Heparin octasaccharide decoy liposomes inhibit replication of multiple viruses

Science.gov (United States)

Hendricks, Gabriel L.; Velazquez, Lourdes; Pham, Serena; Qaisar, Natasha; Delaney, James C.; Viswanathan, Karthik; Albers, Leila; Comolli, James C.; Shriver, Zachary; Knipe, David M.; Kurt-Jones, Evelyn A.; Fygenson, Deborah K.; Trevejo, Jose M.

2016-01-01

Heparan sulfate (HS) is a ubiquitous glycosaminoglycan that serves as a cellular attachment site for a number of significant human pathogens, including respiratory syncytial virus (RSV), human parainfluenza virus 3 (hPIV3), and herpes simplex virus (HSV). Decoy receptors can target pathogens by binding to the receptor pocket on viral attachment proteins, acting as ‘molecular sinks’ and preventing the pathogen from binding to susceptible host cells. Decoy receptors functionalized with HS could bind to pathogens and prevent infection, so we generated decoy liposomes displaying HS-octasaccharide (HS-octa). These decoy liposomes significantly inhibited RSV, hPIV3, and HSV infectivity in vitro to a greater degree than the original HS-octa building block. The degree of inhibition correlated with the density of HS-octa displayed on the liposome surface. Decoy liposomes with HS-octa inhibited infection of viruses to a greater extent than either full-length heparin or HS-octa alone. Decoy liposomes were effective when added prior to infection or following the initial infection of cells in vitro. By targeting the well-conserved receptor-binding sites of HS-binding viruses, decoy liposomes functionalized with HS-octa are a promising therapeutic antiviral agent and illustrate the utility of the liposome delivery platform. PMID:25637710

Regret salience and accountability in the decoy effect

Directory of Open Access Journals (Sweden)

Terry Connolly

2013-03-01

Full Text Available Two experiments examined the impact on the decoy effect of making salient the possibility of post-decision regret, a manipulation that has been shown in several earlier studies to stimulate critical examination and improvement of decision process. Experiment 1 (N = 62 showed that making regret salient eliminated the decoy effect in a personal preference task. Experiment 2 (N = 242 replicated this finding for a different personal preference task and for a prediction task. It also replicated previous findings that external accountability demands do not reduce, and may exacerbate, the decoy effect. We interpret both effects in terms of decision justification, with different justification standards operating for different audiences. The decoy effect, in this account, turns on accepting a weak justification, which may be seen as adequate for an external audience or one's own inattentive self but inadequate under the more critical review triggered by making regret possibilities salient. Seeking justification to others (responding to accountability demands thus maintains or exacerbates the decoy effect; seeking justification to oneself (responding to regret salience reduces or eliminates it. The proposed mechanism provides a theoretical account both of the decoy effect itself and of how regret priming provides an effective debiasing procedure for it.

Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2.

Science.gov (United States)

Van Huffel, S; Delaei, F; Heyninck, K; De Valck, D; Beyaert, R

2001-08-10

The nuclear factor kappaB (NF-kappaB) plays a central role in the regulation of genes implicated in immune responses, inflammatory processes, and apoptotic cell death. The zinc finger protein A20 is a cellular inhibitor of NF-kappaB activation by various stimuli and plays a critical role in terminating NF-kappaB responses. The underlying mechanism for NF-kappaB inhibition by A20 is still unknown. A20 has been shown to interact with several proteins including tumor necrosis factor (TNF) receptor-associated factors 2 and 6, as well as the inhibitory protein of kappaB kinase (IKK) gamma protein. Here we report the cloning and characterization of ABIN-2, a previously unknown protein that binds to the COOH-terminal zinc finger domain of A20. NF-kappaB activation induced by TNF and interleukin-1 is inhibited by overexpression of ABIN-2. The latter also inhibits NF-kappaB activation induced by overexpression of receptor-interacting protein or TNF receptor-associated factor 2. In contrast, NF-kappaB activation by overexpression of IKKbeta or direct activators of the IKK complex, such as Tax, cannot be inhibited by ABIN-2. These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20.

Decoy-state quantum key distribution with two-way classical postprocessing

International Nuclear Information System (INIS)

Ma Xiongfeng; Fung, C.-H.F.; Chen Kai; Lo, H.-K.; Dupuis, Frederic; Tamaki, Kiyoshi

2006-01-01

Decoy states have recently been proposed as a useful method for substantially improving the performance of quantum key distribution (QKD) protocols when a coherent-state source is used. Previously, data postprocessing schemes based on one-way classical communications were considered for use with decoy states. In this paper, we develop two data postprocessing schemes for the decoy-state method using two-way classical communications. Our numerical simulation (using parameters from a specific QKD experiment as an example) results show that our scheme is able to extend the maximal secure distance from 142 km (using only one-way classical communications with decoy states) to 181 km. The second scheme is able to achieve a 10% greater key generation rate in the whole regime of distances. We conclude that decoy-state QKD with two-way classical postprocessing is of practical interest

Exploring decoy effects on computerized task preferences in rhesus monkeys (Macaca mulatta.

Directory of Open Access Journals (Sweden)

Audrey E. Parrish

2018-05-01

Full Text Available The asymmetric dominance effect or decoy effect emerges when a third inferior option is introduced to a choice set. The decoy option, although typically not chosen, impacts relative preference for the original two options. This decisional bias stands in contrast with rational choice theory, which dictates that choice behavior should remain consistent for the original options with the addition of different alternatives to a choice set such as the decoy. In the current study, we assessed the decoy effect in rhesus monkeys using a computerized task battery that introduced two different computerized tasks, including a matching-to-sample task and a psychomotor task called PURSUIT. Decoy tasks were designed such that they were inferior versions of these original task options, requiring longer time to completion (via slowed cursor speeds and subsequently reduced reinforcement rates. Monkeys learned to associate unique icons for each task (including for decoy tasks, and used these icons to select their preferred task from a choice set of two to three task options. Monkeys learned to perform all tasks, but did not show evidence of the decoy effect using this task preference paradigm. We discuss the role of initial task preference (and task biases, task type (symbolic vs. perceptual, and decoy effect sizes in light of these findings. We contrast the current results to previous findings of the decoy effect in rhesus monkeys using a perceptual paradigm as well as to other evidence of the decoy effect in non-primate animal species.

Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction.

Science.gov (United States)

Klaus, Miriam; Prokoph, Nina; Girbig, Mathias; Wang, Xuecong; Huang, Yong-Heng; Srivastava, Yogesh; Hou, Linlin; Narasimhan, Kamesh; Kolatkar, Prasanna R; Francois, Mathias; Jauch, Ralf

2016-05-05

The transcription factor (TF) SOX18 drives lymphatic vessel development in both embryogenesis and tumour-induced neo-lymphangiogenesis. Genetic disruption of Sox18 in a mouse model protects from tumour metastasis and established the SOX18 protein as a molecular target. Here, we report the crystal structure of the SOX18 DNA binding high-mobility group (HMG) box bound to a DNA element regulating Prox1 transcription. The crystals diffracted to 1.75Å presenting the highest resolution structure of a SOX/DNA complex presently available revealing water structure, structural adjustments at the DNA contact interface and non-canonical conformations of the DNA backbone. To explore alternatives to challenging small molecule approaches for targeting the DNA-binding activity of SOX18, we designed a set of five decoys based on modified Prox1-DNA. Four decoys potently inhibited DNA binding of SOX18 in vitro and did not interact with non-SOX TFs. Serum stability, nuclease resistance and thermal denaturation assays demonstrated that a decoy circularized with a hexaethylene glycol linker and terminal phosphorothioate modifications is most stable. This SOX decoy also interfered with the expression of a luciferase reporter under control of a SOX18-dependent VCAM1 promoter in COS7 cells. Collectively, we propose SOX decoys as potential strategy for inhibiting SOX18 activity to disrupt tumour-induced neo-lymphangiogenesis. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Contextual effects and psychological features influencing decoy options: A review and research agenda

Directory of Open Access Journals (Sweden)

David Gonzalez-Prieto

2013-01-01

Full Text Available Purpose: The purpose of this paper is to develop future research proposals aiming to contribute the extant theory which explains decoy effects.Design/methodology/approach: Firstly, a review of the existing literature about decoy options and its interactions with contextual effects that could affect their performance is presented. Next, two research proposals are presented: the introduction of a double decoy choice set and the evaluation of decoy effect under different levels of cognitive effort in a purchasing process.Findings and Originality/value: For the research proposal concerning double decoy choice sets, different hypothesis are introduced based on the different theories aiming to explain the effect of simple decoy choice sets. This hypothesis predict different outcomes for the same experimental design, fact that could provide further support for at least one of the current explanations for decoy effects. Regarding the effect of decoy options under different levels of cognitive effort, implications for experimental design for sequential purchasing process are expected. Especially for those designed with complex options, with many steps or high number of options.Originality/value: Two new research proposal approaches are presented in order enhance the current theory. Moreover, both have managerial implications concerning the real usage of decoy options in reduced choice sets as well as in sequential purchasing processes.

Myc Decoy Oligodeoxynucleotide Inhibits Growth and Modulates Differentiation of Mouse Embryonic Stem Cells as a Model of Cancer Stem Cells.

Science.gov (United States)

Johari, Behrooz; Ebrahimi-Rad, Mina; Maghsood, Faezeh; Lotfinia, Majid; Saltanatpouri, Zohreh; Teimoori-Toolabi, Ladan; Sharifzadeh, Zahra; Karimipoor, Morteza; Kadivar, Mehdi

2017-01-01

Myc (c-Myc) alone activates the embryonic stem cell-like transcriptional module in both normal and transformed cells. Its dysregulation might lead to increased cancer stem cells (CSCs) population in some tumor cells. In order to investigate the potential of Myc decoy oligodeoxynucleotides for differentiation therapy, mouse embryonic stem cells (mESCs) were used in this study as a model of CSCs. To our best of knowledge this is the first report outlining the application of Myc decoy in transcription factor decoy "TFD" strategy for inducing differentiation in mESCs. A 20-mer double-stranded Myc transcription factor decoy and scrambled oligodeoxynucleotides (ODNs) were designed, analyzed by electrophoretic mobility shift (EMSA) assay and transfected into the mESCs under 2 inhibitors (2i) condition. Further investigations were carried out using fluorescence and confocal microscopy, cell proliferation and apoptosis analysis, alkaline phosphatase and embryoid body formation assay, real-time PCR and western blotting. EMSA data showed that Myc decoy ODNs bound specifically to c-Myc protein. They were found to be localized in both cytoplasm and nucleus of mESCs. Our results revealed the potential capability of Myc decoy ODNs to decrease cell viability by (16.1±2%), to increase the number of cells arrested in G0/G1 phases and apoptosis by (14.2±3.1%) and (12.1±3.2%), respectively regarding the controls. Myc decoy could also modulate differentiation in mESCs despite the presence of 2i/LIF in our medium the presence of 2i/LIF in our medium. The optimized Myc decoy ODNs approach might be considered as a promising alternative strategy for differentiation therapy investigations. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Improving decoy databases for protein folding algorithms

KAUST Repository

Lindsey, Aaron

2014-01-01

Copyright © 2014 ACM. Predicting protein structures and simulating protein folding are two of the most important problems in computational biology today. Simulation methods rely on a scoring function to distinguish the native structure (the most energetically stable) from non-native structures. Decoy databases are collections of non-native structures used to test and verify these functions. We present a method to evaluate and improve the quality of decoy databases by adding novel structures and removing redundant structures. We test our approach on 17 different decoy databases of varying size and type and show significant improvement across a variety of metrics. We also test our improved databases on a popular modern scoring function and show that they contain a greater number of native-like structures than the original databases, thereby producing a more rigorous database for testing scoring functions.

Twin Screw Extruder Production of MTTP Decoy Flares SERDP WP-1240

National Research Council Canada - National Science Library

Campbell, Carol

2005-01-01

The objective of this effort is to develop an environmentally acceptable decoy flare formulation and process to produce aircraft decoy flares without the use of HAP or Volatile Organic Compounds (VOC...

Decoys Selection in Benchmarking Datasets: Overview and Perspectives

Science.gov (United States)

Réau, Manon; Langenfeld, Florent; Zagury, Jean-François; Lagarde, Nathalie; Montes, Matthieu

2018-01-01

Virtual Screening (VS) is designed to prospectively help identifying potential hits, i.e., compounds capable of interacting with a given target and potentially modulate its activity, out of large compound collections. Among the variety of methodologies, it is crucial to select the protocol that is the most adapted to the query/target system under study and that yields the most reliable output. To this aim, the performance of VS methods is commonly evaluated and compared by computing their ability to retrieve active compounds in benchmarking datasets. The benchmarking datasets contain a subset of known active compounds together with a subset of decoys, i.e., assumed non-active molecules. The composition of both the active and the decoy compounds subsets is critical to limit the biases in the evaluation of the VS methods. In this review, we focus on the selection of decoy compounds that has considerably changed over the years, from randomly selected compounds to highly customized or experimentally validated negative compounds. We first outline the evolution of decoys selection in benchmarking databases as well as current benchmarking databases that tend to minimize the introduction of biases, and secondly, we propose recommendations for the selection and the design of benchmarking datasets. PMID:29416509

Camouflage, Concealment, and Decoys

Science.gov (United States)

2010-11-26

otherwise dull Note. Use canned milk or powdered eggs to increase the binding properties of field-expedient paints. RADAR-ABSORBING MATERIAL 3-72. RAM... falsification of evidence, inducing him to react in a manner prejudicial to his interests. decoy An imitation in any sense of a person, an object

Adenovirus-Mediated Delivery of Decoy Hyper Binding Sites Targeting Oncogenic HMGA1 Reduces Pancreatic and Liver Cancer Cell Viability.

Science.gov (United States)

Hassan, Faizule; Ni, Shuisong; Arnett, Tyler C; McKell, Melanie C; Kennedy, Michael A

2018-03-30

High mobility group AT-hook 1 (HMGA1) protein is an oncogenic architectural transcription factor that plays an essential role in early development, but it is also implicated in many human cancers. Elevated levels of HMGA1 in cancer cells cause misregulation of gene expression and are associated with increased cancer cell proliferation and increased chemotherapy resistance. We have devised a strategy of using engineered viruses to deliver decoy hyper binding sites for HMGA1 to the nucleus of cancer cells with the goal of sequestering excess HMGA1 at the decoy hyper binding sites due to binding competition. Sequestration of excess HMGA1 at the decoy binding sites is intended to reduce HMGA1 binding at the naturally occurring genomic HMGA1 binding sites, which should result in normalized gene expression and restored sensitivity to chemotherapy. As proof of principle, we engineered the replication defective adenovirus serotype 5 genome to contain hyper binding sites for HMGA1 composed of six copies of an individual HMGA1 binding site, referred to as HMGA-6. A 70%-80% reduction in cell viability and increased sensitivity to gemcitabine was observed in five different pancreatic and liver cancer cell lines 72 hr after infection with replication defective engineered adenovirus serotype 5 virus containing the HMGA-6 decoy hyper binding sites. The decoy hyper binding site strategy should be general for targeting overexpression of any double-stranded DNA-binding oncogenic transcription factor responsible for cancer cell proliferation.

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

Science.gov (United States)

Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

2006-03-01

Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

Importance of the pharmacological profile of the bound ligand in enrichment on nuclear receptors: toward the use of experimentally validated decoy ligands.

Science.gov (United States)

Lagarde, Nathalie; Zagury, Jean-François; Montes, Matthieu

2014-10-27

The evaluation of virtual ligand screening methods is of major importance to ensure their reliability. Taking into account the agonist/antagonist pharmacological profile should improve the quality of the benchmarking data sets since ligand binding can induce conformational changes in the nuclear receptor structure and such changes may vary according to the agonist/antagonist ligand profile. We indeed found that splitting the agonist and antagonist ligands into two separate data sets for a given nuclear receptor target significantly enhances the quality of the evaluation. The pharmacological profile of the ligand bound in the binding site of the target structure was also found to be an additional critical parameter. We also illustrate that active compound data sets for a given pharmacological activity can be used as a set of experimentally validated decoy ligands for another pharmacological activity to ensure a reliable and challenging evaluation of virtual screening methods.

Comparison of four species of snails as potential decoys to intercept schistosome miracidia.

Science.gov (United States)

Laracuente, A; Brown, R A; Jobin, W

1979-01-01

Preliminary studies have shown that various species of aquatic snails may be used as decoys or "sponges" to intercept schistosome miracidia, thereby preventing the miracidia from reaching the snails which normally serve as their intermediate host. In this study, four species of snails were evaluated as candidate decoys for field trials: Marisa cornuarietis, Pomacea australis, Helisoma caribaeum, and Tarebia granifera. In the laboratory all four species caused considerable reductions in the proportion of Biomphalaria glabrata infected by miracidia of Schistosoma mansoni. The most effective decoys were M. cornuarietis and H. caribaeum, both of which caused experimental infection levels of 90% to decrease to 25% when five decoy snails were present for each target snail. When ten decoy snails were present for each target snail, the proportion infected decreased to 1%. M. cornuarietis was chosen as the candidate for field trials because it was found more frequently in Puerto Rico than was H. caribaeum. Initial field trials in two ponds showed that M. cornuarietis blocked infections at a ratio of 6 decoys to 1 target snail, confirming the laboratory results. Further studies in flowing water are needed before the technique can be generally evaluated in an endemic area.

Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors*

Science.gov (United States)

Pontejo, Sergio M.; Alejo, Ali; Alcami, Antonio

2015-01-01

The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. PMID:25940088

The Decoy Effect as a Nudge: Boosting Hand Hygiene With a Worse Option.

Science.gov (United States)

Li, Meng; Sun, Yan; Chen, Hui

2018-05-01

This article provides the first test of the decoy effect as a nudge to influence real-world behavior. The decoy effect is the phenomenon that an additional but worse option can boost the appeal of an existing option. It has been widely demonstrated in hypothetical choices, but its usefulness in real-world settings has been subject to debate. In three longitudinal experiments in food-processing factories, we tested two decoy sanitation options that were worse than the existing sanitizer spray bottle. Results showed that the presence of a decoy, but not an additional copy of the original sanitizer bottle in a different color, drastically increased food workers' hand sanitizer use from the original sanitizer bottle and, consequently, improved workers' passing rate in hand sanitary tests from 60% to 70% to above 90% for 20 days. These findings indicate that the decoy effect can be a powerful nudge technique to influence real-world behavior.

Esculetin attenuates receptor activator of nuclear factor kappa-B ligand-mediated osteoclast differentiation through c-Fos/nuclear factor of activated T-cells c1 signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Baek, Jong Min; Park, Sun-Hyang; Cheon, Yoon-Hee; Ahn, Sung-Jun [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Lee, Myeung Su [Division of Rheumatology, Department of Internal Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Oh, Jaemin, E-mail: jmoh@wku.ac.kr [Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Institute for Skeletal Disease, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kim, Ju-Young, E-mail: kimjy1014@gmail.com [Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

2015-05-29

Esculetin exerts various biological effects on anti-oxidation, anti-tumors, and anti-inflammation. However, the involvement of esculetin in the bone metabolism process, particularly osteoclast differentiation has not yet been investigated. In the present study, we first confirmed the inhibitory effect of esculetin on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation. We then revealed the relationship between esculetin and the expression of osteoclast-specific molecules to elucidate its underlying mechanisms. Esculetin interfered with the expression of c-Fos and nuclear factor of activated T cell c1 (NFATc1) both at the mRNA and protein level with no involvement in osteoclast-associated early signaling pathways, suppressing the expression of various transcription factors exclusively expressed in osteoclasts such as tartrate-resistant acid phosphatase (Trap), osteoclast-associated receptor (Oscar), dendritic cell-specific transmembrane protein (Dcstamp), osteoclast stimulatory transmembrane protein (Ocstamp), cathepsin K, αvβ3 integrin, and calcitonin receptor (Ctr). Additionally, esculetin inhibited the formation of filamentous actin (F-actin) ring-positive osteoclasts during osteoclast differentiation. However, the development of F-actin structures and subsequent bone resorbing activity of mature osteoclasts, which are observed in osteoclast/osteoblast co-culture systems were not affected by esculetin. Taken together, our results indicate for the first time that esculetin inhibits RANKL-mediated osteoclastogenesis via direct suppression of c-Fos and NFATc1 expression and exerts an inhibitory effect on actin ring formation during osteoclastogenesis. - Highlights: • We first investigated the effects of esculetin on osteoclast differentiation and function. • Our data demonstrate for the first time that esculetin can suppress osteoclastogenesis in vitro. • Esculetin acts as an inhibitor of c-Fos and NFATc1 activation. �

Effects of towed-decoys against an anti-air missile with a monopulse seeker

OpenAIRE

Yeh, Jia-Hsin

1995-01-01

This thesis evaluates the protection provided by towed decoys deployed by an aircraft during an engagement against an anti-air missile equipped with a monopulse seeker. The research emphasizes the use of passive decoys. Many of the operational parameters required before the deployment of towed-decoy are investigated, including the strength of reflection, the tether length, the direction of release, under different missile incoming directions. This thesis evaluated two reflection cases. One is...

General Theory of Decoy-State Quantum Cryptography with Dark Count Rate Fluctuation

International Nuclear Information System (INIS)

Xiang, Gao; Shi-Hai, Sun; Lin-Mei, Liang

2009-01-01

The existing theory of decoy-state quantum cryptography assumes that the dark count rate is a constant, but in practice there exists fluctuation. We develop a new scheme of the decoy state, achieve a more practical key generation rate in the presence of fluctuation of the dark count rate, and compare the result with the result of the decoy-state without fluctuation. It is found that the key generation rate and maximal secure distance will be decreased under the influence of the fluctuation of the dark count rate

Fine-scale features on bioreplicated decoys of the emerald ash borer provide necessary visual verisimilitude

Science.gov (United States)

Domingue, Michael J.; Pulsifer, Drew P.; Narkhede, Mahesh S.; Engel, Leland G.; Martín-Palma, Raúl J.; Kumar, Jayant; Baker, Thomas C.; Lakhtakia, Akhlesh

2014-03-01

The emerald ash borer (EAB), Agrilus planipennis, is an invasive tree-killing pest in North America. Like other buprestid beetles, it has an iridescent coloring, produced by a periodically layered cuticle whose reflectance peaks at 540 nm wavelength. The males perform a visually mediated ritualistic mating flight directly onto females poised on sunlit leaves. We attempted to evoke this behavior using artificial visual decoys of three types. To fabricate decoys of the first type, a polymer sheet coated with a Bragg-stack reflector was loosely stamped by a bioreplicating die. For decoys of the second type, a polymer sheet coated with a Bragg-stack reflector was heavily stamped by the same die and then painted green. Every decoy of these two types had an underlying black absorber layer. Decoys of the third type were produced by a rapid prototyping machine and painted green. Fine-scale features were absent on the third type. Experiments were performed in an American ash forest infested with EAB, and a European oak forest home to a similar pest, the two-spotted oak borer (TSOB), Agrilus biguttatus. When pinned to leaves, dead EAB females, dead TSOB females, and bioreplicated decoys of both types often evoked the complete ritualized flight behavior. Males also initiated approaches to the rapidly prototyped decoy, but would divert elsewhere without making contact. The attraction of the bioreplicated decoys was also demonstrated by providing a high dc voltage across the decoys that stunned and killed approaching beetles. Thus, true bioreplication with fine-scale features is necessary to fully evoke ritualized visual responses in insects, and provides an opportunity for developing insecttrapping technologies.

Comparative Biochemical and Functional Analysis of Viral and Human Secreted Tumor Necrosis Factor (TNF) Decoy Receptors.

Science.gov (United States)

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-06-26

The blockade of tumor necrosis factor (TNF) by etanercept, a soluble version of the human TNF receptor 2 (hTNFR2), is a well established strategy to inhibit adverse TNF-mediated inflammatory responses in the clinic. A similar strategy is employed by poxviruses, encoding four viral TNF decoy receptor homologues (vTNFRs) named cytokine response modifier B (CrmB), CrmC, CrmD, and CrmE. These vTNFRs are differentially expressed by poxviral species, suggesting distinct immunomodulatory properties. Whereas the human variola virus and mouse ectromelia virus encode one vTNFR, the broad host range cowpox virus encodes all vTNFRs. We report the first comprehensive study of the functional and binding properties of these four vTNFRs, providing an explanation for their expression profile among different poxviruses. In addition, the vTNFRs activities were compared with the hTNFR2 used in the clinic. Interestingly, CrmB from variola virus, the causative agent of smallpox, is the most potent TNFR of those tested here including hTNFR2. Furthermore, we demonstrate a new immunomodulatory activity of vTNFRs, showing that CrmB and CrmD also inhibit the activity of lymphotoxin β. Similarly, we report for the first time that the hTNFR2 blocks the biological activity of lymphotoxin β. The characterization of vTNFRs optimized during virus-host evolution to modulate the host immune response provides relevant information about their potential role in pathogenesis and may be used to improve anti-inflammatory therapies based on soluble decoy TNFRs. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Parameter optimization in biased decoy-state quantum key distribution with both source errors and statistical fluctuations

Science.gov (United States)

Zhu, Jian-Rong; Li, Jian; Zhang, Chun-Mei; Wang, Qin

2017-10-01

The decoy-state method has been widely used in commercial quantum key distribution (QKD) systems. In view of the practical decoy-state QKD with both source errors and statistical fluctuations, we propose a universal model of full parameter optimization in biased decoy-state QKD with phase-randomized sources. Besides, we adopt this model to carry out simulations of two widely used sources: weak coherent source (WCS) and heralded single-photon source (HSPS). Results show that full parameter optimization can significantly improve not only the secure transmission distance but also the final key generation rate. And when taking source errors and statistical fluctuations into account, the performance of decoy-state QKD using HSPS suffered less than that of decoy-state QKD using WCS.

Virus encoded MHC-like decoys diversify the inhibitory KIR repertoire.

Directory of Open Access Journals (Sweden)

Paola Carrillo-Bustamante

Full Text Available Natural killer (NK cells are circulating lymphocytes that play an important role in the control of viral infections and tumors. Their functions are regulated by several activating and inhibitory receptors. A subset of these receptors in human NK cells are the killer immunoglobulin-like receptors (KIRs, which interact with the highly polymorphic MHC class I molecules. One important function of NK cells is to detect cells that have down-regulated MHC expression (missing-self. Because MHC molecules have non polymorphic regions, their expression could have been monitored with a limited set of monomorphic receptors. Surprisingly, the KIR family has a remarkable genetic diversity, the function of which remains poorly understood. The mouse cytomegalovirus (MCMV is able to evade NK cell responses by coding "decoy" molecules that mimic MHC class I. This interaction was suggested to have driven the evolution of novel NK cell receptors. Inspired by the MCMV system, we develop an agent-based model of a host population infected with viruses that are able to evolve MHC down-regulation and decoy molecules. Our simulations show that specific recognition of MHC class I molecules by inhibitory KIRs provides excellent protection against viruses evolving decoys, and that the diversity of inhibitory KIRs will subsequently evolve as a result of the required discrimination between host MHC molecules and decoy molecules.

Delayed Toxicity Associated with Soluble Anthrax Toxin Receptor Decoy-Ig Fusion Protein Treatment

Science.gov (United States)

Cote, Christopher; Welkos, Susan; Manchester, Marianne; Young, John A. T.

2012-01-01

Soluble receptor decoy inhibitors, including receptor-immunogloubulin (Ig) fusion proteins, have shown promise as candidate anthrax toxin therapeutics. These agents act by binding to the receptor-interaction site on the protective antigen (PA) toxin subunit, thereby blocking toxin binding to cell surface receptors. Here we have made the surprising observation that co-administration of receptor decoy-Ig fusion proteins significantly delayed, but did not protect, rats challenged with anthrax lethal toxin. The delayed toxicity was associated with the in vivo assembly of a long-lived complex comprised of anthrax lethal toxin and the receptor decoy-Ig inhibitor. Intoxication in this system presumably results from the slow dissociation of the toxin complex from the inhibitor following their prolonged circulation. We conclude that while receptor decoy-Ig proteins represent promising candidates for the early treatment of B. anthracis infection, they may not be suitable for therapeutic use at later stages when fatal levels of toxin have already accumulated in the bloodstream. PMID:22511955

Detector decoy quantum key distribution

International Nuclear Information System (INIS)

Moroder, Tobias; Luetkenhaus, Norbert; Curty, Marcos

2009-01-01

Photon number resolving detectors can enhance the performance of many practical quantum cryptographic setups. In this paper, we employ a simple method to estimate the statistics provided by such a photon number resolving detector using only a threshold detector together with a variable attenuator. This idea is similar in spirit to that of the decoy state technique, and is especially suited to those scenarios where only a few parameters of the photon number statistics of the incoming signals have to be estimated. As an illustration of the potential applicability of the method in quantum communication protocols, we use it to prove security of an entanglement-based quantum key distribution scheme with an untrusted source without the need for a squash model and by solely using this extra idea. In this sense, this detector decoy method can be seen as a different conceptual approach to adapt a single-photon security proof to its physical, full optical implementation. We show that in this scenario, the legitimate users can now even discard the double click events from the raw key data without compromising the security of the scheme, and we present simulations on the performance of the BB84 and the 6-state quantum key distribution protocols.

Targeting the MET oncogene by concomitant inhibition of receptor and ligand via an antibody-"decoy" strategy.

Science.gov (United States)

Basilico, Cristina; Modica, Chiara; Maione, Federica; Vigna, Elisa; Comoglio, Paolo M

2018-04-25

MET, a master gene sustaining "invasive growth," is a relevant target for cancer precision therapy. In the vast majority of tumors, wild-type MET behaves as a "stress-response" gene and relies on the ligand (HGF) to sustain cell "scattering," invasive growth and apoptosis protection (oncogene "expedience"). In this context, concomitant targeting of MET and HGF could be crucial to reach effective inhibition. To test this hypothesis, we combined an anti-MET antibody (MvDN30) inducing "shedding" (i.e., removal of MET from the cell surface), with a "decoy" (i.e., the soluble extracellular domain of the MET receptor) endowed with HGF-sequestering ability. To avoid antibody/decoy interaction-and subsequent neutralization-we identified a single aminoacid in the extracellular domain of MET-lysine 842-that is critical for MvDN30 binding and engineered the corresponding recombinant decoyMET (K842E). DecoyMET K842E retains the ability to bind HGF with high affinity and inhibits HGF-induced MET phosphorylation. In HGF-dependent cellular models, MvDN30 antibody and decoyMET K842E used in combination cooperate in restraining invasive growth, and synergize in blocking cancer cell "scattering." The antibody and the decoy unbridle apoptosis of colon cancer stem cells grown in vitro as spheroids. In a preclinical model, built by orthotopic transplantation of a human pancreatic carcinoma in SCID mice engineered to express human HGF, concomitant treatment with antibody and decoy significantly reduces metastatic spread. The data reported indicate that vertical targeting of the MET/HGF axis results in powerful inhibition of ligand-dependent MET activation, providing proof of concept in favor of combined target therapy of MET "expedience." © 2018 UICC.

2006-2008 annual review on aerial infrared decoy flares

Energy Technology Data Exchange (ETDEWEB)

Koch, Ernst-Christian [NATO Munitions Safety Information Analysis Center, Brussels (Belgium)

2009-02-15

The most recent progress in the field of advanced aerial infrared decoy flare technology is documented. 71 references from the public domain are given. Recently, two reviews on progress in the field of aerial infrared decoy flares have been prepared by the author. The fast development in the field already delayed the preparation of the second report by nearly a year.Hence, the objective of the present paper is to report about recent advances in the field of aerial infrared countermeasures and related topics. The paper treats information published between January, 2005 and September, 30, 2008. Depending on the progress, it is intended to report occasionally in the future about new developments and scientific findings in this field. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction.

Science.gov (United States)

Akhter, Nasrin; Shehu, Amarda

2018-01-19

Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

From Extraction of Local Structures of Protein Energy Landscapes to Improved Decoy Selection in Template-Free Protein Structure Prediction

Directory of Open Access Journals (Sweden)

Nasrin Akhter

2018-01-01

Full Text Available Due to the essential role that the three-dimensional conformation of a protein plays in regulating interactions with molecular partners, wet and dry laboratories seek biologically-active conformations of a protein to decode its function. Computational approaches are gaining prominence due to the labor and cost demands of wet laboratory investigations. Template-free methods can now compute thousands of conformations known as decoys, but selecting native conformations from the generated decoys remains challenging. Repeatedly, research has shown that the protein energy functions whose minima are sought in the generation of decoys are unreliable indicators of nativeness. The prevalent approach ignores energy altogether and clusters decoys by conformational similarity. Complementary recent efforts design protein-specific scoring functions or train machine learning models on labeled decoys. In this paper, we show that an informative consideration of energy can be carried out under the energy landscape view. Specifically, we leverage local structures known as basins in the energy landscape probed by a template-free method. We propose and compare various strategies of basin-based decoy selection that we demonstrate are superior to clustering-based strategies. The presented results point to further directions of research for improving decoy selection, including the ability to properly consider the multiplicity of native conformations of proteins.

Antineoplastic Effect of Decoy Oligonucleotide Derived from MGMT Enhancer

Science.gov (United States)

Refael, Miri; Zrihan, Daniel; Siegal, Tali; Lavon, Iris

2014-01-01

Silencing of O(6)-methylguanine-DNA-methyltransferase (MGMT) in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1) within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA) modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN). Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy. PMID:25460932

Antineoplastic effect of decoy oligonucleotide derived from MGMT enhancer.

