WorldWideScience

Sample records for human factors activities

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

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

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

  2. Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors.

    Science.gov (United States)

    Keuper, Michaela; Sachs, Stephan; Walheim, Ellen; Berti, Lucia; Raedle, Bernhard; Tews, Daniel; Fischer-Posovszky, Pamela; Wabitsch, Martin; Hrabě de Angelis, Martin; Kastenmüller, Gabi; Tschöp, Matthias H; Jastroch, Martin; Staiger, Harald; Hofmann, Susanna M

    2017-10-01

    Obesity-associated WAT inflammation is characterized by the accumulation and local activation of macrophages (MΦs), and recent data from mouse studies suggest that macrophages are modifiers of adipocyte energy metabolism and mitochondrial function. As mitochondrial dysfunction has been associated with obesity and the metabolic syndrome in humans, herein we aimed to delineate how human macrophages may affect energy metabolism of white adipocytes. Human adipose tissue gene expression analysis for markers of macrophage activation and tissue inflammation (CD11c, CD40, CD163, CD206, CD80, MCP1, TNFα) in relationship to mitochondrial complex I (NDUFB8) and complex III (UQCRC2) was performed on subcutaneous WAT of 24 women (BMI 20-61 kg/m 2 ). Guided by these results, the impact of secreted factors of LPS/IFNγ- and IL10/TGFβ-activated human macrophages (THP1, primary blood-derived) on mitochondrial function in human subcutaneous white adipocytes (SGBS, primary) was determined by extracellular flux analysis (Seahorse technology) and gene/protein expression. Stepwise regression analysis of human WAT gene expression data revealed that a linear combination of CD40 and CD163 was the strongest predictor for mitochondrial complex I (NDUFB8) and complex III (UQCRC2) levels, independent of BMI. IL10/TGFβ-activated MΦs displayed high CD163 and low CD40 expression and secreted factors that decreased UQCRC2 gene/protein expression and ATP-linked respiration in human white adipocytes. In contrast, LPS/IFNγ-activated MΦs showed high CD40 and low CD163 expression and secreted factors that enhanced adipocyte mitochondrial activity resulting in a total difference of 37% in ATP-linked respiration of white adipocytes (p = 0.0024) when comparing the effect of LPS/IFNγ- vs IL10/TGFβ-activated MΦs. Our data demonstrate that macrophages modulate human adipocyte energy metabolism via an activation-dependent paracrine mechanism. Copyright © 2017 The Authors. Published by Elsevier

  3. Modeling of human factor Va inactivation by activated protein C

    Directory of Open Access Journals (Sweden)

    Bravo Maria

    2012-05-01

    Full Text Available Abstract Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (FXa and its cofactor FVa plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC, an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative

  4. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    OpenAIRE

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H. R.

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that o...

  5. Characterization of the clotting activities of structurally different forms of activated factor IX. Enzymatic properties of normal human factor IXa alpha, factor IXa beta, and activated factor IX Chapel Hill.

    Science.gov (United States)

    Griffith, M J; Breitkreutz, L; Trapp, H; Briet, E; Noyes, C M; Lundblad, R L; Roberts, H R

    1985-01-01

    Two structurally different forms of activated human Factor IX (Factor IXa alpha and IXa beta) have been previously reported to have essentially identical clotting activity in vitro. Although it has been shown that activated Factor IX Chapel Hill, an abnormal Factor IX isolated from the plasma of a patient with mild hemophilia B, and normal Factor IXa alpha are structurally very similar, the clotting activity of activated Factor IX Chapel Hill is much lower (approximately fivefold) than that of normal Factor IXa beta. In the present study we have prepared activated Factor IX by incubating human Factor IX with calcium and Russell's viper venom covalently bound to agarose. Fractionation of the activated Factor IX by high-performance liquid chromatography demonstrated the presence of both Factors IXa alpha and IXa beta. On the basis of active site concentration, determined by titration with antithrombin III, the clotting activities of activated Factor IX Chapel Hill and IXa alpha were similar, but both activities were less than 20% of the clotting activity of Factor IXa beta. Activated Factor IX activity was also measured in the absence of calcium, phospholipid, and Factor VIII, by determination of the rate of Factor X activation in the presence of polylysine. In the presence of polylysine, the rates of Factor X activation by activated Factor IX Chapel Hill, Factor IXa alpha, and Factor IXa beta were essentially identical. We conclude that the clotting activity of activated Factor IX Chapel Hill is reduced when compared with that of Factor IXa beta but essentially normal when compared with that of Factor IXa alpha.

  6. Glycosylated human oxyhaemoglobin activates nuclear factor-kappaB and activator protein-1 in cultured human aortic smooth muscle.

    Science.gov (United States)

    Peiro, Concepcion; Matesanz, Nuria; Nevado, Julian; Lafuente, Nuria; Cercas, Elena; Azcutia, Veronica; Vallejo, Susana; Rodriguez-Manas, Leocadio; Sanchez-Ferrer, Carlos F

    2003-10-01

    Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-kappaB (NF-kappaB), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes. In this study, we analysed whether Amadori-modified human oxyhaemoglobin, glycosylated at either normal (N-Hb) or elevated (E-Hb) levels, can induce cell growth and activate AP-1 and NF-kappaB in cultured human aortic smooth muscle cells (HASMC). E-Hb (1 nm-1 x microm), but not N-Hb, promoted a concentration-dependent increase in cell size from nanomolar concentrations, although it failed to stimulate HASMC proliferation. At 10 nm, E-Hb stimulated both AP-1 and NF-kappaB activity, as assessed by transient transfection, electromobility shift assays or immunofluorescence staining. The effects of E-Hb resembled those of the proinflammatory cytokine tumour necrosis factor-alpha (TNF-alpha). E-Hb enhanced intracellular superoxide anions content and its effects on HASMC were abolished by different ROS scavengers. In conclusion, E-Hb stimulates growth and activates AP-1 and NF-kappaB in human vascular smooth muscle by redox-sensitive pathways, thus suggesting a possible direct role for Amadori adducts in diabetic vasculopathy.

  7. Glycosylated human oxyhaemoglobin activates nuclear factor-κB and activator protein-1 in cultured human aortic smooth muscle

    Science.gov (United States)

    Peiró, Concepción; Matesanz, Nuria; Nevado, Julián; Lafuente, Nuria; Cercas, Elena; Azcutia, Verónica; Vallejo, Susana; Rodríguez-Mañas, Leocadio; Sánchez-Ferrer, Carlos F

    2003-01-01

    Diabetic vessels undergo structural changes that are linked to a high incidence of cardiovascular diseases. Reactive oxygen species (ROS) mediate cell signalling in the vasculature, where they can promote cell growth and activate redox-regulated transcription factors, like activator protein-1 (AP-1) or nuclear factor-κB (NF-κB), which are involved in remodelling and inflammation processes. Amadori adducts, formed through nonenzymatic glycosylation, can contribute to ROS formation in diabetes. In this study, we analysed whether Amadori-modified human oxyhaemoglobin, glycosylated at either normal (N-Hb) or elevated (E-Hb) levels, can induce cell growth and activate AP-1 and NF-κB in cultured human aortic smooth muscle cells (HASMC). E-Hb (1 nM–1 μM), but not N-Hb, promoted a concentration-dependent increase in cell size from nanomolar concentrations, although it failed to stimulate HASMC proliferation. At 10 nM, E-Hb stimulated both AP-1 and NF-κB activity, as assessed by transient transfection, electromobility shift assays or immunofluorescence staining. The effects of E-Hb resembled those of the proinflammatory cytokine tumour necrosis factor-α (TNF-α). E-Hb enhanced intracellular superoxide anions content and its effects on HASMC were abolished by different ROS scavengers. In conclusion, E-Hb stimulates growth and activates AP-1 and NF-κB in human vascular smooth muscle by redox-sensitive pathways, thus suggesting a possible direct role for Amadori adducts in diabetic vasculopathy. PMID:14504138

  8. Advanced Video Activity Analytics (AVAA): Human Factors Evaluation

    Science.gov (United States)

    2015-05-01

    editors. Human Mental Workload. Amsterdam: North Holland Press; 1988. Johnson RR, Popovic DP, Olmstead RE, Stikic M, Levendowski DJ, Berka C. Drowsiness ...E2929 DESERT STORM DRIVE FORT BRAGG NC 28310 59 1 ARMY G1 (PDF) DAPE MR B KNAPP 300 ARMY PENTAGON RM 2C489 WASHINGTON DC 20310

  9. The human milk microbiome and factors influencing its composition and activity.

    Science.gov (United States)

    Gomez-Gallego, Carlos; Garcia-Mantrana, Izaskun; Salminen, Seppo; Collado, María Carmen

    2016-12-01

    Beyond its nutritional aspects, human milk contains several bioactive compounds, such as microbes, oligosaccharides, and other substances, which are involved in host-microbe interactions and have a key role in infant health. New techniques have increased our understanding of milk microbiota composition, but few data on the activity of bioactive compounds and their biological role in infants are available. Whereas the human milk microbiome may be influenced by specific factors - including genetics, maternal health and nutrition, mode of delivery, breastfeeding, lactation stage, and geographic location - the impact of these factors on the infant microbiome is not yet known. This article gives an overview of milk microbiota composition and activity, including factors influencing microbial composition and their potential biological relevance on infants' future health. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Jinah Han

    2015-02-01

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

  11. Regulation and kinetics of platelet-activating factor and leukotriene C-4 synthesis by activated human basophils

    NARCIS (Netherlands)

    Lie, W. J.; Homburg, C. H. E.; Kuijpers, T. W.; Knol, E. F.; Mul, F. P. J.; Roos, D.; Tool, A. T. J.

    2003-01-01

    Background Allergic disease is the result of an interplay of many different cell types, including basophils and mast cells, in combination with various inflammatory lipid mediators, such as platelet-activating factor (PAF) and leukotrienes (LT). LTC4 synthesis by human basophils has been studied

  12. Secretory products of breast cancer cells specifically affect human osteoblastic cells: partial characterization of active factors.

    Science.gov (United States)

    Siwek, B; Lacroix, M; De Pollak, C; Marie, P; Body, J J

    1997-04-01

    The pathogenesis of tumor-induced osteolysis (TIO) following breast cancer metastases in bone remains unclear. We postulated that osteoblasts could be target cells for the secretory products of breast cancer cells. We previously showed that serum-free conditioned medium (CM) of the breast cancer cell line MCF-7 inhibits DNA synthesis by 75% of control values in osteoblast-like cells SaOS-2 and that this effect is only in a minor part due to transforming growth factor beta secretion. To establish the specificity of our observations and to look for other biologically active factors, we have tested the effects of medium conditioned by several cancer and noncancer cell lines (breast, colon, placenta, or fibrosarcoma) on the proliferation of osteoblast-like cells (SaOS-2, MG-63), normal human osteoblasts, human fibrosarcoma cells, and normal human fibroblasts. Culture medium (1:2) of the breast cancer cell lines MCF-7, T-47D, MDA-MB-231, and SK-BR-3 inhibited by 25-50% the proliferation of osteoblast-like cells SaOS-2, MG-63, and normal osteoblasts as evaluated by the MTT survival test or [3H]thymidine incorporation. MCF-7 cells completely inhibited the proliferation of normal human osteoblasts in coculture. This inhibitory effect was reversible and not due to cytotoxicity. Moreover, the cyclic adenosine monophosphate (cAMP) response to parathyroid hormone (PTH) of osteoblast-like cells SaOS-2 was also increased by 100-240% by the same CM. Such activities were, however, not detected in medium from the breast noncancer cell line HBL-100 or in the medium conditioned by non-breast cancer cell lines (COLO 320DM, HT-29, JAR, or HT-1080). Medium from the breast cancer cells had no effect on normal human fibroblasts or fibrosarcoma cells (HT-1080), suggesting the specificity of their action on human osteoblasts. After partial purification by ultrafiltration and size-exclusion chromatography, we found that medium of T-47D cells contained at least three nonprostanoid factors of

  13. The effect of physical activity on the brain derived neurotrophic factor: from animal to human studies.

    Science.gov (United States)

    Zoladz, J A; Pilc, A

    2010-10-01

    It is well documented that physical activity can induce a number of various stimuli which are able to enhance the strength and endurance performance of muscles. Moreover, regular physical activity can preserve or delay the appearance of several metabolic disorders in the human body. Physical exercise is also known to enhance the mood and cognitive functions of active people, although the physiological backgrounds of these effects remain unclear. In recent years, since the pioneering study in the past showed that physical activity increases the expression of the brain derived neurothophic factor (BDNF) in the rat brain, a number of studies were undertaken in order to establish the link between that neurothrophin and post-exercise enhancement of mood and cognitive functions in humans. It was recently demonstrated that physical exercise can increase plasma and/or serum BDNF concentration in humans. It was also reported that physical exercise or electrical stimulation can increase the BDNF expression in the skeletal muscles. In the present review, we report the current state of research concerning the effect of a single bout of exercise and training on the BDNF expression in the brain, in both the working muscles as well as on its concentrations in the blood. We have concluded that there may be potential benefits of the exercise-induced enhancement of the BDNF expression and release in the brain as well as in the peripheral tissues, resulting in the improvement of the functioning of the body, although this effect, especially in humans, requires more research.

  14. Aerospace Human Factors

    Science.gov (United States)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  15. IVI human factors strategy

    Science.gov (United States)

    1999-11-01

    This document focuses on human factors research that supports the Intelligent Vehicle Initiative (IVI). The status of the problem areas within categories used often by the human factors community to organize human factors process is discussed. A simi...

  16. Human Factors Job Aid

    Science.gov (United States)

    1996-12-09

    The purpose of this Human Factors Job Aid is to serve as a desk reference for : human factors integration during system acquisition. The first chapter contains : an overview of the FAA human factors process in system acquisitions. The : remaining eig...

  17. Human Factors Planning Guidelines

    Science.gov (United States)

    1996-01-01

    To ensure human factors considerations are fully incorporated in the system : development, the Integrated Product Team (IPT) or Program Manager initiates a : Human Factors Program (HFP) that addresses the human performance and human : resource parame...

  18. Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Nicholas Chun

    Full Text Available The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB, a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been addressed. We induced regional myocardial I/R injury by transient coronary ligation in WT C57BL/6 mice, a manipulation that resulted in marked myocardial necrosis associated with activation of fB protein and myocardial deposition of C3 activation products. In contrast, in fB-/- mice, the same procedure resulted in significantly reduced myocardial necrosis (% ventricular tissue necrotic; fB-/- mice, 20 ± 4%; WT mice, 45 ± 3%; P < 0.05 and diminished deposition of C3 activation products in the myocardial tissue (fB-/- mice, 0 ± 0%; WT mice, 31 ± 6%; P<0.05. Reconstitution of fB-/- mice with WT serum followed by cardiac I/R restored the myocardial necrosis and activated C3 deposition in the myocardium. In translational human studies we measured levels of activated fB (Bb in intracoronary blood samples obtained during cardio-pulmonary bypass surgery before and after aortic cross clamping (AXCL, during which global heart ischemia was induced. Intracoronary Bb increased immediately after AXCL, and the levels were directly correlated with peripheral blood levels of cardiac troponin I, an established biomarker of myocardial necrosis (Spearman coefficient = 0.465, P < 0.01. Taken together, our results support the conclusion that circulating fB is a crucial pathophysiological amplifier of I/R-induced, complement-dependent myocardial necrosis and identify fB as a potential therapeutic target for prevention of human myocardial I/R injury.

  19. Decrease in platelet activating factor stimulated phosphoinositide turnover during storage of human platelets in plasma

    Energy Technology Data Exchange (ETDEWEB)

    Carter, M.G.; Shukla, S.D. (Univ. of Missouri School of Medicine, Columbia (USA))

    1987-05-01

    Human platelet concentrate from the American Red Cross Blood Center was stored at 24{degree}C in a shaker and aliquots were taken out at time intervals aseptically. Platelet activating factor (PAF) stimulated turnover of phosphoinositide (PPI) was monitored by assaying {sup 32}P incorporation into phosphoinositides using platelet rich plasma (PRP). Platelets in PRP were incubated with 1 {times} 10{sup {minus}7} M PAF at 37{degree}C with gentle shaking and after 5 min their lipids were extracted and analysed by TLC for {sup 32}P-phosphoinositides. The percent stimulation of {sup 32}P incorporation by PAF (over control) into PPI was approximately 250, 100, 60, 25 and 20 on days 1, 2, 3, 5 and 6, respectively. This indicated a dramatic decrease in PAF responsive turnover of platelet PPI during storage. These findings have important implications in relation to PAF receptor activity and viability of platelets at different periods of storage.

  20. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans

    DEFF Research Database (Denmark)

    Huang, T; Larsen, K T; Ried-Larsen, M

    2014-01-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles...... met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational...... studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies....

  1. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  2. Euglena gracilis paramylon activates human lymphocytes by upregulating pro-inflammatory factors.

    Science.gov (United States)

    Russo, Rossella; Barsanti, Laura; Evangelista, Valter; Frassanito, Anna M; Longo, Vincenzo; Pucci, Laura; Penno, Giuseppe; Gualtieri, Paolo

    2017-03-01

    The aim of this study was to verify the activation details and products of human lymphomonocytes, stimulated by different β-glucans, that is Euglena paramylon, MacroGard®, and lipopolysaccharide. We investigated the gene expression of inflammation-related cytokines and mediators, transactivation of relevant transcription factors, and phagocytosis role in cell-glucan interactions, by means of RT-PCR, immunocytochemistry, and colorimetric assay. Our results show that sonicated and alkalized paramylon upregulates pro-inflammatory factors (NO, TNF-α, IL-6, and COX-2) in lymphomonocytes. A clear demonstration of this upregulation is the increased transactivation of NF-kB visualized by immunofluorescence microscopy. Phagocytosis assay showed that internalization is not a mandatory step for signaling cascade to be triggered, since immune activity is not present in the lymphomonocytes that have internalized paramylon granules and particulate MacroGard®. Moreover, the response of Euglena β-glucan-activated lymphomonocytes is much greater than that induced by commercially used β-glucans such as MacroGard®. Our in vitro results indicate that linear fibrous Euglena β-glucan, obtained by sonication and alkaline treatment can act as safe and effective coadjutant of the innate immune system response.

  3. In Vitro Anticancer Activity of Phlorofucofuroeckol A via Upregulation of Activating Transcription Factor 3 against Human Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hyun Ji Eo

    2016-03-01

    Full Text Available Phlorofucofuroeckol A (PFF-A, one of the phlorotannins found in brown algae, has been reported to exert anti-cancer property. However, the molecular mechanism for the anti-cancer effect of PFF-A has not been known. Activating transcription factor 3 (ATF3 has been reported to be associated with apoptosis in colorectal cancer. The present study was performed to investigate the molecular mechanism by which PFF-A stimulates ATF3 expression and apoptosis in human colorectal cancer cells. PFF-A decreased cell viability through apoptosis of human colorectal cancer cells. PFF-A increased ATF3 expression through regulating transcriptional activity. The responsible cis-element for ATF3 transcriptional activation by PFF-A was cAMP response element binding protein (CREB, located between positions −147 and −85 of the ATF3 promoter. Inhibition of p38, c-Jun N-terminal kinases (JNK, glycogen synthase kinase (GSK 3β, and IκB kinase (IKK-α blocked PFF-A-mediated ATF3 expression. ATF3 knockdown by ATF3 siRNA attenuated the cleavage of poly (ADP-ribose polymerase (PARP by PFF-A, while ATF3 overexpression increased PFF-A-mediated cleaved PARP. These results suggest that PFF-A may exert anti-cancer property through inducing apoptosis via the ATF3-mediated pathway in human colorectal cancer cells.

  4. Caveolin-1 influences vascular protease activity and is a potential stabilizing factor in human atherosclerotic disease.

    Directory of Open Access Journals (Sweden)

    Juan A Rodriguez-Feo

    Full Text Available Caveolin-1 (Cav-1 is a regulatory protein of the arterial wall, but its role in human atherosclerosis remains unknown. We have studied the relationships between Cav-1 abundance, atherosclerotic plaque characteristics and clinical manisfestations of atherosclerotic disease.We determined Cav-1 expression by western blotting in atherosclerotic plaques harvested from 378 subjects that underwent carotid endarterectomy. Cav-1 levels were significantly lower in carotid plaques than non-atherosclerotic vascular specimens. Low Cav-1 expression was associated with features of plaque instability such as large lipid core, thrombus formation, macrophage infiltration, high IL-6, IL-8 levels and elevated MMP-9 activity. Clinically, a down-regulation of Cav-1 was observed in plaques obtained from men, patients with a history of myocardial infarction and restenotic lesions. Cav-1 levels above the median were associated with absence of new vascular events within 30 days after surgery [0% vs. 4%] and a trend towards lower incidence of new cardiovascular events during longer follow-up. Consistent with these clinical data, Cav-1 null mice revealed elevated intimal hyperplasia response following arterial injury that was significantly attenuated after MMP inhibition. Recombinant peptides mimicking Cav-1 scaffolding domain (Cavtratin reduced gelatinase activity in cultured porcine arteries and impaired MMP-9 activity and COX-2 in LPS-challenged macrophages. Administration of Cavtratin strongly impaired flow-induced expansive remodeling in mice. This is the first study that identifies Cav-1 as a novel potential stabilizing factor in human atherosclerosis. Our findings support the hypothesis that local down-regulation of Cav-1 in atherosclerotic lesions contributes to plaque formation and/or instability accelerating the occurrence of adverse clinical outcomes. Therefore, given the large number of patients studied, we believe that Cav-1 may be considered as a novel target

  5. Lutein Activates the Transcription Factor Nrf2 in Human Retinal Pigment Epithelial Cells.

    Science.gov (United States)

    Frede, Katja; Ebert, Franziska; Kipp, Anna P; Schwerdtle, Tanja; Baldermann, Susanne

    2017-07-26

    The degeneration of the retinal pigment epithelium caused by oxidative damage is a stage of development in age-related macular degeneration (AMD). The carotenoid lutein is a major macular pigment that may reduce the incidence and progression of AMD, but the underlying mechanism is currently not fully understood. Carotenoids are known to be direct antioxidants. However, carotenoids can also activate cellular pathways resulting in indirect antioxidant effects. Here, we investigate the influence of lutein on the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) target genes in human retinal pigment epithelial cells (ARPE-19 cells) using lutein-loaded Tween40 micelles. The micelles were identified as a suitable delivery system since they were nontoxic in APRE-19 cells up to 0.04% Tween40 and led to a cellular lutein accumulation of 62 μM ± 14 μM after 24 h. Lutein significantly enhanced Nrf2 translocation to the nucleus 1.5 ± 0.4-fold compared to that of unloaded micelles after 4 h. Furthermore, lutein treatment for 24 h significantly increased the transcripts of NAD(P)H:quinone oxidoreductase 1 (NQO1) by 1.7 ± 0.1-fold, glutamate-cysteine ligase regulatory subunit (GCLm) by 1.4 ± 0.1-fold, and heme oxygenase-1 (HO-1) by 1.8 ± 0.3-fold. Moreover, we observed a significant enhancement of NQO1 activity by 1.2 ± 0.1-fold. Collectively, this study indicates that lutein not only serves as a direct antioxidant but also activates Nrf2 in ARPE-19 cells.

  6. Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells.

    Science.gov (United States)

    Mori, Koichiro; Obara, Yutaro; Hirota, Mitsuru; Azumi, Yoshihito; Kinugasa, Satomi; Inatomi, Satoshi; Nakahata, Norimichi

    2008-09-01

    Neurotrophic factors are essential to maintain and organize neurons functionally; thereby neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the JNK pathway; these compounds are not hericenones.

  7. Cyclic mechanical deformation stimulates human lung fibroblast proliferation and autocrine growth factor activity.

    Science.gov (United States)

    Bishop, J E; Mitchell, J J; Absher, P M; Baldor, L; Geller, H A; Woodcock-Mitchell, J; Hamblin, M J; Vacek, P; Low, R B

    1993-08-01

    Cellular hypertrophy and hyperplasia and increased extracellular matrix deposition are features of tissue hypertrophy resulting from increased work load. It is known, for example, that mechanical forces play a critical role in lung development, cardiovascular remodeling following pressure overload, and skeletal muscle growth. The mechanisms involved in these processes, however, remain unclear. Here we examined the effect of mechanical deformation on fibroblast function in vitro. IMR-90 human fetal lung fibroblasts grown on collagen-coated silastic membranes were subjected to cyclical mechanical deformation (10% increase in culture surface area; 1 Hz) for up to 5 days. Cell number was increased by 39% after 2 days of deformation (1.43 +/- .01 x 10(5) cells/membrane compared with control, 1.03 +/- 0.02 x 10(5) cells; mean +/- SEM; P < 0.02) increasing to 163% above control by 4 days (2.16 +/- 0.16 x 10(5) cells compared with 0.82 +/- 0.03 x 10(5) cells; P < 0.001). The medium from mechanically deformed cells was mitogenic for IMR-90 cells, with maximal activity in the medium from cells mechanically deformed for 2 days (stimulating cell replication by 35% compared with media control; P < 0.002). These data suggest that mechanical deformation stimulates human lung fibroblast replication and that this effect is mediated by the release of autocrine growth factors.

  8. Signaling in TRPV1-induced platelet activating factor (PAF) in human esophageal epithelial cells.

    Science.gov (United States)

    Ma, Jie; Harnett, Karen M; Behar, Jose; Biancani, Piero; Cao, Weibiao

    2010-02-01

    Transient receptor potential channel, vanilloid subfamily member 1 (TRPV1) receptors were identified in human esophageal squamous epithelial cell line HET-1A by RT-PCR and by Western blot. In fura-2 AM-loaded cells, the TRPV1 agonist capsaicin caused a fourfold cytosolic calcium increase, supporting a role of TRPV1 as a capsaicin-activated cation channel. Capsaicin increased production of platelet activating factor (PAF), an important inflammatory mediator that acts as a chemoattractant and activator of immune cells. The increase was reduced by the p38 MAP kinase (p38) inhibitor SB203580, by the cytosolic phospholipase A2 (cPLA(2)) inhibitor AACOCF3, and by the lyso-PAF acetyltransferase inhibitor sanguinarin, indicating that capsaicin-induced PAF production may be mediated by activation of cPLA(2), p38, and lyso-PAF acetyltransferase. To establish a sequential signaling pathway, we examined the phosphorylation of p38 and cPLA(2) by Western blot. Capsaicin induced phosphorylation of p38 and cPLA(2). Capsaicin-induced p38 phosphorylation was not affected by AACOCF3. Conversely, capsaicin-induced cPLA(2) phosphorylation was blocked by SB203580, indicating that capsaicin-induced PAF production depends on sequential activation of p38 and cPLA(2). To investigate how p38 phosphorylation may result from TRPV1-mediated calcium influx, we examined a possible role of calmodulin kinase (CaM-K). p38 phosphorylation was stimulated by the calcium ionophore A23187 and by capsaicin, and the response to both agonists was reduced by a CaM inhibitor and by CaM-KII inhibitors, indicating that calcium induced activation of CaM and CaM-KII results in P38 phosphorylation. Acetyl-CoA transferase activity increased in response to capsaicin and was inhibited by SB203580, indicating that p38 phosphorylation in turn causes activation of acetyl-CoA transferase to produce PAF. Thus epithelial cells produce PAF in response to TRPV1-mediated calcium elevation.

  9. Modulation of both activator protein-1 and nuclear factor-kappa B signal transduction of human T cells by amiodarone.

    Science.gov (United States)

    Cheng, Shu-Meng; Lin, Wei-Hsiang; Lin, Chin-Sheng; Ho, Ling-Jun; Tsai, Tsung-Neng; Wu, Chun-Hsien; Lai, Jenn-Haung; Yang, Shih-Ping

    2015-01-01

    Amiodarone, a common and effective antiarrhythmic drug, has been reported to have anti-inflammatory effects such as reducing the activation and movement of neutrophils. However, its effects on human T cells remain unclear. The aim of this study was to elucidate the effects and possible underlying mechanisms of amiodarone on human T cells. We isolated human primary T cells from the peripheral blood of healthy volunteers and performed enzyme-linked immunosorbent assay (ELISA), flow cytometry, electrophoretic mobility shift assay, luciferase assay, and Western blotting to evaluate the modulatory effects of amiodarone on human T cells. We found that amiodarone dose dependently inhibited the production of cytokines, including interleukin-2 (IL-2), IL-4, tumor necrosis factor-alpha, and interferon-gamma in activated human T cells. By flow cytometry, we demonstrated that amiodarone suppressed the expression of IL-2 receptor-alpha (CD25) and CD69, the cell surface markers of activated T cells. Moreover, molecular investigations revealed that amiodarone down-regulated activator protein-1 (AP-1) and nuclear factor kappa-B (NF-κB) DNA-binding activities in activated human T cells and also inhibited DNA binding and transcriptional activities of both AP-1 and NF-κB in Jurkat cells. Finally, by Western blotting, we showed that amiodarone reduced the activation of c-Jun NH(2)-terminal protein kinase and P38 mitogen-activated protein kinase, and suppressed stimuli-induced I-kappa B-alpha degradation in activated human T cells. Through regulation of AP-1 and NF-κB signaling, amiodarone inhibits cytokine production and T cell activation. These results show the pleiotropic effects of amiodarone on human T cells and suggest its therapeutic potential in inflammation-related cardiovascular disorders. © 2014 by the Society for Experimental Biology and Medicine.

  10. Preparation, Characterization, and Determination of Immunological Activities of Transfer Factor Specific to Human Sperm Antigen

    Directory of Open Access Journals (Sweden)

    Jianwei Zhou

    2013-01-01

    Full Text Available Objective. The objective of this study was to prepare, characterize, and determine immunological activities of specific transfer factor (STF specific to human sperm antigen (HSA for the preparation of antisperm contraceptive vaccine that can be used as an immunocontraceptive. Methods. HSA-STF was prepared using the spleens of rabbits vaccinated with HSA. The specific immunological activities were examined by lymphocyte proliferation test (LPT, leukocyte adhesion inhibition test (LAIT, and by determining the concentrations of IL-4, γ-IFN, and IL-21. HSA-STF was a helveolous substance, having a pH value of 7.0±0.4 and UV absorption maxima at 258 ± 6 nm. It contained seventeen amino acids; glycine and glutamic acids were the highest in terms of concentrations (38.8 μg/mL and 36.3 μg/mL, resp.. Results. The concentration of polypeptide was 2.34±0.31 mg/mL, and ribose was 0.717±0.043 mg/mL. The stimulation index for lymphocyte proliferation test was 1.84, and the leukocyte adhesion inhibition rate was 37.7%. There was a statistically significant difference between the cultural lymphocytes with HSA-STF and non-HSA-STF for γ-IFN and IL-21 (P0.05. Conclusion. HSA-STF was prepared and characterized successfully. It had immunological activity which could transfer the immune response specific to HSA and prove to be a potential candidate for the development of male immunocontraceptive agents.

  11. Amantadine inhibits platelet-activating factor induced clathrin-mediated endocytosis in human neutrophils

    Science.gov (United States)

    Eckels, Phillip C.; Banerjee, Anirban; Moore, Ernest E.; McLaughlin, Nathan J. D.; Gries, Lynn M.; Kelher, Marguerite R.; England, Kelly M.; Gamboni-Robertson, Fabia; Khan, Samina Y.

    2009-01-01

    Receptor signaling is integral for adhesion, emigration, phagocytosis, and reactive oxygen species production in polymorphonuclear neutrophils (PMNs). Priming is an important part of PMN emigration, but it can also lead to PMN-mediated organ injury in the host. Platelet-activating factor (PAF) primes PMNs through activation of a specific G protein-coupled receptor. We hypothesize that PAF priming of PMNs requires clathrin-mediated endocytosis (CME) of the PAF receptor (PAFr), and, therefore, amantadine, known to inhibit CME, significantly antagonizes PAF signaling. PMNs were isolated by standard techniques to >98% purity and tested for viability. Amantadine (1 mM) significantly inhibited the PAF-mediated changes in the cellular distribution of clathrin and the physical colocalization [fluorescence resonance energy transfer positive (FRET+)] of early endosome antigen-1 and Rab5a, known components of CME and similar to hypertonic saline, a known inhibitor of CME. Furthermore, amantadine had no effect on the PAF-induced cytosolic calcium flux; however, phosphorylation of p38 MAPK was significantly decreased. Amantadine inhibited PAF-mediated changes in PMN physiology, including priming of the NADPH oxidase and shape change with lesser inhibition of increases in CD11b surface expression and elastase release. Furthermore, rimantadine, an amantadine analog, was a more potent inhibitor of PAF priming of the N-formyl-methionyl-leucyl-phenylalanine-activated oxidase. PAF priming of PMNs requires clathrin-mediated endocytosis that is inhibited when PMNs are pretreated with either amantadine or rimantadine. Thus, amantadine and rimantadine have the potential to ameliorate PMN-mediated tissue damage in humans. PMID:19295175

  12. Preparation, characterization, and determination of immunological activities of transfer factor specific to human sperm antigen.

    Science.gov (United States)

    Zhou, Jianwei; Kong, Cui; Yuan, Zhaohong; Luo, Junmin; Ma, Rui; Yu, Jiang; Cao, Jinghe

    2013-01-01

    OBJECTIVE. The objective of this study was to prepare, characterize, and determine immunological activities of specific transfer factor (STF) specific to human sperm antigen (HSA) for the preparation of antisperm contraceptive vaccine that can be used as an immunocontraceptive. METHODS. HSA-STF was prepared using the spleens of rabbits vaccinated with HSA. The specific immunological activities were examined by lymphocyte proliferation test (LPT), leukocyte adhesion inhibition test (LAIT), and by determining the concentrations of IL-4, γ -IFN, and IL-21. HSA-STF was a helveolous substance, having a pH value of 7.0 ± 0.4 and UV absorption maxima at 258 ± 6 nm. It contained seventeen amino acids; glycine and glutamic acids were the highest in terms of concentrations (38.8 μ g/mL and 36.3 μ g/mL, resp.). RESULTS. The concentration of polypeptide was 2.34 ± 0.31 mg/mL, and ribose was 0.717 ± 0.043 mg/mL. The stimulation index for lymphocyte proliferation test was 1.84, and the leukocyte adhesion inhibition rate was 37.7%. There was a statistically significant difference between the cultural lymphocytes with HSA-STF and non-HSA-STF for γ -IFN and IL-21 (P 0.05). CONCLUSION. HSA-STF was prepared and characterized successfully. It had immunological activity which could transfer the immune response specific to HSA and prove to be a potential candidate for the development of male immunocontraceptive agents.

  13. Regulation of the Human Ghrelin Promoter Activity by Transcription Factors, NF-κB and Nkx2.2

    Directory of Open Access Journals (Sweden)

    Yuki Shiimura

    2015-01-01

    Full Text Available To examine the gene expression of ghrelin, a growth hormone releasing and appetite stimulating hormone from stomach, we constructed human ghrelin promoter-reporter vectors and analyzed the promoter activity. The ghrelin promoter activity was high when cultured cells that express ghrelin mRNA endogenously like TT or ECC10 cells were used, indicating that these cells contain factors necessary for full expression of the human ghrelin gene. The human ghrelin promoter contains both positive and negative regulatory regions. A transient decrease of the promoter activity was found when the reporter vector with the −1600 fragment of the human ghrelin promoter was transfected into cultured cells. We then examined the effect of several transcription factors on the ghrelin promoter activity and found that NF-κB suppressed and that Nkx2.2, a homeodomain-containing transcription factor that is important for ghrelin cell development in pancreas, activates the promoter activity. These transcription factors may be possible targets for the control of ghrelin gene expression.

  14. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference ...

  15. Misfolded proteins activate Factor XII in humans, leading to kallikrein formation without initiating coagulation

    NARCIS (Netherlands)

    Maas, Coen; Govers-Riemslag, Jos W. P.; Bouma, Barend; Schiks, Bettina; Hazenberg, Bouke P. C.; Lokhorst, Henk M.; Hammarstrom, Per; ten Cate, Hugo; de Groot, Philip G.; Bouma, Bonno N.; Gebbink, Martijn F. B. G.

    When blood is exposed to negatively charged surface materials such as glass, an enzymatic cascade known as the contact system becomes activated. This cascade is initiated by autoactivation of Factor XII and leads to both coagulation (via Factor XI) and an inflammatory response (via the

  16. Sun protection factor persistence on human skin during a day without physical activity or ultraviolet exposure

    DEFF Research Database (Denmark)

    Beyer, Ditte Maria; Faurschou, Annesofie; Philipsen, Peter Alshede

    2010-01-01

    Recently, we showed that the sun protection factor (SPF) decreases by a constant factor to reach 55% during a day with activities. Organic sunscreens but not inorganic ones are absorbed through the skin. We wished to determine the SPF decrease caused by absorption by investigating the difference...

  17. Human Factors Tools for Improving Simulation Activities in Continuing Medical Education

    Science.gov (United States)

    Seagull, F. Jacob

    2012-01-01

    Human factors (HF) is a discipline often drawn upon when there is a need to train people to perform complex, high-stakes tasks and effectively assess their performance. Complex tasks often present unique challenges for training and assessment. HF has developed specialized techniques that have been effective in overcoming several of these…

  18. Histamine induces activation of protein kinase D that mediates tissue factor expression and activity in human aortic smooth muscle cells

    Science.gov (United States)

    Hao, Feng; Wu, Daniel Dongwei; Xu, Xuemin

    2012-01-01

    Histamine, an inflammatory mediator, has been shown to influence the pathogenesis of vascular wall cells. However, the molecular basis of its influence is not well understood. Our data reveal that histamine markedly induces protein kinase D (PKD) activation in human aortic smooth muscle cells. PKD belongs to a family of serine/threonine protein kinases, and its function in vascular disease is largely unknown. Our data show that histamine-induced PKD phosphorylation is dependent on the activation of histamine receptor 1 and protein kinase C (PKC). To determine the role of PKD in the histamine pathway, we employed a small-interfering RNA approach to downregulate PKD expression and found that PKD1 and PKD2 are key mediators for expression of tissue factor (TF), which is the key initiator of blood coagulation and is important for thrombosis. Our results show that PKD2 predominantly mediates histamine-induced TF expression via the p38 mitogen-activated protein kinase (MAPK) pathway, whereas PKD1 mediates histamine-induced TF expression through a p38 MAPK-independent pathway. We demonstrate that histamine induces TF expression via the PKC-dependent PKD activation. Our data provide the first evidence that PKD is a new component in histamine signaling in live cells and that PKD has a novel function in the histamine signaling pathway leading to gene expression, as evidenced by TF expression. Importantly, our data reveal a regulatory link from histamine to PKD and TF, providing new insights into the mechanisms of coagulation and the development of atherothrombosis. PMID:23001835

  19. A macroporous bioreactor super activated by the recombinant human transforming growth factor-beta 3

    Directory of Open Access Journals (Sweden)

    Ugo eRipamonti

    2012-06-01

    Full Text Available Macroporous single-phase hydroxyapatite (HA and biphasic HA/β-tricalcium phosphate with 33% post-sinter hydroxyapatite (HA/β-TCP were combined with 25 or 125 µg recombinant human transforming growth factor-β3 (hTGF-β3 to engineer a super activated bioreactor implanted in orthotopic calvarial and heterotopic rectus abdominis muscle sites and harvested on day 30 and 90. Coral-derived calcium carbonate fully converted (100% and partially converted to 5% and 13% hydroxyapatite/calcium carbonate (HA/CC preloaded with 125 and 250 µg hTGF-β3, and 1:5 and 5:1 binary applications of hTGF-β3: hOP-1 by weight, were implanted in the rectus abdominis and harvested on day 20 and 30, respectively, to monitor spatial/temporal morphogenesis by high doses of hTGF-β3. Bone formation was assessed on decalcified paraffin-embedded sections by measuring the fractional volume of newly-formed bone. On day 30 and 90, single phase HA implants showed greater amounts of bone when compared to biphasic specimens; 5 % and 13 % HA/CC pre-loaded with 125 and 250 µg hTGF-β3 showed substantial induction of bone formation; 250 µg hTGF-β3 induced as yet unreported massive induction of bone formation as early as 20 days prominently outside the profile of the macroporous constructs. The induction of bone formation is controlled by the implanted ratio of the recombinant morphogens, i.e. the 1:5 hTGF-β3:hOP-1 ratio by weight was greater than the inverse ratio. The unprecedented tissue induction by single doses of 250 µg hTGF-β3 resulting in rapid bone morphogenesis of vast mineralized ossicles with multiple trabeculations surfaced by contiguous secreting osteoblasts is the novel molecular and morphological frontier for the induction of bone formation in clinical contexts.

  20. Human memory manipulated: dissociating factors contributing to MTL activity, an fMRI study.

    Science.gov (United States)

    Pustina, Dorian; Gizewski, Elke; Forsting, Michael; Daum, Irene; Suchan, Boris

    2012-04-01

    Memory processes are mainly studied with subjective rating procedures. We used a morphing procedure to objectively manipulate the similarity of target stimuli. While undergoing functional magnetic resonance imaging, nineteen subjects performed a encoding and recognition task on face and scene stimuli, varying the degree of manipulation of previously studied targets at 0%, 20%, 40% or 60%. Analyses were performed with parametric modulations for objective stimulus status (morphing level), subjective memory (confidence rating), and reaction times (RTs). Results showed that medial temporal lobe (MTL) activity can be best explained by a combination of subjective and objective factors. Memory success is associated with activity modulation in the hippocampus both for faces and for scenes. Memory failures correlated with lower hippocampal activity for scenes, but not for faces. Activity changed during retrieval on similar areas activated during encoding. There was a considerable impact of RTs on memory-related areas. Objective perceptual identity correlated with activity in the left MTL, while subjective memory experience correlated with activity in the right MTL for both types of material. Overall, the results indicate that MTL activity is heterogeneous, showing both linear and non-linear activity, depending on the factor analyzed. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Human Factors Issues in Aircraft Maintenance Activities:A Holistic Approach

    OpenAIRE

    Tretten, Phillip; Normark, Carl Jörgen

    2014-01-01

    Maintenance software solutions are not designed for the users but instead for experts. Things are too complex and the available information is not applicable to the actual maintenance tasks to be conducted. Research has shown that there is need for easy to use tools that can assist in maintenance planning, maintenance actions, and maintenance reporting. Due the financial and time constraints placed the maintenance process need to become more effective and efficient. By taking a human factors ...

  2. Activation of complement factor B contributes to murine and human myocardial ischemia/reperfusion injury

    OpenAIRE

    Nicholas Chun; Haddadin, Ala S.; Junying Liu; Yunfang Hou; Wong, Karen A.; Daniel Lee; Rushbrook, Julie I.; Karan Gulaya; Roberta Hines; Tamika Hollis; Beatriz Nistal Nuno; Mangi, Abeel A.; Sabet Hashim; Marcela Pekna; Amy Catalfamo

    2017-01-01

    The pathophysiology of myocardial injury that results from cardiac ischemia and reperfusion (I/R) is incompletely understood. Experimental evidence from murine models indicates that innate immune mechanisms including complement activation via the classical and lectin pathways are crucial. Whether factor B (fB), a component of the alternative complement pathway required for amplification of complement cascade activation, participates in the pathophysiology of myocardial I/R injury has not been...

  3. The Cinnamon-derived Dietary Factor Cinnamic Aldehyde Activates the Nrf2-dependent Antioxidant Response in Human Epithelial Colon Cells

    Science.gov (United States)

    Wondrak, Georg T.; Villeneuve, Nicole F.; Lamore, Sarah D.; Bause, Alexandra S.; Jiang, Tao; Zhang, Donna D.

    2011-01-01

    Colorectal cancer (CRC) is a major cause of tumor-related morbidity and mortality worldwide. Recent research suggests that pharmacological intervention using dietary factors that activate the redox sensitive Nrf2/Keap1-ARE signaling pathway may represent a promising strategy for chemoprevention of human cancer including CRC. In our search for dietary Nrf2 activators with potential chemopreventive activity targeting CRC, we have focused our studies on trans-cinnamic aldehyde (cinnamaldeyde, CA), the key flavor compound in cinnamon essential oil. Here we demonstrate that CA and an ethanolic extract (CE) prepared from Cinnamomum cassia bark, standardized for CA content by GC-MS analysis, display equipotent activity as inducers of Nrf2 transcriptional activity. In human colon cancer cells (HCT116, HT29) and non-immortalized primary fetal colon cells (FHC), CA- and CE-treatment upregulated cellular protein levels of Nrf2 and established Nrf2 targets involved in the antioxidant response including heme oxygenase 1 (HO-1) and γ-glutamylcysteine synthetase (γ-GCS, catalytic subunit). CA- and CE-pretreatment strongly upregulated cellular glutathione levels and protected HCT116 cells against hydrogen peroxide-induced genotoxicity and arsenic-induced oxidative insult. Taken together our data demonstrate that the cinnamon-derived food factor CA is a potent activator of the Nrf2-orchestrated antioxidant response in cultured human epithelial colon cells. CA may therefore represent an underappreciated chemopreventive dietary factor targeting colorectal carcinogenesis. PMID:20657484

  4. The Cinnamon-Derived Dietary Factor Cinnamic Aldehyde Activates the Nrf2-Dependent Antioxidant Response in Human Epithelial Colon Cells

    Directory of Open Access Journals (Sweden)

    Georg Thomas Wondrak

    2010-05-01

    Full Text Available Colorectal cancer (CRC is a major cause of tumor-related morbidity and mortality worldwide. Recent research suggests that pharmacological intervention using dietary factors that activate the redox sensitive Nrf2/Keap1-ARE signaling pathway may represent a promising strategy for chemoprevention of human cancer including CRC. In our search for dietary Nrf2 activators with potential chemopreventive activity targeting CRC, we have focused our studies on trans-cinnamic aldehyde (cinnamaldeyde, CA, the key flavor compound in cinnamon essential oil. Here we demonstrate that CA and an ethanolic extract (CE prepared from Cinnamomum cassia bark, standardized for CA content by GC-MS analysis, display equipotent activity as inducers of Nrf2 transcriptional activity. In human colon cancer cells (HCT116, HT29 and non-immortalized primary fetal colon cells (FHC, CA- and CE-treatment upregulated cellular protein levels of Nrf2 and established Nrf2 targets involved in the antioxidant response including heme oxygenase 1 (HO-1 and γ-glutamyl-cysteine synthetase (γ-GCS, catalytic subunit. CA- and CE-pretreatment strongly upregulated cellular glutathione levels and protected HCT116 cells against hydrogen peroxide-induced genotoxicity and arsenic-induced oxidative insult. Taken together our data demonstrate that the cinnamon-derived food factor CA is a potent activator of the Nrf2-orchestrated antioxidant response in cultured human epithelial colon cells. CA may therefore represent an underappreciated chemopreventive dietary factor targeting colorectal carcinogenesis.

  5. 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.

  6. Platelet - activating factor induces leukotriene C4 synthesis by purified human eosinophils

    NARCIS (Netherlands)

    Bruijnzeel, P.L.B.; Kok, P.T.M.; Hamelink, M.L.; Kijne, A.M.; Verhagen, J.

    Platelet-activating factor, at a concentration of 10 μM, was capable of inducing leukotriene C4 synthesis by eosinophils of healthy donors, i.e. (3.1 ± 0.3) × 106 molecules leukotriene C4 /cell (n = 31, mean ± SEM, cell purity 87 ± 2%). Reversed-phase high performance liquid chromatography analysis

  7. The effect of lysolecithin on prostanoid and platelet-activating factor formation by human gall-bladder mucosal cells

    Directory of Open Access Journals (Sweden)

    M. K. Nag

    1995-01-01

    Full Text Available It has been demonstrated that lysolecithin (lysophosphatidyl choline, LPC produces experimental cholecystitis in cats mediated by arachidonic acid metabolites. LPC is a cytolytic agent that has been postulated as a contributing factor in the development of cholecystitis in humans. The purpose of this research was to evaluate the effect of LPC on human gall-bladder mucosal cell phospholipase A2 and cyclooxygenase activity. Gall-bladder mucosal cells were isolated from the gall-bladders of patients undergoing routine cholecystectomy. Fresh, isolated cells were maintained in tissue culture and stimulated with varying doses of LPC. Platelet-activating factor concentration was quantitated as an index of phospholipase A2 activity and prostanoids were measured as an index of cyclooxygenase activity. Also, the effect of LPC on cyclooxygenase 1 and 2 expression in microsomal protein was evaluated. LPC caused dose related increases in 6-keto-PGF1α and PAF produced by human gall-bladder mucosal cells. Exposure of human gall-bladder mucosal cells to LPC failed to elicit expression of constitutive cyclooxygenase-1, while the expression of inducible cyclooxygenase-2 was increased. The results of this study indicate that LPC induces the formation of prostanoids and PAF by human gall-bladder mucosal cells, suggesting that this substance may promote the development of gall-bladder inflammation.

  8. Adenosine Receptor Activation in the “Trigger” Limb of Remote Pre-Conditioning Mediates Human Endothelial Conditioning and Release of Circulating Cardioprotective Factor(s

    Directory of Open Access Journals (Sweden)

    Hussain Contractor, MBChB, DPhil

    2016-10-01

    Full Text Available Remote ischemic pre-conditioning (rIPC has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s; and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.

  9. Platelet activating factor: effects on bronchomotor tone and bronchial responsiveness in human beings.

    Science.gov (United States)

    Chung, K F; Cuss, F M; Barnes, P J

    1989-01-01

    Platelet-activating factor (PAF) is a newly discovered lipid mediator of inflammation. When inhaled by normal volunteers, it induces bronchoconstriction associated with facial flushing and with a transient fall in circulating neutrophils. Of greater interest is its ability to induce prolonged increases in bronchial responsiveness to methacholine. These observations support an important role for PAF in asthama; the availability of specific PAF antagonists will allow us to test this hypothesis.

  10. Lactobacillus acidophilus alleviates platelet-activating factor-induced inflammatory responses in human intestinal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Alip Borthakur

    Full Text Available Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD and necrotizing enterocolitis (NEC. Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF that mediate inflammatory responses in the disease. PAF is known to activate NF-κB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs, requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies examined the potential role of the probiotic Lactobacillus acidophilus in reversing the PAF-induced, Bcl10-dependent NF-κB activation and IL-8 production in IECs. PAF treatment (5 µM×24 h of NCM460 and Caco-2 cells significantly increased nuclear p65 NF-κB levels and IL-8 secretion (2-3-fold, P<0.05, compared to control, which were blocked by pretreatment of the cells for 6 h with L. acidophilus (LA or its culture supernatant (CS, followed by continued treatments with PAF for 24 h. LA-CS also attenuated PAF-induced increase in Bcl10 mRNA and protein levels and Bcl10 promoter activity. LA-CS did not alter PAF-induced interaction of Bcl10 with CARMA3, but attenuated Bcl10 interaction with MALT1 and also PAF-induced ubiquitination of IKKγ. Efficacy of bacteria-free CS of LA in counteracting PAF-induced inflammatory cascade suggests that soluble factor(s in the CS of LA mediate these effects. These results define a novel mechanism by which probiotics counteract PAF-induced inflammation in IECs.

  11. Ionizing radiation activates vascular endothelial growth factor-A transcription in human umbilical vein endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyounji; Kim, Kwang Seok; Jeong, Jae Hoon; Lim, Young Bin [Radiation Cancer Biology Team, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2016-12-15

    Vascular endothelial growth factor (VEGF) is an essential paracrine factor for developmental and pathological angiogenesis. VEGF also exerts its effects in an autocrine manner in VEGF-producing cells. For instance, autocrine VEGF signaling occurs in tumor cells and contributes to key aspects of tumorigenesis, such as in the function of cancer stem cells and tumor initiation, which are independent of angiogenesis. In addition to tumors cells, non-transformed cells also express VEGF. For example, a VEGF dependent intracellular autocrine mechanism is crucial for the survival of hematopoietic stem cells and hematopoiesis. Stereotactic body radiation therapy (SBRT) is a novel treatment modality for early primary cancer and oligometastatic disease. SBRT delivers high-dose hypofractionated radiation, such as 20-60 Gy, to tumors in a single fraction or 2-5 fractions. As VEGF is a critical regulator of functional integrity and viability of vascular endothelial cells, we examined whether high-dose irradiation alters VEGF signaling by measuring the expression levels of VEGFA transcript. It is generally believed that endothelial cells do not produce VEGF in response to radiation. In present study, however, we provide the first demonstration of transcriptional regulation of VEGFA in human vascular endothelial cells by IR treatment. Irradiation with doses higher than 10 Gy in a single exposure triggers up-regulation of VEGFA transcription within 2 hours in HUVECs, whereas irradiation with 10 Gy does not alter VEGFA levels. Our data have shown that high-dose irradiation triggers immediate transactivation of VEGFA in human vascular endothelial cells.

  12. Human factors in aviation

    National Research Council Canada - National Science Library

    Salas, Eduardo; Maurino, Daniel E

    2010-01-01

    .... HFA offers a comprehensive overview of the topic, taking readers from the general to the specific, first covering broad issues, then the more specific topics of pilot performance, human factors...

  13. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  14. Active post-marketing surveillance of the intralesional administration of human recombinant epidermal growth factor in diabetic foot ulcers

    OpenAIRE

    Yera-Alos, Isis B; Alonso-Carbonell, Liuba; Valenzuela-Silva, Carmen M; Tuero-Iglesias, Angela D; Moreira-Mart?nez, Martha; Marrero-Rodr?guez, Ivonne; L?pez-Mola, Ernesto; L?pez-Saura, Pedro A

    2013-01-01

    Background After several exploratory and confirmatory clinical trials, the intralesional administration of human recombinant epidermal growth factor (hrEGF) has been approved for the treatment of advanced diabetic foot ulcers (DFU). The aim of this work was to evaluate the effectiveness and safety of this procedure in medical practice. Methods A prospective, post-marketing active pharmacosurveillance was conducted in 41 hospitals and 19 primary care polyclinics. Patients with DFU received hrE...

  15. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    Directory of Open Access Journals (Sweden)

    Bobek Libuse A

    2007-11-01

    Full Text Available Abstract Background MUC7 12-mer (RKSYKCLHKRCR, a cationic antimicrobial peptide derived from the human low-molecular-weight salivary mucin MUC7, possesses potent antimicrobial activity in vitro. In order to evaluate the potential therapeutic application of the MUC7 12-mer, we examined the effects of mono- and divalent cations, EDTA, pH, and temperature on its antimicrobial activity. Methods Minimal Inhibitory Concentrations (MICs were determined using a liquid growth inhibition assay in 96-well microtiter plates. MUC7 12-mer was added at concentrations of 1.56–50 μM. MICs were determined at three endpoints: MIC-0, MIC-1, and MIC-2 (the lowest drug concentration showing 10%, 25% and 50% of growth, respectively. To examine the effect of salts or EDTA, a checkerboard microdilution technique was used. Fractional inhibitory concentration index (FICi was calculated on the basis of MIC-0. The viability of microbial cells treated with MUC7 12-mer in the presence of sodium or potassium was also determined by killing assay or flow cytometry. Results The MICs of MUC7 12-mer against organisms tested ranged from 6.25–50 μM. For C. albicans, antagonism (FICi 4.5 was observed for the combination of MUC7 12-mer and calcium; however, there was synergism (FICi 0.22 between MUC7 12-mer and EDTA, and the synergism was retained in the presence of calcium at its physiological concentration (1–2 mM. No antagonism but additivity or indifference (FICi 0.55–2.5 was observed for the combination of MUC7 12-mer and each K+, Na+, Mg2+, or Zn2+. MUC7 12-mer peptide (at 25 μM also exerted killing activity in the presence of NaCl, (up to 25 mM for C. albicans and up to 150 mM for E. coli, a physiological concentration of sodium in the oral cavity and serum, respectively and retained candidacidal activity in the presence of KCl (up to 40 mM. The peptide exhibited higher inhibitory activity against C. albicans at pH 7, 8, and 9 than at pH 5 and 6, and temperature up to

  16. Leishmania major infection activates NF-kappaB and interferon regulatory factors 1 and 8 in human dendritic cells.

    Science.gov (United States)

    Jayakumar, Asha; Donovan, Michael J; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

    2008-05-01

    The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not prime human DC for IL-12 production. Here, we report that DC priming by L. major infection results in the early activation of NF-kappaB transcription factors and the up-regulation and nuclear translocation of interferon regulatory factor 1 (IRF-1) and IRF-8. The inhibition of NF-kappaB activation by the pretreatment of DC with caffeic acid phenethyl ester blocks L. major-induced IRF-1 and IRF-8 activation and IL-12 expression. We further demonstrate that IRF-1 and IRF-8 obtained from L. major-infected human DC specifically bind to their consensus binding sites on the IL-12p35 promoter, indicating that L. major infection either directly stimulates a signaling cascade or induces an autocrine pathway that activates IRF-1 and IRF-8, ultimately resulting in IL-12 transcription.

  17. Production of human mutant biologically active hepatocyte growth factor in Chinese hamster ovary cells.

    Science.gov (United States)

    Xu, Dongsheng; Wan, Aini; Peng, Lin; Chen, Yun; He, Yang; Yang, Jianfeng; Jin, Jian

    2017-05-28

    Hepatocyte growth factor (HGF) is a potent multifunctional cytokine that affects proliferation, migration, and morphogenesis of various cells. HGF is secreted as an inactive single-chain precursor protein and activated by the cleavage of serine proteases to form heterodimers. In our current study, the cleavage site of HGF was blocked by replaced Arg 494 of Glu (R494E) that resulted in the single-chain HGF (R494E) unable to be cleaved by serine proteases. We established Chinese hamster ovary (CHO) cells overexpressing HGF (R494E), the expression of HGF (R494E) achieved 12 mg/L and was similar to a previously reported study. The recombinant protein was then purified from culture medium using a two-step chromatographic procedure that resulted in about a 40% recovery rate. The purified HGF (R494E) was obtained as a single-chain active protein. It concluded that HGF (R494E) exhibited a biologically active protein and the overexpressing CHO cell line supplied sufficient material for future studies. The R494E replacement of the cleavage site would be beneficial to the utility of other similar therapeutic proteins.

  18. LGP2 downregulates interferon production during infection with seasonal human influenza A viruses that activate interferon regulatory factor 3.

