppressor T cells, but also accelerates host recovery from cytoreductive agents, resulting in decreased leukopenia and perhaps resistances to secondary infection. Thus, rH IL-2 plus chemotherapy may increase therapeutic activity against neoplastic disease, not only by adding immune stimulation to the direct antitumor effect of the drug but also by allowing delivery of higher, more effective doses of chemotherapy

  7. Impacts of Human Activity on the Microbial Communities of Devon Island, Canadian High Arctic

    Science.gov (United States)

    Bywaters, K. B.; Burton, A. S.; Wallace, S. L.; Glass, B. J.

    2016-09-01

    The impacts of human activities on microbial communities in arctic environments are poorly understood. This project compares the distribution of microbes at the HMP Mars analog site prior to and after human settlement.

  8. Calcium channel activity of purified human synexin and structure of the human synexin gene

    International Nuclear Information System (INIS)

    Synexin is a calcium-dependent membrane binding protein that not only fuses membranes but also acts as a voltage-dependent calcium channel. The authors have isolated and sequenced a set of overlapping cDNA clones for human synexin. The derived amino acid sequence of synexin reveals strong homology in the C-terminal domain with a previously identified class of calcium-dependent membrane binding proteins. These include endonexin II, lipocortin I, calpactin I heavy chain (p36), protein II, and calelectrin 67K. The Mr 51,000 synexin molecule can be divided into a unique, highly hydrophobic N-terminal domain of 167 amino acids and a conserved C-terminal region of 299 amino acids. The latter domain is composed of alternating hydrophobic and hydrophilic segments. Analysis of the entire structure reveals possible insights into such diverse properties as voltage-sensitive calcium channel activity, ion selectivity, affinity for phospholipids, and membrane fusion

  9. Human population and activities in Forsmark. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km{sup 2} near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the

  10. Human population and activities in Forsmark. Site description

    International Nuclear Information System (INIS)

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced.The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations.The data in this description is essential for future evaluations of the impact on the environment and its human population (Environmental Impact Assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments.The actual area for the study is in this report called 'the Forsmark area', an area of 19.5 km2 near Forsmark nuclear power plant. The land use in the Forsmark area differs notably from the land use in Uppsala laen (laen = county). Only 0.04% of the total area is developed (built-up) compared to 4.9% in Uppsala laen and only 4% is agricultural land compared to 25% in the county. Furthermore, there are far more forest, wetlands and water areas in the Forsmark area. The forest area represents as much as 72.5% of the total area.The Forsmark area is uninhabited, and its surroundings are very sparsely populated. In 2002, the population density in Forsmark was 1.8 inhabitants per square kilometre, which was 24 times lower than in Uppsala laen. The population density in the parish has been

  11. Rhythmic Working Memory Activation in the Human Hippocampus

    Directory of Open Access Journals (Sweden)

    Marcin Leszczyński

    2015-11-01

    Full Text Available Working memory (WM maintenance is assumed to rely on a single sustained process throughout the entire maintenance period. This assumption, although fundamental, has never been tested. We used intracranial electroencephalography (EEG recordings from the human hippocampus in two independent experiments to investigate the neural dynamics underlying WM maintenance. We observed periodic fluctuations between two different oscillatory regimes: Periods of “memory activation” were reflected by load-dependent alpha power reductions and lower levels of cross-frequency coupling (CFC. They occurred interleaved with periods characterized by load-independent high levels of alpha power and CFC. During memory activation periods, a relevant CFC parameter (load-dependent changes of the peak modulated frequency correlated with individual WM capacity. Fluctuations between these two periods predicted successful performance and were locked to the phase of endogenous delta oscillations. These results show that hippocampal maintenance is a dynamic rather than constant process and depends critically on a hierarchy of oscillations.

  12. Activation of transforming potential of the human insulin receptor gene

    International Nuclear Information System (INIS)

    A retrovirus containing part of the human insulin receptor (hIR) gene was constructed by replacing ros sequences in the avian sarcoma virus UR2 with hIR cDNA sequences coding for 46 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains of the β subunit of hIR. The resulting virus, named UIR, contains the hIR sequence fused to the 5' portion of the UR2 gag gene coding for p19. UIR is capable of transforming chicken embryo fibroblasts and promoting formation of colonies in soft agar; however, it does not form tumors in vivo. A variant that arose from the parental UIR is capable of efficiently inducing sarcomas in vivo. UIR-transformed cells exhibit higher rates of glucose uptake and growth than normal cells. The 4-kilobase UIR genome codes for a membrane-associated, glycosylated gag-hIR fusion protein of 75 kDa designated P75/sup gag-hir/. P75/sup gag-hir/ contains a protein tyrosine kinase activity that is capable of undergoing autophosphorylation and of phosphorylating foreign substrates in vitro; it is phosphorylated at both serine and tyrosine residues in vivo

  13. Activation of transforming potential of the human insulin receptor gene

    Energy Technology Data Exchange (ETDEWEB)

    Wang, L.H.; Lin, B.; Jong, S.M.J.; Dixon, D.; Ellis, L.; Roth, R.A.; Rutter, W.J.

    1987-08-01

    A retrovirus containing part of the human insulin receptor (hIR) gene was constructed by replacing ros sequences in the avian sarcoma virus UR2 with hIR cDNA sequences coding for 46 amino acids of the extracellular domain and the entire transmembrane and cytoplasmic domains of the ..beta.. subunit of hIR. The resulting virus, named UIR, contains the hIR sequence fused to the 5' portion of the UR2 gag gene coding for p19. UIR is capable of transforming chicken embryo fibroblasts and promoting formation of colonies in soft agar; however, it does not form tumors in vivo. A variant that arose from the parental UIR is capable of efficiently inducing sarcomas in vivo. UIR-transformed cells exhibit higher rates of glucose uptake and growth than normal cells. The 4-kilobase UIR genome codes for a membrane-associated, glycosylated gag-hIR fusion protein of 75 kDa designated P75/sup gag-hir/. P75/sup gag-hir/ contains a protein tyrosine kinase activity that is capable of undergoing autophosphorylation and of phosphorylating foreign substrates in vitro; it is phosphorylated at both serine and tyrosine residues in vivo

  14. Impact of human activities on soil respiration:A review

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Soil respiration is one of the primary fluxes of carbon between soils and the atmosphere.It is produced by rhizosphere respiration and soil microbial respiration.Soil respiration is not only affected by environmental factors,but also changes with the hu-man-induced disturbances of ecosystems.Land-use,the measures of land management,the pollution of soil,and so on can affect soil respiration and change the soil efflux.According to some research,the authors summed up their impacts on soil respiration by human activities through land-use changes and land-management measures among agroecosystem,grassland ecosystem,and for-est ecosystem.The results showed that (1) when adding fertilization to farmland,the soil respiration will increase;(2) fenced land can decrease soil respiration,while soil respiration in the grazed land at a grassland ecosystem will decline with the increasing of grazing intensity;(3) with grassland fertilization;farmland cultivation;fire,fertilization,and cutting of forest,conflicting results were found in the changes of soil respiration.Perhaps plant species,site condition,and measurement season can lead to different results on soil respiration.

  15. Global changes in biogeochemical cycles in response to human activities

    Science.gov (United States)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

    The main objective of our research was to characterize biogeochemical cycles at continental and global scales in both terrestrial and aquatic ecosystems. This characterization applied to both natural ecosystems and those disturbed by human activity. The primary elements of interest were carbon and nitrogen and the analysis sought to quantify standing stocks and dynamic cycling processes. The translocation of major nutrients from the terrestrial landscape to the atmosphere (via trace gases) and to fluvial systems (via leaching, erosional losses, and point source pollution) were of particular importance to this study. Our aim was to develop the first generation of Earth System Models. Our research was organized around the construction and testing of component biogeochemical models which treated terrestrial ecosystem processes, aquatic nutrient transport through drainage basins, and trace gas exchanges at the continental and global scale. A suite of three complementary models were defined within this construct. The models were organized to operate at a 1/2 degree latitude by longitude level of spatial resolution and to execute at a monthly time step. This discretization afforded us the opportunity to understand the dynamics of the biosphere down to subregional scales, while simultaneously placing these dynamics into a global context.

  16. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

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

    Science.gov (United States)

    Norfleet, William; Harris, Bernard

    2009-01-01

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

  18. Activities of nuclear human resource development in nuclear industry

    International Nuclear Information System (INIS)

    Since 2007, the JAIF (Japan Atomic Industrial Forum) had established the nuclear energy human resource development council to make analysis of the issue on nuclear human resource development. The author mainly contributed to develop its road map as a chairman of working group. Questionnaire survey to relevant parties on issues of nuclear human resource development had been conducted and the council identified the six relevant issues and ten recommendations. Both aspects for career design and skill-up program are necessary to develop nuclear human resource at each developing step and four respective central coordinating hubs should be linked to each sector participating in human resource development. (T. Tanaka)

  19. A two-layered approach to recognize high-level human activities

    NARCIS (Netherlands)

    N. Hu; G. Englebienne; B. Kröse

    2014-01-01

    Automated human activity recognition is an essential task for Human Robot Interaction (HRI). A successful activity recognition system enables an assistant robot to provide precise services. In this paper, we present a two-layered approach that can recognize sub-level activities and high-level activi

  20. Reindeer and caribou (Rangifer tarandus response towards human activities

    Directory of Open Access Journals (Sweden)

    Eigil Reimers

    2009-01-01

    Full Text Available We address the question of how human activities and infrastructure influence reindeer/caribou’s (Rangifer tarandus behaviour and habitat use and review studies based on current methodologies. Anthropogenic activities have a direct affect on Rangifer behaviour through the senses hearing, sight and smell, and all of these are important tools for behavioural risk assessment. Short term indirect responses, such as habituation, sensitisation, avoidance, and displacement, develop through neutral, positive or negative associations towards stimulus in terms of Rangifer’s ability to experience, learn, and remember. Long term behavioural responses develop through interaction with predators and, for reindeer, also domestication. A survey of the literature dealing with behavioural studies reveals that although Rangifer in most cases retreat from anthropogenic activities, comfort distances (i.e. distances beyond which animal behaviour or activity are not influenced are relatively short. In most cases, energetic implications appear moderate and small compared to other natural, biotic influences such as disturbance (and death caused by insect and/or predator harassment. Unless obstructing access, physical constructions of various kinds apparently have limited effects on Rangifer behaviour or habitat use. On the other hand, constructions that do obstruct or limit access and recreational or other motorized and non-motorized activities appear to have stronger impacts on avoidance and redistribution of Rangifer. Behavioural effects that might decrease survival and reproduction include retreat from favourable habitat near disturbance sources and reduction of time spent feeding with resulting energy depletion over time. Rangifer habitat use, habitat avoidance, and feeding preferences are governed by a complexity of natural interacting factors. Domestication, habituation and sensitisation are essential in shaping Rangifer’s adaptability, and should be included

  1. Differences in Neural Activation for Object-Directed Grasping in Chimpanzees and Humans

    OpenAIRE

    Hecht, Erin E.; Murphy, Lauren E.; Gutman, David A.; Votaw, John R.; Schuster, David M; Todd M Preuss; Orban, Guy A.; Stout, Dietrich; Parr, Lisa A.

    2013-01-01

    The human faculty for object-mediated action, including tool use and imitation, exceeds that of even our closest primate relatives and is a key foundation of human cognitive and cultural uniqueness. In humans and macaques, observing object-directed grasping actions activates a network of frontal, parietal, and occipitotemporal brain regions, but differences in human and macaque activation suggest that this system has been a focus of selection in the primate lineage. To study the evolution of ...

  2. Human activity and climate variability project - annual report 2002

    International Nuclear Information System (INIS)

    Work is well underway on identifying the spatial and temporal extent, direction and range of trace element transport across Tasmania through analysis of lake sediments; A follow up investigation of sedimentation and pollution in the Nattai River catchment following the devastating 2001 bushfires in the region has been completed; The project has been extended to include investigations of evidence of human impacts in the highly sensitive and ecologically important Great Lakes of coastal NSW. This has involved the expansion of our collaboration to include Geoscience Australia; Contributions have been made to the IGBP HITE project. Further contributions will be made as the evidence gathered is drawn together and interpreted; Over the coming year, focus will be placed on completion of the investigation of the extent of aerial transport of trace elements across Tasmania over the last 200 years as well as evidence for human activity and impacts on the Great Lakes region of NSW. Further investigation of potential climate signals from sites in northern Australia will also be made. The first 12 months of data for all ACE-Asia radon and fine particle sites is now available with preliminary analyses performed; The seasonal variability of background radon concentration at each of the radon monitoring sites has been characterised for the available data; Major components related to industrial pollution and soil sources in China have been identified and quantified; Regional and seasonal variations and trends in aerosol constituents have been measured and compared across more than 2.8Mk2 of sampling area; The Hok Tsui and Kosan detectors were visited for general maintenance and recalibration; A grant application to the APN has been submitted in support of regional inventory analyses based on radon time series; Progress on the processing and interpretation of radon data was presented at the Cape Grim Science Meeting (6-7 February 2002) and the 7th Biennial SPERA Conference on

  3. A Set of Activity-Based Probes to Visualize Human (Immuno)proteasome Activities.

    Science.gov (United States)

    de Bruin, Gerjan; Xin, Bo Tao; Kraus, Marianne; van der Stelt, Mario; van der Marel, Gijsbert A; Kisselev, Alexei F; Driessen, Christoph; Florea, Bogdan I; Overkleeft, Herman S

    2016-03-18

    Proteasomes are therapeutic targets for various cancers and autoimmune diseases. Constitutively expressed proteasomes have three active sites, β1c, β2c, and β5c. Lymphoid tissues also express the immunoproteasome subunits β1i, β2i, and β5i. Rapid and simultaneous measurement of the activity of these catalytic subunits would assist in the discovery of new inhibitors, improve analysis of proteasome inhibitors in clinical trials, and simplify analysis of subunit expression. In this work, we present a cocktail of activity-based probes that enables simultaneous gel-based detection of all six catalytic human proteasome subunits. We used this cocktail to develop specific inhibitors for β1c, β2c, β5c, and β2i, to compare the active-site specificity of clinical proteasome inhibitors, and to demonstrate that many hematologic malignancies predominantly express immunoproteasomes. Furthermore, we show that selective and complete inhibition of β5i and β1i is cytotoxic to primary cells from acute lymphocytic leukemia (ALL) patients. PMID:26511210

  4. Preliminary Research on the Application of Virtual Touch Tissue Quantification in the Myometrium Lesions%声触诊组织量化技术在子宫肌层病变中的应用初探

    Institute of Scientific and Technical Information of China (English)

    耿京; 唐军; 祁文娟

    2012-01-01

    Objective To conduct a preliminary research on the value of applying virtual touch tissue quantification (VTQ) in the assessment of myometrium lesions. Methods VTQ technology was used to examine myometriura lesions of 78 cases of uterine fibroids, 16 cases of uterine adenomyosis and 83 cases of normal uterus wall. Measurement values were recorded and statistical analysis was performed. Results VTQ means of uterine fibroids and denomyosis are respectively 3.58 ?0.76 and 3.53 ?1.08, which are significantly greater than that of normal uterus wall of 2.84 ?0.89 (P<0.05).Conclusion The VTQ showed that the hardness of myometrium lesions of uterine fibroids and adenomyosis had increased significantly compared with those of normal uterus wall, indicating that there is value of applying VTQ in uterine muscle wall lesions.%目的 初步探讨声触诊组织量化技术(VTQ)在子宫肌层病变中的应用价值.方法 应用VTQ技术检测78例子宫肌瘤患者及16例子宫腺肌症患者的宫壁病变区以及83例正常子宫宫壁,并对记录测量数值进行统计分析.结果 子宫肌瘤VTQ均值3.58±0.76、子宫腺肌症VTQ均值3.53±1.08,均明显大于正常子宫宫壁VTQ均值2.84±0.89(P<0.05).结论 正常宫壁与病变宫壁之间弹性比较有统计学差异,说明弹性超声应用在子宫肌壁病变有一定价值.

  5. Recombinant human migration inhibitory factor has adjuvant activity.

    OpenAIRE

    Weiser, W Y; Pozzi, L M; Titus, R G; David, J R

    1992-01-01

    Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA-DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell prolife...

  6. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells.

    OpenAIRE

    Goodwin, R G; Lupton, S; Schmierer, A; Hjerrild, K J; Jerzy, R; Clevenger, W; Gillis, S; Cosman, D; Namen, A E

    1989-01-01

    A cDNA encoding biologically active human interleukin 7 was isolated by hybridization with the homologous murine clone. Nucleotide sequence analysis indicated that this cDNA was capable of encoding a protein of 177 amino acids with a signal sequence of 25 amino acids and a calculated mass of 17.4 kDa for the mature protein. Recombinant human interleukin 7 stimulated the proliferation of murine pre-B cells and was active on cells harvested from human bone marrow that are enriched for B-lineage...

  7. Aminobisphosphonates Synergize with Human Cytomegalovirus To Activate the Antiviral Activity of Vγ9Vδ2 Cells.

    Science.gov (United States)

    Daguzan, Charline; Moulin, Morgane; Kulyk-Barbier, Hanna; Davrinche, Christian; Peyrottes, Suzanne; Champagne, Eric

    2016-03-01

    Human Vγ9Vδ2 T cells are activated through their TCR by neighboring cells producing phosphoantigens. Zoledronate (ZOL) treatment induces intracellular accumulation of the phosphoantigens isopentenyl pyrophosphate and ApppI. Few attempts have been made to use immunomanipulation of Vγ9Vδ2 lymphocytes in chronic viral infections. Although Vγ9Vδ2 T cells seem to ignore human CMV (HCMV)-infected cells, we examined whether they can sense HCMV when a TCR stimulus is provided with ZOL. Fibroblasts treated with ZOL activate Vγ9Vδ2 T cells to produce IFN-γ but not TNF. Following the same treatment, HCMV-infected fibroblasts stimulate TNF secretion and an increased production of IFN-γ, indicating that Vγ9Vδ2 cells can sense HCMV infection. Increased lymphokine production was observed with most clinical isolates and laboratory HCMV strains, HCMV-permissive astrocytoma, or dendritic cells, as well as "naive" and activated Vγ9Vδ2 cells. Quantification of intracellular isopentenyl pyrophosphate/ApppI following ZOL treatment showed that HCMV infection boosts their accumulation. This was explained by an increased capture of ZOL and by upregulation of HMG-CoA synthase and reductase transcription. Using an experimental setting where infected fibroblasts were cocultured with γδ cells in submicromolar concentrations of ZOL, we show that Vγ9Vδ2 cells suppressed substantially the release of infectious particles while preserving uninfected cells. Vγ9Vδ2 cytotoxicity was decreased by HCMV infection of targets whereas anti-IFN-γ and anti-TNF Abs significantly blocked the antiviral effect. Our experiments indicate that cytokines produced by Vγ9Vδ2 T cells have an antiviral potential in HCMV infection. This should lead to in vivo studies to explore the possible antiviral effect of immunostimulation with ZOL in this context. PMID:26819204

  8. Variability of human hepatic UDP-glucuronosyltransferase activity

    NARCIS (Netherlands)

    Little, JM; Lester, R; Kuipers, F; Vonk, R; Mackenzie, PI; Drake, RR; Frame, L; Radominska-Pandya, A

    1999-01-01

    The availability of a unique series of liver samples from human subjects, both control patients (9) and those with liver disease (6; biliary atresia (2), retransplant, chronic tyrosinemia type I, tyrosinemia, Wilson's disease) allowed us to characterize human hepatic UDP-glucuronosyltransferases usi

  9. Human population and activities at Simpevarp. Site description

    International Nuclear Information System (INIS)

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km2 near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km2, three times lower than in Kalmar laen. The demography statistics show no

  10. Human population and activities at Simpevarp. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km{sup 2} near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km{sup 2}, three times lower than in Kalmar laen. The

  11. Human population and activities at Simpevarp. Site description

    Energy Technology Data Exchange (ETDEWEB)

    Miliander, Sofia; Punakivi, Mari; Kylaekorpi, Lasse; Rydgren, Bernt [SwedPower AB, Stockholm (Sweden)

    2004-12-01

    The Swedish Nuclear Fuel and Waste Management Co (SKB) is in the process of selecting a safe and environmentally acceptable location for a deep repository of radioactive waste. Two alternative locations are under investigation. These are Forsmark, Oesthammars kommun (kommun = municipality) and Simpevarp/Laxemar, Oskarshamns kommun. SKB has expressed the importance of describing the humans and their activities in these areas and therefore has this synthesis concerning the human population in Forsmark been produced. The description is a statistical synthesis, mainly based upon statistical data from SCB (Statistics Sweden) that has been collected, processed and analysed. The statistical data has not been verified through site inspections and interviews. When using statistical data, it is advisable to note that the data becomes more unreliable if the areas are small, with small populations. The data in this description is essential for future evaluations of the impact on the environment and its human population (environmental impacts assessments). The data is also important when modelling the potential flows of radio nuclides and calculating the risk of exposure in future safety assessments. The actual area for the study is in this report called 'the Simpevarp area', an area of 127.0 km{sup 2} near Oskarshamn nuclear power plant. The land use in Simpevarp area differs notably from the land use in Kalmar laen. The forest area is far more dominating in Simpevarp area than in Kalmar laen and it represents as much as 89% compared to 63% of the total area. Only 4.4% of the area is arable land compared to 11.6% in Kalmar laen and only 0.3% is of other type (wetlands, bare rock, quarries, pites etc) compared to 15.6% in the county. The main observation is that Simpevarp area is a sparsely populated area located in a relatively lightly populated county. In 2002, the population density was 7.4 inhabitants/km{sup 2}, three times lower than in Kalmar laen. The

  12. Activity of antiretroviral drugs in human infections by opportunistic agents

    Directory of Open Access Journals (Sweden)

    Izabel Galhardo Demarchi

    2012-03-01

    Full Text Available Highly active antiretroviral therapy (HAART is used in patients infected with HIV. This treatment has been shown to significantly decrease opportunist infections such as those caused by viruses, fungi and particularly, protozoa. The use of HAART in HIV-positive persons is associated with immune reconstitution as well as decreased prevalence of oral candidiasis and candidal carriage. Antiretroviral therapy benefits patients who are co-infected by the human immunodeficiency virus (HIV, human herpes virus 8 (HHV-8, Epstein-Barr virus, hepatitis B virus (HBV, parvovirus B19 and cytomegalovirus (CMV. HAART has also led to a significant reduction in the incidence, and the modification of characteristics, of bacteremia by etiological agents such as Staphylococcus aureus, coagulase negative staphylococcus, non-typhoid species of Salmonella, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. HAART can modify the natural history of cryptosporidiosis and microsporidiosis, and restore mucosal immunity, leading to the eradication of Cryptosporidium parvum. A similar restoration of immune response occurs in infections by Toxoplasma gondii. The decline in the incidence of visceral leishmaniasis/HIV co-infection can be observed after the introduction of protease inhibitor therapy. Current findings are highly relevant for clinical medicine and may serve to reduce the number of prescribed drugs thereby improving the quality of life of patients with opportunistic diseases.A terapia HAART (terapia antirretroviral altamente ativa é usada em pacientes infectados pelo vírus da imunodeficiência humana (HIV e demonstrou diminuição significativa de infecções oportunistas, tais como as causadas por vírus, fungos, protozoários e bactérias. O uso da HAART está associado com a reconstituição imunológica e diminuição na prevalência de candidíase oral. A terapia antirretroviral beneficia pacientes co-infectados pelo HIV, v

  13. 77 FR 74517 - Agency Information Collection Activities: Comment Request; Education and Human Resources Project...

    Science.gov (United States)

    2012-12-14

    ... FOUNDATION Agency Information Collection Activities: Comment Request; Education and Human Resources Project...: Education and Human Resources Program Monitoring Clearance. OMB Approval Number: 3145-NEW. Type of Request... parts of the United States and internationally. The Directorate for Education and Human Resources...

  14. Erosion of the Mekong delta: the role of human activities

    Science.gov (United States)

    Anthony, E.; Dussouillez, P.; Goichot, M.; Brunier, G.; Dolique, F.; Nguyen, V.; Loisel, H.; Mangin, A.; Vantrepotte, V.