Directory of Open Access Journals (Sweden)

Tamar Canello

Full Text Available Silencing of O(6-methylguanine-DNA-methyltransferase (MGMT in tumors, mainly through promoter methylation, correlates with a better therapeutic response and with increased survival. Therefore, it is conceivable to consider MGMT as a potential therapeutic target for the treatment of cancers. Our previous results demonstrated the pivotal role of NF-kappaB in MGMT expression, mediated mainly through p65/NF-kappaB homodimers. Here we show that the non-canonical NF-KappaB motif (MGMT-kappaB1 within MGMT enhancer is probably the major inducer of MGMT expression following NF-kappaB activation. Thus, in an attempt to attenuate the transcription activity of MGMT in tumors we designed locked nucleic acids (LNA modified decoy oligonucleotides corresponding to the specific sequence of MGMT-kappaB1 (MGMT-kB1-LODN. Following confirmation of the ability of MGMT-kB1-LODN to interfere with the binding of p65/NF-kappaB to the NF-KappaB motif within MGMT enhancer, the efficacy of the decoy was studied in-vitro and in-vivo. The results of these experiments show that the decoy MGMT-kB1-LODN have a substantial antineoplastic effect when used either in combination with temozolomide or as monotherapy. Our results suggest that MGMT-kB1-LODN may provide a novel strategy for cancer therapy.

Agmatine inhibits nuclear factor-κB nuclear translocation in acute spinal cord compression injury rat model

Directory of Open Access Journals (Sweden)

Doaa M. Samy

2016-09-01

Full Text Available Secondary damage after acute spinal cord compression injury (SCCI exacerbates initial insult. Nuclear factor kappa-B (NF-κB-p65 activation is involved in SCCI deleterious effects. Agmatine (Agm showed neuroprotection against various CNS injuries. However, Agm impact on NF-κB signaling in acute SCCI remains to be investigated. The present study compared the effectiveness of Agm therapy and decompression laminectomy (DL in functional recovery, oxidative stress, inflammatory and apoptotic responses, and modulation of NF-κB activation in acute SCCI rat model. Rats were either sham-operated or subjected to SCCI at T8–9, using 2-Fr. catheter. SCCI rats were randomly treated with DL at T8–9, intraperitoneal Agm (100 mg/kg/day, combined (DL/Agm treatment or saline (n = 16/group. After 28-days of neurological follow-up, spinal cords were either subjected to biochemical measurement of oxidative stress and inflammatory markers or histopathology and immuno-histochemistry for NF-κB-p65 and caspase-3 expression (n = 8/group. Agm was comparable to DL in facilitating neurological functions recovery, reducing inflammation (TNF-α/interleukin-6, and apoptosis. Agm was distinctive in combating oxidative stress. Agm neuroprotective effects were paralleled with inhibition of NF-κB-p65 nuclear translocation. Combined pharmacological and surgical interventions were proved superior in functional recovery. In conclusion, present research suggested a new mechanism for Agm neuroprotection in rats SCCI through inhibition of NF-κB activation.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

Energy Technology Data Exchange (ETDEWEB)

Park, Serk In, E-mail: serkin@korea.edu [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); The BK21 Plus Program for Biomedical Sciences, Korea University College of Medicine, Seoul (Korea, Republic of); Department of Medicine and Center for Bone Biology, Vanderbilt University School of Medicine, Nashville, TN (United States); Park, Sung-Jun [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Laboratory of Obesity and Aging Research, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD (United States); Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of); Park, Yun Gyu, E-mail: parkyg@korea.ac.kr [Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul (Korea, Republic of)

2016-01-15

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

Inhibition of cyclic AMP response element-directed transcription by decoy oligonucleotides enhances tumor-specific radiosensitivity

International Nuclear Information System (INIS)

Park, Serk In; Park, Sung-Jun; Lee, Junghan; Kim, Hye Eun; Park, Su Jin; Sohn, Jeong-Won; Park, Yun Gyu

2016-01-01

The radiation stress induces cytotoxic responses of cell death as well as cytoprotective responses of cell survival. Understanding exact cellular mechanism and signal transduction pathways is important in improving cancer radiotherapy. Increasing evidence suggests that cyclic AMP response element binding protein (CREB)/activating transcription factor (ATF) family proteins act as a survival factor and a signaling molecule in response to stress. We postulated that CREB inhibition via CRE decoy oligonucleotide increases tumor cell sensitization to γ-irradiation-induced cytotoxic stress. In the present study, we demonstrate that CREB phosphorylation and CREB DNA-protein complex formation increased in time- and radiation dose-dependent manners, while there was no significant change in total protein level of CREB. In addition, CREB was phosphorylated in response to γ-irradiation through p38 MAPK pathway. Further investigation revealed that CREB blockade by decoy oligonucleotides functionally inhibited transactivation of CREB, and significantly increased radiosensitivity of multiple human cancer cell lines including TP53- and/or RB-mutated cells with minimal effects on normal cells. We also demonstrate that tumor cells ectopically expressing dominant negative mutant CREB (KCREB) and the cells treated with p38 MAPK inhibitors were more sensitive to γ-irradiation than wild type parental cells or control-treated cells. Taken together, we conclude that CREB protects tumor cells from γ-irradiation, and combination of CREB inhibition plus ionizing radiation will be a promising radiotherapeutic approach. - Highlights: • γ-Irradiation induced CREB phosphorylation and CRE-directed transcription in tumor. • γ-Irradiation-induced transcriptional activation of CREB was via p38 MAPK pathway. • CRE blockade increased radiosensitivity of tumor cells but not of normal cells. • CRE decoy oligonucleotides or p38 MAPK inhibitors can be used as radiosensitizers.

G4-DNA formation in the HRAS promoter and rational design of decoy oligonucleotides for cancer therapy.

Directory of Open Access Journals (Sweden)

Alexandro Membrino

Full Text Available HRAS is a proto-oncogene involved in the tumorigenesis of urinary bladder cancer. In the HRAS promoter we identified two G-rich elements, hras-1 and hras-2, that fold, respectively, into an antiparallel and a parallel quadruplex (qhras-1, qhras-2. When we introduced in sequence hras-1 or hras-2 two point mutations that block quadruplex formation, transcription increased 5-fold, but when we stabilized the G-quadruplexes by guanidinium phthalocyanines, transcription decreased to 20% of control. By ChIP we found that sequence hras-1 is bound only by MAZ, while hras-2 is bound by MAZ and Sp1: two transcription factors recognizing guanine boxes. We also discovered by EMSA that recombinant MAZ-GST binds to both HRAS quadruplexes, while Sp1-GST only binds to qhras-1. The over-expression of MAZ and Sp1 synergistically activates HRAS transcription, while silencing each gene by RNAi results in a strong down-regulation of transcription. All these data indicate that the HRAS G-quadruplexes behave as transcription repressors. Finally, we designed decoy oligonucleotides mimicking the HRAS quadruplexes, bearing (R-1-O-[4-(1-Pyrenylethynyl phenylmethyl] glycerol and LNA modifications to increase their stability and nuclease resistance (G4-decoys. The G4-decoys repressed HRAS transcription and caused a strong antiproliferative effect, mediated by apoptosis, in T24 bladder cancer cells where HRAS is mutated.

Practical long-distance quantum key distribution system using decoy levels

International Nuclear Information System (INIS)

Rosenberg, D; Peterson, C G; Harrington, J W; Rice, P R; Dallmann, N; Tyagi, K T; McCabe, K P; Hughes, R J; Nordholt, J E; Nam, S; Baek, B; Hadfield, R H

2009-01-01

Quantum key distribution (QKD) has the potential for widespread real-world applications, but no secure long-distance experiment has demonstrated the truly practical operation needed to move QKD from the laboratory to the real world due largely to limitations in synchronization and poor detector performance. Here, we report results obtained using a fully automated, robust QKD system based on the Bennett Brassard 1984 (BB84) protocol with low-noise superconducting nanowire single-photon detectors (SNSPDs) and decoy levels to produce a secret key with unconditional security over a record 140.6 km of optical fibre, an increase of more than a factor of five compared with the previous record for unconditionally secure key generation in a practical QKD system.

Lipid-modified G4-decoy oligonucleotide anchored to nanoparticles

DEFF Research Database (Denmark)

Cogoi, S; Jakobsen, U; Pedersen, E B

2016-01-01

KRAS is mutated in >90% of pancreatic ductal adenocarcinomas. As its inactivation leads to tumour regression, mutant KRAS is considered an attractive target for anticancer drugs. In this study we report a new delivery strategy for a G4-decoy oligonucleotide that sequesters MAZ, a transcription fa...

Renin-angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B.

Science.gov (United States)

Saber, Sameh; Mahmoud, Amr A A; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

2018-06-01

Therapeutic interventions for liver fibrosis are still limited due to the complicated molecular pathogenesis. Renin-angiotensin system (RAS) seems to contribute to the development of hepatic fibrosis. Therefore, we aimed to examine the effect of RAS inhibition on CCl 4 -induced liver fibrosis. Mice were treated with silymarin (30 mg·kg -1 ), perindopril (1 mg·kg -1 ), fosinopril (2 mg·kg -1 ), or losartan (10 mg·kg -1 ). The administration of RAS inhibitors improved liver histology and decreased protein expression of alpha smooth muscle actin (α-SMA) and hepatic content of hydroxyproline. These effects found to be mediated via inactivation of nuclear transcription factor kappa B (NFκB) pathway by the inhibition of NFκB p65 phosphorylation at the Ser536 residue and phosphorylation-induced degradation of nuclear factor kappa-B inhibitor alpha (NFκBia) subsequently inhibited NFκB-induced TNF-α and TGF-β1, leading to lower levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and vascular endothelial growth factor (VEGF). We concluded that the tissue affinity of the angiotensin converting enzyme inhibitors (ACEIs) has no impact on its antifibrotic activity and that interfering the RAS either through the inhibition of ACE or the blockade of AT1R has the same therapeutic benefit. These results suggest RAS inhibitors as promising candidates for further clinical trials in the management of hepatic fibrosis.

Quantum secure direct communication network with superdense coding and decoy photons

International Nuclear Information System (INIS)

Deng Fuguo; Li Xihan; Li Chunyan; Zhou Ping; Zhou Hongyu

2007-01-01

A quantum secure direct communication network scheme is proposed with quantum superdense coding and decoy photons. The servers on a passive optical network prepare and measure the quantum signal, i.e. a sequence of the d-dimensional Bell states. After confirming the security of the photons received from the receiver, the sender codes his secret message on them directly. For preventing a dishonest server from eavesdropping, some decoy photons prepared by measuring one photon in the Bell states are used to replace some original photons. One of the users on the network can communicate to any other one. This scheme has the advantage of high capacity, and it is more convenient than others as only a sequence of photons is transmitted in quantum line

Immunodeficiency associated with a nonsense mutation of IKBKB

DEFF Research Database (Denmark)

Nielsen, Christian; Jakobsen, Marianne A; Larsen, Martin Jakob

2014-01-01

We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory insufficie......We report an infant of consanguineous parents of Turkish decent with a novel immunodeficiency associated with homozygosity for a nonsense mutation of the gene encoding Inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ). At five months, she presented with respiratory...... no explanation before whole exome sequencing revealed a novel mutation abrogating signaling through the canonical NF-κB pathway....

Surveillance of Influenza Viruses in Waterfowl Used As Decoys in Andalusia, Spain

Science.gov (United States)

Jurado-Tarifa, Estefanía; Napp, Sebastian; Gómez-Pacheco, Juan Manuel; Fernández-Morente, Manuel; Jaén-Téllez, Juan Antonio; Arenas, Antonio; García-Bocanegra, Ignacio

2014-01-01

A longitudinal study was carried out to determine the seroprevalence of avian influenza viruses (AIVs) in waterfowl used as decoys in Andalusia, southern Spain. A total of 2319 aquatic birds from 193 flocks were analyzed before and after the hunting season 2011–2012. In the first sampling, 403 out of 2319 (18.0%, CI95%: 15.8–19.0) decoys showed antibodies against AIVs by ELISA. The AI seroprevalence was significantly higher in geese (21.0%) than in ducks (11.7%) (P<0.001). Besides, the spatial distribution of AIVs was not homogeneous as significant differences among regions were observed. The prevalence of antibodies against AIVs subtypes H5 and H7 were 1.1% and 0.3%, respectively, using hemagglutination inhibition test (HI). The overall and H5 seroprevalences slightly increased after the hunting period (to 19.2% and 1.4%, respectively), while the H7 seroprevalence remained at the same level (0.3%). The proportion of flocks infected by AIVs was 65.3%, while 11.2% and 4.9% of flocks were positive for H5 and H7, respectively. Viral shedding was not detected in any of the 47 samples positive by both ELISA and HI, tested by RRT-PCR. The individual incidence after the hunting season was 3.4%. The fact that 57 animals seroconverted, 15 of which were confirmed by HI (12 H5 and 3 H7), was indication of contact with AIVs during the hunting period. The results indicate that waterfowl used as decoys are frequently exposed to AIVs and may be potentially useful as sentinels for AIVs monitoring. The seroprevalence detected and the seropositivity against AIVs H5 and H7, suggest that decoys can act as reservoirs of AIVs, which may be of animal and public health concern. PMID:24901946

NF-κB decoy oligodeoxynucleotide mitigates wear particle-associated bone loss in the murine continuous infusion model.

Science.gov (United States)

Lin, Tzu-Hua; Pajarinen, Jukka; Sato, Taishi; Loi, Florence; Fan, Changchun; Córdova, Luis A; Nabeshima, Akira; Gibon, Emmanuel; Zhang, Ruth; Yao, Zhenyu; Goodman, Stuart B

2016-09-01

Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Wear particle-induced chronic inflammation is associated with the development of periprosthetic osteolysis. Modulation of NF-κB signaling in macrophages, osteoclasts, and mesenchymal stem cells could potentially mitigate this disease. In the current study, we examined the effects of local delivery of decoy NF-κB oligo-deoxynucleotide (ODN) on wear particle-induced bone loss in a murine continuous femoral particle infusion model. Ultra-high molecular weight polyethylene particles (UHMWPE) with or without lipopolysaccharide (LPS) were infused via osmotic pumps into hollow titanium rods placed in the distal femur of mice for 4weeks. Particle-induced bone loss was evaluated by μCT, and immunohistochemical analysis of sections from the femur. Particle infusion alone resulted in reduced bone mineral density and trabecular bone volume fraction in the distal femur. The decoy ODN reversed the particle-associated bone volume fraction loss around the implant, irrespective of the presence of LPS. Particle-infusion with LPS increased bone mineral density in the distal femur compared with particle-infusion alone. NF-κB decoy ODN reversed or further increased the bone mineral density in the femur (3-6mm from the distal end) exposed to particles alone or particles plus LPS. NF-κB decoy ODN also inhibited macrophage infiltration and osteoclast number, but had no significant effects on osteoblast numbers in femurs exposed to wear particles and LPS. Our study suggests that targeting NF-κB activity via local delivery of decoy ODN has great potential to mitigate wear particle-induced osteolysis. Total joint replacement is a cost-effective surgical procedure for patients with end-stage arthritis. Chronic inflammation is crucial for the development of wear particle-associated bone loss. Modulation of NF-κB signaling in macrophages (pro-inflammatory cells), osteoclasts (bone

Tumor endothelium marker-8 based decoys exhibit superiority over capillary morphogenesis protein-2 based decoys as anthrax toxin inhibitors.

Directory of Open Access Journals (Sweden)

Chenguang Cai

Full Text Available Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA, lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8 and capillary morphogenesis protein-2 (CMG2 can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA domain of CMG2 (sCMG2, have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8 was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.

DECOY: Documenting Experiences with Cigarettes and Other Tobacco in Young Adults

Science.gov (United States)

Berg, Carla J.; Haardörfer, Regine; Lewis, Michael; Getachew, Betelihem; Lloyd, Steven A.; Thomas, Sarah Fretti; Lanier, Angela; Trepanier, Kelleigh; Johnston, Teresa; Grimsley, Linda; Foster, Bruce; Benson, Stephanie; Smith, Alicia; Barr, Dana Boyd; Windle, Michael

2016-01-01

Objectives We examined psychographic characteristics associated with tobacco use among Project DECOY participants. Methods Project DECOY is a 2-year longitudinal mixed-methods study examining risk for tobacco use among 3418 young adults across 7 Georgia colleges/universities. Baseline measures included sociodemographics, tobacco use, and psychographics using the Values, Attitudes, and Lifestyle Scale. Bivariate and multivariable analyses were conducted to identify correlates of tobacco use. Results Past 30-day use prevalence was: 13.3% cigarettes; 11.3% little cigars/cigarillos (LCCs); 3.6% smokeless tobacco; 10.9% e-cigarettes; and 12.2% hookah. Controlling for sociodemographics, correlates of cigarette use included greater novelty seeking (p fashion orientation (p = .007). Correlates of smokeless tobacco use included greater novelty seeking (p = .006) and less intellectual curiosity (p fashion orientation (p = .044), and self-focused thinking (p = .002), and less social conservatism (p products. PMID:27103410

Towards creating believable decoy project folders for detecting data theft

NARCIS (Netherlands)

Thaler, S.; den Hartog, J.; Petkovic, M.

2016-01-01

Digital data theft is difficult to detect and typically it also takes a long time to discover that data has been stolen. This paper introduces a data-driven approach based on Markov chains to create believable decoy project folders which can assist in detecting potentially ongoing attacks. This can

Genetic diversity and antimicrobial resistance of Campylobacter and Salmonella strains isolated from decoys and raptors.

Science.gov (United States)

Jurado-Tarifa, E; Torralbo, A; Borge, C; Cerdà-Cuéllar, M; Ayats, T; Carbonero, A; García-Bocanegra, I

2016-10-01

Infections caused by thermotolerant Campylobacter spp. and Salmonella spp. are the leading causes of human gastroenteritis worldwide. Wild birds can act as reservoirs of both pathogens. A survey was carried out to determine the prevalence, genetic diversity and antimicrobial resistance of thermotolerant Campylobacter and Salmonella in waterfowl used as decoys and wild raptors in Andalusia (Southern Spain). The overall prevalence detected for Campylobacter was 5.9% (18/306; CI95%: 3.25-8.52) in decoys and 2.3% (9/387; CI95%: 0.82-3.83) in wild raptors. Isolates were identified as C. jejuni, C. coli and C. lari in both bird groups. Salmonella was isolated in 3.3% (10/306; CI95%: 2.3-4.3) and 4.6% (18/394; CI95%: 3.5-5.6) of the decoys and raptors, respectively. Salmonella Enteritidis and Typhimurium were the most frequently identified serovars, although Salmonella serovars Anatum, Bredeney, London and Mikawasima were also isolated. Pulsed-field gel electrophoresis analysis of isolates showed higher genetic diversity within Campylobacter species compared to Salmonella serovars. Campylobacter isolates showed resistance to gentamicin, ciprofloxacin and tetracycline, while resistance to erythromycin and tetracycline was found in Salmonella isolates. The results indicate that both decoys and raptors can act as natural carriers of Campylobacter and Salmonella in Spain, which may have important implications for public and animal health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Diclofenac inhibits tumor necrosis factor-α-induced nuclear factor-κB activation causing synergistic hepatocyte apoptosis.

Science.gov (United States)

Fredriksson, Lisa; Herpers, Bram; Benedetti, Giulia; Matadin, Quraisha; Puigvert, Jordi C; de Bont, Hans; Dragovic, Sanja; Vermeulen, Nico P E; Commandeur, Jan N M; Danen, Erik; de Graauw, Marjo; van de Water, Bob

2011-06-01

Drug-induced liver injury (DILI) is an important clinical problem. It involves crosstalk between drug toxicity and the immune system, but the exact mechanism at the cellular hepatocyte level is not well understood. Here we studied the mechanism of crosstalk in hepatocyte apoptosis caused by diclofenac and the proinflammatory cytokine tumor necrosis factor α (TNF-α). HepG2 cells were treated with diclofenac followed by TNF-α challenge and subsequent evaluation of necrosis and apoptosis. Diclofenac caused a mild apoptosis of HepG2 cells, which was strongly potentiated by TNF-α. A focused apoptosis machinery short interference RNA (siRNA) library screen identified that this TNF-α-mediated enhancement involved activation of caspase-3 through a caspase-8/Bid/APAF1 pathway. Diclofenac itself induced sustained activation of c-Jun N-terminal kinase (JNK) and inhibition of JNK decreased both diclofenac and diclofenac/TNF-α-induced apoptosis. Live cell imaging of GFPp65/RelA showed that diclofenac dampened the TNF-α-mediated nuclear factor kappaB (NF-κB) translocation oscillation in association with reduced NF-κB transcriptional activity. This was associated with inhibition by diclofenac of the TNF-α-induced phosphorylation of the inhibitor of NF-κB alpha (IκBα). Finally, inhibition of IκB kinase β (IKKβ) with BMS-345541 as well as stable lentiviral short hairpin RNA (shRNA)-based knockdown of p65/RelA sensitized hepatocytes towards diclofenac/TNF-α-induced cytotoxicity. Together, our data suggest a model whereby diclofenac-mediated stress signaling suppresses TNF-α-induced survival signaling routes and sensitizes cells to apoptosis. Copyright © 2011 American Association for the Study of Liver Diseases.

Testing the effect of time pressure on asymmetric dominance and compromise decoys in choice

Directory of Open Access Journals (Sweden)

Jonathan Pettibone

2012-07-01

Full Text Available Dynamic, connectionist models of decision making, such as decision field theory (Roe, Busemeyer, and Townsend, 2001, propose that the effect of context on choice arises from a series of pairwise comparisons between attributes of alternatives across time. As such, they predict that limiting the amount of time to make a decision should decrease rather than increase the size of contextual effects. This prediction was tested across four levels of time pressure on both the asymmetric dominance (Huber, Payne, and Puto, 1982 and compromise (Simonson, 1989 decoy effects in choice. Overall, results supported this prediction, with both types of decoy effects found to be larger as time pressure decreased.

Circumvention of nuclear factor kappaB-induced chemoresistance by cytoplasmic-targeted anthracyclines.

Science.gov (United States)

Bilyeu, Jennifer D; Panta, Ganesh R; Cavin, Lakita G; Barrett, Christina M; Turner, Eddie J; Sweatman, Trevor W; Israel, Mervyn; Lothstein, Leonard; Arsura, Marcello

2004-04-01

Nuclear factor kappaB (NF-kappaB) has been implicated in inducible chemoresistance against anthracyclines. In an effort to improve the cytotoxicity of anthracyclines while reducing their cardiotoxic effects, we have developed a novel class of extranuclear-localizing 14-O-acylanthracyclines that bind to the phorbol ester/diacylglycerol-binding C1b domain of conventional and novel protein kinase C (PKC) isoforms, thereby promoting an apoptotic response. Because PKCs have been shown to be involved in NF-kappaB activation, in this report, we determined the mechanism of NF-kappaB activation by N-benzyladriamycin-14-valerate (AD 198) and N-benzyladriamycin-14-pivalate (AD 445), two novel 14-O-acylanthracylines. We show that the induction of NF-kappaB activity in response to drug treatment relies on the activation of PKC-delta and NF-kappaB-activating kinase (NAK), independent of ataxia telengectasia mutated and p53 activities. In turn, NAK activates the IKK complex through phosphorylation of the IKK-2 subunit. We find that neither NF-kappaB activation nor ectopic expression of Bcl-X(L) confers protection from AD 198-induced cell killing. Overall, our data indicate that activation of novel PKC isoforms by cytoplasmic-targeted 14-O-acylanthracyclines promotes an apoptotic response independent of DNA damage, which is unimpeded by inducible activation of NF-kappaB.

Monitoring of West Nile virus, Usutu virus and Meaban virus in waterfowl used as decoys and wild raptors in southern Spain.

Science.gov (United States)

Jurado-Tarifa, E; Napp, S; Lecollinet, S; Arenas, A; Beck, C; Cerdà-Cuéllar, M; Fernández-Morente, M; García-Bocanegra, I

2016-12-01

In the last decade, the number of emerging flaviviruses described worldwide has increased considerably, with wild birds acting as the main reservoir hosts of these viruses. We carried out an epidemiological survey to determine the seroprevalence of antigenically related flaviviruses, particularly West Nile virus (WNV), Usutu virus (USUV) and Meaban virus (MBV), in waterfowl used as decoys and wild raptors in Andalusia (southern Spain), the region considered to have the highest risk of flaviviruses circulation in Spain. The overall flaviviruses seroprevalence according to bELISA was 13.0% in both in decoys (n=1052) and wild raptors (n=123). Specific antibodies against WNV, USUV and MBV were confirmed by micro virus neutralization tests in 12, 38 and 4 of the seropositive decoys, respectively. This is the first study on WNV and USUV infections in decoys and the first report of MBV infections in waterfowl and raptors. Moreover we report the first description of WNV infections in short-toed snake eagle (Circaetus gallicus) and Montagu's harrier (Circus pygargus). The seropositivity obtained indicates widespread but not homogeneous distribution of WNV and USUV in Andalusia. The results also confirm endemic circulation of WNV, USUV and MBV in both decoys and wild raptors in southern Spain. Our results highlight the need to implement surveillance and control programs not only for WNV but also for other related flaviviruses. Further research is needed to determine the eco-epidemiological role that waterfowl and wild raptors play in the transmission of emerging flaviviruses, especially in decoys, given their close interactions with humans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Assessment of semiempirical enthalpy of formation in solution as an effective energy function to discriminate native-like structures in protein decoy sets.

Science.gov (United States)

Urquiza-Carvalho, Gabriel Aires; Fragoso, Wallace Duarte; Rocha, Gerd Bruno

2016-08-05

In this work, we tested the PM6, PM6-DH+, PM6-D3, and PM7 enthalpies of formation in aqueous solution as scoring functions across 33 decoy sets to discriminate native structures or good models in a decoy set. In each set these semiempirical quantum chemistry methods were compared according to enthalpic and geometric criteria. Enthalpically, we compared the methods according to how much lower was the enthalpy of each native, when compared with the mean enthalpy of its set. Geometrically, we compared the methods according to the fraction of native contacts (Q), which is a measure of geometric closeness between an arbitrary structure and the native. For each set and method, the Q of the best decoy was compared with the Q0 , which is the Q of the decoy closest to the native in the set. It was shown that the PM7 method is able to assign larger energy differences between the native structure and the decoys in a set, arguably because of a better description of dispersion interactions, however PM6-DH+ was slightly better than the rest at selecting geometrically good models in the absence of a native structure in the set. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Decoy-state quantum key distribution with both source errors and statistical fluctuations

International Nuclear Information System (INIS)

Wang Xiangbin; Yang Lin; Peng Chengzhi; Pan Jianwei

2009-01-01

We show how to calculate the fraction of single-photon counts of the 3-intensity decoy-state quantum cryptography faithfully with both statistical fluctuations and source errors. Our results rely only on the bound values of a few parameters of the states of pulses.

An Effectiveness Analysis of the Tactical Employment of Decoys

Science.gov (United States)

1994-06-03

desert made it impossible to hide the dense concentration of vehicles in the three assembly areas: 1st Armoured Division in Assembly Area (AA) Murrayfield...North, 24th Armoured Brigade in AA Murrayfield South, and 10th Armoured Division in AA Melting Pot. However, an ingenious combination of decoys and...hood, configured to resemble an ammo carrier, was often draped over tanks to disguise thenm12 To reinforce the story that the British main attack would

Chalepin: A Compound from Ruta angustifolia L. Pers Exhibits Cell Cycle Arrest at S phase, Suppresses Nuclear Factor-Kappa B (NF-κB) Pathway, Signal Transducer and Activation of Transcription 3 (STAT3) Phosphorylation and Extrinsic Apoptotic Pathway in Non-small Cell Lung Cancer Carcinoma (A549).

Science.gov (United States)

Richardson, Jaime Stella Moses; Aminudin, Norhaniza; Abd Malek, Sri Nurestri

2017-10-01

transducer and activation of transcription 3, and extrinsic apoptotic pathway and also its ability to arrest cell cycle in S phase. This compound was from the leaves of Ruta angustifolia L. Pers. It provides new insight on the ability of this plant in suppressing certain cancers, especially the nonsmall cell lung carcinoma according to this study. Abbreviations used: °C: Degree Celsius, ANOVA: Analysis of variance, ATCC: American Type Culture Collection, BCL-2: B-Cell CLL/Lymphoma 2, Bcl-xL: B-cell lymphoma extra-large, BH3: Bcl-2 homology 3, BID: BH3-interacting domain death agonist, BIR: Baculovirus inhibitor of apoptosis protein repeat, Caspases: Cysteinyl aspartate-specific proteases, CDK: Cyclin-dependent kinase, CO 2 : Carbon dioxide, CST: Cell signaling technologies, DISC: Death-inducing signaling complex, DMSO: Dimethyl sulfoxide, DNA: Deoxyribonucleic acid, DR4: Death receptor 4, DR5: Death receptor 5, E1a: Adenovirus early region 1A, ECL: Enhanced chemiluminescence, EDTA: Ethylenediaminetetraacetic acid, ELISA: Enzyme-linked immunosorbent assay, etc.: Etcetera, FADD: Fas-associated protein with death domain, FBS: Fetal bovine serum, FITC: Fluorescein isothiocyanate, G1: Gap 1, G2: Gap 2, HPLC: High-performance liquid chromatography, HRP: Horseradish peroxidase, IAPs: Inhibitor of apoptosis proteins, IC50: Inhibitory concentration at half maximal inhibitory, IKK-α: Inhibitor of nuclear factor kappa-B kinase subunit alpha, IKK-β: Inhibitor of nuclear factor kappa-B kinase subunit beta, IKK-γ: Inhibitor of nuclear factor kappa-B kinase subunit gamma, IKK: IκB kinase, IkBα: Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, m: Meter, M: Mitotic, mm: Millimeter, mRNA: Messenger ribonucleic acid, NaCl: Sodium chloride, NaVO4: Sodium orthovanadate, NEMO: NF-Kappa-B essential modulator, NF-κB: Nuclear factor kappa-light chain-enhancer of activated B cells, NSCLC: Nonsmall cell lung carcinoma, PBS: Phosphate buffered saline, PGE2

Modeling, Simulation, and Analysis of a Decoy State Enabled Quantum Key Distribution System

Science.gov (United States)

2015-03-26

ltsnet.net Colin V. McLaughlin Research Physicist, Advanced Photonics Naval Research Laboratory, Washington, DC 20375 Colin.Mclaughlin@nrl.navy.mil...and dirty version. In this figure, the green and red decoy Y1 yields appear to vary more than the black and blue signal Y1 yields. As illustrated

A decoy set for the thermostable subdomain from chicken villin headpiece, comparison of different free energy estimators

Directory of Open Access Journals (Sweden)

Tosatto Silvio CE

2005-12-01

Full Text Available Abstract Background Estimators of free energies are routinely used to judge the quality of protein structural models. As these estimators still present inaccuracies, they are frequently evaluated by discriminating native or native-like conformations from large ensembles of so-called decoy structures. Results A decoy set is obtained from snapshots taken from 5 long (100 ns molecular dynamics (MD simulations of the thermostable subdomain from chicken villin headpiece. An evaluation of the energy of the decoys is given using: i a residue based contact potential supplemented by a term for the quality of dihedral angles; ii a recently introduced combination of four statistical scoring functions for model quality estimation (FRST; iii molecular mechanics with solvation energy estimated either according to the generalized Born surface area (GBSA or iv the Poisson-Boltzmann surface area (PBSA method. Conclusion The decoy set presented here has the following features which make it attractive for testing energy scoring functions: 1 it covers a broad range of RMSD values (from less than 2.0 Å to more than 12 Å; 2 it has been obtained from molecular dynamics trajectories, starting from different non-native-like conformations which have diverse behaviour, with secondary structure elements correctly or incorrectly formed, and in one case folding to a native-like structure. This allows not only for scoring of static structures, but also for studying, using free energy estimators, the kinetics of folding; 3 all structures have been obtained from accurate MD simulations in explicit solvent and after molecular mechanics (MM energy minimization using an implicit solvent method. The quality of the covalent structure therefore does not suffer from steric or covalent problems. The statistical and physical effective energy functions tested on the set behave differently when native simulation snapshots are included or not in the set and when averaging over the

The relationship of plasma decoy receptor 3 and coronary collateral circulation in patients with coronary artery disease.

Science.gov (United States)

Yan, Youyou; Song, Dandan; Liu, Lulu; Meng, Xiuping; Qi, Chao; Wang, Junnan

2017-11-15

Previously, decoy receptor 3 (DcR3) was found to be a potential angiogenetic factor, while the relationship of DcR3 with coronary collateral circulation formation has not been investigated. In this study, we aimed to investigate whether plasma decoy receptor 3 levels was associated with CCC formation and evaluate its predictive power for CCC status in patients with coronary artery disease. Among patients who underwent coronary angiography with coronary artery disease and had a stenosis of ≥90% were included in our study. Collateral degree was graded according to Rentrope Cohen classification. Patients with grade 2 or 3 collateral degree were enrolled in good CCC group and patients with grade 0 or 1 collateral degree were enrolled in poor CCC group. Plasma DcR3 level was significantly higher in good CCC group (328.00±230.82 vs 194.84±130.63ng/l, p<0.01) and positively correlated with Rentrope grade (p<0.01). In addition, plasma DcR3 was also positively correlated with VEGF-A. Both ROC (receiver operating characteristic curve) and multinomial logistical regression analysis showed that plasma DcR3 displayed potent predictive power for CCC status. Higher plasma DcR3 level was related to better CCC formation and displayed potent predictive power for CCC status. Copyright © 2017. Published by Elsevier Inc.