    Science.gov (United States)

    Malur, Meghana; Gale, Michael; Krug, Robert M

    2012-10-01

    LGP2, a member of the RIG-I-like receptor family, lacks the amino-terminal caspase activation recruitment domains (CARDs) required for initiating the activation of interferon regulatory factor 3 (IRF3) and interferon (IFN) transcription. The role of LGP2 in virus infection is controversial, and the only LGP2 experiments previously carried out with mammalian influenza A viruses employed an attenuated, mouse-adapted H1N1 A/PR/8/34 (PR8) virus that does not encode the NS1 protein. Here we determine whether LGP2 has a role during infection with wild-type, nonattenuated influenza A viruses that have circulated in the human population, specifically two types of seasonal influenza A viruses: (i) H3N2 and H1N1 viruses that activate IRF3 and IFN transcription and (ii) recent H1N1 viruses that block these two activations. In human cells infected with an H3N2 virus that activates IRF3, overexpression of LGP2 or its repressor domain decreased STAT1 activation and IFN-β transcription approximately 10-fold. Overexpression of LGP2 also caused a 10-fold decrease of STAT1 activation during infection with other seasonal influenza A viruses that activate IRF3. Using LGP2(+/+) and LGP2(-/-) mouse cells, we show that endogenous LGP2 decreased IFN production during H3N2 virus infection 3- to 4-fold. In contrast, in both mouse and human cells infected with H1N1 viruses that do not activate IRF3, LGP2 had no detectable role. These results demonstrate that LGP2 downregulates IFN production during infection by seasonal influenza A viruses that activate IRF3 and IFN transcription. It is intriguing that LGP2, a host protein induced during influenza A virus infection, downregulates the host antiviral IFN response.

  19. Improved efficacy of soluble human receptor activator of nuclear factor kappa B (RANK) fusion protein by site-directed mutagenesis.

    Science.gov (United States)

    Son, Young Jun; Han, Jihye; Lee, Jae Yeon; Kim, HaHyung; Chun, Taehoon

    2015-06-01

    Soluble human receptor activator of nuclear factor kappa B fusion immunoglobulin (hRANK-Ig) has been considered as one of the therapeutic agents to treat osteoporosis or diseases associated with bone destruction by blocking the interaction between RANK and the receptor activator of nuclear factor kappa B ligand (RANKL). However, no scientific record showing critical amino acid residues within the structural interface between the human RANKL and RANK complex is yet available. In this study, we produced several mutants of hRANK-Ig by replacement of amino acid residue(s) and tested whether the mutants had increased binding affinity to human RANKL. Based on the results from flow cytometry and surface plasmon resonance analyses, the replacement of E(125) with D(125), or E(125) and C(127) with D(125) and F(127) within loop 3 of cysteine-rich domain 3 of hRANK-Ig increases binding affinity to human RANKL over the wild-type hRANK-Ig. This result may provide the first example of improvement in the efficacy of hRANK-Ig by protein engineering and may give additional information to understand a more defined structural interface between hRANK and RANKL.

  20. Increased expression of protease-activated receptor 4 and Trefoil factor 2 in human colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Guoyu Yu

    Full Text Available Protease-activated receptor 4 (PAR4, a member of G-protein coupled receptors family, was recently reported to exhibit decreased expression in gastric cancer and esophageal squamous cancer, yet increased expression during the progression of prostate cancer. Trefoil factor 2 (TFF2, a small peptide constitutively expressed in the gastric mucosa, plays a protective role in restitution of gastric mucosa. Altered TFF2 expression was also related to the development of gastrointestinal cancer. TFF2 has been verified to promote cell migration via PAR4, but the roles of PAR4 and TFF2 in the progress of colorectal cancer are still unknown. In this study, the expression level of PAR4 and TFF2 in colorectal cancer tissues was measured using real-time PCR (n = 38, western blotting (n=38 and tissue microarrays (n = 66. The mRNA and protein expression levels of PAR4 and TFF2 were remarkably increased in colorectal cancer compared with matched noncancerous tissues, especially in positive lymph node and poorly differentiated cancers. The colorectal carcinoma cell LoVo showed an increased response to TFF2 as assessed by cell invasion upon PAR4 expression. However, after intervention of PAR4 expression, PAR4 positive colorectal carcinoma cell HT-29 was less responsive to TFF2 in cell invasion. Genomic bisulfite sequencing showed the hypomethylation of PAR4 promoter in colorectal cancer tissues and the hypermethylation in the normal mucosa that suggested the low methylation of promoter was correlated to the increased PAR4 expression. Taken together, the results demonstrated that the up-regulated expression of PAR4 and TFF2 frequently occurs in colorectal cancer tissues, and that overexpression of PAR4 may be resulted from promoter hypomethylation. While TFF2 promotes invasion activity of LoVo cells overexpressing PAR4, and this effect was significantly decreased when PAR4 was knockdowned in HT-29 cells. Our findings will be helpful in further investigations into the

  1. Effect of factor V Leiden polymorphism in severe sepsis and on treatment with recombinant human activated protein C.

    Science.gov (United States)

    Yan, S Betty; Nelson, David R

    2004-05-01

    Coagulation activation is part of the acute innate host response to infection that, when uncontrolled, may contribute to organ dysfunction and death. Activated protein C limits excessive coagulation activation by inactivating factors Va and VIIIa. The factor V Leiden mutation (R506Q), a prothrombotic gene polymorphism, disrupts the activity of this natural anticoagulant by rendering factor Va partially resistant to inactivation by activated protein C. Previous findings in the mouse factor V Leiden endotoxemia model and in patients with severe sepsis suggest that factor V Leiden constitutes a rare example of a balanced gene polymorphism that may provide a survival advantage for heterozygous carriers with severe sepsis. We sought to confirm that carriers of this prothrombotic factor V Leiden mutation do not have an increased risk of developing severe sepsis and that carriers with severe sepsis derive similar treatment benefit from recombinant human activated protein C (drotrecogin alfa [activated]) as non-factor V Leiden carriers. Prospective collection of factor V Leiden status from two clinical studies of severe sepsis (PROWESS and ENHANCE). : A total of 447 clinical sites across 25 countries. A total of 3894 adult patients with severe sepsis. Either 24 microg x kg x hr drotrecogin alfa (activated) (n = 3063) or placebo (n = 800) for 96 hrs or no exposure to the study drug (n = 31). The effect of the factor V Leiden carrier status in severe sepsis in the PROWESS study has been previously reported. The combined data on factor V Leiden status from 3894 adult patients with severe sepsis from the PROWESS and ENHANCE (a single-arm, open-label study of drotrecogin alfa [activated]) studies are reported here. At study entry, 3.9% of patients (150/3894) presenting with severe sepsis were heterozygous carriers. No homozygous factor V Leiden carriers were identified. The proportion of factor V Leiden carriers in patients with severe sepsis differs slightly from that

  2. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  3. Prevalence of and Associated Risk Factors for High Risk Human Papillomavirus among Sexually Active Women, Swaziland.

    Directory of Open Access Journals (Sweden)

    Themba G Ginindza

    Full Text Available High risk human papillomavirus (hr-HPV infection and the dual burden of HIV remains a huge challenge in some low-income countries (LICs such as Swaziland with limited or no data. We estimated the prevalence and investigated determinants of hr-HPV, including HIV infection among sexually active women in Swaziland.A total of 655 women aged between 15 and 49 years from five health facilities were randomly enrolled using a cross-sectional study design. Cervical cells were tested for hr-HPV types using GeneXpert HPV Assays.The overall weighted hr-HPV prevalence was 46.2% (95%CI: 42.8-49.5. Of hr-HPV infected women, 12.4% (95%CI: 8.6-17.5 were HPV16-positive, 13.8% (95%CI:12.0-15.8 were positive for HPV18/45, 26.7% (95%CI: 24.2-29.3 for HPV31/33/35/52/58, 7.6% (95%CI: 7.6-11.9 for HPV51/59 and 11.0%, (95%CI: 7.9-15.3 for HPV39/56/66/68. Prevalence of hr-HPV decreased with increasing age. Overall HIV prevalence remained high (42.7%; 95%CI: 35.7-46.2. HIV infection was associated with hr-HPV infection (Adjusted OR = 4.9, 95%CI: 3.043-7.8, p<0.001. Overall hr-HPV/HIV co-infection was 24.4% (95%CI: 20.3-29.1 which was significantly higher among younger age groups (p<0.001. Prevalence of multiple group hr-HPV infection was significantly higher in HIV-positive versus -negative women (27.7% and 12.7% respectively, p<0.001. The presence, absence or unknown of history of STI with HIV did not appear to modify the relationship with hr-HPV (OR = 4.2, 95%CI: 2.6-7.1, OR = 4.6, 95%CI: 2.8-7.7, p<0.001, p<0.001 and OR = 4.1, 95%CI: 1.3-13.4, p<0.021 respectively.The prevalence of hr-HPV infection was high and significantly associated with HIV among sexually active women. Furthermore, the study has provided essential information about the HIV link with hr-HPV infections which may explain the high prevalence among HIV infected women. This can contribute to policy development and planning of prevention strategies incorporating HPV infection prevention especially among

  4. Profiling of Concanavalin A-Binding Glycoproteins in Human Hepatic Stellate Cells Activated with Transforming Growth Factor-β1

    Directory of Open Access Journals (Sweden)

    Yannan Qin

    2014-11-01

    Full Text Available Glycoproteins play important roles in maintaining normal cell functions depending on their glycosylations. Our previous study indicated that the abundance of glycoproteins recognized by concanavalin A (ConA was increased in human hepatic stellate cells (HSCs following activation by transforming growth factor-β1 (TGF-β1; however, little is known about the ConA-binding glycoproteins (CBGs of HSCs. In this study, we employed a targeted glycoproteomics approach using lectin-magnetic particle conjugate-based liquid chromatography-tandem mass spectrometry to compare CBG profiles between LX-2 HSCs with and without activation by TGF-β1, with the aim of discovering novel CBGs and determining their possible roles in activated HSCs. A total of 54 and 77 proteins were identified in the quiescent and activated LX-2 cells, respectively. Of the proteins identified, 14.3% were glycoproteins and 73.3% were novel potential glycoproteins. Molecules involved in protein processing in the endoplasmic reticulum (e.g., calreticulin and calcium signaling (e.g., 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase β-2 [PLCB2] were specifically identified in activated LX-2 cells. Additionally, PLCB2 expression was upregulated in the cytoplasm of the activated LX-2 cells, as well as in the hepatocytes and sinusoidal cells of liver cirrhosis tissues. In conclusion, the results of this study may aid future investigations to find new molecular mechanisms involved in HSC activation and antifibrotic therapeutic targets.

  5. Effect of a heat-stable factor in human placenta on glucosylceramidase, glucosylsphingosine glucosyl hydrolase, and acid beta-glucosidase activities.

    Science.gov (United States)

    Vaccaro, A M; Muscillo, M; Tatti, M; Salvioli, R; Gallozzi, E; Suzuki, K

    1987-12-01

    A new protein activator of glucosylceramidase has recently been found in human placenta. In the present work, it has been compared with a previously reported glucosylceramidase activator, the Gaucher factor. The two activators showed different properties. The Gaucher factor stimulated 100% the 4-methylumbelliferyl-beta-D-glucopyranoside hydrolysis while the placental factor inhibited it 50%. Furthermore, the placental factor neither decreased the Michaelis constant, Km, nor increased the degree of inactivation by conduritol-beta-epoxide as the Gaucher factor does. From these results it has been concluded that the two activators are different substances. The activating effect of the placental factor is specific for the hydrolysis of glucosylceramide; neither the hydrolysis of glucosylsphingosine nor that of the 4-methylumbelliferyl derivative are enhanced by this protein. Owing to its specificity and high level in a human tissue, the placental factor is likely to have a physiological role in the catabolism of glucosylceramide.

  6. Constitutive activation of transcription factor AP-2 is associated with decreased MnSOD expression in transformed human lung fibroblasts.

    Science.gov (United States)

    Zhu, C; Huang, Y; Weydert, C J; Oberley, L W; Domann, F E

    2001-06-01

    Activator protein-2 (AP-2) is a transcription factor with transactivating and transrepressing potential in different promoter contexts. AP-2 contains seven cysteines, and its in vitro DNA binding activity is redox-sensitive. Superoxide dismutase-2 (SOD2), which encodes the antioxidant enzyme manganese superoxide dismutase (MnSOD), is a putative tumor suppressor gene whose loss of expression is associated with the malignant phenotype. SOD2 promoter mutations that generate new AP-2 sites are associated with loss of MnSOD expression in cancer cells. In the current study, we have identified an inverse expression pattern between AP-2 and MnSOD in normal versus transformed human cells. MRC5 cells are a normal human lung fibroblast cell strain that is mortal and senesces after a certain number of passages in vitro. MRC5-VA is a simian virus transformed variant of MRC5. We determined the levels of expression of MnSOD and AP-2 in these two cell types at the levels of mRNA, protein, and activity. Our results indicated that MnSOD expression was significantly decreased in MRC5-VA cells compared with MRC5 cells at each level of investigation, whereas AP-2 showed an opposing pattern of expression and DNA binding activity. These results suggest that AP-2 may participate in the mechanism(s) underlying decreased expression of SOD2 in transformed cells.

  7. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  8. Habitability and Human Factors Contributions to Human Space Flight

    Science.gov (United States)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  9. Characterization of the De Novo Biosynthetic Enzyme of Platelet Activating Factor, DDT-Insensitive Cholinephosphotransferase, of Human Mesangial Cells

    Directory of Open Access Journals (Sweden)

    Alexandros Basilios Tsoupras

    2007-01-01

    Full Text Available Platelet activating factor (PAF, a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT of human mesangial cell (HMC, the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA, dithiothreitol (DTT, divalent cations (Mg2+ and Ca2+, EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass “Dicentrarchus labrax,” and gilthead sea bream “Sparus aurata”. The results indicated that the above compounds can influence PAF-CPT activity of HMC.

  10. Characterization of the De Novo Biosynthetic Enzyme of Platelet Activating Factor, DDT-Insensitive Cholinephosphotransferase, of Human Mesangial Cells

    Science.gov (United States)

    Tsoupras, Alexandros Basilios; Fragopoulou, Elizabeth; Nomikos, Tzortzis; Iatrou, Christos; Antonopoulou, Smaragdi; Demopoulos, Constantinos Alexandros

    2007-01-01

    Platelet activating factor (PAF), a potent inflammatory mediator, is implicated in several proinflammatory/inflammatory diseases such as glomerulonephritis, glomerulosclerosis, atherosclerosis, cancer, allergy, and diabetes. PAF can be produced by several renal cells under appropriate stimuli and it is thought to be implicated in renal diseases. The aim of this study is the characterization of DTT-insensitive cholinephosphotransferase (PAF-CPT) of human mesangial cell (HMC), the main regulatory enzyme of PAF de novo biosynthetic pathway. Microsomal fractions of mesangial cells were isolated and enzymatic activity and kinetic parameters were determined by TLC and in vitro biological test in rabbit washed platelets. The effect of bovine serum albumin (BSA), dithiothreitol (DTT), divalent cations (Mg2+ and Ca2+), EDTA, and various chemicals on the activity of PAF-CPT of HMC was also studied. Moreover, preliminary in vitro tests have been performed with several anti-inflammatory factors such as drugs (simvastatin, IFNa, rupatadine, tinzaparin, and salicylic acid) and bioactive compounds of Mediterranean diet (resveratrol and lipids of olive oil, olive pomace, sea bass “Dicentrarchus labrax,” and gilthead sea bream “Sparus aurata”). The results indicated that the above compounds can influence PAF-CPT activity of HMC. PMID:17710109

  11. Nuclear Factor Erythroid 2 Regulates Human HSC Self-Renewal and T Cell Differentiation by Preventing NOTCH1 Activation

    Directory of Open Access Journals (Sweden)

    Alessandro Di Tullio

    2017-07-01

    Full Text Available Nuclear factor erythroid-derived 2 (NF-E2 has been associated with megakaryocyte maturation and platelet production. Recently, an increased in NF-E2 activity has been implicated in myeloproliferative neoplasms. Here, we investigate the role of NF-E2 in normal human hematopoiesis. Knockdown of NF-E2 in the hematopoietic stem and progenitor cells (HSPCs not only reduced the formation of megakaryocytes but also drastically impaired hematopoietic stem cell activity, decreasing human engraftment in immunodeficient (NSG mice. This phenotype is likely to be related to both increased cell proliferation (p21-mediated and reduced Notch1 protein expression, which favors HSPC differentiation over self-renewal. Strikingly, although NF-E2 silencing in HSPCs did not affect their myeloid and B cell differentiation in vivo, it almost abrogated T cell production in primary hosts, as confirmed by in vitro studies. This effect is at least partly due to Notch1 downregulation in NF-E2-silenced HSPCs. Together these data reveal that NF-E2 is an important driver of human hematopoietic stem cell maintenance and T lineage differentiation.

  12. The forkhead transcription factor Foxl2 is sumoylated in both human and mouse: sumoylation affects its stability, localization, and activity.

    Directory of Open Access Journals (Sweden)

    Mara Marongiu

    Full Text Available The FOXL2 forkhead transcription factor is expressed in ovarian granulosa cells, and mutated FOXL2 causes the blepharophimosis, ptosis and epicanthus inversus syndrome (BPES and predisposes to premature ovarian failure. Inactivation of Foxl2 in mice demonstrated its indispensability for female gonadal sex determination and ovary development and revealed its antagonism of Sox9, the effector of male testis development. To help to define the regulatory activities of FOXL2, we looked for interacting proteins. Based on yeast two-hybrid screening, we found that FOXL2 interacts with PIAS1 and UBC9, both parts of the sumoylation machinery. We showed that human FOXL2 is sumoylated in transfected cell lines, and that endogenous mouse Foxl2 is comparably sumoylated. This modification changes its cellular localization, stability and transcriptional activity. It is intriguing that similar sumoylation and regulatory consequences have also been reported for SOX9, the male counterpart of FOXL2 in somatic gonadal tissues.

  13. The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: A review.

    Science.gov (United States)

    Huang, T; Larsen, K T; Ried-Larsen, M; Møller, N C; Andersen, L B

    2014-02-01

    The purpose of this study was to summarize the effects of physical activity and exercise on peripheral brain-derived neurotrophic factor (BDNF) in healthy humans. Experimental and observational studies were identified from PubMed, Web of Knowledge, Scopus, and SPORT Discus. A total of 32 articles met the inclusion criteria. Evidence from experimental studies suggested that peripheral BDNF concentrations were elevated by acute and chronic aerobic exercise. The majority of the studies suggested that strength training had no influence on peripheral BDNF. The results from most observational studies suggested an inverse relationship between the peripheral BDNF level and habitual physical activity or cardiorespiratory fitness. More research is needed to confirm the findings from the observational studies. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. A Taiwanese Propolis Derivative Induces Apoptosis through Inducing Endoplasmic Reticular Stress and Activating Transcription Factor-3 in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Fat-Moon Suk

    2013-01-01

    Full Text Available Activating transcription factor-(ATF- 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. NBM-TP-007-GS-002 (GS-002 is a Taiwanese propolin G (PPG derivative. In this study, we examined the antitumor effects of GS-002 in human hepatoma Hep3B and HepG2 cells in vitro. First, we found that GS-002 significantly inhibited cell proliferation and induced cell apoptosis in dose-dependent manners. Several main apoptotic indicators were found in GS-002-treated cells, such as the cleaved forms of caspase-3, caspase-9, and poly(ADP-ribose polymerase (PARP. GS-002 also induced endoplasmic reticular (ER stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78, growth arrest- and DNA damage-inducible gene 153 (GADD153, phosphorylated eukaryotic initiation factor 2α (eIF2α, phosphorylated protein endoplasmic-reticular-resident kinase (PERK, and ATF-3. The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK signaling pathways in GS-002-treated cells. Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug.

  15. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Directory of Open Access Journals (Sweden)

    Aude Deschuyteneer

    Full Text Available Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S associated to overhydrated hereditary stomatocytosis (OHSt, a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  16. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Science.gov (United States)

    Deschuyteneer, Aude; Boeckstaens, Mélanie; De Mees, Christelle; Van Vooren, Pascale; Wintjens, René; Marini, Anna Maria

    2013-01-01

    Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs) with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S) associated to overhydrated hereditary stomatocytosis (OHSt), a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C) may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  17. Prediction of human pharmacokinetics of activated recombinant factor VII and B-domain truncated factor VIII from animal population pharmacokinetic models of haemophilia

    DEFF Research Database (Denmark)

    Larsen, Malte Selch; Juul, Rasmus Vestergaard; Groth, Andreas Velsing

    2018-01-01

    Various experimental animal models are used in haemophilia research, however, little is known about how well the different species predict pharmacokinetic (PK) profiles in haemophilia patients. The aim of the current study was to describe the plasma concentration-time profile of recombinant...... activated factor VII (rFVIIa) and recombinant factor VIII (rFVIII) in several experimental animal models using population PK modelling, and apply a simulation-based approach to evaluate how well the developed animal population PK models predict human PK. PK models were developed for rFVIIa and r...... for nonlinear kinetics and gender-specific difference in clearance for rFVIII. The predictive performance of the animal population PK models of rFVIIa and rFVIII revealed significant species-variation. The developed PK models of rFVIIa and rFVIII in monkeys and dogs along with allometric interspecies scaling...

  18. Activation of the Long Terminal Repeat of Human Endogenous Retrovirus K by Melanoma-Specific Transcription Factor MITF-M

    Directory of Open Access Journals (Sweden)

    Iyoko Katoh

    2011-11-01

    Full Text Available The human and Old World primate genomes possess conserved endogenous retrovirus sequences that have been implicated in evolution, reproduction, and carcinogenesis. Human endogenous retrovirus (HERV-K with 5′LTR-gag-pro-pol-env-rec/np9-3′LTR sequences represents the newest retrovirus family that integrated into the human genome 1 to 5 million years ago. Although a high-level expression of HERV-K in melanomas, breast cancers, and terato-carcinomas has been demonstrated, the mechanism of the lineage-specific activation of the long terminal repeat (LTR remains obscure. We studied chromosomal HERV-K expression in MeWo melanoma cells in comparison with the basal expression in human embryonic kidney 293 (HEK293 cells. Cloned LTR of HERV-K (HML-2.HOM was also characterized by mutation and transactivation experiments. We detected multiple transcriptional initiator (Inr sites in the LTR by rapid amplification of complementary DNA ends (5′ RACE. HEK293 and MeWo showed different Inr usage. The most potent Inr was associated with a TATA box and three binding motifs of microphthalmia-associated transcription factor (MITF. Both chromosomal HERV-K expression and the cloned LTR function were strongly activated in HEK293 by transfection with MITF-M, a melanocyte/melanoma–specific isoform of MITF. Coexpression of MITF and the HERV-K core antigen was detected in retinal pigmented epithelium by an immunofluorescence analysis. Although malignant melanoma lines MeWo, G361, and SK-MEL-28 showed enhanced HERV-K transcription compared with normal melanocytes, the level of MITF-M messenger RNA persisted from normal to transformed melanocytes. Thus, MITF-M may be a prerequisite for the pigmented cell lineage–specific function of HERV-K LTR, leading to the high-level expression in malignant melanomas.

  19. The Rho-activating CNF1 toxin from pathogenic E. coli: A risk factor for human cancer development?

    Directory of Open Access Journals (Sweden)

    Fiorentini Carla

    2008-03-01

    Full Text Available Abstract Nowadays, there is increasing evidence that some pathogenic bacteria can contribute to specific stages of cancer development. The concept that bacterial infection could be involved in carcinogenesis acquired a widespread interest with the discovery that H. pylori is able to establish chronic infections in the stomach and that this infection is associated with an increased risk of gastric adenocarcinoma and mucosa associated lymphoid tissue lymphoma. Chronic infections triggered by bacteria can facilitate tumor initiation or progression since, during the course of infection, normal cell functions can come under the control of pathogen factors that directly manipulate the host regulatory pathways and the inflammatory reactions. Renowned publications have recently corroborated the molecular mechanisms that link bacterial infections, inflammation and cancer, indicating certain strains of Escherichia coli as a risk factor for patients with colon cancer. E. coli is a normal inhabitant of the human intestine that becomes highly pathogenic following the acquisition of virulence factors, including a protein toxin named cytotoxic necrotizing factor 1 (CNF1. This toxin permanently activates the small GTP-binding proteins belonging to the Rho family, thus promoting a prominent polymerization of the actin cytoskeleton as well as a number of cellular responses, including changes in protein expression and functional modification of the cell physiology. CNF1 is receiving an increasing attention as a putative factor involved in transformation because of its ability to: (i induce COX2 expression, an immediate-early gene over-expressed in some type of cancers; (ii induce a long-lasting activation of the transcription factor NF-kB, a largely accepted marker of tumor cells; (iii protect epithelial cells from apoptosis; (iv ensue the release of pro-inflammatory cytokines in epithelial and endothelial cells; and (v promote cellular motility. As cancer may

  20. Sox2 is translationally activated by eukaryotic initiation factor 4E in human glioma-initiating cells

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Yuqing; Zhou, Fengbiao; Chen, Hong; Cui, Chunhong; Liu, Dan [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Li, Qiuping [Zhongshan Hospital of Fudan University, Shanghai 200032 (China); Yang, Zhiyuan; Wu, Guoqiang [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Sun, Shuhui [Key Laboratory of Medical Molecular Virology, Ministry of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Gu, Jianxin [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Institutes of Biomedical Sciences of Fudan University, Shanghai 200032 (China); Wei, Yuanyan, E-mail: yywei@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China); Jiang, Jianhai, E-mail: jianhaijiang@fudan.edu.cn [Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai 200032 (China)

    2010-07-09

    Sox2, a master transcription factor, contributes to the generation of induced pluripotent stem cells and plays significant roles in sustaining the self-renewal of neural stem cells and glioma-initiating cells. Understanding the functional differences of Sox2 between glioma-initiating cells and normal neural stem cells would contribute to therapeutic approach for treatment of brain tumors. Here, we first demonstrated that Sox2 could contribute to the self-renewal and proliferation of glioma-initiating cells. The following experiments showed that Sox2 was activated at translational level in a subset of human glioma-initiating cells compared with the normal neural stem cells. Further investigation revealed there was a positive correlation between Sox2 and eukaryotic initiation factor 4E (eIF4E) in glioma tissues. Down-regulation of eIF4E decreased Sox2 protein level without altering its mRNA level in glioma-initiating cells, indicating that Sox2 was activated by eIF4E at translational level. Furthermore, eIF4E was presumed to regulate the expression of Sox2 by its 5' untranslated region (5' UTR) sequence. Our results suggest that the eIF4E-Sox2 axis is a novel mechanism of unregulated self-renewal of glioma-initiating cells, providing a potential therapeutic target for glioma.

  1. Expression of a splice variant of the platelet-activating factor receptor transcript 2 in various human cancer cell lines

    Directory of Open Access Journals (Sweden)

    Ibtissam Youlyouz

    2002-01-01

    Full Text Available Platelet-activating factor receptor (PAF-R transcripts were analysed by reverse transcriptase-polymerase chain reaction in five human cancer cell lines derived from the breast (BT20, SKBR3 and T47D cells, the pancreas (Miapaca cells and the bladder (5637 cells in order to confirm the existence of a splice variant of the PAF-R transcript 2. After cloning and sequencing, we confirmed its existence in all cell lines. It consisted of the PAF-R transcript 2 lengthening with 82 nucleotides from the 3' end of exon 1 of the PAF-R gene. The role of this elongated form of the tissue-type PAF-R transcript in cell physiology remains to be elucidated.

  2. Release of adenosine from human neutrophils stimulated by platelet activating factor, leukotriene B4 and opsonized zymosan

    Directory of Open Access Journals (Sweden)

    S. Sipka

    1992-01-01

    Full Text Available Isolated human polymorphonuclear leukocytes (PMNL stimulated by platelet activating factor (PAF, leukotriene B4 (LTB4 or opsonized zymosan (OZ released adenosine measured by thermospray high performance liquid chromatography mass spectrometry in the cell-free supernatants. Stimulation by PAF or LTB4 resulted in a bellshaped concentration-effect curve; 5 × 10−7 M PAF, 10−8 M LTB4 and 500 μg ml−1 OZ induced peak adenosine release, thus cytotoxic concentrations did not elevate adenosine level in the supernatants. Therefore adenosine release was characteristic of viable cells. As calculated from concentration-effect curves, the rank order of potency for adenosine release was PAF > LTB > OZ. These resuits suggest that adenosine, when bound specifically to membrane receptor sites, may initiate signal transduction, and, in co-operation with other inflammatory mediators, may modulate phagocyte function, e.g. production of chemoluminescence (CL.

  3. Human papillomavirus type 16 E2 protein transcriptionally activates the promoter of a key cellular splicing factor, SF2/ASF.

    Science.gov (United States)

    Mole, Sarah; Milligan, Steven G; Graham, Sheila V

    2009-01-01

    Human papillomavirus (HPV) gene expression is regulated in concert with the epithelial differentiation program. In particular, expression of the virus capsid proteins L1 and L2 is tightly restricted to differentiated epithelial cells. For HPV16, the capsid proteins are encoded by 13 structurally different mRNAs that are produced by extensive alternative splicing. Previously, we demonstrated that upon epithelial differentiation, HPV16 infection upregulates hnRNP A1 and SF2/ASF, both key factors in alternative splicing regulation. Here we cloned a 1-kb region upstream of and including the transcriptional start site of the SF2ASF gene and used it in in vivo transcription assays to demonstrate that the HPV16 E2 transcription factor transactivates the SF2/ASF promoter. The transactivation domain but not the DNA binding domain of the protein is necessary for this. Active E2 association with the promoter was demonstrated using chromatin immunoprecipitation assays. Electrophoretic mobility shift assays indicated that E2 interacted with a region 482 to 684 bp upstream of the transcription initiation site in vitro. This is the first time that HPV16 E2 has been shown to regulate cellular gene expression and the first report of viral regulation of expression of an RNA processing factor. Such E2-mediated control during differentiation of infected epithelial cells may facilitate late capsid protein expression and completion of the virus life cycle.

  4. Activation of TAK1 by Chemotactic and Growth Factors, and Its Impact on Human Neutrophil Signaling and Functional Responses.

    Science.gov (United States)

    Sylvain-Prévost, Stéphanie; Ear, Thornin; Simard, François A; Fortin, Carl F; Dubois, Claire M; Flamand, Nicolas; McDonald, Patrick P

    2015-12-01

    The MAP3 kinase, TAK1, is known to act upstream of IKK and MAPK cascades in several cell types, and is typically activated in response to cytokines (e.g., TNF, IL-1) and TLR ligands. In this article, we report that in human neutrophils, TAK1 can also be activated by different classes of inflammatory stimuli, namely, chemoattractants and growth factors. After stimulation with such agents, TAK1 becomes rapidly and transiently activated. Blocking TAK1 kinase activity with a highly selective inhibitor (5z-7-oxozeaenol) attenuated the inducible phosphorylation of ERK occurring in response to these stimuli but had little or no effect on that of p38 MAPK or PI3K. Inhibition of TAK1 also impaired MEKK3 (but not MEKK1) activation by fMLF. Moreover, both TAK1 and the MEK/ERK module were found to influence inflammatory cytokine expression and release in fMLF- and GM-CSF-activated neutrophils, whereas the PI3K pathway influenced this response independently of TAK1. Besides cytokine production, other responses were found to be under TAK1 control in neutrophils stimulated with chemoattractants and/or GM-CSF, namely, delayed apoptosis and leukotriene biosynthesis. Our data further emphasize the central role of TAK1 in controlling signaling cascades and functional responses in primary neutrophils, making it a promising target for therapeutic intervention in view of the foremost role of neutrophils in several chronic inflammatory conditions. Copyright © 2015 by The American Association of Immunologists, Inc.

  5. Signaling pathways for B cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in human placenta.

    Science.gov (United States)

    Langat, Daudi L; Wheaton, David A; Platt, Jeralyn Sue; Sifers, Travis; Hunt, Joan S

    2008-05-01

    The tumor necrosis superfamily (TNFSF) contains two soluble ligands that are involved in B lymphocyte development, BAFF (B cell activating factor, BlyS, TALL-1, CD257, TNFSF13B) and APRIL (a proliferation inducing ligand, CD256, TNFSF13). These two ligands signal through three receptors: the exclusive BAFF receptor (BAFF-R, CD268, TNFRSF17) and two receptors that recognize both BAFF and APRIL, TACI (transmembrane-activator-1 and calcium-modulator- and cyclophilin ligand-interactor CD267, TNFRSF13B) and BCMA (B cell maturation antigen, CD269, TNFRSF13C). All but BAFF-R are known to be synthesized in term placentas. In this study, expression of the ligands and receptors were distinguished in two embryologically discrete subpopulations of placental cells, villous cytotrophoblast (vCTB) cells and mesenchymal cells (MCs). Real-Time PCR showed that vCTB cells contain low levels of BAFF and APRIL transcripts whereas MCs contain high levels. Both Real-Time PCR and immunohistochemistry identified BAFF-R and BCMA mRNA and proteins in vCTB cells but essentially no TACI. By contrast, MCs contained readily detectable levels of all three receptors. These results illustrating potential autocrine and paracrine pathways for BAFF and APRIL signaling in human placentas suggest that lineage-specific regulation of placental cell viability, differentiation and/or other activities may be novel functions of these proteins.

  6. Human epidermal growth factor receptor (HER-1:HER-3) Fc-mediated heterodimer has broad antiproliferative activity in vitro and in human tumor xenografts.

    Science.gov (United States)

    Sarup, Jay; Jin, Pei; Turin, Lisa; Bai, Xiaomei; Beryt, Malgorzata; Brdlik, Cathleen; Higaki, Jeffrey N; Jorgensen, Brett; Lau, Francis W; Lindley, Peter; Liu, Jim; Ni, Irene; Rozzelle, James; Kumari, Rajendra; Watson, Susan A; Zhang, Juan; Shepard, H Michael

    2008-10-01

    All four members of the human epidermal growth factor (EGF) receptor (HER) family are implicated in human cancers. Although efficacious in a subset of patients, resistance to single-targeted anti-HER therapy [i.e., cetuximab (Erbitux) and trastuzumab (Herceptin)] is often associated with coexpression of other HER family members. This may be overcome by a HER ligand binding molecule that sequesters multiple EGF-like ligands, preventing ligand-dependent receptor activation. Toward this end, we have combined the HER-1/EGFR and HER-3 ligand binding domains, dimerized with fusion of an Fc fragment of human IgG1. This resulted in a mixture of HER-1/Fc homodimer (HFD100), HER-3/Fc homodimer (HFD300), and HER-1/Fc:HER-3/Fc heterodimer (RB200), also termed Hermodulins. The purified first-generation RB200 bound EGF and neuregulin 1 (NRG1)-beta1 ligands, determined by cross-linking and direct binding studies. The binding affinity for both was approximately 10 nmol/L by dissociation-enhanced lanthanide fluorescence immunoassay using europium (Eu)-labeled ligands. Competition studies with RB200 using Eu-EGF or Eu-NRG1-beta1 revealed that RB200 bound HER-1 ligands, including transforming growth factor-alpha and heparin-binding EGF, and HER-3 ligands NRG1-alpha and NRG1-beta3. RB200 inhibited EGF- and NRG1-beta1-stimulated tyrosine phosphorylation of HER family proteins, proliferation of a diverse range of tumor cells in monolayer cell growth assays, tumor cell proliferation as a single agent and in synergy with tyrosine kinase inhibitors, lysophosphatidic acid-stimulated cell proliferation, and tumor growth in two human tumor xenograft nude mouse models. Taken together, the data reveal that RB200 has the potential to sequester multiple HER ligands and interfere with signaling by HER-1, HER-2, and HER-3.

  7. Recombinant human erythropoietin pretreatment alleviates renal glomerular injury induced by cardiopulmonary bypass by reducing transient receptor potential channel 6-nuclear factor of activated T-cells pathway activation.

    Science.gov (United States)

    Liu, Xiaoming; Zhang, Tingting; Xia, Weiliang; Wang, Yingwei; Ma, Ke

    2013-09-01

    Acute renal injury after cardiopulmonary bypass is common and associated with high mortality. We aimed to demonstrate the glomerular protective effects of recombinant human erythropoietin using an in vivo rat cardiopulmonary bypass model and to explore the possible mechanism. Dose-related renal protective effects of recombinant human erythropoietin were studied in phase I. Male Sprague Dawley rats were randomly divided into 5 groups: sham group, cardiopulmonary bypass group, and 3 recombinant human erythropoietin-treated cardiopulmonary bypass groups (bolus doses of 500, 3000, and 5000 U/kg 24 hours before surgery). Blood and urine samples were collected just before surgery and at 2, 4, 24, 48, and 72 hours after surgery. In phase II, rats were divided into 3 groups: sham group, cardiopulmonary bypass group, and 5000 U/kg recombinant human erythropoietin group. Kidneys were harvested at 4, 24, 48, and 72 hours after surgery. Ultra-organization of glomeruli was observed. Glomerular transient receptor potential channel 6 (TRPC6) expression was studied by immunofluorescence and Western blot. Nuclei nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) activity was analyzed by enzyme-linked immunosorbent assays and electrophoretic mobility shift assay. Pretreatment of 5000 U/kg recombinant human erythropoietin decreased the urine protein (72 hours: 7.82 ± 1.13 g/L vs 11.28 ± 1.73 g/L), serum creatinine (72 hours: 35.0 ± 3.5 μmol/L vs 60.7 ± 7.6 μmol/L), and cystatin-C (2 hours: 336.5 ± 28.2 μg/L vs 452.6 ± 63.8 μg/L) compared with the control group (P Cardiopulmonary bypass induced morphologic abnormalities of podocyte foot processes and slit diaphragms, which was improved by recombinant human erythropoietin. Furthermore, recombinant human erythropoietin significantly relieved glomerular TRPC6 increase and NFATc1 activation induced by cardiopulmonary bypass. Pretreatment of 5000 U/kg recombinant human erythropoietin elicited

  8. Kinetic studies on the activation of human factor X. The role of metal ions on the reaction catalyzed by the venom coagulant protein of Viper russelli.

    Science.gov (United States)

    Morris, S; Robey, F A; Kosow, D P

    1978-07-10

    The effect of Ca2+, Mg2+, and Mn2+ on the initial rate of activation of human Factor X by the venom coagulant protein of Vipera russelli has been investigated. Neither Mg2+ nor Mn2+ alone support the reaction. Ca2+ is an essential activator and exhibits cooperative kinetics. Both Mg2+ and Mn2+ enhance the reaction cooperatively when Ca2+ is present at suboptimal concentrations. Similarly, Ca2+ quenches the intrinsic fluorescence of human Factor X in a cooperative manner. While neither Mg2+ nor Mn2+ by themselves affect the fluorescence of human Factor X, they decrease the cooperativity of the Ca2+ binding to the protein as judged by Hill plots of the Ca2+ -induced fluoresence quenching. EPR measurements indicate that there are three high affinity Mn2+ binding sites on human Factor X which can also bind Ca2+. Positive cooperativity was not observed for Mn2+ binding. These data indicate that Ca2+ can cause a conformational change of the Factor X molecule which allows the activation reaction to proceed. We propose that Mn2+ does not support the activation of human Factor X because it cannot induce a necessary conformational change in the absence of Ca2+.

  9. Human Factors in Training

    Science.gov (United States)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  10. Human Factors in Marine Casualties

    Directory of Open Access Journals (Sweden)

    Jelenko Švetak

    2002-05-01

    Full Text Available Human factors play an important role in the origin of accidents,and it is commonly claimed that between seventy andninety-five percent of industrial and transport accidents involvehuman factors, see Figure 1.Some authorities, however, claim that ultimately, all accidentsinvolve human factors.

  11. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    , and the probable mechanism. Methods: After ... Keywords: Mitochondrial transcription factor A, NF-κB, Hypoxia, Human retinal endothelial cell,. Diabetic retinopathy ..... choice for diabetic retinopathy therapy, as TFAM activity clearly affects the ...

  12. Tissue factor activity and ECM-related gene expression in human aortic endothelial cells grown on electrospun biohybrid scaffolds.

    Science.gov (United States)

    Han, Jingjia; Gerstenhaber, Jonathan A; Lazarovici, Philip; Lelkes, Peter I

    2013-05-13

    All blood vessels are lined with a quiescent endothelium, which aids in regulating regular blood flow and avoiding thrombus formation. Current attempts at replacing diseased blood vessels frequently fail due to the intrinsic thrombogenicity of the materials used as vascular grafts. In extending our previous work where we introduced a new candidate scaffolds for vascular grafts electrospun from a blend solution of PLGA, gelatin, and elastin (PGE), this study aimed to evaluate the potential of PGE scaffolds to support nonthrombogenic monolayers of primary isolates of human aortic endothelial cells (HAECs), as assessed by a combination of biochemical, molecular, and bioinformatics-based analyses. After 24 h of culture on 3-D fibrous PGE scaffolds, HAECs formed a confluent, nonthrombogenic, and physiologically competent monolayer, as assessed by tissue factor (TF) gene expression and protein activity assays. The levels of TF mRNA/protein activity in HAECs grown on PGE scaffolds were similar to those on gelatin or collagen IV-coated 2-D surfaces. In addition, bioinformatics-based analysis of a focused microarray containing 84 ECM-related cDNA probes demonstrated that HAECs essentially expressed a histotypic ECM-related "transcriptome" on PGE scaffolds, where cells were more quiescent than cells cultured on 2-D coverslips coated with gelatin (a well-known "inert" substrate for conventional EC culture), but less so than on 2-D PGE films. These data suggest an important role for nanorough substrates (PGE films) in passivating endothelial cells and confirm the crucial effect of substrate composition in this process. Principal component analysis of microarray data on the above substrates (including collagen IV) implied that substrate composition plays a greater role than surface topography in affecting the endothelial ECM-related "transcriptome". Taken together, our findings suggest that electrospun PGE scaffolds are potentially suitable for application in small diameter

  13. Expression of platelet-derived growth factor and its receptors in normal human liver and during active hepatic fibrogenesis.

    Science.gov (United States)

    Pinzani, M; Milani, S; Herbst, H; DeFranco, R; Grappone, C; Gentilini, A; Caligiuri, A; Pellegrini, G; Ngo, D V; Romanelli, R G; Gentilini, P

    1996-03-01

    Expression of platelet-derived growth factor (PDGF) and its receptor (R) subunits was evaluated in normal human liver and in cirrhotic liver tissue by in situ hybridization and immunohistochemistry. In normal liver, PDGF and PDGF-R subunit expression was limited to a few mesenchymal cells of the portal tract stroma and vessels. In cirrhotic liver, PDGF-A and -B chain mRNA expression was markedly increased and was co-distributed with immunoreactivity for PDGF-AA and -BB in infiltrating inflammatory cells and along vascular structures within fibrous septa. These aspects were paralleled by a marked overexpression of PDGF-R alpha- and beta-subunit mRNAs and of the relative immunoreactivities in a wide range of mesenchymal cells in fibrous septa and in perisinusoidal alpha-smooth-muscle-actin-positive cells. In general expression and distribution of PDGF-R subunits appeared to be related to the activation of different mesenchymal cell types involved in the fibroproliferative process. Therefore, we evaluated the expression of PDGF-R subunits in liver tissue specimens with increasing degrees of necroinflammatory activity. The results of this additional study confirmed that expression of PDGF-R subunits is highly correlated with the severity of histological lesions and collagen deposition. Our results, providing evidence for a functional involvement of PDGF/PDGF-R in liver fibrogenesis, greatly support the results of previous in vitro studies and direct attention toward pharmacological strategies able to affect the series of signaling events arising from the autophosphorylation of PDGF-R subunits.

  14. Characteristics of CR3-mediated aggregation in human eosinophils: effect of priming by platelet-activating factor

    NARCIS (Netherlands)

    Koenderman, L.; Kuijpers, T. W.; Blom, M.; Tool, A. T.; Roos, D.; Verhoeven, A. J.

    1991-01-01

    We have used double-color fluorescence-activated cell sorter analysis to characterize the homotypic aggregation response of human eosinophils (EOs). With this method, we demonstrate for the first time that EOs are able to form stable aggregates. The aggregation response induced by the phorbol ester,

  15. Synthesis of platelet-activating factor by human blood platelets and leucocytes. Evidence against selective utilization of cellular ether-linked phospholipids

    NARCIS (Netherlands)

    Sturk, A.; Schaap, M. C.; Prins, A.; ten Cate, J. W.; van den Bosch, H.

    1989-01-01

    Synthesis of platelet activating factor (PAF) in blood platelet suspensions may be due to leucocyte contamination. We therefore investigated PAF synthesis in human blood platelet suspensions and granulocyte- (PMN)-enriched leucocyte suspensions upon stimulation by thrombin and Ca2+-ionophore A23187,

  16. Factor XII Contact Activation.

    Science.gov (United States)

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-11-01

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  17. Heat shock factor activation in human muscles following a demanding intermittent exercise protocol is attenuated with hyperthermia

    DEFF Research Database (Denmark)

    Palomero, J; Broome, C S; Rasmussen, P

    2008-01-01

    AIM: The present study investigated whether increased activation of heat shock factors (HSF) following exercise relates primarily to the increased muscle temperature or to exercise in general. METHODS: Six subjects completed 40 min of intermittent cycling (15s:15s exercise:recovery at 300 +/- 22 W...

  18. Human conjunctival epithelial cell responses to platelet-activating factor (PAF): signal transduction and release of proinflammatory cytokines.

    Science.gov (United States)

    Sharif, Najam A; Xu, Shouxi; Hellberg, Peggy E; Pang, Iok-Hou; Gamache, Daniel A; Yanni, John M

    2009-06-06

    The aims of the study were to characterize the signal transduction responses to platelet-activating factor (PAF) and to monitor the downstream effects of PAF on the production of proinflammatory cytokines in human conjunctival epithelial cells (HCECs). The generation of inositol phosphates ([(3)H]IPs) from [(3)H]phosphoinositide (PI) hydrolysis and the mobilization of intracellular calcium ([Ca(2+)](i)) were evaluated using ion exchange chromatography and Fura-2 fluorescence techniques, respectively. The production of the cytokines (interleukin-6 [IL-6], interleukin-8 [IL-8], and granulocyte macrophage colony-stimulating factor [GM-CSF]) from PAF-stimulated HCECs was quantified using specific ELISA assays. Specific PAF antagonists were used to study the pharmacological aspects of PAF actions in HCECs. PAF (100 nM) maximally stimulated PI turnover in HCECs by 2.3+/-0.02 fold (n=21) above basal levels and with a potency (EC(50)) of 5.9+/-1.7 nM (n=4). PAF or its stabilized analog, methyl carbamyl (mc)PAF (EC(50)=0.8 nM), rapidly mobilized [Ca(2+)](i), which peaked within 30-60 s and remained elevated for 3 min. PAF (10 nM-1 microM) stimulated the release of the proinflammatory cytokines, IL-6, IL-8, and GM-CSF, 1.4-3.5 fold above basal levels. The effects of PAF (100 nM) on PI turnover and [Ca(2+)](i) were potently antagonized by the PAF antagonists, 1-o-hexadecyl-2-o-acetyl-sn-glycero-3-phospho (N,N,N-trimethyl) hexanolamine (IC(50)=0.69 microM; K(i)=38 nM), methyl 2-(phenylthio)ethyl-1,4-dihydro-2,4,6-trimethyl-pyridine-3,5-dicsrboxylate (PCA-42481; IC(50)=0.89 microM; K(i)=50 nM), rac-3-(N-octadecylcarbomoyl)-2-methoxy) propyl-(2-thiazolioethyl) phosphate (CV-3988; IC(50)=13 microM; K(i)=771 nM), and (+/-)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one HCl (SM-10661; IC(50)=14 microM; K(i)=789 nM [n=3 for each antagonist]). PAF-induced production of IL-6, IL-8, and GM-CSF from HCECs was also blocked by these PAF antagonists (IC(50)=4.6- 8.6 microM). HCECs respond

  19. The impact of platelet-activating factor (PAF)-like mediators on the functional activity of neutrophils: anti-inflammatory effects of human PAF-acetylhydrolase

    NARCIS (Netherlands)

    Kuijpers, T. W.; van den Berg, J. M.; Tool, A. T.; Roos, D.

    2001-01-01

    Platelet-activating factor (PAF) is a proinflammatory agent in infectious and inflammatory diseases, partly due to the activation of infiltrating phagocytes. PAF exerts its actions after binding to a monospecific PAF receptor (PAFR). The potent bioactivity is reflected by its ability to activate

  20. Comparison of anti-pathogenic activities of the human and bovine milk N-glycome: Fucosylation is a key factor.

    Science.gov (United States)

    Wang, Wen-Li; Wang, Wei; Du, Ya-Min; Wu, Hong; Yu, Xiao-Bo; Ye, Ke-Ping; Li, Chun-Bao; Jung, Yong-Sam; Qian, Ying-Juan; Voglmeir, Josef; Liu, Li

    2017-11-15

    Health differences between breast- and formula-fed infants have long been apparent despite great efforts in improving the function of baby formula by adjusting the levels of various milk nutritional components. However, the N-glycome, a type of oligosaccharide decorating a diverse range of proteins, has not been extensively studied in milk regarding its biological function. In this study, the anti-pathogenic function of the enzymatically released human and bovine milk N-glycome against 5 food-borne pathogens was investigated. The human milk N-glycome showed significantly higher activity than bovine milk. After enzymatic defucosylation of human and bovine N-glycan pool, UHPLC peak shifts were observed in both suggesting heavy fucosylation of samples. Furthermore, the anti-pathogenic activity of the defulosylated N-glycome decreased significantly, and the significance of functional difference between the two almost disappeared. This result indicates the essential role of fucosylation for the anti-pathogenic function of the milk N-glycome, especially in human milk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Human Factors Evaluation Mentor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — To obtain valid and reliable data, Human Factors Engineering (HFE) evaluations are currently conducted by people with specialized training and experience in HF. HFE...

  2. Factors affecting aspartase activity.

    Science.gov (United States)

    DEPUE, R H; MOAT, A G

    1961-09-01

    Depue, Robert H. (Hahnemann Medical College, Philadelphia), and Albert G. Moat. Factors affecting aspartase activity. J. Bacteriol. 82:383-386. 1961.-Cells of Escherichia coli grown in a glucose-mineral salts medium contain about one-fifth the amount of aspartase activity observed in cells grown in a yeast extract-peptone medium. The aspartase activity of the cells grown in glucose-salts medium would appear to be too low to provide a mechanism for synthesis of amino groups. Aspartase was purified approximately eightfold by ammonium sulfate precipitation and column chromatography of cell-free extracts. The purified preparation was specific for l-aspartic acid and contained no fumarase activity. A divalent metal ion requirement was demonstrated, this requirement being satisfied by cobaltous or manganous ions. The enzyme activity was found to be dependent upon free sulfhydryl groups. Biotin did not appear to be directly involved in the aspartase reaction since high concentrations of avidin did not alter the reaction rate. The Michaelis constant for aspartase with aspartic acid as substrate was determined to be 0.033 m.

  3. Activation-induced tumor necrosis factor receptor-associated factor 3 (Traf3) alternative splicing controls the noncanonical nuclear factor κB pathway and chemokine expression in human T cells.

    Science.gov (United States)

    Michel, Monika; Wilhelmi, Ilka; Schultz, Astrid-Solveig; Preussner, Marco; Heyd, Florian

    2014-05-09

    The noncanonical nuclear factor κB (ncNFκB) pathway regulates the expression of chemokines required for secondary lymphoid organ formation and thus plays a pivotal role in adaptive immunity. Whereas ncNFκB signaling has been well described in stromal cells and B cells, its role and regulation in T cells remain largely unexplored. ncNFκB activity critically depends on the upstream NFκB-inducing kinase (NIK). NIK expression is negatively regulated by the full-length isoform of TNF receptor-associated factor 3 (Traf3) as formation of a NIK-Traf3-Traf2 complex targets NIK for degradation. Here we show that T cell-specific and activation-dependent alternative splicing generates a Traf3 isoform lacking exon 8 (Traf3DE8) that, in contrast to the full-length protein, activates ncNFκB signaling. Traf3DE8 disrupts the NIK-Traf3-Traf2 complex and allows accumulation of NIK to initiate ncNFκB signaling in activated T cells. ncNFκB activity results in expression of several chemokines, among them B cell chemoattractant (CxCL13), both in a model T cell line and in primary human CD4(+) T cells. Because CxCL13 plays an important role in B cell migration and activation, our data suggest an involvement and provide a mechanistic basis for Traf3 alternative splicing and ncNFκB activation in contributing to T cell-dependent adaptive immunity.

  4. Epidermal growth factor-like domain 7 promotes migration and invasion of human trophoblast cells through activation of MAPK, PI3K and NOTCH signaling pathways.

    Science.gov (United States)

    Massimiani, M; Vecchione, L; Piccirilli, D; Spitalieri, P; Amati, F; Salvi, S; Ferrazzani, S; Stuhlmann, H; Campagnolo, L

    2015-05-01

    Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Polyphosphate accelerates factor V activation by factor XIa.

    Science.gov (United States)

    Choi, Sharon H; Smith, Stephanie A; Morrissey, James H

    2015-03-01

    Factor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532-1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.

  6. Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor

    Directory of Open Access Journals (Sweden)

    Manetta J

    2014-08-01

    Full Text Available Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF

  7. Amadori adducts activate nuclear factor-kappaB-related proinflammatory genes in cultured human peritoneal mesothelial cells.

    Science.gov (United States)

    Nevado, Julián; Peiró, Concepción; Vallejo, Susana; El-Assar, Mariam; Lafuente, Nuria; Matesanz, Nuria; Azcutia, Verónica; Cercas, Elena; Sánchez-Ferrer, Carlos F; Rodríguez-Mañas, Leocadio

    2005-09-01

    Diabetes mellitus leads to a high incidence of several so-called complications, sharing similar pathophysiological features in several territories. Previous reports points at early nonenzymatic glycosylation products (Amadori adducts) as mediators of diabetic vascular complications. In the present study, we analysed a possible role for Amadori adducts as stimulators of proinflammatory pathways in human peritoneal mesothelial cells (HPMCs). Cultured HPMCs isolated from 13 different patients (mean age 38.7+/-16 years) were exposed to different Amadori adducts, that is, highly glycated haemoglobin (10 nM) and glycated bovine serum albumin (0.25 mg ml(-1)), as well as to their respective low glycosylation controls. Amadori adducts, but not their respective controls, elicited a marked increase of NF-kappaB activation, as determined by electromobility shift assays and transient transfection experiments. Additionally, Amadori adducts significantly increased the production of NF-kappaB-related proinflammatory molecules, including cytokines, such as TNF-alpha, IL-1beta or IL-6, and enzymes, such as cyclooxygenase-2 and inducible nitric oxide (NO) synthase, this latter leading to the release of NO by HPMCs. The effects of Amadori adducts were mediated by different reactive oxygen and nitrosative species (e.g. superoxide anions, hydroxyl radicals, and peroxynitrite), as they were blunted by coincubation with the appropriate scavengers. Furthermore, NO generated upon exposure to Amadori adducts further stimulated NF-kappaB activation, either directly or after combination with superoxide anions to form peroxynitrite. We conclude that Amadori adducts can favour peritoneal inflammation by exacerbating changes in NO synthesis pathway and triggering NF-kappaB-related proinflammatory signals in human mesothelial cells.

  8. Amadori adducts activate nuclear factor-κB-related proinflammatory genes in cultured human peritoneal mesothelial cells

    Science.gov (United States)

    Nevado, Julián; Peiró, Concepción; Vallejo, Susana; El-Assar, Mariam; Lafuente, Nuria; Matesanz, Nuria; Azcutia, Veronica; Cercas, Elena; Sánchez-Ferrer, Carlos F; Rodríguez-Mañas, Leocadio

    2005-01-01

    Diabetes mellitus leads to a high incidence of several so-called complications, sharing similar pathophysiological features in several territories. Previous reports points at early nonenzymatic glycosylation products (Amadori adducts) as mediators of diabetic vascular complications. In the present study, we analysed a possible role for Amadori adducts as stimulators of proinflammatory pathways in human peritoneal mesothelial cells (HPMCs). Cultured HPMCs isolated from 13 different patients (mean age 38.7±16 years) were exposed to different Amadori adducts, that is, highly glycated haemoglobin (10 nM) and glycated bovine serum albumin (0.25 mg ml−1), as well as to their respective low glycosylation controls. Amadori adducts, but not their respective controls, elicited a marked increase of NF-κB activation, as determined by electromobility shift assays and transient transfection experiments. Additionally, Amadori adducts significantly increased the production of NF-κB-related proinflammatory molecules, including cytokines, such as TNF-α, IL-1β or IL-6, and enzymes, such as cyclooxygenase-2 and inducible nitric oxide (NO) synthase, this latter leading to the release of NO by HPMCs. The effects of Amadori adducts were mediated by different reactive oxygen and nitrosative species (e.g. superoxide anions, hydroxyl radicals, and peroxynitrite), as they were blunted by coincubation with the appropriate scavengers. Furthermore, NO generated upon exposure to Amadori adducts further stimulated NF-κB activation, either directly or after combination with superoxide anions to form peroxynitrite. We conclude that Amadori adducts can favour peritoneal inflammation by exacerbating changes in NO synthesis pathway and triggering NF-κB-related proinflammatory signals in human mesothelial cells. PMID:15997235

  9. Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B

    Science.gov (United States)

    Wäster, P; Rosdahl, I; Öllinger, K

    2014-01-01

    Summary Background Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation. Objectives To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes. Methods Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied. Results UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis. Conclusions We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression. What's already known about this topic? Melanocytes are the target cells of ultraviolet (UV) irradiation, and the cells from which melanoma originates. The mitogen-activated protein kinase signalling pathway is important for regulation of UV-induced cellular responses. Previous studies have strongly implicated the transcription factors

  10. β-Catenin-independent activation of TCF1/LEF1 in human hematopoietic tumor cells through interaction with ATF2 transcription factors.