    2013-12-01

    River deltas are threatened by dams, dykes, flow channelling, and aggregate extraction. These activities outweigh climate change and sea-level rise in causing delta vulnerability1, and will aggravate the impacts to be expected from these effects2. We show here from analysis of: (1) delta channel morphology and sediment budgets, and (2) satellite imagery, that the Mekong delta, considered as the world's third largest, and hitherto strongly prograding, is now in a phase of large-scale erosion. We discuss the mechanistic links involved in erosion and the way these are related to human activities. High-resolution (2.5 m) SPOT 5 images for the years 2003, 2007, 2011/12 covering 405 km of the delta shoreline show an overall retreat rate of over 8 m a year. 75% of the analysed shoreline, i.e., the muddy western sector, is now retreating at rates exceeding 50 m a year in places. The sandy river-mouth sector maintains a semblance of stability, but with strong variations. We attribute erosion to a cascade of morphosedimentary changes linked to sediment mining from the deltaic channels and upstream dam interception. We estimated from Meris satellite imagery an annual 5% decrease in surface suspended concentrations exiting at the mouths of the Mekong over the period 2003-2011 that may reflect increased trapping of mud behind dams in China. We also infer modification of river-mouth and coastal mud storage patterns resulting from a loss of ca. 200 million m3 of delta channel sediments between 1998 and 2008 from aggregate extraction. Dykes have been shown to result in increased channel flow velocities during the high-discharge monsoon season, favouring further channel deepening3. Stronger river-mouth outflow velocities during this season may be leading to export of a greater proportion of mud far offshore of the coastal longshore transport corridor that ensured mud supply to, and past progradation of, the muddy western coast. In contrast, greater seawater penetration in the

  15. Sialic acid content in human saliva and anti-influenza activity against human and avian influenza viruses.

    Science.gov (United States)

    Limsuwat, Nattavatchara; Suptawiwat, Ornpreya; Boonarkart, Chompunuch; Puthavathana, Pilaipan; Wiriyarat, Witthawat; Auewarakul, Prasert

    2016-03-01

    It was shown previously that human saliva has higher antiviral activity against human influenza viruses than against H5N1 highly pathogenic avian influenza viruses, and that the major anti-influenza activity was associated with sialic-acid-containing molecules. To further characterize the differential susceptibility to saliva among influenza viruses, seasonal influenza A and B virus, pandemic H1N1 virus, and 15 subtypes of avian influenza virus were tested for their susceptibility to human and chicken saliva. Human saliva showed higher hemagglutination inhibition (HI) and neutralization (NT) titers against seasonal influenza A virus and the pandemic H1N1 viruses than against influenza B virus and most avian influenza viruses, except for H9N2 and H12N9 avian influenza viruses, which showed high HI and NT titers. To understand the nature of sialic-acid-containing anti-influenza factors in human saliva, α2,3- and α2,6-linked sialic acid was measured in human saliva samples using a lectin binding and dot blot assay. α2,6-linked sialic acid was found to be more abundant than α2,3-linked sialic acid, and a seasonal H1N1 influenza virus bound more efficiently to human saliva than an H5N1 virus in a dot blot analysis. These data indicated that human saliva contains the sialic acid type corresponding to the binding preference of seasonal influenza viruses.

  16. Proteomic Analysis of Intraluminal Thrombus Highlights Complement Activation in Human Abdominal Aortic Aneurysms

    DEFF Research Database (Denmark)

    Martinez-Pinna, Roxana; Madrigal-Matute, Julio; Tarin, Carlos;

    2013-01-01

    To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA).......To identify proteins related to intraluminal thrombus biological activities that could help to find novel pathological mechanisms and therapeutic targets for human abdominal aortic aneurysm (AAA)....

  17. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle

    DEFF Research Database (Denmark)

    Juel, Carsten; Nordsborg, Nikolai Baastrup; Bangsbo, Jens

    2014-01-01

    P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle....

  18. TELOMERASE ACTIVITY IN HUMAN GASTRIC AND COLORECTAL CANCER AND SURROUNDING TISSUES

    Institute of Scientific and Technical Information of China (English)

    CHEN Wen; ZHANG Qiao; WAN De-sen; CUN Ling-yun; WU Cheng-qiu; PAN Zhi-zhong

    1999-01-01

    Objective: To study the telomerase activities in human gastric and colorectal tumors. Methods: The telomerase activity was assayed by the telomeric repeat amplification protocol (TRAP) technique. Forty human tumor samples including 9 colonic, 20 rectal and 11gastric carcinomas and their surrounding tissues were used for the detection. Results: Thirty-six out of 40human tumor samples exhibited telomerase activity regardless of the stages or the differentiation of the tumors. However, only 1 out of 39 tumor surrounding tissues showed telomerase activity. Conclusion: Telomerase may be a good diagnosis biomarker for tumor detection.

  19. Human odontoblast-like cells produce nitric oxide with antibacterial activity upon TLR2 activation

    Directory of Open Access Journals (Sweden)

    Jean-Christophe eFARGES

    2015-06-01

    Full Text Available The penetration of cariogenic oral bacteria into enamel and dentin during the caries process triggers an immune/inflammatory response in the underlying pulp tissue, the reduction of which is considered a prerequisite to dentinogenesis-based pulp regeneration. If the role of odontoblasts in dentin formation is well known, their involvement in the antibacterial response of the dental pulp to cariogenic microorganisms has yet to be elucidated. Our aim here was to determine if odontoblasts produce nitric oxide (NO with antibacterial activity upon activation of Toll-like receptor-2 (TLR2, a cell membrane receptor involved in the recognition of cariogenic Gram-positive bacteria. Human odontoblast-like cells differentiated from dental pulp explants were stimulated with the TLR2 synthetic agonist Pam2CSK4. We found that NOS1, NOS2 and NOS3 gene expression was increased in Pam2CSK4-stimulated odontoblast-like cells compared to unstimulated ones. NOS2 was the most up-regulated gene. NOS1 and NOS3 proteins were not detected in Pam2CSK4-stimulated or control cultures. NOS2 protein synthesis, NOS activity and NO extracellular release were all augmented in stimulated samples. Pam2CSK4-stimulated cell supernatants reduced Streptococcus mutans growth, an effect counteracted by the NOS inhibitor L-NAME. In vivo, the NOS2 gene was up-regulated in the inflamed pulp of carious teeth compared with healthy ones. NOS2 protein was immunolocalized in odontoblasts situated beneath the caries lesion but not in pulp cells from healthy teeth. These results suggest that odontoblasts may participate to the antimicrobial pulp response to dentin-invading Gram-positive bacteria through NOS2-mediated NO production. They might in this manner pave the way for accurate dental pulp healing and regeneration.

  20. Radioimmunoassay for human pancreatic amylase: comparison of human serum amylase by measurement of enzymatic activity and by radioimmunoassay

    International Nuclear Information System (INIS)

    A radioimmunoassay (RIA) for human pancreatic amylase has been developed for the determination of human serum amylase content. The assay was shown to be sensitive (7 ng/mI), reproducible and specific, but human pancreatic amylase and salivary amylase could not be distinguished by the antiserum used. In normal subjects, the mean concentration of amylase determined by the RIA was found to be 122.1 ng/ml (range: 55-250 ng/ml). A good correlation was observed between the concentration of amylase and its enzymatic activity in normal subjects. In some instances with high amylase activity, however, the rise in enzymatic activity was not accompanied by increasing amount of amylase content. (Auth.)

  1. Proliferative activity in the juxtaradicular human periodontal ligament.

    Science.gov (United States)

    Sayaniwas, M; Hilliges, M; Lindskog, S

    1999-08-01

    The aim of the present study was to evaluate cell proliferation, assessed by MIB 1, with respect to the type and the distribution of proliferating cells in the healthy juxtaradicular periodontal ligament (PDL) from completely formed human teeth. Immunohistochemical markers against vimentin, CD68 and S-100 were used to characterize cell type. The applicability of the immunohistochemical method on explants of human PDL was also evaluated. The results indicated that under physiological conditions, the majority of the proliferating cells in the PDL were mesenchymal cells predominantly located paravascularly in the middle third of the PDL. Furthermore, MIB 1 reacting with the Ki-67 antigen together with the avidin-biotin-complex technique was proved to be an efficient marker of cell proliferation in explants of human PDL. PMID:10815567

  2. The effect of dietary fiber on human pancreatic enzyme activity in vitro.

    Science.gov (United States)

    Dunaif, G; Schneeman, B O

    1981-06-01

    Human pancreatic juice was used as a source of amylase, lipase, trypsin, and chymotrypsin. The human pancreatic juice was incubated with one of several dietary fibers, including alfalfa, oat bran, pectin. Solka Floc, wheat bran, and xylan. In addition, the human pancreatic juice was incubated without any fiber, which was used as the control. Incubation with Solka Floc (cellulose) and xylan (a hemicellulose) resulted in a substantial loss of activity in all enzymes assayed. Wheat bran and oat bran decreased amylase and chymotrypsin activity, while alfalfa decreased trypsin and chymotrypsin activity. Incubation with pectin significantly increased amylase and chymotrypsin activity. The mechanism by which sources of dietary fiber can alter enzyme activity is currently unknown. This effect of a dietary component on the activity of human pancreatic enzymes emphasizes the need to investigate further the effects of dietary fiber on digestion and absorption in the small intestine to understand fully its effects on metabolism. PMID:6165234

  3. Endothelin converting enzyme (ECE) activity in human vascular smooth muscle

    OpenAIRE

    Maguire, Janet J.; Johnson, Christopher M.; Mockridge, James W; Davenport, Anthony P

    1997-01-01

    We have characterized the human smooth muscle endothelin converting enzyme (ECE) present in the media of the endothelium-denuded human umbilical vein preparation.Endothelin-1 (ET-1) and ET-2 were potent constrictors of umbilical vein with EC50 values of 9.2 nM and 29.6 nM, respectively. ET-1 was at least 30 times more potent than ET-3 suggesting the presence of constrictor ETA receptors. Little or no response was obtained to the ETB-selective agonist sarafotoxin 6c. These data suggest that en...

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

    Directory of Open Access Journals (Sweden)

    Jenny Coleshill

    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.

  5. Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Birk, Jesper Bratz; Klein, Ditte Kjærsgaard;

    2006-01-01

    5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK...

  6. Pacemaker activity of the human sinoatrial node: Role of the hyperpolarization-activated current, I-f

    NARCIS (Netherlands)

    A.O. Verkerk; A.C.G. van Ginneken; R. Wilders

    2009-01-01

    The mechanism of primary, spontaneous cardiac pacemaker activity of the sinoatrial node (SAN) has extensively been studied in several animal species, but is virtually unexplored in man. Understanding the mechanisms of human SAN pacemaker activity is important for developing new therapeutic approache

  7. Enhanced transcriptional activation by E2 proteins from the oncogenic human papillomaviruses.

    OpenAIRE

    Kovelman, R; Bilter, G K; Glezer, E; Tsou, A Y; Barbosa, M S

    1996-01-01

    A systematic comparison of transcriptional activation by papillomavirus E2 proteins revealed that the E2 proteins from high-risk human papillomaviruses (human papillomavirus type 16 [HPV-16] and HPV-18) are much more active than are the E2 proteins from low-risk HPVs (HPV-6b and HPV-11). Despite the tropism of HPVs for particular epithelial cell types, this difference in transcriptional activation was observed in a number of different epithelial and nonepithelial cells. The enhanced activitie...

  8. Indoleamine-2,3-dioxygenase activity in experimental human endotoxemia

    NARCIS (Netherlands)

    Padberg, Jan-Sören; Van Meurs, Matijs; Kielstein, Jan T; Martens-Lobenhoffer, Jens; Bode-Böger, Stefanie M; Zijlstra, Jan G; Kovesdy, Csaba P; Kümpers, Philipp

    2012-01-01

    UNLABELLED: BACKGROUND: Excessive tryptophan metabolism to kynurenine by the rate-limiting enzyme endothelial indoleamine 2,3-dioxygenase 1 (IDO) controls arterial vessel relaxation and causes hypotension in murine endotoxemia. However, its relevance in human endotoxemia has not been investigated so

  9. Generation of monoclonal antibodies to native active human glycosyltransferases

    DEFF Research Database (Denmark)

    Vester-Christensen, Malene Bech; Bennett, Eric Paul; Clausen, Henrik;

    2013-01-01

    Complex carbohydrates serve a wide range of biological functions in cells and tissues. Their biosynthesis involves more than 200 distinct glycosyltransferases in human cells, and the expression, properties, and topology of these enzymes regulate the glycosylation patterns of proteins and lipids. ...

  10. Neutron activation analysis of manganese in human hair and serum

    International Nuclear Information System (INIS)

    Objective and method of manganese determination in human hair and serum in toxicology are presented considering the occupational exposure of welders. The results are discussed in detail with regard to the frequency distribution and to the reliability of identification of welders and non-welders. (author)

  11. Developmental competence of parthenogenetic mouse and human embryos after chemical or electrical activation.

    Science.gov (United States)

    Versieren, Karen; Heindryckx, Björn; Lierman, Sylvie; Gerris, Jan; De Sutter, Petra

    2010-12-01

    Parthenogenetic reconstruction is one major strategy to create patient-specific stem cells. The aim of this study was to find the best artificial activation protocol for parthenogenetic activation of mouse and human oocytes comparing different methods. In a first set of experiments, in-vivo matured mouse oocytes and human failed-fertilized, in-vitro and in-vivo matured oocytes were artificially activated by a chemical (ionomycin) or electrical stimulus. In a second set of experiments, a combination of activating agents (electrical pulses followed by ionomycin or SrCl(2)) was applied in an aim to improve developmental competence. All embryos were evaluated daily until day 6 after activation. Mouse blastocysts were differentially stained to evaluate blastocyst quality. For mouse oocytes and human failed-fertilized oocytes, blastocyst development was significantly higher after electrical activation (P<0.05). For human in-vitro and in-vivo matured oocytes, blastocyst formation was only obtained after electrical activation of in-vitro matured oocytes. After combining activating agents, no differences in development could be observed. In conclusion, this study revealed that for both mouse and human oocytes development to the blastocyst stage was significantly better after electrical activation compared with chemical activation. Combining activating agents had no further positive effect on developmental potential.

  12. Spatiotemporal Data Mining, Analysis, and Visualization of Human Activity Data

    Science.gov (United States)

    Li, Xun

    2012-01-01

    This dissertation addresses the research challenge of developing efficient new methods for discovering useful patterns and knowledge in large volumes of electronically collected spatiotemporal activity data. I propose to analyze three types of such spatiotemporal activity data in a methodological framework that integrates spatial analysis, data…

  13. Antimicrobial activity of human salivary mucin-derived peptides

    NARCIS (Netherlands)

    Wei, G.

    2008-01-01

    We investigated: a) relationships between molecular properties and antimicrobial functions of MUC7 peptides, b) effects of host physiological factors on the antimicrobial activity of MUC7 peptides, c) enhancement of antifungal activity by combination of MUC7 peptides with EDTA or other agents, d) an

  14. Activated T lymphocytes disappear from circulation during endotoxemia in humans

    DEFF Research Database (Denmark)

    Suarez Krabbe, Karen; Kemp, Helle Bruunsgaard; Qvist, Jesper;

    2002-01-01

    disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis....

  15. Learning to Recognize Human Activities from Soft Labeled Data

    NARCIS (Netherlands)

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

    2014-01-01

    An activity recognition system is a very important component for assistant robots, but training such a system usually requires a large and correctly labeled dataset. Most of the previous works only allow training data to have a single activity label per segment, which is overly restrictive because t

  16. Telomerase activity and telomere length in human hepatocellular carcinoma.

    Science.gov (United States)

    Huang, G T; Lee, H S; Chen, C H; Chiou, L L; Lin, Y W; Lee, C Z; Chen, D S; Sheu, J C

    1998-11-01

    Telomerase activity is activated and telomere length altered in various types of cancers, including hepatocellular carcinoma (HCC). A total of 39 HCC tissues and the corresponding non-tumour livers were analysed and correlated with clinical parameters. Telomere length was determined by terminal restriction fragment assay, and telomerase activity was assayed by telomeric repeat amplification protocol. Telomerase activity was positive in 24 of the 39 tumour tissues (1.15-285.13 total product generated (TPG) units) and in six of the 39 non-tumour liver tissues (1.05-1.73 TPG units). In the 28 cases analysed for telomere length, telomere length was shortened in 11 cases, lengthened in six cases, and unaltered in 11 cases compared with non-tumour tissues. Neither telomere length nor telomerase activity was correlated to any clinical parameters. PMID:10023320

  17. Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity

    Energy Technology Data Exchange (ETDEWEB)

    Forsayeth, J.R.; Caro, J.F.; Sinha, M.K.; Maddux, B.A.; Goldfine, I.D.

    1987-05-01

    Three mouse monoclonal antibodies were produced that reacted with the ..cap alpha.. subunit of the human insulin receptor. All three both immunoprecipitated /sup 125/I-labeled insulin receptors from IM-9 lymphocytes and competitively inhibited /sup 125/I-labeled insulin binding to its receptor. Unlike insulin, the antibodies failed to stimulate receptor autophosphorylation in both intact IM-9 lymphocytes and purified human placental insulin receptors. Moreover, unlike insulin, the antibodies failed to stimulate receptor-mediated phosphorylation of exogenous substrates. However, like insulin, two of the three antibodies stimulated glucose transport in isolated human adipocytes. One antibody, on a molar basis, was as potent as insulin. These studies indicate, therefore, that monoclonal antibodies to the insulin receptor can mimic a major function of insulin without activating receptor kinase activity. They also raise the possibility that certain actions of insulin such as stimulation of glucose transport may not require the activation of receptor kinase activity.

  18. Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity

    International Nuclear Information System (INIS)

    Three mouse monoclonal antibodies were produced that reacted with the α subunit of the human insulin receptor. All three both immunoprecipitated 125I-labeled insulin receptors from IM-9 lymphocytes and competitively inhibited 125I-labeled insulin binding to its receptor. Unlike insulin, the antibodies failed to stimulate receptor autophosphorylation in both intact IM-9 lymphocytes and purified human placental insulin receptors. Moreover, unlike insulin, the antibodies failed to stimulate receptor-mediated phosphorylation of exogenous substrates. However, like insulin, two of the three antibodies stimulated glucose transport in isolated human adipocytes. One antibody, on a molar basis, was as potent as insulin. These studies indicate, therefore, that monoclonal antibodies to the insulin receptor can mimic a major function of insulin without activating receptor kinase activity. They also raise the possibility that certain actions of insulin such as stimulation of glucose transport may not require the activation of receptor kinase activity

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

    International Nuclear Information System (INIS)

    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.)

  20. 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...... D2,S have an impact on the variation in the activity noise. At 1 kHz, the technical background noise influences human activity noise positively. In both octave bands, the human activity noise level varies significantly with the office type, from a call center to a lawyer’s office....

  1. Group B streptococcal infection and activation of human astrocytes.

    Directory of Open Access Journals (Sweden)

    Terri D Stoner

    Full Text Available Streptococcus agalactiae (Group B Streptococcus, GBS is the leading cause of life-threatening meningitis in human newborns in industrialized countries. Meningitis results from neonatal infection that occurs when GBS leaves the bloodstream (bacteremia, crosses the blood-brain barrier (BBB, and enters the central nervous system (CNS, where the bacteria contact the meninges. Although GBS is known to invade the BBB, subsequent interaction with astrocytes that physically associate with brain endothelium has not been well studied.We hypothesize that human astrocytes play a unique role in GBS infection and contribute to the development of meningitis. To address this, we used a well- characterized human fetal astrocyte cell line, SVG-A, and examined GBS infection in vitro. We observed that all GBS strains of representative clinically dominant serotypes (Ia, Ib, III, and V were able to adhere to and invade astrocytes. Cellular invasion was dependent on host actin cytoskeleton rearrangements, and was specific to GBS as Streptococcus gordonii failed to enter astrocytes. Analysis of isogenic mutant GBS strains deficient in various cell surface organelles showed that anchored LTA, serine-rich repeat protein (Srr1 and fibronectin binding (SfbA proteins all contribute to host cell internalization. Wild-type GBS also displayed an ability to persist and survive within an intracellular compartment for at least 12 h following invasion. Moreover, GBS infection resulted in increased astrocyte transcription of interleukin (IL-1β, IL-6 and VEGF.This study has further characterized the interaction of GBS with human astrocytes, and has identified the importance of specific virulence factors in these interactions. Understanding the role of astrocytes during GBS infection will provide important information regarding BBB disruption and the development of neonatal meningitis.

  2. Expression of functionally active sialylated human erythropoietin in plants

    OpenAIRE

    Jez, Jakub; Castilho, Alexandra; Grass, Josephine; Vorauer-Uhl, Karola; Sterovsky, Thomas; Altmann, Friedrich; Steinkellner, Herta

    2013-01-01

    Recombinant human erythropoietin (rhEPO), a glycohormone, is one of the leading biopharmaceutical products. The production of rhEPO is currently restricted to mammalian cell expression systems because of rhEPO's highly complex glycosylation pattern, which is a major determinant for drug-efficacy. Here we evaluate the ability of plants to produce different glycoforms of rhEPO. cDNA constructs were delivered to Nicotiana benthamiana (N. benthamiana) and transiently expressed by a viral based ex...

  3. Managing the Activities Against Trafficking in Human Beings

    OpenAIRE

    Ion GANE

    2012-01-01

    Organized crime has a long history and has permanently adapted to the weaknesses of the legal system, procedures and operational capabilities of the national Law Enforcement Agencies. Economic discomfort appears to be the main reason for illegal migration movement throughout the world. Due to unemployment, many human beings become victims of trafficking- prostitution and slavery. Nevertheless, many of the willing migrants undertake the hazardous travel to their destination country with crimin...

  4. Mud Origin, Characterisation and Human Activities (MOCHA): Final report

    OpenAIRE

    Fettweis, M.; Du Four, I.; Zeelmaekers, E.; Baeteman, C.; Francken, F.; Houziaux, J.-S.; Mathys, M; Nechad, B.; Pison, V.; Vandenberghe, N.; Van den Eynde, D; Van Lancker, V. R. M; Wartel, S.

    2007-01-01

    The cohesive sediments, which are frequently found in the Belgian nearshore zone (southern North Sea), are of different age such as tertiary clays and Holocene, modern and recently deposited muds. The area is characterised by a turbidity maximum. The source areas of the recently deposited muds and the effect of human impact vs. natural processes on the distribution and/or erosion of these sediments have been investigated using historic and recent bottom samples, in situ and remote sensing (sa...

  5. Collaborative Human Engineering Work in Space Exploration Extravehicular Activities (EVA)

    Science.gov (United States)

    DeSantis, Lena; Whitmore, Mihriban

    2007-01-01

    A viewgraph presentation on extravehicular activities in space exploration in collaboration with other NASA centers, industries, and universities is shown. The topics include: 1) Concept of Operations for Future EVA activities; 2) Desert Research and Technology Studies (RATS); 3) Advanced EVA Walkback Test; 4) Walkback Subjective Results; 5) Integrated Suit Test 1; 6) Portable Life Support Subsystem (PLSS); 7) Flex PLSS Design Process; and 8) EVA Information System; 9)

  6. Disturbances of electrodynamic activity affect abortion in human

    OpenAIRE

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

    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 ...

  7. Positive and negative reinforcement activate human auditory cortex.

    Science.gov (United States)

    Weis, Tina; Puschmann, Sebastian; Brechmann, André; Thiel, Christiane M

    2013-01-01

    Prior studies suggest that reward modulates neural activity in sensory cortices, but less is known about punishment. We used functional magnetic resonance imaging and an auditory discrimination task, where participants had to judge the duration of frequency modulated tones. In one session correct performance resulted in financial gains at the end of the trial, in a second session incorrect performance resulted in financial loss. Incorrect performance in the rewarded as well as correct performance in the punishment condition resulted in a neutral outcome. The size of gains and losses was either low or high (10 or 50 Euro cent) depending on the direction of frequency modulation. We analyzed neural activity at the end of the trial, during reinforcement, and found increased neural activity in auditory cortex when gaining a financial reward as compared to gaining no reward and when avoiding financial loss as compared to receiving a financial loss. This was independent on the size of gains and losses. A similar pattern of neural activity for both gaining a reward and avoiding a loss was also seen in right middle temporal gyrus, bilateral insula and pre-supplemental motor area, here however neural activity was lower after correct responses compared to incorrect responses. To summarize, this study shows that the activation of sensory cortices, as previously shown for gaining a reward is also seen during avoiding a loss. PMID:24367318

  8. Positive and negative reinforcement activate human auditory cortex

    Directory of Open Access Journals (Sweden)

    Tina eWeis

    2013-12-01

    Full Text Available Prior studies suggest that reward modulates neural activity in sensory cortices, but less is known about punishment. We used functional magnetic resonance imaging and an auditory discrimination task, where participants had to judge the duration of frequency modulated tones. In one session correct performance resulted in financial gains at the end of the trial, in a second session incorrect performance resulted in financial loss. Incorrect performance in the rewarded as well as correct performance in the punishment condition resulted in a neutral outcome. The size of gains and losses was either low or high (10 or 50 Euro cent depending on the direction of frequency modulation. We analyzed neural activity at the end of the trial, during reinforcement, and found increased neural activity in auditory cortex when gaining a financial reward as compared to gaining no reward and when avoiding financial loss as compared to receiving a financial loss. This was independent on the size of gains and losses. A similar pattern of neural activity for both gaining a reward and avoiding a loss was also seen in right middle temporal gyrus, bilateral insula and pre-supplemental motor area, here however neural activity was lower after correct responses compared to incorrect responses. To summarize, this study shows that the activation of sensory cortices, as previously shown for gaining a reward is also seen during avoiding a loss.