Demand: a total nuclear disarmament

International Nuclear Information System (INIS)

Hessel, Stephane; Jacquard, Albert

2012-01-01

This bibliographical note presents a book, in which the authors make a plea for a total nuclear disarmament. They think that humanity cannot be found in competition, but in emulation, and examine how we can get rid of the nuclear bomb. They discuss the background of nuclear energy, state that nuclear weapons have always been useless and extremely dangerous, consider arms race as crazy and as a crime against humanity, recall that nuclear weapons already made numerous victims (Hiroshima, Nagasaki, nuclear tests), that they are a sword of Damocles over 7 billions human beings, that nuclear winter would be an apocalypse, that the Non Proliferation Treaty is a decoy. They discuss the political role of nuclear weapons, and outline that the only solution is their abolition. They discuss what has already been done and what is still to be done, and formulate a strategy for the future

Rutin has anti-asthmatic effects in an ovalbumin-induced asthmatic ...

African Journals Online (AJOL)

Purpose: To investigate the anti-asthmatic effects of the flavonoid rutin in an ovalbumin (OVA)-induced asthmatic mouse ... protection in asthmatic mice, via downregulation of inflammatory ..... cytokine production by bone marrow-derived dendritic cells stimulated with ... Increased nuclear factor kappaB activity in milk cells of.

Inhibition of nuclear factor kappaB proteins-platinated DNA interactions correlates with cytotoxic effectiveness of the platinum complexes

Czech Academy of Sciences Publication Activity Database

Brabec, Viktor; Kašpárková, Jana; Kostrhunová, Hana; Farrell, N.P.

2016-01-01

Roč. 6, AUG2016 (2016), č. článku 28474. ISSN 2045-2322 R&D Projects: GA MŠk(CZ) LH13096 Institutional support: RVO:68081707 Keywords : interstrand cross-links * group domain proteins Subject RIV: BO - Biophysics Impact factor: 4.259, year: 2016

Effect of particle size on hydroxyapatite crystal-induced tumor necrosis factor alpha secretion by macrophages.

Science.gov (United States)

Nadra, Imad; Boccaccini, Aldo R; Philippidis, Pandelis; Whelan, Linda C; McCarthy, Geraldine M; Haskard, Dorian O; Landis, R Clive

2008-01-01

Macrophages may promote a vicious cycle of inflammation and calcification in the vessel wall by ingesting neointimal calcific deposits (predominantly hydroxyapatite) and secreting tumor necrosis factor (TNF)alpha, itself a vascular calcifying agent. Here we have investigated whether particle size affects the proinflammatory potential of hydroxyapatite crystals in vitro and whether the nuclear factor (NF)-kappaB pathway plays a role in the macrophage TNFalpha response. The particle size and nano-topography of nine different crystal preparations was analyzed by X-ray diffraction, Raman spectroscopy, scanning electron microscopy and gas sorbtion analysis. Macrophage TNFalpha secretion was inversely related to hydroxyapatite particle size (P=0.011, Spearman rank correlation test) and surface pore size (P=0.014). A necessary role for the NF-kappaB pathway was demonstrated by time-dependent I kappaB alpha degradation and sensitivity to inhibitors of I kappaB alpha degradation. To test whether smaller particles were intrinsically more bioactive, their mitogenic activity on fibroblast proliferation was examined. This showed close correlation between TNFalpha secretion and crystal-induced fibroblast proliferation (P=0.007). In conclusion, the ability of hydroxyapatite crystals to stimulate macrophage TNFalpha secretion depends on NF-kappaB activation and is inversely related to particle and pore size, with crystals of 1-2 microm diameter and pore size of 10-50 A the most bioactive. Microscopic calcific deposits in early stages of atherosclerosis may therefore pose a greater inflammatory risk to the plaque than macroscopically or radiologically visible deposits in more advanced lesions.

Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells

International Nuclear Information System (INIS)

Sanlioglu, Ahter D; Dirice, Ercument; Aydin, Cigdem; Erin, Nuray; Koksoy, Sadi; Sanlioglu, Salih

2005-01-01

Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) selectively induces apoptosis in cancer cells but not in normal cells. Despite this promising feature, TRAIL resistance observed in cancer cells seriously challenged the use of TRAIL as a death ligand in gene therapy. The current dispute concerns whether or not TRAIL receptor expression pattern is the primary determinant of TRAIL sensitivity in cancer cells. This study investigates TRAIL receptor expression pattern and its connection to TRAIL resistance in breast cancer cells. In addition, a DcR2 siRNA approach and a complementary gene therapy modality involving IKK inhibition (AdIKKβKA) were also tested to verify if these approaches could sensitize MCF7 breast cancer cells to adenovirus delivery of TRAIL (Ad5hTRAIL). TRAIL sensitivity assays were conducted using Molecular Probe's Live/Dead Cellular Viability/Cytotoxicity Kit following the infection of breast cancer cells with Ad5hTRAIL. The molecular mechanism of TRAIL induced cell death under the setting of IKK inhibition was revealed by Annexin V binding. Novel quantitative Real Time RT-PCR and flow cytometry analysis were performed to disclose TRAIL receptor composition in breast cancer cells. MCF7 but not MDA-MB-231 breast cancer cells displayed strong resistance to adenovirus delivery of TRAIL. Only the combinatorial use of Ad5hTRAIL and AdIKKβKA infection sensitized MCF7 breast cancer cells to TRAIL induced cell death. Moreover, novel quantitative Real Time RT-PCR assays suggested that while the level of TRAIL Decoy Receptor-4 (TRAIL-R4) expression was the highest in MCF7 cells, it was the lowest TRAIL receptor expressed in MDA-MB-231 cells. In addition, conventional flow cytometry analysis demonstrated that TRAIL resistant MCF7 cells exhibited substantial levels of TRAIL-R4 expression but not TRAIL decoy receptor-3 (TRAIL-R3) on surface. On the contrary, TRAIL sensitive MDA-MB-231 cells displayed very low levels of surface TRAIL-R4

RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma

DEFF Research Database (Denmark)

Zhang, Mingzhi; Xu-Monette, Zijun Y; Li, Ling

2016-01-01

It has been well established that nuclear factor kappa-B (NF-κB) activation is important for tumor cell growth and survival. RelA/p65 and p50 are the most common NF-kB subunits and involved in the classical NF-kB pathway. However, the prognostic and biological significance of RelA/p65 is equivoca...

Parallel Assessment of Bone Mineral Density and RANKL/OPG Ratio in Saudi Females

OpenAIRE

AI Hassan; SA Eltarhouny; HE Hashem; SA Algaidi; AR Abdallah; AM Sandokji

2016-01-01

Background: Osteoporosis is a significant risk factor for morbidity, and its high prevalence among Saudi women should be considered to be a public health problem. Quantitative ultrasound was recommended for bone mineral density (BMD) screening. Receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) and their ratio are critical for physiological bone remodelling, and related abnormalities may lead to several osteopathies. Methods: The BMD of 499 Saudi female...

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Swain, A.D.

1981-01-01

This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants. (orig.) [de

Can a pairwise contact potential stabilize native protein folds against decoys obtained by threading?

Science.gov (United States)

Vendruscolo, M; Najmanovich, R; Domany, E

2000-02-01

We present a method to derive contact energy parameters from large sets of proteins. The basic requirement on which our method is based is that for each protein in the database the native contact map has lower energy than all its decoy conformations that are obtained by threading. Only when this condition is satisfied one can use the proposed energy function for fold identification. Such a set of parameters can be found (by perceptron learning) if Mp, the number of proteins in the database, is not too large. Other aspects that influence the existence of such a solution are the exact definition of contact and the value of the critical distance Rc, below which two residues are considered to be in contact. Another important novel feature of our approach is its ability to determine whether an energy function of some suitable proposed form can or cannot be parameterized in a way that satisfies our basic requirement. As a demonstration of this, we determine the region in the (Rc, Mp) plane in which the problem is solvable, i.e., we can find a set of contact parameters that stabilize simultaneously all the native conformations. We show that for large enough databases the contact approximation to the energy cannot stabilize all the native folds even against the decoys obtained by gapless threading.

Factors affecting nuclear development

International Nuclear Information System (INIS)

Stevens, G.H.; Girouard, P.

1995-01-01

Among the factors affecting nuclear development, some depend more or less on public authorities, but many are out of public authorities control (foreign policies, market and deregulation, socials and environmental impacts, public opinion). As far as possible, the following study tries to identify those factors. (D.L.). 2 photos

Field test of a practical secure communication network with decoy-state quantum cryptography.

Science.gov (United States)

Chen, Teng-Yun; Liang, Hao; Liu, Yang; Cai, Wen-Qi; Ju, Lei; Liu, Wei-Yue; Wang, Jian; Yin, Hao; Chen, Kai; Chen, Zeng-Bing; Peng, Cheng-Zhi; Pan, Jian-Wei

2009-04-13

We present a secure network communication system that operated with decoy-state quantum cryptography in a real-world application scenario. The full key exchange and application protocols were performed in real time among three nodes, in which two adjacent nodes were connected by approximate 20 km of commercial telecom optical fiber. The generated quantum keys were immediately employed and demonstrated for communication applications, including unbreakable real-time voice telephone between any two of the three communication nodes, or a broadcast from one node to the other two nodes by using one-time pad encryption.

Power peaking nuclear reliability factors

International Nuclear Information System (INIS)

Hassan, H.A.; Pegram, J.W.; Mays, C.W.; Romano, J.J.; Woods, J.J.; Warren, H.D.

1977-11-01

The Calculational Nuclear Reliability Factor (CNRF) assigned to the limiting power density calculated in reactor design has been determined. The CNRF is presented as a function of the relative power density of the fuel assembly and its radial local. In addition, the Measurement Nuclear Reliability Factor (MNRF) for the measured peak hot pellet power in the core has been evaluated. This MNRF is also presented as a function of the relative power density and radial local within the fuel assembly

Security analysis of the decoy method with the Bennett–Brassard 1984 protocol for finite key lengths

International Nuclear Information System (INIS)

Hayashi, Masahito; Nakayama, Ryota

2014-01-01

This paper provides a formula for the sacrifice bit-length for privacy amplification with the Bennett–Brassard 1984 protocol for finite key lengths, when we employ the decoy method. Using the formula, we can guarantee the security parameter for a realizable quantum key distribution system. The key generation rates with finite key lengths are numerically evaluated. The proposed method improves the existing key generation rate even in the asymptotic setting. (paper)

Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors

NARCIS (Netherlands)

Connolly, Stuart J.; Milling, Truman J.; Eikelboom, John W.; Gibson, C. Michael; Curnutte, John T.; Gold, Alex; Bronson, Michele D.; Lu, Genmin; Conley, Pamela B.; Verhamme, Peter; Schmidt, Jeannot; Middeldorp, Saskia; Cohen, Alexander T.; Beyer-Westendorf, Jan; Albaladejo, Pierre; Lopez-Sendon, Jose; Goodman, Shelly; Leeds, Janet; Wiens, Brian L.; Siegal, Deborah M.; Zotova, Elena; Meeks, Brandi; Nakamya, Juliet; Lim, W. Ting; Crowther, Mark; Connolly, S. C.; Crowther, M.; Eikelboom, J.; Gibson, M.; Milling, T. J.; Albaladejo, P.; Cohen, A.; Lopez-Sendon, J.; Schmidt, J.; Verhamme, P.; Beyer-Westendorf, J.; Wyse, D. G.; Garcia, D.; Prins, M. [=Martin H.; Nakamya, J.; Büller, H. R.; Mahaffey, K.; Alexander, J.; Demchuk, A.; Raskob, G.; Schulman, S.; Meeks, B.; Zotova, E.; Holadyk-Gris, I.; Coppens, M.

2016-01-01

Background Andexanet alfa (andexanet) is a recombinant modified human factor Xa decoy protein that has been shown to reverse the inhibition of factor Xa in healthy volunteers. Methods In this multicenter, prospective, open-label, single-group study, we evaluated 67 patients who had acute major

Surface sensitivity of nuclear-knock-out form factors

International Nuclear Information System (INIS)

Fratamico, G.

1984-01-01

A numerical calculation has been performed to investigate the sensitivity of nuclear-knock-out form factors to nuclear-surface behaviour of bound-state wave functions. The result of our investigation suggests that one can extract the bound-state behaviour at the surface from experimental information on nuclear-knock-out form factors

Human factors in nuclear power plant operations

International Nuclear Information System (INIS)

Swain, A.D.

1980-08-01

This report describes some of the human factors problems in nuclear power plants and the technology that can be employed to reduce those problems. Many of the changes to improve the human factors in existing plants are inexpensive, and the expected gain in human reliability is substantial. The human factors technology is well-established and there are practitioners in most countries that have nuclear power plants

Targeted delivery of curcumin for treating type 2 diabetes.

Science.gov (United States)

Maradana, Muralidhara Rao; Thomas, Ranjeny; O'Sullivan, Brendan J

2013-09-01

Type 2 diabetes is a chronic condition in which cells have reduced insulin signalling, leading to hyperglycemia and long-term complications, including heart, kidney and liver disease. Macrophages activated by dying or stressed cells, induce the transcription factor nuclear factor kappa-B leading to the production of pro-inflammatory cytokines including TNF and IL-6. These inflammatory macrophages in liver and adipose tissue promote insulin resistance, and medications which reduce inflammation and enhance insulin signalling improve glucose control. Curcumin is an anti-oxidant and nuclear factor kappa-B inhibitor derived from turmeric. A number of studies have shown that dietary curcumin reduces inflammation and delays or prevents obesity-induced insulin resistance and associated complications, including atherosclerosis and immune mediate liver disease. Unfortunately dietary curcumin is poorly absorbed by the digestive system and undergoes glucuronidation and excretion rather than being released into the serum and systemically distributed. This confounds understanding of how dietary curcumin exerts its beneficial effects in type 2 diabetes and associated diseases. New improved methods of delivering curcumin are being developed including nanoparticles and lipid/liposome formulations that increase absorption and bioavailability of curcumin. Development and refinement of these technologies will enable cell-directed targeting of curcumin and improved therapeutic outcome. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Key Triggers of Osteoclast-Related Diseases and Available Strategies for Targeted Therapies: A Review

Directory of Open Access Journals (Sweden)

Haidi Bi

2017-12-01

Full Text Available Osteoclasts, the only cells with bone resorption functions in vivo, maintain the balance of bone metabolism by cooperating with osteoblasts, which are responsible for bone formation. Excessive activity of osteoclasts causes many diseases such as osteoporosis, periprosthetic osteolysis, bone tumors, and Paget’s disease. In contrast, osteopetrosis results from osteoclast deficiency. Available strategies for combating over-activated osteoclasts and the subsequently induced diseases can be categorized into three approaches: facilitating osteoclast apoptosis, inhibiting osteoclastogenesis, and impairing bone resorption. Bisphosphonates are representative molecules that function by triggering osteoclast apoptosis. New drugs, such as tumor necrosis factor and receptor activator of nuclear factor kappa-B ligand (RANKL inhibitors (e.g., denosumab have been developed for targeting the receptor activator of nuclear factor kappa-B /RANKL/osteoprotegerin system or CSF-1/CSF-1R axis, which play critical roles in osteoclast formation. Furthermore, vacuolar (H+-ATPase inhibitors, cathepsin K inhibitors, and glucagon-like peptide 2 impair different stages of the bone resorption process. Recently, significant achievements have been made in this field. The aim of this review is to provide an updated summary of the current progress in research involving osteoclast-related diseases and of the development of targeted inhibitors of osteoclast formation.

Diarctigenin, a lignan constituent from Arctium lappa, down-regulated zymosan-induced transcription of inflammatory genes through suppression of DNA binding ability of nuclear factor-kappaB in macrophages.

Science.gov (United States)

Kim, Byung Hak; Hong, Seong Su; Kwon, Soon Woo; Lee, Hwa Young; Sung, Hyeran; Lee, In-Jeong; Hwang, Bang Yeon; Song, Sukgil; Lee, Chong-Kil; Chung, Daehyun; Ahn, Byeongwoo; Nam, Sang-Yoon; Han, Sang-Bae; Kim, Youngsoo

2008-11-01

Diarctigenin was previously isolated as an inhibitor of nitric oxide (NO) production in macrophages from the seeds of Arctium lappa used as an alternative medicine for the treatment of inflammatory disorders. However, little is known about the molecular basis of these effects. Here, we demonstrated that diarctigenin inhibited the production of NO, prostaglandin E(2), tumor necrosis factor-alpha, and interleukin (IL)-1beta and IL-6 with IC(50) values of 6 to 12 miciroM in zymosan- or lipopolysaccharide-(LPS) activated macrophages. Diarctigenin attenuated zymosan-induced mRNA synthesis of inducible NO synthase (iNOS) and also inhibited promoter activities of iNOS and cytokine genes in the cells. Because nuclear factor (NF)-kappaB plays a pivotal role in inflammatory gene transcription, we next investigated the effect of diarctigenin on NF-kappaB activation. Diarctigenin inhibited the transcriptional activity and DNA binding ability of NF-kappaB in zymosan-activated macrophages but did not affect the degradation and phosphorylation of inhibitory kappaB (IkappaB) proteins. Moreover, diarctigenin suppressed expression vector NF-kappaB p65-elicited NF-kappaB activation and also iNOS promoter activity, indicating that the compound could directly target an NF-kappa-activating signal cascade downstream of IkappaB degradation and inhibit NF-kappaB-regulated iNOS expression. Diarctigenin also inhibited the in vitro DNA binding ability of NF-kappaB but did not affect the nuclear import of NF-kappaB p65 in the cells. Taken together, diarctigenin down-regulated zymosan- or LPS-induced inflammatory gene transcription in macrophages, which was due to direct inhibition of the DNA binding ability of NF-kappaB. Finally, this study provides a pharmacological potential of diarctigenin in the NF-kappaB-associated inflammatory disorders.

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Pack, R.W.

1978-01-01

The Electric Power Research Institute has started research in human factors in nuclear power plants. One project, completed in March 1977, reviewed human factors problems in operating power plants and produced a report evaluating those problems. A second project developed computer programs for evaluating operator performance on training simulators. A third project is developing and evaluating control-room design approaches. A fourth project is reviewing human factors problems associated with power-plant maintainability and instrumentation and control technician activities. Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. The Electric Power Research Institute (EPRI) has undertaken four projects studying the application of human factors engineering principles to nuclear power plants. (author)

Importance of human factors on nuclear installations safety

International Nuclear Information System (INIS)

Caruso, G.J.

1990-01-01

Actually, installations safety and, in particular the nuclear installations infer a strong incidence in human factors related to the design and operation of such installations. In general, the experience aims to that the most important accidents have happened as result of the components' failures combination and human failures in the operation of safety systems. Human factors in the nuclear installations may be divided into two areas: economy and human reliability. Human factors treatments for the safety evaluation of the nuclear installations allow to diagnose the weak points of man-machine interaction. (Author) [es

A PCR-Based Method to Construct Lentiviral Vector Expressing Double Tough Decoy for miRNA Inhibition.

Directory of Open Access Journals (Sweden)

Huiling Qiu

Full Text Available DNA vector-encoded Tough Decoy (TuD miRNA inhibitor is attracting increased attention due to its high efficiency in miRNA suppression. The current methods used to construct TuD vectors are based on synthesizing long oligonucleotides (~90 mer, which have been costly and problematic because of mutations during synthesis. In this study, we report a PCR-based method for the generation of double Tough Decoy (dTuD vector in which only two sets of shorter oligonucleotides (< 60 mer were used. Different approaches were employed to test the inhibitory potency of dTuDs. We demonstrated that dTuD is the most efficient method in miRNA inhibition in vitro and in vivo. Using this method, a mini dTuD library against 88 human miRNAs was constructed and used for a high-throughput screening (HTS of AP-1 pathway-related miRNAs. Seven miRNAs (miR-18b-5p, -101-3p, -148b-3p, -130b-3p, -186-3p, -187-3p and -1324 were identified as candidates involved in AP-1 pathway regulation. This novel method allows for an accurate and cost-effective generation of dTuD miRNA inhibitor, providing a powerful tool for efficient miRNA suppression in vitro and in vivo.

Human factor problem in nuclear power generation

International Nuclear Information System (INIS)

Yoshino, Kenji; Fujimoto, Junzo

1999-01-01

Since a nuclear power plant accident at Threemile Island in U.S.A. occurred in March, 1979, twenty years have passed. After the accident, the human factor problem became focussed in nuclear power, to succeed its research at present. For direct reason of human error, most of factors at individual level or work operation level are often listed at their center. Then, it is natural that studies on design of a machine or apparatus suitable for various human functions and abilities and on improvement of relationship between 'human being and machine' and 'human being and working environment' are important in future. Here was, as first, described on outlines of the human factor problem in a nuclear power plant developed at a chance of past important accident, and then was described on educational training for its countermeasure. At last, some concrete researching results obtained by human factor research were introduced. (G.K.)

Effects of acteoside on lipopolysaccharide-induced inflammation in acute lung injury via regulation of NF-κB pathway in vivo and in vitro

Energy Technology Data Exchange (ETDEWEB)

Jing, Wang; Chunhua, Ma, E-mail: machunhuabest@126.com; Shumin, Wang, E-mail: wangshuminch@126.com

2015-06-01

The purpose of the present study was to investigate the protective role of acteoside (AC) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). BalB/c mice intraperitoneally received AC (30, and 60 mg/kg) or dexamethasone (2 mg/kg) 2 h prior to or after intratracheal instillation of LPS. Treatment with AC significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and ameliorated LPS-induced lung histopathological changes. In addition, AC increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content, total cell and neutrophil infiltrations, and levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that AC inhibited the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, inhibitor of nuclear factor kappa-B kinase-α (IKK-α) and inhibitor of nuclear factor kappa-B kinase-β (IKKβ) in LPS-induced inflammation in A549 cells. Our data suggested that LPS evoked the inflammatory response in lung epithelial cells A549. The experimental results indicated that the protective mechanism of AC might be attributed partly to the inhibition of proinflammatory cytokine production and NF-κB activation. - Highlights: • Acteoside inhibited inflammation in LPS-induced lung injury in mice. • Acteoside inhibited inflammation in lung epithelial cells A549. • Acteoside inhibited NF-kB activation in LPS-induced mice and lung epithelial cells A549.

TRAM-Derived Decoy Peptides inhibits the inflammatory response in mouse mammary epithelial cells and a mastitis model in mice.

Science.gov (United States)

Hu, Xiaoyu; Tian, Yuan; Wang, Tiancheng; Zhang, Wenlong; Wang, Wei; Gao, Xuejiao; Qu, Shihui; Cao, Yongguo; Zhang, Naisheng

2015-10-05

It has been proved that TRAM-Derived Decoy peptides have anti-inflammatory properties. In this study, we synthesized a TRAM-Derived decoy peptide (TM6), belongs to TRAM TIR domain, of which sequence is "N"-RQIKIWFQNRRMKWK, KENFLRDTWCNFQFY-"C" and evaluated the effects of TM6 on lipopolysaccharide-induced mastitis in mice. In vivo, LPS-induced mice mastitis model was established by injection of LPS through the duct of mammary gland. TM6 was injected 1h before or after LPS treatment. In vitro, primary mouse mammary epithelial cells were used to investigate the effects of TM6 on LPS-induced inflammatory responses. The results showed that TM6 inhibited LPS-induced mammary gland histopathologic changes, MPO activity, and TNF-α, IL-1β and IL-6 production in mice. In vitro, TM6 significantly inhibited LPS-induced TNF-α and IL-6 production, as well as NF-κB and MAPKs activation. In conclusion, this study demonstrated that TM6 had protective effects on LPS-mastitis and may be a promising therapeutic reagent for mastitis treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Human factors in nuclear safety oversight

International Nuclear Information System (INIS)

Taylor, K.

1989-01-01

The mission of the nuclear safety oversight function at the Savannah River Plant is to enhance the process and nuclear safety of site facilities. One of the major goals surrounding this mission is the reduction of human error. It is for this reason that several human factors engineers are assigned to the Operations assessment Group of the Facility Safety Evaluation Section (FSES). The initial task of the human factors contingent was the design and implementation of a site wide root cause analysis program. The intent of this system is to determine the most prevalent sources of human error in facility operations and to assist in determining where the limited human factors resources should be focused. In this paper the strategy used to educate the organization about the field of human factors is described. Creating an awareness of the importance of human factors engineering in all facets of design, operation, and maintenance is considered to be an important step in reducing the rate of human error

Tumour Necrosis Factor-alpha and Nuclear Factor-kappa B Gene Variants in Sepsis.

Science.gov (United States)

Acar, Leyla; Atalan, Nazan; Karagedik, E Hande; Ergen, Arzu

2018-01-20

The humoral system is activated and various cytokines are released due to infections in tissues and traumatic damage. Nuclear factor-kappa B dimers are encoded by nuclear factor-kappa B genes and regulate transcription of several crucial proteins of inflammation such as tumour necrosis factor-alpha. To investigate the possible effect of polymorphisms on tumour necrosis factor-alpha serum levels with clinical and prognostic parameters of sepsis by determining the nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A) gene polymorphisms and tumour necrosis factor-alpha serum levels. Case-control study. Seventy-two patients with sepsis and 104 healthy controls were included in the study. In order to determine the polymorphisms of nuclear factor-kappa B-1-94 ins/del ATTG and tumour necrosis factor-alpha (-308 G/A), polymerase chain reaction-restriction fragment length polymorphism analysis was performed and serum tumour necrosis factor-alpha levels were determined using an enzyme-linked immunosorbent assay. We observed no significant differences in tumour necrosis factor-alpha serum levels between the study groups. In the patient group, an increase in the tumour necrosis factor-alpha serum levels in patients carrying the tumour necrosis factor-alpha (-308 G/A) A allele compared to those without the A allele was found to be statistically significant. Additionally, an increase in the tumour necrosis factor-alpha serum levels in patients carrying tumour necrosis factor-alpha (-308 G/A) AA genotype compared with patients carrying the AG or GG genotypes was statistically significant. No significant differences were found in these 2 polymorphisms between the patient and control groups (p>0.05). Our results showed the AA genotype and the A allele of the tumour necrosis factor-alpha (-308 G/A) polymorphism may be used as a predictor of elevated tumour necrosis factor-alpha levels in patients with sepsis.

Human Factor on Gravelines Nuclear Power Plants

International Nuclear Information System (INIS)

Duboc, Gerard

1998-01-01

In a first part, the documents describes the commitments by EDF nuclear power plan operations to demands made by the Safety Authority regarding actions in the field of human factors (concerns expressed by the Authority, in-depth analysis, positions on different points raised by the Authority). In a second part, it presents the various actions undertaken in the Gravelines nuclear power station regarding human factors: creation of an 'operator club' (mission and objectives, methods and means, first meetings, tracking file), development of risk analysis strategy, setting up of a human factor engineering mission and example of action in case of a significant event

Free-space measurement-device-independent quantum-key-distribution protocol using decoy states with orbital angular momentum

International Nuclear Information System (INIS)

Wang Le; Zhao Sheng-Mei; Cheng Wei-Wen; Gong Long-Yan

2015-01-01

In this paper, we propose a measurement-device-independent quantum-key-distribution (MDI-QKD) protocol using orbital angular momentum (OAM) in free space links, named the OAM-MDI-QKD protocol. In the proposed protocol, the OAM states of photons, instead of polarization states, are used as the information carriers to avoid the reference frame alignment, the decoy-state is adopted to overcome the security loophole caused by the weak coherent pulse source, and the high efficient OAM-sorter is adopted as the measurement tool for Charlie to obtain the output OAM state. Here, Charlie may be an untrusted third party. The results show that the authorized users, Alice and Bob, could distill a secret key with Charlie’s successful measurements, and the key generation performance is slightly better than that of the polarization-based MDI-QKD protocol in the two-dimensional OAM cases. Simultaneously, Alice and Bob can reduce the number of flipping the bits in the secure key distillation. It is indicated that a higher key generation rate performance could be obtained by a high dimensional OAM-MDI-QKD protocol because of the unlimited degree of freedom on OAM states. Moreover, the results show that the key generation rate and the transmission distance will decrease as the growth of the strength of atmospheric turbulence (AT) and the link attenuation. In addition, the decoy states used in the proposed protocol can get a considerable good performance without the need for an ideal source. (paper)

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

International Nuclear Information System (INIS)

Li Tianshu

2013-01-01

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

The significance of human factors in nuclear activities

International Nuclear Information System (INIS)

Weil, L.; Berg, H.P.

1999-01-01

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

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Hennig, J.; Bohr, E.

1976-04-01

This annotated bibliography is a first attempt to give a survey of the kind of literature which is relevant for the ergonomic working conditions in nuclear power plants. Such a survey seems to be useful in view of the fact that the 'factor human being' comes recently more and more to the fore in nuclear power plants. In this context, the necessity is often pointed out to systematically include our knowledge of the performance capacity and limits of human beings when designing the working conditions for the personnel of nuclear power plants. For this reason, the bibliography is so much intended for the ergonomics experts as for the experts of nuclear engineering. (orig./LN) [de

The human factor in the nuclear industry

International Nuclear Information System (INIS)

Colas, Armand

1998-01-01

After having evoked the progressive reduction and stabilization of significant incidents occurring every year in French nuclear power plants, and the challenges faced by nuclear energy (loss of public confidence, loss of competitiveness), and then outlined the importance of safety to overcome these challenges, the author comments EDF's approach to the human factor. He first highlights the importance of information and communication towards the population. He briefly discusses the meaning of human factors for the nuclear industry, sometimes perceived as the contribution people to the company's safety and performance. He comments the evolution observed in the perception of human error in different industrial or technical environments and situations, and outlines what is at stake to reduce the production of faults and organize a 'hunt for latent defects'

Factor of radioactive waste on nuclear power program

International Nuclear Information System (INIS)

Syed Abdul Malik Syed Zain

2009-01-01

Global warming phenomena and rising oil prices have brought the excitement of open space use of nuclear power. Arguments in favor of this technology range in terms of more environmentally friendly, energy diversification and cost efficiency has prompted the government to widen the choice of nuclear power be considered as a serious alternative. Despite the attractive factors to the use of these powers, there are also factors that stem from the continued development of nuclear power. These include the factor of safety, security, security of fuel supply, and public attention is often associated with radioactive waste management. This article attempts to debate specific to radioactive waste management factors that impact on public acceptance of a country's nuclear power program, especially in Malaysia. Starting from the absence of radioactive waste management policy to model uncertainty of the landfill and complications in selecting a repository site shows the basic infrastructure is still lacking. In addition, previous experience handling thorium waste has not reached a final settlement after several years of implementation. It reinforced the perception about the level of public confidence in the competence and attitude of local workers who are not very encouraging to pursue this advanced.

Factors influencing chemical durability of nuclear waste glasses

International Nuclear Information System (INIS)

Feng, Xiangdong; Bates, J.K.

1993-01-01

A short summary is given of our studies on the major factors that affect the chemical durability of nuclear waste glasses. These factors include glass composition, solution composition, SA/V (ratio of glass surface area to the volume of solution), radiation, and colloidal formation. These investigations have enabled us to gain a better understanding of the chemical durability of nuclear waste glasses and to accumulate.a data base for modeling the long-term durability of waste glass, which will be used in the risk assessment of nuclear waste disposal. This knowledge gained also enhances our ability to formulate optimal waste glass compositions

Hacking on decoy-state quantum key distribution system with partial phase randomization

Science.gov (United States)

Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

2014-04-01

Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

Hacking on decoy-state quantum key distribution system with partial phase randomization.

Science.gov (United States)

Sun, Shi-Hai; Jiang, Mu-Sheng; Ma, Xiang-Chun; Li, Chun-Yan; Liang, Lin-Mei

2014-04-23

Quantum key distribution (QKD) provides means for unconditional secure key transmission between two distant parties. However, in practical implementations, it suffers from quantum hacking due to device imperfections. Here we propose a hybrid measurement attack, with only linear optics, homodyne detection, and single photon detection, to the widely used vacuum + weak decoy state QKD system when the phase of source is partially randomized. Our analysis shows that, in some parameter regimes, the proposed attack would result in an entanglement breaking channel but still be able to trick the legitimate users to believe they have transmitted secure keys. That is, the eavesdropper is able to steal all the key information without discovered by the users. Thus, our proposal reveals that partial phase randomization is not sufficient to guarantee the security of phase-encoding QKD systems with weak coherent states.

The impact of chromatin modification on the development of chronic complications in patients with diabetes

Directory of Open Access Journals (Sweden)

Małgorzata Wegner

2015-08-01

Full Text Available Diabetes is a chronic, metabolic disease. Over 347 million people worldwide have diabetes. Chronic complications (retinopathy, nephropathy or neuropathy are the major dangerous outcome of this disease. Recent studies indicate a significant role of epigenetic regulation in the development of chronic complications in patients with diabetes. Hyperglycemia could cause abnormal regulation of the activity of enzymes participating in the post-translational histone modifications (PTHMs and initiation of changes in patterns of DNA methylation. It leads to modification of chromatin structure. These epigenetic abnormalities result in changes in the expression of genes involved in development of chronic inflammation, such as NF-KAPPAB (nuclear factor kappaB gene, TNFα (tumor necrosis factor a gene, IL6 (interleukin 6 gene or MCP1 (monocyte chemoattractant protein 1 gene. It enhances endothelial cell dysfunction, which plays an important role in development of chronic, diabetic complications. In addition, caused by hyperglycemia epigenetic modifications changes in structure of chromatin explains “metabolic memory”, a phenomenon of presence of pathological pathways related to the prolonged hyperglycemia in the past, despite maintaining good metabolic control later on.

Human and organizational factors in nuclear safety

International Nuclear Information System (INIS)

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

2015-01-01

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)

Uranium, a factor limiting nuclear energy?

International Nuclear Information System (INIS)

Ohnemus, J.

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this step was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken into account: stocks, resources, and reserves. To clarify the situation, this article outlines important aspects of short and long term uranium supplies, and analyzes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the influence of the price of uranium on the cost of electricity generation? Among other results, it is found that comprehensive sources of low-price uranium and nuclear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig.)

