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Sample records for human ether-a-go-go related

  1. Calpain activation by ROS mediates human ether-a-go-go-related gene protein degradation by intermittent hypoxia.

    Science.gov (United States)

    Wang, N; Kang, H S; Ahmmed, G; Khan, S A; Makarenko, V V; Prabhakar, N R; Nanduri, J

    2016-03-01

    Human ether-a-go-go-related gene (hERG) channels conduct delayed rectifier K(+) current. However, little information is available on physiological situations affecting hERG channel protein and function. In the present study we examined the effects of intermittent hypoxia (IH), which is a hallmark manifestation of sleep apnea, on hERG channel protein and function. Experiments were performed on SH-SY5Y neuroblastoma cells, which express hERG protein. Cells were exposed to IH consisting of alternating cycles of 30 s of hypoxia (1.5% O2) and 5 min of 20% O2. IH decreased hERG protein expression in a stimulus-dependent manner. A similar reduction in hERG protein was also seen in adrenal medullary chromaffin cells from IH-exposed neonatal rats. The decreased hERG protein was associated with attenuated hERG K(+) current. IH-evoked hERG protein degradation was not due to reduced transcription or increased proteosome/lysomal degradation. Rather it was mediated by calcium-activated calpain proteases. Both COOH- and NH2-terminal sequences of the hERG protein were the targets of calpain-dependent degradation. IH increased reactive oxygen species (ROS) levels, intracellular Ca(2+) concentration ([Ca(2+)]i), calpain enzyme activity, and hERG protein degradation, and all these effects were prevented by manganese-(111)-tetrakis-(1-methyl-4-pyridyl)-porphyrin pentachloride, a membrane-permeable ROS scavenger. These results demonstrate that activation of calpains by ROS-dependent elevation of [Ca(2+)]i mediates hERG protein degradation by IH. Copyright © 2016 the American Physiological Society.

  2. Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel*

    Science.gov (United States)

    Chen, Jeffery; Guo, Jun; Yang, Tonghua; Li, Wentao; Lamothe, Shawn M.; Kang, Yudi; Szendrey, John A.; Zhang, Shetuan

    2015-01-01

    The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel (IKr). A reduction in the hERG current causes long QT syndrome, which predisposes affected individuals to ventricular arrhythmias and sudden death. We reported previously that hERG channels in the plasma membrane undergo vigorous internalization under low K+ conditions. In the present study, we addressed whether hERG internalization occurs under normal K+ conditions and whether/how internalized channels are recycled back to the plasma membrane. Using patch clamp, Western blot, and confocal imaging analyses, we demonstrated that internalized hERG channels can effectively recycle back to the plasma membrane. Low K+-enhanced hERG internalization is accompanied by an increased rate of hERG recovery in the plasma membrane upon reculture following proteinase K-mediated clearance of cell-surface proteins. The increased recovery rate is not due to enhanced protein synthesis, as hERG mRNA expression was not altered by low K+ exposure, and the increased recovery was observed in the presence of the protein biosynthesis inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling of hERG channels. Interfering with Rab11 function not only delayed hERG recovery in cells after exposure to low K+ medium but also decreased hERG expression and function in cells under normal culture conditions. We concluded that the recycling pathway plays an important role in the homeostasis of plasma membrane-bound hERG channels. PMID:26152716

  3. The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr) and human ether-a-go-go-related gene (hERG) expression.

    Science.gov (United States)

    Teah, Yi Fan; Abduraman, Muhammad Asyraf; Amanah, Azimah; Adenan, Mohd Ilham; Sulaiman, Shaida Fariza; Tan, Mei Lan

    2017-09-01

    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and I kr blocker. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Effect of beta-adrenoceptor blockers on human ether-a-go-go-related gene (HERG) potassium channels

    DEFF Research Database (Denmark)

    Dupuis, Delphine S; Klaerke, Dan A; Olesen, Søren-Peter

    2005-01-01

    Patients with congenital long QT syndrome may develop arrhythmias under conditions of increased sympathetic tone. We have addressed whether some of the beta-adrenoceptor blockers commonly used to prevent the development of these arrhythmias could per se block the cardiac HERG (Human Ether....... These data showed that HERG blockade by beta-adrenoceptor blockers occurred only at high micromolar concentrations, which are significantly above the recently established safe margin of 100 (Redfern et al., 2003).......-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) blocked the HERG channel with similar affinity, whereas the beta1-receptor antagonists metoprolol and atenolol showed weak effects. Further, the four compounds blocked HERG channels expressed in a mammalian HEK293 cell line...

  5. Bag1 Co-chaperone Promotes TRC8 E3 Ligase-dependent Degradation of Misfolded Human Ether a Go-Go-related Gene (hERG) Potassium Channels.

    Science.gov (United States)

    Hantouche, Christine; Williamson, Brittany; Valinsky, William C; Solomon, Joshua; Shrier, Alvin; Young, Jason C

    2017-02-10

    Cardiac long QT syndrome type 2 is caused by mutations in the human ether a go-go-related gene (hERG) potassium channel, many of which cause misfolding and degradation at the endoplasmic reticulum instead of normal trafficking to the cell surface. The Hsc70/Hsp70 chaperones assist the folding of the hERG cytosolic domains. Here, we demonstrate that the Hsp70 nucleotide exchange factor Bag1 promotes hERG degradation by the ubiquitin-proteasome system at the endoplasmic reticulum to regulate hERG levels and channel activity. Dissociation of hERG complexes containing Hsp70 and the E3 ubiquitin ligase CHIP requires the interaction of Bag1 with Hsp70, but this does not involve the Bag1 ubiquitin-like domain. The interaction with Bag1 then shifts hERG degradation to the membrane-anchored E3 ligase TRC8 and its E2-conjugating enzyme Ube2g2, as determined by siRNA screening. TRC8 interacts through the transmembrane region with hERG and decreases hERG functional expression. TRC8 also mediates degradation of the misfolded hERG-G601S disease mutant, but pharmacological stabilization of the mutant structure prevents degradation. Our results identify TRC8 as a previously unknown Hsp70-independent quality control E3 ligase for hERG. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. The human ether-a-go-go-related gene (hERG) current inhibition selectively prolongs action potential of midmyocardial cells to augment transmural dispersion.

    Science.gov (United States)

    Yasuda, C; Yasuda, S; Yamashita, H; Okada, J; Hisada, T; Sugiura, S

    2015-08-01

    The majority of drug induced arrhythmias are related to the prolongation of action potential duration following inhibition of rapidly activating delayed rectifier potassium current (I(Kr)) mediated by the hERG channel. However, for arrhythmias to develop and be sustained, not only the prolongation of action potential duration but also its transmural dispersion are required. Herein, we evaluated the effect of hERG inhibition on transmural dispersion of action potential duration using the action potential clamp technique that combined an in silico myocyte model with the actual I(Kr) measurement. Whole cell I(Kr) current was measured in Chinese hamster ovary cells stably expressing the hERG channel. The measured current was coupled with models of ventricular endocardial, M-, and epicardial cells to calculate the action potentials. Action potentials were evaluated under control condition and in the presence of 1, 10, or 100 μM disopyramide, an hERG inhibitor. Disopyramide dose-dependently increased the action potential durations of the three cell types. However, action potential duration of M-cells increased disproportionately at higher doses, and was significantly different from that of epicardial and endocardial cells (dispersion of repolarization). By contrast, the effects of disopyramide on peak I(Kr) and instantaneous current-voltage relation were similar in all cell types. Simulation study suggested that the reduced repolarization reserve of M-cell with smaller amount of slowly activating delayed rectifier potassium current levels off at longer action potential duration to make such differences. The action potential clamp technique is useful for studying the mechanism of arrhythmogenesis by hERG inhibition through the transmural dispersion of repolarization.

  7. Acute alteration of cardiac ECG, action potential, I{sub Kr} and the human ether-a-go-go-related gene (hERG) K{sup +} channel by PCB 126 and PCB 77

    Energy Technology Data Exchange (ETDEWEB)

    Park, Mi-Hyeong; Park, Won Sun; Jo, Su-Hyun, E-mail: suhyunjo@kangwon.ac.kr

    2012-07-01

    Polychlorinated biphenyls (PCBs) have been known as serious persistent organic pollutants (POPs), causing developmental delays and motor dysfunction. We have investigated the effects of two PCB congeners, 3,3′,4,4′-tetrachlorobiphenyl (PCB 77) and 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) on ECG, action potential, and the rapidly activating delayed rectifier K{sup +} current (I{sub Kr}) of guinea pigs' hearts, and hERG K{sup +} current expressed in Xenopus oocytes. PCB 126 shortened the corrected QT interval (QTc) of ECG and decreased the action potential duration at 90% (APD{sub 90}), and 50% of repolarization (APD{sub 50}) (P < 0.05) without changing the action potential duration at 20% (APD{sub 20}). PCB 77 decreased APD{sub 20} (P < 0.05) without affecting QTc, APD{sub 90}, and APD{sub 50}. The PCB 126 increased the I{sub Kr} in guinea-pig ventricular myocytes held at 36 °C and hERG K{sup +} current amplitude at the end of the voltage steps in voltage-dependent mode (P < 0.05); however, PCB 77 did not change the hERG K{sup +} current amplitude. The PCB 77 increased the diastolic Ca{sup 2+} and decreased Ca{sup 2+} transient amplitude (P < 0.05), however PCB 126 did not change. The results suggest that PCB 126 shortened the QTc and decreased the APD{sub 90} possibly by increasing I{sub Kr}, while PCB 77 decreased the APD{sub 20} possibly by other modulation related with intracellular Ca{sup 2+}. The present data indicate that the environmental toxicants, PCBs, can acutely affect cardiac electrophysiology including ECG, action potential, intracellular Ca{sup 2+}, and channel activity, resulting in toxic effects on the cardiac function in view of the possible accumulation of the PCBs in human body. -- Highlights: ► PCBs are known as serious environmental pollutants and developmental disruptors. ► PCB 126 shortened QT interval of ECG and action potential duration. ► PCB 126 increased human ether-a-go-go-related K{sup +} current and I{sub Kr}.

  8. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Becerra, Rocio [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Diaz, Lorenza, E-mail: lorenzadiaz@gmail.com [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Camacho, Javier [Department of Pharmacology, Centro de Investigacion y de Estudios Avanzados, Instituto Politecnico Nacional, Av. Instituto Politecnico Nacional 2508, San Pedro Zacatenco 07360, Mexico, D.F. (Mexico); Barrera, David; Ordaz-Rosado, David; Morales, Angelica [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Ortiz, Cindy Sharon [Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Avila, Euclides [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico); Bargallo, Enrique [Department of Breast Tumors, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Arrecillas, Myrna [Department of Pathology, Instituto Nacional de Cancerologia, Av. San Fernando No. 22, Tlalpan 14080, Mexico, D.F. (Mexico); Halhali, Ali; Larrea, Fernando [Department of Reproductive Biology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, Tlalpan 14000 Mexico, D.F. (Mexico)

    2010-02-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  9. Calcitriol inhibits Ether-a go-go potassium channel expression and cell proliferation in human breast cancer cells

    International Nuclear Information System (INIS)

    Garcia-Becerra, Rocio; Diaz, Lorenza; Camacho, Javier; Barrera, David; Ordaz-Rosado, David; Morales, Angelica; Ortiz, Cindy Sharon; Avila, Euclides; Bargallo, Enrique; Arrecillas, Myrna; Halhali, Ali; Larrea, Fernando

    2010-01-01

    Antiproliferative actions of calcitriol have been shown to occur in many cell types; however, little is known regarding the molecular basis of this process in breast carcinoma. Ether-a-go-go (Eag1) potassium channels promote oncogenesis and are implicated in breast cancer cell proliferation. Since calcitriol displays antineoplastic effects while Eag1 promotes tumorigenesis, and both factors antagonically regulate cell cycle progression, we investigated a possible regulatory effect of calcitriol upon Eag1 as a mean to uncover new molecular events involved in the antiproliferative activity of this hormone in human breast tumor-derived cells. RT real-time PCR and immunocytochemistry showed that calcitriol suppressed Eag1 expression by a vitamin D receptor (VDR)-dependent mechanism. This effect was accompanied by inhibition of cell proliferation, which was potentiated by astemizole, a nonspecific Eag1 inhibitor. Immunohistochemistry and Western blot demonstrated that Eag1 and VDR abundance was higher in invasive-ductal carcinoma than in fibroadenoma, and immunoreactivity of both proteins was located in ductal epithelial cells. Our results provide evidence of a novel mechanism involved in the antiproliferative effects of calcitriol and highlight VDR as a cancer therapeutic target for breast cancer treatment and prevention.

  10. Mechanism of action of a novel human ether-a-go-go-related gene channel activator

    DEFF Research Database (Denmark)

    Casis, Oscar; Olesen, Søren-Peter; Sanguinetti, Michael C

    2005-01-01

    depolarizations, NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. The fully activated current-voltage relationship revealed that the drug increased outward but not inward currents, consistent with altered inactivation...

  11. Improved functional expression of recombinant human ether-a-go-go (hERG K+ channels by cultivation at reduced temperature

    Directory of Open Access Journals (Sweden)

    Hamilton Bruce

    2007-12-01

    Full Text Available Abstract Background HERG potassium channel blockade is the major cause for drug-induced long QT syndrome, which sometimes cause cardiac disrhythmias and sudden death. There is a strong interest in the pharmaceutical industry to develop high quality medium to high-throughput assays for detecting compounds with potential cardiac liability at the earliest stages of drug development. Cultivation of cells at lower temperature has been used to improve the folding and membrane localization of trafficking defective hERG mutant proteins. The objective of this study was to investigate the effect of lower temperature maintenance on wild type hERG expression and assay performance. Results Wild type hERG was stably expressed in CHO-K1 cells, with the majority of channel protein being located in the cytoplasm, but relatively little on the cell surface. Expression at both locations was increased several-fold by cultivation at lower growth temperatures. Intracellular hERG protein levels were highest at 27°C and this correlated with maximal 3H-dofetilide binding activity. In contrast, the expression of functionally active cell surface-associated hERG measured by patch clamp electrophysiology was optimal at 30°C. The majority of the cytoplasmic hERG protein was associated with the membranes of cytoplasmic vesicles, which markedly increased in quantity and size at lower temperatures or in the presence of the Ca2+-ATPase inhibitor, thapsigargin. Incubation with the endocytic trafficking blocker, nocodazole, led to an increase in hERG activity at 37°C, but not at 30°C. Conclusion Our results are consistent with the concept that maintenance of cells at reduced temperature can be used to boost the functional expression of difficult-to-express membrane proteins and improve the quality of assays for medium to high-throughput compound screening. In addition, these results shed some light on the trafficking of hERG protein under these growth conditions.

  12. Local anesthetic interaction with human ether-a-go-go-related gene (HERG) channels: role of aromatic amino acids Y652 and F656

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Schmitt, Nicole; Friederich, Patrick

    2005-01-01

    was to determine the effect of the mutations Y652A and F656A in the putative drug binding region of HERG on the inhibition by bupivacaine, ropivacaine, and mepivacaine. METHODS: The authors examined the inhibition of wild-type and mutant HERG channels, transiently expressed in Chinese hamster ovary cells...... by bupivacaine, ropivacaine, and mepivacaine. Whole cell patch clamp recordings were performed at room temperature. RESULTS: Inhibition of HERG wild-type and mutant channels by the different local anesthetics was concentration dependent, stereoselective, and reversible. The sensitivity decreased in the order...... bupivacaine > ropivacaine > mepivacaine for wild-type and mutant channels. The mutant channels were approximately 4-30 times less sensitive to the inhibitory action of the different local anesthetics than the wild-type channel. The concentration-response data were described by Hill functions (bupivacaine...

  13. Activation of human ether-a-go-go-related gene potassium channels by the diphenylurea 1,3-bis-(2-hydroxy-5-trifluoromethyl-phenyl)-urea (NS1643)

    DEFF Research Database (Denmark)

    Hansen, Rie Schultz; Diness, Thomas Goldin; Christ, Torsten

    2005-01-01

    The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased repolari......The cardiac action potential is generated by a concerted action of different ion channels and transporters. Dysfunction of any of these membrane proteins can give rise to cardiac arrhythmias, which is particularly true for the repolarizing potassium channels. We suggest that an increased......M. Application of NS1643 also resulted in a prolonged postrepolarization refractory time. Finally, cardiomyocytes exposed to NS1643 resisted reactivation by small depolarizing currents mimicking early afterdepolarizations. In conclusion, HERG channel activation by small molecules such as NS1643 increases...

  14. PK/PD Modelling of the QT Interval: a Step Towards Defining the Translational Relationship Between In Vitro, Awake Beagle Dogs, and Humans.

    Science.gov (United States)

    Marostica, Eleonora; Van Ammel, Karel; Teisman, Ard; Gallacher, David; Van Bocxlaer, Jan; De Ridder, Filip; Boussery, Koen; Vermeulen, An

    2016-07-01

    Inhibiting the human ether-a-go-go-related gene (hERG)-encoded potassium ion channel is positively correlated with QT-interval prolongation in vivo, which is considered a risk factor for the occurrence of Torsades de Pointes (TdP). A pharmacokinetic/pharmacodynamic model was developed for four compounds that reached the clinic, to relate drug-induced QT-interval change in awake dogs and humans and to derive a translational scaling factor a 1. Overall, dogs were more sensitive than humans to QT-interval change, an a 1 of 1.5 was found, and a 10% current inhibition in vitro produced a higher percent QT-interval change in dogs as compared to humans. The QT-interval changes in dogs were predictive for humans. In vitro and in vivo information could reliably describe the effects in humans. Robust translational knowledge is likely to reduce the need for expensive thorough QT studies; therefore, expanding this work to more compounds is recommended.

  15. Predictive lethal proarrhythmic risk evaluation using a closed-loop-circuit cell network with human induced pluripotent stem cells derived cardiomyocytes

    Science.gov (United States)

    Nomura, Fumimasa; Hattori, Akihiro; Terazono, Hideyuki; Kim, Hyonchol; Odaka, Masao; Sugio, Yoshihiro; Yasuda, Kenji

    2016-06-01

    For the prediction of lethal arrhythmia occurrence caused by abnormality of cell-to-cell conduction, we have developed a next-generation in vitro cell-to-cell conduction assay, i.e., a quasi in vivo assay, in which the change in spatial cell-to-cell conduction is quantitatively evaluated from the change in waveforms of the convoluted electrophysiological signals from lined-up cardiomyocytes on a single closed loop of a microelectrode of 1 mm diameter and 20 µm width in a cultivation chip. To evaluate the importance of the closed-loop arrangement of cardiomyocytes for prediction, we compared the change in waveforms of convoluted signals of the responses in the closed-loop circuit arrangement with that of the response of cardiomyocyte clusters using a typical human ether a go-go related gene (hERG) ion channel blocker, E-4031. The results showed that (1) waveform prolongation and fluctuation both in the closed loops and clusters increased depending on the E-4031 concentration increase. However, (2) only the waveform signals in closed loops showed an apparent temporal change in waveforms from ventricular tachycardia (VT) to ventricular fibrillation (VF), which is similar to the most typical cell-to-cell conductance abnormality. The results indicated the usefulness of convoluted waveform signals of a closed-loop cell network for acquiring reproducible results acquisition and more detailed temporal information on cell-to-cell conduction.

  16. In Silico Predictions of hERG Channel Blockers in Drug Discovery

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Sørensen, Flemming Steen

    2011-01-01

    The risk for cardiotoxic side effects represents a major problem in clinical studies of drug candidates and regulatory agencies have explicitly recommended that all new drug candidates should be tested for blockage of the human Ether-a-go-go Related-Gene (hERG) potassium channel. Indeed, several ...

  17. Long QT 1 mutation KCNQ1A344V increases local anesthetic sensitivity of the slowly activating delayed rectifier potassium current

    DEFF Research Database (Denmark)

    Siebrands, Cornelia C; Binder, Stephan; Eckhoff, Ulrike

    2006-01-01

    BACKGROUND: Anesthesia in patients with long QT syndrome (LQTS) is a matter of concern. Congenital LQTS is most frequently caused by mutations in KCNQ1 (Kv7.1), whereas drug-induced LQTS is a consequence of HERG (human ether-a-go-go-related gene) channel inhibition. The aim of this study was to i...

  18. Validation of visualized transgenic zebrafish as a high throughput model to assay bradycardia related cardio toxicity risk candidates.

    Science.gov (United States)

    Wen, Dingsheng; Liu, Aiming; Chen, Feng; Yang, Julin; Dai, Renke

    2012-10-01

    Drug-induced QT prolongation usually leads to torsade de pointes (TdP), thus for drugs in the early phase of development this risk should be evaluated. In the present study, we demonstrated a visualized transgenic zebrafish as an in vivo high-throughput model to assay the risk of drug-induced QT prolongation. Zebrafish larvae 48 h post-fertilization expressing green fluorescent protein in myocardium were incubated with compounds reported to induce QT prolongation or block the human ether-a-go-go-related gene (hERG) K⁺ current. The compounds sotalol, indapaminde, erythromycin, ofoxacin, levofloxacin, sparfloxacin and roxithromycin were additionally administrated by microinjection into the larvae yolk sac. The ventricle heart rate was recorded using the automatic monitoring system after incubation or microinjection. As a result, 14 out of 16 compounds inducing dog QT prolongation caused bradycardia in zebrafish. A similar result was observed with 21 out of 26 compounds which block hERG current. Among the 30 compounds which induced human QT prolongation, 25 caused bradycardia in this model. Thus, the risk of compounds causing bradycardia in this transgenic zebrafish correlated with that causing QT prolongation and hERG K⁺ current blockage in established models. The tendency that high logP values lead to high risk of QT prolongation in this model was indicated, and non-sensitivity of this model to antibacterial agents was revealed. These data suggest application of this transgenic zebrafish as a high-throughput model to screen QT prolongation-related cardio toxicity of the drug candidates. Copyright © 2012 John Wiley & Sons, Ltd.

  19. Synthesis and biological evaluation of pyrrolidine derivatives as novel and potent sodium channel blockers for the treatment of ischemic stroke.

    Science.gov (United States)

    Seki, Maki; Tsuruta, Osamu; Tatsumi, Ryo; Soejima, Aki

    2013-07-15

    A novel series of pyrrolidine derivatives as Na(+) channel blockers was synthesized and evaluated for their inhibitory effects on neuronal Na(+) channels. Structure-activity relationship (SAR) studies of a pyrrolidine analogue 2 led to the discovery of 5e as a potent Na(+) channel blocker with a low inhibitory action against human ether-a-go-go-related gene (hERG) channels. Compound 5e showed remarkably neuroprotective activity in a rat transient middle cerebral artery occlusion (MCAO) model, suggesting that 5e would act as a neuroprotectant for ischemic stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. New binding site on common molecular scaffold provides HERG channel specificity of scorpion toxin BeKm-1

    DEFF Research Database (Denmark)

    Korolkova, Yuliya V; Bocharov, Eduard V; Angelo, Kamilla

    2002-01-01

    The scorpion toxin BeKm-1 is unique among a variety of known short scorpion toxins affecting potassium channels in its selective action on ether-a-go-go-related gene (ERG)-type channels. BeKm-1 shares the common molecular scaffold with other short scorpion toxins. The toxin spatial structure...... resolved by NMR consists of a short alpha-helix and a triple-stranded antiparallel beta-sheet. By toxin mutagenesis study we identified the residues that are important for the binding of BeKm-1 to the human ERG K+ (HERG) channel. The most critical residues (Tyr-11, Lys-18, Arg-20, Lys-23) are located...

  1. The discovery of tropane-derived CCR5 receptor antagonists.

    Science.gov (United States)

    Armour, Duncan R; de Groot, Marcel J; Price, David A; Stammen, Blanda L C; Wood, Anthony; Perros, Manos; Burt, Catherine

    2006-04-01

    The development of compound 1, a piperidine-based CCR5 receptor antagonist with Type I CYP2D6 inhibition, into the tropane-derived analogue 5, is described. This compound, which is devoid of CYP2D6 liabilities, is a highly potent ligand for the CCR5 receptor and has broad-spectrum activity against a range of clinically relevant HIV isolates. The identification of human ether a-go-go-related gene channel inhibition within this series is described and the potential for QTc interval prolongation discussed. Furthermore, structure activity relationship (SAR) around the piperidine moiety is also described.

  2. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    , men også arbejdssociologien, arbejdspsykologien og human resource development. Den første retning udsprang af de såkaldte Hawthorne-eksperimenter og psykologen Elton Mayos bearbejdelse af resultaterne derfra. Den anden er en løsere gruppering bestående af navne som Abraham Maslow og Frederick Herzberg...

  3. Human Relations Class. A Syllabus.

    Science.gov (United States)

    Guillen, Mary A.

    A junior high level human relations class develops human interaction and oral communication skills. A week-by-week syllabus contains the following components: introduction of the students to each other and to the principles of body language, transactional analysis, and group interaction; behavior contracts; group dynamics topics and exercises;…

  4. [Projective identification in human relations].

    Science.gov (United States)

    Göka, Erol; Yüksel, Fatih Volkan; Göral, F Sevinç

    2006-01-01

    Melanie Klein, one of the pioneers of Object Relations Theory, first defined "projective identification", which is regarded as one of the most efficacious psychoanalytic concepts after the discovery of the "unconscious". Examination of the literature on "projective identification" shows that there are various perspectives and theories suggesting different uses of this concept. Some clinicians argue that projective identification is a primitive defense mechanism observed in severe psychopathologies like psychotic disorder and borderline personality disorder, where the intra-psychic structure has been damaged severely. Others suggest it to be an indispensable part of the transference and counter-transference between the therapist and the patient during psychotherapy and it can be used as a treatment material in the therapy by a skillful therapist. The latter group expands the use of the concept through normal daily relationships by stating that projective identification is one type of communication and part of the main human relation mechanism operating in all close relationships. Therefore, they suggest that projective identification has benign forms experienced in human relations as well as malign forms seen in psychopathologies. Thus, discussions about the definition of the concept appear complex. In order to clarify and overcome the complexity of the concept, Melanie Klein's and other most important subsequent approaches are discussed in this review article. Thereby, the article aims to explain its important function in understanding the psychopathologies, psychotherapeutic relationships and different areas of normal human relations.

  5. Data on the construction of a recombinant HEK293 cell line overexpressing hERG potassium channel and examining the presence of hERG mRNA and protein expression

    Directory of Open Access Journals (Sweden)

    Yi Fan Teah

    2017-10-01

    Full Text Available The data presented in this article are related to the research article entitled “The effects of deoxyelephantopin on the cardiac delayed rectifier potassium channel current (IKr and human ether-a-go-go-related gene (hERG expression” (Y.F. Teah, M.A. Abduraman, A. Amanah, M.I. Adenan, S.F. Sulaiman, M.L. Tan [1], which the possible hERG blocking properties of deoxyelephantopin were investigated. This article describes the construction of human embryonic kidney 293 (HEK293 cells overexpressing HERG potassium channel and verification of the presence of hERG mRNA and protein expression in this recombinant cell line.

  6. Molecular Basis of Cardiac Delayed Rectifier Potassium Channel Function and Pharmacology.

    Science.gov (United States)

    Wu, Wei; Sanguinetti, Michael C

    2016-06-01

    Human cardiomyocytes express 3 distinct types of delayed rectifier potassium channels. Human ether-a-go-go-related gene (hERG) channels conduct the rapidly activating current IKr; KCNQ1/KCNE1 channels conduct the slowly activating current IKs; and Kv1.5 channels conduct an ultrarapid activating current IKur. Here the authors provide a general overview of the mechanistic and structural basis of ion selectivity, gating, and pharmacology of the 3 types of cardiac delayed rectifier potassium ion channels. Most blockers bind to S6 residues that line the central cavity of the channel, whereas activators interact with the channel at 4 symmetric binding sites outside the cavity. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Towards a Structural View of Drug Binding to hERG K+ Channels.

    Science.gov (United States)

    Vandenberg, Jamie I; Perozo, Eduardo; Allen, Toby W

    2017-10-01

    The human ether-a-go-go-related gene (hERG) K + channel is of great medical and pharmaceutical relevance. Inherited mutations in hERG result in congenital long-QT syndrome which is associated with a markedly increased risk of cardiac arrhythmia and sudden death. hERG K + channels are also remarkably susceptible to block by a wide range of drugs, which in turn can cause drug-induced long-QT syndrome and an increased risk of sudden death. The recent determination of the near-atomic resolution structure of the hERG K + channel, using single-particle cryo-electron microscopy (cryo-EM), provides tremendous insights into how these channels work. It also suggests a way forward in our quest to understand why these channels are so promiscuous with respect to drug binding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Verapamil for cluster headache. Clinical pharmacology and possible mode of action

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Tfelt-Hansen, Jacob

    2009-01-01

    is therefore limited. The clinical use of verapamil in cluster headache is reviewed and several relevant drug interactions are mentioned. Finally, its possible mode of action in cluster headache is discussed. The effect of verapamil in cluster headache most likely takes place in the hypothalamus......Verapamil is used mainly in cardiovascular diseases. High-dose verapamil (360-720 mg) is, however, currently the mainstay in the prophylactic treatment of cluster headache. The oral pharmacokinetics are variable. The pharmacodynamic effect of verapamil, the effect on blood pressure, also varies.......Verapamil is an L-type calcium channel blocker but it is also a blocker of other calcium channels (T-, P-, and possibly N- and Q-type Ca(2+) channels) and the human ether-a-go-go-related gene potassium channel. With so many different actions of verapamil, it is impossible at the present time to single out a certain...

  9. Design, synthesis, and evaluation of 4,6-diaminonicotinamide derivatives as novel and potent immunomodulators targeting JAK3.

    Science.gov (United States)

    Nakajima, Yutaka; Aoyama, Naohiro; Takahashi, Fumie; Sasaki, Hiroshi; Hatanaka, Keiko; Moritomo, Ayako; Inami, Masamichi; Ito, Misato; Nakamura, Koji; Nakamori, Fumihiro; Inoue, Takayuki; Shirakami, Shohei

    2016-10-01

    In organ transplantation, T cell-mediated immune responses play a key role in the rejection of allografts. Janus kinase 3 (JAK3) is specifically expressed in hematopoietic cells and associated with regulation of T cell development via interleukin-2 signaling pathway. Here, we designed novel 4,6-diaminonicotinamide derivatives as immunomodulators targeting JAK3 for prevention of transplant rejection. Our optimization of C4- and C6-substituents and docking calculations to JAK3 protein confirmed that the 4,6-diaminonicotinamide scaffold resulted in potent inhibition of JAK3. We also investigated avoidance of human ether-a-go-go related gene (hERG) inhibitory activity. Selected compound 28 in combination with tacrolimus prevented allograft rejection in a rat heterotopic cardiac transplantation model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. NGO Duties in Relation to Human Rights

    NARCIS (Netherlands)

    Philips, J.P.M.|info:eu-repo/dai/nl/298979446

    2010-01-01

    This paper investigates the moral duties that human rights NGOs, such as Amnesty International, and development NGOs, such as Oxfam, have in relation to human rights – especially in relation to the human right to a decent standard of living. The mentioned NGOs are powerful new agents on the global

  11. Human relations in SMEs from Arequipa

    Directory of Open Access Journals (Sweden)

    Walter Lizandro Arias Gallegos

    2014-02-01

    Full Text Available The present research settles as aim, to determine the kind of human relations which prevail in small and medium enterprises (SMEs at Paucarpata district from Arequipa City. In order to, we use the Human Relations Questionnaire with acceptable levels of validity and reliability (α = 0,648 and discriminate between four types of human relations: unsecure, collaborative, selfish and hostile. The results point that predominant human relations in SMEs are the hostile type, and make us to suppose that work conditions don’t benefit employees and could even have negative consequences in their job performance and welfare.

  12. HUMAN RELATIONS LABORATORY TRAINING STUDENT NOTEBOOK.

    Science.gov (United States)

    Springport High School, MI.

    THE MAJOR OBJECTIVE OF THIS NOTEBOOK IS TO HELP THOSE STUDENTS INTERESTED IN TAKING PART IN THE SPRINGPORT HIGH SCHOOL HUMAN RELATIONS TRAINING LABORATORIES TO BETTER UNDERSTAND THEMSELVES, SOCIETY, AND HUMAN EMOTIONS SO THAT THEY MAY DEVELOP SOCIALLY AND EMOTIONALLY. THE SUBJECT MATTER OF THE NOTEBOOK IS DIVIDED INTO FOUR MAJOR AREAS--(1)…

  13. Journal of Religion and Human Relations

    African Journals Online (AJOL)

    The Journal of Religion and Human Relations (JORAHR) is an academic journal with focus ... The impact of philosophy in the interpretation of African values with particular ... Judeo - Igbo traditional religious conception of sin: socio – religious ...

  14. Design strategies for human relations in services

    NARCIS (Netherlands)

    Snelders, H.M.J.J.; Perik, E.M.; Secomandi, F.

    2014-01-01

    This paper investigates the degree of control that designers might have over human relations in services. For this purpose, a number of speculative service designs were devised to address work-related stress. We focus on three of the generated designs, where design interventions have made changes to

  15. Group & Intergroup Relations in Living Human Systems.

    Science.gov (United States)

    1980-06-01

    organizational diagnosis , the group is itself a living human system. A group may be underbounded, overbounded, or optimally bounded. The state of group...very im- portant to understand and to use in order to conduct organizational diagnosis " using group methods. 2 -43 (Alderfer, 1977b). The group...Boundary Relations and Organizational Diagnosis . In H. Meltzer and F.W. Wickert (eds.) Humanizing Organizational Behavior. Springfield, Illinois: Thomas

  16. Human dignity: intrinsic or relative value?

    Science.gov (United States)

    Thiel, Marie-Jo

    2010-09-01

    Is human dignity an intrinsic value? Or is it a relative value, depending on the perception or assessment of quality of life? History had delineated some of its key features, but the advent of human rights and the Holocaust put special emphasis on this notion, particularly in the field of bioethics. But if modern medicine regards human dignity as crucial, it tends to support this notion while assessing and measuring it. The quality of life becomes the gauge for measuring human dignity, starting from a distinction between a viable and a non-viable existence, which may eventually lead to assisted death, or to letting die. This article argues that the concept of quality of life is of great relevant for medical practice, but on the condition of not being used as a standard to measure the dignity of the individual. Rather, the quality of life should be regarded as an imperative posed by human dignity, which is necessarily intrinsic. If the quality of life measures dignity, humankind is divided into two categories: lives worthy of living, and lives unworthy of living, and society becomes a jungle. Raising the quality of life as a requirement of the inherent human dignity does not solve automatically all problems and does not eliminate a feeling of unworthiness. But it ensures its 'human' value: the equal respect for every human being.

  17. Human errors related to maintenance and modifications

    International Nuclear Information System (INIS)

    Laakso, K.; Pyy, P.; Reiman, L.

    1998-01-01

    The focus in human reliability analysis (HRA) relating to nuclear power plants has traditionally been on human performance in disturbance conditions. On the other hand, some studies and incidents have shown that also maintenance errors, which have taken place earlier in plant history, may have an impact on the severity of a disturbance, e.g. if they disable safety related equipment. Especially common cause and other dependent failures of safety systems may significantly contribute to the core damage risk. The first aim of the study was to identify and give examples of multiple human errors which have penetrated the various error detection and inspection processes of plant safety barriers. Another objective was to generate numerical safety indicators to describe and forecast the effectiveness of maintenance. A more general objective was to identify needs for further development of maintenance quality and planning. In the first phase of this operational experience feedback analysis, human errors recognisable in connection with maintenance were looked for by reviewing about 4400 failure and repair reports and some special reports which cover two nuclear power plant units on the same site during 1992-94. A special effort was made to study dependent human errors since they are generally the most serious ones. An in-depth root cause analysis was made for 14 dependent errors by interviewing plant maintenance foremen and by thoroughly analysing the errors. A more simple treatment was given to maintenance-related single errors. The results were shown as a distribution of errors among operating states i.a. as regards the following matters: in what operational state the errors were committed and detected; in what operational and working condition the errors were detected, and what component and error type they were related to. These results were presented separately for single and dependent maintenance-related errors. As regards dependent errors, observations were also made

  18. Human Rights in Sino-American Relations

    National Research Council Canada - National Science Library

    Day, Jana

    2002-01-01

    .... Key among these has been human rights, which both countries view differently. Whereas the United States emphasizes individual civil and political liberties, the People's Republic of China (PRC...

  19. Logical Relation of Human Rights and Religion

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Talebi

    2013-04-01

    Full Text Available Before establishing any kind of rights for human being, the man should be first known. The best approach to know human being is to utilize the knowledge and teachings that God has given us as the Creator of man. He knows better than anyone else the man whom He has created. This article tries to show that the Man who has (human rights is not that human being as we are used to know him by popular experimental view, but is an existent that is constantly moving on the path of absolute perfection with the aim of achieving the status of the perfect man. To prove this, at this writing, first the concept of right has been studied with an epistemological and ontological look, and look then the concepts of human and religion will be considered.and investigated. Finally, different kinds of the rights of right owners, which one of these rights is human rights, are discussed. Human rights are those rights that belong to every individual because he/she is a human being. -free framework, which has constituted the basis of mainstream conceptions of Universal Declaration of Human Rights. Criticizing the deontological view, this article defends the teleological approach toward the universality of human rights, based on contemporary philosophical hermeneutics specially Paul Ricoeur’s outlook. I argue that this approach can provide the philosophical requirements for interaction between the universality of human rights on one hand and the cultural and local contents of various societies on the other hand and offers a “thick” conception of human rights principles. قبل از اثبات هر نوع حق برای بشر باید ابتدا بشر را شناخت. بهترین شیوه شناسایی بشر استفاده از معارفی است که خدای متعال به عنوان خالق بشر در اختیار ما قرار داده است. او بهتر از هرکس بشری را که ساخته است می‌شناسد. این مقاله درصدد

  20. Human Metabolism and Interactions of Deployment-Related Chemicals

    National Research Council Canada - National Science Library

    Hodgson, Ernest

    2003-01-01

    This study examines the human-metabolism and metabolic interactions of a subset of deployment-related chemicals, including chlorpyrifos, DEET, permethrin, pyridostigmine bromide, and sulfur mustard metabolites...

  1. Human Immunodeficiency Virus Related Knowledge, Risk ...

    African Journals Online (AJOL)

    There was poor HIV preventive practices; indicating ... Gyawali, et al.: HIV related knowledge, risk perception and practices among married women. Annals of Medical .... of this study correspond to the Indian, Nigerian and Iranian studies cited ...

  2. Cyborg intentionality : rethinking the phenomenology of human- technology relations

    NARCIS (Netherlands)

    Verbeek, Peter P.C.C.

    2008-01-01

    This article investigates the types of intentionality involved in human-technology relations. It aims to augment Don Ihde's analysis of the relations between human beings and technological artifacts, by analyzing a number of concrete examples at the limits of Ihde's analysis. The article

  3. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Science.gov (United States)

    Yan, Meng; Zhang, Kaiping; Shi, Yanhui; Feng, Lifang; Lv, Lin; Li, Baoxin

    2015-01-01

    Berberine (BBR), an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG) potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293) cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652) and phenylalanine (Phe656) in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. PMID:26543354

  4. Caco-2 Permeability Studies and In Vitro hERG Liability Assessment of Tryptanthrin and Indolinone.

    Science.gov (United States)

    Jähne, Evelyn A; Eigenmann, Daniela E; Moradi-Afrapoli, Fahimeh; Verjee, Sheela; Butterweck, Veronika; Hebeisen, Simon; Hettich, Timm; Schlotterbeck, Götz; Smieško, Martin; Hamburger, Matthias; Oufir, Mouhssin

    2016-08-01

    Tryptanthrin and (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolinone (indolinone) were recently isolated from Isatis tinctoria as potent anti-inflammatory and antiallergic alkaloids, and shown to inhibit COX-2, 5-LOX catalyzed leukotriene synthesis, and mast cell degranulation at low µM to nM concentrations. To assess their suitability for oral administration, we screened the compounds in an in vitro intestinal permeability assay using human colonic adenocarcinoma cells. For exact quantification of the compounds, validated UPLC-MS/MS methods were used. Tryptanthrin displayed high permeability (apparent permeability coefficient > 32.0 × 10(-6) cm/s) across the cell monolayer. The efflux ratio below 2 ( 10 µM) and indolinone (IC50 of 24.96 µM). The analysis of compounds using various in silico methods confirmed favorable pharmacokinetic properties, as well as a slight inhibition of the human ether-a-go-go-related gene potassium channel at micromolar concentrations. Georg Thieme Verlag KG Stuttgart · New York.

  5. Micro- and nanofabrication methods for ion channel reconstitution in bilayer lipid membranes

    Science.gov (United States)

    Tadaki, Daisuke; Yamaura, Daichi; Arata, Kohei; Ohori, Takeshi; Ma, Teng; Yamamoto, Hideaki; Niwano, Michio; Hirano-Iwata, Ayumi

    2018-03-01

    The self-assembled bilayer lipid membrane (BLM) forms the basic structure of the cell membrane and serves as a major barrier against ion movement. Ion channel proteins function as gated pores that permit ion permeation across the BLM. The reconstitution of ion channel proteins in artificially formed BLMs represents a well-defined system for investigating channel functions and screening drug effects on ion channels. In this review, we will discuss our recent microfabrication approaches to the formation of stable BLMs containing ion channel proteins as a potential platform for next-generation drug screening systems. BLMs formed in a microaperture having a tapered edge exhibited highly stable properties, such as a lifetime of ∼65 h and tolerance to solution changes even after the incorporation of the human ether-a-go-go-related gene (hERG) channel. We also explore a new method of efficiently incorporating human ion channels into BLMs by centrifugation. Our approaches to the formation of stable BLMs and efficient channel incorporation markedly improve the experimental efficiency of BLM reconstitution systems, leading to the realization of a BLM-based high-throughput platform for functional assays of various ion channels.

  6. [Ethics and laws related to human subject research].

    Science.gov (United States)

    Chiu, Hui-Ju; Lee, Ya-Ling; Chang, Su-Fen

    2011-10-01

    Advances in medical technology rely on human subject research to test the effects on real patients of unproven new drugs, equipment and techniques. Illegal human subject research happens occasionally and has led to subject injury and medical disputes. Familiarity with the laws and established ethics related to human subject research can minimize both injury and disputes. History is a mirror that permits reflection today on past experience. Discussing the Nuremberg Code, the Declaration of Helsinki and Belmont Report, this article describes the laws, ethics, history and news related to human subject research as well as the current definition and characteristics of human subject research. Increasing numbers of nurses serve as research nurses and participate in human subject research. The authors hope this article can increase research nurse knowledge regarding laws and ethics in order to protect human research subjects adequately.

  7. Role of the activation gate in determining the extracellular potassium dependency of block of HERG by trapped drugs.

    Science.gov (United States)

    Pareja, Kristeen; Chu, Elaine; Dodyk, Katrina; Richter, Kristofer; Miller, Alan

    2013-01-01

    Drug induced long QT syndrome (diLQTS) results primarily from block of the cardiac potassium channel HERG (human-ether-a-go-go related gene). In some cases long QT syndrome can result in the lethal arrhythmia torsade de pointes, an arrhythmia characterized by a rapid heart rate and severely compromised cardiac output. Many patients requiring medication present with serum potassium abnormalities due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, and aging. Extracellular potassium influences HERG channel inactivation and can alter block of HERG by some drugs. However, block of HERG by a number of drugs is not sensitive to extracellular potassium. In this study, we show that block of WT HERG by bepridil and terfenadine, two drugs previously shown to be trapped inside the HERG channel after the channel closes, is insensitive to extracellular potassium over the range of 0 mM to 20 mM. We also show that bepridil block of the HERG mutant D540K, a mutant channel that is unable to trap drugs, is dependent on extracellular potassium, correlates with the permeant ion, and is independent of HERG inactivation. These results suggest that the lack of extracellular potassium dependency of block of HERG by some drugs may in part be related to the ability of these drugs to be trapped inside the channel after the channel closes.

  8. Modeling of the hERG K+ Channel Blockage Using Online Chemical Database and Modeling Environment (OCHEM).

    Science.gov (United States)

    Li, Xiao; Zhang, Yuan; Li, Huanhuan; Zhao, Yong

    2017-12-01

    Human ether-a-go-go related gene (hERG) K+ channel plays an important role in cardiac action potential. Blockage of hERG channel may result in long QT syndrome (LQTS), even cause sudden cardiac death. Many drugs have been withdrawn from the market because of the serious hERG-related cardiotoxicity. Therefore, it is quite essential to estimate the chemical blockage of hERG in the early stage of drug discovery. In this study, a diverse set of 3721 compounds with hERG inhibition data was assembled from literature. Then, we make full use of the Online Chemical Modeling Environment (OCHEM), which supplies rich machine learning methods and descriptor sets, to build a series of classification models for hERG blockage. We also generated two consensus models based on the top-performing individual models. The consensus models performed much better than the individual models both on 5-fold cross validation and external validation. Especially, consensus model II yielded the prediction accuracy of 89.5 % and MCC of 0.670 on external validation. This result indicated that the predictive power of consensus model II should be stronger than most of the previously reported models. The 17 top-performing individual models and the consensus models and the data sets used for model development are available at https://ochem.eu/article/103592. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Fluoroethoxy-1,4-diphenethylpiperidine and piperazine derivatives: Potent and selective inhibitors of [3H]dopamine uptake at the vesicular monoamine transporter-2.

    Science.gov (United States)

    Hankosky, Emily R; Joolakanti, Shyam R; Nickell, Justin R; Janganati, Venumadhav; Dwoskin, Linda P; Crooks, Peter A

    2017-12-15

    A small library of fluoroethoxy-1,4-diphenethyl piperidine and fluoroethoxy-1,4-diphenethyl piperazine derivatives were designed, synthesized and evaluated for their ability to inhibit [ 3 H]dopamine (DA) uptake at the vesicular monoamine transporter-2 (VMAT2) and dopamine transporter (DAT), [ 3 H]serotonin (5-HT) uptake at the serotonin transporter (SERT), and [ 3 H]dofetilide binding at the human-ether-a-go-go-related gene (hERG) channel. The majority of the compounds exhibited potent inhibition of [ 3 H]DA uptake at VMAT2, Ki changes in the nanomolar range (K i  = 0.014-0.073 µM). Compound 15d exhibited the highest affinity (K i  = 0.014 µM) at VMAT2, and had 160-, 5-, and 60-fold greater selectivity for VMAT2 vs. DAT, SERT and hERG, respectively. Compound 15b exhibited the greatest selectivity (>60-fold) for VMAT2 relative to all the other targets evaluated, and 15b had high affinity for VMAT2 (K i  = 0.073 µM). Compound 15b was considered the lead compound from this analog series due to its high affinity and selectivity for VMAT2. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. The N-terminal tail of hERG contains an amphipathic α-helix that regulates channel deactivation.

    Directory of Open Access Journals (Sweden)

    Chai Ann Ng

    Full Text Available The cytoplasmic N-terminal domain of the human ether-a-go-go related gene (hERG K+ channel is critical for the slow deactivation kinetics of the channel. However, the mechanism(s by which the N-terminal domain regulates deactivation remains to be determined. Here we show that the solution NMR structure of the N-terminal 135 residues of hERG contains a previously described Per-Arnt-Sim (PAS domain (residues 26-135 as well as an amphipathic α-helix (residues 13-23 and an initial unstructured segment (residues 2-9. Deletion of residues 2-25, only the unstructured segment (residues 2-9 or replacement of the α-helix with a flexible linker all result in enhanced rates of deactivation. Thus, both the initial flexible segment and the α-helix are required but neither is sufficient to confer slow deactivation kinetics. Alanine scanning mutagenesis identified R5 and G6 in the initial flexible segment as critical for slow deactivation. Alanine mutants in the helical region had less dramatic phenotypes. We propose that the PAS domain is bound close to the central core of the channel and that the N-terminal α-helix ensures that the flexible tail is correctly orientated for interaction with the activation gating machinery to stabilize the open state of the channel.

  11. A radiolabeled peptide ligand of the hERG channel, [125I]-BeKm-1

    DEFF Research Database (Denmark)

    Angelo, Kamilla; Korolkova, Yuliya V; Grunnet, Morten

    2003-01-01

    The wild-type scorpion toxin BeKm-1, which selectively blocks human ether-a-go-go related (hERG) channels, was radiolabeled with iodine at tyrosine 11. Both the mono- and di-iodinated derivatives were found to be biologically active. In electrophysiological patch-clamp recordings mono-[127I]-BeKm-1...... had a concentration of half-maximal inhibition (IC50 value) of 27 nM, while wild-type BeKm-1 inhibited hERG channels with an IC50 value of 7 nM. Mono-[125I]-BeKm-1 was found to bind in a concentration-dependent manner and with picomolar affinity to hERG channel protein in purified membrane vesicles...... of [125I]-BeKm-1 to the hERG channel to an IC50 of 7 nM. In autoradiographic studies on rat hearts, binding of [125I]-BeKm-1 was dose-dependent and could partially be displaced by the addition of excess amounts of non-radioactive BeKm-1. The density of the radioactive signal was equally distributed...

  12. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

    Science.gov (United States)

    Nogawa, Hisashi; Kawai, Tomoyuki

    2014-10-15

    Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Voltage-sensing domain mode shift is coupled to the activation gate by the N-terminal tail of hERG channels.

    Science.gov (United States)

    Tan, Peter S; Perry, Matthew D; Ng, Chai Ann; Vandenberg, Jamie I; Hill, Adam P

    2012-09-01

    Human ether-a-go-go-related gene (hERG) potassium channels exhibit unique gating kinetics characterized by unusually slow activation and deactivation. The N terminus of the channel, which contains an amphipathic helix and an unstructured tail, has been shown to be involved in regulation of this slow deactivation. However, the mechanism of how this occurs and the connection between voltage-sensing domain (VSD) return and closing of the gate are unclear. To examine this relationship, we have used voltage-clamp fluorometry to simultaneously measure VSD motion and gate closure in N-terminally truncated constructs. We report that mode shifting of the hERG VSD results in a corresponding shift in the voltage-dependent equilibrium of channel closing and that at negative potentials, coupling of the mode-shifted VSD to the gate defines the rate of channel closure. Deletion of the first 25 aa from the N terminus of hERG does not alter mode shifting of the VSD but uncouples the shift from closure of the cytoplasmic gate. Based on these observations, we propose the N-terminal tail as an adaptor that couples voltage sensor return to gate closure to define slow deactivation gating in hERG channels. Furthermore, because the mode shift occurs on a time scale relevant to the cardiac action potential, we suggest a physiological role for this phenomenon in maximizing current flow through hERG channels during repolarization.

  14. Indolcarboxamide is a preclinical candidate for treating multidrug-resistant tuberculosis.

    Science.gov (United States)

    Rao, Srinivasa P S; Lakshminarayana, Suresh B; Kondreddi, Ravinder R; Herve, Maxime; Camacho, Luis R; Bifani, Pablo; Kalapala, Sarath K; Jiricek, Jan; Ma, Ng L; Tan, Bee H; Ng, Seow H; Nanjundappa, Mahesh; Ravindran, Sindhu; Seah, Peck G; Thayalan, Pamela; Lim, Siao H; Lee, Boon H; Goh, Anne; Barnes, Whitney S; Chen, Zhong; Gagaring, Kerstin; Chatterjee, Arnab K; Pethe, Kevin; Kuhen, Kelli; Walker, John; Feng, Gu; Babu, Sreehari; Zhang, Lijun; Blasco, Francesca; Beer, David; Weaver, Margaret; Dartois, Veronique; Glynne, Richard; Dick, Thomas; Smith, Paul W; Diagana, Thierry T; Manjunatha, Ujjini H

    2013-12-04

    New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). We have identified and characterized the indolcarboxamides as a new class of antitubercular bactericidal agent. Genetic and lipid profiling studies identified the likely molecular target of indolcarboxamides as MmpL3, a transporter of trehalose monomycolate that is essential for mycobacterial cell wall biosynthesis. Two lead candidates, NITD-304 and NITD-349, showed potent activity against both drug-sensitive and multidrug-resistant clinical isolates of Mtb. Promising pharmacokinetic profiles of both compounds after oral dosing in several species enabled further evaluation for efficacy and safety. NITD-304 and NITD-349 were efficacious in treating both acute and chronic Mtb infections in mouse efficacy models. Furthermore, dosing of NITD-304 and NITD-349 for 2 weeks in exploratory rat toxicology studies revealed a promising safety margin. Finally, neither compound inhibited the activity of major cytochrome P-450 enzymes or the hERG (human ether-a-go-go related gene) channel. These results suggest that NITD-304 and NITD-349 should undergo further development as a potential treatment for multidrug-resistant TB.

  15. Analysis for Human-related Events during the Overhaul

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Tae; Kim, Min Chull; Choi, Dong Won; Lee, Durk Hun [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2011-10-15

    The event frequency due to human error is decreasing among 20 operating Nuclear Power Plants (NPPs) excluding the NPP (Shin-Kori unit-1) in the commissioning stage since 2008. However, the events due to human error during an overhaul (O/H) occur annually (see Table I). An analysis for human-related events during the O/H was performed. Similar problems were identified for each event from the analysis and also, organizational and safety cultural factors were also identified

  16. Journal of Religion and Human Relations: Editorial Policies

    African Journals Online (AJOL)

    The Journal of Religion and Human Relations (JORAHR) is an academic journal with focus on religious and ... Peer Review Process ... that making research freely available to the public supports a greater global exchange of knowledge.

  17. Relational adaptivity - enacting human-centric systems design

    DEFF Research Database (Denmark)

    Petersen, Kjell Yngve

    2016-01-01

    Human centered design approaches places the experiencing human at the center of concern, situated in relation to the dynamics of the environmental condition and the variables of the system of control and sensing. Taking the approach of enacted design methods to enforce the experience...... of the inhabitant as core in human-centered design solutions, the intelligence of the connected sensors is suggested to be developed as an actual learning and self-adjusting adaptive environment, where the adaptive system is part of a negotiation with users on the qualities of the environment. We will present...... a fully functional sketching environment for adaptive sensor-control systems, which enable integration of the complex situation of everyday activities and human well-being. The proposed sketching environment allows for the development of sensor systems related to lighting conditions and human occupancy...

  18. Genomic signatures of diet-related shifts during human origins.

    Science.gov (United States)

    Babbitt, Courtney C; Warner, Lisa R; Fedrigo, Olivier; Wall, Christine E; Wray, Gregory A

    2011-04-07

    There are numerous anthropological analyses concerning the importance of diet during human evolution. Diet is thought to have had a profound influence on the human phenotype, and dietary differences have been hypothesized to contribute to the dramatic morphological changes seen in modern humans as compared with non-human primates. Here, we attempt to integrate the results of new genomic studies within this well-developed anthropological context. We then review the current evidence for adaptation related to diet, both at the level of sequence changes and gene expression. Finally, we propose some ways in which new technologies can help identify specific genomic adaptations that have resulted in metabolic and morphological differences between humans and non-human primates.

  19. Human evolution and osteoporosis-related spinal fractures.

    Directory of Open Access Journals (Sweden)

    Meghan M Cotter

    Full Text Available The field of evolutionary medicine examines the possibility that some diseases are the result of trade-offs made in human evolution. Spinal fractures are the most common osteoporosis-related fracture in humans, but are not observed in apes, even in cases of severe osteopenia. In humans, the development of osteoporosis is influenced by peak bone mass and strength in early adulthood as well as age-related bone loss. Here, we examine the structural differences in the vertebral bodies (the portion of the vertebra most commonly involved in osteoporosis-related fractures between humans and apes before age-related bone loss occurs. Vertebrae from young adult humans and chimpanzees, gorillas, orangutans, and gibbons (T8 vertebrae, n = 8-14 per species, male and female, humans: 20-40 years of age were examined to determine bone strength (using finite element models, bone morphology (external shape, and trabecular microarchitecture (micro-computed tomography. The vertebrae of young adult humans are not as strong as those from apes after accounting for body mass (p<0.01. Human vertebrae are larger in size (volume, cross-sectional area, height than in apes with a similar body mass. Young adult human vertebrae have significantly lower trabecular bone volume fraction (0.26±0.04 in humans and 0.37±0.07 in apes, mean ± SD, p<0.01 and thinner vertebral shells than apes (after accounting for body mass, p<0.01. Since human vertebrae are more porous and weaker than those in apes in young adulthood (after accounting for bone mass, even modest amounts of age-related bone loss may lead to vertebral fracture in humans, while in apes, larger amounts of bone loss would be required before a vertebral fracture becomes likely. We present arguments that differences in vertebral bone size and shape associated with reduced bone strength in humans is linked to evolutionary adaptations associated with bipedalism.

  20. Similarity or dissimilarity in the relations between human service organizations.

    Science.gov (United States)

    Bruynooghe, Kevin; Verhaeghe, Mieke; Bracke, Piet

    2008-01-01

    Exchange theory and homophily theory give rise to counteracting expectations for the interaction between human service organizations. Based on arguments of exchange theory, more interaction is expected between dissimilar organizations having complementary resources. Based on arguments of homophily theory, organizations having similar characteristics are expected to interact more. Interorganizational relations between human service organizations in two regional networks in Flanders are examined in this study. Results indicate that human service organizations tend to cooperate more with similar organizations as several homophily effects but not one effect of dissimilarity were found to be significant. The results of this study contribute to the understanding of interorganizational networks of human service organizations and have implications for the development of integrated care.

  1. The Reconfigured Body. Human-animal relations in xenotransplantation

    Directory of Open Access Journals (Sweden)

    Kristofer Hansson

    2011-12-01

    Full Text Available The article explores issues concerning the reconfiguration of human and animal bodies in modern biotechnology. The examples are based on xenotransplantation: Transplantation of cells, tissue and organs from animals to humans. Three thematic issues that emerged from xenotransplantation research in Sweden in the 1990s and early 2000s are examined in the article. The first issue concerns how the pig was introduced as a donor animal in xenotransplantation and, at the same time, dehumanized in relation to what is human. Baboons and chimpanzees that had previously been used in xenotransplantation now became an ethically problematic choice, and were in stead humanized. The second issue concerns the introduction of transgenic and cloned pigs as commoditized objects. The biotechnological development reconfigured the pig’s cells, tissue and organs to become more human-like. The third issue concerns the risk that pigs contain retrovirus that could infect the transplanted patients. The human body became part of a network of both animal and retrovirus. Boundlessness between human and animal bodies appears in these three thematic phases and is analysed from a cultural perspective.

  2. Neurolinguistic Relativity: How Language Flexes Human Perception and Cognition.

    Science.gov (United States)

    Thierry, Guillaume

    2016-09-01

    The time has come, perhaps, to go beyond merely acknowledging that language is a core manifestation of the workings of the human mind and that it relates interactively to all aspects of thinking. The issue, thus, is not to decide whether language and human thought may be ineluctably linked (they just are), but rather to determine what the characteristics of this relationship may be and to understand how language influences-and may be influenced by-nonverbal information processing. In an attempt to demystify linguistic relativity, I review neurolinguistic studies from our research group showing a link between linguistic distinctions and perceptual or conceptual processing. On the basis of empirical evidence showing effects of terminology on perception, language-idiosyncratic relationships in semantic memory, grammatical skewing of event conceptualization, and unconscious modulation of executive functioning by verbal input, I advocate a neurofunctional approach through which we can systematically explore how languages shape human thought.

  3. The relative importance of climatic gradient versus human ...

    African Journals Online (AJOL)

    The study aimed to investigate the relative significance of effects of climatic variability and human disturbance on the population structure of the threatened species Afzelia africana Sm. ex Pers. in the Republic of Benin in West Africa. Forest inventory data such as regeneration density, tree diameter and total height were ...

  4. Effects of Systematic Human Relations Training on Inmate Participants

    Science.gov (United States)

    Davis, E. Duane; And Others

    1976-01-01

    The present study was conducted to determine the applicability of human relations training in the rehabilitation of selected prisoners in a Southern prison. Inmates who participated in the study were able to learn discrimination between helpful and nonhelpful communication and to make positive gains in their work behavior. (Author)

  5. Expression of human soluble tumor necrosis factor (TNF)-related ...

    African Journals Online (AJOL)

    DR NJ TONUKARI

    2011-06-06

    Jun 6, 2011 ... bio-technique in bacterial (Lin et al., 2007), yeast (Xu et al., 2003) ... biological activity, such as human somatotropin (hST) .... sion way with chloroplast transit peptide (Wang et al., .... chloroplast protein synthesis capacity by massive expression of a ... necrosis factor-related apoptosis-inducing ligand in vivo.

  6. Novel Parvovirus and Related Variant in Human Plasma

    Science.gov (United States)

    Fryer, Jacqueline F.; Kapoor, Amit; Minor, Philip D.; Delwart, Eric

    2006-01-01

    We report a novel parvovirus (PARV4) and related variants in pooled human plasma used in the manufacture of plasma-derived medical products. Viral DNA was detected by using highly selective polymerase chain reaction assays; 5% of pools tested positive, and amounts of DNA ranged from 106 copies/mL plasma. PMID:16494735

  7. Human Relations: The Cornerstone of a Roeper Education

    Science.gov (United States)

    Lutz, Lori A.; Nichols, Susannah

    2016-01-01

    This article traces the evolution of a moral philosophy curriculum originally taught by George A. Roeper in the earliest years of The Roeper School. The first author, a student at The Roeper School in the 1960s and 1970s, describes the impact of the class George Roeper called "Human Relations" on her life. Returning to the School as a…

  8. Pathogenesis of age-related bone loss in humans.

    Science.gov (United States)

    Khosla, Sundeep

    2013-10-01

    Although data from rodent systems are extremely useful in providing insights into possible mechanisms of age-related bone loss, concepts evolving from animal models need to ultimately be tested in humans. This review provides an update on mechanisms of age-related bone loss in humans based on the author's knowledge of the field and focused literature reviews. Novel imaging, experimental models, biomarkers, and analytic techniques applied directly to human studies are providing new insights into the patterns of bone mass acquisition and loss as well as the role of sex steroids, in particular estrogen, on bone metabolism and bone loss with aging in women and men. These studies have identified the onset of trabecular bone loss at multiple sites that begins in young adulthood and remains unexplained, at least based on current paradigms of the mechanisms of bone loss. In addition, estrogen appears to be a major regulator of bone metabolism not only in women but also in men. Studies assessing mechanisms of estrogen action on bone in humans have identified effects of estrogen on RANKL expression by several different cell types in the bone microenvironment, a role for TNF-α and IL-1β in mediating effects of estrogen deficiency on bone, and possible regulation of the Wnt inhibitor, sclerostin, by estrogen. There have been considerable advances in our understanding of age-related bone loss in humans. However, there are also significant gaps in knowledge, particularly in defining cell autonomous changes in bone in human studies to test or validate concepts emerging from studies in rodents. Decision Editor: Luigi Ferrucci, MD, PhD.