  9. Human-Computer Interaction and Operators' Performance Optimizing Work Design with Activity Theory

    CERN Document Server

    Bedny, Gregory Z

    2010-01-01

    Directed to a broad and interdisciplinary audience, this book provides a complete account of what has been accomplished in applied and systemic-structural activity theory. It presents a new approach to applied psychology and the study of human work that has derived from activity theory. The selected articles demonstrate the basic principles of studying human work and particularly computer-based work in complex sociotechnical systems. The book includes examples of applied and systemic-structural activity theory to HCI and man-machine-systems, aviation, safety, design and optimization of human p

  10. Noise-driven activation in human intermittent control: a double-well potential model

    CERN Document Server

    Zgonnikov, Arkady

    2014-01-01

    In controlling unstable systems humans switch intermittently between the passive and active behavior instead of controlling the system in a continuous manner. The notion of noise-driven control activation provides a richer alternative to the conventional threshold-based models of intermittent motor control. The present study represents the control activation as a random walk in a continuously changing double-well potential. The match between the proposed model and the previous data on human balancing of virtual stick prompts that the double-well approach can aid in explaining complex dynamics of human behavior in control processes.

  11. 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.

  12. 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.

  13. Mutagenic activity and heterocyclic amine content of the human diet

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M.G.; Dolbeare, F.A.; Cunningham, P.L.; Felton, J.S.

    1993-01-15

    The mutagenic activity and the mass amount of heterocyclic amines responsible for the mutagenic activity have been measured in some cooked foods. Cooked meats are the predominant source of mutagenic activity in the diet with values ranging from 0 to 10,000 revertants per gram reported in the Ames/Salmonelia test with strain TA98. Several heterocyclic amines are present and have been quantified using solid-phase extraction followed by HPLC. Frying at higher temperatures and for longer times produces the greatest mutagenic response, and concomitantly, the largest amounts of heterocyclic amines. Most of the mutagenic activity in fried meat samples can be accounted for by MelQx, DiMelQx and IQ, although other heterocylic amines are present and PHIP mutagenic activity becomes significant at higher temperatures. Non-meat products such as baked breads can also form significant mutagenic activity, particularly when overcooked. Commercially prepared hamburgers made from meat substitutes such as tofu, wheat gluten or tempeh and fried at 210{degrees}C have up to 10% of the mutagenic activity of a fried beef patty cooked under the same conditions. When detected, amounts of heterocyclic amines in fried beef patties range from a total of 0.35 ng/g for commercial beef hamburgers to 142 ng/g for a beef patty cooked over a barbecue. Dietary intake is expected to have a large range, from less than one microgram per day to over 50 micrograms per day based on current knowledge of known heterocyclic amine chemicals and heterocyclic amine-containing foods.

  14. Micrurus snake venoms activate human complement system and generate anaphylatoxins

    Directory of Open Access Journals (Sweden)

    Tanaka Gabriela D

    2012-01-01

    Full Text Available Abstract Background The genus Micrurus, coral snakes (Serpentes, Elapidae, comprises more than 120 species and subspecies distributed from the south United States to the south of South America. Micrurus snake bites can cause death by muscle paralysis and further respiratory arrest within a few hours after envenomation. Clinical observations show mainly neurotoxic symptoms, although other biological activities have also been experimentally observed, including cardiotoxicity, hemolysis, edema and myotoxicity. Results In the present study we have investigated the action of venoms from seven species of snakes from the genus Micrurus on the complement system in in vitro studies. Several of the Micrurus species could consume the classical and/or the lectin pathways, but not the alternative pathway, and C3a, C4a and C5a were generated in sera treated with the venoms as result of this complement activation. Micrurus venoms were also able to directly cleave the α chain of the component C3, but not of the C4, which was inhibited by 1,10 Phenanthroline, suggesting the presence of a C3α chain specific metalloprotease in Micrurus spp venoms. Furthermore, complement activation was in part associated with the cleavage of C1-Inhibitor by protease(s present in the venoms, which disrupts complement activation control. Conclusion Micrurus venoms can activate the complement system, generating a significant amount of anaphylatoxins, which may assist due to their vasodilatory effects, to enhance the spreading of other venom components during the envenomation process.

  15. Immune parameters differentiating active from latent tuberculosis infection in humans.

    Science.gov (United States)

    Lee, Ji Yeon; Jung, Young Won; Jeong, Ina; Joh, Joon-Sung; Sim, Soo Yeon; Choi, Boram; Jee, Hyeon-Gun; Lim, Dong-Gyun

    2015-12-01

    Tuberculosis remains a highly prevalent infectious disease worldwide. Identification of the immune parameters that differentiate active disease from latent infection will facilitate the development of efficient control measures as well as new diagnostic modalities for tuberculosis. Here, we investigated the cytokine production profiles of monocytes and CD4(+) T lymphocytes upon encountering mycobacterial antigens. In addition, cytokines and lipid mediators with immune-modulating activities were examined in plasma samples ex vivo. Comparison of these parameters in active tuberculosis patients and healthy subjects with latent infection revealed that, active tuberculosis was associated with diminished Th1-type cytokine secretion from CD4(+) T cells and less augmented inflammatory cytokine secretion from monocytes induced by IFN-γ than that in latent tuberculosis infection. In addition, a higher plasma concentration of lipoxin A4 and lower ratio of prostaglandin E2 to lipoxin A4 were observed in active cases than in latent infections. These findings have implications for preparing new therapeutic strategies and for differential diagnosis of the two types of tuberculosis infection.

  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

    2016-01-01

    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. PMID:27399696

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

    Directory of Open Access Journals (Sweden)

    Hiram Ponce

    2016-07-01

    Full Text Available 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.

  18. 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

    2016-01-01

    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. PMID:27399696

  19. Biohazards for human activities on the Moon and Mars

    Science.gov (United States)

    Kminek, G.; Schmitt, D.

    Exobiological research on Mars is a key element of the Aurora Exploration Program. It has been acknowledged that it is essential to have a better understanding of a potential Martian biosphere before sending humans. Reason for that is not so much the fact that humans will contaminate Mars once they have landed, but to understand the presence of a biosphere on Mars as a potential hazard to human exploration. A biological hazard could come from either extinct life in the form of toxins that would only affect the crew, or from extant life in the form of pathogens that could affect the terrestrial biosphere using the human mission as a host. Both threats are very small, but cannot be neglected due to a lack of adequate information. There is no biological hazard that can be expected on the surface of the Moon. However, the Apollo missions showed clearly the problems that the all-penetrating lunar dust can generate within a few days of surface operations. Mars, like the Moon, is a dusty planet. And it is the dust that is the major carrier for any contamination - be it biological or chemical. Therefore it is of utmost importance to better understand the hazardous potential of Martian dust in order to establish risk factors for potential biological hazards. This requires dedicated in-situ and sample return missions. However, any robotic missions could realistically only assess whether biological hazards are widespread on Mars or not. They will not be capable to asses the biological hazard in areas that can only be explored by a crew. Hence, it is necessary to develop capabilities to keep the Martian dust out of the habitation area. A new ESA-study on decontamination procedures for EVA-suits, habitat areas, and waste, will partly address these issues. The logical next step would be to go to the Moon and test technologies and procedures for isolating the habitat (including the EVA-suit) from the dust on the Moon where there is no danger of biological contamination in case of

  20. Biological activity of Terminalia arjuna on Human Pathogenic Microorganisms

    Directory of Open Access Journals (Sweden)

    Tariq Javed

    2016-01-01

    Full Text Available World’s population relies chiefly on traditional medicinal plants, using their extracts or active constituents. Terminalia arjuna of family Combretaceae reported to be effective as aphrodisiac, expectorant, tonic, styptic, antidysenteric, sweet, acrid, purgative, laxative, astringent, diuretic, astringent, cirrhosis, cardioprotective and cancer treatment.   In present study, antibacterial, antifungal, brine shrimp lethality and phytotoxic effect of Terminalia arjuna was performed. Our results showed that methanolic extract of Terminalia arjuna leaves has moderate antifungal effect against Microsporm canis and fruit extract possess good antibacterial activity against Staphylococus aureus  and  Preudomonas aeroginosa. Moreover, Dichloromethane extract of Terminalia arjuna bark and fruit posses moderate phytotoxic activity

  1. 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.

  2. A mathematical model of human thymidine kinase 2 activity

    DEFF Research Database (Denmark)

    Radivoyevitch, Tom; Munch-Petersen, Birgitte; Wang, Liya;

    2011-01-01

    _ The mitochondrial enzyme thymidine kinase 2 (TK2) phosphorylates deoxythymidine (dT) and deoxycytidine (dC) to form dTMP and dCMP, which in cells rapidly become the negative-feedback end-products dTTP and dCTP. TK2 kinetic activity exhibits Hill coefficients of ∼0.5 (apparent negative...... cooperativity) for dT and ∼1 for dC. We present a mathematical model of TK2 activity that is applicable if TK2 exists as two monomer forms in equilibrium....

  3. In-Vitro Archaeacidal Activity of Biocides against Human-Associated Archaea

    OpenAIRE

    Saber Khelaifia; Jean Michel Brunel; Michel Drancourt

    2013-01-01

    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 inclu...

  4. Effect of human colostrum on interleukin-2 production and natural killer cell activity.

    OpenAIRE

    Sirota, L.; Straussberg, R; Notti, I.; Bessler, H

    1995-01-01

    The effect of human colostrum on the production of interleukin-2 (IL-2) and on natural killer (NK) cell activity by peripheral blood mononuclear cells (PBMC) was investigated in 50 healthy women. At concentrations as low as 0.5%, human colostrum stimulated IL-2 production; at a higher concentration (10%), IL-2 secretion was inhibited. A time and dose dependent inhibitory effect of colostrum on NK cytotoxicity was also observed. This inhibition could be reversed by the addition of human recomb...

  5. Biological activity of Terminalia arjuna on Human Pathogenic Microorganisms

    OpenAIRE

    Tariq Javed; Sana Riaz; Muhammad Uzair; Gulam Mustafa; Ayesha Mohyuddin; Bashir Ahmad Ch.

    2016-01-01

    World’s population relies chiefly on traditional medicinal plants, using their extracts or active constituents. Terminalia arjuna of family Combretaceae reported to be effective as aphrodisiac, expectorant, tonic, styptic, antidysenteric, sweet, acrid, purgative, laxative, astringent, diuretic, astringent, cirrhosis, cardioprotective and cancer treatment.   In present study, antibacterial, antifungal, brine shrimp lethality and phytotoxic effect of Terminalia arjuna was performed. Our results...

  6. Hsp60 is actively secreted by human tumor cells.

    Directory of Open Access Journals (Sweden)

    Anna M Merendino

    Full Text Available BACKGROUND: Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination. METHODOLOGY/PRINCIPAL FINDINGS: Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts. CONCLUSIONS/SIGNIFICANCE: Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors.

  7. Concurrent multitasking : From neural activity to human cognition

    NARCIS (Netherlands)

    Nijboer, Menno

    2016-01-01

    Multitasking has become an important part of our daily lives. This delicate juggling act between several activities occurs when people drive, when they are working, and even when they should be paying attention in the classroom. While multitasking is typically considered as something to avoid, there

  8. Identification of human gustatory cortex by activation likelihood estimation

    NARCIS (Netherlands)

    Veldhuizen, M.G.; Albrecht, J.; Zelano, C.; Boesveldt, S.; Breslin, P.; Lundstrom, J.N.

    2011-01-01

    Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been in

  9. Mission Activity Planning for Humans and Robots on the Moon

    Science.gov (United States)

    Weisbin, C.; Shelton, K.; Lincoln, W.; Elfes, A.; Smith, J.H.; Mrozinski, J.; Hua, H.; Adumitroaie, V.; Silberg, R.

    2008-01-01

    A series of studies is conducted to develop a systematic approach to optimizing, both in terms of the distribution and scheduling of tasks, scenarios in which astronauts and robots accomplish a group of activities on the Moon, given an objective function (OF) and specific resources and constraints. An automated planning tool is developed as a key element of this optimization system.

  10. Mechanisms regulating regional cerebral activation during dynamic handgrip in humans

    DEFF Research Database (Denmark)

    Williamson, James; Friedman, D B; Mitchell, J H;

    1996-01-01

    type of afferent input required for this cerebral activation. The rCBF was measured at +5.0 and +9.0 cm above the orbitomeatal (OM) plane in 13 subjects during 1) rest; 2) dynamic left-hand contractions; 3) postcontraction ischemia (metaboreceptor afferents); and 4) biceps brachii tendon vibration...

  11. Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

    DEFF Research Database (Denmark)

    Pedersen, Pernille Barbre; Vilmann, Peter; Bar-Shalom, Daniel;

    2013-01-01

    PURPOSE: To characterize human gastric fluid with regard to rheological properties and gastric lipase activity. In addition, traditional physicochemical properties were determined. METHODS: Fasted HGA were collected from 19 healthy volunteers during a gastroscopic examination. Rheological charact...

  12. The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

    NARCIS (Netherlands)

    Timmers, H.J.L.M.; Rongen, G.A.P.J.M.; Karemaker, J.M.; Wieling, W.; Marres, H.A.M.; Lenders, J.W.M.

    2004-01-01

    The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemorecepto

  13. Ecobiological assessment of a freshwater lake at Schirmacher Oasis, East Antarctica, with reference to human activities

    Digital Repository Service at National Institute of Oceanography (India)

    Ingole, B.S.; Dhargalkar, V.K.

    The scale and magnitude of probable impact of human activities over a decade (1983-1994) on the freshwater lake Priyadarshini, at Schirmacher Oasis, East Antarctica, was assessed through an ecological study conducted over an annual cycle during...

  14. The Long and the Short of It: Comments on Multiple Timescale Studies of Human Activity.

    Science.gov (United States)

    Lemke, Jay L.

    2001-01-01

    Comments on four articles in a special issue of the Journal of the Learning Sciences on methodology in learning sciences. Analyzes the articles within a general model seeking to analyze human activity across multiple time scales. (Author/MM)

  15. Human Ebola virus infection results in substantial immune activation.

    Science.gov (United States)

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  16. 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

  17. Eleanor Roosevelt and the Declaration of Human Rights: A Simulation Activity.

    Science.gov (United States)

    Gilbert, Sally; Shollenberger, Kathy

    2001-01-01

    Provides a brief background on Eleanor Roosevelt and the Declaration of Human Rights. Presents a lesson wherein students simulate the creation of the Declaration of Human Rights and consider the leadership skills of Eleanor Roosevelt. Explains that the activity requires three class periods and some student preparation before the lesson. (CMK)

  18. New method in the criminalistics: neutron-activation analysis of the human hair

    International Nuclear Information System (INIS)

    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.)

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

    Science.gov (United States)

    Lamprecht, Björn; Bonifer, Constanze; Mathas, Stephan

    2010-11-01

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

  20. Pharmacology of the human red cell voltage-dependent cation channel Part I. Activation by clotrimazole and analogues

    DEFF Research Database (Denmark)

    Barksmann, Trine Lyberth; Kristensen, Berit I.; Christophersen, Palle.;

    2004-01-01

    Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators......Human red cells, Nonselective voltage dependent cation channel, NSVDC channel, Gárdos channel blockers, NSVDC channel activators...

  1. 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...

  2. 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...

  3. A Systematic Approach to Identify Markers of Distinctly Activated Human Macrophages

    Directory of Open Access Journals (Sweden)

    Bayan eSudan

    2015-05-01

    Full Text Available Polarization has been a useful concept for describing activated macrophage phenotypes and gene expression profiles. However, macrophage activation status within tumors and other settings are often inferred based on only a few markers. Complicating matters for relevance to human biology, many of the best studied macrophage activation markers have been best characterized in mice and sometimes are not similarly regulated in human macrophages. To identify novel markers of activated human macrophages, gene expression profiles for human macrophages of a single donor subjected to 33 distinct activating conditions were obtained and a set of putative activation markers were subsequently evaluated in macrophages from multiple donors using integrated fluidic circuit (IFC-based RT-PCR. Using unsupervised hierarchical clustering of the microarray screen, highly-altered transcripts (>4-fold change in expression sorted the macrophage transcription profiles into two major and 13 minor clusters. Among the 1874 highly-altered transcripts, over 100 were uniquely altered in one major or two related minor clusters. IFC PCR-derived data confirmed the microarray results and to show the kinetics of expression of potential macrophage activation markers. Transcripts encoding chemokines, cytokines, and cell surface were prominent in our analyses. The activation markers identified by this study could be used to better characterize tumor-associated macrophages from biopsies as well as other macrophage populations collected from human clinical samples.

  4. Sustained Inflammasome Activity in Macrophages Impairs Wound Healing in Type 2 Diabetic Humans and Mice

    OpenAIRE

    Rita E Mirza; Fang, Milie M.; Eileen M Weinheimer-Haus; Ennis, William J.; Koh, Timothy J.

    2014-01-01

    The hypothesis of this study was that sustained activity of the Nod-like receptor protein (NLRP)-3 inflammasome in wounds of diabetic humans and mice contributes to the persistent inflammatory response and impaired healing characteristic of these wounds. Macrophages (Mp) isolated from wounds on diabetic humans and db/db mice exhibited sustained inflammasome activity associated with low level of expression of endogenous inflammasome inhibitors. Soluble factors in the biochemical milieu of thes...

  5. Differential complement activation and susceptibility to human serum bactericidal action by Vibrio species.

    OpenAIRE

    1983-01-01

    The ability of Vibrio vulnificus to resist human serum bactericidal action and to activate human complement was compared with similar cultures of Vibrio cholerae and Vibrio parahaemolyticus. Both V. vulnificus and V. parahaemolyticus had similar survival rates in sera and were much more resistant to killing than was V. cholerae. In contrast, V. vulnificus activated significantly less serum complement than did V. cholerae and V. parahaemolyticus. The relative ability of V. vulnificus to surviv...

  6. Management of human resources in the physical activity and sport: concepts and perspectives

    OpenAIRE

    Campos Izquierdo, Antonio

    2010-01-01

    The management proper of human resources in organizations of physical activity and sport is essential to ensure the quality, efficiency and professionalism of service offered and even, if not done the right way can produce the benefits become a nuisance and risks to health, safety and education of citizens and for society as such. The perspective of management and organization of human resources in the states of physical activity and sport should be comprehensive, integrated and cross, which ...

  7. MD-2 determinants of nickel and cobalt-mediated activation of human TLR4.

    Directory of Open Access Journals (Sweden)

    Alja Oblak

    Full Text Available Recent findings unexpectedly revealed that human TLR4 can be directly activated by nickel ions. This activation is due to the coordination of nickel by a cluster of histidine residues on the ectodomain of human TLR4, which is absent in most other species. We aimed to elucidate the role of MD-2 in the molecular mechanism of TLR4/MD-2 activation by nickel, as nickel binding site on TLR4 is remote from MD-2, which directly binds the endotoxin as the main pathological activator of TLR4. We identified MD-2 and TLR4 mutants which abolished TLR4/MD-2 receptor activation by endotoxin but could nevertheless be significantly activated by nickel, which acts in synergy with LPS. Human TLR4/MD-2 was also activated by cobalt ions, while copper and cadmium were toxic in the tested concentration range. Activation of TLR4 by cobalt required MD-2 and was abolished by human TLR4 mutations of histidine residues at positions 456 and 458. We demonstrated that activation of TLR4 by nickel and cobalt ions can trigger both the MyD88-dependent and the -independent pathway. Based on our results we propose that predominantly hydrophobic interactions between MD-2 and TLR4 contribute to the stabilization of the TLR4/MD-2/metal ion complex in a conformation that enables activation.

  8. Baseline brain activity fluctuations predict somatosensory perception in humans

    OpenAIRE

    Boly, M; Balteau, E.; Schnakers, C; Degueldre, C.; Moonen, G.; Luxen, A.; Phillips, C.; Peigneux, P; Maquet, P; Laureys, S.

    2007-01-01

    In perceptual experiments, within-individual fluctuations in perception are observed across multiple presentations of the same stimuli, a phenomenon that remains only partially understood. Here, by means of thulium–yttrium/aluminum–garnet laser and event-related functional MRI, we tested whether variability in perception of identical stimuli relates to differences in prestimulus, baseline brain activity. Results indicate a positive relationship between conscious perception of low-intensity so...

  9. Human Receptor Activation by Aroclor 1260, a Polychlorinated Biphenyl Mixture

    OpenAIRE

    Wahlang, Banrida; Falkner, K. Cameron; Clair, Heather B.; Al-Eryani, Laila; Prough, Russell A.; States, J. Christopher; Coslo, Denise M.; Omiecinski, Curtis J.; Cave, Matthew C.

    2014-01-01

    Polychlorinated biphenyls (PCBs) are persistent environmental toxicants, present in 100% of U.S. adults and dose-dependently associated with obesity and non-alcoholic fatty liver disease (NAFLD). PCBs are predicted to interact with receptors previously implicated in xenobiotic/energy metabolism and NAFLD. These receptors include the aryl hydrocarbon receptor (AhR), pregnane xenobiotic receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptors (PPARs), ...

  10. Functional structure of spontaneous sleep slow oscillation activity in humans.

    Directory of Open Access Journals (Sweden)

    Danilo Menicucci

    Full Text Available BACKGROUND: During non-rapid eye movement (NREM sleep synchronous neural oscillations between neural silence (down state and neural activity (up state occur. Sleep Slow Oscillations (SSOs events are their EEG correlates. Each event has an origin site and propagates sweeping the scalp. While recent findings suggest a SSO key role in memory consolidation processes, the structure and the propagation of individual SSO events, as well as their modulation by sleep stages and cortical areas have not been well characterized so far. METHODOLOGY/PRINCIPAL FINDINGS: We detected SSO events in EEG recordings and we defined and measured a set of features corresponding to both wave shapes and event propagations. We found that a typical SSO shape has a transition to down state, which is steeper than the following transition from down to up state. We show that during SWS SSOs are larger and more locally synchronized, but less likely to propagate across the cortex, compared to NREM stage 2. Also, the detection number of SSOs as well as their amplitudes and slopes, are greatest in the frontal regions. Although derived from a small sample, this characterization provides a preliminary reference about SSO activity in healthy subjects for 32-channel sleep recordings. CONCLUSIONS/SIGNIFICANCE: This work gives a quantitative picture of spontaneous SSO activity during NREM sleep: we unveil how SSO features are modulated by sleep stage, site of origin and detection location of the waves. Our measures on SSOs shape indicate that, as in animal models, onsets of silent states are more synchronized than those of neural firing. The differences between sleep stages could be related to the reduction of arousal system activity and to the breakdown of functional connectivity. The frontal SSO prevalence could be related to a greater homeostatic need of the heteromodal association cortices.

  11. Exosomes: novel effectors of human platelet lysate activity

    OpenAIRE

    E Torreggiani; F Perut; Roncuzzi, L; N Zini; SR Baglìo; N Baldini

    2014-01-01

    Despite the popularity of platelet-rich plasma (PRP) and platelet lysate (PL) in orthopaedic practice, the mechanism of action and the effectiveness of these therapeutic tools are still controversial. So far, the activity of PRP and PL has been associated with different growth factors (GF) released during platelet degranulation. This study, for the first time, identifies exosomes, nanosized vesicles released in the extracellular compartment by a number of elements, including platelets, as one...

  12. Rate-invariant recognition of humans and their activities.

    Science.gov (United States)

    Veeraraghavan, Ashok; Srivastava, Anuj; Roy-Chowdhury, Amit K; Chellappa, Rama

    2009-06-01

    Pattern recognition in video is a challenging task because of the multitude of spatio-temporal variations that occur in different videos capturing the exact same event. While traditional pattern-theoretic approaches account for the spatial changes that occur due to lighting and pose, very little has been done to address the effect of temporal rate changes in the executions of an event. In this paper, we provide a systematic model-based approach to learn the nature of such temporal variations (time warps) while simultaneously allowing for the spatial variations in the descriptors. We illustrate our approach for the problem of action recognition and provide experimental justification for the importance of accounting for rate variations in action recognition. The model is composed of a nominal activity trajectory and a function space capturing the probability distribution of activity-specific time warping transformations. We use the square-root parameterization of time warps to derive geodesics, distance measures, and probability distributions on the space of time warping functions. We then design a Bayesian algorithm which treats the execution rate function as a nuisance variable and integrates it out using Monte Carlo sampling, to generate estimates of class posteriors. This approach allows us to learn the space of time warps for each activity while simultaneously capturing other intra- and interclass variations. Next, we discuss a special case of this approach which assumes a uniform distribution on the space of time warping functions and show how computationally efficient inference algorithms may be derived for this special case. We discuss the relative advantages and disadvantages of both approaches and show their efficacy using experiments on gait-based person identification and activity recognition. PMID:19398409

  13. Powerful Bactericidal Activity of Moxifloxacin in Human Leprosy▿

    OpenAIRE

    Pardillo, Fe Eleanor F.; Burgos, Jasmin; Fajardo, Tranquilino T.; Cruz, Eduardo Dela; Abalos, Rodolfo M.; Paredes, Rose Maria D.; Andaya, Cora Evelyn S.; Gelber, Robert H.