Uranium, a factor limiting nuclear energy?

International Nuclear Information System (INIS)

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this step was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken into account: stocks, resources, and reserves. To clarify the situation, this article outlines important aspects of short and long term uranium supplies, and analyzes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the influence of the price of uranium on the cost of electricity generation? Among other results, it is found that comprehensive sources of low-price uranium and nuclear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig./GL)

Development of human factors engineering guide for nuclear power project

International Nuclear Information System (INIS)

Wu Dangshi; Sheng Jufang

1997-01-01

'THE PRACTICAL GUIDE FOR APPLICATION OF HUMAN FACTORS ENGINEERING TO NUCLEAR POWER PROJECT (First Draft, in Chinese)', which was developed under a research program sponsored by National Nuclear Safety Administration (NNSA) is described briefly. It is hoped that more conscious, more systematical and more comprehensive application of Human Factors Engineering to the nuclear power projects from the preliminary feasibility studies up to the commercial operation will benefit the safe, efficient and economical operations of nuclear power plants in China

U.S. Nuclear Regulatory Commission human factors program plan

International Nuclear Information System (INIS)

1986-04-01

The purpose of the U.S. Nuclear Regulatory Commission (NRC) Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design and operation of nuclear facilities. This revised plan addresses human factors issues related to the operation of nuclear power plants (NPPs). The three issues of concern are (1) the activities planned to provide the technical bases to resolve the remaining tasks related to human factors as described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the need to address the additional human factors efforts that were identified during implementation of the Action Plan; and (3) the actual fulfillment of those developmental activities specified in Revision 1 of this plan. The plan represents a systematic approach for addressing high priority human factors concerns important to NPP safety in FY 1986 through 1987

Decoy-state BB84 protocol using space division multiplexing in silicon photonics

DEFF Research Database (Denmark)

Bacco, Davide; Ding, Yunhong; Dalgaard, Kjeld

2017-01-01

Quantum key distribution (QKD), a technique based on quantum physics, provides unconditional secure quantum keys to be shared between two or more clients (Alice and Bob) [1]. Most QKD systems are implemented in a point-to-point link using bulky and expensive devices. Consequently a large scale...... experiments have already demonstrated conventional binary QKD systems, using polarization and phase reference degrees of freedom [2, 3]. In this paper, we show the first silicon chip-to-chip decoy-state BB84 protocol based on spatial degrees of freedom (the cores of a multi-core fiber-MCF-). By tuning...... the superposition of the quantum state between cores, combined with a positive/negative phase relation. A train of weak coherent pulses (5 kHz repetition and 10 ns wide) are injected into the transmitter chip (Alice), where multiple variable optical attenuators (VOAs) are used to decrease the number of photons per...

US Nuclear Regulatory Commission human-factors program plan

International Nuclear Information System (INIS)

1983-08-01

The purpose of the NRC Human Factors Program Plan is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This initial plan addresses nuclear power plants (NPP) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, The NRC Action Plan Developed as a Result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements, and (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-83 through FY-85 time frame

Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

Science.gov (United States)

Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A; Manna, Sunil K

2010-02-19

The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.

Organizational factors in nuclear safety

International Nuclear Information System (INIS)

Wilpert, Bernhard

2000-01-01

The overall picture of factors which contributed to the event presents a panorama of a NPP where organizational and managerial characteristics were intricately intertwined and emerged as crucial for a general deterioration of the plant's capabilities to continually correct its deficiencies and optimize its operations. In the following author shall attempt to first cover various important efforts to modeling organizational factors relevant to safety. The second part of my presentation will offer an attempt towards an integrative model. The third part concludes with an agenda for research and practice. Most of the twelve different approaches above attempt to consider safety relevant organizational factors by way of pragmatic classifications. Together with their sub-categories we can count close to 160 different factors on various levels of abstraction. This is tantamount to say that most approaches lack systematic theoretical underpinnings. Thus then arises the question whether we need to develop a generic model, which promises to encompass these three major approaches altogether. Practical issues emerge particularly in the domain of organizational development, i.e. the goal oriented efforts to change the structures and the functioning of nuclear operations in such a way that the desired outputs in terms safety and reliability result in a sustained fashion. Again, these practical concerns are intimately related to developments and advances in theory and methodology. Only a close cooperation among scientists from various disciplines and of practitioners holds the promise of adequately understanding and use of organizational factors in future improving the safety record of nuclear industry worldwide. (S.Y.)

Scandoside Exerts Anti-Inflammatory Effect Via Suppressing NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages

Directory of Open Access Journals (Sweden)

Jingyu He

2018-02-01

Full Text Available The iridoids of Hedyotis diffusa Willd play an important role in the anti-inflammatory process, but the specific iridoid with anti-inflammatory effect and its mechanism has not be thoroughly studied. An iridoid compound named scandoside (SCA was isolated from H. diffusa and its anti-inflammatory effect was investigated in lipopolysaccharide (LPS-induced RAW 264.7 macrophages. Its anti-inflammatory mechanism was confirmed by in intro experiments and molecular docking analyses. As results, SCA significantly decreased the productions of nitric oxide (NO, prostaglandin E2 (PGE2, tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and inhibited the levels of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (COX-2, TNF-α and IL-6 messenger RNA (mRNA expression in LPS-induced RAW 264.7 macrophages. SCA treatment suppressed the phosphorylation of inhibitor of nuclear transcription factor kappa-B alpaha (IκB-α, p38, extracellular signal-regulated kinase (ERK and c-Jun N-terminal kinase (JNK. The docking data suggested that SCA had great binding abilities to COX-2, iNOS and IκB. Taken together, the results indicated that the anti-inflammatory effect of SCA is due to inhibition of pro-inflammatory cytokines and mediators via suppressing the nuclear transcription factor kappa-B (NF-κB and mitogen-activated protein kinase (MAPK signaling pathways, which provided useful information for its application and development.

The Nuclear Energy Factor In Indian Politics

Directory of Open Access Journals (Sweden)

A. A. Boyko

2017-01-01

Full Text Available Nuclear energy is a key branch of the world power system. The nuclear energy development is viewed by India as one of the ways to resolve the problem of the energy supply. In 2008 the country gained more opportunities for developing nuclear power sector and solving the national power deficit problem after NSG lifted restrictions on nuclear trade. This resulted in foreign companies emerging on the Indian nuclear market. In 2011 after the major emergency at Fukushima Daiichi Nuclear Power Plant in Japan India faced numerous anti-nuclear protests backed by NGOs, including those with foreign funding, and political parties. The article deals with the question of the political role this anti-nuclear opposition plays in India. According to some researchers the protests are organized by the competitors in order to compromise the business of a Russian company Rosatom in India. However, such demonstrations are spread throughout the country and directed against the competitors of Rosatom as well. The article comes to conclusion that the protests are just a reflection of the political fights in India where nuclear energy is a significant political factor.

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

Science.gov (United States)

Agrawal, Anil Kumar; Pielka, Ewa; Lipinski, Artur; Jelen, Michal; Kielan, Wojciech; Agrawal, Siddarth

2018-01-01

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Uranium - a factor limiting nuclear energy?

International Nuclear Information System (INIS)

Ohnemus, J.

2006-01-01

Nuclear power has been back as a topic of public debate since early this year. A special subject under discussion is the extension of nuclear power plant life. Hardly had it been on the agenda, when interested parties announced that this st ep was impossible because uranium reserves were no longer sufficient. A variety of terms are being used in this discussion without their meaning being taken int o account: stocks, resources, and reserves. To clarify the situation, this artic le outlines important aspects of short and long term uranium supplies, and analy zes their meaning. Here are some of the most important issues under consideration: - For what period of time is there really enough uranium? - Is uranium becoming the limiting factor in the use of nuclear power? - Is uranium really a 'sustainable' energy resource? - Will higher prices extend the range? - What is the in fluence of the price of uranium on the cost of electricity generation? Among oth er results, it is found that comprehensive sources of low-price uranium and nucl ear fuels are, or can be made, available worldwide. Consequently, the 'range' is beyond the time frames currently mentioned, also as a function of technological factors, i.e. reaching several hundred years. It is also important to note that nuclear power - ensures greater independence of volatile imported sources, - guarantees reliably low electricity prices, - has a huge potential of environmental protection, and - is a clean source of energy. (orig.)

Sledování markerů oxidačního stresu u modelu chronického zánětu tlustého střeva

OpenAIRE

Hocková, Erika

2010-01-01

Crohn's disease and ulcerative colitis are both entities of inflammatory bowel disease (IBD). The nuclear transcription factor kappaB (NFκB) family consists of five different members, which are namely p65 (RelA), c-Rel, RelB, p50 and p52. NFκB has ability to promote the expression of various proinflammatory genes, to influence the course of mucosal inflammation and to mediate different cell-type specific effects. Bilirubin is an endogenous substance with anti-oxidative and anti-inflammatory e...

Separating form factor and nuclear model effects in quasielastic neutrino-nucleus scattering

Science.gov (United States)

Wieske, Joseph

2017-09-01

When studying neutrino oscillations an understanding of charged current quasielastic (CCQE) neutrino-nucleus scattering is imperative. This interaction depends on a nuclear model as well as knowledge of form factors. In the past, CCQE data from the MiniBooNE experiment was analyzed assuming the Relativistic Fermi Gas (RFG) nuclear model, an axial dipole form factor in, and using the the z-expansion for the axial form factor in. We present the first analysis that combines a non-RFG nuclear model, in particular the Correlated Fermi Gas nuclear model (CFG) of, and the z expansion for the axial form factor. This will allow us to separate form factor and nuclear model effects in CCQE scattering. This project was supported through the Wayne State University REU program under NSF Grant PHY-1460853 and by the DOE Grant DE-SC0007983.

Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

Science.gov (United States)

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-10-01

Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

Are Toll-Like Receptors and Decoy Receptors Involved in the Immunopathogenesis of Systemic Lupus Erythematosus and Lupus-Like Syndromes?

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Giuliana Guggino

2012-01-01

Full Text Available In this paper we focus our attention on the role of two families of receptors, Toll-like receptors (TLR and decoy receptors (DcR involved in the generation of systemic lupus erythematosus (SLE and lupus-like syndromes in human and mouse models. To date, these molecules were described in several autoimmune disorders such as rheumatoid arthritis, antiphospholipids syndrome, bowel inflammation, and SLE. Here, we summarize the findings of recent investigations on TLR and DcR and their role in the immunopathogenesis of the SLE.

Human factor analysis and preventive countermeasures in nuclear power plant

International Nuclear Information System (INIS)

Li Ye

2010-01-01

Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization. Which is defined as individual factors, including psychological factors, physiological characteristics, health status, level of knowledge and interpersonal skills; The technical factors including technology, equipment, tools, working order, etc.; The organizational factors including management, information exchange, education, working environment, team building and leadership management,etc The analysis found that organizational factors can directly or indirectly affect the behavior of staff and technical factors, is the most basic human error factor. Based on this nuclear power plant to reduce human error and measures the response. (authors)

Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo.

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Qin Wang

Full Text Available VEGF family factors are known to be the principal stimulators of abnormal angiogenesis, which play a fundamental role in tumor and various ocular diseases. Inhibition of VEGF is widely applied in antiangiogenic therapy. Conbercept is a novel decoy receptor protein constructed by fusing VEGF receptor 1 and VEGF receptor 2 extracellular domains with the Fc region of human immunoglobulin. In this study, we systematically evaluated the binding affinity of conbercept with VEGF isoforms and PlGF by using anti-VEGF antibody (Avastin as reference. BIACORE and ELISA assay results indicated that conbercept could bind different VEGF-A isoforms with higher affinity than reference. Furthermore, conbercept could also bind VEGF-B and PlGF, whereas Avastin showed no binding. Oxygen-induced retinopathy model showed that conbercept could inhibit the formation of neovasularizations. In tumor-bearing nude mice, conbercept could also suppress tumor growth very effectively in vivo. Overall, our study have demonstrated that conbercept could bind with high affinity to multiple VEGF isoforms and consequently provide remarkable anti-angiogenic effect, suggesting the possibility to treat angiogenesis-related diseases such as cancer and wet AMD etc.

Mitochondria mediate tumor necrosis factor-alpha/NF-kappaB signaling in skeletal muscle myotubes

Science.gov (United States)

Li, Y. P.; Atkins, C. M.; Sweatt, J. D.; Reid, M. B.; Hamilton, S. L. (Principal Investigator)

1999-01-01

Tumor necrosis factor-alpha (TNF-alpha) is implicated in muscle atrophy and weakness associated with a variety of chronic diseases. Recently, we reported that TNF-alpha directly induces muscle protein degradation in differentiated skeletal muscle myotubes, where it rapidly activates nuclear factor kappaB (NF-kappaB). We also have found that protein loss induced by TNF-alpha is NF-kappaB dependent. In the present study, we analyzed the signaling pathway by which TNF-alpha activates NF-kappaB in myotubes differentiated from C2C12 and rat primary myoblasts. We found that activation of NF-kappaB by TNF-alpha was blocked by rotenone or amytal, inhibitors of complex I of the mitochondrial respiratory chain. On the other hand, antimycin A, an inhibitor of complex III, enhanced TNF-alpha activation of NK-kappaB. These results suggest a key role of mitochondria-derived reactive oxygen species (ROS) in mediating NF-kappaB activation in muscle. In addition, we found that TNF-alpha stimulated protein kinase C (PKC) activity. However, other signal transduction mediators including ceramide, Ca2+, phospholipase A2 (PLA2), and nitric oxide (NO) do not appear to be involved in the activation of NF-kappaB.

Nuclear modification factor using Tsallis non-extensive statistics

Energy Technology Data Exchange (ETDEWEB)

Tripathy, Sushanta; Garg, Prakhar; Kumar, Prateek; Sahoo, Raghunath [Indian Institute of Technology Indore, Discipline of Physics, School of Basic Sciences, Simrol (India); Bhattacharyya, Trambak; Cleymans, Jean [University of Cape Town, UCT-CERN Research Centre and Department of Physics, Rondebosch (South Africa)

2016-09-15

The nuclear modification factor is derived using Tsallis non-extensive statistics in relaxation time approximation. The variation of the nuclear modification factor with transverse momentum for different values of the non-extensive parameter, q, is also observed. The experimental data from RHIC and LHC are analysed in the framework of Tsallis non-extensive statistics in a relaxation time approximation. It is shown that the proposed approach explains the R{sub AA} of all particles over a wide range of transverse momentum but does not seem to describe the rise in R{sub AA} at very high transverse momenta. (orig.)

Geologic factors in nuclear waste disposal

International Nuclear Information System (INIS)

Towse, D.

1978-07-01

The study of geosciences and their relation to nuclear waste disposal and management entails analyzing the hydrology, chemistry, and geometry of the nuclear waste migration process. Hydrologic effects are determined by analyzing the porosity and permeability (natural and induced) of rock as well as pressures and gradients, dispersion, and aquifer length of the system. Chemistry parameters include radionuclide retardation factors and waste dissolution rate. Geometric parameters (i.e., parameters with dimension) evaluated include repository layer thickness, fracture zone area, tunnel length, and aquifer length. The above parameters act as natural barriers or controls to nuclear waste migration, and are evaluated in three potential geologic media: salt, shale, and crystalline rock deposits. Parametric values are assigned that correspond to many existing situations. These values, in addition to other important inputs, are lumped as a hydrology input into a computer simulation program used to model and calculate nuclear waste migration from the repository to the biosphere, and potential individual and population dose and radiation effects. These results are preliminary and show trends only; they do not represent an actual risk analysis

US Nuclear Regulatory Commission Human Factors Program Plan. Revision 1

International Nuclear Information System (INIS)

1984-09-01

The purpose of the NRC Human Factors Program Plan (NUREG-0985) is to ensure that proper consideration is given to human factors in the design, operation, and maintenance of nuclear facilities. This revised plan addresses nuclear power plants (NPPs) and describes (1) the technical assistance and research activities planned to provide the technical bases for the resolution of the remaining human factors related tasks described in NUREG-0660, THE NRC Action Plan developed as a result of the TMI-2 Accident, and NUREG-0737, Clarification of TMI Action Plan Requirements; (2) the additional human factors efforts identified during implementation of the Action Plan that should receive NRC attention; (3) conduct of developmental activities specified in NUREG-0985 during FY-83; and (4) the impact of Section 306 of the Nuclear Waste Policy Act of 1982, PL 97-425. The plan represents a systematic and comprehensive approach for addressing human factors concerns important to NPP safety in the FY-84 through FY-86 time frame

Human factors methods in DOE nuclear facilities

International Nuclear Information System (INIS)

Bennett, C.T.; Banks, W.W.; Waters, R.J.

1993-01-01

The US Department of Energy (DOE) is in the process of developing a series of guidelines for the use of human factors standards, procedures, and methods to be used in nuclear facilities. This paper discusses the philosophy and process being used to develop a DOE human factors methods handbook to be used during the design cycle. The following sections will discuss: (1) basic justification for the project; (2) human factors design objectives and goals; and (3) role of human factors engineering (HFE) in the design cycle

Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells

International Nuclear Information System (INIS)

Yoon, Hana; Oh, Young Taek; Lee, Jung Yeon; Choi, Ji Hyun; Lee, Ju Hie; Baik, Hyung Hwan; Kim, Sung Soo; Choe, Wonchae; Yoon, Kyung-Sik; Ha, Joohun; Kang, Insug

2008-01-01

AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca 2+ /calmodulin-dependent protein kinase kinase (CaMKK) β. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKα1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-κB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-κB activation

Nuclear modification factor for J/ψ production in nucleus-nucleus collisions

International Nuclear Information System (INIS)

Xu Xiaoming; Zhou Jie

2011-01-01

The STAR Collaboration has offered an eminent nuclear modification factor of J/ψ at high p T and midrapidity produced in Cu-Cu collisions at √ s NN= 200 GeV. Recalling a prediction, we can understand that the feature of high-p T nuclear modification factor is related to cc produced by 2 → 1 and 2 → 2 partonic processes in deconfined matter, particularly in the prethermal stage and to the recombination of c and c-bar. The nuclear modification factor at high p T is sensitive to the earliest form of deconfined matter that does not have a temperature.(authors)

Research of human factor in nuclear power plants

International Nuclear Information System (INIS)

Nopp, I.

1983-01-01

The question is discussed of the study of the human factor with regard to the reliability of nuclear power plant operation. The reliability of the human factor is the result of the functional fitness, motivation, working conditions and working regime of personnel. (J.B.)

Human factor engineering applied to nuclear power plant design

International Nuclear Information System (INIS)

Manrique, A.; Valdivia, J.C.; Jimenez, A.

2001-01-01

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)

Hepatitis C Virus NS3 Mediated Microglial Inflammation via TLR2/TLR6 MyD88/NF-κB Pathway and Toll Like Receptor Ligand Treatment Furnished Immune Tolerance.

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Ayilam Ramachandran Rajalakshmy

Full Text Available Recent evidence suggests the neurotrophic potential of hepatitis C virus (HCV. HCV NS3 protein is one of the potent antigens of this virus mediating inflammatory response in different cell types. Microglia being the immune surveillance cells in the central nervous system (CNS, the inflammatory potential of NS3 on microglia was studied. Role of toll like receptor (TLR ligands Pam2CSK3 and Pam3CSK4 in controlling the NS3 mediated microglial inflammation was studied using microglial cell line CHME3.IL (Interleukin-8, IL-6, TNF-α (Tumor nicrosis factor alpha and IL-1β gene expressions were measured by semi quantitative RT-PCR (reverse transcription-PCR. ELISA was performed to detect IL-8, IL-6, TNF-α, IL-1β and IL-10 secretion. FACS (Flourescent activated cell sorting was performed to quantify TLR1, TLR2, TLR6, MyD88 (Myeloid differntiation factor 88, IkB-α (I kappaB alpha and pNF-κB (phosphorylated nuclear factor kappaB expression. Immunofluorescence staining was performed for MyD88, TLR6 and NF-κB (Nuclear factor kappaB. Student's t-test or One way analysis of variance with Bonferoni post hoc test was performed and p < 0.05 was considered significant.Microglia responded to NS3 by secreting IL-8, IL-6, TNF-α and IL-1β via TLR2 or TLR6 mediated MyD88/NF-κB pathway. Transcription factor NF-κB was involved in activating the cytokine gene expression and the resultant inflammatory response was controlled by NF-κB inhibitor, Ro106-9920, which is known to down regulate pro-inflammatory cytokine secretion. Activation of the microglia by TLR agonists Pam3CSK4 and Pam2CSK4 induced immune tolerance against NS3. TLR ligand treatment significantly down regulated pro-inflammatory cytokine secretion in the microglia. IL-10 secretion was suggested as the possible mechanism by which TLR agonists induced immune tolerance. NS3 as such was not capable of self-inducing immune tolerance in microglia.In conclusion, NS3 protein was capable of activating

IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese.

Science.gov (United States)

Wang, Shiyan; Tian, Linwei; Zeng, Zhirong; Zhang, Mingdong; Wu, Kaichun; Chen, Minhu; Fan, Daiming; Hu, Pinjin; Sung, Joseph J Y; Yu, Jun

2010-02-05

Nuclear factor of kappa B inhibitor alpha (I kappaB alpha) protein is implicated in regulating a variety of cellular process from inflammation to tumorigenesis. The objective of this study was to investigate the susceptibility of rs2233408 T/C genotype in the promoter region of I kappaB alpha to gastric cancer and the association of this polymorphism with clinicopathologic variables in gastric cancer patients. A population-based case-control study was conducted between 1999 and 2006 in Guangdong Province, China. A total of 564 gastric cancer patients and 566 healthy controls were enrolled in this study. rs2233408 genotypes in I kappaB alpha were analyzed by TaqMan SNP genotyping assay. Both rs2233408 T homozygote (TT) and T heterozygotes (TC and TT) had significantly reduced gastric cancer risk (TT: OR = 0.250, 95% CI = 0.069-0.909, P = 0.035; TC and TT: OR = 0.721, 95% CI = 0.530-0.981, P = 0.037), compared with rs2233408 C homozygote (CC). rs2233408 T heterozygotes were significantly associated with reduced risk of intestinal-type gastric cancer with ORs of 0.648 (95% CI = 0.459-0.916, P = 0.014), but not with the diffuse or mix type of gastric cancer. The association between rs2233408 T heterozygotes and gastric cancer appeared more apparent in the older patients (age>40) (OR = 0.674, 95% CI = 0.484-0.939, P = 0.02). rs2233408 T heterozygotes was associated with non-cardiac gastric cancer (OR = 0.594, 95% CI = 0.411-0.859, P = 0.006), but not with cardiac gastric cancer. However, rs2233408 polymorphism was not associated with the prognosis of gastric cancer patients. I kappaB alpha rs2233408 T heterozygotes were associated with reduced risk of gastric cancer, especially for the development of certain subtypes of gastric cancer in Chinese population.

Nuclear energy - stabilising factor in the world economy

International Nuclear Information System (INIS)

Legassov, V.; Feoktistov, L.; Kouzmine, I.

1986-01-01

One of the most important factors for international stability is the development of the economy, reducing the risk of local armed conflicts which could escalate into world-wide nuclear war. Economic progress which plays such a vital part is in turn heavily dependent on energy supplies. The article takes a brief look at the role of nuclear power in this context. (B.M.S.)

Human Factors in Nuclear Reactor Accidents

International Nuclear Information System (INIS)

Mustafa, M.E.

2016-01-01

While many people would blame nature for the disaster of the “Fukushima Daiichi” accident, experts considered this accident to be also a human-induced disaster. This confirmed the importance of human errors which have been getting a growing interest in the nuclear field after the Three Mile Island accident. Personnel play an important role in design, operation, maintenance, planning, and management. The interface between machine and man is known as a human factor. In the present work, the human factors that have to be considered were discussed. The effect of the control room configuration and equipment design effect on the human behavior was also discussed. Precise reviewing of person’s qualifications and experience was focused. Insufficient training has been a major cause of human error in the nuclear field. The effective training issues were introduced. Avoiding complicated operational processes and non responsive management systems was stressed. Distinguishing between the procedures for normal and emergency operations was emphasised. It was stated that human error during maintenance and testing activities could cause a serious accident. This is because safety systems do not cover much more risk probabilities in the maintenance and testing activities like they do in the normal operation. In nuclear industry, the need for a classification and identification of human errors has been well recognised. As a result of this, human reliability must be assessed. These errors are analyzed by a probabilistic safety assessment which deals with errors in reading, listening and implementing procedures but not with cognitive errors. Much efforts must be accomplished to consider cognitive errors in the probabilistic safety assessment. The ways of collecting human factor data were surveyed. The methods for identifying safe designs, helping decision makers to predict how proposed or current policies will affect safety, and comprehensive understanding of the relationship

Review of EPRI Nuclear Human Factors Program

International Nuclear Information System (INIS)

Hanes, L.F.; O'Brien, J.F.

1996-01-01

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

Nuclear Regulatory Commission Human Factors Program Plan. Revision 2

International Nuclear Information System (INIS)

1986-04-01

This document is the Second Annual Revision to the NRC Human Factors Program Plan. The first edition was published in August 1983. Revision 1 was published in July of 1984. Purpose of the NRC Human Factors Program is to ensure that proper consideration is given to human factors in the design and operation of nuclear power plants. This document describes the plans of the Office of Nuclear Reactor Regulation to address high priority human factors concerns of importance to reactor safety in FY 1986 and FY 1987. Revision 2 of the plan incorporates recent Commission decisions and policies bearing on the human factors aspects of reactor safety regulation. With a few exceptions, the principal changes from prior editions reflect a shift from developing new requirements to staff evaluation of industry progress in resolving human factors issues. The plan addresses seven major program elements: (1) Training, (2) Licensing Examinations, (3) Procedures, (4) Man-Machine Interface, (5) Staffing and Qualifications, (6) Management and Organization, and (7) Human Performance

Personality Factors and Nuclear Power Plant Operators: Initial License Success

Science.gov (United States)

DeVita-Cochrane, Cynthia

Commercial nuclear power utilities are under pressure to effectively recruit and retain licensed reactor operators in light of poor candidate training completion rates and recent candidate failures on the Nuclear Regulatory Commission (NRC) license exam. One candidate failure can cost a utility over $400,000, making the successful licensing of new operators a critical path to operational excellence. This study was designed to discover if the NEO-PI-3, a 5-factor measure of personality, could improve selection in nuclear utilities by identifying personality factors that predict license candidate success. Two large U.S. commercial nuclear power corporations provided potential participant contact information and candidate results on the 2014 NRC exam from their nuclear power units nation-wide. License candidates who participated (n = 75) completed the NEO-PI-3 personality test and results were compared to 3 outcomes on the NRC exam: written exam, simulated operating exam, and overall exam result. Significant correlations were found between several personality factors and both written and operating exam outcomes on the NRC exam. Further, a regression analysis indicated that personality factors, particularly Conscientiousness, predicted simulated operating exam scores. The results of this study may be used to support the use of the NEO-PI-3 to improve operator selection as an addition to the current selection protocol. Positive social change implications from this study include support for the use of a personality measure by utilities to improve their return-on-investment in candidates and by individual candidates to avoid career failures. The results of this study may also positively impact the public by supporting the safe and reliable operation of commercial nuclear power utilities in the United States.

CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys.

Directory of Open Access Journals (Sweden)

Qingzhen Hou

Full Text Available Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the 'easy' targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the 'hard' targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale.

Quality management in the nuclear industry: the human factor

International Nuclear Information System (INIS)

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)

Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Executive summary

International Nuclear Information System (INIS)

Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

1982-08-01

This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

Human factors guidelines for nuclear power plant applications

International Nuclear Information System (INIS)

Ketchel, J.

1993-01-01

In 1989, Waters et al. reported to the Human Factors Society on developing human factors criteria for a new reactor plant. They correctly indicated that much of the guidance documentation in human factors engineering has derived from MIL-STD-1472 and its antecedents. Guidelines for human-computer interface have sprung primarily from the Smith and Mosier compendium and its source documents. NUREG-0700, which is currently being updated, was developed by the US Nuclear Regulatory Commission (NRC) as a general evaluation guide for inspecting control rooms. In addition, the Electric Power Research Institute, Institute of Nuclear Power Operations, US Department of Energy, the NRC, and others have published a number of specialized documents on a range of subjects. The number of guidelines and standards has grown in the past few years to an impressive number, including those published by international organizations and professional societies. This paper provides an update on current efforts to provide appropriate guidance for the power industry and, perhaps more importantly, offers a perspective on how users should think about using the available materials and what else is needed. The Electric Power Research Institute (EPRI) continues to be one of the principal participants in providing guidance to the utilities. Human factors guidelines is indeed a timely topic, currently of great interest to EPRI's constituents and to designers of new and upgraded nuclear power plants (NPMs) in the Advanced Light Water Reactor and the Instrumentation and Control Upgrade Initiative programs

Human factors design guidelines for maintainability of Department of Energy nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

1985-06-18

Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed.

Human factors design guidelines for maintainability of Department of Energy nuclear facilities

International Nuclear Information System (INIS)

Bongarra, J.P. Jr.; VanCott, H.P.; Pain, R.F.; Peterson, L.R.; Wallace, R.I.

1985-01-01

Intent of these guidelines is to provide design and design review teams of DOE nuclear facilities with human factors principles to enhance the design and aid in the inspection of DOE nuclear facilities, systems, and equipment. These guidelines are concerned with design features of DOE nuclear facilities which can potentially affect preventive and corrective maintenance of systems within DOE nuclear facilities. Maintenance includes inspecting, checking, troubleshooting, adjusting, replacing, repairing, and servicing activities. Other factors which influence maintainability such as repair and maintenance suport facilities, maintenance information, and various aspects of the environment are also addressed

Key Factors for Nuclear Being Economic after Fukushima

Energy Technology Data Exchange (ETDEWEB)

Roh, Myung Sub; Park, Seo Yeon [KEPCO International Nuclear Graduate School, Ulju (Korea, Republic of)

2012-05-15

It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

Key Factors for Nuclear Being Economic after Fukushima

International Nuclear Information System (INIS)

Roh, Myung Sub; Park, Seo Yeon

2012-01-01

It is hard to overstate the importance of electricity to the standard of living and the quality of life in a country. Electricity demand grows with population and with the changing nature, level and composition of economic and social activity. Civilization, industrialization and urbanization are, of course, key factors. It, historically, has shown that each major nuclear accident has caused a re-examination of the risk of nuclear power leading to more stringent safety requirement and higher costs. The Fukushima accident and its likely impact on future nuclear power development are difficult to foresee. The accident was a tragedy for the people affected and seriously undermined public confidence in the safety of nuclear power. A number of countries announced reviews of their programs, some took steps toward phasing out nuclear power entirely, and others reemphasized their expansion plans. The Korean nuclear community is carry out many ambitious projects for last three decades continuously and facing the another challenges relating to the future nuclear power economics and difficulty in financing new investment. In order to meet the above economic objective, it is strongly recommended that great emphasis should be placed on maintaining the nuclear economics without jeopardizing safety such as design simplification, standardization, shortening of construction period, increased availability, etc

Human factors aspects of advanced instrumentation in the nuclear industry

International Nuclear Information System (INIS)

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

Factor Analysis and Framework Development for Incorporating Public Trust on Nuclear Safety issues

Energy Technology Data Exchange (ETDEWEB)

Cho, Seongkyung; Lee, Gyebong [The Myongji Univ., Seoul (Korea, Republic of); Lee, Gihyung; Lee, Gyehwi; Jeong, Jina [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2014-05-15

The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization in charge of nuclear safety in Korea, realized that a more fundamental and systematic analysis of activities is needed to actively meet the greater variety of concerns people have and increase the reliability of the results of regulation. Nuclear safety, a highly specialized field, has previously been discussed primarily from the viewpoint of the engineers who deal with the technology, but now 'public trust in nuclear safety' has to be viewed from the standpoint of the general public and from the socio-cultural perspective. Specific measures must be taken to examine which factors affect public trust and how we can secure and reproduce those factors to gain it. Also, an efficient system for incorporating public trust in nuclear safety must be established. In this study, various case studies were examined to identify the factors that affect public trust in nuclear safety. First, nuclear safety laws and information disclosure systems of major countries were examined by investigating data and conducting in-depth interviews. To explore a public framework concerning nuclear safety, big data of social media were analyzed. Also, Q methodology was used to analyze the risk schemata of the opinion leaders living in areas near nuclear power plants. Several surveys were conducted to analyze the amount of trust the public had in nuclear safety as well as their awareness of nuclear safety issues. Based on these analyses, factors affecting public trust in nuclear safety were extracted, and measures to build systems incorporating public trust in nuclear safety were proposed. This study addresses the public trust in nuclear safety on condition that the safety is ensured technically and mechanically.

Factor Analysis and Framework Development for Incorporating Public Trust on Nuclear Safety issues

International Nuclear Information System (INIS)

Cho, Seongkyung; Lee, Gyebong; Lee, Gihyung; Lee, Gyehwi; Jeong, Jina

2014-01-01

The Korea Institute of Nuclear Safety (KINS), a regulatory expert organization in charge of nuclear safety in Korea, realized that a more fundamental and systematic analysis of activities is needed to actively meet the greater variety of concerns people have and increase the reliability of the results of regulation. Nuclear safety, a highly specialized field, has previously been discussed primarily from the viewpoint of the engineers who deal with the technology, but now 'public trust in nuclear safety' has to be viewed from the standpoint of the general public and from the socio-cultural perspective. Specific measures must be taken to examine which factors affect public trust and how we can secure and reproduce those factors to gain it. Also, an efficient system for incorporating public trust in nuclear safety must be established. In this study, various case studies were examined to identify the factors that affect public trust in nuclear safety. First, nuclear safety laws and information disclosure systems of major countries were examined by investigating data and conducting in-depth interviews. To explore a public framework concerning nuclear safety, big data of social media were analyzed. Also, Q methodology was used to analyze the risk schemata of the opinion leaders living in areas near nuclear power plants. Several surveys were conducted to analyze the amount of trust the public had in nuclear safety as well as their awareness of nuclear safety issues. Based on these analyses, factors affecting public trust in nuclear safety were extracted, and measures to build systems incorporating public trust in nuclear safety were proposed. This study addresses the public trust in nuclear safety on condition that the safety is ensured technically and mechanically

The human factor and organization to support nuclear power plant operators

International Nuclear Information System (INIS)

Naumov, V.I.