  9. Some human-related problems in radiation protection

    International Nuclear Information System (INIS)

    Yoshizawa, Yasuo

    1980-01-01

    Radiation protection includes both human and source-related problems. The human problems have not only medical but also social aspects, such as labor management. Special attention should be paid to the fact that the subject of radiation protection is not a human being as living thing but as member of society. ICRP recommended that conditions of work can be divided into two classed, working condition A and B, according to annual exposure. This application is of great value to radiation protection practice. Nevertheless the legal regulations do not adopt it yet. The present condition of the medical surveillance of radiation workers is not appropriate from the scientific standpoint. This is the difficult problem which is caused by the delay of the legal application of ICRP recommendation. Compensation for occupational radiation hazards should be overlooked. This problem have been investigated by an authorized committee, but a number of unsolved problems still remain. (author)

  10. Work-related threats and violence in human service sectors

    DEFF Research Database (Denmark)

    Andersen, Lars Peter Sønderbo; Hogh, Annie; Biering, Karin

    2018-01-01

    BACKGROUND: Threats and violence at work are major concerns for employees in many human service sectors. The prevention of work-related violence is a major challenge for employees and management. OBJECTIVE: The purpose of this study was to identify prospective associations between psycho-social w......BACKGROUND: Threats and violence at work are major concerns for employees in many human service sectors. The prevention of work-related violence is a major challenge for employees and management. OBJECTIVE: The purpose of this study was to identify prospective associations between psycho...... rewards at work, low role clarity, many role conflicts, many work-family conflicts and low organizational justice had statistically significant associations with high levels of work-related threats. Furthermore, high emotional demands, low predictability, low role clarity, many role conflicts, many work......-family conflicts, low supervisor quality and low support from nearest supervisor had statistically significant associations with high levels of work-related violence. Finally, across the four sectors both similar and different associations between psycho-social work environment and work-related violence...

  11. DRUMS: a human disease related unique gene mutation search engine.

    Science.gov (United States)

    Li, Zuofeng; Liu, Xingnan; Wen, Jingran; Xu, Ye; Zhao, Xin; Li, Xuan; Liu, Lei; Zhang, Xiaoyan

    2011-10-01

    With the completion of the human genome project and the development of new methods for gene variant detection, the integration of mutation data and its phenotypic consequences has become more important than ever. Among all available resources, locus-specific databases (LSDBs) curate one or more specific genes' mutation data along with high-quality phenotypes. Although some genotype-phenotype data from LSDB have been integrated into central databases little effort has been made to integrate all these data by a search engine approach. In this work, we have developed disease related unique gene mutation search engine (DRUMS), a search engine for human disease related unique gene mutation as a convenient tool for biologists or physicians to retrieve gene variant and related phenotype information. Gene variant and phenotype information were stored in a gene-centred relational database. Moreover, the relationships between mutations and diseases were indexed by the uniform resource identifier from LSDB, or another central database. By querying DRUMS, users can access the most popular mutation databases under one interface. DRUMS could be treated as a domain specific search engine. By using web crawling, indexing, and searching technologies, it provides a competitively efficient interface for searching and retrieving mutation data and their relationships to diseases. The present system is freely accessible at http://www.scbit.org/glif/new/drums/index.html. © 2011 Wiley-Liss, Inc.

  12. Plasticity of the human auditory cortex related to musical training.

    Science.gov (United States)

    Pantev, Christo; Herholz, Sibylle C

    2011-11-01

    During the last decades music neuroscience has become a rapidly growing field within the area of neuroscience. Music is particularly well suited for studying neuronal plasticity in the human brain because musical training is more complex and multimodal than most other daily life activities, and because prospective and professional musicians usually pursue the training with high and long-lasting commitment. Therefore, music has increasingly been used as a tool for the investigation of human cognition and its underlying brain mechanisms. Music relates to many brain functions like perception, action, cognition, emotion, learning and memory and therefore music is an ideal tool to investigate how the human brain is working and how different brain functions interact. Novel findings have been obtained in the field of induced cortical plasticity by musical training. The positive effects, which music in its various forms has in the healthy human brain are not only important in the framework of basic neuroscience, but they also will strongly affect the practices in neuro-rehabilitation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Human Rights, Fundamental Freedoms and Universal Values in International Relations

    Directory of Open Access Journals (Sweden)

    Lev S. Voronkov

    2016-01-01

    Full Text Available The author analyzes the evolution of human rights and fundamental freedoms in domestic political life of individual states and in international relations as well over the latest two centuries. The article traces the role of struggle for liberal political human rights and civilian freedoms in the dismantling of the feudal-absolutist regimes as well as the challenges of radical left-wing (communist and far right-wing (national-socialistic threats to be met by the supporters of liberal political rights and civil freedoms in the interwar period. The list of human rights and fundamental freedoms had constantly been updating in the postwar period, including by the efforts of the UNO and other international organizations, and fixing in different international documents. The author emphasizes the import role of the Conference on Security and Cooperation in Europe (CSCE in transforming the issues of human rights and fundamental freedoms into the essential element of public diplomacy of contemporary states. He traces the process of the increasing utilization of liberal political rights and civilian freedoms, which are usually the effective tools for domestic democratic transformation, within the framework of diplomatic practice of European and North-American states, aimed at ensuring their political and economic interests on the world stage. In this regard the author addresses the attempts of Western countries to legalize "humanitarian"interventions in circumvention of the UN Security Council. The article emphasizes the necessity to replenish the understanding of universal human rights and freedoms by the values, developed both by the international community within the framework of implementing the Millennium Development Goals and by various countries and peoples, which in sum constitute the modern international civilizational baggage.

  14. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  15. The human hippocampus: cognitive maps or relational memory?

    Science.gov (United States)

    Kumaran, Dharshan; Maguire, Eleanor A

    2005-08-03

    The hippocampus is widely accepted to play a pivotal role in memory. Two influential theories offer competing accounts of its fundamental operating mechanism. The cognitive map theory posits a special role in mapping large-scale space, whereas the relational theory argues it supports amodal relational processing. Here, we pit the two theories against each other using a novel paradigm in which the relational processing involved in navigating in a city was matched with similar navigational and relational processing demands in a nonspatial (social) domain. During functional magnetic resonance imaging, participants determined the optimal route either between friends' homes or between the friends themselves using social connections. Separate brain networks were engaged preferentially during the two tasks, with hippocampal activation driven only by spatial relational processing. We conclude that the human hippocampus appears to have a bias toward the processing of spatial relationships, in accordance with the cognitive map theory. Our results both advance our understanding of the nature of the hippocampal contribution to memory and provide insights into how social networks are instantiated at the neural level.

  16. Memory-related brain lateralisation in birds and humans.

    Science.gov (United States)

    Moorman, Sanne; Nicol, Alister U

    2015-03-01

    Visual imprinting in chicks and song learning in songbirds are prominent model systems for the study of the neural mechanisms of memory. In both systems, neural lateralisation has been found to be involved in memory formation. Although many processes in the human brain are lateralised--spatial memory and musical processing involves mostly right hemisphere dominance, whilst language is mostly left hemisphere dominant--it is unclear what the function of lateralisation is. It might enhance brain capacity, make processing more efficient, or prevent occurrence of conflicting signals. In both avian paradigms we find memory-related lateralisation. We will discuss avian lateralisation findings and propose that birds provide a strong model for studying neural mechanisms of memory-related lateralisation. Copyright © 2014. Published by Elsevier Ltd.

  17. Economic Burden of Human Papillomavirus-Related Diseases in Italy

    Science.gov (United States)

    Baio, Gianluca; Capone, Alessandro; Marcellusi, Andrea; Mennini, Francesco Saverio; Favato, Giampiero

    2012-01-01

    Introduction Human papilloma virus (HPV) genotypes 6, 11, 16, and 18 impose a substantial burden of direct costs on the Italian National Health Service that has never been quantified fully. The main objective of the present study was to address this gap: (1) by estimating the total direct medical costs associated with nine major HPV-related diseases, namely invasive cervical cancer, cervical dysplasia, cancer of the vulva, vagina, anus, penis, and head and neck, anogenital warts, and recurrent respiratory papillomatosis, and (2) by providing an aggregate measure of the total economic burden attributable to HPV 6, 11, 16, and 18 infection. Methods For each of the nine conditions, we used available Italian secondary data to estimate the lifetime cost per case, the number of incident cases of each disease, the total economic burden, and the relative prevalence of HPV types 6, 11, 16, and 18, in order to estimate the aggregate fraction of the total economic burden attributable to HPV infection. Results The total direct costs (expressed in 2011 Euro) associated with the annual incident cases of the nine HPV-related conditions included in the analysis were estimated to be €528.6 million, with a plausible range of €480.1–686.2 million. The fraction attributable to HPV 6, 11, 16, and 18 was €291.0 (range €274.5–315.7 million), accounting for approximately 55% of the total annual burden of HPV-related disease in Italy. Conclusions The results provided a plausible estimate of the significant economic burden imposed by the most prevalent HPV-related diseases on the Italian welfare system. The fraction of the total direct lifetime costs attributable to HPV 6, 11, 16, and 18 infections, and the economic burden of noncervical HPV-related diseases carried by men, were found to be cost drivers relevant to the making of informed decisions about future investments in programmes of HPV prevention. PMID:23185412

  18. Relative clock verifies endogenous bursts of human dynamics

    Science.gov (United States)

    Zhou, Tao; Zhao, Zhi-Dan; Yang, Zimo; Zhou, Changsong

    2012-01-01

    Temporal bursts are widely observed in many human-activated systems, which may result from both endogenous mechanisms like the highest-priority-first protocol and exogenous factors like the seasonality of activities. To distinguish the effects from different mechanisms is thus of theoretical significance. This letter reports a new timing method by using a relative clock, namely the time length between two consecutive events of an agent is counted as the number of other agents' events appeared during this interval. We propose a model, in which agents act either in a constant rate or with a power-law inter-event time distribution, and the global activity either keeps unchanged or varies periodically vs. time. Our analysis shows that the bursts caused by the heterogeneity of global activity can be eliminated by setting the relative clock, yet the bursts from real individual behaviors still exist. We perform extensive experiments on four large-scale systems, the search engine by AOL, a social bookmarking system —Delicious, a short-message communication network, and a microblogging system —Twitter. Seasonality of global activity is observed, yet the bursts cannot be eliminated by using the relative clock.

  19. Human capital and risk aversion in relational incentive contracts

    International Nuclear Information System (INIS)

    Kvaloey, Ola

    2003-01-01

    This paper examines a self-enforced relational incentive contract between a risk neutral principal and a risk averse agent where the agent's human capital is essential in ex post realization of values. I analyse the effect of outside options on the optimal bonus level, showing how the presence of ex post outside options may impede desirable degrees of performance pay. The effect of risk aversion and incentive responsiveness is analysed by allowing for linear contracts. I show that the first order effect of these parameters are the same as in verifiable contracts, but second order effects show that the optimal bonus level's sensitivity to risk aversion and incentive responsiveness increases with the discount factor. The analysis has interesting implications on firm boundaries and specificity choices. (author)

  20. Seasonal variations in health-related human physical activity.

    Science.gov (United States)

    Reilly, Thomas; Peiser, Benny

    2006-01-01

    There are profound fluctuations in climate that occur within the annual cycle of seasonal changes. The severity of these changes depends on latitude of location and prevailing topography. Living creatures have evolved means of coping with seasonal extremes. Endogenous circannual cycles, at least in humans, appear to have been masked by mechanisms employed to cope with environmental changes. Physical activity levels tend to be lower in winter than in summer, mediating effects on health-related fitness. In athletes, seasonal changes are dictated by requirements of the annual programme of competitive engagements rather than an inherent circannual rhythm. Injury rates are influenced by seasonal environmental factors, notably in field sports. Season of birth has been related to susceptibility to selected morbidities, including mental ill-health. In age-restricted sports, there is a date-of-birth bias favouring those individuals born early in the competitive year. Trainers and selectors should acknowledge this trend if they are to avoid omitting gifted individuals, born later in the year, from talent development programmes.

  1. Absolutely relative or relatively absolute: violations of value invariance in human decision making.

    Science.gov (United States)

    Teodorescu, Andrei R; Moran, Rani; Usher, Marius

    2016-02-01

    Making decisions based on relative rather than absolute information processing is tied to choice optimality via the accumulation of evidence differences and to canonical neural processing via accumulation of evidence ratios. These theoretical frameworks predict invariance of decision latencies to absolute intensities that maintain differences and ratios, respectively. While information about the absolute values of the choice alternatives is not necessary for choosing the best alternative, it may nevertheless hold valuable information about the context of the decision. To test the sensitivity of human decision making to absolute values, we manipulated the intensities of brightness stimuli pairs while preserving either their differences or their ratios. Although asked to choose the brighter alternative relative to the other, participants responded faster to higher absolute values. Thus, our results provide empirical evidence for human sensitivity to task irrelevant absolute values indicating a hard-wired mechanism that precedes executive control. Computational investigations of several modelling architectures reveal two alternative accounts for this phenomenon, which combine absolute and relative processing. One account involves accumulation of differences with activation dependent processing noise and the other emerges from accumulation of absolute values subject to the temporal dynamics of lateral inhibition. The potential adaptive role of such choice mechanisms is discussed.

  2. Hippocampal sleep features: relations to human memory function

    Directory of Open Access Journals (Sweden)

    Michele eFerrara

    2012-04-01

    Full Text Available The recent spread of intracranial EEG recordings techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific pattern of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, NREM sleep in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate sleep

  3. Hippocampal Sleep Features: Relations to Human Memory Function

    Science.gov (United States)

    Ferrara, Michele; Moroni, Fabio; De Gennaro, Luigi; Nobili, Lino

    2012-01-01

    The recent spread of intracranial electroencephalographic (EEG) recording techniques for presurgical evaluation of drug-resistant epileptic patients is providing new information on the activity of different brain structures during both wakefulness and sleep. The interest has been mainly focused on the medial temporal lobe, and in particular the hippocampal formation, whose peculiar local sleep features have been recently described, providing support to the idea that sleep is not a spatially global phenomenon. The study of the hippocampal sleep electrophysiology is particularly interesting because of its central role in the declarative memory formation. Recent data indicate that sleep contributes to memory formation. Therefore, it is relevant to understand whether specific patterns of activity taking place during sleep are related to memory consolidation processes. Fascinating similarities between different states of consciousness (wakefulness, REM sleep, non-REM sleep) in some electrophysiological mechanisms underlying cognitive processes have been reported. For instance, large-scale synchrony in gamma activity is important for waking memory and perception processes, and its changes during sleep may be the neurophysiological substrate of sleep-related deficits of declarative memory. Hippocampal activity seems to specifically support memory consolidation during sleep, through specific coordinated neurophysiological events (slow waves, spindles, ripples) that would facilitate the integration of new information into the pre-existing cortical networks. A few studies indeed provided direct evidence that rhinal ripples as well as slow hippocampal oscillations are correlated with memory consolidation in humans. More detailed electrophysiological investigations assessing the specific relations between different types of memory consolidation and hippocampal EEG features are in order. These studies will add an important piece of knowledge to the elucidation of the ultimate

  4. Team management in the 21 st century: A human relations theory ...

    African Journals Online (AJOL)

    Team management in the 21 st century: A human relations theory angle. ... a team is about understanding human relation, that is, the manager understanding the ... The problem ranges from membership isolation to lack of communication and ...

  5. Comprehensive Control of Human Papillomavirus Infections and Related Diseases

    Science.gov (United States)

    Bosch, F. Xavier; Broker, Thomas R.; Forman, David; Moscicki, Anna-Barbara; Gillison, Maura L.; Doorbar, John; Stern, Peter L.; Stanley, Margaret; Arbyn, Marc; Poljak, Mario; Cuzick, Jack; Castle, Philip E.; Schiller, John T.; Markowitz, Lauri E.; Fisher, William A.; Canfell, Karen; Denny, Lynette A.; Franco, Eduardo L.; Steben, Marc; Kane, Mark A.; Schiffman, Mark; Meijer, Chris J.L.M.; Sankaranarayanan, Rengaswamy; Castellsagué, Xavier; Kim, Jane J.; Brotons, Maria; Alemany, Laia; Albero, Ginesa; Diaz, Mireia; de Sanjosé, Silvia

    2014-01-01

    Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of

  6. Global burden of human papillomavirus and related diseases.

    Science.gov (United States)

    Forman, David; de Martel, Catherine; Lacey, Charles J; Soerjomataram, Isabelle; Lortet-Tieulent, Joannie; Bruni, Laia; Vignat, Jerome; Ferlay, Jacques; Bray, Freddie; Plummer, Martyn; Franceschi, Silvia

    2012-11-20

    The worldwide prevalence of infection with human papillomavirus (HPV) in women without cervical abnormalities is 11-12% with higher rates in sub-Saharan Africa (24%), Eastern Europe (21%) and Latin America (16%). The two most prevalent types are HPV16 (3.2%) and HPV18 (1.4%). Prevalence increases in women with cervical pathology in proportion to the severity of the lesion reaching around 90% in women with grade 3 cervical intraepithelial neoplasia and invasive cancer. HPV infection has been identified as a definite human carcinogen for six types of cancer: cervix, penis, vulva, vagina, anus and oropharynx (including the base of the tongue and tonsils). Estimates of the incidence of these cancers for 2008 due to HPV infection have been calculated globally. Of the estimated 12.7 million cancers occurring in 2008, 610,000 (Population Attributable Fraction [PAF]=4.8%) could be attributed to HPV infection. The PAF varies substantially by geographic region and level of development, increasing to 6.9% in less developed regions of the world, 14.2% in sub-Saharan Africa and 15.5% in India, compared with 2.1% in more developed regions, 1.6% in Northern America and 1.2% in Australia/New Zealand. Cervical cancer, for which the PAF is estimated to be 100%, accounted for 530,000 (86.9%) of the HPV attributable cases with the other five cancer types accounting for the residual 80,000 cancers. Cervical cancer is the third most common female malignancy and shows a strong association with level of development, rates being at least four-fold higher in countries defined within the low ranking of the Human Development Index (HDI) compared with those in the very high category. Similar disparities are evident for 5-year survival-less than 20% in low HDI countries and more than 65% in very high countries. There are five-fold or greater differences in incidence between world regions. In those countries for which reliable temporal data are available, incidence rates appear to be

  7. USER principle as relating the human environmental management

    International Nuclear Information System (INIS)

    Kernakis

    2005-01-01

    The environmental variable can be understood as the resulting biosphere space that has suffered the occurrence of pre-biotic, biotic and anthropic processes. This necessary expansion of the environmental frontier allows understand clearly the magnitude the great complexity of the process immersed in the current environmental problematic. This, taking into account the analysis of the reference systems used by the different species to face their interaction with the nature. Hence, it is necessary to evaluate the human referential process of reality, as a responsible specie of the derange shown by the Environmental Mother Eve. The latest hominid development of an Artificial Reference System (ARS) (linguistic symbols), points to the constitution of the casual factor that triggers such an environmental problematic. The expansive dynamics accomplished by the ARS has not always made reference to the natural ambience that created them. The formulation of the Unprivilegeness of Symbolic Endogenous Referents (USER) Principle (Kernakis 1986, 1997), as a necessary epistemological consequence of the Special Relativity from Einstein, entails to the reversion of the local privileges created by the ARS, stating a referential crisis as alternative to a potential environmental collapse. AII these could lead to the most intra-specific understanding with the nature, antonomastical fragmented by the privileges of the ARS. Such integration species-nature would allow to make possible an spontaneous natural-cultural arranging of the environmental balance

  8. Reconcilable differences? Human diversity, cultural relativity, and sense of community.

    Science.gov (United States)

    Townley, Greg; Kloos, Bret; Green, Eric P; Franco, Margarita M

    2011-03-01

    Sense of community (SOC) is one of the most widely used and studied constructs in community psychology. As proposed by Sarason in (The Psychological sense of community: prospects for a community psychology, Jossey-Bass, San Francisco, 1974), SOC represents the strength of bonding among community members. It is a valuable component of community life, and it has been linked to positive mental health outcomes, citizen participation, and community connectedness. However, promotion of SOC can become problematic in community psychology praxis when it conflicts with other core values proposed to define the field, namely values of human diversity, cultural relativity, and heterogeneity of experience and perspective. Several commentators have noted that promotion of SOC can conflict with multicultural diversity because it tends to emphasize group member similarity and appears to be higher in homogeneous communities. In this paper, we introduce the idea of a community-diversity dialectic as part of praxis and research in community psychology. We argue that systematic consideration of cultural psychology perspectives can guide efforts to address a community-diversity dialectic and revise SOC formulations that ultimately will invigorate community research and action. We provide a working agenda for addressing this dialectic, proposing that systematic consideration of the creative tension between SOC and diversity can be beneficial to community psychology.

  9. Trends in human papillomavirus-related oropharyngeal cancer in Israel.

    Science.gov (United States)

    Amit, Moran; Ilana, Kaplan; Avraham, Sharon Pelles; Binenbaum, Yoav; Bachar, Gideon; Billan, Salem; Zaarura, Suliman; Czerninski, Rakefet; Bar-Tov, Matan; Maly, Alexander; Akrish, Sharon; Gil, Ziv

    2016-04-01

    The role of human papillomavirus (HPV) infection in oropharyngeal cancer (SCC) is well established. The annual incidence of oropharyngeal SCC in Israel is considerably lower than that in the United States. The purpose of this study was to assess the rate of HPV-related oropharyngeal SCC in Israel. The cohort included patients with oropharyngeal SCC who were treated during 1999 to 2011 in Israel. HPV typing was carried out using reverse hybridization and immunohistochemistry. Of the 74 patients analyzed, 25 (33.7%) had detectable HPV DNA. Patients in the HPV-positive group tended to be younger, with a higher rate of nodal metastases, and no history of smoking (p Israel as approximately 3-fold lower than in Western countries. Low exposure to HPV-16, a lower rate of transformation, to cancer or protective genetic factors may contribute to the lower rate of oropharyngeal SCC in Israel. © 2015 Wiley Periodicals, Inc. Head Neck 38: E274-E278, 2016. © 2015 Wiley Periodicals, Inc.

  10. Escitalopram block of hERG potassium channels.

    Science.gov (United States)

    Chae, Yun Ju; Jeon, Ji Hyun; Lee, Hong Joon; Kim, In-Beom; Choi, Jin-Sung; Sung, Ki-Wug; Hahn, Sang June

    2014-01-01

    Escitalopram, a selective serotonin reuptake inhibitor, is the pharmacologically active S-enantiomer of the racemic mixture of RS-citalopram and is widely used in the treatment of depression. The effects of escitalopram and citalopram on the human ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney cells were investigated using voltage-clamp and Western blot analyses. Both drugs blocked hERG currents in a concentration-dependent manner with an IC50 value of 2.6 μM for escitalopram and an IC50 value of 3.2 μM for citalopram. The blocking of hERG by escitalopram was voltage-dependent, with a steep increase across the voltage range of channel activation. However, voltage independence was observed over the full range of activation. The blocking by escitalopram was frequency dependent. A rapid application of escitalopram induced a rapid and reversible blocking of the tail current of hERG. The extent of the blocking by escitalopram during the depolarizing pulse was less than that during the repolarizing pulse, suggesting that escitalopram has a high affinity for the open state of the hERG channel, with a relatively lower affinity for the inactivated state. Both escitalopram and citalopram produced a reduction of hERG channel protein trafficking to the plasma membrane but did not affect the short-term internalization of the hERG channel. These results suggest that escitalopram blocked hERG currents at a supratherapeutic concentration and that it did so by preferentially binding to both the open and the inactivated states of the channels and by inhibiting the trafficking of hERG channel protein to the plasma membrane.

  11. Age-related changes in human tendo calcaneus collagen fibrils

    International Nuclear Information System (INIS)

    Sargon, Mustafa F.; Ozlu, Korhan; Oken, Fuad

    2005-01-01

    The ruptures of tendo calcaneus often occur between the age group of 30-45 years as described by several text books. It is also described that some diseases and drugs are said to be responsible in the etiology; however, there are no studies related with the detailed histological structure of collagen fibrils found in the tendon in the age groups of humans. In view there of, this study was aimed to obtain further information on the etiology and to find an answer regarding the frequency the ruptures occurring between the age of 30-45 years in human. In the study, the biopsy specimen taken from 28 patients age (1-68) years who had undergone surgery due to tendo calcaneus ruptures or acilloplasty operations were examined by transmission electron microscope. All the specimens were prepared according to routine electronic microscope tissue preparation technique. The patients were divided into 7 age groups (1-9, 10-19, 20-29, 30-39, 40-49, 50-59, >60 years) and there were 4 patients in each group. The transverse diameters of collagen fibers were measured from the ultra thin sections and statistical analysis of the results were performed. The study was carried out in the electron microscopy laboratory of the Anatomy Department of Hacettepe University, Ankara, Turkey between January 2004 and September 2004. The diameters of the collagen fibers were higher in the 20-29 year-old groups compared to other groups and it showed a statistically significant difference. In patients who were in the 30-39 year old group or older, the diameters of the collagen fibers were lesser than the 20-29 year-old group. However, an increase was observed in the collagen fibril concentration of these groups. In examination of the specimens of patients who were under 20-year old, the diameter of the collagen fibers were less than 20-29 year -old group. The electron microscopic appearance of the tissue sample of a one year-old patient had a specific organization and in this patient, both the

  12. Advancements in Violin-Related Human-Computer Interaction

    DEFF Research Database (Denmark)

    Overholt, Daniel

    2014-01-01

    of human intelligence and emotion is at the core of the Musical Interface Technology Design Space, MITDS. This is a framework that endeavors to retain and enhance such traits of traditional instruments in the design of interactive live performance interfaces. Utilizing the MITDS, advanced Human...

  13. The Functions of Selected Human Rights Institutions and Related Role-Players in the Protection of Human Rights in Zimbabwe

    Directory of Open Access Journals (Sweden)

    Howard Chitimira

    2016-12-01

    Full Text Available Various violations of the human rights of ordinary people and human rights defenders have been reported in Zimbabwe since the late 1980s. It is widely acknowledged that such violations have been perpetrated mostly by the government through its different organs for political and other related reasons. Human rights violations were also easily committed against ordinary people and human rights defenders because there was no Constitution that adequately protected such people's fundamental human rights (including their civil and political rights and their socio-economic rights in Zimbabwe. Given this background, the article discusses the protection of human rights in Zimbabwe, in the light of the Zimbabwe Constitution Amendment Act 20 of 2013 (Zimbabwe Constitution 2013. This is done in order to investigate whether the promotion, protection, enforcement and respect for human rights in Zimbabwe has now improved. To this end, the functions of selected national human rights institutions and other related role-players, namely civil society, the judiciary, the law enforcement organs and the Zimbabwe Human Rights Commission, are briefly discussed first. Secondly, the functions of selected regional and international institutions, namely the Southern African Development Community, the African Union and the United Nations are discussed in relation to the protection of human rights in Zimbabwe. Thereafter, concluding remarks and possible recommendations that could be utilised to combat human rights violations and enhance the protection of human rights in Zimbabwe are provided.

  14. [Histopathological changes in human placentas related to hypertensive disorders].

    Science.gov (United States)

    Artico, Luciano Guimarães; Madi, José Mauro; Godoy, Alessandra Eifler Guerra; Coelho, Celso Piccoli; Rombaldi, Renato Luís; Artico, Graziela Rech

    2009-01-01

    to determine the prevalence of histopathological changes, in human placentas, related to hypertensive syndromes. a transversal study that compares histopathological changes identified in 43 placentae from hypertensive pregnant women (HypPr), with the ones from 33 placentae from normotensive pregnant women (NorPr). The weight, volume and macroscopic and microscopic occurrence of infarctions, clots, hematomas, atherosis (partial obliteration, thickness of layers and presence of blood vessels hyalinization) and Tenney-Parker changes (absent, discreet and prominent), as well as the locating of infarctions and clots (central, peripheral or the association of both) have been analyzed. The chi2 and t Student tests have been used for the statistical analysis, as well as medians, standard deviations and ratios. It has been considered as significant, p<0.05. the macroscopic study of HypPr placentae have presented lower weight (461.1 versus 572.1 g) and volume (437.4 versus 542.0 cm(3)), higher infarction (51.2 versus 45.5%; p<0.05: OR=1.15) and clots (51.2 versus 15.1%; p<0.05; OR=5.4) ratios, as compared to the NorPr's. In the HypPr and NorPr, microscopic clots have occurred in 83.7 versus 45.5% (p<0.05; OR=4.3), respectively. Atherosis and Tenney-Parker changes have been statistically associated to the hypertensive syndromes (p<0.05). the obtained data allow us to associate lower placentary weight and volume, higher ratio of macro and microscopic infarction, clots, atherosis and Tenney-Parker changes to placentae of gestations occurring with hypertensive syndromes.

  15. Effect of microculture on cell metabolism and biochemistry: do cells get stressed in microchannels?

    Science.gov (United States)

    Su, Xiaojing; Theberge, Ashleigh B; January, Craig T; Beebe, David J

    2013-02-05

    Microfluidics is emerging as a promising platform for cell culture, enabling increased microenvironment control and potential for integrated analysis compared to conventional macroculture systems such as well plates and Petri dishes. To advance the use of microfluidic devices for cell culture, it is necessary to better understand how miniaturization affects cell behavior. In particular, microfluidic devices have significantly higher surface-area-to-volume ratios than conventional platforms, resulting in lower volumes of media per cell, which can lead to cell stress. We investigated cell stress under a variety of culture conditions using three cell lines: parental HEK (human embryonic kidney) cells and transfected HEK cells that stably express wild-type (WT) and mutant (G601S) human ether-a-go-go related gene (hERG) potassium channel protein. These three cell lines provide a unique model system through which to study cell-type-specific responses in microculture because mutant hERG is known to be sensitive to environmental conditions, making its expression a particularly sensitive readout through which to compare macro- and microculture. While expression of WT-hERG was similar in microchannel and well culture, the expression of mutant G601S-hERG was reduced in microchannels. Expression of the endoplasmic reticulum (ER) stress marker immunoglobulin binding protein (BiP) was upregulated in all three cell lines in microculture. Using BiP expression, glucose consumption, and lactate accumulation as readouts we developed methods for reducing ER stress including properly increasing the frequency of media replacement, reducing cell seeding density, and adjusting the serum concentration and buffering capacity of culture medium. Indeed, increasing the buffering capacity of culture medium or frequency of media replacement partially restored the expression of the G601S-hERG in microculture. This work illuminates how biochemical properties of cells differ in macro- and

  16. Cholesterol regulates HERG K+ channel activation by increasing phospholipase C β1 expression.

    Science.gov (United States)

    Chun, Yoon Sun; Oh, Hyun Geun; Park, Myoung Kyu; Cho, Hana; Chung, Sungkwon

    2013-01-01

    Human ether-a-go-go-related gene (HERG) K(+) channel underlies the rapidly activating delayed rectifier K(+) conductance (IKr) during normal cardiac repolarization. Also, it may regulate excitability in many neuronal cells. Recently, we showed that enrichment of cell membrane with cholesterol inhibits HERG channels by reducing the levels of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] due to the activation of phospholipase C (PLC). In this study, we further explored the effect of cholesterol enrichment on HERG channel kinetics. When membrane cholesterol level was mildly increased in human embryonic kidney (HEK) 293 cells expressing HERG channel, the inactivation and deactivation kinetics of HERG current were not affected, but the activation rate was significantly decelerated at all voltages tested. The application of PtdIns(4,5)P2 or inhibitor for PLC prevented the effect of cholesterol enrichment, while the presence of antibody against PtdIns(4,5)P2 in pipette solution mimicked the effect of cholesterol enrichment. These results indicate that the effect of cholesterol enrichment on HERG channel is due to the depletion of PtdIns(4,5)P2. We also found that cholesterol enrichment significantly increases the expression of β1 and β3 isoforms of PLC (PLCβ1, PLCβ3) in the membrane. Since the effects of cholesterol enrichment on HERG channel were prevented by inhibiting transcription or by inhibiting PLCβ1 expression, we conclude that increased PLCβ1 expression leads to the deceleration of HERG channel activation rate via downregulation of PtdIns(4,5)P2. These results confirm a crosstalk between two plasma membrane-enriched lipids, cholesterol and PtdIns(4,5)P2, in the regulation of HERG channels.

  17. Rehabilitating drug-induced long-QT promoters: in-silico design of hERG-neutral cisapride analogues with retained pharmacological activity.

    Science.gov (United States)

    Durdagi, Serdar; Randall, Trevor; Duff, Henry J; Chamberlin, Adam; Noskov, Sergei Y

    2014-03-08

    The human ether-a-go-go related gene 1 (hERG1), which codes for a potassium ion channel, is a key element in the cardiac delayed rectified potassium current, IKr, and plays an important role in the normal repolarization of the heart's action potential. Many approved drugs have been withdrawn from the market due to their prolongation of the QT interval. Most of these drugs have high potencies for their principal targets and are often irreplaceable, thus "rehabilitation" studies for decreasing their high hERG1 blocking affinities, while keeping them active at the binding sites of their targets, have been proposed to enable these drugs to re-enter the market. In this proof-of-principle study, we focus on cisapride, a gastroprokinetic agent withdrawn from the market due to its high hERG1 blocking affinity. Here we tested an a priori strategy to predict a compound's cardiotoxicity using de novo drug design with molecular docking and Molecular Dynamics (MD) simulations to generate a strategy for the rehabilitation of cisapride. We focused on two key receptors, a target interaction with the (adenosine) receptor and an off-target interaction with hERG1 channels. An analysis of the fragment interactions of cisapride at human A2A adenosine receptors and hERG1 central cavities helped us to identify the key chemical groups responsible for the drug activity and hERG1 blockade. A set of cisapride derivatives with reduced cardiotoxicity was then proposed using an in-silico two-tier approach. This set was compared against a large dataset of commercially available cisapride analogs and derivatives. An interaction decomposition of cisapride and cisapride derivatives allowed for the identification of key active scaffolds and functional groups that may be responsible for the unwanted blockade of hERG1.

  18. Interaction between the cardiac rapidly (IKr) and slowly (IKs) activating delayed rectifier potassium channels revealed by low K+-induced hERG endocytic degradation.

    Science.gov (United States)

    Guo, Jun; Wang, Tingzhong; Yang, Tonghua; Xu, Jianmin; Li, Wentao; Fridman, Michael D; Fisher, John T; Zhang, Shetuan

    2011-10-07

    Cardiac repolarization is controlled by the rapidly (I(Kr)) and slowly (I(Ks)) activating delayed rectifier potassium channels. The human ether-a-go-go-related gene (hERG) encodes I(Kr), whereas KCNQ1 and KCNE1 together encode I(Ks). Decreases in I(Kr) or I(Ks) cause long QT syndrome (LQTS), a cardiac disorder with a high risk of sudden death. A reduction in extracellular K(+) concentration ([K(+)](o)) induces LQTS and selectively causes endocytic degradation of mature hERG channels from the plasma membrane. In the present study, we investigated whether I(Ks) compensates for the reduced I(Kr) under low K(+) conditions. Our data show that when hERG and KCNQ1 were expressed separately in human embryonic kidney (HEK) cells, exposure to 0 mM K(+) for 6 h completely eliminated the mature hERG channel expression but had no effect on KCNQ1. When hERG and KCNQ1 were co-expressed, KCNQ1 significantly delayed 0 mM K(+)-induced hERG reduction. Also, hERG degradation led to a significant reduction in KCNQ1 in 0 mM K(+) conditions. An interaction between hERG and KCNQ1 was identified in hERG+KCNQ1-expressing HEK cells. Furthermore, KCNQ1 preferentially co-immunoprecipitated with mature hERG channels that are localized in the plasma membrane. Biophysical and pharmacological analyses indicate that although hERG and KCNQ1 closely interact with each other, they form distinct hERG and KCNQ1 channels. These data extend our understanding of delayed rectifier potassium channel trafficking and regulation, as well as the pathology of LQTS.

  19. Mechanism and pharmacological rescue of berberine-induced hERG channel deficiency

    Directory of Open Access Journals (Sweden)

    Yan M

    2015-10-01

    Full Text Available Meng Yan,1 Kaiping Zhang,1 Yanhui Shi,1 Lifang Feng,1 Lin Lv,1 Baoxin Li1,2 1Department of Pharmacology, Harbin Medical University, 2State-Province Key Laboratory of Biopharmaceutical Engineering, Harbin, Heilongjiang, People’s Republic of China Abstract: Berberine (BBR, an isoquinoline alkaloid mainly isolated from plants of Berberidaceae family, is extensively used to treat gastrointestinal infections in clinics. It has been reported that BBR can block human ether-a-go-go-related gene (hERG potassium channel and inhibit its membrane expression. The hERG channel plays crucial role in cardiac repolarization and is the target of diverse proarrhythmic drugs. Dysfunction of hERG channel can cause long QT syndrome. However, the regulatory mechanisms of BBR effects on hERG at cell membrane level remain unknown. This study was designed to investigate in detail how BBR decreased hERG expression on cell surface and further explore its pharmacological rescue strategies. In this study, BBR decreases caveolin-1 expression in a concentration-dependent manner in human embryonic kidney 293 (HEK293 cells stably expressing hERG channel. Knocking down the basal expression of caveolin-1 alleviates BBR-induced hERG reduction. In addition, we found that aromatic tyrosine (Tyr652 and phenylalanine (Phe656 in S6 domain mediate the long-term effect of BBR on hERG by using mutation techniques. Considering both our previous and present work, we propose that BBR reduces hERG membrane stability with multiple mechanisms. Furthermore, we found that fexofenadine and resveratrol shorten action potential duration prolongated by BBR, thus having the potential effects of alleviating the cardiotoxicity of BBR. Keywords: berberine, hERG, cavoline-1, cardiotoxicity, LQTS, pharmacological rescue

  20. Channel sialic acids limit hERG channel activity during the ventricular action potential.

    Science.gov (United States)

    Norring, Sarah A; Ednie, Andrew R; Schwetz, Tara A; Du, Dongping; Yang, Hui; Bennett, Eric S

    2013-02-01

    Activity of human ether-a-go-go-related gene (hERG) 1 voltage-gated K(+) channels is responsible for portions of phase 2 and phase 3 repolarization of the human ventricular action potential. Here, we questioned whether and how physiologically and pathophysiologically relevant changes in surface N-glycosylation modified hERG channel function. Voltage-dependent hERG channel gating and activity were evaluated as expressed in a set of Chinese hamster ovary (CHO) cell lines under conditions of full glycosylation, no sialylation, no complex N-glycans, and following enzymatic deglycosylation of surface N-glycans. For each condition of reduced glycosylation, hERG channel steady-state activation and inactivation relationships were shifted linearly by significant depolarizing ∼9 and ∼18 mV, respectively. The hERG window current increased significantly by 50-150%, and the peak shifted by a depolarizing ∼10 mV. There was no significant change in maximum hERG current density. Deglycosylated channels were significantly more active (20-80%) than glycosylated controls during phases 2 and 3 of action potential clamp protocols. Simulations of hERG current and ventricular action potentials corroborated experimental data and predicted reduced sialylation leads to a 50-70-ms decrease in action potential duration. The data describe a novel mechanism by which hERG channel gating is modulated through physiologically and pathophysiologically relevant changes in N-glycosylation; reduced channel sialylation increases hERG channel activity during the action potential, thereby increasing the rate of action potential repolarization.

  1. Relative biological effectiveness if alpha radiation for human lung exposure

    International Nuclear Information System (INIS)

    Yarmoshenko, I.; Kirdin, I.; Zhukovsky, M.

    2006-01-01

    Full text of publication follows: The concept of RBE, which introduced by ICRP and ICRU about 50 years ago to compare biological effects of ionizing radiation of different types, still continues to be the essential element of current and projected radiation protection systems in terms of deriving quantities (quality factor and radiation weighting factor). For example, RBE for the stochastic effects induction has to be considered for appropriate radiation weighting of the absorbed dose while estimating equivalent dose. Simulation of lung cancer radiation risk for the cases of inhalation of radon progeny and incorporation of plutonium in lung in comparison with external reference radiation allows assessment of RBE for alpha-radiation. Specific radiation risk models were developed by results of the direct epidemiological studies and used for such simulation. Simulation included published risk models for nuclear workers of the Mayak facilities in the former Soviet Union exposed to incorporated plutonium (Kreisheimer et al., 2003; Gilbert et al., 2004) and underground miners exposed to radon progenies (BEIR VI, 1999). Additionally lung cancer risk model was developed for a case of population indoor radon exposure. Lung cancer risk related to external exposure is estimated using the risk model develop ed using data of Life Span Study of Japanese atomic bomb survivors. By results of lifetime lung cancer risk simulation using Monte Carlo approach estimated median value of RBE in case of indoor radon exposure is 1.5 (with 90% range 0.4 to 7). In case of the two models developed by BEIR VI for lung cancer risk due to radon exposure in underground miners the median values of RBE are 2.1 and 4.4 (with 90% ranges 0.3 to 17 and 0.7 to 45) respectively.Two different models for lung cancer risk related to plutonium exposure resulted in close estimates of RBE: median value of 12 and 13 (with 90% range 4 to 104 and 4 to 136) respectively. Considerable discrepancy between RBE

  2. Attenuation of ischemia/reperfusion-induced inhibition of the rapid component of delayed rectifier potassium current by Isosteviol through scavenging reactive oxygen species.

    Science.gov (United States)

    Yin, Chunxia; Chen, Yaoxu; Wu, Huanlin; Xu, Danping; Tan, Wen

    2017-12-01

    Isosteviol has been demonstrated to play a protective role during ischemia reperfusion (I/R) myocardial infarction. However, the underlying electrophysiological mechanisms of isosteviol are still unknown. Our previous study showed that the rapid component of the delayed rectifier potassium channel (I Kr ) plays an important role in the prolongation of I/R-induced QT interval-related arrhythmia. This study aimed to investigate whether isosteviol could attenuate I/R-induced prolongation of the action potential duration (APD) along with inhibition of I Kr , and we aimed to clarify the electrophysiological mechanism of isosteviol to determine its cardioprotective effects in guinea pigs. We observed that the APD 90 were 298.5±41.6ms in control, 528.6±56.7ms during I/R, and reduced to 327.8±40.5ms after 10μmol/L of isosteviol treatment. The I Kr currents were 1.44±0.06 pA·pF -1 in the control group, 0.50±0.07pA·pF -1 during I/R, and recovered to 1.20±0.12pA·pF -1 after 10μmol/L of isoteviol treatment. Moreover, isosteviol reduced the over-production of reactive oxygen species (ROS) during I/R. Importantly, isosteviol does not affect the I Kr and human ether-a-go-go-related gene currents of normal cardiomyocytes. It attenuated the I/R-induced inhibition of I Kr due to reduced over-production of ROS. Furthermore, isosteviol is safe and has no cardiotoxicity, and it might be beneficial for coronary reperfusion therapy. Copyright © 2017. Published by Elsevier B.V.

  3. Voltage-dependent gating of hERG potassium channels

    Directory of Open Access Journals (Sweden)

    Yen May eCheng

    2012-05-01

    Full Text Available The mechanisms by which voltage-gated channels sense changes in membrane voltage and energetically couple this with opening of the ion conducting pore has been the source of significant interest. In voltage-gated potassium (Kv channels, much of our knowledge in this area comes from Shaker-type channels, for which voltage-dependent gating is quite rapid. In these channels, activation and deactivation are associated with rapid reconfiguration of the voltage-sensing domain unit that is electromechanically coupled, via the S4-S5 linker helix, to the rate-limiting opening of an intracellular pore gate. However, fast voltage-dependent gating kinetics are not typical of all Kv channels, such as Kv11.1 (human ether-a-go-go related gene, hERG, which activates and deactivates very slowly. Compared to Shaker channels, our understanding of the mechanisms underlying slow hERG gating is much poorer. Here, we present a comparative review of the structure-function relationships underlying voltage-dependent gating in Shaker and hERG channels, with a focus on the roles of the voltage sensing domain and the S4-S5 linker that couples voltage sensor movements to the pore. Measurements of gating current kinetics and fluorimetric analysis of voltage sensor movement are consistent with models suggesting that the hERG activation pathway contains a voltage independent step, which limits voltage sensor transitions. Constraints upon hERG voltage sensor movement may result from loose packing of the S4 helices and additional intra-voltage sensor counter charge interactions. More recent data suggest that key amino acid differences in the hERG voltage sensing unit and S4-S5 linker, relative to fast activating Shaker-type Kv channels, may also contribute to the increased stability of the resting state of the voltage sensor.

  4. Humanness and (im)morality in group relations

    OpenAIRE

    Henriques, Ana Patrícia Matos

    2017-01-01

    Tese de Doutoramento em Psicologia na área de especialidade - Psicologia Social Morality is a valued dimension within and between groups (Ellemers, Pagliaro, & Barreto, 2013; Leach, Bilali, & Pagliaro, 2015), that has been consistently pointed out as part of what makes us uniquely human (Demoulin et al., 2004; Leyens et al., 2000; Haslam, 2006). On the other hand, the extent to which we see others as fully human also impacts on other’s moral status (Bastian, Laham, Wilson, Haslam, & Koval,...

  5. An NMR investigation of the structure, function and role of the hERG channel selectivity filter in the long QT syndrome.

    Science.gov (United States)

    Gravel, Andrée E; Arnold, Alexandre A; Dufourc, Erick J; Marcotte, Isabelle

    2013-06-01

    The human ether-a-go-go-related gene (hERG) voltage-gated K(+) channels are located in heart cell membranes and hold a unique selectivity filter (SF) amino acid sequence (SVGFG) as compared to other K(+) channels (TVGYG). The hERG provokes the acquired long QT syndrome (ALQTS) when blocked, as a side effect of drugs, leading to arrhythmia or heart failure. Its pore domain - including the SF - is believed to be a cardiotoxic drug target. In this study combining solution and solid-state NMR experiments we examine the structure and function of hERG's L(622)-K(638) segment which comprises the SF, as well as its role in the ALQTS using reported active drugs. We first show that the SF segment is unstructured in solution with and without K(+) ions in its surroundings, consistent with the expected flexibility required for the change between the different channel conductive states predicted by computational studies. We also show that the SF segment has the potential to perturb the membrane, but that the presence of K(+) ions cancels this interaction. The SF moiety appears to be a possible target for promethazine in the ALQTS mechanism, but not as much for bepridil, cetirizine, diphenhydramine and fluvoxamine. The membrane affinity of the SF is also affected by the presence of drugs which also perturb model DMPC-based membranes. These results thus suggest that the membrane could play a role in the ALQTS by promoting the access to transmembrane or intracellular targets on the hERG channel, or perturbing the lipid-protein synergy. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Molecular determinants of interactions between the N-terminal domain and the transmembrane core that modulate hERG K+ channel gating.

    Directory of Open Access Journals (Sweden)

    Jorge Fernández-Trillo

    Full Text Available A conserved eag domain in the cytoplasmic amino terminus of the human ether-a-go-go-related gene (hERG potassium channel is critical for its slow deactivation gating. Introduction of gene fragments encoding the eag domain are able to restore normal deactivation properties of channels from which most of the amino terminus has been deleted, and also those lacking exclusively the eag domain or carrying a single point mutation in the initial residues of the N-terminus. Deactivation slowing in the presence of the recombinant domain is not observed with channels carrying a specific Y542C point mutation in the S4-S5 linker. On the other hand, mutations in some initial positions of the recombinant fragment also impair its ability to restore normal deactivation. Fluorescence resonance energy transfer (FRET analysis of fluorophore-tagged proteins under total internal reflection fluorescence (TIRF conditions revealed a substantial level of FRET between the introduced N-terminal eag fragments and the eag domain-deleted channels expressed at the membrane, but not between the recombinant eag domain and full-length channels with an intact amino terminus. The FRET signals were also minimized when the recombinant eag fragments carried single point mutations in the initial portion of their amino end, and when Y542C mutated channels were used. These data suggest that the restoration of normal deactivation gating by the N-terminal recombinant eag fragment is an intrinsic effect of this domain directed by the interaction of its N-terminal segment with the gating machinery, likely at the level of the S4-S5 linker.

  7. Indexing molecules for their hERG liability.

    Science.gov (United States)

    Rayan, Anwar; Falah, Mizied; Raiyn, Jamal; Da'adoosh, Beny; Kadan, Sleman; Zaid, Hilal; Goldblum, Amiram

    2013-07-01

    The human Ether-a-go-go-Related-Gene (hERG) potassium (K(+)) channel is liable to drug-inducing blockage that prolongs the QT interval of the cardiac action potential, triggers arrhythmia and possibly causes sudden cardiac death. Early prediction of drug liability to hERG K(+) channel is therefore highly important and preferably obligatory at earlier stages of any drug discovery process. In vitro assessment of drug binding affinity to hERG K(+) channel involves substantial expenses, time, and labor; and therefore computational models for predicting liabilities of drug candidates for hERG toxicity is of much importance. In the present study, we apply the Iterative Stochastic Elimination (ISE) algorithm to construct a large number of rule-based models (filters) and exploit their combination for developing the concept of hERG Toxicity Index (ETI). ETI estimates the molecular risk to be a blocker of hERG potassium channel. The area under the curve (AUC) of the attained model is 0.94. The averaged ETI of hERG binders, drugs from CMC, clinical-MDDR, endogenous molecules, ACD and ZINC, were found to be 9.17, 2.53, 3.3, -1.98, -2.49 and -3.86 respectively. Applying the proposed hERG Toxicity Index Model on external test set composed of more than 1300 hERG blockers picked from chEMBL shows excellent performance (Matthews Correlation Coefficient of 0.89). The proposed strategy could be implemented for the evaluation of chemicals in the hit/lead optimization stages of the drug discovery process, improve the selection of drug candidates as well as the development of safe pharmaceutical products. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  8. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial.

    Science.gov (United States)

    Wedam, Erich F; Bigelow, George E; Johnson, Rolley E; Nuzzo, Paul A; Haigney, Mark C P

    2007-12-10

    Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-a-go-go-related gene (hERG)-associated channel in vitro and represents a risk for QT prolongation. To compare the effects of 3 known hERG-associated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioid-addicted subjects. We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioid-addicted participants in a 17-week randomized double-blind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ radical R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or >490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; P methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; P methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P = .08 for the levomethadyl group, P = .01 for the methadone group). Buprenorphine is associated with less QTc prolongation than levomethadyl or methadone and may be a safe alternative.

  9. The etomidate analog ET-26 HCl retains superior myocardial performance: Comparisons with etomidate in vivo and in vitro.

    Science.gov (United States)

    Liu, Xingxing; Song, Haibo; Yang, Jun; Zhou, Cheng; Kang, Yi; Yang, Linghui; Liu, Jin; Zhang, Wensheng

    2018-01-01

    (R)-2-methoxyethyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate hydrochloride (ET-26 HCl) is a novel etomidate analogue. The purpose of this study was to characterize whether ET-26 HCl could retain the superior myocardial performance of etomidate in vivo and in vitro. In vivo, the influence of ET-26 HCl and etomidate on the cardiac function of dogs was confirmed using echocardiography and electrocardiogram. In vitro, a Langendorff preparation was used to examine direct myocardial performance in isolated rat hearts, and a whole-cell patch-clamp technique was used to study effects on the human ether-a-go-go-related gene (hERG) channel. In vivo, after a single bolus administration of ET-26 HCl or etomidate, no significant difference in echocardiography and electrocardiogram parameters was observed. No arrhythmia occurred and no QT interval prolongation happened during the study period. In the in vitro Langendorff preparation, none of the cardiac parameters were abnormal, and the hERG recordings showed that ET-26 HCl and etomidate inhibited the tail current of the hERG in a concentration-dependent manner with an IC50 of 742.51 μM and 263.60 μM, respectively. In conclusion, through an in vivo experiment and a whole organ preparation, the current study found that ET-26 HCl can maintain a myocardial performance that is similar to that of etomidate. In addition, the electrophysiology study indicated that ET-26 HCl and etomidate inhibited the hERG at a supra-therapeutic concentration.

  10. Fast stochastic simulation of biochemical reaction systems by alternative formulations of the chemical Langevin equation

    KAUST Repository

    Mélykúti, Bence

    2010-01-01

    The Chemical Langevin Equation (CLE), which is a stochastic differential equation driven by a multidimensional Wiener process, acts as a bridge between the discrete stochastic simulation algorithm and the deterministic reaction rate equation when simulating (bio)chemical kinetics. The CLE model is valid in the regime where molecular populations are abundant enough to assume their concentrations change continuously, but stochastic fluctuations still play a major role. The contribution of this work is that we observe and explore that the CLE is not a single equation, but a parametric family of equations, all of which give the same finite-dimensional distribution of the variables. On the theoretical side, we prove that as many Wiener processes are sufficient to formulate the CLE as there are independent variables in the equation, which is just the rank of the stoichiometric matrix. On the practical side, we show that in the case where there are m1 pairs of reversible reactions and m2 irreversible reactions there is another, simple formulation of the CLE with only m1 + m2 Wiener processes, whereas the standard approach uses 2 m1 + m2. We demonstrate that there are considerable computational savings when using this latter formulation. Such transformations of the CLE do not cause a loss of accuracy and are therefore distinct from model reduction techniques. We illustrate our findings by considering alternative formulations of the CLE for a human ether a-go-go related gene ion channel model and the Goldbeter-Koshland switch. © 2010 American Institute of Physics.

  11. Compounds that correct F508del-CFTR trafficking can also correct other protein trafficking diseases: an in vitro study using cell lines

    Directory of Open Access Journals (Sweden)

    Sampson Heidi M

    2013-01-01

    Full Text Available Abstract Background Many genetic diseases are due to defects in protein trafficking where the mutant protein is recognized by the quality control systems, retained in the endoplasmic reticulum (ER, and degraded by the proteasome. In many cases, the mutant protein retains function if it can be trafficked to its proper cellular location. We have identified structurally diverse correctors that restore the trafficking and function of the most common mutation causing cystic fibrosis, F508del-CFTR. Most of these correctors do not act directly as ligands of CFTR, but indirectly on other pathways to promote folding and correction. We hypothesize that these proteostasis regulators may also correct other protein trafficking diseases. Methods To test our hypothesis, we used stable cell lines or transient transfection to express 2 well-studied trafficking disease mutations in each of 3 different proteins: the arginine-vasopressin receptor 2 (AVPR2, also known as V2R, the human ether-a-go-go-related gene (KCNH2, also known as hERG, and finally the sulfonylurea receptor 1 (ABCC8, also known as SUR1. We treated cells expressing these mutant proteins with 9 structurally diverse F508del-CFTR correctors that function through different cellular mechanisms and assessed whether correction occurred via immunoblotting and functional assays. Results were deemed significantly different from controls by a one-way ANOVA (p  Results Here we show that F508del-CFTR correctors RDR1, KM60 and KM57 also correct some mutant alleles of other protein trafficking diseases. We also show that one corrector, the cardiac glycoside ouabain, was found to alter the glycosylation of all mutant alleles tested. Conclusions Correctors of F508del-CFTR trafficking might have broader applications to other protein trafficking diseases.

  12. The Role of Human in Relation between Urban Life & Philosophy

    Directory of Open Access Journals (Sweden)

    Qodratullah Qorbani

    2015-06-01

    Full Text Available Historical documents show that urban life and urbanization is the first manifestation of complete form of human life, and it seems that most of human thoughts, like philosophies, were shaped in the cities and urbanizations. It means that the urban life is a society which has many social factors like: social classes and groups, economy, political power, organizations, family, cultures and geographical and environmental circumstances, that they cause to form many thoughts like human philosophies, then we see that most of past philosophers were in the cities in where urbanization was formed and thinkers could think by using of elements which are grown in such urbanizations. So, the being of urban life is necessary for making philosophical thoughts, because there are such social factors of urban living, can effect human's thinking and shape his/her worldview. But we can see the role of humankinds as a free existent who has divine position, intellect and freedom, then, he/she can manage, control and change the impacts of urban factors on philosophical thought. It means that effects of urbanizations and cultures as clear manifestation of urban life on philosophies is possible only by using of human‘s will and thinking as the central factor of the urban life and philosophy, while he/she can control and change these impacts. In fact, although human is under the impact of social and urban factors, he/she is not determined absolutely, but has freedom and intellect to control and change them. So, there is no place for absolute determinism due to social forces of urban life, but it seems there is a kind of intermediate state between absolute determinism and libertarianism. In this paper, it is tries to analysis the role of social and urban factors as the most important elements of the urban life on philosophy and philosophical thinking, and to argue that how human can manage this process.

  13. [Didactic psychodrama: strategy for the humanization of work relations].

    Science.gov (United States)

    Saeki, Toyoko; Corrêa, Adriana Kátia; de Mello Souza, Maria Conceição Bernardo; Zanetti, Maria Lúcia

    2002-01-01

    The aim of this study is to analyze the use of pedagogical psychodrama as a strategy for reflecting on the humanization of health care. Five meetings were held from May to June 2000. In these meetings the following themes were developed: context of work in emergencies; updating of the personal and professional, individual and group reference, and acknowledgement of users. In view of the need of rethinking humanization in emergency care, we consider that the psychodrama approach alerted health professionals for the necessary commitment and responsibility in their work.

  14. Relation between HLA genes, human skin volatiles and attractiveness of humans to malaria mosquitoes

    NARCIS (Netherlands)

    Verhulst, N.O.; Beijleveld, H.; Qiu, Y.T.; Maliepaard, C.A.; Verduyn, W.; Haasnoot, G.W.; Claas, F.H.J.; Mumm, R.; Bouwmeester, H.J.; Takken, W.; Loon, van J.J.A.; Smallegange, R.C.

    2013-01-01

    Chemical cues are considered to be the most important cues for mosquitoes to find their hosts and humans can be ranked for attractiveness to mosquitoes based on the chemical cues they emit. Human leukocyte antigen (HLA) genes are considered to be involved in the regulation of human body odor and may

  15. The human being and the climate, a dangerous relation

    International Nuclear Information System (INIS)

    Bard, E.

    2005-11-01

    The author is analyzing the global warming problem, the human being liability facing the society debate, in front of scientific, economic and political challenges. He presents an history of the climatology from the antiquity to today and enhances the mechanisms involved in the climatic changes, and their effects on the environment and the earth. (A.L.B.)

  16. A multidisciplinary framework for (teaching) human product relations

    NARCIS (Netherlands)

    Eggink, Wouter; van der Bijl-Brouwer, Mieke; Boks, C.; McMahon, C.; Ion, W.; Parkinson, B

    2010-01-01

    In this paper we introduce a framework for dealing with the complexity of human-product relationships. The actual framework is a matrix of design perspectives, with three cooperating disciplines on the one hand and three levels of abstraction on the other hand. Basis of the framework is the notion

  17. Inequity among human service professionals : Measurement and relation to burnout

    NARCIS (Netherlands)

    VanDierendonck, D; Schaufeli, W.B; Buunk, Abraham (Bram)

    1996-01-01

    This research investigated the impact on burnout of inequity experienced by human service professionals. Two studies were conducted, among therapists working with inmates in a forensic psychiatric center (N = 112) and among staff members of an institute for the direct care of mentally disabled (N =

  18. Lipid metabolism in peroxisomes in relation to human disease

    NARCIS (Netherlands)

    Wanders, R. J.; Tager, J. M.

    1998-01-01

    Peroxisomes were long believed to play only a minor role in cellular metabolism but it is now clear that they catalyze a number of important functions. The importance of peroxisomes in humans is stressed by the existence of a group of genetic diseases in man in which one or more peroxisomal

  19. Health Disparity in Human Papilloma Virus Related Infections | Poku ...

    African Journals Online (AJOL)

    In spite of the volume of information of Human Papilloma Virus (HPV) and the HPV vaccines, there are racial and gender differences in the knowledge and awareness of HPV among Guyanese. The study aimed to assess the knowledge and attitude towards HPV infection, cervical cancer and HPV vaccines. The study was ...

  20. Operational safety related human engineering research in Finland

    International Nuclear Information System (INIS)

    Haapanen, P.; Wahlstroem, B.

    1984-01-01

    Human errors contribute considerably to the total risk of the nuclear power plants as was clearly demonstrated at the TMI-accident in 1979. This fact was recognized early in Finland and a comprehensive research program was established in the second half of the 1970s. This paper gives a short description of some research projects in this program. (author)

  1. A Relational Hermeneutical Approach to Human Rights Education

    Science.gov (United States)

    Al-Daraweesh, Fuad

    2010-01-01

    This research is an effort to transcend the debate of universalism and cultural relativism by offering a new conceptualization of human rights. The conceptualization is presented through the development of a theoretical framework in the form of an epistemology. The research articulates and defends the epistemology, which is grounded on…

  2. Relating Eye Activity Measures to Human Controller Remnant Characteristics

    NARCIS (Netherlands)

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

    2016-01-01

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

  3. Human health risk assessment related to cyanotoxins exposure.

    Science.gov (United States)

    Funari, Enzo; Testai, Emanuela

    2008-01-01

    This review focuses on the risk assessment associated with human exposure to cyanotoxins, secondary metabolites of an ubiquitous group of photosynthetic procariota. Cyanobacteria occur especially in eutrophic inland and coastal surface waters, where under favorable conditions they attain high densities and may form blooms and scums. Cyanotoxins can be grouped according to their biological effects into hepatotoxins, neurotoxins, cytotoxins, and toxins with irritating potential, also acting on the gastrointestinal system. The chemical and toxicological properties of the main cyanotoxins, relevant for the evaluation of possible risks for human health, are presented. Humans may be exposed to cyanotoxins via several routes, with the oral one being by far the most important, occurring by ingesting contaminated drinking water, food, some dietary supplements, or water during recreational activities. Acute and short-term toxic effects have been associated in humans with exposure to high levels of cyanotoxins in drinking and bathing waters. However, the chronic exposure to low cyanotoxin levels remains a critical issue. This article identifies the actual risky exposure scenarios, provides toxicologically derived reference values, and discusses open issues and research needs.

  4. Revisiting human behaviour in relation to HIV/AIDS | Bandawe ...

    African Journals Online (AJOL)

    It is widely recognised that human behaviour change is a key element in the fight against HIV/AIDS. The reality of the situation however is that the current approaches to instigating sexual behaviour change appear to have borne little fruit. This paper shall argue that in the fight against HIV/AIDS, a fundamental error is made ...

  5. Praxis and Pedagogy as Related to the Arts and Humanities

    Science.gov (United States)

    Mulcahy, D. G.

    2010-01-01

    Based on a review of its historical evolution and the contributions of significant writers in the field, this article addresses perennial questions of purpose, content and pedagogy in education in the arts and humanities and, more broadly, liberal education. Taking cognizance of the educational significance of service-learning and practical…

  6. Human Metabolism and Interactions of Deployment-Related Chemicals

    National Research Council Canada - National Science Library

    Hodgson, Ernest; Brimfield, Alan A; Goldstein, Joyce E; Rose, Randy L; Wallace, Andrew D

    2008-01-01

    .... The metabolism of chlorpyrifos, DEET, permethrin, pyridostigmine bromide, sulfur mustard, naphthalene and nonane as well as a number of their metabolites and related chemicals was investigated...

  7. Relative significance of natural irradiation vs all human exposures

    International Nuclear Information System (INIS)

    Jammet, H.

    1985-01-01

    A review is made of the fundamentals allowing to quantitatively express the importance of the various sources of human exposure by an individual or collective approach. Following a summary of the components of normal exposure to natural sources, the various human actions at the origin of enhanced exposure are studied: 1) those modifying the relationship between natural sources and man (dwelling conditions, coal burning, geothermal energy production, exploitation of phosphate rock); 2) those creating new artificial sources (nuclear explosions in the atmosphere, nuclear power production, medical use of radiation and radionuclides). The effective dose equivalent commitments for these sources are compared with those necessarily involved by continuous normal exposure to the natural sources of exposure [fr

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

    International Nuclear Information System (INIS)

    Sanchez, Aretha

    2009-01-01

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

  9. DNA-Related Pathways Defective in Human Premature Aging

    OpenAIRE

    Bohr, Vilhelm A.