    2008-01-01

    In a clinical trial of moxifloxacin in eight multibacillary leprosy patients, moxifloxacin proved highly effective. In all trial patients, a single 400-mg dose of moxifloxacin resulted in significant killing (P ≤ 0.006) of Mycobacterium leprae, ranging from 82% to 99%, with a mean of 91%. In all instances, no viable bacilli were detected with an additional 3 weeks of daily therapy, this observed rapid bactericidal activity being matched previously only by rifampin. On moxifloxacin therapy, sk...

  14. Autonomic activity during sleep predicts memory consolidation in humans.

    Science.gov (United States)

    Whitehurst, Lauren N; Cellini, Nicola; McDevitt, Elizabeth A; Duggan, Katherine A; Mednick, Sara C

    2016-06-28

    Throughout history, psychologists and philosophers have proposed that good sleep benefits memory, yet current studies focusing on the relationship between traditionally reported sleep features (e.g., minutes in sleep stages) and changes in memory performance show contradictory findings. This discrepancy suggests that there are events occurring during sleep that have not yet been considered. The autonomic nervous system (ANS) shows strong variation across sleep stages. Also, increases in ANS activity during waking, as measured by heart rate variability (HRV), have been correlated with memory improvement. However, the role of ANS in sleep-dependent memory consolidation has never been examined. Here, we examined whether changes in cardiac ANS activity (HRV) during a daytime nap were related to performance on two memory conditions (Primed and Repeated) and a nonmemory control condition on the Remote Associates Test. In line with prior studies, we found sleep-dependent improvement in the Primed condition compared with the Quiet Wake control condition. Using regression analyses, we compared the proportion of variance in performance associated with traditionally reported sleep features (model 1) vs. sleep features and HRV during sleep (model 2). For both the Primed and Repeated conditions, model 2 (sleep + HRV) predicted performance significantly better (73% and 58% of variance explained, respectively) compared with model 1 (sleep only, 46% and 26% of variance explained, respectively). These findings present the first evidence, to our knowledge, that ANS activity may be one potential mechanism driving sleep-dependent plasticity. PMID:27298366

  15. The effect of anti-human plasminogen monoclonal antibodies on Glu-plasminogen activation by plasminogen activators

    Directory of Open Access Journals (Sweden)

    M. Akrami

    2006-07-01

    Full Text Available Background: Human plasminogen is a plasma glycoprotein synthesized mainly in the liver. Conversion of plasminogen to plasmin by plasminogen activators is a key event in the fibrinolytic system. In this study, we investigated the effects of two anti-human plasminogen monoclonal antibodies, A1D12 and MC2B8 on Glu-plasminogen activation in presence of u-PA, t-PA and streptokinase. Methods: Producing of Hybridoma antibodies was performed by fusion of spleen cells from BALB/C mice immunized with Glu-plasminogen and NS1 myeloma cells. Antibody binding to Human Glu-plasminogen was assessed using an ELISA assay. Activation of plasminogen was determined by measuring plasmin generation using the chromogenic substrate S-2251 and the effect of monoclonal antibodies, A1D12 and MC2B8 on plasminogen activation in solution was then evaluated. Initial rates and kinetic parameters of plasminogen activation in the presence of monoclonal antibodies were calculated. The effect of the monoclonal antibody MC2B8 on the rate of plasmin hydrolysis was measured. The effect of F(ab'2 fragment of A1D12 on u-PA catalyzed-plasminogen activation also compared with the effect of the whole antibody in this reaction. Results: ELISA assay showed that the antibodies reacted well with antigens. A1D12 increased the maximum velocity (Vmax of plasminogen activation by each of the three plasminogen activators and MC2B8 decreased it. In all activation reactions, the KM value of plasminogen activation did not significantly change in the presence of antibody A1D12 whereas antibody MC2B8 increased the KM value of plasminogen activation by u-PA, fibrin monomer dependent t-PA and streptokinase. Monoclonal antibody MC2B8 had no significant effect on plasmin hydrolysis rate of synthetic substrate S-2251. Activation rate of plasminogen by u-PA in the lower concentration of F (ab2 fragment of A1D12 was identical to activation in the presence of the whole antibody. Conclusion: The binding of

  16. 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.

  17. Ornithine decarboxylase, mitogen-activated protein kinase and matrix metalloproteinase-2 expressions in human colon tumors

    Institute of Scientific and Technical Information of China (English)

    Takahiro Nemoto; Shunichiro Kubota; Hideyuki Ishida; Nobuo Murata; Daijo Hashimoto

    2005-01-01

    AIM: To investigate the expressions of omithine decarboxylase (ODC), MMP-2, and Erk, and their relationship in human colon tumors.METHODS: ODC activity, MMP-2 expression, and mitogenactivated protein (MAP) kinase activity (Erk phosphorylation) were determined in 58 surgically removed human colon tumors and their adjacent normal tissues, using [1-14C]-ornithine as a substrate, ELISA assay, and Western blotting, respectively.RESULTS: ODC activity, MMP-2 expression, and Erk phosphorylation were significantly elevated in colon tumors, compared to those in adjacent normal tissues. A significant correlation was observed between ODC activities and MMP-2 levels.CONCLUSION: This is the first report showing a significant correlation between ODC activities and MMP-2 levels in human colon tumors. As MMP-2 is involved in cancer invasion and metastasis, and colon cancer overexpresses ODC, suppression of ODC expression may be a rational approach to treat colon cancer which overexpresses ODC.

  18. Human activities recognition by head movement using partial recurrent neural network

    Science.gov (United States)

    Tan, Henry C. C.; Jia, Kui; De Silva, Liyanage C.

    2003-06-01

    Traditionally, human activities recognition has been achieved mainly by the statistical pattern recognition methods or the Hidden Markov Model (HMM). In this paper, we propose a novel use of the connectionist approach for the recognition of ten simple human activities: walking, sitting down, getting up, squatting down and standing up, in both lateral and frontal views, in an office environment. By means of tracking the head movement of the subjects over consecutive frames from a database of different color image sequences, and incorporating the Elman model of the partial recurrent neural network (RNN) that learns the sequential patterns of relative change of the head location in the images, the proposed system is able to robustly classify all the ten activities performed by unseen subjects from both sexes, of different race and physique, with a recognition rate as high as 92.5%. This demonstrates the potential of employing partial RNN to recognize complex activities in the increasingly popular human-activities-based applications.

  19. Withaferin A inhibits activation of signal transducer and activator of transcription 3 in human breast cancer cells

    OpenAIRE

    Lee, Joomin; Hahm, Eun-Ryeong; Singh, Shivendra V

    2010-01-01

    We have shown previously that withaferin A (WA), a promising anticancer constituent of Ayurvedic medicine plant Withania somnifera, inhibits growth of human breast cancer cells in culture and in vivo in association with apoptosis induction. The present study builds on these observations and demonstrates that WA inhibits constitutive as well as interleukin-6 (IL-6)-inducible activation of signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor act...

  20. Human activity helps prey win the predator-prey space race.

    Science.gov (United States)

    Muhly, Tyler B; Semeniuk, Christina; Massolo, Alessandro; Hickman, Laura; Musiani, Marco

    2011-03-02

    Predator-prey interactions, including between large mammalian wildlife species, can be represented as a "space race", where prey try to minimize and predators maximize spatial overlap. Human activity can also influence the distribution of wildlife species. In particular, high-human disturbance can displace large carnivore predators, a trait-mediated direct effect. Predator displacement by humans could then indirectly benefit prey species by reducing predation risk, a trait-mediated indirect effect of humans that spatially decouples predators from prey. The purpose of this research was to test the hypothesis that high-human activity was displacing predators and thus indirectly creating spatial refuge for prey species, helping prey win the "space race". We measured the occurrence of eleven large mammal species (including humans and cattle) at 43 camera traps deployed on roads and trails in southwest Alberta, Canada. We tested species co-occurrence at camera sites using hierarchical cluster and nonmetric multidimensional scaling (NMS) analyses; and tested whether human activity, food and/or habitat influenced predator and prey species counts at camera sites using regression tree analysis. Cluster and NMS analysis indicated that at camera sites humans co-occurred with prey species more than predator species and predator species had relatively low co-occurrence with prey species. Regression tree analysis indicated that prey species were three times more abundant on roads and trails with >32 humans/day. However, predators were less abundant on roads and trails that exceeded 18 humans/day. Our results support the hypothesis that high-human activity displaced predators but not prey species, creating spatial refuge from predation. High-human activity on roads and trails (i.e., >18 humans/day) has the potential to interfere with predator-prey interactions via trait-mediated direct and indirect effects. We urge scientist and managers to carefully consider and quantify the

  1. Human activity helps prey win the predator-prey space race.

    Directory of Open Access Journals (Sweden)

    Tyler B Muhly

    Full Text Available Predator-prey interactions, including between large mammalian wildlife species, can be represented as a "space race", where prey try to minimize and predators maximize spatial overlap. Human activity can also influence the distribution of wildlife species. In particular, high-human disturbance can displace large carnivore predators, a trait-mediated direct effect. Predator displacement by humans could then indirectly benefit prey species by reducing predation risk, a trait-mediated indirect effect of humans that spatially decouples predators from prey. The purpose of this research was to test the hypothesis that high-human activity was displacing predators and thus indirectly creating spatial refuge for prey species, helping prey win the "space race". We measured the occurrence of eleven large mammal species (including humans and cattle at 43 camera traps deployed on roads and trails in southwest Alberta, Canada. We tested species co-occurrence at camera sites using hierarchical cluster and nonmetric multidimensional scaling (NMS analyses; and tested whether human activity, food and/or habitat influenced predator and prey species counts at camera sites using regression tree analysis. Cluster and NMS analysis indicated that at camera sites humans co-occurred with prey species more than predator species and predator species had relatively low co-occurrence with prey species. Regression tree analysis indicated that prey species were three times more abundant on roads and trails with >32 humans/day. However, predators were less abundant on roads and trails that exceeded 18 humans/day. Our results support the hypothesis that high-human activity displaced predators but not prey species, creating spatial refuge from predation. High-human activity on roads and trails (i.e., >18 humans/day has the potential to interfere with predator-prey interactions via trait-mediated direct and indirect effects. We urge scientist and managers to carefully consider and

  2. Human B cells have an active phagocytic capability and undergo immune activation upon phagocytosis of Mycobacterium tuberculosis.

    Science.gov (United States)

    Zhu, Qi; Zhang, Min; Shi, Ming; Liu, Yang; Zhao, Qing; Wang, Wenjing; Zhang, Guangyun; Yang, Longxiu; Zhi, Jin; Zhang, Lin; Hu, Gengyao; Chen, Pin; Yang, Yining; Dai, Wen; Liu, Tingting; He, Ying; Feng, Guodong; Zhao, Gang

    2016-04-01

    The paradigm that B cells are nonphagocytic was taken for granted for a long time until phagocytic B cells were found in early vertebrate animals. Thereafter, limited evidence has shown that human B cells may also internalize bacteria. However, whether human B cells can actively phagocytose bacteria has been less extensively investigated; in particular, the mechanisms and significance of the phagocytosis require clarification. Here, we show that the human Raji B cell line can phagocytose both live and dead Mycobacterium tuberculosis (Mtb), and the phagocytosed Mtb in turn affects the immune functions of the B cells. After incubation of Raji cells with Mtb, our confocal microscopy, electron microscopy and flow cytometry data showed that Raji cells effectively engulfed Mtb as well as latex beads. The phagocytic rate was proportional to the incubation time and the amount of Mtb or beads added. Additionally, we found that normal human serum could enhance the ability of Raji cells to phagocytose Mtb, while heat-inactivated serum reversed this promoting effect. The phagocytic process of B cells could partially be inhibited by cytochalasin B, an actin inhibitor. Importantly, the phagocytosed Mtb could regulate B cell immune functions, such as stimulating IgM production and upregulating the expression of the antigen-presenting costimulatory molecules CD80 and CD86. Therefore, our results provide the first evidence that human B cells can phagocytose Mtb in an active manner that is independent of bacterial viability, and phagocytosed Mtb can in turn regulate the immune activation of B cells.

  3. Human Activities on the Deep Seafloor in the North East Atlantic: An Assessment of Spatial Extent

    Science.gov (United States)

    Benn, Angela R.; Weaver, Philip P.; Billet, David S. M.; van den Hove, Sybille; Murdock, Andrew P.; Doneghan, Gemma B.; Le Bas, Tim

    2010-01-01

    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 each human activity

  4. 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

  5. MOHAWC. Models of human activities in work contexts

    International Nuclear Information System (INIS)

    The overall objective of the MOHAWC Action is to formulate and extend a unifying framework for cognitive studies of human agents coping with complex work domains. Central issues are methods for analysis and representation of knowledge about complex domains, analysis of cognitive control, mental models and heuristics applied in complex work domains, distributed decision making and forms of cooperative work, the role of tacit knowledge in agents' performance in complex work domains, and cognitive simulation methods for testing models of cognitive performance. The nature of computer mediated work and how such work should be designed and organised to be optimally effective and satisfying is considered. The focus is mainly on various forms of process industry, such as nuclear power and steel production. Dynamic decision making, where the decision-maker has to make a series of interdependent decisions under conditions where the state of the system with which he or she is working changes, both as a consequence of the decision maker's actions and autonomously, and where the decisions must be made in real time is analysed. MOHAWC taxonomy has played a central role as a framework for identifying important research problems and for integrating results. The Risoe team has contributed a major analysis of and illustration of how the MOHAWC taxonomy can be used in the design of interfaces. (AB) (97 refs.)

  6. Purinergic effects on Na,K-ATPase activity differ in rat and human skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Carsten Juel

    Full Text Available P2Y receptor activation may link the effect of purines to increased maximal in vitro activity of the Na,K-ATPase in rat muscle. The hypothesis that a similar mechanism is present in human skeletal muscle was investigated with membranes from rat and human skeletal muscle.Membranes purified from rat and human muscles were used in the Na,K-ATPase assay. Incubation with ADP, the stable ADP analogue MeS-ADP and UDP increased the Na+ dependent Na,K-ATPase activity in rat muscle membranes, whereas similar treatments of human muscle membranes lowered the Na,K-ATPase activity. UTP incubation resulted in unchanged Na,K-ATPase activity in humans, but pre-incubation with the antagonist suramin resulted in inhibition with UTP, suggesting that P2Y receptors are involved. The Na,K-ATPase in membranes from both rat and human could be stimulated by protein kinase A and C activation. Thus, protein kinase A and C activation can increase Na,K-ATPase activity in human muscle but not via P2Y receptor stimulation.The inhibitory effects of most purines (with the exception of UTP in human muscle membranes are probably due to mass law inhibition of ATP hydrolysis. This inhibition could be blurred in rat due to receptor mediated activation of the Na,K-ATPase. The different effects could be related to a high density of ADP sensitive P2Y1 and P2Y13 receptors in rat, whereas the UTP sensitive P2Y11 could be more abundant in human. Alternatively, rat could possesses a mechanism for protein-protein interaction between P2Y receptors and the Na,K-ATPase, and this mechanism could be absent in human skeletal muscle (perhaps with the exception of the UTP sensitive P2Y11 receptor.Rat muscle is not a reliable model for purinergic effects on Na,K-ATPase in human skeletal muscle.

  7. Analysis of human enamel and dentine by neutron activation analysis

    International Nuclear Information System (INIS)

    Determination of trace elements in dental tissues has been of great interest to study the correlation between element composition and caries as well as food habits of individuals. In the present study dentine and enamel samples from healthy individuals were analysed by neutron activation analysis. The teeth were provided form dental clinics, and they were previously washed using purified water and acetone. Then they were dried at 40 deg C and ground in a agate mortar. The samples and element standards were irradiated with thermal neutrons at the IEA-R1 nuclear reactor. Long irradiations of 8 h under thermal neutron flux of 5x1012 n cm-2 s-1 were used for Ca, Na, Sr and Zn determinations. In short irradiations of 15 s and under neutron flux of 1012 n cm-2 s-1 the elements Mg, Mn, Na e Sr were determined. The induced gamma activities of the samples and standards were measured using a hyperpure Ge detector coupled to a gamma ray spectrometer. Elemental concentrations were calculated by comparative method. Results obtained showed that Ca, Mg and Na are present in both tissues at the level of percentages and the elements Mn, Sr and Zn at the μg g-1 levels. For quality control of the results the certified reference materials NIST 1400 Bone Ash and NIST 1486 Bone Meal were analysed. (author)

  8. Functional activity of human hepatocytes under traumatic disease.

    Science.gov (United States)

    Kudryavtseva, M V; Stein, G I; Shashkov, B V; Kudryavtsev, B N

    1998-03-01

    Absorption and fluorescent cytophotometry techniques were applied to studies of RNA as well as of total glycogen and its fractions as the parameters of functional activity of the hepatocytes in patients with severe mechanical trauma, both with and without autointoxication (AI). Slides were stained with gallocyanine-chromalums to determine the RNA content and were processed by the fluorescent PAS-reaction for the glycogen content. To trace the dynamics of RNA and glycogen contents in the liver punction biopsies were done in the same patients. A quick increase in the RNA content took place in both groups of patients at the first period (within the first 3 days) of traumatic disease. At the second period of disease the hepatocyte RNA content in patients without AI was found to decrease up to the initial level whereas that in patients with AI increased on the average by 36% of the initial values. The total glycogen content in hepatocytes of all the patients changed insignificantly in the course of disease but its labile fraction in patients with AI decreased to 70% of the total. The increase of hepatocyte synthetic activity and the maintenance of the high glycogen level are indicative of the large compensatory potential of the liver that enables it to carry an intensive functional load under AI conditions. PMID:9570502

  9. Evaluation of accuracy, precision and determination limit in the human hair analysis using neutron activation method

    International Nuclear Information System (INIS)

    The accuracy, precision and determination limit were evaluated for determination of Al, As, Br, Ca, Cd, Cl, Co, Cr, Cu, Fe, Hg, K, Mg, Mn, Na, Sb, Sc, Se, V and Zn in human head hair by instrumental neutron activation analysis. The precision was examined by analyzing human hair sample, and the results of relative standard deviations obtained ranged from 3.9 to 16.2%. The results accuracy was evaluated by using reference materials GBW 09101 Human Hair and NIES 5 Human Hair. Currie criterion was used for calculation of the determination limit. (author). 8 refs., 2 tabs

  10. Classification of human activity on water through micro-Dopplers using deep convolutional neural networks

    Science.gov (United States)

    Kim, Youngwook; Moon, Taesup

    2016-05-01

    Detecting humans and classifying their activities on the water has significant applications for surveillance, border patrols, and rescue operations. When humans are illuminated by radar signal, they produce micro-Doppler signatures due to moving limbs. There has been a number of research into recognizing humans on land by their unique micro-Doppler signatures, but there is scant research into detecting humans on water. In this study, we investigate the micro-Doppler signatures of humans on water, including a swimming person, a swimming person pulling a floating object, and a rowing person in a small boat. The measured swimming styles were free stroke, backstroke, and breaststroke. Each activity was observed to have a unique micro-Doppler signature. Human activities were classified based on their micro-Doppler signatures. For the classification, we propose to apply deep convolutional neural networks (DCNN), a powerful deep learning technique. Rather than using conventional supervised learning that relies on handcrafted features, we present an alternative deep learning approach. We apply the DCNN, one of the most successful deep learning algorithms for image recognition, directly to a raw micro-Doppler spectrogram of humans on the water. Without extracting any explicit features from the micro-Dopplers, the DCNN can learn the necessary features and build classification boundaries using the training data. We show that the DCNN can achieve accuracy of more than 87.8% for activity classification using 5- fold cross validation.

  11. Temperament, character and serotonin activity in the human brain

    DEFF Research Database (Denmark)

    Tuominen, L; Salo, J; Hirvonen, J;

    2013-01-01

    The psychobiological model of personality by Cloninger and colleagues originally hypothesized that interindividual variability in the temperament dimension 'harm avoidance' (HA) is explained by differences in the activity of the brain serotonin system. We assessed brain serotonin transporter (5-HTT......-existing Temperament and Character Inventory (TCI) scores. A total of 22 subjects free of psychiatric and somatic disorders were included in the matched high- and low-HA groups. The main outcome measure was regional 5-HTT binding potential (BPND) in high- and low-HA groups estimated with PET and [11C]N,N-dimethyl-2......-(2-amino-4-methylphenylthio)benzylamine ([11C]MADAM). In secondary analyses, 5-HTT BPND was correlated with other TCI dimensions....

  12. Plasma dihydroxyphenylalanine (DOPA) is independent of sympathetic activity in humans

    DEFF Research Database (Denmark)

    Eldrup, E; Christensen, N J; Andreasen, J;

    1989-01-01

    To clarify the origin of plasma DOPA (3,4-Dihydroxyphenylalanine), the relationship between plasma DOPA and acute or chronic changes in sympathetic activity has been studied. Plasma DOPA and noradrenaline (NA) concentrations were measured by reverse-phase high-performance liquid chromatography with...... electrochemical detection. Administration of clonidine to healthy men decreased plasma NE markedly compared to no drug. Plasma DOPA decreased slightly but significantly with time, but values were identical after clonidine compared to no drug. Baseline plasma NE concentrations were significantly reduced in...... diabetic patients with autonomic neuropathy compared to diabetics without neuropathy, whereas baseline plasma DOPA concentrations were similar in the three groups investigated: 6.55 (5.03-7.26, median [interquartile range], n = 8) nmol l-1 in diabetics with neuropathy, 7.41 (5.79-7.97, n = 8) nmol l-1 in...

  13. The role of active brown adipose tissue in human metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

    2016-02-15

    The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

  14. Synergistic Structure in the Speed Dependent Modulation of Muscle Activity in Human Walking

    NARCIS (Netherlands)

    Buurke, Tom J W; Lamoth, Claudine J C; van der Woude, Lucas H V; Otter, den A. Rob

    2016-01-01

    Recently, a modular organisation has been proposed to simplify control of the large number of muscles involved in human walking. Although previous research indicates that a single set of modular activation patterns can account for muscle activity at different speeds, these studies only provide indir

  15. Human Capital and Economic Activity in Urban America. Staff Report No. 332

    Science.gov (United States)

    Abel, Jaison R.; Gabe, Todd M.

    2010-01-01

    We examine the relationship between human capital and economic activity in U.S. metropolitan areas, extending the literature in two ways. First, we utilize new data on metropolitan area GDP to measure economic activity. Results show that a one-percentage-point increase in the proportion of residents with a college degree is associated with about a…

  16. 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)

  17. Activity in human reward-sensitive brain areas in strongly context dependent

    NARCIS (Netherlands)

    Nieuwenhuis, S.; Heslenfeld, D.J.; Mars, R.B.; Alting von Geusau, N.J.; Holroyd, C.B.; Yeung, N.

    2005-01-01

    Functional neuroimaging research in humans has identified a number of brain areas that are activated by the delivery of primary and secondary reinforcers. The present study investigated how activity in these reward-sensitive regions is modulated by the context in which rewards and punishments are ex

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

    International Nuclear Information System (INIS)

    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)

  19. 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...

  20. Tissue plasminogen activator and urokinase plasminogen activator in human epileptogenic pathologies

    NARCIS (Netherlands)

    A.M. Iyer; E. Zurolo; K. Boer; J.C. Baayen; F. Giangaspero; A. Arcella; G.C. Di Gennaro; V. Esposito; W.G.M. Spliet; P.C. van Rijen; D. Troost; J.A. Gorter; E. Aronica

    2010-01-01

    A growing body of evidence demonstrates the involvement of plasminogen activators (PAs) in a number of physiologic and pathologic events in the CNS. Induction of both tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) has been observed in different experimental models of ep

  1. Viewing the motion of human body parts activates different regions of premotor, temporal, and parietal cortex.

    Science.gov (United States)

    Wheaton, Kylie J; Thompson, James C; Syngeniotis, Ari; Abbott, David F; Puce, Aina

    2004-05-01

    Activation of premotor and temporoparietal cortex occurs when we observe others movements, particularly relating to objects. Viewing the motion of different body parts without the context of an object has not been systematically evaluated. During a 3T fMRI study, 12 healthy subjects viewed human face, hand, and leg motion, which was not directed at or did not involve an object. Activation was identified relative to static images of the same human face, hand, and leg in both individual subject and group average data. Four clear activation foci emerged: (1) right MT/V5 activated to all forms of viewed motion; (2) right STS activated to face and leg motion; (3) ventral premotor cortex activated to face, hand, and leg motion in the right hemisphere and to leg motion in the left hemisphere; and (4) anterior intraparietal cortex (aIP) was active bilaterally to viewing hand motion and in the right hemisphere leg motion. In addition, in the group data, a somatotopic activation pattern for viewing face, hand, and leg motion occurred in right ventral premotor cortex. Activation patterns in STS and aIP were more complex--typically activation foci to viewing two types of human motion showed some overlap. Activation in individual subjects was similar; however, activation to hand motion also occurred in the STS with a variable location across subjects--explaining the lack of a clear activation focus in the group data. The data indicate that there are selective responses to viewing motion of different body parts in the human brain that are independent of object or tool use.