1993-01-01

Analysis reveals three basic factors which affect the safety of nuclear power reactors: (1) Internal physical properties of the reactor which provide self protection under breakdown and accident conditions; (2) The reliability of technical systems which provide monitoring, control, accident prevention, heat release, and localization of hazardous products during accidents; (3) Reliability of the reactor control personnel. The last of these factors is usually called the human factor. From published data, this factor makes a large contribution to the downtime and accident statistics at nuclear power plants: from 30 to 80% in various countries. Today the importance of the human factor in operating a nuclear power units is rather well recognized. Current ideas on how to increase the reliability of a human operator are reflected in IAEA recommendations and domestic official documents. The concept of 'a culture of safety' is introduced. Basic types of actions to increase the reliability of personnel who control a nuclear reactor are discussed, including: (1) The qualifying and psychological selection and the training of candidates on the operator's obligations. (2) The automation of routine operations which do not require the operator's intellect. (3) Perfecting the work place, information input to the operator, and the organization of the controls

Free-space measurement-device-independent quantum-key-distribution protocol using decoy states with orbital angular momentum

Science.gov (United States)

Wang, Le; Zhao, Sheng-Mei; Gong, Long-Yan; Cheng, Wei-Wen

2015-12-01

In this paper, we propose a measurement-device-independent quantum-key-distribution (MDI-QKD) protocol using orbital angular momentum (OAM) in free space links, named the OAM-MDI-QKD protocol. In the proposed protocol, the OAM states of photons, instead of polarization states, are used as the information carriers to avoid the reference frame alignment, the decoy-state is adopted to overcome the security loophole caused by the weak coherent pulse source, and the high efficient OAM-sorter is adopted as the measurement tool for Charlie to obtain the output OAM state. Here, Charlie may be an untrusted third party. The results show that the authorized users, Alice and Bob, could distill a secret key with Charlie’s successful measurements, and the key generation performance is slightly better than that of the polarization-based MDI-QKD protocol in the two-dimensional OAM cases. Simultaneously, Alice and Bob can reduce the number of flipping the bits in the secure key distillation. It is indicated that a higher key generation rate performance could be obtained by a high dimensional OAM-MDI-QKD protocol because of the unlimited degree of freedom on OAM states. Moreover, the results show that the key generation rate and the transmission distance will decrease as the growth of the strength of atmospheric turbulence (AT) and the link attenuation. In addition, the decoy states used in the proposed protocol can get a considerable good performance without the need for an ideal source. Project supported by the National Natural Science Foundation of China (Grant Nos. 61271238 and 61475075), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20123223110003), the Natural Science Research Foundation for Universities of Jiangsu Province of China (Grant No. 11KJA510002), the Open Research Fund of Key Laboratory of Broadband Wireless Communication and Sensor Network Technology, Ministry of Education, China (Grant No. NYKL2015011), and the

Critical human-factors issues in nuclear-power regulation and a recommended comprehensive human-factors long-range plan. Critical discussion of human factors areas of concern

International Nuclear Information System (INIS)

Hopkins, C.O.; Snyder, H.L.; Price, H.E.; Hornick, R.J.; Mackie, R.R.; Smillie, R.J.; Sugarman, R.C.

1982-08-01

This comprehensive long-range human factors plan for nuclear reactor regulation was developed by a Study Group of the Human Factors Society, Inc. This Study Group was selected by the Executive Council of the Society to provide a balanced, experienced human factors perspective to the applications of human factors scientific and engineering knowledge to nuclear power generation. The report is presented in three volumes. Volume 1 contains an Executive Summary of the 18-month effort and its conclusions. Volume 2 summarizes all known nuclear-related human factors activities, evaluates these activities wherever adequate information is available, and describes the recommended long-range (10-year) plan for human factors in regulation. Volume 3 elaborates upon each of the human factors issues and areas of recommended human factors involvement contained in the plan, and discusses the logic that led to the recommendations

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

International Nuclear Information System (INIS)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim; Tjønneland, Anne; Vogel, Ulla

2010-01-01

Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC) risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X receptor (PXR, NR1I2) A-24381C (rs1523127), C8055T (rs2276707), A7635G (rs6785049), liver X receptor (LXR-β, NR1H3) C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09) whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03). PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

Directory of Open Access Journals (Sweden)

Andersen Vibeke

2010-09-01

Full Text Available Abstract Background Transcription factors and nuclear receptors constitute a link between exposure to heterocyclic amines and polycyclic aromatic hydrocarbons from meat and tobacco smoke and colorectal cancer (CRC risk. The aim of this study was to investigate if polymorphisms in nuclear factor kappa-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1 -94 insertion/deletion ATTG (rs28362491, pregnane X receptor (PXR, NR1I2 A-24381C (rs1523127, C8055T (rs2276707, A7635G (rs6785049, liver X receptor (LXR-β, NR1H3 C-rs1405655T, T-rs2695121C were assessed together with lifestyle factors in a nested case-cohort study of 378 CRC cases and 756 random participants from the Danish prospective Diet, Cancer and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR = 1.45, 95% confidence interval (95% CI: 1.10-1.92. There was interaction between this polymorphism and intake of red and processed meat in relation to CRC risk. Carriers of NFkB -94deletion were at 3% increased risk pr 25 gram meat per day (95% CI: 0.98-1.09 whereas homozygous carriers of the insertion were not at increased risk (p for interaction = 0.03. PXR and LXR polymorphisms were not associated with CRC risk. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role for NFkB in CRC aetiology.

Hemistepsin A ameliorates acute inflammation in macrophages via inhibition of nuclear factor-κB and activation of nuclear factor erythroid 2-related factor 2.

Science.gov (United States)

Kim, Jae Kwang; Lee, Ji Eun; Jung, Eun Hye; Jung, Ji Yun; Jung, Dae Hwa; Ku, Sae Kwang; Cho, Il Je; Kim, Sang Chan

2018-01-01

Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata (Bunge) Bunge. We investigated the anti-inflammatory effects of HsA and sought to determine its mechanisms of action in macrophages. HsA pretreatment inhibited nitric oxide production, and reduced the expression of iNOS and COX-2 in Toll-like receptor ligand-stimulated RAW 264.7 cells. Additionally, HsA decreased the secretion of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated Kupffer cells as well as in RAW 264.7 cells. HsA inhibited phosphorylation of IKKα/β and degradation of IκBα, resulting in decreased nuclear translocation of nuclear factor-κB (NF-κB) and its transcriptional activity. Moreover, HsA phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2), increased expression levels of antioxidant genes, and attenuated LPS-stimulated H 2 O 2 production. Phosphorylation of p38 and c-Jun N-terminal kinase was required for HsA-mediated Nrf2 phosphorylation. In a D-galactosamine/LPS-induced liver injury model, HsA ameliorated D-galactosamine/LPS-induced hepatocyte degeneration and inflammatory cells infiltration. Moreover, immunohistochemical analyses using nitrotyrosine, 4-hydroxynonenal, and cleaved poly (ADP-ribose) polymerase antibodies revealed that HsA protected the liver from oxidative stress. Furthermore, HsA reduced the numbers of proinflammatory cytokine-positive cells in hepatic tissues. Thus, these results suggest HsA may be a promising natural product to manage inflammation-mediated tissue injuries through inhibition of NF-κB and activation of Nrf2. Copyright © 2017 Elsevier Ltd. All rights reserved.

Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

Energy Technology Data Exchange (ETDEWEB)

Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

2016-04-22

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

International Nuclear Information System (INIS)

Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

2016-01-01

Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

Availability improvement factors at Taipower's nuclear power plant system

International Nuclear Information System (INIS)

Chen, J.H.

1985-01-01

Sufficient electricity to meet the needs of a growing industrial economy, is one of the most important factors in the total economic development of a nation. Currently, nuclear power is considered one of the most economical and available sources of energy. To keep pace with Taiwan's rapid economic development, while also observing our government's policy of diversifying the requirements for imported forms of energy, Taiwan Power Company has embarked upon an ambitious of nuclear power plant construction. This paper discusses the improvement of Taiwan's nuclear power plants. At the present time, Taipower has completed three nuclear power plants. Two of these are located in northern Taiwan, along the East China Sea, while the third is on the southern tip of Taiwan, bordering the South China Sea. These three plants, each with two nuclear generating units, comprise a total nuclear generating capacity of 5144 MWe

Capacity factor of nuclear power stations in Japan in fiscal year 1984

International Nuclear Information System (INIS)

Agawa, Takashi

1985-01-01

In Japan presently a total of 28 nuclear power plants are in operation with aggregate capacity 20,561 MW, 22 % of the total power generation. Around 1975 there occurred such as stress corrosion cracking and to repair them much time was consumed, leading to the low capacity factor. With such troubles removed, in fiscal 1984, the capacity factor on average of the nuclear power stations is 73.9 %, the highest so far. Contributing to this are long period of the continuous operation, short period of the periodical inspection and increase in the in-operation capacity factor. Contents are the following : construction state of nuclear power stations, operation state in fiscal 1984, causes leading to the high capacity factor, future directions. (Mori, K.)

Nuclear safety and human factors: the French factory of expertise

International Nuclear Information System (INIS)

Rolina, G.

2009-01-01

The French regulation of the nuclear safety is based on the maintaining of a deep technical dialogue between the nuclear safety authority, the I.R.S.N. (Institute of radiation protection and nuclear safety) and the nuclear operators. This type of risk management is called 'french coking' by the Anglo-Saxons, followers of stricter regulatory approach, more readable by the civil society. This technical dialogue is not without quality, especially in the field of human and organizational factors where it allows to improve the know how situation that stays incomplete. (N.C.)

Human factor in the process of nuclear power development

International Nuclear Information System (INIS)

Enenkl, V.

The building up of nuclear power requires the training not only of personnel but of the whole population as well. Professional workers in nuclear power facilities production and personnel operating the equipment of nuclear power plants must be on a high technical and managerial level. The important quality of such personnel is their reliability and responsibility. The human factor influences the level, quality and thereby also the service-life of the machines and equipment and their operation. The improvement of the quality of work in nuclear power production depends on upgrading the scientific and technical level of workers and personnel, their training, in-service education and the raising of the social standing. (B.H.)

Correction factors for photon spectrometry in nuclear parameters study

International Nuclear Information System (INIS)

Patrao, Karla Cristina de Souza

2004-10-01

The goal of this work was the determination, using metrologic severity, the factors of correction for coincidences XX, Xγ and γγ and the factors of transference of efficiency for use in gamma spectrometry. On this way, it was carried through by determination of nuclear parameters of a nuclide used in medicine diagnostic ( 201 Tl) and the standardization of two environmental samples, of regular and irregular geometry, proceeding from the residual (ashes and slag) from the nuclear industry. The results shows that this adopted methodology is valid, and it allows its application for many different nuclides, including complex decay schema nuclides, using only photons spectrometry techniques on semiconductor detectors. (author)

Benchmark of four popular virtual screening programs: construction of the active/decoy dataset remains a major determinant of measured performance.

Science.gov (United States)

Chaput, Ludovic; Martinez-Sanz, Juan; Saettel, Nicolas; Mouawad, Liliane

2016-01-01

In a structure-based virtual screening, the choice of the docking program is essential for the success of a hit identification. Benchmarks are meant to help in guiding this choice, especially when undertaken on a large variety of protein targets. Here, the performance of four popular virtual screening programs, Gold, Glide, Surflex and FlexX, is compared using the Directory of Useful Decoys-Enhanced database (DUD-E), which includes 102 targets with an average of 224 ligands per target and 50 decoys per ligand, generated to avoid biases in the benchmarking. Then, a relationship between these program performances and the properties of the targets or the small molecules was investigated. The comparison was based on two metrics, with three different parameters each. The BEDROC scores with α = 80.5, indicated that, on the overall database, Glide succeeded (score > 0.5) for 30 targets, Gold for 27, FlexX for 14 and Surflex for 11. The performance did not depend on the hydrophobicity nor the openness of the protein cavities, neither on the families to which the proteins belong. However, despite the care in the construction of the DUD-E database, the small differences that remain between the actives and the decoys likely explain the successes of Gold, Surflex and FlexX. Moreover, the similarity between the actives of a target and its crystal structure ligand seems to be at the basis of the good performance of Glide. When all targets with significant biases are removed from the benchmarking, a subset of 47 targets remains, for which Glide succeeded for only 5 targets, Gold for 4 and FlexX and Surflex for 2. The performance dramatic drop of all four programs when the biases are removed shows that we should beware of virtual screening benchmarks, because good performances may be due to wrong reasons. Therefore, benchmarking would hardly provide guidelines for virtual screening experiments, despite the tendency that is maintained, i.e., Glide and Gold display better

A 7-mer knowledge-based potential for detecting native protein structures from decoys

DEFF Research Database (Denmark)

Røgen, Peter

for faster sampling methods. Background: The C-alpha atoms define a polygonal curve in 3-space which is smoothened by the method presented in [1] and is illustrated below. The geometry of a 7-mer is described by two numbers that describe how stretched and curved the smoothening of the 7-mer is. These two...... numbers are called length and distance excess, c.f. [2], and give one point in the length - distance excess - plane, LDE-plane. Method: Given a sequence of amino acids, we break it down to all its 7-mers and search a database of known 3d-structures for similar 7-mer sequences. For the query 7-mer we...... define an energy function in the LDE-plane. This energy is given by the 7-mer found and depends linearly on some design parameters. The energy function of the full query sequence, F, is then a sum over all 7-mers. For a protein P and a decoy D we ideally want F(D)-F(P)=constant.RMSD( D , P ), where 0...

Statistical factors affecting the success of nuclear operations

International Nuclear Information System (INIS)

Sunder, S.; Stephenson, J.R.; Hochman, D.

1999-01-01

In this article, the authors present a statistical analysis to determine the operational, financial, technical, and managerial factors that most significantly affect the success of nuclear operations. The study analyzes data for over 70 nuclear plants and 40 operating companies over a period of five years in order to draw conclusions that they hope will be of interest to utility companies and public utility commissions as they seek ways to improve rates of success in nuclear operations. Some of these conclusions will not be surprising--for example, that older plants have heavier maintenance requirements--but others are less intuitive. For instance, the observation that operators of fewer plants have lower costs suggests that any experience curve benefits associated with managing multiple nuclear facilities is overshadowed by the logistic problems of multiple facilities. After presenting a brief history of nuclear power in America, the authors outline the motivations of the study and the methodology of their analysis. They end the article with the results of the study and discuss some of the managerial implications of these findings

A report on human factors in nuclear safety

International Nuclear Information System (INIS)

1983-03-01

Following the Three Mile Island incident of 1979, studies were undertaken by the Atomic Energy Control Board (AECB), in-house and through outside consultants, to address the role of human factors in the regulatory process. This report by the Advisory Committee on Nuclear Safety (ACNS) comments briefly on these studies and offers suggestions which would promote a more formal treatment of human factors by the AECB

Human factors engineering applied to Control Centre Design of a research nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R., E-mail: larissapfarias@ymail.com [Instituto de Engenharia Nuclear (DENN/SEESC/IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Lab, de Usabilidade e Confiabilidade Humana; Monteiro, Beany G. [Universidade Federal do Rio Janeiro (UFRJ), Rio Janeiro, RJ (Brazil). Departamento de Desenho Industrial

2017-07-01

The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

Human factors engineering applied to Control Centre Design of a research nuclear reactor

International Nuclear Information System (INIS)

Farias, Larissa P. de; Santos, Isaac J.A. Luquetti dos; Carvalho, Paulo V.R.; Monteiro, Beany G.

2017-01-01

The Human Factors Engineering (HFE) program is an essential aspect for the design of nuclear installations. The overall aim of the HFE program is the improvement of the operational reliability and safety of plant operation. The HFE program main purpose is to ensure that human factor practices are incorporated into the plant design, emphasizing man-machine interface issues and design improvement of the nuclear reactor Control Centre. The Control Centre of nuclear reactor is a combination of control rooms, control suites and local control stations, which are functionally connected and located on the reactor site. The objective of this paper is to present a design approach for the Control Centre of a nuclear reactor used to produce radioisotopes and for nuclear research, including human factor issues. The design approach is based on participatory design principles, using human factor standards, ergonomic guidelines, and the participation of a multidisciplinary team during all design phases. Using the information gathered, an initial sketch 3D of the Control Centre was developed. (author)

Human factors engineering plan for reviewing nuclear plant modernization programs

International Nuclear Information System (INIS)

O'Hara, John; Higgins, James

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

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.

Relationship between organizational factors, safety culture and PSA in nuclear power plant operations

International Nuclear Information System (INIS)

Joksimovich, V.; Orvis, D.D.

1997-01-01

There are four nuclear safety imperatives or ''4Ms'': machine (hardware, design, QA/QC), milieux (operating conditions, environment, natural phenomena), man (human reliability) and management (organizational and management influences). Nuclear safety evaluations as well as evolution of its most powerful tool, Probabilistic Safety Assessment (PSA), followed chronologically the 4M constituents. The nuclear industry worldwide, and the nuclear safety regulators in particular, have been preoccupied with the first M almost to the point of obsession with belated and only intuitive interest in the third and fourth M (human dimension). Human factors or economics in the nuclear industry was an afterthought. Human reliability was essentially born in the aftermath of the Three Mile Island (TMI) accident. Impact of organizational factors on nuclear safety is only in the early stages of R and D. This paper describes some of the concepts being pursued by APG to link organizational factors and safety culture to Human Reliability Analysis (HRA) and to integrate such into probabilistic safety assessment (PSA), e.g. [APG, 1993]. (author). 11 refs, 4 figs, 1 tab

Radiation-induced Epstein-Barr virus reactivation in gastric cancer cells with latent EBV infection.

Science.gov (United States)

Nandakumar, Athira; Uwatoko, Futoshi; Yamamoto, Megumi; Tomita, Kazuo; Majima, Hideyuki J; Akiba, Suminori; Koriyama, Chihaya

2017-07-01

Epstein-Barr virus, a ubiquitous human herpes virus with oncogenic activity, can be found in 6%-16% of gastric carcinomas worldwide. In Epstein-Barr virus-associated gastric carcinoma, only a few latent genes of the virus are expressed. Ionizing irradiation was shown to induce lytic Epstein-Barr virus infection in lymphoblastoid cell lines with latent Epstein-Barr virus infection. In this study, we examined the effect of ionizing radiation on the Epstein-Barr virus reactivation in a gastric epithelial cancer cell line (SNU-719, an Epstein-Barr virus-associated gastric carcinoma cell line). Irradiation with X-ray (dose = 5 and 10 Gy; dose rate = 0.5398 Gy/min) killed approximately 25% and 50% of cultured SNU-719 cells, respectively, in 48 h. Ionizing radiation increased the messenger RNA expression of immediate early Epstein-Barr virus lytic genes (BZLF1 and BRLF1), determined by real-time reverse transcription polymerase chain reaction, in a dose-dependent manner at 48 h and, to a slightly lesser extent, at 72 h after irradiation. Similar findings were observed for other Epstein-Barr virus lytic genes (BMRF1, BLLF1, and BcLF1). After radiation, the expression of transforming growth factor beta 1 messenger RNA increased and reached a peak in 12-24 h, and the high-level expression of the Epstein-Barr virus immediate early genes can convert latent Epstein-Barr virus infection into the lytic form and result in the release of infectious Epstein-Barr virus. To conclude, Ionizing radiation activates lytic Epstein-Barr virus gene expression in the SNU-719 cell line mainly through nuclear factor kappaB activation. We made a brief review of literature to explore underlying mechanism involved in transforming growth factor beta-induced Epstein-Barr virus reactivation. A possible involvement of nuclear factor kappaB was hypothesized.

A regulatory perspective on human factors in nuclear power

International Nuclear Information System (INIS)

Whitfield, D.

1987-01-01

This paper sets out the approaches being taken by the United Kingdom Nuclear Installations Inspectorate (NII) to monitoring the application of human factors principles and practice in the UK industry. The role of NII is outlined, the development of human factors concerns is reviewed, the assessment of the Sizewell 'B' safety case is presented as a particular example, and pertinent future developments in the human factors discipline are proposed. (author)

Factors which could limit the nuclear fuel cycle development

International Nuclear Information System (INIS)

Pecqueur, M.; Barre, B.

1977-01-01

The nuclear fuel cycle is a most important industry for the energy future of the world. It has also a leading part as regards the physical continuity of energy supply of the countries engaged in the nuclear field. The development of this industry is subject to the economic or political constraints involved by the availability of raw materials, technologies or production means. The various limiting factors which could affect the different stages of the fuel cycle are linked with the technical, economic and financial aspects, with the impact on the environment, nuclear safety, risks of non-pacific uses and proliferation of arms. Interesting to note is also the correlation between the fuel cycle development and the problems of energy independence and security of nuclear programs. As a conclusion, the nuclear fuel cycle industry is confronted to difficulties due to its extremely rapid growth (doubling time 5 years) which only few heavy industries have encountered for long periods. It is more over submitted to the political and safety constraints always linked with nuclear matters. The task is therefore a difficult one. But the objective is worth-while since it is a condition to the development of nuclear industry [fr

on skin keratinocytes by nuclear factor-kappa B

African Journals Online (AJOL)

DR. NJ TONUKARI

2012-06-21

Jun 21, 2012 ... Effects of advanced glycation end-products (AGEs) on ... AGE levels, nuclear factor-kappa B (NF-κB) localization and cell viability were measured in vivo. ..... and related alteration in NF-κB activity, we treated normal cells by ...

Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls.

Science.gov (United States)

Baud, Véronique; Karin, Michael

2009-01-01

Nuclear factor kappaB (NF-kappaB) transcription factors have a key role in many physiological processes such as innate and adaptive immune responses, cell proliferation, cell death, and inflammation. It has become clear that aberrant regulation of NF-kappaB and the signalling pathways that control its activity are involved in cancer development and progression, as well as in resistance to chemotherapy and radiotherapy. This article discusses recent evidence from cancer genetics and cancer genome studies that support the involvement of NF-kappaB in human cancer, particularly in multiple myeloma. The therapeutic potential and benefit of targeting NF-kappaB in cancer, and the possible complications and pitfalls of such an approach, are explored.

A paralogous decoy protects Phytophthora sojae apoplastic effector PsXEG1 from a host inhibitor.

Science.gov (United States)

Ma, Zhenchuan; Zhu, Lin; Song, Tianqiao; Wang, Yang; Zhang, Qi; Xia, Yeqiang; Qiu, Min; Lin, Yachun; Li, Haiyang; Kong, Liang; Fang, Yufeng; Ye, Wenwu; Wang, Yan; Dong, Suomeng; Zheng, Xiaobo; Tyler, Brett M; Wang, Yuanchao

2017-02-17

The extracellular space (apoplast) of plant tissue represents a critical battleground between plants and attacking microbes. Here we show that a pathogen-secreted apoplastic xyloglucan-specific endoglucanase, PsXEG1, is a focus of this struggle in the Phytophthora sojae -soybean interaction. We show that soybean produces an apoplastic glucanase inhibitor protein, GmGIP1, that binds to PsXEG1 to block its contribution to virulence. P. sojae , however, secretes a paralogous PsXEG1-like protein, PsXLP1, that has lost enzyme activity but binds to GmGIP1 more tightly than does PsXEG1, thus freeing PsXEG1 to support P. sojae infection. The gene pair encoding PsXEG1 and PsXLP1 is conserved in many Phytophthora species, and the P. parasitica orthologs PpXEG1 and PpXLP1 have similar functions. Thus, this apoplastic decoy strategy may be widely used in Phytophthora pathosystems. Copyright © 2017, American Association for the Advancement of Science.

Deletion of hepatocyte nuclear factor-1-beta in an infant with prune belly syndrome.

Science.gov (United States)

Haeri, Sina; Devers, Patricia L; Kaiser-Rogers, Kathleen A; Moylan, Vincent J; Torchia, Beth S; Horton, Amanda L; Wolfe, Honor M; Aylsworth, Arthur S

2010-08-01

Prune belly syndrome is a rare congenital disorder characterized by deficiency of abdominal wall muscles, cryptorchidism, and urinary tract anomalies. We have had the opportunity to study a baby with prune belly syndrome associated with an apparently de novo 1.3-megabase interstitial 17q12 microdeletion that includes the hepatocyte nuclear factor-1-beta gene at 17q12. One previous patient, an adult, has been reported with prune belly syndrome and a hepatocyte nuclear factor-1-beta microdeletion. Hepatocyte nuclear factor-1-beta is a widely expressed transcription factor that regulates tissue-specific gene expression and is expressed in numerous tissues including mesonephric duct derivatives, the renal tubule of the metanephros, and the developing prostate of the mouse. Mutations in hepatocyte nuclear factor-1-beta cause the "renal cysts and diabetes syndrome," isolated renal cystic dysplasia, and a variety of other malformations. Based on its expression pattern and the observation of two affected cases, we propose that haploinsufficiency of hepatocyte nuclear factor-1-beta may be causally related to the production of the prune belly syndrome phenotype through a mechanism of prostatic and ureteral hypoplasia that results in severe obstructive uropathy with urinary tract and abdominal distension. Copyright Thieme Medical Publishers.

Economic benefits of power factor correction at a nuclear facility

International Nuclear Information System (INIS)

Boger, R.M.; Dalos, W.; Juguilon, M.E.

1986-01-01

The economic benefits of correcting poor power factor at an operating nuclear facility are shown. A project approach for achieving rapid return of investment without disrupting plant availability is described. Examples of technical problems associated with using capacitors for power factor correction are presented

Calculating the Unit Cost Factors for Decommissioning Cost Estimation of the Nuclear Research Reactor

International Nuclear Information System (INIS)

Jeong, Kwan Seong; Lee, Dong Gyu; Jung, Chong Hun; Lee, Kune Woo

2006-01-01

The estimated decommissioning cost of nuclear research reactor is calculated by applying a unit cost factor-based engineering cost calculation method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and establishment of composition factors are based. Decommissioning cost of nuclear research reactor is composed of labor cost, equipment and materials cost. Labor cost of decommissioning costs in decommissioning works are calculated on the basis of working time consumed in decommissioning objects. In this paper, the unit cost factors and work difficulty factors which are needed to calculate the labor cost in estimating decommissioning cost of nuclear research reactor are derived and figured out.

Scoring protein interaction decoys using exposed residues (SPIDER): a novel multibody interaction scoring function based on frequent geometric patterns of interfacial residues.

Science.gov (United States)

Khashan, Raed; Zheng, Weifan; Tropsha, Alexander

2012-08-01

Accurate prediction of the structure of protein-protein complexes in computational docking experiments remains a formidable challenge. It has been recognized that identifying native or native-like poses among multiple decoys is the major bottleneck of the current scoring functions used in docking. We have developed a novel multibody pose-scoring function that has no theoretical limit on the number of residues contributing to the individual interaction terms. We use a coarse-grain representation of a protein-protein complex where each residue is represented by its side chain centroid. We apply a computational geometry approach called Almost-Delaunay tessellation that transforms protein-protein complexes into a residue contact network, or an undirectional graph where vertex-residues are nodes connected by edges. This treatment forms a family of interfacial graphs representing a dataset of protein-protein complexes. We then employ frequent subgraph mining approach to identify common interfacial residue patterns that appear in at least a subset of native protein-protein interfaces. The geometrical parameters and frequency of occurrence of each "native" pattern in the training set are used to develop the new SPIDER scoring function. SPIDER was validated using standard "ZDOCK" benchmark dataset that was not used in the development of SPIDER. We demonstrate that SPIDER scoring function ranks native and native-like poses above geometrical decoys and that it exceeds in performance a popular ZRANK scoring function. SPIDER was ranked among the top scoring functions in a recent round of CAPRI (Critical Assessment of PRedicted Interactions) blind test of protein-protein docking methods. Copyright © 2012 Wiley Periodicals, Inc.

Human factors in the Canadian nuclear industry: future needs

International Nuclear Information System (INIS)

Harrison, F.

2008-01-01

Currently the industry is facing refurbishment and new builds. At present most licensees in Canada do not have sufficient numbers of Human Factors staff. As a result, the activities of the CNSC are too often focused on providing guidance regarding the application of Human Factors, in addition to reviewing work submitted by the licensee. Greater efficiencies for both the licensee and the CNSC could be realized if licensee staff had greater Human Factors expertise. Strategies for developing Human Factors expertise should be explored through cooperative partnerships with universities, which could be encouraged to include Human Factors courses specific to nuclear. (author)

Factors affecting the next generation of nuclear power

International Nuclear Information System (INIS)

Remick, F.J.

1990-01-01

For both financial, environmental and health reasons, and because of external and internal factors affecting this nation's energy supply, nuclear power will likely play a part in supplying this nation's energy in the coming decades. I believe this to be true for some other parts of the world as well. Even some severe critics of the nuclear power industry and the NRC might agree with me on this point. Increasing concern with the environmental consequences of the burning of fossil fuels has led some former opponents of the use of nuclear power to balance anew the risks and benefits of nuclear power and to modify to some degree their former opposition. A related concern with the adequacy of the energy supply is leading others to modify their positions. According to analyses done by the U.S. Department of Energy, after 1994 the United States will no longer be able to assure all its citizens a reliable supply of electricity. Already, many areas of the country are in need of additional electric capacity. In both Sweden and Switzerland, similar concerns have led to the adoption by many of more compromising positions. Some critics of nuclear power may in the end still reject it as an alternative, but, with the increased pressures on the environment and on our energy supply, nuclear power is an alternative which cannot be rejected without the most serious consideration. This should be, I believe, a point of consensus among us. In sum, there is a future for nuclear power in the sense that there is a use for it

Factors affecting the next generation of nuclear power

Energy Technology Data Exchange (ETDEWEB)

Remick, F J [Nuclear Regulatory Commission, Washington, DC (United States)

1990-07-01

For both financial, environmental and health reasons, and because of external and internal factors affecting this nation's energy supply, nuclear power will likely play a part in supplying this nation's energy in the coming decades. I believe this to be true for some other parts of the world as well. Even some severe critics of the nuclear power industry and the NRC might agree with me on this point. Increasing concern with the environmental consequences of the burning of fossil fuels has led some former opponents of the use of nuclear power to balance anew the risks and benefits of nuclear power and to modify to some degree their former opposition. A related concern with the adequacy of the energy supply is leading others to modify their positions. According to analyses done by the U.S. Department of Energy, after 1994 the United States will no longer be able to assure all its citizens a reliable supply of electricity. Already, many areas of the country are in need of additional electric capacity. In both Sweden and Switzerland, similar concerns have led to the adoption by many of more compromising positions. Some critics of nuclear power may in the end still reject it as an alternative, but, with the increased pressures on the environment and on our energy supply, nuclear power is an alternative which cannot be rejected without the most serious consideration. This should be, I believe, a point of consensus among us. In sum, there is a future for nuclear power in the sense that there is a use for it.

A novel nonsteroidal antifibrotic oligo decoy containing the TGF-beta element found in the COL1A1 gene which regulates murine schistosomiasis liver fibrosis.

Science.gov (United States)

Boros, D L; Singh, K P; Gerard, H C; Hudson, A P; White, S L; Cutroneo, K R

2005-08-01

Schistosomiasis mansoni disseminated worm eggs in mice and humans induce granulomatous inflammations and cumulative fibrosis causing morbidity and possibly mortality. In this study, intrahepatic and I.V. injections of a double-stranded oligodeoxynucleotide decoy containing the TGF-beta regulatory element found in the distal promoter of the COL1A1 gene into worm-infected mice suppressed TGF-beta1, COL1A1, tissue inhibitor of metalloproteinase-1, and decreased COL3A1 mRNAs to a lesser extent. Sequence comparisons within the mouse genome found homologous sequences within the COL3A1, TGF-beta1, and TIMP-1 5' flanking regions. Cold competition gel mobility shift assays using these homologous sequences with 5' and 3' flanking regions found in the natural COL1A1 gene showed competition. Competitive gel mobility assays in a separate experiment showed no competition using a 5-base mutated or scrambled sequence. Explanted liver granulomas from saline-injected mice incorporated 10.45 +/- 1.7% (3)H-proline into newly synthesized collagen, whereas decoy-treated mice showed no collagen synthesis. Compared with the saline control schistosomiasis mice phosphorothioate double-stranded oligodeoxynucleotide treatment decreased total liver collagen content (i.e. hydroxy-4-proline) by 34%. This novel molecular approach has the potential to be employed as a novel antifibrotic treatment modality. (c) 2005 Wiley-Liss, Inc.

Overall analysis of the cost key factors for the nuclear energy

International Nuclear Information System (INIS)

Caero, M.