    Directory of Open Access Journals (Sweden)

    Luca Grumolato

    Full Text Available The role of Wnt signaling in embryonic development and stem cell maintenance is well established and aberrations leading to the constitutive up-regulation of this pathway are frequent in several types of human cancers. Upon ligand-mediated activation, Wnt receptors promote the stabilization of β-catenin, which translocates to the nucleus and binds to the T-cell factor/lymphoid enhancer factor (TCF/LEF family of transcription factors to regulate the expression of Wnt target genes. When not bound to β-catenin, the TCF/LEF proteins are believed to act as transcriptional repressors. Using a specific lentiviral reporter, we identified hematopoietic tumor cells displaying constitutive TCF/LEF transcriptional activation in the absence of β-catenin stabilization. Suppression of TCF/LEF activity in these cells mediated by an inducible dominant-negative TCF4 (DN-TCF4 inhibited both cell growth and the expression of Wnt target genes. Further, expression of TCF1 and LEF1, but not TCF4, stimulated TCF/LEF reporter activity in certain human cell lines independently of β-catenin. By a complementary approach in vivo, TCF1 mutants, which lacked the ability to bind to β-catenin, induced Xenopus embryo axis duplication, a hallmark of Wnt activation, and the expression of the Wnt target gene Xnr3. Through generation of different TCF1-TCF4 fusion proteins, we identified three distinct TCF1 domains that participate in the β-catenin-independent activity of this transcription factor. TCF1 and LEF1 physically interacted and functionally synergized with members of the activating transcription factor 2 (ATF2 family of transcription factors. Moreover, knockdown of ATF2 expression in lymphoma cells phenocopied the inhibitory effects of DN-TCF4 on the expression of target genes associated with the Wnt pathway and on cell growth. Together, our findings indicate that, through interaction with ATF2 factors, TCF1/LEF1 promote the growth of hematopoietic malignancies in the

  11. Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

    Science.gov (United States)

    Vandomme, Jerome; Touil, Yasmine; Ostyn, Pauline; Olejnik, Cecile; Flamenco, Pilar; El Machhour, Raja; Segard, Pascaline; Masselot, Bernadette; Bailliez, Yves; Formstecher, Pierre

    2014-01-01

    Dental pulp stem cells (DPSCs) remain quiescent until activated in response to severe dental pulp damage. Once activated, they exit quiescence and enter regenerative odontogenesis, producing reparative dentin. The factors and signaling molecules that control the quiescence/activation and commitment to differentiation of human DPSCs are not known. In this study, we determined that the inhibition of insulin-like growth factor 1 receptor (IGF-1R) and p38 mitogen-activated protein kinase (p38 MAPK) signaling commonly activates DPSCs and promotes their exit from the G0 phase of the cell cycle as well as from the pyronin Ylow stem cell compartment. The inhibition of these two pathways, however, inversely determines DPSC fate. In contrast to p38 MAPK inhibitors, IGF-1R inhibitors enhance dental pulp cell sphere-forming capacity and reduce the cells' colony-forming capacity without inducing cell death. The inverse cellular changes initiated by IGF-1R and p38 MAPK inhibitors were accompanied by inverse changes in the levels of active signal transducer and activator of transcription 3 (STAT3) factor, inactive glycogen synthase kinase 3, and matrix extracellular phosphoglycoprotein, a marker of early odontoblast differentiation. Our data suggest that there is cross talk between the IGF-1R and p38 MAPK signaling pathways in DPSCs and that the signals provided by these pathways converge at STAT3 and inversely regulate its activity to maintain quiescence or to promote self-renewal and differentiation of the cells. We propose a working model that explains the possible interactions between IGF-1R and p38 MAPK at the molecular level and describes the cellular consequences of these interactions. This model may inspire further fundamental study and stimulate research on the clinical applications of DPSC in cellular therapy and tissue regeneration. PMID:24266654

  12. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  13. Human factors in automotive innovation

    NARCIS (Netherlands)

    Terken, J.; Ham, J.; Hoedemaeker, M.

    2011-01-01

    Many automotive innovations affect the driver's task and/or the driving experience. In this paper we argue that successful innovation in these cases requires that due attention is given to Human Factors issues in the course of the innovation process. We support this claim by examples from several

  14. Human factors in software development

    Energy Technology Data Exchange (ETDEWEB)

    Curtis, B.

    1986-01-01

    This book presents an overview of ergonomics/human factors in software development, recent research, and classic papers. Articles are drawn from the following areas of psychological research on programming: cognitive ergonomics, cognitive psychology, and psycholinguistics. Topics examined include: theoretical models of how programmers solve technical problems, the characteristics of programming languages, specification formats in behavioral research and psychological aspects of fault diagnosis.

  15. Human factors and team performance

    NARCIS (Netherlands)

    Haerkens, M.H.T.M.

    2017-01-01

    Despite modern equipment, increasing emphasis on patient safety, and excellent training facilities medical care frequently results in unintentional harm to patients. Human Factors (HF) appear to play an important role in adverse events, especially in high risk clinical departments. A sound safety

  16. Use of activated recombinant human factor VII (rhFVIIa) for colonic polypectomies in patients with cirrhosis and coagulopathy.

    Science.gov (United States)

    Anantharaju, Abhinandana; Mehta, Kapil; Mindikoglu, Ayse L; Van Thiel, David H

    2003-07-01

    The prevalence of colonic polyps in patients with cirrhosis appears to be higher than that of the general population. The current practice for a polypectomy in a coagulopathic cirrhotic patient involves the reversal of the coagulopathy using fresh frozen plasma (FFP) prior to the polypectomy, usually at a second colonoscopy. The use of FFP is associated with many problems, particularly that of volume overload. Here we report four cases with advanced cirrhosis and severe coagulopathy that underwent polypectomies by snare cautery after an intravenous bolus infusion of recombinant human factor VIIa (rhFVIIa). The dose used was 120 microg/kg, which provided normalization of the coagulation parameters for 10-16 hr. The immediate use of rhFVIIa reduced the utilization of resources and enabled the performance of the polypectomies at the initial colonoscopy. No postpolypectomy bleeding was noted. The high cost of the drug is the only obstacle to a wider use of rhFVIIa for this purpose. The cost of the drug, however, is offset substantially by the cost of hospitalization for the administration of FFP, the cost of a second colonoscopy, and the charges associated with a second utilization of the endoscopy suite.

  17. Expression of a fusion protein of human ciliary neurotrophic factor and soluble CNTF-receptor and identification of its activity.

    Science.gov (United States)

    Sun, Yi; Pia, März; Uwe, Otten; Ge, Ji-Guang; Stefan, Rose-John

    2003-01-01

    Ciliary neurotrophic factor (CNTF) has pleiotropic actions on many neuronal populations as well as on glia. Signal transduction by CNTF requires that it bind first to CNTF-R, permitting the recruitment of gp130 and LIF-R, forming a tripartite receptor complex. Cells that only express gp130 and LIF-R, but not CNTF-R are refractory to stimulation by CNTF. On many target cells CNTF only acts in the presence of its specific agonistic soluble receptors. We engineered a soluble fusion protein by linking the COOH-terminus of sCNTF-R to the NH2-terminus of CNTF. Recombinant CNTF/sCNTF-R fusion protein (Hyper-CNTF) was successfully expressed in COS-7 cells. The apparent molecular mass of the Hyper-CNTF protein was estimated from western blots to be 75 kDa. Proliferation assays of transfected BAF/3 cells in response to CNTF and Hyper-CNTF were used to verify the activity of the cytokines. The proliferative results confirmed that CNTF required homodimerization of the gp130, CNTF-R and LIF-R receptor subunit whereas Hyper-CNTF required heterodimerization of the gp130 and LIF-R receptor subunit. We concluded that the fusion protein Hyper-CNTF had superagonistic activity on target cells expressing gp130 and LIF-R, but lacking membrane-bound CNTF-R.

  18. AMPK activation represses the human gene promoter of the cardiac isoform of acetyl-CoA carboxylase: Role of nuclear respiratory factor-1

    Energy Technology Data Exchange (ETDEWEB)

    Adam, Tasneem; Opie, Lionel H. [Hatter Cardiovascular Research Institute, Faculty of Health Sciences, University of Cape Town, Observatory 7925 (South Africa); Essop, M. Faadiel, E-mail: mfessop@sun.ac.za [Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch 7600 (South Africa)

    2010-07-30

    Research highlights: {yields} AMPK inhibits acetyl-CoA carboxylase beta gene promoter activity. {yields} Nuclear respiratory factor-1 inhibits acetyl-CoA carboxylase beta promoter activity. {yields} AMPK regulates acetyl-CoA carboxylase beta at transcriptional level. -- Abstract: The cardiac-enriched isoform of acetyl-CoA carboxylase (ACC{beta}) produces malonyl-CoA, a potent inhibitor of carnitine palmitoyltransferase-1. AMPK inhibits ACC{beta} activity, lowering malonyl-CoA levels and promoting mitochondrial fatty acid {beta}-oxidation. Previously, AMPK increased promoter binding of nuclear respiratory factor-1 (NRF-1), a pivotal transcriptional modulator controlling gene expression of mitochondrial proteins. We therefore hypothesized that NRF-1 inhibits myocardial ACC{beta} promoter activity via AMPK activation. A human ACC{beta} promoter-luciferase construct was transiently transfected into neonatal cardiomyocytes {+-} a NRF-1 expression construct. NRF-1 overexpression decreased ACC{beta} gene promoter activity by 71 {+-} 4.6% (p < 0.001 vs. control). Transfections with 5'-end serial promoter deletions revealed that NRF-1-mediated repression of ACC{beta} was abolished with a pPII{beta}-18/+65-Luc deletion construct. AMPK activation dose-dependently reduced ACC{beta} promoter activity, while NRF-1 addition did not further decrease it. We also investigated NRF-1 inhibition in the presence of upstream stimulatory factor 1 (USF1), a known transactivator of the human ACC{beta} gene promoter. Here NRF-1 blunted USF1-dependent induction of ACC{beta} promoter activity by 58 {+-} 7.5% (p < 0.001 vs. control), reversed with a dominant negative NRF-1 construct. NRF-1 also suppressed endogenous USF1 transcriptional activity by 55 {+-} 6.2% (p < 0.001 vs. control). This study demonstrates that NRF-1 is a novel transcriptional inhibitor of the human ACC{beta} gene promoter in the mammalian heart. Our data extends AMPK regulation of ACC{beta} to the transcriptional level.

  19. Human Factors in Space Exploration

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    The exploration of space is one of the most fascinating domains to study from a human factors perspective. Like other complex work domains such as aviation (Pritchett and Kim, 2008), air traffic management (Durso and Manning, 2008), health care (Morrow, North, and Wickens, 2006), homeland security (Cooke and Winner, 2008), and vehicle control (Lee, 2006), space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts (Perrow, 1999; Woods et ai, 1994). Nearly the entire gamut of human factors issues - for example, human-automation interaction (Sheridan and Parasuraman, 2006), telerobotics, display and control design (Smith, Bennett, and Stone, 2006), usability, anthropometry (Chaffin, 2008), biomechanics (Marras and Radwin, 2006), safety engineering, emergency operations, maintenance human factors, situation awareness (Tenney and Pew, 2006), crew resource management (Salas et aI., 2006), methods for cognitive work analysis (Bisantz and Roth, 2008) and the like -- are applicable to astronauts, mission control, operational medicine, Space Shuttle manufacturing and assembly operations, and space suit designers as they are in other work domains (e.g., Bloomberg, 2003; Bos et al, 2006; Brooks and Ince, 1992; Casler and Cook, 1999; Jones, 1994; McCurdy et ai, 2006; Neerincx et aI., 2006; Olofinboba and Dorneich, 2005; Patterson, Watts-Perotti and Woods, 1999; Patterson and Woods, 2001; Seagull et ai, 2007; Sierhuis, Clancey and Sims, 2002). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on sorne of the latest research results as well as the latest challenges still facing the field.

  20. The role of caspase 3 and BclxL in the action of interleukin 7 (IL-7): a survival factor in activated human T cells

    DEFF Research Database (Denmark)

    Amos, C L; Woetmann, A; Nielsen, M

    1998-01-01

    The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL-2)-dependent, activated, primary, human T lymphocytes (hT cells) was examined. IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mitogen in these T ...... of apoptosis. A clear role for IL-7 as a survival factor for cytokine withdrawal and glucocorticoid induced apoptosis in activated primary hT cells is implicated. In addition, regulation of BclxL and downstream inhibition of Caspase 3 activity may mediate this rescue signal.......The effects of interleukin 7 (IL-7) on apoptosis in interleukin 2 (IL-2)-dependent, activated, primary, human T lymphocytes (hT cells) was examined. IL-7 (like IL-2) rescued cells from apoptosis, as measured by their cellular DNA profile and fragmentation. IL-2 also acted as a mitogen in these T...... 23-kDa band, which was recognized by the anti-Bc1-2 antibody, was induced by dexamthasone and suppressed by IL-7 and IL-2. This protein was subject to independent regulation as compared to the p26 Bc1-2 protein, suggesting that it may be a novel factor, possibly involved in the regulation...

  1. Activation of CD40 by soluble recombinant human CD40 ligand inhibits human glioma cells proliferation via nuclear factor-κB signaling pathway.

    Science.gov (United States)

    Zhang, Yong; Huang, Tao; Hu, Yi; Wang, Yu

    2012-10-01

    As CD40 transduces activation signals involved in inflammatory and immune disorders, we explored the expression and response to CD40 engagement in human glioma cell lines in this study. The CD40 expression in BT-325 and U251 cells was flow cytometrically detected. The cells were incubated with srhCD40L for 72 h to assess its effects on cell growth in vitro. TNF-α expression was quantified by real-time PCR, and protein expression was analyzed by ELISA. The I-κb mRNA was detected by RT-PCR. I-κB expression decreased after stimulation with 1 μg/mL srhCD40L, but it was upregulated after the cells were pretreated with CD40 antibody. srhCD40L significantly inhibited the proliferation of the CD40+ human glioma cells. The stimulation of CD40+ glioma cells with soluble CD40L (CD154) up-regulated the expression of TNF-α at both mRNA and protein levels. We are led to conclude that CD40L/CD40 could inhibit human glioma cells through I-κb signaling pathway. Interferon-γ can augment CD40 expression and the inhibitory effect of CD40 ligand on cell growth in vitro. These results suggest that srhCD40L may benefit the therapy strategy of glioma.

  2. Transcription factor-induced activation of cardiac gene expression in human c-kit+ cardiac progenitor cells.

    Directory of Open Access Journals (Sweden)

    Tareq Al-Maqtari

    Full Text Available Although transplantation of c-kit+ cardiac progenitor cells (CPCs significantly alleviates post-myocardial infarction left ventricular dysfunction, generation of cardiomyocytes by exogenous CPCs in the recipient heart has often been limited. Inducing robust differentiation would be necessary for improving the efficacy of the regenerative cardiac cell therapy. We assessed the hypothesis that differentiation of human c-kit+ CPCs can be enhanced by priming them with cardiac transcription factors (TFs. We introduced five different TFs (Gata4, MEF2C, NKX2.5, TBX5, and BAF60C into CPCs, either alone or in combination, and then examined the expression of marker genes associated with the major cardiac cell types using quantitative RT-PCR. When introduced individually, Gata4 and TBX5 induced a subset of myocyte markers. Moreover, Gata4 alone significantly induced smooth muscle cell and fibroblast markers. Interestingly, these gene expression changes brought by Gata4 were also accompanied by morphological changes. In contrast, MEF2C and NKX2.5 were largely ineffective in initiating cardiac gene expression in CPCs. Surprisingly, introduction of multiple TFs in different combinations mostly failed to act synergistically. Likewise, addition of BAF60C to Gata4 and/or TBX5 did not further potentiate their effects on cardiac gene expression. Based on our results, it appears that GATA4 is able to potentiate gene expression programs associated with multiple cardiovascular lineages in CPCs, suggesting that GATA4 may be effective in priming CPCs for enhanced differentiation in the setting of stem cell therapy.

  3. A direct thrombin inhibitor suppresses protein C activation and factor Va degradation in human plasma: Possible mechanisms of paradoxical enhancement of thrombin generation.

    Science.gov (United States)

    Kamisato, Chikako; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2016-05-01

    We have demonstrated that antithrombin (AT)-independent thrombin inhibitors paradoxically increase thrombin generation (TG) in human plasma in a thrombomodulin (TM)- and protein C (PC)-dependent manner. We determined the effects of AT-independent thrombin inhibitors on the negative-feedback system, activation of PC and production and degradation of factor Va (FVa), as possible mechanisms underlying the paradoxical enhancement of TG. TG in human plasma containing 10nM TM was assayed by means of the calibrated automated thrombography. As an index of PC activation, plasma concentration of activated PC-PC inhibitor complex (aPC-PCI) was measured. The amounts of FVa heavy chain and its degradation product (FVa(307-506)) were examined by western blotting. AT-independent thrombin inhibitors, melagatran and dabigatran (both at 25-600nM) and 3-30μg/ml active site-blocked thrombin (IIai), increased peak levels of TG. Melagatran, dabigatran and IIai significantly decreased plasma concentration of aPC-PCI complex at 25nM or more, 75nM or more, and 10 and 30μg/ml, respectively. Melagatran (300nM) significantly increased FVa and decreased FVa(307-506). In contrast, a direct factor Xa inhibitor edoxaban preferentially inhibited thrombin generation (≥25nM), and higher concentrations were required to inhibit PC activation (≥150nM) and FVa degradation (300nM). The present study suggests that the inhibitions of protein C activation and subsequent degradation of FVa and increase in FVa by antithrombin-independent thrombin inhibitors may contribute to the paradoxical TG enhancement, and edoxaban may inhibit PC activation and FVa degradation as a result of TG suppression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Space operations and the human factor

    Science.gov (United States)

    Brody, Adam R.

    1993-10-01

    Although space flight does not put the public at high risk, billions of dollars in hardware are destroyed and the space program halted when an accident occurs. Researchers are therefore applying human-factors techniques similar to those used in the aircraft industry, albeit at a greatly reduced level, to the spacecraft environment. The intent is to reduce the likelihood of catastrophic failure. To increase safety and efficiency, space human factors researchers have simulated spacecraft docking and extravehicular activity rescue. Engineers have also studied EVA suit mobility and aids. Other basic human-factors issues that have been applied to the space environment include antropometry, biomechanics, and ergonomics. Workstation design, workload, and task analysis currently receive much attention, as do habitability and other aspects of confined environments. Much work also focuses on individual payloads, as each presents its own complexities.

  5. Ketamine inhibits transcription factors activator protein 1 and nuclear factor-kappaB, interleukin-8 production, as well as CD11b and CD16 expression: studies in human leukocytes and leukocytic cell lines.

    Science.gov (United States)

    Welters, Ingeborg D; Hafer, Georg; Menzebach, Axel; Mühling, Jörg; Neuhäuser, Christoph; Browning, Paul; Goumon, Yannick

    2010-03-01

    Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription factors activator protein 1 (AP-1) and nuclear factor-kappaB (NF-kappaB) in human leukocyte-like cell lines and in human blood neutrophils. Electric mobility shift assays were used to investigate ketamine's effects on nuclear binding activity of both transcription factors in U937 cells, and a whole blood flow cytometric technique was used for AP-1 and NF-kappaB determination in leukocytes. Cell lines with different expression patterns of opioid and N-methyl-D-aspartate receptors were used for reverse transcription-polymerase chain reaction to investigate receptors involved in ketamine signaling. Ketamine's effect on interleukin-8 production was assessed in a whole blood assay. Ketamine inhibited both transcription factors in a concentration-dependent manner. These effects did not depend on opiate or N-methyl-D-aspartate receptors. Ketamine also reduced interleukin-8 production in whole blood and expression of CD11b and CD16 on neutrophils. The immunoinhibitory effects of ketamine are at least in part caused by inhibition of transcription factors NF-kappaB and AP-1, which regulate production of proinflammatory mediators. However, signaling mechanisms different from those present in the central nervous system are responsible for ketamine-mediated immunomodulation.

  6. Effects of rupatadine, a new dual antagonist of histamine and platelet-activating factor receptors, on human cardiac Kv1.5 channels

    OpenAIRE

    Caballero, Ricardo; Valenzuela, Carmen; Longobardo, Mónica; Tamargo, Juan; Delpón, Eva

    1999-01-01

    The effects of rupatadine, a new dual antagonist of both histamine H1 and platelet-activating factor receptors, were studied on human cloned hKv1.5 channels expressed in Ltk− cells using the whole-cell patch-clamp technique.Rupatadine produced a use- and concentration-dependent block of hKv1.5 channels (KD=2.4±0.7 μM) and slowed the deactivation of the tail currents, thus inducing the ‘crossover' phenomenon.Rupatadine-induced block was voltage-dependent increasing in the voltage range for cha...

  7. Effects of interferon-γ and granulocyte colony-stimulating factor on antifungal activity of human polymorphonuclear neutrophils against Candida albicans grown as biofilms or planktonic cells.

    Science.gov (United States)

    Katragkou, Alphaspasia; Simitsopoulou, Maria; Chatzimoschou, Athanasios; Georgiadou, Elpiniki; Walsh, Thomas J; Roilides, Emmanuel

    2011-09-01

    Candida albicans is a leading cause of biofilm-related infections. As Candida biofilms are recalcitrant to host defenses, we sought to determine the effects of interferon-γ and granulocyte colony-stimulating factor, two pro-inflammatory cytokines, on the antifungal activities of human polymorphonuclear neutrophils (PMNs) against C. albicans biofilms, using an in vitro biofilm model. Priming of PMNs by these cytokines augmented fungal damage of planktonic cells; however, priming of PMNs did not have the same effect against Candida biofilms. Biofilm phenotype appears to play an important role in protecting C. albicans from the innate immune system. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Factor XIII and tranexamic acid but not recombinant factor VIIa attenuate tissue plasminogen activator-induced hyperfibrinolysis in human whole blood.

    Science.gov (United States)

    Dirkmann, Daniel; Görlinger, Klaus; Gisbertz, Caroline; Dusse, Fabian; Peters, Jürgen

    2012-06-01

    Hyperfibrinolysis is a pathological state that often results in depletion of coagulation factors and platelets and can contribute to bleeding. Factor XIII (FXIII) and thrombin activatable fibrinolysis inhibitor have key roles in protecting clots against fibrinolysis. We tested the hypotheses that FXIII concentrate, prothrombin complex concentrate (PCC), recombinant factor VIIa (rFVIIa), and tranexamic acid (TA) inhibit fibrinolysis to different degrees, and that platelets contribute to antifibrinolysis. Hyperfibrinolysis was induced by addition of recombinant tissue plasminogen activator (r-tPA) (final concentration: 100 ng · mL(-1)) to citrated whole blood obtained from 13 healthy volunteers. To assess inhibition of fibrinolysis, we added to the assays FXIII-A(2)B(2) (0.42 U · mL(-1)), PCC (0.42 U · mL(-1)), rFVIIa (final concentration: 1.6 μg · mL(-1)), TA (final concentration: 0.33 mg · mL(-1)), or saline. Coagulation was analyzed by rotational thromboelastometry (ROTEM®) using the clot lysis index (CLI) after 45 and 60 minutes in extrinsically activated assays, with (FIBTEM®) and without (EXTEM®) inhibition of platelet function by cytochalasin D. After r-tPA-evoked fibrinolysis (CLI45: median 78%; 72/85.5, 25th/75th percentile), FXIII (90%; 82.5/96, P = 0.025), PCC (89%; 74/91, P = 0.0465), and TA (94%; 92/96, P = 0.001) but not rFVIIa (79%; 72/86.5, P = 1.0) significantly attenuated the decrease in CLI. Similarly, CLI60 increased only with FXIII (66%; 33/90.5, P = 0.017) and TA (90%; 89/92, P = 0.001) compared with r-tPA alone (21%; 7/59). After abolition of platelet function by cytochalasin D, only TA (95%; 89/97.5, P = 0.0025) and PCC (84%; 70.5/90, P = 0.0305) but not FXIII or rFVIIa significantly increased CLI45 and CLI60 (TA: 89%; 84.5/96, P = 0.01 and PCC: 55%; 29.5/60, P = 0.0405) compared with r-tPA alone (CLI45: 59%; 40.5/72.5 and CLI60: 10%; 0/30). In thromboelastometric assays using whole blood, only TA, FXIII, and PCC significantly

  9. Human factors and team performance

    OpenAIRE

    Haerkens, M.H.T.M.

    2017-01-01

    Despite modern equipment, increasing emphasis on patient safety, and excellent training facilities medical care frequently results in unintentional harm to patients. Human Factors (HF) appear to play an important role in adverse events, especially in high risk clinical departments. A sound safety climate is considered essential, as it is positively related to safety outcomes. This thesis focused on HF and critical team performance in clinical medicine. First, an overview of existing literatur...

  10. Human factors in waste management

    Energy Technology Data Exchange (ETDEWEB)

    Moray, N. [Univ. of Illinois, Urbana, IL (United States)

    1994-10-01

    This article examines the role of human factors in radioactive waste management. Although few problems and ergonomics are special to radioactive waste management, some problems are unique especially with long term storage. The entire sociotechnical system must be looked at in order to see where improvement can take place because operator errors, as seen in Chernobyl and Bhopal, are ultimately the result of management errors.

  11. Protein extract of ultraviolet-irradiated human skin keratinocytes promote the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and 4.

    Science.gov (United States)

    Wang, Xiao-Yong; Tao, Cheng-Jun; Wu, Qiao-Yun; Yuan, Cheng-Da

    2013-02-01

    In this study, we investigated whether the protein extract of ultraviolet-irradiated human skin keratinocytes can activate Toll-like receptor 2 and Toll-like receptor 4 of Langerhans cells and induce the downstream gene expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3. The protein expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells and the protein expression of HSP60, HSP70 and β-defensin 2 in keratinocytes were examined using Western blot analysis. Langerhans cells were pretreated with or without Toll-like receptor 2 and Toll-like receptor 4 siRNA. We found that the protein extract of ultraviolet-irradiated keratinocytes upregulated the expression of mitogen-activated protein kinases, nuclear factor-κB and interferon regulatory factor-3 in Langerhans cells via Toll-like receptor 2 and Toll-like receptor 4. We also found that ultraviolet radiation upregulated the expression HSP60, HSP70 and β-defensin 2 in keratinocytes. Our previous study demonstrated that ultraviolet radiation upregulated Toll-like receptor 2 and Toll-like receptor 4 expression in Langerhans cells. Ultraviolet radiation also upregulated mitogen-activated protein kinases and nuclear factor-κB/p65 expression via Toll-like receptor 2 and Toll-like receptor 4, and upregulated interferon regulatory factor-3 expression partially via Toll-like receptor 4. So we conclude that ultraviolet radiation can directly or indirectly activate keratinocytes to induce endogenous ligands which stimulate Toll-like receptor 2- or Toll-like receptor 4-dependent signaling cascade in Langerhans cells, sequentially influence innate and adaptive immune responses. © 2013 John Wiley & Sons A/S.

  12. Growth Factor-Activated Stem Cell Circuits and Stromal Signals Cooperatively Accelerate Non-Integrated iPSC Reprogramming of Human Myeloid Progenitors

    Science.gov (United States)

    Park, Tea Soon; Huo, Jeffrey S.; Peters, Ann; Talbot, C. Conover; Verma, Karan; Zimmerlin, Ludovic; Kaplan, Ian M.; Zambidis, Elias T.

    2012-01-01

    Nonviral conversion of skin or blood cells into clinically useful human induced pluripotent stem cells (hiPSC) occurs in only rare fractions (∼0.001%–0.5%) of donor cells transfected with non-integrating reprogramming factors. Pluripotency induction of developmentally immature stem-progenitors is generally more efficient than differentiated somatic cell targets. However, the nature of augmented progenitor reprogramming remains obscure, and its potential has not been fully explored for improving the extremely slow pace of non-integrated reprogramming. Here, we report highly optimized four-factor reprogramming of lineage-committed cord blood (CB) myeloid progenitors with bulk efficiencies of ∼50% in purified episome-expressing cells. Lineage-committed CD33+CD45+CD34− myeloid cells and not primitive hematopoietic stem-progenitors were the main targets of a rapid and nearly complete non-integrated reprogramming. The efficient conversion of mature myeloid populations into NANOG+TRA-1-81+ hiPSC was mediated by synergies between hematopoietic growth factor (GF), stromal activation signals, and episomal Yamanaka factor expression. Using a modular bioinformatics approach, we demonstrated that efficient myeloid reprogramming correlated not to increased proliferation or endogenous Core factor expressions, but to poised expression of GF-activated transcriptional circuits that commonly regulate plasticity in both hematopoietic progenitors and embryonic stem cells (ESC). Factor-driven conversion of myeloid progenitors to a high-fidelity pluripotent state was further accelerated by soluble and contact-dependent stromal signals that included an implied and unexpected role for Toll receptor-NFκB signaling. These data provide a paradigm for understanding the augmented reprogramming capacity of somatic progenitors, and reveal that efficient induced pluripotency in other cell types may also require extrinsic activation of a molecular framework that commonly regulates self

  13. The Testicular and Epididymal Expression Profile of PLCζ in Mouse and Human Does Not Support Its Role as a Sperm-Borne Oocyte Activating Factor

    Science.gov (United States)

    Aarabi, Mahmoud; Yu, Yang; Xu, Wei; Tse, Man Y.; Pang, Stephen C.; Yi, Young-Joo; Sutovsky, Peter; Oko, Richard

    2012-01-01

    Phospholipase C zeta (PLCζ) is a candidate sperm-borne oocyte activating factor (SOAF) which has recently received attention as a potential biomarker of human male infertility. However, important SOAF attributes of PLCζ, including its developmental expression in mammalian spermiogenesis, its compartmentalization in sperm head perinuclear theca (PT) and its release into the ooplasm during fertilization have not been established and are addressed in this investigation. Different detergent extractions of sperm and head/tail fractions were compared for the presence of PLCζ by immunoblotting. In both human and mouse, the active isoform of PLCζ was detected in sperm fractions other than PT, where SOAF is expected to reside. Developmentally, PLCζ was incorporated as part of the acrosome during the Golgi phase of human and mouse spermiogenesis while diminishing gradually in the acrosome of elongated spermatids. Immunofluorescence localized PLCζ over the surface of the postacrosomal region of mouse and bull and head region of human spermatozoa leading us to examine its secretion in the epididymis. While previously thought to have strictly a testicular expression, PLCζ was found to be expressed and secreted by the epididymal epithelial cells explaining its presence on the sperm head surface. In vitro fertilization (IVF) revealed that PLCζ is no longer detectable after the acrosome reaction occurs on the surface of the zona pellucida and thus is not incorporated into the oocyte cytoplasm for activation. In summary, we show for the first time that PLCζ is compartmentalized as part of the acrosome early in human and mouse spermiogenesis and is secreted during sperm maturation in the epididymis. Most importantly, no evidence was found that PLCζ is incorporated into the detergent-resistant perinuclear theca fraction where SOAF resides. PMID:22428063

  14. The testicular and epididymal expression profile of PLCζ in mouse and human does not support its role as a sperm-borne oocyte activating factor.

    Directory of Open Access Journals (Sweden)

    Mahmoud Aarabi

    Full Text Available Phospholipase C zeta (PLCζ is a candidate sperm-borne oocyte activating factor (SOAF which has recently received attention as a potential biomarker of human male infertility. However, important SOAF attributes of PLCζ, including its developmental expression in mammalian spermiogenesis, its compartmentalization in sperm head perinuclear theca (PT and its release into the ooplasm during fertilization have not been established and are addressed in this investigation. Different detergent extractions of sperm and head/tail fractions were compared for the presence of PLCζ by immunoblotting. In both human and mouse, the active isoform of PLCζ was detected in sperm fractions other than PT, where SOAF is expected to reside. Developmentally, PLCζ was incorporated as part of the acrosome during the Golgi phase of human and mouse spermiogenesis while diminishing gradually in the acrosome of elongated spermatids. Immunofluorescence localized PLCζ over the surface of the postacrosomal region of mouse and bull and head region of human spermatozoa leading us to examine its secretion in the epididymis. While previously thought to have strictly a testicular expression, PLCζ was found to be expressed and secreted by the epididymal epithelial cells explaining its presence on the sperm head surface. In vitro fertilization (IVF revealed that PLCζ is no longer detectable after the acrosome reaction occurs on the surface of the zona pellucida and thus is not incorporated into the oocyte cytoplasm for activation. In summary, we show for the first time that PLCζ is compartmentalized as part of the acrosome early in human and mouse spermiogenesis and is secreted during sperm maturation in the epididymis. Most importantly, no evidence was found that PLCζ is incorporated into the detergent-resistant perinuclear theca fraction where SOAF resides.

  15. Effect of Follicular Fluid and Platelet-Activating Factor on Lactate Dehydrogenase C Expression in Human Asthenozoospermic Samples

    Directory of Open Access Journals (Sweden)

    Tahereh Esmaeilpour

    2014-01-01

    Full Text Available Background: Application of follicular fluid (FF and platelet-activating factor (PAF in artificial insemination improves sperm motility. Lactate dehydrogenase C (LDH-C is a key enzyme for sperm motility. In this study, the effects of FF and PAF on the sperm motility index and LDH-C expression were investigated. Moreover, LDH-C expression was compared between asthenozoospermic and normozoospermic samples. Methods: The expression of LDH-C was examined by quantitative real-time polymerase chain reaction (q-RT PCR and western blotting after it was treated with optimized concentrations of FF and PAF in twenty asthenozoospermic samples. Also, LDH-C expression was evaluated in five normozoospermic samples. Results: Samples with 75% FF and 100 nM of PAF had an increase in their percentages of progressive and slowly motile sperms and a decrease in their percentages of non-progressive and non-motile sperms. Moreover, LDH-C mRNA transcripts were not changed following PAF and FF treatment, and LDH-C protein was detected in highly progressive motile specimens treated with FF in the asthenozoospermic samples. Furthermore, LDH-C expression was more detectable in the normal sperms. Conclusion: Our results indicated that PAF had more beneficial effects than FF on sperm motility in the asthenozoospermic samples (P=0.0001, although the LDH-C expressions of the sperms were not changed significantly in both groups. We found no association between LDH-C expression and sperm motility after FF and PAF actions. This finding, however, requires further investigation. The fact that LDH-C protein was detected in the normozoospermic, but not asthenozoospermic, samples could be cited as a reason for the infertility in these patients.

  16. In Vitro Effect of Activated Recombinant Factor VII (rFVIIa) on Coagulation Properties of Human Blood at Hypothermic Temperatures

    Science.gov (United States)

    2007-11-01

    hemostatic defects (i.e., factor VIIa deficiency, acquired von Willebrand disease, uremia, and liver disease) for controlling acute bleeding episodes... acquired haemophilia with recombinant factor VIIa: a multicentre study. Thromb Haemost. 1997;78:1463–1467. 14. Shapiro AD, Gilchrist GS, Hoots WK...2005;3:742–751. 47. Butenas S, Brummel KE, Branda RF, Paradis SG, Mann KG. Mechanism of factor VIIa-dependent coagulation in hemophilia blood. Blood

  17. Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells.

    Science.gov (United States)

    Chan, Chien-Pin; Tsai, Yao-Ting; Chen, Yao-Li; Hsu, Yu-Wen; Tseng, Joseph T; Chuang, Hung-Yi; Shiurba, Robert; Lee, Mei-Hsien; Wang, Jaw-Yuan; Chang, Wei-Chiao

    2015-02-01

    Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 μM lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture. © 2013 Wiley Periodicals, Inc.

  18. A hepatoprotective Lindera obtusiloba extract suppresses growth and attenuates insulin like growth factor-1 receptor signaling and NF-kappaB activity in human liver cancer cell lines

    Directory of Open Access Journals (Sweden)

    Stroh Thorsten

    2011-05-01

    Full Text Available Abstract Background In traditional Chinese and Korean medicine, an aqueous extract derived from wood and bark of the Japanese spice bush Lindera obtusiloba (L.obtusiloba is applied to treat inflammations and chronic liver diseases including hepatocellular carcinoma. We previously demonstrated anti-fibrotic effects of L.obtusiloba extract in hepatic stellate cells. Thus, we here consequently examine anti-neoplastic effects of L.obtusiloba extract on human hepatocellular carcinoma (HCC cell lines and the signaling pathways involved. Methods Four human HCC cell lines representing diverse stages of differentiation were treated with L.obtusiloba extract, standardized according to its known suppressive effects on proliferation and TGF-β-expression. Beside measurement of proliferation, invasion and apoptosis, effects on signal transduction and NF-κB-activity were determined. Results L.obtusiloba extract inhibited proliferation and induced apoptosis in all HCC cell lines and provoked a reduced basal and IGF-1-induced activation of the IGF-1R signaling cascade and a reduced transcriptional NF-κB-activity, particularly in the poorly differentiated SK-Hep1 cells. Pointing to anti-angiogenic effects, L.obtusiloba extract attenuated the basal and IGF-1-induced expression of hypoxia inducible factor-1α, vascular endothelial growth factor, peroxisome proliferator-activated receptor-γ, cyclooxygenase-2 and inducible nitric oxide synthase. Conclusions The traditional application of the extract is confirmed by our experimental data. Due to its potential to inhibit critical receptor tyrosine kinases involved in HCC progression via the IGF-1 signaling pathway and NF-κB, the standardized L.obtusiloba extract should be further analysed for its active compounds and explored as (complementary treatment option for HCC.

  19. Co-operation of the transcription factor hepatocyte nuclear factor-4 with Sp1 or Sp3 leads to transcriptional activation of the human haem oxygenase-1 gene promoter in a hepatoma cell line.

    Science.gov (United States)

    Takahashi, Shigeru; Matsuura, Naomi; Kurokawa, Takako; Takahashi, Yuji; Miura, Takashi

    2002-11-01

    We reported previously that the 5'-flanking region (nucleotides -1976 to -1655) of the human haem oxygenase-1 ( hHO-1 ) gene enhances hHO-1 promoter activity in human hepatoma HepG2 cells, but not in HeLa cells [Takahashi, Takahashi, Ito, Nagano, Shibahara and Miura (1999) Biochim. Biophys. Acta 1447, 231-235]. To define more precisely the regulatory elements involved, in the present study we have functionally dissected this region and localized the enhancer to a 50 bp fragment (-1793 to -1744). Site-direct mutagenesis analysis revealed that two regions were responsible for this enhancer activity, i.e. a hepatocyte nuclear factor-4 (HNF-4) homologous region and a GC box motif homologous region. Mutation in either region alone moderately decreased enhancer activity. However, mutations in both regions reduced promoter activity to the basal level. Electrophoretic mobility-shift assays demonstrated that the P5-2 fragment (-1793 to -1744) interacted with at least two nuclear factors, i.e. HNF-4 and Sp1/Sp3. Co-transfection experiments using Drosophila SL2 cells revealed that HNF-4 and Sp1/Sp3 synergistically stimulated the enhancer activity of the P5-2 fragment. These results indicate that co-operation of HNF-4 with Sp1 or Sp3 leads to the activation of hHO-1 gene expression in hepatoma cells.

  20. Aspirin inhibits Chlamydia pneumoniae : Induced nuclear factor-kappa B activation, cytokine expression, and bacterial development in human endothelial cells

    NARCIS (Netherlands)

    Tiran, A; Gruber, HJ; Graier, WF; Wagner, AH; van Leeuwen, EBM; Tiran, B

    Objective-Chlamydia pneumoniae has been associated with atherosclerosis. Infection of vascular endothelial cells with C pneumoniae increases the expression of proatherogenic cytokines mediated by nuclear factor (NF)-kappaB, a transcription factor. The present study was designed to test the effect of

  1. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells.

    Directory of Open Access Journals (Sweden)

    Dana Galuska

    Full Text Available Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC in control and hyperglycemic conditions.HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86Rb(+ uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM. DNA binding activity was determined by electrical mobility shift assay (EMSA. Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase α(1-subunit protein expression, accompanied with increase in (86Rb(+ uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase α(1-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, but not 10 nM of C-peptide increased PKCε phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6, concomitant with Na,K-ATPase α(1-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase α(1-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing.Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C-peptide. Most likely C-peptide stimulates sodium pump expression via activation of ZEB, a transcription factor that has not been previously implicated in C

  2. 14 CFR 460.15 - Human factors.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's ability...

  3. Granulocyte colony-stimulating factor increases CD4+ T cell counts of human immunodeficiency virus-infected patients receiving stable, highly active antiretroviral therapy

    DEFF Research Database (Denmark)

    Aladdin, H; Ullum, H; Dam Nielsen, S.

    2000-01-01

    Thirty human immunodeficiency virus (HIV)-infected patients with CD4+ T cell counts factor (G-CSF; 0.3 mg/mL 3 times...... a week) for 12 weeks. Blood samples were collected at specified time points. G-CSF treatment enhanced the total lymphocyte count (P=.002) and increased CD3+ (P=.005), CD4+ (P=.03), and CD8+ (P=.004) T cell counts as well as numbers of CD3-CD16+CD56+ NK cells (P=.001). The increases in CD4+ and CD8+ cell...... counts resulted from increases in CD45RO+ memory T cells and cells expressing the CD38 activation marker. Lymphocyte proliferative responses to phytohemagglutinin and Candida antigen decreased, whereas NK cell activity and plasma HIV RNA did not change during G-CSF treatment. After 24 weeks, all immune...

  4. Trefoil factors in human milk

    DEFF Research Database (Denmark)

    Vestergaard, Else Marie; Nexø, Ebba; Wendt, A

    2008-01-01

    We measured concentrations of the gastrointestinal protective peptides Trefoil factors in human milk. By the use of in-house ELISA we detected high amounts of TFF3, less TFF1 and virtually no TFF2 in human breast milk obtained from 46 mothers with infants born extremely preterm (24-27 wk gestation......), preterm (28-37 wk gestation), and full term (38-42 wk gestation). Samples were collected during the first, second, third to fourth weeks and more than 4 wks postpartum. Median (range) TFF1 [TFF3] concentrations in human milk were 320 (30-34000) [1500 (150-27,000)] pmol/L in wk 1, 120 (30-720) [310 (50......-7100)] pmol/L in wk 2, 70 (20-670) [120 (20-650)] pmol/L in wks 3 to 4, and 60 (30-2500) [80 (20-540)] pmol/L in > 4 wks after delivery. The lowest concentrations of TFF1 and TFF3 were found later than 2 wks after birth. In conclusion, TFF was present in term and preterm human milk with rapidly declining...

  5. Direct anti-inflammatory effects of granulocyte colony-stimulating factor (G-CSF) on activation and functional properties of human T cell subpopulations in vitro.

    Science.gov (United States)

    Malashchenko, Vladimir Vladimirovich; Meniailo, Maxsim Evgenievich; Shmarov, Viacheslav Anatolievich; Gazatova, Natalia Dinislamovna; Melashchenko, Olga Borisovna; Goncharov, Andrei Gennadievich; Seledtsova, Galina Victorovna; Seledtsov, Victor Ivanovich

    2018-03-01

    We investigated the direct effects of human granulocyte colony-stimulating factor (G-CSF) on functionality of human T-cell subsets. CD3 + T-lymphocytes were isolated from blood of healthy donors by positive magnetic separation. T cell activation with particles conjugated with antibodies (Abs) to human CD3, CD28 and CD2 molecules increased the proportion of cells expressing G-CSF receptor (G-CSFR, CD114) in all T cell subpopulations studied (CD45RA + /CD197 + naive T cells, CD45RA - /CD197 + central memory T cells, CD45RA - /CD197 - effector memory T cells and CD45RA + /CD197 - terminally differentiated effector T cells). Upon T-cell activation in vitro, G-CSF (10.0 ng/ml) significantly and specifically enhanced the proportion of CD114 + T cells in central memory CD4 + T cell compartment. A dilution series of G-CSF (range, 0.1-10.0 ng/ml) was tested, with no effect on the expression of CD25 (interleukin-2 receptor α-chain) on activated T cells. Meanwhile, G-CSF treatment enhanced the proportion of CD38 + T cells in CD4 + naïve T cell, effector memory T cell and terminally differentiated effector T cell subsets, as well as in CD4 - central memory T cells and terminally differentiated effector T cells. G-CSF did not affect IL-2 production by T cells; relatively low concentrations of G-CSF down-regulated INF-γ production, while high concentrations of this cytokine up-regulated IL-4 production in activated T cells. The data obtained suggests that G-CSF could play a significant role both in preventing the development of excessive and potentially damaging inflammatory reactivity, and in constraining the expansion of potentially cytodestructive T cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Human factors evaluation of an in-vehicle active traffic and demand management (ATDM) system : final report.

    Science.gov (United States)

    2016-02-15

    This research study focused on the development and subsequent evaluation of an in-vehicle Active Traffic and Demand Management (ATDM) system deployed on Interstate 66 in Northern Virginia. The ATDM elements inside the vehicle allowed drivers to remai...

  7. Leishmania major Infection Activates NF-κB and Interferon Regulatory Factors 1 and 8 in Human Dendritic Cells▿

    OpenAIRE

    Jayakumar, Asha; Donovan, Michael J.; Tripathi, Vinita; Ramalho-Ortigao, Marcelo; McDowell, Mary Ann

    2008-01-01

    The salient feature of dendritic cells (DC) is the initiation of appropriate adaptive immune responses by discriminating between pathogens. Using a prototypic model of intracellular infection, we previously showed that Leishmania major parasites prime human DC for efficient interleukin-12 (IL-12) secretion. L. major infection is associated with self-limiting cutaneous disease and powerful immunity. In stark contrast, the causative agent of visceral leishmaniasis, Leishmania donovani, does not...

  8. Rupatadine inhibits inflammatory mediator release from human laboratory of allergic diseases 2 cultured mast cells stimulated by platelet-activating factor.

    Science.gov (United States)

    Alevizos, Michail; Karagkouni, Anna; Vasiadi, Magdalini; Sismanopoulos, Nikolaos; Makris, Michael; Kalogeromitros, Dimitrios; Theoharides, Theoharis C

    2013-12-01

    Mast cells are involved in allergy and inflammation by the secretion of multiple mediators, including histamine, cytokines, and platelet-activating factor (PAF), in response to different triggers, including emotional stress. PAF has been associated with allergic inflammation, but there are no clinically available PAF inhibitors. To investigate whether PAF could stimulate human mast cell mediator release and whether rupatadine (RUP), a dual histamine-1 and PAF receptor antagonist, could inhibit the effect of PAF on human mast cells. Laboratory of allergic diseases 2 cultured mast cells were stimulated with PAF (0.001, 0.01, and 0.1 μmol/L) and substance P (1 μmol/L) with or without pretreatment with RUP (2.5 and 25 μmol/L), which was added 10 minutes before stimulation. Release of β-hexosaminidase was measured in supernatant fluid by spectrophotoscopy, and histamine, interleukin-8, and tumor necrosis factor were measured by enzyme-linked immunosorbent assay. PAF stimulated a statistically significant release of histamine, interleukin-8, and tumor necrosis factor (0.001-0.1 μmol/L) that was comparable to that stimulated by substance P. Pretreatment with RUP (25 μmol/L) for 10 minutes inhibited this effect. In contrast, pretreatment of laboratory of allergic diseases 2 cells with diphenhydramine (25 μmol/L) did not inhibit mediator release, suggesting that the effect of RUP was not due to its antihistaminic effect. PAF stimulates human mast cell release of proinflammatory mediators that is inhibited by RUP. This action endows RUP with additional properties in treating allergic inflammation. Copyright © 2013 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  9. HUMAN POTENTIAL AS A STRATEGIC FACTOR OF REGIONAL DEVELOPMENT

    OpenAIRE

    A.M. Korobeynikov

    2008-01-01

    The article gives an insight of human potential as the strategic factor of regional development. The matter of human potential and its role in regional reproducing process is considered; regional intellectual potential as an integral part of human potential is analysed. The author outlines major directions of active social policy, aimed to develop regional human potential.

  10. Human Factors in Human-Systems Integration

    Science.gov (United States)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  11. Human Factors Checklist: Think Human Factors - Focus on the People

    Science.gov (United States)

    Miller, Darcy; Stelges, Katrine; Barth, Timothy; Stambolian, Damon; Henderson, Gena; Dischinger, Charles; Kanki, Barbara; Kramer, Ian

    2016-01-01

    A quick-look Human Factors (HF) Checklist condenses industry and NASA Agency standards consisting of thousands of requirements into 14 main categories. With support from contractor HF and Safety Practitioners, NASA developed a means to share key HF messages with Design, Engineering, Safety, Project Management, and others. It is often difficult to complete timely assessments due to the large volume of HF information. The HF Checklist evolved over time into a simple way to consider the most important concepts. A wide audience can apply the checklist early in design or through planning phases, even before hardware or processes are finalized or implemented. The checklist is a good place to start to supplement formal HF evaluation. The HF Checklist was based on many Space Shuttle processing experiences and lessons learned. It is now being applied to ground processing of new space vehicles and adjusted for new facilities and systems.

  12. Ligand-Independent Activation of Platelet-Derived Growth Factor Receptor β during Human Immunodeficiency Virus-Transactivator of Transcription and Cocaine-Mediated Smooth Muscle Hyperplasia.

    Science.gov (United States)

    Dalvi, Pranjali N; Gupta, Vijayalaxmi G; Griffin, Brooke R; O'Brien-Ladner, Amy; Dhillon, Navneet K

    2015-09-01

    Our previous study supports an additive effect of cocaine to human immunodeficiency virus infection in the development of pulmonary arteriopathy through enhancement of proliferation of pulmonary smooth muscle cells (SMCs), while also suggesting involvement of platelet-derived growth factor receptor (PDGFR) activation in the absence of further increase in PDGF-BB ligand. Redox-related signaling pathways have been shown to regulate tyrosine kinase receptors independent of ligand binding, so we hypothesized that simultaneous treatment of SMCs with transactivator of transcription (Tat) and cocaine may be able to indirectly activate PDGFR through modulation of reactive oxygen species (ROS) without the need for PDGF binding. We found that blocking the binding of ligand using suramin or monoclonal IMC-3G3 antibody significantly reduced ligand-induced autophosphorylation of Y1009 without affecting ligand-independent transphosphorylation of Y934 residue on PDGFRβ in human pulmonary arterial SMCs treated with both cocaine and Tat. Combined treatment of human pulmonary arterial SMCs with cocaine and Tat resulted in augmented production of superoxide radicals and hydrogen peroxide when compared with either treatment alone. Inhibition of this ROS generation prevented cocaine- and Tat-mediated Src activation and transphosphorylation of PDGFRβ at Y934 without any changes in phosphorylation of Y1009, in addition to attenuation of smooth muscle hyperplasia. Furthermore, pretreatment with an Src inhibitor, PP2, also suppressed cocaine- and Tat-mediated enhanced Y934 phosphorylation and smooth muscle proliferation. Finally, we report total abrogation of cocaine- and Tat-mediated synergistic increase in cell proliferation on inhibition of both ligand-dependent and ROS/Src-mediated ligand-independent phosphorylation of PDGFRβ.

  13. Quantitative Prediction of Human Renal Clearance and Drug-Drug Interactions of Organic Anion Transporter Substrates Using In Vitro Transport Data: A Relative Activity Factor Approach.

    Science.gov (United States)

    Mathialagan, Sumathy; Piotrowski, Mary A; Tess, David A; Feng, Bo; Litchfield, John; Varma, Manthena V

    2017-04-01

    Organic anion transporters (OATs) are important in the renal secretion, and thus, the clearance, of many drugs; and their functional change can result in pharmacokinetic variability. In this study, we applied transport rates measured in vitro using OAT-transfected human embryonic kidney cells to predict human renal secretory and total renal clearance of 31 diverse drugs. Selective substrates to OAT1 (tenofovir), OAT2 (acyclovir and ganciclovir), and OAT3 (benzylpenicillin, oseltamivir acid) were used to obtain relative activity factors (RAFs) for these individual transporters by relating in vitro transport clearance (after physiologic scaling) to in vivo secretory clearance. Using the estimated RAFs (0.64, 7.3, and 4.1, respectively, for OAT1, OAT2, and OAT3, respectively) and the in vitro active clearances, renal secretory clearance and total renal clearance were predicted with average fold errors (AFEs) of 1.89 and 1.40, respectively. The results show that OAT3-mediated transport play a predominant role in renal secretion for 22 of the 31 drugs evaluated. This mechanistic static approach was further applied to quantitatively predict renal drug-drug interactions (AFE ∼1.6) of the substrate drugs with probenecid, a clinical probe OAT inhibitor. In conclusion, the proposed in vitro-in vivo extrapolation approach is the first comprehensive attempt toward mechanistic modeling of renal secretory clearance based on routinely employed in vitro cell models. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

  14. 4-Methylthio-3-butenyl isothiocyanate mediates nuclear factor (erythroid-derived 2)-like 2 activation by regulating reactive oxygen species production in human esophageal epithelial cells.

    Science.gov (United States)

    Hirata, Tadashi; Cho, Young-Man; Suzuki, Isamu; Toyoda, Takeshi; Akagi, Jun-Ichi; Nakamura, Yasushi; Numazawa, Satoshi; Ogawa, Kumiko

    2018-01-01

    4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1, NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells treated with 10 μM MTBITC. Reactive oxygen species (ROS) tended to increase when Het-1A cells were treated with MTBITC, and the increases in ROS and Nrf2 expression in the cells treated with MTBITC were completely abolished by treatment with N-acetyl-l-cysteine. We also examined the relationships between Nrf2 activation and mitogen-activated protein kinase (MAPK) signaling by western blot analysis. MTBITC induced extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 phosphorylation in Het-1A cells; however, MTBITC did not affect the relationship between Nrf2 activation and MAPK responses. In the present study, we found that MTBITC induced Nrf2 activation and cytoprotective genes via ROS production in Het-1A cells. These results suggest that MTBITC may have the potential for preventing esophageal carcinogenesis through modification of carcinogen metabolism by phase II enzyme induction via ROS production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

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

  16. The Adaptor Protein p62 Mediates Nuclear Factor κB Activation in Response to Inflammation and Facilitates the Formation of Prolabor Mediators in Human Myometrium.

    Science.gov (United States)

    Lappas, Martha

    2017-05-01

    Preventing spontaneous preterm birth is one of the most important issues facing perinatal medicine today. The pathophysiology of preterm labor, the single biggest cause of preterm birth, is poorly understood. Inflammation, however, plays a significant role in the terminal processes of human labor, which include myometrial contractions. Nuclear factor κB (NF-κB) drives the transcription of proinflammatory mediators involved in the terminal effector pathways of human labor and delivery. Recent studies in nongestational tissues have shown that the adaptor protein p62 interacts with NF-κB to induce inflammation. The aim of this study was to determine the role of p62 in the genesis of NF-κB-induced proinflammatory and prolabur mediators. Human spontaneous term labor was associated with increased p62 messenger RNA (mRNA) and protein expression in myometrium. Myometrial cells treated with proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-α) also significantly increased p62 mRNA and protein expression. Functional studies using p62 small interfering RNA (siRNA) demonstrated a significant attenuation of TNF-α- and IL-1β-induced proinflammatory cytokines (IL-6) and chemokine (IL-8 and monocyte chemoattractant protein 1 [MCP-1]) mRNA expression and secretion, expression of cyclooxygenase 2, release of prostaglandin F 2α (PGF 2α ), and expression of the prostaglandin F receptor (FP). In addition, siRNA knockdown of p62 significantly suppressed IL-1β- and TNF-α-induced NF-κB activation. Collectively, these studies suggest that p62 is involved in the genesis of NF-κB-induced proinflammatory and prolabor mediators.

  17. The Effect of Progestins on Tumor Necrosis Factor α-Induced Matrix Metalloproteinase-9 Activity and Gene Expression in Human Primary Amnion and Chorion Cells In Vitro.

    Science.gov (United States)

    Allen, Terrence K; Feng, Liping; Nazzal, Matthew; Grotegut, Chad A; Buhimschi, Irina A; Murtha, Amy P

    2015-05-01

    Current treatment modalities for preventing preterm premature rupture of membranes are limited, but progestins may play a role. Tumor necrosis factor α (TNFα) enhances matrix metalloproteinase-9 (MMP-9) gene expression and activity in fetal membranes, contributing to membrane weakening and rupture. We previously demonstrated that progestins attenuate TNFα-induced MMP-9 activity in a cytotrophoblast cell line. However, whether they have a similar effect in primary amnion and chorion cells of fetal membranes is unknown. In this study, we evaluated the effect of progestins on basal and TNFα-induced MMP-9 activity and gene expression in primary chorion and amnion cells harvested from the fetal membranes of term nonlaboring patients. Primary amnion and chorion cells were isolated from fetal membranes obtained from term uncomplicated nonlaboring patients following elective cesarean delivery (n = 11). Confluent primary amnion and chorion cell cultures were both pretreated with vehicle (control), progesterone (P4), 17α-hydroxyprogesterone caproate (17P), or medroxyprogesterone acetate (MPA) at 10 M concentration for 6 hours followed by stimulation with TNFα at 10 ng/mL for an additional 24 hours. Cell cultures pretreated with the vehicle only served as the unstimulated control and the vehicle stimulated with TNFα served as the stimulated control. Both controls were assigned a value of 100 units. Cell culture medium was harvested for MMP-9 enzymatic activity quantification using gelatin zymography. Total RNA was extracted for quantifying MMP-9 gene expression using real-time quantitative PCR. Basal MMP-9 activity and gene expression data were normalized to the unstimulated control. TNFα-stimulated MMP-9 activity and gene expression were normalized to the stimulated control. The primary outcome was the effect of progestins on TNFα-induced MMP-9 enzymatic activity in term human primary amnion and chorion cells in vitro. Secondary outcomes included the effect of

  18. Platelet-activating factor induces histamine release from human skin mast cells in vivo, which is reduced by local nerve blockade.

    Science.gov (United States)

    Petersen, L J; Church, M K; Skov, P S

    1997-05-01

    Intradermal injection of platelet-activating factor (PAF) causes wheal and flare reactions, which are inhibited by antihistamines. However, PAF does not release histamine from human dispersed skin mast cells in vitro. The purpose of this study was to investigate the extent and possible mechanisms of PAF-induced histamine release in human skin in vivo with the use of dermal microdialysis. Hollow dialysis fibers were inserted into the upper dermis in forearm skin and each fiber was perfused with Krebs-Ringer bicarbonate solution at a rate of 3.0 microliters/min. PAF (4.5 to 36 mumol/L), lyso-PAF (36 mumol/L), vehicle (negative control), and codeine 750 or 250 mumol/L (positive control) were injected intradermally above separate fibers. Dialysate was collected in 2-minute fractions for 20 minutes and histamine analyzed spectrofluorometrically. PAF, but not lyso-PAF, caused statistically significant dose-related histamine release and wheal and flare reactions. Intradermal mepivacaine administration significantly abrogated flare reactions by PAF and codeine and inhibited histamine release and wheal reactions by PAF but not by codeine. Long-term topical capsaicin administration inhibited histamine release and wheal reactions by PAF but not by codeine. It inhibited flare reactions induced by both compounds. PAF did not release histamine from blood basophils. These data suggest that PAF induced histamine release from mast cells in intact human skin indirectly via neurogenic activation. Further, on the intradermal injection of PAF histamine release and the skin responses, the wheal and the flare, are differentially regulated by neurogenic components.

  19. Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

    Science.gov (United States)

    Fischer, Adam P; Miles, Sarah L

    2017-02-01

    Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with pascorbic acid as an adjuvant cancer therapy remains under investigated. While AA and A2P were capable of modulating HIF-1α protein accumulation/activity, DHA supplementation resulted in minimal intracellular vitamin C activity with decreased ability to inhibit HIF-1α activity and malignant potential in advanced melanoma. Restoring AA dependent regulation of HIF-1α in malignant cells may prove beneficial in reducing chemotherapy resistance and improving treatment outcomes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Calorie restriction decreases murine and human pancreatic tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression in an insulin-like growth factor-1-dependent manner.