  2. Human Dcp2: a catalytically active mRNA decapping enzyme located in specific cytoplasmic structures

    OpenAIRE

    van Dijk, Erwin; Cougot, Nicolas; Meyer, Sylke; Babajko, Sylvie; Wahle, Elmar; Séraphin, Bertrand

    2002-01-01

    We have cloned cDNAs for the human homologues of the yeast Dcp1 and Dcp2 factors involved in the major (5′–3′) and NMD mRNA decay pathways. While yeast Dcp1 has been reported to be the decapping enzyme, we show that recombinant human Dcp2 (hDcp2) is enzymatically active. Dcp2 activity appears evolutionarily conserved. Mutational and biochemical analyses indicate that the hDcp2 MutT/Nudix domain mediates this activity. hDcp2 generates m7GDP and 5′-phosphorylated mRNAs that are 5′–3′ exonucleas...

  3. Anticancer Activities of Substituted Cinnamic Acid Phenethyl Esters on Human Cancer Cell Lines

    Institute of Scientific and Technical Information of China (English)

    LIShu-chun; LIHui; ZHANGFa; LIZhong-jun; CUIJing-rong

    2003-01-01

    Caffeic acid phenethyl ester (CAPE) and sixteen substituted cinnamic acid phenethyl esters were prepared via conventional procedures in order to test their in vitro anticancer activities by either MTT assay or SRB assay on six different human cancer cell lines. The results indicated that in the concentration of 10μmol·L-1 the lead compmuM CAPE possessed anficancer activities against human HL-60, Bel-7402, and Hela cell lines, and two other compounds possessed potent anticancer activities against Bel-7402 and Hela cell lines.

  4. Activation of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) inhibits human breast cancer cell line tumorigenicity

    OpenAIRE

    Yao, Pei-Li; Morales, Jose L.; Zhu, Bokai; Kang, Boo-Hyon; Gonzalez, Frank J; Peters, Jeffrey M.

    2014-01-01

    The effect of activation and over-expression of the nuclear receptor PPARβ/δ in human MDA-MB-231 (ER−) and MCF7 (ER+) breast cancer cell lines was examined. Target gene induction by ligand activation of PPARβ/δ was increased by over-expression of PPARβ/δ compared to controls. Over-expression of PPARβ/δ caused a decrease in cell proliferation in MCF7 and MDA-MB-231 cells compared to controls while ligand activation of PPARβ/δ further inhibited proliferation of MCF7 but not MDA-MB-231 cells. Ov...

  5. Sensor Data Acquisition and Processing Parameters for Human Activity Classification

    Directory of Open Access Journals (Sweden)

    Sebastian D. Bersch

    2014-03-01

    Full Text Available It is known that parameter selection for data sampling frequency and segmentation techniques (including different methods and window sizes has an impact on the classification accuracy. For Ambient Assisted Living (AAL, no clear information to select these parameters exists, hence a wide variety and inconsistency across today’s literature is observed. This paper presents the empirical investigation of different data sampling rates, segmentation techniques and segmentation window sizes and their effect on the accuracy of Activity of Daily Living (ADL event classification and computational load for two different accelerometer sensor datasets. The study is conducted using an ANalysis Of VAriance (ANOVA based on 32 different window sizes, three different segmentation algorithm (with and without overlap, totaling in six different parameters and six sampling frequencies for nine common classification algorithms. The classification accuracy is based on a feature vector consisting of Root Mean Square (RMS, Mean, Signal Magnitude Area (SMA, Signal Vector Magnitude (here SMV, Energy, Entropy, FFTPeak, Standard Deviation (STD. The results are presented alongside recommendations for the parameter selection on the basis of the best performing parameter combinations that are identified by means of the corresponding Pareto curve.

  6. Altered behavior in spotted hyenas associated with increased human activity

    Science.gov (United States)

    Boydston, Erin E.; Kapheim, Karen M.; Watts, Heather E.; Szykman, Micaela; Holekamp, Kay E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996–98 with that observed several years earlier and found many differences. Female hyenas in 1996–98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988–90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988–90. Finally, hyenas occurred in smaller groups in 1996–98 than in 1988–90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction.

  7. Altered behaviour in spotted hyenas associated with increased human activity

    Science.gov (United States)

    Boydston, E.E.; Kapheim, K.M.; Watts, H.E.; Szykman, M.; Holekamp, K.E.

    2003-01-01

    To investigate how anthropogenic activity might affect large carnivores, we studied the behaviour of spotted hyenas (Crocuta crocuta) during two time periods. From 1996 to 1998, we documented the ecological correlates of space utilization patterns exhibited by adult female hyenas defending a territory at the edge of a wildlife reserve in Kenya. Hyenas preferred areas near dense vegetation but appeared to avoid areas containing the greatest abundance of prey, perhaps because these were also the areas of most intensive livestock grazing. We then compared hyena behaviour observed in 1996-98 with that observed several years earlier and found many differences. Female hyenas in 1996-98 were found farther from dens, but closer to dense vegetation and to the edges of their territory, than in 1988-90. Recent females also had larger home ranges, travelled farther between consecutive sightings, and were more nocturnal than in 1988-90. Finally, hyenas occurred in smaller groups in 1996-98 than in 1988-90. We also found several changes in hyena demography between periods. We next attempted to explain differences observed between time periods by testing predictions of hypotheses invoking prey abundance, climate, interactions with lions, tourism and livestock grazing. Our data were consistent with the hypothesis that increased reliance on the reserve for livestock grazing was responsible for observed changes. That behavioural changes were not associated with decreased hyena population density suggests the behavioural plasticity typical of this species may protect it from extinction. ?? 2003 The Zoological Society of London.

  8. Fluvial deposits as an archive of early human activity

    Science.gov (United States)

    Mishra, S.; White, M. J.; Beaumont, P.; Antoine, P.; Bridgland, D. R.; Limondin-Lozouet, N.; Santisteban, J. I.; Schreve, D. C.; Shaw, A. D.; Wenban-Smith, F. F.; Westaway, R. W. C.; White, T. S.

    2007-11-01

    River terraces are well established as an important source of Lower and Middle Palaeolithic artefacts in Europe, large collections having been assembled there during the years of manual gravel extraction. Now that many terrace sequences can be reliably dated and correlated with the oceanic record, potentially useful patterns can be recognized in the distribution of artefacts. The earliest appearance of artefacts in terrace staircases, marking the arrival of the first tool-making hominins in the region in question, is the first of several archaeological markers within fluvial sequences. The Lower to Middle Palaeolithic transition, with the appearance of Levallois, is another. Others may be more regional in significance: the occurrences of Clactonian (Mode 1) industry, twisted ovate handaxes and bout coupé handaxes, for example. IGCP Project no. 449 instigated the compilation of fluvial records from all over the 'old world'. Comparison between British and Central European sequences confirms the established view that there is a demarcation between handaxe making in the west and flake/core industries in the east. Other centres of activity reported here have been in the Middle East (Syria), South Africa and India. Data from such areas will be key in deciphering the story of the earlier 'out-of-Africa' migration, that by pre-Homo sapiens people. There is clear evidence for diachroneity between the first appearances of different industries, in keeping with the well-established idea of northward migration.

  9. Energy efficiency and human activity: Past trends, future prospects

    International Nuclear Information System (INIS)

    This book, sponsored by the Stockholm Environmental Institute (SEI), presents a detailed analysis of changes in world energy use over the past twenty years. It considers the future prospects of energy demand, and discusses ways of restraining growth in consumption in order to meet environmental and economic development goals. Based on a decade of research by the authors and their colleagues at Lawrence Berkeley Laboratory in collaboration with the SEI, it presents information on energy use and the forces shaping it in the industrial, developing, and formerly planned economies. Looking separately at industry, passenger travel, freight transport, and the residential and service sectors, the authors describe the impact on energy use of growth in activity, structural change, and change in energy intensities, and discuss the role of energy prices and energy conservation policies in the industrial countries and the former Soviet Union. The book presents an overview of the potential for improving energy efficiency, and discusses the policies that could help realize the potential. While calling for strong action by governments and the private sector, the authors stress the importance of considering the full range of factors that will shape realization of the energy efficiency potential around the world

  10. Energy and human activity: Steps toward a sustainable future

    International Nuclear Information System (INIS)

    The potential for improving energy efficiency is enormous, but exploitation of this resource has slowed in recent years. This is regrettable for several reasons. First, not incorporating higher efficiency now often means passing up opportunities that will be more expensive or even impossible to implement in the future. This is especially true for long-lived capital, such as new buildings. Second, reduced research and development into new efficiency options will make it more difficult to accelerate the pace of efficiency improvements in the future. Finally, the flow of more efficient technologies to the non-OECD countries will be hindered by the slowdown in efficiency improvement in the OECD countries. Well-designed policies can help recapture the momentum that has been lost. Some key steps for stimulating more careful use of energy are: rationalize energy pricing and gradually internalize environmental externalities; improve present energy-using capital; implement energy-efficiency standards or agreements for new products and buildings; encourage higher energy efficiency in new products and buildings; promote international cooperation for R ampersand D technology transfer; adjust policies that encourage energy-intensive activities; and promote population restraint worldwide. 25 refs

  11. Human retinal pigment epithelial cells inhibit proliferation and IL2R expression of activated T cells

    DEFF Research Database (Denmark)

    Kaestel, Charlotte G; Jørgensen, Annette; Nielsen, Mette;

    2002-01-01

    The purpose of this study was to characterize the effects of human retinal pigment epithelial (RPE) cells on activated T cells. Activated T cells were cocultured with adult and foetal human RPE cells whereafter apoptosis and proliferation were determined by flow cytometry and (3)H......-Thymidine incorporation assay, respectively. T cells and RPE cells were cultured directly together or in a transwell system for determination of the effect of cell contact. The importance of cell surface molecules was examined by application of a panel of blocking antibodies (CD2, CD18, CD40, CD40L, CD54, CD58......) in addition to use of TCR negative T cell lines. The expression of IL2R-alpha -beta and -gamma chains of activated T cells was analysed by flow cytometry after incubation of T cells alone or with RPE cells. Human RPE cells were found to inhibit the proliferation of activated T cells by a cell contact...

  12. Regression-Based Feature Selection on Large Scale Human Activity Recognition

    Directory of Open Access Journals (Sweden)

    Hussein Mazaar

    2016-02-01

    Full Text Available In this paper, we present an approach for regression-based feature selection in human activity recognition. Due to high dimensional features in human activity recognition, the model may have over-fitting and can’t learn parameters well. Moreover, the features are redundant or irrelevant. The goal is to select important discriminating features to recognize the human activities in videos. R-Squared regression criterion can identify the best features based on the ability of a feature to explain the variations in the target class. The features are significantly reduced, nearly by 99.33%, resulting in better classification accuracy. Support Vector Machine with a linear kernel is used to classify the activities. The experiments are tested on UCF50 dataset. The results show that the proposed model significantly outperforms state-of-the-art methods.

  13. 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.

  14. Development and application of human cell lines engineered to metabolically activate structurally diverse environmental mutagens

    Science.gov (United States)

    Crespi, C. I.; Langenbach, Robert; Gonzalez, Frank J.; Gelboin, Harry V.; Penman, B. W.

    1993-03-01

    Cytochromes P450 are responsible for the mutagenic/carcinogenic activation of many environmental promutagens/procarcinogens. These enzymes are present at highest concentrations in liver in vivo but are markedly absent in tester organisms for most in vitro mutagenicity test systems. Two approaches have been used to supply needed metabolic activation, incorporation of an extracellular activating system, usually derived from a rodent liver and introduction of activating enzymes into the target cell. The latter approach appears to result in a more sensitive testing system because of the close proximity of the activating enzymes and the target DNA. Human cell lines have been developed which stably express human cytochromes P450 and other cDNAs which have been introduced individually or in combination. The resulting cell lines are exquisitely sensitive to exposure to promutagens and procarcinogens. Mutagenicity is measured at the hypoxanthine phosphoribosyl transferase (hprt) and thymidine kinase (tk) gene loci. The most versatile cell line, designated MCL-5, stably express five cDNAs encoding all of the human hepatic P450s known to be principally responsible for known human procarcinogen activation. The induction of mutation is observed in MCL-5 cells upon exposure to ng/ml levels of model compounds such as nitrosamines, aflatoxin B1 and benzo(a)pyrene. A lower volume mutagenicity assay has been developed for use with samples available in limited amounts. Human lymphoblast mutation assays have been used to screen for mutagenic activity sediment samples from a polluted watershed. Two sediment samples were found to have mutagenic activity to human lymphoblasts.

  15. Serum inflammatory mediators as markers of human Lyme disease activity.

    Science.gov (United States)

    Soloski, Mark J; Crowder, Lauren A; Lahey, Lauren J; Wagner, Catriona A; Robinson, William H; Aucott, John N

    2014-01-01

    Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low) of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005) in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG), CXCL10 (IP-10) and CCL19 (MIP3B) were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively). There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01) and the decrease correlates with chemokine levels (p = 0.0375). The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

  16. Serum inflammatory mediators as markers of human Lyme disease activity.

    Directory of Open Access Journals (Sweden)

    Mark J Soloski

    Full Text Available Chemokines and cytokines are key signaling molecules that orchestrate the trafficking of immune cells, direct them to sites of tissue injury and inflammation and modulate their states of activation and effector cell function. We have measured, using a multiplex-based approach, the levels of 58 immune mediators and 7 acute phase markers in sera derived from of a cohort of patients diagnosed with acute Lyme disease and matched controls. This analysis identified a cytokine signature associated with the early stages of infection and allowed us to identify two subsets (mediator-high and mediator-low of acute Lyme patients with distinct cytokine signatures that also differed significantly (p<0.0005 in symptom presentation. In particular, the T cell chemokines CXCL9 (MIG, CXCL10 (IP-10 and CCL19 (MIP3B were coordinately increased in the mediator-high group and levels of these chemokines could be associated with seroconversion status and elevated liver function tests (p = 0.027 and p = 0.021 respectively. There was also upregulation of acute phase proteins including CRP and serum amyloid A. Consistent with the role of CXCL9/CXCL10 in attracting immune cells to the site of infection, CXCR3+ CD4 T cells are reduced in the blood of early acute Lyme disease (p = 0.01 and the decrease correlates with chemokine levels (p = 0.0375. The levels of CXCL9/10 did not relate to the size or number of skin lesions but elevated levels of serum CXCL9/CXCL10 were associated with elevated liver enzymes levels. Collectively these results indicate that the levels of serum chemokines and the levels of expression of their respective chemokine receptors on T cell subsets may prove to be informative biomarkers for Lyme disease and related to specific disease manifestations.

  17. Inhibition of human immunodeficiency virus type 1 activity by purified human breast milk mucin (MUC1) in an inhibition assay.

    Science.gov (United States)

    Habte, Habtom H; de Beer, Corena; Lotz, Zoë E; Tyler, Marilyn G; Kahn, Delawir; Mall, Anwar S

    2008-01-01

    It has been reported that breast-feeding is responsible for approximately 40% of the HIV transmissions from HIV-positive mothers to children. Human breast milk, however, is known to contain numerous biologically active components which protect breast-fed infants against bacteria, viruses, and toxins. The purpose of this study was to purify and characterize breast milk mucin and to determine its anti-HIV-1 activity in an HIV inhibition assay. Sepharose CL-4B column chromatography and caesium chloride isopycnic density gradient purification were used to isolate and purify the mucin. Following Western blotting and amino acid analysis, an HIV-1 inhibition assay was carried out to determine the anti-HIV-1 activity of crude breast milk and purified milk mucin (MUC1) by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells). SDS-PAGE analysis of the mucin, together with its amino acid composition and Western blotting, suggested that this purified mucin from human breast milk was MUC1. The HIV inhibition assay revealed that while the purified milk mucin (MUC1) inhibited the HIV-1 activity by approximately 97%, there was no inhibition of the HIV-1 activity by crude breast milk. Although the reason for this is not clear, it is likely that because the MUC1 in crude milk is enclosed by fat globules, there may not be any physical contact between the mucin and the virus in the crude breast milk. Thus, there is a need to free the mucin from the fat globules for it to be effective against the virus. PMID:17878743

  18. Effect of nutritional status on human paraoxonase-1 activity in patients with chronic kidney disease

    OpenAIRE

    Sztanek Ferenc (1982-) (orvos); Seres Ildikó (1954-) (biokémikus); Harangi Mariann (1974-) (belgyógyász, endokrinológus); Lőcsey Lajos (1946-2013) (belgyógyász, nephrológus); Koncsos Péter (1982-) (belgyógyász); Paragh György (1953-) (belgyógyász, kardiológus, endokrinológus, lipidológus, sürgősségi orvostani szakorvos, belgyógyászati angiológiai minősített orvos)

    2012-01-01

    Background and methods: The association between nutritional status, antioxidant human paraoxonase-1 (PON1) activity and low grade inflammation in hemodialized (HD) patients with chronic kidney disease (CKD) is unclear. The aim of this study was to determine PON1 paraoxonase and lactonase activities, ADMA, adiponectin and leptin concentrations, and to clarify the relationship between paraoxonase activity and a set of cardiovascular risk factors in malnourished, normal weight and obese HD patie...

  19. Differential Effects of Tacrolimus versus Sirolimus on the Proliferation, Activation and Differentiation of Human B Cells

    OpenAIRE

    Traitanon, Opas; Mathew, James M.; La Monica, Giovanna; Xu, Luting; Mas, Valeria; Gallon, Lorenzo

    2015-01-01

    The direct effect of immunosuppressive drugs calcineurin inhibitor (Tacrolimus, TAC) and mTOR inhibitor (Sirolimus, SRL) on B cell activation, differentiation and proliferation is not well documented. Purified human B cells from healthy volunteers were stimulated through the B Cell Receptor with Anti-IgM + anti-CD40 + IL21 in the absence / presence of TAC or SRL. A variety of parameters of B cell activity including activation, differentiation, cytokine productions and proliferation were monit...

  20. 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.

  1. Expression, processing and transcriptional regulation of granulysin in short-term activated human lymphocytes

    OpenAIRE

    Groscurth Peter; Dumrese Claudia; Sundstrom Hanna; Walch Michael; Latinovic-Golic Sonja; Ziegler Urs

    2007-01-01

    Abstract Background Granulysin, a cytotoxic protein expressed in human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of intracellular microbes. Expression and transcription have been partially characterised in vitro and four transcripts (NKG5, 519, 520, and 522) were identified. However, only a single protein product of 15 kDa was found, which is subsequently processed to an active 9 kDa protein. Results In this study we investigated generatio...

  2. Comparison of fusion methods based on DST and DBN in human activity recognition

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Ambient assistive living environments require sophisticated information fusion and reasoning techniques to accurately identify activities of a person under care. In this paper, we explain, compare and discuss the application of two powerful fusion methods, namely dynamic Bayesian networks (DBN) and Dempster-Shafer theory (DST), for human activity recognition. Both methods are described, the implementation of activity recognition based on these methods is explained, and model acquisition and composition are ...

  3. Assessing human mirror activity with EEG mu rhythm: A meta-analysis.

    Science.gov (United States)

    Fox, Nathan A; Bakermans-Kranenburg, Marian J; Yoo, Kathryn H; Bowman, Lindsay C; Cannon, Erin N; Vanderwert, Ross E; Ferrari, Pier F; van IJzendoorn, Marinus H

    2016-03-01

    A fundamental issue in cognitive neuroscience is how the brain encodes others' actions and intentions. In recent years, a potential advance in our knowledge on this issue is the discovery of mirror neurons in the motor cortex of the nonhuman primate. These neurons fire to both execution and observation of specific types of actions. Researchers use this evidence to fuel investigations of a human mirror system, suggesting a common neural code for perceptual and motor processes. Among the methods used for inferring mirror system activity in humans are changes in a particular frequency band in the electroencephalogram (EEG) called the mu rhythm. Mu frequency appears to decrease in amplitude (reflecting cortical activity) during both action execution and action observation. The current meta-analysis reviewed 85 studies (1,707 participants) of mu that infer human mirror system activity. Results demonstrated significant effect sizes for mu during execution (Cohen's d = 0.46, N = 701) as well as observation of action (Cohen's d = 0.31, N = 1,508), confirming a mirroring property in the EEG. A number of moderators were examined to determine the specificity of these effects. We frame these meta-analytic findings within the current discussion about the development and functions of a human mirror system, and conclude that changes in EEG mu activity provide a valid means for the study of human neural mirroring. Suggestions for improving the experimental and methodological approaches in using mu to study the human mirror system are offered. PMID:26689088

  4. Probiotic Potential of Lactobacillus Strains with Antimicrobial Activity against Some Human Pathogenic Strains

    Directory of Open Access Journals (Sweden)

    Parisa Shokryazdan

    2014-01-01

    Full Text Available The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits.

  5. Arylesterase Phenotype-Specific Positive Association Between Arylesterase Activity and Cholinesterase Specific Activity in Human Serum

    Directory of Open Access Journals (Sweden)

    Yutaka Aoki

    2014-01-01

    Full Text Available Context: Cholinesterase (ChE specific activity is the ratio of ChE activity to ChE mass and, as a biomarker of exposure to cholinesterase inhibitors, has a potential advantage over simple ChE activity. Objective: To examine the association of several potential correlates (serum arylesterase/paraoxonase activity, serum albumin, sex, age, month of blood collection, and smoking with plasma ChE specific activity. Methods: We analyzed data from 195 cancer-free controls from a nested case-control study, accounting for potential confounding. Results: Arylesterase activity had an independent, statistically significant positive association with ChE specific activity, and its magnitude was the greatest for the arylesterase phenotype corresponding to the QQ PON1192 genotype followed by phenotypes corresponding to QR and RR genotypes. Serum albumin was positively associated with ChE specific activity. Conclusions: Plasma arylesterase activity was positively associated with plasma ChE specific activity. This observation is consistent with protection conferred by a metabolic phenotype resulting in reduced internal dose.

  6. Studying the Anti-aging Effect of Human Growth Hormone on Human Fibroblast Cells via Telomerase Activity

    Directory of Open Access Journals (Sweden)

    Nader Chaparzadeh

    2010-01-01

    Full Text Available Objective: In recent years, studies have focused on the telomerase for cancer treatmentby repressing telomerase in cancerous cells or prevent cell aging by activating it in theaged cells. Thus, in these studies natural and synthetic agents have been used to repressor activate telomerase. In this research, we investigated the effects of human growth hormone(hGH on aging via evaluation of telomerase activity.Materials and Methods: Primary human foreskin fibroblast cells were isolated, culturedand treated with different concentrations of hGH. BrdU and MTT cell proliferation assaysand cells number counting. Cell aging was assayed by the senescence sensitivegalactosidase staining method. Telomerase activity was measured with a telomerasePCR ELISA kit.Data were analyzed with SPSS software (one-way ANOVA and univariateANOVA.Results: Our results indicated that cells treated with a lower concentration (0.1, 1 ng/mlof hGH had more green color cells (aged cells. Furthermore, cell proliferation increasedwith increasing hGH concentrations (10 to 100 ng/ml which was significant in comparisonwith untreated control cells. TRAP assay results indicated that telomerase activityincreased with increasing hGH concentration, but there was no significant difference. Additionally,more rapid cell growth and telomerase activity was noted in the absence of H2O2when compared with the presence of H2O2, which was significantly different.Conclusion: Although increasing cell proliferation along with increasing hGH concentrationwas confirmed by all cell proliferation assays, only the cell counting test was statisticallysignificant. Thus, it is inconclusive that hGH (up to 100 ng/ml has an anti-agingeffect. Also, because there was no significant difference in the telomerase activity results(in spite of increasing progress along with increasing hGH concentration we can not certainlyconclude that hGH (up to 100 ng/ml impacts telomerase activity.