1996-01-01

In 1995, 25,8 % of the world electricity consumption was of nuclear origin, while in the EU this figure is increased up to 50,6 %. In order to maintain and even to increase its share in the electricity generation, Nuclear Energy needs to achieve a good economic performance as a base load source when compared with its competitors, basically coal and gas fired plants. Fossil-fired generation costs have declined over the past ten years, mainly due to lower fossil fuel prices. This factor together with the recently observed tendency of higher discount rates to be applied are challenging the attractiveness of the nuclear energy. Nuclear energy is a capital intensive option. Taken into account extensive standardization programs has been established aiming at cost reductions as well as to increase efficiency of nuclear energy utilization, among their main purposes. Externalities play an important role, as they are already internalized in nuclear generation costs. This is not true for many existing coal-fired plants. Even a great uncertainly exists on greenhouse gas effects. Also decisions on greenhouse gas control and their impact on carbonaceous fuel generation costs cannot be clearly predicted, even in the immediate future. Macroeconomic factors like employment, competitiveness, energy conservation, energy availability, energy demand control, etc are positively influenced by the use of nuclear energy. A sustainable economic development cannot be achieved only relying on fossil fuel generation. As a wrap up sustainable development demands nuclear energy in order to cover the future objectives of energy availability, environmental control and energy cost control. (author)

Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions

OpenAIRE

Nefiodov, A. V.; Plunien, G.; Soff, G.

2002-01-01

The influence of nuclear polarization on the bound-electron $g$ factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron $g$ factor in highly charged ions.

Nuclear-polarization correction to the bound-electron g factor in heavy hydrogenlike ions.

Science.gov (United States)

Nefiodov, A V; Plunien, G; Soff, G

2002-08-19

The influence of nuclear polarization on the bound-electron g factor in heavy hydrogenlike ions is investigated. Numerical calculations are performed for the K- and L-shell electrons taking into account the dominant virtual nuclear excitations. This determines the ultimate limit for tests of QED utilizing measurements of the bound-electron g factor in highly charged ions.

Main factors affecting the fixing work about nuclear engineering and its discussion

International Nuclear Information System (INIS)

Zhang Zhihua; Liu Yaoguan; Qian Dazhi; Liu Hangang; Xu Xianqi; Deng Yue

2010-01-01

Main factors to the impact of the fixing work about nuclear engineering such as project design, construction, plan program, document, preparation, order, locale management, surveillance, quality assurance system and so on were presented. These factors were analyzed and discussed in this paper. Some measures and suggestions were put forward to accelerate construction fixing plan and insure good quality. We wish provide some references and help for someone engaged with construction of nuclear engineering. (authors)

Overview of factors affecting the leachability of nuclear waste forms

International Nuclear Information System (INIS)

Stone, J.A.

1980-01-01

An overview of various factors that affect the leachability of nuclear waste forms is presented. The factors affect primarily the leaching system (temperature, for example), the leachant (pH, for example), or the solid being leached (surface condition, for example). A qualitative understanding exists of the major factors affecting leaching, but further studies are needed to establish leaching mechanisms and develop predictive models. 67 refs

The human factor in the organisation and regulation of nuclear safety

International Nuclear Information System (INIS)

Bordes, F.; Savagner, J.-M.; Snanoudj, G.

1981-10-01

The TMI accident has brought to light the importance of the human factor in the safe operation of complex installations such as nuclear power plants. On this basis, the paper outlines the institutional framework for nuclear safety in France and reports on EDF practices in human resources management as well as in the improvement of working premises (control rooms) to optimize human behaviour in accident conditions. Finally, the interaction of labour laws on nuclear law in connection with safety is described. (NEA) [fr

Production and Functional Characterization of Murine Osteoclasts Differentiated from ER-Hoxb8-Immortalized Myeloid Progenitor Cells.

Directory of Open Access Journals (Sweden)

Frank Zach

Full Text Available In vitro differentiation into functional osteoclasts is routinely achieved by incubation of embryonic stem cells, induced pluripotent stem cells, or primary as well as cryopreserved spleen and bone marrow-derived cells with soluble receptor activator of nuclear factor kappa-B ligand and macrophage colony-stimulating factor. Additionally, osteoclasts can be derived from co-cultures with osteoblasts or by direct administration of soluble receptor activator of nuclear factor kappa-B ligand to RAW 264.7 macrophage lineage cells. However, despite their benefits for osteoclast-associated research, these different methods have several drawbacks with respect to differentiation yields, time and animal consumption, storage life of progenitor cells or the limited potential for genetic manipulation of osteoclast precursors. In the present study, we therefore established a novel protocol for the differentiation of osteoclasts from murine ER-Hoxb8-immortalized myeloid stem cells. We isolated and immortalized bone marrow cells from wild type and genetically manipulated mouse lines, optimized protocols for osteoclast differentiation and compared these cells to osteoclasts derived from conventional sources. In vitro generated ER-Hoxb8 osteoclasts displayed typical osteoclast characteristics such as multi-nucleation, tartrate-resistant acid phosphatase staining of supernatants and cells, F-actin ring formation and bone resorption activity. Furthermore, the osteoclast differentiation time course was traced on a gene expression level. Increased expression of osteoclast-specific genes and decreased expression of stem cell marker genes during differentiation of osteoclasts from ER-Hoxb8-immortalized myeloid progenitor cells were detected by gene array and confirmed by semi-quantitative and quantitative RT-PCR approaches. In summary, we established a novel method for the quantitative production of murine bona fide osteoclasts from ER-Hoxb8 stem cells generated from

A Study on the Allowable Safety Factor of Cut-Slopes for Nuclear Facilities

Energy Technology Data Exchange (ETDEWEB)

Kim, Myung Soo; Yee, Eric [KEPCO International Nuclear Graduate School, Ulsan (Korea, Republic of)

2015-10-15

In this study, the issues of allowable safety factor design criteria for cut-slopes in nuclear facilities is derived through case analysis, a proposed construction work slope design criteria that provides relatively detailed conditions can be applied in case of the dry season and some unclear parts of slope design criteria be modified in case of the rainy season. This safety factor can be further subdivided into two; normal and earthquake factors, a factor of 1.5 is applied for normal conditions and a factor of 1.2 is applied for seismic conditions. This safety factor takes into consideration the effect of ground water and rainfall conditions. However, no criteria for the case of cut-slope in nuclear facilities and its response to seismic conditions is clearly defined, this can cause uncertainty in design. Therefore, this paper investigates the allowable safety factor for cut-slopes in nuclear facilities, reviews conditions of both local and international cut-slope models and finally suggests an alternative method of analysis. It is expected that the new design criteria adequately ensures the stability of the cut-slope to reflect clear conditions for both the supervising and design engineers.

Factor analysis for the adoption of nuclear technology in diagnosis and treatment of chronic diseases

International Nuclear Information System (INIS)

Sato, Renato Cesar; Zouain, Desiree Moraes

2012-01-01

To identify and evaluate latent variables (variables that are not directly observed) for adopting and using nuclear technologies in diagnosis and treatment of chronic diseases. The measurement and management of these latent factors are important for health care due to complexities of the sector. Methods: An exploratory factor analysis study was conducted among 52 physicians practicing in the areas of Cardiology, Neurology and Oncology in the State of Sao Paulo who agreed to participate in the study between 2009 and 2010. Data were collected using an attitude measurement questionnaire, and analyzed according to the principal component method with Varimax rotation. Results: The component matrix after factor rotation showed three elucidative groups arranged according to demand for nuclear technology: clinical factors, structural factors, and technological factors. Clinical factors included questionnaire answers referring to medical history, previous interventions, complexity and chronicity of the disease. Structural factors included patient age, physician's practice area, and payment ability. Technological factors included prospective growth in the use of nuclear technology and availability of services. Conclusions: The clinical factors group dimension identified in the study included patient history, prior interventions, and complexity and chronicity of the disease. This dimension is the main motivating for adopting nuclear technology in diagnosis and treatment of chronic diseases. (author)

Human factor engineering applied to nuclear power plant design

International Nuclear Information System (INIS)

Manrique, A.; Valdivia, J.C.

2007-01-01

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. 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. Such a plan should state: -) Activities to be performed, and -) Creation of a Human Factor Engineering team adequately qualified. The Human Factor Engineering team is an integral part of the design team and is strongly linked to the engineering organizations but simultaneously has independence to act and is free to evaluate designs and propose changes in order to enhance human behavior. TECNATOM S.A. (a Spanish company) has been a part of the Design and Human Factor Engineering Team and has collaborated in the design of an advanced Nuclear Power Plant, developing methodologies and further implementing those methodologies in the design of the plant systems through the development of the plant systems operational analysis and of the man-machine interface design. The methodologies developed are made up of the following plans: -) Human Factor Engineering implementation in the Man-Machine Interface design; -) Plant System Functional Requirement Analysis; -) Allocation of Functions to man/machine; -) Task Analysis; -) Human-System Interface design; -) Control Room Verification and -) Validation

Human factor in the problem of Russian nuclear industry safety

International Nuclear Information System (INIS)

Abramova, V.

2002-01-01

The approach to human factor definition, considered in the paper, consists of recognition of as many as possible factors for developing a complete list of factors, which have influence on mistakes or successful work of NPP personnel. Safety culture is considered as the main factor. The enhancement in nuclear power industry includes an optimization of organizational structures and development of personnel safety attitudes. The organizational factors, as possible root causes for human errors, need to be identified, assessed and improved. The organizational activities taken in Russia are presented

Organisational factors. Their definition and influence on nuclear safety. Final report

International Nuclear Information System (INIS)

Baumont, G.; Wahlstroem, B.; Sola, R.; Williams, J.; Frischknecht, A.; Wilpert, B.; Rollenhagen, C.

2000-12-01

The importance of organisational factors in the operational safety and efficiency of nuclear power plants (NPP) has been recognised by many organisations around the world. Despite this recognition, however, there are as yet very few methods by which organisational factors can be systematically assessed and improved. The majority of research efforts applied so far have tended to be modest and scattered. The ORFA project was created as a remedy to these problems. The objective of the project is to create a better understanding of how organisation and management factors influence nuclear safety. A key scientific objective of the project is to identify components of a theoretical framework, which would help in understanding the relationships between organisational factors and nuclear safety. Three work packages were planned. First, a review of literature listed out the identified factors and methods for assessing them. Then, a draft version of the present report was prepared to clarify the environment context and the main issues of the topics. This draft was discussed at the ORFA seminar in Madrid 21-22 October 1999. During the seminar views and comments were collected on preliminary results of the project. Finally, this information has been integrated in the present and other reports and will be used to give further guidance to the European Commission in the development of forthcoming research programmes in the field. The project has addressed nuclear safety taking a broad perspective, which reflected and took into account the views of senior NPP management and regulators. The questions discussed during the project have been: how can organisational factors be included in safety assessments, how can good and bad operational practices be identified, which methods can be used for detecting weak signals of deteriorating performance, how should incidents be analysed with respect to organisational factors to give the largest learning benefit, how can data on organisational

Discussion on verification criterion and method of human factors engineering for nuclear power plant controller

International Nuclear Information System (INIS)

Yang Hualong; Liu Yanzi; Jia Ming; Huang Weijun

2014-01-01

In order to prevent or reduce human error and ensure the safe operation of nuclear power plants, control device should be verified from the perspective of human factors engineering (HFE). The domestic and international human factors engineering guidelines about nuclear power plant controller were considered, the verification criterion and method of human factors engineering for nuclear power plant controller were discussed and the application examples were provided for reference in this paper. The results show that the appropriate verification criterion and method should be selected to ensure the objectivity and accuracy of the conclusion. (authors)

Nucleus accumbens inflammation mediates anxiodepressive behavior and compulsive sucrose seeking elicited by saturated dietary fat

Directory of Open Access Journals (Sweden)

Léa Décarie-Spain

2018-04-01

Full Text Available Objective: The incidence of depression is significantly compounded by obesity. Obesity arising from excessive intake of high-fat food provokes anxiodepressive behavior and elicits molecular adaptations in the nucleus accumbens (NAc, a region well-implicated in the hedonic deficits associated with depression and in the control of food-motivated behavior. To determine the etiology of diet-induced depression, we studied the impact of different dietary lipids on anxiodepressive behavior and metabolic and immune outcomes and the contribution of NAc immune activity. Methods: Adult C57Bl/6 mice were subjected to isocaloric high-fat/high-sucrose diets (HFD, enriched in either saturated or monounsaturated fat, or a control low-fat diet (LFD. Metabolic responses, anxiodepressive behavior, and plasma and NAc inflammatory markers were assessed after 12 weeks. In separate experiments, an adenoviral construct inhibiting IKKβ, an upstream component of the nuclear factor kappa-b (NFkB pathway, was a priori injected into the NAc. Results: Both HFDs resulted in obesity and hyperleptinemia; however, the saturated HFD uniquely triggered anxiety-like behavior, behavioral despair, hyperinsulinemia, glucose intolerance, peripheral inflammation, and multiple pro-inflammatory signs in the NAc, including reactive gliosis, increased expression of cytokines, antigen-presenting markers and NFкB transcriptional activity. Selective NAc IKKβ inhibition reversed the upregulated expression of inflammatory markers, prevented anxiodepressive behavior and blunted compulsive sucrose-seeking in mice fed the saturated HFD. Conclusions: Metabolic inflammation and NFкB-mediated neuroinflammatory responses in the NAc contribute to the expression of anxiodepressive behavior and heightened food cravings caused by a diet high in saturated fat and sugar. Keywords: Diet-induced obesity, Dietary fatty acids, Nuclear factor kappa-b, Neuroinflammation, Depression, Anxiety, Food reward

Regulation of IFN regulatory factor 4 expression in human T cell leukemia virus-I-transformed T cells.

Science.gov (United States)

Sharma, Sonia; Grandvaux, Nathalie; Mamane, Yael; Genin, Pierre; Azimi, Nazli; Waldmann, Thomas; Hiscott, John

2002-09-15

IFN regulatory factor (IRF)-4 is a lymphoid/myeloid-restricted member of the IRF transcription factor family that plays an essential role in the homeostasis and function of mature lymphocytes. IRF-4 expression is tightly regulated in resting primary T cells and is transiently induced at the mRNA and protein levels after activation by Ag-mimetic stimuli such as TCR cross-linking or treatment with phorbol ester and calcium ionophore (PMA/ionomycin). However, IRF-4 is constitutively upregulated in human T cell leukemia virus type I (HTLV-I) infected T cells as a direct gene target for the HTLV-I Tax oncoprotein. In this study we demonstrate that chronic IRF-4 expression in HTLV-I-infected T lymphocytes is associated with a leukemic phenotype, and we examine the mechanisms by which continuous production of IRF-4 is achieved in HTLV-I-transformed T cells. IRF-4 expression in HTLV-1-infected cells is driven through activation of the NF-kappaB and NF-AT pathways, resulting in the binding of p50, p65, and c-Rel to the kappaB1 element and p50, c-Rel, and NF-ATp to the CD28RE element within the -617 to -209 region of the IRF-4 promoter. Furthermore, mutation of either the kappaB1 or CD28RE sites blocks Tax-mediated transactivation of the human IRF-4 promoter in T cells. These experiments constitute the first detailed analysis of human IRF-4 transcriptional regulation within the context of HTLV-I infection and transformation of CD4(+) T lymphocytes.

Absence of prognostic value of nuclear shape factor analysis in colorectal carcinoma: relevance of interobserver and intraobserver variability.

Science.gov (United States)

Di Fabio, Francesco; Shrier, Ian; Bégin, Louis R; Gordon, Philip H

2008-12-01

Several retrospective studies, including our previous investigation, have shown a prognostic value of nuclear shape factor in colorectal carcinomas. This prospective study was designed to assess the reliability of nuclear shape factor determined by nuclear morphometry and to confirm its prognostic value. Ninety-eight patients who underwent colorectal carcinoma resection were prospectively enrolled. Measurement of nuclear shape factor was performed by using a computer-based image analysis system. Nuclear shape factor was defined as the degree of circularity of the nucleus (1.0 for a perfect circle and values by American Joint Committee on Cancer stage were: 0.73 (0.07) in Stage I, 0.74 (0.06) in Stage II, and 0.75 (0.05) in Stage III carcinomas (P = 0.78, ANOVA). The intraobserver agreement was poor for observer A (r = 0.28) and practically nonexistent for observer B (r = -0.004, Pearson correlation). The intraclass coefficient for interobserver agreement was practically nonexistent. No significant association between nuclear shape factor and ten-year survival was found. Our prospective results, as opposed to our previous retrospective results, suggest that the reliability for nuclear shape factor morphometric analysis is very poor. We failed to confirm a prognostic value for nuclear shape factor in colorectal carcinoma.

Evidence for site-specific occupancy of the mitochondrial genome by nuclear transcription factors.

Directory of Open Access Journals (Sweden)

Georgi K Marinov

Full Text Available Mitochondria contain their own circular genome, with mitochondria-specific transcription and replication systems and corresponding regulatory proteins. All of these proteins are encoded in the nuclear genome and are post-translationally imported into mitochondria. In addition, several nuclear transcription factors have been reported to act in mitochondria, but there has been no comprehensive mapping of their occupancy patterns and it is not clear how many other factors may also be found in mitochondria. Here we address these questions by using ChIP-seq data from the ENCODE, mouseENCODE and modENCODE consortia for 151 human, 31 mouse and 35 C. elegans factors. We identified 8 human and 3 mouse transcription factors with strong localized enrichment over the mitochondrial genome that was usually associated with the corresponding recognition sequence motif. Notably, these sites of occupancy are often the sites with highest ChIP-seq signal intensity within both the nuclear and mitochondrial genomes and are thus best explained as true binding events to mitochondrial DNA, which exist in high copy number in each cell. We corroborated these findings by immunocytochemical staining evidence for mitochondrial localization. However, we were unable to find clear evidence for mitochondrial binding in ENCODE and other publicly available ChIP-seq data for most factors previously reported to localize there. As the first global analysis of nuclear transcription factors binding in mitochondria, this work opens the door to future studies that probe the functional significance of the phenomenon.

Transforming growth factor-beta 1 (TGF-beta1) promotes IL-2 mRNA expression through the up-regulation of NF-kappaB, AP-1 and NF-AT in EL4 cells.

Science.gov (United States)

Han, S H; Yea, S S; Jeon, Y J; Yang, K H; Kaminski, N E

1998-12-01

Transforming growth factor beta1 (TGF-beta1) has been previously shown to modulate interleukin 2 (IL-2) secretion by activated T-cells. In the present studies, we determined that TGF-beta1 induced IL-2 mRNA expression in the murine T-cell line EL4, in the absence of other stimuli. IL-2 mRNA expression was significantly induced by TGF-beta1 (0.1-1 ng/ml) over a relatively narrow concentration range, which led to the induction of IL-2 secretion. Under identical condition, we examined the effect of TGF-beta1 on the activity of nuclear factor AT (NF-AT), nuclear factor kappaB (NF-kappaB), activator protein-1 (AP-1) and octamer, all of which contribute to the regulation of IL-2 gene expression. Electrophoretic mobility shift assays showed that TGF-beta1 markedly increased NF-AT, NF-kappaB and AP-1 binding to their respective cognate DNA binding sites, whereas octamer binding remained constant, as compared with untreated cells. Employing a reporter gene expression system with p(NF-kappaB)3-CAT, p(NF-AT)3-CAT and p(AP-1)3-CAT, TGF-beta1 treatment of transfected EL4 cells induced a dose-related increase in chloramphenicol acetyltransferase activity that correlated well with the DNA binding profile found in the electrophoretic mobility shift assay studies. These results show that TGF-beta1, in the absence of any additional stimuli, up-regulates the activity of key transcription factors involved in IL-2 gene expression, including NF-AT, NF-kappaB and AP-1, to help promote IL-2 mRNA expression by EL4 cells.

Synergistic nuclear import of NeuroD1 and its partner transcription factor, E47, via heterodimerization

International Nuclear Information System (INIS)

Mehmood, Rashid; Yasuhara, Noriko; Oe, Souichi; Nagai, Masahiro; Yoneda, Yoshihiro

2009-01-01

The transition from undifferentiated pluripotent cells to terminally differentiated neurons is coordinated by a repertoire of transcription factors. NeuroD1 is a type II basic helix loop helix (bHLH) transcription factor that plays critical roles in neuronal differentiation and maintenance in the central nervous system. Its dimerization with E47, a type I bHLH transcription factor, leads to the transcriptional regulation of target genes. Mounting evidence suggests that regulating the localization of transcription factors contributes to the regulation of their activity during development as defects in their localization underlie a variety of developmental disorders. In this study, we attempted to understand the nuclear import mannerisms of NeuroD1 and E47. We found that the nuclear import of NeuroD1 and E47 is energy-dependent and involves the Ran-mediated pathway. Herein, we demonstrate that NeuroD1 and E47 can dimerize inside the cytoplasm before their nuclear import. Moreover, this dimerization promotes nuclear import as the nuclear accumulation of NeuroD1 was enhanced in the presence of E47 in an in vitro nuclear import assay, and NLS-deficient NeuroD1 was successfully imported into the nucleus upon E47 overexpression. NeuroD1 also had a similar effect on the nuclear accumulation of NLS-deficient E47. These findings suggest a novel role for dimerization that may promote, at least partially, the nuclear import of transcription factors allowing them to function efficiently in the nucleus.

Regression analysis of nuclear plant capacity factors

International Nuclear Information System (INIS)

Stocks, K.J.; Faulkner, J.I.

1980-07-01

Operating data on all commercial nuclear power plants of the PWR, HWR, BWR and GCR types in the Western World are analysed statistically to determine whether the explanatory variables size, year of operation, vintage and reactor supplier are significant in accounting for the variation in capacity factor. The results are compared with a number of previous studies which analysed only United States reactors. The possibility of specification errors affecting the results is also examined. Although, in general, the variables considered are statistically significant, they explain only a small portion of the variation in the capacity factor. The equations thus obtained should certainly not be used to predict the lifetime performance of future large reactors

Psychological factors affecting public acceptance of nuclear energy. Comparative analysis focusing on regional characteristics and degree of knowledge

International Nuclear Information System (INIS)

Kimura, Hiroshi; Suzuki, Atsuyuki; Furuta, Kazuo

2003-01-01

The purpose of this research is to clarify how psychological factors' impact on public acceptance of nuclear energy varies with where they live and their degree of knowledge. For this purpose, we carried out questionnaire survey about nuclear energy at three urban areas and two nuclear power plant siting areas. After collecting data, we applied factor analysis to the data, and found four factors which construct cognitive structure of nuclear energy. Using multiple regression analysis, we evaluated the impact of the four factors on two issues: the decision for or against nuclear policy and the reaction to nuclear power plant siting, and compared changes of the impact by where respondents live and their degree of knowledge. Consequently, we found that the impact of all four factors on the two issues varies with where respondents live. We also found that the impact of respondents' degree of knowledge to four factors varies with where they live. (author)

Human factors methods for nuclear control room design. Volume I. Human factors enhancement of existing nuclear control rooms. Final report

International Nuclear Information System (INIS)

Seminara, J.L.; Seidenstein, S.; Eckert, S.K.; Smith, D.L.

1979-11-01

Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. Human factors approaches were applied in the design of representative nuclear power plant control panels. First, methods for upgrading existing operational control panels were examined. Then, based on detailed human factors analyses of operator information and control requirements, designs of reactor, feedwater, and turbine-generator control panels were developed to improve the operator-control board interface, thereby reducing the potential for operator errors. In addition to examining present-generation concepts, human factors aspects of advanced systems and of hybrid combinations of advanced and conventional designs were investigated. Special attention was given to warning system designs. Also, a survey was conducted among control board designers to (1) develop an overview of design practices in the industry, and (2) establish appropriate measures leading to a more systematic concern for human factors in control board design

Organizational factors and nuclear power plant safety

International Nuclear Information System (INIS)

Haber, S.B.

1995-01-01

There are many organizations in our society that depend on human performance to avoid incidents involving significant adverse consequences. As our culture and technology have become more sophisticated, the management of risk on a broad basis has become more and more critical. The safe operation of military facilities, chemical plants, airlines, and mass transit, to name a few, are substantially dependent on the performance of the organizations that operate those facilities. The nuclear power industry has, within the past 15 years, increased the attention given to the influence of human performance in the safe operation of nuclear power plants (NPP). While NPPs have been designed through engineering disciplines to intercept and mitigate events that could cause adverse consequences, it has been clear from various safety-related incidents that human performance also plays a dominant role in preventing accidents. Initial efforts following the 1979 Three Mile Island incident focused primarily on ergonomic factors (e.g., the best design of control rooms for maximum performance). Greater attention was subsequently directed towards cognitive processes involved in the use of NPP decision support systems and decision making in general, personnel functions such as selection systems, and the influence of work scheduling and planning on employees' performance. Although each of these approaches has contributed to increasing the safety of NPPS, during the last few years, there has been a growing awareness that particular attention must be paid to how organizational processes affect NPP personnel performance, and thus, plant safety. The direct importance of organizational factors on safety performance in the NPP has been well-documented in the reports on the Three Mile Island and Chernobyl accidents as well as numerous other events, especially as evaluated by the U.S. Nuclear Regulatory Commission (NRC)

Study of greenhouse gases emission factor for nuclear power chain of China

International Nuclear Information System (INIS)

Ma Zhonghai; Pan Ziqiang; Xie Jianlun; Xiu Binglin

2001-01-01

The Greenhouse Gases Emission Factor (GGEF) for nuclear power chain of China is calculated based on Life Cycle Analysis method and the definition of full energy chain. There is no greenhouse gases released directly from nuclear power plant. The greenhouse gases emission from nuclear power plant is mainly from coal-fired electricity supply to nuclear power plant for its normal operation and the production of construction materials those are used in the nuclear power plant. The total GGEF of nuclear power chain in China is 13.71 g-co 2 /kWh. It is necessary to regulate un-rational power source mix and to use the energy sources in rational way for reducing the greenhouse gas effect. Nuclear power for electricity generation is one of effective ways to reduce greenhouse gases emission and retard the greenhouse effect

Thermodynamics for the Formation of Double-Stranded DNA-Single-Walled Carbon Nanotube Hybrids.

Science.gov (United States)

Shiraki, Tomohiro; Tsuzuki, Akiko; Toshimitsu, Fumiyuki; Nakashima, Naotoshi

2016-03-24

For the first time, the thermodynamics are described for the formation of double-stranded DNA (ds-DNA)-single-walled carbon nanotube (SWNT) hybrids. This treatment is applied to the exchange reaction of sodium cholate (SC) molecules on SWNTs and the ds-DNAs d(A)20 -d(T)20 and nuclear factor (NF)-κB decoy. UV/Vis/near-IR spectroscopy with temperature variations was used for analyzing the exchange reaction on the SWNTs with four different chiralities: (n,m)=(8,3), (6,5), (7,5), and (8,6). Single-stranded DNAs (ss-DNAs), including d(A)20 and d(T)20, are also used for comparison. The d(A)20-d(T)20 shows a drastic change in its thermodynamic parameters around the melting temperature (Tm ) of the DNA oligomer. No such Tm dependency was measured, owing to high Tm in the NF-κB decoy DNA and no Tm in the ss-DNA. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

International Nuclear Information System (INIS)

Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim

2014-01-01

Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations

Calmodulin-dependent nuclear import of HMG-box family nuclear factors: importance of the role of SRY in sex reversal.

Science.gov (United States)

Kaur, Gurpreet; Delluc-Clavieres, Aurelie; Poon, Ivan K H; Forwood, Jade K; Glover, Dominic J; Jans, David A

2010-08-15

The HMG (high-mobility group)-box-containing chromatin-remodelling factor SRY (sex-determining region on the Y chromosome) plays a key role in sex determination. Its role in the nucleus is critically dependent on two NLSs (nuclear localization signals) that flank its HMG domain: the C-terminally located 'beta-NLS' that mediates nuclear transport through Impbeta1 (importin beta1) and the N-terminally located 'CaM-NLS' which is known to recognize the calcium-binding protein CaM (calmodulin). In the present study, we examined a number of missense mutations in the SRY CaM-NLS from human XY sex-reversed females for the first time, showing that they result in significantly reduced nuclear localization of GFP (green fluorescent protein)-SRY fusion proteins in transfected cells compared with wild-type. The CaM antagonist CDZ (calmidazolium chloride) was found to significantly reduce wild-type SRY nuclear accumulation, indicating dependence of SRY nuclear import on CaM. Intriguingly, the CaM-NLS mutants were all resistant to CDZ's effects, implying a loss of interaction with CaM, which was confirmed by direct binding experiments. CaM-binding/resultant nuclear accumulation was the only property of SRY found to be impaired by two of the CaM-NLS mutations, implying that inhibition of CaM-dependent nuclear import is the basis of sex reversal in these cases. Importantly, the CaM-NLS is conserved in other HMG-box-domain-containing proteins such as SOX-2, -9, -10 and HMGN1, all of which were found for the first time to rely on CaM for optimal nuclear localization. CaM-dependent nuclear translocation is thus a common mechanism for this family of important transcription factors.

Nuclear Factor-kappaB in Autoimmunity: Man and Mouse.

Science.gov (United States)

Miraghazadeh, Bahar; Cook, Matthew C

2018-01-01

NF-κB (nuclear factor-kappa B) is a transcription complex crucial for host defense mediated by innate and adaptive immunity, where canonical NF-κB signaling, mediated by nuclear translocation of RelA, c-Rel, and p50, is important for immune cell activation, differentiation, and survival. Non-canonical signaling mediated by nuclear translocation of p52 and RelB contributes to lymphocyte maturation and survival and is also crucial for lymphoid organogenesis. We outline NF-κB signaling and regulation, then summarize important molecular contributions of NF-κB to mechanisms of self-tolerance. We relate these mechanisms to autoimmune phenotypes described in what is now a substantial catalog of immune defects conferred by mutations in NF-κB pathways in mouse models. Finally, we describe Mendelian autoimmune syndromes arising from human NF-κB mutations, and speculate on implications for understanding sporadic autoimmune disease.

What factors facilitate regulatory competence in supervising the safety of nuclear technology?

International Nuclear Information System (INIS)

Mishar, Marina

2012-01-01

The proposed utilization of nuclear energy for electricity generation as the alternative energy source requires Atomic Energy Licensing Board (AELB), the Malaysian nuclear regulatory body taking key role in supervising the safety of the program. This study looked into factors influencing the competency of current AELB human resource as technical competency has been identified as one of the main contributors to the success of a civil nuclear power program. The four quadrant competency model developed by International Atomic Energy Agency was utilized as the required competency. A comprehensive study on 81 personnel from five states in different geographic regions of the country were carried out to investigate the impact of six factors related to competency (educational level, years of working experience, trainings attended, participation in technical committees, numbers of technical papers written and number of technical presentation presented) on four dependent measures in the areas of regulatory competency (legal basis, technical disciplines, regulatory practices and personal and interpersonal effectiveness). Multiple regression (method enter) identified factors that had significant contribution to level of competency while stepwise regression resulted in identifying predictors to enhance competencies. Results were mixed but each of the independent factors is a predictor to different competencies. This study had identified the best predictors that could significantly contribute to the enhancement of regulatory. (author)

Organizational factors and reoccurrence protection on the JCO nuclear critical accident

International Nuclear Information System (INIS)

Takano, Kenichi

2000-01-01

A nuclear critical accident formed at a nuclear fuel conversion factory in Tokai-mura on September, 1999 became gradually clear not to be a simple human error formed at a level of workmen but to be an organizational error or accident relating to various organizational factors. As a nuclear power facility adopts a depth protection system fundamentally, a large accident with serious danger would not form only by a single trouble and a human error and unless some factors overlaps. By reviewing recent serious accidents and troubles, all of them seem to have a keyword of 'organizational factor'. In the JCO accident, there are some organizational factors such as a climate deviating from a manual, insufficient and loose check against change of procedure, reduction of operators from a reason of profit priority, attitude on priority of working efficiency, and so forth, which are partially common to the Chernobyl accident. Recently, accidents and troubles impossible to make them a cause of simple human error by a person but to have to say an organizational error, have increased. This trend seems to depend upon not only complication and scale-up of technology system but also graduate change of social and management systems operating them. Therefore, it seems to be necessary to introduce a concept of depth protection (multiple protection) in order to keep its reliability and safety when complicating and scaling-up of system. (G.K.)

Establishing a value chain for human factors in nuclear power plantcontrol room modernization

Energy Technology Data Exchange (ETDEWEB)

Joe, Jeffrey Clark [Idaho National Laboratory; Thomas, Kenneth David [Idaho National Laboratory; Boring, Ronald Laurids [Idaho National Laboratory

2015-07-01

Commercial nuclear power plants in the United States (U.S.) have operated reliably and efficiently for decades. With the life extensions of plants now being planned for operation beyond their original operating licenses, there are opportunities to achieve even greater efficiencies, while maintaining high operational reliabilities, with strategic, risk- and economically-informed, upgrades to plant systems and infrastructure. The U.S. Department of Energy’s Light Water Reactor Sustainability (LWRS) program supports the commercial nuclear industry’s modernization efforts through research and development (R&D) activities across many areas to help establish the technical and economic bases for modernization activities. The Advanced Instrumentation, Information, and Control Systems Technologies pathway is one R&D focus area for the LWRS program, and has researchers at Idaho National Laboratory working with select utility partners to use human factors and instrumentation and controls R&D to help modernize the plant’s main control room. However, some in the nuclear industry have not been as enthusiastic about using human factors R&D to inform life extension decision making. Part of the reason for this may stem from uncertainty decision-makers have regarding how human factors fits into the value chain for nuclear power plant control room modernization. This paper reviews past work that has attempted to demonstrate the value of human factors, and then describes the value chain concept, how it applies to control room modernization, and then makes a case for how and why human factors is an essential link in the modernization value chain.

Development of new Z-factors for the evaluation of the circumferential surface crack in nuclear pipes

International Nuclear Information System (INIS)

Choi, Y.H.; Chung, Y.K.; Park, Y.W.; Lee, J.B.