    2002-01-01

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular path...

  10. Industrial Buying Behavior Related to Human Resource Consulting Services

    DEFF Research Database (Denmark)

    Grünbaum, Niels Nolsøe; Hollensen, Svend; Kahle, Lynn

    2013-01-01

    The purpose of this article is to extend the understanding of the industrial buying process in connection with purchasing professional business (B2B) services, specifically human resource (HR) consulting services. Early B2B buying-behavior literature strongly emphasizes the rational aspects...... of buying behavior in B2B services. Based on a comprehensive exploratory study of Danish companies’ purchases of HR consulting services, the authors provide insights into the factors that determine how Danish companies choose a consulting services supplier. Five hypotheses are developed based...

  11. Electrophysiological CNS-processes related to associative learning in humans.

    Science.gov (United States)

    Christoffersen, Gert R J; Schachtman, Todd R

    2016-01-01

    The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Human-centred automation programme: review of experiment related studies

    International Nuclear Information System (INIS)

    Grimstad, Tone; Andresen, Gisle; Skjerve, Ann Britt Miberg

    2000-04-01

    Twenty-three empirical studies concerning automation and performance have been reviewed. The purposes of the review are to support experimental studies in the Human-Centred Automation (HCA) programme and to develop a general theory on HCA. Each study was reviewed with regard to twelve study characteristics: domain, type of study, purpose, definition of automation, variables, theoretical basis, models of operator performance, methods applied, experimental design, outcome, stated scope of results, strengths and limitations. Seven of the studies involved domain experts, the rest used students as participants. The majority of the articles originated from the aviation domain: only the study conducted in HAMMLAB considered process control in power plants. In the experimental studies, the independent variable was level of automation, or reliability of automation, while the most common dependent variables were workload, situation awareness, complacency, trust, and criteria of performance, e.g., number of correct responses or response time. Although the studies highlight important aspects of human-automation interaction, it is still unclear how system performance is affected. Nevertheless, the fact that many factors seem to be involved is taken as support for the system-oriented approach of the HCA programme. In conclusion, the review provides valuable input both to the design of experiments and to the development of a general theory. (Author). refs

  13. mRNA related to insulin family in human placenta

    International Nuclear Information System (INIS)

    Younes, M.A.; D'Agostino, J.B.; Frazier, M.L.; Besch, P.K.

    1986-01-01

    The authors have previously reported that human term placenta contains mRNA displaying sequence homology to a rat preproinsulin I cDNA clone (p119). When placental poly(A + ) RNA was analyzed for homology to p119 by RNA/DNA blot hybridization, prominent hybridization was observed which was found by densitometric analysis to be three-fold higher than control. To further characterize this insulin-like message, a cDNA library was generated (approx.7000 transformants) using normal term cesarean-sectioned tissue to prepare placental poly(A + ) RNA templates. Five hundred transformants were initially screened by colony hybridization using a 32 P-labeled rat preproinsulin I cDNA as probe. Of the ten initial positives obtained, three were found to be true positives based on Southern hybridization analyses of the recombinant plasmids. Using Taq I digested pBr322 as a size marker, the cDNAs were found to be approximately 300 bp in length. Preliminary DNA sequencing using the Sanger dideoxy chain termination method has revealed that one of these clones displays significant homology to the 5' region of human insulin-like growth factors I and II

  14. mRNA related to insulin family in human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Younes, M.A.; D' Agostino, J.B.; Frazier, M.L.; Besch, P.K.

    1986-03-01

    The authors have previously reported that human term placenta contains mRNA displaying sequence homology to a rat preproinsulin I cDNA clone (p119). When placental poly(A/sup +/) RNA was analyzed for homology to p119 by RNA/DNA blot hybridization, prominent hybridization was observed which was found by densitometric analysis to be three-fold higher than control. To further characterize this insulin-like message, a cDNA library was generated (approx.7000 transformants) using normal term cesarean-sectioned tissue to prepare placental poly(A/sup +/) RNA templates. Five hundred transformants were initially screened by colony hybridization using a /sup 32/P-labeled rat preproinsulin I cDNA as probe. Of the ten initial positives obtained, three were found to be true positives based on Southern hybridization analyses of the recombinant plasmids. Using Taq I digested pBr322 as a size marker, the cDNAs were found to be approximately 300 bp in length. Preliminary DNA sequencing using the Sanger dideoxy chain termination method has revealed that one of these clones displays significant homology to the 5' region of human insulin-like growth factors I and II.

  15. Human resource issues related to an expanding nuclear power programme

    International Nuclear Information System (INIS)

    2006-05-01

    The IAEA Technical Working Group on Training and Qualification of Nuclear Power Plant Personnel recommended that the IAEA develop guidelines on human resource management (including staffing) and training/education programmes for new nuclear power plant (NPP) designs. This recommendation was made in recognition that these future NPPs may have significantly different needs in this area compared to operating plants, and if so, NPP operating organizations should integrate these needs into their planning for future NPP projects. This report is primarily intended for use by NPP operating organizations that already have units in operation and that are considering adding to their fleet. Therefore, the addition of both new and current designs are addressed in this report. However, it should also be of value to those organizations that are considering the initial implementation of nuclear power, as well as decision makers in government, and in other nuclear industry organizations

  16. Verruco-papillary lesions in relation to human papilloma virus

    Directory of Open Access Journals (Sweden)

    Charu Kapoor

    2013-01-01

    Full Text Available Plethora of pathologic conditions may affect the normal morphologic characteristics and intactness of the oral mucosa, presenting as surface alterations.The prevalence of the different types of HPV worldwide has implications for the effectiveness of HPV vaccinations against HPV-induced carcinogenesis. This article discusses HPV related lesions with emphasis on verrucopapillary lesions.

  17. Penerapan Human Relations Dalam Meningkatkan Motivsi Kerja Karyawan di Valentino Boutique Hotel Makassar

    OpenAIRE

    MIRYANTI, INDHIRA; Sultan, Muh. Iqbal; Farid, Muh.

    2011-01-01

    Tujuan Penelitian ini adalah : ( 1 ) Untuk mengetahui Penerapan human relations dalam meningkatkan motivasi kerja karyawan Valentino Boutique Hotel Makassar. ( 2 ) Untuk mengetahui factor ??? factor yang berpengaruh pada human relations untuk meningkatkan motivasi kerja pada Valentino Boutique Hotel Makassar. Penelitian ini dilaksanakan di Valentino Boutique Hotel Makassar. Methode penelitian yang dilakukan adalah analisis deskriptif kualitatif. Sumber data berasal dari observasi study pus...

  18. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    International Nuclear Information System (INIS)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation

  19. Advances in radiation biology: Relative radiation sensitivities of human organ systems. Volume 12

    Energy Technology Data Exchange (ETDEWEB)

    Lett, J.T.; Altman, K.I.; Ehmann, U.K.; Cox, A.B.

    1987-01-01

    This volume is a thematically focused issue of Advances in Radiation Biology. The topic surveyed is relative radiosensitivity of human organ systems. Topics considered include relative radiosensitivities of the thymus, spleen, and lymphohemopoietic systems; relative radiosensitivities of the small and large intestine; relative rediosensitivities of the oral cavity, larynx, pharynx, and esophagus; relative radiation sensitivity of the integumentary system; dose response of the epidermal; microvascular, and dermal populations; relative radiosensitivity of the human lung; relative radiosensitivity of fetal tissues; and tolerance of the central and peripheral nervous system to therapeutic irradiation.

  20. Planetary protection issues related to human missions to Mars

    Science.gov (United States)

    Debus, A.; Arnould, J.

    2008-09-01

    In accordance with the United Nations Outer Space Treaties [United Nations, Agreement Governing the Activities of States on the Moon and Other Celestial Bodies, UN doc A/RES/34/68, resolution 38/68 of December 1979], currently maintained and promulgated by the Committee on Space Research [COSPAR Planetary Protection Panel, Planetary Protection Policy accepted by the COSPAR Council and Bureau, 20 October 2002, amended 24 March 2005, http://www.cosparhq.org/scistr/PPPolicy.htm], missions exploring the Solar system must meet planetary protection requirements. Planetary protection aims to protect celestial bodies from terrestrial contamination and to protect the Earth environment from potential biological contamination carried by returned samples or space systems that have been in contact with an extraterrestrial environment. From an exobiology perspective, Mars is one of the major targets, and several missions are currently in operation, in transit, or scheduled for its exploration. Some of them include payloads dedicated to the detection of life or traces of life. The next step, over the coming years, will be to return samples from Mars to Earth, with a view to increasing our knowledge in preparation for the first manned mission that is likely to take place within the next few decades. Robotic missions to Mars shall meet planetary protection specifications, currently well documented, and planetary protection programs are implemented in a very reliable manner given that experience in the field spans some 40 years. With regards to sample return missions, a set of stringent requirements has been approved by COSPAR [COSPAR Planetary Protection Panel, Planetary Protection Policy accepted by the COSPAR Council and Bureau, 20 October 2002, amended 24 March 2005, http://www.cosparhq.org/scistr/PPPolicy.htm], and technical challenges must now be overcome in order to preserve the Earth’s biosphere from any eventual contamination risk. In addition to the human dimension of

  1. Radiation-related damage to the developing human brain

    International Nuclear Information System (INIS)

    Schull, W.J.; Yoshimaru, Hiroshi; Kyorin Univ., Tokyo

    1989-01-01

    The authors summarize the significant dose-related effects on brain development which have emerged largely within the last six years of study of prenatally exposed A-bomb survivors. The results are described primarily in terms of the DS86 estimates and differences between these and the older T65DR dose estimates are discussed. The severe mental retardation sample was based on 1598 individuals taken from the PE-86 sample, and the intelligence test scores considered from the same sample involved 1673 children. The authors also discuss some of the recent neurobiological developments that appear relevant to an understanding of the biological bases of dose-related events observed, and suggest future research that may contribute either to further delineation of exposure consequences or to the explanation of the cellular and molecular origins of observed effects. (UK)

  2. Human immunodeficiencies related to APC/T cell interaction

    Directory of Open Access Journals (Sweden)

    Marinos eKallikourdis

    2015-08-01

    Full Text Available The primary event for initiating adaptive immune responses is the encounter between T lymphocytes and antigen presenting cells (APC in the T cell area of secondary lymphoid organs and the formation of highly organized inter-cellular junctions referred to as the immune synapses. In vivo live-cell imaging of APC-T cell interactions combined to functional studies unveiled that T cell fate is dictated, in large part, by the stability of the initial contact. Immune cell interaction is equally important during delivery of T cell help to B cells and for the killing of target cells by cytotoxic T cells and NK cells. The critical role of contact dynamics and synapse stability on the immune response is well illustrated by human immune deficiencies in which disease pathogenesis is linked to altered adhesion or defective cross-talk between the synaptic partners. Here we will discuss in details the mechanisms of defective APC-T cell communications in Wiskott-Aldrich syndrome (WAS and in warts, hypogammaglobulinemia, infections, myelokathexis syndrome (WHIM. In addition, we will summarize the evidences pointing to a compromised conjugate formation in WIP deficiency, DOCK8 deficiency and X-linked lymphoproliferative syndrome.

  3. How do different humanness measures relate? Confronting the attribution of secondary emotions, human uniqueness, and human nature traits.

    Science.gov (United States)

    Martínez, Rocío; Rodriguez-Bailon, Rosa; Moya, Miguel; Vaes, Jeroen

    2017-01-01

    The present research examines the relationship between the infrahumanization approach and the two-dimensional model of humanness: an issue that has received very little empirical attention. In Study 1, we created three unknown groups (Humanized, Animalized, and Mechanized) granting/denying them Human Nature (HN) and Human Uniqueness (HU) traits. The attribution of primary/secondary emotions was measured. As expected, participants attributed more secondary emotions to the humanized compared to dehumanized groups. Importantly, both animalized and mechanized groups were attributed similar amounts of secondary emotions. In Study 2, the groups were described in terms of their capacity to express secondary emotions. We measured the attribution of HN/HU traits. Results showed that the infrahumanized group was denied both HU/HN traits. The results highlight the importance of considering the common aspects of both approaches in understanding processes of dehumanization.

  4. "Nutraceuticals" in relation to human skeletal muscle and exercise.

    Science.gov (United States)

    Deane, Colleen S; Wilkinson, Daniel J; Phillips, Bethan E; Smith, Kenneth; Etheridge, Timothy; Atherton, Philip J

    2017-04-01

    Skeletal muscles have a fundamental role in locomotion and whole body metabolism, with muscle mass and quality being linked to improved health and even lifespan. Optimizing nutrition in combination with exercise is considered an established, effective ergogenic practice for athletic performance. Importantly, exercise and nutritional approaches also remain arguably the most effective countermeasure for muscle dysfunction associated with aging and numerous clinical conditions, e.g., cancer cachexia, COPD, and organ failure, via engendering favorable adaptations such as increased muscle mass and oxidative capacity. Therefore, it is important to consider the effects of established and novel effectors of muscle mass, function, and metabolism in relation to nutrition and exercise. To address this gap, in this review, we detail existing evidence surrounding the efficacy of a nonexhaustive list of macronutrient, micronutrient, and "nutraceutical" compounds alone and in combination with exercise in relation to skeletal muscle mass, metabolism (protein and fuel), and exercise performance (i.e., strength and endurance capacity). It has long been established that macronutrients have specific roles and impact upon protein metabolism and exercise performance, (i.e., protein positively influences muscle mass and protein metabolism), whereas carbohydrate and fat intakes can influence fuel metabolism and exercise performance. Regarding novel nutraceuticals, we show that the following ones in particular may have effects in relation to 1 ) muscle mass/protein metabolism: leucine, hydroxyl β-methylbutyrate, creatine, vitamin-D, ursolic acid, and phosphatidic acid; and 2 ) exercise performance: (i.e., strength or endurance capacity): hydroxyl β-methylbutyrate, carnitine, creatine, nitrates, and β-alanine. Copyright © 2017 the American Physiological Society.

  5. Sex-related variation in human behavior and the brain

    Science.gov (United States)

    Hines, Melissa

    2010-01-01

    Male and female fetuses differ in testosterone concentrations beginning as early as week 8 of gestation. This early hormone difference exerts permanent influences on brain development and behavior. Contemporary research shows that hormones are particularly important for the development of sex-typical childhood behavior, including toy choices, which until recently were thought to result solely from sociocultural influences. Prenatal testosterone exposure also appears to influence sexual orientation and gender identity, as well as some, but not all, sex-related cognitive, motor and personality characteristics. Neural mechanisms responsible for these hormone-induced behavioral outcomes are beginning to be identified, and current evidence suggests involvement of the hypothalamus and amygdala, as well as interhemispheric connectivity, and cortical areas involved in visual processing. PMID:20724210

  6. Human resource management and labour relations in the Indian industrial sector

    OpenAIRE

    Rai, Soumi

    2012-01-01

    This paper addresses gaps in research related to study and understanding of Human Resource Management in the context of Indian Automobile sector. The review is based on the available and published literature in peer reviewed journals of reputation and academic standing. A total of 138 papers were reviewed related to the general context of Human Resource Management practices. Of these, about 65 papers were found relevant and relating to understanding of HRM practices in India specifically in t...

  7. [Constant or break? On the relations between human genetics and eugenics in the Twentieth Century].

    Science.gov (United States)

    Germann, Pascal

    2015-07-01

    The history of human genetics has been a neglected topic in history of science and medicine for a long time. Only recently, have medical historians begun to pay more attention to the history of human heredity. An important research question deals with the interconnections between human genetics and eugenics. This paper addresses this question: By focusing on a Swiss case study, the investigation of the heredity of goiter, I will argue that there existed close but also ambiguous relations between heredity research and eugenics in the twentieth century. Studies on human heredity often produced evidence that challenged eugenic aims and ideas. Concurrently, however, these studies fostered visions of genetic improvement of human populations.

  8. Mapping and annotating obesity-related genes in pig and human genomes.

    Science.gov (United States)

    Martelli, Pier Luigi; Fontanesi, Luca; Piovesan, Damiano; Fariselli, Piero; Casadio, Rita

    2014-01-01

    Background. Obesity is a major health problem in both developed and emerging countries. Obesity is a complex disease whose etiology involves genetic factors in strong interplay with environmental determinants and lifestyle. The discovery of genetic factors and biological pathways underlying human obesity is hampered by the difficulty in controlling the genetic background of human cohorts. Animal models are then necessary to further dissect the genetics of obesity. Pig has emerged as one of the most attractive models, because of the similarity with humans in the mechanisms regulating the fat deposition. Results. We collected the genes related to obesity in humans and to fat deposition traits in pig. We localized them on both human and pig genomes, building a map useful to interpret comparative studies on obesity. We characterized the collected genes structurally and functionally with BAR+ and mapped them on KEGG pathways and on STRING protein interaction network. Conclusions. The collected set consists of 361 obesity related genes in human and pig genomes. All genes were mapped on the human genome, and 54 could not be localized on the pig genome (release 2012). Only for 3 human genes there is no counterpart in pig, confirming that this animal is a good model for human obesity studies. Obesity related genes are mostly involved in regulation and signaling processes/pathways and relevant connection emerges between obesity-related genes and diseases such as cancer and infectious diseases.

  9. Humanity as a Contested Concept: Relations between Disability and ‘Being Human’

    Directory of Open Access Journals (Sweden)

    Paul van Trigt

    2016-11-01

    Full Text Available This editorial presents the theme and approach of the themed issue “Humanity as a Contested Concept: Relations between Disability and ‘Being Human’”. The way in which the concept of humanity is or must be related to disability is critically investigated from different disciplinary perspectives in the themed issue, which is, moreover, situated in the field of disability studies and related to discussions about posthumanism. The argument is made that humanity is a concept that needs to be constantly reflected upon from a disability studies perspective. Finally, the contributions of the themed issue are briefly outlined.

  10. Research on Human-Error Factors of Civil Aircraft Pilots Based On Grey Relational Analysis

    Directory of Open Access Journals (Sweden)

    Guo Yundong

    2018-01-01

    Full Text Available In consideration of the situation that civil aviation accidents involve many human-error factors and show the features of typical grey systems, an index system of civil aviation accident human-error factors is built using human factor analysis and classification system model. With the data of accidents happened worldwide between 2008 and 2011, the correlation between human-error factors can be analyzed quantitatively using the method of grey relational analysis. Research results show that the order of main factors affecting pilot human-error factors is preconditions for unsafe acts, unsafe supervision, organization and unsafe acts. The factor related most closely with second-level indexes and pilot human-error factors is the physical/mental limitations of pilots, followed by supervisory violations. The relevancy between the first-level indexes and the corresponding second-level indexes and the relevancy between second-level indexes can also be analyzed quantitatively.

  11. George Herbert Mead on Humans and Other Animals: Social Relations After Human-Animal Studies

    OpenAIRE

    Rhoda Wilkie; Andrew McKinnon

    2013-01-01

    The turn towards nonhuman animals within sociology has shed a critical light on George Herbert Mead, his apparent prioritisation of language and the anthropocentric focus of Symbolic Interactionism (SI). Although Herbert Blumer canonised Mead as the founder of this perspective he also played a key role in excising the evolutionary and 'more-than-human' components in Mead's work. This intervention not only misrepresented Mead's intellectual project, it also made symbols the predominant concern...

  12. Event-related potential correlates of emergent inference in human arbitrary relational learning.

    Science.gov (United States)

    Wang, Ting; Dymond, Simon

    2013-01-01

    Two experiments investigated the functional-anatomical correlates of cognition supporting untrained, emergent relational inference in a stimulus equivalence task. In Experiment 1, after learning a series of conditional relations involving words and pseudowords, participants performed a relatedness task during which EEG was recorded. Behavioural performance was faster and more accurate on untrained, indirectly related symmetry (i.e., learn AB and infer BA) and equivalence trials (i.e., learn AB and AC and infer CB) than on unrelated trials, regardless of whether or not a formal test for stimulus equivalence relations had been conducted. Consistent with previous results, event related potentials (ERPs) evoked by trained and emergent trials at parietal and occipital sites differed only for those participants who had not received a prior equivalence test. Experiment 2 further replicated and extended these behavioural and ERP findings using arbitrary symbols as stimuli and demonstrated time and frequency differences for trained and untrained relatedness trials. Overall, the findings demonstrate convincingly the ERP correlates of intra-experimentally established stimulus equivalence relations consisting entirely of arbitrary symbols and offer support for a contemporary cognitive-behavioural model of symbolic categorisation and relational inference. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Speculative prototypes and alien ethnographies: Experimenting with relations beyond the human

    DEFF Research Database (Denmark)

    Jönsson, Li; Ulv Lenskjold, Tau

    2017-01-01

    This article concerns the role of speculative design prototypes as a means of intervening into everyday life contexts in order to explore, and possibly enable, new kinds of relations between humans and non-human beings. By addressing a human de-centring through design, the aim is to explore what ...... kind of new possibilities might arise when design speculation meets a practice of doing what can be called an ‘alien ethnography’....

  14. Human rights responsibilities of pharmaceutical companies in relation to access to medicines.

    Science.gov (United States)

    Lee, Joo-Young; Hunt, Paul

    2012-01-01

    Although access to medicines is a vital feature of the right to the highest attainable standard of health ("right to health"), almost two billion people lack access to essential medicines, leading to immense avoidable suffering. While the human rights responsibility to provide access to medicines lies mainly with States, pharmaceutical companies also have human rights responsibilities in relation to access to medicines. This article provides an introduction to these responsibilities. It briefly outlines the new UN Guiding Principles on Business and Human Rights and places the human rights responsibilities of pharmaceutical companies in this context. The authors draw from the work of the first UN Special Rapporteur on the right to the highest attainable standard of health, in particular the Human Rights Guidelines for Pharmaceutical Companies in Relation to Access to Medicines that he presented to the UN General Assembly in 2008, and his UN report on GlaxoSmithKline (GSK). While the Guiding Principles on Business and Human Rights are general human rights standards applicable to all business entities, the Human Rights Guidelines for Pharmaceutical Companies consider the specific human rights responsibilities of one sector (pharmaceutical companies) in relation to one area of activity (access to medicines). The article signals the human rights responsibilities of all pharmaceutical companies, with particular attention to patent-holding pharmaceutical companies. Adopting a right-to-health "lens," the article discusses GSK and accountability. The authors argue that human rights should shape pharmaceutical companies' policies, and provide standards in relation to which pharmaceutical companies could, and should, be held accountable. They conclude that it is now crucial to devise independent, accessible, transparent, and effective mechanisms to monitor pharmaceutical companies and hold them publicly accountable for their human rights responsibilities. © 2012 American

  15. Artificial companions: empathy and vulnerability mirroring in human-robot relations

    NARCIS (Netherlands)

    Coeckelbergh, Mark

    2010-01-01

    Under what conditions can robots become companions and what are the ethical issues that might arise in human-robot companionship relations? I argue that the possibility and future of robots as companions depends (among other things) on the robot’s capacity to be a recipient of human empathy, and

  16. A Challenge for Developers: Preserving the Interactivity of Human Relations in a Standalone Application.

    Science.gov (United States)

    Mazur, F. E.

    1993-01-01

    Describes the efforts taken by the Cornell Interactive Theater Ensemble to provide interactive human relations training on date rape using live dramatizations, video with facilitated audience participation, and an electronic multimedia format with decision trees for interactive involvement. (EA)

  17. The Promotion and Integration of Human Rights in EU External Trade Relations

    Directory of Open Access Journals (Sweden)

    Samantha Velluti

    2016-09-01

    Full Text Available The European Union (EU has made the upholding of human rights an integral part of its external trade relations and requires that all trade, cooperation, partnership and association agreements with third countries, including unilateral trade instruments, contain with varying modalities and intensity a commitment to the respect for human rights. The paper discusses selected aspects of the EU’s promotion and integration of human rights in its external trade relations and assesses the impact of the changes introduced by the 2009 Treaty of Lisbon (ToL on EU practice.

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

  19. Attitudes About Human Trafficking: Individual Differences Related to Belief and Victim Blame.

    Science.gov (United States)

    Cunningham, Katherine C; Cromer, Lisa DeMarni

    2016-01-01

    Human trafficking is believed to oppress millions of people worldwide. Despite increased media attention and public awareness campaigns in recent years, no empirical research has examined public attitudes about human trafficking. The present study examined gender, sexual trauma history, and attitudes about human trafficking as they related to belief of a sex-trafficking scenario and willingness to blame the victim for the situation. Undergraduate students (N = 409) at a large private university in the Northeastern United States completed measures in which they responded to a vignette portraying sex trafficking in the United States. Participants also reported their personal trauma history and completed a Human Trafficking Myths Scale. Results indicated that gender and human trafficking myth acceptance, but not sexual trauma history, were significantly related to participants' belief of the sex-trafficking scenario and their perception of the victim's responsibility. Potential implications and directions for future research are discussed. © The Author(s) 2014.

  20. Human fibroblasts display a differential focal adhesion phenotype relative to chimpanzee.

    Science.gov (United States)

    Advani, Alexander S; Chen, Annie Y; Babbitt, Courtney C

    2016-01-01

    There are a number of documented differences between humans and our closest relatives in responses to wound healing and in disease susceptibilities, suggesting a differential cellular response to certain environmental factors. In this study, we sought to look at a specific cell type, fibroblasts, to examine differences in cellular adhesion between humans and chimpanzees in visualized cells and in gene expression. We have found significant differences in the number of focal adhesions between primary human and chimpanzee fibroblasts. Additionally, we see that adhesion related gene ontology categories are some of the most differentially expressed between human and chimpanzee in normal fibroblast cells. These results suggest that human and chimpanzee fibroblasts may have somewhat different adhesive properties, which could play a role in differential disease phenotypes and responses to external factors. © The Author(s) 2016. Published by Oxford University Press on behalf of the Foundation for Evolution, Medicine, and Public Health.

  1. A relation between calculated human body exergy consumption rate and subjectively assessed thermal sensation

    DEFF Research Database (Denmark)

    Simone, Angela; Kolarik, Jakub; Iwamatsu, Toshiya

    2011-01-01

    occupants, it is reasonable to consider both the exergy flows in building and those within the human body. Until now, no data have been available on the relation between human-body exergy consumption rates and subjectively assessed thermal sensation. The objective of the present work was to relate thermal...... sensation data, from earlier thermal comfort studies, to calculated human-body exergy consumption rates. The results show that the minimum human body exergy consumption rate is associated with thermal sensation votes close to thermal neutrality, tending to the slightly cool side of thermal sensation....... Generally, the relationship between air temperature and the exergy consumption rate, as a first approximation, shows an increasing trend. Taking account of both convective and radiative heat exchange between the human body and the surrounding environment by using the calculated operative temperature, exergy...

  2. Ultrastructural age-related changes in the sensory corpuscles of the human genital skin.

    Science.gov (United States)

    Tammaro, A; Parisella, F R; Cavallotti, C; Persechino, S; Cavallotti, C

    2013-01-01

    In human genital skin the majority of superficial sensory corpuscles is represented by glomerular corpuscles. These corpuscles show an own morphology. Our aim is to compare the ultra-structure of superficial sensory corpuscles in the penis skin of younger and older subjects. In this report the ultra-structure of the sensitive corpuscle in the penis skin of the younger and older subjects was compared, showing that the genital skin of the older humans contains more simple complexes than the younger ones. Our findings support the view that the age-related changes that can be observed in human glomerular genital corpuscles are consistent with an increase of the simple complexes and a strong decrease of the poly-lamellar one in the older people. These findings demonstrate that human genital corpuscles underwent age-related changes. Moreover our morphological findings can be correlated in relation to the clinical evolution of the sensitivity in the genital skin.

  3. Pengembangan Human Relation Perspektif Nilai-nilai al-Qur’an

    Directory of Open Access Journals (Sweden)

    Ahmad Fauzi

    2015-09-01

    Full Text Available Not least the manager (leader who failed to carry out its duties and functions. This is largely due to the lack of attention to the human relations aspect in building a spirit of togetherness as one of the most dominant factor in the success of management. Since the beginning of its creation, mankind has been designed as a creature who can not live alone. Therefore, one man inevitably need to Communicate and Interact with other human beings. This study intends to examine the conceptual meaning of human relations and the urgency with psychological and sociological approach in the perspective of the values of the Koran, Because The Qur’anic principle is to guide human life. The shift in the orientation of this communication is Inseparable from the human relations that is increasingly widespread and seamless, everyone can relate to anyone who desired, Including Westerners and their world. The existence of two human relationships that must be Followed by two cultures is then led to the change tendency of the relations between the two models

  4. Concentration and distribution of dioxins and related compounds in various human organs

    Energy Technology Data Exchange (ETDEWEB)

    Iida, T.; Hirakawa, H.; Hori, T.; Tobiishi, K.; Matsueda, T. [Fukuoka Inst. of Health and Environmental Sciences, Dazaifu, Fukuoka (Japan); Todaka, T. [Japan Food Hygiene Association, Tokyo (Japan); Watanabe, S. [Tokyo Univ. of Agriculture, Tokyo (Japan); Yamada, T. [Keio Univ. School of Medicine, Tokyo (Japan)

    2004-09-15

    Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho coplanar polychlorinated biphenyls (Non-Co-PCBs) and mono-ortho coplanar polychlorinated biphenyls (Mono-Co-PCBs) accumulate in the human body due to their highly lipophilic properties. In recent years, there has been some concern about the potential health effects of dioxins and related chemicals for the general population of humans. Although there exists an enormous amount of data on this subject, most of it is from breast milk and blood, due to ease of collection; information concerning concentrations and distribution in various human organs hardly exists. Therefore, new data concerning various human tissues is required to evaluate the pathophysiological significance of dioxins and related compounds in humans. The aim of this study was to investigate the concentration levels and distribution of dioxins and related compounds in various human organ tissues. We previously reported on the concentration levels in the human liver and adipose tissues from 28 donors. In this paper, we determined the concentrations of dioxin-like isomers in 8 organs, including blood, lungs, liver, bile, spleen, pancreas, kidney and mesentery fat from 20 donors.

  5. Human rights on the thin red line between universality and relativity

    Directory of Open Access Journals (Sweden)

    Avramović Dragutin

    2014-01-01

    Full Text Available Human rights represent an open legal and political concept with a very wide value variable. Academic discussions on human rights nature have mostly commenced after the World War II during the trend of human rights internationalization, reaching their climax after the Cold war. This paper examines actual theories on human rights, from those accepting them as universal, up to those marking another pole, favoring idea of absolute relativity of human rights. The author asserts that the most acceptable should be a middle solution, standing of moderate relativism or position of relative universalism of human rights. He claims that only a very limited circle of basic, 'substantial' human rights, having been accepted through an intercultural consensus, may pretend to be treated as universal. Out of that narrow sphere, there are many other human rights whose meaning and interpretation depend strongly upon concrete cultural context. The author points that in those cases it is important to respect a relativistic discourse and that the only solution should be explored within an intercultural and inter-civilizational dialogue, where non-western values should be equally treated as the western ones.

  6. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment

    DEFF Research Database (Denmark)

    Kessel, Line; Lundeman, Jesper Holm; Herbst, Kristina

    2010-01-01

    To characterize age-related changes in the transmission of light through noncataractous human lenses.......To characterize age-related changes in the transmission of light through noncataractous human lenses....

  7. EDUCATION, WORK AND THEIR RELATIONS THROUGHOUT HISTORY OF HUMANITY IN DIFFERENT MODES OF PRODUCTION OF EXISTENCE

    Directory of Open Access Journals (Sweden)

    Denize Cristina Kaminski Ferreira

    2011-12-01

    Full Text Available The present article has as objective to analyze the relation between education and work throughout the history of the humanity, for in such a way, the starting point is the conceptualization of the related categories, as well as the exposition of its variations and relation in the different ways of material production of the existence human being (primitive community, slavery society, feudal system and capitalism, aiming at to apprehend the multiple influences that both exert between itself, in order to make possible a bigger understanding of the historical and social evolution of the man

  8. Prediction and characterization of human ageing-related proteins by using machine learning.

    Science.gov (United States)

    Kerepesi, Csaba; Daróczy, Bálint; Sturm, Ádám; Vellai, Tibor; Benczúr, András

    2018-03-06

    Ageing has a huge impact on human health and economy, but its molecular basis - regulation and mechanism - is still poorly understood. By today, more than three hundred genes (almost all of them function as protein-coding genes) have been related to human ageing. Although individual ageing-related genes or some small subsets of these genes have been intensively studied, their analysis as a whole has been highly limited. To fill this gap, for each human protein we extracted 21000 protein features from various databases, and using these data as an input to state-of-the-art machine learning methods, we classified human proteins as ageing-related or non-ageing-related. We found a simple classification model based on only 36 protein features, such as the "number of ageing-related interaction partners", "response to oxidative stress", "damaged DNA binding", "rhythmic process" and "extracellular region". Predicted values of the model quantify the relevance of a given protein in the regulation or mechanisms of the human ageing process. Furthermore, we identified new candidate proteins having strong computational evidence of their important role in ageing. Some of them, like Cytochrome b-245 light chain (CY24A) and Endoribonuclease ZC3H12A (ZC12A) have no previous ageing-associated annotations.

  9. Women's awareness of the human papilloma virus and related health problems.

    Science.gov (United States)

    Akyuz, Aygul; Yılmaz, Cevriye; Yenen, Müfit Cemal; Yavan, Tülay; Kılıç, Ayşe

    2011-12-01

    This paper is a report of a study of women's awareness of the human papilloma virus and related health problems. Cervical cancer is an important cause of mortality, making up approximately 12% of all cancers in women. Awareness on the part of carriers of human papilloma virus is crucial in preventing transmission of the infection and protecting against cervical cancer. The study was performed as a cross-sectional descriptive study. The study consists of 79 human papilloma virus-positive women who had not been diagnosed with cervical cancer and 150 women who had not been diagnosed with human papilloma virus. Data were collected via questionnaires between November 2007 and April 2008. Percentages and chi-square test were used. A significantly higher percentage of women with positive human papilloma virus knew the definition of human papilloma virus, the fact that it is transmitted via sexual contact and that it can lead to cervical cancer than did women with negative human papilloma virus. It was established that approximately half the women with positive human papilloma virus presented at the hospital with a genital wart. None of the women knew that a Pap smear test was a necessary tool in the prevention of cervical cancer. Women with positive human papilloma virus have insufficient knowledge of human papilloma virus, sexually transmitted diseases, the health risks associated with human papilloma virus and the means of preventing these risks. It is therefore necessary to evaluate the education of health workers, and especially of nurses, on human papilloma virus and its prevention. © 2011 Blackwell Publishing Ltd.

  10. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia

    OpenAIRE

    Muñoz, José F.; Gauthier, Gregory M.; Desjardins, Christopher A.; Gallo, Juan E.; Holder, Jason; Sullivan, Thomas D.; Marty, Amber J.; Carmen, John C.; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret

    2015-01-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated...

  11. Human fertility variation, size-related obstetrical performance and the evolution of sexual stature dimorphism

    OpenAIRE

    Guégan, Jean-François; Teriokhin, A.T.; Thomas, F.

    2000-01-01

    In several animal species, change in sexual size dimorphism is a correlated response to selection on fecundity. In humans, different hypotheses have been proposed to explain the variation of sexual dimorphism in stature, but no consensus has yet emerged. In this paper, we evaluate from a theoretical and an empirical point of view the hypothesis that the extent of sexual dimorphism in human populations results from the interaction between fertility and size-related obstetric complications. We ...

  12. Nuclear safety regulation on nuclear safety equipment activities in relation to human and organizational factors

    International Nuclear Information System (INIS)

    Li Tianshu

    2013-01-01

    Based on years of knowledge in nuclear safety supervision and experience of investigating and dealing with violation events in repair welding of DFHM, this paper analyzes major faults in manufacturing and maintaining activities of nuclear safety equipment in relation to human and organizational factors. It could be deducted that human and organizational factors has definitely become key features in the development of nuclear energy and technology. Some feasible measures to reinforce supervision on nuclear safety equipment activities have also been proposed. (author)

  13. Concentrations of trace elements in human tissues and relation of ratios of mutual metals to the human health

    International Nuclear Information System (INIS)

    Ling-wei, X.; Shao-xian, L.; Xiao-juan, Z.

    1989-01-01

    According to the experimental results, the concentrations and concentrations in order, of trace elements in human tissues among Changsha's People in China are reported. The authors particularly present that the ratios of mutual metals (M/N) in normal physiological tissues and fluids are very important factors which indicate the metabolic situations of trace elements in the body and as the indices which evaluate the situation of human health. (M and N mean the concentrations of different trace elements in the tissues or fluids, respectively.) Up to now, it is still an interesting field to study the functions of trace elements for the human health. There are previously some reports about the concentrations of trace elements in normal physiological tissues/ or organs and fluids of human body. These provide very valuable data for biological medicine. In the study presented atomic absorption method was adopted in order to determine the concentrations of Zn, Cu, Mn, Ni, Pb and Cd in human tissues (liver, spleen, kidney, bone, lung, pancreas, heart and artery and muscle) at autopsy. The authors suggest that trace elements, are contained in the body in an aproportional way, in normal physiological tissues and fluids, and the ratios may directly indicate metabolic situation of trace elements in the body which further reveal the mystery of trace elements for human health. Therefore, the ratios M/N as an indicator of health is more proper than that only using concentrations of trace elements. Schroeder (1973) reported that incidence of heart disease is related to the imbalance of ration Zn/Cd and Zn/Cu rather than the concentrations of Zn, Cd, Cu, and the intellectual development also depends on the proper proportion among copper, cadmium, lead, zinc in the body

  14. An interdisciplinary review of current and future approaches to improving human-predator relations.

    Science.gov (United States)

    Pooley, S; Barua, M; Beinart, W; Dickman, A; Holmes, G; Lorimer, J; Loveridge, A J; Macdonald, D W; Marvin, G; Redpath, S; Sillero-Zubiri, C; Zimmermann, A; Milner-Gulland, E J

    2017-06-01

    In a world of shrinking habitats and increasing competition for natural resources, potentially dangerous predators bring the challenges of coexisting with wildlife sharply into focus. Through interdisciplinary collaboration among authors trained in the humanities, social sciences, and natural sciences, we reviewed current approaches to mitigating adverse human-predator encounters and devised a vision for future approaches to understanding and mitigating such encounters. Limitations to current approaches to mitigation include too much focus on negative impacts; oversimplified equating of levels of damage with levels of conflict; and unsuccessful technical fixes resulting from failure to engage locals, address hidden costs, or understand cultural (nonscientific) explanations of the causality of attacks. An emerging interdisciplinary literature suggests that to better frame and successfully mitigate negative human-predator relations conservation professionals need to consider dispensing with conflict as the dominant framework for thinking about human-predator encounters; work out what conflicts are really about (they may be human-human conflicts); unravel the historical contexts of particular conflicts; and explore different cultural ways of thinking about animals. The idea of cosmopolitan natures may help conservation professionals think more clearly about human-predator relations in both local and global context. These new perspectives for future research practice include a recommendation for focused interdisciplinary research and the use of new approaches, including human-animal geography, multispecies ethnography, and approaches from the environmental humanities notably environmental history. Managers should think carefully about how they engage with local cultural beliefs about wildlife, work with all parties to agree on what constitutes good evidence, develop processes and methods to mitigate conflicts, and decide how to monitor and evaluate these. Demand for

  15. Gender-related differences in the human rights needs of patients with mental illness.

    Science.gov (United States)

    Vijayalakshmi, Poreddi; Reddemma, Konduru; Math, Suresh Bada

    2012-06-01

    Individuals with mental illness commonly experience human rights violations while seeking to meet their basic needs. There is lack of research in developing countries on gender-related differences in human rights needs. This study investigated gender differences in perceived human rights needs at the family and community levels in individuals with mental illness in India. This descriptive study surveyed 100 asymptomatic individuals with mental illness at a tertiary care center. Subject selection employed a random sampling method. Data were collected using face-to-face interviews based on a structured needs assessment questionnaire. Data were analyzed and interpreted using descriptive and inferential statistics. Subjects enjoyed a satisfactory level of fulfillment in the physical dimension of human rights needs, which included food, housing, and clothing. Men expressed lower satisfaction than women with perceived human rights needs fulfillment in the emotional dimension. This included fear of family members (χ = 9.419, p human rights needs fulfillment in social and ethical dimensions. The former included freedom to leave the home (χ = 11.277, p human rights needs of people with mental illness and that legislation must be strengthened to meet the human rights needs of this disadvantaged population.

  16. Concomitant Human Herpes Virus 6 and nivolumab-related pneumonitis: Potential pathogenetic insights

    Directory of Open Access Journals (Sweden)

    Periklis G. Foukas

    2018-01-01

    Full Text Available The development of immune system modulating agents, such as immune checkpoint inhibitors (ICIs, has revolutionized cancer treatment. Nivolumab, a human monoclonal antibody against PD-1, has emerged as an efficient treatment for various malignancies, including non-small cell lung cancer (NSCLC; however, it is associated with important immune related side-effects, attributed to organ-specific inflammation, such as immune-mediated pneumonitis, a relatively uncommon, albeit potentially fatal adverse event. We herein present the unique case of severe interstitial pneumonitis with concomitant detection of Human Herpes Virus 6 (HHV-6 in a nivolumab treated patient with NSCLC. Potential pathogenetic mechanisms are discussed.

  17. Age-related changes of MAO-A and -B distribution in human and mouse brain.

    Science.gov (United States)

    Mahy, N; Andrés, N; Andrade, C; Saura, J

    2000-01-01

    Age-related changes of MAO-A and -B were studied in human and BL/C57 mouse brain areas (substantia nigra, putamen and cerebellum). [3H]Ro41-1049 and [3H]lazabemide were used as selective radioligands to image and quantify MAO-A and MAO-B respectively by enzyme autoradiography. MAO-A binding was higher in mouse, whereas MAO-B binding was higher in human. With aging, mouse MAO-A was significantly reduced between 4 and 8 weeks and remained unchanged until 19 months followed by a slight increase between 19 and 25 months. In contrast, no clear variation was observed in humans between the age of 17-93 years. In most of the structures studied a clear age-related increase in MAO-B was observed beginning in mouse brain at 4 weeks, whereas in human tissue this increase started at the age of 50-60 years. These results show marked differences in the levels and variations of mouse and human MAO-A and -B associated with aging and should be taken into account when extrapolating experimental data from mouse to human.

  18. Factors of human capital related to project success in health care work units.

    Science.gov (United States)

    Suhonen, Marjo; Paasivaara, Leena

    2011-03-01

    To explore factors of human capital related to project success that employees expect from nurse managers. Human capital refers to those resources that managers working with projects possess, such as abilities, knowledge and qualities of character. The data were collected by open interviews (n=14) with nurses, public health nurses and nurse managers working in primary health care and a hospital. Data analysis was carried out using qualitative content analysis. The main factors of human capital related to project success proved to be as follows: (1) management of enthusiastic project culture, (2) management of regeneration and (3) management of emotional intelligence. Future research is needed on the kind of means nurse managers use in human capital management in projects and how they see their possibilities in managing human capital. Human capital management skills should be underlined as an important competence area when recruiting a nurse manager. The success of health care projects cannot be improved only through education or by training of nurse managers; in addition, projects need nurse managers who understand workplace spirituality and have high emotional intelligence. © 2011 The Authors. Journal compilation © 2011 Blackwell Publishing Ltd.

  19. Intrinsic interactive reinforcement learning - Using error-related potentials for real world human-robot interaction.

    Science.gov (United States)

    Kim, Su Kyoung; Kirchner, Elsa Andrea; Stefes, Arne; Kirchner, Frank

    2017-12-14

    Reinforcement learning (RL) enables robots to learn its optimal behavioral strategy in dynamic environments based on feedback. Explicit human feedback during robot RL is advantageous, since an explicit reward function can be easily adapted. However, it is very demanding and tiresome for a human to continuously and explicitly generate feedback. Therefore, the development of implicit approaches is of high relevance. In this paper, we used an error-related potential (ErrP), an event-related activity in the human electroencephalogram (EEG), as an intrinsically generated implicit feedback (rewards) for RL. Initially we validated our approach with seven subjects in a simulated robot learning scenario. ErrPs were detected online in single trial with a balanced accuracy (bACC) of 91%, which was sufficient to learn to recognize gestures and the correct mapping between human gestures and robot actions in parallel. Finally, we validated our approach in a real robot scenario, in which seven subjects freely chose gestures and the real robot correctly learned the mapping between gestures and actions (ErrP detection (90% bACC)). In this paper, we demonstrated that intrinsically generated EEG-based human feedback in RL can successfully be used to implicitly improve gesture-based robot control during human-robot interaction. We call our approach intrinsic interactive RL.

  20. A relation between calculated human body exergy consumption rate and subjectively assessed thermal sensation

    Energy Technology Data Exchange (ETDEWEB)

    Simone, Angela; Kolarik, Jakub; Olesen, Bjarne W. [ICIEE/BYG, Technical University of Denmark (Denmark); Iwamatsu, Toshiya [Faculty of Urban Environmental Science, Tokyo Metropolitan University (Japan); Asada, Hideo [Architech Consulting Co., Tokyo (Japan); Dovjak, Mateja [Faculty of Civil and Geodetic Engineering, University of Ljubljana (Slovenia); Schellen, Lisje [Eindhoven University of Technology, Faculty of Architecture Building and Planning (Netherlands); Shukuya, Masanori [Laboratory of Building Environment, Tokyo City University, Yokohama (Japan)

    2011-01-15

    Application of the exergy concept to research on the built environment is a relatively new approach. It helps to optimize climate conditioning systems so that they meet the requirements of sustainable building design. As the building should provide a healthy and comfortable environment for its occupants, it is reasonable to consider both the exergy flows in building and those within the human body. Until now, no data have been available on the relation between human-body exergy consumption rates and subjectively assessed thermal sensation. The objective of the present work was to relate thermal sensation data, from earlier thermal comfort studies, to calculated human-body exergy consumption rates. The results show that the minimum human body exergy consumption rate is associated with thermal sensation votes close to thermal neutrality, tending to the slightly cool side of thermal sensation. Generally, the relationship between air temperature and the exergy consumption rate, as a first approximation, shows an increasing trend. Taking account of both convective and radiative heat exchange between the human body and the surrounding environment by using the calculated operative temperature, exergy consumption rates increase as the operative temperature increases above 24 C or decreases below 22 C. With the data available so far, a second-order polynomial relationship between thermal sensation and the exergy consumption rate was established. (author)

  1. A Quantitative Index to Support Recurrence Prevention Plans of Human-Related Events

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yochan; Park, Jinkyun; Jung, Wondea [KAERI, Daejeon (Korea, Republic of); Kim, Do Sam; Lee, Durk Hun [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

    2015-05-15

    In Korea, HuRAM+ (Human related event Root cause Analysis Method plus) was developed to scrutinize the causes of the human-related events. The information of the human-related events investigated by the HuRAM+ method has been also managed by a database management system, R-tracer. It is obvious that accumulating data of human error causes aims to support plans that reduce recurrences of similar events. However, in spite of the efforts for the development of the human error database, it was indicated that the database does not provide useful empirical basis for establishment of the recurrence prevention plans, because the framework to interpret the collected data and apply the insights from the data into the prevention plants has not been developed yet. In this paper, in order to support establishment of the recurrence prevention plans, a quantitative index, Human Error Repeat Interval (HERI), was proposed and its applications to human error prevention were introduced. In this paper, a quantitative index, the HERI was proposed and the statistics of HERIs were introduced. These estimations can be employed to evaluate effects of recurrence prevention plans to human errors. If a mean HERI score is low and the linear trend is not positive, it can be suspected that the recurrence prevention plans applied every human-related event has not been effectively propagated. For reducing repetitive error causes, the system design or operational culture can be reviewed. If there is a strong and negative trend, systematic investigation of the root causes behind these trends is required. Likewise, we expect that the HERI index will provide significant basis for establishing or adjusting prevention plans of human errors. The accurate estimation and application of HERI scores is expected to be done after accumulating more data. When a scatter plot of HERIs is fitted by two or more models, a statistical model selection method can be employed. Some criteria have been introduced by

  2. A Quantitative Index to Support Recurrence Prevention Plans of Human-Related Events

    International Nuclear Information System (INIS)

    Kim, Yochan; Park, Jinkyun; Jung, Wondea; Kim, Do Sam; Lee, Durk Hun

    2015-01-01

    In Korea, HuRAM+ (Human related event Root cause Analysis Method plus) was developed to scrutinize the causes of the human-related events. The information of the human-related events investigated by the HuRAM+ method has been also managed by a database management system, R-tracer. It is obvious that accumulating data of human error causes aims to support plans that reduce recurrences of similar events. However, in spite of the efforts for the development of the human error database, it was indicated that the database does not provide useful empirical basis for establishment of the recurrence prevention plans, because the framework to interpret the collected data and apply the insights from the data into the prevention plants has not been developed yet. In this paper, in order to support establishment of the recurrence prevention plans, a quantitative index, Human Error Repeat Interval (HERI), was proposed and its applications to human error prevention were introduced. In this paper, a quantitative index, the HERI was proposed and the statistics of HERIs were introduced. These estimations can be employed to evaluate effects of recurrence prevention plans to human errors. If a mean HERI score is low and the linear trend is not positive, it can be suspected that the recurrence prevention plans applied every human-related event has not been effectively propagated. For reducing repetitive error causes, the system design or operational culture can be reviewed. If there is a strong and negative trend, systematic investigation of the root causes behind these trends is required. Likewise, we expect that the HERI index will provide significant basis for establishing or adjusting prevention plans of human errors. The accurate estimation and application of HERI scores is expected to be done after accumulating more data. When a scatter plot of HERIs is fitted by two or more models, a statistical model selection method can be employed. Some criteria have been introduced by

  3. Victims of ‘private’ crimes and application of human rights in interpersonal relations

    Directory of Open Access Journals (Sweden)

    Reiter Axelle

    2013-01-01

    Full Text Available International human rights law has been challenged because of its alleged inability to safeguard the rights of the most vulnerable victims of violence. Whereas in real life they are often marginalized and effectively left without adequate protection, this is not to be attributed to the absence of an appropriate normative framework but rather to the contempt, lack of enforcement and systemic neglect of their claims. This paper proposes to find a ‘cure’ inside international human rights law, by strengthening the mechanisms that permit a horizontal application of human rights standards in private relations. The paper is divided in four sections. The first section describes the problematic at hand, focusing in particular on violence against women and children. The three subsequent sections then analyze the avenues open to victims in order to claim a ‘third-party’ application of human rights treaties against non-state actors who have violated their fundamental rights.

  4. Sex ratio at birth and mortality rates are negatively related in humans.

    Directory of Open Access Journals (Sweden)

    Madhukar Shivajirao Dama

    Full Text Available Evolutionary theory posits that resource availability and parental investment ability could signal offspring sex selection, in order to maximize reproductive returns. Non-human studies have provided evidence for this phenomenon, and maternal condition around the time of conception has been identified as most important factor that influence offspring sex selection. However, studies on humans have reported inconsistent results, mostly due to use of disparate measures as indicators of maternal condition. In the present study, the cross-cultural differences in human natal sex ratio were analyzed with respect to indirect measures of condition namely, life expectancy and mortality rate. Multiple regression modeling suggested that mortality rates have distinct predictive power independent of cross-cultural differences in fertility, wealth and latitude that were earlier shown to predict sex ratio at birth. These findings suggest that sex ratio variation in humans may relate to differences in parental and environmental conditions.

  5. Potential human factors research relating to modern technology in nuclear power plants

    International Nuclear Information System (INIS)

    Ketchel, J.; Fink, R.; Hanes, L.; Williges, R.; Williges, B.

    1994-01-01

    This paper discusses proposed human factors research to address advanced human-machine interface technology in nuclear power plants. It relates to a current EPRI project to identify a prioritized list of specific research issues that could be assessed to improve control room and other user interface areas. The project seeks to bridge the gap between the functional requirements of advanced design initiatives and the human factors research needed to support them. It seeks to identify potential benefits to be expected, as well as potential problems that might be introduced by advanced technology. It provides an organized approach to identifying human factors research needs, information already available, and measures of performance and effectiveness that might be used to assess the value of potential improvements. Those parts of the proposed plan that are subsequently approved by EPRI management and by the utility advisory committee will provide a basis for recommending research priorities

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

    International Nuclear Information System (INIS)

    Nishiwaki, Yasushi

    1988-01-01

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

  7. Axon guidance pathways served as common targets for human speech/language evolution and related disorders.

    Science.gov (United States)

    Lei, Huimeng; Yan, Zhangming; Sun, Xiaohong; Zhang, Yue; Wang, Jianhong; Ma, Caihong; Xu, Qunyuan; Wang, Rui; Jarvis, Erich D; Sun, Zhirong

    2017-11-01

    Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data. In normal human populations, we found the affected amino acid sites were well fixed and accompanied with significantly more associated protein-coding SNPs in the same genes than the rest genes. Diseased individuals with speech/language disorders have significant more low frequency protein coding SNPs but they preferentially occurred outside the affected genes. Such patients' SNPs were enriched in several functional categories including two axon guidance pathways (mediated by netrin and semaphorin) that interact with ROBO-SLITs. Four of the six patients have homozygous missense SNPs on PRAME gene family, one youngest gene family in human lineage, which possibly acts upon retinoic acid receptor signaling, similarly as FOXP2, to modulate axon guidance. Taken together, we suggest the axon guidance pathways (e.g. ROBO-SLIT, PRAME gene family) served as common targets for human speech/language evolution and related disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Relative influences of climate change and human activity on the onshore distribution of polar bears

    Science.gov (United States)

    Wilson, Ryan R.; Regehr, Eric V.; St. Martin, Michelle; Atwood, Todd C.; Peacock, Elizabeth; Miller, Susanne; Divoky, George J.

    2017-01-01

    Climate change is altering habitat for many species, leading to shifts in distributions that can increase levels of human-wildlife conflict. To develop effective strategies for minimizing human-wildlife conflict, we must understand the relative influences that climate change and other factors have on wildlife distributions. Polar bears (Ursus maritimus) are increasingly using land during summer and autumn due to sea ice loss, leading to higher incidents of conflict and concerns for human safety. We sought to understand the relative influence of sea ice conditions, onshore habitat characteristics, and human-provisioned food attractants on the distribution and abundance of polar bears while on shore. We also wanted to determine how mitigation measures might reduce human-polar bear conflict associated with an anthropogenic food source. We built a Bayesian hierarchical model based on 14 years of aerial survey data to estimate the weekly number and distribution of polar bears on the coast of northern Alaska in autumn. We then used the model to predict how effective two management options for handling subsistence-harvested whale remains in the community of Kaktovik, Alaska might be. The distribution of bears on shore was most strongly influenced by the presence of whale carcasses and to a lesser extent sea ice and onshore habitat conditions. The numbers of bears on shore were related to sea ice conditions. The two management strategies for handling the whale carcasses reduced the estimated number of bears near Kaktovik by > 75%. By considering multiple factors associated with the onshore distribution and abundance of polar bears we discerned what role human activities played in where bears occur and how successful efforts to manage the whale carcasses might be for reducing human-polar bear conflict.

  9. Stable iodine contents in human milk related to dietary algae consumption

    International Nuclear Information System (INIS)

    Muramatsu, Yasuyuki; Sumiya, Misako; Ohmomo, Yoichiro

    1983-01-01

    Studies were carried out to investigate iodine contents in human milk with relation to dietary algae consumption by nursing women and to estimate stable iodine intake by breast-fed babies. The iodine contents in human milk collected from the Tokai-mura area showed a fairly wide variation ranging from 80 to 7,000 μg/l, though the highest frequency was around 150 μg/l. It was observed that high contents were closely related to the intake of tangle (Konbu), Laminariaceae, specifically tangle stock and/or tangle shavings (Tororokonbu) as soup. The temporal increase was followed by the rapid decrease when the mothers stopped taking the tangle stock and/or tangle shavings soup. It was observed that water-extractability of iodine from tangle was much higher than that from the other algae, and the water-extractable iodine was absorbable to the human body. (author)

  10. Prediction of the Ebola Virus Infection Related Human Genes Using Protein-Protein Interaction Network.

    Science.gov (United States)

    Cao, HuanHuan; Zhang, YuHang; Zhao, Jia; Zhu, Liucun; Wang, Yi; Li, JiaRui; Feng, Yuan-Ming; Zhang, Ning

    2017-01-01

    Ebola hemorrhagic fever (EHF) is caused by Ebola virus (EBOV). It is reported that human could be infected by EBOV with a high fatality rate. However, association factors between EBOV and host still tend to be ambiguous. According to the "guilt by association" (GBA) principle, proteins interacting with each other are very likely to function similarly or the same. Based on this assumption, we tried to obtain EBOV infection-related human genes in a protein-protein interaction network using Dijkstra algorithm. We hope it could contribute to the discovery of novel effective treatments. Finally, 15 genes were selected as potential EBOV infection-related human genes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Time-related contact angle measurements with human plasma on biomaterial surfaces

    NARCIS (Netherlands)

    Rakhorst, G; Van der Mei, HC; van Oeveren, W; Spijker, HT; Busscher, HJ

    Axisymmetric drop shape analysis by profile (ADSA-P) was used to assess in time contact angle changes of human plasma drops placed on four different biomaterials. Results were related with conventional blood compatibility measurements: albumin adsorption, fibrinogen adsorption and platelet adhesion.

  12. Toward a 21st-Century Understanding of Humans' Relation to Nature: Two Hats?

    Science.gov (United States)

    Rennie, Scott

    2008-01-01

    From its inception, environmental education (EE) has shouldered the imposition of impartiality on its methods and practices. Considering the reality of global climate change, the author urges the adoption of the more accurate theory of humans' relation to the natural world. This theory necessitates partiality toward healthy, functioning natural…

  13. The Human Relations Class at Sir Winston Churchill Secondary School. Research Report.

    Science.gov (United States)

    Gilbert, Katherine J.

    Human Relations was a program offered to Grade 10 students at Churchill Secondary School during the 1971-72 school year in lieu of four courses. The emphasis of the program was on the development of students as people who were more aware of themselves, of other people, and of the environment. The class took part in a variety of activities during…

  14. A Feminist Posthumanist Political Ecology of Education for Theorizing Human-Animal Relations/Relationships

    Science.gov (United States)

    Lloro-Bidart, Teresa

    2017-01-01

    This paper contributes to a nascent conversation in environmental education (EE) research by using ethnographic data and extant theory to develop a feminist posthumanist political ecology of education for theorizing human-animal relations/relationships. Specifically, I (1) engage feminist methodologies and theories; (2) give epistemological and…

  15. Social Capital, Human Capital and Parent-Child Relation Quality: Interacting for Children's Educational Achievement?

    Science.gov (United States)

    von Otter, Cecilia; Stenberg, Sten-Åke

    2015-01-01

    We analyse the utility of social capital for children's achievement, and if this utility interacts with family human capital and the quality of the parent-child relationship. Our focus is on parental activities directly related to children's school work. Our data stem from a Swedish cohort born in 1953 and consist of both survey and register data.…

  16. Snake scales, partial exposure, and the Snake Detection Theory: A human event-related potentials study

    NARCIS (Netherlands)

    J.W. van Strien (Jan); L.A. Isbell (Lynne A.)

    2017-01-01

    textabstractStudies of event-related potentials in humans have established larger early posterior negativity (EPN) in response to pictures depicting snakes than to pictures depicting other creatures. Ethological research has recently shown that macaques and wild vervet monkeys respond strongly to

  17. Human Resource Development (HRD) Evaluation and Principles Related to the Public Interest

    Science.gov (United States)

    Russ-Eft, Darlene F.

    2009-01-01

    This paper examines the issues involved in the use of ethical standards related to social responsibility using the two ethical codes: the American Evaluation Association "Guiding Principles for Evaluators" and the Academy of Human Resource Development "Standards on Ethics and Integrity." This examination will take the perspective of an internal…

  18. Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe.

    Science.gov (United States)

    Annan, Augustina; Baldwin, Heather J; Corman, Victor Max; Klose, Stefan M; Owusu, Michael; Nkrumah, Evans Ewald; Badu, Ebenezer Kofi; Anti, Priscilla; Agbenyega, Olivia; Meyer, Benjamin; Oppong, Samuel; Sarkodie, Yaw Adu; Kalko, Elisabeth K V; Lina, Peter H C; Godlevska, Elena V; Reusken, Chantal; Seebens, Antje; Gloza-Rausch, Florian; Vallo, Peter; Tschapka, Marco; Drosten, Christian; Drexler, Jan Felix

    2013-03-01

    We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.

  19. Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe

    Science.gov (United States)

    Annan, Augustina; Baldwin, Heather J.; Corman, Victor Max; Klose, Stefan M.; Owusu, Michael; Nkrumah, Evans Ewald; Badu, Ebenezer Kofi; Anti, Priscilla; Agbenyega, Olivia; Meyer, Benjamin; Oppong, Samuel; Sarkodie, Yaw Adu; Kalko, Elisabeth K.V.; Lina, Peter H.C.; Godlevska, Elena V.; Reusken, Chantal; Seebens, Antje; Gloza-Rausch, Florian; Vallo, Peter; Tschapka, Marco; Drosten, Christian

    2013-01-01

    We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats. PMID:23622767

  20. Affective Education: A Teacher's Manual to Promote Student Self-Actualization and Human Relations Skills.

    Science.gov (United States)

    Snyder, Thomas R.

    This teacher's manual presents affective education as a program to promote student self-actualization and human relations skills. Abraham Maslow's hierarchy of needs and Erik Erikson's life stages of psychosocial development form the conceptual base for this program. The goals and objectives of this manual are concerned with problem-solving…

  1. Structure and Function of Human Tyrosinase and Tyrosinase-Related Proteins

    NARCIS (Netherlands)

    Lai, Xuelei; Wichers, Harry J.; Soler-Lopez, Montserrat; Dijkstra, Bauke W.

    2018-01-01

    Melanin is the main pigment responsible for the color of human skin, hair and eye. Its biosynthesis requires three melanogenic enzymes, tyrosinase (TYR), and the tyrosinase-related proteins TYRP1 and TYRP2. The difficulty of isolating pure and homogeneous proteins from endogenous sources has

  2. Structure of Human Tyrosinase Related Protein 1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis

    NARCIS (Netherlands)

    Lai, Xuelei; Wichers, Harry J.; Soler-Lopez, Montserrat; Dijkstra, Bauke W.