  7. 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

  8. 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

  9. The effect of human activities and their associated noise on ungulate behavior.

    Directory of Open Access Journals (Sweden)

    Casey L Brown

    Full Text Available BACKGROUND: The effect of anthropogenic noise on terrestrial wildlife is a relatively new area of study with broad ranging management implications. Noise has been identified as a disturbance that has the potential to induce behavioral responses in animals similar to those associated with predation risk. This study investigated potential impacts of a variety of human activities and their associated noise on the behavior of elk (Cervus elaphus and pronghorn (Antilocapra americana along a transportation corridor in Grand Teton National Park. METHODOLOGY/PRINCIPAL FINDINGS: We conducted roadside scan surveys and focal observations of ungulate behavior while concurrently recording human activity and anthropogenic noise. Although we expected ungulates to be more responsive with greater human activity and noise, as predicted by the risk disturbance hypothesis, they were actually less responsive (less likely to perform vigilant, flight, traveling and defensive behaviors with increasing levels of vehicle traffic, the human activity most closely associated with noise. Noise levels themselves had relatively little effect on ungulate behavior, although there was a weak negative relationship between noise and responsiveness in our scan samples. In contrast, ungulates did increase their responsiveness with other forms of anthropogenic disturbance; they reacted to the presence of pedestrians (in our scan samples and to passing motorcycles (in our focal observations. CONCLUSIONS: These findings suggest that ungulates did not consistently associate noise and human activity with an increase in predation risk or that they could not afford to maintain responsiveness to the most frequent human stimuli. Although reduced responsiveness to certain disturbances may allow for greater investment in fitness-enhancing activities, it may also decrease detections of predators and other environmental cues and increase conflict with humans.

  10. MODEL OF ACTIVITY OF THE ENTERPRISE AS MODEL OF ACTIVITY OF THE HUMAN: SEARCH ANALYSIS

    Directory of Open Access Journals (Sweden)

    Ruslan Flerovich Vildanov

    2014-09-01

    Full Text Available Actualized demand of manufactury company's efficiency from the point of quality charachteristics. Reveal unbreakable connection of man and organisation, on example of the comparative analysis of man's and manufacture company's activities. Studing models of company's and men's activities in order to reveal similarity. In order of their implementation to the economics assumes opportunity of using scientific methods, which use for studying functions, vital activities and behavior of the men.

  11. The 2001 activities and the 3rd workshop of the human resources development project in FNCA

    International Nuclear Information System (INIS)

    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)

  12. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-12-01

    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.

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

    International Nuclear Information System (INIS)

    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

  15. Activity-based computing: computational management of activities reflecting human intention

    DEFF Research Database (Denmark)

    Bardram, Jakob E; Jeuris, Steven; Houben, Steven

    2015-01-01

    An important research topic in artificial intelligence is automatic sensing and inferencing of contextual information, which is used to build computer models of the user’s activity. One approach to build such activity-aware systems is the notion of activity-based computing (ABC). ABC is a computing...... paradigm that has been applied in personal information management applications as well as in ubiquitous, multidevice, and interactive surface computing. ABC has emerged as a response to the traditional application- and file-centered computing paradigm, which is oblivious to a notion of a user’s activity...

  16. 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

    interstitial increase in growth factors that are known potentially to stimulate synthesis of collagen and other extracellular matrix proteins. Taken together, human tendon tissue mounts a vigorous acute and chronic response to mechanical loading in terms of metabolic-circulatory changes as well...

  17. Activation of endoplasmic reticulum stress is involved in the activity of icariin against human lung adenocarcinoma cells.

    Science.gov (United States)

    Di, Shouyin; Fan, Chongxi; Yang, Yang; Jiang, Shuai; Liang, Miaomiao; Wu, Guiling; Wang, Bodong; Xin, Zhenlong; Hu, Wei; Zhu, Yifang; Li, Weimiao; Zhou, Yongan; Li, Xiaofei; Yan, Xiaolong

    2015-09-01

    In this study, we investigated the anticancer activity of icariin (ICA) against human lung adenocarcinoma cells in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process. ICA treatment resulted in a dose- and time-dependent decrease in the viability of human lung adenocarcinoma A549 cells. Additionally, ICA exhibited potent anticancer activity, as evidenced by reductions in A549 cell adhesion, migration and intracellular glutathione (GSH) levels and increases in the apoptotic index, Caspase 3 activity, and reactive oxygen species. Furthermore, ICA treatment increased the expression of ERS-related molecules (p-PERK, ATF6, GRP78, p-eIF2α, and CHOP), up-regulated the apoptosis-related protein PUMA and down-regulated the anti-apoptosis-related protein Bcl2. The down-regulation of ERS signaling using PERK siRNA desensitized lung adenocarcinoma cells to ICA treatment, whereas the up-regulation of ERS signaling using thapsigargin (THA) sensitized lung adenocarcinoma cells to ICA treatment. Additionally, ICA inhibited the growth of human lung adenocarcinoma A549 cell xenografts by increasing the expression of ERS-related molecules (p-PERK and CHOP), up-regulating PUMA, and down-regulating Bcl2. These data indicate that ICA is a potential inhibitor of lung adenocarcinoma cell growth by targeting ERS signaling and suggest that the activation of ERS signaling may represent a novel therapeutic intervention for lung adenocarcinoma.

  18. Response of ESV to Climate Change and Human Activities in the Yanqi Basin, Xinjiang, China

    Science.gov (United States)

    Rusuli, Yusufujiang; Sidik, Halida; Gupur, Adila; Hong, Jiang; Kadir, Rayila

    2016-04-01

    Ecosystem goods and services refer to the dependence of economic wealth and human well-being on natural systems. It is a common knowledge that the changing of structure and function of the ecosystem due to climate change and human activities. It is a priority issue to study on various spatiotemporal scales, the sensitivity of ecosystems to climate change and anthropogenic pressure in inland areas. In an effort to better understand the influence of climate change and human activities on ecosystem services, we evaluated the change in ESV of the Yanqi Basin in Xinjiang, China from 1973 to 2014 employing methods of MK, MK Sneyers, ESV and dynamic degree of LUCC. The Landsat images, digital elevation model (DEM) and metrological data were applied to assessing the ESV and its change. According to the degree of effects of the climate change and human activities, the research area was divided into two parts: the mountain area and the plain oasis area at a contour of 1400 m above sea level. According to type and affect, the land cover was classified as water, wetland, desert, fields, glacier, warm shrub grassland, cold meadow steppe and highland vegetation. We analyzed the relationship between the variation of ESV and precipitation, and evaporation and then quantitatively differentiated the influence of climate change and human activities on ESV. Results show that: (1) distinct change points of precipitation and evaporation in mountain and plain oasis of the Yanqi basin were detected by the MK-Sneyers test. The precipitation increased and the evaporation declined in mountain and plain oasis in the same way. Enlargement of agricultural areas to accommodate an increased population and socio-economic development was detected by conversion matrix of LUCC in oasis area. As a result, the variation of ESV was caused by climate change and human activities jointly; (2) the declining trend of ESV in the mountain area was mainly caused by shrinking of the glacier area; (3) ESV was

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

    International Nuclear Information System (INIS)

    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

  20. Multi-Agent System for Managing Human Activities in Space Operations

    Science.gov (United States)

    Schrenkenghost, Debra; Bonasso, R. Peter

    2006-01-01

    In manned space operations today, the astronauts' activity schedules are preplanned and adjusted daily on Earth. We have developed the Distributed Collaboration and Interaction (DCI) multi-agent system to investigate automating aspects of human activity management. The DCI System assists (1) plan generation, (2) human activity tracking, (3) plan revision, and (4) mixed initiative interaction with the plan. We have deployed and evaluated the DCI system at JSC to assist control engineers in managing anomaly handling activities for automated life support systems. DCI operated round the clock for 20 months in the Water Research Facility at JSC. Using this software, we reduced anomaly response time by engineers from up to 10 hours in previous tests to under an hour. Based on this evaluation, we conclude that agent assistance for schedule management has potential to improve astronaut activity awareness and reduce response time in situations where crew are interrupted to handle anomalies.

  1. Glutathione peroxidase activity in cell cultures from differentregions of human epididymis

    Institute of Scientific and Technical Information of China (English)

    Enrique Castellón; Hernán Rioseco; Juan Rojas; Michel Royer; Eduardo Salas; Héctor Contreras; Christian Huidobro

    2005-01-01

    Aim: To study the secretory activity and androgen regulation of glutathione peroxidase (GPx) in epithelial cell cultures from human epididymis. Methods: Tissue was obtained from patients undergoing therapeutic orchidectomy for prostatic cancer. Epithelial cell cultures were obtained from the caput, corpus and cauda epididymides. Enzymatic activity was measured in conditioned media by colorimetric methods in absence or presence of 1, 10 or 100 nmol.L-1from corpus and cauda than caput epididymidis. The presence of different concentrations of testosterone increase enzyme activity in cell cultures from all epididymal regions. Addition of flutamide reverses the androgen dependent increase of GPx activity. Conclusion: GPx activity is secreted from human epididymal cells in a region dependent manner and is regulated by androgens.

  2. 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......  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...

  3. Vascular Endothelial Growth Factor Receptor 3 Controls Neural Stem Cell Activation in Mice and Humans

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

    Full Text Available Neural stem cells (NSCs continuously produce new neurons within the adult mammalian hippocampus. NSCs are typically quiescent but activated to self-renew or differentiate into neural progenitor cells. The molecular mechanisms of NSC activation remain poorly understood. Here, we show that adult hippocampal NSCs express vascular endothelial growth factor receptor (VEGFR 3 and its ligand VEGF-C, which activates quiescent NSCs to enter the cell cycle and generate progenitor cells. Hippocampal NSC activation and neurogenesis are impaired by conditional deletion of Vegfr3 in NSCs. Functionally, this is associated with compromised NSC activation in response to VEGF-C and physical activity. In NSCs derived from human embryonic stem cells (hESCs, VEGF-C/VEGFR3 mediates intracellular activation of AKT and ERK pathways that control cell fate and proliferation. These findings identify VEGF-C/VEGFR3 signaling as a specific regulator of NSC activation and neurogenesis in mammals.

  4. 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

    2016-07-01

    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. PMID:26296149

  5. Establishment of human T cell clones exhibiting natural killer-like activity

    OpenAIRE

    Alam, Shahabuddin; Katakura, Yoshinori; Shirahata, Sanetaka

    1999-01-01

    We have succeeded in establishing a method to reproducibly immortalize human T cells by oncogene(s) transfection (Alam, 1997). This study was based on our previous discoveries that these immortalized T cell lines contained T cells which showed cytotoxicity against K562 cells in MHC-nonrestricted manner. Then we attempted to obtain human T cell clones exhibiting natural killer-like activity. Here, we tried to establish clones from these immortalized T cell lines by limiting dilution after stim...

  6. Induction of procoagulant activity on human endothelial cells by Streptococcus pneumoniae.

    OpenAIRE

    Geelen, S; Bhattacharyya, C; Tuomanen, E

    1992-01-01

    The inflammatory response in infection caused by gram-negative organisms involves induction of procoagulant activity (PCA) on human endothelial cells. Although infections caused by gram-positive organisms are also associated with fibrin formation and thrombosis, the bacterial determinants inducing PCA are unknown. This study shows that intact pneumococci and the pneumococcal cell wall efficiently induce PCA on human endothelial cells. Upon exposure of endothelial cells to pneumococci, PCA was...

  7. Immunomodulating Activity of Agaricus brasiliensis KA21 in Mice and in Human Volunteers

    OpenAIRE

    Ying Liu; Yasushi Fukuwatari; Ko Okumura; Kazuyoshi Takeda; Ken-ichi Ishibashi; Mai Furukawa; Naohito Ohno; Kazu Mori; Ming Gao; Masuro Motoi

    2008-01-01

    We performed studies on murine models and human volunteers to examine the immunoenhancing effects of the naturally outdoor-cultivated fruit body of Agaricus brasiliensis KA21 (i.e. Agaricus blazei). Antitumor, leukocyte-enhancing, hepatopathy-alleviating and endotoxin shock-alleviating effects were found in mice. In the human study, percentage body fat, percentage visceral fat, blood cholesterol level and blood glucose level were decreased, and natural killer cell activity was increased. Take...

  8. Benzo(a)pyrene activation and detoxification by human pulmonary alveolar macrophages and lymphocytes

    International Nuclear Information System (INIS)

    Comparisons of pulmonary alveolar macrophages and circulating lymphocytes from five smokers and five nonsmokers for their ability to metabolize benzo(a)pyrene as determined by high pressure liquid chromatography were carried out. Utilizing this approach, further investigation of activation and detoxification by several human cell types could provide the basis for more precise and comprehensive studies of carcinogen and drug metabolism in the human lung, and for a better assessment of cancer risk in selected populations

  9. Murine eosinophil differentiation factor. An eosinophil-specific colony- stimulating factor with activity for human cells

    OpenAIRE

    1986-01-01

    A purified murine lymphokine, eosinophil differentiation factor (EDF), was found to be a selective stimulus for the clonal proliferation and differentiation of murine eosinophil progenitor cells, establishing it as the murine eosinophil colony-stimulating factor (Eo-CSF). EDF was also active on human eosinophil progenitors and mature blood eosinophils, but had no effect on neutrophil or macrophage precursor cells, nor on blood neutrophils. In culture of human bone marrow cells, EDF stimulated...

  10. Measurement of factor v activity in human plasma using a microplate coagulation assay.

    Science.gov (United States)

    Tilley, Derek; Levit, Irina; Samis, John A

    2012-09-09

    In response to injury, blood coagulation is activated and results in generation of the clotting protease, thrombin. Thrombin cleaves fibrinogen to fibrin which forms an insoluble clot that stops hemorrhage. Factor V (FV) in its activated form, FVa, is a critical cofactor for the protease FXa and accelerator of thrombin generation during fibrin clot formation as part of prothrombinase (1, 2). Manual FV assays have been described (3, 4), but they are time consuming and subjective. Automated FV assays have been reported (5-7), but the analyzer and reagents are expensive and generally provide only the clot time, not the rate and extent of fibrin formation. The microplate platform is preferred for measuring enzyme-catalyzed events because of convenience, time, cost, small volume, continuous monitoring, and high-throughput (8, 9). Microplate assays have been reported for clot lysis (10), platelet aggregation (11), and coagulation Factors (12), but not for FV activity in human plasma. The goal of the method was to develop a microplate assay that measures FV activity during fibrin formation in human plasma. This novel microplate method outlines a simple, inexpensive, and rapid assay of FV activity in human plasma. The assay utilizes a kinetic microplate reader to monitor the absorbance change at 405 nm during fibrin formation in human plasma (Figure 1) (13). The assay accurately measures the time, initial rate, and extent of fibrin clot formation. It requires only μl quantities of plasma, is complete in 6 min, has high-throughput, is sensitive to 24-80 pM FV, and measures the amount of unintentionally activated (1-stage activity) and thrombin-activated FV (2-stage activity) to obtain a complete assessment of its total functional activity (2-stage activity - 1-stage activity). Disseminated intravascular coagulation (DIC) is an acquired coagulopathy that most often develops from pre-existing infections (14). DIC is associated with a poor prognosis and increases mortality

  11. AMP-activated protein kinase (AMPK) regulates the insulin-induced activation of the nitric oxide synthase in human platelets.

    Science.gov (United States)

    Fleming, Ingrid; Schulz, Christian; Fichtlscherer, Birgit; Kemp, Bruce E; Fisslthaler, Beate; Busse, Rudi

    2003-11-01

    Little is known about the signaling cascades that eventually regulate the activity of the endothelial nitric oxide synthase (eNOS) in platelets. Here, we investigated the effects of insulin on the phosphorylation and activation of eNOS in washed human platelets and in endothelial cells. Insulin activated the protein kinase Akt in cultured endothelial cells and increased the phosphorylation of eNOS on Ser(1177) but failed to increase endothelial cyclic GMP levels or to elicit the relaxation of endothelium-intact porcine coronary arteries. In platelets, insulin also elicited the activation of Akt as well as the phosphorylation of eNOS and initiated NO production which was associated with increased cyclic GMP levels and the inhibition of thrombin-induced aggregation. The insulin-induced inhibition of aggregation was accompanied by a decreased Ca(2+) response to thrombin and was also prevented by N(omega) nitro-L-arginine. In platelets, but not in endothelial cells, insulin induced the activation of the AMP-activated protein kinase (AMPK), a metabolic stress-sensing kinase which was sensitive to the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin and the AMPK inhibitor iodotubercidin. Moreover, the insulin-mediated inhibition of thrombin-induced aggregation was prevented by iodotubercidin. Insulin-independent activation of the AMPK using 5-aminoimidazole-4-carboxamide ribonucleoside, increased platelet eNOS phosphorylation, increased cyclic GMP levels and attenuated platelet aggregation. These results highlight the differences in the signal transduction cascade activated by insulin in endothelial cells and platelets, and demonstrate that insulin stimulates the formation of NO in human platelets, in the absence of an increase in Ca(2+), by acti-vating PI3-K and AMPK which phosphorylates eNOS on Ser(1177).

  12. Vav3 oncogene activates estrogen receptor and its overexpression may be involved in human breast cancer

    Directory of Open Access Journals (Sweden)

    Dong Zhongyun

    2008-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion 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.

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

    Science.gov (United States)

    Queiroz, R A; Soriano, E P; Carvalho, M V D; Caldas-Junior, A F; Souza, E H A; Coelho-Junior, L G T M; Campello, R I C; Almeida, A C; Farias, R C A P; Vasconcellos, A

    2016-07-25

    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. PMID:27463832

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

    International Nuclear Information System (INIS)

    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.)

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

    Science.gov (United States)

    Queiroz, R A; Soriano, E P; Carvalho, M V D; Caldas-Junior, A F; Souza, E H A; Coelho-Junior, L G T M; Campello, R I C; Almeida, A C; Farias, R C A P; Vasconcellos, A

    2016-07-25

    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. Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

    International Nuclear Information System (INIS)

    Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues. Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography. In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues. These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum

  17. Methodologic basis for the radioimmunoassay of endogenous LH-like activity in human prostatic tissue

    International Nuclear Information System (INIS)

    The aim of this study was to develop a technique for the radioimmunological determination of the activity of LH-like substances in the human prostate. The material comprised 19 specimens of prostatic tissue obtained during transbladder extirpation in patients with benign prostatic hyperplasia. Tissues of human testes and human sceletal muscle were used as controls. The method adopted for LH extraction from the membrane fraction of human prostatic tissue appeared to be sufficiently specific, accurate and sensitive for routine laboratory investigations. The concentrations of the LH-like immunoreactivity in human testicular tissue was found to be 57, 46 and 70 mU per g of the membrane fraction while those of the prostatic gland tissues ranged from 34 to 155 mU per g of the membrane fraction. However such LH-like substance was not found in human sceletal muscle tissue. It seems that the LH-type activity is an indirect proof for the existence of LH receptors in the human prostate. (orig.)

  18. Dexamethasone down-regulates, the activity of promoter from human al (Ⅱ) procollagen gene

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate the effects of dexamethasone on the promoter activity of human al(1) procollagen gene.Methods Fibroblasts from human skin were primary cultured and subcultured. (1) The effects of dexamethasone on the human skin fibroblasts were determined by BrdU incorporation into DNA of fibroblasts. (2) Three plasmids containing various engths of 5' flanksequence of human al(1) procollagen gene and CAT as reporter gene were constructed, and were transfected into the human skin fi-broblasts by FuGENE Transfecfion Reagent. The effects of dexamethasone on 3 plasmids were determined by CAT - ELlSA. Results (1)After 24h of treatment on the fibroblasts with 110-9 ~110-4mol/L examethasone in DMEM containing 2% or 10% FCS, BrdU in-corporation into DNA showed no difference ( P > 0.05) . (2) the 3 plasmids were transfected into fibroblasts and then treated with 110-5mol/L and 110-6mol/L dexamethasones for 24h, relative CAT values were different belwent dexamethasone and control,higher dexamethasone(110 -5mol/L} and lower examethasone(110 -6mol/L) ( P <0. 05) . ConcluSion Dexamethasone has noeffects on the proliferation of human skin fibroblasts, and it has negative effect on the promoter activity of human al(1) procollagengene, which is dose- dependent.

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

    International Nuclear Information System (INIS)

    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.)

  20. Active surveillance of Q fever in human and animal population of Cyprus

    Directory of Open Access Journals (Sweden)

    Psaroulaki Anna

    2006-03-01

    Full Text Available Abstract Background A long-term active surveillance of Q fever was conducted in Cyprus organized in two phases. Methods Following serological tests and identification of seropositive humans and animals for C. burnetii in two villages (VIL1 and VIL2, all seronegative individuals were followed up for one year on a monthly basis by trained physicians to detect possible seroconversion for Q fever. In the second phase of the study, active surveillance for one year was conducted in the entire Cyprus. Physicians were following specific case definition criteria for Q fever. Standardized questionnaires, a geographical information system on a regional level, Immunofluorescence Assay (IFA examinations and shell vial technique were used. Results Eighty-one seronegative humans and 239 seronegative animals from both villages participated in the first phase surveillance period of Q fever. Despite the small number of confirmed clinical cases (2 humans and 1 goat, a significant percentage of new seropositives for C. burnetii (44.4% of human participants and 13.8% of animals was detected at the end of the year. During the second phase of surveillance, 82 humans, 100 goats, and 76 sheep were considered suspected cases of Q fever. However, only 9 human, 8 goat, and 4 sheep cases were serologically confirmed, while C. burnetii was isolated from three human and two animal samples. The human incidence rate was estimated at 1.2 per 100,000 population per year. Conclusion A small number of confirmed clinical cases of Q fever were observed despite the high seroprevalence for C. burnetii in human and animal population of Cyprus. Most of the cases in the local population of Cyprus appear to be subclinical. Moreover further studies should investigate the role of ticks in the epidemiology of Q fever and their relation to human seropositivity.

  1. 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.

  2. Human activity response and prevention strategies on soil and water loss in Sichuan Province

    Institute of Scientific and Technical Information of China (English)

    FANG Yiping; CHEN Guojie

    2003-01-01

    Ten major factors have been selected to judge the degree of disturbance from human activity and the corresponding relationship of the impact on soil and water loss in Sichuan Province. Correlation analysis has demonstrated that stock-carrying capacity, percentage of land reclamation, population density, GDP per capita, mineral modulus and percentage of forest coverage are the 6 most relevant human activity factors. The analysis on the degree of disturbance has shown that population pressure, excessive or unreasonable activities in development of resources and destructive behavior of humans are the main causes of soil and water loss. Consequently, solving the various problems in the negative activity of humans and regulating human behavior are the first tasks that should be tackled in the conservation of water and soil. In the new era, the prevention and rectification of soil and water loss are measures based on the foundation of the ecosystem, which is a kind of management strategy for sustainable development. The foundation of this method is made up of the system innovations and breakthroughs in terms of aims, philosophy, measures, and aspects of the prevention and rectification of soil and water loss, simultaneous advance from the conceptual, policy, spatial, technical and mode levels and system integration on the treatment strategies.

  3. Intein-mediated Rapid Purification of Recombinant Human Pituitary Adenylate Cyclase Activating Polypeptide

    Institute of Scientific and Technical Information of China (English)

    Rong-jie YU; An HONG; Yun DAI; Yuan GAO

    2004-01-01

    In order to obtain the recombinant human PACAP efficiently by intein-mediated single column purification, a gene encoding human PACAP was synthesized and cloned into Escherichia coli expression vector pKYB. The recombinant vector pKY-PAC was transferred into E. coli ER2566 cells and the target protein was over-expressed as a fusion to the N-terminus of a self-cleavable affinity tag. After the PACAPintein-CBD fusion protein was purified by chitin-affinity chromatography, the self-cleavage activity of the intein was induced by DTT and the rhPACAP was released from the chitin-bound intein tag. The activity of the rhPACAP to stimulate cyclic AMP accumulation was detected using the human pancreas carcinoma cells SW1990. Twenty-two milligrams of rhPACAP with the purity over 98% was obtained by single column purification from 1 liter of induced culture. The preliminary biological assay indicated that the rhPACAP, which has an extra Met at its N-terminus compared with the native human PACAP, had the similar activity of stimulating cAMP accumulation with the standard PACAP38 in the SW1990 cells. A new efficient production procedure of the active recombinant human PACAP was established.

  4. Centrifugal force induces human ligamentum flavum fibroblasts inflammation through activation of JNK and p38 pathways.