1997-01-01

The purpose of this study is to develop new Z-factors to evaluate the behavior of a circumferential surface crack in nuclear pipe. Z-factor is a load multiplier used in the Z-factor method, which is one of the ASME Code Sec. XI's recommendations for the estimation of a surface crack in nuclear pipe. It has been reported that the load carrying capacities predicted from the current ASME Code Z-factors, are not well in agreement with the experimental results for nuclear pipes with a surface crack. In this study, new Z-factors for ferritic base metal, ferritic submerged arc welding (SAW) weld metal, austenitic base metal, and austenitic SAW weld metal are obtained by use of the surface crack for thin pipe (SC.TNP) method based on GE/EPRI method. The desirability of both the SC.TNP method and the new Z-factors is examined using the results from 48 pipe fracture experiments for nuclear pipes with a circumferential surface crack. The results show that the SC.TNP method is good for describing the circumferential surface crack behavior and the new Z-factors are well in agreement with the measured Z-factors for both ferritic and austenitic pipes. (orig.)

The human factor in operating nuclear power plants during crisis situations

International Nuclear Information System (INIS)

Schnauder, H.; Smidt, D.

1981-10-01

Human factors in nuclear power plant operation are a main part of safety analyses. A considerable reduction in the influence of human factors has been obtained through ergonomic control room design, automation, clearly formulated operating manuals, and appropriate personnel education and training. These precautions are directed primarily at skill- and rule-based behaviour and are intended for normal operation and design accidents. In addition, one can construct an area of uncommon and very rare events where a partial failure of the safety systems is assumed. This is an area of knowledge-based behaviour. This report describes and assesses the present situation in German nuclear power plants. Recommendations for further research activity are made and, as a main result, for improvements in knowledge-based behaviour. (orig.) [de

b-jet tagged nuclear modification factors in heavy ion collisions with CMS

CERN Document Server

Jung, Kurt

2014-01-01

The energy loss of jets in heavy-ion collisions is expected to depend on the flavor of the fragmenting parton. Thus, measurements of jet quenching as a function of flavor place powerful constraints on the thermodynamical and transport properties of the hot and dense medium. Measurements of the nuclear modification factors of the heavy-flavor-tagged jets in both PbPb and pPb collisions can quantify such energy loss effects. Specifically, pPb measurements provide crucial insights into the behavior of the cold nuclear matter effect, which is required to fully understand the hot and dense medium effects on jets in PbPb collisions. In this talk, we present the b-jet spectra and the first measurement of the nuclear modification factors as a function of transverse momentum and pseudorapidity, using the high statistics pp, pPb and PbPb data taken in 2011 and 2013.

Engineering factors influencing Corbicula fouling in nuclear-service water systems

International Nuclear Information System (INIS)

Henager, C.H.; Johnson, K.I.; Page, T.L.

1983-06-01

Corbicula fouling is a continuing problem in nuclear-service water systems. More knowledge of biological and engineering factors is needed to develop effective detection and control methods. A data base on Corbicula fouling was compiled from nuclear and non-nuclear power stations and industries using raw water. This data base was used in an analysis to identify systems and components which are conducive to fouling by Corbicula. Bounds on several engineering parameters such as velocity and temperature which support Corbicula growth are given. Service water systems found in BWR and PWR reactors are listed and those that show fouling are identified. Possible safety implications of Corbicula fouling are discussed for specific service water systems. Several effective control methods in current use include backflushing with heated water, centrifugal strainers, and continuous chlorination during spawning seasons

Economic Conditions and Factors Affecting New Nuclear Power Deployment

Energy Technology Data Exchange (ETDEWEB)

Harrison, Thomas J [ORNL

2014-10-01

This report documents work performed in support of the US Department of Energy Office of Nuclear Energy’s Advanced Small Modular Reactor (AdvSMR) program. The report presents information and results from economic analyses to describe current electricity market conditions and those key factors that may impact the deployment of AdvSMRs or any other new nuclear power plants. Thus, this report serves as a reference document for DOE as it moves forward with its plans to develop advanced reactors, including AdvSMRs. For the purpose of this analysis, information on electricity markets and nuclear power plant operating costs will be combined to examine the current state of the nuclear industry and the process required to successfully move forward with new nuclear power in general and AdvSMRs in particular. The current electricity market is generally unfavorable to new nuclear construction, especially in deregulated markets with heavy competition from natural gas and subsidized renewables. The successful and profitable operation of a nuclear power plant (or any power plant) requires the rate at which the electricity is sold to be sufficiently greater than the cost to operate. The wholesale rates in most US markets have settled into values that provide profits for most operating nuclear power plants but are too low to support the added cost of capital recovery for new nuclear construction. There is a strong geographic dependence on the wholesale rate, with some markets currently able to support new nuclear construction. However, there is also a strong geographic dependence on pronuclear public opinion; the areas where power prices are high tend to have unfavorable views on the construction of new nuclear power plants. The use of government-backed incentives, such as subsidies, can help provide a margin to help justify construction projects that otherwise may not seem viable. Similarly, low interest rates for the project will also add a positive margin to the economic

Major factors influencing craft productivity in nuclear power plant construction

International Nuclear Information System (INIS)

Borcherding, J.D.; Sebastian, S.J.

1980-01-01

This paper reports on a research study whose objective was to determine the most influential factors adversely affecting craft productivity in nuclear power plant construction from the perspective of the tradesmen employed at the sites. Data were collected through the use of a questionnaire survey and group interview sessions, predominantly with workmen, at six nuclear power plant construction projects. Craftsmen were chosen as the major data base because of their awareness of how their time would actually be spent on the project. Topics considered include the factors influencing craft productivity, material availability, redoing work, crew interfacing, overcrowded work areas, instruction time, inspection delays, craft turnover, craft absenteeism, foreman changes, foreman incompetence, engineering design lead time, comprehensive scheduling of the design function, the responsibility of the utility, value engineering, plant standardization, the effective utilization of the planning and scheduling system, and the labor-management committee

Safety review for human factors engineering and control rooms of nuclear power plants

International Nuclear Information System (INIS)

Yang Mengzhuo

1998-01-01

Safety review for human factors engineering and control rooms of nuclear power plants (NPP) is in a forward position of science and technology, which began at American TMI severe accident and had been implemented in China. The importance and the significance of the safety review are expounded, the requirements of its scope and profundity are explained in detail. In addition, the situation of the technical document system for nuclear safety regulation on human factors engineering and control rooms of NPP in China is introduced briefly, on which the safety review is based

MAZ-binding G4-decoy with locked nucleic acid and twisted intercalating nucleic acid modifications suppresses KRAS in pancreatic cancer cells and delays tumor growth in mice

DEFF Research Database (Denmark)

Cogoi, Susanna; Zorzet, Sonia; Rapozzi, Valentina

2013-01-01

and stability, two polycyclic aromatic hydrocarbon units (TINA or AMANY) were inserted internally, to cap the quadruplex. The most active G4-decoy (2998), which had two para-TINAs, strongly suppressed KRAS expression in Panc-1 cells. It also repressed their metabolic activity (IC50 = 520 nM), and it inhibited...... cell growth and colony formation by activating apoptosis. We finally injected 2998 and control oligonucleotides 5153, 5154 (2 nmol/mouse) intratumorally in SCID mice bearing a Panc-1 xenograft. After three treatments, 2998 reduced tumor xenograft growth by 64% compared with control and increased...

Human factors design review guidelines for advanced nuclear control room technologies

International Nuclear Information System (INIS)

O'Hara, J.; Brown, W.; Granda, T.; Baker, C.

1991-01-01

Advanced control rooms (ACRs) for future nuclear power plants are being designed utilizing computer-based technologies. The US Nuclear Regulatory Commission reviews the human engineering aspects of such control rooms to ensure that they are designed to good human factors engineering principles and that operator performance and reliability are appropriately supported in order to protect public health and safety. This paper describes the rationale, general approach, and initial development of an NRC Advanced Control Room Design Review Guideline. 20 refs., 1 fig

Factors influencing the decommissioning of large-scale nuclear plants

International Nuclear Information System (INIS)

Large, J.H.

1988-01-01

The decision-making process involving the decommissioning of the UK graphite moderated, gas-cooled nuclear power stations is complex. There are timing, engineering, waste disposal, cost and lost generation capacity factors to consider and the overall decision of when and how to proceed with decommissioning may include political and public tolerance dimensions. For the final stage of decommissioning the nuclear industry could either completely dismantle the reactor island leaving a green-field site or, alternatively, the reactor island could be maintained indefinitely with additional super- and substructure containment. At this time the first of these options, or deferred decommissioning, prevails and with this the nuclear industry has expressed considerable confidence that the technology required will become available with passing time, that acceptable radioactive waste disposal methods and facilities will be available and that the eventual costs of decommissioning will not escalate without restraint. If the deferred decommissioning strategy is wrong and it is not possible to completely dismantle the reactor islands a century into the future, then it may be too late to effect sufficient longer term containment to maintain the reactor hulks in a reliable condition. With respect to the final decommissioning of large-scale nuclear plant, it is concluded that the nuclear industry does not know quite how to do it, when it will be attempted and when it will be completed, and they do not know how much it will eventually cost. (author)

A HUMAN FACTORS META MODEL FOR U.S. NUCLEAR POWER PLANT CONTROL ROOM MODERNIZATION

Energy Technology Data Exchange (ETDEWEB)

Joe, Jeffrey C.

2017-03-01

Over the last several years, the United States (U.S.) Department of Energy (DOE) has sponsored human factors research and development (R&D) and human factors engineering (HFE) activities through its Light Water Reactor Sustainability (LWRS) program to modernize the main control rooms (MCR) of commercial nuclear power plants (NPP). Idaho National Laboratory (INL), in partnership with numerous commercial nuclear utilities, has conducted some of this R&D to enable the life extension of NPPs (i.e., provide the technical basis for the long-term reliability, productivity, safety, and security of U.S. NPPs). From these activities performed to date, a human factors meta model for U.S. NPP control room modernization can now be formulated. This paper discusses this emergent HFE meta model for NPP control room modernization, with the goal of providing an integrated high level roadmap and guidance on how to perform human factors R&D and HFE for those in the U.S. nuclear industry that are engaging in the process of upgrading their MCRs.

Factors determining the long term back end nuclear fuel cycle strategy and future nuclear systems. Proceedings of a technical committee meeting

International Nuclear Information System (INIS)

2002-05-01

The Technical Committee Meeting (TCM) was held in Vienna on 8-10 November 1999; it was organized by the International Atomic Energy Agency and attended by 26 participants from 16 Member States. The purpose of the meeting was to exchange information among experts on the back end fuel cycle strategies adopted by Member States; to identify key factors determining the long-term back end fuel cycle strategies; and to assess the applicability of these factors to future nuclear systems. Issues associated with the back end fuel cycle supporting a country's nuclear power programme are technical, economic, institutional and political. This TCM provided an opportunity to address these issues and their impacts to the back end fuel cycles, as well as to identify and assess factors affecting the back end fuel cycle strategies. The discussion was organized ib the following topical sessions: the nuclear fuel cycle; spent fuel management; waste management and repository; plutonium management. This document contains a summary of the meeting and 22 individual papers presented by participants. Each of the papers was indexed separately

Factors determining the long term back end nuclear fuel cycle strategy and future nuclear systems. Proceedings of a technical committee meeting

Energy Technology Data Exchange (ETDEWEB)

NONE

2002-05-01

The Technical Committee Meeting (TCM) was held in Vienna on 8-10 November 1999; it was organized by the International Atomic Energy Agency and attended by 26 participants from 16 Member States. The purpose of the meeting was to exchange information among experts on the back end fuel cycle strategies adopted by Member States; to identify key factors determining the long-term back end fuel cycle strategies; and to assess the applicability of these factors to future nuclear systems. Issues associated with the back end fuel cycle supporting a country's nuclear power programme are technical, economic, institutional and political. This TCM provided an opportunity to address these issues and their impacts to the back end fuel cycles, as well as to identify and assess factors affecting the back end fuel cycle strategies. The discussion was organized ib the following topical sessions: the nuclear fuel cycle; spent fuel management; waste management and repository; plutonium management. This document contains a summary of the meeting and 22 individual papers presented by participants. Each of the papers was indexed separately.

Human-factor operating concept for Borssele Nuclear Power Station

International Nuclear Information System (INIS)

Wieman, J.L.

1995-01-01

The safety level in the operation of a reactor is determined basically by human beings. The Borssele Nuclear Power Station has carried out measures for improving the man-machine interface through training and operating instructions for the shift personnel. The retrofitting of control technology relevant to safety engineering should avoid operating instructions which can cause potential failures. A safety study has shown that the remaining risk following all retrofitting measures remains dependent to the extent of 80% on human factors and that human factors as a whole have a positive effect on reactor safety. (orig.) [de

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients.

Science.gov (United States)

Jafarzadeh, Abdollah; Nemati, Maryam; Rezayati, Mohammad Taghi; Nabizadeh, Mansooreh; Ebrahimi, Medhi

2013-07-01

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (ppeptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (ppeptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies

International Nuclear Information System (INIS)

2001-01-01

In co-operation with the OECD Nuclear Energy Agency (NEA), the Halden Reactor Project organised a Summer School on ''Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies'' in the period August 27-August 31, 2001. The Summer School was intended for scientists, engineers and technicians working for nuclear installations, engineering companies, industry and members of universities and research institutes, who wanted to broaden their nuclear background by getting acquainted with Man-Technology-Organisation-related subjects and issues. The Summer School should also serve to transfer knowledge to the ''young generation'' in the nuclear field. The following presentations were given: (1) Overview of the Nuclear Community and Current issues, (2) The Elements of Safety Culture; Evaluation of Events, (3) Quality Management (QM), (4) Probabilistic Risk Assessment (PSA), (5) Human Behaviour from the Viewpoint of Industrial Psychology, (6) Technical tour of the Halden Project Experimental Facilities, (7) Human Factors in Control Room Design, (8) Computerised Operator Support Systems (COSSs) and (9) Artificial Intelligence; a new Approach. Most of the contributions are overhead figures from spoken lectures

Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

In co-operation with the OECD Nuclear Energy Agency (NEA), the Halden Reactor Project organised a Summer School on ''Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies'' in the period August 27-August 31, 2001. The Summer School was intended for scientists, engineers and technicians working for nuclear installations, engineering companies, industry and members of universities and research institutes, who wanted to broaden their nuclear background by getting acquainted with Man-Technology-Organisation-related subjects and issues. The Summer School should also serve to transfer knowledge to the ''young generation'' in the nuclear field. The following presentations were given: (1) Overview of the Nuclear Community and Current issues, (2) The Elements of Safety Culture; Evaluation of Events, (3) Quality Management (QM), (4) Probabilistic Risk Assessment (PSA), (5) Human Behaviour from the Viewpoint of Industrial Psychology, (6) Technical tour of the Halden Project Experimental Facilities, (7) Human Factors in Control Room Design, (8) Computerised Operator Support Systems (COSSs) and (9) Artificial Intelligence; a new Approach. Most of the contributions are overhead figures from spoken lectures.

Studies on human factors in nuclear power plants

International Nuclear Information System (INIS)

Tsukuda, H.; Miyaoka, S.

1988-01-01

In order to raise the reliability and safety of nuclear power plants to the highest possible level, improvements to the mechanical system alone are not sufficient. Human factors must be systematically analysed and the causes and mechanisms of human error clarified to allow the development of countermeasures that will reduce error as much as possible. The paper introduces research in two areas, fundamental clarification of human behavioural, physiological and psychological characteristics to aid in the development of preventive measures for reducing error, and studies involving analysis of actual cases of accidents and failures related to man along with development of countermeasures to prevent the recurrence of such cases. The paper especially considers the latter area. The Human Performance Evaluation System (HPES) developed by the Institute of Nuclear Power Operations (INPO) in the USA was applied on a trial basis to 31 recent accidents and failures at Japanese nuclear power plants. The effectiveness of and possible improvement to HPES were considered. Also, cases that were not directly linked to accidents or failures were analysed using a method developed independently in Japan using data collected from a survey of approximately 3,000 power plant personnel. Fundamental research on human behaviour, physiology and psychology are also introduced. (author). 4 figs

Conserved Fever Pathways across Vertebrates: A Herpesvirus Expressed Decoy TNF-α Receptor Delays Behavioral Fever in Fish.

Science.gov (United States)

Rakus, Krzysztof; Ronsmans, Maygane; Forlenza, Maria; Boutier, Maxime; Piazzon, M Carla; Jazowiecka-Rakus, Joanna; Gatherer, Derek; Athanasiadis, Alekos; Farnir, Frédéric; Davison, Andrew J; Boudinot, Pierre; Michiels, Thomas; Wiegertjes, Geert F; Vanderplasschen, Alain

2017-02-08

Both endotherms and ectotherms (e.g., fish) increase their body temperature to limit pathogen infection. Ectotherms do so by moving to warmer places, hence the term "behavioral fever." We studied the manifestation of behavioral fever in the common carp infected by cyprinid herpesvirus 3, a native carp pathogen. Carp maintained at 24°C died from the infection, whereas those housed in multi-chamber tanks encompassing a 24°C-32°C gradient migrated transiently to the warmest compartment and survived as a consequence. Behavioral fever manifested only at advanced stages of infection. Consistent with this, expression of CyHV-3 ORF12, encoding a soluble decoy receptor for TNF-α, delayed the manifestation of behavioral fever and promoted CyHV-3 replication in the context of a temperature gradient. Injection of anti-TNF-α neutralizing antibodies suppressed behavioral fever, and decreased fish survival in response to infection. This study provides a unique example of how viruses have evolved to alter host behavior to increase fitness. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Public opinion factors regarding nuclear power

Energy Technology Data Exchange (ETDEWEB)

Benson, B.

1991-12-31

This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry`s practices are aligned with public opinion, a more favorable regulatory climate is possible.

Public opinion factors regarding nuclear power

Energy Technology Data Exchange (ETDEWEB)

Benson, B.

1991-01-01

This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry's practices are aligned with public opinion, a more favorable regulatory climate is possible.

Public opinion factors regarding nuclear power

International Nuclear Information System (INIS)

Benson, B.

1991-01-01

This paper is an effort to identify, as comprehensively as possible, public concerns about nuclear power, and to assess, where possible, the relative importance of these concerns as they relate to government regulation of and policy towards nuclear power. It is based on some two dozen in-depth interviews with key communicators representing the nuclear power industry, the environmental community, and government, as well as on the parallel efforts in our research project: (1) review of federal court case law, (2) a selective examination of the Nuclear Regulatory Commission (NRC) administrative process, and (3) the preceding George Mason University research project in this series. The paper synthesizes our findings about public attitudes towards nuclear power as expressed through federal court case law, NRC administrative law, public opinion surveys, and direct personal interviews. In so doing, we describe the public opinion environment in which the nuclear regulatory process must operate. Our premise is that public opinion ultimately underlies the approaches government agencies take towards regulating nuclear power, and that, to the degree that the nuclear power industry's practices are aligned with public opinion, a more favorable regulatory climate is possible

Cellular and molecular mechanisms of chronic rhinosinusitis and potential therapeutic strategies: review on cytokines, nuclear factor kappa B and transforming growth factor beta.

Science.gov (United States)

Phan, N T; Cabot, P J; Wallwork, B D; Cervin, A U; Panizza, B J

2015-07-01

Chronic rhinosinusitis is characterised by persistent inflammation of the sinonasal mucosa. Multiple pathophysiological mechanisms are likely to exist. Previous research has focused predominantly on T-helper type cytokines to highlight the inflammatory mechanisms. However, proteins such as nuclear factor kappa B and transforming growth factor beta are increasingly recognised to have important roles in sinonasal inflammation and tissue remodelling. This review article explores the roles of T-helper type cytokines, nuclear factor kappa B and transforming growth factor beta in the pathophysiological mechanisms of chronic rhinosinusitis. An understanding of these mechanisms will allow for better identification and classification of chronic rhinosinusitis endotypes, and, ultimately, improved therapeutic strategies.

Human factors in maintenance: Development and research in Swedish nuclear power plants

International Nuclear Information System (INIS)

Salo, I.; Svensson, Ola

2001-11-01

The present report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects

Human factors in maintenance: development and research in Swedish nuclear power plants

International Nuclear Information System (INIS)

Salo, I.; Svenson, O.

2001-11-01

The report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects. (au)

Human factors in maintenance: Development and research in Swedish nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Salo, I. [Lund Univ. (Sweden). Dept. of Psychology; Svensson, Ola [Stockholm Univ. (Sweden). Dept. of Psychology

2001-11-01

The present report investigated previously completed, ongoing, and planned research and development projects focusing human factors and maintenance work carried out at Swedish nuclear power plants and SKI. In addition, needs for future research and development works were also investigated. Participants from all nuclear power plants and SKI were included in the study. Participants responded to a set of questions in an interview. The interviews also generated a list of future research and development projects.

Transferring aviation human factors technology to the nuclear power industry

International Nuclear Information System (INIS)

Montemerlo, M.D.

1981-01-01

The purpose of this paper is to demonstrate the availability of aviation safety technology and research on problems which are sufficiently similar to those faced by the nuclear power industry that an agressive effort to adapt and transfer that technology and research is warranted. Because of time and space constraints, the scope of this paper is reduced from a discussion of all of aviation safety technology to the human factors of air carrier safety. This area was selected not only because of similarities in the human factors challenges shared by both industries (e.g. selection, training, evaluation, certification, etc.) but because experience in aviation has clearly demonstrated that human error contributes to a substantially greater proportion of accidents and incidents than does equipment failure. The Congress of the United States has placed a great deal of emphasis on investigating and solving human factors problems in aviation. A number of recent examples of this interest and of the resulting actions are described. The opinions of prominent aviation organizations as to the human factors problems most in need of research are presented, along with indications of where technology transfer to the nuclear power industry may be viable. The areas covered include: fatigue, crew size, information transfer, resource management, safety data-bases, the role of automation, voice and data recording systems, crew distractions, the management of safety regulatory agencies, equipment recertification, team training, crew work-load, behavioural factors, human factors of equipment design, medical problems, toxicological factors, the use of simulators for training and certification, determining the causes of human errors, the politics of systems improvement, and importance of both safety and public perception of safety if the industry is to be viable. (author)

UNC Nuclear Industries' human-factored approach to the operating or maintenance procedure

International Nuclear Information System (INIS)

Nelson, A.A.; Clark, J.E.

1982-01-01

The development of Human Factors Engineering (HFE) and UNC Nuclear Industries' (UNC) commitment to minimizing the potential for human error in the performance of operating or maintenance procedures have lead to a procedure upgrade program. Human-factored procedures were developed using information from many sources including, but not limited to, operators, a human factors specialist, engineers and supervisors. This has resulted in the Job Performance Aid (JPA). This paper presents UNC's approach to providing human-factored operating and maintenance procedures

Factors determining the UK's back-end nuclear fuel cycle strategy and future nuclear systems

International Nuclear Information System (INIS)

Dunn, M.J.; Ainsworth, Z.E.

2002-01-01

Nuclear generating capacity in the UK is static with no units currently under construction. The AGRs and the UK's only PWR, Sizewell B, are operated by British Energy Generation Ltd (BEGL) and British Energy Generation (UK) Ltd (BEG(UK)L), who are subsidiaries of British Energy plc (BE) which was privatised in July 1996. Ownership of the Magnox stations, which were excluded from this privatisation, has now been transferred to BNFL.Government policy on spent fuel management in the UK is that it is for the owners of the spent fuel to decide on the appropriate spent fuel management options, based on their own commercial judgement, subject to meeting the necessary regulatory requirements. The main factors which have predominantly determined UK utility decisions on spent fuel management, to date, have been based on the technical considerations of the spent fuel characteristics, economic attractiveness of the options and at reactor site spent fuel storage capacities. To date, reprocessing has been the dominant form of spent fuel treatment in the UK. Spent fuel storage facilities consist of a mixture of at-reactor stores and large, centralised ponds associated with the reprocessing activities which take place at the Sellafield site. BEGL and BEG(UK)L have contracts for the lifetime arisings of AGR fuel which allow for all AGR spent fuel to be sent to Sellafield for reprocessing or long-term storage. The prompt reprocessing of all Magnox fuel will continue, and spent PWR fuel will continue to be stored at the reactor site in the short to medium term. It is likely that a combination of factors, which are discussed later in this paper, will continue to affect back-end nuclear fuel cycle strategy and future nuclear systems. (author)

Battelle's human factors program for the US Nuclear Regulatory Commission

International Nuclear Information System (INIS)

Shikiar, R.

1983-10-01

Battelle has been involved in a programmatic effort of technical assistance to the Division of Human Factors Safety of the NRC. This program involves the efforts of over 75 professionals engaged in over 20 projects. These projects span the areas of human factors engineering, procedures, examinations, training, staffing and qualifications, and utility management and organization. All of these bear, one way or another, on the role of operators in nuclear power plants. This programmatic effort can be viewed as part of an integrative approach to system safety

Nuclear localization of Src-family tyrosine kinases is required for growth factor-induced euchromatinization

International Nuclear Information System (INIS)

Takahashi, Akinori; Obata, Yuuki; Fukumoto, Yasunori; Nakayama, Yuji; Kasahara, Kousuke; Kuga, Takahisa; Higashiyama, Yukihiro; Saito, Takashi; Yokoyama, Kazunari K.; Yamaguchi, Naoto

2009-01-01

Src-family kinases (SFKs), which participate in various signaling events, are found at not only the plasma membrane but also several subcellular compartments, including the nucleus. Nuclear structural changes are frequently observed during transcription, cell differentiation, senescence, tumorigenesis, and cell cycle. However, little is known about signal transduction in the alteration of chromatin texture. Here, we develop a pixel imaging method for quantitatively evaluating chromatin structural changes. Growth factor stimulation increases euchromatic hypocondensation and concomitant heterochromatic hypercondensation in G 1 phase, and the levels reach a plateau by 30 min, sustain for at least 5 h and return to the basal levels after 24 h. Serum-activated SFKs in the nucleus were more frequently detected in the euchromatin areas than the heterochromatin areas. Nuclear expression of kinase-active SFKs, but not unrelated Syk kinase, drastically increases both euchromatinization and heterochromatinization in a manner dependent on the levels of nuclear tyrosine phosphorylation. However, growth factor stimulation does not induce chromatin structural changes in SYF cells lacking SFKs, and reintroduction of one SFK member into SYF cells can, albeit insufficiently, induce chromatin structural changes. These results suggest that nuclear tyrosine phosphorylation by SFKs plays an important role in chromatin structural changes upon growth factor stimulation.

Analysis on nuclear power plant control room system design and improvement based on human factor engineering

International Nuclear Information System (INIS)

Gao Feng; Liu Yanzi; Sun Yongbin

2014-01-01

The design of nuclear power plant control room system is a process of improvement with the implementation of human factor engineering theory and guidance. The method of implementation human factor engineering principles into the nuclear power plant control room system design and improvement was discussed in this paper. It is recommended that comprehensive address should be done from control room system function, human machine interface, digital procedure, control room layout and environment design based on the human factor engineering theory and experience. The main issues which should be paid more attention during the control room system design and improvement also were addressed in this paper, and then advices and notices for the design and improvement of the nuclear power plant control room system were afforded. (authors)

Fermi liquid, clustering, and structure factor in dilute warm nuclear matter

Science.gov (United States)

Röpke, G.; Voskresensky, D. N.; Kryukov, I. A.; Blaschke, D.

2018-02-01

Properties of nuclear systems at subsaturation densities can be obtained from different approaches. We demonstrate the use of the density autocorrelation function which is related to the isothermal compressibility and, after integration, to the equation of state. This way we connect the Landau Fermi liquid theory well elaborated in nuclear physics with the approaches to dilute nuclear matter describing cluster formation. A quantum statistical approach is presented, based on the cluster decomposition of the polarization function. The fundamental quantity to be calculated is the dynamic structure factor. Comparing with the Landau Fermi liquid theory which is reproduced in lowest approximation, the account of bound state formation and continuum correlations gives the correct low-density result as described by the second virial coefficient and by the mass action law (nuclear statistical equilibrium). Going to higher densities, the inclusion of medium effects is more involved compared with other quantum statistical approaches, but the relation to the Landau Fermi liquid theory gives a promising approach to describe not only thermodynamic but also collective excitations and non-equilibrium properties of nuclear systems in a wide region of the phase diagram.

Critique of the Council on Economic Priorities test ''power plant performance: nuclear and coal capacity factors and economics''

International Nuclear Information System (INIS)

Simard, R.L.

1977-01-01

The Council on Economic Priorities (CEP) has assembled capacity factor data on most U.S. nuclear and coal-fired units in operation, performed a regression analysis upon capacity factor as a function of intrinsic unit variables such as size and age, and attempted a comparison of the economics of typical nuclear and coal-fired units using the resultant fitted-capacity factors. The report points out inadequacies in the CEP data base, the lack of predictive value in the results of the regression analysis, and inconsistencies in the economic evaluation of nuclear and coal-fired units

Nuclear exclusion of transcription factors associated with apoptosis in developing nervous tissue

Directory of Open Access Journals (Sweden)

R. Linden

1999-07-01

Full Text Available Programmed cell death in the form of apoptosis involves a network of metabolic events and may be triggered by a variety of stimuli in distinct cells. The nervous system contains several neuron and glial cell types, and developmental events are strongly dependent on selective cell interactions. Retinal explants have been used as a model to investigate apoptosis in nervous tissue. This preparation maintains the structural complexity and cell interactions similar to the retina in situ, and contains cells in all stages of development. We review the finding of nuclear exclusion of several transcription factors during apoptosis in retinal cells. The data reviewed in this paper suggest a link between apoptosis and a failure in the nucleo-cytoplasmic partition of transcription factors. It is argued that the nuclear exclusion of transcription factors may be an integral component of apoptosis both in the nervous system and in other types of cells and tissues.

Human factors review of nuclear power plant control room design. Final report

International Nuclear Information System (INIS)

Seminara, J.L.; Gonzalez, W.R.; Parsons, S.O.

1976-11-01

The human factors aspects of five representative nuclear power plant control rooms were evaluated using such methods as a checklist guided observation system, structured interviews with operators and trainers, direct observations of operator behavior, task analyses and procedure evaluation, and historical error analyses. The human factors aspects of design practices are illustrated, and many improvements in current practices are suggested. The study recommends that a detailed set of applicable human factors standards be developed to stimulate a uniform and systematic concern for human factors in design considerations

The unit cost factors and calculation methods for decommissioning - Cost estimation of nuclear research facilities

International Nuclear Information System (INIS)

Kwan-Seong Jeong; Dong-Gyu Lee; Chong-Hun Jung; Kune-Woo Lee

2007-01-01

Available in abstract form only. Full text of publication follows: The uncertainties of decommissioning costs increase high due to several conditions. Decommissioning cost estimation depends on the complexity of nuclear installations, its site-specific physical and radiological inventories. Therefore, the decommissioning costs of nuclear research facilities must be estimated in accordance with the detailed sub-tasks and resources by the tasks of decommissioning activities. By selecting the classified activities and resources, costs are calculated by the items and then the total costs of all decommissioning activities are reshuffled to match with its usage and objectives. And the decommissioning cost of nuclear research facilities is calculated by applying a unit cost factor method on which classification of decommissioning works fitted with the features and specifications of decommissioning objects and establishment of composition factors are based. Decommissioning costs of nuclear research facilities are composed of labor cost, equipment and materials cost. Of these three categorical costs, the calculation of labor costs are very important because decommissioning activities mainly depend on labor force. Labor costs in decommissioning activities are calculated on the basis of working time consumed in decommissioning objects and works. The working times are figured out of unit cost factors and work difficulty factors. Finally, labor costs are figured out by using these factors as parameters of calculation. The accuracy of decommissioning cost estimation results is much higher compared to the real decommissioning works. (authors)

Nuclear Wiskott–Aldrich syndrome protein co-regulates T cell factor 1-mediated transcription in T cells

Directory of Open Access Journals (Sweden)

Nikolai V. Kuznetsov

2017-10-01

Full Text Available Abstract Background The Wiskott–Aldrich syndrome protein (WASp family of actin-nucleating factors are present in the cytoplasm and in the nucleus. The role of nuclear WASp for T cell development remains incompletely defined. Methods We performed WASp chromatin immunoprecipitation and deep sequencing (ChIP-seq in thymocytes and spleen CD4+ T cells. Results WASp was enriched at genic and intergenic regions and associated with the transcription start sites of protein-coding genes. Thymocytes and spleen CD4+ T cells showed 15 common WASp-interacting genes, including the gene encoding T cell factor (TCF12. WASp KO thymocytes had reduced nuclear TCF12 whereas thymocytes expressing constitutively active WASpL272P and WASpI296T had increased nuclear TCF12, suggesting that regulated WASp activity controlled nuclear TCF12. We identify a putative DNA element enriched in WASp ChIP-seq samples identical to a TCF1-binding site and we show that WASp directly interacted with TCF1 in the nucleus. Conclusions These data place nuclear WASp in proximity with TCF1 and TCF12, essential factors for T cell development.

Molecular evidence for the existence of lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel/NF-kB pathways in disk abalone (Haliotis discus discus).