    2017-01-01

    Tyrosinase-related protein 1 (TYRP1) is one of three tyrosinase-like glycoenzymes in human melanocytes that are key to the production of melanin, the compound responsible for the pigmentation of skin, eye, and hair. Difficulties with producing these enzymes in pure form have hampered the

  3. Human Performance on the Traveling Salesman and Related Problems: A Review

    Science.gov (United States)

    MacGregor, James N.; Chu, Yun

    2011-01-01

    The article provides a review of recent research on human performance on the traveling salesman problem (TSP) and related combinatorial optimization problems. We discuss what combinatorial optimization problems are, why they are important, and why they may be of interest to cognitive scientists. We next describe the main characteristics of human…

  4. The Contextual Cat: Human-Animal Relations and Social Meaning in Anglo-Saxon England.

    Science.gov (United States)

    Poole, Kristopher

    2015-01-01

    The growing popularity of relational approaches to agency amongst archaeologists has led to increased attention on the specific contexts of interaction between humans and their material worlds. Within such viewpoints, non-humans are perceived as agents in their own right and placed on an equal footing with humans, with both acting to generate social categories in past cultures. However, to date, the focus of these interpretative models has been overwhelmingly directed towards inanimate objects. Animals are generally absent from these discussions, despite their ubiquity in past societies and the frequently central roles they held within daily lives and social relations. Moreover, living animals are set apart from material culture because, like humans, they are usually aware of their environs and are capable of physically responding to them. This ability to 'act back' would have made human-animal interactions extremely dynamic and thus offers different conceptual challenges to archaeologists than when faced with objects. This paper demonstrates that the notion of performativity, combined with understanding of animals themselves, can help to comprehend these relations. It does so by focusing on one particular species, the domestic cat, in relation to Anglo-Saxon England. The characteristics and behaviour of these animals affected the ways in which humans perceived and interacted with them, so that just one individual cat could be categorised in a range of different ways. The classification of animals was thus just as fluid, if not more so, as that of objects and highlights the need to incorporate the former into reconstructions of the social in archaeological research.

  5. Humans (really) are animals: picture-book reading influences 5-year-old urban children's construal of the relation between humans and non-human animals.

    Science.gov (United States)

    Waxman, Sandra R; Herrmann, Patricia; Woodring, Jennie; Medin, Douglas L

    2014-01-01

    What is the relation between humans and non-human animals? From a biological perspective, we view humans as one species among many, but in the fables and films we create for children, we often offer an anthropocentric perspective, imbuing non-human animals with human-like characteristics. What are the consequences of these distinctly different perspectives on children's reasoning about the natural world? Some have argued that children universally begin with an anthropocentric perspective and that acquiring a biological perspective requires a basic conceptual change (cf. Carey, 1985). But recent work reveals that this anthropocentric perspective, evidenced in urban 5-year-olds, is not evident in 3-year-olds (Herrmann etal., 2010). This indicates that the anthropocentric perspective is not an obligatory first step in children's reasoning about biological phenomena. In the current paper, we introduced a priming manipulation to assess whether 5-year-olds' reasoning about a novel biological property is influenced by the perspectives they encounter in children's books. Just before participating in a reasoning task, each child read a book about bears with an experimenter. What varied was whether bears were depicted from an anthropomorphic (Berenstain Bears) or biological perspective (Animal Encyclopedia). The priming had a dramatic effect. Children reading the Berenstain Bears showed the standard anthropocentric reasoning pattern, but those reading the Animal Encyclopedia adopted a biological pattern. This offers evidence that urban 5-year-olds can adopt either a biological or a human-centered stance, depending upon the context. Thus, children's books and other media are double-edged swords. Media may (inadvertently) support human-centered reasoning in young children, but may also be instrumental in redirecting children's attention to a biological model.

  6. Humans (really) are animals: picture-book reading influences 5-year-old urban children’s construal of the relation between humans and non-human animals

    Science.gov (United States)

    Waxman, Sandra R.; Herrmann, Patricia; Woodring, Jennie; Medin, Douglas L.

    2014-01-01

    What is the relation between humans and non-human animals? From a biological perspective, we view humans as one species among many, but in the fables and films we create for children, we often offer an anthropocentric perspective, imbuing non-human animals with human-like characteristics. What are the consequences of these distinctly different perspectives on children’s reasoning about the natural world? Some have argued that children universally begin with an anthropocentric perspective and that acquiring a biological perspective requires a basic conceptual change (cf. Carey, 1985). But recent work reveals that this anthropocentric perspective, evidenced in urban 5-year-olds, is not evident in 3-year-olds (Herrmann etal., 2010). This indicates that the anthropocentric perspective is not an obligatory first step in children’s reasoning about biological phenomena. In the current paper, we introduced a priming manipulation to assess whether 5-year-olds’ reasoning about a novel biological property is influenced by the perspectives they encounter in children’s books. Just before participating in a reasoning task, each child read a book about bears with an experimenter. What varied was whether bears were depicted from an anthropomorphic (Berenstain Bears) or biological perspective (Animal Encyclopedia). The priming had a dramatic effect. Children reading the Berenstain Bears showed the standard anthropocentric reasoning pattern, but those reading the Animal Encyclopedia adopted a biological pattern. This offers evidence that urban 5-year-olds can adopt either a biological or a human-centered stance, depending upon the context. Thus, children’s books and other media are double-edged swords. Media may (inadvertently) support human-centered reasoning in young children, but may also be instrumental in redirecting children’s attention to a biological model. PMID:24672493

  7. Spotted hyaena space use in relation to human infrastructure inside a protected area.

    Science.gov (United States)

    Belton, Lydia E; Cameron, Elissa Z; Dalerum, Fredrik

    2016-01-01

    Increasing human population growth has led to elevated levels of human-carnivore conflict. However, some carnivore populations have adapted to urban environments and the resources they supply. Such associations may influence carnivore ecology, behaviour and life-history. Pockets of urbanisation sometimes occur within protected areas, so that anthropogenic influences on carnivore biology are not necessarily confined to unprotected areas. In this study we evaluated associations between human infrastructure and related activity and space use of spotted hyaenas within one of the largest protected areas in South Africa, the Kruger National Park. Home range size was smaller for the dominant female of a clan living in close proximity to humans than that of the dominant female of a clan without direct access to human infrastructure. The home range including human infrastructure was also used less evenly during the night, presumably when the animals were active. Within this home range, a village area was preferred during the night, when the least modified areas within the village were preferred and administration and highly modified areas were avoided. During the day, however, there were no preference or avoidance of the village area, but all habitats except unmodified habitats within the village area were avoided. We suggest that human infrastructure and associated activity influenced hyaena space use, primarily through alterations in the spatial distribution of food. However, these effects may have been indirectly caused by habitat modification that generated favourable hunting habitat rather than a direct effect caused by access to human food such as garbage. Because of the often pivotal effects of apex predators in terrestrial ecosystems, we encourage further work aimed to quantify how human presence influences large carnivores and associated ecosystem processes within protected areas.

  8. The genomic distribution of intraspecific and interspecific sequence divergence of human segmental duplications relative to human/chimpanzee chromosomal rearrangements

    Directory of Open Access Journals (Sweden)

    Eichler Evan E

    2008-08-01

    Full Text Available Abstract Background It has been suggested that chromosomal rearrangements harbor the molecular footprint of the biological phenomena which they induce, in the form, for instance, of changes in the sequence divergence rates of linked genes. So far, all the studies of these potential associations have focused on the relationship between structural changes and the rates of evolution of single-copy DNA and have tried to exclude segmental duplications (SDs. This is paradoxical, since SDs are one of the primary forces driving the evolution of structure and function in our genomes and have been linked not only with novel genes acquiring new functions, but also with overall higher DNA sequence divergence and major chromosomal rearrangements. Results Here we take the opposite view and focus on SDs. We analyze several of the features of SDs, including the rates of intraspecific divergence between paralogous copies of human SDs and of interspecific divergence between human SDs and chimpanzee DNA. We study how divergence measures relate to chromosomal rearrangements, while considering other factors that affect evolutionary rates in single copy DNA. Conclusion We find that interspecific SD divergence behaves similarly to divergence of single-copy DNA. In contrast, old and recent paralogous copies of SDs do present different patterns of intraspecific divergence. Also, we show that some relatively recent SDs accumulate in regions that carry inversions in sister lineages.

  9. Analysis of the intellectual structure of human space exploration research using a bibliometric approach: Focus on human related factors

    Science.gov (United States)

    Lee, Tai Sik; Lee, Yoon-Sun; Lee, Jaeho; Chang, Byung Chul

    2018-02-01

    Human space exploration (HSE) is an interdisciplinary field composed of a range of subjects that have developed dramatically over the last few decades. This paper investigates the intellectual structure of HSE research with a focus on human related factors. A bibliometric approach with quantitative analytical techniques is applied to study the development and growth of the research. This study retrieves 1921 papers on HSE related to human factors from the year 1990 to the year 2016 from Web of Science and constructs a critical citation network composed of 336 papers. Edge-betweenness-based clustering is used to classify the citation network into twelve distinct research clusters based on four research themes: "biological risks from space radiation," "health and performance during long-duration spaceflight," "program and in-situ resources for HSE missions," and "habitat and life support systems in the space environment." These research themes are also similar to the classification results of a co-occurrence analysis on keywords for a total of 1921 papers. Papers with high centrality scores are identified as important papers in terms of knowledge flow. Moreover, the intermediary role of papers in exchanging knowledge between HSE sub-areas is identified using brokerage analysis. The key-route main path highlights the theoretical development trajectories. Due to the recent dramatic increase in investment by international governments and the private sector, the theoretical development trajectories of key research themes have been expanding from furthering scientific and technical knowledge to include various social and economic issues, thus encouraging massive public participation. This study contributes to an understanding of research trends and popular issues in the field of HSE by introducing a powerful way of determining major research themes and development trajectories. This study will help researchers seek the underlying knowledge diffusion flow from multifaceted

  10. Impact of DNA mismatch repair system alterations on human fertility and related treatments.

    Science.gov (United States)

    Hu, Min-hao; Liu, Shu-yuan; Wang, Ning; Wu, Yan; Jin, Fan

    2016-01-01

    DNA mismatch repair (MMR) is one of the biological pathways, which plays a critical role in DNA homeostasis, primarily by repairing base-pair mismatches and insertion/deletion loops that occur during DNA replication. MMR also takes part in other metabolic pathways and regulates cell cycle arrest. Defects in MMR are associated with genomic instability, predisposition to certain types of cancers and resistance to certain therapeutic drugs. Moreover, genetic and epigenetic alterations in the MMR system demonstrate a significant relationship with human fertility and related treatments, which helps us to understand the etiology and susceptibility of human infertility. Alterations in the MMR system may also influence the health of offspring conceived by assisted reproductive technology in humans. However, further studies are needed to explore the specific mechanisms by which the MMR system may affect human infertility. This review addresses the physiological mechanisms of the MMR system and associations between alterations of the MMR system and human fertility and related treatments, and potential effects on the next generation.

  11. Task types and error types involved in the human-related unplanned reactor trip events

    International Nuclear Information System (INIS)

    Kim, Jae Whan; Park, Jin Kyun

    2008-01-01

    In this paper, the contribution of task types and error types involved in the human-related unplanned reactor trip events that have occurred between 1986 and 2006 in Korean nuclear power plants are analysed in order to establish a strategy for reducing the human-related unplanned reactor trips. Classification systems for the task types, error modes, and cognitive functions are developed or adopted from the currently available taxonomies, and the relevant information is extracted from the event reports or judged on the basis of an event description. According to the analyses from this study, the contributions of the task types are as follows: corrective maintenance (25.7%), planned maintenance (22.8%), planned operation (19.8%), periodic preventive maintenance (14.9%), response to a transient (9.9%), and design/manufacturing/installation (6.9%). According to the analysis of the error modes, error modes such as control failure (22.2%), wrong object (18.5%), omission (14.8%), wrong action (11.1%), and inadequate (8.3%) take up about 75% of the total unplanned trip events. The analysis of the cognitive functions involved in the events indicated that the planning function had the highest contribution (46.7%) to the human actions leading to unplanned reactor trips. This analysis concludes that in order to significantly reduce human-induced or human-related unplanned reactor trips, an aide system (in support of maintenance personnel) for evaluating possible (negative) impacts of planned actions or erroneous actions as well as an appropriate human error prediction technique, should be developed

  12. Task types and error types involved in the human-related unplanned reactor trip events

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jae Whan; Park, Jin Kyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-12-15

    In this paper, the contribution of task types and error types involved in the human-related unplanned reactor trip events that have occurred between 1986 and 2006 in Korean nuclear power plants are analysed in order to establish a strategy for reducing the human-related unplanned reactor trips. Classification systems for the task types, error modes, and cognitive functions are developed or adopted from the currently available taxonomies, and the relevant information is extracted from the event reports or judged on the basis of an event description. According to the analyses from this study, the contributions of the task types are as follows: corrective maintenance (25.7%), planned maintenance (22.8%), planned operation (19.8%), periodic preventive maintenance (14.9%), response to a transient (9.9%), and design/manufacturing/installation (6.9%). According to the analysis of the error modes, error modes such as control failure (22.2%), wrong object (18.5%), omission (14.8%), wrong action (11.1%), and inadequate (8.3%) take up about 75% of the total unplanned trip events. The analysis of the cognitive functions involved in the events indicated that the planning function had the highest contribution (46.7%) to the human actions leading to unplanned reactor trips. This analysis concludes that in order to significantly reduce human-induced or human-related unplanned reactor trips, an aide system (in support of maintenance personnel) for evaluating possible (negative) impacts of planned actions or erroneous actions as well as an appropriate human error prediction technique, should be developed.

  13. Predominant CD4 T-lymphocyte tropism of human herpesvirus 6-related virus.

    OpenAIRE

    Takahashi, K; Sonoda, S; Higashi, K; Kondo, T; Takahashi, H; Takahashi, M; Yamanishi, K

    1989-01-01

    Human herpesvirus 6 (HHV-6)-related virus was isolated from CD4+ CD8- and CD3+ CD4+ mature T lymphocytes but could not be isolated from CD4- CD8+, CD4- CD8-, and CD3- T cells in the peripheral blood of exanthem subitum patients. HHV-6-related virus predominantly infected CD4+ CD8+, CD4+ CD8-, and CD3+ CD4+ cells with mature phenotypes and rarely infected CD4- CD8+ cells from cord blood mononuclear cells, which suggested predominant CD4 mature T-lymphocyte tropism of HHV-6-related virus.

  14. Age-related changes in spectral transmittance of the human crystalline lens in situ.

    Science.gov (United States)

    Sakanishi, Yoshihito; Awano, Masakazu; Mizota, Atsushi; Tanaka, Minoru; Murakami, Akira; Ohnuma, Kazuhiko

    2012-01-01

    It was the aim of this study to measure spectral transmission of the human crystalline lens in situ. The crystalline lens was illuminated by one of four light-emitting diodes of different colors. The relative spectral transmittance of the human crystalline lens was measured with the Purkinje-Sanson mirror images over a wide range of ages. The study evaluated 36 crystalline lenses of 28 subjects aged 21-76 years. There was a significant correlation between the age and spectral transmittance for blue light. Spectral transmittance of the crystalline lens in situ could be measured with Purkinje-Sanson mirror images. Copyright © 2012 S. Karger AG, Basel.

  15. Detection of a human intracisternal A-type retroviral particle antigenically related to HIV

    Science.gov (United States)

    Garry, R. F.; Fermin, C. D.; Hart, D. J.; Alexander, S. S.; Donehower, L. A.; Luo-Zhang, H.

    1990-01-01

    Sjogren's syndrome is an autoimmune disease that is characterized by dryness of the mouth and eyes. The loss of salivary and lacrimal gland function is accompanied by lymphocytic infiltration. Because similar symptoms and glandular pathology are observed in certain persons infected with human immunodeficiency virus (HIV), a search was initiated for a possible retroviral etiology in this syndrome. A human intracisternal A-type retroviral particle that is antigenically related to HIV was detected in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjogren's syndrome. Comparison of this retroviral particle to HIV indicates that they are distinguishable by several ultrastructural, physical, and enzymatic criteria.

  16. Discovery of a novel hepatovirus (Phopivirus of seals) related to human Hepatitis A Virus

    Science.gov (United States)

    Anthony. S.J.,; St. Leger, J.A; Liang, E.; Hicks, A.L.; Sanchez-Leon, M.D; Ip, Hon S.; Jain, K.; Lefkowitch, J. H.; Navarrete-Macias, I.; Knowles, N.; Goldstein, T.; Pugliares, K.; Rowles, T.; Lipkin, W.I.

    2015-01-01

    Describing the viral diversity of wildlife can provide interesting and useful insights into the natural history of established human pathogens. In this study, we describe a previously unknown picornavirus in harbor seals (tentatively named phopivirus) that is related to human hepatitis A virus (HAV). We show that phopivirus shares several genetic and phenotypic characteristics with HAV, including phylogenetic relatedness across the genome, a specific and seemingly quiescent tropism for hepatocytes, structural conservation in a key functional region of the type III internal ribosomal entry site (IRES), and a codon usage bias consistent with that of HAV.

  17. Relativity

    CERN Document Server

    Einstein, Albert

    2013-01-01

    Time magazine's ""Man of the Century"", Albert Einstein is the founder of modern physics and his theory of relativity is the most important scientific idea of the modern era. In this short book, Einstein explains, using the minimum of mathematical terms, the basic ideas and principles of the theory that has shaped the world we live in today. Unsurpassed by any subsequent books on relativity, this remains the most popular and useful exposition of Einstein's immense contribution to human knowledge.With a new foreword by Derek Raine.

  18. Justice relations as determinative factor of “human - state” relation in the J.Rawls’s theory

    Directory of Open Access Journals (Sweden)

    Z. O. Burychko

    2014-04-01

    Full Text Available The conceptualization of relationshuman ­ state” in J. Rawls’s theory is revealed in the article. It is concluded, that this relationship is determineted on value level by justice, which understands as fairness. Justice is the main virtue of social institutions, and in this case, if the institutions are unjust, their activity should be discarded or revised. Based on liberal ideas, justice linked to the notion of freedom, particularly in J. Rawls’s theory are described? That in the faire societies the equal freedom of citizens is regarded as being established beforehand state. The main principles of relations are the principle of participation and paternalism. Participation means the involvement of citizens in the constitutional process, the national process and participation in self­government. Paternalism is understood as the rational intervention of state in society in aim to prevent irrational expressions of relations between people. Conditions intervention: it must be justified by the apparent inability or lack of will; must match the understanding of justice as fairness, and based on sustainable interests. It is concluded, that the theory of J. Rawls resulting from the analytical experiment leaves a lot of questions as to achieve justice as fairness in the activities of individuals and social institutions.

  19. Identification and detection of a novel human endogenous retrovirus-related gene, and structural characterization of its related elements

    Directory of Open Access Journals (Sweden)

    Qiaoyi Liang

    2009-01-01

    Full Text Available Up-regulation of human endogenous retroviruses (HERVs is associated with many diseases, including cancer. In this study, an H family HERV (HERV-H-related gene was identified and characterized. Its spliced transcript lacks protein-coding capacity and may belong to the emerging class of noncoding RNAs (ncRNAs. The 1.3-kb RNA consisting of four exons is transcribed from an Alu element upstream of a 5.0-kb structurally incomplete HERV-H element. RT-PCR and quantitative RT-PCR results indicated that expression of this HERV-related transcript was negatively associated with colon, stomach, and kidney cancers. Its expression was induced upon treatment with DNA methylation and histone deacetylation inhibitors. A BLAT search using long terminal repeats (LTRs identified 50 other LTR homogenous HERV-H elements. Further analysis of these elements revealed that all are structurally incomplete and only five exert transcriptional activity. The results presented here recommend further investigation into a potentially functional HERV-H-related ncRNA.

  20. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  1. Review: Selenium contamination, fate, and reactive transport in groundwater in relation to human health

    Science.gov (United States)

    Bailey, Ryan T.

    2017-06-01

    Selenium (Se) is an essential micro-nutrient for humans, but can be toxic at high levels of intake. Se deficiency and Se toxicity are linked with serious diseases, with some regions worldwide experiencing Se deficiency due to Se-poor rocks and soils and other areas dealing with Se toxicity due to the presence of Se-enriched geologic materials. In addition, Se is consumed primarily through plants that take up Se from soil and through animal products that consume these plants. Hence, the soil and groundwater system play important roles in determining the effect of Se on human health. This paper reviews current understanding of Se fate and transport in soil and groundwater systems and its relation to human health, with a focus on alluvial systems, soil systems, and the interface between alluvial systems and Cretaceous shale that release Se via oxidation processes. The review focuses first on the relation between Se and human health, followed by a summary of Se distribution in soil-aquifer systems, with an emphasis on the quantitative relationship between Se content in soil and Se concentration in underlying groundwater. The physical, chemical, and microbial processes that govern Se fate and transport in subsurface systems then are presented, followed by numerical modeling techniques used to simulate these processes in study regions and available remediation strategies for either Se-deficient or Se-toxic regions. This paper can serve as a guide to any field, laboratory or modeling study aimed at assessing Se fate and transport in groundwater systems and its relation to human health.

  2. Human papillomavirus infection is not related with prostatitis-related symptoms: results from a case-control study

    Directory of Open Access Journals (Sweden)

    Riccardo Bartoletti

    2014-04-01

    Full Text Available PurposeTo investigate the relationship between human papillomavirus (HPV infection and prostatitis-related symptoms.Materials and MethodsAll young heterosexual patients with prostatitis-related symptoms attending the same Center from January 2005 to December 2010 were eligible for this case-control study. Sexually active asymptomatic men were considered as the control group. All subjects underwent clinical examination, Meares-Stamey test and DNA-HPV test. Patients with prostatitis-related symptoms and asymptomatic men were compared in terms of HPV prevalence. Moreover, multivariable Cox proportional hazards regression analysis was performed to determine the association between HPV infection and prostatitis-related symptoms.ResultsOverall, 814 out of 2,938 patients (27.7% and 292 out of 1,081 controls (27.0% proved positive to HPV. The HPV genotype distribution was as follows: HR-HPV 478 (43.3%, PHR-HPV 77 (6.9%, LR-HPV 187 (16.9% and PNG-HPV 364 (32.9%. The most common HPV genotypes were: 6, 11, 16, 26, 51, 53 and 81. No difference was found between the two groups in terms of HPV infection (OR 1.03; 95% CI 0.88-1.22; p = 0.66. We noted a statistically significant increase in HPV infection over the period 2005 to 2010 (p < 0.001 in both groups. Moreover, we found a statistically significant increase in HPV 16 frequency from 2005 to 2010 (p = 0.002.ConclusionsThis study highlights that prostatitis-like symptoms are unrelated to HPV infection. Secondary, we highlight the high prevalence of asymptomatic HPV infection among young heterosexual men.

  3. Different alpha crystallin expression in human age-related and congenital cataract lens epithelium.

    Science.gov (United States)

    Yang, Jing; Zhou, Sheng; Guo, Minfei; Li, Yuting; Gu, Jianjun

    2016-05-28

    The purpose of this study was to investigate the different expressions of αA-crystallin and αB-crystallin in human lens epithelium of age-related and congenital cataracts. The central part of the human anterior lens capsule approximately 5 mm in diameter together with the adhering epithelial cells, were harvested and processed within 6 hours after cataract surgery from age-related and congenital cataract patients or from normal eyes of fresh cadavers. The mRNA and soluble protein levels of αA-crystallin and αB-crystallin in the human lens epithelium were detected by real-time PCR and western blots, respectively. The mRNA and soluble protein expressions of αA-crystallin and αB-crystallin in the lens epithelium were both reduced in age-related and congenital cataract groups when compared with the normal control group. However, the degree of α-crystallin loss in the lens epithelium was highly correlated with different cataract types. The α-crystallin expression of the lens epithelium was greatly reduced in the congenital cataract group but only moderately decreased in the age-related cataract group. The reduction of αA-crystallin soluble protein levels in the congenital cataract group was approximately 2.4 fold decrease compared with that of the age-related cataract group, while an mRNA fold change of 1.67 decrease was observed for the age-related cataract group. Similarly, the reduction of soluble protein levels of αB-crystallin in the congenital cataract group was approximately a 1.57 fold change compared with that of the age-related cataract group. A 1.75 fold change for mRNA levels compared with that of the age-related cataract group was observed. The results suggest that the differential loss of α-crystallin in the human lens epithelium could be associated with the different mechanisms of cataractogenesis in age-related versus congenital cataracts, subsequently resulting in different clinical presentations.

  4. The Relation of Visual Signs In The Narrative Structure of MTV Exit Human Trafficking Campaign Video

    Directory of Open Access Journals (Sweden)

    Winny Gunarti

    2013-08-01

    Full Text Available Human trafficking is a violation of the human rights. One of the campaign to fight against this crime takes the form of a digital campaign that aired on television and internet.   This study discusses the narrative structure of human trafficking campaign video from non-profit organization MTV Exit in 2012. This video campaign combines art collage and graphic art in its narrative structure. Nonverbal visual elements displayed in the form of a digital photo collage with animated illustrations setting. We consider this video campaign quite interesting as it is visually inform the public about the importance of safe migration through the visual signs in the narrative structure. This study analyzes qualitatively the relation of nonverbal visual signs in the narrative collage and illustration. Denotative and connotative analysis with structural semiotics approach is needed to understand the meaning of visual signs in the context of humans as cultural beings in their communities. This study is expected to be a model example of visual communication campaigns that can foster public awareness of the issue of human trafficking, especially for young women and children as young generation.

  5. Disentangling the relative effects of bushmeat availability on human nutrition in central Africa

    Science.gov (United States)

    Fa, John E.; Olivero, Jesús; Real, Raimundo; Farfán, Miguel A.; Márquez, Ana L.; Vargas, J. Mario; Ziegler, Stefan; Wegmann, Martin; Brown, David; Margetts, Barrie; Nasi, Robert

    2015-02-01

    We studied links between human malnutrition and wild meat availability within the Rainforest Biotic Zone in central Africa. We distinguished two distinct hunted mammalian diversity distributions, one in the rainforest areas (Deep Rainforest Diversity, DRD) containing taxa of lower hunting sustainability, the other in the northern rainforest-savanna mosaic, with species of greater hunting potential (Marginal Rainforest Diversity, MRD). Wild meat availability, assessed by standing crop mammalian biomass, was greater in MRD than in DRD areas. Predicted bushmeat extraction was also higher in MRD areas. Despite this, stunting of children, a measure of human malnutrition, was greater in MRD areas. Structural equation modeling identified that, in MRD areas, mammal diversity fell away from urban areas, but proximity to these positively influenced higher stunting incidence. In DRD areas, remoteness and distance from dense human settlements and infrastructures explained lower stunting levels. Moreover, stunting was higher away from protected areas. Our results suggest that in MRD areas, forest wildlife rational use for better human nutrition is possible. By contrast, the relatively low human populations in DRD areas currently offer abundant opportunities for the continued protection of more vulnerable mammals and allow dietary needs of local populations to be met.

  6. Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

    Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic t...... imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...

  7. Humans (really are animals: Picture-book reading influences five-year-old urban children’s construal of the relation between humans and non-human animals

    Directory of Open Access Journals (Sweden)

    Sandra R Waxman

    2014-03-01

    Full Text Available What is the relation between humans and nonhuman animals? From a biological perspective, we view humans as one species among many, but in the fables and films we create for children, we often offer an anthropocentric perspective, imbuing nonhuman animals with human-like characteristics. What are the consequences of these distinctly different perspectives on children’s reasoning about the natural world? Some have argued that children universally begin with an anthropocentric perspective and that acquiring a biological perspective requires a basic conceptual change (cf. Carey 1985. But recent work reveals that this anthropocentric perspective, evidenced in urban five-year-olds, is not evident in three-year-olds (Herrmann et al. 2010. This indicates that the anthropocentric perspective is not an obligatory first step in children’s reasoning about biological phenomena. In the current paper, we introduced a priming manipulation to assess whether five-year-olds’ reasoning about a novel biological property is influenced by the perspectives they encounter in children’s books. Just before participating in a reasoning task, each child read a book about bears with an experimenter. What varied was whether bears were depicted from an anthropomorphic (Berenstain Bears or biological perspective (Animal Encyclopedia. The priming had a dramatic effect. Children reading the Berenstain Bears showed the standard anthropocentric reasoning pattern, but those reading the Animal Encyclopedia adopted a biological pattern. This offers evidence that urban five-year-olds can adopt either a biological or a human-centered stance, depending upon the context. Thus, children’s books and other media are double-edged swords. Media may (inadvertently support human-centered reasoning in young children, but may also be instrumental in redirecting children’s attention to a biological model.

  8. Evaluating a national science and technology program using the human capital and relational asset perspectives.

    Science.gov (United States)

    Hung, Chia-Liang; Chou, Jerome Chih-Lung; Roan, Hung-Wei

    2010-11-01

    The purpose of this research is to evaluate the performance of the National Science and Technology Program (NSTP) by targeting the Taiwan National Telecommunication Program (NTP) initiated in 1998. The Taiwan telecommunications industry has prospered, currently occupying key positions in global markets even though NTP seldom contributes positively to patent citation performance. Hence, the authors of this study investigate the qualitative perspective of intellectual capital rather than quantitative technological indices. The current study focuses on both human capital and relational assets through surveys of 53 principal investigators of NTP projects and 63 industrial R&D managers of telecommunications corporations in the Taiwan market. Results show that NSTP member quality and the flow of employment are good indicators of human capital and that both perform better than the middle value in the case of Taiwan NTP. In addition, we find that industrial participants are more likely to share R&D resources than other academic researchers with higher intention of co-publishing, co-funding, and sharing equipment and facilities. The industrial NTP participants also have higher expectations regarding achieving advanced technology breakthroughs in contrast to non-NTP industrial interviewees. Moreover, industrial participants with greater industry-university cooperation intensity indeed obtain a particular advantage, that is, greater knowledge acquisition from other fields related to the effect of knowledge spillovers through the particular NSTP linkage. Accordingly, from the perspectives of human capital and relational assets, the authors conclude by articulating the importance of absorptive capacity resulting from good human capital and knowledge spillover contributed by relational assets within governmental technology policy and NSTP programming. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  9. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

  10. Spatial Assessment of Forest Ecosystem Functions and Services using Human Relating Factors for SDG

    Science.gov (United States)

    Song, C.; Lee, W. K.; Jeon, S. W.; Kim, T.; Lim, C. H.

    2015-12-01

    Application of ecosystem service concept in environmental related decision making could be numerical and objective standard for policy maker between preserving and developing perspective of environment. However, pursuing maximum benefit from natural capital through ecosystem services caused failure by losing ecosystem functions through its trade-offs. Therefore, difference between ecosystem functions and services were demonstrated and would apply human relating perspectives. Assessment results of ecosystem functions and services can be divided 3 parts. Tree growth per year set as the ecosystem function factor and indicated through so called pure function map. After that, relating functions can be driven such as water conservation, air pollutant purification, climate change regulation, and timber production. Overall process and amount are numerically quantified. These functional results can be transferred to ecosystem services by multiplying economic unit value, so function reflecting service maps can be generated. On the other hand, above services, to implement more reliable human demand, human reflecting service maps are also be developed. As the validation, quantified ecosystem functions are compared with former results through pixel based analysis. Three maps are compared, and through comparing difference between ecosystem function and services and inversed trends in function based and human based service are analysed. In this study, we could find differences in PF, FRS, and HRS in relation to based ecosystem conditions. This study suggests that the differences in PF, FRS, and HRS should be understood in the decision making process for sustainable management of ecosystem services. Although the analysis is based on in sort existing process separation, it is important to consider the possibility of different usage of ecosystem function assessment results and ecosystem service assessment results in SDG policy making. Furthermore, process based functional approach

  11. Analysis of 'human element related trip case book in Korean NPPs' using organizational factors

    International Nuclear Information System (INIS)

    Kim, S. Y.; Kim, Y. I.; Lee, Y. S.; Kim, C. S.; Jung, C. H.; Jung, W. D.

    2002-01-01

    There have been no studies appling organizational factors to data analysis in Korean NPPs. In this paper, data in 'human element related trip case book in Korean NPPs' are analyzed and categorized by the 20 organizational factors of NRC-BNL according to the cause of reactor trip. These inform us how organizational factors affected on the safety of Korean NPPs. Consequently important organizational factor are identified through which it is known that NPP organization would have a tendency

  12. Application of high-throughput sequencing in understanding human oral microbiome related with health and disease

    OpenAIRE

    Chen, Hui; Jiang, Wen

    2014-01-01

    The oral microbiome is one of most diversity habitat in the human body and they are closely related with oral health and disease. As the technique developing,, high throughput sequencing has become a popular approach applied for oral microbial analysis. Oral bacterial profiles have been studied to explore the relationship between microbial diversity and oral diseases such as caries and periodontal disease. This review describes the application of high-throughput sequencing for characterizati...

  13. Extract the Relational Information of Static Features and Motion Features for Human Activities Recognition in Videos

    Directory of Open Access Journals (Sweden)

    Li Yao

    2016-01-01

    Full Text Available Both static features and motion features have shown promising performance in human activities recognition task. However, the information included in these features is insufficient for complex human activities. In this paper, we propose extracting relational information of static features and motion features for human activities recognition. The videos are represented by a classical Bag-of-Word (BoW model which is useful in many works. To get a compact and discriminative codebook with small dimension, we employ the divisive algorithm based on KL-divergence to reconstruct the codebook. After that, to further capture strong relational information, we construct a bipartite graph to model the relationship between words of different feature set. Then we use a k-way partition to create a new codebook in which similar words are getting together. With this new codebook, videos can be represented by a new BoW vector with strong relational information. Moreover, we propose a method to compute new clusters from the divisive algorithm’s projective function. We test our work on the several datasets and obtain very promising results.

  14. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels

    Directory of Open Access Journals (Sweden)

    Weiyun Huang

    2017-02-01

    Full Text Available ABSTRACT Voltage-gated sodium (Nav channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Nav channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Nav channels, with Nav1.1 and Nav1.5 each harboring more than 400 mutations. Nav channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Nav channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Cav channel Cav1.1 provides a template for homology-based structural modeling of the evolutionarily related Nav channels. In this Resource article, we summarized all the reported disease-related mutations in human Nav channels, generated a homologous model of human Nav1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Nav channels, the analysis presented here serves as the base framework for mechanistic investigation of Nav channelopathies and for potential structure-based drug discovery.

  15. Structure-based assessment of disease-related mutations in human voltage-gated sodium channels.

    Science.gov (United States)

    Huang, Weiyun; Liu, Minhao; Yan, S Frank; Yan, Nieng

    2017-06-01

    Voltage-gated sodium (Na v ) channels are essential for the rapid upstroke of action potentials and the propagation of electrical signals in nerves and muscles. Defects of Na v channels are associated with a variety of channelopathies. More than 1000 disease-related mutations have been identified in Na v channels, with Na v 1.1 and Na v 1.5 each harboring more than 400 mutations. Na v channels represent major targets for a wide array of neurotoxins and drugs. Atomic structures of Na v channels are required to understand their function and disease mechanisms. The recently determined atomic structure of the rabbit voltage-gated calcium (Ca v ) channel Ca v 1.1 provides a template for homology-based structural modeling of the evolutionarily related Na v channels. In this Resource article, we summarized all the reported disease-related mutations in human Na v channels, generated a homologous model of human Na v 1.7, and structurally mapped disease-associated mutations. Before the determination of structures of human Na v channels, the analysis presented here serves as the base framework for mechanistic investigation of Na v channelopathies and for potential structure-based drug discovery.

  16. Group B streptococcus activates transcriptomic pathways related to premature birth in human extraplacental membranes in vitro.

    Science.gov (United States)

    Park, Hae-Ryung; Harris, Sean M; Boldenow, Erica; McEachin, Richard C; Sartor, Maureen; Chames, Mark; Loch-Caruso, Rita

    2018-03-01

    Streptococcus agalactiae (group B streptococcus [GBS]) infection in pregnant women is the leading cause of infectious neonatal morbidity and mortality in the United States. Although inflammation during infection has been associated with preterm birth, the contribution of GBS to preterm birth is less certain. Moreover, the early mechanisms by which GBS interacts with the gestational tissue to affect adverse pregnancy outcomes are poorly understood. We hypothesized that short-term GBS inoculation activates pathways related to inflammation and premature birth in human extraplacental membranes. We tested this hypothesis using GBS-inoculated human extraplacental membranes in vitro. In agreement with our hypothesis, a microarray-based transcriptomics analysis of gene expression changes in GBS-inoculated membranes revealed that GBS activated pathways related to inflammation and preterm birth with significant gene expression changes occurring as early as 4 h postinoculation. In addition, pathways related to DNA replication and repair were downregulated with GBS treatment. Conclusions based on our transcriptomics data were further supported by responses of prostaglandin E2 (PGE2), and matrix metalloproteinases 1 (MMP1) and 3 (MMP3), all of which are known to be involved in parturition and premature rupture of membranes. These results support our initial hypothesis and provide new information on molecular targets of GBS infection in human extraplacental membranes.

  17. Citizenship, human rights, and dementia: Towards a new embodied relational ethic of sexuality.

    Science.gov (United States)

    Kontos, Pia; Grigorovich, Alisa; Kontos, Alexis P; Miller, Karen-Lee

    2016-05-01

    Sexual citizenship and sexual rights scholarship have made important contributions to broadening citizenship and more fully accommodating rights related to sexuality. However, this scholarship has concentrated primarily on the sexuality and intimacy-related needs of younger people and those who are not cognitively impaired. Consequently, it has inadvertently served to marginalize persons living with dementia who reside in long-term residential care settings. We argue that supporting sexual rights for persons with dementia requires a particular human rights ontology for citizenship-one that recognizes that corporeality is a fundamental source of self-expression, interdependence, and reciprocal engagement. This is an ontology that underpins our model of relational citizenship and that grounds our articulation of an ethic of embodied relational sexuality. In our view, this ethic offers important direction for the development of policy, legislation, and clinical guidelines to support sexual rights for persons with dementia in long-term residential care. © The Author(s) 2016.

  18. Movement-related theta rhythm in humans: coordinating self-directed hippocampal learning.

    Directory of Open Access Journals (Sweden)

    Raphael Kaplan

    Full Text Available The hippocampus is crucial for episodic or declarative memory and the theta rhythm has been implicated in mnemonic processing, but the functional contribution of theta to memory remains the subject of intense speculation. Recent evidence suggests that the hippocampus might function as a network hub for volitional learning. In contrast to human experiments, electrophysiological recordings in the hippocampus of behaving rodents are dominated by theta oscillations reflecting volitional movement, which has been linked to spatial exploration and encoding. This literature makes the surprising cross-species prediction that the human hippocampal theta rhythm supports memory by coordinating exploratory movements in the service of self-directed learning. We examined the links between theta, spatial exploration, and memory encoding by designing an interactive human spatial navigation paradigm combined with multimodal neuroimaging. We used both non-invasive whole-head Magnetoencephalography (MEG to look at theta oscillations and Functional Magnetic Resonance Imaging (fMRI to look at brain regions associated with volitional movement and learning. We found that theta power increases during the self-initiation of virtual movement, additionally correlating with subsequent memory performance and environmental familiarity. Performance-related hippocampal theta increases were observed during a static pre-navigation retrieval phase, where planning for subsequent navigation occurred. Furthermore, periods of the task showing movement-related theta increases showed decreased fMRI activity in the parahippocampus and increased activity in the hippocampus and other brain regions that strikingly overlap with the previously observed volitional learning network (the reverse pattern was seen for stationary periods. These fMRI changes also correlated with participant's performance. Our findings suggest that the human hippocampal theta rhythm supports memory by coordinating

  19. Relative Efficacy of Human Social Interaction and Food as Reinforcers for Domestic Dogs and Hand-Reared Wolves

    Science.gov (United States)

    Feuerbacher, Erica; Wynne, Clive D. L.

    2012-01-01

    Despite the intimate relationship dogs share with humans in Western society, we know relatively little about the variables that produce and maintain dog social behavior towards humans. One possibility is that human social interaction is itself a reinforcer for dog behavior. As an initial assessment of the variables that might maintain dog social…

  20. Metal status in human endometrium: Relation to cigarette smoking and histological lesions

    International Nuclear Information System (INIS)

    Rzymski, Piotr; Rzymski, Paweł; Tomczyk, Katarzyna; Niedzielski, Przemysław; Jakubowski, Karol; Poniedziałek, Barbara; Opala, Tomasz

    2014-01-01

    Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility. - Highlights: • Cd, Cr, Ni, Pb and Zn are detectable in human endometrium. • Mean metal content in human endometrium decreases in Cr>Pb>Zn>Ni>Cd order. • Cigarettes smoking increases endometrial content of Cd and Pb. • Lesioned endometrial tissue was characterized by higher metal contents

  1. Pollutant Transport and Fate: Relations Between Flow-paths and Downstream Impacts of Human Activities

    Science.gov (United States)

    Thorslund, J.; Jarsjo, J.; Destouni, G.

    2017-12-01

    relatively scale at which most studies and implementations are currently made. These suggestions can help bridge critical knowledge gaps, as needed for improving water quality predictions and mitigation solutions under human and environmental changes.

  2. Metal status in human endometrium: Relation to cigarette smoking and histological lesions

    Energy Technology Data Exchange (ETDEWEB)

    Rzymski, Piotr, E-mail: rzymskipiotr@ump.edu.pl [Department of Biology and Environmental Protection, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznań (Poland); Rzymski, Paweł; Tomczyk, Katarzyna [Department of Mother' s and Child' s Health, Gynecologic and Obstetrical University Hospital, Poznan University of Medical Sciences, Poznań (Poland); Niedzielski, Przemysław; Jakubowski, Karol [Department of Analytical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań (Poland); Poniedziałek, Barbara [Department of Biology and Environmental Protection, Poznan University of Medical Sciences, Rokietnicka 8, 60-806 Poznań (Poland); Opala, Tomasz [Department of Mother' s and Child' s Health, Gynecologic and Obstetrical University Hospital, Poznan University of Medical Sciences, Poznań (Poland)

    2014-07-15

    Human endometrium is a thick, blood vessel-rich, glandular tissue which undergoes cyclic changes and is potentially sensitive to the various endogenous and exogenous compounds supplied via the hematogenous route. As recently indicated, several metals including Cd, Pb, Cr and Ni represent an emerging class of potential metalloestrogens and can be implicated in alterations of the female reproductive system including endometriosis and cancer. In the present study, we investigated the content of five metals: Cd, Cr, Ni, Pb and Zn in 25 samples of human endometrium collected from Polish females undergoing diagnostic or therapeutic curettage of the uterine cavity. The overall mean metal concentration (analyzed using microwave induced plasma atomic emission spectrometry MIP-OES) decreased in the following order: Cr>Pb>Zn>Ni>Cd. For the first time it was demonstrated that cigarette smoking significantly increases the endometrial content of Cd and Pb. Concentration of these metals was also positively correlated with years of smoking and the number of smoked cigarettes. Tissue samples with recognized histologic lesions (simple hyperplasia, polyposis and atrophy) were characterized by a 2-fold higher Cd level. No relation between the age of the women and metal content was found. Our study shows that human endometrium can be a potential target of metal accumulation within the human body. Quantitative analyses of endometrial metal content could serve as an additional indicator of potential impairments of the menstrual cycle and fertility. - Highlights: • Cd, Cr, Ni, Pb and Zn are detectable in human endometrium. • Mean metal content in human endometrium decreases in Cr>Pb>Zn>Ni>Cd order. • Cigarettes smoking increases endometrial content of Cd and Pb. • Lesioned endometrial tissue was characterized by higher metal contents.

  3. HSC extrinsic sex-related and intrinsic autoimmune disease-related human B-cell variation is recapitulated in humanized mice.

    Science.gov (United States)

    Borsotti, Chiara; Danzl, Nichole M; Nauman, Grace; Hölzl, Markus A; French, Clare; Chavez, Estefania; Khosravi-Maharlooei, Mohsen; Glauzy, Salome; Delmotte, Fabien R; Meffre, Eric; Savage, David G; Campbell, Sean R; Goland, Robin; Greenberg, Ellen; Bi, Jing; Satwani, Prakash; Yang, Suxiao; Bathon, Joan; Winchester, Robert; Sykes, Megan

    2017-10-24

    B cells play a major role in antigen presentation and antibody production in the development of autoimmune diseases, and some of these diseases disproportionally occur in females. Moreover, immune responses tend to be stronger in female vs male humans and mice. Because it is challenging to distinguish intrinsic from extrinsic influences on human immune responses, we used a personalized immune (PI) humanized mouse model, in which immune systems were generated de novo from adult human hematopoietic stem cells (HSCs) in immunodeficient mice. We assessed the effect of recipient sex and of donor autoimmune diseases (type 1 diabetes [T1D] and rheumatoid arthritis [RA]) on human B-cell development in PI mice. We observed that human B-cell levels were increased in female recipients regardless of the source of human HSCs or the strain of immunodeficient recipient mice. Moreover, mice injected with T1D- or RA-derived HSCs displayed B-cell abnormalities compared with healthy control HSC-derived mice, including altered B-cell levels, increased proportions of mature B cells and reduced CD19 expression. Our study revealed an HSC-extrinsic effect of recipient sex on human B-cell reconstitution. Moreover, the PI humanized mouse model revealed HSC-intrinsic defects in central B-cell tolerance that recapitulated those in patients with autoimmune diseases. These results demonstrate the utility of humanized mouse models as a tool to better understand human immune cell development and regulation.

  4. NASA Human Integration Design Handbook (HIDH): Revitalization of Space-Related Human Factors, Environmental and Habitability Data

    Science.gov (United States)

    Russo, Dane; Pickett, Lynn; Tillman, Barry; Foley, Tico

    2007-01-01

    This chart illustrates the contents for NASA's Human Integration Design Handbook, which is being developed as a new reference handbook for designing systems which accomodate the capabilities and limitations of the human crew.

  5. A Murine Herpesvirus Closely Related to Ubiquitous Human Herpesviruses Causes T-Cell Depletion.

    Science.gov (United States)

    Patel, Swapneel J; Zhao, Guoyan; Penna, Vinay R; Park, Eugene; Lauron, Elvin J; Harvey, Ian B; Beatty, Wandy L; Plougastel-Douglas, Beatrice; Poursine-Laurent, Jennifer; Fremont, Daved H; Wang, David; Yokoyama, Wayne M

    2017-05-01

    The human roseoloviruses human herpesvirus 6A (HHV-6A), HHV-6B, and HHV-7 comprise the Roseolovirus genus of the human Betaherpesvirinae subfamily. Infections with these viruses have been implicated in many diseases; however, it has been challenging to establish infections with roseoloviruses as direct drivers of pathology, because they are nearly ubiquitous and display species-specific tropism. Furthermore, controlled study of infection has been hampered by the lack of experimental models, and until now, a mouse roseolovirus has not been identified. Herein we describe a virus that causes severe thymic necrosis in neonatal mice, characterized by a loss of CD4 + T cells. These phenotypes resemble those caused by the previously described mouse thymic virus (MTV), a putative herpesvirus that has not been molecularly characterized. By next-generation sequencing of infected tissue homogenates, we assembled a contiguous 174-kb genome sequence containing 128 unique predicted open reading frames (ORFs), many of which were most closely related to herpesvirus genes. Moreover, the structure of the virus genome and phylogenetic analysis of multiple genes strongly suggested that this virus is a betaherpesvirus more closely related to the roseoloviruses, HHV-6A, HHV-6B, and HHV-7, than to another murine betaherpesvirus, mouse cytomegalovirus (MCMV). As such, we have named this virus murine roseolovirus (MRV) because these data strongly suggest that MRV is a mouse homolog of HHV-6A, HHV-6B, and HHV-7. IMPORTANCE Herein we describe the complete genome sequence of a novel murine herpesvirus. By sequence and phylogenetic analyses, we show that it is a betaherpesvirus most closely related to the roseoloviruses, human herpesviruses 6A, 6B, and 7. These data combined with physiological similarities with human roseoloviruses collectively suggest that this virus is a murine roseolovirus (MRV), the first definitively described rodent roseolovirus, to our knowledge. Many biological and

  6. Human Papillomavirus Infection Among 2460 Men in Denmark: Prevalence in Relation to Age Using 2 Human Papillomavirus DNA Testing Methods.

    Science.gov (United States)

    Hebnes, Julie Buchholt; Munk, Christian; Nøhr, Bugge; Nielsen, Ann; Jørgensen, Hans Ole; Iftner, Thomas; Kjaer, Susanne Krüger

    2015-08-01

    It is crucial to understand the epidemiology and natural history of human papillomavirus (HPV) infection in both men and women, to prevent the increasing HPV-related disease burden in men. Data on HPV prevalence among men in the general population are limited. In this cross-sectional population-based study, we aimed to estimate genital HPV infection prevalence in Danish men using 2 different test methods. Penile swab samples from 2460 male employees and conscripts at military barracks in Denmark were tested for HPV DNA with the hybrid capture 2 (HC2) method, and a polymerase chain reaction (PCR) assay, Inno-LiPA. The overall and age- and type-specific prevalence of HPV infection with 95% confidence intervals (CIs) were estimated, and the correlation between the 2 assays was assessed. The overall HPV prevalence was 22.2% (95% CI, 20.6-23.9) in the HC2 test and 41.8% (95% CI, 39.9-43.8) with PCR. Of the PCR-positive samples, 50.9% were negative in the HC2 test. Of 183 PCR-positive samples that could not be genotyped (HPVX), 88.0% (95% CI, 83.2-92.7) were HC2 negative. The most prevalent types were HPV-51, HPV-16, HPV-66, HPV-53, and HPV-6. The prevalence of high-risk and low-risk HPV peaked among men aged 20 to 29 years, whereas the HPVX prevalence increased with age. Human papillomavirus is highly prevalent in the general male population of Denmark, with HPV-16 and HPV-51 being the most prevalent. Polymerase chain reaction detects twice as many positive samples as HC2 but includes HPVX, possibly representing cutaneous HPV types found on normal genital skin.

  7. Human cultural and related remains from Me Aure Cave (site WMD007), Moindou, New Caledonia

    International Nuclear Information System (INIS)

    Grant-Mackie, J.A.; Sand, C.; Valentin, F.; Fitzgerald, B.M.; Richer de Forges, B.

    2013-01-01

    In 1995 a small cave near Me Aure (site WMD007) on the west coast of New Caledonia, about 120 km northwest of Noumea, was excavated and found to contain mainly owl and human midden deposits. Some of the contents have already been documented and the present paper completes the study by reporting the human-related materials, including human bone fragments, pottery sherds, bones of four rodent species, and marine mollusc and crab remains. Each of these material classes are reported separately by the authors responsible for their analysis, and the results and interpretations based on each line of evidence are compared and contrasted. The human bone and pottery data suggest a temporally constrained deposit (2750-2350 BP) that has experienced stratigraphic disturbance. This result raises doubt about the un-mixed nature of the deposit emphasized in earlier publications and it urges instead the conclusion that the Me Aure stratigraphy consists mostly of a redeposited set of horizons. If this conclusion is correct, interpretations already published relying on a fixed chronology, especially about vegetation change and avifauna depletion or early aroid introduction will need to be reconsidered. The site constitutes the first in New Caledonia for which a cave deposit has now been fully analysed. (author). 36 refs., 11 figs., 9 tabs.

  8. Low-altitude outbreaks of human fascioliasis related with summer rainfall in Gilan province, Iran

    Directory of Open Access Journals (Sweden)

    Abdoreza Salahi-Moghaddam

    2011-11-01

    Full Text Available Following human fascioliasis outbreaks in 1988 and 1999 in Gilan province, northern Iran, efforts are now made to shed light on the seasonal pattern of fascioliasis transmission in this endemic area, taking into account snail host populations, climatic conditions and human cases. Populations of the intermediate host snail (Lymnaea spp. peak in May and November, while there is a fourfold increase in the rate of human fascioliasis in February compared to that of September. Transmission is likely to occur mainly in late autumn and sporadically in late spring. Rainfall, seasonally analysed in periods of 3 years, indicates that accumulated summer rainfall may be related with the 1988 and 1999 human fascioliasis outbreaks. Although a more detailed picture, based on the analysis of further abiotic and biotic factors influencing fascioliasis transmission in this area, is required to substantiate this hypothesis, our results serve as the first step of a geographical information system project concerning the epidemiological study of fascioliasis in Iran. This local-scale study concerning the effects of climate change and natural disasters on the spread of fascioliasis aims to facilitate the understanding of what goes on at the regional scale in this respect.

  9. Low-altitude outbreaks of human fascioliasis related with summer rainfall in Gilan province, Iran.

    Science.gov (United States)

    Salahi-Moghaddam, Abdoreza; Habibi-Nokhandam, Majid; Fuentes, Màrius V

    2011-11-01

    Following human fascioliasis outbreaks in 1988 and 1999 in Gilan province, northern Iran, efforts are now made to shed light on the seasonal pattern of fascioliasis transmission in this endemic area, taking into account snail host populations, climatic conditions and human cases. Populations of the intermediate host snail (Lymnaea spp.) peak in May and November, while there is a fourfold increase in the rate of human fascioliasis in February compared to that of September. Transmission is likely to occur mainly in late autumn and sporadically in late spring. Rainfall, seasonally analysed in periods of 3 years, indicates that accumulated summer rainfall may be related with the 1988 and 1999 human fascioliasis outbreaks. Although a more detailed picture, based on the analysis of further abiotic and biotic factors influencing fascioliasis transmission in this area, is required to substantiate this hypothesis, our results serve as the first step of a geographical information system project concerning the epidemiological study of fascioliasis in Iran. This local-scale study concerning the effects of climate change and natural disasters on the spread of fascioliasis aims to facilitate the understanding of what goes on at the regional scale in this respect.

  10. Expression of Ras-related C3 botulinum toxin substrate 1 (RAC1) in human cholesteatoma.

    Science.gov (United States)

    Lee, No Hee; Chang, Ji-Won; Choi, June; Jung, Hak Hyun; Im, Gi Jung

    2013-02-01

    Ras-related C3 botulinum toxin substrate 1 (RAC1) is a 21-kDa signaling G protein that functions as a pleiotropic regulator of many cellular processes including epithelial differentiation. RAC1 activates the nicotinamide adenine dinucleotide phosphate oxidase complex which promotes formation of reactive oxygen species and degradation enzymes. RAC1 has been associated with rapid epithelial differentiation and invasive properties in human cholesteatoma. This study aimed to identify the presence of RAC1 in human cholesteatoma and analyze its functional role as a regulator of proteolysis and overgrowth. Tissue samples from human cholesteatoma and normal postaural skin were obtained from patients during otologic surgery for cholesteatoma. The expression of RAC1 mRNA was quantified by real-time RT-PCR, and localization of RAC1 expression was confirmed using immunohistochemical staining. Expression of RAC1 mRNA in the epithelium of cholesteatoma was significantly elevated 2.94 fold on average, compared with normal control skin. RAC1 expression in the suprabasal and basal layer of cholesteatoma epithelium was stronger than normal control skin. Our results suggest that RAC1 can be associated with rapid epithelial differentiation and invasive properties of human cholesteatoma.

  11. Natural landscape features, human-related attractants, and conflict hotspots: A spatial analysis of human-grizzly bear conflicts

    Science.gov (United States)

    Wilson, S.M.; Madel, M.J.; Mattson, D.J.; Graham, J.M.; Burchfield, J.A.; Belsky, J.M.

    2005-01-01

    There is a long history of conflict in the western United States between humans and grizzly bears (Ursus arctos) involving agricultural attractants. However, little is known about the spatial dimensions of this conflict and the relative importance of different attractants. This study was undertaken to better understand the spatial and functional components of conflict between humans and grizzly bears on privately owned agricultural lands in Montana. Our investigations focused on spatial associations of rivers and creeks, livestock pastures, boneyards (livestock carcass dump sites), beehives, and grizzly bear habitat with reported human-grizzly bear conflicts during 1986-2001. We based our analysis on a survey of 61 of 64 livestock producers in our study in the Rocky Mountain East Front, Montana. With the assistance of livestock and honey producers, we mapped the locations of cattle and sheep pastures, boneyards, and beehives. We used density surface mapping to identify seasonal clusters of conflicts that we term conflict hotspots. Hotspots accounted for 75% of all conflicts and encompassed approximately 8% of the study area. We also differentiated chronic (4 or more years of conflicts) from non-chronic hotspots (fewer than 4 years of conflict). The 10 chronic hotpots accounted for 58% of all conflicts. Based on Monte Carlo simulations, we found that conflict locations were most strongly associated with rivers and creeks followed by sheep lambing areas and fall sheep pastures. Conflicts also were associated with cattle calving areas, spring cow-calf pastures, summer and fall cattle pastures, and boneyards. The Monte Carlo simulations indicated associations between conflict locations and unprotected beehives at specific analysis scales. Protected (fenced) beehives were less likely to experience conflicts than unprotected beehives. Conflicts occurred at a greater rate in riparian and wetland vegetation than would be expected. The majority of conflicts occurred in a

  12. Stress markers in relation to job strain in human service organizations.

    Science.gov (United States)

    Ohlson, C G; Söderfeldt, M; Söderfeldt, B; Jones, I; Theorell, T

    2001-01-01

    Workers in human service organizations are often confronted with conflicting demands in providing care or education. The aim of this cross-sectional study was to relate levels of endocrine stress markers to perceived job strain in two human service organizations. Employees in two local units of the social insurance organization and two local units of the individual and family care sections of the social welfare in Sweden were selected and 103 employees participated (56% participation rate). The perceived job strain was assessed with a standardized questionnaire containing questions of the demand-control model. Questions specially designed to measure emotional demands were also included. The stress markers cortisol, prolactin, thyroid-stimulating hormone, testosterone and IgA and IgG were analysed in blood samples. The main finding was an association between high emotional strain and increased levels of prolactin. The levels of cortisol, but none of the other four stress markers, increased slightly with emotional strain. Emotional strain experienced in human service work may cause psychological stress. The increase in prolactin was modest but consistent with findings in other published studies on stress-related endocrine alterations. Copyright 2001 S. Karger AG, Basel.

  13. Time-related factors in the study of risks in animals and humans

    International Nuclear Information System (INIS)

    Gilbert, E.S.; Park, J.F.; Buschbom, R.L.

    1989-01-01

    Data from epidemiological studies of humans exposed to potentially harmful substances are usually analyzed using methods that account for the dependence of risks on time-related factors such as age and follow-up period. Recently developed statistical procedures allow modeling of the age-specific risks as a function of dose as well as factors such as age at exposure, time since exposure, exposure duration, and dose rate. These procedures potentially allow more rigorous inferences and clearer understanding of the patterns of risk observed in epidemiological studies than has been available in the past. Statistical procedures that consider time-related factors can also be applied to laboratory animal data, providing information that is useful for the problems involved in extrapolating from animal studies to humans. By applying such procedures to data on exposure to the same substance in different species (including humans) or to different substances in the same species, better understanding of the relationship of risks across species and across substances can be achieved. In addition, such statistical procedures allow appropriate treatment of exposure that is accumulated over time and lead to improved understanding of patterns of risk over time. The approach is illustrated using data from a lifespan study of beagle dogs exposed to inhaled Pu

  14. Hardiness in relation to organisational commitment in the Human Resource Management field

    Directory of Open Access Journals (Sweden)

    Nadia Ferreira

    2012-09-01

    Research purpose: The study empirically investigated the relationship between an individual’s hardiness (measured by the Personal Views Survey II [PVS-II] and organisational commitment (measured by the Organisational Commitment Scale. Motivation for the study: Research on an individual’s hardiness profile as an aspect of their career well-being and success and how these attributes influence their psychological attachment to the organisation, is needed to guide human resource career development support practices aimed at retaining valuable staff. Research design, approach and method: A quantitative survey was conducted on a convenience sample of predominantly Black (92.2% and female (71% employed adults (N = 355 at managerial and staff levels in the human resource management field. Main findings: Correlational and multiple regression analyses revealed a number of significant relationships between the two variables. Practical/managerial implications: Managers and human resource practitioners need to recognise how people’s hardiness relates to their sense of psychological attachment to the organisation. Organisations concerned with the retention and well-being of their equity staff members need to find a way to enhance and develop their hardiness and commitment. Contribution/value-add: The research contributes new insights into and knowledge of the factors that influence their employees’ hardiness and how these relate to their organisational commitment. The results may be used to inform career development support interventions that aim to increase employees’ sense of career well-being and success.

  15. The normative dimensions of extending the human lifespan by age-related biomedical innovations.

    Science.gov (United States)

    Ehni, Hans-Joerg; Marckmann, Georg

    2008-10-01

    The current normative debate on age-related biomedical innovations and the extension of the human lifespan has important shortcomings. Mainly, the complexity of the different normative dimensions relevant for ethical and/or juridicial norms is not fully developed and the normative quality of teleological and deontological arguments is not properly distinguished. This article addresses some of these shortcomings and develops the outline of a more comprehensive normative framework covering all relevant dimensions. Such a frame necessarily has to include conceptions of a good life on the individual and societal levels. Furthermore, as a third dimension, a model for the access to and the just distribution of age-related biomedical innovations and technologies extending the human lifespan will be developed. It is argued that such a model has to include the different levels of the general philosophical theories of distributive justice, including social rights and theories of just health care. Furthermore, it has to show how these theories can be applied to the problem area of aging and extending the human lifespan.

  16. Incidence trends of human papillomavirus-related head and neck cancer in Taiwan, 1995-2009.

    Science.gov (United States)

    Hwang, Tzer-Zen; Hsiao, Jenn-Ren; Tsai, Chia-Rung; Chang, Jeffrey S

    2015-07-15

    Recent studies suggested that human papillomavirus (HPV) is an emerging risk factor of head and neck cancer (HNC), particularly for oropharyngeal cancer. Studies from the West showed a rising trend of HPV-related HNC despite a decrease of the overall HNC incidence. In contrast, the overall HNC incidence in Taiwan has continued to rise. It is not clear whether the incidence trends of HPV-related HNC in Taiwan have a similar pattern to those from countries with an overall decreasing incidence of HNC. This study examined the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan using data from the Taiwan Cancer Registry. Our results showed that the incidence trends of HPV-related and HPV-unrelated HNC in Taiwan both rose during 1995-2009. The incidence of HPV-related HNC (1.3 per 100,000 in 1995 to 3.3 in 2009, annual percentage change (APC) = 6.9, p Taiwan has continued to increase, the most rapid rise is in the HPV-related HNC. This suggests that similar to the Western world, HPV-related HNC is becoming an important public health issue in Taiwan. © 2014 UICC.

  17. Long-Term Forecasting the Development of Relations Between Local Human Civilizations: Conclusions and Proposals

    Directory of Open Access Journals (Sweden)

    Alexei I. Podberezkin

    2016-01-01

    Full Text Available The article is the form of scientific report on the results of three year long project on methodology of long term forecasting the development of the system of international relations. The methodology is based on the following assumptions: input information is accurate and complete; international relations constitute a system, scenarios for different levels of international relations development are hierarchically interdependent; the speed of development is different on various levels of international relations; various national capabilities affect the development; elites affect international relations; civil society affect international relations. Based on this assumption the author builds the most probable scenario of intercivilizational relations which is military coercive interaction. The role of soft power will increase its share in the toolkit of the confrontational politics. To win in this confrontation it is necessary to review the current practices of strategic forecasting and planning and to rebuild the entire military organization of the Russian army. The principal condition for the victory is development of national human capital, as well as the formation of the national ideology.

  18. The Issues of Human Rights in the India-U.S. Relations

    Directory of Open Access Journals (Sweden)

    Zakharov Aleksey I.