    Directory of Open Access Journals (Sweden)

    Alison E Harvey

    Full Text Available Calorie restriction (CR prevents obesity and has potent anticancer effects that may be mediated through its ability to reduce serum growth and inflammatory factors, particularly insulin-like growth factor (IGF-1 and protumorigenic cytokines. IGF-1 is a nutrient-responsive growth factor that activates the inflammatory regulator nuclear factor (NF-κB, which is linked to many types of cancers, including pancreatic cancer. We hypothesized that CR would inhibit pancreatic tumor growth through modulation of IGF-1-stimulated NF-κB activation and protumorigenic gene expression. To test this, 30 male C57BL/6 mice were randomized to either a control diet consumed ad libitum or a 30% CR diet administered in daily aliquots for 21 weeks, then were subcutaneously injected with syngeneic mouse pancreatic cancer cells (Panc02 and tumor growth was monitored for 5 weeks. Relative to controls, CR mice weighed less and had decreased serum IGF-1 levels and smaller tumors. Also, CR tumors demonstrated a 70% decrease in the expression of genes encoding the pro-inflammatory factors S100a9 and F4/80, and a 56% decrease in the macrophage chemoattractant, Ccl2. Similar CR effects on tumor growth and NF-κB-related gene expression were observed in a separate study of transplanted MiaPaCa-2 human pancreatic tumor cell growth in nude mice. In vitro analyses in Panc02 cells showed that IGF-1 treatment promoted NF-κB nuclear localization, increased DNA-binding of p65 and transcriptional activation, and increased expression of NF-κB downstream genes. Finally, the IGF-1-induced increase in expression of genes downstream of NF-κB (Ccdn1, Vegf, Birc5, and Ptgs2 was decreased significantly in the context of silenced p65. These findings suggest that the inhibitory effects of CR on Panc02 pancreatic tumor growth are associated with reduced IGF-1-dependent NF-κB activation.

  1. Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study).

    Science.gov (United States)

    Munoz-Cano, R; Ainsua-Enrich, E; Torres-Atencio, I; Martin, M; Sánchez-Lopez, J; Bartra, J; Picado, C; Mullol, J; Valero, A

    Platelet-activating factor (PAF) is a lipid mediator involved in the pathophysiology of several allergic diseases, for example, in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives: To compare the ability of rupatadine to inhibit PAF-induced MC degranulation with that of desloratadine and levocetirizine and to confirm the dual anti-H1 and anti-PAF activity of rupatadine. The human MC line LAD2 and primary MCs (human lung tissue MCs [hLMCs]) were used. MC mediator release was evaluated using the b-hexosaminidase and histamine release assay. The effects of rupatadine (H1 antagonist + PAF receptor antagonist), desloratadine, and levocetirizine (H1 antagonists) on LAD2 and hLMCs were compared. The PAF receptor antagonists WEB2086, BN52021, and CV6209 were also tested. PAF receptor protein expression was evaluated in both LAD2 and hLMCs. CV6209 and rupatadine inhibited PAF-induced MC degranulation in both LAD2 and hLMCs. In LAD2, rupatadine (5 and 10 µM) and levocetirizine (5 µM), but not desloratadine, inhibited PAF-induced b-hexosaminidase release. Rupatadine (1-10 µM), levocetirizine (1-10 µM), and desloratadine (10 µM) inhibited PAF-induced histamine release. Rupatadine at 10 µM had an inhibitory effect on hLMC degranulation, but levocetirizine and desloratadine did not. This study shows that rupatadine and, to a lesser extent, levocetirizine, but not desloratadine, inhibit PAF-induced degranulation in both LAD2 and hLMCs. These findings support the dual antihistamine and anti-PAF effect of rupatadine in allergic disorders.

  2. [Mycoplasma genitalium lipid-associated membrane proteins induce human monocytic cell express proinflammatory cytokines and apoptosis by activating nuclear factor kappaB].

    Science.gov (United States)

    Qiu, Hong; Wu, Yi-Mou; You, Xiao-Xing; Yu, Ming-Jun; Zeng, Yan-Hua

    2007-10-01

    Designed to investigate the potential pathogenicity of Mycoplasma genitalium (M. genitalium) and its molecular mechanisms responsible for the induction of proinflammatory cytokines gene expression in human monocytic cells (THP-1) stimulated by lipid-associated membrane proteins (LAMPs) prepared from M. genitalium. THP-1 cells were stimulated with LAMPs to analyze the production of proinflammatory cytokines and the expression of mRNA was detected by RT-PCR. Cell apoptosis was detected in THP-1 cells by Annexin V-propidium iodide staining. The activity of transcriptional factors, NF-kappaB, was examined in THP-1 cells treated with LAMPs by EMSA. The effects of pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF-kappaB, on the production of proinflammatory cytokines, the expression of mRNA and apoptosis were also examined in THP-1 cells treated with LAMPs. M. genitalium LAMPs stimulate THP-1 cells to produce TNF-alpha, IL-1beta and IL-6 in dose- and time-dependent manner. The mRNA levels and cell apoptosis are also downregulated in response to LAMPs stimulation and inhibited by PDTC treatment. M. genitalium LAMPs are found to trigger NF-kappaB activation, a possible mechanism for the induction of mRNA expression and the cell apoptosis. This study demonstrated that M. genitalium may be an important etiological factor of certain disease due to the ability of LAMPs to stimulated the expression of mRNA and apoptosis, which is probably mediated through the activation of NF-kappaB.

  3. Integrating human factors into process hazard analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kariuki, S.G. [Technische Universitaet Berlin, Institute of Process and Plant Technology, Sekr. TK0-1, Strasse des 17. Juni 135, 10623 Berlin (Germany); Loewe, K. [Technische Universitaet Berlin, Institute of Process and Plant Technology, Sekr. TK0-1, Strasse des 17. Juni 135, 10623 Berlin (Germany)]. E-mail: katharina.loewe@tu-berlin.de

    2007-12-15

    A comprehensive process hazard analysis (PHA) needs to address human factors. This paper describes an approach that systematically identifies human error in process design and the human factors that influence its production and propagation. It is deductive in nature and therefore considers human error as a top event. The combinations of different factors that may lead to this top event are analysed. It is qualitative in nature and is used in combination with other PHA methods. The method has an advantage because it does not look at the operator error as the sole contributor to the human failure within a system but a combination of all underlying factors.

  4. Human factors for a sustainable future.

    Science.gov (United States)

    Thatcher, Andrew; Yeow, Paul H P

    2016-11-01

    Current human activities are seriously eroding the ability of natural and social systems to cope. Clearly we cannot continue along our current path without seriously damaging our own ability to survive as a species. This problem is usually framed as one of sustainability. As concerned professionals, citizens, and humans there is a strong collective will to address what we see as a failure to protect the natural and social environments that supports us. While acknowledging that we cannot do this alone, human factors and ergonomics needs to apply its relevant skills and knowledge to assist where it can in addressing the commonly identified problem areas. These problems include pollution, climate change, renewable energy, land transformation, and social unrest amongst numerous other emerging global problems. The issue of sustainability raises two fundamental questions for human factors and ergonomics: which system requires sustaining and what length of time is considered sustainable? In this paper we apply Wilson (2014) parent-sibling-child model to understanding what is required of an HFE sustainability response. This model is used to frame the papers that appear in this Special Issue. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Advanced glycation end products induce brain-derived neurotrophic factor release from human platelets through the Src-family kinase activation.

    Science.gov (United States)

    Furukawa, Kazuo; Fuse, Ichiro; Iwakura, Yuriko; Sotoyama, Hidekazu; Hanyu, Osamu; Nawa, Hiroyuki; Sone, Hirohito; Takei, Nobuyuki

    2017-02-08

    Brain-derived neurotrophic factor (BDNF) exerts beneficial effects not only on diabetic neuropathies but also on cardiovascular injury. There is argument regarding the levels of serum BDNF in patients with diabetes mellitus (DM). Because BDNF in peripheral blood is rich in platelets, this may represent dysregulation of BDNF release from platelets. Here we focused on advanced glycation end products (AGEs), which are elevated in patients with DM and have adverse effects on cardiovascular functions. The aim of this study is to elucidate the role of AGEs in the regulation of BDNF release from human platelets. Platelets collected from peripheral blood of healthy volunteers were incubated with various concentrations of AGE (glycated-BSA) at 37 °C for 5 min with or without BAPTA-AM, a cell permeable Ca(2+) chelator, or PP2, a potent inhibitor of Src family kinases (SFKs). Released and cellular BDNF were measured by ELISA and calculated. Phosphorylation of Src and Syk, a downstream kinase of SFKs, in stimulated platelets was examined by Western blotting and immunoprecipitation. AGE induced BDNF release from human platelets in a dose-dependent manner, which was dependent on intracellular Ca(2+) and SFKs. We found that AGE induced phosphorylation of Src and Syk. AGE induces BDNF release from human platelets through the activation of the Src-Syk-(possibly phospholipase C)-Ca(2+) pathway. Considering the toxic action of AGEs and the protective roles of BDNF, it can be hypothesized that AGE-induced BDNF release is a biological defense system in the early phase of diabetes. Chronic elevation of AGEs may induce depletion or downregulation of BDNF in platelets during the progression of DM.

  6. Human Activity Recognition using Smartphone

    OpenAIRE

    Rasekh, Amin; Chen, Chien-An; Lu, Yan

    2014-01-01

    Human activity recognition has wide applications in medical research and human survey system. In this project, we design a robust activity recognition system based on a smartphone. The system uses a 3-dimentional smartphone accelerometer as the only sensor to collect time series signals, from which 31 features are generated in both time and frequency domain. Activities are classified using 4 different passive learning methods, i.e., quadratic classifier, k-nearest neighbor algorithm, support ...

  7. Virulence factors of Staphylococcus aureus induce Erk-MAP kinase activation and c-Fos expression in S9 and 16HBE14o- human airway epithelial cells.

    Science.gov (United States)

    Below, Sabine; Konkel, Anne; Zeeck, Cathrin; Müller, Christian; Kohler, Christian; Engelmann, Susanne; Hildebrandt, Jan-Peter

    2009-03-01

    Part of the innate defense of bronchial epithelia against bacterial colonization is regulated secretion of salt, water, and mucus as well as defensins and cytokines involving MAP kinase activation and alterations in early gene expression. We tested two different types of immortalized human airway epithelial cells (S9, 16HBE14o-) for activation of Erk-type MAP kinases and for expression of c-Fos on treatment with Staphylococcus aureus culture supernatants from the stationary growth phase [optical density (OD)(540 nm) = 10] or with recombinant S. aureus hemolysins A and B (Hla, Hlb). OD10 supernatants activated Erk-type MAP kinases and c-Fos expression in a concentration-dependent manner. Hla induced Erk-type kinase phosphorylation in S9 but not in 16HBE14o- cells. Hlb induced Erk activation in either cell type. Basal and stimulated levels of Erk-type MAP kinase phosphorylation were sensitive to the Mek1 inhibitor PD-98059, indicating that the bacterial products activated the entire signaling cascade that coregulates IL-8 induction and secretion. While c-Fos expression was enhanced by OD10 supernatants, Hla, and Hlb in S9 cells, 16HBE14o- cells responded to OD10 supernatant and Hlb but not to Hla. In S9 cells, PD-98059 suppressed c-Fos upregulation by OD10 supernatant, Hla, or Hlb, indicating that c-Fos expression requires activation of Erk-type MAP kinases. In 16HBE14o- cells, however, c-Fos expression by OD10 supernatant was sensitive to PD-98059, while that induced by Hlb was not. This indicates that ingredients of OD10 supernatants other than Hla or Hlb are activating Erk-type MAP kinases in 16HBE14o- cells and that other intracellular signaling systems apart from Erk-type MAP kinases contribute to Hlb-mediated regulation of c-Fos. Thus interaction of bacterial factors with airway epithelial cells may be highly cell type specific.

  8. A national case-control study identifies human socio-economic status and activities as risk factors for tick-borne encephalitis in Poland.

    Directory of Open Access Journals (Sweden)

    Pawel Stefanoff

    Full Text Available BACKGROUND: Tick-borne encephalitis (TBE is endemic to Europe and medically highly significant. This study, focused on Poland, investigated individual risk factors for TBE symptomatic infection. METHODS AND FINDINGS: In a nation-wide population-based case-control study, of the 351 TBE cases reported to local health departments in Poland in 2009, 178 were included in the analysis. For controls, of 2704 subjects (matched to cases by age, sex, district of residence selected at random from the national population register, two were interviewed for each case and a total of 327 were suitable for the analysis. Questionnaires yielded information on potential exposure to ticks during the six weeks (maximum incubation period preceding disease onset in each case. Independent associations between disease and socio-economic factors and occupational or recreational exposure were assessed by conditional logistic regression, stratified according to residence in known endemic and non-endemic areas. Adjusted population attributable fractions (PAF were computed for significant variables. In endemic areas, highest TBE risk was associated with spending ≥10 hours/week in mixed forests and harvesting forest foods (adjusted odds ratio 19.19 [95% CI: 1.72-214.32]; PAF 0.127 [0.064-0.193], being unemployed (11.51 [2.84-46.59]; 0.109 [0.046-0.174], or employed as a forester (8.96 [1.58-50.77]; 0.053 [0.011-0.100] or non-specialized worker (5.39 [2.21-13.16]; 0.202 [0.090-0.282]. Other activities (swimming, camping and travel to non-endemic regions reduced risk. Outside TBE endemic areas, risk was greater for those who spent ≥10 hours/week on recreation in mixed forests (7.18 [1.90-27.08]; 0.191 [0.065-0.304] and visited known TBE endemic areas (4.65 [0.59-36.50]; 0.058 [-0.007-0.144], while travel to other non-endemic areas reduced risk. CONCLUSIONS: These socio-economic factors and associated human activities identified as risk factors for symptomatic TBE in Poland

  9. Development of Human Factor Management Requirements and Human Error Classification for the Prevention of Railway Accident

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Sang Log; Park, Chan Woo; Shin, Seung Ryoung [Korea Railroad Research Institute, Uiwang (Korea, Republic of)

    2008-08-15

    Railway accident analysis results show that accidents cased by human factors are not decreasing, whereas H/W related accidents are steadily decreasing. For the efficient management of human factors, many expertise on design, conditions, safety culture and staffing are required. But current safety management activities on safety critical works are focused on training, due to the limited resource and information. In order to improve railway safety, human factors management requirements for safety critical worker and human error classification is proposed in this report. For this accident analysis, status of safety measure on human factor, safety management system on safety critical worker, current safety planning is analysis.

  10. Human Factors Military Lexicon: Auditory Displays

    National Research Council Canada - National Science Library

    Letowski, Tomasz

    2001-01-01

    .... In addition to definitions specific to auditory displays, speech communication, and audio technology, the lexicon includes several terms unique to military operational environments and human factors...

  11. NASA information sciences and human factors program

    Science.gov (United States)

    Holcomb, Lee; Hood, Ray; Montemerlo, Melvin; Jenkins, James; Smith, Paul; Dibattista, John; Depaula, Ramon; Hunter, Paul; Lavery, David

    1991-01-01

    The FY-90 descriptions of technical accomplishments are contained in seven sections: Automation and Robotics, Communications, Computer Sciences, Controls and Guidance, Data Systems, Human Factors, and Sensor Technology.

  12. Human factors engineering program review model

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  13. Human Factors in Aeronautics at NASA

    Science.gov (United States)

    Mogford, Richard

    2016-01-01

    This is a briefing to a regularly meeting DoD group called the Human Systems Community of Interest: Mission Effectiveness. I was asked to address human factors in aeronautics at NASA. (Exploration (space) human factors has apparently already been covered.) The briefing describes human factors organizations at NASA Ames and Langley. It then summarizes some aeronautics tasks that involve the application of human factors in the development of specific tools and capabilities. The tasks covered include aircrew checklists, dispatch operations, Playbook, Dynamic Weather Routes, Traffic Aware Strategic Aircrew Requests, and Airplane State Awareness and Prediction Technologies. I mention that most of our aeronautics work involves human factors as embedded in development tasks rather than basic research.

  14. Response to platelet-activating factor in human platelets stored and aged in plasma. Decrease in aggregation, phosphoinositide turnover, and receptor affinity

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, S.D.; Morrison, W.J.; Klachko, D.M.

    1989-07-01

    Human platelet concentrates were stored in polyolefin bags at 22 to 24 degrees C on a horizontal shaker for up to 8 days. At different intervals, aliquots of platelet-rich plasma (PRP) were removed aseptically and five variables, i.e., platelet counts, morphology, platelet-activating factor (PAF)-stimulated aggregation, phosphoinositide turnover, and (3H)PAF binding to platelet receptors, were studied. The number of platelets did not change during the 8 days of storage. Scanning electron microscopy of the platelets revealed a gradual morphologic change from biconcave flat discs to irregular, crenated forms. The PAF-induced aggregation of platelets declined with time of storage. A decrease to 50 percent of the Day 1 aggregatory response to PAF was evident on Day 2, and there was a further decline to about 20 percent by Day 6. Similarly, PAF receptor-coupled phosphoinositide turnover, as monitored by 32P incorporation into individual phosphoinositides, decreased dramatically with storage. After 2 to 3 days of storage, the phosphoinositide turnover was reduced to 50 percent of the original response, and it continued to decline to about 25 percent of original response by Day 5 or 6. The binding of (3H)PAF to washed human platelets indicated subtle changes between Days 2 and 4, which became more noticeable by Day 6. These results have raised the possibility of changes in the number of the receptors and/or their affinity for the ligand during storage. We conclude that although the number of platelets was maintained during storage for 8 days, a general deterioration of their responses to PAF occurred at the levels of cell surface receptor, transmembrane signaling (phosphoinositide turnover), and response (aggregation).

  15. Factor VII-activating protease

    DEFF Research Database (Denmark)

    Ramanathan, Ramshanker; Gram, Jørgen B; Sand, Niels Peter R

    2017-01-01

    : Factor VII-activating protease (FSAP) may regulate development of cardiovascular disease (CVD). We evaluated sex differences in FSAP measures and examined the association between FSAP and coronary artery calcification (CAC) in a middle-aged population. Participants were randomly selected citizens...

  16. Human Modeling for Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  17. Human Modeling For Ground Processing Human Factors Engineering Analysis

    Science.gov (United States)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over that last few years using human modeling for human factors engineering analysis for design of spacecraft and launch vehicles. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the different types of human modeling used currently and in the past at Kennedy Space Center (KSC) currently, and to explain the future plans for human modeling for future spacecraft designs.

  18. Cyber Vigilance: The Human Factor

    Science.gov (United States)

    2016-10-21

    also suggest vulnerability to denial & deception (D&D) tactics which would effectively hack the human rather than the machine. 15. SUBJECT TERMS...deception (D&D) tactics which would effectively hack the human rather than the machine. INTRODUCTION ]Jn a world of asymmetric conflict in which the...arcsines of the percentage of correct detections. This analysis indicated statistically significant main effects for signal probability, F( I, 20) = 4.26

  19. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, H; Jensen, Ole N; Moiseeva, Elena P

    2003-01-01

    /ionization time of flight mass spectrometry (MALDI-TOF MS). One of these spots was identified as galectin-1. We examined whether PC3 CM, recombinant galectin-1 alone, or combined with insulin-like growth factor-I (IGF-I) had any effects on the proliferation or differentiation of human bone marrow stromal (h...

  20. Circulating factors induce coronary endothelial cell activation following exposure to inhaled diesel exhaust and nitrogen dioxide in humans: Evidence from a novel translational in vitro model**

    Science.gov (United States)

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  1. Human Factors Simulation in Construction Management Education

    Science.gov (United States)

    Jaeger, M.; Adair, D.

    2010-01-01

    Successful construction management depends primarily on the representatives of the involved construction project parties. In addition to effective application of construction management tools and concepts, human factors impact significantly on the processes of any construction management endeavour. How can human factors in construction management…

  2. Human factors in healthcare level one

    CERN Document Server

    Rosenorn-Lanng, Debbie

    2014-01-01

    The majority of errors, litigation, and complaints in the health service are due to 'human factors', yet the term is still not widely understood and is sometimes used interchangeably to refer to team training or communication skills. Although including these, the subject of 'human factors' goes far beyond this to look at systems, environmental influences, and interactions with equipment, in addition to self-awareness and human interaction. All of these aspects are captured inHuman Factors in Healthcare and are built into a new framework: the SHEEP model, which breaks down into five key areas:

  3. Effects of rupatadine, a new dual antagonist of histamine and platelet-activating factor receptors, on human cardiac kv1.5 channels.

    Science.gov (United States)

    Caballero, R; Valenzuela, C; Longobardo, M; Tamargo, J; Delpón, E

    1999-11-01

    1. The effects of rupatadine, a new dual antagonist of both histamine H1 and platelet-activating factor receptors, were studied on human cloned hKv1.5 channels expressed in Ltk- cells using the whole-cell patch-clamp technique. 2. Rupatadine produced a use- and concentration-dependent block of hKv1.5 channels (KD=2.4+/-0.7 micronM) and slowed the deactivation of the tail currents, thus inducing the 'crossover' phenomenon. 3. Rupatadine-induced block was voltage-dependent increasing in the voltage range for channel opening suggesting an open channel interaction. At potentials positive to +10 mV the blockade decreased with a shallow voltage-dependence. Moreover, rupatadine also modified the voltage-dependence of hKv1.5 channel activation, which exhibited two components, the midpoint of the steeper component averaging -25. 2+/-2.7 mV. 4. When the intracellular K+ concentration ([K+]i) was lowered to 25% the voltage-dependent unblock observed at positive potentials was suppressed and the activation curve in the presence of rupatadine did not exhibit two components even when the midpoint of the activation curve was shifted to more negative potentials (-30. 3+/-1.3 mV). 5. On channels mutated on the residue R485 (R485Y) which is located on the external entryway of the pore the rupatadine-induced block did not decrease at potentials positive to +10 mV. In contrast, on V512M channels rupatadine reproduced all the features of the blockade observed on wild type channels. 6. All these results suggest that rupatadine blocks hKv1.5 channels binding to an external and to an internal binding site but only at concentrations much higher than therapeutic plasma levels in man. Efflux of K+ promotes the unbinding from the external site. Furthermore, rupatadine binds to an internal site and dramatically modifies the voltage-dependence of channel opening.

  4. Coding Human Factors Observations in Surgery.

    Science.gov (United States)

    Cohen, Tara N; Wiegmann, Douglas A; Reeves, Scott T; Boquet, Albert J; Shappell, Scott A

    The reliability of the Human Factors Analysis and Classification System (HFACS) for classifying retrospective observational human factors data in the cardiovascular operating room is examined. Three trained analysts independently used HFACS to categorize observational human factors data collected at a teaching and nonteaching hospital system. Results revealed that the framework was substantially reliable overall (Study I: k = 0.635; Study II: k = 0.642). Reliability increased when only preconditions for unsafe acts were investigated (Study I: k =0.660; Study II: k = 0.726). Preconditions for unsafe acts were the most commonly identified issues, with HFACS categories being similarly populated across both hospitals. HFACS is a reliable tool for systematically categorizing observational data of human factors issues in the operating room. Findings have implications for the development of a HFACS tool for proactively collecting observational human factors data, eliminating the necessity for classification post hoc.

  5. Basic fibroblast growth factor/vascular endothelial growth factor in the serum from severe burn patients stimulates the proliferation of cultured human umbilical cord mesenchymal stem cells via activation of Notch signaling pathways.

    Science.gov (United States)

    Liu, Ling-Ying; Hou, Yu-Sen; Chai, Jia-Ke; Hu, Quan; Duan, Hong-Jie; Yu, Yong-Hui; Yin, Hui-Nan; Hao, Dai-Feng; Feng, Guang; Li, Tao; Du, Jun-Dong

    2013-11-01

    Mesenchymal stem cells (MSCs) are the leading cellular constituents used in regenerative medicine. MSCs repair and reconstruct wounds of acute traumata and radiation-induced burns through proliferation, differentiation, and trophic activity. However, repair effect of MSCs on severe burn wounds remain to be clarified because severe burns are much more complex traumata than radiation-induced burns. Survival and proliferation of MSCs in microenvironments affected by severe burns are very important for improving wound repair/regeneration. This study aimed to elucidate the survival and proliferation effects and the potential proliferation mechanism of serum from severe burn patients (BPS) on human umbilical cord MSCs (hUCMSCs) in vitro. The hUCMSCs were isolated, cultured, and identified. Next, we evaluated the effects of BPS on cell numbers, cell cycle progression, cyclin D expression, and key proteins and genes of the Notch signaling pathway. Putative mechanisms underlying the proliferation of hUCMSCs were investigated. BPS markedly increased the number of hUCMSCs, and the results of the cell cycle studies indicated that BPS induced cell cycle progression into the M phase. Cyclin D expression was higher with BPS than in the control group. Moreover, Notch-1, a key determinant of hUCMSC activation and proliferation, and its target gene Hes-1 were overexpressed after BPS treatment. Proliferation numbers of hUCMSC, rate of proliferation period (G2/M+S), and the expression of cyclin D, Notch-1, and Hes-1 were markedly decreased by Notch signaling inhibitors (DAPT/GSI). In the case of BPS, basic fibroblast growth factor and vascular endothelial growth factor were the key factors that promoted hUCMSC proliferation. This study provides novel evidence for the role of BPS in the survival and rapid proliferation of hUCMSCs and suggests that these cells could be used for cell therapy-based clinical applications for treating severe burns. Furthermore, hUCMSC proliferation was

  6. Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration.

    OpenAIRE

    Presta, M; Moscatelli, D; Joseph-Silverstein, J; Rifkin, D B

    1986-01-01

    A 17,500-dalton protein which stimulates plasminogen activator production in cultured bovine capillary endothelial cells has been purified from a SK-Hep-1 human hepatoma cell lysate by using heparin affinity chromatography and fast protein-liquid ion exchange chromatography. The purified molecule stimulated plasminogen activator production in a dose-dependent manner between 0.01 and 1 ng/ml. It also stimulated collagenase synthesis, DNA synthesis, and motility in capillary endothelial cells i...

  7. Accounting for the human factor

    Science.gov (United States)

    Gilligan, Jonathan M.

    2018-01-01

    One of the greatest sources of uncertainty about future climate change is the path greenhouse gas emissions will take. Now research using a coupled model of human behaviour and climate finds that individual behaviour can significantly alter emissions trajectories and global temperature.

  8. Human factors in safety and business management.

    Science.gov (United States)

    Vogt, Joachim; Leonhardt, Jorg; Koper, Birgit; Pennig, Stefan

    2010-02-01

    Human factors in safety is concerned with all those factors that influence people and their behaviour in safety-critical situations. In aviation these are, for example, environmental factors in the cockpit, organisational factors such as shift work, human characteristics such as ability and motivation of staff. Careful consideration of human factors is necessary to improve health and safety at work by optimising the interaction of humans with their technical and social (team, supervisor) work environment. This provides considerable benefits for business by increasing efficiency and by preventing incidents/accidents. The aim of this paper is to suggest management tools for this purpose. Management tools such as balanced scorecards (BSC) are widespread instruments and also well known in aviation organisations. Only a few aviation organisations utilise management tools for human factors although they are the most important conditions in the safety management systems of aviation organisations. One reason for this is that human factors are difficult to measure and therefore also difficult to manage. Studies in other domains, such as workplace health promotion, indicate that BSC-based tools are useful for human factor management. Their mission is to develop a set of indicators that are sensitive to organisational performance and help identify driving forces as well as bottlenecks. Another tool presented in this paper is the Human Resources Performance Model (HPM). HPM facilitates the integrative assessment of human factors programmes on the basis of a systematic performance analysis of the whole system. Cause-effect relationships between system elements are defined in process models in a first step and validated empirically in a second step. Thus, a specific representation of the performance processes is developed, which ranges from individual behaviour to system performance. HPM is more analytic than BSC-based tools because HPM also asks why a certain factor is

  9. IL-2 Expression in Activated Human Memory FOXP3(+) Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors of  T Cell Activation.

    Science.gov (United States)

    Bendfeldt, Hanna; Benary, Manuela; Scheel, Tobias; Steinbrink, Kerstin; Radbruch, Andreas; Herzel, Hanspeter; Baumgrass, Ria

    2012-01-01

    The human CD4(+)FOXP3(+) T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3(+)Treg cells. We used the anergic behavior of FOXP3(+)Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing cells within the memory FOXP3(+) T cell population. In contrast to IL-2-non-expressing FOXP3(+) cells, IL-2-expressing FOXP3(+) cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels of the transcription factors NFATc2, c-Fos, NF-κBp65, and c-Jun. An approach combining flow cytometric measurements with statistical interpretation for quantitative transcription factor analysis suggests that the physiological expression levels not only of FOXP3 but also of NFATc2, c-Jun, c-Fos, and NF-κBp65 are limiting for the decision whether IL-2 is expressed or not in activated peripheral human memory FOXP3(+) cells. These findings demonstrate that concomitant high levels of NFATc2, c-Jun, c-Fos, and NF-κBp65 lead in addition to potential IL-2 expression in those FOXP3(+) cells with low levels of FOXP3. We hypothesize that not only the level of FOXP3 expression but also the amounts of the four transcription factors studied represent determining factors for the anergic phenotype of FOXP3(+) Treg cells.

  10. IL-2 Expression in Activated Human Memory FOXP3+ Cells Critically Depends on the Cellular Levels of FOXP3 as Well as of Four Transcription Factors of  T Cell Activation

    Science.gov (United States)

    Bendfeldt, Hanna; Benary, Manuela; Scheel, Tobias; Steinbrink, Kerstin; Radbruch, Andreas; Herzel, Hanspeter; Baumgrass, Ria

    2012-01-01

    The human CD4+FOXP3+ T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3+Treg cells. We used the anergic behavior of FOXP3+Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-non-expressing cells within the memory FOXP3+ T cell population. In contrast to IL-2-non-expressing FOXP3+ cells, IL-2-expressing FOXP3+ cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels of the transcription factors NFATc2, c-Fos, NF-κBp65, and c-Jun. An approach combining flow cytometric measurements with statistical interpretation for quantitative transcription factor analysis suggests that the physiological expression levels not only of FOXP3 but also of NFATc2, c-Jun, c-Fos, and NF-κBp65 are limiting for the decision whether IL-2 is expressed or not in activated peripheral human memory FOXP3+ cells. These findings demonstrate that concomitant high levels of NFATc2, c-Jun, c-Fos, and NF-κBp65 lead in addition to potential IL-2 expression in those FOXP3+ cells with low levels of FOXP3. We hypothesize that not only the level of FOXP3 expression but also the amounts of the four transcription factors studied represent determining factors for the anergic phenotype of FOXP3+ Treg cells. PMID:22969764

  11. IL-2 expression in activated human memory FOXP3+ cells critically depends on the cellular levels of FOXP3 as well as of four transcription factors of T cell activation

    Directory of Open Access Journals (Sweden)

    Hanna eBendfeldt

    2012-08-01

    Full Text Available The human CD4+FOXP3+ T cell population is heterogeneous and consists of various subpopulations which remain poorly defined. Anergy and suppression are two main functional characteristics of FOXP3+Treg cells. We used the anergic behavior of FOXP3+Treg cells for a better discrimination and characterization of such subpopulations. We compared IL-2-expressing with IL-2-nonexpressing cells within the memory FOXP3+ T cell population. In contrast to IL-2 nonexpressing FOXP3+ cells, IL-2-expressing FOXP3+ cells exhibit intermediate characteristics of Treg and Th cells concerning the Treg cell markers CD25, GITR, and Helios. Besides lower levels of FOXP3, they also have higher levels of the transcription factors NFATc2, c-Fos, NF-Bp65, and c-Jun. An approach combining flow cytometric measurements with statistical interpretation for quantitative transcription factor analysis suggest that the physiological expression levels not only of FOXP3 but also of NFATc2, c-Jun, c-Fos, and NF-Bp65 are limiting for the decision whether IL-2 is expressed or not in activated peripheral human memory FOXP3+ cells. These findings demonstrate that concomitant high levels of NFATc2, c-Jun, c-Fos, and NF-Bp65 lead in addition to potential IL-2 expression in those FOXP3+ cells with low levels of FOXP3. We hypothesize that not only the level of FOXP3 expression but also the amounts of the four transcription factors studied represent determining factors for the anergic phenotype of FOXP3+ Treg cells.

  12. [Immunoexpression and clinical significance of interleukin-21 and receptor activator of nuclear factor κB ligand in human periapical granulomas and radicular cysts].

    Science.gov (United States)

    Hu, Juhua; Li, Qian; Wang, Yanqing; Li, Song

    2015-06-01

    This study aimed to detect the immunoexpression of interleukin-21 (IL-21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated. A total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated. IL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92±6.57 and 36.80± 6.81, whereas those of RANKL were 68.81±18.59 and 36.12±14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05). This study demonstrated that IL-21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes.

  13. Transcriptional regulation of Hb-α and Hb-β through nuclear factor E2-related factor-2 (Nrf2) activation in human vaginal cells: A novel mechanism of cellular adaptability to oxidative stress.

    Science.gov (United States)

    Saha, Debarchana; Koli, Swanand; Reddy, Kudumula Venkata Rami

    2017-06-01

    Hemoglobin (Hb), a major protein involved in transport of oxygen (O2 ), is expressed by erythroid lineages. Until recently, it was not known whether non-erythroid cells express Hb. The objective was to evaluate the expression and functional significance of Hb-α and Hb-β in human primary vaginal epithelial cells (hPVECs) and decipher downstream signaling. RT-PCR, qRT-PCR, flow cytometry, Western blot, immunofluorescence were used to evaluate the expression of Hb-α, Hb-β, and nuclear factor E2-related factor-2(Nrf2) after hydrogen peroxide (H2 O2 ) induction. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay were used to determine the binding efficiency of Nrf2 on the Hb-α promoter. Stimulation of hPVECs and human vaginal epithelial cell line, VK2/E6E7 with H2 O2 augmented the expression of Hb-α, Hb-β, Nrf2, heme oxygenase-1 (HO-1), and reactive oxygen species (ROS). Treatment of these cells with Nrf2 inhibitor, trigonelline (Trig) inhibited Hb-α and Hb-β expressions. Hb-α and Hb-β overexpression downregulated H2 O2 -induced ROS. The presence of Nrf2 binding domain was demonstrated within Hb-α promoter. The results revealed for the first time that Hb-α and Hb-β were induced by oxidative stress through the activation of Nrf2. Overexpression of Hb-α and Hb-β ameliorated H2 O2 -induced oxidative stress, indicating one of the possible mechanism(s) to protect hPVECS from oxidative stress. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Human Factors Directions for Civil Aviation

    Science.gov (United States)

    Hart, Sandra G.

    2002-01-01

    Despite considerable progress in understanding human capabilities and limitations, incorporating human factors into aircraft design, operation, and certification, and the emergence of new technologies designed to reduce workload and enhance human performance in the system, most aviation accidents still involve human errors. Such errors occur as a direct or indirect result of untimely, inappropriate, or erroneous actions (or inactions) by apparently well-trained and experienced pilots, controllers, and maintainers. The field of human factors has solved many of the more tractable problems related to simple ergonomics, cockpit layout, symbology, and so on. We have learned much about the relationships between people and machines, but know less about how to form successful partnerships between humans and the information technologies that are beginning to play a central role in aviation. Significant changes envisioned in the structure of the airspace, pilots and controllers' roles and responsibilities, and air/ground technologies will require a similarly significant investment in human factors during the next few decades to ensure the effective integration of pilots, controllers, dispatchers, and maintainers into the new system. Many of the topics that will be addressed are not new because progress in crucial areas, such as eliminating human error, has been slow. A multidisciplinary approach that capitalizes upon human studies and new classes of information, computational models, intelligent analytical tools, and close collaborations with organizations that build, operate, and regulate aviation technology will ensure that the field of human factors meets the challenge.

  15. Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor.

    Science.gov (United States)

    Wang, Gen; Barrett, John W; Stanford, Marianne; Werden, Steven J; Johnston, James B; Gao, Xiujuan; Sun, Mei; Cheng, Jin Q; McFadden, Grant

    2006-03-21

    We demonstrate that the susceptibility of human cancer cells to be infected and killed by an oncolytic poxvirus, myxoma virus (MV), is related to the basal level of endogenous phosphorylated Akt. We further demonstrate that nonpermissive tumor cells will switch from resistant to susceptible for MV infection after expression of ectopically active Akt (Myr-Akt) and that permissive cancer cells can be rendered nonpermissive by blocking Akt activation with a dominant-negative inhibitor of Akt. Finally, the activation of Akt by MV involves the formation of a complex between the viral host range ankyrin-repeat protein, M-T5, and Akt. We conclude that the Akt pathway is a key restriction determinant for permissiveness of human cancer cells by MV.

  16. Fundamentals of systems ergonomics/human factors.

    Science.gov (United States)

    Wilson, John R

    2014-01-01

    Ergonomics/human factors is, above anything else, a systems discipline and profession, applying a systems philosophy and systems approaches. Many things are labelled as system in today's world, and this paper specifies just what attributes and notions define ergonomics/human factors in systems terms. These are obviously a systems focus, but also concern for context, acknowledgement of interactions and complexity, a holistic approach, recognition of emergence and embedding of the professional effort involved within organization system. These six notions are illustrated with examples from a large body of work on rail human factors. Copyright © 2013. Published by Elsevier Ltd.

  17. Frequency and risk factors for prevalent, incident, and persistent genital carcinogenic human papillomavirus infection in sexually active women: community based cohort study.

    Science.gov (United States)

    Oakeshott, Pippa; Aghaizu, Adamma; Reid, Fiona; Howell-Jones, Rebecca; Hay, Phillip E; Sadiq, S Tariq; Lacey, Charles J; Beddows, Simon; Soldan, Kate

    2012-06-22

    To investigate frequency and risk factors for prevalent, incident, and persistent carcinogenic human papillomavirus (HPV) in young women before the introduction of immunisation against HPV types 16 and 18 for schoolgirls. Cohort study 20 London universities and further education colleges. 2185 sexually active female students, mean age 21 years (range 16-27), 38% from ethnic minorities, who took part in the POPI (prevention of pelvic infection) chlamydia screening trial in 2004-08 and who provided duplicate, self taken vaginal swabs and completed questionnaires at baseline. At follow-up, a median of 16 months later, 821 women (38%) returned repeat vaginal swabs by post. In 2009-10, stored samples were tested for HPV. Samples from 404/2185 (18.5% (95% CI 16.9% to 20.2%)) of the cohort were positive for carcinogenic HPV at baseline, including 15.0% (327) positive for non-vaccine carcinogenic genotypes. Reporting two or more sexual partners in the previous year and concurrent Chlamydia trachomatis or bacterial vaginosis were independent risk factors for prevalent vaginal HPV infection. Infection with one or more new HPV types was found in 17.7% (145/821) of follow-up samples, giving an estimated annual incidence of carcinogenic HPV infection of 12.9% (95% CI 11.0% to 15.0%). Incident infection was more common in women reporting two or more partners in the previous year, agedcarcinogenic HPV infection, 20 (14% (8.3% to 19.7%) had infection with the same carcinogenic HPV type(s) detected after 12-28 months. Of these women, 13 (65%) had redetected infection with HPV 16 or 18, and nine (45%) with non-vaccine carcinogenic HPV genotypes. In the first UK cohort study of carcinogenic HPV in young women in the community, multiple sexual partners was an independent predictor of both prevalent and incident infection. Infection with non-vaccine carcinogenic genotypes was common. Although current HPV vaccines offer partial cross protection against some non-vaccine carcinogenic HPV

  18. Human factors challenges for advanced process control

    Energy Technology Data Exchange (ETDEWEB)

    Stubler, W.F.; O`Hara, J..M.

    1996-08-01

    New human-system interface technologies provide opportunities for improving operator and plant performance. However, if these technologies are not properly implemented, they may introduce new challenges to performance and safety. This paper reports the results from a survey of human factors considerations that arise in the implementation of advanced human-system interface technologies in process control and other complex systems. General trends were identified for several areas based on a review of technical literature and a combination of interviews and site visits with process control organizations. Human factors considerations are discussed for two of these areas, automation and controls.

  19. The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity

    DEFF Research Database (Denmark)

    Fonnes, Siv; Holzknecht, Barbara Juliane; Gasbjerg, Lærke Smidt

    2017-01-01

    BACKGROUND: Treatment of secondary peritonitis includes surgery and antimicrobial agents. Antimicrobial agents are often administered intravenously, however, the alternative route intraperitoneal administration could be considered. Investigations must be conducted prior to clinical application....... Therefore, we aimed to investigate the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor with regard to its chemical properties and the solution's stability. In addition, the antibacterial effect of the mixed drug solution was compared...

  20. Human factors and information transfer

    Science.gov (United States)

    Lee, Alfred T.

    1989-01-01

    Key problem areas in the management and transfer of information in the National Airspace System, contributing to human errors are identified. Information-management aspects supporting the user's ability to assess prevailing situations accurately with adequate time to make an informed decision are considered. The relationship between judgment biases and requirements for managing weather information is illustrated by examining such hazardous weather phenomena as microbursts and windshears. The system of air-ground communication relying almost exclusively on voice transmissions is discussed, and recommendations in the areas of communications procedures and technology development are provided.

  1. The cell-penetrating peptide domain from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) has anti-inflammatory activity in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jue-Yeon; Seo, Yoo-Na; Park, Hyun-Jung [Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Park, Yoon-Jeong, E-mail: parkyj@snu.ac.kr [Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Department of Dental Regenerative Biotechnology, Dental Research Institute and School of Dentistry, Seoul National University, Seoul (Korea, Republic of); Chung, Chong-Pyoung, E-mail: ccpperio@snu.ac.kr [Research Center, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul (Korea, Republic of); Department of Periodontology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer HBP sequence identified from HB-EGF has cell penetration activity. Black-Right-Pointing-Pointer HBP inhibits the NF-{kappa}B dependent inflammatory responses. Black-Right-Pointing-Pointer HBP directly blocks phosphorylation and degradation of I{kappa}B{alpha}. Black-Right-Pointing-Pointer HBP inhibits nuclear translocation of NF-{kappa}B p65 subunit. -- Abstract: A heparin-binding peptide (HBP) sequence from human heparin-binding epidermal growth factor-like growth factor (HB-EGF) was identified and was shown to exhibit cell penetration activity. This cell penetration induced an anti-inflammatory reaction in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. HBP penetrated the cell membrane during the 10 min treatment and reduced the LPS-induced production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (TNF-{alpha} and IL-6) in a concentration-dependent manner. Additionally, HBP inhibited the LPS-induced upregulation of cytokines, including TNF-{alpha} and IL-6, and decreased the interstitial infiltration of polymorphonuclear leukocytes in a lung inflammation model. HBP inhibited NF-{kappa}B-dependent inflammatory responses by directly blocking the phosphorylation and degradation of I{kappa}B{alpha} and by subsequently inhibiting the nuclear translocation of the p65 subunit of NF-{kappa}B. Taken together, this novel HBP may be potentially useful candidate for anti-inflammatory treatments and can be combined with other drugs of interest to transport attached molecules into cells.

  2. Human factors issues for interstellar spacecraft

    Science.gov (United States)

    Cohen, Marc M.; Brody, Adam R.

    1991-01-01

    Developments in research on space human factors are reviewed in the context of a self-sustaining interstellar spacecraft based on the notion of traveling space settlements. Assumptions about interstellar travel are set forth addressing costs, mission durations, and the need for multigenerational space colonies. The model of human motivation by Maslow (1970) is examined and directly related to the design of space habitat architecture. Human-factors technology issues encompass the human-machine interface, crew selection and training, and the development of spaceship infrastructure during transtellar flight. A scenario for feasible instellar travel is based on a speed of 0.5c, a timeframe of about 100 yr, and an expandable multigenerational crew of about 100 members. Crew training is identified as a critical human-factors issue requiring the development of perceptual and cognitive aids such as expert systems and virtual reality.

  3. Development of an electronic Human Factor Management Program (e HFMP)

    Energy Technology Data Exchange (ETDEWEB)

    Sung, Chan Ho; Kim, Young Gab; Jung, Yeon Sub [KHNP Central Research Institute, Daejeon (Korea, Republic of)

    2012-10-15

    Human error is one of main contributors of reactor trip in nuclear power plants. Therefore, HFE application is essential in every field of nuclear power plants such as operating, maintenance, and plant design. However, HFE is an unfamiliar term and field for plant staffs. Lots of activities has been carried out to reduce human error and to enhance human performance. During these efforts, it is frequently asked where human factor guidelines are, and how the guidelines are applied to their usual activities. This paper explains e HFMP for this purpose.

  4. Human Factors in Railroad Operations : Initial Studies

    Science.gov (United States)

    1972-01-01

    This report summarizes the progress of a year's work in providing support in human factors to the Federal Railroad Administration. The principal topics include: (a) a description of the locomotive engineer's job, particularly with regard to its inher...

  5. Implementing human factors in clinical practice

    OpenAIRE

    Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

    2014-01-01

    Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have rece...

  6. Antimicrobial factors in human milk.

    Science.gov (United States)

    Reddy, V; Bhaskaram, C; Raghuramulu, N; Jagadeesan, V

    1977-03-01

    Levels of immunoglobulins, lactoferrin and lysozyme were determined in milk samples obtained from well-nourished and under-nourished Indian women at different stages of lactation. The concentration of immunoglobulins and lactoferrin was higher in colostrum than in mature milk while the lysozyme levels showed a progressive increase with the period of lactation. There were no significant differences in the levels between the two groups of women. Administration of iron did not alter either the total or percentage saturation of lactoferrin in milk. These results indicate that antibacterial factors in milk are not influenced by the nutritional status of the mother and that iron supplementation does not interfere with the bacteriostatic function of lactoferrin.

  7. Development of human factors design review guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1997-10-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 12 refs., 5 figs., 2 tabs.

  8. Biodiversity loss in Ghana: The human factor | Bennett-Lartey ...

    African Journals Online (AJOL)

    Loss of biodiversity in Ghana is due to human activities and other environmental factors. The country loses a great proportion of its biodiversity, due mainly to unacceptable practices like slash and burn agriculture, surface mining, construction activities and bushfires. Various conservation measures practiced in Ghana have ...

  9. Research on disaster prevention by human factor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bok Youn; Kang, Chang Hee; Kang, Sun Duck; Jo, Young Do [Korea Institute of Geology Mining and Materials, Taejon (Korea)

    1998-12-01

    Mining, by its very nature, requires workers and technology to function in an unpredictable environment that can not easily be engineered to accommodate human factors. Miners' physical and cognitive capabilities are sometimes stretched to the point that 'human error' in performance result. Mine safety researchers estimate that 50-85% of all mining injuries are due, in large part, to human error. Further research suggests that the primary causes of these errors in performance lie outside the individual and can be minimized by improvements in equipment design, work environments, work procedures and training. The human factors research is providing the science needed to determine which aspects of the mining environment can be made more worker-friendly and how miners can work more safely in environments that can not be improved. Underground mines have long been recognized as an innately hazardous and physically demanding work environment. Recently, mining is becoming a more complicated process as more sophisticated technologies are introduced. The more complicated or difficult the tasks to be performed, the more critical it is to have a systematic understanding of the humans, the technology, the environments, and how they interact. Human factors is a key component in solving most of today's mine safety and health problems. Human factors research primarily centered around solving problems in the following four areas: 1) How mining methods and equipment affect safety, 2) Evaluating the fit between miner's physical capabilities and the demands of their job, 3) Improving miner's ability to perceive and react to hazards, 4) Understanding how organizational and managerial variables influence safety. Human factor research was begun during the World war II. National Coal Board (British Coal) of Great Britain commenced ergonomics in 1969, and Bureau of Mine of United States started human factor researches in same year. Japan has very short history

  10. Psychosocial factors underlying physical activity

    Directory of Open Access Journals (Sweden)

    Ji Cheng-Ye

    2007-09-01

    of physical activity on academic achievement and other factors beyond physical health; barriers of not having enough time and having too many assignments perceived to hinder frequent physical activity; and parental approval. More rigorous research on psychosocial determinants with close-ended items developed from these open-ended data and with larger sample sizes of students is necessary. Research with parents and school staff will be needed to understand the perceptions of these stakeholder groups key to creating the students' social environment.

  11. Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes.

    Science.gov (United States)

    van der Sluis, Renée M; Derking, Ronald; Breidel, Seyguerney; Speijer, Dave; Berkhout, Ben; Jeeninga, Rienk E

    2014-04-01

    HIV-1 transcription depends on cellular transcription factors that bind to sequences in the long-terminal repeat (LTR) promoter. Each HIV-1 subtype has a specific LTR promoter configuration, and minor sequence changes in transcription factor binding sites (TFBSs) or their arrangement can influence transcriptional activity, virus replication and latency properties. Previously, we investigated the proviral latency properties of different HIV-1 subtypes in the SupT1 T cell line. Here, subtype-specific latency and replication properties were studied in primary PHA-activated T lymphocytes. No major differences in latency and replication capacity were measured among the HIV-1 subtypes. Subtype B and AE LTRs were studied in more detail with regard to a putative AP-1 binding site using luciferase reporter constructs. c-Jun, a member of the AP-1 transcription factor family, can activate both subtype B and AE LTRs, but the latter showed a stronger response, reflecting a closer match with the consensus AP-1 binding site. c-Jun overexpression enhanced Tat-mediated transcription of the viral LTR, but in the absence of Tat inhibited basal promoter activity. Thus, c-Jun can exert a positive or negative effect via the AP-1 binding site in the HIV-1 LTR promoter, depending on the presence or absence of Tat.

  12. An Exon-Specific U1snRNA Induces a Robust Factor IX Activity in Mice Expressing Multiple Human FIX Splicing Mutants

    Directory of Open Access Journals (Sweden)

    Dario Balestra

    2016-01-01

    Full Text Available In cellular models we have demonstrated that a unique U1snRNA targeting an intronic region downstream of a defective exon (Exon-specific U1snRNA, ExSpeU1 can rescue multiple exon-skipping mutations, a relevant cause of genetic disease. Here, we explored in mice the ExSpeU1 U1fix9 toward two model Hemophilia B-causing mutations at the 5′ (c.519A > G or 3′ (c.392-8T > G splice sites of F9 exon 5. Hydrodynamic injection of wt-BALB/C mice with plasmids expressing the wt and mutant (hFIX-2G5′ss and hFIX-8G3′ss splicing-competent human factor IX (hFIX cassettes resulted in the expression of hFIX transcripts lacking exon 5 in liver, and in low plasma levels of inactive hFIX. Coinjection of U1fix9, but not of U1wt, restored exon inclusion of variants and in the intrinsically weak FIXwt context. This resulted in appreciable circulating hFIX levels (mean ± SD; hFIX-2G5′ss, 1.0 ± 0.5 µg/ml; hFIX-8G3′ss, 1.2 ± 0.3 µg/ml; and hFIXwt, 1.9 ± 0.6 µg/ml, leading to a striking shortening (from ≃100 seconds of untreated mice to ≃80 seconds of FIX-dependent coagulation times, indicating a hFIX with normal specific activity. This is the first proof-of-concept in vivo that a unique ExSpeU1 can efficiently rescue gene expression impaired by distinct exon-skipping variants, which extends the applicability of ExSpeU1s to panels of mutations and thus cohort of patients.

  13. Learning Latent Factor Models of Human Travel

    OpenAIRE

    Guerzhoy, Michael; Hertzmann, Aaron

    2012-01-01

    NIPS Workshop on Social Network and Social Media Analysis; International audience; This paper describes probability models for human travel, using latent factors learned from data. The latent factors represent interpretable properties: travel distance cost, desirability of destinations, and affinity between locations. Individuals are clustered into distinct styles of travel. The latent factors combine in a multiplicative manner, and are learned using Maximum Likelihood. The resulting models e...

  14. Human factors and safety in emergency medicine

    Science.gov (United States)

    Schaefer, H. G.; Helmreich, R. L.; Scheidegger, D.

    1994-01-01

    A model based on an input process and outcome conceptualisation is suggested to address safety-relevant factors in emergency medicine. As shown in other dynamic and demanding environments, human factors play a decisive role in attaining high quality service. Attitudes held by health-care providers, organisational shells and work-cultural parameters determine communication, conflict resolution and workload distribution within and between teams. These factors should be taken into account to improve outcomes such as operational integrity, job satisfaction and morale.

  15. Tumor Necrosis Factor-Alpha and Receptor Activator of Nuclear Factor-κB Ligand Augment Human Macrophage Foam-Cell Destruction of Extracellular Matrix Through Protease-Mediated Processes

    DEFF Research Database (Denmark)

    Skjøt-Arkil, Helene; Barascuk, Natasha; Larsen, Lise Korsager

    2012-01-01

    , a major component of extracellular matrix (ECM) in plaques, and to establish whether the pro-inflammatory molecules, tumor necrosis factor (TNF)-alpha, and receptor activator of nuclear factor-κB ligand (RANK-L) increase this degradation. CD14+ monocytes isolated from peripheral blood were differentiated...

  16. Nutrition, Physical Activity, and Obesity - Behavioral Risk Factor Surveillance System

    Data.gov (United States)

    U.S. Department of Health & Human Services — This dataset includes data on adult's diet, physical activity, and weight status from Behavioral Risk Factor Surveillance System. This data is used for DNPAO's Data,...

  17. Physical activity and human health

    Directory of Open Access Journals (Sweden)

    Paulina Wojciechowska

    2015-01-01

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

  18. Effectiveness of human factors simulator; Eficiencia del simulador de factores humanos

    Energy Technology Data Exchange (ETDEWEB)

    Moragas, F.

    2015-07-01

    En 2011, ANAV started the exploitation of the Human Factors Simulator installed in TECNATOM Training Center located in L'Hospital de L'Infant Tarragona. AVAN's Strategic Plan includes the Action Plan for the improvement of human behavior. The plan includes improving the efficiency of the efficiency of the human factors simulator. It is proposed to improve the efficiency into two different terms: winning effectiveness in modeling behaviors, and interweaving the activities in the simulator with the actual strategy of promoting Safety culture and human behaviour. (Author)

  19. Transforming growth factor-β-activated kinase 1 (TAK1 is required for human FcγRIIIb-induced neutrophil extracellular trap (NET formation

    Directory of Open Access Journals (Sweden)

    Omar Rafael Alemán

    2016-07-01

    Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. Several stimuli, including bacteria, fungi, and parasites, and some pharmacological compounds such as PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. Recently, it was reported that FcγRIIIb crosslinking induced NET formation similarly to PMA stimulation. Direct crosslinking of FcγRIIA or integrins did not promote NET formation. FcγRIIIb-induced NET formation presented different kinetics from PMA-induced NET formation, suggesting differences in signaling. Because FcγRIIIb also induces a strong activation of ERK and nuclear factor Elk-1, and the transforming growth factor-β-activated kinase 1 (TAK1 has recently been implicated in ERK signaling, in the present report, we explored the role of TAK1 in the signaling pathway activated by FcγRIIIb leading to NET formation. FcγRIIIb was stimulated by specific monoclonal antibodies and NET formation was evaluated in the presence or absence of pharmacological inhibitors. The antibiotic LL Z1640-2, a selective inhibitor of TAK1 prevented FcγRIIIb-induced, but not PMA-induced NET formation. Both PMA and FcγRIIIb crosslinkng induced phosphorylation of ERK. But, LL Z1640-2 only inhibited the FcγRIIIb-mediated activation of ERK. Also, only FcγRIIIb, similarly to transforming growth factor-β, induced TAK1 phosphorylation. A MEK (ERK kinase specific inhibitor was able to prevent ERK phosphorylation induced by both PMA and FcγRIIIb. These data show for the first time that FcγRIIIb crosslinking activates TAK1 and that this kinase is required for triggering the MEK/ERK signaling pathway to NETosis.

  20. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    Science.gov (United States)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  1. Human Factors Plan for the Aeronautical Information Subsystem

    Science.gov (United States)

    1994-10-01

    This human factors plan covers the human factors effort for the development of the Aeronautical Information Subsystem (AIS) of the Operational Data Management System (ODMS). Broadly the goals of the human factors effort are to provide a user interfac...

  2. Information sciences and human factors overview

    Science.gov (United States)

    Holcomb, Lee B.

    1988-01-01

    An overview of program objectives of the Information Sciences and Human Factors Division of NASA's Office of Aeronautics and Space Technology is given in viewgraph form. Information is given on the organizational structure, goals, the research and technology base, telerobotics, systems autonomy in space operations, space sensors, humans in space, space communications, space data systems, transportation vehicle guidance and control, spacecraft control, and major program directions in space.

  3. Annotated bibliography of human factors applications literature

    Energy Technology Data Exchange (ETDEWEB)

    McCafferty, D.B.

    1984-09-30

    This bibliography was prepared as part of the Human Factors Technology Project, FY 1984, sponsored by the Office of Nuclear Safety, US Department of Energy. The project was conducted by Lawrence Livermore National Laboratory, with Essex Corporation as a subcontractor. The material presented here is a revision and expansion of the bibliographic material developed in FY 1982 as part of a previous Human Factors Technology Project. The previous bibliography was published September 30, 1982, as Attachment 1 to the FY 1982 Project Status Report.

  4. Human genetic factors in tuberculosis: an update.

    Science.gov (United States)

    van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

    2017-09-01

    Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

  5. Antitumor activity of a combination of trastuzumab (Herceptin) and oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2-overexpressing pancreatic cancer.

    Science.gov (United States)

    Saeki, Hiroyuki; Yanoma, Shunsuke; Takemiya, Shouji; Sugimasa, Yukio; Akaike, Makoto; Yukawa, Norio; Rino, Yasushi; Imada, Toshio

    2007-08-01

    The cytotoxic effect of trastuzumab in combination with oral fluoropyrimidine S-1 on human epidermal growth factor receptor 2 (HER2)-overexpressing human pancreatic cancer cell line TRG in vitro and in vivo was investigated. HER2 expression in TRG was analyzed by RT-PCR and flow cytometry. For in vitro experiments, 5-fluorouracil (5-FU) was used instead of S-1. In vivo studies were conducted with TRG xenografts in athymic mice. Trastuzumab (10 mg/kg) was administered intraperitoneally once a week for 4 weeks. S-1 (10 mg/kg) was administered orally 5 days a week for 4 weeks. The results showed that TRG cells were positive for HER2 mRNA and overexpressed HER2 protein. Either trastuzumab or 5-FU concentration-dependently inhibited the growth of TRG cells. The combination of trastuzumab and 5-FU resulted in a significant inhibition of growth of TRG cells compared to either agent alone (P<0.001). Incubation of TRG cells with peripheral blood mononuclear cells after treatment with trastuzumab enhanced the antiproliferative effect of trastuzumab, which could be the result of antibody-dependent cellular cytotoxicity. The combination of trastuzumab and S-1 resulted in a significant reduction in xenograft volume compared to each agent alone (P<0.0001). In conclusion, this study showed that combination therapy with trastuzumab and S-1 may be effective for HER2-overexpressing pancreatic cancer patients.