    Science.gov (United States)

    Chao, Yuan-Hung; Tsuang, Yang-Hwei; Sun, Jui-Sheng; Sun, Man-Ger; Chen, Ming-Hong

    2012-01-01

    Inflammation has been proposed to be an important causative factor in ligamentum flavum hypertrophy. However, the mechanisms of mechanical load on inflammation of ligamentum flavum remain unclear. In this study, we used an in vitro model of human ligamentum flavum fibroblasts subjected to centrifugal force to elucidate the effects of mechanical load on cultured human ligamentum flavum fibroblasts; we further studied its molecular and biochemical mechanisms. Human ligamentum flavum fibroblasts were obtained from six patients undergoing lumbar spine surgery. Monolayer cultures of human ligamentum flavum fibroblasts were subjected to different magnitudes of centrifugal forces. Cell viability, cell death, biochemical response, and molecular response to centrifugal forces were analyzed. It was found that centrifugal stress significantly suppressed cell viability without inducing cell death. Centrifugal force at 67.1 g/cm(2) for 60 min significantly increases the production of prostaglandin E2 and nitric oxide as well as gene expression of proinflammatory cytokines, including interleukin (IL)-1α, IL-1β and IL-6, showed that centrifugal force-dependent induction of cyclooxygense-2 and inducible NO synthase required JNK and p38 mitogen-activated protein kinase, but not ERK 1/2 activities. This study suggested that centrifugal force does induce inflammatory responses in human ligamentum flavum fibroblasts. The activation of both JNK and p38 mitogen-activated protein kinase mechanotransduction cascades is a crucial intracellular mechanism that mediates cyclooxygense-2/prostaglandin E2 and inducible NO synthase/nitric oxide production.

  5. The genome of Bifidobacterium pseudocatenulatum IPLA 36007, a human intestinal strain with isoflavone-activation activity

    OpenAIRE

    Alegría, Ángel; Delgado, Susana; Guadamuro, Lucía; Flórez García, Ana Belén; Felis, Giovanna E.; Torriani, Sandra; Mayo Pérez, Baltasar

    2014-01-01

    Background Bifidobacterium species, including Bifidobacterium pseudocatenulatum, are among the dominant microbial populations of the human gastrointestinal tract. They are also major components of many commercial probiotic products. Resident and transient bifidobacteria are thought to have several beneficial health effects. However, our knowledge of how these bacteria interact and communicate with host cells remains poor. This knowledge is essential for scientific support of their purported h...

  6. The relationship between human skeletal muscle pyruvate dehydrogenase phosphatase activity and muscle aerobic capacity.

    Science.gov (United States)

    Love, Lorenzo K; LeBlanc, Paul J; Inglis, J Greig; Bradley, Nicolette S; Choptiany, Jon; Heigenhauser, George J F; Peters, Sandra J

    2011-08-01

    Pyruvate dehydrogenase (PDH) is a mitochondrial enzyme responsible for regulating the conversion of pyruvate to acetyl-CoA for use in the tricarboxylic acid cycle. PDH is regulated through phosphorylation and inactivation by PDH kinase (PDK) and dephosphorylation and activation by PDH phosphatase (PDP). The effect of endurance training on PDK in humans has been investigated; however, to date no study has examined the effect of endurance training on PDP in humans. Therefore, the purpose of this study was to examine differences in PDP activity and PDP1 protein content in human skeletal muscle across a range of muscle aerobic capacities. This association is important as higher PDP activity and protein content will allow for increased activation of PDH, and carbohydrate oxidation. The main findings of this study were that 1) PDP activity (r(2) = 0.399, P = 0.001) and PDP1 protein expression (r(2) = 0.153, P = 0.039) were positively correlated with citrate synthase (CS) activity as a marker for muscle aerobic capacity; 2) E1α (r(2) = 0.310, P = 0.002) and PDK2 protein (r(2) = 0.229, P =0.012) are positively correlated with muscle CS activity; and 3) although it is the most abundant isoform, PDP1 protein content only explained ∼ 18% of the variance in PDP activity (r(2) = 0.184, P = 0.033). In addition, PDP1 in combination with E1α explained ∼ 38% of the variance in PDP activity (r(2) = 0.383, P = 0.005), suggesting that there may be alternative regulatory mechanisms of this enzyme other than protein content. These data suggest that with higher muscle aerobic capacity (CS activity) there is a greater capacity for carbohydrate oxidation (E1α), in concert with higher potential for PDH activation (PDP activity). PMID:21596918

  7. Hepatic cytochrome P450 activity, abundance, and expression throughout human development

    Energy Technology Data Exchange (ETDEWEB)

    Sadler, Natalie C.; Nandhikonda, Premchendar; Webb-Robertson, Bobbie-Jo M.; Ansong, Charles; Anderson, Lindsey N.; Smith, Jordan N.; Corley, Richard A.; Wright, Aaron T.

    2016-07-01

    Cytochrome P450s are Phase I metabolic enzymes that play critical roles in the biotransformation of endogenous compounds and xenobiotics. The expression and activity of P450 enzymes can vary considerably throughout human development, especially when comparing fetal development to neonates, children, and adults. In an effort to develop a more comprehensive understanding of the ontogeny of P450 expression and activity we employed a multi-omic characterization of P450 transcript expression, protein abundance, and functional activity. To quantify the functional activity of individual P450s we employ activity-based protein profiling, which uses modified mechanism-based inhibitors of P450s as chemical probes, in tandem with proteomic analyses to quantify activity. Our results reveal life-stage-dependent variability in P450 expression, abundance, and activity throughout human development and frequent discordant relationships between expression and activity. The results were used to distribute P450s into three general classes based upon developmental stage of expression and activity. We have significantly expanded the knowledge of P450 ontogeny, particularly at the level of individual P450 activity. We anticipate that our ontogeny results will be useful for enabling predictive therapeutic dosing, and for avoiding potentially adverse and harmful reactions during maturation from both therapeutic drugs and environmental xenobiotics.

  8. Influence of activating hormones on human platelet membrane Ca/sup 2 +/-ATPase activity

    Energy Technology Data Exchange (ETDEWEB)

    Resink, T.J.; Dimitrov, D.; Stucki, S.; Buehler, F.R.

    1986-07-16

    Intact platelets were pretreated with hormones and thereafter membranes were prepared and Ca/sup 2 +/-ATPase activity determined. Thrombin decreased the V/sub max/ of Ca/sup 2 +/-ATPase after pretreatment of intact platelets. Platelet activating factor, vasopressin and ADP also decreased Ca/sup 2 +/-ATPase activity. 12-O-tetradecanoylphorbol-13-acetate (TPA) or A23187 or ionomycin alone had no effect, while the simultaneous pretreatment with TPA and Ca/sup 2 +/-ionophore decreased Ca/sup 2 +/-ATPase activity. cAMP elevating agents prostaglandin E/sub 1/ (PGE/sub 1/) and forskolin had no influence per se on Ca/sup 2 +/-ATPase, but antagonized the inhibitory effect of thrombin. The data suggest a close connection between phosphoinositide metabolism and the Ca/sup 2 +/-ATPase system.

  9. Eugenol--the active principle from cloves inhibits 5-lipoxygenase activity and leukotriene-C4 in human PMNL cells.

    Science.gov (United States)

    Raghavenra, H; Diwakr, B T; Lokesh, B R; Naidu, K A

    2006-01-01

    Polymorphonuclear leukocytes (PMNL) play an important role in the modulation of inflammatory conditions in humans. PMNL cells recruited at the site of inflammation, release inflammatory mediators such as leukotrienes, proteolytic enzymes and reactive oxygen species. Among these, leukotrienes are implicated in pathophysiology of allergic and inflammatory disorders like asthma, allergic rhinitis, arthritis, inflammatory bowel disease and psoriasis. 5-lipoxygenase (5-LO) is the key enzyme in biosynthetic pathway of leukotrienes. Our earlier studies showed that spice phenolic active principles significantly inhibit 5-LO enzyme in human PMNLs. In this study we have further characterized the inhibitory mechanism of eugenol, the active principle of spice-clove on 5-LO enzyme and also its effect on leukotriene C((4)) (LTC(4)). Substrate dependent enzyme kinetics showed that the inhibitory effect of eugenol on 5-LO was of a non-competitive nature. Further, eugenol was found to significantly inhibit the formation of LTC(4) in calcium ionophore A23187 and arachidonic acid (AA) stimulated PMNL cells. These data clearly suggest that eugenol inhibits 5-LO by non-competitive mechanism and also inhibits formation of LTC(4) in human PMNL cells and thus may have beneficial role in modulating 5-LO pathway in human PMNL cells.

  10. Comparison of xenobiotic metabolizing enzyme activities in ex vivo human skin and reconstructed human skin models from SkinEthic.

    Science.gov (United States)

    Eilstein, Joan; Léreaux, Guillaume; Budimir, Natali; Hussler, Georges; Wilkinson, Simon; Duché, Daniel

    2014-09-01

    Skin function is not limited to a physical barrier. According to its total surface area, it is also considered as an extra-hepatic metabolizing organ. In vitro engineered human skins have been developed to replace limited ex vivo normal human skin samples (NHS). Thus, assessing and comparing skin models from SkinEthic [Episkin™, RHE™ and the full thickness model (FTM)] with NHS in terms of metabolic capability are essential. The apparent activities of main cutaneous isoforms of cytochrome P450-dependent monooxygenases (CYP1A1/1B1, 2B6/2C18/2E1, 3A5/3A7), esterase, glutathione-S-[(GST), A, M, P, T], N-acetyl-(NAT1), uridinyl-diphosphate glucuronyl-(UDPGT 1A family) and sulfo-(SULT1A1) transferases were determined using probe substrates. Mean activities indicative of CYP1A1/1B1 (expressed as pmol/mg protein/6 h) in RHE™ (2.8) and FTM (2.6) were very similar to NHS (3.0) while Episkin™ showed a higher activity (9.1). Activities of CYP3A5/3A7 in FTM (3.3) and Episkin™ (3.6) were similar to NHS (3.8) while activity in RHE™ (13.3) was higher. CYP2B6/2C18/2E1 activity was below LOQ (0.5) in all skin models and NHS. Comparable intrinsic metabolic clearances were measured between NHS and skin models for esterase, UDPGT, GST and NAT1 activities. SULT1A1 activity toward probe substrates was not detected in skin models and observed at the limit of detection in NHS. Weak cytochrome P450-dependent monooxygenases, high esterase and transferase activities suggested that NHS and skin models exhibited limited functionalization and much greater detoxification (hydrolytic and conjugating) capacities. These results demonstrate that skin models are similar to NHS in terms of metabolic functionality toward xenobiotics investigated and useful tools to assess both the local efficiency and safety of cosmetics. PMID:24658324

  11. Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds.

    Science.gov (United States)

    Pincemail, J; Deby, C; Thirion, A; de Bruyn-Dister, M; Goutier, R

    1988-05-15

    Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the MPO/H2O2/Cl- system.

  12. Detection of type V collagen-degrading enzyme activity in human liver.

    Directory of Open Access Journals (Sweden)

    Kobayashi,Michio

    1986-06-01

    Full Text Available Type V collagen-degrading enzyme activity was detected as a metalloprotease acting at neutral pH in the human liver. Type V collagen extracted from human placenta and labeled with [1-14C] acetic anhydride was used as the substrate in the assay. Four major degradation products with relatively high molecular weights were observed upon polyacrylamide gel electrophoresis of the incubation mixture of type V collagen and liver homogenate. The significance of the measurement of this enzyme activity was discussed in relation to the clarification of the mechanism of liver fibrosis.

  13. Screening of Fungi from Chinese Medical Plants for Anti-Human Immunodeficiency Virus Type 1 Activity

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to isolate anti-human immunodeficiency virus (HIV) agents from natural products, 97 ethanolic extracts of 90 fungi were tested for their inhibitory activity on HIV-1. Most of the extracts tested were relatively non-toxic to human lymphocytic MT-4 cells, but extracts of some fungi exhibited potent anti-HIV activity in an in vitro 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay with a selectivity index greater than 3. Most fungi were isolated from Dendrobium sp. and Taxus sp.

  14. Single amino acid changes that render human IFN-alpha 2 biologically active on mouse cells.

    OpenAIRE

    Weber, H.; Valenzuela, D; Lujber, G; Gubler, M; Weissmann, C

    1987-01-01

    Human IFN-alpha 1 and IFN-alpha 2 differ in 28 of 166 amino acids and show very different specific antiviral activities on human and murine cells. We have identified, by hybrid scanning and site-directed mutagenesis, three residues in IFN-alpha 2, in positions 121, 125 and 132 which, when replaced individually or jointly by their IFN-alpha 1 counterparts, modify its activity on mouse cells by up to 400-fold. We argue that these residues are involved in direct contacts with the mouse interfero...

  15. A humanized anti-M2 scFv shows protective in vitro activity against influenza

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M [Los Alamos National Laboratory; Velappan, Nileena [Los Alamos National Laboratory; Schmidt, Jurgen G [Los Alamos National Laboratory

    2008-01-01

    M2 is one of the most conserved influenza proteins, and has been widely prospected as a potential universal vaccine target, with protection predominantly mediated by antibodies. In this paper we describe the creation of a humanized single chain Fv from 14C2, a potent monoclonal antibody against M2. We show that the humanized scFv demonstrates similar activity to the parental mAb: it is able to recognize M2 in its native context on cell surfaces and is able to show protective in vitro activity against influenza, and so represents a potential lead antibody candidate for universal prophylactic or therapeutic intervention in influenza.

  16. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    Science.gov (United States)

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  17. Activation of AMP-activated protein kinase stimulates the nuclear localization of glyceraldehyde 3-phosphate dehydrogenase in human diploid fibroblasts

    OpenAIRE

    Kwon, Hyun Jin; Rhim, Ji Heon; Jang, Ik-Soon; Kim, Go-Eun; Park, Sang Chul; Yeo, Eui-Ju

    2010-01-01

    In addition to its well-known glycolytic activity, GAPDH displays multiple functions, such as nuclear RNA export, DNA replication and repair, and apoptotic cell death. This functional diversity depends on its intracellular localization. In this study, we explored the signal transduction pathways involved in the nuclear translocation of GAPDH using confocal laser scanning microscopy of immunostained human diploid fibroblasts (HDFs). GAPDH was present mainly in the cytoplasm when cultured wi...

  18. Single motor unit activity in human extraocular muscles during the vestibulo-ocular reflex.

    Science.gov (United States)

    Weber, Konrad P; Rosengren, Sally M; Michels, Rike; Sturm, Veit; Straumann, Dominik; Landau, Klara

    2012-07-01

    Motor unit activity in human eye muscles during the vestibulo-ocular reflex (VOR) is not well understood, since the associated head and eye movements normally preclude single unit recordings. Therefore we recorded single motor unit activity following bursts of skull vibration and sound, two vestibular otolith stimuli that elicit only small head and eye movements. Inferior oblique (IO) and inferior rectus (IR) muscle activity was measured in healthy humans with concentric needle electrodes. Vibration elicited highly synchronous, short-latency bursts of motor unit activity in the IO (latency: 10.5 ms) and IR (14.5 ms) muscles. The activation patterns of the two muscles were similar, but reciprocal, with delayed activation of the IR muscle. Sound produced short-latency excitation of the IO muscle (13.3 ms) in the eye contralateral to the stimulus. Simultaneous needle and surface recordings identified the IO as the muscle of origin of the vestibular evoked myogenic potential (oVEMP) thus validating the physiological basis of this recently developed clinical test of otolith function. Single extraocular motor unit recordings provide a window into neural activity in humans that can normally only be examined using animal models and help identify the pathways of the translational VOR from otoliths to individual eye muscles.

  19. 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.

  20. Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes

    International Nuclear Information System (INIS)

    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

  1. Systems biology of coagulation initiation: kinetics of thrombin generation in resting and activated human blood.

    Directory of Open Access Journals (Sweden)

    Manash S Chatterjee

    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

  2. Activation of calcineurin in human failing heart ventricle by endothelin-1, angiotensin II and urotensin II.

    Science.gov (United States)

    Li, Joan; Wang, Jianchun; Russell, Fraser D; Molenaar, Peter

    2005-06-01

    1 The calcineurin (CaN) enzyme-transcriptional pathway is critically involved in hypertrophy of heart muscle in some animal models. Currently there is no information concerning the regulation of CaN activation by endogenous agonists in human heart. 2 Human right ventricular trabeculae from explanted human (14 male/2 female) failing hearts were set up in a tissue bath and electrically paced at 1 Hz and incubated with or without 100 nM endothelin-1 (ET-1), 10 M, angiotensin-II (Ang II) or 20 nM human urotensin-II (hUII) for 30 min. Tissues from four patients were incubated with 200 nM tacrolimus (FK506) for 30 min and then incubated in the presence or absence of ET-1 for a further 30 min. 3 ET-1 increased contractile force in all 13 patients (P0.1). FK506 had no effect on contractile force (P=0.12). 4 ET-1, Ang II and hUII increased calcineurin activity by 32, 71 and 15%, respectively, while FK506 reduced activity by 34%. ET-1 in the presence of FK506 did not restore calcineurin activity (P=0.1). 5 There was no relationship between basal CaN activity and expression levels in the right ventricle. Increased levels of free phosphate were detected in ventricular homogenates that were incubated with PKC(epsilon) compared to samples incubated without PKC(epsilon). 6 Endogenous cardiostimulants which activate G(alpha)q-coupled receptors increase the activity of calcineurin in human heart following acute (30 min) exposure. PKC may contribute to this effect by increasing levels of phosphorylated calcineurin substrate.

  3. 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.

  4. Human Activities in Natura 2000 Sites: A Highly Diversified Conservation Network

    Science.gov (United States)

    Tsiafouli, Maria A.; Apostolopoulou, Evangelia; Mazaris, Antonios D.; Kallimanis, Athanasios S.; Drakou, Evangelia G.; Pantis, John D.

    2013-05-01

    The Natura 2000 network was established across the European Union's (EU) Member States with the aim to conserve biodiversity, while ensuring the sustainability of human activities. However, to what kind and to what extent Natura 2000 sites are subject to human activities and how this varies across Member States remains unspecified. Here, we analyzed 111,269 human activity records from 14,727 protected sites in 20 Member States. The frequency of occurrence of activities differs among countries, with more than 86 % of all sites being subjected to agriculture or forestry. Activities like hunting, fishing, urbanization, transportation, and tourism are more frequently recorded in south European sites than in northern or eastern ones. The observed variations indicate that Natura 2000 networks are highly heterogeneous among EU Member States. Our analysis highlights the importance of agriculture in European landscapes and indicates possible targets for policy interventions at national, European, or "sub-European" level. The strong human presence in the Natura 2000 network throughout Member States, shows that conservation initiatives could succeed only by combining social and ecological sustainability and by ensuring the integration of policies affecting biodiversity.

  5. Influence of organophosphorus pesticides on peroxidase and chlorination activity of human myeloperoxidase.

    Science.gov (United States)

    Lazarević-Pašti, Tamara; Momić, Tatjana; Radojević, Miloš M; Vasić, Vesna

    2013-09-01

    Inhibitory effects of five organophosphorus pesticides (diazinon, malathion, chlorpyrifos, azinphos-methyl and phorate) and their oxo-analogs on human myeloperoxidase (MPO) activity were investigated. While inspecting separately peroxidase and chlorination activity, it was observed that investigated OPs affect peroxidase activity, but not chlorination activity. Among investigated pesticides, malathion and malaoxon have showed the highest power to inhibit MPO peroxidase activity with IC50 values of the order of 3×10(-7) and 5×10(-9) M, respectively. It was proposed that inhibition trend is rendered by molecular structure which invokes steric hindrance for OPs interaction with MPO active center responsible for peroxidase activity. In addition, it was concluded that physiological function of MPO is not affected by any of the investigated OPs. PMID:25149236

  6. Mathematical modeling of gap junction coupling and electrical activity in human β-cells

    Science.gov (United States)

    Loppini, Alessandro; Braun, Matthias; Filippi, Simonetta; Gram Pedersen, Morten

    2015-12-01

    Coordinated insulin secretion is controlled by electrical coupling of pancreatic β-cells due to connexin-36 gap junctions. Gap junction coupling not only synchronizes the heterogeneous β-cell population, but can also modify the electrical behavior of the cells. These phenomena have been widely studied with mathematical models based on data from mouse β-cells. However, it is now known that human β-cell electrophysiology shows important differences to its rodent counterpart, and although human pancreatic islets express connexin-36 and show evidence of β-cell coupling, these aspects have been little investigated in human β-cells. Here we investigate theoretically, the gap junction coupling strength required for synchronizing electrical activity in a small cluster of cells simulated with a recent mathematical model of human β-cell electrophysiology. We find a lower limit for the coupling strength of approximately 20 pS (i.e., normalized to cell size, ˜2 pS pF-1) below which spiking electrical activity is asynchronous. To confront this theoretical lower bound with data, we use our model to estimate from an experimental patch clamp recording that the coupling strength is approximately 100-200 pS (10-20 pS pF-1), similar to previous estimates in mouse β-cells. We then investigate the role of gap junction coupling in synchronizing and modifying other forms of electrical activity in human β-cell clusters. We find that electrical coupling can prolong the period of rapid bursting electrical activity, and synchronize metabolically driven slow bursting, in particular when the metabolic oscillators are in phase. Our results show that realistic coupling conductances are sufficient to promote synchrony in small clusters of human β-cells as observed experimentally, and provide motivation for further detailed studies of electrical coupling in human pancreatic islets.

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

    Directory of Open Access Journals (Sweden)

    Patricia Marie Legler

    2014-07-01

    Full Text Available 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.

  9. Mapping the homodimer interface of an optimized, artificial, transmembrane protein activator of the human erythropoietin receptor.

    Directory of Open Access Journals (Sweden)

    Emily B Cohen

    Full Text Available Transmembrane proteins constitute a large fraction of cellular proteins, and specific interactions involving membrane-spanning protein segments play an important role in protein oligomerization, folding, and function. We previously isolated an artificial, dimeric, 44-amino acid transmembrane protein that activates the human erythropoietin receptor (hEPOR in trans. This artificial protein supports limited erythroid differentiation of primary human hematopoietic progenitor cells in vitro, even though it does not resemble erythropoietin, the natural ligand of this receptor. Here, we used a directed-evolution approach to explore the structural basis for the ability of transmembrane proteins to activate the hEPOR. A library that expresses thousands of mutants of the transmembrane activator was screened for variants that were more active than the original isolate at inducing growth factor independence in mouse cells expressing the hEPOR. The most active mutant, EBC5-16, supports erythroid differentiation in human cells with activity approaching that of EPO, as assessed by cell-surface expression of glycophorin A, a late-stage marker of erythroid differentiation. EBC5-16 contains a single isoleucine to serine substitution at position 25, which increases its ability to form dimers. Genetic studies confirmed the importance of dimerization for activity and identified the residues constituting the homodimer interface of EBC5-16. The interface requires a GxxxG dimer packing motif and a small amino acid at position 25 for maximal activity, implying that tight packing of the EBC5-16 dimer is a crucial determinant of activity. These experiments identified an artificial protein that causes robust activation of its target in a natural host cell, demonstrated the importance of dimerization of this protein for engagement of the hEPOR, and provided the framework for future structure-function studies of this novel mechanism of receptor activation.

  10. [The influence of aging on autonomic nervous system activity and gastric myoelectric activity in humans].