    2016-10-01

    Full Text Available The article presents a brief overview of India-U.S. relations during the period of Narendra Modi’s government and Barack Obama’s administration. The author analyzes the dynamics of cooperation development after the victory of Bharatiya Janata Party in the 2014 Parliamentary elections in India and studies the key directions of bilateral agenda. The current condition of India-U.S. strategic dialogue and the influence of human rights issues on the countries’ cooperation are characterized. Since 2014 the states’ cooperation has been growing rapidly. The bilateral investment, trade and economic interdependence have significantly increased. Some experts and mass media note that Barack Obama and Narendra Modi are having friendly relations. From a different angle, a number of agreements between countries still remain unaccomplished. For instance, the U.S. support for India’s permanent seat in the United Nations Security Council, its accession to APEC and the implementation of nuclear deal have yet to be turned into achievement. Together with strengthening the bilateral strategic dialogue, the U.S. has intensified the criticism of India’s human rights record. The main part of it includes the cases of religious intolerance, which are observed in the United States Commission on International Religious Freedom reports and the remarks given by U.S. lawmakers and official representatives, including the Ambassador to India. Washington’s careful attention to the human rights issues and religious violence in particular is one of the major irritants in the U.S.-India relations. The engagement of Indian Americans in the local U.S. politics and their lobbying efforts in the context of U.S.-India relations are revealed. The author outlines the near-terms perspectives of bilateral cooperation.

  19. A study on the air pollution related human diseases in Thiruvananthapuram City, Kerala

    Energy Technology Data Exchange (ETDEWEB)

    Bency, K.T.; Jansy, J.; Thakappan, B.; Kumar, B.; Sreelekha, T.T.; Hareendran, N.K.; Nair, P.K.K.; Krishnan Nair, M. [National Inst. of Environmental Health, Thiruvananthapuram, Kerala (India). Regional Cancer Centre

    2005-07-01

    This paper contains the results of a study that examined the impacts of air pollution on human health in Thiruvananthapuram City, India. The study compared health impacts arising from air pollution in three different zones including residential, commercial, and industrial. The paper presents the findings from the study according to each of these zones and presents conclusions.The study found that each zone had its individual environmental problems which were characterized by specific diseases. In the residential zone, there was a prevalence of diseases such as breast cancer and cardiac-related problems as well as dietary problems linked to obesity. In the industrial zone, respiratory illnesses related to air pollution were prevalent. Cardiac and vector-borne diseases, related to environmental hazards like waste water stagnation, dust and solid waste problem, were high in the commercial zone. 14 refs., 3 figs.

  20. Human Brucellosis in Maghreb: Existence of a Lineage Related to Socio-Historical Connections with Europe

    Science.gov (United States)

    Lounes, Nedjma; Cherfa, Moulay-Ali; Le Carrou, Gilles; Bouyoucef, Abdellah; Jay, Maryne; Garin-Bastuji, Bruno; Mick, Virginie

    2014-01-01

    Despite control/eradication programs, brucellosis, major worldwide zoonosis due to the Brucella genus, is endemic in Northern Africa and remains a major public health problem in the Maghreb region (Algeria/Morocco/Tunisia). Brucella melitensis biovar 3 is mostly involved in human infections and infects mainly small ruminants. Human and animal brucellosis occurrence in the Maghreb seems still underestimated and its epidemiological situation remains hazy. This study summarizes official data, regarding Brucella melitensis infections in Algeria, from 1989 to 2012, with the purpose to provide appropriate insights concerning the epidemiological situation of human and small ruminant brucellosis in Maghreb. Algeria and Europe are closely linked for historical and economical reasons. These historical connections raise the question of their possible impact on the genetic variability of Brucella strains circulating in the Maghreb. Other purpose of this study was to assess the genetic diversity among Maghreb B. melitensis biovar 3 strains, and to investigate their possible epidemiological relationship with European strains, especially with French strains. A total of 90 B. melitensis biovar 3 Maghreb strains isolated over a 25 year-period (1989–2014), mainly from humans, were analysed by MLVA-16. The obtained results were compared with genotypes of European B. melitensis biovar 3 strains. Molecular assays showed that Algerian strains were mainly distributed into two distinct clusters, one Algerian cluster related to European sub-cluster. These results led to suggest the existence of a lineage resulting from socio-historical connections between Algeria and Europe that might have evolved distinctly from the Maghreb autochthonous group. This study provides insights regarding the epidemiological situation of human brucellosis in the Maghreb and is the first molecular investigation regarding B. melitensis biovar 3 strains circulating in the Maghreb. PMID:25517901

  1. A comparison of age-related changes in axial prestretch in human carotid arteries and in human abdominal aorta.

    Science.gov (United States)

    Horný, Lukáš; Adámek, Tomáš; Kulvajtová, Markéta

    2017-02-01

    It is known that large arteries in situ are subjected to significant axial prestretch. This prestretch plays an important physiological role in optimizing the biomechanical response of an artery. It is also known that the prestretch declines with age. However, a detailed description of age-related changes in prestretch is available only for the abdominal aorta and for the femoropliteal artery. Our study presents results of measurements of axial prestretch in 229 left common carotid arteries excised in autopsies. It was found that the prestretch of the carotid artery correlates significantly with age ([Formula: see text], p value Wilcoxon signed-rank test) and simultaneously that carotid media contains a lower number of elastic membranes (median/IQR: 26.5/11.8 vs. 31.5/11.8, [Formula: see text] in the Wilcoxon signed-rank test). This could be a reason for the different extent of the prestretch observed in aorta and in carotid artery. Our data sample also contains 5 measurements of the axial prestretch in abdominal aortas suffering from an aneurysm. It was found that aneurysmatic aortas also exhibit axial retraction when excised from in situ position. To the best of our knowledge, this is the first time that detailed data characterizing axial prestretch of the human left common carotid artery have been presented.

  2. The psychosocial burden of human papillomavirus related disease and screening interventions.

    Science.gov (United States)

    Pirotta, M; Ung, L; Stein, A; Conway, E L; Mast, T C; Fairley, C K; Garland, S

    2009-12-01

    (i) To assess the psychosocial burden of testing for human papillomavirus (HPV) related genital disease or of a HPV-related diagnosis; (ii) to compare an instrument specifically designed to measure HPV-related psychosocial burden with other generic quality of life (QoL) instruments. A cross-sectional design. Researchers recruited women from outpatient clinics at a major tertiary women's hospital and a sexual health centre who completed surveys within 3 months of receiving 331 women, 18-45 years, who had experienced a normal cervical Papanicolaou (Pap) result, an abnormal Pap result, biopsy confirmed cervical intraepithelial neoplasia (CIN) or external genital warts (EGW). The HPV impact profile (HIP) designed to assess the psychosocial impact of HPV; two general health-related QoL surveys-the EuroQoL VAS and the Sheehan disability scale; and a HPV knowledge survey. Response rate was 78%. Significant psychosocial impacts were found for women screened for, or having a diagnosis of, HPV-related genital disease. The largest impact was in women with CIN 2/3 and EGW. This HPV-related psychosocial impact was most sensitively detected with the HIP. Relative to generic measures of QoL, the HIP provided insight into the full range of psychosocial impacts of HPV testing and diagnoses. Clinicians need to be aware of the potential psychosocial impact of testing for or diagnosing HPV-related genital disease, in particular CIN 2/3 and EGW. The HIP survey is a more sensitive measure of the psychosocial impact of HPV-related genital disease than generic QoL surveys.

  3. A Human Open Field Test Reveals Thigmotaxis Related to Agoraphobic Fear.

    Science.gov (United States)

    Walz, Nora; Mühlberger, Andreas; Pauli, Paul

    2016-09-01

    Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia. A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square. Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia. This study is the first to our knowledge to verify the translational validity of the OFT and to reveal that thigmotaxis, an evolutionarily adaptive behavior shown by most species, is related to agoraphobia, a pathologic fear of open spaces, and anxiety sensitivity, a risk factor for agoraphobia. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  4. Pleasant and unpleasant odors influence hedonic evaluations of human faces: an event-related potential study.

    Directory of Open Access Journals (Sweden)

    Stephanie Jane Cook

    2015-12-01

    Full Text Available Odors can alter hedonic evaluations of human faces, but the neural mechanisms of such effects are poorly understood. The present study aimed to analyze the neural underpinning of odor-induced changes in evaluations of human faces in an odor-priming paradigm, using event-related potentials (ERPs. Healthy, young participants (N = 20 rated neutral faces presented after a three second pulse of a pleasant odor (jasmine, unpleasant odor (methylmercaptan, or no-odor control (clean air. Neutral faces presented in the pleasant odor condition were rated more pleasant than the same faces presented in the no-odor control condition, which in turn were rated more pleasant than faces in the unpleasant odor condition. Analysis of face-related potentials revealed four clusters of electrodes significantly affected by odor condition at specific time points during long-latency epochs (600−950 ms. In the 620−640 ms interval, two scalp-time clusters showed greater negative potential in the right parietal electrodes in response to faces in the pleasant odor condition, compared to those in the no-odor and unpleasant odor conditions. At 926 ms, face-related potentials showed greater positivity in response to faces in the pleasant and unpleasant odor conditions at the left and right lateral frontal-temporal electrodes, respectively. Our data shows that odor-induced shifts in evaluations of faces were associated with amplitude changes in the late (> 600 and ultra-late (> 900 ms latency epochs. The observed amplitude changes during the ultra-late epoch are consistent with a left/right hemisphere bias towards pleasant/unpleasant odor effects. Odors alter evaluations of human faces, even when there is a temporal lag between presentation of odors and faces. Our results provide an initial understanding of the neural mechanisms underlying effects of odors on hedonic evaluations.

  5. Detection and genetic characterization of a novel parvovirus distantly related to human bufavirus in domestic pigs.

    Science.gov (United States)

    Hargitai, Renáta; Pankovics, Péter; Kertész, Attila Mihály; Bíró, Hunor; Boros, Ákos; Phan, Tung Gia; Delwart, Eric; Reuter, Gábor

    2016-04-01

    In this study, a novel parvovirus (strain swine/Zsana3/2013/HUN, KT965075) was detected in domestic pigs and genetically characterized by viral metagenomics and PCR methods. The novel parvovirus was distantly related to the human bufaviruses and was detected in 19 (90.5 %) of the 21 and five (33.3 %) of the 15 faecal samples collected from animals with and without cases of posterior paraplegia of unknown etiology from five affected farms and one control farm in Hungary, respectively. Swine/Zsana3/2013/HUN is highly prevalent in domestic pigs and potentially represents a novel parvovirus species in the subfamily Parvovirinae.

  6. Age-related variations in the microstructure of human tibial cancellous bone

    DEFF Research Database (Denmark)

    Ding, M.; Odgaard, A.; Linde, F.

    2002-01-01

    -related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16-85 years. These specimens were micro-computed tomography (micro-CT) scanned......, and microstructural properties were determined. The specimens were then tested in compression to obtain Young's modulus. The degree of anisotropy, mean marrow space volume, and bone surface-to-volume ratio increased significantly with age. Bone volume fraction, mean trabecular volume, and bone surface density...

  7. Human cortical activity related to unilateral movements. A high resolution EEG study.

    Science.gov (United States)

    Urbano, A; Babiloni, C; Onorati, P; Babiloni, F

    1996-12-20

    In the present study a modern high resolution electroencephalography (EEG) technique was used to investigate the dynamic functional topography of human cortical activity related to simple unilateral internally triggered finger movements. The sensorimotor area (M1-S1) contralateral to the movement as well as the supplementary motor area (SMA) and to a lesser extent the ipsilateral M1-S1 were active during the preparation and execution of these movements. These findings suggest that both hemispheres may cooperate in both planning and production of simple unilateral volitional acts.

  8. Happiness and Human Relations: The Role of Materialistic Values. An ABM Illustration

    Directory of Open Access Journals (Sweden)

    Mariano Rojas

    2014-03-01

    Full Text Available This paper argues that a person’s happiness must be understood as a phenomenon that emerges not only from her individual condition but also from her place in society. Understanding that a person is socially immersed implies giving a greater role to social interactions and social structure. The paper presents a simple model to take into consideration the role of human relations. An agent-based model (ABM is used to illustrate the implementation of the model in understanding people’s happiness.

  9. Social Robotic Experience and Media Communication Practices: An Exploration on the Emotional and Ritualized Human-technology-relations

    Directory of Open Access Journals (Sweden)

    Christine Linke

    2013-01-01

    Full Text Available This article approaches the subject of social robots by focusing on the emotional relations people establish with media and information and communication technology (ICTs in their everyday life. It examines human-technology-relation from a social studies point of view, seeking to raise questions that enable us to make a connection between the research on human relationships and the topic of human-technology relation, especially human-humanoid-relation. In order to explore the human-technology-relations, theoretical ideas of a mediatization of communication and of a ritual interaction order are applied. Ritual theory is particularly used to enable a focus on emotion as a significant dimension in analyzing social technologies. This explorative article refers to empirical findings regarding media communication practices in close relationships. It argues that following the developed approach regarding mediatized and ritualized relational practices, useful insights for a conceptualization of the human-social robot relation can be achieved. The article concludes with remarks regarding the challenge of an empirical approach to human-social robot-relations.

  10. Concept Analysis: Health-Promoting Behaviors Related to Human Papilloma Virus (HPV) Infection.

    Science.gov (United States)

    McCutcheon, Tonna; Schaar, Gina; Parker, Karen L

    2015-01-01

    The concept of health-promoting behaviors incorporates ideas presented in the Ottawa Charter of Public Health and the nursing-based Health Promotion Model. Despite the fact that the concept of health-promoting behaviors has a nursing influence, literature suggests nursing has inadequately developed and used this concept within nursing practice. A further review of literature regarding health promotion behaviors and the human papilloma virus suggest a distinct gap in nursing literature. This article presents a concept analysis of health-promoting behaviors related to the human papilloma virus in order to encourage the application of the concept into nursing practice, promote continued nursing research regarding this concept, and further expand the application of health-promoting behaviors to other situations and populations within the nursing discipline. Attributes of health-promoting behaviors are presented and include empowerment, participation, community, and a positive concept of health. Antecedents, consequences, and empirical referents are also presented, as are model, borderline, and contrary cases to help clarify the concept. Recommendations for human papilloma virus health-promoting behaviors within the nursing practice are also provided. © 2014 Wiley Periodicals, Inc.

  11. The Seven Deadly Tensions of Health-Related Human Information Behavior

    Directory of Open Access Journals (Sweden)

    J. David Johnson

    2015-08-01

    Full Text Available Tensions are a ubiquitous feature of social life and are manifested in a number of particular forms: contradictory logics, competing demands, clashes of ideas, contradictions, dialectics, irony, paradoxes, and/or dilemmas. This essay aims to explore in detail tensions surrounding seven common findings of the information seeking literature relating to: interpersonal communication, accessibility, level of skill, individual preferences, psychological limits, inertia, and costs. Our incomplete understanding of these tensions can lead us to suggest resolutions that do not recognize their underlying dualities. Human information behavior stands at the intersection of many important theoretical and policy issues (e.g., personalized medicine. Policy makers need to be more attuned to these basic tensions of information seeking recognizing the real human limits they represent to informing the public. So, even if you build a great information system, people will not necessarily use it because of the force of these underlying tensions. While rationality rules systems, irrationality rules people. The proliferation of navigator roles over the last several years is actually a hopeful sign: recognition that people need a human interface to inform them about our ever more complex health care systems.

  12. Here, there be dragons: charting autophagy-related alterations in human tumors.

    Science.gov (United States)

    Lebovitz, Chandra B; Bortnik, Svetlana B; Gorski, Sharon M

    2012-03-01

    Macroautophagy (or autophagy) is a catabolic cellular process that is both homeostatic and stress adaptive. Normal cells rely on basal levels of autophagy to maintain cellular integrity (via turnover of long-lived proteins and damaged organelles) and increased levels of autophagy to buoy cell survival during various metabolic stresses (via nutrient and energy provision through lysosomal degradation of cytoplasmic components). Autophagy can function in both tumor suppression and tumor progression, and is under investigation in clinical trials as a novel target for anticancer therapy. However, its role in cancer pathogenesis has yet to be fully explored. In particular, it remains unknown whether in vitro observations will be applicable to human cancer patients. Another outstanding question is whether there exists tumor-specific selection for alterations in autophagy function. In this review, we survey reported mutations in autophagy genes and key autophagy regulators identified in human tumor samples and summarize the literature regarding expression levels of autophagy genes and proteins in various cancer tissues. Although it is too early to draw inferences from this collection of in vivo studies of autophagy-related alterations in human cancers, their results highlight the challenges that must be overcome before we can accurately assess the scope of autophagy's predicted role in tumorigenesis.

  13. The Contribution of Equitation Science to Minimising Horse-Related Risks to Humans

    Directory of Open Access Journals (Sweden)

    Melissa Starling

    2016-02-01

    Full Text Available Equitation science is an evidence-based approach to horse training and riding that focuses on a thorough understanding of both equine ethology and learning theory. This combination leads to more effective horse training, but also plays a role in keeping horse riders and trainers safe around horses. Equitation science underpins ethical equitation, and recognises the limits of the horse’s cognitive and physical abilities. Equitation is an ancient practice that has benefited from a rich tradition that sees it flourishing in contemporary sporting pursuits. Despite its history, horse-riding is an activity for which neither horses nor humans evolved, and it brings with it significant risks to the safety of both species. This review outlines the reasons horses may behave in ways that endanger humans and how training choices can exacerbate this. It then discusses the recently introduced 10 Principles of Equitation Science and explains how following these principles can minimise horse-related risk to humans and enhance horse welfare.

  14. The etiology of human age-related cataract. Proteins don't last forever.

    Science.gov (United States)

    Truscott, Roger J W; Friedrich, Michael G

    2016-01-01

    It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification. Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses. The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein-protein interactions are disrupted and lens opacification ensues. Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Legal Issues Related to Donation of Organs, Tissues and Cells of Human Origin

    Directory of Open Access Journals (Sweden)

    Gabriela Mironov

    2010-06-01

    Full Text Available Scientific developments, positive changes in attitude of the man and the new legal framework allow the donation of organs, tissues and cells of human origin. In this context it is necessary to clarifywhether the donation covered by the special law is, legally, one and the same as that covered by the Romanian Civil Code in force and qualified the successor’s right to accept or reject late withdrawals for transplantation. The right to life and physical integrity is personal patrimony; it is a subjective civil right that has no economic content and it cannot be measured in money. Consequently, the content of these rights can not be expressed in money, the property does not belong to their owner. Given the above view, "the right of disposal" to donation of organs, tissues and cells of human origin is an attribute of ownership, right to life and physical integrity, as a personal right that is an intimate attribute patrimonial related to the person’s right to dispose of his body as it wishes, within the law. Addressing these issues it is necessary to clarify the legal consequences of donating organs, tissues and cells of human origin, considering that medical activities are becoming more numerous.

  16. Drosophila melanogaster Models of Metal-Related Human Diseases and Metal Toxicity.

    Science.gov (United States)

    Calap-Quintana, Pablo; González-Fernández, Javier; Sebastiá-Ortega, Noelia; Llorens, José Vicente; Moltó, María Dolores

    2017-07-06

    Iron, copper and zinc are transition metals essential for life because they are required in a multitude of biological processes. Organisms have evolved to acquire metals from nutrition and to maintain adequate levels of each metal to avoid damaging effects associated with its deficiency, excess or misplacement. Interestingly, the main components of metal homeostatic pathways are conserved, with many orthologues of the human metal-related genes having been identified and characterized in Drosophila melanogaster . Drosophila has gained appreciation as a useful model for studying human diseases, including those caused by mutations in pathways controlling cellular metal homeostasis. Flies have many advantages in the laboratory, such as a short life cycle, easy handling and inexpensive maintenance. Furthermore, they can be raised in a large number. In addition, flies are greatly appreciated because they offer a considerable number of genetic tools to address some of the unresolved questions concerning disease pathology, which in turn could contribute to our understanding of the metal metabolism and homeostasis. This review recapitulates the metabolism of the principal transition metals, namely iron, zinc and copper, in Drosophila and the utility of this organism as an experimental model to explore the role of metal dyshomeostasis in different human diseases. Finally, a summary of the contribution of Drosophila as a model for testing metal toxicity is provided.

  17. Microarray evaluation of age-related changes in human dental pulp.

    Science.gov (United States)

    Tranasi, Michelangelo; Sberna, Maria Teresa; Zizzari, Vincenzo; D'Apolito, Giuseppe; Mastrangelo, Filiberto; Salini, Luisa; Stuppia, Liborio; Tetè, Stefano

    2009-09-01

    The dental pulp undergoes age-related changes that could be ascribed to physiological, defensive, or pathological irritant-induced changes. These changes are regulated by pulp cell activity and by a variety of extracellular matrix (ECM) macromolecules, playing important roles in growth regulation, tissue differentiation and organization, formation of calcified tissue, and defense mechanisms and reactions to inflammatory stimuli. The aim of this research was to better understand the genetic changes that underlie the histological modification of the dental pulp in aging. The gene expression profile of the human dental pulp in young and older subjects was compared by RNA microarray analysis that allowed to simultaneously analyze the expression levels of thousands of genes. Data were statistically analyzed by Significance Analysis of Microarrays (SAM) Ingenuity Pathway Analysis (IPA) software. Semiquantitative and real-time reverse-transcriptase polymerase chain reaction analyses were performed to confirm the results. Microarray analysis revealed several differentially expressed genes that were categorized in growth factors, transcription regulators, apoptosis regulators, and genes of the ECM. The comparison analysis showed a high expression level of the biological functions of cell and tissue differentiation, development, and proliferation and of the immune, lymphatic, and hematologic system in young dental pulp, whereas the pathway of apoptosis was highly expressed in older dental pulp. Expression profile analyses of human dental pulp represent a sensible and useful tool for the study of mechanisms involved in differentiation, growth and aging of human dental pulp in physiological and pathological conditions.

  18. Glucose modulates food-related salience coding of midbrain neurons in humans.

    Science.gov (United States)

    Ulrich, Martin; Endres, Felix; Kölle, Markus; Adolph, Oliver; Widenhorn-Müller, Katharina; Grön, Georg

    2016-12-01

    Although early rat studies demonstrated that administration of glucose diminishes dopaminergic midbrain activity, evidence in humans has been lacking so far. In the present functional magnetic resonance imaging study, glucose was intravenously infused in healthy human male participants while seeing images depicting low-caloric food (LC), high-caloric food (HC), and non-food (NF) during a food/NF discrimination task. Analysis of brain activation focused on the ventral tegmental area (VTA) as the origin of the mesolimbic system involved in salience coding. Under unmodulated fasting baseline conditions, VTA activation was greater during HC compared with LC food cues. Subsequent to infusion of glucose, this difference in VTA activation as a function of caloric load leveled off and even reversed. In a control group not receiving glucose, VTA activation during HC relative to LC cues remained stable throughout the course of the experiment. Similar treatment-specific patterns of brain activation were observed for the hypothalamus. The present findings show for the first time in humans that glucose infusion modulates salience coding mediated by the VTA. Hum Brain Mapp 37:4376-4384, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Cultural relations between Hungary and Albania during the period of Humanism and Renaissance

    Directory of Open Access Journals (Sweden)

    Muhamet Mala

    2016-07-01

    Full Text Available Cultural Hungarian-Albanian relations during the Middle Ages are characterized by a relatively poor intensity. Actually, relations between these two countries are more intense in the political field and especially through the partnership between Gjergj Kastrioti Skanderbeg and John Hunyadi. Regarding the origin, the Hungarian culture identity is rather distinct from the Albanian one. Lack of cultural contacts, among others, was conditioned also by the fact that these relations were held under war circumstances and their primary aim was the common defense from Ottoman attacks. Actually, the Albanian medieval culture remained a Mediterranean culture with elements of Byzantine influence in the continental and southern areas. Meanwhile, Hungary belonged to Central Europe, which, even though far away from Mediterranean cultural mainstream, sought to be influenced by this culture, namely by the Renaissance that emanated exactly in the Mediterranean region. It was Matthias Corvinus effort, regarding the cultural influence of the Mediterranean and Renaissance in Hungary but also the fact that Hungary possessed some of the most important towns of the Adriatic coast and particularly Ragusa. This city was the center where cultural relations between Albanian and Hungary started and became intensified in the religious, intellectual and human field.

  20. Loss of urban forest canopy and the related effects on soundscape and human directed attention

    Science.gov (United States)

    Laverne, Robert James Paul

    The specific questions addressed in this research are: Will the loss of trees in residential neighborhoods result in a change to the local soundscape? The investigation of this question leads to a related inquiry: Do the sounds of the environment in which a person is present affect their directed attention?. An invasive insect pest, the Emerald Ash Borer (Agrilus planipennis ), is killing millions of ash trees (genus Fraxinus) throughout North America. As the loss of tree canopy occurs, urban ecosystems change (including higher summer temperatures, more stormwater runoff, and poorer air quality) causing associated changes to human physical and mental health. Previous studies suggest that conditions in urban environments can result in chronic stress in humans and fatigue to directed attention, which is the ability to focus on tasks and to pay attention. Access to nature in cities can help refresh directed attention. The sights and sounds associated with parks, open spaces, and trees can serve as beneficial counterbalances to the irritating conditions associated with cities. This research examines changes to the quantity and quality of sounds in Arlington Heights, Illinois. A series of before-and-after sound recordings were gathered as trees died and were removed between 2013 and 2015. Comparison of recordings using the Raven sound analysis program revealed significant differences in some, but not all measures of sound attributes as tree canopy decreased. In general, more human-produced mechanical sounds (anthrophony) and fewer sounds associated with weather (geophony) were detected. Changes in sounds associated with animals (biophony) varied seasonally. Monitoring changes in the proportions of anthrophony, biophony and geophony can provide insight into changes in biodiversity, environmental health, and quality of life for humans. Before-tree-removal and after-tree-removal sound recordings served as the independent variable for randomly-assigned human volunteers as

  1. Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

    Science.gov (United States)

    Lau, Cia-Hin; Suh, Yousin

    2017-01-01

    The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

  2. The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa

    Science.gov (United States)

    De Vuyst, Hugo; Alemany, Laia; Lacey, Charles; Chibwesha, Carla J.; Sahasrabuddhe, Vikrant; Banura, Cecily; Denny, Lynette; Parham, Groesbeck P.

    2014-01-01

    Despite the scarcity of high quality cancer registries and lack of reliable mortality data, it is clear that human papillomavirus (HPV)-associated diseases, particularly cervical cancer, are major causes of morbidity and mortality in sub-Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in the world and the disease is the most common cause of cancer death among women in the region. The high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services. In addition, it appears that the prevalence of HPV in women with normal cytology is higher than in more developed areas of the world, at an average of 24%. There is, however, significant regional variation in SSA, with the highest incidence of HPV infection and cervical cancer found in Eastern and Western Africa. It is expected that, due to aging and growth of the population, but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, cervical cancer incidence and mortality rates in SSA will rise over the next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also relatively more frequent compared with other world regions. Data on other HPV-related anogenital cancers including those of the vulva, vagina, anus, and penis, are limited. Genital warts are common and associated with HPV types 6 and 11. HIV infection increases incidence and prevalence of all HPV-associated diseases. Sociocultural determinants of HPV-related disease, as well as the impact of forces that result in social destabilization, demand further study. Strategies to reduce the excessive burden of HPV-related diseases in SSA include age-appropriate prophylactic HPV vaccination, cervical cancer prevention services for women of the reproductive

  3. Feature Extraction of Event-Related Potentials Using Wavelets: An Application to Human Performance Monitoring

    Science.gov (United States)

    Trejo, Leonard J.; Shensa, Mark J.; Remington, Roger W. (Technical Monitor)

    1998-01-01

    This report describes the development and evaluation of mathematical models for predicting human performance from discrete wavelet transforms (DWT) of event-related potentials (ERP) elicited by task-relevant stimuli. The DWT was compared to principal components analysis (PCA) for representation of ERPs in linear regression and neural network models developed to predict a composite measure of human signal detection performance. Linear regression models based on coefficients of the decimated DWT predicted signal detection performance with half as many f ree parameters as comparable models based on PCA scores. In addition, the DWT-based models were more resistant to model degradation due to over-fitting than PCA-based models. Feed-forward neural networks were trained using the backpropagation,-, algorithm to predict signal detection performance based on raw ERPs, PCA scores, or high-power coefficients of the DWT. Neural networks based on high-power DWT coefficients trained with fewer iterations, generalized to new data better, and were more resistant to overfitting than networks based on raw ERPs. Networks based on PCA scores did not generalize to new data as well as either the DWT network or the raw ERP network. The results show that wavelet expansions represent the ERP efficiently and extract behaviorally important features for use in linear regression or neural network models of human performance. The efficiency of the DWT is discussed in terms of its decorrelation and energy compaction properties. In addition, the DWT models provided evidence that a pattern of low-frequency activity (1 to 3.5 Hz) occurring at specific times and scalp locations is a reliable correlate of human signal detection performance.

  4. Late Holocene vegetation changes in relation with climate fluctuations and human activities in Languedoc (Southern France)

    Science.gov (United States)

    Azuara, J.; Combourieu-Nebout, N.; Lebreton, V.; Mazier, F.; Müller, S. D.; Dezileau, L.

    2015-09-01

    Holocene climate fluctuations and human activities since the Neolithic have shaped present-day Mediterranean environments. Separating anthropogenic effects from climatic impacts to reconstruct Mediterranean paleoenvironments over the last millennia remains a challenging issue. High resolution pollen analyses were undertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamics over the last 4500 years. Results are compared with climatic, historical and archeological archives. A long-term aridification trend is highlighted during the Late Holocene and three superimposed arid events are recorded at 4600-4300, 2800-2400 and 1300-1100 cal BP. These periods of climatic instability coincide in time with the rapid climatic events depicted in the Atlantic Ocean (Bond et al., 2001). From the Bronze Age (4000 cal BP) to the end of the Iron Age (around 2000 cal BP), the spread of evergreen taxa and loss of forest cover result from anthropogenic impact. The Antiquity is characterized by a major reforestation event related to the concentration of rural activities and populations in coastal plains leading to forest recovery in the mountains. A major regional deforestation occurred at the beginning of the High Middle Ages. Around 1000 cal BP, forest cover is minimal while cover of olive, chestnut and walnut expands in relation to increasing human influence. The present day vegetation dominated by Mediterranean shrubland and pines has been in existence since the beginning of the 20th century.

  5. Late Holocene vegetation changes in relation with climate fluctuations and human activity in Languedoc (southern France)

    Science.gov (United States)

    Azuara, J.; Combourieu-Nebout, N.; Lebreton, V.; Mazier, F.; Müller, S. D.; Dezileau, L.

    2015-12-01

    Holocene climate fluctuations and human activity since the Neolithic have shaped present-day Mediterranean environments. Separating anthropogenic effects from climatic impacts to better understand Mediterranean paleoenvironmental changes over the last millennia remains a challenging issue. High-resolution pollen analyses were undertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamics over the last 4500 years. Results are compared with climatic, historical and archeological archives. A long-term aridification trend is highlighted during the late Holocene, and three superimposed arid events are recorded at 4600-4300, 2800-2400 and 1300-1100 cal BP. These periods of high-frequency climate variability coincide in time with the rapid climatic events observed in the Atlantic Ocean (Bond et al., 2001). From the Bronze Age (4000 cal BP) to the end of the Iron Age (around 2000 cal BP), the spread of sclerophyllous taxa and loss of forest cover result from anthropogenic impact. Classical Antiquity is characterized by a major reforestation event related to the concentration of rural activity and populations in coastal plains leading to forest recovery in the mountains. A major regional deforestation occurred at the beginning of the High Middle Ages. Around 1000 cal BP, forest cover is minimal while the cover of olive, chestnut and walnut expands in relation to increasing human influence. The present-day vegetation dominated by Mediterranean shrubland and pines has been in existence since the beginning of the 20th century.

  6. Human-Chromatin-Related Protein Interactions Identify a Demethylase Complex Required for Chromosome Segregation

    Directory of Open Access Journals (Sweden)

    Edyta Marcon

    2014-07-01

    Full Text Available Chromatin regulation is driven by multicomponent protein complexes, which form functional modules. Deciphering the components of these modules and their interactions is central to understanding the molecular pathways these proteins are regulating, their functions, and their relation to both normal development and disease. We describe the use of affinity purifications of tagged human proteins coupled with mass spectrometry to generate a protein-protein interaction map encompassing known and predicted chromatin-related proteins. On the basis of 1,394 successful purifications of 293 proteins, we report a high-confidence (85% precision network involving 11,464 protein-protein interactions among 1,738 different human proteins, grouped into 164 often overlapping protein complexes with a particular focus on the family of JmjC-containing lysine demethylases, their partners, and their roles in chromatin remodeling. We show that RCCD1 is a partner of histone H3K36 demethylase KDM8 and demonstrate that both are important for cell-cycle-regulated transcriptional repression in centromeric regions and accurate mitotic division.

  7. Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

    Science.gov (United States)

    Lissner, Michelle M; Thomas, Brandon J; Wee, Kathleen; Tong, Ann-Jay; Kollmann, Tobias R; Smale, Stephen T

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

  8. Analyses of natural resources in 10 CFR Part 60 as related to inadvertent human intrusion

    International Nuclear Information System (INIS)

    Miklas, M.P.; Lefevre, H.E.

    1993-01-01

    The purpose of this paper is to examine the intent of the regulatory language of the portions of 10 CFR Part 60 which deal with considerations of the natural resources of a proposed geologic repository for high-level radioactive wastes as they relate to inadvertent human intrusion. Four Potentially Adverse Conditions (PAC) the requirements of 10 CFR 60.21(c)(13) are shown to be related to natural resources. Groundwater is identified as a natural resource known to be present at Yucca Mountain, Nevada. For economic considerations of natural resources, the open-quotes foreseeable futureclose quotes is thought to be no more than 50 years. Two of the topics addressed by the PACs, subsurface mining and drilling at a proposed repository site, are pre-site-characterization activities which must be evaluated in the context of repository performance criteria set by the US EPA standard, 40 CFR Part 191. An alternative US DOE compliance demonstration to another PAC, 10 CFR 60.122(c)(17), might be to use an open-quotes explorationist perspectiveclose quotes of natural resource assessment. The Commission intends for DOE to evaluate the likelihood and consequence of inadvertent human intrusion into a geologic repository as a result of exploration or exploitation of natural resources within or near a proposed high-level radioactive waste geologic repository

  9. Hardiness in relation to organisational commitment in the Human Resource Management field

    Directory of Open Access Journals (Sweden)

    Nadia Ferreira

    2012-02-01

    Full Text Available Orientation: Employees’ hardiness is increasingly recognised as an aspect of their well-being and feelings of career success. Psychological well-being and feelings of subjective career success have positive implications for the motivation, satisfaction, performance and commitment of young talented staff.Research purpose: The study empirically investigated the relationship between an individual’s hardiness (measured by the Personal Views Survey II [PVS-II] and organisational commitment (measured by the Organisational Commitment Scale.Motivation for the study: Research on an individual’s hardiness profile as an aspect of their career well-being and success and how these attributes influence their psychological attachment to the organisation, is needed to guide human resource career development support practices aimed at retaining valuable staff.Research design, approach and method: A quantitative survey was conducted on a convenience sample of predominantly Black (92.2% and female (71% employed adults (N = 355 at managerial and staff levels in the human resource management field.Main findings: Correlational and multiple regression analyses revealed a number of significant relationships between the two variables.Practical/managerial implications: Managers and human resource practitioners need to recognise how people’s hardiness relates to their sense of psychological attachment to the organisation. Organisations concerned with the retention and well-being of their equity staff members need to find a way to enhance and develop their hardiness and commitment.Contribution/value-add: The research contributes new insights into and knowledge of the factors that influence their employees’ hardiness and how these relate to their organisational commitment. The results may be used to inform career development support interventions that aim to increase employees’ sense of career well-being and success.

  10. Female human resource professionals’ job embeddedness in relation to commitment foci: An exploratory study

    Directory of Open Access Journals (Sweden)

    Ingrid L. Potgieter

    2018-06-01

    Full Text Available Orientation: Managers and human resource practitioners who are concerned about managing talent as a critical resource need to recognise how employees’ job embeddedness relates to their commitment foci within the organisation. By understanding this relationship, gaps can be identified and talent can be managed optimally. Research purpose: The purpose of the study was, firstly, to establish whether a significant relationship exists between job embeddedness and a set of commitment foci and, secondly, to identify the variables that contribute the most to the relationship. Motivation for the study: Organisations increasingly devote more attention to initiatives that enhance the commitment and job embeddedness of their employees in order to assist in the design of a sound talent management plan to close the talent gaps. Research approach, design and method: A quantitative approach was used in this study, utilising a cross-sectional survey design to achieve the objective of the study. Descriptive statistics, Pearson’s product-moment correlations and canonical correlation analysis were conducted. The participants were primarily black women at an early stage of their career, who were employed in the human resource management field in a professional capacity. Main findings: The results indicated that job embeddedness significantly and positively accounted for the variance in organisational and occupational commitment foci of the participants. Practical and managerial implications: Human resource practitioners and managers need to consider how the job embeddedness of employees – specifically female employees – affects their commitment foci in developing talent management plans as part of the organisational strategy. Conclusions: The findings of the study provided empirical confirmation of theoretical views on the psychological aspects that keep employees embedded in their jobs and how these aspects relate to their commitment foci.

  11. Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

    Science.gov (United States)

    Veber, Daniela; Scalabrino, Giuseppe

    2015-12-15

    We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. An approach to classifying human resources constraints to attaining health-related Millennium Development Goals

    Directory of Open Access Journals (Sweden)

    Wyss Kaspar

    2004-07-01

    Full Text Available Abstract Background For any wide-ranging effort to scale up health-related priority interventions, human resources for health (HRH are likely to be a key to success. This study explores constraints related to human resources in the health sector for achieving the Millennium Development Goals (MDGs in low-income countries. Methods and framework The analysis drew on information from a variety of publicly-available sources and principally on data presented in published papers in peer-reviewed journals. For classifying HRH constraints an analytical framework was used that considers constraints at five levels: individual characteristics, the health service delivery level, the health sector level, training capacities and the sociopolitical and economic context of a country. Results and discussion At individual level, the decision to enter, remain and serve in the health sector workforce is influenced by a series of social, economic, cultural and gender-related determinants. For example, to cover the health needs of the poorest it is necessary to employ personnel with specific social, ethnic and cultural characteristics. At health-service level, the commitment of health staff is determined by a number of organizational and management factors. The workplace environment has a great impact not only on health worker performance, but also on the comprehensiveness and efficiency of health service delivery. At health-sector level, the use of monetary and nonmonetary incentives is of crucial importance for having the accurate skill mix at the appropriate place. Scaling up of priority interventions is likely to require significant investments in initial and continuous training. Given the lead time required to produce new health workers, such investments must occur in the early phases of scaling up. At the same time coherent national HRH policies are required for giving direction on HRH development and linking HRH into health-sector reform issues, the scaling

  13. Human Prolactin Point Mutations and Their Projected Effect on Vasoinhibin Generation and Vasoinhibin-Related Diseases

    Directory of Open Access Journals (Sweden)

    Jakob Triebel

    2017-11-01

    Full Text Available BackgroundA dysregulation of the generation of vasoinhibin hormones by proteolytic cleavage of prolactin (PRL has been brought into context with diabetic retinopathy, retinopathy of prematurity, preeclampsia, pregnancy-induced hypertension, and peripartum cardiomyopathy. Factors governing vasoinhibin generation are incompletely characterized, and the composition of vasoinhibin isoforms in human tissues or compartments, such as the circulation, is unknown. The aim of this study was to determine the possible contribution of PRL point mutations to the generation of vasoinhibins as well as to project their role in vasoinhibin-related diseases.MethodsProlactin sequences, point mutations, and substrate specificity information about the PRL cleaving enzymes cathepsin D, matrix metalloproteinases 8 and 13, and bone-morphogenetic protein 1 were retrieved from public databases. The consequences of point mutations in regard to their possible effect on vasoinhibin levels were projected on the basis of a score indicating the suitability of a particular sequence for enzymatic cleavage that result in vasoinhibin generation. The relative abundance and type of vasoinhibin isoforms were estimated by comparing the relative cleavage efficiency of vasoinhibin-generating enzymes.ResultsSix point mutations leading to amino acid substitutions in vasoinhibin-generating cleavage sites were found and projected to either facilitate or inhibit vasoinhibin generation. Four mutations affecting vasoinhibin generation in cancer tissues were found. The most likely composition of the relative abundance of vasoinhibin isoforms is projected to be 15 > 17.2 > 16.8 > 17.7 > 18 kDa vasoinhibin.ConclusionProlactin point mutations are likely to influence vasoinhibin levels by affecting the proteolysis efficiency of vasoinhibin-generating enzymes and should be monitored in patients with vasoinhibin-related diseases. Attempts to characterize vasoinhibin-related diseases

  14. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    International Nuclear Information System (INIS)

    Yagi, Yukihiro; Nakamura, Yuji; Kitahara, Ken; Harada, Takuma; Kato, Kazuhiko; Ninomiya, Tomohisa; Cao, Xin; Ohara, Hiroshi; Izumi-Nakaseko, Hiroko; Suzuki, Kokichi; Ando, Kentaro

    2014-01-01

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I Kr inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P 1,3,4,5 and S1P 1,5 receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P 1 in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not observed by

  15. The role of hERG1 ion channels in epithelial-mesenchymal transition and the capacity of riluzole to reduce cisplatin resistance in colorectal cancer cells.

    Science.gov (United States)

    Fortunato, Angelo

    2017-08-01

    The transition of cells from the epithelial to the mesenchymal state (EMT) plays an important role in tumor progression. EMT allows cells to acquire mobility, stem-like behavior and resistance to apoptosis and drug treatment. These features turn EMT into a central process in tumor biology. Ion channels are attractive targets for the treatment of cancer since they play critical roles in controlling a wide range of physiological processes that are frequently deregulated in cancer. Here, we investigated the role of ether-a-go-go-related 1 (hERG1) ion channels in the EMT of colorectal cancer cells. We studied the epithelial-mesenchymal profile of different colorectal cancer-derived cell lines and the expression of hERG1 potassium channels in these cell lines using real-time PCR. Next, we knocked down hERG1 expression in HCT116 cells using lentivirus mediated RNA interference and characterized the hERG1 silenced cells in vitro and in vivo. Finally, we investigated the capacity of riluzole, an ion channel-modulating drug used in humans to treat amyotrophic lateral sclerosis, to reduce the resistance of the respective colorectal cancer cells to the chemotherapeutic drug cisplatin. We found that of the colorectal cancer-derived cell lines tested, HCT116 showed the highest mesenchymal profile and a high hERG1 expression. Subsequent hERG1 expression knockdown induced a change in cell morphology, which was accompanied by a reduction in the proliferative and tumorigenic capacities of the cells. Notably, we found that hERG1expression knockdown elicited a reversion of the EMT profile in HCT116 cells with a reacquisition of the epithelial-like profile. We also found that riluzole increased the sensitivity of HCT116 cisplatin-resistant cells to cisplatin. Our data indicate that hERG1 plays a role in the EMT of colorectal cancer cells and that its knockdown reduces the proliferative and tumorigenic capacities of these cells. In addition, we conclude that riluzole may be used in

  16. Analysis of Onset Mechanisms of a Sphingosine 1-Phosphate Receptor Modulator Fingolimod-Induced Atrioventricular Conduction Block and QT-Interval Prolongation

    Energy Technology Data Exchange (ETDEWEB)

    Yagi, Yukihiro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Nakamura, Yuji [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kitahara, Ken [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Harada, Takuma [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Kato, Kazuhiko; Ninomiya, Tomohisa [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Cao, Xin [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Ohara, Hiroshi [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Division of Cardiovascular Medicine, Department of Internal Medicine, Faculty of Medicine, Toho University, 6-11-1 Omori-nishi, Ota-ku, Tokyo 143–8541 (Japan); Izumi-Nakaseko, Hiroko [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); Suzuki, Kokichi [Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., 760 Morooka-cho, Kohoku-ku, Yokohama, Kanagawa 222–8567 (Japan); Ando, Kentaro [Department of Pharmacology, Faculty of Medicine, Toho University, 5-21-16 Omori-nishi, Ota-ku, Tokyo 143–8540 (Japan); and others

    2014-11-15

    Fingolimod, a sphingosine 1-phosphate (S1P) receptor subtype 1, 3, 4 and 5 modulator, has been used for the treatment of patients with relapsing forms of multiple sclerosis, but atrioventricular conduction block and/or QT-interval prolongation have been reported in some patients after the first dose. In this study, we directly compared the electropharmacological profiles of fingolimod with those of siponimod, a modulator of sphingosine 1-phosphate receptor subtype 1 and 5, using in vivo guinea-pig model and in vitro human ether-a-go-go-related gene (hERG) assay to better understand the onset mechanisms of the clinically observed adverse events. Fingolimod (0.01 and 0.1 mg/kg) or siponimod (0.001 and 0.01 mg/kg) was intravenously infused over 10 min to the halothane-anaesthetized guinea pigs (n = 4), whereas the effects of fingolimod (1 μmol/L) and siponimod (1 μmol/L) on hERG current were examined (n = 3). The high doses of fingolimod and siponimod induced atrioventricular conduction block, whereas the low dose of siponimod prolonged PR interval, which was not observed by that of fingolimod. The high dose of fingolimod prolonged QT interval, which was not observed by either dose of siponimod. Meanwhile, fingolimod significantly inhibited hERG current, which was not observed by siponimod. These results suggest that S1P receptor subtype 1 in the heart could be one of the candidates for fingolimod- and siponimod-induced atrioventricular conduction block since S1P receptor subtype 5 is localized at the brain, and that direct I{sub Kr} inhibition may play a key role in fingolimod-induced QT-interval prolongation. - Highlights: • Fingolimod and siponimod are S1P{sub 1,3,4,5} and S1P{sub 1,5} receptor modulators, respectively. • Fingolimod and siponimod induced AV block in the halothane-anesthetized guinea pigs. • S1P{sub 1} in the hearts may be the target of fingolimod- and siponimod-induced AV block. • Fingolimod directly inhibited hERG current, which was not

  17. Mitragynine and its potential blocking effects on specific cardiac potassium channels

    Energy Technology Data Exchange (ETDEWEB)

    Tay, Yea Lu; Teah, Yi Fan; Chong, Yoong Min [Malaysian Institute of Pharmaceuticals & Nutraceuticals, NIBM, Ministry of Science, Technology & Innovation (MOSTI), Pulau Pinang (Malaysia); Jamil, Mohd Fadzly Amar [Clinical Research Center, Hospital Seberang Jaya, Kementerian Kesihatan Malaysia, Pulau Pinang (Malaysia); Kollert, Sina [Institute of Physiology, University of Wurzburg, Wurzburg (Germany); Adenan, Mohd Ilham [Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA (UiTM), Selangor Darul Ehsan (Malaysia); Wahab, Habibah Abdul [Pharmaceutical Design & Simulation (PhDS) Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Pulau Pinang (Malaysia); Döring, Frank; Wischmeyer, Erhard [Institute of Physiology, University of Wurzburg, Wurzburg (Germany); Tan, Mei Lan, E-mail: tanml@usm.my [Malaysian Institute of Pharmaceuticals & Nutraceuticals, NIBM, Ministry of Science, Technology & Innovation (MOSTI), Pulau Pinang (Malaysia); Advanced Medical and Dental Institute, Universiti Sains Malaysia, Pulau Pinang (Malaysia)

    2016-08-15

    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac I{sub Kr} current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, I{sub K1}, a Kir current mediated by Kir2.1 channel and I{sub KACh}, a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC{sub 50} value of 1.62 μM and 1.15 μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit I{sub KACh} current with an IC{sub 50} value of 3.32 μM but has no significant effects on I{sub K1}. Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. - Highlights: • The potential cardiac potassium channel blocking properties of mitragynine were investigated. • Mitragynine blocks hERG channel and I{sub Kr} in hERG-transfected HEK293 cells and hERG cRNA-injected Xenopus oocytes. • Mitragynine inhibits the hERG protein but not the mRNA expression. • Mitragynine

  18. Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells.

    Directory of Open Access Journals (Sweden)

    Dahai Yu

    Full Text Available The human ether-a-go-go-related gene (hERG potassium channel conducts rapid delayed rectifier potassium currents (IKr and contributes to phase III cardiac action potential repolarization. Drugs inhibit hERG channels by binding to aromatic residues in hERG helixes. Berberine (BBR has multiple actions, and its hydrogenated derivative dihydroberberine (DHB is a potential candidate for developing new drugs. Previous studies have demonstrated that BBR blocks hERG channels and prolongs action potential duration (APD. Our present study aimed to investigate the effects and mechanism of DHB on hERG channels. Protein expression and the hERG current were analyzed using western blotting and patch-clamp, respectively. DHB inhibited the hERG current concentration-dependently after instantaneous perfusion, accelerated channel inactivation by directly binding tyrosine (Tyr652 and phenylalanine (Phe656, and decreased mature (155-kDa and simultaneously increased immature (135-kDa hERG expression, respectively. This suggests disruption of forward trafficking of hERG channels. Besides, DHB remarkably reduced heat shock protein 90 (Hsp90 expression and its interaction with hERG, indicating that DHB disrupted hERG trafficking by impairing channel folding. Meanwhie, DHB enhanced the expression of cleaved activating transcription factor-6 (ATF-6, a biomarker of unfolded protein response (UPR. Expression of calnexin and calreticulin, chaperones activated by ATF-6 to facilitate channel folding, were also increased, which indicating UPR activation. Additionally, the degradation rate of mature 155-kDa hERG increased following DHB exposure. In conclusion, we demonstrated that DHB acutely blocked hERG channels by binding the aromatic Tyr652 and Phe656. DHB may decrease hERG plasma membrane expression through two pathways involving disruption of forward trafficking of immature hERG channels and enhanced degradation of mature hERG channels. Furthermore, forward trafficking was

  19. Mitragynine and its potential blocking effects on specific cardiac potassium channels

    International Nuclear Information System (INIS)

    Tay, Yea Lu; Teah, Yi Fan; Chong, Yoong Min; Jamil, Mohd Fadzly Amar; Kollert, Sina; Adenan, Mohd Ilham; Wahab, Habibah Abdul; Döring, Frank; Wischmeyer, Erhard; Tan, Mei Lan

    2016-01-01

    Mitragyna speciosa Korth is known for its euphoric properties and is frequently used for recreational purposes. Several poisoning and fatal cases involving mitragynine have been reported but the underlying causes remain unclear. Human ether-a-go-go-related gene (hERG) encodes the cardiac I Kr current which is a determinant of the duration of ventricular action potentials and QT interval. On the other hand, I K1 , a Kir current mediated by Kir2.1 channel and I KACh , a receptor-activated Kir current mediated by GIRK channel are also known to be important in maintaining the cardiac function. This study investigated the effects of mitragynine on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells and Xenopus oocytes. The effects on Kir2.1 and GIRK channels currents were also determined in the oocytes. The hERG tail currents following depolarization pulses were inhibited by mitragynine with an IC 50 value of 1.62 μM and 1.15 μM in the transfected cell line and Xenopus oocytes, respectively. The S6 point mutations of Y652A and F656A attenuated the inhibitor effects of mitragynine, indicating that mitragynine interacts with these high affinity drug-binding sites in the hERG channel pore cavity which was consistent with the molecular docking simulation. Interestingly, mitragynine does not affect the hERG expression at the transcriptional level but inhibits the protein expression. Mitragynine is also found to inhibit I KACh current with an IC 50 value of 3.32 μM but has no significant effects on I K1 . Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks. - Highlights: • The potential cardiac potassium channel blocking properties of mitragynine were investigated. • Mitragynine blocks hERG channel and I Kr in hERG-transfected HEK293 cells and hERG cRNA-injected Xenopus oocytes. • Mitragynine inhibits the hERG protein but not the mRNA expression. • Mitragynine inhibits GIRK channel. • Simultaneous

  20. Impacts of human-related practices on Ommatissus lybicus infestations of date palm in Oman.

    Directory of Open Access Journals (Sweden)

    Khalifa M Al-Kindi

    Full Text Available Date palm cultivation is economically important in the Sultanate of Oman, with significant financial investments coming from both the government and private individuals. However, a widespread Dubas bug (DB (Ommatissus lybicus Bergevin infestation has impacted regions including the Middle East, North Africa, Southeast Russia, and Spain, resulting in widespread damages to date palms. In this study, techniques in spatial statistics including ordinary least squares (OLS, geographically weighted regression (GRW, and exploratory regression (ER were applied to (a model the correlation between DB infestations and human-related practices that include irrigation methods, row spacing, palm tree density, and management of undercover and intercropped vegetation, and (b predict the locations of future DB infestations in northern Oman. Firstly, we extracted row spacing and palm tree density information from remote sensed satellite images. Secondly, we collected data on irrigation practices and management by using a simple questionnaire, augmented with spatial data. Thirdly, we conducted our statistical analyses using all possible combinations of values over a given set of candidate variables using the chosen predictive modelling and regression techniques. Lastly, we identified the combination of human-related practices that are most conducive to the survival and spread of DB. Our results show that there was a strong correlation between DB infestations and several human-related practices parameters (R2 = 0.70. Variables including palm tree density, spacing between trees (less than 5 x 5 m, insecticide application, date palm and farm service (pruning, dethroning, remove weeds, and thinning, irrigation systems, offshoots removal, fertilisation and labour (non-educated issues, were all found to significantly influence the degree of DB infestations. This study is expected to help reduce the extent and cost of aerial and ground sprayings, while facilitating the

  1. The role of human resource management in open innovation: exploring the relation between HR practices and OI

    OpenAIRE

    Paul, Svenja

    2013-01-01

    How do human resource practices strengthen open innovation activities? This inductive study of six cases led to propositions exploring that question. I thereby investigated the role of human resource management in open innovation, specifically the relation between HR practices and an employee's willingness to embrace open innovation.

  2. Are We Hoping For A Bounce A Study On Resilience And Human Relations In A High Reliability Organization

    Science.gov (United States)

    2016-03-01

    negatively impact the organization’s resilience when faced with workplace stressors (Gittell, 2008, p. 26). Consequently, this reduces an organization’s...2014). Organizational resilience and the challenge for human resource management: Conceptualizations and frameworks for theory and practice. Paper...A BOUNCE? A STUDY ON RESILIENCE AND HUMAN RELATIONS IN A HIGH RELIABILITY ORGANIZATION by Robert D. Johns March 2016 Thesis Advisor

  3. Relating dynamic brain states to dynamic machine states: Human and machine solutions to the speech recognition problem.

    Directory of Open Access Journals (Sweden)

    Cai Wingfield

    2017-09-01

    Full Text Available There is widespread interest in the relationship between the neurobiological systems supporting human cognition and emerging computational systems capable of emulating these capacities. Human speech comprehension, poorly understood as a neurobiological process, is an important case in point. Automatic Speech Recognition (ASR systems with near-human levels of performance are now available, which provide a computationally explicit solution for the recognition of words in continuous speech. This research aims to bridge the gap between speech recognition processes in humans and machines, using novel multivariate techniques to compare incremental 'machine states', generated as the ASR analysis progresses over time, to the incremental 'brain states', measured using combined electro- and magneto-encephalography (EMEG, generated as the same inputs are heard by human listeners. This direct comparison of dynamic human and machine internal states, as they respond to the same incrementally delivered sensory input, revealed a significant correspondence between neural response patterns in human superior temporal cortex and the structural properties of ASR-derived phonetic models. Spatially coherent patches in human temporal cortex responded selectively to individual phonetic features defined on the basis of machine-extracted regularities in the speech to lexicon mapping process. These results demonstrate the feasibility of relating human and ASR solutions to the problem of speech recognition, and suggest the potential for further studies relating complex neural computations in human speech comprehension to the rapidly evolving ASR systems that address the same problem domain.

  4. Estimation of utility weights for human papilloma virus-related health states according to disease severity.

    Science.gov (United States)

    Ock, Minsu; Park, Jeong-Yeol; Son, Woo-Seung; Lee, Hyeon-Jeong; Kim, Seon-Ha; Jo, Min-Woo

    2016-11-28

    A cost-utility study of a human papilloma virus (HPV) vaccine requires that the utility weights for HPV-related health states (i.e., cervical intraepithelial neoplasia (CIN), cervical cancer, and condyloma) be evaluated. The aim of the present study was to determine the utility weights for HPV-related health states. Hypothetical standardised health states related to HPV were developed based on patient education material and previous publications. To fully reflect disease progression from diagnosis to prognosis, each health state comprised four parts (diagnosis, symptoms, treatment, and progression and prognosis). Nine-hundred members from the Korean general population evaluated the HPV-related health states using a visual analogue scale (VAS) and a standard gamble (SG) approach, which were administered face-to-face via computer-assisted interview. The mean utility values were calculated for each HPV-related health state. According to the VAS, the highest utility (0.73) was HPV-positive status, followed by condyloma (0.66), and CIN grade I (0.61). The lowest utility (0.18) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.42). SG revealed that the highest utility (0.83) was HPV-positive status, followed by condyloma (0.78), and CIN grade I (0.77). The lowest utility (0.43) was cervical cancer requiring chemotherapy without surgery, followed by cervical cancer requiring chemoradiation therapy (0.60). This study was based on a large sample derived from the general Korean population; therefore, the calculated utility weights might be useful for evaluating the economic benefit of cancer screening and HPV vaccination programs.

  5. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Directory of Open Access Journals (Sweden)

    José F Muñoz

    2015-10-01

    Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics

  6. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

    Science.gov (United States)

    Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A

    2015-10-01

    Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution

  7. Accurate measurement of stable isotopes 46Ca and 48Ca in human feces, plasma, and urine in relation to human nutrition of calcium

    International Nuclear Information System (INIS)

    Janghorbani, M.; Sundaresan, A.; Young, V.R.

    1981-01-01

    A method based on Radiochemical Neutron Activation Analysis (RNAA) is described which allows simultaneous measurement of two stable isotopes of calcium, 46 Ca and 48 Ca, in human feces, plasma, and urine for the purpose of studying human nutrition and metabolism of calcium. It is shown that these measurements can be made with relative analytical precision of 1-5% depending on the particulars of a given experiment. The method has been applied in humans and data are given showing that kinetics of plasma appearance of 46 Ca administered orally with food can be readily investigated. This method allows investigation of a number of important nutritional and metabolic issues in all human population groups without regard to radioisotope safety considerations, and should prove especially helpful in relation to studies of calcium bioavailability from different foods in a variety of population groups for whom use of radiocalcium is not warranted. (Auth.)

  8. Is passive stiffness in human muscles related to the elasticity of tendon structures?

    Science.gov (United States)

    Kubo, K; Kanehisa, H; Fukunaga, T

    2001-08-01

    The purpose of this study was to examine in vivo whether passive stiffness in human muscles was related to the elasticity of tendon structures and to performance during stretch-shortening cycle exercise. Passive torque of plantar flexor muscles was measured during passive stretch from 90 degrees (anatomical position) to 65 degrees of dorsiflexion at a constant velocity of 5 degrees.s-1. The slope of the linear portion of the passive torque-angle curve during stretching was defined as the passive stiffness of the muscle. The elongation of the tendon and aponeurosis of the medial gastrocnemius muscle (MG) was directly measured using ultrasonography during ramp isometric plantar flexion up to the voluntary maximum. The relationship between the estimated muscle force of MG and tendon elongation was fitted to a linear regression, the slope of which was defined as the stiffness of the tendon. In addition, the dynamic torques during maximal voluntary concentric plantar flexion with and without prior eccentric contraction were determined at a constant velocity of 120 degrees.s-1. There were no significant correlations between passive stiffness and either the tendon stiffness (r = 0.19, P > 0.05) or the relative increase in torque with prior eccentric contraction (r = -0.19, P > 0.05). However, tendon stiffness was negatively correlated to the relative increase in torque output (r = -0.42, P tendon structures, and had no favourable effect on the muscle performance during stretch-shortening cycle exercise.

  9. Concentrations of AMH and inhibin-B in relation to follicular diameter in normal human small antral follicles

    DEFF Research Database (Denmark)

    Andersen, Claus Yding; Schmidt, Kirsten Tryde; Kristensen, Stine Gry

    2010-01-01

    The aim of the present study was to determine the intrafollicular concentrations of anti-Müllerian hormone (AMH), inhibin-B and steroids in normal human small antral follicles and to relate them to follicular size....

  10. Levels of perfluorooctanesulfonate and related fluorochemicals in human blood from the general population of Korea

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jae-Ho; Kim, Sun-Young; Shin, Im-Hee [Catholic Univ. of Daegu, School of Medicine, Dept. of Pharmacology/Toxicology, Daegu (Korea); Kannan, K. [Wardsworth Center, New York State Dept. of Health and Dept. of Env. Health and Tox., SUNY, Albany, NY (United States)

    2004-09-15

    Perfluorooctanesulfonate (PFOS) was found to be widespread in human populations and wildlife Major applications of these POSF-based products have included surfactants in: specialty paper and packaging products, carpet, upholstery, and textile products and in certain insecticide formulation. Depending on the specific functional derivatization or the degree of polymerization, such POSF based products may degrade or metabolize to PFOS, a stable and persistent end product that has the potential to bioaccumulate in the food chain. The mechanisms and pathways leading to the presence of PFOS in human blood are not well characterized but likely involve environmental and dietary exposure to PFOS or to precursor molecules of PFOS. PFOS and related perfluorinated compounds have recently been detected at low parts per billion (nanogram per milliliter) concentrations in the general population from 10 different countries including Korea. In the present report, the levels of perfluoroalkylated compounds in the general population from Korea were analyzed with respect to occupation, smoking status, sex, age and socio-economic status. The degree of association between the four target fluorochemicals measured in this study (PFOS, PFHxS, PFOA, and PFOSA) were also analyzed by linear regression to determine the potential association between their sources of exposure.

  11. Event-related brain potential correlates of human auditory sensory memory-trace formation.

    Science.gov (United States)

    Haenschel, Corinna; Vernon, David J; Dwivedi, Prabuddh; Gruzelier, John H; Baldeweg, Torsten

    2005-11-09

    The event-related potential (ERP) component mismatch negativity (MMN) is a neural marker of human echoic memory. MMN is elicited by deviant sounds embedded in a stream of frequent standards, reflecting the deviation from an inferred memory trace of the standard stimulus. The strength of this memory trace is thought to be proportional to the number of repetitions of the standard tone, visible as the progressive enhancement of MMN with number of repetitions (MMN memory-trace effect). However, no direct ERP correlates of the formation of echoic memory traces are currently known. This study set out to investigate changes in ERPs to different numbers of repetitions of standards, delivered in a roving-stimulus paradigm in which the frequency of the standard stimulus changed randomly between stimulus trains. Normal healthy volunteers (n = 40) were engaged in two experimental conditions: during passive listening and while actively discriminating changes in tone frequency. As predicted, MMN increased with increasing number of standards. However, this MMN memory-trace effect was caused mainly by enhancement with stimulus repetition of a slow positive wave from 50 to 250 ms poststimulus in the standard ERP, which is termed here "repetition positivity" (RP). This RP was recorded from frontocentral electrodes when participants were passively listening to or actively discriminating changes in tone frequency. RP may represent a human ERP correlate of rapid and stimulus-specific adaptation, a candidate neuronal mechanism underlying sensory memory formation in the auditory cortex.

  12. Snake scales, partial exposure, and the Snake Detection Theory: A human event-related potentials study

    Science.gov (United States)

    Van Strien, Jan W.; Isbell, Lynne A.