  6. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhi, Xiuyi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053 (China); Giroux-Leprieur, Etienne [ER2 GRC UPMC04 Theranoscan, Pierre et Marie Curie University, Tenon Hospital, 4 Rue de La Chine, 75020, Paris (France); Respiratory Diseases and Thoracic Oncology Department, Ambroise Pare Hospital – APHP, Versailles Saint Quentin en Yvelines University, 9 Avenue Charles de Gaulle, 92100, Boulogne-Billancourt (France); Wislez, Marie [ER2 GRC UPMC04 Theranoscan, Pierre et Marie Curie University, Tenon Hospital, 4 Rue de La Chine, 75020, Paris (France); Hu, Mu; Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing, 100053 (China); Shi, Huaiyin [Department of Pathology, Chinese PLA General Hospital, Fu-xing Road #28, Beijing, 100853 (China); Du, Kaiqi, E-mail: kaiqidu_zhejiang@163.com [Department of Cardiothoracic Surgery, Chinese People' s Armed Police Force, Zhejiang Corps Hospital, Jiaxing, Zhejiang Province (China); Wang, Lei, E-mail: leiwang_hebei@163.com [Department of Human Anatomy, Hebei Medical University, Hebei Province (China)

    2015-10-02

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.

  7. The proinflammatory cytokines interleukin-1α and tumor necrosis factor α promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes.

    Science.gov (United States)

    Caglič, Dejan; Repnik, Urška; Jedeszko, Christopher; Kosec, Gregor; Miniejew, Catherine; Kindermann, Maik; Vasiljeva, Olga; Turk, Vito; Wendt, K Ulrich; Sloane, Bonnie F; Goldring, Mary B; Turk, Boris

    2013-02-01

    Osteoarthritis and rheumatoid arthritis are destructive joint diseases that involve the loss of articular cartilage. Degradation of cartilage extracellular matrix is believed to occur due to imbalance between the catabolic and anabolic processes of resident chondrocytes. Previous work has suggested that various lysosomal cysteine cathepsins participate in cartilage degeneration; however, their exact roles in disease development and progression have not been elucidated. In order to study degradation processes under conditions resembling the in vivo milieu of the cartilage, we cultivated chondrocytes on a type II collagen-containing matrix. Stimulation of the cultivated chondrocytes with interleukin-1α and/or tumor necrosis factor α resulted in a time-dependent increase in cathepsin S expression and induced its secretion into the conditioned media. Using a novel bioluminescent activity-based probe, we were able to demonstrate a significant increase in proteolytic activity of cathepsin S in the conditioned media of proinflammatory cytokine-stimulated chondrocytes. For the first time, cathepsin S was demonstrated to be secreted from chondrocytes upon stimulation with the proinflammatory cytokines, and displayed proteolytic activity in culture supernatants. Its stability at neutral pH and potent proteolytic activity on extracellular matrix components mean that cathepsin S may contribute significantly to cartilage degradation and may thus be considered a potential drug target in joint diseases.

  8. The In Vitro Effect of Acidic-Pepsin on Nuclear Factor KappaB Activation and Its Related Oncogenic Effect on Normal Human Hypopharyngeal Cells.

    Directory of Open Access Journals (Sweden)

    Clarence T Sasaki

    Full Text Available Extra-esophageal carcinogenesis has been widely discussed in relation to the chronic effects of laryngopharyngeal reflux and most prominently with pepsin historically central to this discussion. With refluxate known to include gastric (pepsin and duodenal (bile fluids, we recently demonstrated the mechanistic role of NF-κB in mediating the preneoplastic effects of acidic-bile. However, the role of pepsin in promoting hypopharyngeal premalignant events remains historically unclear. Here, we investigate the in vitro effect of acidic-pepsin on the NF-κB oncogenic pathway to better define its potential role in hypopharyngeal neoplasia.Human hypopharyngeal primary cells (HHPC and keratinocytes (HHK were repetitively exposed to physiologic pepsin concentrations (0.1 mg/ml at pH 4.0, 5.0 and 7.0. Cellular localization of phospho-NF-κB and bcl-2 was determined using immunofluorescence and western blotting. NF-κB transcriptional activity was tested by luc reporter and qPCR. Analysis of DNA content of pepsin treated HHK and HHPC was performed using Fluorescence-activated-cell sorting assay. To explore a possible dose related effect, pepsin concentration was reduced from 0.1 to 0.05 and 0.01 mg/ml.At physiologic concentration, acidic-pepsin (0.1 mg/ml at pH 4.0 is lethal to most normal hypopharyngeal cells. However, in surviving cells, no NF-κB transcriptional activity is noted. Acidic-pepsin fails to activate the NF-κB or bcl-2, TNF-α, EGFR, STAT3, and wnt5α but increases the Tp53 mRNAs, in both HHPC and HHK. Weakly acidic-pepsin (pH 5.0 and neutral-pepsin (pH 7.0 induce mild activation of NF-κB with increase in TNF-α mRNAs, without oncogenic transcriptional activity. Lower concentrations of pepsin at varying pH do not produce NF-κB activity or transcriptional activation of the analyzed genes.Our findings in vitro do not support the role of acidic-pepsin in NF-κB related hypopharyngeal carcinogenesis.

  9. Induction of human neuronal cells by defined transcription factors

    Science.gov (United States)

    Pang, Zhiping P.; Yang, Nan; Vierbuchen, Thomas; Ostermeier, Austin; Fuentes, Daniel R.; Yang, Troy Q.; Citri, Ami; Sebastiano, Vittorio; Marro, Samuele; Südhof, Thomas C.; Wernig, Marius

    2011-01-01

    Summary Somatic cell nuclear transfer, cell fusion, or expression of lineage-specific factors have been shown to induce cell-fate changes in diverse somatic cell types1–12. We recently observed that forced expression of a combination of three transcription factors, Brn2 (also known as Pou3f2), Ascl1, and Myt1l can efficiently convert mouse fibroblasts into functional induced neuronal (iN) cells13. Here, we show that the same three factors can generate functional neurons from human pluripotent stem cells as early as 6 days after transgene activation. When combined with the basic helix-loop-helix transcription factor NeuroD1, these factors could also convert fetal and postnatal human fibroblasts into iN cells displaying typical neuronal morphologies and expressing multiple neuronal markers, even after downregulation of the exogenous transcription factors. Importantly, the vast majority of human iN cells were able to generate action potentials and many matured to receive synaptic contacts when co-cultured with primary mouse cortical neurons. Our data demonstrate that non-neural human somatic cells, as well as pluripotent stem cells, can be directly converted into neurons by lineage-determining transcription factors. These methods may facilitate robust generation of patient-specific human neurons for in vitro disease modeling or future applications in regenerative medicine. PMID:21617644

  10. Integrating Data and Networks: Human Factors

    Science.gov (United States)

    Chen, R. S.

    2012-12-01

    The development of technical linkages and interoperability between scientific networks is a necessary but not sufficient step towards integrated use and application of networked data and information for scientific and societal benefit. A range of "human factors" must also be addressed to ensure the long-term integration, sustainability, and utility of both the interoperable networks themselves and the scientific data and information to which they provide access. These human factors encompass the behavior of both individual humans and human institutions, and include system governance, a common framework for intellectual property rights and data sharing, consensus on terminology, metadata, and quality control processes, agreement on key system metrics and milestones, the compatibility of "business models" in the short and long term, harmonization of incentives for cooperation, and minimization of disincentives. Experience with several national and international initiatives and research programs such as the International Polar Year, the Group on Earth Observations, the NASA Earth Observing Data and Information System, the U.S. National Spatial Data Infrastructure, the Global Earthquake Model, and the United Nations Spatial Data Infrastructure provide a range of lessons regarding these human factors. Ongoing changes in science, technology, institutions, relationships, and even culture are creating both opportunities and challenges for expanded interoperability of scientific networks and significant improvement in data integration to advance science and the use of scientific data and information to achieve benefits for society as a whole.

  11. Mitochondrial transcription factor A protects human retinal ...

    African Journals Online (AJOL)

    Purpose: To investigate the impact of mitochondrial transcription factor A (TFAM), as a modulator of NF-κB, on proliferation of hypoxia-induced human retinal endothelial cell (HREC), and the probable mechanism. Methods: After exposure to hypoxia (1 % O2) for 5 days, cell proliferation and cell cycle of HREC were ...

  12. Human and Mechanical Factors in Ergometry.

    Science.gov (United States)

    Ellis, M. J.; Hubbard, R. P.

    Analysis of the human and mechanical factors inherent in ergometry suggest many strategies for the improvement of experiments related to exertion. The resistive principles of gravitation, friction, elasticity, viscosity, magnetism, and inertia used in ergometers impose different restraints on experiments. The suitability of different resistive…

  13. Salinity levels as a factor of phyto planktonic structure and diversity remediation in a lagoon impact by human activities. (Bolmon Lagoon, Mediterranean Coast, France)

    Energy Technology Data Exchange (ETDEWEB)

    Fayolle, S.; Charpy-Roubaud, C.; Ollivier, A.; Maasri, A.; Franquet, E.

    2009-07-01

    The Bolmon lagoon (south-eastern France) is located in the coastal hinterland of the Mediterranean Sea. It is connected to the salty Berre pond and in the other hand receives fresh waters from the La Cadiere River. This hyper-shallow lagoon has been classified in the early 70's as {beta} mixo-mesohaline. Bolmon lagoon is important for human activities (tourism, fishing) and for the preservation of the diversity of marine and birds species. In the last decades, the intensive urbanisation of its drainage basin induced a high eutrophication of its waters and, as a consequence, drastic modifications in the biodiversity and in the functioning os this ecosystem. (Author)

  14. The influence of marital factors on genital human papilloma virus ...

    African Journals Online (AJOL)

    Aim: To study the association between marital factors and human papilloma virus (HPV) infection of the cervix. Method: The subjects were 450 randomly selected sexually active women attending the antenatal, postnatal, gynaecology and family planning clinics in the Department of Obstetrics and Gynaecology of the ...

  15. Sexual orientation and risk factors for Human Immunodeficiency ...

    African Journals Online (AJOL)

    The issue of homosexuality attracts global debate, given that this constitutes risk factor for sexually transmitted diseases. An exploration of socio-cultural, religious and sexual activities of lesbian, gay, bisexual, transgender and intersex sector would inform future Human Immunodeficiency Virus programming.

  16. Human splicing factor ASF/SF2 encodes for a repressor domain required for its inhibitory activity on pre-mRNA splicing.

    Science.gov (United States)

    Dauksaite, Vita; Akusjärvi, Göran

    2002-04-12

    The essential splicing factor ASF/SF2 activates or represses splicing depending on where on the pre-mRNA it binds. We have shown previously that ASF/SF2 inhibits adenovirus IIIa pre-mRNA splicing by binding to an intronic repressor element. Here we used MS2-ASF/SF2 fusion proteins to show that the second RNA binding domain (RBD2) is both necessary and sufficient for the splicing repressor function of ASF/SF2. Furthermore, we show that the completely conserved SWQDLKD motif in ASF/SF2-RBD2 is essential for splicing repression. Importantly, this heptapeptide motif is unlikely to be directly involved in RNA binding given its position within the predicted structure of RBD2. The activity of the ASF/SF2-RBD2 domain in splicing was position-dependent. Thus, tethering RBD2 to the IIIa intron resulted in splicing repression, whereas RBD2 binding at the second exon had no effect on IIIa splicing. The splicing repressor activity of RBD2 was not unique to the IIIa pre-mRNA, as binding of RBD2 at an intronic position in the rabbit beta-globin pre-mRNA also resulted in splicing inhibition. Taken together, our results suggest that ASF/SF2 encode distinct domains responsible for its function as a splicing enhancer or splicing repressor protein.

  17. Induction of epithelial-mesenchymal transition via activation of epidermal growth factor receptor contributes to sunitinib resistance in human renal cell carcinoma cell lines.

    Science.gov (United States)

    Mizumoto, Atsushi; Yamamoto, Kazuhiro; Nakayama, Yuko; Takara, Kohji; Nakagawa, Tsutomu; Hirano, Takeshi; Hirai, Midori

    2015-11-01

    Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some patients do not respond to treatment with this drug. We aimed to study the association between sunitinib sensitivity and epithelial-mesenchymal transition (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN, and Caki-1) were used, and then we evaluated cell viability, EMT regulatory proteins, and signal transduction with sunitinib treatment. Cell viability of 786-O cells was maintained after treatment with sunitinib. After treatment with sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an increase in the phosphorylation of extracellular signal-regulated kinase, nuclear translocation of β-catenin, and expression of mesenchymal markers. These results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells, but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line generated by continuous exposure to sunitinib, displayed increased phosphorylation of EGFR. Cell viability in the presence of sunitinib was decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR activation and upregulated mesenchymal markers. Thus, we postulate that resistance to sunitinib in RCC may be associated with EMT caused by activation of EGFR. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  18. Human Factors Principles in Information Dashboard Design

    Energy Technology Data Exchange (ETDEWEB)

    Hugo, Jacques V.; St. Germain, Shawn

    2016-06-01

    When planning for control room upgrades, nuclear power plants have to deal with a multitude of engineering and operational impacts. This will inevitably include several human factors considerations, including physical ergonomics of workstations, viewing angles, lighting, seating, new communication requirements, and new concepts of operation. In helping nuclear power utilities to deal with these challenges, the Idaho National Laboratory (INL) has developed effective methods to manage the various phases of the upgrade life cycle. These methods focus on integrating human factors engineering processes with the plant’s systems engineering process, a large part of which is the development of end-state concepts for control room modernization. Such an end-state concept is a description of a set of required conditions that define the achievement of the plant’s objectives for the upgrade. Typically, the end-state concept describes the transition of a conventional control room, over time, to a facility that employs advanced digital automation technologies in a way that significantly improves system reliability, reduces human and control room-related hazards, reduces system and component obsolescence, and significantly improves operator performance. To make the various upgrade phases as concrete and as visible as possible, an end-state concept would include a set of visual representations of the control room before and after various upgrade phases to provide the context and a framework within which to consider the various options in the upgrade. This includes the various control systems, human-system interfaces to be replaced, and possible changes to operator workstations. This paper describes how this framework helps to ensure an integrated and cohesive outcome that is consistent with human factors engineering principles and also provide substantial improvement in operator performance. The paper further describes the application of this integrated approach in the

  19. Two distinct disulfide bonds formed in human heat shock transcription factor 1 act in opposition to regulate its DNA binding activity.

    Science.gov (United States)

    Lu, Ming; Kim, Hee-Eun; Li, Chun-Ri; Kim, Sol; Kwak, Im-Jung; Lee, Yun-Ju; Kim, So-Sun; Moon, Ji-Young; Kim, Cho Hee; Kim, Dong-Kyoo; Kang, Ho Sung; Park, Jang-Su

    2008-06-03

    Under circumstances of heat stress, heat shock transcription factor 1 (HSF1) plays important roles in heat shock protein expression. In this study, an increasing concentration of dithiothreitol (DTT) was found to either enhance or inhibit the heat-induced trimerization of HSF1, suggesting the involvement of dual redox-dependent HSF1 activation mechanisms. Our in vitro experiments show that the heat-induced bonding between the cysteine C36 and C103 residues of HSF1 forms an intermolecular disulfide covalent bond (SS-I bond) and that it directly causes HSF1 to trimerize and bond to DNA. Gel filtration assays show that HSF1 can form intermolecular hydrophobic interaction-mediated (iHI-m) noncovalent oligomers. However, the lack of a trimerization domain prevents HSF1 activation, which suggests that iHI-m noncovalent trimerization is a precondition of SS-I bond formation. On the other hand, intramolecular SS-II bond (in which the C153, C373, and C378 residues of HSF1 participate) formation inhibits this iHI-m trimerization, thereby preventing SS-I bond formation and DNA binding. Thus, HSF1 activation is regulated positively by intermolecular SS-I bond formation and negatively by intramolecular SS-II bond formation. Importantly, these two SS bonds confer different DTT sensitivities (the SS-II bond is more sensitive). Therefore, a low concentration of DTT cleaves the SS-II bond but not the SS-I bond and thus improves DNA binding of HSF1, whereas a high concentration DTT cuts both SS bonds and inhibits HSF1 activation. We propose that these interesting effects further explain cellular HSF1 trimerization, DNA binding, and transcription when cells are under stress.

  20. Human factors systems approach to healthcare quality and patient safety

    Science.gov (United States)

    Carayon, Pascale; Wetterneck, Tosha B.; Rivera-Rodriguez, A. Joy; Hundt, Ann Schoofs; Hoonakker, Peter; Holden, Richard; Gurses, Ayse P.

    2013-01-01

    Human factors systems approaches are critical for improving healthcare quality and patient safety. The SEIPS (Systems Engineering Initiative for Patient Safety) model of work system and patient safety is a human factors systems approach that has been successfully applied in healthcare research and practice. Several research and practical applications of the SEIPS model are described. Important implications of the SEIPS model for healthcare system and process redesign are highlighted. Principles for redesigning healthcare systems using the SEIPS model are described. Balancing the work system and encouraging the active and adaptive role of workers are key principles for improving healthcare quality and patient safety. PMID:23845724

  1. Capturing the Value: Earth Applications of Space Human Factors Research

    Science.gov (United States)

    Connors, Mary M.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    This paper details how the Space Human Factors/Life Sciences program at Ames Research Center (ARC) has provided, and continues to provide, a variety of Earth-based benefits. These benefits will be considered under five categories: aeronautics, space-like environments, general applications, human/automation interaction, and methodology. The human factors work at ARC includes a range of activities whose products serve the aerospace community. Some areas of research focus specifically on aeronautical requirements; others are driven by space needs. However, the symbiosis between these two domains allows a sharing of resources, and the insights and experimental results gathered in one domain can often be applied in the other. Aeronautics is an industry whose survival is generally viewed as critical to American competitiveness, and where benefits can result in a very high payoff. The ability to apply space-initiated research to aeronautical requirements represents one example of bringing space benefits down to Earth. The second-order value of space human factors research goes well beyond the aerospace community. Spaceflight shares with a number of other activities certain environmental characteristics that drive human factors engineering design and procedural specification. Spaceflight is an isolated activity, conducted under severely confined conditions, with a high level of risk, and where provisions are restricted and opportunities for outside help are limited. A number of Earth-based activities including submarines and other naval vessels, oil rigs, remote weather stations, and scientific and polar expeditions, share many of these characteristics. These activities serve as testbeds for space-related research and, in turn, space-related research provides beneficial insight to the conduct of these activities.

  2. Human Factors in the Management of Production

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Alting, Leo

    2006-01-01

    The ‘Human factor’ is a major issue when optimizing manufacturing systems. The development in recommendations on how to handle this factor in the management of production reflects the change in dominating challenges faced by production in society. Presently, industrial societies are meeting new...... challenges. Qualitative interviews with Danish stakeholders in the education of engineers (BA & MA) confirm the picture given in international literature. Therefore, the didactics concerning the ‘human factor’ in the curriculum on production management has to reflect these changes. This paper concludes...

  3. Insulin-Like Growth Factor 1/Mammalian Target of Rapamycin and AMP-Activated Protein Kinase Signaling Involved in the Effects of Metformin in the Human Endometrial Cancer.

    Science.gov (United States)

    Cai, Dongge; Sun, Hongli; Qi, Yanhua; Zhao, Xiaogui; Feng, Minjuan; Wu, Xiaoling

    2016-11-01

    Metformin is a well-tolerated biguanide drug used for decades to treat type 2 diabetes mellitus. In recent years, long-term administration of metformin has been found to reduce carcinogenic risk for cancers derived from various tissues. However, its cellular and molecular mechanisms of anticancer action in the endometrial cancer (EC) have not yet been fully elucidated. Sixty patients diagnosed as endometrial carcinoma were grouped into (n = 30) and non-treatment mixed (n = 30) for analysis. Thirty healthy donors are control groups. We attempt to investigate the interaction of metformin, insulin-like growth factor 1 (IGF-1) expression, and phosphorylated mammalian target of rapamycin (p-mTOR) and AMP-activated protein kinase (p-AMPK). We found that high IGF-1 plasma concentrations in women with EC were reversed by conventional antidiabetic doses of metformin in the present work. In parallel, the activation of AMPK and suppression of mTOR seemed to play an important role for the effect of metformin in patients with EC. This pilot trial presents biological evidence consistent with antiproliferative effects of metformin in women with EC in the clinical setting.

  4. Heterologous expression of a truncated form of human recombinant vascular endothelial growth factor-A and its biological activity in wound healing

    Directory of Open Access Journals (Sweden)

    Mohsen Khaki

    2017-07-01

    Full Text Available Objective(s: Vascular endothelial growth factor (VEGF is one of the most effective proteins in angiogenesis, mesenchymal stem cells (MSCs differentiation and wound healing. These abilities are therapeutic potential of VEGF in diabetic retinopathy, nephropathy and other tissue damage circumstances. In this study, recombinant VEGF was produced in Escherichia coli (E. coli system and then biological activity of this protein was evaluated in animal wound healing. Materials and Methods: E. coli BL21 (DE3 competent cells were transformed with pET32a-VEGF clone and induced by isopropyl-β-D-thio-galactoside (IPTG. The recombinant protein was purified byaffinity chromatography. Recombinant VEGF-A-based ointment (VEGF/Vaseline 0.8 mg/100 w/w was used for external wound (25×15mm thickness healing in animal model. In vivo activity of ointment was evaluated by clinical evidences and cytological microscopic assessment. Results: The recombinant protein with molecular weight of 45 kilodaltons (kDa and concentration of 0.8 mg/ml was produced.Immunoblotting data showed that the antigenic region of VEGF can be expressed in E. coli and the recombinant protein has similar epitopes with close antigenic properties to the natural form. Macroscopic findings and microscopic data showed that the recombinant VEGF-A ointment was effective on excisional wound healing. Conclusion: Recombinant VEGF-A produced by pET32a in E. coli, possesses acceptable structure and has wound healing capability.

  5. Telomerase activity in human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Griffith, J.

    2000-10-01

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

  6. Tumor angiogenic factor and human skin tumors.

    Science.gov (United States)

    Wolf, J E; Hubler, W R

    1975-03-01

    A transparent acrylic hamster cheek-pouch chamber was used to investigate the elaboration of a tumor angiogenic factor (TAF) by human cutaneous neoplasms; direct tumor implantations, transfilter diffusion, and soluble tumor extracts were used in the study. A diffusible and filterable TAF was extracted from cutaneous tumors and produced distinctive patterns of sequential vasodilatation, tortuosity, and neovascular proliferation in the cheek-pouch membrane. Malignant human neoplasms (eg, melanoma, basal cell epithelioma, squamous cell carcinoma, lymphoma) produced striking neovascularization; vascular tumors (eg, Kaposi sarcoma, pyogenic granuloma, vascular histiocytoma) stimulated dramatic hyperemia and ectasia. Angiogenesis was conspicuously absent after implantation of control materials and nevoid or normal cutaneous components (with the exception of epidermis). Tumor angiogenic factor appears to induce direct stimulation of endothelial cell mitosis and may be essential for survival of nutritionally ravenous neoplastic tissues. The interference with TAF has therapeutic implications.

  7. The development of human factors technologies -The development of human factors experimental evaluation techniques-

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Bong Sik; Oh, In Suk; Cha, Kyung Hoh; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-07-01

    In this year, we studied the followings: (1) Development of operator mental workload evaluation techniques, (2) Development of a prototype for preliminary human factors experiment, (3) Suitability test of information display on a large scale display panel, (4) Development of guidelines for VDU-based control room design, (5) Development of integrated test facility (ITF). (6) Establishment of an eye tracking system, and we got the following results: (1) Mental workload evaluation techniques for MMI evaluation, (2) PROTOPEX (PROTOtype for preliminary human factors experiment) for preliminary human factors experiments, (3) Usage methods of APTEA (Analysis-Prototyping-Training-Experiment-Analysis) experiment design, (4) Design guidelines for human factors verification, (5) Detail design requirements and development plan of ITF, (6) Eye movement measurement system. 38 figs, 20 tabs, 54 refs. (Author).

  8. Use of Computers in Human Factors Engineering

    Science.gov (United States)

    1974-11-01

    CODING OF UPDATES); (3) DISPLAY MODES AND SENSORY MODALITIES (GRCUP VS INIVIDUAL DISPLAYS, MULTISENSORY DISPLAYS); AND (4) COMPUTER AIDS TO THE DECISION...OF HUMAN FACTORS AND BIOTECHNOLOGY (HF-BIO) ORGANIZATIONS; GROWTH OF THE PROFESSION, TURNOVER RATES, REPORTING LEVELS, GROUP COMPOSITION...PROJECTED GROWTH OF FIELD, HF-810 EDUCATIONAL PROGRAMS, DEGREES OFFERED, APPRENTICESHIPS* NUMBER OF STUDENTS TRAINED, PROBLEMS ’ ASbOCIATED WITH THE MF-BIO

  9. Canadian Ranger Rifle: Human Factors Requirements Validation

    Science.gov (United States)

    2010-08-01

    operations in remote, isolated, and coastal communities of Canada2 3. CR are comprised of approximately 4111 Inuit , First Nations, Métis, and non...was varied in gender, rank, age, years as a CR, patrol, and culture . Furthermore the operating environments of the CR varied from the arctic, to...while differences were observed in the culture between CRPGs. Page 32 CRR: Human Factors Requirements Validation Humansystems® 5.3 Technical

  10. Cyclosporin A promotes proliferating cell nuclear antigen expression and migration of human cytotrophoblast cells via the mitgen-activated protein kinase-3/1-mediated nuclear factor-κB signaling pathways.

    Science.gov (United States)

    Wang, Song-Cun; Yu, Min; Li, Yan-Hong; Piao, Hai-Lan; Tang, Chuan-Lin; Sun, Chan; Zhu, Rui; Li, Ming Qing; Jin, Li-Ping; Li, Da-Jin; Du, Mei-Rong

    2013-01-01

    Our previous studies have demonstrated that cyclosporin A (CsA) promotes the proliferation and migration of human trophoblasts via the mitgen-activated protein kinase-3/1 (MAPK3/1) pathway. In the present study, we further investigated the role of nuclear factor (NF)-κB in the CsA-induced trophoblast proliferating cell nuclear antigen (PCNA) expression and migration, and its relationship to MAPK3/1 signal. Flow cytometry was used to analyze the expression of PCNA in trophoblasts. The migration of human primary trophoblasts was determined by wound-healing assay and transwell migration assay. Western blot analysis was performed to evaluate the activation of NF-κB p65 and NF-κB inhibitory protein I-κB in human trophoblasts. We found that treatment with CsA promotes PCNA expression and migration of human trophoblast in a dose-associated manner. Blocking of the MAPK3/1 signal abrogated the enhanced PCNA expression and migration in trophoblasts by CsA. In addition, CsA increased the phosphorylation of NF-κB p65 and the inhibitor I-κB in human trophoblasts in a time-related manner. Pretreatment with MAPK3/1 inhibitor U0126 abrogated the phosphorylation of NF-κB p65 and I-κB. Accordingly, the CsA-induced enhancement of PCNA expression and migration in trophoblasts was also decreased. This CsA-induced enhancement in the expression and migration of trophoblasts was abolished by pretreatment with pyrrolidine dithiocarbamate, a specific NF-κB inhibitor. Thus, our results suggest that CsA promotes PCNA expression and migration of human trophoblasts via MAPK-mediated NF-κB activation.

  11. Improving Safety through Human Factors Engineering.

    Science.gov (United States)

    Siewert, Bettina; Hochman, Mary G

    2015-10-01

    Human factors engineering (HFE) focuses on the design and analysis of interactive systems that involve people, technical equipment, and work environment. HFE is informed by knowledge of human characteristics. It complements existing patient safety efforts by specifically taking into consideration that, as humans, frontline staff will inevitably make mistakes. Therefore, the systems with which they interact should be designed for the anticipation and mitigation of human errors. The goal of HFE is to optimize the interaction of humans with their work environment and technical equipment to maximize safety and efficiency. Special safeguards include usability testing, standardization of processes, and use of checklists and forcing functions. However, the effectiveness of the safety program and resiliency of the organization depend on timely reporting of all safety events independent of patient harm, including perceived potential risks, bad outcomes that occur even when proper protocols have been followed, and episodes of "improvisation" when formal guidelines are found not to exist. Therefore, an institution must adopt a robust culture of safety, where the focus is shifted from blaming individuals for errors to preventing future errors, and where barriers to speaking up-including barriers introduced by steep authority gradients-are minimized. This requires creation of formal guidelines to address safety concerns, establishment of unified teams with open communication and shared responsibility for patient safety, and education of managers and senior physicians to perceive the reporting of safety concerns as a benefit rather than a threat. © RSNA, 2015.

  12. Human reliability, error, and human factors in power generation

    CERN Document Server

    Dhillon, B S

    2014-01-01

    Human reliability, error, and human factors in the area of power generation have been receiving increasing attention in recent years. Each year billions of dollars are spent in the area of power generation to design, construct/manufacture, operate, and maintain various types of power systems around the globe, and such systems often fail due to human error. This book compiles various recent results and data into one volume, and eliminates the need to consult many diverse sources to obtain vital information.  It enables potential readers to delve deeper into a specific area, providing the source of most of the material presented in references at the end of each chapter. Examples along with solutions are also provided at appropriate places, and there are numerous problems for testing the reader’s comprehension.  Chapters cover a broad range of topics, including general methods for performing human reliability and error analysis in power plants, specific human reliability analysis methods for nuclear power pl...

  13. Human Factors in Accidents Involving Remotely Piloted Aircraft

    Science.gov (United States)

    Merlin, Peter William

    2013-01-01

    This presentation examines human factors that contribute to RPA mishaps and provides analysis of lessons learned. RPA accident data from U.S. military and government agencies were reviewed and analyzed to identify human factors issues. Common contributors to RPA mishaps fell into several major categories: cognitive factors (pilot workload), physiological factors (fatigue and stress), environmental factors (situational awareness), staffing factors (training and crew coordination), and design factors (human machine interface).

  14. FACTORS THAT AFFECTING HUMAN ISLET ISOLATION

    Science.gov (United States)

    Sakuma, Yasunaru; Ricordi, Camillo; Miki, Atsushi; Yamamoto, Toshihiko; Pileggi, Antonello; Khan, Aisha; Alejandro, Rodolfo; Inverardi, Luca; Ichii, Hirohito

    2008-01-01

    More than 10,000 IEQ/kg recipient weight islets are often necessary to achieve insulin independence in patients with type 1 diabetes. Several studies have identified high BMI donor and pancreas size are important factors for the success of human islet isolation. However, donor shortage underscores the need to improve isolation outcomes from lower BMI pancreas donors and/or small pancreata. Aim of this study was to identify the critical factors affecting isolation outcome. The data from 207 isolations performed from 2002 to 2006 were analyzed with respect to donor characteristics, pancreas condition and processing variables. More than 3,000 IEQ/g pancreas weight were considered as an acceptable isolation outcome (AIO). AIO were obtained from donors with a BMI>30kg/m2 (p=0.002). The pancreatic surface integrity was also a significant factor towards AIO (p=0.02). Moreover, a longer digestion time (p=0.04) and the proportion of trapped islet negatively affected AIO rates (p=0.004). As previously reported, pancreata from high BMI donors were suitable for islet isolation and transplantation, as they yielded higher total islet particle numbers and higher IEQ/g. Although BMI and pancreas size are not controllable due to organ donor shortage, factors such as pancreatic surface integrity, shorter digestion and lower proportions of trapped islet were found to be significant factors to obtain higher rates of AIO. The development of better protocol and systematic training of processing and procurement teams will be of assistance in increasing the number of successful human islet isolations. PMID:18374062

  15. Architecture of human translation initiation factor 3

    Science.gov (United States)

    Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M.; Smith, Duane; Gu, Yu; Cate, Jamie; Nogales, Eva

    2013-01-01

    SUMMARY Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans. PMID:23623729

  16. Does solar activity affect human happiness?

    Science.gov (United States)

    Kristoufek, Ladislav

    2018-03-01

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

  17. Alternative Control Technologies: Human Factors Issues

    Science.gov (United States)

    1998-10-01

    the late 60’s and has been installed in a variety of Theta angle (angle of fan bea when onedo hle intersecting Tea angle)_. Surveyin Fingure 2...7-11 24. Sutter, E.E., "The Visual Evoked Response as a Communication Channel", in "Proceedings: IEEE Symposium on Biosensors ", IEEE, 1984, pp 95-100...interactive communication", IBM Hursley Human Symposium on Biosensors ", IEEE, 1984, pp 95-100. Factors Laboratory Report, 1983. Taheri, B., Smith, R.L

  18. Review of EPRI Nuclear Human Factors Program

    Energy Technology Data Exchange (ETDEWEB)

    Hanes, L.F.; O`Brien, J.F. [Electric Power Research Institute, Palo Alto, CA (United States)

    1996-03-01

    The Electric Power Research Institute (EPRI) Human Factors Program, which is part of the EPRI Nuclear Power Group, was established in 1975. Over the years, the Program has changed emphasis based on the shifting priorities and needs of the commercial nuclear power industry. The Program has produced many important products that provide significant safety and economic benefits for EPRI member utilities. This presentation will provide a brief history of the Program and products. Current projects and products that have been released recently will be mentioned.

  19. Diabetes technology and the human factor.

    Science.gov (United States)

    Liberman, A; Buckingham, B; Phillip, M

    2011-02-01

    When developing new technologies for human use the developer should take into consideration not only the efficacy and safety of the technology but also the desire and capabilities of the potential user. Any chronic disease is a challenge for both the patient and his/her caregivers. This statement is especially true in the case of patients with type 1 diabetes mellitus (T1DM) where adherence to therapy is crucial 24 hours a day 365 days a year. No vacation days are possible for the T1DM patient. It is therefore obvious why any new technology which is developed for helping patients cope with the disease should take into consideration the 'human factor' before, during and after the production process starts. There is no doubt that technology has changed the life of patients with T1DM in the last few decades, but despite the availability of new meters, new syringes, new sophisticated insulin pumps and continuous glucose sensors and communication tools, these technologies have not been well utilised by many patients. It is therefore important to understand why the technology is not always utilised and to find new ways to maximise use and benefits from the technology to as many patients as possible. The present chapter will review papers published in the last year where the patient's ability or willingness was an important factor in the success of the technology. We will try to understand why insulin pumps, glucose sensors and self-monitoring of blood glucose (SMBG) are not used enough or appropriately, whether there is a specific group that finds it more difficult than others to adopt new technologies and what can be done to overcome that issue. For this chapter we chose articles from a Public Medicine review of the literature related to human factors affecting the outcome of studies and of user acceptance of continuous glucose monitoring, insulin infusion pump therapy. We also searched the literature in the field of psychology in order to accurately define the problems

  20. Human and organizational factors in nuclear safety; Factores humanos y organizativos en la seguridad nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.; Barrientos, M.; Gil, B.

    2015-07-01

    Nuclear installations are socio technical systems where human and organizational factors, in both utilities and regulators, have a significant impact on safety. Three Mile Island (TMI) accident, original of several initiatives in the human factors field, nevertheless became a lost opportunity to timely acquire lessons related to the upper tiers of the system. Nowadays, Spanish nuclear installations have integrated in their processes specialists and activities in human and organizational factors, promoted by the licensees After many years of hard work, Spanish installations have achieved a better position to face new challenges, such as those posed by Fukushima. With this experience, only technology-centered action plan would not be acceptable, turning this accident in yet another lost opportunity. (Author)

  1. Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes

    NARCIS (Netherlands)

    van der Sluis, Renée M.; Derking, Ronald; Breidel, Seyguerney; Speijer, Dave; Berkhout, Ben; Jeeninga, Rienk E.

    2014-01-01

    HIV-1 transcription depends on cellular transcription factors that bind to sequences in the long-terminal repeat (LTR) promoter. Each HIV-1 subtype has a specific LTR promoter configuration, and minor sequence changes in transcription factor binding sites (TFBSs) or their arrangement can influence

  2. Postures and Motions Library Development for Verification of Ground Crew Human Factors Requirements

    Science.gov (United States)

    Stambolian, Damon; Henderson, Gena; Jackson, Mariea Dunn; Dischinger, Charles

    2013-01-01

    Spacecraft and launch vehicle ground processing activities require a variety of unique human activities. These activities are being documented in a primitive motion capture library. The library will be used by human factors engineering analysts to infuse real to life human activities into the CAD models to verify ground systems human factors requirements. As the primitive models are being developed for the library, the project has selected several current human factors issues to be addressed for the Space Launch System (SLS) and Orion launch systems. This paper explains how the motion capture of unique ground systems activities is being used to verify the human factors engineering requirements for ground systems used to process the SLS and Orion vehicles, and how the primitive models will be applied to future spacecraft and launch vehicle processing.

  3. Purification of human platelet-derived growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Raines, E.W.; Ross, R.

    1985-01-01

    The paper describes a method for purification of human platelet-derived growth factor (PDGF) from outdated platelet-rich plasma (PRP) using commonly available laboratory reagents and yielding a mitogen purified 800,000-fold over the starting material. (/sup 3/H)thymidine incorporation into DNA of cultured cells responsive to PDGF represents the most readily available method to follow its purification and define the biological activity of a purified preparation. Other assays to quantitate PDGF include radioreceptor assay and radioimmunoassay.

  4. Human health and social factors in winter climates

    Energy Technology Data Exchange (ETDEWEB)

    Pressman, N. (Waterloo Univ., ON (Canada). School of Urban and Regional Planning)

    1991-01-01

    This presentation examines the broad theme of human needs with specific reference to a range of winter-induced problems. Both physiological and psychological aspects are analyzed vis-a-vis thermal comfort and human behavioural response. The use of public space suggets that social activity is very different in winter when compared with summer. However, such activity can be increased through employing planning and design strategies. For example, the outdoor season can be extended by up to six weeks by applying microclimate principles. If more intense levels of social interaction are desired - when people tend to be confined indoors - proximity and density will be important factors influencing such contact, thereby contributing to a reduction of stress and isolation. Since winter conditions spawn unique problems, special solutions will be required to combat them. It is essential to create a better 'fit' between human requirements and the corresponding built environment. (orig.).

  5. CCR7 Mediates TGF-β1-Induced Human Malignant Glioma Invasion, Migration, and Epithelial-Mesenchymal Transition by Activating MMP2/9 Through the Nuclear Factor KappaB Signaling Pathway.

    Science.gov (United States)

    Zheng, Yanyan; Miu, Yiting; Yang, Xiaokai; Yang, Xiaoguo; Zhu, Meijia

    2017-10-01

    Chemokine receptor 7 (CCR7) has emerged as an inducer of invasion, migration, and epithelial-mesenchymal transition (EMT) in cancer. In this research, human malignant glioma cells were stimulated with transforming growth factor beta 1 (TGF-β1) and siCCR7. The data show that CCR7 mediates TGF-β1-induced EMT, migration, and invasion in U251 and U87 cells and that these effects of TGF-β1 were reversed by treatment with siCCR7 or a CCR7 neutralizing antibody. Importantly, the TGF-β1-mediated increase in nuclear factor kappaB (NF-κB) activity in human glioma cells was reduced by treatment with siCCR7 or a CCR7 neutralizing antibody. Furthermore, CCR7 was shown to mediate TGF-β1-induced glioma cancer cell migration by activating matrix metalloproteinase 2 (MMP2)/9. Our results indicate that CCR7 mediates TGF-β1-induced MMP2/9 expression through NF-κB signaling, thus facilitating glioma cell migration, invasion, and EMT, all of which progressively increase with glioblastoma progression. These findings indicate that CCR7 is a potential therapeutic target for malignant glioma.

  6. PAX 8 activates the enhancer of the human thyroperoxidase gene.

    OpenAIRE

    Esposito, C.; Miccadei, S; Saiardi, A.; Civitareale, D.

    1998-01-01

    In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its exogenous expression induces the enhancer act...

  7. Human Factors of Remotely Piloted Aircraft

    Science.gov (United States)

    Hobbs, Alan Neville

    2014-01-01

    The civilian use of remotely piloted, or unmanned aircraft is expected to increase rapidly in the years ahead. Despite being referred to as unmanned some of the major challenges confronting this emerging sector relate to human factors. As unmanned aircraft systems (UAS) are introduced into civil airspace, a failure to adequately consider human factors could result in preventable accidents that may not only result in loss of life, but may also undermine public confidence in remotely piloted operations. Key issues include pilot situational awareness, collision avoidance in the absence of an out-the-window view, the effects of time delays in communication and control systems, control handovers, the challenges of very long duration flights, and the design of the control station. Problems have included poor physical layout of controls, non-intuitive automation interfaces, an over-reliance on text displays, and complicated sequences of menu selection to perform routine tasks. Some of the interface problems may have been prevented had an existing regulation or cockpit design principle been applied. In other cases, the design problems may indicate a lack of suitable guidance material.

  8. Improving human performance: Industry factors influencing the ability to perform

    Directory of Open Access Journals (Sweden)

    Güera Massyn Romo

    2013-03-01

    Full Text Available Learning interventions and new technologies that aim to improve human performance must take cognisance of industry factors inhibiting human performance. The dynamic and fast pace nature of the Information and Communication Technologies (ICT and the engineering industries do not lend themselves to proper skills planning and management. These industries experience real skills gaps, to some of which they contribute by themselves. This study reports on these performance-inhibiting factors such as the underutilisation of available skills, tolerance for individual preferences, and dynamically, and informally refining a role objective while an employee is occupying a certain role. The important professional skills required by individuals to cope with these real life factors are also explored in the skills gaps management context. Moreover, these industries need a profile they refer to as Special Forces, which denotes a high calibre of worker that possesses well-developed professional skills whilst having advanced technical expertise and sufficient experience. This resource profile is required largely due to the poor management of human resource processes in practice and the current reported lack of adequate skills. Furthermore, this study refers to the recent lack of a working definition for these Special Forces leading to the omitted active development of these profiles in industry today, which appears to become a key human performance inhibiting factor.

  9. Key factors of enterprise innovation activity

    Directory of Open Access Journals (Sweden)

    Pichugina Maryna Anatoliivna

    2015-02-01

    Full Text Available The article deals with the studies of factors and conditions that define enterprise innovative activity. It is distinguished factors that influence the orientation on innovation of a company and factors that influence the innovation ability. It is noted an interdependence between innovative ability, orientation and activity. The article is also dedicated to analyses of influence specific industry characteristics and inner view of enterprise. It is discussed the influence of such factors as knowledge base, the organizational learning mechanisms, an external openness and the structure of innovative connections on the company opportunities to innovate. It is tried to focus on the impact of the environment on enterprise capabilities.

  10. Activation of human microglia by fibrillar prion protein-related peptides is enhanced by amyloid-associated factors SAP and C1q

    NARCIS (Netherlands)

    Veerhuis, Robert; Boshuizen, Ronald S.; Morbin, Michela; Mazzoleni, Giulia; Hoozemans, Jeroen J. M.; Langedijk, Johannes P. M.; Tagliavini, Fabrizio; Langeveld, Jan P. M.; Eikelenboom, Piet

    2005-01-01

    Complement activation products C1q and C3d, serum amyloid P component (SAP) and activated glial cells accumulate in amyloid deposits of conformationally changed prion protein (PrPSc) in Creutzfeldt-Jakob disease, Gerstmann-Straussier-Scheinker disease and scrapie-infected mouse brain. Biological

  11. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells

    DEFF Research Database (Denmark)

    Galuska, Dana; Pirkmajer, Sergej; Barres, Romain

    2011-01-01

    Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity...

  12. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  13. Multi-function displays : a guide for human factors evaluation.

    Science.gov (United States)

    2013-11-01

    This guide is designed to assist aircraft certification personnel and avionics : manufacturers in evaluating the human factors aspects of Multi-function Displays : (MFDs) for FAA certification. The guide focuses specifically on human factors and : do...

  14. Human factors quantification via boundary identification of flight performance margin

    Directory of Open Access Journals (Sweden)

    Yang Changpeng

    2014-08-01

    Full Text Available A systematic methodology including a computational pilot model and a pattern recognition method is presented to identify the boundary of the flight performance margin for quantifying the human factors. The pilot model is proposed to correlate a set of quantitative human factors which represent the attributes and characteristics of a group of pilots. Three information processing components which are influenced by human factors are modeled: information perception, decision making, and action execution. By treating the human factors as stochastic variables that follow appropriate probability density functions, the effects of human factors on flight performance can be investigated through Monte Carlo (MC simulation. Kernel density estimation algorithm is selected to find and rank the influential human factors. Subsequently, human factors are quantified through identifying the boundary of the flight performance margin by the k-nearest neighbor (k-NN classifier. Simulation-based analysis shows that flight performance can be dramatically improved with the quantitative human factors.

  15. Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma.

    Science.gov (United States)

    Pasello, Giulia; Urso, Loredana; Silic-Benussi, Micol; Schiavon, Marco; Cavallari, Ilaria; Marulli, Giuseppe; Nannini, Nazarena; Rea, Federico; Ciminale, Vincenzo; Favaretto, Adolfo

    2014-07-01

    Malignant pleural mesothelioma (MPM) is an aggressive, currently incurable tumor with increasing incidence in industrialized countries. Tumor necrosis factor-related, apoptosis-inducing ligand (TRAIL) is a member of the TNF family, which induces cancer cell death through extrinsic apoptotic pathway, while sparing normal cells. The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo. In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice. Results demonstrated a significant increase of apoptosis in cell lines treated with CPT compared with those receiving CP or T as single agents. This synergistic effect was dependent on the ability of CP to increase the expression of the TRAIL receptors DR4 and DR5 in a p53 manner. The CPT combination was also effective in blocking the growth of MPM cell lines in a SCID mice preclinical model. CPT increases MPM cell death in vitro and in vivo compared with CP. In vitro results suggest that chemotherapy sensitizes MPM to TRAIL-dependent apoptosis through p53 activation and subsequent upregulation of DRs.

  16. The Activation-Induced Assembly of an RNA/Protein Interactome Centered on the Splicing Factor U2AF2 Regulates Gene Expression in Human CD4 T Cells.

    Directory of Open Access Journals (Sweden)

    Thomas C Whisenant

    Full Text Available Activation of CD4 T cells is a reaction to challenges such as microbial pathogens, cancer and toxins that defines adaptive immune responses. The roles of T cell receptor crosslinking, intracellular signaling, and transcription factor activation are well described, but the importance of post-transcriptional regulation by RNA-binding proteins (RBPs has not been considered in depth. We describe a new model expanding and activating primary human CD4 T cells and applied this to characterizing activation-induced assembly of splicing factors centered on U2AF2. We immunoprecipitated U2AF2 to identify what mRNA transcripts were bound as a function of activation by TCR crosslinking and costimulation. In parallel, mass spectrometry revealed the proteins incorporated into the U2AF2-centered RNA/protein interactome. Molecules that retained interaction with the U2AF2 complex after RNAse treatment were designated as "central" interactome members (CIMs. Mass spectrometry also identified a second class of activation-induced proteins, "peripheral" interactome members (PIMs, that bound to the same transcripts but were not in physical association with U2AF2 or its partners. siRNA knockdown of two CIMs and two PIMs caused changes in activation marker expression, cytokine secretion, and gene expression that were unique to each protein and mapped to pathways associated with key aspects of T cell activation. While knocking down the PIM, SYNCRIP, impacts a limited but immunologically important set of U2AF2-bound transcripts, knockdown of U2AF1 significantly impairs assembly of the majority of protein and mRNA components in the activation-induced interactome. These results demonstrated that CIMs and PIMs, either directly or indirectly through RNA, assembled into activation-induced U2AF2 complexes and play roles in post-transcriptional regulation of genes related to cytokine secretion. These data suggest an additional layer of regulation mediated by the activation

  17. Effects of Rupatadine on Platelet- Activating Factor-Induced Human Mast Cell Degranulation Compared With Desloratadine and Levocetirizine (The MASPAF Study)

    National Research Council Canada - National Science Library

    2017-01-01

    ..., in the amplification of mast cell (MC) activation in anaphylaxis. Rupatadine is an antihistamine with a demonstrated anti-PAF effect, although its capacity to inhibit PAF-induced MC degranulation has not been fully evaluated. Objectives...

  18. factors affecting implementation of practical activities in science

    African Journals Online (AJOL)

    Temechegn

    Academically less prepared students of secondary schools prefer humanities and social sciences than science and technology in higher education. The majority of students in schools of the study area join social science. Therefore assessing factors affecting implementation of practical activities in science education in study ...

  19. Development of a Field Management Standard for Improving Human Factors

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Young Su [Chosun University, Gwangju (Korea, Republic of); Son, Il Moon [Dongmyung University, Busan (Korea, Republic of); Son, Byung Chang [Korea Nazarene University, Cheonan (Korea, Republic of); Kwak, Hyo Yean [Suwon Science Collage, Suwon (Korea, Republic of)

    2009-07-15

    This project is to develop a management guideline for improving human performances as a part of the Human Factors Management System of Kori unit 1 which is managing all of human factors items such as man-machine system interfaces, work procedures, work environments, and human reliabilities in nuclear power plants. Human factors engineering includes an human factors suitability analysis and improvement of human works, an analysis of accidents by human error, an improvement of work environment, an establishment of human factors management rules and a development of human resources to manage and perform those things consistently. For assisting these human factors engineering tasks, we developed human factors management guidelines, checklists and work procedures to be used in staffing, qualification, training, and human information requirements and workload. We also provided a software tool for managing the above items. Additionally, contents and an item pool for a human factors qualifying examination and training programs were developed. A procedures improvement and a human factors V and V on the Kori unit 1 have been completed as a part of this project, too

  20. Humanism Factors and Islam Viewpoint from Motahri's Point of View

    Science.gov (United States)

    Yousefi, Zargham; Yousefy, Alireza; Keshtiaray, Narges

    2015-01-01

    The aim of this research is to criticize liberal humanism based on Islam viewpoint emphasizing Motahri's point of view. In this paper, the researchers tried to identify liberalism humanism factors with analytical look in order to present a new categorization called "main factor of liberal humanism". Then, each factor was studied and…

  1. Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

    NARCIS (Netherlands)

    Lindeman, J.H.N.; Abdul-Hussien, H.; Schaapherder, A.F.M.; Bockel, J.H. van; Thüsen, J.H. vonder; Roelen, D.L.; Kleemann, R.

    2008-01-01

    Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in

  2. Helicobacter pylori Induced Phosphatidylinositol-3-OH Kinase/mTOR Activation Increases Hypoxia Inducible Factor-1α to Promote Loss of Cyclin D1 and G0/G1 Cell Cycle Arrest in Human Gastric Cells.

    Science.gov (United States)

    Canales, Jimena; Valenzuela, Manuel; Bravo, Jimena; Cerda-Opazo, Paulina; Jorquera, Carla; Toledo, Héctor; Bravo, Denisse; Quest, Andrew F G

    2017-01-01

    Helicobacter pylori (H. pylori) is a human gastric pathogen that has been linked to the development of several gastric pathologies, such as gastritis, peptic ulcer, and gastric cancer. In the gastric epithelium, the bacterium modifies many signaling pathways, resulting in contradictory responses that favor both proliferation and apoptosis. Consistent with such observations, H. pylori activates routes associated with cell cycle progression and cell cycle arrest. H. pylori infection also induces the hypoxia-induced factor HIF-1α, a transcription factor known to promote expression of genes that permit metabolic adaptation to the hypoxic environment in tumors and angiogenesis. Recently, however, also roles for HIF-1α in the repair of damaged DNA and inhibition of gene expression were described. Here, we investigated signaling pathways induced by H. pylori in gastric cells that favor HIF-1α expression and the consequences thereof in infected cells. Our results revealed that H. pylori promoted PI3K/mTOR-dependent HIF-1α induction, HIF-1α translocation to the nucleus, and activity as a transcription factor as evidenced using a reporter assay. Surprisingly, however, transcription of known HIF-1α effector genes evaluated by qPCR analysis, revealed either no change (LDHA and GAPDH), statistically insignificant increases SLC2A1 (GLUT-1) or greatly enhance transcription (VEGFA), but in an HIF-1α-independent manner, as quantified by PCR analysis in cells with shRNA-mediated silencing of HIF-1α. Instead, HIF-1α knockdown facilitated G1/S progression and increased Cyclin D1 protein half-life, via a post-translational pathway. Taken together, these findings link H. pylori-induced PI3K-mTOR activation to HIF-1α induced G0/G1 cell cycle arrest by a Cyclin D1-dependent mechanism. Thus, HIF-1α is identified here as a mediator between survival and cell cycle arrest signaling activated by H. pylori infection.

  3. Human rights education (HRE) and transnational activism

    NARCIS (Netherlands)

    Mihr, A.; Schmitz, Hans-Peter

    2007-01-01

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

  4. Human Factors in Virtual Reality Development

    Science.gov (United States)

    Kaiser, Mary K.; Proffitt, Dennis R.; Null, Cynthia H. (Technical Monitor)

    1995-01-01

    This half-day tutorial will provide an overview of basic perceptual functioning as it relates to the design of virtual environment systems. The tutorial consists of three parts. First, basic issues in visual perception will be presented, including discussions of the visual sensations of brightness and color, and the visual perception of depth relationships in three-dimensional space (with a special emphasis on motion -specified depth). The second section will discuss the importance of conducting human-factors user studies and evaluations. Examples and suggestions on how best to get help with user studies will be provided. Finally, we will discuss how, by drawing on their complementary competencies, perceptual psychologists and computer engineers can work as a team to develop optimal VR systems, technologies, and techniques.

  5. Human factors and ergonomics for primary care.

    Science.gov (United States)

    Bowie, Paul; Jeffcott, Shelly

    2016-03-01

    In the second paper of this series, we provide a brief overview of the scientific discipline of human factors and ergonomics (HFE). Traditionally the HFE focus in healthcare has been in acute hospital settings which are perceived to exhibit characteristics more similar to other high-risk industries already applying related principles and methods. This paper argues that primary care is an area which could benefit extensively from an HFE approach, specifically in improving the performance and well-being of people and organisations. To this end, we define the purpose of HFE, outline its three specialist sub-domains (physical, cognitive and organisational HFE) and provide examples of guiding HFE principles and practices. Additionally, we describe HFE issues of significance to primary care education, improvement and research and outline early plans for building capacity and capability in this setting.

  6. Human Factors and Simulation in Emergency Medicine.

    Science.gov (United States)

    Hayden, Emily M; Wong, Ambrose H; Ackerman, Jeremy; Sande, Margaret K; Lei, Charles; Kobayashi, Leo; Cassara, Michael; Cooper, Dylan D; Perry, Kimberly; Lewandowski, William E; Scerbo, Mark W

    2017-09-19

    This consensus group from the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change through Health Care Simulation: Systems, Competency, and Outcomes" held in Orlando, Florida, on May 16, 2017, focused on the use of human factors (HF) and simulation in the field of emergency medicine (EM). The HF discipline is often underutilized within EM but has significant potential in improving the interface between technologies and individuals in the field. The discussion explored the domain of HF, its benefits in medicine, how simulation can be a catalyst for HF work in EM, and how EM can collaborate with HF professionals to effect change. Implementing HF in EM through health care simulation will require a demonstration of clinical and safety outcomes, advocacy to stakeholders and administrators, and establishment of structured collaborations between HF professionals and EM, such as in this breakout group. © 2017 by the Society for Academic Emergency Medicine.

  7. The novel triterpenoid RTA 408 protects human retinal pigment epithelial cells against H2O2-induced cell injury via NF-E2-related factor 2 (Nrf2 activation

    Directory of Open Access Journals (Sweden)

    Xiaobin Liu

    2016-08-01

    Full Text Available Oxidative stress-induced retinal pigment epithelial (RPE cell damage is an important factor in the pathogenesis of age-related macular degeneration (AMD. Previous studies have shown that RTA 408, a synthetic triterpenoid compound, potently activates Nrf2. This study aimed to investigate the protective effects of RTA 408 in cultured RPE cells during oxidative stress and to determine the effects of RTA 408 on Nrf2 and its downstream target genes. Primary human RPE cells were pretreated with RTA 408 and then incubated in 200 μM H2O2 for 6 h. Cell viability was measured with the WST-8 assay. Apoptosis was quantitatively measured by annexin V/propidium iodide (PI double staining and Hoechst 33342 fluorescent staining. Reduced (GSH and oxidized glutathione (GSSG were measured using colorimetric assays. Nrf2 activation and its downstream effects on phase II enzymes were examined by Western blot. Treatment of RPE cells with nanomolar ranges (10 and 100 nM of RTA 408 markedly attenuated H2O2-induced viability loss and apoptosis. RTA 408 pretreatment significantly protected cells from oxidative stress-induced GSH loss, GSSG formation and decreased ROS production. RTA 408 activated Nrf2 and increased the expression of its downstream genes, such as HO-1, NQO1, SOD2, catalase, Grx1, and Trx1. Consequently, the enzyme activities of NQO1, Grx1, and Trx1 were fully protected by RTA 408 pretreatment under oxidative stress. Moreover, knockdown of Nrf2 by siRNA significantly reduced the cytoprotective effects of RTA 408. In conclusion, our data suggest that RTA 408 protect primary human RPE cells from oxidative stress-induced damage by activating Nrf2 and its downstream genes.

  8. Influence of vascular endothelial growth factor stimulation and serum deprivation on gene activation patterns of human adipose tissue-derived stromal cells

    DEFF Research Database (Denmark)

    Tratwal, Josefine; Mathiasen, Anders Bruun; Juhl, Morten

    2015-01-01

    INTRODUCTION: Stimulation of mesenchymal stromal cells and adipose tissue-derived stromal cells (ASCs) with vascular endothelial growth factor (VEGF) has been used in multiple animal studies and clinical trials for regenerative purposes. VEGF stimulation is believed to promote angiogenesis and VEGF...... stimulation is usually performed under serum deprivation. Potential regenerative molecular mechanisms are numerous and the role of contributing factors is uncertain. The aim of the current study was to investigate the effect of in vitro serum deprivation and VEGF stimulation on gene expression patterns...... of ASCs. METHODS: Gene expressions of ASCs cultured in complete medium, ASCs cultured in serum-deprived medium and ASCs stimulated with VEGF in serum-deprived medium were compared. ASC characteristics according to criteria set by the International Society of Cellular Therapy were confirmed by flow...

  9. Energy monitoring system based on human activity in the workplace

    Science.gov (United States)

    Mustafa, Nur Hanim; Husain, Mohd Nor; Aziz, Mohamad Zoinol Abidin Abdul; Othman, Mohd Azlishah; Malek, Fareq

    2015-05-01

    Human behaviors always related to day routine activities in a smart house directly give the significant factor to manage energy usage in human life. An Addition that, the factor will contribute to the best efficiency of the system. This paper will focus on the monitoring efficiency based on duration time in office hours around 8am until 5pm which depend on human behavior at working place. Besides that, the correlation coefficient method is used to show the relation between energy consumption and energy saving based on the total hours of time energy spent. In future, the percentages of energy monitoring system usage will be increase to manage energy saving based on human behaviors. This scenario will help to see the human activity in the workplace in order to get the energy saving and support world green environment.

  10. Human factors engineering checklists for application in the SAR process

    Energy Technology Data Exchange (ETDEWEB)

    Overlin, T.K.; Romero, H.A.; Ryan, T.G.