    Science.gov (United States)

    Thor, P J; Kolasińska-Kloch, W; Pitala, A; Janik, A; Kopp, B; Sibiga, W

    1999-01-01

    The study was performed on 84 healthy volunteers (33 women, 52 men) of age 20-71 years with no history of the circulatory or gastrointestinal system disease. The gastric myoelectrical activity (EGG) was recorded with the cutaneous electrodes--electrogastrography Synectics (Sweden). The activity of the cardiac autonomic nervous system was measured by HRV (heart rate variability) recorded with EGG and computer assisted programme Proster (Poland). Subject were divided into 5 groups according to the decade of age (20-70). Percentage of basal electrical rhythm (BER) dysrhythmias increased (1.9 +/- 0.5% vs 21.1 +/- 3.2% in fasting and 2.4 +/- 1.2% vs 24.6 +/- 5% postprandially but decrease of the EGG amplitude after the meal was observed (270 +/- 20% vs 90 +/- 7%) in youngest and oldest group respectively. With the ageing the cardiac sympathetic and parasympathetic activity (LF and HF) decreased in first and last group respectively. In the forth decade in man and women the sympathetic activity system prevalence expressed by the LF/HF rate increased (1.09 +/- 0.2 vs. 2.14 +/- 0.5) (p < 0.05). The results of our study suggest the deleterious influence of the ageing on the of autonomic system activity as shown by changes in HRV and dysrhythmia of the gastric slow waves in EGG. PMID:10909474

  11. Effects of C-reactive protein and pentosan polysulphate on human complement activation.

    Science.gov (United States)

    Klegeris, Andis; Singh, Edith A; McGeer, Patrick L

    2002-07-01

    Complement (C) activation is believed to play an adverse role in several chronic degenerative disease processes, including atherosclerosis, myocardial infarction and Alzheimer's disease. We developed several in vitro quantitative assays to evaluate processes which activate C in human serum, and to assess candidates which might block that activation. Binding of C-reactive protein (CRP) to immobilized cell surfaces was used as a tissue-based method of activation, while immunoglobulin G in solution was used as a surrogate antibody method. Activation was assessed by deposition of C fragments on fixed cell surfaces, or by capture of C5b-9 from solution. We observed that several cell lines, including SH-SY5Y, U-937, THP-1 and ECV304, bound CRP and activated C following attachment of cells to a plastic surface by means of air drying. Treatment of human neuroblastoma SH-SY5Y cells with the reactive oxygen intermediates generated by xanthine (Xa) - xanthine oxidase (XaOx) prior to air drying or by hydrogen peroxide solutions after air drying, enhanced C activation, possibly through oxidation of the cell lipid membrane. Several C inhibitors were tested for their effectiveness in blocking these systems. Pentosan polysulphate (PPS), an orally active agent, blocked C activation in the same concentration range of 1-1000 microg/ml as heparin, dextran sulphate, compstatin and fucoidan. PPS may have practical application as a C inhibitor. PMID:12100726

  12. Activation of human colon mast cells through proteinase activated receptor-2

    Institute of Scientific and Technical Information of China (English)

    Shao-Heng He; Yong-Song He; Hua Xie

    2004-01-01

    AIM: To investigate the ability of agonists of PAR-2 to rtimulate release of tryptase and histamine from human colon mast cells and the potential mechanisms.METHODS: Enzymatically dispersed cells from human colons were challenged with tc-LIGRLO, tc-OLRGIL, SLIGKV,VKGILS, trypsin, anti-IgE or calcium ionophore A23187, and the cell supernatante after challenge were collected. Tryptase release was determined with a sandwich ELISA procedure and histamine release was measured using a glass fibrebased fluorometric assay.RESULTS: Both PAR-2 agonists tc-LIGRLO-NH2 and SLIGKVNH2 were able to induce dose dependent release of tryptase and histamine from colon mast cells. More than 2.5 fold increase in both tryptase and histamine release was provoked by 100 μmol/mL tc-LIGRLO-NH2, in compariSon with only 2.0 fold increase being stimulated by SLIGKV-NH2. The reverse peptides tc-OLRGIL-NH2 and VKGILS -NH2 at the concentrations tested had no effect on the release of these two mediators. The maximum tryptase release elicited by tc-LIGRLO-NH2 was similar to that induced by anti-IgE(10 μg/mL) or calcium ionophore (1 μg/mL), though the latter was a more potent stimulus for histamine release. Both histamine and tryptase release in response to tc-LIGRLONH2 were completed within 3 min. Trypsin at concentrations from 1.0 to 100 μg/mL was capable of provoking a dose dependent release of tryptase as well as histamine with a maximum of 16 ng/mL tryptase and 14 ng/mL histamine release being achieved. An approximately 80% and 70% inhibition of trypsin induced release of tryptase and histamine were observed with SBTI, respectively. Pretreatment of cells with metabolic inhibitors or pertussis toxin abolished the actions of tc-LIGRLO-NH2, SLIGKV-NH2 and trypsin.CONCLUSION: The agonists of PAR-2 and trypsin are potent secretagogues of human colon mast cells, which are likely to contribute to the development of inflammatory disorders in human gut.

  13. Activation of human natural killer cells by the soluble form of cellular prion protein

    International Nuclear Information System (INIS)

    Cellular prion protein (PrPC) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrPC in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrPC protein on human natural killer (NK) cells. Recombinant soluble PrPC protein was generated by fusion of human PrPC with the Fc portion of human IgG1 (PrPC-Fc). PrPC-Fc binds to the surface of human NK cells, particularly to CD56dim NK cells. PrPC-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrPC-Fc facilitated the IL-15-induced proliferation of NK cells. PrPC-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrPC-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrPC-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrPC (PrPC-Fc) was generated by fusion of human PrPC with IgG1 Fc portion. • PrPC-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrPC-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrPC-Fc protein activates human NK cells via the ERK and JNK signaling pathways

  14. Activation of human natural killer cells by the soluble form of cellular prion protein

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Yeon-Jae [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Hafis Clinic, Seoul (Korea, Republic of); Sung, Pil Soo; Jang, Young-Soon; Choi, Young Joon [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Bum-Chan [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Park, Su-Hyung [Laboratory of Translational Immunology and Vaccinology, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of); Park, Young Woo [Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Shin, Eui-Cheol, E-mail: ecshin@kaist.ac.kr [Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon (Korea, Republic of)

    2015-08-21

    Cellular prion protein (PrP{sup C}) is widely expressed in various cell types, including cells of the immune system. However, the specific roles of PrP{sup C} in the immune system have not been clearly elucidated. In the present study, we investigated the effects of a soluble form of recombinant PrP{sup C} protein on human natural killer (NK) cells. Recombinant soluble PrP{sup C} protein was generated by fusion of human PrP{sup C} with the Fc portion of human IgG{sub 1} (PrP{sup C}-Fc). PrP{sup C}-Fc binds to the surface of human NK cells, particularly to CD56{sup dim} NK cells. PrP{sup C}-Fc induced the production of cytokines and chemokines and the degranulation of granzyme B from NK cells. In addition, PrP{sup C}-Fc facilitated the IL-15-induced proliferation of NK cells. PrP{sup C}-Fc induced phosphorylation of ERK-1/2 and JNK in NK cells, and inhibitors of the ERK or the JNK pathways abrogated PrP{sup C}-Fc-induced cytokine production in NK cells. In conclusion, the soluble form of recombinant PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways. - Highlights: • Recombinant soluble PrP{sup C} (PrP{sup C}-Fc) was generated by fusion of human PrP{sup C} with IgG1 Fc portion. • PrP{sup C}-Fc protein induces the production of cytokines and degranulation from human NK cells. • PrP{sup C}-Fc protein enhances the IL-15-induced proliferation of human NK cells. • PrP{sup C}-Fc protein activates human NK cells via the ERK and JNK signaling pathways.

  15. Antifungal activity in human urine and serum after ingestion of garlic (Allium sativum).

    OpenAIRE

    Caporaso, N; Smith, S M; Eng, R H

    1983-01-01

    A fresh extract of garlic (Allium sativum) was administered orally to human volunteers. At intervals, serum and urine were collected and assayed for antifungal activity. The maximum tolerable dose was determined to be 25 ml of garlic extract. Larger amounts caused severe burning sensations in the esophagus and the stomach and vomiting. After oral ingestion of 25 ml of the extract, anticandidal and anticryptococcal activities were detected in undiluted serum 0.5 and 1 h after ingestion. No det...

  16. Cold but not sympathomimetics activates human brown adipose tissue in vivo

    OpenAIRE

    Cypess, Aaron M.; Chen, Yih-Chieh; Sze, Cathy; Wang, Ke; English, Jeffrey; Chan, Onyee; Holman, Ashley R.; Tal, Ilan; Palmer, Matthew R.; Kolodny, Gerald M.; Kahn, C. Ronald

    2012-01-01

    As potential activators of brown adipose tissue (BAT), mild cold exposure and sympathomimetic drugs have been considered as treatments for obesity and diabetes, but whether they activate the same pathways is unknown. In 10 healthy human volunteers, we found that the sympathomimetic ephedrine raised blood pressure, heart rate, and energy expenditure, and increased multiple circulating metabolites, including glucose, insulin, and thyroid hormones. Cold exposure also increased blood pressure and...

  17. Human thymic epithelial cells directly induce activation of autologous immature thymocytes.

    OpenAIRE

    Denning, S M; Kurtzberg, J; Le, P. T.; Tuck, D T; Singer, K H; Haynes, B. F.

    1988-01-01

    To study the role that epithelial cells of the thymic microenvironment play in promoting activation of immature CD7+, CD2+, CD4-, CD8- (double-negative) human thymocytes, we have isolated thymocyte subsets from normal postnatal thymus and have cocultured autologous double-negative thymocytes with pure populations of thymic epithelial (TE) cells. We report that TE cells directly activate double-negative thymocytes to proliferate and that TE cells enhance the ability of double-negative thymocyt...

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

    OpenAIRE

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

    2013-01-01

    The glucose-activated transcription factor carbohydrate response element binding protein (ChREBP) induces the expression of hepatic glycolytic and lipogenic genes. The farnesoid X receptor (FXR) is a nuclear bile acid receptor controlling bile acid, lipid, and glucose homeostasis. FXR negatively regulates hepatic glycolysis and lipogenesis in mouse liver. The aim of this study was to determine whether FXR regulates the transcriptional activity of ChREBP in human hepatocytes and to unravel the...

  19. Antitumor activity of Bulgarian herb Tribulus terrestris L. on human breast cancer cells

    OpenAIRE

    Svetla Angelova; Zlatina Gospodinova; Maria Krasteva; Georgi Antov; Valentin Lozanov; Tsanko Markov; Stefan Bozhanov; Elena Georgieva; Vanio Mitev

    2013-01-01

    Medicinal plants have been intensively studied as a source of antitumor compounds. Due to the beneficial climate conditions Bulgarian herbs have high pharmacological potential. Currently, the antitumor effect of the Bulgarian medicinal plant Tribulus terrestris L. on human cancer cell lines is not studied. The main active compounds of the plant are the steroid saponins.The present study aims to analyze the effect on cell viability and apoptotic activity of total extract and saponin fraction o...

  20. 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...

  1. Time-invariant person-specific frequency templates in human brain activity

    OpenAIRE

    Doron, Itai; Hulata, Eyal; Baruchi, Itay; Towle, Vernon L.; Ben-Jacob, Eshel

    2006-01-01

    The various human brain tasks are performed at different locations and time scales. Yet, we discovered the existence of time-invariant (above an essential time scale) partitioning of the brain activity into personal state-specific frequency bands. For that, we perform temporal and ensemble averaging of best wavelet packet bases from multi-electrode EEG recordings. These personal frequency-bands provide new templates for quantitative analyses of brain function, e.g., normal vs. epileptic activ...

  2. Human Daily Activities Indexing in Videos from Wearable Cameras for Monitoring of Patients with Dementia Diseases

    CERN Document Server

    Karaman, Svebor; Mégret, Rémi; Dovgalecs, Vladislavs; Dartigues, Jean-François; Gaëstel, Yann

    2010-01-01

    Our research focuses on analysing human activities according to a known behaviorist scenario, in case of noisy and high dimensional collected data. The data come from the monitoring of patients with dementia diseases by wearable cameras. We define a structural model of video recordings based on a Hidden Markov Model. New spatio-temporal features, color features and localization features are proposed as observations. First results in recognition of activities are promising.

  3. Chronic hypoxia inhibits MMP-2 activation and cellular invasion in human cardiac myofibroblasts

    OpenAIRE

    Riches, Kirsten; Morley, Michael E.; Turner, Neil A; O'Regan, David J; Ball, Stephen G; Peers, Chris; Porter, Karen E

    2009-01-01

    Cardiac myofibroblasts are pivotal to adaptive remodelling after myocardial infarction (MI). These normally quiescent cells invade and proliferate as a wound healing response, facilitated by activation of matrix metalloproteinases, particularly MMP-2. Following MI these reparative events occur under chronically hypoxic conditions yet the mechanisms by which hypoxia might modulate MMP-2 activation and cardiac myofibroblast invasion have not been investigated. Human cardiac myofibroblasts cultu...

  4. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M;

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....

  5. The winter day as a constraint for human activity in Western Europe

    OpenAIRE

    Martín-Olalla, José-María

    2016-01-01

    Time use surveys in Denmark, Spain, France, Ireland, Italy and United Kingdom are analyzed to provide start, noon and end times for the main activities of a society: labor (the focus of this preprint), sleeping and eating. Also, the location at home is analyzed. Local times are converted into mean solar times and compared to latitude. Observed trends allow to unveil the winter day as a restriction for the human activity. Alternatively, apparently large time differences set forth by clocks, be...

  6. Lingual lipase activity in the orosensory detection of fat by humans

    OpenAIRE

    Kulkarni, Bhushan V.; Mattes, Richard D.

    2014-01-01

    Lingual lipase generates nonesterified fatty acids (NEFA) from dietary fats during oral processing by lipolysis. Lingual lipase in rodents has strong lipolytic activity and plays a critical role in oral detection of fats. The functional activity of lingual lipase during oral processing of high-fat foods in humans remains poorly characterized. Five commonly consumed high-fat foods varying in physical states and fatty acid composition (almond, almond butter, olive oil, walnut, and coconut) were...

  7. Single amino acid substitutions dissociate fibrinogen-clotting and thrombomodulin-binding activities of human thrombin.

    OpenAIRE

    Wu, Q Y; Sheehan, J P; Tsiang, M; Lentz, S R; Birktoft, J J; Sadler, J E

    1991-01-01

    Thrombin is a serine protease that acts as a procoagulant by clotting fibrinogen and activating platelets and as an anticoagulant by activating protein C in a thrombomodulin-dependent reaction. Fibrinogen and thrombomodulin bind competitively to an anion-binding exosite on thrombin. We prepared recombinant normal human thrombin and mutant thrombins with single amino acid substitutions in order to localize and distinguish the fibrinogen- and thrombomodulin-binding sites. Normal and mutant thro...

  8. Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles

    OpenAIRE

    Robin Mesnage; Nicolas Defarge; Joël Spiroux de Vendômois; Gilles-Eric Séralini

    2014-01-01

    Pesticides are used throughout the world as mixtures called formulations. They contain adjuvants, which are often kept confidential and are called inerts by the manufacturing companies, plus a declared active principle, which is usually tested alone. We tested the toxicity of 9 pesticides, comparing active principles and their formulations, on three human cell lines (HepG2, HEK293, and JEG3). Glyphosate, isoproturon, fluroxypyr, pirimicarb, imidacloprid, acetamiprid, tebuconazole, epoxiconazo...

  9. 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

  10. Antibiofilm Activity of the Brown Alga Halidrys siliquosa against Clinically Relevant Human Pathogens

    OpenAIRE

    Alessandro Busetti; Thompson, Thomas P.; Diana Tegazzini; Julianne Megaw; Maggs, Christine A.; Gilmore, Brendan F.

    2015-01-01

    The marine brown alga Halidrys siliquosa is known to produce compounds with antifouling activity against several marine bacteria. The aim of this study was to evaluate the antimicrobial and antibiofilm activity of organic extracts obtained from the marine brown alga H. siliquosa against a focused panel of clinically relevant human pathogens commonly associated with biofilm-related infections. The partially fractionated methanolic extract obtained from H. siliquosa collected along the shores o...

  11. Identification of Functionally Relevant Lysine Residues That Modulate Human Farnesoid X Receptor Activation

    OpenAIRE

    Sun, An-Qiang; Luo, Yuhuan; Backos, Donald S.; Xu, Shuhua; Balasubramaniyan, Natarajan; Reigan, Philip; Suchy, Frederick J.

    2013-01-01

    Base amino acid lysine residues play an important role in regulation of nuclear receptors [e.g., farnesyl X receptor (FXR)], leading to enhanced or suppressed biologic activity. To understand the molecular mechanisms and the subsequent effects in modulating FXR functions in diverse biologic processes, we individually replaced eight highly conserved lysine residues of human FXR (hFXR) with arginine. The effects of each mutated FXR on target gene activation, subcellular localization, protein-pr...

  12. Interleukin 2-dependent release of interleukin 3 activity by T4+ human T-cell clones.

    OpenAIRE

    Ythier, A A; Abbud-Filho, M; Williams, J.M.; Loertscher, R; Schuster, M W; Nowill, A; Hansen, J A; Maltezos, D; Strom, T.B.

    1985-01-01

    We have isolated and studied two alloreactive, T4+, human lymphocyte clones that release interleukin 2 (IL-2) and interleukin 3 (IL-3) bioactivities upon stimulation with IL-2, alloantigen, or Sepharose-conjugated antibodies directed against the T3 protein. Anti-IL-2 receptor monoclonal antibodies block IL-2-, alloantigen-, or anti-T3-stimulated IL-3 release. Hence, release of IL-3 activity in each circumstance is rigorously dependent upon activation of the IL-2 receptor. Even low, nonmitogen...

  13. Exercise stimulates the mitogen-activated protein kinase pathway in human skeletal muscle.

    OpenAIRE

    Aronson, D; Violan, M A; Dufresne, S D; Zangen, D; FIELDING, R.A.; Goodyear, L J

    1997-01-01

    Physical exercise can cause marked alterations in the structure and function of human skeletal muscle. However, little is known about the specific signaling molecules and pathways that enable exercise to modulate cellular processes in skeletal muscle. The mitogen-activated protein kinase (MAPK) cascade is a major signaling system by which cells transduce extracellular signals into intracellular responses. We tested the hypothesis that a single bout of exercise activates the MAPK signaling pat...

  14. PAR-2 activation, PGE2, and COX-2 in human asthmatic and nonasthmatic airway smooth muscle cells

    NARCIS (Netherlands)

    Chambers, Linda S; Black, Judith L; Ge, Qi; Carlin, Stephen M; Au, Wendy W; Poniris, Maree; Thompson, Joanne; Johnson, Peter R; Burgess, Janette K

    2003-01-01

    The protease-activated receptor-2 (PAR-2) is present on human airway smooth muscle (ASM) cells and can be activated by mast cell tryptase, trypsin, or an activating peptide (AP). Trypsin induced significant increases in PGE2 release from human ASM cells after 6 and 24 h and also induced cyclooxygena

  15. Cytotoxic activities of amentoflavone against human breast and cervical cancers are mediated by increasing of PTEN expression levels due to peroxisomes proliferate-activated receptor {gamma} activation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eunjung; Shin, Soyoung; Lee, Jeeyoung; Lee, So Jung; Kim, Jinkyoung; Yoon, Doyoung; Kim, Yangmee [Konkuk Univ., Seoul (Korea, Republic of); Woo, Eunrhan [Chosun Univ., Gwangju (Korea, Republic of)

    2012-07-15

    Human peroxisomes proliferate-activated receptor gamma (hPPAR{gamma}) has been implicated in numerous pathologies, including obesity, diabetes, and cancer. Previously, we verified that amentoflavone is an activator of hPPAR{gamma} and probed the molecular basis of its action. In this study, we investigated the mechanism of action of amentoflavone in cancer cells and demonstrated that amentoflavone showed strong cytotoxicity against MCF-7 and HeLa cancer cell lines. We showed that hPPAR{gamma} expression in MCF-7 and HeLa cells is specifically stimulated by amentoflavone, and suggested that amentoflavone-induced cytotoxic activities are mediated by activation of hPPAR{gamma} in these two cancer cell lines. Moreover, amentoflavone increased PTEN levels in these two cancer cell lines, indicating that the cytotoxic activities of amentoflavone are mediated by increasing of PTEN expression levels due to hPPAR{gamma} activation.

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

    Science.gov (United States)

    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 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. PMID:27015604

  17. Human and Drosophila cryptochromes are light activated by flavin photoreduction in living cells.

    Directory of Open Access Journals (Sweden)

    Nathalie Hoang

    2008-07-01

    Full Text Available Cryptochromes are a class of flavoprotein blue-light signaling receptors found in plants, animals, and humans that control plant development and the entrainment of circadian rhythms. In plant cryptochromes, light activation is proposed to result from photoreduction of a protein-bound flavin chromophore through intramolecular electron transfer. However, although similar in structure to plant cryptochromes, the light-response mechanism of animal cryptochromes remains entirely unknown. To complicate matters further, there is currently a debate on whether mammalian cryptochromes respond to light at all or are instead activated by non-light-dependent mechanisms. To resolve these questions, we have expressed both human and Drosophila cryptochrome proteins to high levels in living Sf21 insect cells using a baculovirus-derived expression system. Intact cells are irradiated with blue light, and the resulting cryptochrome photoconversion is monitored by fluorescence and electron paramagnetic resonance spectroscopic techniques. We demonstrate that light induces a change in the redox state of flavin bound to the receptor in both human and Drosophila cryptochromes. Photoreduction from oxidized flavin and subsequent accumulation of a semiquinone intermediate signaling state occurs by a conserved mechanism that has been previously identified for plant cryptochromes. These results provide the first evidence of how animal-type cryptochromes are activated by light in living cells. Furthermore, human cryptochrome is also shown to undergo this light response. Therefore, human cryptochromes in exposed peripheral and/or visual tissues may have novel light-sensing roles that remain to be elucidated.

  18. Intra-urban human mobility and activity transition: evidence from social media check-in data.

    Directory of Open Access Journals (Sweden)

    Lun Wu

    Full Text Available Most existing human mobility literature focuses on exterior characteristics of movements but neglects activities, the driving force that underlies human movements. In this research, we combine activity-based analysis with a movement-based approach to model the intra-urban human mobility observed from about 15 million check-in records during a yearlong period in Shanghai, China. The proposed model is activity-based and includes two parts: the transition of travel demands during a specific time period and the movement between locations. For the first part, we find the transition probability between activities varies over time, and then we construct a temporal transition probability matrix to represent the transition probability of travel demands during a time interval. For the second part, we suggest that the travel demands can be divided into two classes, locationally mandatory activity (LMA and locationally stochastic activity (LSA, according to whether the demand is associated with fixed location or not. By judging the combination of predecessor activity type and successor activity type we determine three trip patterns, each associated with a different decay parameter. To validate the model, we adopt the mechanism of an agent-based model and compare the simulated results with the observed pattern from the displacement distance distribution, the spatio-temporal distribution of activities, and the temporal distribution of travel demand transitions. The results show that the simulated patterns fit the observed data well, indicating that these findings open new directions for combining activity-based analysis with a movement-based approach using social media check-in data.

  19. Explosive vocal activity for attracting human attention is related to domestication in silver fox.

    Science.gov (United States)

    Gogoleva, Svetlana S; Volodin, Ilya A; Volodina, Elena V; Kharlamova, Anastasia V; Trut, Lyudmila N

    2011-02-01

    Domestication affects behavioral and vocal responses, involved in communication with humans; in particular, those that attract human attention. In this study, we found that silver foxes of Tame strain, experimentally domesticated for a few tenses of generation, displayed bursts of vocal activity during the first minute after appearance of an unfamiliar human, that faded quickly during the remaining time of the test, when the experimenter stayed passively before the cage. Distinctively, foxes of Aggressive strain, artificially selected for tenses of generation for aggressive behavior toward humans, and the control group of Unselected for behavior silver foxes kept steady levels of vocal activity for the duration of the tests. We found also that Aggressive foxes vocalized for a larger proportion of time than Unselected foxes for all 5 min of the test. We discuss the obtained data in relation to proposal effects of domestication on mechanisms directed to involving people into human-animal interactions and structural similarity between human laughter and vocalization of Tame foxes.

  20. Active site proton delivery and the lyase activity of human CYP17A1

    Energy Technology Data Exchange (ETDEWEB)

    Khatri, Yogan; Gregory, Michael C.; Grinkova, Yelena V.; Denisov, Ilia G.; Sligar, Stephen G., E-mail: s-sligar@illinois.edu

    2014-01-03

    Highlights: •The disruption of PREG/PROG hydroxylation activity by T306A showed the participation of Cpd I. •T306A supports the involvement of a nucleophilic peroxo-anion during lyase activity. •The presence of cytochrome b{sub 5} augments C–C lyase activity. •Δ5-Steroids are preferred substrates for CYP17 catalysis. -- Abstract: Cytochrome P450 CYP17A1 catalyzes a series of reactions that lie at the intersection of corticoid and androgen biosynthesis and thus occupies an essential role in steroid hormone metabolism. This multifunctional enzyme catalyzes the 17α-hydroxylation of Δ4- and Δ5-steroids progesterone and pregnenolone to form the corresponding 17α-hydroxy products through its hydroxylase activity, and a subsequent 17,20-carbon–carbon scission of pregnene-side chain produce the androgens androstenedione (AD) and dehydroepiandrosterone (DHEA). While the former hydroxylation reaction is believed to proceed through a conventional “Compound I” rebound mechanism, it has been suggested that the latter carbon cleavage is initiated by an iron-peroxy intermediate. We report on the role of Thr306 in CYP17 catalysis. Thr306 is a member of the conserved acid/alcohol pair thought to be essential for the efficient delivery of protons required for hydroperoxoanion heterolysis and formation of Compound I in the cytochromes P450. Wild type and T306A CYP17A1 self-assembled in Nanodiscs were used to quantitate turnover and coupling efficiencies of CYP17’s physiological Δ4- and Δ5-substrates. We observed that T306A co-incorporated in Nanodiscs with its redox partner cytochrome P450 oxidoreductase, coupled NADPH only by 0.9% and 0.7% compared to the wild type (97% and 22%) during the conversion of pregnenolone and progesterone, respectively, to the corresponding 17-OH products. Despite increased oxidation of pyridine nucleotide, hydroxylase activity was drastically diminished in the T306A mutant, suggesting a high degree of uncoupling in which reducing