    2017-01-01

    Studies of event-related potentials in humans have established larger early posterior negativity (EPN) in response to pictures depicting snakes than to pictures depicting other creatures. Ethological research has recently shown that macaques and wild vervet monkeys respond strongly to partially exposed snake models and scale patterns on the snake skin. Here, we examined whether snake skin patterns and partially exposed snakes elicit a larger EPN in humans. In Task 1, we employed pictures with close-ups of snake skins, lizard skins, and bird plumage. In task 2, we employed pictures of partially exposed snakes, lizards, and birds. Participants watched a random rapid serial visual presentation of these pictures. The EPN was scored as the mean activity (225–300 ms after picture onset) at occipital and parieto-occipital electrodes. Consistent with previous studies, and with the Snake Detection Theory, the EPN was significantly larger for snake skin pictures than for lizard skin and bird plumage pictures, and for lizard skin pictures than for bird plumage pictures. Likewise, the EPN was larger for partially exposed snakes than for partially exposed lizards and birds. The results suggest that the EPN snake effect is partly driven by snake skin scale patterns which are otherwise rare in nature. PMID:28387376

  13. Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation.

    Science.gov (United States)

    Taziaux, Melanie; Staphorsius, Annemieke S; Ghatei, Mohammad A; Bloom, Stephen R; Swaab, Dick F; Bakker, Julie

    2016-06-01

    Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown. Our objectives were to determine the following: 1) when during development the sex difference in kisspeptin expression in the infundibular nucleus would emerge and 2) whether this sex difference is related to sexual orientation or transsexuality. Postmortem hypothalamic tissues were collected by The Netherlands Brain Bank, and sections were stained for kisspeptin by immunohistochemistry. Hypothalami of 43 control subjects were categorized into three periods: infant/prepubertal (six girls, seven boys), adult (11 women, seven men), and elderly (six aged women, six aged men). Eight male-to-female (MTF) transsexuals, three HIV(+) heterosexual men, and five HIV(+) homosexual men were also analyzed. We estimated the total number of kisspeptin-immunoreactive neurons within the infundibular nucleus. Quantitative analysis confirmed that the human infundibular kisspeptin system exhibits a female-dominant sex difference. The number of kisspeptin neurons is significantly greater in the infant/prepubertal and elderly periods compared with the adult period. Finally, in MTF transsexuals, but not homosexual men, a female-typical kisspeptin expression was observed. These findings suggest that infundibular kisspeptin neurons are sensitive to circulating sex steroid hormones throughout life and that the sex reversal observed in MTF transsexuals might reflect, at least partially, an atypical brain sexual differentiation.

  14. Pharmacological manipulations in animal models of anorexia and binge eating in relation to humans.

    Science.gov (United States)

    van Gestel, M A; Kostrzewa, E; Adan, R A H; Janhunen, S K

    2014-10-01

    Eating disorders, such as anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorders (BED), are described as abnormal eating habits that usually involve insufficient or excessive food intake. Animal models have been developed that provide insight into certain aspects of eating disorders. Several drugs have been found efficacious in these animal models and some of them have eventually proven useful in the treatment of eating disorders. This review will cover the role of monoaminergic neurotransmitters in eating disorders and their pharmacological manipulations in animal models and humans. Dopamine, 5-HT (serotonin) and noradrenaline in hypothalamic and striatal regions regulate food intake by affecting hunger and satiety and by affecting rewarding and motivational aspects of feeding. Reduced neurotransmission by dopamine, 5-HT and noradrenaline and compensatory changes, at least in dopamine D2 and 5-HT(2C/2A) receptors, have been related to the pathophysiology of AN in humans and animal models. Also, in disorders and animal models of BN and BED, monoaminergic neurotransmission is down-regulated but receptor level changes are different from those seen in AN. A hypofunctional dopamine system or overactive α2-adrenoceptors may contribute to an attenuated response to (palatable) food and result in hedonic binge eating. Evidence for the efficacy of monoaminergic treatments for AN is limited, while more support exists for the treatment of BN or BED with monoaminergic drugs. © 2014 The British Pharmacological Society.

  15. Biological Roles of Aberrantly Expressed Glycosphingolipids and Related Enzymes in Human Cancer Development and Progression

    Directory of Open Access Journals (Sweden)

    Dinghao Zhuo

    2018-05-01

    Full Text Available Glycosphingolipids (GSLs, which consist of a hydrophobic ceramide backbone and a hydrophilic carbohydrate residue, are an important type of glycolipid expressed in surface membranes of all animal cells. GSLs play essential roles in maintenance of plasma membrane stability, in regulation of numerous cellular processes (including adhesion, proliferation, apoptosis, and recognition, and in modulation of signal transduction pathways. GSLs have traditionally been classified as ganglio-series, lacto-series, or globo-series on the basis of their diverse types of oligosaccharide chains. Structures and functions of specific GSLs are also determined by their oligosaccharide chains. Different cells and tissues show differential expression of GSLs, and changes in structures of GSL glycan moieties occur during development of numerous types of human cancer. Association of GSLs and/or related enzymes with initiation and progression of cancer has been documented in 100s of studies, and many such GSLs are useful markers or targets for cancer diagnosis or therapy. In this review, we summarize (i recent studies on aberrant expression and distribution of GSLs in common human cancers (breast, lung, colorectal, melanoma, prostate, ovarian, leukemia, renal, bladder, gastric; (ii biological functions of specific GSLs in these cancers.

  16. Human factor H-related protein 2 (CFHR2 regulates complement activation.

    Directory of Open Access Journals (Sweden)

    Hannes U Eberhardt

    Full Text Available Mutations and deletions within the human CFHR gene cluster on chromosome 1 are associated with diseases, such as dense deposit disease, CFHR nephropathy or age-related macular degeneration. Resulting mutant CFHR proteins can affect complement regulation. Here we identify human CFHR2 as a novel alternative pathway complement regulator that inhibits the C3 alternative pathway convertase and terminal pathway assembly. CFHR2 is composed of four short consensus repeat domains (SCRs. Two CFHR2 molecules form a dimer through their N-terminal SCRs, and each of the two C-terminal ends can bind C3b. C3b bound CFHR2 still allows C3 convertase formation but the CFHR2 bound convertases do not cleave the substrate C3. Interestingly CFHR2 hardly competes off factor H from C3b. Thus CFHR2 likely acts in concert with factor H, as CFHR2 inhibits convertases while simultaneously allowing factor H assisted degradation by factor I.

  17. Investigating the sex-related geometric variation of the human cranium.

    Science.gov (United States)

    Bertsatos, Andreas; Papageorgopoulou, Christina; Valakos, Efstratios; Chovalopoulou, Maria-Eleni

    2018-01-29

    Accurate sexing methods are of great importance in forensic anthropology since sex assessment is among the principal tasks when examining human skeletal remains. The present study explores a novel approach in assessing the most accurate metric traits of the human cranium for sex estimation based on 80 ectocranial landmarks from 176 modern individuals of known age and sex from the Athens Collection. The purpose of the study is to identify those distance and angle measurements that can be most effectively used in sex assessment. Three-dimensional landmark coordinates were digitized with a Microscribe 3DX and analyzed in GNU Octave. An iterative linear discriminant analysis of all possible combinations of landmarks was performed for each unique set of the 3160 distances and 246,480 angles. Cross-validated correct classification as well as multivariate DFA on top performing variables reported 13 craniometric distances with over 85% classification accuracy, 7 angles over 78%, as well as certain multivariate combinations yielding over 95%. Linear regression of these variables with the centroid size was used to assess their relation to the size of the cranium. In contrast to the use of generalized procrustes analysis (GPA) and principal component analysis (PCA), which constitute the common analytical work flow for such data, our method, although computational intensive, produced easily applicable discriminant functions of high accuracy, while at the same time explored the maximum of cranial variability.

  18. The action of sennosides and related compounds on human colon and rectum 1

    Science.gov (United States)

    Hardcastle, J. D.; Wilkins, J. L.

    1970-01-01

    The direct action of intraluminal senna and related compounds on the human colon and rectum has been investigated. Motility was recorded by balloon kymography with recording units inserted into well established transverse colostomies or into the rectum. The motility of the colon was not changed by intraluminal senna glycosides but the introduction of senna previously incubated with faeces or Esch. coli stimulated the colon to peristalt. The peristalsis was similar to that stimulated by rheinanthrone, an oxanthrone produced by chemical hydrolysis and reduction of senna. Both activated senna and rheinanthrone appeared to act in the colon by contact stimulation. No peristaltic response was stimulated in the rectum, either with activated senna or with rheinanthrone. PMID:4929273

  19. Plasticity and function of human skeletal muscle in relation to disuse and rehabilitation

    DEFF Research Database (Denmark)

    Suetta, Charlotte

    2017-01-01

    not be achieved with the use of neuromuscular electrical stimulation or conventional rehabilitation efforts alone. Collectively, these findings strongly underline the importance of implementing resistive exercises in future rehabilitation programs for elderly individuals. In addition, comparing young and old able...... gains in myofibre area, in parallel with smaller increases in satellite cell number despite no age-related differences were observed in factors known to promote skeletal muscle hypertrophy and myogenic stem cell proliferation (IGF-Ea, MGF, MyoD, myogenin, HGF). Moreover, an age-specific regulation...... and satellite cell proliferation in the acute phase of re-loading, these data indicates that myostatin play an important role in the impaired ability of aged human skeletal muscle....

  20. Human event-related brain potentials to auditory periodic noise stimuli.

    Science.gov (United States)

    Kaernbach, C; Schröger, E; Gunter, T C

    1998-02-06

    Periodic noise is perceived as different from ordinary non-repeating noise due to the involvement of echoic memory. Since this stimulus does not contain simple physical cues (such as onsets or spectral shape) that might obscure sensory memory interpretations, it is a valuable tool to study sensory memory functions. We demonstrated for the first time that the processing of periodic noise can be tapped by event-related brain potentials (ERPs). Human subjects received repeating segments of noise embedded in non-repeating noise. They were instructed to detect the periodicity inherent to the stimulation. We observed a central negativity time-locked on the periodic segment that correlated to the subjects behavioral performance in periodicity detection. It is argued that the ERP result indicates an enhancement of sensory-specific processing.

  1. Human resource in tourism and hospitality industry: Relation between level of education and job satisfaction

    Directory of Open Access Journals (Sweden)

    Kovačević Bojana

    2012-01-01

    Full Text Available The paper offers a concise summary of current problems including the impact of education on (dissatisfaction of human resources in tourism and hospitality industry. In recent years, many researches have been focused on the phenomena of the relation between level of education and job satisfaction of the employees in tourism organizations as it is well known that employee satisfaction enhance competitiveness and efficiency in business. A current issue was set as the fundamental goal in designing this paper, and the basic parameter of the research is employee satisfaction with business operations and working conditions, or to be more precise, examining the extent of (dissatisfaction with the given segments depending on the employees' educational level. This paper represents a synthesis of the electronic research, the analysis of available references, as well as the use of descriptive, analytical and synthetic methods, and it will result in a critical analysis and confirmation (denial of certain hypotheses.

  2. Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

    Directory of Open Access Journals (Sweden)

    Tracy A. Brennan

    2014-05-01

    Full Text Available A major medical challenge in the elderly is osteoporosis and the high risk of fracture. Telomere dysfunction is a cause of cellular senescence and telomere shortening, which occurs with age in cells from most human tissues, including bone. Telomere defects contribute to the pathogenesis of two progeroid disorders characterized by premature osteoporosis, Werner syndrome and dyskeratosis congenital. It is hypothesized that telomere shortening contributes to bone aging. We evaluated the skeletal phenotypes of mice with disrupted telomere maintenance mechanisms as models for human bone aging, including mutants in Werner helicase (Wrn−/−, telomerase (Terc−/− and Wrn−/−Terc−/− double mutants. Compared with young wild-type (WT mice, micro-computerized tomography analysis revealed that young Terc−/− and Wrn−/−Terc−/− mice have decreased trabecular bone volume, trabecular number and trabecular thickness, as well as increased trabecular spacing. In cortical bone, young Terc−/− and Wrn−/−Terc−/− mice have increased cortical thinning, and increased porosity relative to age-matched WT mice. These trabecular and cortical changes were accelerated with age in Terc−/− and Wrn−/−Terc−/− mice compared with older WT mice. Histological quantification of osteoblasts in aged mice showed a similar number of osteoblasts in all genotypes; however, significant decreases in osteoid, mineralization surface, mineral apposition rate and bone formation rate in older Terc−/− and Wrn−/−Terc−/− bone suggest that osteoblast dysfunction is a prominent feature of precocious aging in these mice. Except in the Wrn−/− single mutant, osteoclast number did not increase in any genotype. Significant alterations in mechanical parameters (structure model index, degree of anistrophy and moment of inertia of the Terc−/− and Wrn−/−Terc−/− femurs compared with WT mice were also observed. Young Wrn

  3. Productive human immunodeficiency virus infection levels correlate with AIDS-related manifestations in the patient

    International Nuclear Information System (INIS)

    Mathez, D.; Paul, D.; de Belilovsky, C.; Sultan, Y.; Deleuze, J.; Gorin, I.; Saurin, W.; Decker, R.; Leibowitch, J.

    1990-01-01

    Mononuclear cells were obtained from 71 human immunodeficiency virus type 1 (HIV-1) seropositive subjects presenting and first visit either as asymptomatic or with minor symptoms and with CD4 lymphocytes greater than 550 per mm3 (group A, 35 patients) or as patients with AIDS, AIDS-related illnesses, or CD4 lymphocytes less than 400 per mm3 (group B, 36 patients). After 1-5 years of follow-up, 13 patients of group A had essentially retained their initial status (asymptomatics); the 22 others had suffered clinical or immunological deterioration (progressors). Frozen cells were thawed and submitted to lethal gamma-irradiation in vitro (4500 rads; 1 rad = 0.01 Gy) before they were cultured with normal phytohemagglutinin-stimulated lymphocytes to determine radiation-resistant HIV expression ex vivo (R-HEV). HIV antigenemia correlated with R-HEV values in 142 samples (r = 0.92, P less than 0.001) but was a less sensitive predictor of disease than R-HEV. R-HEV was detected in all specimens from patients with major AIDS-related illnesses or HIV-associated CD4 lymphopenia. In 77% of the progressors from group A, R-HEV detection preceded the onset of AIDS-associated disease or CD4 lymphopenia by 1 year (average). Conversely, R-HEV was low or was not detected in 36 sequential specimens from the 13 patients who remained asymptomatic over the following 2-5 years. Thus, persistently low HIV expression in vivo predicted a nondiseased state, whereas higher HIV expression levels seemed necessary for disease to occur. These data indicate that R-HEV is related to productive HIV infection in vivo, the latter acting as a determinant of AIDS-related illnesses. In view of this, measurement of HIV expression levels in the patient should be useful in antiviral efficacy trials

  4. Human Papillomavirus Vaccination Counseling in Pediatric Training: Are We Discussing Otolaryngology-Related Manifestations?

    Science.gov (United States)

    Gnagi, Sharon H; Gnagi, Forrest T; Schraff, Scott A; Hinni, Michael L

    2016-07-01

    Demonstrate the need for increased education regarding otolaryngology-related manifestations of human papillomavirus (HPV). Highlight a need to incorporate otolaryngology-related manifestations of HPV in vaccine counseling. Survey. Tertiary care academic children's hospital. Pediatric residents, fellows, and staff. An online survey was made available regarding HPV education and vaccination. Participants (N = 348) initiated the survey representing 28.4%, 25.6%, and 19.0% postgraduate year 1, 2, and 3 residents, respectively, as well as 17.5% chief residents/fellows and 9.5% attendings. Participants rated their prior education as none or fair regarding recurrent respiratory papillomatosis (63.8%) and oropharyngeal squamous cell carcinoma (68.3%). In contrast, 60.6% and 70.9% rated their education on genital warts and cervical cancer correspondingly as good or excellent. When asked what was routinely discussed during HPV vaccine counseling, 63.3% reported "never" discussing recurrent respiratory papillomatosis and 52.9% "never" discussing oropharyngeal squamous cell carcinoma. A range from 92.7% to 95.5% responded that there was a need for increased education regarding HPV and its role in recurrent respiratory papillomatosis and oropharyngeal squamous cell carcinoma. Increased education about HPV and its otolaryngology-related manifestations should be undertaken to increase provider, patient, and parent awareness of recurrent respiratory papillomatosis and oropharyngeal squamous cell carcinoma. We propose that discussing the risks of otolaryngology-related disease be routinely included in HPV vaccination counseling. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

  5. Relations between urban bird and plant communities and human well-being and connection to nature.

    Science.gov (United States)

    Luck, Gary W; Davidson, Penny; Boxall, Dianne; Smallbone, Lisa

    2011-08-01

    By 2050, 70% of the world's population will live in urban areas. In many cases urbanization reduces the richness and abundance of native species. Living in highly modified environments with fewer opportunities to interact directly with a diversity of native species may adversely affect residents' personal well-being and emotional connection to nature. We assessed the personal well-being, neighborhood well-being (a measure of a person's satisfaction with their neighborhood), and level of connection to nature of over 1000 residents in 36 residential neighborhoods in southeastern Australia. We modeled these response variables as a function of natural features of each neighborhood (e.g., species richness and abundance of birds, density of plants, and amount of vegetation cover) and demographic characteristics of surveyed residents. Vegetation cover had the strongest positive relations with personal well-being, whereas residents' level of connection to nature was weakly related to variation in species richness and abundance of birds and density of plants. Demographic characteristics such as age and level of activity explained the greatest proportion of variance in well-being and connection to nature. Nevertheless, when controlling for variation in demographic characteristics (examples were provided above), neighborhood well-being was positively related to a range of natural features, including species richness and abundance of birds, and vegetation cover. Demographic characteristics and how well-being was quantified strongly influenced our results, and we suggest demography and metrics of well-being must be considered when attempting to determine relations between the urban environment and human well-being. © 2011 Society for Conservation Biology.

  6. Preventing human papillomavirus-related cancers: we are all in this together.

    Science.gov (United States)

    Dilley, Sarah; Scarinci, Isabel; Kimberlin, David; Straughn, J Michael

    2017-06-01

    Human papillomavirus-related cancers, which include cervical, vulvovaginal, anal, and oropharyngeal cancers, are on the rise in the United States. Although the human papillomavirus vaccine has been on the market for 10 years, human papillomavirus vaccination rates are well below national goals. Research identified many barriers and facilitators to human papillomavirus vaccination, and provider recommendation remains the most important factor in parental and patient decisions to vaccinate. While much of the burden of human papillomavirus vaccine provision falls on pediatricians and primary care providers, they cannot do it alone. As clinicians who care for a large proportion of human papillomavirus-related conditions, obstetrician-gynecologists and other women's health care providers must share the responsibility for vaccination of eligible patients. Obstetrician-gynecologists can support the efforts to eradicate human papillomavirus-related disease in their patients and their families via multiple avenues, including providing the human papillomavirus vaccine and being community leaders in support of vaccination. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Harnessing the Risk-Related Data Supply Chain: An Information Architecture Approach to Enriching Human System Research and Operations Knowledge

    Science.gov (United States)

    Buquo, Lynn E.; Johnson-Throop, Kathy A.

    2011-01-01

    An Information Architecture facilitates the understanding and, hence, harnessing of the human system risk-related data supply chain which enhances the ability to securely collect, integrate, and share data assets that improve human system research and operations. By mapping the risk-related data flow from raw data to useable information and knowledge (think of it as a data supply chain), the Human Research Program (HRP) and Space Life Science Directorate (SLSD) are building an information architecture plan to leverage their existing, and often shared, IT infrastructure.

  8. Unsteady-state human-body exergy consumption rate and its relation to subjective assessment of dynamic thermal environments

    DEFF Research Database (Denmark)

    Schweiker, Marcel; Kolarik, Jakub; Dovjak, Mateja

    2016-01-01

    of the present study confirmed previously indicated trends that lowest human body exergy consumption rate is associated with thermal sensation close to neutrality. Moreover, higher acceptability was in general associated with lower human body exergy consumption rate. (C) 2016 Elsevier B.V. All rights reserved.......Few examples studied applicability of exergy analysis on human thermal comfort. These examples relate the human-body exergy consumption rate with subjectively obtained thermal sensation votes and had been based on steady-state calculation methods. However, humans are rarely exposed to steady...... between the human-body exergy consumption rate and subjective assessment of thermal environment represented by thermal sensation as well as to extend the investigation towards thermal acceptability votes. Comparison of steady-state and unsteady-state model showed that results from both models were...

  9. Case report: human papilloma virus type 120-related papillomatosis mimicking laryngeal carcinoma.

    Science.gov (United States)

    Belvisi, Valeria; Martellucci, Salvatore; Garbuglia, Anna Rosa; Del Borgo, Cosmo; Martellucci, Stanislao; Baiocchini, Andrea; Manicone, Anna Maria; Bagni, Oreste; Mastroianni, Claudio Maria; Gallo, Andrea

    2017-10-01

    The relationship between human papilloma virus (HPV) and upper respiratory tract pathology was better understood in recent years and represents now an issue of particular interest in carcinogenesis and in immunocompromised host. We describe a case in which a rare genotype HPV-related papillomatosis mimics laryngeal carcinoma in an immunocompromised host. A 54-year-old woman with a history of HIV-HCV coinfection and anal and laryngeal cancer successfully treated some years before was hospitalized for severe dyspnea, cough and dysphagia. Fiberoptic endoscopic evaluation raised the suspicion of tumor relapse showing the presence of a large glottic-supraglottic ulcerated mass. Several laryngeal biopsies demonstrated koilocytosis and p16 expression, according to a possible HPV infection, and focal figures of mild dysplasia of epithelium. 18 F-FDG PET/CT did not show high glycolytic activity at laryngeal level. An invasive upper respiratory tract papillomatosis in an immunocompromised host was suspected because of the patient's clinical improvement after antiretroviral therapy. Pharyngeal swab and oral rinse harboured the same HPV120 genotype sequence, a betapapillomavirus of recent description and not yet related to any similar clinical presentations.

  10. Unsuspected human immunodeficiency virus infection presenting as immunoglobulin G4-related lymphadenopathy: a case report.

    Science.gov (United States)

    Yu, Hsing-Tse; Lee, Chen-Hsiang; Huang, Shun-Chen; Yu, Shan-Fu

    2018-01-01

    Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition characterized by infiltration of the involved organs by IgG4-bearing plasma cells. The prevalence of autoimmune diseases, associated with or occurring in patients with human immunodeficiency virus (HIV) infection, has been increasing. We describe a 58-year-old man with an undiagnosed HIV infection, which presented as chronic cervical lymphadenopathy with an elevated serum IgG4 and a very high IgE. Histologically, lymph nodes showed expanded sinusoids and burnt-out germinal centers with increased plasmacytic infiltration and collagen fiber deposition. The absolute number of IgG4+ plasma cells and the IgG4+/IgG+ plasma cell ratio was increased. The lymph nodes were enlarged and clinically the patient improved after steroid treatment. Nine months later, he was diagnosed with acquired immune deficiency syndrome, following presentation with a cavitary left lung lesion. Immunohistochemical studies on the previously resected lymph node revealed complete absence of CD4+ T-lymphocytes and increased CD8+ T-lymphocytes. The pathologic findings met the criteria of both HIV infection and IgG4-related lymphadenopathy. Our case demonstrates that further investigations for underlying HIV infection in a case of IgG4-RD are critical, especially when extremely elevated IgE is concomitantly present.

  11. Estrogen-related receptor gamma and hearing function: evidence of a role in humans and mice.

    Science.gov (United States)

    Nolan, Lisa S; Maier, Hannes; Hermans-Borgmeyer, Irm; Girotto, Giorgia; Ecob, Russell; Pirastu, Nicola; Cadge, Barbara A; Hübner, Christian; Gasparini, Paolo; Strachan, David P; Davis, Adrian; Dawson, Sally J

    2013-08-01

    Since estrogen is thought to protect pre-menopausal women from age-related hearing loss, we investigated whether variation in estrogen-signalling genes is linked to hearing status in the 1958 British Birth Cohort. This analysis implicated the estrogen-related receptor gamma (ESRRG) gene in determining adult hearing function and was investigated further in a total of 6134 individuals in 3 independent cohorts: (i) the 1958 British Birth Cohort; (ii) a London ARHL case-control cohort; and (iii) a cohort from isolated populations of Italy and Silk Road countries. Evidence of an association between the minor allele of single nucleotide polymorphism (SNP) rs2818964 and hearing status was found in females, but not in males in 2 of these cohorts: p = 0.0058 (London ARHL) and p = 0.0065 (Carlantino, Italy). Furthermore, assessment of hearing in Esrrg knock-out mice revealed a mild 25-dB hearing loss at 5 weeks of age. At 12 weeks, average hearing thresholds in female mice((-/-)) were 15 dB worse than in males((-/-)). Together these data indicate ESRRG plays a role in maintenance of hearing in both humans and mice. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Trends in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma Incidence, Vermont 1999-2013.

    Science.gov (United States)

    Owosho, Adepitan A; Wiley, Rashidah; Stansbury, Tessie; Gbadamosi, Semiu O; Ryder, Jon S

    2018-02-09

    This study examines trends in age-adjusted incidence rates of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) in comparison to oral cavity proper squamous cell carcinoma (OSCC) in the population of Vermont from 1999 to 2013. Data on cases of oral and pharynx cancers diagnosed in Vermont between 1999 and 2013 were obtained from the Vermont cancer registry. The age-adjusted incidence rates and annual percentage change of HPV-related OPSCC and OSCC were calculated using Joinpoint trend analysis. Four hundred and thirty-one cases of HPV-related OPSCC were diagnosed from 1999 to 2013. Males constituted 83% (P < 0.0001) of the cases and the 6th decade of life marked the highest incidence. The overall age-adjusted incidence rates for HPV-related OPSCC significantly increased (from 2.39 to 3.86 per 100,000, P < 0.0001). In males, it significantly increased (from 3.62 to 6.93 per 100,000, P < 0.0001), while in females it remained stable (from 1.18 to 1.02 per 100,000, P = 0.28) during 1999-2013. The average rate of HPV-related OPSCC significantly increased by 4.4% annually (P = 0.004). In males the average rate significantly increased by 5.3% annually (P = 0.001) and in females the rate increased by 0.37% annually (P = 0.87). In contrast, age-adjusted overall incidence rates for OSCC significantly decreased (from 3.99 to 3.35 per 100,000, P = 0.018). The overall rate of OSCC decreased by 0.96% annually (P = 0.37) and the highest incidence of cases was in the 7th decade of life. In conclusion, there was an increasing trend of HPV-related OPSCC, specifically in males, and there appears to be a decreasing trend of OSCC in Vermont.

  13. RELATIVE EFFICACY OF HUMAN SOCIAL INTERACTION AND FOOD AS REINFORCERS FOR DOMESTIC DOGS AND HAND-REARED WOLVES

    Science.gov (United States)

    Feuerbacher, Erica N; Wynne, Clive D. L

    2012-01-01

    Despite the intimate relationship dogs share with humans in Western society, we know relatively little about the variables that produce and maintain dog social behavior towards humans. One possibility is that human social interaction is itself a reinforcer for dog behavior. As an initial assessment of the variables that might maintain dog social behavior, we compared the relative efficacy of brief human social interaction to a small piece of food as a reinforcer for an arbitrary response (nose touch). We investigated this in three populations of canids: shelter dogs, owned dogs, and hand-reared wolves. Across all three canid populations, brief social interaction was a relatively ineffective reinforcer compared to food for most canids, producing lower responding and longer latencies than food. PMID:22851794

  14. How Does Adult Attachment Affect Human Recognition of Love-related and Sex-related Stimuli: An ERP Study

    Science.gov (United States)

    Hou, Juan; Chen, Xin; Liu, Jinqun; Yao, Fangshu; Huang, Jiani; Ndasauka, Yamikani; Ma, Ru; Zhang, Yuting; Lan, Jing; Liu, Lu; Fang, Xiaoyi

    2016-01-01

    In the present study, we investigated the relationship among three emotion-motivation systems (adult attachment, romantic love, and sex). We recorded event-related potentials in 37 healthy volunteers who had experienced romantic love while they viewed SEX, LOVE, FRIEND, SPORT, and NEUTRAL images. We also measured adult attachment styles, level of passionate love and sexual attitudes. As expected, results showed that, firstly, response to love-related image-stimuli and sex-related image-stimuli on the electrophysiological data significantly different on N1, N2, and positive slow wave (PSW) components. Secondly, the different adult attachment styles affected individuals’ recognition processing in response to love-related and sex-related images, especially, to sex-related images. Further analysis showed that voltages elicited by fearful attachment style individuals were significantly lower than voltages elicited by secure and dismissing attachment style individuals on sex-related images at frontal sites, on N1 and N2 components. Thirdly, from behavior data, we found that adult attachment styles were not significantly related to any dimension of sexual attitudes but were significantly related to passionate love scale (PLS) total points. Thus, the behavior results were not in line with the electrophysiological results. The present study proved that adult attachment styles might mediate individuals’ lust and attraction systems. PMID:27199830

  15. Differences in Moral Judgment on Animal and Human Ethics Issues between University Students in Animal-Related, Human Medical and Arts Programs.

    Science.gov (United States)

    Verrinder, Joy M; Ostini, Remo; Phillips, Clive J C

    2016-01-01

    Moral judgment in relation to animal ethics issues has rarely been investigated. Among the research that has been conducted, studies of veterinary students have shown greater use of reasoning based on universal principles for animal than human ethics issues. This study aimed to identify if this was unique to students of veterinary and other animal-related professions. The moral reasoning of first year students of veterinary medicine, veterinary technology, and production animal science was compared with that of students in non-animal related disciplines of human medicine and arts. All students (n = 531) completed a moral reasoning test, the VetDIT, with animal and human scenarios. When compared with reasoning on human ethics issues, the combined group of students evaluating animal ethics issues showed higher levels of Universal Principles reasoning, lower levels of Personal Interest reasoning and similar levels of Maintaining Norms reasoning. Arts students showed more personal interest reasoning than students in most animal-related programs on both animal and human ethics issues, and less norms-based reasoning on animal ethics issues. Medical students showed more norms-based reasoning on animal ethics issues than all of the animal-related groups. There were no differences in principled reasoning on animal ethics issues between program groups. This has implications for animal-related professions and education programs showing that students' preference for principled reasoning on animal ethics issues is not unique to animal-related disciplines, and highlighting the need to develop student (and professional) capacity to apply principled reasoning to address ethics issues in animal industries to reduce the risk of moral distress.

  16. Differences in Moral Judgment on Animal and Human Ethics Issues between University Students in Animal-Related, Human Medical and Arts Programs

    Science.gov (United States)

    Verrinder, Joy M.; Ostini, Remo; Phillips, Clive J. C.

    2016-01-01

    Moral judgment in relation to animal ethics issues has rarely been investigated. Among the research that has been conducted, studies of veterinary students have shown greater use of reasoning based on universal principles for animal than human ethics issues. This study aimed to identify if this was unique to students of veterinary and other animal-related professions. The moral reasoning of first year students of veterinary medicine, veterinary technology, and production animal science was compared with that of students in non-animal related disciplines of human medicine and arts. All students (n = 531) completed a moral reasoning test, the VetDIT, with animal and human scenarios. When compared with reasoning on human ethics issues, the combined group of students evaluating animal ethics issues showed higher levels of Universal Principles reasoning, lower levels of Personal Interest reasoning and similar levels of Maintaining Norms reasoning. Arts students showed more personal interest reasoning than students in most animal-related programs on both animal and human ethics issues, and less norms-based reasoning on animal ethics issues. Medical students showed more norms-based reasoning on animal ethics issues than all of the animal-related groups. There were no differences in principled reasoning on animal ethics issues between program groups. This has implications for animal-related professions and education programs showing that students’ preference for principled reasoning on animal ethics issues is not unique to animal-related disciplines, and highlighting the need to develop student (and professional) capacity to apply principled reasoning to address ethics issues in animal industries to reduce the risk of moral distress. PMID:26934582

  17. Potential impact of climate change on air pollution-related human health effects.

    Science.gov (United States)

    Tagaris, Efthimios; Liao, Kuo-Jen; Delucia, Anthony J; Deck, Leland; Amar, Praveen; Russell, Armistead G

    2009-07-01

    The potential health impact of ambient ozone and PM2.5 concentrations modulated by climate change over the United States is investigated using combined atmospheric and health modeling. Regional air quality modeling for 2001 and 2050 was conducted using CMAQ Modeling System with meteorology from the GISS Global Climate Model, downscaled regionally using MM5,keeping boundary conditions of air pollutants, emission sources, population, activity levels, and pollution controls constant. BenMap was employed to estimate the air pollution health outcomes at the county, state, and national level for 2050 caused by the effect of meteorology on future ozone and PM2.5 concentrations. The changes in calculated annual mean PM2.5 concentrations show a relatively modest change with positive and negative responses (increasing PM2.5 levels across the northeastern U.S.) although average ozone levels slightly decrease across the northern sections of the U.S., and increase across the southern tier. Results suggest that climate change driven air quality-related health effects will be adversely affected in more then 2/3 of the continental U.S. Changes in health effects induced by PM2.5 dominate compared to those caused by ozone. PM2.5-induced premature mortality is about 15 times higher then that due to ozone. Nationally the analysis suggests approximately 4000 additional annual premature deaths due to climate change impacts on PM2.5 vs 300 due to climate change-induced ozone changes. However, the impacts vary spatially. Increased premature mortality due to elevated ozone concentrations will be offset by lower mortality from reductions in PM2.5 in 11 states. Uncertainties related to different emissions projections used to simulate future climate, and the uncertainties forecasting the meteorology, are large although there are potentially important unaddressed uncertainties (e.g., downscaling, speciation, interaction, exposure, and concentration-response function of the human health studies).

  18. Outcomes of surgically treated human papillomavirus-related oropharyngeal squamous cell carcinoma with N3 disease.

    Science.gov (United States)

    Zenga, Joseph; Haughey, Bruce H; Jackson, Ryan S; Adkins, Douglas R; Aranake-Chrisinger, John; Bhatt, Neel; Gay, Hiram A; Kallogjeri, Dorina; Martin, Eliot J; Moore, Eric J; Paniello, Randal C; Rich, Jason T; Thorstad, Wade L; Nussenbaum, Brian

    2017-09-01

    To evaluate outcomes for patients with pathological N3 (pN3) neck disease from human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) and determine variables predictive of survival. Retrospective case series with chart review. This study was conducted between 1998 and 2013 and included patients with HPV-related OPSCC treated with surgery with or without adjuvant therapy and who had pN3 nodal disease. The primary outcome was disease-specific survival (DSS). Secondary outcomes included overall survival (OS), disease-free survival (DFS), adverse events, and gastrostomy tube rates. Thirty-nine patients were included, of whom 36 (90%) underwent adjuvant therapy. Median follow-up was 39 months (range, 2-147 months). Mean age was 56 years, and 87% were male. Seventeen patients (44%) underwent selective neck dissection, whereas six (15%) underwent radical (n = 2) or extended radical (n = 4) neck dissection. Ninety-two percent had extracapsular extension. Five-year Kaplan-Meier estimated DSS, OS, and DFS were 89% (95% confidence interval [CI]: 79%-99%), 87% (95% CI: 75%-99%), and 84% (95% CI: 72%-96%), respectively. The disease recurrence rate was 10% (5% regional, 5% distant metastasis). Patients with less than 5 pathologically positive lymph nodes (P = .041) had improved DFS. Patients with HPV-related OPSCC and pN3 nodal disease treated with surgery and adjuvant therapy have very favorable long-term survival and regional control. Patients with five or more pathologically positive lymph nodes may be at higher risk for recurrence. 4. Laryngoscope, 127:2033-2037, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

  19. Loss-of-function of neuroplasticity-related genes confers risk for human neurodevelopmental disorders.

    Science.gov (United States)

    Smith, Milo R; Glicksberg, Benjamin S; Li, Li; Chen, Rong; Morishita, Hirofumi; Dudley, Joel T

    2018-01-01

    High and increasing prevalence of neurodevelopmental disorders place enormous personal and economic burdens on society. Given the growing realization that the roots of neurodevelopmental disorders often lie in early childhood, there is an urgent need to identify childhood risk factors. Neurodevelopment is marked by periods of heightened experience-dependent neuroplasticity wherein neural circuitry is optimized by the environment. If these critical periods are disrupted, development of normal brain function can be permanently altered, leading to neurodevelopmental disorders. Here, we aim to systematically identify human variants in neuroplasticity-related genes that confer risk for neurodevelopmental disorders. Historically, this knowledge has been limited by a lack of techniques to identify genes related to neurodevelopmental plasticity in a high-throughput manner and a lack of methods to systematically identify mutations in these genes that confer risk for neurodevelopmental disorders. Using an integrative genomics approach, we determined loss-of-function (LOF) variants in putative plasticity genes, identified from transcriptional profiles of brain from mice with elevated plasticity, that were associated with neurodevelopmental disorders. From five shared differentially expressed genes found in two mouse models of juvenile-like elevated plasticity (juvenile wild-type or adult Lynx1-/- relative to adult wild-type) that were also genotyped in the Mount Sinai BioMe Biobank we identified multiple associations between LOF genes and increased risk for neurodevelopmental disorders across 10,510 patients linked to the Mount Sinai Electronic Medical Records (EMR), including epilepsy and schizophrenia. This work demonstrates a novel approach to identify neurodevelopmental risk genes and points toward a promising avenue to discover new drug targets to address the unmet therapeutic needs of neurodevelopmental disease.

  20. Relative source contributions for perchlorate exposures in a lactating human cohort

    Energy Technology Data Exchange (ETDEWEB)

    Kirk, Andrea B. [University of North Texas Health Sciences Center (United States); Dyke, Jason V. [University of Texas at Arlington (United States); Ohira, Shin-Ichi [Kumamoto University (Japan); Dasgupta, Purnendu K., E-mail: Dasgupta@uta.edu [University of Texas at Arlington (United States)

    2013-01-15

    Perchlorate is an iodine-uptake inhibitor and common contaminant of food and drinking water. Understanding the amount of perchlorate exposure occurring through non-water sources is essential for accurate estimates of human exposure levels, and establishment of drinking water limits for this pervasive contaminant. The study objective was to determine the amount of perchlorate intake derived from diet rather than water. Subjects provided drinking water samples, detailed fluid-intake records, 24 h urine collections and four milk samples for nine days. Samples were analyzed for perchlorate by isotope dilution ion chromatography–tandem mass spectrometry. Amounts of perchlorate derived from drinking water and dietary sources were calculated for each individual. Water of local origin was found to contribute a minor fraction of perchlorate intake. Estimated fraction intake from drinking water ranged from 0 to 36%. The mean and median dose of perchlorate derived from non-water sources by lactating women was 0.18 μg/kg/day (range: 0.06 to 0.36 μg/kg/day.) Lactating women consumed more fluid (mean 2.424 L/day) than has been assumed in recent risk assessments for perchlorate. The data reported here indicate that lactating women may be exposed to perchlorate through dietary sources at markedly higher levels than estimated previously. Exposures to perchlorate from non-water sources may be higher than recent estimates, including those used to develop drinking water standards. - Highlights: ► Residence in an area with perchlorate-contaminated water may be a poor predictor of exposure. ► Exposures to perchlorate from food are likely underestimated. ► The relative contributions for human perchlorate exposures should be weighted more heavily towards non-water sources.

  1. Modulation of whistle production related to training sessions in bottlenose dolphins (Tursiops truncatus) under human care.

    Science.gov (United States)

    Lopez Marulanda, Juliana; Adam, Olivier; Delfour, Fabienne

    2016-11-01

    Bottlenose dolphins are highly social cetaceans with an extensive sound production including clicks, burst-pulsed sounds, and whistles. Some whistles, known as signature whistles, are individually specific. These acoustic signatures are commonly described as being emitted in contexts of stress during forced isolation and as group cohesion calls. Interactions between humans and captive dolphins is largely based on positive reinforcement conditioning within several training/feeding sessions per day. Vocal behavior of dolphins during these interactions might vary. To investigate this, we recorded 10 bottlenose dolphins of Parc Asterix dolphinarium (France) before, during and after 10 training sessions for a total duration of 7 hr and 32 min. We detected 3,272 whistles with 2,884 presenting a quality good enough to be categorized. We created a catalog of whistle types by visual categorization verified by five naive judges (Fleiss' Kappa Test). We then applied the SIGID method to identify the signatures whistles present in our recordings. We found 279 whistles belonging to one of the four identified signature whistle types. The remaining 2,605 were classified as non-signature whistles. The non-signature whistles emission rate was higher during and after the training sessions than before. Emission rate of three signature whistles types significantly increased afterwards as compared to before the training sessions. We suggest that dolphins use their signature whistles when they return to their intraspecific social interactions succeeding scheduled and human-organized training sessions. More observations are needed to make conclusions about the function of signature whistles in relation to training sessions. Zoo Biol. 35:495-504, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  2. Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

    International Nuclear Information System (INIS)

    Mameli, Giuseppe; Astone, Vito; Khalili, Kamel; Serra, Caterina; Sawaya, Bassel E.; Dolei, Antonina

    2007-01-01

    Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1 promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNFα, interferon-γ, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-β is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNFα had the ability to activate the ERVWE1 promoter through an NF-κB-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNFα enhances the binding of the p65 subunit of NF-κB, to its cognate site within the promoter. The effect of TNFα is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNFα-mediated induction of syncytin-1 in multiple sclerosis

  3. Aspartame Intake Relates to Coronary Plaque Burden and Inflammatory Indices in Human Immunodeficiency Virus.

    Science.gov (United States)

    Hall, Leangelo N; Sanchez, Laura R; Hubbard, Jane; Lee, Hang; Looby, Sara E; Srinivasa, Suman; Zanni, Markella V; Stanley, Takara L; Lo, Janet; Grinspoon, Steven K; Fitch, Kathleen V

    2017-01-01

    Dietary sweeteners may contribute to metabolic dysregulation and cardiovascular disease (CVD), but this has not been assessed in human immunodeficiency virus (HIV). One hundred twenty-four HIV-infected and 56 non-HIV-infected participants, without history of known coronary artery disease were included. Dietary intake was assessed using a 4-day food record. Coronary plaque was determined using cardiac computed tomography angiography. Human immunodeficiency virus-infected participants had significantly greater intake of dietary sweeteners, including total sugar ( P = .03) and added sugar ( P = .009); intake of aspartame (artificial sweetener) was greater among aspartame consumers with HIV versus non-HIV consumers ( P = .03). Among HIV-infected participants, aspartame intake was significantly associated with coronary plaque ( P = .002) and noncalcified plaque ( P = .007) segments, as well as markers of inflammation/immune activation (monocyte chemoattractant protein 1 and lipoprotein-associated phospholipase A 2 ), which may contribute to increased atherogenesis. In multivariable regression modeling, aspartame remained an independent predictor of plaque in HIV. In contrast, among non-HIV-infected participants, no sweetener type was shown to relate to plaque characteristics. We demonstrate increased intake of dietary sweeteners and a potential novel association between aspartame intake, plaque burden, and inflammation in HIV. Our data suggest that aspartame may contribute to CVD risk in HIV. Further studies should address potential mechanisms by which aspartame may contribute to increased plaque burden and cardiovascular benefits of dietary strategies targeting aspartame intake in HIV. © The Author 2017. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

  4. Thermal Conductivity of Human Bone in Cryoprobe Freezing as Related to Density.

    Science.gov (United States)

    Walker, Kyle E; Baldini, Todd; Lindeque, Bennie G

    2017-03-01

    Cryoprobes create localized cell destruction through freezing. Bone is resistant to temperature flow but is susceptible to freezing necrosis at warmer temperatures than tumor cells. Few studies have determined the thermal conductivity of human bone. No studies have examined conductivity as related to density. The study goal was to examine thermal conductivity in human bone while comparing differences between cancellous and cortical bone. An additional goal was to establish a relationship between bone density and thermal conductivity. Six knee joints from 5 cadavers were obtained. The epiphyseal region was sliced in half coronally prior to inserting an argon-circulating cryoprobe directed away from the joint line. Thermistor thermometers were placed perpendicularly at measured increments, and the freezing cycle was recorded until steady-state conditions were achieved. For 2 cortical samples, the probe was placed intramedullary in metaphyseal samples and measurements were performed radially from the central axis of each sample. Conductivity was calculated using Fournier's Law and then plotted against measured density of each sample. Across samples, density of cancellous bone ranged from 0.86 to 1.38 g/mL and average thermal conductivity ranged between 0.404 and 0.55 W/mK. Comparatively, cortical bone had a density of 1.70 to 1.86 g/mL and thermal conductivity of 0.0742 to 0.109 W/mK. A strong 2-degree polynomial correlation was seen (R 2 =0.8226, P<.001). Bone is highly resistant to temperature flow. This resistance varies and inversely correlates strongly with density. This information is clinically relevant to maximize tumor ablation while minimizing morbidity through unnecessary bone loss and damage to surrounding structures. [Orthopedics. 2017; 40(2):90-94.]. Copyright 2016, SLACK Incorporated.

  5. Activated effects of parathyroid hormone-related protein on human hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Fen-Fen Liang

    Full Text Available BACKGROUND & AIMS: After years of experiments and clinical studies, parathyroid hormone-related protein(PTHrP has been shown to be a bone formation promoter that elicits rapid effects with limited adverse reaction. Recently, PTHrP was reported to promote fibrosis in rat kidney in conjunction with transforming growth factor-beta1 (TGF-β1, which is also a fibrosis promoter in liver. However, the effect of PTHrP in liver has not been determined. In this study, the promoting actions of PTHrP were first investigated in human normal hepatic stellate cells (HSC and LX-2 cell lines. METHODS: TGF-β1, alpha-smooth muscle actin (α-SMA, matrix metalloproteinase 2 (MMP-2, and collagen I mRNA were quantified by real-time polymerase chain reaction (PCR after HSCs or LX-2 cells were treated with PTHrP(1-36 or TGF-β1. Protein levels were also assessed by western-blot analysis. Alpha-SMA were also detected by immunofluorescence, and TGF-β1 secretion was measured with enzyme-linked immunosorbent assay (ELISA of HSC cell culture media. RESULTS: In cultured human HSCs, mRNA and protein levels of α-SMA, collagen I, MMP-2, and TGF-β1 were increased by PTHrP treatment. A similar increasing pattern was also observed in LX-2 cells. Moreover, PTHrP significantly increased TGF-β1 secretion in cultured media from HSCs. CONCLUSIONS: PTHrP activated HSCs and promoted the fibrosis process in LX-2 cells. These procedures were probably mediated via TGF-β1, highlighting the potential effects of PTHrP in the liver.

  6. The Role of Human Papillomavirus (HPV)-Related Stigma on HPV Vaccine Decision-Making among College Males

    Science.gov (United States)

    Jones, Georden; Perez, Samara; Huta, Veronika; Rosberger, Zeev; Lebel, Sophie

    2016-01-01

    Objective: The goals of the present study are (1) to identify sociodemographic and psychosocial predictors of human papillomavirus (HPV)-related stigma and (2) to examine the relationship between HPV-related stigma in predicting HPV vaccine decision-making among college males. Participants: Six hundred and eighty college males aged 18--26 from 3…

  7. Industry and traffic related particles and their role in human health

    Energy Technology Data Exchange (ETDEWEB)

    Oravisjaervi, K.

    2013-11-01

    Combustion generated ultrafine particles have been found to be responsible for adverse effects on human health. New emission reduction technologies and fuels will change the composition of particle emissions. It is important to confirm that the new reduction technologies are designed to minimise the adverse health effects. In this doctoral thesis the potential health effects caused by traffic and industrially generated particles were studied using epidemiological, experimental and in silico studies. The effects of short-term changes in PM2.5 on the respiratory health of symptomatic children living near a steel works were studied to investigate whether specific sources of PM2.5 have the possible health effects. The PM2.5 emission sources were identified: long-range transport, a steel works, soil and street dust and a mechanical engineering works. Significant associations were not found between respiratory symptoms and PM2.5 or the sources markers. The deposition of traffic-related particles into the human respiratory system was computed using the lung deposition model. Particle size distribution was measured from diesel- and compressed natural gas (CNG)-fuelled busses and an off-road diesel engine under different combustion situations. The majority of the measured traffic-related particle numbers reach the alveolar region of the lungs. There were differences in the deposition of particles when different catalysts, engines or fuels were used. CNG or a diesel particulate filter (DPF) significantly reduced lung exposure to particles. Also physical activity, age and gender affected the deposition of particles. The diesel particles comprised compounds (carcinogenic PAHs, transition metals), which may have the ability to generate reactive oxygen. This study provides new knowledge how of the emission abatement technologies and fuels affects particle number and their composition, as well health hazards. Cleaner technology (CNG, DPF), emits significantly fewer particles in

  8. Can male vaccination reduce the burden of human papillomavirus-related disease in the United States?

    Science.gov (United States)

    Low, Garren M I; Attiga, Yasser S; Garg, Gaurav; Schlegal, Richard; Gallicano, G Ian

    2012-06-01

    Human papillomavirus (HPV) can cause cervical cancer, as well as a number of other diseases in both men and women. Both sexes play a role in transmission of the disease, but the cost-effectiveness of HPV vaccination differs between them. It is necessary to determine the best allocation of limited resources between these two populations to produce the most effective strategy for reducing the burden from HPV-related disease. This literature review intends to elucidate the economic and social considerations that will lead to maximum utilization of vaccination programs, which in turn will reduce the burden of HPV-related disease. Current outreach in the United States is based on vaccination against HPV as a means for combating cervical cancer in women. If we are to include males, however, new marketing strategies must focus on educating patients about the full range of the vaccine's benefits. Men who have sex with men (MSM) are also unprotected against HPV in the current system. Social considerations alone may not be enough, however, as economic prediction models suggest that the associated costs outweigh the benefits in most circumstances. Taking this into account, our review also considers alternate methods of maximizing prevention of HPV-associated disease. The most prudent programs will include physician involvement in patient education and the implementation of structured vaccination and screening programs. Unfortunately, many countries do not have the necessary resources to undertake national vaccination programs. HPV testing and cytology screening for women and MSM may be the most financially reasonable option for many countries.

  9. Maculoplasty for age-related macular degeneration: reengineering Bruch's membrane and the human macula.

    Science.gov (United States)

    Del Priore, Lucian V; Tezel, Tongalp H; Kaplan, Henry J

    2006-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment). In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.

  10. Estimate of oxygen consumption and intracellular zinc concentration of human spermatozoa in relation to motility.

    Science.gov (United States)

    Henkel, Ralf R; Defosse, Kerstin; Koyro, Hans-Wilhelm; Weissmann, Norbert; Schill, Wolf-Bernhard

    2003-03-01

    To investigate the human sperm oxygen/energy consumption and zinc content in relation to motility. In washed spermatozoa from 67 ejaculates, the oxygen consumption was determined. Following calculation of the total oxygen consumed by the Ideal Gas Law, the energy consumption of spermatozoa was calculated. In addition, the zinc content of the sperm was determined using an atomic absorption spectrometer. The resulting data were correlated to the vitality and motility. The oxygen consumption averaged 0.24 micromol/10(6) sperm x 24h, 0.28 micromol/10(6) live sperm x 24h and 0.85 micromol/10(6) live motile sperm x 24h. Further calculations revealed that sperm motility was the most energy consuming process (164.31 mJ/10(6) motile spermatozoa x 24h), while the oxygen consumption of the total spermatozoa was 46.06 mJ/10(6) spermatozoa x 24h. The correlation of the oxygen/energy consumption and zinc content with motility showed significant negative correlations (r= -0.759; P<0.0001 and r=-0.441; P<0.0001, respectively). However, when correlating sperm energy consumption with the zinc content, a significant positive relation (r=0.323; P=0.01) was observed. Poorly motile sperm are actually wasting the available energy. Moreover, our data clearly support the "Geometric Clutch Model" of the axoneme function and demonstrate the importance of the outer dense fibers for the generation of sperm motility, especially progressive motility.

  11. Practical Insights from Initial Studies Related to Human Error Analysis Project (HEAP)

    International Nuclear Information System (INIS)

    Follesoe, Knut; Kaarstad, Magnhild; Droeivoldsmo, Asgeir; Hollnagel, Erik; Kirwan; Barry

    1996-01-01

    This report presents practical insights made from an analysis of the three initial studies in the Human Error Analysis Project (HEAP), and the first study in the US NRC Staffing Project. These practical insights relate to our understanding of diagnosis in Nuclear Power Plant (NPP) emergency scenarios and, in particular, the factors that influence whether a diagnosis will succeed or fail. The insights reported here focus on three inter-related areas: (1) the diagnostic strategies and styles that have been observed in single operator and team-based studies; (2) the qualitative aspects of the key operator support systems, namely VDU interfaces, alarms, training and procedures, that have affected the outcome of diagnosis; and (3) the overall success rates of diagnosis and the error types that have been observed in the various studies. With respect to diagnosis, certain patterns have emerged from the various studies, depending on whether operators were alone or in teams, and on their familiarity with the process. Some aspects of the interface and alarm systems were found to contribute to diagnostic failures while others supported performance and recovery. Similar results were found for training and experience. Furthermore, the availability of procedures did not preclude the need for some diagnosis. With respect to HRA and PSA, it was possible to record the failure types seen in the studies, and in some cases to give crude estimates of the failure likelihood for certain scenarios. Although these insights are interim in nature, they do show the type of information that can be derived from these studies. More importantly, they clarify aspects of our understanding of diagnosis in NPP emergencies, including implications for risk assessment, operator support systems development, and for research into diagnosis in a broader range of fields than the nuclear power industry. (author)

  12. Cystoisosporiasis-related human acalculous cholecystitis: the need for increased awareness

    Directory of Open Access Journals (Sweden)

    Mahmoud Agholi

    2016-11-01

    Full Text Available Cholecystitis is one of the common surgical indications affecting human beings in many countries. A variety of infectious agents can be associated with acute or chronic acalculous cholecystitis, especially in HIV/AIDS patients. In this investigation, the authors aim to describe two cases of histologically and molecularly documented cystoisosporiasis (syn. isosporiasis as the cause of chronic acalculous cholecystitis in two immunodeficient patients. During microscopic examinations of more than 2500 diarrheic patients’ samples, 11 cases of cystoisosporiasis-related recurrent persistent/chronic diarrhea were detected. A review of the medical records of Cystoisospora belli (syn. Isospora belli-positive patients showed that two of them, i.e. a patient with prolonged corticosteroid therapy and an AIDS patient, several months prior to fecal examinations had undergone cholecystectomy due to acalculous cholecystitis. The study was continued by a review of the histopathological investigation of the recuts prepared from the excised gallbladder tissue sections and stained with hematoxylin and eosin in order to detect a possible specific clinical correlation with cystoisosporiasis. Light microscopic examination revealed the presence of various developmental stages of a coccidial parasite, namely Cystoisospora belli , in both patients’ gallbladder tissue sections. To the best of our knowledge, C. bellii -associated cholecystitis has not been previously reported in a patient with prolonged corticosteroid therapy.

  13. Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome.

    Science.gov (United States)

    Tvarijonaviciute, Asta; Ceron, Jose J; Holden, Shelley L; Cuthbertson, Daniel J; Biourge, Vincent; Morris, Penelope J; German, Alexander J

    2012-08-28

    Recently, metabolic syndrome (MS) has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs.Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%). The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD), which included a measure of adiposity (using a 9-point body condition score [BCS]), systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP) were measured using validated assays. Systolic blood pressure (P = 0.008), cholesterol (P = 0.003), triglyceride (P = 0.018), and fasting insulin (P disease associations and outcomes of weight loss.

  14. Components of postprandial thermogenesis in relation to meal frequency in humans.

    Science.gov (United States)

    LeBlanc, J; Mercier, I; Nadeau, A

    1993-12-01

    Experiments on dogs have shown that the size of the meal has no effect on the early cephalic postprandial thermogenesis, and that four small meals are more thermogenic than a larger meal with the same total caloric content as the four meals. A study was repeated on human subjects who were fed during alternating weeks either one large meal (653 kcal (1 kcal = 4.1855 kJ)) or four small meals (163 kcal) at 40-min intervals. Oxygen consumption and respiratory exchange ratio determinations indicated (i) larger overall increase in postprandial thermogenesis with the four meals than with one meal and (ii) an enhancement of glucose utilization with the large meal compared with greater lipid utilization with the four meals. On the basis of indirect evidence from previous investigations it is suggested that the enhanced thermogenesis observed in the four-meal experiment is due to lipid mobilization caused by repeated stimulation of the sympathetic nervous system with palatable food. Blood analysis indicated a reduced elevation of plasma glucose in the four-meal experiment. The variations of insulin and C-peptide exactly paralleled those observed for glucose. It is concluded that the increased frequency of feeding significantly reduces insulin secretion in subjects fed a relatively high carbohydrate meal. In addition to this beneficial effect, increasing the number of meals increased thermogenesis and fat utilization.

  15. PVC flooring is related to human uptake of phthalates in infants.

    Science.gov (United States)

    Carlstedt, F; Jönsson, B A G; Bornehag, C-G

    2013-02-01

    Polyvinyl chloride (PVC) flooring material contains phthalates, and it has been shown that such materials are important sources for phthalates in indoor dust. Phthalates are suspected endocrine-disrupting chemicals (EDCs). Consecutive infants between 2 and 6 months old and their mothers were invited. A questionnaire about indoor environmental factors and family lifestyle was used. Urinary metabolites of the phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP), butylbenzyl phthalate (BBzP), and dietylhexyl phthalate (DEHP) were measured in the urine of the children. Of 209 invited children, 110 (52%) participated. Urine samples were obtained from 83 of these. Urine levels of the BBzP metabolite monobenzyl phthalate (MBzP) was significantly higher in infants with PVC flooring in their bedrooms (P flooring material may increase the human uptake of phthalates in infants. Urinary levels of phthalate metabolites during early life are associated with the use of PVC flooring in the bedroom, body area, and the use of infant formula. This study shows that the uptake of phthalates is not only related to oral uptake from, for example, food but also to environmental factors such as building materials. This new information should be considered when designing indoor environment, especially for children. © 2012 John Wiley & Sons A/S.

  16. Common raven occurrence in relation to energy transmission line corridors transiting human-altered sagebrush steppe

    Science.gov (United States)

    Coates, Peter S.; Howe, Kristy B.; Casazza, Michael L.; Delehanty, David J.

    2014-01-01

    Energy-related infrastructure and other human enterprises within sagebrush steppe of the American West often results in changes that promote common raven (Corvus corax; hereafter, raven) populations. Ravens, a generalist predator capable of behavioral innovation, present a threat to many species of conservation concern. We evaluate the effects of detailed features of an altered landscape on the probability of raven occurrence using extensive raven survey (n= 1045) and mapping data from southern Idaho, USA. We found nonlinear relationships between raven occurrence and distances to transmission lines, roads, and facilities. Most importantly, raven occurrence was greater with presence of transmission lines up to 2.2 km from the corridor.We further explain variation in raven occurrence along anthropogenic features based on the amount of non-native vegetation and cover type edge, such that ravens select fragmented sagebrush stands with patchy, exotic vegetative introgression. Raven occurrence also increased with greater length of edge formed by the contact of big sagebrush (Artemisia tridentate spp.) with non-native vegetation cover types. In consideration of increasing alteration of sagebrush steppe, these findings will be useful for planning energy transmission corridor placement and other management activities where conservation of sagebrush obligate species is a priority.

  17. Volcano related atmospheric toxicants in Hilo and Hawaii Volcanoes National Park: implications for human health.

    Science.gov (United States)

    Michaud, Jon-Pierre; Krupitsky, Dmitry; Grove, John S; Anderson, Bruce S

    2005-08-01

    Volcanic fog (vog) from Kilauea volcano on the island of Hawaii includes a variety of chemical species including sulfur compounds and traces of metals such as mercury. The metal species seen tended to be in the nanograms per cubic meter range, whereas oxides of sulfur: SO2 and SO3 and sulfate aerosols, were in the range of micrograms per cubic meter and rarely even as high as a few milligrams per cubic meter of air (nominally ppb to ppm). These sulfur species are being investigated for associations with both acute and chronic changes in human health status. The sulfate aerosols tend to be less than 1 microm in diameter and tend to dominate the mass of this submicron size mode. The sulfur chemistry is dynamic, changing composition from predominantly sulfur dioxide and trioxide gasses near the volcano, to predominantly sulfate aerosols on the west side of the island. Time, concentration and composition characteristics of submicron aerosols and sulfur dioxide are described with respect to the related on-going health studies and public health management concerns. Exposures to sulfur dioxide and particulate matter equal to or less than 1 microm in size were almost always below the national ambient air quality standards (NAAQS). These standards do not however consider the acidic nature and submicron size of the aerosol, nor the possibility of the aerosol and the sulfur dioxide interacting in their toxicity. Time series plots, histograms and descriptive statistics of hourly averages give the reader a sense of some of the exposures observed.

  18. 12th international conference on human retrovirology: HTLV and related retroviruses

    Directory of Open Access Journals (Sweden)

    Lairmore Michael D

    2005-10-01

    Full Text Available Abstract The 12th International Conference on Human Retrovirology: HTLV and Related Retroviruses, was held at the Half Moon Hotel in Montego Bay, Jamaica, from June 22nd to June 25th 2005. The scientific conference, sponsored by the International Retrovirology Association, is held biennially at rotating international venues around the world. The meeting brings together basic scientists, epidemiologists and clinical researchers to discuss findings to prevent HTLV infection or develop new therapies against HTLV-mediated diseases. The Association fosters the education and training of young scientists to bring new approaches to the complex problems of HTLV research, such as translational research to bring findings from the laboratory into clinical trials that benefit HTLV-infected patients. The breadth and quality of research presentations and workshops at the 12th International Conference indicate that these goals are being accomplished. As HTLV research enters its third decade a new generation of scientists face many challenges. However, HTLV scientists and clinicians displayed exciting new approaches and discoveries during plenary talks and poster sessions. The conference encouraged research in HTLV infections and disease, fostered collaborations, and stimulated new partnerships between clinicians and scientists to encourage clinical trials and novel therapeutic interventions.

  19. Relative biological effectiveness of high energy protons for a human melanoma

    International Nuclear Information System (INIS)

    Petrovic, I.; Ristic-Fira, A.; Todorovic, D.; Valastro, I.; Cirrone, P.; Cuttone, G.

    2005-01-01

    Relative biological effectiveness (RBE) for the survival of human melanoma cells induced by high linear energy transfer (LET) protons was investigated. Exponentially growing HTB140 cells were irradiated close to the Bragg peak maximum of the 62 MeV protons, as well as with 60 Co γ-rays, over single doses, ranging from 8-24 Gy. Clonogenic survival and cell viability were assessed up to 48 h post-irradiation, therefore considered as early inactivation effects. Dose dependent cell inactivation induced by high LET protons was observed. Surviving fractions have shown great overlapping with estimated cell viability, both with the increase of dose and with prolonged cell incubation. Evaluated RBEs were higher with the rise of dose, being in the range from 2 to 3. All analyzes performed have demonstrated a very radio-resistant nature of HTB140 melanoma cells. However, high LET protons are able to inactivate these cells in a larger extent compared to the effects of γ-rays. (author)

  20. Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

    International Nuclear Information System (INIS)

    Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D. Wade; De Vries, George H.