    1995-03-01

    This technical report was produced to assist the preparers and reviewers of the human factors portions of the SAR in completing their assigned tasks regarding analysis and/or review of completed analyses. The checklists, which are the main body of the report, and the subsequent tables, were developed to assist analysts in generating the needed analysis data to complete the human engineering analysis for the SAR. The technical report provides a series of 19 human factors engineering (HFE) checklists which support the safety analyses of the US Department of Energy`s (DOE) reactor and nonreactor facilities and activities. The results generated using these checklists and in the preparation of the concluding analyses provide the technical basis for preparing the human factors chapter, and subsequent inputs to other chapters, required by DOE as a part of the safety analysis reports (SARs). This document is divided into four main sections. The first part explains the origin of the checklists, the sources utilized, and other information pertaining to the purpose and scope of the report. The second part, subdivided into 19 sections, is the checklists themselves. The third section is the glossary which defines terms that could either be unfamiliar or have specific meanings within the context of these checklists. The final section is the subject index in which the glossary terms are referenced back to the specific checklist and page the term is encountered.

  11. Identification of heparin-binding EGF-like growth factor (HB-EGF as a biomarker for lysophosphatidic acid receptor type 1 (LPA1 activation in human breast and prostate cancers.

    Directory of Open Access Journals (Sweden)

    Marion David

    Full Text Available Lysophosphatidic acid (LPA is a natural bioactive lipid with growth factor-like functions due to activation of a series of six G protein-coupled receptors (LPA₁₋₆. LPA receptor type 1 (LPA₁ signaling influences the pathophysiology of many diseases including cancer, obesity, rheumatoid arthritis, as well as lung, liver and kidney fibrosis. Therefore, LPA₁ is an attractive therapeutic target. However, most mammalian cells co-express multiple LPA receptors whose co-activation impairs the validation of target inhibition in patients because of missing LPA receptor-specific biomarkers. LPA₁ is known to induce IL-6 and IL-8 secretion, as also do LPA₂ and LPA₃. In this work, we first determined the LPA induced early-gene expression profile in three unrelated human cancer cell lines expressing different patterns of LPA receptors (PC3: LPA₁,₂,₆; MDA-MB-231: LPA1,2; MCF-7: LPA₂,₆. Among the set of genes upregulated by LPA only in LPA₁-expressing cells, we validated by QPCR and ELISA that upregulation of heparin-binding EGF-like growth factor (HB-EGF was inhibited by LPA₁-₃ antagonists (Ki16425, Debio0719. Upregulation and downregulation of HB-EGF mRNA was confirmed in vitro in human MDA-B02 breast cancer cells stably overexpressing LPA₁ (MDA-B02/LPA₁ and downregulated for LPA₁ (MDA-B02/shLPA1, respectively. At a clinical level, we quantified the expression of LPA₁ and HB-EGF by QPCR in primary tumors of a cohort of 234 breast cancer patients and found a significantly higher expression of HB-EGF in breast tumors expressing high levels of LPA₁. We also generated human xenograph prostate tumors in mice injected with PC3 cells and found that a five-day treatment with Ki16425 significantly decreased both HB-EGF mRNA expression at the primary tumor site and circulating human HB-EGF concentrations in serum. All together our results demonstrate that HB-EGF is a new and relevant biomarker with potentially high value in

  12. Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gregori Casals

    2013-11-01

    Full Text Available Background: The molecular mechanisms by which myocardial ischemia translates into ventricular remodeling remain unclear. Methods: We investigated whether hypoxia and proinflammatory cytokines are specific inducers of remodeling signals in an in vitro model of cultured adult human ventricular myocytes (AC16 cells. Results:Hypoxia modified the ratio of matrix remodeling factors by increasing the aminoterminal propeptide of type III procollagen (PIIINP and reducing tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1 secretion in AC16 cells. These effects, however, were not associated with either modifications in expression of matrix metalloproteinase type 2, collagen-I or metalloproteinase activity. Hypoxia does, actually increase the production of the cardiac antifibrogenic growth factors, Apelin and VEGF, through an Hypoxia Inducible Factor type 1-dependent mechanism. Concerning proinflammatory signaling pathways, IL1β emerged as a powerful inducer of matrix turnover, since it significantly enhanced PIIINP, TIMP-1 and hyaluronic acid production and increased metalloproteinase activity. In contrast, TNFα did not modify matrix turnover but markedly induced the production of Apelin and VEGF. Conclusion: Hypoxia and increased TNFα activity likely exert cardioprotective actions by activating the cardiac antifibrogenic factors Apelin and VEGF. In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.

  13. A point mutation at tyrosine-809 in the human colony-stimulating factor 1 receptor impairs mitogenesis without abrogating tyrosine kinase activity, association with phosphatidylinositol 3-kinase, or induction of c-fos and junB genes

    Energy Technology Data Exchange (ETDEWEB)

    Roussel, M.F. (Univ. of Tennessee, Memphis (USA)); Shurtleff, S.A.; Downing, J.R. (Saint Jude Children' s Research Hospital, Memphis, TN (USA)); Sherr, C.J. (Univ. of Tennessee College of Medicine, Memphis (USA) Saint Jude Children' s Research Hospital, Memphis, TN (USA))

    1990-09-01

    Substitution of phenylalanine for tyrosine-809 in the human colony-stimulating factor 1 receptor (CSF-1R) inhibited its ability to transduce ligand-dependent mitogenic signals in mouse NIH 3T3 cells. When combined with an activating mutation at codon 301 that induces constitutive CSF-1R tyrosine kinase activity, the codon 809 mutation suppressed ligand-independent cell transformation. Comparative mapping tryptic phosphopeptides from mutant and wild-type CSF-1R indicated that tyrosine-809 is a site of ligand-dependent receptor phosphorylation in vivo. The mutant receptor was active as a tyrosine kinase in vitro and in vivo, underwent CSF-1-dependent association with a phosphatidylinositol 3-kinase, and induced expression of the protooncogenes c-fos and junB, underscoring its ability to trigger some of the known cellular responses to CSF-1. The mutant receptor is likely to be impaired in its ability to interact with critical cellular effectors whose activity is required for mitogenesis.

  14. Stromal Interaction Molecule 1 (STIM1) and Orai1 Mediate Histamine-evoked Calcium Entry and Nuclear Factor of Activated T-cells (NFAT) Signaling in Human Umbilical Vein Endothelial Cells*

    Science.gov (United States)

    Zhou, Meng-Hua; Zheng, Hongying; Si, Hongjiang; Jin, Yixin; Peng, Jasmine M.; He, Lian; Zhou, Yubin; Muñoz-Garay, Carlos; Zawieja, David C.; Kuo, Lih; Peng, Xu; Zhang, Shenyuan L.

    2014-01-01

    Histamine is an important immunomodulator involved in allergic reactions and inflammatory responses. In endothelial cells, histamine induces Ca2+ mobilization by releasing Ca2+ from the endoplasmic reticulum and eliciting Ca2+ entry across the plasma membrane. Herein, we show that histamine-evoked Ca2+ entry in human umbilical vein endothelial cells (HUVECs) is sensitive to blockers of Ca2+ release-activated Ca2+ (CRAC) channels. RNA interference against STIM1 or Orai1, the activating subunit and the pore-forming subunit of CRAC channels, respectively, abolishes this histamine-evoked Ca2+ entry. Furthermore, overexpression of dominant-negative CRAC channel subunits inhibits while co-expression of both STIM1 and Orai1 enhances histamine-induced Ca2+ influx. Interestingly, gene silencing of STIM1 or Orai1 also interrupts the activation of calcineurin/nuclear factor of activated T-cells (NFAT) pathway and the production of interleukin 8 triggered by histamine in HUVECs. Collectively, these results suggest a central role of STIM1 and Orai1 in mediating Ca2+ mobilization linked to inflammatory signaling of endothelial cells upon histamine stimulation. PMID:25190815

  15. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  16. Mouse and human eosinophils degranulate in response to platelet-activating factor (PAF) and lysoPAF via a PAF-receptor-independent mechanism: evidence for a novel receptor.

    Science.gov (United States)

    Dyer, Kimberly D; Percopo, Caroline M; Xie, Zhihui; Yang, Zhao; Kim, John Dongil; Davoine, Francis; Lacy, Paige; Druey, Kirk M; Moqbel, Redwan; Rosenberg, Helene F

    2010-06-01

    Platelet-activating factor (PAF [1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine]) is a phospholipid mediator released from activated macrophages, mast cells, and basophils that promotes pathophysiologic inflammation. Eosinophil responses to PAF are complex and incompletely elucidated. We show in this article that PAF and its 2-deacetylated metabolite (lysoPAF) promote degranulation (release of eosinophil peroxidase) via a mechanism that is independent of the characterized PAFR. Specifically, we demonstrate that receptor antagonists CV-3988 and WEB-2086 and pertussis toxin have no impact on PAF- or lysoPAF-mediated degranulation. Furthermore, cultured mouse eosinophils from PAFR(-/-) bone marrow progenitors degranulate in response to PAF and lysoPAF in a manner indistinguishable from their wild-type counterparts. In addition to PAF and lysoPAF, human eosinophils degranulate in response to lysophosphatidylcholine, but not phosphatidylcholine, lysophosphatidylethanolamine, or phosphatidylethanolamine, demonstrating selective responses to phospholipids with a choline head-group and minimal substitution at the sn-2 hydroxyl. Human eosinophils release preformed cytokines in response to PAF, but not lysoPAF, also via a PAFR-independent mechanism. Mouse eosinophils do not release cytokines in response to PAF or lysoPAF, but they are capable of doing so in response to IL-6. Overall, our work provides the first direct evidence for a role for PAF in activating and inducing degranulation of mouse eosinophils, a crucial feature for the interpretation of mouse models of PAF-mediated asthma and anaphylaxis. Likewise, we document and define PAF and lysoPAF-mediated activities that are not dependent on signaling via PAFR, suggesting the existence of other unexplored molecular signaling pathways mediating responses from PAF, lysoPAF, and closely related phospholipid mediators.

  17. Induction of reactive oxygen species-mediated apoptosis by purified Schisandrae semen essential oil in human leukemia U937 cells through activation of the caspase cascades and nuclear relocation of mitochondrial apoptogenic factors.

    Science.gov (United States)

    Yu, Gyeong Jin; Choi, Il-Whan; Kim, Gi-Young; Hwang, Hye Jin; Kim, Byung Woo; Kim, Cheol Min; Kim, Wun-Jae; Yoo, Young Hyun; Choi, Yung Hyun

    2015-10-01

    The aim of this study was to evaluate the beneficial effects of Schisandrae semen essential oil (SSeo) on apoptosis events and the mechanisms associated with these effects in human leukemia U937 cells. The treatment of U937 cells with SSeo significantly inhibited survival and induced apoptosis. Schisandrae semen essential oil treatment increased the levels of death receptors and Fas, and activated caspases accompanied by proteolytic degradation of poly(ADP-ribose)-polymerase, which was associated with the downregulation of members of the inhibitor of apoptosis protein family protein expression; however, a pan-caspase inhibitor reversed SSeo-induced apoptosis. Treating the cells with SSeo also caused truncation of Bid, translocation of proapoptotic Bax to the mitochondria, and loss of mitochondrial membrane permeabilization, thereby inducing the release of cytochrome c into the cytosol. Subsequently, SSeo upregulated the translocation of mitochondrial apoptogenic factors, such as endonuclease G and apoptosis-inducing factor, into the nucleus during the apoptotic process. Notably, SSeo immediately increased the generation of intracellular reactive oxygen species (ROS); however, pretreatment with N-acetylcysteine, a common ROS quencher, almost completely blocked SSeo-induced apoptosis. Taken together, these findings indicate that SSeo caused ROS- and caspase-dependent cell death involving mitochondrial dysfunction and nuclear translocation of mitochondrial proapoptosis proteins. Based on our data, the consumption of Schisandrae semen or its essential oil is a good natural therapeutic agent for anticancer activity and regression. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. The science of human factors: separating fact from fiction.

    Science.gov (United States)

    Russ, Alissa L; Fairbanks, Rollin J; Karsh, Ben-Tzion; Militello, Laura G; Saleem, Jason J; Wears, Robert L

    2013-10-01

    Interest in human factors has increased across healthcare communities and institutions as the value of human centred design in healthcare becomes increasingly clear. However, as human factors is becoming more prominent, there is growing evidence of confusion about human factors science, both anecdotally and in scientific literature. Some of the misconceptions about human factors may inadvertently create missed opportunities for healthcare improvement. The objective of this article is to describe the scientific discipline of human factors and provide common ground for partnerships between healthcare and human factors communities. The primary goal of human factors science is to promote efficiency, safety and effectiveness by improving the design of technologies, processes and work systems. As described in this article, human factors also provides insight on when training is likely (or unlikely) to be effective for improving patient safety. Finally, we outline human factors specialty areas that may be particularly relevant for improving healthcare delivery and provide examples to demonstrate their value. The human factors concepts presented in this article may foster interdisciplinary collaborations to yield new, sustainable solutions for healthcare quality and patient safety.

  19. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke

    Directory of Open Access Journals (Sweden)

    Shukla SD

    2016-07-01

    Full Text Available Shakti D Shukla,1,* Rory L Fairbairn,1,* David A Gell,1 Roger D Latham,1 Sukhwinder S Sohal,1,2 Eugene H Walters,1 Ronan F O’Toole11Breathe Well Centre, School of Medicine, Faculty of Health, University of Tasmania, Hobart, TAS, Australia; 2School of Health Sciences, Faculty of Health, University of Tasmania, Launceston, TAS, Australia*These authors contributed equally to this workBackground: COPD is emerging as the third largest cause of human mortality worldwide after heart disease and stroke. Tobacco smoking, the primary risk factor for the development of COPD, induces increased expression of platelet-activating factor receptor (PAFr in the lung epithelium. Nontypeable Haemophilus influenzae (NTHi and Streptococcus pneumoniae adhere to PAFr on the luminal surface of human respiratory tract epithelial cells.Objective: To investigate PAFr as a potential drug target for the prevention of infections caused by the main bacterial drivers of acute exacerbations in COPD patients, NTHi and S. pneumoniae.Methods: Human bronchial epithelial BEAS-2B cells were exposed to cigarette smoke extract (CSE. PAFr expression levels were determined using immunocytochemistry and quantitative polymerase chain reaction. The epithelial cells were challenged with either NTHi or S. pneumoniae labeled with fluorescein isothiocyanate, and bacterial adhesion was measured using immunofluorescence. The effect of a well-evaluated antagonist of PAFr, WEB-2086, on binding of the bacterial pathogens to BEAS-2B cells was then assessed. In silico studies of the tertiary structure of PAFr and the binding pocket for PAF and its antagonist WEB-2086 were undertaken.Results: PAFr expression by bronchial epithelial cells was upregulated by CSE, and significantly associated with increased bacterial adhesion. WEB-2086 reduced the epithelial adhesion by both NTHi and S. pneumoniae to levels observed for non-CSE-exposed cells. Furthermore, it was nontoxic toward the bronchial epithelial

  20. Golimumab, a human antibody to tumour necrosis factor {alpha} given by monthly subcutaneous injections, in active rheumatoid arthritis despite methotrexate therapy: the GO-FORWARD Study.

    Science.gov (United States)

    Keystone, E C; Genovese, M C; Klareskog, L; Hsia, E C; Hall, S T; Miranda, P C; Pazdur, J; Bae, S-C; Palmer, W; Zrubek, J; Wiekowski, M; Visvanathan, S; Wu, Z; Rahman, M U

    2009-06-01

    The phase III GO-FORWARD study examined the efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate therapy. Patients were randomly assigned in a 3 : 3 : 2 : 2 ratio to receive placebo injections plus methotrexate capsules (group 1, n = 133), golimumab 100 mg injections plus placebo capsules (group 2, n = 133), golimumab 50 mg injections plus methotrexate capsules (group 3, n = 89), or golimumab 100 mg injections plus methotrexate capsules (group 4, n = 89). Injections were administered subcutaneously every 4 weeks. The co-primary endpoints were the proportion of patients with 20% or greater improvement in the American College of Rheumatology criteria (ACR20) at week 14 and the change from baseline in the health assessment questionnaire-disability index (HAQ-DI) score at week 24. The proportion of patients who achieved an ACR20 response at week 14 was 33.1% in the placebo plus methotrexate group, 44.4% (p = 0.059) in the golimumab 100 mg plus placebo group, 55.1% (p = 0.001) in the golimumab 50 mg plus methotrexate group and 56.2% (p<0.001) in the golimumab 100 mg plus methotrexate group. At week 24, median improvements from baseline in HAQ-DI scores were 0.13, 0.13 (p = 0.240), 0.38 (p<0.001) and 0.50 (p<0.001), respectively. During the placebo-controlled portion of the study (to week 16), serious adverse events occurred in 2.3%, 3.8%, 5.6% and 9.0% of patients and serious infections occurred in 0.8%, 0.8%, 2.2% and 5.6%, respectively. The addition of golimumab to methotrexate in patients with active RA despite methotrexate therapy significantly reduced the signs and symptoms of RA and improved physical function.

  1. Information Presentation: Human Research Program - Space Human Factors and Habitability, Space Human Factors Engineering Project

    Science.gov (United States)

    Holden, Kristina L.; Sandor, Aniko; Thompson, Shelby G.; Kaiser, Mary K.; McCann, Robert S.; Begault, D. R.; Adelstein, B. D.; Beutter, B. R.; Wenzel, E. M.; Godfroy, M.; hide

    2010-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. The major areas of work, or subtasks, within this DRP are: 1) Displays, 2) Controls, 3) Electronic Procedures and Fault Management, and 4) Human Performance Modeling. This DRP is a collaborative effort between researchers atJohnson Space Center and Ames Research Center. T

  2. Human blood platelets lack nitric oxide synthase activity.

    Science.gov (United States)

    Böhmer, Anke; Gambaryan, Stepan; Tsikas, Dimitrios

    2015-01-01

    Reports on expression and functionality of nitric oxide synthase (NOS) activity in human blood platelets and erythrocytes are contradictory. We used a specific gas chromatography-mass spectrometry (GC-MS) method to detect NOS activity in human platelets. The method measures simultaneously [(15)N]nitrite and [(15)N]nitrate formed from oxidized (15)N-labeled nitric oxide ((15)NO) upon its NOS-catalyzed formation from the substrate l-[guanidino-(15)N2]-arginine. Using this GC-MS assay, we did not detect functional NOS in non-stimulated platelets and in intact platelets activated by various agonists (adenosine diphosphate, collagen, thrombin, or von Willebrand factor) or lysed platelets. l-[guanidino-nitro]-Arginine-inhibitable NOS activity was measured after addition of recombinant human endothelial NOS to lysed platelets. Previous and recent studies from our group challenge expression and functionality of NOS in human platelets and erythrocytes.

  3. Sensing Human Activity: GPS Tracking.

    Science.gov (United States)

    van der Spek, Stefan; van Schaick, Jeroen; de Bois, Peter; de Haan, Remco

    2009-01-01

    THE ENHANCEMENT OF GPS TECHNOLOGY ENABLES THE USE OF GPS DEVICES NOT ONLY AS NAVIGATION AND ORIENTATION TOOLS, BUT ALSO AS INSTRUMENTS USED TO CAPTURE TRAVELLED ROUTES: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands) for one week. The question posed in this paper is: what is the value of GPS as 'sensor technology' measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research.

  4. Sensing Human Activity: GPS Tracking

    Science.gov (United States)

    van der Spek, Stefan; van Schaick, Jeroen; de Bois, Peter; de Haan, Remco

    2009-01-01

    The enhancement of GPS technology enables the use of GPS devices not only as navigation and orientation tools, but also as instruments used to capture travelled routes: as sensors that measure activity on a city scale or the regional scale. TU Delft developed a process and database architecture for collecting data on pedestrian movement in three European city centres, Norwich, Rouen and Koblenz, and in another experiment for collecting activity data of 13 families in Almere (The Netherlands) for one week. The question posed in this paper is: what is the value of GPS as ‘sensor technology’ measuring activities of people? The conclusion is that GPS offers a widely useable instrument to collect invaluable spatial-temporal data on different scales and in different settings adding new layers of knowledge to urban studies, but the use of GPS-technology and deployment of GPS-devices still offers significant challenges for future research. PMID:22574061

  5. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  6. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  7. Pengalokasian Tenaga Kerja dengan Human Factor Engineering di PT. Pelindo I

    Directory of Open Access Journals (Sweden)

    Yusnawati Yusnawati

    2017-05-01

    Full Text Available Indonesia Port Corporation I (PT Pelabuhan Indonesia I (Persero or PT. Pelindo I is one of the Indonesian state-owned enterprises which manages port services in western Indonesia. Shipyard unit (Unit Galangan Kapal (UGK is a branch of PT. Pelindo I. At present, a problem arises if more than 2 ships are being repaired at once in the unit, UGK scheduling overlaps the repairing activities. In order to solve the problem, study of human factor is important. Human factor is the study of the limitations, capabilities, and human behavior, as well as its interaction with the product, environment, equipment and the establishment of tasks and activities. One part of the human factor is the human factor in system design. In order to improve the effectiveness of the system, the human factor must be involved in each phase of the design process in the system design. This includes a number of activities to obtain input specification work, therefore the working methods and the optimal amount of labor can be determined. Human factors engineering is the application of science that utilizes research on the human factor and use the basic knowledge to design, to repair and to install the system. This research method is causal, searching for the causes which led to delays in the completion of ship repairing. Through human factor engineering approach to the allocation of labor increased by 12.23 per cent of the actual conditions, so that the delay of ship repair were not found during normal conditions.

  8. Human Factors of CC-130 Operations. Volume 5: Human Factors in Decision Making

    Science.gov (United States)

    1998-02-01

    ATG study team describes the development of a proposed new training programme devoted to Human Factors in Decision Making ( HFDM ). It is envisaged that...the HFDM training syllabus would replace existing Aircrew Co- ordination Training (ACT) within the CC-130 community. The proposed training can be...processing. The differences lie less in the content than in the way the material is organised and shaped by theory. The proposed HFDM training is based

  9. Human Factors Aspects of Operating Small Reactors

    Energy Technology Data Exchange (ETDEWEB)

    OHara, J.M.; Higgins, J.; Deem, R. (BNL); Xing, J.; DAgostino, A. (NRC)

    2010-11-07

    The nuclear-power community has reached the stage of proposing advanced reactor designs to support power generation for decades to come. They are considering small modular reactors (SMRs) as one approach to meet these energy needs. While the power output of individual reactor modules is relatively small, they can be grouped to produce reactor sites with different outputs. Also, they can be designed to generate hydrogen, or to process heat. Many characteristics of SMRs are quite different from those of current plants, and so may require a concept of operations (ConOps) that also is different. The U.S. Nuclear Regulatory Commission (NRC) has begun examining the human factors engineering- (HFE) and ConOps- aspects of SMRs; if needed, they will formulate guidance to support SMR licensing reviews. We developed a ConOps model, consisting of the following dimensions: Plant mission; roles and responsibilities of all agents; staffing, qualifications, and training; management of normal operations; management of off-normal conditions and emergencies; and, management of maintenance and modifications. We are reviewing information on SMR design to obtain data about each of these dimensions, and have identified several preliminary issues. In addition, we are obtaining operations-related information from other types of multi-module systems, such as refineries, to identify lessons learned from their experience. Here, we describe the project's methodology and our preliminary findings.

  10. Draft revision of human factors guideline HF-010

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Chul; Lee, Yong Hee; Oh, In Seok; Lee, Jung Woon [KAERI, Taejon (Korea, Republic of); Cha, Woo Chang [Kumoh National Institute of Technology, Gumi (Korea, Republic of); Lee, Dhong Ha [Suwon University, Suwon (Korea, Republic of)

    2003-05-01

    The Application of Human Factors to the design of Man-Machine Interfaces System(MMIS) in the nuclear power plant is essential to the safety and productivity of the nuclear power plants, human factors standards and guidelines as well as human factors analysis methods and experiments are weightily used to the design application. A Korean engineering company has developed a human factors engineering guideline, so-call HF-010, and has used it for human factors design, however the revision of HF-010 is necessary owing to lack of the contents related to the advanced MMI(Man-Machine Interfaces). As the results of the reviews of HF-010, it is found out that the revision of Section 9. Computer Displays of HF-010 is urgent, thus the revision was drafted on the basis of integrated human factors design guidelines for VDT, human factors design guidelines for PMAS SPADES display, human factors design guidelines for PMAS alarm display, and human factors design guidelines for electronic displays developed by the surveillance and operation support project of KOICS. The draft revision of HF-010 Section 9 proposed in this report can be utilized for the human factors design of the advanced MMI, and the high practical usability of the draft can be kept up through the continuous revision according to the advancement of digital technology.

  11. Beta2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis.

    Science.gov (United States)

    Nomura, Takeo; Huang, Wen-Chin; Zhau, Haiyen E; Wu, Daqing; Xie, Zhihui; Mimata, Hiromitsu; Zayzafoon, Majd; Young, Andrew N; Marshall, Fray F; Weitzmann, M Neale; Chung, Leland W K

    2006-12-15

    Beta(2)-microglobulin (beta2M), a soluble protein secreted by cancer and host inflammatory cells, has various biological functions, including antigen presentation. Because aberrant expression of beta2M has been reported in human renal cell carcinoma, we investigated the effects of beta2M overexpression on cancer cell growth and analyzed its molecular signaling pathway. We established clonal cell lines that overexpressed beta2M in human renal cell carcinoma (SN12C) cells and then examined cell growth in vitro and in vivo and studied the beta2M-mediated downstream cell signaling pathway. Our results showed that beta2M expression positively correlates with (a) in vitro growth on plastic dishes and as Matrigel colonies, (b) cell invasion and migration in Boyden chambers, and (c) vascular endothelial growth factor (VEGF) expression and secretion by cells. We found, in addition, that beta2M mediates its action through increased phosphorylation of cyclic AMP-responsive element-binding protein (CREB) via the protein kinase A-CREB axis, resulting in increased VEGF expression and secretion. In convergence with this signal axis, beta2M overexpression also activated both phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Beta2M overexpression induced accelerated growth of SN12C in mouse subcutis and bone. Interrupting the beta2M signaling pathway using small interfering RNA led to apoptosis with increased activation of caspase-3 and caspase-9 and cleaved poly(ADP-ribose) polymerase. Our results showed for the first time that the beta2M-protein kinase A-CREB-VEGF signaling axis plays a crucial role in support of renal cell carcinoma growth and progression and reveals a novel therapeutic target.

  12. Timing of nurses activities: human resources management

    Directory of Open Access Journals (Sweden)

    Hamid Hosein Poor

    2016-11-01

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

  13. Humanized birth in high risk pregnancy: barriers and facilitating factors.

    Science.gov (United States)

    Behruzi, Roxana; Hatem, Marie; Goulet, Lise; Fraser, William; Leduc, Nicole; Misago, Chizuru

    2010-02-01

    The medical model of childbearing assumes that a pregnancy always has the potential to turn into a risky procedure. In order to advocate humanized birth in high risk pregnancy, an important step involves the enlightenment of the professional's preconceptions on humanized birth in such a situation. The goal of this paper is to identify the professionals' perception of the potential obstacles and facilitating factors for the implementation of humanized care in high risk pregnancies. Twenty-one midwives, obstetricians, and health administrator professionals from the clinical and academic fields were interviewed in nine different sites in Japan from June through August 2008. The interviews were audio taped, and transcribed with the participants' consent. Data was subsequently analyzed using content analysis qualitative methods. Professionals concurred with the concept that humanized birth is a changing and promising process, and can often bring normality to the midst of a high obstetric risk situation. No practice guidelines can be theoretically defined for humanized birth in a high risk pregnancy, as there is no conflict between humanized birth and medical intervention in such a situation. Barriers encountered in providing humanized birth in a high risk pregnancy include factors such as: the pressure of being responsible for the safety of the mother and the fetus, lack of the women's active involvement in the decision making process and the heavy burden of responsibility on the physician's shoulders, potential legal issues, and finally, the lack of midwifery authority in providing care at high risk pregnancy. The factors that facilitate humanized birth in a high risk include: the sharing of decision making and other various responsibilities between the physicians and the women; being caring; stress management, and the fact that the evolution of a better relationship and communication between the health professional and the patient will lead to a stress

  14. Integrated Extravehicular Activity Human Research Plan: 2017

    Science.gov (United States)

    Abercromby, Andrew

    2017-01-01

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

  15. An investigation on factors influencing on human resources productivity

    Directory of Open Access Journals (Sweden)

    Masoumeh Seifi Divkolaii

    2014-05-01

    Full Text Available Human resources development is one of the most important components of any organization and detecting important factors influencing on human resources management plays essential role on the success of the firms. In this paper, we present an empirical investigation to determine different factors influencing productivity of human resources of Islamic Republic of Iran Broadcasting (IRIB in province of Mazandaran, Iran. The study uses analytical hierarchy process (AHP to rank 17 important factors and determines that personal characteristics were the most important factors followed by management related factors and environmental factors. In terms of personal characteristics, job satisfaction plays essential role on human resources development. In terms of managerial factors, paying attention on continuous job improvement by receiving appropriate training is the most important factor followed by welfare facilities for employees and using a system of reward/punishment in organization. Finally, in terms of environmental factors, occupational safety is number one priority followed by organizational rules and regulations.

  16. Human milk composition: nutrients and bioactive factors.

    Science.gov (United States)

    Ballard, Olivia; Morrow, Ardythe L

    2013-02-01

    This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Human factors in aviation maintenance, phase five : progress report.

    Science.gov (United States)

    1996-01-01

    The fifth phase of research on human factors in aviation maintenance continued to look at the human's role in the aviation maintenance system via investigations, demonstrations, and evaluations of the research program outputs. This report describes t...

  18. An investigation on factors influencing on human resources productivity

    National Research Council Canada - National Science Library

    Masoumeh Seifi Divkolaii

    2014-01-01

    Human resources development is one of the most important components of any organization and detecting important factors influencing on human resources management plays essential role on the success of the firms...

  19. Assessment of plasma brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) concentrations in treatment-naïve humans with multiple sclerosis.

    Science.gov (United States)

    Kochanowski, Jan; Uchman, Dorota; Litwiniuk, Anna; Kalisz, Malgorzata; Wolinska-Witort, Ewa; Martynska, Lidia; Baranowska, Boguslawa; Bik, Wojciech

    2015-01-01

    Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) characterized by coexisting processes of inflammation, demyelination, axonal neurodegeneration and gliosis. Autoimmune processes play a pivotal role in the disease. The immune system may be modulated by neurotrophins and neurotrophin factors. Aim of the study was to assess plasma levels of brain-derived neurotrophic factor (BDNF), activity-dependent neurotrophin protein (ADNP) and vasoactive intestinal peptide (VIP) in treatment-naïve humans with newly diagnosed multiple sclerosis. We also elucidated the potential influence of selected inflammatory agents on peripheral concentration of BDNF and ADNP. The study population comprised of 31 untreated patients with MS and 36 controls from a single hospital centre. Assessment of BDNF and ADNP was performed with use of ELISA methods. VIP was measured with RIA. Selected cytokine levels (IL 6, IL 10, and TNF α) were evaluated with ELISA tests. Statistical analyses were performed. We failed to find any significant differences between ADNP, BDNF, VIP, CRP levels and concentration of cytokines between individuals with MS and the controls. No correlation was observed between ADNP, BDNF and VIP as the first parameter and CRP, IL 6, IL 10, TNFα levels and the Expanded Disability Status Scale score in MS. Newly diagnosed, treatment-naïve patients with MS have comparable levels of plasma BDNF, ADNP and VIP to those of healthy controls.

  20. Human error analysis of commercial aviation accidents using the human factors analysis and classification system (HFACS)

    Science.gov (United States)

    2001-02-01

    The Human Factors Analysis and Classification System (HFACS) is a general human error framework : originally developed and tested within the U.S. military as a tool for investigating and analyzing the human : causes of aviation accidents. Based upon ...

  1. Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

    Science.gov (United States)

    Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.

    2010-01-01

    As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities.

  2. Discussing the Effective Factors on Maintenance of Human Resources

    OpenAIRE

    Bahare Shahriari

    2016-01-01

    In this research, the author has elaborated on detection of effective factors on maintenance and retention of human resources. Since human resources are the most resources for obtaining competitive advantage, it is essential to pay attention to different dimensions of human resources management. One of these dimensions is retention of human resources. Factors such as providing correct and valid information at the time of recruitment, assigning tasks based on competence, existence of a clear c...

  3. Rapid Prototyping and the Human Factors Engineering Process

    Science.gov (United States)

    2016-08-29

    Rapid prototyping and the human factors • • engineering process David Beevis* and Gaetan St Denist *Senior Human Factors Engineer, Defence and...qr-..2. 9 Rapid prototyping or ’virtual prototyping ’ of human-machine interfaces offers the possibility of putting the human operator ’in the loop...8217 without the effort and cost associated with conventional man-in-the-loop simulation. Advocates suggest that rapid prototyping is compatible with

  4. A human activity approach to User Interfaces

    DEFF Research Database (Denmark)

    Bødker, Susanne

    1989-01-01

    the work situations in which computer-based artifacts are used: The framework deals with the role of the user interface in purposeful human work. Human activity theory is used in this analysis. The purpose of this article is to make the reader curious and hopefully open his or her eyes to a somewhat...... different way of thinking about the user interface. The article applies examples of real-life interfaces to support this process, but it does not include a systematic presentation of empirical results. I focus on the role of the computer application in use. Thus, it is necessary to consider human-computer...... interaction and other related work conditions. I deal with human experience and competence as being rooted in the practice of the group that conducts the specific work activity. The main conclusions are: The user interface cannot be seen independently of the use activity (i.e., the professional, socially...

  5. Development of a Human Factors Management Guideline for the MMI

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Woo Chang; Kang, Young Ju; Jung, Seong Hae [Kumoh National Institute of Technology, Gumi (Korea, Republic of); Lee, Dong Ha [The University of Suwon, Suwon (Korea, Republic of); Jung, Kwang Tae [Korea University of Technology and Education, Cheonan (Korea, Republic of)

    2009-07-15

    The objective of this project is to develop human factors guidelines of MMI devices, maintenance tasks, and operating procedures. The scope of guidelines covers interface components between the operation or maintenance personnel and a system. It also includes human factor consideration items for emergency operating procedures. Various design guidelines and technical papers related to evaluation of MMI devices and information displays were collected and reviewed to identify the appropriate human factors issues for human interface devices. From the collected issues, the evaluation issues and items to be used in the guidelines for a nuclear power plant have been developed through the consensus of the design review expertise. For developing human factor guidelines of the emergency operating procedures, we have researched on human errors of emergency operations in the nuclear power plant in the 1st year, on the deficiencies of the human factor aspects in the writing guidelines of emergency operating procedures in the 2nd year. A new writing and management guideline for emergency operating procedures were developed in the 3rd year. This report consists of three parts ; (1) human factors guidelines for MMI devices, (2) human factors guidelines for the maintenance tasks of NPP devices, (3) human factors guidelines for the management of operating procedures

  6. Effect of BN 52021, a specific antagonist of platelet activating factor (PAF-acether), on calcium movements and phosphatidic acid production induced by PAF-acether in human platelets

    Energy Technology Data Exchange (ETDEWEB)

    Simon, M.F.; Chap, H.; Braquet, P.; Douste-Blazy, L.

    1987-02-15

    /sup 32/P-labelled human platelets loaded with quin 2 and pretreated with aspirin were stimulated with 1-100 nM platelet activating factor (PAF-acether or 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in a medium containing the ADP-scavenging system creatine phosphate/creatine phosphokinase. Under these conditions, PAF-acether evoked a characteristic fluorescence change allowing to quantify elevations in cytoplasmic free Ca/sup 2 +/ from internal stores (Ca/sup 2 +/ mobilization) or from external medium (Ca/sup 2 +/ influx), as well as an increased production of phosphatidic acid, reflecting phospholipase C activation. These effects, which can be attributed to PAF-acether only and not to released products such as ADP or thromboxane A2, were strongly inhibited in a dose-dependent manner by BN 52021, a specific antagonist of PAF-acether isolated from Ginkgo biloba. As the drug remained inactive against the same effects elicited by thrombin, it is concluded that BN 52021 does not interfere directly with the mechanism of transmembrane signalling involving inositol-phospholipids or (and) some putative receptor-operated channels, but rather acts on the binding of PAF-acether to its presumed membrane receptor.

  7. A Human Factors Analysis of EVA Time Requirements

    Science.gov (United States)

    Pate, Dennis W.

    1997-01-01

    Human Factors Engineering (HFE) is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. During the summer of 1995, a human factors motion and time study was initiated with the goals of developing a database of EVA task times and developing a method of utilizing the database to predict how long an EVA should take. Initial development relied on the EVA activities performed during the STS-61 (Hubble) mission. The first step of the study was to become familiar with EVA's, the previous task-time studies, and documents produced on EVA's. After reviewing these documents, an initial set of task primitives and task-time modifiers was developed. Data was collected from videotaped footage of two entire STS-61 EVA missions and portions of several others, each with two EVA astronauts. Feedback from the analysis of the data was used to further refine the primitives and modifiers used. The project was continued during the summer of 1996, during which data on human errors was also collected and analyzed. Additional data from the STS-71 mission was also collected. Analysis of variance techniques for categorical data was used to determine which factors may affect the primitive times and how much of an effect they have. Probability distributions for the various task were also generated. Further analysis of the modifiers and interactions is planned.

  8. The chemokine CXCL12 mediates the anti-amyloidogenic action of painless human nerve growth factor

    OpenAIRE

    Capsoni, Simona; Malerba, Francesca; Carucci, Nicola Maria; Rizzi, Caterina; Criscuolo, Chiara; Origlia, Nicola; Calvello, Mariantonietta; Viegi, Alessandro; Meli, Giovanni; Cattaneo, Antonino

    2016-01-01

    Abstract Nerve growth factor is a therapeutic candidate for Alzheimer?s disease. Due to its pain-inducing activity, in current clinical trials nerve growth factor is delivered locally into the brain by neurosurgery, but data on the efficacy of local nerve growth factor delivery in decreasing amyloid-? deposition are not available. To reduce the nerve growth factor pain-inducing side effects, thus avoiding the need for local brain injection, we developed human painless nerve growth factor (hNG...

  9. Conformal displays: human factor analysis of innovative landing aids

    Science.gov (United States)

    Schmerwitz, Sven; Lueken, Thomas; Doehler, Hans-Ullrich; Peinecke, Niklas; Ernst, Johannes M.; da Silva Rosa, David L.

    2017-05-01

    In the past couple of years, research on display content for helicopter operations headed in a new direction. The already reached goals could evolve into a paradigm change for information visualization. Technology advancements allow implementing three-dimensional and conformal content on a helmet-mounted see-through device. This superimposed imagery inherits the same optical flow as the environment. It is supposed to ease switching between display information and environmental cues. The concept is neither pathbreaking nor new, but it has not been successfully established in aviation yet. Nevertheless, there are certainly some advantages to expect-at least from perspective of a human-centered system design. Within the following pages, the next generation displays will be presented and discussed with a focus on human factors. Beginning with recalling some human factor related research facts, an experiment comparing the former two-dimensional research displays will be presented. Before introducing the DLR conformal symbol set and the three experiments about an innovative drift, indication related research activities toward conformal symbol sets will be addressed.

  10. Personal reflections from the fifth editor of Human Factors.

    Science.gov (United States)

    Williges, Robert C

    2008-06-01

    The fifth editor of Human Factors provides reflections on journal publication spanning four volumes printed from 1976 to 1980. During that period, most of the publication and management activities were handled by volunteer efforts of the editor, the editorial board, and the editor's organization. Electronic word processing was not readily available, and most publication tasks required laborious clerical support, resulting in long publication lags. The editor provides reflection on the steps taken by the Human Factors and Ergonomics Society to separate editorial and production activities during that period to provide more support for the journal editorial duties. This resulted in the Society becoming its own publisher, building the beginning of a publication staff in the central office, and increasing the published page count. Rigorous editorial reviews were used to improve the scientific quality of the journal. The publication emphasis was on empirical research, but theoretical articles and research reviews were also considered for publication. Regular journal articles, short research notes, and special topics were published as ways to broaden the scientific coverage and shorten the publication lag.

  11. Human factors in space station architecture 1: Space station program implications for human factors research

    Science.gov (United States)

    Cohen, M. M.

    1985-01-01

    The space station program is based on a set of premises on mission requirements and the operational capabilities of the space shuttle. These premises will influence the human behavioral factors and conditions on board the space station. These include: launch in the STS Orbiter payload bay, orbital characteristics, power supply, microgravity environment, autonomy from the ground, crew make-up and organization, distributed command control, safety, and logistics resupply. The most immediate design impacts of these premises will be upon the architectural organization and internal environment of the space station.

  12. Ketamine inhibits transcription factors activator protein 1 and nuclear factor-kappaB, interleukin-8 production, as well as CD11b and CD16 expression: studies in human leukocytes and leukocytic cell lines.

    NARCIS (Netherlands)

    Welters, I.D.; Hafer, G.; Menzebach, A.; Muhling, J.; Neuhauser, C.; Browning, P.; Goumon, Y.

    2010-01-01

    BACKGROUND: Recent data indicate that ketamine exerts antiinflammatory actions. However, little is known about the signaling mechanisms involved in ketamine-induced immune modulation. In this study, we investigated the effects of ketamine on lipopolysaccharide-induced activation of transcription

  13. Capillary growth in human skeletal muscle: physiological factors and the balance between pro-angiogenic and angiostatic factors

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Hoier, Birgitte

    2014-01-01

    In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either by me...... addresses physiological signals and angiogenic factors in skeletal muscle with a focus on human data.......In human skeletal muscle, the capillary net readily adapts according to the level of muscular activity to allow for optimal diffusion conditions for oxygen from the blood to the muscle. Animal studies have demonstrated that stimulation of capillary growth in skeletal muscle can occur either...... angiogenesis. A number of such regulatory proteins have been described in skeletal muscle in animal and cell models but also in human skeletal muscle. Important pro-angiogenic factors in skeletal muscle are vascular endothelial growth factor, endothelial nitric oxide synthase and angiopoietin 2, whereas...

  14. Human factors/ergonomics as a systems discipline? "The human use of human beings" revisited

    DEFF Research Database (Denmark)

    Hollnagel, Erik

    2014-01-01

    Discussions of the possible future of Human factors/ergonomics (HFE) usually take the past for granted in the sense that the future of HFE is assumed to be more of the same. This paper argues that the nature of work in the early 2010s is so different from the nature of work when HFE was formulated...

  15. EFFECTIVE HUMAN CAPITAL MANAGEMENT AS KEY FACTOR OF INNOVATION DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Никита Сергеевич Иванов

    2013-12-01

    Full Text Available Issues connected with particularities and mechanisms of human capital management are considered in the article; appropriateness of investments into it in the conditions of modern production is assessed. Motivation system to encourage high labor productivity, working experience, skills and the level of education, health – all this must be reflected in the wage size and facilitate formation of human capital in the process of company management. Education and activity aimed for health care include current costs for the sake of future benefits. Individuals and the companies differ by a degree of readiness to make such long-term investments. Proper use of natural abilities of a man as a function of human capital management is its integral part. It can be illustrated in such a way: natural abilities of a man to some extent are like lease of land which brings profit. The key factor here is investments into growth of human capital and its quality.DOI: http://dx.doi.org/10.12731/2218-7405-2013-10-13

  16. Endoplasmic reticulum stress induced by tunicamycin increases resistin messenger ribonucleic acid through the pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase-activating transcription factor 4-CAAT/enhancer binding protein-α homologous protein pathway in THP-1 human monocytes.

    Science.gov (United States)

    Hamada, Junpei; Onuma, Hiroshi; Ochi, Fumihiro; Hirai, Hiroki; Takemoto, Koji; Miyoshi, Akiko; Matsushita, Manami; Kadota, Yuko; Ohashi, Jun; Kawamura, Ryoichi; Takata, Yasunori; Nishida, Wataru; Hashida, Seiichi; Ishii, Eiichi; Osawa, Haruhiko

    2016-05-01

    Resistin, secreted from adipocytes, causes insulin resistance in mice. In humans, the resistin gene is mainly expressed in monocytes and macrophages. Tunicamycin is known to induce endoplasmic reticulum (ER) stress, and reduce resistin gene expression in 3T3-L1 mouse adipocytes. The aim of the present study was to examine whether ER stress affects resistin gene expression in human monocytes. The relationship between resistin messenger ribonucleic acid (mRNA) and ER stress markers mRNA was analyzed by reverse transcription polymerase chain reaction in isolated monocytes of 30 healthy volunteers. The effect of endotoxin/lipopolysaccharides or tunicamycin on resistin gene expression was analyzed in THP-1 human monocytes. Signaling pathways leading to resistin mRNA were assessed by the knockdown using small interfering RNA or overexpression of key molecules involved in unfolded protein response. Resistin mRNA was positively associated with immunoglobulin heavy chain-binding protein (BiP) or CAAT/enhancer binding protein-α homologous protein (CHOP) mRNA in human isolated monocytes. In THP-1 cells, lipopolysaccharides increased mRNA of BiP, pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase (PERK) and CHOP, as well as resistin. Tunicamycin also increased resistin mRNA. This induction appeared to be dose- and time-dependent. Tunicamycin-induced resistin mRNA was inhibited by chemical chaperone, 4-phenylbutyric acid. The knockdown of either PERK, activating transcription factor 4 (ATF4) or CHOP reduced tunicamycin-induced resistin mRNA. Conversely, overexpression of ATF4 or CHOP increased resistin mRNA. Endoplasmic reticulum stress induced by tunicamycin increased resistin mRNA through the PERK-ATF4-CHOP pathway in THP-1 human monocytes. ER stress could lead to insulin resistance through enhanced resistin gene expression in human monocytes.

  17. NAS Human Factors Safety Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory conducts an integrated program of research on the relationship of factors concerning individuals, work groups, and organizations as employees perform...

  18. Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Jun [Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Xiang, Jun-Jian, E-mail: txjj@jnu.edu.cn [Laboratory of Antibody Engineering, College of Life Sciences and Technologies, Jinan University, Guangzhou 510632 (China); Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Li, Dan [Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Deng, Ning; Wang, Hong; Gong, Yi-Ping [Laboratory of Antibody Engineering, College of Life Sciences and Technologies, Jinan University, Guangzhou 510632 (China)

    2010-04-09

    Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10{sup -9} M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

  19. Understanding human dynamics in microblog posting activities

    Science.gov (United States)

    Jiang, Zhihong; Zhang, Yubao; Wang, Hui; Li, Pei

    2013-02-01

    Human activity patterns are an important issue in behavior dynamics research. Empirical evidence indicates that human activity patterns can be characterized by a heavy-tailed inter-event time distribution. However, most researchers give an understanding by only modeling the power-law feature of the inter-event time distribution, and those overlooked non-power-law features are likely to be nontrivial. In this work, we propose a behavior dynamics model, called the finite memory model, in which humans adaptively change their activity rates based on a finite memory of recent activities, which is driven by inherent individual interest. Theoretical analysis shows a finite memory model can properly explain various heavy-tailed inter-event time distributions, including a regular power law and some non-power-law deviations. To validate the model, we carry out an empirical study based on microblogging activity from thousands of microbloggers in the Celebrity Hall of the Sina microblog. The results show further that the model is reasonably effective. We conclude that finite memory is an effective dynamics element to describe the heavy-tailed human activity pattern.

  20. Deep Human Parsing with Active Template Regression.

    Science.gov (United States)

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

    2015-12-01

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

  1. Human Factors for Flight Deck Certification Personnel

    Science.gov (United States)

    1993-07-01

    This document is a compilation of proceedings and lecture material on human : performance capabilities that was presented to FAA flight deck certification : personnel. A five-day series of lectures was developed to provide certification : specialists...

  2. Structure of active dimeric human telomerase.

    Science.gov (United States)

    Sauerwald, Anselm; Sandin, Sara; Cristofari, Gaël; Scheres, Sjors H W; Lingner, Joachim; Rhodes, Daniela

    2013-04-01

    Telomerase contains a large RNA subunit, TER, and a protein catalytic subunit, TERT. Whether telomerase functions as a monomer or dimer has been a matter of debate. Here we report biochemical and labeling data that show that in vivo-assembled human telomerase contains two TERT subunits and binds two telomeric DNA substrates. Notably, catalytic activity requires both TERT active sites to be functional, which demonstrates that human telomerase functions as a dimer. We also present the three-dimensional structure of the active full-length human telomerase dimer, determined by single-particle EM in negative stain. Telomerase has a bilobal architecture with the two monomers linked by a flexible interface. The monomer reconstruction at 23-Å resolution and fitting of the atomic structure of the TERT subunit from beetle Tribolium castaneum into the EM density reveals the spatial relationship between RNA and protein subunits, providing insights into telomerase architecture.

  3. Human epidermal growth factor receptor (HER 2)/neu expression ...

    African Journals Online (AJOL)

    use

    2011-11-23

    Nov 23, 2011 ... 3Department of Pathology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, China. 4Department of ... To investigate the relationship between the expression/amplification of human epidermal growth factor receptor ... epidermal growth factor receptor family; HER 2, human epidermal ...

  4. WHO DOES WHAT IN HUMAN FACTORS/ERGONOMICS IN MALAYSIA?

    Science.gov (United States)

    Ahasan, Rabiul

    2014-12-01

    Individuals' expertise in human factors and ergonomics in Malaysia was studied with a view to aiding in gauging the confusion and conjectures of the expertise in this area. The choices and preferences of individuals in dealing with the current issues of human factors and ergonomics were examined. The authors suggest the ways to meet ethical challenges in their work and professions.

  5. Human Factors in Training - Space Medicine Proficiency Training

    Science.gov (United States)

    Connell, Erin; Arsintescu, Lucia

    2009-01-01

    The early Constellation space missions are expected to have medical capabilities very similar to those currently on the Space Shuttle and International Space Station (ISS). For Crew Exploration Vehicle (CEV) missions to ISS, medical equipment will be located on ISS, and carried into CEV in the event of an emergency. Flight Surgeons (FS) on the ground in Mission Control will be expected to direct the Crew Medical Officer (CMO) during medical situations. If there is a loss of signal and the crew is unable to communicate with the ground, a CMO would be expected to carry out medical procedures without the aid of a FS. In these situations, performance support tools can be used to reduce errors and time to perform emergency medical tasks. Work on medical training has been conducted in collaboration with the Medical Training Group at the Space Life Sciences Directorate and with Wyle Lab which provides medical training to crew members, Biomedical Engineers (BMEs), and to flight surgeons under the JSC Space Life Sciences Directorate s Bioastronautics contract. The space medical training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at Johnson Space Center have recently investigated medical performance support tools for CMOs on-orbit, and FSs on the ground, and researchers at the Ames Research Center performed a literature review on medical errors. The work proposed for FY10 continues to build on this strong collaboration with the Space Medical Training Group and previous research. This abstract focuses on two areas of work involving Performance Support Tools for Space Medical Operations. One area of research building on activities from FY08, involved the feasibility of just-in-time (JIT) training techniques and concepts for real-time medical procedures. In Phase 1

  6. Human factors in preventing complications in anaesthesia: a systematic review.

    Science.gov (United States)

    Jones, C P L; Fawker-Corbett, J; Groom, P; Morton, B; Lister, C; Mercer, S J

    2018-01-01

    Human factors in anaesthesia were first highlighted by the publication of the Anaesthetists Non-Technical Skills Framework, and since then an awareness of their importance has gradually resulted in changes in routine clinical practice. This review examines recent literature around human factors in anaesthesia, and highlights recent national reports and guidelines with a focus on team working, communication, situation awareness and human error. We highlight the importance of human factors in modern anaesthetic practice, using the example of complex trauma. © 2018 The Association of Anaesthetists of Great Britain and Ireland.

  7. Hemoglobin is a co-factor of human trypanosome lytic factor

    DEFF Research Database (Denmark)

    Widener, Justin; Nielsen, Marianne Jensby; Shiflett, April

    2007-01-01

    Trypanosome lytic factor (TLF) is a high-density lipoprotein (HDL) subclass providing innate protection to humans against infection by the protozoan parasite Trypanosoma brucei brucei. Two primate-specific plasma proteins, haptoglobin-related protein (Hpr) and apolipoprotein L-1 (ApoL-1), have been....... HDL particles recovered by immunoaffinity absorption, with either anti-Hpr or anti-ApoL-1, were identical in protein composition and specific activity for T. b. brucei killing. Here, we show that TLF-bound Hpr strongly binds Hb and that addition of Hb stimulates TLF killing of T. b. brucei...... that triggers the activation of TLF by the formation of Hpr-Hb complexes, leading to enhanced binding, trypanolytic activity, and clearance of parasites....

  8. Human Reliability Analysis for Design: Using Reliability Methods for Human Factors Issues

    Energy Technology Data Exchange (ETDEWEB)

    Ronald Laurids Boring

    2010-11-01

    This paper reviews the application of human reliability analysis methods to human factors design issues. An application framework is sketched in which aspects of modeling typically found in human reliability analysis are used in a complementary fashion to the existing human factors phases of design and testing. The paper provides best achievable practices for design, testing, and modeling. Such best achievable practices may be used to evaluate and human system interface in the context of design safety certifications.

  9. Carbohydrates and Activity of Natural and Recombinant Tissue Factor*

    Science.gov (United States)

    Krudysz-Amblo, Jolanta; Jennings, Mark E.; Mann, Kenneth G.; Butenas, Saulius

    2010-01-01

    The effect of glycosylation on tissue factor (TF) activity was evaluated, and site-specific glycosylation of full-length recombinant TF (rTF) and that of natural TF from human placenta (pTF) were studied by liquid chromatography-tandem mass spectrometry. The amidolytic activity of the TF·factor VIIa (FVIIa) complex toward a fluorogenic substrate showed that the catalytic efficiency (Vmax) of the complex increased in the order rTF1–243 (Escherichia coli) carbohydrates significantly influence the activity of TF proteins. Carbohydrate analysis revealed glycosylation on asparagines 11, 124, and 137 in both rTF1–263 and pTF. The carbohydrates of rTF1–263 contain high mannose, hybrid, and fucosylated glycans. Natural pTF contains no high mannose glycans but is modified with hybrid, highly fucosylated, and sialylated sugars. PMID:19955571

  10. Information Technology: A challenge to the Human Factors Society?

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1988-01-01

    In his presidential address at the annual meeting of the Human Factors Society, Julian Christensen urged the members of the society to spread the gospel and to persuade the members of other professional societies such as psychologists,sociologists and engineers to join the Human Factors Society......, the argument being that advanced technology requires a cross-disciplinary approach to human factors problems. In the present note, I would like to support this presidential effort. In fact, I will go further in that direction and argue that the present fast pace of information technology threatens to overrun...... the methodological capability of the human factors profession. In the following sections, I will briefly review this development, as I see it, and outline the approach to human factors problems needed in advanced technological systems....

  11. Human Factors and Computer Interfaces--Implications for Artificial Intelligence.

    Science.gov (United States)

    Norris, Cathleen A.

    1987-01-01

    This second in a series of articles on artificial intelligence emphasizes human factors. The design of video display units and keyboards is discussed, the organizational structure of human memory is described, humans are examined as information processors using inductive and deductive reasoning, and educational implications are explored. (LRW)

  12. Human factors process failure modes and effects analysis (HF PFMEA) software tool

    Science.gov (United States)

    Chandler, Faith T. (Inventor); Valentino, William D. (Inventor); Philippart, Monica F. (Inventor); Relvini, Kristine M. (Inventor); Bessette, Colette I. (Inventor); Shedd, Nathaneal P. (Inventor)

    2011-01-01

    Methods, computer-readable media, and systems for automatically performing Human Factors Process Failure Modes and Effects Analysis for a process are provided. At least one task involved in a process is identified, where the task includes at least one human activity. The human activity is described using at least one verb. A human error potentially resulting from the human activity is automatically identified, the human error is related to the verb used in describing the task. A likelihood of occurrence, detection, and correction of the human error is identified. The severity of the effect of the human error is identified. The likelihood of occurrence, and the severity of the risk of potential harm is identified. The risk of potential harm is compared with a risk threshold to identify the appropriateness of corrective measures.

  13. Mutational analysis of leucine 47 in human epidermal growth factor.

    Science.gov (United States)

    Matsunami, R K; Yette, M L; Stevens, A; Niyogi, S K

    1991-07-01

    Seven site-specific mutants (including changes to other hydrophobic, charged, and heterocyclic amino acids) of leucine 47 of human epidermal growth factor (EGF) were generated by protein engineering and characterized for their activity in three assays: radioreceptor competition binding in membrane fractions, the stimulation of the EGF receptor's tyrosine kinase activity, and the stimulation of thymidine uptake in tissue culture cells. K1/2 (concentration required for half maximum response) values for each of the mutants are reported in the three assays. The results show that the native leucine residue is quite important for EGF activity. Substitutions are tolerated to different degrees, depending upon hydrophobicity and size of the side chain. Substitution with ionic residues led to the most drastic reduction in activity. One-dimensional nuclear magnetic resonance spectroscopy, at physiological pH, of several of the mutants did not detect any major structural perturbations which would account for the loss of activity. The results suggest that the side chain of leucine 47, because of its charge neutrality, size, and hydrophobicity, is highly important, although not absolutely essential for the interaction of EGF with its receptor. A striking finding was the lower (compared with wild type) Vmax values of the mutants in the tyrosine kinase reaction, but these low Vmax mutants, in cell culture experiments, were able to stimulate at high concentrations a growth response equivalent to wild type EGF.

  14. Human factors aspects of advanced instrumentation in the nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Carter, R.J.

    1989-01-01

    An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs.

  15. Human Milk Composition: Nutrients and Bioactive Factors

    Science.gov (United States)

    Ballard, Olivia; Morrow, Ardythe L.

    2013-01-01

    Synopsis The composition of human milk is the biologic norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules, e.g., lactoferrin, are being investigated as novel therapeutic agents. A dynamic, bioactive fluid, human milk changes in composition from colostrum to late lactation, and varies within feeds, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Pasteurized donor milk is now commonly provided to high risk infants and most mothers in the U.S. express and freeze their milk at some point in lactation for future infant feedings. Many milk proteins are degraded by heat treatment and freeze-thaw cycles may not have the same bioactivity after undergoing these treatments. This article provides an overview of the composition of human milk, sources of its variation, and its clinical relevance. PMID:23178060

  16. Mechanisms of Hepatocyte Growth Factor Activation in Cancer Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Kawaguchi, Makiko; Kataoka, Hiroaki, E-mail: mejina@med.miyazaki-u.ac.jp [Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692 (Japan)

    2014-09-29

    Hepatocyte growth factor/scatter factor (HGF/SF) plays critical roles in cancer progression through its specific receptor, MET. HGF/SF is usually synthesized and secreted as an inactive proform (pro-HGF/SF) by stromal cells, such as fibroblasts. Several serine proteases are reported to convert pro-HGF/SF to mature HGF/SF and among these, HGF activator (HGFA) and matriptase are the most potent activators. Increased activities of both proteases have been observed in various cancers. HGFA is synthesized mainly by the liver and secreted as an inactive pro-form. In cancer tissues, pro-HGFA is likely activated by thrombin and/or human kallikrein 1-related peptidase (KLK)-4 and KLK-5. Matriptase is a type II transmembrane serine protease that is expressed by most epithelial cells and is also synthesized as an inactive zymogen. Matriptase activation is likely to be mediated by autoactivation or by other trypsin-like proteases. Recent studies revealed that matriptase autoactivation is promoted by an acidic environment. Given the mildly acidic extracellular environment of solid tumors, matriptase activation may, thus, be accelerated in the tumor microenvironment. HGFA and matriptase activities are regulated by HGFA inhibitor (HAI)-1 (HAI-1) and/or HAI-2 in the pericellular microenvironment. HAIs may have an important role in cancer cell biology by regulating HGF/SF-activating proteases.

  17. Flavopiridol suppresses tumor necrosis factor-induced activation of activator protein-1, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase (MAPK), p44/p42 MAPK, and Akt, inhibits expression of antiapoptotic gene products, and enhances apoptosis through cytochrome c release and caspase activation in human myeloid cells.

    Science.gov (United States)

    Takada, Yasunari; Sethi, Gautam; Sung, Bokyung; Aggarwal, Bharat B

    2008-05-01

    Although flavopiridol, a semisynthetic flavone, was initially thought to be a specific inhibitor of cyclin-dependent kinases, it has now been shown that flavopiridol mediates antitumor responses through mechanism(s) yet to be defined. We have shown previously that flavopiridol abrogates tumor necrosis factor (TNF)-induced nuclear factor-kappaB (NF-kappaB) activation. In this report, we examined whether this flavone affects other cellular responses activated by TNF. TNF is a potent inducer of activator protein-1 (AP-1), and flavopiridol abrogated this activation in a dose- and time-dependent manner. Flavopiridol also suppressed AP-1 activation induced by various carcinogens and inflammatory stimuli. When examined for its effect on other signaling pathways, flavopiridol inhibited TNF-induced activation of various mitogen-activated protein kinases, including c-Jun NH(2)-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and p44/p42 MAPK. It is noteworthy that this flavone also suppressed TNF-induced activation of Akt, a cell survival kinase, and expression of various antiapoptotic proteins, such as IAP-1, IAP-2, XIAP, Bcl-2, Bcl-xL, and TRAF-1. Flavopiridol also inhibited the TNF-induced induction of intercellular adhesion molecule-1, c-Myc, and c-Fos, all known to mediate tumorigenesis. Moreover, TNF-induced apoptosis was enhanced by flavopiridol through activation of the bid-cytochrome-caspase-9-caspase-3 pathway. Overall, our results clearly suggest that flavopiridol interferes with the TNF cell-signaling pathway, leading to suppression of antiapoptotic mechanisms and enhancement of apoptosis.

  18. Scaling behavior of online human activity

    Science.gov (United States)

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

    2012-11-01

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

  19. Causes of death and factors associated with early death among human immunodeficiency virus (HIV)-infected persons in Singapore: pre-highly active antiretroviral therapy (HAART) and Peri-HAART.

    Science.gov (United States)

    Chow, Angela; Tey, Jeannie; Win, Mar Kyaw; Leo, Yee Sin

    2012-12-01

    Highly active antiretroviral therapy (HAART) has greatly changed the epidemiology of human immunodefi ciency virus (HIV) mortality. The aim of this study is to compare the causes of death and factors associated with early death in HIV-infected persons in the pre- and peri-highly active antiretroviral therapy (HAART) periods. We conducted a retrospective review of 483 HIV-infected persons who were diagnosed with HIV from 1985 to 2000, and had died within 5 years of the diagnosis. We examined the temporal change in the primary causes of death between those who were diagnosed in the pre-HAART (1985 to 1995) and peri-HAART (1996 to 2000) periods, and compared the demographic and clinical characteristics of the 2 groups. During the peri-HAART period, HIV encephalopathy, cryptococcal meningitis, and lymphoma were no longer the leading causes of death. Opportunistic infections remained important causes of death. Early deaths from the peri-HAART period were older (60 years and above) at diagnosis (Adj OR 7.50; 95% CI, 1.78 to 31.58), more likely to be divorced (Adj OR 5.05, 95% CI, 1.96 to 13.02) and tended to have a low baseline CD4 cell count of deaths from the pre-HAART period. In the peri-HAART era, HIV-infected persons who died within 5 years of diagnosis were those who were older (≥60 years), divorced, or who presented with very late-stage disease (CD4 HIV testing and treatment should be developed for these subpopulations.

  20. LINE-1 Retrotransposition Activity in Human Genomes

    Science.gov (United States)

    Beck, Christine R.; Collier, Pamela; Macfarlane, Catriona; Malig, Maika; Kidd, Jeffrey M.; Eichler, Evan E.; Badge, Richard M.; Moran, John V.

    2010-01-01

    Summary Long Interspersed Element-1 (LINE-1 or L1) sequences comprise the bulk of retrotransposition activity in the human genome; however, the abundance of highly active or ‘hot’ L1s in the human population remains largely unexplored. Here, we used a fosmid-based, paired-end DNA sequencing strategy to identify 68 full-length L1s which are differentially present among individuals but are absent from the human genome reference sequence. The majority of these L1s were highly active in a cultured cell retrotransposition assay. Genotyping 26 elements revealed that two L1s are only found in Africa and that two more are absent from the H952 subset of the Human Genome Diversity Panel. Therefore, these results suggest that ‘hot’ L1s are more abundant in the human population than previously appreciated, and that ongoing L1 retrotransposition continues to be a major source of inter-individual genetic variation. PMID:20602998

  1. The Human Factors of Sensor Fusion

    Science.gov (United States)

    2008-05-01

    be a tank, so humans typically would not deductively identify a moving object as a tank versus a cow versus a cloud versus a tuning fork, but they...figure 8 and is called the Mackworth (1948) vigilance curve. This curve involved the results of detecting changes in the ticking of a clock over

  2. Circulating factors induce coronary endothelial ceIl activation foIlowing exposure to inhaled diesel exhaust and nitrogen dioxide in humans :Evidence from a novel translational in vitro model

    Science.gov (United States)

    The vascular toxicity of inhaled agents may be caused by soluble factors that are released into the systemic circulation. To confirm this in a straightforward manner, we obtained plasma from healthy human volunteers before and after exposure to diesel exhaust (DE) and nitrogen di...

  3. River channel sensitivity to change in the context of human activities and natural factors: an 80-year record of channel morphodynamics on the lower Santa Clara River, Ventura County, California

    Science.gov (United States)

    Downs, P. W.; Dusterhoff, S. R.; Sears, W. A.

    2010-12-01

    River channel adjustments arise from the application of numerous catchment-based stressors operating at different space and time scales. Natural stressors include the impact of climatic phenomena and their inheritance; human stressors include both direct and indirect factors whose impacts have grown in magnitude and intensity during the Anthropocene, especially since about 1945. Consequently, the sensitivity of river channel morphodynamics is likely to have changed also, with implications for landform understanding and river management. Reconstructing channel morphodynamics during the Anthropocene requires interpreting multiple historical and secondary data sources to document changes at sufficient (i.e., reach-scale) resolution: for the 60-km lower Santa Clara River (LSCR), Ventura County, California, we used flow, sediment and precipitation records, repeat aerial photographs, LiDAR data, repeat topographic surveys, in-channel vegetation data, field observations, numerical modeling of high flow events, and narrative accounts. The catchment historical context since European-American settlement includes periods dominated by ranching and colonization (ca.1820-1890), irrigations and diversions (ca.1890-1955), dams and river modifications (1955-1990), and urban population growth (1990-present). Natural stressors were investigated based on the correlation of instantaneous flood peaks with annual rainfall records in this semi-arid setting. Successful prediction of the majority of gauged floods since about 1950 allows a flood sequence to be reconstructed back to 1873. Floods are clustered and of considerably greater magnitude in El Nino years of the El Nino-Southern Oscillation. The great majority of sediment transport thus occurs in El Nino years so that the dominant discharge is the largest discharge on record, in contrast to humid-region alluvial rivers. Responding to these stressors, the average width of the active channel bed has become narrower by almost 50% (1938

  4. MEASURING CHOLINESTERASE ACTIVITY IN HUMAN SALIVA.

    Science.gov (United States)

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

  5. Human Relations. Discussion Topics and Activities.

    Science.gov (United States)

    Lee, Marilyn; And Others

    Designed primarily for students in the intermediate grades, this document provides discussion topics, poetry, and activities to help students: (1) recognize the uniqueness of themselves and others; (2) become aware of their uniqueness as members of the human family; (3) become aware of individual differences, emotions, and feelings; (4) recognize…

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

    African Journals Online (AJOL)

    Purpose: To develop processes for effective isolation and purification of recombinant human plasminogen activator (rhPA) from transgenic rabbit milk. Methods: Immunoaffinity chromatography was selected and improved by a special polyol-responsive monoclonal antibody (PR-mAb). Alteplase was used as immunogen ...

  7. Brain activation during human male ejaculation revisited

    NARCIS (Netherlands)

    Georgiadis, Janniko R.; Reinders, A. A. T. Simone; Van der Graaf, Ferdinand H. C. E.; Paans, Anne M. J.; Kortekaas, Rudie

    2007-01-01

    In a prior [O-15]-H2O positron emission tomographic study we reported brain regions involved in human male ejaculation. Here, we used another, more recently acquired data set to evaluate the methodological approach of this previous study, and discovered that part of the reported activation pattern

  8. Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors

    Science.gov (United States)

    Harun-Or-Rashid, Mohammad; Konjusha, Dardan; Galindo-Romero, Caridad

    2016-01-01

    Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR) system and extracellular signal-regulated kinase (ERK) signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Müller cells as well as the human Müller cell line MIO-M1. The Müller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Müller cells and the human Müller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173) EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2), EGFR-inhibitor (AG1478), EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001), consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Müller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in which endothelins

  9. Endothelin B Receptors on Primary Chicken Müller Cells and the Human MIO-M1 Müller Cell Line Activate ERK Signaling via Transactivation of Epidermal Growth Factor Receptors.

    Directory of Open Access Journals (Sweden)

    Mohammad Harun-Or-Rashid

    Full Text Available Injury to the eye or retina triggers Müller cells, the major glia cell of the retina, to dedifferentiate and proliferate. In some species they attain retinal progenitor properties and have the capacity to generate new neurons. The epidermal growth factor receptor (EGFR system and extracellular signal-regulated kinase (ERK signaling are key regulators of these processes in Müller cells. The extracellular signals that modulate and control these processes are not fully understood. In this work we studied whether endothelin receptor signaling can activate EGFR and ERK signaling in Müller cells. Endothelin expression is robustly upregulated at retinal injury and endothelin receptors have been shown to transactivate EGFRs in other cell types. We analyzed the endothelin signaling system in chicken retina and cultured primary chicken Müller cells as well as the human Müller cell line MIO-M1. The Müller cells were stimulated with receptor agonists and treated with specific blockers to key enzymes in the signaling pathway or with siRNAs. We focused on endothelin receptor mediated transactivation of EGFRs by using western blot analysis, quantitative reverse transcriptase PCR and immunocytochemistry. The results showed that chicken Müller cells and the human Müller cell line MIO-M1 express endothelin receptor B. Stimulation by the endothelin receptor B agonist IRL1620 triggered phosphorylation of ERK1/2 and autophosphorylation of (Y1173 EGFR. The effects could be blocked by Src-kinase inhibitors (PP1, PP2, EGFR-inhibitor (AG1478, EGFR-siRNA and by inhibitors to extracellular matrix metalloproteinases (GM6001, consistent with a Src-kinase mediated endothelin receptor response that engage ligand-dependent and ligand-independent EGFR activation. Our data suggest a mechanism for how injury-induced endothelins, produced in the retina, may modulate the Müller cell responses by Src-mediated transactivation of EGFRs. The data give support to a view in

  10. Organization of von Willebrand factor on surface-activated platelets.

    Science.gov (United States)

    Escolar, G; White, J G

    1993-12-01

    The distribution and organization of von Willebrand factor (vWF) multimers on platelets after surface activation have not been fully characterized. In the present study, washed human platelets were allowed to interact with Formvar-coated, electron microscope grids for 20 minutes at 37 degrees C and then fixed. After fixation, cells were washed and then incubated with buffer alone, human plasma, human plasma preincubated with ristocetin (1.2 mg/mL), purified human vWF plus ristocetin, or bovine plasma. Macromolecular complexes were revealed by ultrastructural immunocytochemistry employing a polyclonal antibody against vWF and protein A-gold (PAG) as the electron-dense probe. vWF multimers were not present in discoid platelets but appeared on the central zone of dendritic cells and over larger central areas of fully spread platelets. Exposure to human plasma alone did not affect the distribution of electron-dense probes for vWF in central regions of surface-activated cells. Incubation of spread platelets with ristocetin-activated human plasma or bovine plasma resulted in the appearance of randomly dispersed, mottled areas of increased density covering the surface from edge to edge. Exposure to vWF antibody and PAG resulted in specific labeling of the dense areas in a serpentine, linear array. The gold-probe distribution suggested that the vWF multimers were not superimposed and were distributed in a random, irregular manner from edge to edge with label-free, clear areas between them. The results extend previous observations demonstrating that glycoprotein Ib-IX receptors are not spontaneously cleared from the plasma membranes of surface-activated platelets by showing that the receptor function of glycoprotein Ib-IX complex remains unchanged.

  11. Human Resource Managements as a part of the Human Factors Management Program(HFMP) for Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Kim, DaeHo; Lee, YongHee; Lee, JungWoon [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Younggab [Korea Hydro and Nuclear Power Co. LTD, Daejeon (Korea, Republic of)

    2007-10-15

    Programs for the effective implementation and management of human factor issues in nuclear power plants (NPPs) should contain technical criteria, an establishment of a job process, and activities for job improvements and be a system through which human factors can be managed in an integrated way. Human factors to be managed should include those related to an operation of plants as well as those related to a plant design as mentioned in NUREG-0800(2004), NUREG- 0711(2004), and NUREG-0700(2002). Human factor items to be managed for an operation of plants are listed in the PSR (Periodic Safety Review) items defined in the Enforcement of Regulation of the Atomic Energy Act. They are procedures, a work management system including a shift work management, a qualification management of plant personnel, training, a work amount assessment, a MMI (Man Machine Interface), and the use of experience. Among these factors, factors related to a human resource management include work management systems and the status of a work management including shift work, a qualification management ensuring qualified workers on duty at all times, and the systems for and the status of training and education. This paper addresses the scope of a human resource management, guidelines and procedures to be developed for a human resource management, and considerations critical in the development of guidelines and procedures.

  12. Human Factors Standards and implementation plan for waste management programs

    Energy Technology Data Exchange (ETDEWEB)

    Banks, W.W.

    1993-04-01

    The Department of Energy (DOE) is dedicated to assuring safety and public confidence by conducting a thorough assessment and upgrade of its nuclear policies and procedures. To ensure that DOE field operations protect the health and safety of employees, the general public and the environment, new operational procedures, standards, and implementation plans are both required and forthcoming from DOE Headquarters, NE-74. Part of this effort requires the establishment and integration of human factors engineering design standards and implementation methods to reduce the probability of human error, human injury and radiological exposure. Human Factors professionals work to assure that technology is designed and utilized safely and efficiently to serve the needs and capabilities of the people who must use this technology. The primary goal of human factors engineering is to ensure compatibility and congruence between the people, equipment, tasks, procedures and training so as to minimize human error and assure that ``total systems performance and reliability`` are achieved.

  13. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

    Directory of Open Access Journals (Sweden)

    Meng-Hwan Lee

    2014-01-01

    Full Text Available Production of biopharmaceuticals from transgenic animal milk is a cost-effective method for highly complex proteins that cannot be efficiently produced using conventional systems such as microorganisms or animal cells. Yields of recombinant human factor IX (rhFIX produced from transgenic porcine milk under the control of the bovine α-lactalbumin promoter reached 0.25 mg/mL. The rhFIX protein was purified from transgenic porcine milk using a three-column purification scheme after a precipitation step to remove casein. The purified protein had high specific activity and a low ratio of the active form (FIXa. The purified rhFIX had 11.9 γ-carboxyglutamic acid (Gla residues/mol protein, which approached full occupancy of the 12 potential sites in the Gla domain. The rhFIX was shown to have a higher isoelectric point and lower sialic acid content than plasma-derived FIX (pdFIX. The rhFIX had the same N-glycosylation sites and phosphorylation sites as pdFIX, but had a higher specific activity. These results suggest that rhFIX produced from porcine milk is physiologically active and they support the use of transgenic animals as bioreactors for industrial scale production in milk.

  14. Food choice and intake: the human factor.

    Science.gov (United States)

    Mela, D J

    1999-08-01

    Human perceptions and selection of food are derived from the prevailing and momentary food, agro-economic and cultural environment, cognitive and biological characteristics of individuals, and the real and perceived intrinsic and extrinsic attributes of foods themselves. The range of items typically chosen and consumed within a given population is largely determined by interaction of the external environmental context with guiding sets of implicit and explicit social and psychobiological 'rules'. Within the rather broad limits of biology, individual food choices and intake behaviours relate to and reflect aspects of food availability, existing habitual behaviours, learning mechanisms, and individual beliefs and expectations. Many of the relevant features of these variables are uniquely human, together determining what is 'food', when, how, by and with whom it is chosen and eaten, and in what quantities. They also provide the opportunities for individuals to establish and maintain a relatively stable set of culturally and biologically determined affective responses ('likes') and intake behaviours. Understanding of the potential contribution of these influences under different conditions can serve to explain many of the observed characteristics of human eating, and highlight potential avenues for intervention.

  15. Usability: Human Research Program - Space Human Factors and Habitability

    Science.gov (United States)

    Sandor, Aniko; Holden, Kritina L.

    2009-01-01

    The Usability project addresses the need for research in the area of metrics and methodologies used in hardware and software usability testing in order to define quantifiable and verifiable usability requirements. A usability test is a human-in-the-loop evaluation where a participant works through a realistic set of representative tasks using the hardware/software under investigation. The purpose of this research is to define metrics and methodologies for measuring and verifying usability in the aerospace domain in accordance with FY09 focus on errors, consistency, and mobility/maneuverability. Usability metrics must be predictive of success with the interfaces, must be easy to obtain and/or calculate, and must meet the intent of current Human Systems Integration Requirements (HSIR). Methodologies must work within the constraints of the aerospace domain, be cost and time efficient, and be able to be applied without extensive specialized training.

  16. Human Factors in Aviation Maintenance. Phase 1

    Science.gov (United States)

    1991-11-01

    are attributed to pilot error, Wciger factors can affect hardware design and manufacture; the and Rosman (1989) have data which indicates that about...I-P. aircrafrt SPONSOR USAF DEVELOPER Rockwell International Corporation, Los Angeles, California. LIFE 1981 DESCRIPTION The b,-B Central Integrated

  17. Extraction of human factors issues caused by application of the advanced HSI technology and development of human factor issue management system

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Sang Moon; Lee, Jung Woon; Park, Jae Chang; Oh, In Seok [Korea Atomic Energy Research Institute, Taejon (Korea)

    1999-01-01

    A comprehensive literature survey was performed in this study to collect human performance issues related to the advanced HSI design features. The literature from not only nuclear industry but also other industries was collected and reviewed. The issues were categorized into the following advanced HSI design features: devices characteristics, levels of automation, information design and management, display management, computerized controls, alarm systems, computerized procedures, staffing and crew coordination, and operator support systems. The classified issues were described with the description framework. Then, the relationship of issues to HSI design process such as human factors analyses, human factors design, and human factors verification and validation was investigated. Finally, the issue management system of server-client environment was developed using Microsoft's Active Server Page technology and Access 97. (author). 18 refs., 6 figs.

  18. Human Factors in Training: Space Medical Proficiency Training

    Science.gov (United States)

    Byrne, Vicky E.; Barshi, I.; Arsintescu, L.; Connell, E.

    2010-01-01

    The early Constellation space missions are expected to have medical capabilities very similar to those currently on the Space Shuttle and the International Space Station (ISS). For Crew Exploration Vehicle (CEV) missions to the ISS, medical equipment will be located on the ISS, and carried into CEV in the event of an emergency. Flight surgeons (FS) on the ground in Mission Control will be expected to direct the crew medical officer (CMO) during medical situations. If there is a loss of signal and the crew is unable to communicate with the ground, a CMO would be expected to carry out medical procedures without the aid of a FS. In these situations, performance support tools can be used to reduce errors and time to perform emergency medical tasks. The space medical training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). This is a joint project consisting of human factors team from the Ames Research Center (ARC) with Immanuel Barshi as Principal Investigator and the Johnson Space Center (JSC). Human factors researchers at JSC have recently investigated medical performance support tools for CMOs on-orbit, and FSs on the ground, and researchers at the Ames Research Center performed a literature review on medical errors. Work on medical training has been conducted in collaboration with the Medical Training Group at the Johnson Space Center (JSC) and with Wyle Laboratories that provides medical training to crew members, biomedical engineers (BMEs), and to flight surgeons under the Bioastronautics contract. One area of research building on activities from FY08, involved the feasibility of just-in-time (JIT) training techniques and concepts for real-time medical procedures. A second area of research involves FS performance support tools. Information needed by the FS during the ISS mission

  19. Antiglucocorticoid activity of hepatocyte nuclear factor-6.

    Science.gov (United States)

    Pierreux, C E; Stafford, J; Demonte, D; Scott, D K; Vandenhaute, J; O'Brien, R M; Granner, D K; Rousseau, G G; Lemaigre, F P

    1999-08-03

    Glucocorticoids exert their effects on gene transcription through ubiquitous receptors that bind to regulatory sequences present in many genes. These glucocorticoid receptors are present in all cell types, yet glucocorticoid action is controlled in a tissue-specific way. One mechanism for this control relies on tissue-specific transcriptional activators that bind in the vicinity of the glucocorticoid receptor and are required for receptor action. We now describe a gene-specific and tissue-specific inhibitory mechanism through which glucocorticoid action is repressed by a tissue-restricted transcription factor, hepatocyte nuclear factor-6 (HNF-6). HNF-6 inhibits the glucocorticoid-induced stimulation of two genes coding for enzymes of liver glucose metabolism, namely 6-phosphofructo-2-kinase and phosphoenolpyruvate carboxykinase. Binding of HNF-6 to DNA is required for inhibition of glucocorticoid receptor activity. In vitro and in vivo experiments suggest that this inhibition is mediated by a direct HNF-6/glucocorticoid receptor interaction involving the amino-terminal domain of HNF-6 and the DNA-binding domain of the receptor. Thus, in addition to its known property of stimulating transcription of liver-expressed genes, HNF-6 can antagonize glucocorticoid-stimulated gene transcription.

  20. Splenic embolization in a Jehovah's Witness: role of recombinant human factor VIIa.

    Science.gov (United States)

    Mindikoglu, Ayse L; Anantharaju, Abhinandana; George, Magdalene; Leone, Nancy; Bejna, Judy; Van Thiel, David H

    2003-01-01

    A case of a 50-year-old Jehovah's Witness with cryptogenic cirrhosis, severe portal hypertension and a coagulopathy, who underwent splenic embolization to improve the platelet count after receiving recombinant human Factor VIIa, is reported. Following the infusion of recombinant human Factor VIIa, the coagulopathy was rapidly corrected and it became possible to safely embolize her spleen. The changes in prothrombin time, international normalized ratio and activated partial thromboplastin time as well as thrombomodulin, tissue factor and plasminogen activator inhibitor after the infusion are presented. As a result of the splenic embolization, her platelet count normalized and she has been listed for liver transplantation.

  1. Human Factors for Flight Deck Certification Personnel

    Science.gov (United States)

    1993-07-01

    of synchrony with each other because of the different shift rates. Thus there is kind of a "double whammy" to readaptation . Different things are lost...any over-the- shoulder evaluations, such as sitting behind the pilot and observing a specific pilot activity or sitting behind a controller team and

  2. Human Factors Considerations of Undergrounds in Insurgencies

    Science.gov (United States)

    1966-09-01

    Arthur J . Halligan of the U.S. Army Intelligence School, Fort Holabird, Maryland, provided valuable sug- gestions based upon his experience in...agencies have diplomatic immunity and, if arrested for espionage activities, are not jailed but de- clared persona non grata and forced to leave the

  3. Human factors in resuscitation: Lessons learned from simulator studies

    Directory of Open Access Journals (Sweden)

    Hunziker S

    2010-01-01

    Full Text Available Medical algorithms, technical skills, and repeated training are the classical cornerstones for successful cardiopulmonary resuscitation (CPR. Increasing evidence suggests that human factors, including team interaction, communication, and leadership, also influence the performance of CPR. Guidelines, however, do not yet include these human factors, partly because of the difficulties of their measurement in real-life cardiac arrest. Recently, clinical studies of cardiac arrest scenarios with high-fidelity video-assisted simulations have provided opportunities to better delineate the influence of human factors on resuscitation team performance. This review focuses on evidence from simulator studies that focus on human factors and their influence on the performance of resuscitation teams. Similar to studies in real patients, simulated cardiac arrest scenarios revealed many unnecessary interruptions of CPR as well as significant delays in defibrillation. These studies also showed that human factors play a major role in these shortcomings and that the medical performance depends on the quality of leadership and team-structuring. Moreover, simulated video-taped medical emergencies revealed that a substantial part of information transfer during communication is erroneous. Understanding the impact of human factors on the performance of a complex medical intervention like resuscitation requires detailed, second-by-second, analysis of factors involving the patient, resuscitative equipment such as the defibrillator, and all team members. Thus, high-fidelity simulator studies provide an important research method in this challenging field.

  4. Factors governing risk of cougar attacks on humans

    Science.gov (United States)

    Mattson, David; Logan, Kenneth; Sweanor, Linda

    2011-01-01

    Since the 1980s wildlife managers in the United States and Canada have expressed increasing concern about the physical threat posed by cougars (Puma concolor) to humans. We developed a conceptual framework and analyzed 386 human–cougar encounters (29 fatal attacks, 171 instances of nonfatal contact, and 186 close-threatening encounters) to provide information relevant to public safety. We conceived of human injury and death as the outcome of 4 transitions affected by different suites of factors: (1) a human encountering a cougar: (2) given an encounter, odds that the cougar would be aggressive; (3) given aggression, odds that the cougar would attack; and (4) given an attack, odds that the human would die. We developed multivariable logistic regression models to explain variation in odds at transitions three and four using variables pertaining to characteristics of involved people and cougars. Young (≤ 2.5 years) or unhealthy (by weight, condition, or disease) cougars were more likely than any others to be involved in close (typically adults were more likely than juveniles to kill the victim (32% versus 9% fatality, respectively). During close encounters, victims who used a weapon killed the involved cougar in 82% of cases. Other mitigating behaviors (e.g., yelling, backing away, throwing objects, increasing stature) also substantially lessened odds of attack. People who were moving quickly or erratically when an encounter happened (running, playing, skiing, snowshoeing, biking, ATV-riding) were more likely to be attacked and killed compared to people who were less active (25% versus 8% fatality). Children (≤ 10 years) were more likely than single adults to be attacked, but intervention by people of any age reduced odds of a child’s death by 4.6×. Overall, cougar attacks on people in Canada and the United States were rare (currently 4 to 6/year) compared to attacks by large felids and wolves (Canis lupus) in Africa and Asia (hundreds to thousands/year).

  5. A HUMAN FACTORS ENGINEERING PROCESS TO SUPPORT HUMAN-SYSTEM INTERFACE DESIGN IN CONTROL ROOM MODERNIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Kovesdi, C.; Joe, J.; Boring, R.

    2017-05-01

    The primary objective of the United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program is to sustain operation of the existing commercial nuclear power plants (NPPs) through a multi-pathway approach in conducting research and development (R&D). The Advanced Instrumentation, Information, and Control (II&C) System Technologies pathway conducts targeted R&D to address aging and reliability concerns with legacy instrumentation and control (I&C) and other information systems in existing U.S. NPPs. Control room modernization is an important part following this pathway, and human factors experts at Idaho National Laboratory (INL) have been involved in conducting R&D to support migration of new digital main control room (MCR) technologies from legacy analog and legacy digital I&C. This paper describes a human factors engineering (HFE) process that supports human-system interface (HSI) design in MCR modernization activities, particularly with migration of old digital to new digital I&C. The process described in this work is an expansion from the LWRS Report INL/EXT-16-38576, and is a requirements-driven approach that aligns with NUREG-0711 requirements. The work described builds upon the existing literature by adding more detail around key tasks and decisions to make when transitioning from HSI Design into Verification and Validation (V&V). The overall objective of this process is to inform HSI design and elicit specific, measurable, and achievable human factors criteria for new digital technologies. Upon following this process, utilities should have greater confidence with transitioning from HSI design into V&V.

  6. Human factors dimensions in the evolution of increasingly automated control rooms for near-earth satellites

    Science.gov (United States)

    Mitchell, C. M.

    1982-01-01

    The NASA-Goddard Space Flight Center is responsible for the control and ground support for all of NASA's unmanned near-earth satellites. Traditionally, each satellite had its own dedicated mission operations room. In the mid-seventies, an integration of some of these dedicated facilities was begun with the primary objective to reduce costs. In this connection, the Multi-Satellite Operations Control Center (MSOCC) was designed. MSOCC represents currently a labor intensive operation. Recently, Goddard has become increasingly aware of human factors and human-machine interface issues. A summary is provided of some of the attempts to apply human factors considerations in the design of command and control environments. Current and future activities with respect to human factors and systems design are discussed, giving attention to the allocation of tasks between human and computer, and the interface for the human-computer dialogue.

  7. Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment.

    Science.gov (United States)

    Bell, T; Crown, J P; Lang, I; Bhattacharyya, H; Zanotti, G; Randolph, S; Kim, S; Huang, X; Huang Bartlett, C; Finn, R S; Slamon, D

    2016-05-01

    Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities.

  8. Human factors in aviation maintenance, phase two : progress report.

    Science.gov (United States)

    1993-04-01

    In this second phase of research on Human Factors in Aviation Maintenance, the emphasis has evolved from problem definition to development of demonstrations and prototypes. These demonstrations include a computer-based training simulation for trouble...

  9. Human Factors Guidelines for the Evaluation of the Locomotive Cab

    Science.gov (United States)

    1995-09-01

    This document presents human factors guidelines for the evaluation of the locomotive cab. These guidelines are part of : an effort to evaluate working conditions and safety in the locomotive cab. The guidelines will serve as a decision : making tool ...

  10. Human factors issues in aircraft maintenance and inspection.

    Science.gov (United States)

    1989-10-01

    The Federal Aviation Administration sponsored a two-day meeting in October 1988 to address issues of human factors and inspection. Presentations were given by some 13 individuals representing the full spectrum of interests in commercial aviation. Pre...

  11. Factors associated with pentosidine accumulation in the human vitreous

    NARCIS (Netherlands)

    Van Deemter, Marielle; Bank, Ruud A.; Vehof, Jelle; Hooymans, Johanna M. M.; Los, Leonoor I.

    Purpose: To explore factors associated with pentosidine accumulation in the human vitreous. Methods: Vitreous samples were obtained during trans pars plana vitrectomy for macular hole or rhegmatogenous retinal detachment. Patient characteristics included age, gender, and diabetes mellitus. Ocular

  12. Human factors survey of advanced instrumentation and controls

    Energy Technology Data Exchange (ETDEWEB)

    Carter, R.J.

    1989-01-01

    A survey oriented towards identifying the human factors issues in regard to the use of advanced instrumentation and controls (I C) in the nuclear industry was conducted. A number of United States (US) and Canadian nuclear vendors and utilities were participants in the survey. Human factors items, subsumed under the categories of computer-generated displays (CGD), controls, organizational support, training, and related topics, were discussed. The survey found the industry to be concerned about the human factors issues related to the implementation of advanced I C. Fifteen potential human factors problems were identified. They include: the need for an advanced I C guideline equivalent to NUREG-0700; a role change in the control room from operator to supervisor; information overload; adequacy of existing training technology for advanced I C; and operator acceptance and trust. 11 refs., 1 tab.

  13. Human Factors Engineering Aspects of Modifications in Control Room Modernization

    Energy Technology Data Exchange (ETDEWEB)

    Hugo, Jacques [Idaho National Lab. (INL), Idaho Falls, ID (United States); Clefton, Gordon [Idaho National Lab. (INL), Idaho Falls, ID (United States); Joe, Jeffrey [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2017-06-01

    This report describes the basic aspects of control room modernization projects in the U.S. nuclear industry and the need for supplementary guidance on the integration of human factors considerations into the licensing and regulatory aspects of digital upgrades. The report pays specific attention to the integration of principles described in NUREG-0711 (Human Factors Engineering Program Review Model) and how supplementary guidance can help to raise general awareness in the industry regarding the complexities of control room modernization projects created by many interdependent regulations, standards and guidelines. The report also describes how human factors engineering principles and methods provided by various resources and international standards can help in navigating through the process of licensing digital upgrades. In particular, the integration of human factors engineering guidance and requirements into the process of licensing digital upgrades can help reduce uncertainty related to development of technical bases for digital upgrades that will avoid the introduction of new failure modes.

  14. Inhibition of inflammatory factors by parthenolide in human renal ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    inflammatory effects of parthenolide (PTN) in human ... Hence, PTN may be considered a promising drug with potent anti-inflammatory effect in addition to its ..... Anti-inflammatory effects of pigment epithelium-derived factor in diabetic ...

  15. Cognitive human factors for telemedicine systems.

    Science.gov (United States)

    Piazza, Matteo; Giorgino, Toni; Azzini, Ivano; Stefanelli, Mario; Luo, Roger

    2004-01-01

    The recent integration of telephony systems with information and communication technology (ICT) enables the development of innovative tools for telemedicine. The dissemination and widespread acceptance of telephone-based care monitoring systems challenge the researcher to deal with the cognitive factors involved in the patient-physician interaction, and the way they should be to shape up the technological solutions. This paper proposes a model that describes the impact of socio-cognitive factors in the complex process of health care management. The model has been used to design and develop a telephone system for the management of hypertensive patient within the EU funded Homey project. The knowledge existed in a widely accepted guideline for the care of hypertension has been represented and augmented through the proposed cognitive model. The final product is an intelligent system able to manage an adaptive dialogue. It monitors patients' adherence and increases their involvement by promoting self-care through frequent virtual visits, which is complementary to the traditional face-to-face encounters with their primary care physicians.

  16. Expression of sterol regulatory element-binding transcription factor (SREBF 2 and SREBF cleavage-activating protein (SCAP in human atheroma and the association of their allelic variants with sudden cardiac death

    Directory of Open Access Journals (Sweden)

    Kytömäki Leena

    2008-12-01

    Full Text Available Abstract Background Disturbed cellular cholesterol homeostasis may lead to accumulation of cholesterol in human atheroma plaques. Cellular cholesterol homeostasis is controlled by the sterol regulatory element-binding transcription factor 2 (SREBF-2 and the SREBF cleavage-activating protein (SCAP. We investigated whole genome expression in a series of human atherosclerotic samples from different vascular territories and studied whether the non-synonymous coding variants in the interacting domains of two genes, SREBF-2 1784G>C (rs2228314 and SCAP 2386A>G, are related to the progression of coronary atherosclerosis and the risk of pre-hospital sudden cardiac death (SCD. Methods Whole genome expression profiling was completed in twenty vascular samples from carotid, aortic and femoral atherosclerotic plaques and six control samples from internal mammary arteries. Three hundred sudden pre-hospital deaths of middle-aged (33–69 years Caucasian Finnish men were subjected to detailed autopsy in the Helsinki Sudden Death Study. Coronary narrowing and areas of coronary wall covered with fatty streaks or fibrotic, calcified or complicated lesions were measured and related to the SREBF-2 and SCAP genotypes. Results Whole genome expression profiling showed a significant (p = 0.02 down-regulation of SREBF-2 in atherosclerotic carotid plaques (types IV-V, but not in the aorta or femoral arteries (p = NS for both, as compared with the histologically confirmed non-atherosclerotic tissues. In logistic regression analysis, a significant interaction between the SREBF-2 1784G>C and the SCAP 2386A>G genotype was observed on the risk of SCD (p = 0.046. Men with the SREBF-2 C allele and the SCAP G allele had a significantly increased risk of SCD (OR 2.68, 95% CI 1.07–6.71, compared to SCAP AA homologous subjects carrying the SREBF-2 C allele. Furthermore, similar trends for having complicated lesions and for the occurrence of thrombosis were found, although the

  17. Human Factors in Nuclear Power Engineering in Polish Conditions

    OpenAIRE

    Agnieszka Kaczmarek-Kacprzak; Martin Catlow

    2014-01-01

    The paper “Human factors in nuclear power engineering in Polish conditions” focuses on analysis of dynamics of preparing Polish society to build fi rst nuclear power plant in XXI century in Poland. Authors compare experience from constructing nuclear power plant Sizewell B (Great Britain) and Sizewell C, which is in preparation phase with polish nuclear power program. Paper includes aspects e.g. of creating nuclear safety culture and social opinion about investment. Human factors in nuclear p...

  18. Human factors and medication errors: a case study.

    Science.gov (United States)

    Gluyas, Heather; Morrison, Paul

    2014-12-15

    Human beings are error prone. A significant component of human error is flaws inherent in human cognitive processes, which are exacerbated by situations in which the individual making the error is distracted, stressed or overloaded, or does not have sufficient knowledge to undertake an action correctly. The scientific discipline of human factors deals with environmental, organisational and job factors, as well as human and individual characteristics, which influence behaviour at work in a way that potentially gives rise to human error. This article discusses how cognitive processing is related to medication errors. The case of a coronial inquest into the death of a nursing home resident is used to highlight the way people think and process information, and how such thinking and processing may lead to medication errors.

  19. Human Factors in Financial Trading: An Analysis of Trading Incidents.

    Science.gov (United States)

    Leaver, Meghan; Reader, Tom W

    2016-09-01

    This study tests the reliability of a system (FINANS) to collect and analyze incident reports in the financial trading domain and is guided by a human factors taxonomy used to describe error in the trading domain. Research indicates the utility of applying human factors theory to understand error in finance, yet empirical research is lacking. We report on the development of the first system for capturing and analyzing human factors-related issues in operational trading incidents. In the first study, 20 incidents are analyzed by an expert user group against a referent standard to establish the reliability of FINANS. In the second study, 750 incidents are analyzed using distribution, mean, pathway, and associative analysis to describe the data. Kappa scores indicate that categories within FINANS can be reliably used to identify and extract data on human factors-related problems underlying trading incidents. Approximately 1% of trades (n = 750) lead to an incident. Slip/lapse (61%), situation awareness (51%), and teamwork (40%) were found to be the most common problems underlying incidents. For the most serious incidents, problems in situation awareness and teamwork were most common. We show that (a) experts in the trading domain can reliably and accurately code human factors in incidents, (b) 1% of trades incur error, and (c) poor teamwork skills and situation awareness underpin the most critical incidents. This research provides data crucial for ameliorating risk within financial trading organizations, with implications for regulation and policy. © 2016, Human Factors and Ergonomics Society.

  20. Human factors in industrial systems: 40 years on.

    Science.gov (United States)

    Drury, Colin G

    2008-06-01

    I evaluate the contribution of a pioneering Human Factors special issue on human factors in industrial systems. Papers on the content of the journal's first 10 years showed that industrial human factors/ergonomics (HF/E) in 1969 was quite a rarity in the journal and the society. The 12 papers in the special issue are reviewed briefly and show a wide range of topics, including traditional industrial engineering, physical HF/E, and more mainstream applications of HF/E in this domain similar to those in military and aerospace domains. The evaluation is through citations, later journal content, society technical group membership, and specific influences of Harris's own paper in the issue. The expected direct citation influence of this special issue was not found: Citation counts were in line with all papers in Human Factors. However, other journals have been founded in North America that serve industrial HF/E and provide an outlet for more papers per year than Human Factors. In addition, the industrial domain is well represented in the Human Factors and Ergonomics Society. Finally, Harris's paper has been influential in the specific area of HF/E in inspection. Industrial HF/E is now more accepted within the HF/E community, although largely in the physical ergonomics subspecialty. There is now evidence of use of HF/E techniques more broadly in industry, including service as well manufacturing enterprises.

  1. Development of human factors design review guidelines(II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 11 refs., 2 figs., 2 tabs.

  2. Development of human factors design review guidelines(III)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-02-15

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994.

  3. Human Factor Assessment in Support of Joint Operations

    Science.gov (United States)

    2012-05-04

    witnessed such abuse first-hand and observes, “In the U.S. Navy we find that commanders using (aviation) human factors councils as a ‘ witch hunt’ to...Princeton, NJ: Princeton University Press, 1976. Coffman, David W. Operational Art and the Human Dimension of Warfare in the 21 st

  4. Bringing organizational factors to the fore of human error management

    Energy Technology Data Exchange (ETDEWEB)

    Embrey, D. (Human Reliability Associates Ltd., Parbold (United Kingdom))

    1991-10-01

    Human performance problems account for more than half of all significant events at nuclear power plants, even when these did not necessarily lead to severe accidents. In dealing with the management of human error, both technical and organizational factors need to be taken into account. Most important, a long-term commitment from senior management is needed. (author).

  5. Prevalence of malaria and human blood factors among patients in ...

    African Journals Online (AJOL)

    Background: Malaria has been and is still a major protozoan disease affecting the human population. Erythrocyte polymorphisms (mainly in blood groups and genotypes) influence the susceptibility to severe malaria. Aim: This study is aimed at assessing the prevalence malaria in relation to human blood factor and to ...

  6. Traditional Values, Socio-Cultural Factors and Human Resource ...

    African Journals Online (AJOL)

    The paper assesses the effects of traditional values (collective conceptions of what is considered good, desirable and proper or bad, undesirable and improper in a given society) and socio-cultural factors (these are models of life, human rights, value systems, customs, beliefs and arts) on human resource management ...

  7. THE ROLE OF HUMAN FACTOR IN INNOVATION

    Directory of Open Access Journals (Sweden)

    Suzana DEMYEN

    2017-12-01

    Full Text Available Innovation is a concept that has attracted the attention of researchers increasingly intensely over the past ten years. We speak of innovation as a concept found in a great variety of research, both economic and social, or engineering. At present, Romania is one of the modest innovators with an innovation performance below 50% of the EU average. It is therefore an improvement in the overall situation, but a starting point would be to understand the link between innovation and human resource, that is, the role of the latest in the innovation process. We speak of innovation both at the organization level and at the national level, and it is a lasting process that can not be achieved in a short time. It presupposes dedication, resources and knowledge, many of which lead to the need for specialized centers. Research in Romania is mainly conducted in the university environment, but although the number of doctoral graduates is high, a major challenge at the general level remains the underfinancing of this sector.

  8. Role of activity in human dynamics

    Science.gov (United States)

    Zhou, T.; Kiet, H. A. T.; Kim, B. J.; Wang, B.-H.; Holme, P.

    2008-04-01

    The human society is a very complex system; still, there are several non-trivial, general features. One type of them is the presence of power-law-distributed quantities in temporal statistics. In this letter, we focus on the origin of power laws in rating of movies. We present a systematic empirical exploration of the time between two consecutive ratings of movies (the interevent time). At an aggregate level, we find a monotonous relation between the activity of individuals and the power law exponent of the interevent time distribution. At an individual level, we observe a heavy-tailed distribution for each user, as well as a negative correlation between the activity and the width of the distribution. We support these findings by a similar data set from mobile phone text-message communication. Our results demonstrate a significant role of the activity of individuals on the society-level patterns of human behavior. We believe this is a common character in the interest-driven human dynamics, corresponding to (but different from) the universality classes of task-driven dynamics.

  9. Human Factors Throughout the Life Cycle: Lessons Learned from the Shuttle Program. [Human Factors in Ground Processing

    Science.gov (United States)

    Kanki, Barbara G.

    2011-01-01

    With the ending of the Space Shuttle Program, it is critical that we not forget the Human Factors lessons we have learned over the years. At every phase of the life cycle, from manufacturing, processing and integrating vehicle and payload, to launch, flight operations, mission control and landing, hundreds of teams have worked together to achieve mission success in one of the most complex, high-risk socio-technical enterprises ever designed. Just as there was great diversity in the types of operations performed at every stage, there was a myriad of human factors that could further complicate these human systems. A single mishap or close call could point to issues at the individual level (perceptual or workload limitations, training, fatigue, human error susceptibilities), the task level (design of tools, procedures and aspects of the workplace), as well as the organizational level (appropriate resources, safety policies, information access and communication channels). While we have often had to learn through human mistakes and technological failures, we have also begun to understand how to design human systems in which individuals can excel, where tasks and procedures are not only safe but efficient, and how organizations can foster a proactive approach to managing risk and supporting human enterprises. Panelists will talk about their experiences as they relate human factors to a particular phase of the shuttle life cycle. They will conclude with a framework for tying together human factors lessons-learned into system-level risk management strategies.

  10. The productivity from a human perspective: Dimensions and factors

    Directory of Open Access Journals (Sweden)

    Mirza Marvel Cequea

    2011-11-01

    Full Text Available Purpose: The purpose of this paper is to review the literature, for both theoretical foundations and empirical research, in order to establish relationships between the variables related to human factors and their impact on productivity.Design/methodology/approach: The strategy employed corresponds to a descriptive non-experimental design, which is the establishment of three criteria for the literature review, in order to narrow down the topic to research works relating productivity with the human factor. This was investigated in databases and journals dealing with related topics, in addition to consulting doctoral theses and published books concerning the influence of human factors on productivity. About 250 papers which were considered the most relevant for the research were selected.Findings:  As a result of this exploration the classification of the factors in two dimensions that are manifested in people when they act in organizations was highlighted: the psychological and the psychosocial dimension. Human factors included in these dimensions are: individual factors (motivation, skills, job satisfaction, identification, commitment and involvement with the organization, group factors (participation, cohesion and management conflict and organizational factors (organizational culture, organizational climate and leadership. All these factors have an impact on the productivity of the organization and are addressed in this research.Originality/value: The selected variables were used to formulate a model that incorporates the human factors identified and considers the phenomenon in a comprehensive manner. It will be addressed through multivariate analysis, with the possible application of structural equations in order to assess the causal relationships that may exist between factors and productivity.

  11. Local Risk Factors in Genital Human Papilloma Virus Infection in ...

    African Journals Online (AJOL)

    cervical cancer and identified other risk factors. Molecular epidemiologic evidence clearly indicates that certain types of. HPV are the principal cause of invasive cancer and cervical intraepithelial neoplasia.[3]. Local Risk Factors in Genital Human Papilloma Virus. Infection in Cervical Smears. Ojiyi EC, Dike IE, Okeudo C, ...

  12. Effects of recombinant human nerve growth factor on cervical cancer ...

    African Journals Online (AJOL)

    Nerve growth factor (NGF) plays a crucial role in the life of the sympathetic and sensory nervous systems. However, the roles of NGF to cervical cancer remain deeply unknown. This study investigated the effect of recombinant human nerve growth factor (rhNGF) on cervical cancer. It was found that the proliferation of hela ...

  13. Factors Sustaining Human Trafficking In The Contemporary Society ...

    African Journals Online (AJOL)

    Factors sustaining human trafficking in the contemporary society were investigated. One hundred and forty participants were used in generating the items that formed the questionnaire. While four hundred participants were used for the main study, seven leading factors were endorsed by majority of the participants as ...

  14. Enhancing the Human Factors Engineering Role in an Austere Fiscal Environment

    Science.gov (United States)

    Stokes, Jack W.

    2003-01-01

    An austere fiscal environment in the aerospace community creates pressures to reduce program costs, often minimizing or sometimes even deleting the human interface requirements from the design process. With an assumption that the flight crew can recover real time from a poorly human factored space vehicle design, the classical crew interface requirements have been either not included in the design or not properly funded, though carried as requirements. Cost cuts have also affected quality of retained human factors engineering personnel. In response to this concern, planning is ongoing to correct the acting issues. Herein are techniques for ensuring that human interface requirements are integrated into a flight design, from proposal through verification and launch activation. This includes human factors requirements refinement and consolidation across flight programs; keyword phrases in the proposals; closer ties with systems engineering and other classical disciplines; early planning for crew-interface verification; and an Agency integrated human factors verification program, under the One NASA theme. Importance is given to communication within the aerospace human factors discipline, and utilizing the strengths of all government, industry, and academic human factors organizations in an unified research and engineering approach. A list of recommendations and concerns are provided in closing.

  15. Role of activating transcription factor 3 (ATF3) in endoplasmic reticulum (ER) stress-induced sensitization of p53-deficient human colon cancer cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis through up-regulation of death receptor 5 (DR5) by zerumbone and celecoxib.

    Science.gov (United States)

    Edagawa, Makoto; Kawauchi, Junya; Hirata, Manabu; Goshima, Hiroto; Inoue, Makoto; Okamoto, Tatsuro; Murakami, Akira; Maehara, Yoshihiko; Kitajima, Shigetaka

    2014-08-01

    Death receptor 5 (DR5) is a death domain-containing transmembrane receptor that triggers cell death upon binding to its ligand, TNF-related apoptosis-inducing ligand (TRAIL), and a combination of TRAIL and agents that increase the expression of DR5 is expected to be a novel anticancer therapy. In this report, we demonstrate that the stress response gene ATF3 is required for endoplasmic reticulum stress-mediated DR5 induction upon zerumbone (ZER) and celecoxib (CCB) in human p53-deficient colorectal cancer cells. Both agents activated PERK-eIF2α kinases and induced the expression of activating transcription factor 4 (ATF4)-CCAAT enhancer-binding protein (C/EBP) homologous protein, which were remarkably suppressed by reactive oxygen species scavengers. In the absence of ATF3, the induction of DR5 mRNA and protein was abrogated significantly, and this was associated with reduced cell death by cotreatment of TRAIL with ZER or CCB. By contrast, exogenous expression of ATF3 caused a more rapid and elevated expression of DR5, resulting in enhanced sensitivity to apoptotic cell death by TRAIL/ZER or TRAIL/CCB. A reporter assay demonstrated that at least two ATF/cAMP response element motifs as well as C/EBP homologous protein motif at the proximal region of the human DR5 gene promoter were required for ZER-induced DR5 gene transcription. Taken together, our results provide novel insights into the role of ATF3 as an essential transcription factor for p53-independent DR5 induction upon both ZER and CCB treatment, and this may be a useful biomarker for TRAIL-based anticancer therapy. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Study on Performance Shaping Factors (PSFs) Quantification Method in Human Reliability Analysis (HRA)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ar Ryum; Jang, Inseok Jang; Seong, Poong Hyun [Korea Advanced Institute of Science and Technology, Daejon (Korea, Republic of); Park, Jinkyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Kim, Jong Hyun [KEPCO, Ulsan (Korea, Republic of)

    2015-05-15

    The purpose of HRA implementation is 1) to achieve the human factor engineering (HFE) design goal of providing operator interfaces that will minimize personnel errors and 2) to conduct an integrated activity to support probabilistic risk assessment (PRA). For these purposes, various HRA methods have been developed such as technique for human error rate prediction (THERP), simplified plant analysis risk human reliability assessment (SPAR-H), cognitive reliability and error analysis method (CREAM) and so on. In performing HRA, such conditions that influence human performances have been represented via several context factors called performance shaping factors (PSFs). PSFs are aspects of the human's individual characteristics, environment, organization, or task that specifically decrements or improves human performance, thus respectively increasing or decreasing the likelihood of human errors. Most HRA methods evaluate the weightings of PSFs by expert judgment and explicit guidance for evaluating the weighting is not provided. It has been widely known that the performance of the human operator is one of the critical factors to determine the safe operation of NPPs. HRA methods have been developed to identify the possibility and mechanism of human errors. In performing HRA methods, the effect of PSFs which may increase or decrease human error should be investigated. However, the effect of PSFs were estimated by expert judgment so far. Accordingly, in order to estimate the effect of PSFs objectively, the quantitative framework to estimate PSFs by using PSF profiles is introduced in this paper.

  17. 2014 Space Human Factors Engineering Standing Review Panel

    Science.gov (United States)

    Steinberg, Susan

    2014-01-01

    The 2014 Space Human Factors Engineering (SHFE) Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Space Human Factors and Habitability (SHFH) Element, representatives from the Human Research Program (HRP), the National Space Biomedical Research Institute (NSBRI), and NASA Headquarters on November 17, 2014 (list of participants is in Section XI of this report). The SRP reviewed the updated research plans for the Risk of Incompatible Vehicle/Habitat Design (HAB Risk) and the Risk of Performance Errors Due to Training Deficiencies (Train Risk). The SRP also received a status update on the Risk of Inadequate Critical Task Design (Task Risk), the Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI Risk), and the Risk of Inadequate Human-Computer Interaction (HCI Risk).

  18. Human Factors in Nuclear Power Engineering in Polish Conditions

    Directory of Open Access Journals (Sweden)

    Agnieszka Kaczmarek-Kacprzak

    2014-09-01

    Full Text Available The paper “Human factors in nuclear power engineering in Polish conditions” focuses on analysis of dynamics of preparing Polish society to build fi rst nuclear power plant in XXI century in Poland. Authors compare experience from constructing nuclear power plant Sizewell B (Great Britain and Sizewell C, which is in preparation phase with polish nuclear power program. Paper includes aspects e.g. of creating nuclear safety culture and social opinion about investment. Human factors in nuclear power engineering are as well important as relevant economical and technical factors, but very often negligible. In Poland where history about Czarnobyl is still alive, and social opinion is created on emotions after accident in Fukushima, human factors are crucial and should be under comprehensive consideration.

  19. Human factors in waste management - potential and reality

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, J.S. [Benchmarking Environmental Corp., Albuquerque, NM (United States)

    1996-12-31

    There is enormous potential for human factors contributions in the realm of waste management. The reality, however, is very different from the potential. This is particularly true for low-level and low-level mixed-waste management. The hazards are less severe; therefore, health and safety requirements (including human factors) are not as rigorous as for high-level waste. High-level waste management presents its own unique challenges and opportunities. Waste management is strongly driven by regulatory compliance. When regulations are flexible and open to interpretation and the environment is driven so strongly by regulatory compliance, standard practice is to drop {open_quotes}nice to have{close_quotes} features, like a human factors program, to save money for complying with other requirements. The challenge is to convince decision makers that human factors can help make operations efficient and cost-effective, as well as improving safety and complying with regulations. A human factors program should not be viewed as competing with compliance efforts; in fact, it should complement them and provide additional cost-effective means of achieving compliance with other regulations. Achieving this synergy of human factors with ongoing waste management operations requires educating program and facility managers and other technical specialists about human factors and demonstrating its value {open_quotes}through the back door{close_quotes} on existing efforts. This paper describes ongoing projects at Los Alamos National Laboratory (LANL) in support of their waste management groups. It includes lessons learned from hazard and risk analyses, safety analysis reports, job and task analyses, operating procedure development, personnel qualification/certification program development, and facility- and job-specific training program and course development.

  20. [Th2 differentiation features of Mycobacterium tuberculosis heat resistant antigen-activated human γδT cells and the regulation of transcription factor T-bet/GATA-3 on differentiation].

    Science.gov (United States)

    Zhu, Anyou; Lv, Hezuo; Zhang, Lunjun; Hu, Jianguo; Wang, Fengchao; Li, Baiqing

    2015-01-01

    To investigate Th2 differentiation features of Mycobacterium tuberculosis heat resistant antigens (MTB-HAg)-activated human γδT cells and the regulation of transcription factor T-box expression in T cells (T-bet) and GATA-binding protein 3 (GATA-3) on differentiation. Peripheral blood mononuclear cells (PBMCs) were stimulated with MTB-HAg to generate MTB-HAg-activated T cells (MTBAT) and expanded in the neutral condition or Th2 polarizing condition. After restimulation for 6 hours with phorbol myristate acetate (PMA, 10 ng/mL), ionomycin (500 ng/mL) and monensin (2.5 μmol/L), intracellular cytokines (IFN-γ, IL-4) of γδT cells and αβT cells among MTBAT were detected by four-color fluorescence mAb staining combined with flow cytometry. The highly purified γδT cells and CD4⁺ T cells were sorted by flow cytometer from MTBAT that were cultured in neutral and Th2 polarizing conditions for 28 days. The expressions of T-bet and GATA-3 mRNA in purified γδT cells and CD4⁺ T cells were determined by reverse transcription PCR (RT-PCR) technique. γδT cells among MTBAT cultured in the neutral or Th2 polarizing condition predominantly produced IFN-γ, whereas the percentage of IFN-γ⁺ αβT cells significantly decreased in the Th2 polarizing condition as the culture time went by. Compared with the neutral condition, Th0 type (IFN-γ⁺ IL-4⁺) γδT cells significantly increased, and Th2 type (IFN-γ⁻ IL-4⁺) αβT cells also significantly increased in the Th2 polarizing condition. RT-PCR showed that mRNA expression of T-bet was still at a high level in γδT cells that were expanded in the Th2 polarizing condition, but at a low level in Th2 polarized CD4⁺ T cells. Moreover, the mRNA expressions of GATA-3 in both Th2 polarized γδT cells and CD4⁺T cells were up-regulated. In the Th2 polarizing condition, the majority of γδT cells in MTBAT still remained Th1 profile, whereas the portion of γδT cells differentiated into Th0 type cells. Both

  1. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

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

    Science.gov (United States)

    Campling, Barbara G; Kuryatov, Alexander; Lindstrom, Jon

    2013-01-01

    The behavioral effects of nicotine and other nicotinic agonists are mediated by AChRs in the brain. The relative contribution of acute activation versus chronic desensitization of AChRs is unknown. Sustained "smoldering activation" occurs over a range of agonist concentrations at which activated and desensitized AChRs are present in equilibrium. We used a fluorescent dye sensitive to changes in membrane potential to examine the effects of acute activation and chronic desensitization by nicotinic AChR agonists on cell lines expressing human α4β2, α3β4 and α7 AChRs. We examined the effects of acute and prolonged application of nicotine and the partial agonists varenicline, cytisine and sazetidine-A on these AChRs. The range of concentrations over which nicotine causes smoldering activation of α4β2 AChRs was centered at 0.13 µM, a level found in smokers. However, nicotine produced smoldering activation of α3β4 and α7 AChRs at concentrations well above levels found in smokers. The α4β2 expressing cell line contains a mixture of two stoichiometries, namely (α4β2)2β2 and (α4β2)2α4. The (α4β2)2β2 stoichiometry is more sensitive to activation by nicotine. Sazetidine-A activates and desensitizes only this stoichiometry. Varenicline, cytisine and sazetidine-A were partial agonists on this mixture of α4β2 AChRs, but full agonists on α3β4 and α7 AChRs. It has been reported that cytisine and varenicline are most efficacious on the (α4β2)2α4 stoichiometry. In this study, we distinguish the dual effects of activation and desensitization of AChRs by these nicotinic agonists and define the range of concentrations over which smoldering activation can be sustained.