    2006-01-01

    Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells

  1. Down-regulation of a calmodulin-related gene during transformation of human mammary epithelial cells

    International Nuclear Information System (INIS)

    Yaswen, P.; Smoll, A.; Stampfer, M.R.; Peehl, D.M.; Trask, D.K.; Sager, R.

    1990-01-01

    A human cDNA library obtained from cultured normal mammary epithelial cells (HMECs) was searched by subtractive hybridization for genes whose decrease in expression might be relevant to epithelial transformation. One clone identified by this procedure corresponded to a 1.4 kilobase mRNA, designated NB-1, whose expression was decreased >50-fold in HMECs tumorigenically transformed in vitro after exposure to benzo[α]pyrene and Kirsten sarcoma virus. Sequence analysis of NB-1 cDNA revealed an open reading frame with a high degree of homology to calmodulin. NB-1 expression could be demonstrated by polymerase chain reaction amplification in normal breast, prostate, cervix, and epidermal tissues. The presence of NB-1 transcripts was variable in primary breast carcinoma tissues and undetectable in tumor-derived cell lines of breast, prostate, or other origins. NB-1 mRNA expression could be down-regulated in cultured HMECs by exposure to reconstituted extracellular matrix material, while exposure to transforming growth factor type β increased its relative abundance. The protein encoded by NB-1 may have Ca 2 plus binding properties and perform functions similar to those of authentic calmodulin. Its possible roles in differentiation and/or suppression of tumorigenicity in epithelial tissues remain to be examined

  2. Relative impact of human leukocyte antigen mismatching and graft ischemic time after lung transplantation.

    Science.gov (United States)

    Brugière, Olivier; Thabut, Gabriel; Suberbielle, Caroline; Reynaud-Gaubert, Martine; Thomas, Pascal; Pison, Christophe; Saint Raymond, Christel; Mornex, Jean-François; Bertocchi, Michèle; Dromer, Claire; Velly, Jean-François; Stern, Marc; Philippe, Bruno; Dauriat, Gaëlle; Biondi, Giuseppina; Castier, Yves; Fournier, Michel

    2008-06-01

    Recent data strongly suggest that human leukocyte antigen (HLA) mismatching has a negative impact on development of bronchiolitis obliterans syndrome (BOS) and survival after lung transplantation (LTx). Because HLA matching is sometimes achieved by extending ischemic time in other solid-organ transplantation models and ischemic time is a risk factor per se for death after LTx, we sought to compare the theoretical benefit of HLA matching with the negative impact of lengthened ischemic time. In this collaborative study we compared the relative impact of HLA mismatching and ischemic time on BOS and survival in 182 LTx recipients. Using multivariate analyses, we observed a lower incidence of BOS (hazard ratio [HR] = 1.70, 95% confidence interval [CI]: 1.1 to 2.7, p = 0.03) and enhanced survival (HR = 1.91, 95% CI: 1.24 to 2.92, p = 0.01) in patients with zero or one HLA-A mismatch compared with those having two HLA-A mismatches. This beneficial effect on survival was equivalent to a reduction of ischemic time of 168 minutes. We observed a reduced incidence of BOS and a better survival rate in patients well-matched at the HLA-A locus, associated with an opposite effect of an enhanced ischemic time. This suggests that graft ischemic time should be taken into account in future studies of prospective HLA matching in LTx.

  3. Selective attention modulates human auditory brainstem responses: relative contributions of frequency and spatial cues.

    Directory of Open Access Journals (Sweden)

    Alexandre Lehmann

    Full Text Available Selective attention is the mechanism that allows focusing one's attention on a particular stimulus while filtering out a range of other stimuli, for instance, on a single conversation in a noisy room. Attending to one sound source rather than another changes activity in the human auditory cortex, but it is unclear whether attention to different acoustic features, such as voice pitch and speaker location, modulates subcortical activity. Studies using a dichotic listening paradigm indicated that auditory brainstem processing may be modulated by the direction of attention. We investigated whether endogenous selective attention to one of two speech signals affects amplitude and phase locking in auditory brainstem responses when the signals were either discriminable by frequency content alone, or by frequency content and spatial location. Frequency-following responses to the speech sounds were significantly modulated in both conditions. The modulation was specific to the task-relevant frequency band. The effect was stronger when both frequency and spatial information were available. Patterns of response were variable between participants, and were correlated with psychophysical discriminability of the stimuli, suggesting that the modulation was biologically relevant. Our results demonstrate that auditory brainstem responses are susceptible to efferent modulation related to behavioral goals. Furthermore they suggest that mechanisms of selective attention actively shape activity at early subcortical processing stages according to task relevance and based on frequency and spatial cues.

  4. Expression of iron-related genes in human brain and brain tumors

    Directory of Open Access Journals (Sweden)

    Britton Robert S

    2009-04-01

    Full Text Available Abstract Background Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (HAMP, HFE, neogenin (NEO1, transferrin receptor 1 (TFRC, transferrin receptor 2 (TFR2, and hemojuvelin (HFE2 in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines. Results Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens. Conclusion These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.

  5. A Survey on the HFE-related Technologies for the Improvements of Human Performance of Safety Personnel in Rail System

    International Nuclear Information System (INIS)

    Koo, I. S.; Park, G. O.; Suh, S. M.; Sim, Y. R.; Go, J. H.; Jeong, J. H.; Son, C. H.

    2005-08-01

    Many studies have shown that the most cases of rail accidents have occurred because of performing his/her tasks in inappropriate way. It is generally recognised that the rail system without human element could never be happened quite long time. So human element in rail system is going to be the major factor to the next tragic accident. This state-of-the-art report describes three major HFE-related technologies, training simulator, the integrated test facility for human factors engineering, and human performance evaluation system, that are used in the other industries including nuclear power industry for the purpose of increasing rail safety through out the improvement of human task performance. Base on this report, the way of developing those technologies that should be applied to the korean rail system is presented

  6. Report on {open_quotes}inspection of human subject research in intelligence and intelligence-related projects{close_quotes}

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-01-16

    Executive Order 12333, {open_quotes}United States Intelligence Activities,{close_quotes} (1) designates the Department`s intelligence element as a member of the Intelligence Community, and (2) states that no agency within the Intelligence community shall sponsor, contract for or conduct research on human subjects except in accordance with guidelines issued by the Department of Health and Human Services. The Federal policy for the Protection of Human Subjects, which was based on Department of Health and Human Services regulations, was promulgated in Title 10 Code of Federal Regulations Part 745 by the Department of Energy. The purpose of this inspection was to review the internal control procedures used by the Office of Nonproliferation and National Security to manage selected intelligence and intelligence-related projects that involve human subject research.

  7. A Survey on the HFE-related Technologies for the Improvements of Human Performance of Safety Personnel in Rail System

    Energy Technology Data Exchange (ETDEWEB)

    Koo, I. S.; Park, G. O.; Suh, S. M.; Sim, Y. R.; Go, J. H.; Jeong, J. H.; Son, C. H

    2005-08-15

    Many studies have shown that the most cases of rail accidents have occurred because of performing his/her tasks in inappropriate way. It is generally recognised that the rail system without human element could never be happened quite long time. So human element in rail system is going to be the major factor to the next tragic accident. This state-of-the-art report describes three major HFE-related technologies, training simulator, the integrated test facility for human factors engineering, and human performance evaluation system, that are used in the other industries including nuclear power industry for the purpose of increasing rail safety through out the improvement of human task performance. Base on this report, the way of developing those technologies that should be applied to the korean rail system is presented.

  8. Refractive indices of human skin tissues at eight wavelengths and estimated dispersion relations between 300 and 1600 nm

    International Nuclear Information System (INIS)

    Ding Huafeng; Lu, Jun Q; Wooden, William A; Kragel, Peter J; Hu Xinhua

    2006-01-01

    The refractive index of human skin tissues is an important parameter in characterizing the optical response of the skin. We extended a previously developed method of coherent reflectance curve measurement to determine the in vitro values of the complex refractive indices of epidermal and dermal tissues from fresh human skin samples at eight wavelengths between 325 and 1557 nm. Based on these results, dispersion relations of the real refractive index have been obtained and compared in the same spectral region

  9. The relation between flexibility of human resources and performance indexes of selected hospitals of Tehran Medical Sciences University

    Directory of Open Access Journals (Sweden)

    Noushin Alibakhshi

    2016-12-01

    Full Text Available Today, flexibility has turned to one of important issues in management theories and policies and most current discussions about flexibility patterns focus on management policies, so that these patterns are one of important aspects of human resources strategic management. This study was performed with the aim of assessing the flexibility rate of human resources and performance indexes of Tehran Medical Sciences University hospitals and determining the possible relation between these variables. The present study is descriptive – analytical which was conducted in cross-sectional form in 2015. The statistical population was selected by stratifies random sampling method as 317 persons from nursing, administrative and financial personnel of 5 hospitals of Tehran Medical Sciences University. Data collecting toll was hospitals performance indexes form and Wright & Snell flexibility questionnaire of human resources. Data analysis was performed using SPSS 18 software and with the aid of descriptive statistical indexes and linear regression analysis. The results showed that personnel ( human resources had high flexibility = 4.16.\tthere was a significant relation between total flexibility and the index of bed circulation so that by one unit increase in bed circulation space, normally, the average of total flexibility decreased 0.64 units ( p-value<0.05. The results showed that human resources of Tehran Medical Sciences University hospitals have high flexibility, so authorities and policy makers are suggested to adopt policies of human resources management for creating flexibility in human resources and improving hospitals performance and amending hospitals status.

  10. Cost analysis of Human Papillomavirus-related cervical diseases and genital warts in Swaziland.

    Directory of Open Access Journals (Sweden)

    Themba G Ginindza

    Full Text Available Human papillomavirus (HPV has proven to be the cause of several severe clinical conditions on the cervix, vulva, vagina, anus, oropharynx and penis. Several studies have assessed the costs of cervical lesions, cervical cancer (CC, and genital warts. However, few have been done in Africa and none in Swaziland. Cost analysis is critical in providing useful information for economic evaluations to guide policymakers concerned with the allocation of resources in order to reduce the disease burden.A prevalence-based cost of illness (COI methodology was used to investigate the economic burden of HPV-related diseases. We used a top-down approach for the cost associated with hospital care and a bottom-up approach to estimate the cost associated with outpatient and primary care. The current study was conducted from a provider perspective since the state bears the majority of the costs of screening and treatment in Swaziland. All identifiable direct medical costs were considered for cervical lesions, cervical cancer and genital warts, which were primary diagnoses during 2015. A mix of bottom up micro-costing ingredients approach and top-down approaches was used to collect data on costs. All costs were computed at the price level of 2015 and converted to dollars ($.The total annual estimated direct medical cost associated with screening, managing and treating cervical lesions, CC and genital warts in Swaziland was $16 million. The largest cost in the analysis was estimated for treatment of high-grade cervical lesions and cervical cancer representing 80% of the total cost ($12.6 million. Costs for screening only represented 5% of the total cost ($0.9 million. Treatment of genital warts represented 6% of the total cost ($1million.According to the cost estimations in this study, the economic burden of HPV-related cervical diseases and genital warts represents a major public health issue in Swaziland. Prevention of HPV infection with a national HPV immunization

  11. [Analysis on willingness to receive human papillomavirus vaccination among risk males and related factors].

    Science.gov (United States)

    Meng, Xiaojun; Jia, Tianjian; Zhang, Xuan; Zhu, Chen; Chen, Xin; Zou, Huachun

    2015-10-01

    To understand the willingness to receive human papillomavirus (HPV) vaccination of men who have sex with men (MSM) and the male clients of sexually transmitted disease (STD) clinics and related factors in China. MSM were enrolled from the community through snowball sampling and male clients of STD clinics were enrolled from a sexual health clinic through convenience sampling in Wuxi, China. A questionnaire survey on the subjects' socio-demographic characteristics and the awareness of HPV was conducted. A total of 186 MSM and 182 STD clients were recruited. The awareness rates of HPV were 18.4% and 23.1%, respectively and the awareness rates of HPV vaccination were 10.2% and 15.4%, respectively. STD clinic clients (70.9%) were more likely to receive HPV vaccination than MSM (34.9%) (χ² = 47.651, P<0.01). Only 26.2% of MSM and 20.2% of STD clinic clients were willing to receive free HPV vaccination before the age of 20 years. Multivariate logistic regression analysis showed that MSM who had passive anal sex (OR=2.831, 95% CI: 1.703-13.526) , MSM who never used condom in anal sex in the past 6 months (OR=3.435, 95% CI: 1.416-20.108) , MSM who had been diagnosed with STDs (OR=1.968, 95% CI: 1.201-8.312) and STD clinic clients who had commercial sex with females in the past 3 months (OR=1.748, 95% CI: 1.207-8.539) , STD clinic clients who never used condom in commercial sex in the past 3 months (OR=1.926, 95% CI: 1.343-5.819) and STD clinic clients who had been diagnosed with STDs in past 12 months (OR=2.017, 95% CI: 1.671-7.264) were more likely to receive free HPV vaccination. Sexually active MSM and male clients in STD clinics in China had lower awareness of the HPV related knowledge. Their willing to receive HPV vaccination were influenced by their behavior related factors. It is necessary to strengthen the health education about HPV and improve people's awareness of HPV vaccination.

  12. The Relation between Law and Fraternity as a Promotional Instrument for Human Dignity in Labor Law

    OpenAIRE

    Guilherme Domingos de Luca; Lafayette Pozzoli

    2015-01-01

    Examine in this study as a problem, the relationship of law and Fraternity as a promotional instrument of Human Dignity in Labour Law, pointing out the means by which positive law has constitutionalized the fundamental guarantees of man labor law. Understand the relationship of human labor versus the dignity of the human person, and the idea of fraternity as a promotional function. The research was based on bibliographic compared. The main object is to understand the role of the fraternity an...

  13. The One Human Problem, Its Solution, and Its Relation to UFO Phenomen

    Science.gov (United States)

    1977-01-01

    thought process. Animal and human experiments clearly demonstrated that biofield inception from two or more minds may be cyborged , even in the mind...and body of one peorson or one animal, just as the two hemispheres of the human cerebrum are presently cyborged in one human brain. The biofield...University Press, 1973. 4. Thomas E. Bearden, Ficld, Formon, Superspace, and Inceptive Cyborg : A Paraphysical Theory of Noncausal Phenomena December 1974

  14. Low-altitude outbreaks of human fascioliasis related with summer rainfall in Gilan province, Iran

    OpenAIRE

    Abdoreza Salahi-Moghaddam; Majid Habibi-Nokhandam; Màrius V. Fuentes

    2011-01-01

    Following human fascioliasis outbreaks in 1988 and 1999 in Gilan province, northern Iran, efforts are now made to shed light on the seasonal pattern of fascioliasis transmission in this endemic area, taking into account snail host populations, climatic conditions and human cases. Populations of the intermediate host snail (Lymnaea spp.) peak in May and November, while there is a fourfold increase in the rate of human fascioliasis in February compared to that of September. Transmission is like...

  15. Collection of human reaction times and supporting health related data for analysis of cognitive and physical performance

    Directory of Open Access Journals (Sweden)

    Petr Brůha

    2018-04-01

    Full Text Available Smoking, excessive drinking, overeating and physical inactivity are well-established risk factors decreasing human physical performance. Moreover, epidemiological work has identified modifiable lifestyle factors, such as poor diet and physical and cognitive inactivity that are associated with the risk of reduced cognitive performance. Definition, collection and annotation of human reaction times and suitable health related data and metadata provides researchers with a necessary source for further analysis of human physical and cognitive performance. The collection of human reaction times and supporting health related data was obtained from two groups comprising together 349 people of all ages - the visitors of the Days of Science and Technology 2016 held on the Pilsen central square and members of the Mensa Czech Republic visiting the neuroinformatics lab at the University of West Bohemia. Each provided dataset contains a complete or partial set of data obtained from the following measurements: hands and legs reaction times, color vision, spirometry, electrocardiography, blood pressure, blood glucose, body proportions and flexibility. It also provides a sufficient set of metadata (age, gender and summary of the participant's current life style and health to allow researchers to perform further analysis. This article has two main aims. The first aim is to provide a well annotated collection of human reaction times and health related data that is suitable for further analysis of lifestyle and human cognitive and physical performance. This data collection is complemented with a preliminarily statistical evaluation. The second aim is to present a procedure of efficient acquisition of human reaction times and supporting health related data in non-lab and lab conditions. Keywords: Reaction time, Health related data, Cognitive and physical performance, Chronic disease, Data acquisition, Data collection, Software for data collection

  16. Free-ranging dogs show age related plasticity in their ability to follow human pointing.

    Science.gov (United States)

    Bhattacharjee, Debottam; N, Nikhil Dev; Gupta, Shreya; Sau, Shubhra; Sarkar, Rohan; Biswas, Arpita; Banerjee, Arunita; Babu, Daisy; Mehta, Diksha; Bhadra, Anindita

    2017-01-01

    Differences in pet dogs' and captive wolves' ability to follow human communicative intents have led to the proposition of several hypotheses regarding the possession and development of social cognitive skills in dogs. It is possible that the social cognitive abilities of pet dogs are induced by indirect conditioning through living with humans, and studying free-ranging dogs can provide deeper insights into differentiating between innate abilities and conditioning in dogs. Free-ranging dogs are mostly scavengers, indirectly depending on humans for their sustenance. Humans can act both as food providers and as threats to these dogs, and thus understanding human gestures can be a survival need for the free-ranging dogs. We tested the responsiveness of such dogs in urban areas toward simple human pointing cues using dynamic proximal points. Our experiment showed that pups readily follow proximal pointing and exhibit weaker avoidance to humans, but stop doing so at the later stages of development. While juveniles showed frequent and prolonged gaze alternations, only adults adjusted their behaviour based on the reliability of the human experimenter after being rewarded. Thus free-ranging dogs show a tendency to respond to human pointing gestures, with a certain level of behavioural plasticity that allows learning from ontogenic experience.

  17. [The relationships among occupational and organizational commitment, human relations in the workplace, and well-being in nurses].

    Science.gov (United States)

    Sawada, Tadayuki

    2013-12-01

    This study examined the relationship among human relations in the workplace, job involvement, affective commitment and continuance commitment with occupational and organizational commitment, and well-being. Questionnaires were completed by 855 female nurses who worked in four public hospitals (mean age = 32.6 years). The results of factor analysis showed that each component of the vocational constructs was distinguishable from the others. Path analysis showed that human relations in the workplace directly influenced job involvement and affective commitment both to the occupation and to the organization. Job involvement in turn directly influenced affective commitment and continuance commitment to the occupation. Job involvement also influenced affective commitment to the organization directly, and indirectly through affective commitment to the occupation. Finally, it was found that human relations in the workplace and affective commitment to the occupation positively influenced well-being; continuance commitment to the occupation was a negative influence. Theoretical and practical implications are discussed.

  18. The intensity of the 1602 cm-1 band in human cells is related to mitochondrial activity

    NARCIS (Netherlands)

    Pully, V.V.; Otto, Cornelis

    2009-01-01

    We report a Raman band at 1602 cm−1 in the spectra of human cells, which previously had only been observed in mitochondria of yeast cells. This band, which has not yet been assigned to a particular molecular species, was found to occur in HeLa cells, peripheral blood lymphocytes, human mesenchymal

  19. Local Cytokine Concentrations and Oxygen Pressure Are Related to Maturation of the Collateral Circulation in Humans

    NARCIS (Netherlands)

    Schirmer, Stephan H.; van Royen, Niels; Moerland, Perry D.; Fledderus, Joost O.; Henriques, José P.; van der Schaaf, René J.; Vis, Marije M.; Baan, Jan; Koch, Karel T.; Horrevoets, Anton J. G.; Hoefer, Imo E.; Piek, Jan J.

    2009-01-01

    Objectives Our aim was to determine cytokine and oxygen gradients over the collateral circulation in humans. Background The molecular background of the maturation of the collateral circulation in response to coronary narrowing is poorly understood in humans, partly because of difficulties in

  20. Abstract robots with an attitude : applying interpersonal relation models to human-robot interaction

    NARCIS (Netherlands)

    Hiah, J.L.; Beursgens, L.; Haex, R.; Perez Romero, L.M.; Teh, Y.; Bhomer, ten M.; Berkel, van R.E.A.; Barakova, E.I.

    2013-01-01

    This paper explores new possibilities for social interaction between a human user and a robot with an abstract shape. The social interaction takes place by simulating behaviors such as submissiveness and dominance and analyzing the corresponding human reactions. We used an object that has no

  1. Re-Thinking Relations in Human Rights Education: The Politics of Narratives

    Science.gov (United States)

    Adami, Rebecca

    2014-01-01

    Human Rights Education (HRE) has traditionally been articulated in terms of cultivating better citizens or world citizens. The main preoccupation in this strand of HRE has been that of bridging a gap between universal notions of a human rights subject and the actual locality and particular narratives in which students are enmeshed. This…

  2. Multi-stream CNN: Learning representations based on human-related regions for action recognition

    NARCIS (Netherlands)

    Tu, Zhigang; Xie, Wei; Qin, Qianqing; Poppe, R.W.; Veltkamp, R.C.; Li, Baoxin; Yuan, Junsong

    2018-01-01

    The most successful video-based human action recognition methods rely on feature representations extracted using Convolutional Neural Networks (CNNs). Inspired by the two-stream network (TS-Net), we propose a multi-stream Convolutional Neural Network (CNN) architecture to recognize human actions. We

  3. The relation between humans and knowledge sharing in Malaysia : Empirical evidence from Malaysian managers

    NARCIS (Netherlands)

    Boom, I.; Pennink, Barteld

    2012-01-01

    This paper explores whether there is a relationship between humanness and the willingness to share knowledge in Malaysia. Furthermore, the differences between the Malay, Chinese and Indian ethnicities are researched for the presence of humanness and the willingness to share knowledge. Two hundred

  4. Human relations in a nonviolent perspective between “openess to thou” and creative management of conflitcs

    Directory of Open Access Journals (Sweden)

    Gabriella FALCICCHIO

    2016-09-01

    Full Text Available The nonviolent perspective radically modifies the relations between human beings and among other living creatures. The non – destructive and openness principle leads to see in the other a “you” that, even during interpersonal or social conflicts, does not become an enemy, but must still be considered akin, close, recognizable as human, capable of doing good. This vision changes the quality of conflicts which are not denied or avoided and therefore do not decrease. On the contrary, they increase because a positive dynamic of relation transformation is established.

  5. Trace metals in Antarctica related to climate change and increasing human impact.

    Science.gov (United States)

    Bargagli, R

    2000-01-01

    in most samples of atmospheric particulates, snow, ice, soils, and marine sediments from Antarctica can be taken as global background levels. Comparison between the results of trace element surveys in marine waters of the Southern Ocean and in other seas is practically impossible. The upwelling or subduction of water masses, the seasonality in ice cover and in phytoplankton biomass, the low fallout of atmospheric dust, and many other peculiar characteristics of the Southern Ocean make concentrations of trace metals in surface waters quite variable in space and time. The depletion of nutrients in surface waters, which is a regular feature of many marine environments, rarely occurs in the Southern Ocean. Waters in some regions are characterized by very low concentrations of Fe and Mn, whereas in others the content of Cd is relatively high at the beginning of summer and may decrease about one order of magnitude during the phytoplankton bloom. Although in most Antarctic coastal ecosystems the input of metals from geochemical and anthropogenic sources and from long-range transport is negligible, concentrations of Cd in the waters and biota may be higher than in waters and related species of organisms from polluted coastal areas. Like the Southern Ocean, Antarctic lakes have many peculiar characteristics. They are often perennially ice covered and without outlet, and their water, which is gained only from short-term melting of snow and glaciers in summer, is lost mainly by sublimation of surface ice. Several lakes are distinctly stratified: the water under the ice may be cool, rich in oxygen, and among the cleanest and clearest of natural waters, whereas water near the bottom becomes anoxic, tepid, and richer in major and trace elements. Considering the specificity of Antarctic environments, to evaluate the extent and consequences of global changes and increasing human activities in Antarctica itself, research on the biogeochemistry of trace metals and monitoring programs

  6. The Impact of Future Emissions Changes on Air Pollution Concentrations and Related Human Health Effects

    Science.gov (United States)

    Mikolajczyk, U.; Suppan, P.; Williams, M.

    2015-12-01

    Quantification of potential health benefits of reductions in air pollution on the local scale is becoming increasingly important. The aim of this study is to conduct health impact assessment (HIA) by utilizing regionally and spatially specific data in order to assess the influence of future emission scenarios on human health. In the first stage of this investigation, a modeling study was carried out using the Weather Research and Forecasting (WRF) model coupled with Chemistry to estimate ambient concentrations of air pollutants for the baseline year 2009, and for the future emission scenarios in southern Germany. Anthropogenic emissions for the baseline year 2009 are derived from the emission inventory provided by the Netherlands Organization of Applied Scientific Research (TNO) (Denier van der Gon et al., 2010). For Germany, the TNO emissions were replaced by gridded emission data with a high spatial resolution of 1/64 x 1/64 degrees. Future air quality simulations are carried out under different emission scenarios, which reflect possible energy and climate measures in year 2030. The model set-up included a nesting approach, where three domains with horizontal resolution of 18 km, 6 km and 2 km were defined. The simulation results for the baseline year 2009 are used to quantify present-day health burdens. Concentration-response functions (CRFs) for PM2.5 and NO2 from the WHO Health risks of air Pollution in Europe (HRAPIE) project were applied to population-weighted mean concentrations to estimate relative risks and hence to determine numbers of attributable deaths and associated life-years lost. In the next step, future health impacts of projected concentrations were calculated taking into account different emissions scenarios. The health benefits that we assume with air pollution reductions can be used to provide options for future policy decisions to protect public health.

  7. Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

    Energy Technology Data Exchange (ETDEWEB)

    Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.; Walker, John R.; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carriere, Frederic (CNRS-UMR); (Toronto)

    2008-10-02

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

  8. Cortical thickness development of human primary visual cortex related to the age of blindness onset.

    Science.gov (United States)

    Li, Qiaojun; Song, Ming; Xu, Jiayuan; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2017-08-01

    Blindness primarily induces structural alteration in the primary visual cortex (V1). Some studies have found that the early blind subjects had a thicker V1 compared to sighted controls, whereas late blind subjects showed no significant differences in the V1. This implies that the age of blindness onset may exert significant effects on the development of cortical thickness of the V1. However, no previous research used a trajectory of the age of blindness onset-related changes to investigate these effects. Here we explored this issue by mapping the cortical thickness trajectory of the V1 against the age of blindness onset using data from 99 blind individuals whose age of blindness onset ranged from birth to 34 years. We found that the cortical thickness of the V1 could be fitted well with a quadratic curve in both the left (F = 11.59, P = 3 × 10 -5 ) and right hemispheres (F = 6.54, P = 2 × 10 -3 ). Specifically, the cortical thickness of the V1 thinned rapidly during childhood and adolescence and did not change significantly thereafter. This trend was not observed in the primary auditory cortex (A1), primary motor cortex (M1), or primary somatosensory cortex (S1). These results provide evidence that an onset of blindness before adulthood significantly affects the cortical thickness of the V1 and suggest a critical period for cortical development of the human V1.

  9. Quantifying Age-Related Differences in Human Reaching while Interacting with a Rehabilitation Robotic Device

    Directory of Open Access Journals (Sweden)

    Vivek Yadav

    2010-01-01

    Full Text Available New movement assessment and data analysis methods are developed to quantify human arm motion patterns during physical interaction with robotic devices for rehabilitation. These methods provide metrics for future use in diagnosis, assessment and rehabilitation of subjects with affected arm movements. Specifically, the current study uses existing pattern recognition methods to evaluate the effect of age on performance of a specific motion, reaching to a target by moving the end-effector of a robot (an X-Y table. Differences in the arm motion patterns of younger and older subjects are evaluated using two measures: the principal component analysis similarity factor (SPCA to compare path shape and the number of Fourier modes representing 98% of the path ‘energy’ to compare the smoothness of movement, a particularly important variable for assessment of pathologic movement. Both measures are less sensitive to noise than others previously reported in the literature and preserve information that is often lost through other analysis techniques. Data from the SPCA analysis indicate that age is a significant factor affecting the shapes of target reaching paths, followed by reaching movement type (crossing body midline/not crossing and reaching side (left/right; hand dominance and trial repetition are not significant factors. Data from the Fourier-based analysis likewise indicate that age is a significant factor affecting smoothness of movement, and movements become smoother with increasing trial number in both younger and older subjects, although more rapidly so in younger subjects. These results using the proposed data analysis methods confirm current practice that age-matched subjects should be used for comparison to quantify recovery of arm movement during rehabilitation. The results also highlight the advantages that these methods offer relative to other reported measures.

  10. Sodium lauryl sulfate-induced irritation in the human face: regional and age-related differences.

    Science.gov (United States)

    Marrakchi, S; Maibach, H I

    2006-01-01

    The particular sensitivity of the human face to care products prompted us to study irritation induced by sodium lauryl sulfate (SLS) in its various regions. We examined regional and age-related differences, correlating basal transepidermal water loss (TEWL) and capacitance to SLS irritation. SLS (2% aq.) was applied under occlusion for 1 h to the forehead, cheek, nose, nasolabial and perioral areas, chin, neck and forearm to two groups of subjects--one with 10 subjects with an average age of 25.2 +/- 4.7 years and another with 10 subjects with an average age of 73.7 +/- 3.9 years. TEWL was measured before and 1 h and 23 h after patch removal. Baseline stratum corneum hydration was also measured. Irritation was assessed by the changes in TEWL (deltaTEWL = TEWL after patch removal - basal TEWL) after corrections to the control. In the younger group, all areas of the face and the neck reacted to SLS, whereas the forearm did not. In the older group, the nose, perioral area and forearm did not react. In both age groups, some significant differences between the regions of the face were detected. The younger group showed higher changes in TEWL than the older group in all the areas studied, but only in the chin and nasolabial area were the differences statistically significant. Significant correlations were found between basal TEWL and deltaTEWL in 5 of the 7 areas which reacted to SLS. Baseline TEWL is one parameter that correlates with the susceptibility of the face to this irritant. 2006 S. Karger AG, Basel

  11. How awareness changes the relative weights of evidence during human decision-making.

    Science.gov (United States)

    de Lange, Floris P; van Gaal, Simon; Lamme, Victor A F; Dehaene, Stanislas

    2011-11-01

    Human decisions are based on accumulating evidence over time for different options. Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information? We examined the influence of awareness on decision-making using combined behavioral methods and magneto-encephalography (MEG). Participants were required to make decisions by accumulating evidence over a series of visually presented arrow stimuli whose visibility was modulated by masking. Behavioral results showed that participants could accumulate evidence under both high and low visibility. However, a top-down strategic modulation of the flow of incoming evidence was only present for stimuli with high visibility: once enough evidence had been accrued, participants strategically reduced the impact of new incoming stimuli. Also, decision-making speed and confidence were strongly modulated by the strength of the evidence for high-visible but not low-visible evidence, even though direct priming effects were identical for both types of stimuli. Neural recordings revealed that, while initial perceptual processing was independent of visibility, there was stronger top-down amplification for stimuli with high visibility than low visibility. Furthermore, neural markers of evidence accumulation over occipito-parietal cortex showed a strategic bias only for highly visible sensory information, speeding up processing and reducing neural computations related to the decision process. Our results indicate that the level of awareness of information changes decision-making: while accumulation of evidence already exists under low visibility conditions, high visibility allows evidence to be accumulated up to a higher level, leading to important strategical top-down changes in decision-making. Our results therefore suggest a potential role of awareness in deploying flexible strategies for biasing information acquisition in line with one's expectations and goals.

  12. How awareness changes the relative weights of evidence during human decision-making.

    Directory of Open Access Journals (Sweden)

    Floris P de Lange

    2011-11-01

    Full Text Available Human decisions are based on accumulating evidence over time for different options. Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information? We examined the influence of awareness on decision-making using combined behavioral methods and magneto-encephalography (MEG. Participants were required to make decisions by accumulating evidence over a series of visually presented arrow stimuli whose visibility was modulated by masking. Behavioral results showed that participants could accumulate evidence under both high and low visibility. However, a top-down strategic modulation of the flow of incoming evidence was only present for stimuli with high visibility: once enough evidence had been accrued, participants strategically reduced the impact of new incoming stimuli. Also, decision-making speed and confidence were strongly modulated by the strength of the evidence for high-visible but not low-visible evidence, even though direct priming effects were identical for both types of stimuli. Neural recordings revealed that, while initial perceptual processing was independent of visibility, there was stronger top-down amplification for stimuli with high visibility than low visibility. Furthermore, neural markers of evidence accumulation over occipito-parietal cortex showed a strategic bias only for highly visible sensory information, speeding up processing and reducing neural computations related to the decision process. Our results indicate that the level of awareness of information changes decision-making: while accumulation of evidence already exists under low visibility conditions, high visibility allows evidence to be accumulated up to a higher level, leading to important strategical top-down changes in decision-making. Our results therefore suggest a potential role of awareness in deploying flexible strategies for biasing information acquisition in line with one's expectations and goals.

  13. Food-producing animals and their health in relation to human health

    Directory of Open Access Journals (Sweden)

    Guillermo Téllez

    2015-02-01

    Full Text Available The fields of immunology, microbiology, and nutrition converge in an astonishing way. Dietary ingredients have a profound effect on the composition of the gut microflora, which in turn regulates the physiology of metazoans. As such, nutritional components of the diet are of critical importance not only for meeting the nutrient requirements of the host, but also for the microbiome. During their coevolution, bacterial microbiota has established multiple mechanisms to influence the eukaryotic host, generally in a beneficial fashion. The microbiome encrypts a variety of metabolic functions that complements the physiology of their hosts. Over a century ago Eli Metchnikoff proposed the revolutionary idea to consume viable bacteria to promote health by modulating the intestinal microflora. The idea is more applicable now than ever, since bacterial antimicrobial resistance has become a serious worldwide problem both in medical and agricultural fields. The impending ban of antibiotics in animal feed due to the current concern over the spread of antibiotic resistance genes makes a compelling case for the development of alternative prophylactics. Nutritional approaches to counteract the debilitating effects of stress and infection may provide producers with useful alternatives to antibiotics. Improving the disease resistance of animals grown without antibiotics will benefit the animals’ health, welfare, and production efficiency, and is also a key strategy in the effort to improve the microbiological safe status of animal-derived food products (e.g. by poultry, rabbits, ruminants, or pigs. This review presents some of the alternatives currently used in food-producing animals to influence their health in relation to human health.

  14. Neutron Exposures in Human Cells: Bystander Effect and Relative Biological Effectiveness

    Science.gov (United States)

    Seth, Isheeta; Schwartz, Jeffrey L.; Stewart, Robert D.; Emery, Robert; Joiner, Michael C.; Tucker, James D.

    2014-01-01

    Bystander effects have been observed repeatedly in mammalian cells following photon and alpha particle irradiation. However, few studies have been performed to investigate bystander effects arising from neutron irradiation. Here we asked whether neutrons also induce a bystander effect in two normal human lymphoblastoid cell lines. These cells were exposed to fast neutrons produced by targeting a near-monoenergetic 50.5 MeV proton beam at a Be target (17 MeV average neutron energy), and irradiated-cell conditioned media (ICCM) was transferred to unirradiated cells. The cytokinesis-block micronucleus assay was used to quantify genetic damage in radiation-naïve cells exposed to ICCM from cultures that received 0 (control), 0.5, 1, 1.5, 2, 3 or 4 Gy neutrons. Cells grown in ICCM from irradiated cells showed no significant increase in the frequencies of micronuclei or nucleoplasmic bridges compared to cells grown in ICCM from sham irradiated cells for either cell line. However, the neutron beam has a photon dose-contamination of 5%, which may modulate a neutron-induced bystander effect. To determine whether these low doses of contaminating photons can induce a bystander effect, cells were irradiated with cobalt-60 at doses equivalent to the percent contamination for each neutron dose. No significant increase in the frequencies of micronuclei or bridges was observed at these doses of photons for either cell line when cultured in ICCM. As expected, high doses of photons induced a clear bystander effect in both cell lines for micronuclei and bridges (pbystander effect in these cells. Finally, neutrons had a relative biological effectiveness of 2.0±0.13 for micronuclei and 5.8±2.9 for bridges compared to cobalt-60. These results may be relevant to radiation therapy with fast neutrons and for regulatory agencies setting standards for neutron radiation protection and safety. PMID:24896095

  15. Obesity-related metabolic dysfunction in dogs: a comparison with human metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Tvarijonaviciute Asta

    2012-08-01

    Full Text Available Abstract Background Recently, metabolic syndrome (MS has gained attention in human metabolic medicine given its associations with development of type 2 diabetes mellitus and cardiovascular disease. Canine obesity is associated with the development of insulin resistance, dyslipidaemia, and mild hypertension, but the authors are not aware of any existing studies examining the existence or prevalence of MS in obese dogs. Thirty-five obese dogs were assessed before and after weight loss (median percentage loss 29%, range 10-44%. The diagnostic criteria of the International Diabetes Federation were modified in order to define canine obesity-related metabolic dysfunction (ORMD, which included a measure of adiposity (using a 9-point body condition score [BCS], systolic blood pressure, fasting plasma cholesterol, plasma triglyceride, and fasting plasma glucose. By way of comparison, total body fat mass was measured by dual-energy X-ray absorptiometry, whilst total adiponectin, fasting insulin, and high-sensitivity C-reactive protein (hsCRP were measured using validated assays. Results Systolic blood pressure (P = 0.008, cholesterol (P = 0.003, triglyceride (P = 0.018, and fasting insulin (P P = 0.001. However, hsCRP did not change with weight loss. Prior to weight loss, 7 dogs were defined as having ORMD, and there was no difference in total fat mass between these dogs and those who did not meet the criteria for ORMD. However, plasma adiponectin concentration was less (P = 0.031, and plasma insulin concentration was greater (P = 0.030 in ORMD dogs. Conclusions In this study, approximately 20% of obese dogs suffer from ORMD, and this is characterized by hypoadiponectinaemia and hyperinsulinaemia. These studies can form the basis of further investigations to determine path genetic mechanisms and the health significance for dogs, in terms of disease associations and outcomes of weight loss.

  16. Parathyroid hormone related protein concentration in human serum and CSF correlates with age.

    Science.gov (United States)

    Kushnir, Mark M; Peterson, Lisa K; Strathmann, Frederick G

    2018-02-01

    Parathyroid Hormone-Related Protein (PTHrP) is involved in intracellular calcium (Ca) regulation, and has been demonstrated to participate in regulation of Ca in brain cells, activation of neurons, and modulation of pain. However, there are conflicting reports regarding the presence of PTHrP in CSF. PTHrP and Ca were quantified in paired CSF and serum samples using mass spectrometry-based methods. Associations between PTHrP and Ca concentrations with age, sex and concentrations of nine CSF diagnostic markers in a set of 140 paired serum and CSF patient samples were evaluated. The observed median PTHrP concentration in CSF was 51 times higher than in serum; the median concentration of Ca in CSF was 1.8 times lower than in serum. We observed positive correlation between concentrations of PTHrP in CSF and serum (p=0.013). Distribution of PTHrP concentrations in serum was associated with age (p=0.0068) and the concentrations were higher in women. In samples with serum calcium concentrations within the reference intervals (n=118), central 95% distribution of concentrations for Ca-CSF, PTHrP-serum and PTHrP-CSF were 5.4 (4.5-6.1) mg/dL, 1.2 (0.5-2.5) pmol/L, 62 (22-125) pmol/L, respectively. Our data demonstrate that PTHrP is a normal constituent of human CSF with median concentrations 51 fold higher than in serum. Elevated serum PTHrP concentrations were positively correlated with age and significantly higher in women. Our data suggest that CSF could be a significant source of circulating PTHrP. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  17. β-cryptoxanthin regulates bone resorption related-cytokine production in human periodontal ligament cells.

    Science.gov (United States)

    Nishigaki, Masaru; Yamamoto, Toshiro; Ichioka, Hiroaki; Honjo, Ken-Ichi; Yamamoto, Kenta; Oseko, Fumishige; Kita, Masakazu; Mazda, Osam; Kanamura, Narisato

    2013-07-01

    β-cryptoxanthin (β-cry) is a type of carotenoid found in certain fruits and vegetables. Although it has been shown that β-cry inhibits alveolar bone resorption, the molecular mechanisms for this have not yet been clarified. In the present study, we investigated the effects of β-cry on bone resorption related-cytokine production in human periodontal ligament (hPDL) cells. hPDL cells were stimulated with β-cry (1×10(-7)mol/l), mechanical stress (1 or 6MPa), and P. gingivalis. The production of interleukin (IL)-1β, IL-6, IL-8, tumour necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by RT-PCR and ELISA. The production of IL-1β, IL-6, IL-8, and TNF-α was not induced in hPDL cells after stimulation with β-cry, although these cytokines were produced after stimulation with P. gingivalis. On the other hand, IL-6 and IL-8 were produced after exposure to 6MPa of mechanical stress. The production of IL-6 and IL-8 was significantly decreased by the addition of β-cry. Furthermore, β-cry up-regulated the production of OPG, but not RANKL. β-cry inhibited the production of IL-6 and IL-8 induced by mechanical stress and periodontopathogenic bacteria in hPDL cells. Moreover, β-cry up-regulated OPG production. These results suggest that β-cry may prevent bone resorption in periodontitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Gene expression markers of age-related inflammation in two human cohorts.

    Science.gov (United States)

    Pilling, Luke C; Joehanes, Roby; Melzer, David; Harries, Lorna W; Henley, William; Dupuis, Josée; Lin, Honghuang; Mitchell, Marcus; Hernandez, Dena; Ying, Sai-Xia; Lunetta, Kathryn L; Benjamin, Emelia J; Singleton, Andrew; Levy, Daniel; Munson, Peter; Murabito, Joanne M; Ferrucci, Luigi

    2015-10-01

    Chronically elevated circulating inflammatory markers are common in older persons but mechanisms are unclear. Many blood transcripts (>800 genes) are associated with interleukin-6 protein levels (IL6) independent of age. We aimed to identify gene transcripts statistically mediating, as drivers or responders, the increasing levels of IL6 protein in blood at older ages. Blood derived in-vivo RNA from the Framingham Heart Study (FHS, n=2422, ages 40-92 yrs) and InCHIANTI study (n=694, ages 30-104 yrs), with Affymetrix and Illumina expression arrays respectively (>17,000 genes tested), were tested for statistical mediation of the age-IL6 association using resampling techniques, adjusted for confounders and multiple testing. In FHS, IL6 expression was not associated with IL6 protein levels in blood. 102 genes (0.6% of 17,324 expressed) statistically mediated the age-IL6 association of which 25 replicated in InCHIANTI (including 5 of the 10 largest effect genes). The largest effect gene (SLC4A10, coding for NCBE, a sodium bicarbonate transporter) mediated 19% (adjusted CI 8.9 to 34.1%) and replicated by PCR in InCHIANTI (n=194, 35.6% mediated, p=0.01). Other replicated mediators included PRF1 (perforin, a cytolytic protein in cytotoxic T lymphocytes and NK cells) and IL1B (Interleukin 1 beta): few other cytokines were significant mediators. This transcriptome-wide study on human blood identified a small distinct set of genes that statistically mediate the age-IL6 association. Findings are robust across two cohorts and different expression technologies. Raised IL6 levels may not derive from circulating white cells in age related inflammation. Published by Elsevier Inc.

  19. Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine-Related Cystitis in Humans

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    Yao Chou Tsai

    2016-09-01

    Full Text Available Purpose The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC in humans. Methods Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1, E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS, inducible nitric oxide synthase (iNOS, β-3 adrenergic receptors (β3-ARs, and the P2X3 receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens. Results The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3 was not significantly different between the KC and control specimens. Conclusions The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.

  20. Quantifying the demographic cost of human-related mortality to a raptor population

    Science.gov (United States)

    Hunt, W. Grainger; Wiens, David; Law, Peter R.; Fuller, Mark R.; Hunt, Teresa L.; Driscoll, Daniel E.; Jackman, Ronald E.

    2017-01-01

    Raptors are exposed to a wide variety of human-related mortality agents, and yet population-level effects are rarely quantified. Doing so requires modeling vital rates in the context of species life-history, behavior, and population dynamics theory. In this paper, we explore the details of such an analysis by focusing on the demography of a resident, tree-nesting population of golden eagles (Aquila chrysaetos) in the vicinity of an extensive (142 km2) windfarm in California. During 1994–2000, we tracked the fates of >250 radio-marked individuals of four life-stages and conducted five annual surveys of territory occupancy and reproduction. Collisions with wind turbines accounted for 41% of 88 uncensored fatalities, most of which were subadults and nonbreeding adults (floaters). A consistent overall male preponderance in the population meant that females were the limiting sex in this territorial, monogamous species. Estimates of potential population growth rate and associated variance indicated a stable breeding population, but one for which any further decrease in vital rates would require immigrant floaters to fill territory vacancies. Occupancy surveys 5 and 13 years later (2005 and 2013) showed that the nesting population remained intact, and no upward trend was apparent in the proportion of subadult eagles as pair members, a condition that would have suggested a deficit of adult replacements. However, the number of golden eagle pairs required to support windfarm mortality was large. We estimated that the entire annual reproductive output of 216–255 breeding pairs would have been necessary to support published estimates of 55–65 turbine blade-strike fatalities per year. Although the vital rates forming the basis for these calculations may have changed since the data were collected, our approach should be useful for gaining a clearer understanding of how anthropogenic mortality affects the health of raptor populations, particularly those species with delayed

  1. Radiosensitization and relative mechanisms of vanillin derivative BVAN08 on human glioma U-251 cells

    International Nuclear Information System (INIS)

    Wang Shubin; Zhang Bo; Sun Weijian; Wang Yu; Liu Xiaodan; Xu Qinzhi; Zhou Pingkun

    2010-01-01

    Objective: To provide more convincing evidences and experimental data for exploring vanillin derivative BVAN08, 6-bromine-5-hydroxy-4-methoxy-benzaldehyde, as a new anticancer drug, and to investigate the effect on the growth, radiosensitization of human glioma cell line U-251 and the relative mechanism. Methods: The effect of BVAN08 on cell proliferation of U-251 and radiosensitivity to 60 Co γ-rays (irradiation dose rate 2.3 Gy/min) were analyzed with MTT and colony-forming ability assay. Change in cellular morphology was observed by using light microscope. Change in cell cycle and apoptosis was detected with flow cytometry. The autophagy was observed by using TEM (irradiation dose rate is transmission electron microscope). DNA-PKcs protein level was detected through Western blot analysis. Results: BVAN08 exhibited a dose- and time-dependent inhibition on the proliferation of U-251 cells during the concentration range of 10-100 mol/L (t=1.83-3.07, P 50 at 48 h and 72 h after administration with BVAN08 were 55.3 and 52.7 mol/L, respectively. Obvious G 2 /M arrest was induced in U-251 cells after 4 h administration with BVAN08, and reached peck at 12 h. The G 2 /M population reached 63.3% in U-251 cells after 12 h administration of 60 μmol/L BVAN08 and kept increasing with the time, while both apoptosis and autophagic cell death were induced. The most effective radiosensitization time for BVAN08 treatment was 12 h before irradiation. The enhancement ratio of radiosensitivity was 3.14 for 20 μmol/L of BVAN08 12 h before 2 Gy irradiation. Conclusions: BVAN08 can induce apoptosis as radiosensitizing effect might be associated with the induction of G 2 /M arrest and inhibition of DNA-PKcs expression. BVAN08 seemed to be a promising radiosensitizing anticancer drug. (authors)

  2. Age at menopause and menopause-related symptoms in human immunodeficiency virus-infected Thai women.

    Science.gov (United States)

    Boonyanurak, Pongrak; Bunupuradah, Torsak; Wilawan, Kittisak; Lueanyod, Aksorn; Thongpaeng, Parawee; Chatvong, Duangjai; Sophonphan, Jiratchaya; Saeloo, Siriporn; Ananworanich, Jintanat; Chaithongwongwatthana, Surasith

    2012-07-01

    There are limited data for age at menopause (AM) and menopause-related symptoms in human immunodeficiency virus (HIV)-infected Asian women. We investigated AM and menopause-related symptoms in HIV-infected Thai women. HIV-infected Thai women 40 years or older who did not receive any hormone therapy in the 8-week period preceding the study were enrolled. Participants completed the Menopause-Specific Quality of Life survey for their symptoms in the past 30 days. Menopause was defined as having the last menstrual period more than 1 year ago. Multivariate Cox proportional hazard regression analysis was used to identify factors associated with menopause. Two hundred sixty-eight HIV-infected women were enrolled; their median age was 44.6 (41.8-48.7) years, and the ratio of their Centers for Disease Control and Prevention clinical classifications (A:B:C) was 53%:34%:13%; 95% were using highly active antiretroviral therapy. The median (interquartile range [IQR]) CD4 count was 575 (437-758) cells/μL, and 93% had HIV-RNA of less than 1.7log10 copies/mL. Among the 55 women who had reached menopause, the mean (SD) AM was 47.3 (5.1) years. The mean (SD) AM in our study was earlier than the previous report of 49.5 (3.6) years in non-HIV-infected Thai women (difference, -2.2 y; 95% CI, -3.2 to -1.2, P menopause were Centers for Disease Control and Prevention clinical classification B or C (hazard ratio, 1.7; 95% CI, 1.0-3.03, P = 0.04), and no sexual act in the past month (hazard ratio, 4.9; 95% CI, 1.5-16.0, P = 0.01). No associations of later age of menarche, parity, marital status, educational level, income, body mass index, CD4 count, and HIV-RNA with menopause were found. AM in HIV-infected Thai women was 47.3 years, which is significantly earlier than the findings of a previous AM report on non-HIV-infected women. Postmenopausal HIV-infected women had more vasomotor and sexual symptoms. More studies are needed to investigate the cause and appropriate interventions for

  3. The clinical significance of thymidylate synthase expression in human papillomavirus-related oropharyngeal squamous carcinoma

    International Nuclear Information System (INIS)

    Kato, Hisayuki; Yui, Takehiro; Okada, Tatsuyoshi; Urano, Makoto; Sakurai, Kazuo; Naito, Kensei; Yamamoto, Naoki

    2012-01-01

    The focus of human papilloma virus (HPV), particulary HPV 16 is on the role of carcinogenic and prognostic factors on oropharyngeal squamous carcinoma (OSCC). However, it remains unclear why patients with HPV-positive tumors have better outcomes than those with HPV-negative tumors. Thymidylate synthase (TS) is one of the initial key enzymes in the 5-fluouracil (5-FU) metabolic pathway. Clinical studies showed that intratumoural TS level was related to the response to 5-FU-based chemotherapy in patients with several types of cancer such as gastroenterological and head and neck cancers. We investigated the prevalence of HPV infection and TS expression in the patients with OSCC and evaluated the prognostic implications according to the HPV status and TS expression. We evaluated for high-risk HPV types (HPV 16, 18, 31, 33, 51, 52, 58) using a real-time polymerase chain reaction (RT-PCR) assay on archival biopsies from 54 patients with OSCC. Immunohistochemical assessments for TS were also performed. HPV was positive in 22 (40.7%) of 54 samples. Of these positive cases, 21 (95%) carried HPV 16 and only 1 (5%) HPV58 sequences. TS was overexpressed in 25 (46.3%) of 54 samples. Of these, 19 (76.0%) had an HPV-negative status and 21 (84.0%) were heavy smokers. TS overexpression was associated with the patients with HPV-negative tumors (P=0.02) and heavy smokers (p=0.012). Univariate analysis revealed that HPV positive status (77.3% vs. 29.0%; p=0.006) significantly improved overall survival. Conversely, no remarkable prognostic difference was observed on immunohistochemical analysis of TS expression. A multivariate analysis using Cox's proportional hazard model showed that early T stage (T1-2), early N stage (N0-1), and positive HPV status were significantly independent predictors for superior overall survival. Our studies suggested that positive HPV status was most strongly associated with a favorable prognosis in the patients with OSCC. TS expression has an unusual aspect

  4. Preliminary study on the time-related changes of the infrared thermal images of the human body

    Science.gov (United States)

    Li, Ziru; Zhang, Xusheng; Lin, Gang; Chen, Zhigang

    2009-08-01

    It is of great importance to study the manifestations and the influencing factors of the time-related changes of infrared thermal images (ITI) of human body since the variable body surface temperature distribution seriously affected the application of ITI in medicine. In this paper, manifestations of time-related changes of the ITI of human body from three double-blind randomized trials and their correlation with meteorological factors (e.g. temperature, pressure, humidity, cold front passage and tropical cyclone landing) were studied. The trials were placebo or drug controlled studying the influences of Chinese medicine health food (including Shengsheng capsule with immunity adjustment function, Shengan capsule with sleep improvement function and Shengyi capsule with the function of helping to decrease serum lipid) on the ITI of human body. In the first thirty-six days of the trials images were scanned every six days and image data in the seven observation time spots (including the 0, 6, 12, 18, 24, 30, 36 day of the trial) were used for the time-related study. For every subject the scanned time was fixed in the day within two hours. The ITI features which could reflect the functions of the health foods were studied. The indexes of the features were relative magnitude (temperature difference between the viewing area and the reference area). Results showed that the variation tendencies of the trial group and control group were basically the same in placebo controlled trials and some of the long-term effects of Chinese medicine health food could be reflected significantly in certain time spots in the first thirty-six days. Time-related changes of the ITI of human body were closely related with meteorological factors but there were other influencing factors still need to be studied. As the ITI of human body could reflect the influences of Chinese medicine health foods and are closely related with meteorology, there are bright prospects for the application of ITI in

  5. [Penal and non-penal legislative policy in relation to human biotechnology].

    Science.gov (United States)

    Romeo Casabona, Carlos María

    2007-01-01

    The Spanish legislator has introduced a set of legislative novelties in the field of human biotechnology or is about to do so. This will be done either through the reform of some laws or through the approval of new laws, that is, without previous regulatory references available. The greater part of these novelties turn on research with cells or cell lines of human origin, specifically those from human embryos and through the use of diverse techniques, such as reproductive cloning and non-reproductive ('therapeutic') cloning.

  6. Phylogenetic relations of humans and African apes from DNA sequences in the Psi eta-globin region

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, M.M.; Slightom, J.L.; Goodman, M.

    1987-10-16

    Sequences from the upstream and downstream flanking DNA regions of the Psi eta-globin locus in Pan troglodytes (common chimpanzee), Gorilla gorilla (gorilla), and Pongo pygmaeus (orangutan, the closest living relative to Homo, Pan, and Gorilla) provided further data for evaluating the phylogenetic relations of humans and African apes. These newly sequenced orthologs (an additional 4.9 kilobase pairs (kbp) for each species) were combined with published Psi eta-gene sequences and then compared to the same orthologous stretch (a continuous 7.1-kbp region) available for humans. Phylogenetic analysis of these nucleotide sequences by the parsimony method indicated (i) that human and chimpanzee are more closely related to each other than either is to gorilla and (ii) that the slowdown in the rate of sequence evolution evident in higher primates is especially pronounced in humans. These results indicate that features unique to African apes (but not to humans) are primitive and that even local molecular clocks should be applied with caution.

  7. Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women.

    Science.gov (United States)

    Williams, Janet E; Carrothers, Janae M; Lackey, Kimberly A; Beatty, Nicola F; York, Mara A; Brooker, Sarah L; Shafii, Bahman; Price, William J; Settles, Matthew L; McGuire, Mark A; McGuire, Michelle K

    2017-09-01

    Background: The human milk microbiome has been somewhat characterized, but little is known about changes over time and relations with maternal factors such as nutrient intake. Objective: We sought to characterize the human milk microbiome and described associations with maternal nutrient intake, time postpartum, delivery mode, and body mass index (BMI; in kg/m 2 ). Methods: Milk samples ( n = 104) and 24-h diet recalls were collected 9 times from 21 healthy lactating women from day 2 to 6 mo postpartum. Women were classified by BMI as healthy weight (milk microbiome was relatively constant over time, although there were small changes in some of the lesser-abundant genera. Relative abundances of several taxa were associated with BMI, delivery mode, and infant sex. For instance, overweight and obese mothers produced milk with a higher relative abundance of Granulicatella than did healthy-weight women (1.8% ± 0.6% compared with 0.4% ± 0.2%, respectively; P milk microbiome are complex and may include maternal nutrient intake, maternal BMI, delivery mode, and infant sex. Future studies designed to investigate the relation between maternal nutrient intake and the milk microbiome should strive to also evaluate dietary supplement usage and analyze the collected milk for its nutrient content.

  8. Thermal behavior of human eye in relation with change in blood perfusion, porosity, evaporation and ambient temperature.

    Science.gov (United States)

    Rafiq, Aasma; Khanday, M A

    2016-12-01

    Extreme environmental and physiological conditions present challenges for thermal processes in body tissues including multi-layered human eye. A mathematical model has been formulated in this direction to study the thermal behavior of the human eye in relation with the change in blood perfusion, porosity, evaporation and environmental temperatures. In this study, a comprehensive thermal analysis has been performed on the multi-layered eye using Pennes' bio-heat equation with appropriate boundary and interface conditions. The variational finite element method and MATLAB software were used for the solution purpose and simulation of the results. The thermoregulatory effect due to blood perfusion rate, porosity, ambient temperature and evaporation at various regions of human eye was illustrated mathematically and graphically. The main applications of this model are associated with the medical sciences while performing laser therapy and other thermoregulatory investigation on human eye. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Barriers and Health Beliefs Related to Weight Management Among Veterans With Human Immunodeficiency Virus.

    Science.gov (United States)

    Munro, Shannon; Dinatale, Emily; Hartley, Sarah; St Jacques, Monica; Oursler, Kris Ann

    2017-01-01

    The success of antiretroviral therapy has led to dramatic changes in causes of morbidity and mortality among U.S. Veterans with human immunodeficiency virus (HIV). Among the 25,000 Veterans treated for HIV, 70% are over age 50 and the rate of obesity has doubled in this population. Veterans with HIV have a 50% increased risk of myocardial infarction yet have limited presence in prevention-related programs designed to lower cardiovascular disease risk. This mixed methods study (focus groups, Schwarzer and Renner physical activity, and nutrition self-efficacy questionnaires) was used to explore factors related to health behavior and identify barriers that overweight Veterans with HIV face in enrolling in the MOVE weight management program. Institutional review board approval was granted before the start of the study. All participants were recruited from the Infectious Disease clinic if they met national inclusion criteria for the MOVE weight management program and had not previously participated in the program. Transcribed audio recordings were independently analyzed and coded by four of the researchers using an exploratory process to obtain consensus regarding themes. An interrater reliability analysis for the Kappa statistic was performed to determine consistency among raters. The relationship between physical activity self-efficacy scores and nutrition self-efficacy scores was tested using Spearman's correlation coefficient. The median age of the sample was 56 with high rates of diabetes (36%), hypertension (73%), hyperlipidemia (36%), and tobacco use history (82%). External barriers to participation were discussed in addition to 8 other themes, which influence treatment engagement for Veterans with obesity and HIV including adaptation, stigma, self-management, and support. Veterans held strong beliefs about responsibility and commitment to their health and wanted to assume an active and informed role in their health care. Veterans with high levels of perceived

  10. Presence of human papillomavirus in semen in relation to semen quality.

    Science.gov (United States)

    Luttmer, Roosmarijn; Dijkstra, Maaike G; Snijders, Peter J F; Hompes, Peter G A; Pronk, Divera T M; Hubeek, Isabelle; Berkhof, Johannes; Heideman, Daniëlle A M; Meijer, Chris J L M

    2016-02-01

    Is the presence of human papillomavirus (HPV) in semen associated with impairment of semen quality? In a large cohort of males seeking fertility evaluation, no associations were observed between seminal HPV presence and semen parameters. HPV is commonly detected in semen samples. Whether the presence of HPV is related to impairment of semen quality, remains unclear. This cross-sectional study included a cohort of 430 males. Male partners in couples seeking fertility evaluation provided one semen sample per person. Semen samples were tested for HPV-DNA using GP5+/6+-PCR. Sperm concentration was counted and motility was assessed in a Makler counting chamber at a magnification of ×200. The presence of antisperm antibodies was assessed by a mixed agglutination reaction (MAR)-test. Overall HPV was detected in 14.9% (64/430) of semen samples, including 2.1% (9/430) that contained both high-risk (hr) HPV and low-risk (lr) HPV types, 8.8% (38/430) with exclusively hrHPV types and 4.0% (17/430) with exclusively lrHPV types. The presence of HPV in semen was not associated with the age of the participants, seminal pH, semen volume, total sperm count, sperm concentration, progressive motility or the presence of antisperm antibodies. This study did not observe an association between HPV presence in semen and impairment of semen quality. However, we cannot exclude an effect of seminal HPV on early embryo development and clinical reproductive outcomes. As HPV is frequently present in semen, screening of donor semen for HPV should be considered to prevent iatrogenic cervical HPV infections in the recipient. However our findings do not support standardized HPV testing of semen in the diagnostic work-up of subfertile couples. This study was sponsored by an unrestricted grant of Stichting Researchfonds Pathology Amsterdam, the Netherlands. P.J.F.S. has been on the speakers bureau of Roche, Gen-Probe, Abbott, Qiagen and Seegene and has been a consultant for Crucell B.V. J.B. has been

  11. Development of advanced methods and related software for human reliability evaluation within probabilistic safety analyses

    International Nuclear Information System (INIS)

    Kosmowski, K.T.; Mertens, J.; Degen, G.; Reer, B.

    1994-06-01

    Human Reliability Analysis (HRA) is an important part of Probabilistic Safety Analysis (PSA). The first part of this report consists of an overview of types of human behaviour and human error including the effect of significant performance shaping factors on human reliability. Particularly with regard to safety assessments for nuclear power plants a lot of HRA methods have been developed. The most important of these methods are presented and discussed in the report, together with techniques for incorporating HRA into PSA and with models of operator cognitive behaviour. Based on existing HRA methods the concept of a software system is described. For the development of this system the utilization of modern programming tools is proposed; the essential goal is the effective application of HRA methods. A possible integration of computeraided HRA within PSA is discussed. The features of Expert System Technology and examples of applications (PSA, HRA) are presented in four appendices. (orig.) [de

  12. Neuropsychological Aspects Observed in a Nuclear Plant Simulator and its Relation with Human Reliability Analysis

    International Nuclear Information System (INIS)

    Prado, E.A.P. do; Martins, M.; Pinheiro, A.; Silveira, J.

    2016-01-01

    This paper will discuss preliminary results of an evaluation methodology for the analysis and quantification of errors in manual (human) operation by training cognitive parameters and skill levels in the complex control system operation using Neuropsychophysiology and Neuro feedback equipment. The research was conducted using a game (nuclear power plant simulator) that simulates concepts of operation of a nuclear plant with a split sample evaluating aspects of learning and knowledge in the nuclear area. Operators were monitored using biomarkers (ECG, EEG, GSR, face detection and eye tracking) and the results were analyzed by Statistical multivariate techniques. An important component in the evaluation of complex systems is the human reliability during operation. Human reliability refers to the probability of the human element perform the tasks scheduled during the defined period for system operation when tested under specified environmental conditions, and additionally not to take any action detrimental to system operation.