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

    Directory of Open Access Journals (Sweden)

    Barbara G Campling

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

  4. Human myelopoiesis in culture of liquid medium lacking colony stimulating factors: therapeutic implications for cancer patients with leukopenia.

    Science.gov (United States)

    Diamandopoulos, G T

    1994-01-01

    Patients with cancer often develop leukopenia caused by chemotherapy. Since their treatment with human colony stimulating factors (CSFs) has limitations, it is imperative to determine if CSFs are essential in regulating human myelopoiesis. For this purpose, human primary precursor myeloid cells were cultured in media lacking exogenous human CSFs and stem cell factor (SCF), and supplemented with human sera, or with fetal bovine or other types of animal sera. Cells cultured in human sera survive well, proliferate actively, and differentiate toward granulocytes. Most cells cultured in fetal bovine serum die, few differentiate toward monocytes-macrophages. Cells cultured in other types of animal sera die rapidly. Antibodies neutralizing human serum's CSFs and SCF do not abolish its myeloregulatory activity. It is concluded that cell growth factors other than CSFs and SCF present in human serum regulate human myelopoiesis in vitro. These findings bear important therapeutic implication for patients with cancer having leukopenia.

  5. Human population, economic activities, and wild bird conservation in Mexico: factors influencing their relationships at two different geopolitical scales Población humana, actividades económicas y conservación de aves silvestres en México: factores que influencian sus relaciones en dos escalas geopolíticas diferentes

    Directory of Open Access Journals (Sweden)

    Xavier López-Medellín

    2011-12-01

    Full Text Available Population growth poses threats to biodiversity, specifically to sensitive species. Therefore, an understanding of the conflict between biodiversity and human population is needed to enable long-term planning of development and conservation policies by state and federal governments and society based on limitations and potentials of environments. We used a geopolitical approach to analyze data on human demography, economic activities, natural vegetation, avian diversity, and protected areas of the 32 states of Mexico and the 30 districts of the state of Oaxaca. Using factor analysis, we identified the biodiversity-rich geopolitical units that have a large human population and are developing intense economic activities. We then carried out a series of linear regressions between the resulting factors to test whether they were related, suggesting areas where conservation conflicts may exist, and found that relations between human activities and natural resources vary from region to region. These results help us identify geopolitical units that require detailed studies of the interactions between population and natural resources, and also highlight the importance of using geopolitical scales as study units, where most conservation and development policies are determined, to inform local stakeholders and decision makers.El crecimiento humano representa amenazas para la biodiversidad, especialmente para especies sensibles. Se necesita conocer a fondo el conflicto que representa el crecimiento de la población para la biodiversidad y llevar a cabo políticas y acciones a largo plazo de actividades de desarrollo y conservación evaluadas por gobiernos federales y estatales, basándose en las limitaciones y potenciales de los ecosistemas. Utilizamos una aproximación geopolítica para analizar variables de demografía humana, actividades económicas, superficie de vegetación, diversidad de aves y áreas protegidas de los 32 estados de México y los 30

  6. Understanding Usability Work as a Human Activity

    DEFF Research Database (Denmark)

    Nørgaard, Mie

    Three core themes are explored in eight papers: Usability work as a human activity, usability practice and methods, and persuasiveness of evaluation results and feedback. We explore how usability work is much more than methods and work procedures, and argue that maturing our understanding...... of usability work to include a human perspective, is crucial to downstream utility—how usability work impacts the on-going development process. Our work shows that cross-professional collaboration is subject to challenges that arise from stakeholders having conflicting priorities, procedures and personalities....... Such challenges include evaluation results lacking relevance, poor timing of evaluation results, little respect for other disciplines, and difficulties sharing important information about a design. The studies of practical usability work suggest that user researchers working with computer games and task oriented...

  7. Physical Human Activity Recognition Using Wearable Sensors

    Directory of Open Access Journals (Sweden)

    Ferhat Attal

    2015-12-01

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

  8. Physical Human Activity Recognition Using Wearable Sensors

    Science.gov (United States)

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

    2015-01-01

    This paper presents a review of different classification techniques used to recognize human activities from wearable inertial sensor data. Three inertial sensor units were used in this study and were worn by healthy subjects at key points of upper/lower body limbs (chest, right thigh and left ankle). Three main steps describe the activity recognition process: sensors’ placement, data pre-processing and data classification. Four supervised classification techniques namely, k-Nearest Neighbor (k-NN), Support Vector Machines (SVM), Gaussian Mixture Models (GMM), and Random Forest (RF) as well as three unsupervised classification techniques namely, k-Means, Gaussian mixture models (GMM) and Hidden Markov Model (HMM), are compared in terms of correct classification rate, F-measure, recall, precision, and specificity. Raw data and extracted features are used separately as inputs of each classifier. The feature selection is performed using a wrapper approach based on the RF algorithm. Based on our experiments, the results obtained show that the k-NN classifier provides the best performance compared to other supervised classification algorithms, whereas the HMM classifier is the one that gives the best results among unsupervised classification algorithms. This comparison highlights which approach gives better performance in both supervised and unsupervised contexts. It should be noted that the obtained results are limited to the context of this study, which concerns the classification of the main daily living human activities using three wearable accelerometers placed at the chest, right shank and left ankle of the subject. PMID:26690450

  9. Transcriptional Activity of Human Endogenous Retroviruses in Human Peripheral Blood Mononuclear Cells

    Directory of Open Access Journals (Sweden)

    Emanuela Balestrieri

    2015-01-01

    Full Text Available Human endogenous retroviruses (HERVs have been implicated in human physiology and in human pathology. A better knowledge of the retroviral transcriptional activity in the general population and during the life span would greatly help the debate on its pathologic potential. The transcriptional activity of four HERV families (H, K, W, and E was assessed, by qualitative and quantitative PCR, in PBMCs from 261 individuals aged from 1 to 80 years. Our results show that HERV-H, HERV-K, and HERV-W, but not HERV-E, are transcriptionally active in the test population already in the early childhood. In addition, the transcriptional levels of HERV-H, HERV-K, and HERV-W change significantly during the life span, albeit with distinct patterns. Our results, reinforce the hypothesis of a physiological correlation between HERVs activity and the different stages of life in humans. Studies aiming at identifying the factors, which are responsible for these changes during the individual’s life, are still needed. Although the observed phenomena are presumably subjected to great variability, the basal transcriptional activity of each individual, also depending on the different ages of life, must be carefully considered in all the studies involving HERVs as causative agents of disease.

  10. 49 CFR 225.12 - Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human...

    Science.gov (United States)

    2010-10-01

    ... employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement..., AND INVESTIGATIONS § 225.12 Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement. (a) Rail Equipment...

  11. Applied human factors research at the NASA Johnson Space Center Human-Computer Interaction Laboratory

    Science.gov (United States)

    Rudisill, Marianne; Mckay, Timothy D.

    1990-01-01

    The applied human factors research program performed at the NASA Johnson Space Center's Human-Computer Interaction Laboratory is discussed. Research is conducted to advance knowledge in human interaction with computer systems during space crew tasks. In addition, the Laboratory is directly involved in the specification of the human-computer interface (HCI) for space systems in development (e.g., Space Station Freedom) and is providing guidelines and support for HCI design to current and future space missions.

  12. Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

    Science.gov (United States)

    Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.

    2010-01-01

    As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities. Historically, engineering-dominated organizations have tended to view good Human Factors (HF) as a desire rather than a requirement in system design and development. Our field has made significant gains in the past decade, however; the Department of Defense, for example, now recognizes Human-System Integration (HSI), of which HF is a component, as an integral part of their divisions hardware acquisition processes. And our own agency was far more accepting of HF/HSI requirements during the most recent vehicle systems definition than in any prior cycle. Nonetheless, HF subject matter experts at NASA often find themselves in catch up mode... coping with legacy systems (hardware and software) and procedures that were designed with little regard for the human element, and too often with an attitude of we can deal with any operator issues during training. Our challenge, then, is to segregate the true knowledge gaps in Space Human Factors from the prior failures to incorporate best (or even good) HF design principles. Further, we strive to extract the overarching core HF issues from the point-design-specific concerns that capture the operators (and managers) attention. Generally, our approach embraces a 3M approach to Human Factors: Measurement, Modeling, and Mitigation. Our first step is to measure human performance, to move from subjective anecdotes to objective, quantified data. Next we model the phenomenon, using appropriate methods in

  13. UPDATING THE NRC GUIDANCE FOR HUMAN FACTORS ENGINEERING REVIEWS.

    Energy Technology Data Exchange (ETDEWEB)

    O HARA,J.M.; BROWN,W.S.; HIGGINS,J.C.; PERSENSKY,J.J.; LEWIS,P.M.; BONGARRA,J.

    2002-09-15

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) aspects of nuclear plants. NUREG-0800 (Standard Review Plan), Chapter 18, ''Human Factors Engineering,'' is the principal NRC staff guidance document. Two main documents provide the review criteria to support the evaluations. The HFE Program Review Model (NUREG-0711) addresses the design process from planning to verification and validation to design implementation. The Human-System Interface Design Review Guidelines (NUREG-0700) provides the guidelines for the review of the HFE aspects of human-system interface technology, such as alarms, information systems, controls, and control room design. Since these documents were published in 1994 and 1996 respectively, they have been used by NRC staff, contractors, nuclear industry organizations, as well as by numerous organizations outside the nuclear industry. Using feedback from users and NRC research conducted in recent years, both documents have been revised and updated. This was done to ensure that they remain state-of-the-art evaluation tools for changing nuclear industry issues and emerging technologies. This paper describes the methodology used to revise and update the documents and summarizes the changes made to each and their current contents. Index Terms for this report are: Control system human factors, Ergonomics, Human factors, Nuclear power generation safety.

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

    Science.gov (United States)

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

    2014-09-22

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

  15. Factors associated with active white enamel lesions.

    Science.gov (United States)

    Ferreira, M A F; Mendes, N S

    2005-09-01

    The aim of this study was to assess the factors associated with the presence of active white enamel lesions among public school students in the city of Natal, Brazil. A convenience sample of 300 boys and girls aged between 7 and 12 years was selected among the pupils attending public schools in the city of Natal. Only those children presenting with opaque and rough-surface white lesions in a region of biofilm accumulation on the vestibular surface of permanent upper incisors were included. The investigation took the form of a cross-sectional study. A chart containing individual data was used, and a clinical examination was performed to determine the oral health status of the children, including caries (DMF-s(1), DMF-s(2), DMFdmf, dmf and total number of teeth with caries) and oral hygiene status (Gingival Bleeding Index and Visible Plaque Index). Data underwent descriptive analysis and analysis of variance, and chi-square tests were used for the comparison of continuous and dichotomous variables between groups with one, two, or three or more white lesions. On average, each child presented with 2.3 teeth affected by white lesions, relatively high indices of dental caries and poor oral hygiene, with an 85% rate of localized plaque on the surfaces of teeth with lesions. The presence of visible plaque was statistically significant between the three groups, based on the number of lesions (P = 0.006), indicating a positive association between the number of lesions and the presence of biofilm. There is a strong association between the presence of dental biofilm, high indices of caries and active white enamel lesions. Full professional effort is needed in order to motivate children to carry out oral hygiene sufficient for the adequate control of dental biofilm.

  16. The contributions of human factors and ergonomics to a sustainable minerals industry.

    Science.gov (United States)

    Horberry, Tim; Burgess-Limerick, Robin; Fuller, Ruth

    2013-01-01

    This article describes examples of the application of human factors research and development work to a sustainable minerals industry. It begins by outlining human-related aspects of the minerals industry and the key human factors work previously undertaken in this domain. The focus then switches to sustainability in the minerals industry. Sustainability principles are introduced and illustrations provided of how human factors research and development work fits within such a framework. Three case studies of human factors in the minerals industry research are presented and the sustainability implications in each case study are highlighted. Finally, future trends related to human factors work in a sustainable minerals industry are addressed, in particular the opportunities and possible adverse consequences that increasing deployment of mining automation might bring. Minerals industries are a major global activity with significant sustainability implications. Aspects of sustainability in mining are examined using three case studies. These illustrate the contribution of human factors/ergonomics in reducing risks; developing emergency response management systems; and the value of participatory ergonomics in improving the design of mining equipment.

  17. Factors determining human-to-human transmissibility of zoonotic pathogens via contact.

    Science.gov (United States)

    Richard, Mathilde; Knauf, Sascha; Lawrence, Philip; Mather, Alison E; Munster, Vincent J; Müller, Marcel A; Smith, Derek; Kuiken, Thijs

    2017-02-01

    The pandemic potential of zoonotic pathogens lies in their ability to become efficiently transmissible amongst humans. Here, we focus on contact-transmitted pathogens and discuss the factors, at the pathogen, host and environmental levels that promote or hinder their human-to-human transmissibility via the following modes of contact transmission: skin contact, sexual contact, respiratory contact and multiple route contact. Factors common to several modes of transmission were immune evasion, high viral load, low infectious dose, crowding, promiscuity, and co-infections; other factors were specific for a pathogen or mode of contact transmission. The identification of such factors will lead to a better understanding of the requirements for human-to-human spread of pathogens, as well as improving risk assessment of newly emerging pathogens. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. How consumer physical activity monitors could transform human physiology research.

    Science.gov (United States)

    Wright, Stephen P; Hall Brown, Tyish S; Collier, Scott R; Sandberg, Kathryn

    2017-03-01

    A sedentary lifestyle and lack of physical activity are well-established risk factors for chronic disease and adverse health outcomes. Thus, there is enormous interest in measuring physical activity in biomedical research. Many consumer physical activity monitors, including Basis Health Tracker, BodyMedia Fit, DirectLife, Fitbit Flex, Fitbit One, Fitbit Zip, Garmin Vivofit, Jawbone UP, MisFit Shine, Nike FuelBand, Polar Loop, Withings Pulse O 2 , and others have accuracies similar to that of research-grade physical activity monitors for measuring steps. This review focuses on the unprecedented opportunities that consumer physical activity monitors offer for human physiology and pathophysiology research because of their ability to measure activity continuously under real-life conditions and because they are already widely used by consumers. We examine current and potential uses of consumer physical activity monitors as a measuring or monitoring device, or as an intervention in strategies to change behavior and predict health outcomes. The accuracy, reliability, reproducibility, and validity of consumer physical activity monitors are reviewed, as are limitations and challenges associated with using these devices in research. Other topics covered include how smartphone apps and platforms, such as the Apple ResearchKit, can be used in conjunction with consumer physical activity monitors for research. Lastly, the future of consumer physical activity monitors and related technology is considered: pattern recognition, integration of sleep monitors, and other biosensors in combination with new forms of information processing. Copyright © 2017 the American Physiological Society.

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

    Directory of Open Access Journals (Sweden)

    Oniga Stefan

    2015-12-01

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

  20. Infrastructural and Human Factors Affecting Safety Outcomes of Cyclists

    Directory of Open Access Journals (Sweden)

    Sergio Useche

    2018-01-01

    Full Text Available The increasing number of registered road crashes involving cyclists during the last decade and the high proportion of road crashes resulting in severe injuries and fatalities among cyclists constitutes a global issue for community health, urban development and sustainability. Nowadays, the incidence of many risk factors for road crashes of cyclists remains largely unexplained. Given the importance of this issue, the present study has been conducted with the aim of determining relationships between infrastructural, human factors and safety outcomes of cyclists. Objectives: This study aimed, first, to examine the relationship between key infrastructural and human factors present in cycling, bicycle-user characteristics and their self-reported experience with road crashes. And second, to determine whether a set of key infrastructural and human factors may predict their self-reported road crashes. Methods: For this cross-sectional study, a total of 1064 cyclists (38.8% women, 61.2% men; M = 32.8 years of age from 20 different countries across Europe, South America and North America, participated in an online survey composed of four sections: demographic data and cycling-related factors, human factors, perceptions on infrastructural factors and road crashes suffered. Results: The results of this study showed significant associations between human factors, infrastructural conditions and self-reported road crashes. Also, a logistic regression model found that self-reported road crashes of cyclists could be predicted through variables such as age, riding intensity, risky behaviours and problematic user/infrastructure interactions. Conclusions: The results of this study suggest that self-reported road crashes of cyclists are influenced by features related to the user and their interaction with infrastructural characteristics of the road.

  1. Human factors dealing with the International Asteroid Mission

    Science.gov (United States)

    Human factors encompass many concerns in the 2.83 year International Asteroid Mission (IAM) mission from the initial crew selection to the final readaptation to Earth environment. These factors include radiation, physical deconditioning, crew selection and interaction, psychosocial issues, and health maintenance. The main theme that runs throughout the group's work is the lack of current available research into the problem areas. This stems from the relatively short mission durations in the last 30 years of spaceflight and thus no heavy emphasis in the human factors area. In short, no one has been in space for 3 years and thus we do not know what the effects of a three year flight are. It will be one of the goals in the IAM mission to do some research that may contribute to the fundamental knowledge of preparing for how humans can live in space.

  2. Human factors issues in the intensive care unit.

    Science.gov (United States)

    Harder, Kathleen A; Marc, David

    2013-01-01

    In the context of an aging population, more critically ill patients, and a change in intensive care unit (ICU) services stemming from advances in technology, prevalent medical errors and staff burnout in the ICU are not surprising. The ICU provides ample opportunity for human factors experts to apply their knowledge about the strengths and weaknesses of human capabilities to design more effective care delivery. Human factors experts design work processes, technology, and environmental factors to effectively and constructively channel the attention and behavior of those providing care; a few areas of focus can have marked impacts on care delivery and patient outcomes. In this review, we focus on these 3 areas and investigate the solutions and problems addressed by previous research.

  3. Human factors of intelligent computer aided display design

    Science.gov (United States)

    Hunt, R. M.

    1985-01-01

    Design concepts for a decision support system being studied at NASA Langley as an aid to visual display unit (VDU) designers are described. Ideally, human factors should be taken into account by VDU designers. In reality, although the human factors database on VDUs is small, such systems must be constantly developed. Human factors are therefore a secondary consideration. An expert system will thus serve mainly in an advisory capacity. Functions can include facilitating the design process by shortening the time to generate and alter drawings, enhancing the capability of breaking design requirements down into simpler functions, and providing visual displays equivalent to the final product. The VDU system could also discriminate, and display the difference, between designer decisions and machine inferences. The system could also aid in analyzing the effects of designer choices on future options and in ennunciating when there are data available on a design selections.

  4. Quality management in the nuclear industry: the human factor

    Energy Technology Data Exchange (ETDEWEB)

    1990-01-01

    In the nuclear industry it is vital to understand the 'human factor' with regard to plant performance and plant safety. A proper management system ensures that personnel perform their duties correctly. 'Quality Management in the Nuclear Industry: the Human Factor', was a conference organized by the Institution of Mechanical Engineers in October 1990. The conference covered a wide range of topics on an international level including: standards, licensing and regulatory procedures; selection assessment and training of personnel; feedback from experience of good practice and of deviations; management and support of personnel performance; modelling and evaluation of human factors. The papers presented at the conference are contained in this volume. All twenty papers are indexed separately. (author).

  5. A human factors design of a nuclear plant analyzer

    Energy Technology Data Exchange (ETDEWEB)

    Byeon, Seung Nam; Lee, Dong Hoon; Park, Chan Woo [Kyounghee Univ., Seoul (Korea, Republic of)

    2000-12-15

    The project consists of four key stages as follows : based on the review of various literature, human factors design principles and processes are identified, the literature reviewed in the project includes NUREG-0700, research papers for MMI, human factors handbooks, and laboratory reports, after the design principles and processes are determined, a design checklist is developed to evaluate the user interface of NPA, the design checklist consists of seven different categories such as display screen, menu interface, form-fillin, alphanumeric characters, symbols, color, and highlighting, NPA was tested with the design checklist for conformance to the human factors design principles, the expert reviews are performed to evaluate a graphic user interface of NPA, the application of the design checklist and the subjective opinion of the expert identify the design included in the user interface of NPA, based on the thorough analysis of design defects, design guidelines are recommended to improve the user interface of NPA.

  6. Human factor engineering applied to nuclear power plant design

    Energy Technology Data Exchange (ETDEWEB)

    Manrique, A. [TECNATOM SA, BWR General Electric Business Manager, Madrid (Spain); Valdivia, J.C. [TECNATOM SA, Operation Engineering Project Manager, Madrid (Spain); Jimenez, A. [TECNATOM SA, Operation Engineering Div. Manager, Madrid (Spain)

    2001-07-01

    For the design and construction of new nuclear power plants as well as for maintenance and operation of the existing ones new man-machine interface designs and modifications are been produced. For these new designs Human Factor Engineering must be applied the same as for any other traditional engineering discipline. Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. Additionally, the big saving achieved by a nuclear power plant having an operating methodology which significantly decreases the risk of operating errors makes it necessary and almost vital its implementation. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. (author)

  7. Automotive Technology and Human Factors Research: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Motoyuki Akamatsu

    2013-01-01

    Full Text Available This paper reviews the history of automotive technology development and human factors research, largely by decade, since the inception of the automobile. The human factors aspects were classified into primary driving task aspects (controls, displays, and visibility, driver workspace (seating and packaging, vibration, comfort, and climate, driver’s condition (fatigue and impairment, crash injury, advanced driver-assistance systems, external communication access, and driving behavior. For each era, the paper describes the SAE and ISO standards developed, the major organizations and conferences established, the major news stories affecting vehicle safety, and the general social context. The paper ends with a discussion of what can be learned from this historical review and the major issues to be addressed. A major contribution of this paper is more than 180 references that represent the foundation of automotive human factors, which should be considered core knowledge and should be familiar to those in the profession.

  8. Addressing the human factors issues associated with control room modifications

    Energy Technology Data Exchange (ETDEWEB)

    O`Hara, J.; Stubler, W. [Brookhaven National Lab., Upton, NY (United States). Dept. of Advanced Technology; Kramer, J. [Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Regulatory Research

    1998-03-01

    Advanced human-system interface (HSI) technology is being integrated into existing nuclear plants as part of plant modifications and upgrades. The result of this trend is that hybrid HSIs are created, i.e., HSIs containing a mixture of conventional (analog) and advanced (digital) technology. The purpose of the present research is to define the potential effects of hybrid HSIs on personnel performance and plant safety and to develop human factors guidance for safety reviews of them where necessary. In support of this objective, human factors issues associated with hybrid HSIs were identified. The issues were evaluated for their potential significance to plant safety, i.e., their human performance concerns have the potential to compromise plant safety. The issues were then prioritized and a subset was selected for design review guidance development.

  9. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    anchorage-independent growth of normal cells and was, therefore, considered as an "oncogenic" growth factor. Later, its immunohistochemical presence in normal human cells as well as its biological effects in normal human tissues have been demonstrated. The aim of the present investigation was to elucidate...... the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF......-alpha was found to be widely distributed in cells of normal human tissues derived from all three germ layers, most often in differentiated cells. In epithelial cells, three different kinds of staining patterns were observed, either diffuse cytoplasmic, cytoplasmic in the basal parts of the cells, or distinctly...

  10. Human factors engineering plan for reviewing nuclear plant modernization programs

    Energy Technology Data Exchange (ETDEWEB)

    O' Hara, John; Higgins, James [Brookhaven National Laboratory, Upton, NY (United States)

    2004-12-01

    The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation.

  11. The spatial structure of transnational human activity.

    Science.gov (United States)

    Deutschmann, Emanuel

    2016-09-01

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

  12. Novel innate cancer killing activity in humans

    Directory of Open Access Journals (Sweden)

    Lovato James

    2011-08-01

    Full Text Available Abstract Background In this study, we pilot tested an in vitro assay of cancer killing activity (CKA in circulating leukocytes of 22 cancer cases and 25 healthy controls. Methods Using a human cervical cancer cell line, HeLa, as target cells, we compared the CKA in circulating leukocytes, as effector cells, of cancer cases and controls. The CKA was normalized as percentages of total target cells during selected periods of incubation time and at selected effector/target cell ratios in comparison to no-effector-cell controls. Results Our results showed that CKA similar to that of our previous study of SR/CR mice was present in human circulating leukocytes but at profoundly different levels in individuals. Overall, males have a significantly higher CKA than females. The CKA levels in cancer cases were lower than that in healthy controls (mean ± SD: 36.97 ± 21.39 vs. 46.28 ± 27.22. Below-median CKA was significantly associated with case status (odds ratio = 4.36; 95% Confidence Interval = 1.06, 17.88 after adjustment of gender and race. Conclusions In freshly isolated human leukocytes, we were able to detect an apparent CKA in a similar manner to that of cancer-resistant SR/CR mice. The finding of CKA at lower levels in cancer patients suggests the possibility that it may be of a consequence of genetic, physiological, or pathological conditions, pending future studies with larger sample size.

  13. Human Health/Human Factors Considerations in Trans-Lunar Space

    Science.gov (United States)

    Moore, E. Cherice; Howard, Robert; Mendeck, Gavin

    2014-01-01

    The human factors insights of how they are incorporated into the vehicle are crucial towards designing and planning the internal designs necessary for future spacecraft and missions. The adjusted mission concept of supporting the Asteroid Redirect Crewed Mission will drive some human factors changes on how the Orion will be used and will be reassessed so as to best contribute to missions success. Recognizing what the human factors and health functional needs are early in the design process and how to integrate them will improve this and future generations of space vehicles to achieve mission success and continue to minimize risks.

  14. Insulin-like growth factor-1-mediated AKT activation postpones the onset of ultraviolet B-induced apoptosis, providing more time for cyclobutane thymine dimer removal in primary human keratinocytes.

    Science.gov (United States)

    Decraene, David; Agostinis, Patrizia; Bouillon, Roger; Degreef, Hugo; Garmyn, Marjan

    2002-09-06

    Insulin-like growth factor-1 (IGF-1) acts as a potent survival factor in numerous cell lines, primarily through activation of the AKT signaling pathway. Although some targets of this pathway have known anti-apoptotic functions, its relationship with the improved survival of cells after exposure to environmental stresses, including UVB, remains largely unclear. We report that in growth factor-deprived keratinocytes, IGF-1 significantly and consistently delayed the onset of UVB-induced apoptosis by >7 h. This delay allowed IGF-1-supplemented keratinocytes to repair significantly more cyclobutane thymine dimers than their growth factor-deprived counterparts. This increase in cyclobutane thymine removal resulted in enhanced survival if the amount of DNA damage was not too high. To increase cell survival after UVB irradiation, IGF-1 supplementation was required only during this initial time period in which extra repair was executed. Finally, we show that IGF-1 mediated this delay in the onset of UVB-induced apoptosis through activation of the AKT signaling pathway. We therefore believe that the AKT signaling pathway increases cell survival after a genotoxic insult such as UVB irradiation not by inhibiting the apoptotic stimulus, but only by postponing the induction of apoptosis, giving the DNA repair mechanism more time to work.

  15. Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

    Science.gov (United States)

    Alexander, Tiffaney Miller

    2017-01-01

    Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Safety within space exploration ground processing operations, the identification and/or classification of underlying contributors and causes of human error must be identified, in order to manage human error. This research provides a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

  16. Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

    Science.gov (United States)

    Alexander, Tiffaney Miller

    2017-01-01

    Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Quality within space exploration ground processing operations, the identification and or classification of underlying contributors and causes of human error must be identified, in order to manage human error.This presentation will provide a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

  17. Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

    Science.gov (United States)

    Alexander, Tiffaney Miller

    2017-01-01

    Research results have shown that more than half of aviation, aerospace and aeronautics mishaps/incidents are attributed to human error. As a part of Safety within space exploration ground processing operations, the identification and/or classification of underlying contributors and causes of human error must be identified, in order to manage human error. This research provides a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

  18. NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health

    Science.gov (United States)

    Holubec, Keith; Connolly, Janis

    2010-01-01

    This slide presentation reviews the history, and development of NASA-STD-3001, NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health, and the related Human Integration Design Handbook. Currently being developed from NASA-STD-3000, this project standard currently in review will be available in two volumes, (i.e., Volume 1 -- VCrew Health and Volume 2 -- Human Factors, Habitability, and Environmental Health) and the handbook will be both available as a pdf file and as a interactive website.

  19. Meeting Human Reliability Requirements through Human Factors Design, Testing, and Modeling

    Energy Technology Data Exchange (ETDEWEB)

    R. L. Boring

    2007-06-01

    In the design of novel systems, it is important for the human factors engineer to work in parallel with the human reliability analyst to arrive at the safest achievable design that meets design team safety goals and certification or regulatory requirements. This paper introduces the System Development Safety Triptych, a checklist of considerations for the interplay of human factors and human reliability through design, testing, and modeling in product development. This paper also explores three phases of safe system development, corresponding to the conception, design, and implementation of a system.

  20. Human Factors and Habitability Challenges for Mars Missions

    Science.gov (United States)

    Whitmore, Mihriban

    2015-01-01

    As NASA is planning to send humans deeper into space than ever before, adequate crew health and performance will be critical for mission success. Within the NASA Human Research Program (HRP), the Space Human Factors and Habitability (SHFH) team is responsible for characterizing the risks associated with human capabilities and limitations with respect to long-duration spaceflight, and for providing mitigations (e.g., guidelines, technologies, and tools) to promote safe, reliable and productive missions. SHFH research includes three domains: Advanced Environmental Health (AEH), Advanced Food Technology (AFT), and Space Human Factors Engineering (SHFE). The AEH portfolio focuses on understanding the risk of microbial contamination of the spacecraft and on the development of standards for exposure to potential toxins such as chemicals, bacteria, fungus, and lunar/Martian dust. The two risks that the environmental health project focuses on are adverse health effects due to changes in host-microbe interactions, and risks associated with exposure to dust in planetary surface habitats. This portfolio also proposes countermeasures to these risks by making recommendations that relate to requirements for environmental quality, foods, and crew health on spacecraft and space missions. The AFT portfolio focuses on reducing the mass, volume, and waste of the entire integrated food system to be used in exploration missions, and investigating processing methods to extend the shelf life of food items up to five years, while assuring that exploration crews will have nutritious and palatable foods. The portfolio also delivers improvements in both the food itself and the technologies for storing and preparing it. SHFE sponsors research to establish human factors and habitability standards and guidelines in five risk areas, and provides improved design concepts for advanced crew interfaces and habitability systems. These risk areas include: Incompatible vehicle/habitat design

  1. Prevalence of Telomerase Activity in Human Cancer

    Directory of Open Access Journals (Sweden)

    Chi-Hau Chen

    2011-05-01

    Full Text Available Telomerase activity has been measured in a wide variety of cancerous and non-cancerous tissue types, and the vast majority of clinical studies have shown a direct correlation between it and the presence of cancerous cells. Telomerase plays a key role in cellular immortality and tumorigenesis. Telomerase is activated in 80–90% of human carcinomas, but not in normal somatic cells, therefore, its detection holds promise as a diagnostic marker for cancer. Measurable levels of telomerase have been detected in malignant cells from various samples: tissue from gestational trophoblastic neoplasms; squamous carcinoma cells from oral rinses; lung carcinoma cells from bronchial washings; colorectal carcinoma cells from colonic luminal washings; bladder carcinoma cells from urine or bladder washings; and breast carcinoma or thyroid cancer cells from fine needle aspirations. Such clinical tests for telomerase can be useful as non-invasive and cost-effective methods for early detection and monitoring of cancer. In addition, telomerase activity has been shown to correlate with poor clinical outcome in late-stage diseases such as non-small cell lung cancer, colorectal cancer, and soft tissue sarcomas. In such cases, testing for telomerase activity can be used to identify patients with a poor prognosis and to select those who might benefit from adjuvant treatment. Our review of the latest medical advances in this field reveals that telomerase holds great promise as a biomarker for early cancer detection and monitoring, and has considerable potential as the basis for developing new anticancer therapies.

  2. Electronic cigarettes: incorporating human factors engineering into risk assessments

    OpenAIRE

    Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

    2014-01-01

    Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through Januar...

  3. Development of Human Factors Ontology for Business Knowledge Management

    OpenAIRE

    Monica Philippart; Waldemar Karwowski

    2011-01-01

    Employee knowledge and cognitive skills are key assets to achieving business success, yet are often mismanaged. By promoting the human-centered design approach, the discipline of human factors and ergonomics (HF/E) can significantly contribute to optimizing business processes through effective management of employee knowledge. However, a comprehensive methodology is needed to help organizations integrate the HF/E principles across various business processes. This paper introduces a novel meth...

  4. Crowds, not Drones: Modeling Human Factors in Interactive Crowdsourcing

    OpenAIRE

    Basu Roy, Senjuti; Lykourentzou, Ioanna; Thirumuruganathan, Saravanan; Amer-Yahia, Sihem; Das, Gautam

    2013-01-01

    International audience; In this vision paper, we propose SmartCrowd, an intelligent and adaptive crowdsourcing framework. Contrary to existing crowdsourcing systems, where the process of hiring workers (crowd), learning their skills, and evaluating the accuracy of tasks they perform are fragmented, siloed, and often ad-hoc, SmartCrowd foresees a paradigm shift in that process, considering unpredictability of human nature, namely human factors. SmartCrowd offers opportunities in making crowdso...

  5. A Human Factors Framework for Payload Display Design

    Science.gov (United States)

    Dunn, Mariea C.; Hutchinson, Sonya L.

    1998-01-01

    During missions to space, one charge of the astronaut crew is to conduct research experiments. These experiments, referred to as payloads, typically are controlled by computers. Crewmembers interact with payload computers by using visual interfaces or displays. To enhance the safety, productivity, and efficiency of crewmember interaction with payload displays, particular attention must be paid to the usability of these displays. Enhancing display usability requires adoption of a design process that incorporates human factors engineering principles at each stage. This paper presents a proposed framework for incorporating human factors engineering principles into the payload display design process.

  6. Human Factors Vehicle Displacement Analysis: Engineering In Motion

    Science.gov (United States)

    Atencio, Laura Ashley; Reynolds, David; Robertson, Clay

    2010-01-01

    While positioned on the launch pad at the Kennedy Space Center, tall stacked launch vehicles are exposed to the natural environment. Varying directional winds and vortex shedding causes the vehicle to sway in an oscillating motion. The Human Factors team recognizes that vehicle sway may hinder ground crew operation, impact the ground system designs, and ultimately affect launch availability . The objective of this study is to physically simulate predicted oscillation envelopes identified by analysis. and conduct a Human Factors Analysis to assess the ability to carry out essential Upper Stage (US) ground operator tasks based on predicted vehicle motion.

  7. Human factors engineering report for the cold vacuum drying facility

    Energy Technology Data Exchange (ETDEWEB)

    IMKER, F.W.

    1999-06-30

    The purpose of this report is to present the results and findings of the final Human Factors Engineering (HFE) technical analysis and evaluation of the Cold Vacuum Drying Facility (CVDF). Ergonomics issues are also addressed in this report, as appropriate. This report follows up and completes the preliminary work accomplished and reported by the Preliminary HFE Analysis report (SNF-2825, Spent Nuclear Fuel Project Cold Vacuum Drying Facility Human Factors Engineering Analysis: Results and Findings). This analysis avoids redundancy of effort except for ensuring that previously recommended HFE design changes have not affected other parts of the system. Changes in one part of the system may affect other parts of the system where those changes were not applied. The final HFE analysis and evaluation of the CVDF human-machine interactions (HMI) was expanded to include: the physical work environment, human-computer interface (HCI) including workstation and software, operator tasks, tools, maintainability, communications, staffing, training, and the overall ability of humans to accomplish their responsibilities, as appropriate. Key focal areas for this report are the process bay operations, process water conditioning (PWC) skid, tank room, and Central Control Room operations. These key areas contain the system safety-class components and are the foundation for the human factors design basis of the CVDF.

  8. Analysis of factor XIa, factor IXa and tissue factor activity in burn patients.

    Science.gov (United States)

    Shupp, Jeffrey W; Prior, Shannon M; Jo, Daniel Y; Moffatt, Lauren T; Mann, Kenneth G; Butenas, Saulius

    2017-10-09

    An elevated procoagulant activity observed in trauma patients is, in part, related to tissue factor (TF) located on blood cells and microparticles. However, analysis of trauma patient plasma indicates that there are other contributor(s) to the procoagulant activity. We hypothesize that factor (F)XIa and FIXa are responsible for an additional procoagulant activity in burn patients. Multiple time-point plasma samples from 56 burn patients (total number of samples was 471; up to 20 time-points/patient collected in 3 weeks following admission) were evaluated in a thrombin generation assay using inhibitory antibodies to TF, FIXa and FXIa. Due to the limited volume of some samples, not all were analyzed for all three proteins. At admission, 10 of 53 patients (19%) had active TF, 53 of 55 (96%) had FXIa and 48 of 55 (87%) had FIXa in their plasma. 34 patients of 56 enrolled (61%) showed TF activity at one or more time-points. All patients had FXIa and 96% had FIXa at one or more time-points. Overall, TF was observed in 99 of 455 samples analyzed (22%), FXIa in 424 of 471 (90%) and FIXa in 244 of 471 (52%). The concentration of TF was relatively low and varied between 0 and 2.1pM, whereas that of FXIa was higher, exceeding 100pM in some samples. The majority of samples with FIXa had it at sub-nanomolar concentrations. No TF, FXIa and FIXa activity was detected in plasma from healthy individuals. For the first time reported, the majority of plasma samples from burn patients have active FXIa and FIXa, with a significant fraction of them having active TF. The concentration of all three proteins varies in a wide range. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  9. Human factors evaluation of teletherapy: Literature review. Volume 5

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, K.; Kaye, R.D.; Jones, R. [Hughes Training, Inc., Falls Church, VA (United States); Morisseau, D.S.; Serig, D.L. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Systems Technology

    1995-07-01

    A series of human factors evaluations were undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multidisciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation therapists, conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was performed initially to guide subsequent evaluations in the areas of workplace environment, system-user interfaces, procedures, training, and organizational practices. To further acquire an in-depth and up-to-date understanding of the practice of teletherapy in support of these evaluations, a systematic literature review was conducted. Factors that have a potential impact on the accuracy of treatment delivery were of primary concern. The present volume is the literature review. The volume starts with an overview of the multiphased nature of teletherapy, and then examines the requirement for precision, the increasing role of quality assurance, current conceptualizations of human error, and the role of system factors such as the workplace environment, user-system interfaces, procedures, training, and organizational practices.

  10. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised......Trefoil factors (TTFs) are small, compact proteins coexpressed with mucins in the gastrointestinal tract. Three trefoil factors are known in mammals: TFF1, TFF2, and TFF3. They are implicated to play diverse roles in maintenance and repair of the gastrointestinal channel. We compared the expression...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...

  11. Human factors guidelines for large-screen displays

    Energy Technology Data Exchange (ETDEWEB)

    Collier, Steve

    2005-09-15

    Any control-room project (including upgrades or evolutionary improvements to existing control-rooms) is well advised at the outset first to gather and update related background material for the design. This information-gathering exercise should also take into account experience from similar projects and operating experience. For these reasons, we decided to use our research, and experience in large-screen display design with several clients to update human factors guidance for large-screen displays, to take into account new ergonomics guidelines, operating experience, and work from similar projects. To write the updated guidelines, we drew on much of our experience across several departments at IFE, including research funded by the HRP programme, and experience with individual clients. Guidance here is accordingly focused mainly on recent areas of technical and human innovations in the man-machine interface. One particular area of focus was on the increasing use of large-screen display systems in modern control-rooms, and on how guidelines could be adapted and supplemented for their design. Guidance or reference to recommended sources is also given for control suite arrangement and layout, control-room layout, workstation layout, design of displays and controls, and design of the work environment, especially insofar as these ergonomic issues interact with the effectiveness of modern displays, in particular large screen displays. The work shows that there can be synergy between HRP research and bilateral activities: the one side offers a capability to develop tools and guidelines, while the other side gives an opportunity to test and refine these in practice, to the benefit of both parties. (Author)

  12. An Integrated Suite of Tools to support Human Factors Engineering

    Energy Technology Data Exchange (ETDEWEB)

    Jacques V Hugo

    2001-08-01

    Human Factors Engineering (HFE) work for the nuclear industry imposes special demands on the practitioner in terms of the scope, complexity and safety requirements for humans in nuclear installations. Unfortunately HFE lags behind other engineering disciplines in the development and use of modern, powerful tools for the full range of analysis and design processes. HFE does not appear to be an attractive market for software and hardware developers and as a result, HFE practitioners usually have to rely on inefficient general-purpose tools like standard office software, or they have to use expensive special-purpose tools that offer only part of the solution they require and which also do not easily integrate with other tools. There have been attempts to develop generic software tools to support the HFE analyst and also to achieve some order and consistency in format and presentation. However, in spite of many years of development, very few tools have emerged that have achieved these goals. This would suggest the need for special tools, but existing commercial products have been found inadequate and to date not a single tool has been developed that adequately supports the special requirements of HFE work for the nuclear industry. This paper describes an integrated suite of generic as well as purpose-built tools that facilitate information solicitation, issues tracking, work domain analysis, functional requirements analysis, function allocation, operational sequence analysis, task analysis and development of HSI design requirements. In combination, this suite of tools supports the analytical as well as the representational aspects of key HFE activities primarily for new NPPs, including capturing information from subject matter experts and various source documents directly into the appropriate tool and then linking, analyzing and extending that information further to represent detailed functional and task information, and ultimately HSI design requirements. The paper

  13. With eloquence and humanity? Human factors/ergonomics in sustainable human development.

    Science.gov (United States)

    Moore, Dave; Barnard, Tim

    2012-12-01

    This article is based on a keynote presentation given at the 18th Congress of the International Ergonomics Association in Recife, Brazil, February 2012. It considers new, and not so new, approaches and practical roles for the emerging field of human factors/ergonomics (HFE) in sustainable development (SD).The material for this article was largely drawn from the literature in the fields of human development, sustainability, climate change mitigation and adaptation, and social/environmental impact assessment. Identifying the role of HFE in SD is not a simple one and from the outset is complicated by the widely differing ideas in the sustainability literature about what exactly it is we are hoping to sustain. Is it individual companies, business models, cultures, or the carrying capacity of our planet? Or combinations of these? For the purposes of this article, certain assumptions are made, and various emerging opportunities and responsibilities associated with our changing world of work are introduced. First, there are new versions of traditional tasks for us, such as working with the people and companies in the renewable energy sectors. Beyond this, however, it is suggested that there are emerging roles for HFE professionals in transdisciplinary work where we might play our part, for example, in tackling the twinned issues of climate change and human development in areas of significant poverty. In particular we have the tools and capabilities to help define and measure what groups have reason to value, and wish to sustain. It is suggested, that to do this effectively, however, will require a philosophical shift, or perhaps just a philosophical restatement at a collective level, regarding who and what we ultimately serve.

  14. Azithromycin distinctively modulates classical activation of human monocytes in vitro

    Science.gov (United States)

    Vrančić, M; Banjanac, M; Nujić, K; Bosnar, M; Murati, T; Munić, V; Stupin Polančec, D; Belamarić, D; Parnham, MJ; Eraković Haber, V

    2012-01-01

    BACKGROUND AND PURPOSE Azithromycin has been reported to modify activation of macrophages towards the M2 phenotype. Here, we have sought to identify the mechanisms underlying this modulatory effect of azithromycin on human monocytes, classically activated in vitro. EXPERIMENTAL APPROACH Human blood monocytes were primed with IFN-γ for 24 h and activated with LPS for 24 h. Azithromycin, anti-inflammatory and lysosome-affecting agents were added 2 h before IFN-γ. Cytokine and chemokine expression was determined by quantitative PCR and protein release by ELISA. Signalling molecules were determined by Western blotting and transcription factor activation quantified with a DNA-binding ELISA kit. KEY RESULTS Azithromycin (1.5–50 µM) dose-dependently inhibited gene expression and/or release of M1 macrophage markers (CCR7, CXCL 11 and IL-12p70), but enhanced CCL2, without altering TNF-α or IL-6. Azithromycin also enhanced the gene expression and/or release of M2 macrophage markers (IL-10 and CCL18), and the pan-monocyte marker CD163, but inhibited that of CCL22. The Toll-like receptor (TLR) 4 signalling pathway was modulated, down-regulating NF-κB and STAT1 transcription factors. The inhibitory profile of azithromycin differed from that of dexamethasone, the phosphodiesterase-4 inhibitor roflumilast and the p38 kinase inhibitor SB203580 but was similar to that of the lysosomotropic drug chloroquine. Effects of concanamycin and NH4Cl, which also act on lysosomes, differed significantly. CONCLUSIONS AND IMPLICATIONS Azithromycin modulated classical activation of human monocytes by inhibition of TLR4-mediated signalling and possible effects on lysosomal function, and generated a mediator expression profile that differs from that of monocyte/macrophage phenotypes so far described. PMID:21726210

  15. Human solvent exposure. Factors influencing the pharmacokinetics and acute toxicity

    DEFF Research Database (Denmark)

    Bælum, Jesper

    1991-01-01

    The purpose of this review has been to discuss human and environmental factors which may influence the acute irritative and neurotoxic effects of organic solvents. The review is based on a field study and on four human experimental studies. Several studies have shown that printers and other workers...... exposed to mixtures of solvents experience an increased frequency of work related irritative and neurological symptoms although the exposure has been far below the occupational exposure limits. A series of controlled human exposure studies was carried out. Different groups of persons were exposed...

  16. Human Factors Operability Timeline Analysis to Improve the Processing Flow of the Orion Spacecraft

    Science.gov (United States)

    Stambolian, Damon B.; Schlierf, Roland; Miller, Darcy; Posada, Juan; Haddock, Mike; Haddad, Mike; Tran, Donald; Henderon, Gena; Barth, Tim

    2011-01-01

    This slide presentation reviews the use of Human factors and timeline analysis to have a more efficient and effective processing flow. The solution involved developing a written timeline of events that included each activity within each functional flow block. Each activity had computer animation videos and pictures of the people involved and the hardware. The Human Factors Engineering Analysis Tool (HFEAT) was improved by modifying it to include the timeline of events. The HFEAT was used to define the human factors requirements and design solutions were developed for these requirements. An example of a functional flow block diagram is shown, and a view from one of the animations (i.e., short stack pallet) is shown and explained.

  17. Human factors issues in the use of night vision devices

    Science.gov (United States)

    Kaiser, Mary K.; Foyle, David C.

    1991-01-01

    An account is given of the critical human factors that arise in field data on the differences between night vision displays and unaided day vision. Attention is given to the findings of empirical studies of performance on rotorcraft-flight-relevant perceptual tasks in which depth and distance perception are critical factors. Suggestions are made for man-machine-critical component design modifications in current night vision systems.

  18. Activation of human peroxisome-activated receptor-gamma ...

    Science.gov (United States)

    Obesity in children has become an epidemic and recent research suggests a possible contribution from exposure to environmental chemicals. Several chemicals, such as phthalates, brominated flame retardants, and perfluorinated chemicals, are common in house dust on floors where children play and are suspected obesogens. Obesogens can act via a mechanism that involves activation of peroxisome proliferator-activated receptor-gamma (PPARy). A previous study found that dust collected from children’s homes binds to PPARy. Here, we investigated the ability of house dust to activate PPARy in a transiently transfected cell assay. Dust samples were collected in 2012 from carpeted and hardwood floors in children’s homes using thimbles fitted into a vacuum cleaner hose (“TEO” samples), or from homes in an adult cohort NIEHS study. Dust was extracted with 50:50 hexane:acetone, sonicated, centrifuged, and the organic layer collected. This was repeated 2X. The extracts were filtered to remove particulates, dried with purified nitrogen, and reconstituted in DMS0 at 200 ug/ul. COS-1 cells were transfected for 24 hrs with a human PPARy vector containing a luciferase reporter, and exposed for 24 hrs to negative controls water or DMSO (0.1%), positive controls Troglitazone (3 uM in water) or Rosiglitazone (100 nM in DMSO), or dust extracts serially diluted in DMEM at 50, 100, and 200 ug/ml in 0.1% DMSO. Cells were lysed and luciferase activity was measured. Data were log-tra

  19. Linguistic threat activates the human amygdala

    Science.gov (United States)

    Isenberg, N.; Silbersweig, D.; Engelien, A.; Emmerich, S.; Malavade, K.; Beattie, B.; Leon, A. C.; Stern, E.

    1999-01-01

    Studies in animals demonstrate a crucial role for the amygdala in emotional and social behavior, especially as related to fear and aggression. Whereas lesion and functional-imaging studies in humans indicate the amygdala’s participation in assessing the significance of nonverbal as well as paralinguistic cues, direct evidence for its role in the emotional processing of linguistic cues is lacking. In this study, we use a modified Stroop task along with a high-sensitivity neuroimaging technique to target the neural substrate engaged specifically when processing linguistic threat. Healthy volunteer subjects were instructed to name the color of words of either threat or neutral valence, presented in different color fonts, while neural activity was measured by using H215O positron-emission tomography. Bilateral amygdalar activation was significantly greater during color naming of threat words than during color naming of neutral words. Associated activations were also noted in sensory-evaluative and motor-planning areas of the brain. Thus, our results demonstrate the amygdala’s role in the processing of danger elicited by language. In addition, the results reinforce the amygdala’s role in the modulation of the perception of, and response to, emotionally salient stimuli. The current study further suggests conservation of phylogenetically older mechanisms of emotional evaluation in the context of more recently evolved linguistic function. PMID:10468630

  20. Human Research Program Space Human Factors Engineering (SHFE) Standing Review Panel (SRP)

    Science.gov (United States)

    Wichansky, Anna; Badler, Norman; Butler, Keith; Cummings, Mary; DeLucia, Patricia; Endsley, Mica; Scholtz, Jean

    2009-01-01

    The Space Human Factors Engineering (SHFE) Standing Review Panel (SRP) evaluated 22 gaps and 39 tasks in the three risk areas assigned to the SHFE Project. The area where tasks were best designed to close the gaps and the fewest gaps were left out was the Risk of Reduced Safety and Efficiency dire to Inadequate Design of Vehicle, Environment, Tools or Equipment. The areas where there were more issues with gaps and tasks, including poor or inadequate fit of tasks to gaps and missing gaps, were Risk of Errors due to Poor Task Design and Risk of Error due to Inadequate Information. One risk, the Risk of Errors due to Inappropriate Levels of Trust in Automation, should be added. If astronauts trust automation too much in areas where it should not be trusted, but rather tempered with human judgment and decision making, they will incur errors. Conversely, if they do not trust automation when it should be trusted, as in cases where it can sense aspects of the environment such as radiation levels or distances in space, they will also incur errors. This will be a larger risk when astronauts are less able to rely on human mission control experts and are out of touch, far away, and on their own. The SRP also identified 11 new gaps and five new tasks. Although the SRP had an extremely large quantity of reading material prior to and during the meeting, we still did not feel we had an overview of the activities and tasks the astronauts would be performing in exploration missions. Without a detailed task analysis and taxonomy of activities the humans would be engaged in, we felt it was impossible to know whether the gaps and tasks were really sufficient to insure human safety, performance, and comfort in the exploration missions. The SRP had difficulty evaluating many of the gaps and tasks that were not as quantitative as those related to concrete physical danger such as excessive noise and vibration. Often the research tasks for cognitive risks that accompany poor task or

  1. Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.

    Directory of Open Access Journals (Sweden)

    Junwei Yang

    Full Text Available Platelet-activating factor (PAF plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH, which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.

  2. Human factors with nonhumans - Factors that affect computer-task performance

    Science.gov (United States)

    Washburn, David A.

    1992-01-01

    There are two general strategies that may be employed for 'doing human factors research with nonhuman animals'. First, one may use the methods of traditional human factors investigations to examine the nonhuman animal-to-machine interface. Alternatively, one might use performance by nonhuman animals as a surrogate for or model of performance by a human operator. Each of these approaches is illustrated with data in the present review. Chronic ambient noise was found to have a significant but inconsequential effect on computer-task performance by rhesus monkeys (Macaca mulatta). Additional data supported the generality of findings such as these to humans, showing that rhesus monkeys are appropriate models of human psychomotor performance. It is argued that ultimately the interface between comparative psychology and technology will depend on the coordinated use of both strategies of investigation.

  3. Lipopolysaccharide and platelet-activating factor stimulate expression of platelet-activating factor acetylhydrolase via distinct signaling pathways

    Science.gov (United States)

    Abdel-al, Mohammed; Ditmyer, Marcia; Patel, Nipa

    2011-01-01

    Objectives This study was designed to investigate and characterize the ability of platelet-activating factor (PAF) to induce the expression of platelet-activating factor acetylhydrolase (PAF-AH). Methods Ribonuclease protection assays and quantitative real-time PCR were used to investigate the ability of lipopolysaccharide (LPS) and PAF to regulate PAF-AH mRNA expression in human monocyte–macrophage 6 (MM6) cells. Pharmacological inhibitors of mitogen activated protein kinases (MAPK) and PAF receptor antagonists were used to investigate the mechanism of regulation of PAF-AH. Results PAF-AH mRNA levels were increased upon exposure to LPS or PAF in a dose-dependent manner. LPS elicited a more potent and rapid increase in PAF-AH expression than the PAF-stimulated response. However, when administered concomitantly, PAF augmented the LPS-stimulated response. LPS-stimulated PAF-AH expression was susceptible to partial inhibition by a p38 MAPK inhibitor and PAF receptor antagonists. PAF-induced up-regulation of PAF-AH levels was solely mediated via the PAF receptor and was p38 MAPK-independent. Conclusion The proinflammatory mediators, LPS and PAF, increased levels of PAF-AH mRNA via distinct signaling pathways. PMID:21432021

  4. Integrating human factors and artificial intelligence in the development of human-machine cooperation

    NARCIS (Netherlands)

    Maanen, P.P. van; Lindenberg, J.; Neericx, M.A.

    2005-01-01

    Increasing machine intelligence leads to a shift from a mere interactive to a much more complex cooperative human-machine relation requiring a multidisciplinary development approach. This paper presents a generic multidisciplinary cognitive engineering method CE+ for the integration of human factors

  5. Human factors in organizational design and management VI

    NARCIS (Netherlands)

    Vink, P.; Koningsveld, E.A.P.; Dhondt, S.

    1998-01-01

    This book contains proceedings of the Sixth International Symposium on Human Factors in Organizational Design and Management held in The Hague, The Netherlands, August 19-22, 1998. The Symposium was sponsored jointly by the International Ergonomics Society, the Dutch Ergonomics Society, NIA TNO and

  6. Human factors issues of tactice displays for military environments

    NARCIS (Netherlands)

    Erp, J.B.F. van; Self, B.P.

    2008-01-01

    The overall goal of this chapter is to give the reader insights into the human factors issues related to the use of tactile displays. Torso-mounted displays, which are particularly suited for direction and orientation cues, are emphasized. First, perceptual issues relevant to tactile stimulation are

  7. Investigation of Multiple Human Factors in Personalized Learning

    Science.gov (United States)

    Chen, Sherry Y.; Huang, Pei-Ren; Shih, Yu-Cheng; Chang, Li-Ping

    2016-01-01

    In the past decade, a number of personalized learning systems have been developed and they mainly focus on learners' prior knowledge. On the other hand, previous research suggested that gender differences and cognitive styles have great effects on student learning. To this end, this study examines how human factors, especially gender differences…

  8. A Virtual Campus Based on Human Factor Engineering

    Science.gov (United States)

    Yang, Yuting; Kang, Houliang

    2014-01-01

    Three Dimensional or 3D virtual reality has become increasingly popular in many areas, especially in building a digital campus. This paper introduces a virtual campus, which is based on a 3D model of The Tourism and Culture College of Yunnan University (TCYU). Production of the virtual campus was aided by Human Factor and Ergonomics (HF&E), an…

  9. Factors affecting the transmission of human onchocerciasis by ...

    African Journals Online (AJOL)

    Factors affecting the transmission of human onchocerciasis by Simulium damnosum sensu lato were the focus of a study carried out in River Lewa, Etikpe, a fringe savanna village in Ikom LGA in Cross River State, Nigeria. The duration of the study was six months (August 1999 to January 2000). The thrust of the study was ...

  10. Risk factors for genital human papillomavirus among men in Tanzania

    DEFF Research Database (Denmark)

    Olesen, Tina Bech; Mwaiselage, Julius; Iftner, Thomas

    2017-01-01

    The objective of the study was to assess risk factors for Human Papillomavirus (HPV) among men in Tanzania, both overall and in relation to HIV status. In a cross-sectional study conducted among 1,813 men in Tanzania, penile swabs were tested for HPV using Hybrid Capture 2 (HC2). Study participan...

  11. Human Factors Evaluation of Advanced Electric Power Grid Visualization Tools

    Energy Technology Data Exchange (ETDEWEB)

    Greitzer, Frank L.; Dauenhauer, Peter M.; Wierks, Tamara G.; Podmore, Robin

    2009-04-01

    This report describes initial human factors evaluation of four visualization tools (Graphical Contingency Analysis, Force Directed Graphs, Phasor State Estimator and Mode Meter/ Mode Shapes) developed by PNNL, and proposed test plans that may be implemented to evaluate their utility in scenario-based experiments.

  12. Risk factors and distribution of oncogenic strains of human ...

    African Journals Online (AJOL)

    Risk factors and distribution of oncogenic strains of human papilloma virus in women presenting for cervical cancer screening in Port Harcourt, Nigeria. ... Results were presented in tables, test of significance and association done using student's t-test and Odds ratio, with P value < 0.05 as significant. Results: The age range ...

  13. Prevalence And Risk Factors For Human Pappiloma Virus Infection ...

    African Journals Online (AJOL)

    Human Pappiloma Virus (HPV) infection is a disease of global public health importance, culminating into a high risk of cervical cancer. Most of the risk factors are modifiable, thus making HPV itself preventable. Efforts towards community HPV prevention and vaccination have not yielded the desired results, most especially ...

  14. Preliminary report of Goddard/University Human Factors Research Group

    Science.gov (United States)

    Truszkowski, W.

    1983-01-01

    The three major concerns which greatly influence the initial efforts and priorities in the human factors arena are outlined. These concerns are an increased awareness of the: (1) over riding data driven aspects of current command/control systems; (2) complexity of existing man/system interface mechanisms; and (3) great extent of the manual intervention required in present systems.

  15. SafetyNet. Human factors safety training on the Internet

    DEFF Research Database (Denmark)

    Hauland, G.; Pedrali, M.

    2002-01-01

    This report describes user requirements to an Internet based distance learning system of human factors training, i.e. the SafetyNet prototype, within the aviation (pilots and air traffic control), maritime and medical domains. User requirements totraining have been elicited through 19 semi...

  16. Human Factors Research in Aircrew Performance and Training

    Science.gov (United States)

    1989-08-01

    WORKLOAD PREDICTION MODEL Dr. David B. Hamilton and Dr. Sandra M. Szabo, Project Directors The Army’s Air/Land Battle 2000 scenario presents a high-threat...measurement to workload scale development. In R. C. Sugarman (Ed.), Proceedings of the 25th annual meeting of the Human Factors Society (pp. 522-526). Santa

  17. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anet