  13. Review of Methods Related to Assessing Human Performance in Nuclear Power Plant Control Room Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Katya L Le Blanc; Ronald L Boring; David I Gertman

    2001-11-01

    With the increased use of digital systems in Nuclear Power Plant (NPP) control rooms comes a need to thoroughly understand the human performance issues associated with digital systems. A common way to evaluate human performance is to test operators and crews in NPP control room simulators. However, it is often challenging to characterize human performance in meaningful ways when measuring performance in NPP control room simulations. A review of the literature in NPP simulator studies reveals a variety of ways to measure human performance in NPP control room simulations including direct observation, automated computer logging, recordings from physiological equipment, self-report techniques, protocol analysis and structured debriefs, and application of model-based evaluation. These methods and the particular measures used are summarized and evaluated.

  14. Ipilimumab in Treating Patients With Metastatic or Recurrent Human Papilloma Virus-Related Cervical Cancer

    Science.gov (United States)

    2018-05-23

    Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Human Papillomavirus Infection; Recurrent Cervical Carcinoma; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVB Cervical Cancer AJCC v6 and v7

  15. Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation

    NARCIS (Netherlands)

    Taziaux, Melanie; Staphorsius, Annemieke S; Ghatei, Mohammad A; Bloom, Stephen R; Swaab, Dick F; Bakker, Julie

    CONTEXT: Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental

  16. The Relation between Law and Fraternity as a Promotional Instrument for Human Dignity in Labor Law

    Directory of Open Access Journals (Sweden)

    Guilherme Domingos de Luca

    2015-12-01

    Full Text Available Examine in this study as a problem, the relationship of law and Fraternity as a promotional instrument of Human Dignity in Labour Law, pointing out the means by which positive law has constitutionalized the fundamental guarantees of man labor law. Understand the relationship of human labor versus the dignity of the human person, and the idea of fraternity as a promotional function. The research was based on bibliographic compared. The main object is to understand the role of the fraternity and the right to promote dignity in labor law. Specifically, to understand the role of the principle of brotherhood and human dignity in the protection of labor Fundamental Rights. It is a guided research in the hypothetical-deductive research method, starting from the hypothesis that the community contributes to the correct application of the law as the dignity of labor instrument.

  17. Humoral and cell-mediated immune response against human retinal antigens in relation to ocular onchocerciasis

    NARCIS (Netherlands)

    van der Lelij, A.; Rothova, A.; Stilma, J. S.; Vetter, J. C.; Hoekzema, R.; Kijlstra, A.

    1990-01-01

    Autoimmune mechanisms are thought to be involved in the pathogenesis of the chorioretinal changes in ocular onchocerciasis. The humoral autoimmune response was determined by measuring serum levels of autoantibodies, directed against human S-antigen and interphotoreceptor retinoid binding protein

  18. Humans and viticulture in Sardinia: the history and social relations as signs of identity of the wine-growing area

    OpenAIRE

    Benedetto, Graziella; Carboni, Donatella; Corinto, Gian Luigi

    2014-01-01

    The premise of this paper is that viticulture is an expression of history and social relations. In this sense, we embrace a post-modern vision of development that characterized both economic and cultural geography and agricultural economics. Such an approach does consider culture as an element of mediation between humans and the nature, placing it at the heart of the wine-growing territory. So history and social relations have influenced the today spatial densification by types of grape and t...

  19. Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI)

    Science.gov (United States)

    2014-01-01

    Andersson G (2009) The role of anxiety sensitivity and behavioral avoidance in tinnitus disability. IntJAudiol 48:295-299. Hiller W, Goebel G (1999...Parallel Human and Animal Models of Blast- and Concussion-Induced Tinnitus and Related Traumatic Brain Injury (TBI) PRINCIPAL INVESTIGATOR...Induced Tinnitus and Related Traumatic Brain Injury (TBI) 5b. GRANT NUMBER W81XWH-11-2-0031 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S

  20. [Study of work accidents related to human body fluids exposure among health workers at a university hospital].

    Science.gov (United States)

    Balsamo, Ana Cristina; Felli, Vanda Elisa Andres

    2006-01-01

    This descriptive and exploratory study from a quantitative approach aimed to characterize workers who were victims of work accidents related to human body fluids exposure and to evaluate the accident victim care protocol. The population consisted of 48 workers who were victims of work accidents involving exposure to human body fluids, from July 2000 to June 2001. Data were collected through a form and interviews. Results showed that nursing workers presented higher accident risk levels and that 87.50% involved piercing and cutting material, such as needles and butterflies (70%). As to the accident-related situation/activity, the workers indicated that 25% were due to an "inadequate act during the procedure"; 19.64% mentioned that "it happened" and 29.17% answered that they did not have any suggestion. This study provided important tools to review and elaborate strategies to prevent accidents involving exposure to human body fluids.

  1. Soil, grain and water chemistry in relation to human selenium responsive diseases in Enshi District, China

    OpenAIRE

    Fordyce, F.M.; Zhang, Guangdi; Green, K.; Xinping, Liu

    2000-01-01

    Selenium deficiency (Keshan Disease) and toxicity diseases in humans occur within 20 km of each other in Enshi District in China and have been linked to environmental levels of Se. Low concentrations of Se are associated with Jurassic siltstones and sandstones, whereas high concentrations occur in areas underlain by Permian carbonaceous strata. Although these broad relationships between Se in the environment and the human population have been established previously, not all villages underlain...

  2. Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF

    NARCIS (Netherlands)

    Nagy, R. A.; van Montfoort, A. P. A.; Dikkers, A.; van Echten-Arends, J.; Homminga, I.; Land, J. A.; Hoek, A.; Tietge, U. J. F.

    STUDY QUESTION: Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? SUMMARY ANSWER: BAconcentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid

  3. The role of human values and relations in the employment of people with work-relevant disabilities

    NARCIS (Netherlands)

    Kuiper, L.; Bakker, M.; van der Klink, J.J.L.

    2016-01-01

    The aim of this study is to discuss the role of human values and relations in the employment of people with work-relevant disabilities. Purpose: Finding and maintaining a paid job is known to be more difficult for people with a disability. The aim of the study is to explore the use which people with

  4. Comment on: withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health

    DEFF Research Database (Denmark)

    Hammerum, Anette Marie; Heuer, Ole Eske; Lester, Camilla H.

    2007-01-01

    In response to a review titled 'Withdrawal of growth-promoting antibiotics in Europe and its effects in relation to human health', published in this Journal by Ian Phillips, we hereby comment on the review. Phillips makes use of data from the Danish Integrated Antimicrobial Resistance Monitoring...

  5. Influence of the relative humidity and the temperature on the in-vivo friction behaviour of human skin

    NARCIS (Netherlands)

    Klaassen, M.; Schipper, D. J.; Masen, M.A.

    2016-01-01

    Both temperature and relative humidity are known to influence the frictional behaviour of human skin. However, literature does not completely cover to what extent both parameters play a role. Measurements were conducted using an in-house built reciprocating tribometer inside an enclosure in which

  6. Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in dividing but not in differentiating human epidermal keratinocytes

    NARCIS (Netherlands)

    Jansen, Bastiaan J. H.; van Ruissen, Fred; Cerneus, Stefanie; Cloin, Wendy; Bergers, Mieke; van Erp, Piet E. J.; Schalkwijk, Joost

    2003-01-01

    Using serial analysis of gene expression we have previously identified the expression of several pro-apoptotic and anti-apoptotic genes in cultured human primary epidermal keratinocytes, including tumor necrosis factor related apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis

  7. Age-related liquefaction of the human vitreous body : LM and TEM evaluation of the role of proteoglycans and collagen

    NARCIS (Netherlands)

    Los, Leonoor I.; van der Worp, Roelofje J; van Luyn, Marja J. A.; Hooymans, Johanna M. M.

    PURPOSE. To evaluate morphologic aspects of age-related liquefaction of the human vitreous body by fight and electron microscopy to provide a basis from which future studies directed at the pathogenesis of this phenomenon can be undertaken. The study focuses on changes in fibrillar Collagen and

  8. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, A.; Gorgels, T.G.M.F.; ten Brink, J.B.; van der Spek, P.J.; Bossers, K.; Heine, V.M.; Bergen, A.A.

    2015-01-01

    Background The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  9. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles : Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G M F; Ten Brink, Jacoline B; van der Spek, Peter J; Bossers, Koen; Heine, Vivi M; Bergen, Arthur A

    2015-01-01

    BACKGROUND: The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to

  10. Comparison of Mouse and Human Retinal Pigment Epithelium Gene Expression Profiles: Potential Implications for Age-Related Macular Degeneration

    NARCIS (Netherlands)

    Bennis, Anna; Gorgels, Theo G. M. F.; ten Brink, Jacoline B.; van der Spek, Peter J.; Bossers, Koen; Heine, Vivi M.; Bergen, Arthur A.

    2015-01-01

    The human retinal pigment epithelium (RPE) plays an important role in the pathogenesis of age related macular degeneration (AMD). AMD is the leading cause of blindness worldwide. There is currently no effective treatment available. Preclinical studies in AMD mouse models are essential to develop new

  11. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study

    NARCIS (Netherlands)

    Weber, Rainer; Sabin, Caroline A.; Friis-Møller, Nina; Reiss, Peter; El-Sadr, Wafaa M.; Kirk, Ole; Dabis, Francois; Law, Matthew G.; Pradier, Christian; de Wit, Stephane; Akerlund, Börje; Calvo, Gonzalo; D'Arminio Monforte, Antonella; Rickenbach, Martin; Ledergerber, Bruno; Phillips, Andrew N.; Lundgren, Jens D.

    2006-01-01

    BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related

  12. Distinct pattern of TP53 mutations in human immunodeficiency virus-related head and neck squamous cell carcinoma.

    Science.gov (United States)

    Gleber-Netto, Frederico O; Zhao, Mei; Trivedi, Sanchit; Wang, Jiping; Jasser, Samar; McDowell, Christina; Kadara, Humam; Zhang, Jiexin; Wang, Jing; William, William N; Lee, J Jack; Nguyen, Minh Ly; Pai, Sara I; Walline, Heather M; Shin, Dong M; Ferris, Robert L; Carey, Thomas E; Myers, Jeffrey N; Pickering, Curtis R

    2018-01-01

    Human immunodeficiency virus-infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non-HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non-HIV-related HNSCC. The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non-HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non-HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2018;124:84-94. © 2017 American Cancer Society. © 2017 American Cancer Society.

  13. Relative or Absolute Freedom of Expression as One of Human Rights In Islamic and Western Foundations

    Directory of Open Access Journals (Sweden)

    Badri Borandegi

    2010-11-01

    Full Text Available Freedom of expression is a human right. Some experts agree with absolute freedom of expression. For them, the freedom of expression makes all options to be heard; the extent of people’s participation to increase, democracy to be protected and dogmatic rituals to be challenged. Some experts have opposed absolute freedom of expression. Comparing to poisonous food they believe that those who are aware of toxic thoughts, should prevent their circulation in the society. Does Islam accept relative or absolute freedom of expression? This paper is trying to answer this question through dealing with the Islamic and Western foundations of freedom of expression. pirits and Gods, caused human freedom and his control of his destiny and paved the way for the priority of existence to belief. In fact, for this reason and also for superior position of morality in religions, religions must be regard as a supporter of human rights. آزادی بیان یکی از مؤلفه‌‌های حقوق بشر است. عد‌های از صاحب‌نظران با آزادی مطلق بیان موافقند. به نظر آنها، آزادی بیان موجب شنیده شدن صدای همه اعم از موافق و مخالف، بالا رفتن میزان مشارکت در جامعه، حفاظت از مردم‌سالاری و مبارزه با آیین‌‌های جزمی‌می‌شود. عد‌های با آزادی مطلق بیان مخالفت کرده‌اند و با بیان تمثیل جلوگیری از توزیع غذای مسموم اظهار می‌دارند که باید کسانی که آگاهند از انتشار افکار مسموم در جامعه جلوگیری کنند. آیا اسلام، آزادی مطلق بیان را می‌پذیرد و یا محدوده و خطوط قرمزی را برای آن تعریف می‌کند؟ مقاله حاضر درصدد است که ضمن پاسخ به این سؤال، با استفاده از

  14. Expanding the landscape of chromatin modification (CM-related functional domains and genes in human.

    Directory of Open Access Journals (Sweden)

    Shuye Pu

    2010-11-01

    Full Text Available Chromatin modification (CM plays a key role in regulating transcription, DNA replication, repair and recombination. However, our knowledge of these processes in humans remains very limited. Here we use computational approaches to study proteins and functional domains involved in CM in humans. We analyze the abundance and the pair-wise domain-domain co-occurrences of 25 well-documented CM domains in 5 model organisms: yeast, worm, fly, mouse and human. Results show that domains involved in histone methylation, DNA methylation, and histone variants are remarkably expanded in metazoan, reflecting the increased demand for cell type-specific gene regulation. We find that CM domains tend to co-occur with a limited number of partner domains and are hence not promiscuous. This property is exploited to identify 47 potentially novel CM domains, including 24 DNA-binding domains, whose role in CM has received little attention so far. Lastly, we use a consensus Machine Learning approach to predict 379 novel CM genes (coding for 329 proteins in humans based on domain compositions. Several of these predictions are supported by very recent experimental studies and others are slated for experimental verification. Identification of novel CM genes and domains in humans will aid our understanding of fundamental epigenetic processes that are important for stem cell differentiation and cancer biology. Information on all the candidate CM domains and genes reported here is publicly available.

  15. Ugly but tasty: A systematic review of possible human and animal health risks related to entomophagy.

    Science.gov (United States)

    Testa, Marco; Stillo, Michela; Maffei, Giulia; Andriolo, Violetta; Gardois, Paolo; Zotti, Carla Maria

    2017-11-22

    According to many recent studies, the use of insects as food seems to be convenient, sustainable, economical and healthy. The objective of this study is to analyze the possible effects of insect consumption on human and animal health. A systematic review of the literature was performed using the PubMed, Scopus and CAB databases. Of the 6026 items initially retrieved, 70 were eligible for inclusion; 40 studies analyzed the use of insects in human foods or drugs, while 30 analyzed the use of insects in animal feed. In humans, the most commonly analyzed risks are nutrient malabsorption, growth alteration, chemical and microbiological contamination and allergy risk. Studies of animals focus on growth alteration, nutrient malabsorption and hematic and qualitative meat alteration. In recent years, researchers have shifted their focus from the possible use of edible insects in animal feed to their use as possible nutrient sources for humans. The results suggest that, if properly treated and preserved, products derived from insects are safe and efficient sources of nutrients for animals. Further studies are needed to evaluate the possible effects of prolonged insect consumption on human health.

  16. THE CONTEMPORARY INTERNATIONAL LAW. A RELATION BETWEEN HUMAN RIGHTS AND THE INTERNATIONAL HUMANITARIAN LAW

    Directory of Open Access Journals (Sweden)

    JEANNETTE IRIGOIN BARRENE

    2018-01-01

    Full Text Available During an armed conflict, a change in the application of the human right regulations and international humanitarian law can be observed in the practice of contemporary international law. It is possible to observe at UN and International Courts’ levels an interesting trend in the sense of considering the application of both systems simultaneously in cases of international crisis as well as in internal conflicts. This innovation in contemporary international law can be observed initially in the change experimented by the legislation of the Human Rights’ European Court and specially and clearer in the Human Rights’ Inter American Court, which in cases against Honduras, Colombia, Paraguay and other countries, states that the State, being warrantor of the efficient protection of civil population, must apply and honor not only the Human Rights’ American Convention, but also the articles 13th and 14th of the II protocol of the Geneva Conventions of 1949. The convergence of both branches of the Law, and its application may help to achieve a better defense and efficiency of the fundamental rights of the human being.

  17. In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

    International Nuclear Information System (INIS)

    Whitson, M.E.; Griffin, G.D.; Novelli, G.D.; Solomon, A.

    1981-01-01

    Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by 51 Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes

  18. In vitro sensitization of human lymphocytes to a myeloma cell-related antigen

    Energy Technology Data Exchange (ETDEWEB)

    Whitson, M.E. (Univ. of South Carolina, Columbia); Griffin, G.D.; Novelli, G.D.; Solomon, A.

    1981-01-01

    Peripheral blood lymphocytes from normal human donors were cocultivated with cells from two established human multiple myeloma cell lines, RPMI 8226 and K-737, and with lymphoblastoid cells from a third B cell line, RAMM. After a comparison of three methods of lymphocyte sensitization, a 6-day incubation protocol with equal numbers of normal lymphocytes and mitomycin C-treated tumor cells was selected. Cells fom the RPMI 8226 myeloma line stimulated the differentiation of lymphocytes into cytotoxic effector cells as measured by /sup 51/Cr release from labeled target cells. The RPMI 8226-sensitized lymphocytes were cytotoxic for myeloma cells (RPMI 8226 and K-737) and for lymphoblastoid cells (RAMM) but not for cells from human lung tumor lines (A549, A427, MB9812), a breast carcinoma line (ALAB), a normal diploid fibroblast line (HSBP), or normal lymphocytes.

  19. Rapid detection of human fecal Eubacterium species and related genera by nested PCR method.

    Science.gov (United States)

    Kageyama, A; Benno, Y

    2001-01-01

    PCR procedures based on 16S rDNA gene sequence specific for seven Eubacterium spp. and Eggerthella lenta that predominate in the human intestinal tract were developed, and used for direct detection of these species in seven human feces samples. Three species of Eggerthella lenta, Eubacterium rectale, and Eubacterium eligens were detected from seven fecal samples. Eubacterium biforme was detected from six samples. It was reported that E. rectale, E. eligens, and E. biforme were difficult to detect by traditional culture method, but the nested PCR method is available for the detection of these species. This result shows that the nested PCR method utilizing a universal primer pair, followed by amplification with species-specific primers, would allow rapid detection of Eubacterium species in human feces.

  20. Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

    Science.gov (United States)

    Funari, Vincent A; Winkler, Michael; Brown, Jordan; Dimitrijevich, Slobodan D; Ljubimov, Alexander V; Saghizadeh, Mehrnoosh

    2013-01-01

    MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC) in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6) and diabetic (n=6) central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR) and by in situ hybridization (ISH) in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR) or their inhibitors (antagomirs) using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

  1. Differentially expressed wound healing-related microRNAs in the human diabetic cornea.

    Directory of Open Access Journals (Sweden)

    Vincent A Funari

    Full Text Available MicroRNAs are powerful gene expression regulators, but their corneal repertoire and potential changes in corneal diseases remain unknown. Our purpose was to identify miRNAs altered in the human diabetic cornea by microarray analysis, and to examine their effects on wound healing in cultured telomerase-immortalized human corneal epithelial cells (HCEC in vitro. Total RNA was extracted from age-matched human autopsy normal (n=6 and diabetic (n=6 central corneas, Flash Tag end-labeled, and hybridized to Affymetrix® GeneChip® miRNA Arrays. Select miRNAs associated with diabetic cornea were validated by quantitative RT-PCR (Q-PCR and by in situ hybridization (ISH in independent samples. HCEC were transfected with human pre-miR™miRNA precursors (h-miR or their inhibitors (antagomirs using Lipofectamine 2000. Confluent transfected cultures were scratch-wounded with P200 pipette tip. Wound closure was monitored by digital photography. Expression of signaling proteins was detected by immunostaining and Western blot. Using microarrays, 29 miRNAs were identified as differentially expressed in diabetic samples. Two miRNA candidates showing the highest fold increased in expression in the diabetic cornea were confirmed by Q-PCR and further characterized. HCEC transfection with h-miR-146a or h-miR-424 significantly retarded wound closure, but their respective antagomirs significantly enhanced wound healing vs. controls. Cells treated with h-miR-146a or h-miR-424 had decreased p-p38 and p-EGFR staining, but these increased over control levels close to the wound edge upon antagomir treatment. In conclusion, several miRNAs with increased expression in human diabetic central corneas were found. Two such miRNAs inhibited cultured corneal epithelial cell wound healing. Dysregulation of miRNA expression in human diabetic cornea may be an important mediator of abnormal wound healing.

  2. Improvements in or relating to antibodies active against human hemoglobin Asub(1C)

    International Nuclear Information System (INIS)

    Javid, J.; Cerami, A.; Koenig, R.J.; Pettis, P.K.

    1980-01-01

    A method is described for preparing an antibody against human hemoglobin Asub(1c) which is substantially free of cross-reactivity against the human hemoglobins A 0 , Asub(1a) and Asub(1b). The antibodies are collected from cats, goats or sheep following injections of purified hemoglobin Asub(1c) antigen since these animals do not naturally produce hemoglobin Asub(1c). A radioimmunoassay method is also described whereby these antibodies are used to determine the quantity of hemoglobin Asub(1c) in blood samples. This is a useful technique in the diagnosis of diabetes mellitus. (U.K.)

  3. Functional neuroanatomy of human cortex cerebri in relation to wanting sex and having it.

    Science.gov (United States)

    Georgiadis, Janniko R

    2015-04-01

    Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual responsiveness by providing a comprehensive overview of the empirical evidence for cerebral cortical involvement. To this end I will structure relevant human brain research data to fit the sexual pleasure cycle template-wanting sex, having sex, inhibiting sex-arguing that going through these sexual response phases requires adequate shifting between functional cortical networks. The relevance of this notion for understanding certain sexual dysfunctions is discussed. © 2015 Wiley Periodicals, Inc.

  4. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  5. Choice of organic foods is related to perceived consequences for human health and to environmentally friendly behaviour.

    Science.gov (United States)

    Magnusson, Maria K; Arvola, Anne; Hursti, Ulla Kaisa Koivisto; Aberg, Lars; Sjödén, Per-Olow

    2003-04-01

    We designed a questionnaire concerned with attitudes and behaviour towards organic foods, environmentally friendly behaviour (EFB), and perceived consequences of organic food choice in terms of human health, the environment and animal welfare. It was mailed in 1998 to a random nation-wide sample of 2000 Swedish citizens, ages 18-65 years, and 1154 (58%) responded. Self-reported purchase of organic foods was most strongly related to perceived benefit for human health. Performance of EFBs such as refraining from car driving was also a good predictor of purchase frequency. The results indicate that egoistic motives are better predictors of the purchase of organic foods than are altruistic motives.

  6. Walk-related mimic word activates the extrastriate visual cortex in the human brain: an fMRI study.

    Science.gov (United States)

    Osaka, Naoyuki

    2009-03-02

    I present an fMRI study demonstrating that a mimic word highly suggestive of human walking, heard by the ear with eyes closed, significantly activates the visual cortex located in extrastriate occipital region (BA19, 18) and superior temporal sulcus (STS) while hearing non-sense words that do not imply walk under the same task does not activate these areas in humans. I concluded that BA19 and 18 would be a critical region for generating visual images of walking and related intentional stance, respectively, evoked by an onomatopoeia word that implied walking.

  7. Gastric and Peritoneal Involvement of Human Herpes Virus 8 Related Kaposi Sarcoma in a Patient with Acquired Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Nuno Ribeiro Ferreira

    2015-09-01

    Full Text Available Kaposi's sarcoma (KS is one of the most frequent neoplastic diseases in patients infected with human immunodeficiency virus (HIV. The authors report the case of a 40-year-old male with ascites, peripheral edema and peritoneal carcinomatosis secondary to a gastric KS related to human herpes virus type 8 (HHV-8. The patient had severe immunodeficiency, with a TCD4+ count of 86 cells/µl and newly diagnosed acquired immunodeficiency syndrome. His clinical condition rapidly deteriorated, with multiorgan failure, and he died without the possibility of initiating antiretroviral therapy or chemotherapy. To the authors’ knowledge, carcinomatosis is a rare feature in KS.

  8. Amniotic oxytocin and vasopressin in relation to human fetal development and labour

    NARCIS (Netherlands)

    Oosterbaan, H. P.; Swaab, D. F.

    1989-01-01

    Previous experiments in rats revealed increased amniotic oxytocin (OXT) levels in the course of normal development and increased vasopressin (AVP) levels in retarded fetal growth. In order to see whether similar changes would also occur in human, OXT and AVP levels were determined in amniotic fluid,

  9. Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure

    International Nuclear Information System (INIS)

    Spurgeon, David J.; Lawlor, Alan; Hooper, Helen L.; Wadsworth, Richard; Svendsen, Claus; Thomas, Laura D.K.; Ellis, James K.; Bundy, Jacob G.; Keun, Hector C.; Jarup, Lars

    2011-01-01

    The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment. - Highlights: → Environmental measurements indicate smelter pollution of a surrounding urban area. → Life-style and biology influenced U-Cd more than measured environmental levels. → Limited contact with outdoor environments may limit Cd uptake in urban populations. → Better life-style data could improve the attribution of human Cd exposure routes. → Measured Cd levels provide limited added exposure insight over dispersion models. - Measured and modelled environmental cadmium concentrations provide limited additional explanation of human urinary cadmium concentrations.

  10. Biodiversity and human-pathogenicity of Phialophora verrucosa and relatives in Chaetothyriales

    NARCIS (Netherlands)

    Li, Y.; Xiao, J.; Hoog, , de G.S.; Wang, X.; Wan, Z.; Yu, J.; Liu, W.; Li, R.

    2017-01-01

    Phialophora as defined by its type species P. verrucosa is a genus of Chaetothyriales, and a member of the group known as ‘black yeasts and relatives’. Phialophora verrucosa has been reported from mutilating human infections such as chromoblastomycosis, disseminated phaeohyphomycosis and mycetoma,

  11. Relating friction on the human skin to the hydration and temperature of the skin

    NARCIS (Netherlands)

    Veijgen, N.K.; Masen, Marc Arthur; van der Heide, Emile

    2013-01-01

    The human skin is constantly in interaction with materials and products. Therefore, skin friction is relevant to all people. In the literature, the frictional properties of the skin have been linked to a large variety of variables, like age, gender and hydration. The present study compares the data

  12. The Relative Effectiveness of Human Tutoring, Intelligent Tutoring Systems, and Other Tutoring Systems

    Science.gov (United States)

    VanLehn, Kurt

    2011-01-01

    This article is a review of experiments comparing the effectiveness of human tutoring, computer tutoring, and no tutoring. "No tutoring" refers to instruction that teaches the same content without tutoring. The computer tutoring systems were divided by their granularity of the user interface interaction into answer-based, step-based, and…

  13. Formation of hydroxyl radicals in the human lens is related to the severity of nuclear cataract

    DEFF Research Database (Denmark)

    Garner, B; Davies, Michael Jonathan; Truscott, R J

    2000-01-01

    Recent studies have identified specific hydroxylated amino acid oxidation products which strongly suggest the presence of hydroxyl radical (HO.)-damaged proteins in human cataractous lenses. In the present study, the ability of early stage (type II) and advanced (type IV) nuclear cataractous lens...

  14. Palmitate and stearate binding to human serum albumin. Determination of relative binding constants

    DEFF Research Database (Denmark)

    Vorum, H; Fisker, K; Honoré, B

    1997-01-01

    Multiple binding equilibria of two apparently insoluble ligands, palmitate and stearate, to defatted human serum albumin were studied in a 66 mM sodium phosphate buffer (pH 7.4) at 37 degrees C, by determination of dialytic exchange rates of ligands among identical equilibrium solutions. The expe...

  15. The dose-response relation in human volunteers for gastro-intestinal pathogens

    NARCIS (Netherlands)

    Teunis PFM; Heijden OG van der; Giessen JWB van der; Havelaar AH; MGB

    1996-01-01

    Published data on infection of human hosts with various protozoa, bacteria, and viruses causing gastro-enteritis are used to establish a quantitative relationship between ingested dose and the risk of infection. For all data sets analysed, this relationship is determined by fitting either an

  16. Late Holocene vegetation changes in relation with climate fluctuations and human activities in Languedoc (Southern France)

    OpenAIRE

    J. Azuara; N. Combourieu-Nebout; V. Lebreton; F. Mazier; S. D. Müller; L. Dezileau

    2015-01-01

    Holocene climate fluctuations and human activities since the Neolithic have shaped present-day Mediterranean environments. Separating anthropogenic effects from climatic impacts to reconstruct Mediterranean paleoenvironments over the last millennia remains a challenging issue. High resolution pollen analyses were undertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamics ove...

  17. CCL2 enhances pluripotency of human induced pluripotent stem cells by activating hypoxia related genes

    NARCIS (Netherlands)

    Hasegawa, Yuki; Tang, Dave; Takahashi, Naoko; Hayashizaki, Yoshihide; Forrest, Alistair R R; Suzuki, Harukazu; Clevers, Hans

    2014-01-01

    Standard culture of human induced pluripotent stem cells (hiPSCs) requires basic Fibroblast Growth Factor (bFGF) to maintain the pluripotent state, whereas hiPSC more closely resemble epiblast stem cells than true naïve state ES which requires LIF to maintain pluripotency. Here we show that

  18. Evolutionary relationships within a subgroup of HERV-K-related human endogenous retroviruses

    NARCIS (Netherlands)

    Zsíros, J.; Jebbink, M. F.; Lukashov, V. V.; Voûte, P. A.; Berkhout, B.

    1998-01-01

    The prototype endogenous retrovirus HERV-K10 was identified in the human genome by its homology to the exogenous mouse mammary tumour virus. By analysis of a short 244 bp segment of the reverse transcriptase (RT) gene of other HERV-K10-like sequences, it has become clear that these elements

  19. How awareness changes the relative weights of evidence during human decision-making

    NARCIS (Netherlands)

    de Lange, F.P.; van Gaal, S.; Lamme, V.A.F.; Dehaene, S.

    2011-01-01

    Human decisions are based on accumulating evidence over time for different options. Here we ask a simple question: How is the accumulation of evidence affected by the level of awareness of the information? We examined the influence of awareness on decision-making using combined behavioral methods

  20. Functional evaluation of DNA repair in human biopsies and their relation to other cellular biomarkers

    Czech Academy of Sciences Publication Activity Database

    Slyšková, Jana; Langie, S. A. S.; Collins, A. R.; Vodička, Pavel

    2014-01-01

    Roč. 116, č. 5 (2014) ISSN 1664-8021 R&D Projects: GA ČR(CZ) GAP304/12/1585 Institutional support: RVO:68378041 Keywords : base excision repair * nucleotide excision repair * human solid tissue Subject RIV: EB - Genetics ; Molecular Biology

  1. Megabase replication domains along the human genome: relation to chromatin structure and genome organisation.

    Science.gov (United States)

    Audit, Benjamin; Zaghloul, Lamia; Baker, Antoine; Arneodo, Alain; Chen, Chun-Long; d'Aubenton-Carafa, Yves; Thermes, Claude

    2013-01-01

    In higher eukaryotes, the absence of specific sequence motifs, marking the origins of replication has been a serious hindrance to the understanding of (i) the mechanisms that regulate the spatio-temporal replication program, and (ii) the links between origins activation, chromatin structure and transcription. In this chapter, we review the partitioning of the human genome into megabased-size replication domains delineated as N-shaped motifs in the strand compositional asymmetry profiles. They collectively span 28.3% of the genome and are bordered by more than 1,000 putative replication origins. We recapitulate the comparison of this partition of the human genome with high-resolution experimental data that confirms that replication domain borders are likely to be preferential replication initiation zones in the germline. In addition, we highlight the specific distribution of experimental and numerical chromatin marks along replication domains. Domain borders correspond to particular open chromatin regions, possibly encoded in the DNA sequence, and around which replication and transcription are highly coordinated. These regions also present a high evolutionary breakpoint density, suggesting that susceptibility to breakage might be linked to local open chromatin fiber state. Altogether, this chapter presents a compartmentalization of the human genome into replication domains that are landmarks of the human genome organization and are likely to play a key role in genome dynamics during evolution and in pathological situations.

  2. Estrogen receptor-alpha distribution in the human hypothalamus in relation to sex and endocrine status

    NARCIS (Netherlands)

    Kruijver, Frank P. M.; Balesar, Rawien; Espila, Ana M.; Unmehopa, Unga A.; Swaab, Dick F.

    2002-01-01

    The present study reports the first systematic rostrocaudal distribution of estrogen receptor-a immunoreactivity (ERalpha-ir) in the human hypothalamus and its adjacent areas in young adults. Postmortem material taken from 10 subjects (five male and five female), between 20 and 39 years of age, was

  3. Somatic gene mutation in the human in relation to radiation risk

    International Nuclear Information System (INIS)

    Mendelsohn, M.L.

    1992-01-01

    This report discusses the measurement of somatic gene-mutation frequencies in the human. We ask the following questions. How well can they be measured? Do they respond to radiation? Can they also function as a dosimeter? What do they tell us about the somatic mutation theory of carcinogenesis?

  4. Functional Neuroanatomy of Human Cortex Cerebri in Relation to Wanting Sex and Having It

    NARCIS (Netherlands)

    Georgiadis, Janniko R.

    Neuroanatomical textbooks typically restrict the central nervous system control of sexual responsiveness to the hypothalamus, brainstem and spinal cord. However, for all its primitive functions human sex is surprisingly complex and versatile. This review aims to extend the neuroanatomy of sexual

  5. Human vision model in relation to characteristics of shapes for the Mach band effect.

    Science.gov (United States)

    Wu, Bo-Wen; Fang, Yi-Chin

    2015-10-01

    For human vision to recognize the contours of objects means that, as the contrast variation at the object's edges increases, so will the Mach band effect of human vision. This paper more deeply investigates the relationship between changes in the contours of an object and the Mach band effect of human vision. Based on lateral inhibition and the Mach band effect, we studied subjects' eyes as they watched images of different shapes under a fixed brightness at 34  cd/m2, with changes of contrast and spatial frequency. Three types of display were used: a television, a computer monitor, and a projector. For each display used, we conducted a separate experiment for each shape. Although the maximum values for the contrast sensitivity function curves of the displays were different, their variations were minimal. As the spatial frequency changed, the diminishing effect of the different lines also was minimal. However, as the shapes at the contour intersections were modified by the Mach band effect, a greater degree of variation occurred. In addition, as the spatial frequency at a contour intersection increased, the Mach band effect became lower, along with changes in the corresponding contrast sensitivity function curve. Our experimental results on the characteristics of human vision have led to what we believe is a new vision model based on tests with different shapes. This new model may be used for future development and implementation of an artificial vision system.

  6. Human natural killer cell committed thymocytes and their relation to the T cell lineage

    NARCIS (Netherlands)

    Sánchez, M. J.; Spits, H.; Lanier, L. L.; Phillips, J. H.

    1993-01-01

    Recent studies have demonstrated that mature natural killer (NK) cells can be grown from human triple negative (TN; CD3-, CD4-, CD8-) thymocytes, suggesting that a common NK/T cell precursor exists within the thymus that can give rise to both NK cells and T cells under appropriate conditions. In the

  7. Outdoor and indoor cadmium distributions near an abandoned smelting works and their relations to human exposure

    Energy Technology Data Exchange (ETDEWEB)

    Spurgeon, David J., E-mail: dasp@ceh.ac.uk [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Lawlor, Alan [Centre for Ecology and Hydrology, Lancaster, Bailrigg, Lancaster LA1 4AP (United Kingdom); Hooper, Helen L. [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Wadsworth, Richard [Centre for Ecology and Hydrology, Lancaster, Bailrigg, Lancaster LA1 4AP (United Kingdom); Svendsen, Claus [Centre for Ecology and Hydrology, Maclean Building, Benson Lane, Crowmarsh Gifford, Wallingford, Oxon, OX10 8BB (United Kingdom); Thomas, Laura D.K. [MRC-HPA Centre for Environment and Health, Department of Epidemiology and Public health, Imperial College London (United Kingdom); Ellis, James K.; Bundy, Jacob G.; Keun, Hector C. [Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, South Kensington, London SW7 2AZ (United Kingdom); Jarup, Lars [MRC-HPA Centre for Environment and Health, Department of Epidemiology and Public health, Imperial College London (United Kingdom)

    2011-12-15

    The relationship of measured or modelled Cd concentrations in soil, house dust and available to plants with human urinary Cd concentrations were assessed in a population living around a Cd/Pb/Zn smelter in the UK. Modelled air concentrations explained 35% of soil Cd variation indicating the smelter contributed to soil Cd loads. Multi-variate analysis confirmed a significant role of biological and life-style factors in determining urinary Cd levels. Significant correlations of urinary Cd with soil, house dust and modelled plant available Cd concentrations were not, however, found. Potential reasons for the absence of clear relationships include limited environmental contact in urban populations; the role of undefined factors in determining exposure; and the limited spatial scope of the survey which did not sample from the full pollution gradient. Further, the absence of any significant relationship indicates that environmental measures provide limited advantage over atmospheric model outputs for first stage human exposure assessment. - Highlights: > Environmental measurements indicate smelter pollution of a surrounding urban area. > Life-style and biology influenced U-Cd more than measured environmental levels. > Limited contact with outdoor environments may limit Cd uptake in urban populations. > Better life-style data could improve the attribution of human Cd exposure routes. > Measured Cd levels provide limited added exposure insight over dispersion models. - Measured and modelled environmental cadmium concentrations provide limited additional explanation of human urinary cadmium concentrations.

  8. Human Resource Management Strategies and Teacher's Efficiency within Schools: A Co-Relational Study

    Science.gov (United States)

    Hashmi, Kiran

    2014-01-01

    The aim of the paper is to study Human Resource Management and Development (HRMD) strategies and their effect on teachers' efficiency within the Catholic Board of Education (CBE) schools of Pakistan whose teachers are graduates in educational leadership courses from a private teacher education institutes in Karachi. The study endeavored to build a…

  9. Water distribution and related morphology in human stratum corneum at different hydration levels

    NARCIS (Netherlands)

    Bouwstra, J.A.; Graaff, de A.; Gooris, G.S.; Nijsse, J.; Wiechers, J.W.; Aelst, van A.C.

    2003-01-01

    This study focused on the water distribution in human stratum corneum and on the swelling of the corneocytes. For this purpose stratum corneum was hydrated to various levels and used either for Fourier transform infrared spectroscopy or for cryo-scanning electron microscopy. The images were analyzed

  10. Relating the Capabilities of the Handicapped to the Human Attribute Requirements of Jobs: Appendixes.

    Science.gov (United States)

    Ohio State Univ., Columbus. National Center for Research in Vocational Education.

    Twenty-five appendixes from a study attempting to match capabilities of the handicapped to the human attribute requirements of three jobs (general secretary, automotive mechanic, and business data programmer) are presented. Appendixes include information on such topics as data analysis for identification of key tasks; job descriptions for the…

  11. Studies on the subunits of human glycoprotein hormones in relation to reproduction

    International Nuclear Information System (INIS)

    Hagen, C.

    1977-01-01

    In this review summarising present knowledge of the biological and immunological activity of the subunits of human glycoprotein hormones, the specificity of the α-subunit and β-subunit radioimmunoassays are discussed. The crossreaction studies performed with the α-subunit radioimmunoassays are aummarised in one table while those with the β-subunit radioimmunoassays are presented in a second table. (JIW)

  12. Journal of Religion and Human Relations - Vol 1, No 2 (2009)

    African Journals Online (AJOL)

    The English Language and the Human-Psyche Trafficking: A Discourse on the Context of Superstratum as an Agent of Loss of Tribal Values · EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT DOWNLOAD FULL TEXT DOWNLOAD FULL TEXT. E Chukwu ...

  13. Prediction of human errors by maladaptive changes in event-related brain networks

    NARCIS (Netherlands)

    Eichele, T.; Debener, S.; Calhoun, V.D.; Specht, K.; Engel, A.K.; Hugdahl, K.; Cramon, D.Y. von; Ullsperger, M.

    2008-01-01

    Humans engaged in monotonous tasks are susceptible to occasional errors that may lead to serious consequences, but little is known about brain activity patterns preceding errors. Using functional Mill and applying independent component analysis followed by deconvolution of hemodynamic responses, we

  14. Macular pigment carotenoids in the retina and occipital cortex are related in humans

    Science.gov (United States)

    Objectives: Lutein and zeaxanthin are dietary carotenoids that preferentially accumulate in the macular region of the retina. Together with mesozeaxanthin, a conversion product of lutein in the macula, they form the macular pigment. Lutein is also the predominant carotenoid in human brain tissue and...

  15. Human-related factors regulate the spatial ecology of domestic cats in sensitive areas for conservation.

    Directory of Open Access Journals (Sweden)

    Joaquim P Ferreira

    Full Text Available BACKGROUND: Domestic cats ranging freely in natural areas are a conservation concern due to competition, predation, disease transmission or hybridization with wildcats. In order to improve our ability to design effective control policies, we investigate the factors affecting their numbers and space use in natural areas of continental Europe. METHODOLOGY/PRINCIPAL FINDINGS: We describe the patterns of cat presence, abundance and space use and analyse the associated environmental and human constraints in a well-preserved Mediterranean natural area with small scattered local farms. We failed in detecting cats in areas away from human settlements (trapping effort above 4000 trap-nights, while we captured 30 individuals near inhabited farms. We identified 130 cats, all of them in farms still in use by people (30% of 128 farms. All cats were free-ranging and very wary of people. The main factor explaining the presence of cats was the presence of people, while the number of cats per farm was mostly affected by the occasional food provisioning with human refuse and the presence of people. The home ranges of eight radio tagged cats were centred at inhabited farms. Males went furthest away from the farms during the mating season (3.8 km on average, maximum 6.3 km, using inhabited farms as stepping-stones in their mating displacements (2.2 km of maximum inter-farm distance moved. In their daily movements, cats notably avoided entering in areas with high fox density. CONCLUSIONS: The presence, abundance and space use of cats were heavily dependent on human settlements. Any strategy aiming at reducing their impact in areas of conservation concern should aim at the presence of settlements and their spatial spread and avoid any access to human refuse. The movements of domestic cats would be limited in areas with large patches of natural vegetation providing good conditions for other carnivore mammals such as red foxes.

  16. Novel recombinant human lactoferrin: differential activation of oxidative stress related gene expression.

    Science.gov (United States)

    Kruzel, Marian L; Actor, Jeffrey K; Zimecki, Michał; Wise, Jasen; Płoszaj, Paulina; Mirza, Shaper; Kruzel, Mark; Hwang, Shen-An; Ba, Xueqing; Boldogh, Istvan

    2013-12-01

    Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. The aim of this study was to scale-up expression and purification of rhLF in a CHO expression system, verify its glycan primary structure, and assess its biological properties in cell culture models. A stable CHO cell line producing >200mg/L of rhLF was developed and established. rhLF was purified by a single-step cation-exchange chromatography procedure. The highly homogenous rhLF has a molecular weight of approximately 80 kDa. MALDI-TOF mass spectrometric analysis revealed N-linked, partially sialylated glycans at two glycosylation sites, typical for human milk LF. This novel rhLF showed a protective effect against oxidative stress in a similar manner to its natural counterpart. In addition, rhLF revealed a modulatory effect on cellular redox via upregulation of key antioxidant enzymes. These data imply that the CHO-derived rhLF is fully compatible with the native molecule, thus it has promise for human therapeutic applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Allergenicity of milk of different animal species in relation to human milk

    Directory of Open Access Journals (Sweden)

    Robert Pastuszka

    2016-12-01

    Full Text Available Protein content in cow milk (with over 20 proteins, and peptides may also occur as a result of enzymatic hydrolysis ranges from 2.5% to 4.2% and is about 1.5-2 times higher than in human milk. Its most important allergens are considered to be β-lactoglobulin (absent in human milk and αs1-casein. The most similar in composition to human milk is horse and donkey milk. It contains considerably more whey proteins (35-50% than cow milk (about 20%, and the concentration of the most allergenic casein fraction αs1 is 1.5-2.5 g/l. In comparison, the content of αs1-casein in cow milk is about 10 g/l. β-lactoglobulin present in donkey milk is a monomer, while in milk of ruminants it is a dimer. Like human milk, it contains a substantial amount of lactose (about 7%, which determines its flavour and facilitates calcium absorption. The high lysozyme content (about 1 g/l gives it antibacterial properties (compared to trace amounts in ruminants. Camel milk is also more digestible and induces fewer allergic reactions, because it lacks β-lactoglobulin, and its β-casein has a different structure. It also contains (compared to cow milk more antibacterial substances such as lysozyme, lactoferrin and immunoglobulins, and furthermore the number of immunoglobulins is compatible with human ones. Goat milk components have a higher degree of assimilability as compared to cow milk. Its main protein is β-casein, with total protein content depending on the αs1-casein genetic variant. Goats with the ‘0’ variant do not synthesize this allergenic protein. Clinical and immunochemical studies indicate, however, that it cannot be a substitute for cow milk without the risk of an anaphylactic reaction.

  18. A cross-sectional epidemiological study of domestic animals related to human leptospirosis cases in Nicaragua.

    Science.gov (United States)

    Flores, Byron J; Pérez-Sánchez, Tania; Fuertes, Héctor; Sheleby-Elías, Jessica; Múzquiz, José Luis; Jirón, William; Duttmann, Christianne; Halaihel, Nabil

    2017-06-01

    Leptospirosis is one of the most extended zoonosis worldwide and humans become infected most commonly through contact with the urine of carrier animals, either directly or via contaminated water or soil. The aim in this study was to analyse the epidemiological behaviour of Leptospira spp., from domestic animals around the sites of human leptospirosis cases in Nicaragua, from 2007 through 2013. We report the results of a cross-sectional epidemiological study with a non-probability sampling of blood (n=3050) and urine (n=299) from Domestic Animals (DA) around the sites of human leptospirosis cases in Nicaragua. We analysed data obtained through Microscopic Agglutination Test (MAT), in-vitro culture, real time PCR and sequencing of lfb1 locus. Frequencies of 30.31% (95% CI: 28.66-31.95) and 15.38% (95% CI: 11.12-19.64) were obtained from serological test and from in-vitro culture, respectively. Although similar frequencies from serology test (P≥0.05) were found in DA species, in-vitro culture frequencies were significantly higher from bovine, equine and sheep (P<0.05) in comparison with swine and canine species. Ten serogroups of pathogenic Leptospira spp. were encountered, with the highest presence of Icterohaemorrhagiae serogroup 34.65% (95% CI: 29.35-39.94). We identified 7 samples homologous to L. interrogans species Pyrogenes serovar and 3 samples as L. noguchii Louisiana or Panama serovars by analysis of lfb1 sequences. We were able to establish a temporal and spatial correlation from DA and cumulative incidence of human cases. Therefore an effective epidemiological surveillance should be implemented with a specific control program toward DA in order to reduce human leptospirosis incidence. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS.

    Science.gov (United States)

    Pan, David Z; Garske, Kristina M; Alvarez, Marcus; Bhagat, Yash V; Boocock, James; Nikkola, Elina; Miao, Zong; Raulerson, Chelsea K; Cantor, Rita M; Civelek, Mete; Glastonbury, Craig A; Small, Kerrin S; Boehnke, Michael; Lusis, Aldons J; Sinsheimer, Janet S; Mohlke, Karen L; Laakso, Markku; Pajukanta, Päivi; Ko, Arthur

    2018-04-17

    Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes.

  20. From Human-Nature to Cultureplace in Education via an Exploration of Unity and Relation in the Work of Peirce and Dewey

    Science.gov (United States)

    Quay, John

    2017-01-01

    In outdoor education discourse the notion of relation is often employed to convey basic connections between humanity and nature as human-nature relationships, yet the sense of relation itself is rarely questioned. Drawing on the work of Peirce and Dewey, I explore the ramifications of a more nuanced understanding of relation, specifically how…

  1. Energy-Water-Land Nexus: The relative contributions of climate and human systems on global water scarcity

    Science.gov (United States)

    Hejazi, M. I.; Chen, M.; Turner, S. W. D.; Graham, N. T.; Vernon, C. R.; Li, X.; Kim, S. H.; Link, R. P.

    2017-12-01

    There is a growing consensus that energy, water, and land systems are interconnected and should be analyzed as such. New tools are required to represent the interactions between population, economic growth, energy, land, and water resources in a dynamically evolving system. Here we use the Global Change Assessment Model (GCAM) to investigate the relative contributions of climate and human systems on water scarcity regionally and globally under a wide range of scenarios. The model accounts for a variety of human activities, including changing demands for water for agriculture, power generation, industry, and public supply. We find that these activities exert a larger influence on water scarcity than climate in 93% of river basins globally. This work highlights the importance of accounting for human activities in hydrologic modeling applications and how they may change under different pathways of how land use and agricultural systems, energy systems, and economies may evolve in the future.

  2. Expression analyses of human cleft palate tissue suggest a role for osteopontin and immune related factors in palatal development

    DEFF Research Database (Denmark)

    Jakobsen, L.P.; Borup, R.; Vestergaard, J.

    2009-01-01

    . Moreover, selected differentially expressed genes were analyzed by quantitative RT-PCR, and by immunohistochemical staining of craniofacial tissue from human embryos. Osteopontin (SPP1) and other immune related genes were significantly higher expressed in palate tissue from patients with CLP compared to CP...... and palate (CLP). In order to understand the biological basis in these cleft lip and palate subgroups better we studied the expression profiles in human tissue from patients with CL/P. In each of the CL/P subgroups, samples were obtained from three patients and gene expression analysis was performed...... and immunostaining in palatal shelves against SPP1, chemokine receptor 4 (CXCR4) and serglycin (PRG1) in human embryonic craniofacial tissue were positive, supporting a role for these genes in palatal development. However, gene expression profiles are subject to variations during growth and therefore we recommend...

  3. Modeling Treatment Response for Lamin A/C Related Dilated Cardiomyopathy in Human Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Lee, Yee-Ki; Lau, Yee-Man; Cai, Zhu-Jun; Lai, Wing-Hon; Wong, Lai-Yung; Tse, Hung-Fat; Ng, Kwong-Man; Siu, Chung-Wah

    2017-07-28

    Precision medicine is an emerging approach to disease treatment and prevention that takes into account individual variability in the environment, lifestyle, and genetic makeup of patients. Patient-specific human induced pluripotent stem cells hold promise to transform precision medicine into real-life clinical practice. Lamin A/C (LMNA)-related cardiomyopathy is the most common inherited cardiomyopathy in which a substantial proportion of mutations in the LMNA gene are of nonsense mutation. PTC124 induces translational read-through over the premature stop codon and restores production of the full-length proteins from the affected genes. In this study we generated human induced pluripotent stem cells-derived cardiomyocytes from patients who harbored different LMNA mutations (nonsense and frameshift) to evaluate the potential therapeutic effects of PTC124 in LMNA -related cardiomyopathy. We generated human induced pluripotent stem cells lines from 3 patients who carried distinctive mutations (R225X, Q354X, and T518fs) in the LMNA gene. The cardiomyocytes derived from these human induced pluripotent stem cells lines reproduced the pathophysiological hallmarks of LMNA -related cardiomyopathy. Interestingly, PTC124 treatment increased the production of full-length LMNA proteins in only the R225X mutant, not in other mutations. Functional evaluation experiments on the R225X mutant further demonstrated that PTC124 treatment not only reduced nuclear blebbing and electrical stress-induced apoptosis but also improved the excitation-contraction coupling of the affected cardiomyocytes. Using cardiomyocytes derived from human induced pluripotent stem cells carrying different LMNA mutations, we demonstrated that the effect of PTC124 is codon selective. A premature stop codon UGA appeared to be most responsive to PTC124 treatment. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  4. Molecular characterization of a human G20P[28] rotavirus a strain with multiple genes related to bat rotaviruses.

    Science.gov (United States)

    Esona, Mathew D; Roy, Sunando; Rungsrisuriyachai, Kunchala; Gautam, Rashi; Hermelijn, Sandra; Rey-Benito, Gloria; Bowen, Michael D

    2018-01-01

    Group A rotaviruses are the major cause of severe gastroenteritis in the young of mammals and birds. This report describes characterization of an unusual G20P[28] rotavirus strain detected in a 24month old child from Suriname. Genomic sequence analyses revealed that the genotype constellation of the Suriname strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] was G20-P[28]-I13-R13-C13-M12-A23-N13-T15-E20-H15. Genes VP1, VP2, VP3, NSP1, NSP2, NSP3, NSP4 and NSP5 were recently assigned novel genotypes by the Rotavirus Classification Working Group (RCWG). Three of the 11 gene segments (VP7, VP4, VP6) were similar to cognate gene sequences of bat-like human rotavirus strain Ecu534 from Ecuador and the VP7, NSP3 and NSP5 gene segments of strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] were found to be closely related to gene sequences of bat rotavirus strain 3081/BRA detected in Brazil. Although distantly related, the VP1 gene of the study strain and bat strain BatLi09 detected in Cameroon in 2014 are monophyletic. The NSP1 gene was found to be most closely related to human strain QUI-35-F5 from Brazil. These findings suggest that strain RVA/Human-wt/SUR/2014735512/2013/G20P[28] represents a zoonotic infection from a bat host. Published by Elsevier B.V.

  5. Preparation of the requirements for the safety regulation related to human and organizational factors

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-08-15

    The outline of the project in the current fiscal year is to investigate and analyze issues associated with Human and Organizational Factors involved in incidents of nuclear facilities, and to study and develop evaluation methods of these countermeasures. The guideline to evaluate licensee's safety culture and root cause analysis (RCA) had been developed for further improving safety on nuclear power plants at 2007. These guidelines have been used at regulatory inspection since that time. Based on experience of using these existing guidelines, some activities for improving guidelines are now under investigation; these are selecting candidate quantitative indicators for safety culture evaluation and researching good practices for RCA issues. JNES implemented human factor analysis about 18 domestic events including the Fukushima Dai-ichi nuclear power plant accident. (author)

  6. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    International Nuclear Information System (INIS)

    Gunther, W.E.; Higgins, J.C.; Aggarwal, S.K.

    1991-01-01

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance

  7. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    Energy Technology Data Exchange (ETDEWEB)

    Gunther, W.E.; Higgins, J.C. [Brookhaven National Lab., Upton, NY (United States); Aggarwal, S.K. [Nuclear Regulatory Commission, Washington, DC (United States)

    1991-12-31

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance.

  8. The effect of plant aging on equipment qualification and human performance issues related to license renewal

    Energy Technology Data Exchange (ETDEWEB)

    Gunther, W.E.; Higgins, J.C. (Brookhaven National Lab., Upton, NY (United States)); Aggarwal, S.K. (Nuclear Regulatory Commission, Washington, DC (United States))

    1991-01-01

    The aging of nuclear power plants is one of the most important issues facing the nuclear industry worldwide. Aging encompasses as forms of degradation to nuclear power plant components, systems, and structures that result from exposure to environmental conditions or from operational stresses. Both the degradation from aging and actions taken to address the aging, such as increased maintenance and testing, can significantly impact human performance in the plant. Research into the causes and effects of aging as obtained through the assessment of operating experience and testing have raised questions regarding the adequacy of existing industry standards for addressing the concerns raised by this research. This paper discusses these issues, with particular emphasis in the area of equipment qualification and human performance.

  9. Human Rights Degradations Related to Natural Law: Philosophical-Juridic Self-Legitimation of Franquism

    Directory of Open Access Journals (Sweden)

    César López Rodríguez

    2017-11-01

    Full Text Available This essay identifies the problematic theoretical nature of human rights under Franco's regime, in the light of either a traditionalist or a totalitarian objective natural right's discursive hegemony. This contradictory theoretical alternative was already present in Ramiro de Maeztu's legal-political doctrine, which as the theoretical seed of the regime, led to those contradictions as embodied in two authors: F. Elías de Tejada and L. Legaz Lacambra. Drawing on a political critique of the text itself, the conclusion evinces the doctrinal state of human rights in the current Spanish constitutional system, exposing its contradictions as derived not from a traditionalist or a totalitarian objective natural right but from a subjective natural right.

  10. Walrus history around the North Water: Human-animal relations in a long-term perspective.

    Science.gov (United States)

    Gotfredsen, Anne Birgitte; Appelt, Martin; Hastrup, Kirsten

    2018-04-01

    This article highlights the relationship between walruses and humans in and around the North Water polynya in a long-term perspective. The present study draws on a combination of biological, archaeological, archaeo-zoological, historical, and ethnographic sources covering the period from the 8th century AD to the late 20th century. The study demonstrates that the walrus was an important resource of meat, blubber, and other products throughout all the studied periods, if always supplemented by other kinds of game. It is suggested that walrus distribution and behaviour, as well as hunting strategies and technologies historically constituted a powerful component not only in forming human action and social life in the region but also in serving as an imaginative resource. It is further argued that the walrus and the walrus hunt still play a significant role in the present community living on the edge of the North Water, even if the hunt is increasingly circumscribed due to changing ice conditions.

  11. Search for virus-related genetic information in human tumors DNA by the transfection method

    Energy Technology Data Exchange (ETDEWEB)

    Knyazev, P G; Perevozchikov, A P; Korobitsyn, L P; Zhudina, A I; Kuznetsov, O K; Savost' yanov, G A; Dyad' kova, A M; Sejts, I F [Nauchno-Issledovatel' skij Inst. Onkologii, Leningrad (USSR)

    1979-01-01

    DNA preparations from the blood cells of a patient suffering from acute myeloid leukemia, from tissues of polymorphous cell rhabdomyosarcoma, synovial sarcoma and neurinoma were studied. The production of virus-like RNA-containing particles (according to radioisotope analysis and the content of reverse transcriptase in these particles) was observed in cultures of embryonic human cells treated with DNA from the cells of leukemia patient.

  12. Androgen regulated genes in human prostate xenografts in mice: relation to BPH and prostate cancer.

    Directory of Open Access Journals (Sweden)

    Harold D Love

    2009-12-01

    Full Text Available Benign prostatic hyperplasia (BPH and prostate carcinoma (CaP are linked to aging and the presence of androgens, suggesting that androgen regulated genes play a major role in these common diseases. Androgen regulation of prostate growth and development depends on the presence of intact epithelial-stromal interactions. Further, the prostatic stroma is implicated in BPH. This suggests that epithelial cell lines are inadequate to identify androgen regulated genes that could contribute to BPH and CaP and which could serve as potential clinical biomarkers. In this study, we used a human prostate xenograft model to define a profile of genes regulated in vivo by androgens, with an emphasis on identifying candidate biomarkers. Benign transition zone (TZ human prostate tissue from radical prostatectomies was grafted to the sub-renal capsule site of intact or castrated male immunodeficient mice, followed by the removal or addition of androgens, respectively. Microarray analysis of RNA from these tissues was used to identify genes that were; 1 highly expressed in prostate, 2 had significant expression changes in response to androgens, and, 3 encode extracellular proteins. A total of 95 genes meeting these criteria were selected for analysis and validation of expression in patient prostate tissues using quantitative real-time PCR. Expression levels of these genes were measured in pooled RNAs from human prostate tissues with varying severity of BPH pathologic changes and CaP of varying Gleason score. A number of androgen regulated genes were identified. Additionally, a subset of these genes were over-expressed in RNA from clinical BPH tissues, and the levels of many were found to correlate with disease status. Our results demonstrate the feasibility, and some of the problems, of using a mouse xenograft model to characterize the androgen regulated expression profiles of intact human prostate tissues.

  13. Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells

    International Nuclear Information System (INIS)

    Su, Ming-Wei; Yu, Sung-Liang; Lin, Wen-Chang; Tsai, Ching-Hui; Chen, Po-Hua; Lee, Yungling Leo

    2016-01-01

    Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke. - Highlights: • We conducted a smoke reduction trial program and investigated the causal relationship between smoke and gene regulation. • MicroRNA and mRNA expression changes were examined in human PBMC. • MicroRNAs are important in regulating disease-causal genes after tobacco smoke reduction.

  14. Late Holocene vegetation changes in relation with climate fluctuations and human activity in Languedoc (southern France)

    OpenAIRE

    Azuara , J; Combourieu-Nebout , N; Lebreton , V; Mazier , F; Müller , S D; Dezileau , L ,

    2015-01-01

    International audience; Holocene climate fluctuations and human activity since the Neolithic have shaped present-day Mediter-ranean environments. Separating anthropogenic effects from climatic impacts to better understand Mediterranean pale-oenvironmental changes over the last millennia remains a challenging issue. High-resolution pollen analyses were un-dertaken on two cores from the Palavasian lagoon system (Hérault, southern France). These records allow reconstruction of vegetation dynamic...

  15. All in transition: human resource management and labour relations in the Chinese industrial sector

    OpenAIRE

    Yu, Nan

    2012-01-01

    This discussion paper is a literature study reviewing the development of human resource management in China, with a particular focus (where possible) on the automobile industry. It presents the Chinese context for HRM discussing the normative debate about the adaptation of Western management methods and the heritage of Chinese philosophy and values, and it describes the economic, cultural, and transition-specific factors which influence HRM in China. In more detail, the paper deals with work ...

  16. Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells

    Energy Technology Data Exchange (ETDEWEB)

    Su, Ming-Wei [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Yu, Sung-Liang [Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Lin, Wen-Chang [Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China); Tsai, Ching-Hui [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Chen, Po-Hua [School of Medicine, National Taiwan University, Taipei, Taiwan (China); Lee, Yungling Leo, E-mail: leolee@ntu.edu.tw [Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan (China); Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan (China)

    2016-08-15

    Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressed genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke. - Highlights: • We conducted a smoke reduction trial program and investigated the causal relationship between smoke and gene regulation. • MicroRNA and mRNA expression changes were examined in human PBMC. • MicroRNAs are important in regulating disease-causal genes after tobacco smoke reduction.

  17. Instrumental neutron activation analysis of human hair and related radiotracer experiments on washing and leaching

    International Nuclear Information System (INIS)

    Das, H.A.; Hoede, D.; Sloot, H.A. van der; Herber, R.F.M.

    1981-11-01

    The work done under the IAEA-contract 2440/RB is summarized. The aim was to develop a fast and reliable system for the determination of tracer elements in human head hair by instrumental neutron activation analysis (INAA) and radiotracer washing experiments. The standardized procedure for INAA was applied to hair samples collected by the Coronel Laboratory of the University of Amsterdam. The correlation between trace element contents is considered

  18. Kisspeptin Expression in the Human Infundibular Nucleus in Relation to Sex, Gender Identity, and Sexual Orientation.

    OpenAIRE

    Taziaux, Mélanie; Staphorsius, Annemieke S.; Ghatei, Mohammad A.; Bloom, Stephen R.; Swaab, Dick F.; Bakker, Julie

    2016-01-01

    CONTEXT: Since the discovery of its central role in reproduction, our functional neuroanatomical knowledge of the hypothalamic kisspeptin system is predominantly based on animal studies. Although sex differences in kisspeptin expression have been shown in humans in adulthood, the developmental origin of this sex difference is unknown. OBJECTIVES: Our objectives were to determine the following: 1) when during development the sex difference in kisspeptin expression in the infundibular nucleus w...

  19. Human leukocyte antigen-G polymorphism in relation to expression, function, and disease

    DEFF Research Database (Denmark)

    Larsen, Margit Hørup; Hviid, Thomas

    2009-01-01

    Human leukocyte antigen-G (HLA-G) is a nonclassical class Ib molecule belonging to the major histocompatibility complex. HLA-G appears to play a role in the suppression of immune responses and contribute to long-term immune escape or tolerance. The focus of this review is polymorphism in the HLA......-G gene and protein and its possible importance in expression, function, and disease associations....

  20. Effects of Fluid Load on Human Urine Characteristics Related to Workplace Drug testing

    Science.gov (United States)

    2012-03-01

    Human.subject.participation.was.approved. by.the.Institutional.Review.Boards.of.the.University.of. Oklahoma.Health. Sciences. Center. (OUHSC),.Okla- homa . City,. OK,. and. of...Ju st A fte r F lu id In ta ke (S am pl e 3) A t S to m ac h C le ar an ce (S am pl e 4) A t F irs t U rg e (S am pl e 5