Science.gov (United States)

De Zoysa, Mahanama; Nikapitiya, Chamilani; Oh, Chulhong; Whang, Ilson; Lee, Jae-Seong; Jung, Sung-Ju; Choi, Cheol Young; Lee, Jehee

2010-01-01

The lipopolysaccharide-induced TNF-alpha factor (LITAF) and Rel family nuclear factor kappaB (Rel/NF-kB) are two important transcription factors which play major roles in the regulating inflammatory cytokine, apoptosis and immune related genes. Here, we report the discovery of disk abalone LITAF (AbLITAF) and Rel/NF-kB (AbRel/NF-kB) homologues and their immune responses. Full-length cDNA of AbLITAF consists of 441 bp open reading frame (ORF) that translates into putative peptide of 147 aa. Analysis of AbLITAF sequence showed it has characteristic LITAF (Zn(+2)) binding domain with two CXXC motifs. Phylogenetic analysis results further revealed that AbLITAF is a member of LITAF family. AbRel/NF-kB is 584 aa protein that contains several characteristic motifs including Rel homology domain (RHD), Rel protein signature, DNA binding motif, nuclear localization signal (NLS) and transcription factor immunoglobulin - like fold (TIG) similar to their invertebrate and vertebrate counterparts. Tissue specific analysis results showed that both AbLITAF and AbRel/NF-kB mRNA was expressed ubiquitously in all selected tissues in constitutive manner. However, constitutive expression of AbLITAF was higher than AbRel/NF-kB in all tissues except mantle. Upon immune challenge by bacteria (Vibrio alginolyticus, Vibrio parahemolyticus and Lysteria monocytogenes) and viral hemoragic septicemia virus (VHSV), AbLITAF showed the significant up-regulation in gills while AbRel/NF-kB transcription was not change significantly. Based on transcriptional response against immune challenge, we could suggest that regulation of TNF-alpha expression may have occurred mainly by LITAF activation rather than NF-kB in disk abalone. The cumulative data from other molluscs and our data with reference to TNF-alpha, LITAF and Rel/NF-kB from disk abalone provide strong evidence that LITAF and NF-kB are independent pathways likely to occur throughout the Phylum mollusca. 2010 Elsevier Ltd. All rights reserved.

Nuclear medicine - factors influencing the choice and use of radionuclides in diagnosis and therapy

International Nuclear Information System (INIS)

Anon.

1983-01-01

This report addresses the many factors which influence the choice of the proper radiopharmaceutical drug product for the diagnosis or treatment of a specific disease or condition in a human subject. The Report examines the historical factors that influence the choice of radionuclides, the factors that influence the localization of radionuclides in tissues, the factors that influence the choice of instruments, and include an evaluation of the nuclear medicine procedures that could be selected and their clinical usefulness. In examining these factors the desirable characteristics of the radiopharmaceutical drug products of the measurement systems are identified. The methods of dose determination and the assumptions used in determination of dose are developed. There is also a section on radiation effects. A chapter on guidelines for procedures in nuclear medicine and some general and specific recommendations for protection of patients conclude the body of the text

Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

In co-operation with the OECD Nuclear Energy Agency (NEA), the Halden Reactor Project organised a Summer School on ''Safe Operation of Nuclear Power Plants: Impacts of Human and Organisational Factors and Emerging Technologies'' in the period August 27-August 31, 2001. The Summer School was intended for scientists, engineers and technicians working for nuclear installations, engineering companies, industry and members of universities and research institutes, who wanted to broaden their nuclear background by getting acquainted with Man-Technology-Organisation-related subjects and issues. The Summer School should also serve to transfer knowledge to the ''young generation'' in the nuclear field. The following presentations were given: (1) Overview of the Nuclear Community and Current issues, (2) The Elements of Safety Culture; Evaluation of Events, (3) Quality Management (QM), (4) Probabilistic Risk Assessment (PSA), (5) Human Behaviour from the Viewpoint of Industrial Psychology, (6) Technical tour of the Halden Project Experimental Facilities, (7) Human Factors in Control Room Design, (8) Computerised Operator Support Systems (COSSs) and (9) Artificial Intelligence; a new Approach. Most of the contributions are overhead figures from spoken lectures.

Nuclear Power and Resource Efficiency—A Proposal for a Revised Primary Energy Factor

Directory of Open Access Journals (Sweden)

Ola Eriksson

2017-06-01

Full Text Available Measuring resource efficiency can be achieved using different methods, of which primary energy demand is commonly used. The primary energy factor (PEF is a figure describing how much energy from primary resources is being used per unit of energy delivered. The PEF for nuclear power is typically 3, which refers to thermal energy released from fission in relation to electricity generated. Fuel losses are not accounted for. However; nuclear waste represents an energy loss, as current plans for nuclear waste management mostly include final disposal. Based on a literature review and mathematical calculations of the power-to-fuel ratio for nuclear power, PEF values for the open nuclear fuel cycle (NFC option of nuclear power and different power mixes are calculated. These calculations indicate that a more correct PEF for nuclear power would be 60 (range 32–88; for electricity in Sweden (41% nuclear power PEF would change from 1.8 to 25.5, and the average PEF for electricity in the European Union (EU would change from 2.5 to 18. The results illustrate the poor resource efficiency of nuclear power, which paves the way for the fourth generation of nuclear power and illustrates the policy implication of using PEFs which are inconsistent with current waste management plans.

Inhibitors of nuclear factor kappa B cause apoptosis in cultured macrophages

Directory of Open Access Journals (Sweden)

E. E. Mannick

1997-01-01

Full Text Available The precise role of the transcription factor nuclear factor kappa B (NF- κB in the regulation of cell survival and cell death is still unresolved and may depend on cell type and position in the cell cycle. The aim of this study was to determine if three pharmacologic inhibitors of NF-κB, pyrrolidine dithiocarbamate, N-tosyl-L-lysl chloromethyl ketone and calpain I inhibitor, induce apoptosis in a murine macrophage cell line (RAW 264.7 at doses similar to those required for NF-κB inhibition. We found that each of the three inhibitors resulted in a dose- and time-dependent increase in morphologic indices of apoptosis in unstimulated, LPS-stimulated and TNF-stimulated cells. Lethal doses were consistent with those required for NF- κB inhibition. We conclude that nuclear NF-κB activation may represent an important survival mechanism in macrophages.

The contribution of nuclear training staff to human factors work in the CEGB and Nuclear Electric PLC

International Nuclear Information System (INIS)

Madden, V.J.

1990-01-01

The staff and simulators of utility's nuclear training function are being utilized in support of a wide range of human factor related activities. In addition to work on man machines interface review, operating procedures, operator support system and VDU format design and validation for the Magnox and AGR series of nuclear power plants, support is also being provided to the PWR Project Team through staff who have undergone extensive and comprehensive overseas PWR training programs. This paper discusses how recent initiatives in connection with a survey on operator stress and the possible use of psychometric testing in support of the selection of reactor desk engineers are also being supported

Human factors considerations for expert systems in the nuclear industry

International Nuclear Information System (INIS)

Nelson, W.R.

1988-01-01

This paper discusses the general human factors issues relative to the development and implementation of expert systems for the nuclear industry. It summarizes the relevant research that addresses these issues, and identifies those areas that need the most effort for success. Since much of the prominent work for the application of expert systems has focused on computerized aids for decision making in emergencies, this paper draws from this area for its examples. This area tends to highlight the issues because of the safety-critical nature of the application. The same issues, however, are relevant to other applications of expert systems in the nuclear industry as well, even though the consequences of failure may not be as dramatic

Factors affecting economic performance of nuclear power projects in the USA and abroad

International Nuclear Information System (INIS)

Braun, C.

1988-01-01

Trends in nuclear power economics in the USA, as well as in other large power programmes, are reviewed in this paper. The current US coal/nuclear economic situation, the implications for operating cost improvements and the potential for the introduction of new low-cost nuclear units are discussed. The average economic advantage of nuclear over coal plants has been significantly eroded over the last four years, though the rate of decline has recently slowed. Discussion of an average plant's performance indices is always imprecise, given the wide distribution of the costs data. However, several nuclear power plants can be identified whose total generation costs in 1985 were less than coal units' variable costs or total generation expenses. It is concluded that the impact of new, low-cost plants on improving the overall US nuclear/coal economics will require a long time to make itself felt. In the near term the most cost effective methods for improving US nuclear power economics are a reduction in operating expenses and an increase in average plant capacity factors. (author). 9 refs, 9 figs

Human factors engineering measures taken by nuclear power plant owners/operators for optimisation of the man-machine interface

International Nuclear Information System (INIS)

Eisgruber, H.

1996-01-01

Both operating results and human factors studies show that man is able to meet the requirements in this working environment. Hence the degree of human reliability required by the design basis of nuclear power plants is ensured. This means: - Nuclear technology for electricity generation is justifiable from the human factors point of view. - The chief opponent is not right in saying that man is not able to cope with the risks and challenges brought about by nuclear technology applications. The human factors concept for optimisation or configuration of the man-machine systems represents an additional endeavor on the part of nuclear power plant operators within the framework of their responsibilities. Human factors analyses meet with good response by the personnel, as analysis results and clarification of causes of accident scenarios contribute to relieve the personnel (exoneration) and find ways for remedial action. (orig./DG) [de

Over-expression of SR-cyclophilin, an interaction partner of nuclear pinin, releases SR family splicing factors from nuclear speckles

International Nuclear Information System (INIS)

Lin, C.-L.; Leu, Steve; Lu, M.-C.; Ouyang Pin

2004-01-01

Pre-mRNA splicing takes place within a dynamic ribonucleoprotein particle called the spliceosome and occurs in an ordered pathway. Although it is known that spliceosome consists of five small nuclear RNAs and at least 50 proteins, little is known about how the interaction among the proteins changes during splicing. Here we identify that SR-cyp, a Moca family of nuclear cyclophilin, interacts and colocalizes with nuclear pinin (pnn), a SR-related protein involving in pre-mRNA splicing. Nuclear pnn interacts with SR-cyp via its C-terminal RS domain. Upon SR-cyp over-expression, however, the subnuclear distribution of nuclear pnn is altered, resulting in its redistribution from nuclear speckles to a diffuse nucleoplasmic form. The diffuse subnuclear distribution of nuclear pnn is not due to epitope masking, accelerated protein turnover or post-translational modification. Furthermore, we find that SR-cyp regulates the subnuclear distribution of other SR family proteins, including SC35 and SRm300, in a similar manner as it does on nuclear pnn. This result is significant because it suggests that SR-cyp plays a general role in modulating the distribution pattern of SR-like and SR proteins, similar to that of Clk (cdc2-like kinase)/STY on SR family splicing factors. SR-cyp might direct its effect via either alteration of protein folding/conformation or of protein-protein interaction and thus may add another control level of regulation of SR family proteins and modification of their functions

Importance of nuclear station load factor in applied ro energy policies

International Nuclear Information System (INIS)

Gomes, Daniel de Souza

2015-01-01

Load factor is the ration between the energy produced by a station and the energy it would have produced running at maximum power. The factor intends for all types of commercial reactors. Nuclear plants continuously provide over 11% of the world's electricity. The reactors for which data were available generated 618.7 TWh of electricity in 2014. Typical load factor was around 75% in worldwide during the first quarter of 2015. In this manner, it obtained from an average, three-monthly or yearly. The regular load factor of the reactors in operation was around 56% in 1970. While, in 1980's decade, we have an increase to 63%, the same situation occurred in next the decade and suffering increasing to 73%. Currently, the load factor reaches 78%. Accidents are seasonal factors, with the occurrence of reduction of power generation plants. In 2015 in January, there are over 437 operable commercial reactors in 31 countries, with over 377,728 MWe of full capacity. In Brazil, total capacity is 1901 MWe, with around 2.8% of electricity energy consumed. The primary objective of this study was to find a forecast model that express the evolution of the load factor in the next years. In recent years occur an extensive development of pressurized water reactors in Asia. The periodicity of seasonal effects on the performance of nuclear power plants due to aging. However, the impact of plant age depended on new technologies that allow the growth of the performance. The accident of Fukushima was an inflection point for energy policies. The event produced a trend that reduced the load in the world. (author)

l-2-Oxothiazolidine-4-Carboxylic Acid or α-Lipoic Acid Attenuates Airway Remodeling: Involvement of Nuclear Factor-κB (NF-κB, Nuclear Factor Erythroid 2p45-Related Factor-2 (Nrf2, and Hypoxia-Inducible Factor (HIF

Directory of Open Access Journals (Sweden)

Heung Bum Lee

2012-06-01

Full Text Available Reactive oxygen species (ROS play a crucial role in the pathogenesis of acute and chronic respiratory diseases. Antioxidants have been found to ameliorate airway inflammation and hyperresponsiveness in animal models employing short-term exposure to allergen. However, little data are available on the effect of antioxidants on airway remodeling and signaling pathways in chronic asthma. In the present study, we used a long-term exposure murine model of allergic airway disease to evaluate the effects of an antioxidant, l-2-oxothiazolidine-4-carboxylic acid (OTC or α-lipoic acid (LA on airway remodeling, focusing on the ROS-related hypoxia-inducible signaling. Long-term challenge of ovalbumin (OVA increased ROS production, airway inflammation, and airway hyperresponsiveness, and developed features of airway remodeling such as excessive mucus secretion, subepithelial fibrosis, and thickening of the peribronchial smooth muscle layer. Administration of OTC or LA reduced these features of asthma, including airway remodeling, which was accompanied by suppression of transforming growth factor-β1, vascular endothelial growth factor, and T-helper 2 cytokines. In addition, OVA-induced activation of nuclear factor-κB (NF-κB, nuclear factor erythroid 2p45-related factor-2 (Nrf2, hypoxia-inducible factor (HIF-1α, and HIF-2α was reduced by OTC or LA. Our results also showed that OTC or LA down-regulated phosphoinositide 3-kinase activity and decreased phosphorylation of p38 mitogen-activated protein kinase but not extracellular signal-regulated kinase 1/2 or c-Jun N-terminal kinase. These findings demonstrate that OTC and LA can inhibit activation of NF-κB, Nrf2, and HIF, leading to attenuate allergen-induced airway remodeling.

A human factors data bank for French nuclear power plants

International Nuclear Information System (INIS)

Villemeur, A.; Mosneron-Dupin, F.; Bouissou, M.; Meslin, T.

1986-01-01

CONFUCIUS is a computerized data bank developed by Electricite de France to study human factors in nuclear power plants. A detailed and homogeneous grouping of described operation and maintenance errors as well as of performance times is possible with CONFUCIUS. It also incorporates a selection of statistical treatment softwares. Readily usable and modifiable, the system can easily evolve. It allows a wide range of applications (safety analysis, event analysis, training, human factors engineering, probabilistic analysis). Data derived from the analysis of significant events reported in power plants and from the analysis of simulator tests are used as inputs into this data bank

Macrophages control vascular stem/progenitor cell plasticity through tumor necrosis factor-α-mediated nuclear factor-κB activation.

Science.gov (United States)

Wong, Mei Mei; Chen, Yikuan; Margariti, Andriani; Winkler, Bernhard; Campagnolo, Paola; Potter, Claire; Hu, Yanhua; Xu, Qingbo

2014-03-01

Vascular lineage differentiation of stem/progenitor cells can contribute to both tissue repair and exacerbation of vascular diseases such as in vein grafts. The role of macrophages in controlling vascular progenitor differentiation is largely unknown and may play an important role in graft development. This study aims to identify the role of macrophages in vascular stem/progenitor cell differentiation and thereafter elucidate the mechanisms that are involved in the macrophage- mediated process. We provide in vitro evidence that macrophages can induce endothelial cell (EC) differentiation of the stem/progenitor cells while simultaneously inhibiting their smooth muscle cell differentiation. Mechanistically, both effects were mediated by macrophage-derived tumor necrosis factor-α (TNF-α) via TNF-α receptor 1 and canonical nuclear factor-κB activation. Although the overexpression of p65 enhanced EC (or attenuated smooth muscle cell) differentiation, p65 or TNF-α receptor 1 knockdown using lentiviral short hairpin RNA inhibited EC (or rescued smooth muscle cell) differentiation in response to TNF-α. Furthermore, TNF-α-mediated EC differentiation was driven by direct binding of nuclear factor-κB (p65) to specific VE-cadherin promoter sequences. Subsequent experiments using an ex vivo decellularized vessel scaffold confirmed an increase in the number of ECs and reduction in smooth muscle cell marker expression in the presence of TNF-α. The lack of TNF-α in a knockout mouse model of vein graft decreased endothelialization and significantly increased thrombosis formation. Our study highlights the role of macrophages in directing vascular stem/progenitor cell lineage commitment through TNF-α-mediated TNF-α receptor 1 and nuclear factor-κB activation that is likely required for endothelial repair in vascular diseases such as vein graft.

Human factors in nuclear power plant operation

International Nuclear Information System (INIS)

Sabri, Z.A.; Husseiny, A.A.

1980-01-01

An extensive effort is being devoted to developing a comprehensive human factor program that encompasses establishment of a data base for human error prediction using past operation experience in commercial nuclear power plants. Some of the main results of such an effort are reported including data retrieval and classification systems which have been developed to assist in estimation of operator error rates. Also, statistical methods are developed to relate operator error data to reactor type, age, and specific technical design features. Results reported in this paper are based on an analysis of LER's covering a six-year period for LWR's. Developments presently include a computer data management program, statistical model, and detailed error taxonomy

NF-kappaB and p53 are the dominant apoptosis-inducing transcription factors elicited by the HIV-1 envelope.

Science.gov (United States)

Perfettini, Jean-Luc; Roumier, Thomas; Castedo, Maria; Larochette, Nathanael; Boya, Patricia; Raynal, Brigitte; Lazar, Vladimir; Ciccosanti, Fabiola; Nardacci, Roberta; Penninger, Josef; Piacentini, Mauro; Kroemer, Guido

2004-03-01

The coculture of cells expressing the HIV-1 envelope glycoprotein complex (Env) with cells expressing CD4 results into cell fusion, deregulated mitosis, and subsequent cell death. Here, we show that NF-kappaB, p53, and AP1 are activated in Env-elicited apoptosis. The nuclear factor kappaB (NF-kappaB) super repressor had an antimitotic and antiapoptotic effect and prevented the Env-elicited phosphorylation of p53 on serine 15 and 46, as well as the activation of AP1. Transfection with dominant-negative p53 abolished apoptosis and AP1 activation. Signs of NF-kappaB and p53 activation were also detected in lymph node biopsies from HIV-1-infected individuals. Microarrays revealed that most (85%) of the transcriptional effects of HIV-1 Env were blocked by the p53 inhibitor pifithrin-alpha. Macroarrays led to the identification of several Env-elicited, p53-dependent proapoptotic transcripts, in particular Puma, a proapoptotic "BH3-only" protein from the Bcl-2 family known to activate Bax/Bak. Down modulation of Puma by antisense oligonucleotides, as well as RNA interference of Bax and Bak, prevented Env-induced apoptosis. HIV-1-infected primary lymphoblasts up-regulated Puma in vitro. Moreover, circulating CD4+ lymphocytes from untreated, HIV-1-infected donors contained enhanced amounts of Puma protein, and these elevated Puma levels dropped upon antiretroviral therapy. Altogether, these data indicate that NF-kappaB and p53 cooperate as the dominant proapoptotic transcription factors participating in HIV-1 infection.

Critical factors supporting the confidence in U.S. nuclear power industries

International Nuclear Information System (INIS)

Yoshida, Tomoaki

2004-01-01

The risk informed regulation in U.S. is summarized and factors supporting the confidence in U.S. nuclear power industries are thought to be helpful to our country for improving the state of nuclear power industries. In U.S., on the basis of clear Regulatory Guide, an entrepreneur constructs and practices corrective action of nonconformance. A regulatory commission submitted by the nation watches their movements. The movements related to regulatory are opened to the people and they make a thousand preparations for the rule to make correct the insufficient part. These above system get good results in U.S. It is important in Japan that we are not going to get away with anything on the system satisfied above conditions and practice. The risk informed regulation, effectiveness of risk informed regulation supporting conditions, a part of NRC (Nuclear Regulatory Commission) and entrepreneur are described. (S.Y.)

Role of zinc finger structure in nuclear localization of transcription factor Sp1

International Nuclear Information System (INIS)

Ito, Tatsuo; Azumano, Makiko; Uwatoko, Chisana; Itoh, Kohji; Kuwahara, Jun

2009-01-01

Transcription factor Sp1 is localized in the nucleus and regulates gene expression. Our previous study demonstrated that the carboxyl terminal region of Sp1 containing 3-zinc finger region as DNA binding domain can also serve as nuclear localization signal (NLS). However, the nuclear transport mechanism of Sp1 has not been well understood. In this study, we performed a gene expression study on mutant Sp1 genes causing a set of amino acid substitutions in zinc finger domains to elucidate nuclear import activity. Nuclear localization of the GFP-fused mutant Sp1 proteins bearing concomitant substitutions in the first and third zinc fingers was highly inhibited. These mutant Sp1 proteins had also lost the binding ability as to the GC box sequence. The results suggest that the overall tertiary structure formed by the three zinc fingers is essential for nuclear localization of Sp1 as well as dispersed basic amino acids within the zinc fingers region.

Factors affecting the cost and competitiveness of nuclear electricity

International Nuclear Information System (INIS)

Bertel, E.; Stevens, G.H.

1996-01-01

The general context in which are carried out the investment choices of the electric sector has evolved in a significant way during these last years and the changes are to a certain extent irreversible. Economic globalization, deregulation of the electricity market, privatisation of electricity producers, and increasing awareness of environmental issues are modifying the policy-making landscape and the criteria and priorities of decision-makers in the power sector. Competitiveness remains a cornerstone for evaluating and choosing alternative technologies in the process of planning and decision-making for electricity system expansion or power plant replacement. Nevertheless, the production costs analysis inserts factors which were not taking before into account as for instance social impacts, health and environmental effects. These new approaches better reveal the total costs of the different production means. They will certainly lead to different choices than those based on the whole comparison of direct costs supported by producers. The economic studies carried out by the Nuclear Energy Agency of the OECD (NEA) cover all the preceding aspects and give objective information on the competitiveness of nuclear electricity. The nuclear industry has today the necessary means to take up the challenges of the electricity new markets. (O.M.)

Basic factors to forecast maintenance cost and failure processes for nuclear power plants

International Nuclear Information System (INIS)

Popova, Elmira; Yu, Wei; Kee, Ernie; Sun, Alice; Richards, Drew; Grantom, Rick

2006-01-01

Two types of maintenance interventions are usually administered at nuclear power plants: planned and corrective. The cost incurred includes the labor (manpower) cost, cost for new parts, or emergency order of expensive items. At the plant management level there is a budgeted amount of money to be spent every year for such operations. It is very important to have a good forecast for this cost since unexpected events can trigger it to a very high level. In this research we present a statistical factor model to forecast the maintenance cost for the incoming month. One of the factors is the expected number of unplanned (due to failure) maintenance interventions. We introduce a Bayesian model for the failure rate of the equipment, which is input to the cost forecasting model. The importance of equipment reliability and prediction in the commercial nuclear power plant is presented along with applicable governmental and industry organization requirements. A detailed statistical analysis is performed on a set of maintenance cost and failure data gathered at the South Texas Project Nuclear Operating Company (STPNOC) in Bay City, Texas, USA

Orphan nuclear receptor TR4 and fibroblast growth factor 1 in metabolism

NARCIS (Netherlands)

Liu, Weilin

2016-01-01

Metabolic homeostasis is achieved, in part, through the coordinated activities of members of the Nuclear Receptor (NR) family, a superfamily of ligand-modulated transcription factors (TFs) that mediate responses to a wide range of lipophilic signaling molecules including lipids, steroids, retinoids,

Research on cognitive reliability model for main control room considering human factors in nuclear power plants

International Nuclear Information System (INIS)

Jiang Jianjun; Zhang Li; Wang Yiqun; Zhang Kun; Peng Yuyuan; Zhou Cheng

2012-01-01

Facing the shortcomings of the traditional cognitive factors and cognitive model, this paper presents a Bayesian networks cognitive reliability model by taking the main control room as a reference background and human factors as the key points. The model mainly analyzes the cognitive reliability affected by the human factors, and for the cognitive node and influence factors corresponding to cognitive node, a series of methods and function formulas to compute the node cognitive reliability is proposed. The model and corresponding methods can be applied to the evaluation of cognitive process for the nuclear power plant operators and have a certain significance for the prevention of safety accidents in nuclear power plants. (authors)

Human Factors Engineering Review Model for advanced nuclear power reactors

International Nuclear Information System (INIS)

O'Hara, J.; Higgins, J.; Goodman, C.; Galletti, G.: Eckenrode, R.

1993-01-01

One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model's rationale, scope, objectives, development, general characteristics. and application

Ultimate capacity and influenced factors analysis of nuclear RC containment subjected to internal pressure

International Nuclear Information System (INIS)

Song Chenning; Hou Gangling; Zhou Guoliang

2014-01-01

Ultimate compressive bearing capacity, influenced factors and its rules of nuclear RC containment are key problems of safety assessment, accident treatment and structure design, etc. Ultimate compressive bearing capacity of nuclear RC containment is shown by concrete damaged plasticity model and steel double liner model of ABAQUS. The study shows that the concrete of nuclear RC containment cylinder wall becomes plastic when the internal pressure is up to 0.87 MPa, the maximum tensile strain of steel liner exceeds 3000 × 10 6 and nuclear RC containment reaches ultimate status when the internal pressure is up to 1.02 MPa. The result shows that nuclear RC containment is in elastic condition under the design internal pressure and the bearing capacity meets requirement. Prestress and steel liner play key parts in the ultimate internal pressure and failure mode of nuclear RC containment. The study results have value for the analysis of ultimate compressive bearing capacity, structure design and safety assessment. (authors)

Human factors methods for nuclear control room design. Volume 2. Human factors survey of control room design practices

International Nuclear Information System (INIS)

Seminara, J.L.; Parsons, S.O.

1979-11-01

An earlier review of the control rooms of operating nuclear power plants identified many design problems having potential for degrading operator performance. As a result, the formal application of human factors principles was found to be needed. This report demonstrates the use of human factors in the design of power plant control rooms. The approaches shown in the report can be applied to operating power plants, as well as to those in the design stage. This study documents human factors techniques required to provide a sustained concern for the man-machine interface from control room concept definition to system implementation

Key Response Planning Factors for the Aftermath of Nuclear Terrorism

Energy Technology Data Exchange (ETDEWEB)

Buddemeier, B R; Dillon, M B

2009-01-21

Despite hundreds of above-ground nuclear tests and data gathered from Hiroshima and Nagasaki, the effects of a ground-level, low-yield nuclear detonation in a modern urban environment are still the subject of considerable scientific debate. Extensive review of nuclear weapon effects studies and discussions with nuclear weapon effects experts from various federal agencies, national laboratories, and technical organizations have identified key issues and bounded some of the unknowns required to support response planning for a low-yield, ground-level nuclear detonation in a modern U.S. city. This study, which is focused primarily upon the hazards posed by radioactive fallout, used detailed fallout predictions from the advanced suite of three-dimensional (3-D) meteorology and plume/fallout models developed at Lawrence Livermore National Laboratory (LLNL), including extensive global Key Response Planning Factors for the Aftermath of Nuclear Terrorism geographical and real-time meteorological databases to support model calculations. This 3-D modeling system provides detailed simulations that account for complex meteorology and terrain effects. The results of initial modeling and analysis were presented to federal, state, and local working groups to obtain critical, broad-based review and feedback on strategy and messaging. This effort involved a diverse set of communities, including New York City, National Capitol Regions, Charlotte, Houston, Portland, and Los Angeles. The largest potential for reducing casualties during the post-detonation response phase comes from reducing exposure to fallout radiation. This can be accomplished through early, adequate sheltering followed by informed, delayed evacuation.B The response challenges to a nuclear detonation must be solved through multiple approaches of public education, planning, and rapid response actions. Because the successful response will require extensive coordination of a large number of organizations, supplemented by

Human factors review of nuclear power plant control room design. Summary report

International Nuclear Information System (INIS)

Seminara, J.L.; Gonzalez, W.R.; Parsons, S.O.

1976-11-01

Human factors engineering is an interdisciplinary specialty concerned with influencing the design of equipment systems, facilities, and operational environments to promote safe, efficient, and reliable operator performance. The human factors aspects of five representative nuclear power plant control rooms were evaluated using such methods as a checklist-guided observation system, structured interviews with operators and trainers, direct observations of operator behavior, task analyses and procedure evaluation, and historical error analyses. The human factors aspects of design practices are illustrated, and many improvements in current practices are suggested. The study recommends that a detailed set of applicable human factors standards be developed to stimulate a uniform and systematic concern for human factors in design considerations

Human factor as nuclear safety element

International Nuclear Information System (INIS)

Valeca, S.C.; Preda, M.; Valeca, M.; Ana, E. M.; Popescu, D.

2008-01-01

National nuclear power system is based on western technology, it covers almost 20% from national need and could be briefly described by: - Safety and economic performances of Cernavoda NPP Unit 1; - Reduced influence on environment, population and workers; - Excellent ranking (place 4) among CANDU units from all over the world. Also, the national nuclear power system plays a major role in Romanian power policy accomplishment: - Energy safety and independence assurance; - Decrease of production of greenhouse effect gases; - Preserve the stability and adequacy of energy cost. 'Nuclear Safety' concept covers all the activities resulting from nuclear fuel cycle. By taking into account the international experience, the related activities are estimated to last around 70 years in Romania: - 10 years for site description and selection, design, manufacturing and commissioning activities; - 40 years for Nuclear Power Plant operation, maintenance and modernization activities; - 20 years for preservation and decommissioning activities. The above mentioned activities requires human resources, qualified and specialized in the following areas: - research and development; - equipment design, manufacturing and operation; - components construction and assembly, operation and maintenance. (authors)

Heat and nuclear radiation as risk factors for male infertility: results of a French case-control study

International Nuclear Information System (INIS)

Thonneau, P.F.; Rachou, E.; Ducot, B.; Multigner, L.; Velez de la Calle, J.P.; Le Martelot, M.T.

1998-01-01

Very few studies have investigated the possible effects of environmental radiation and heat exposure on male reproductive function. We conducted a case control study to evaluate the various infertility risk factors in the military population of the french town of Brest to investigate an apparently high incidence of infertility in couples in which the man may have been exposed to occupational nuclear radiation. These findings suggest that in addition to well known medical factors, 'potential' exposure to heat or nuclear radiation could also be risk factors for infertility. (N.C.)

Quantum shielding effects on the Gamow penetration factor for nuclear fusion reaction in quantum plasmas

Science.gov (United States)

Lee, Myoung-Jae; Jung, Young-Dae

2017-01-01

The quantum shielding effects on the nuclear fusion reaction process are investigated in quantum plasmas. The closed expression of the classical turning point for the Gamow penetration factor in quantum plasmas is obtained by the Lambert W-function. The closed expressions of the Gamow penetration factor and the cross section for the nuclear fusion reaction in quantum plasmas are obtained as functions of the plasmon energy and the relative kinetic energy by using the effective interaction potential with the WKB analysis. It is shown that the influence of quantum screening suppresses the Sommerfeld reaction factor. It is also shown that the Gamow penetration factor increases with an increase of the plasmon energy. It is also shown that the quantum shielding effect enhances the deuterium formation by the proton-proton reaction in quantum plasmas. In addition, it is found that the energy dependences on the reaction cross section and the Gamow penetration factor are more significant in high plasmon-energy domains.

Dose factors to calculate the radiation exposure due to radioactive waste air from nuclear facilities

International Nuclear Information System (INIS)

Brenk, H.D.; Vogt, K.J.

1977-01-01

An evaluation of the environmental impact of nuclear plants according to paragraph 45 of the Radiation Protection Directive of the Federal Republic of Germany requires the calculation of dose conversion factors indicating the correlation between the contaminated medium and individual radiation exposure. The present study is to be conceived as a contribution to discussion on this subject. For the determination of radiation exposure caused by the waste air of nuclear plants, models are being specified for computing the dose conversion factors for the external exposure pathways of β-submersion, γ-submersion and γ-radiation from contaminated ground as well as the internal exposure pathways of inhalation and ingestion, which further elaborate and improve the models previously applied, especially as far as the ingestion pathway is concerned, which distinguishes between 6 major food categories. The computer models are applied to those radionuclides which are significan for nuclear emitters, in particular nuclear light-water power stations. The results obtained for the individual exposure pathways and affected organs are specified in the form of tables. For this purpose, calculations were first of all carried out for the so-called 'reference man'. The results can be transferred to population groups with different consumption habits (e.g. vegetarians) by the application of correction factors. The models are capable of being extended with a view to covering other age groups. (orig.) [de

Research and development on the human factors technologies for nuclear power plants in Korea

International Nuclear Information System (INIS)

Sim, B.S.; Lee, J.W.; Cheon, S.W.

1996-01-01

This paper introduces our research project on the development of human factors technologies for nuclear power plants in Korea. The project is divided into two sub-projects. The first sub-project is the development of human factors experimental evaluation techniques, which aims to develop the techniques for experimental design, experimental measurement and data collection/analysis, and to construct an integrated test facility (ITF) suitable for the experimental evaluation of man-machine interfaces (MMIs) at an advanced control room. The second is the development of human behavior analysis techniques, which has two research areas: one is the development of a task simulation analyzer and the other is human error case studies for nuclear power plants. (author)

Factors relevant to the sealing of nuclear facilities

International Nuclear Information System (INIS)

1991-05-01

This report reviews and summaries the factors to be considered in the design, construction and surveillance of confinement structures for damaged nuclear facilities. General engineering, design and environmental considerations are included, both from the standpoint of the mitigation of near-term effects by virtue of interim confinement, and from the standpoint of the acceptability of the structure for long-term confinement. Factors which influence optimization of the design and the construction sequence are reviewed, including the nature of the accident, natural conditions of the site, and thermal and radiation effects. Safety criteria are presented from the standpoint of regulatory requirements, radiological consequences, and monitoring/surveillance requirements for both interim and long-term confinement. Methodologies related to concrete fabrication technology and other construction techniques appropriate for building confinement structures are discussed. Long-term considerations relative to the future of the site for in-place storage/disposal of the waste, and possible future reuse of the site are also included

Identification of a phosphorylation-dependent nuclear localization motif in interferon regulatory factor 2 binding protein 2.

Directory of Open Access Journals (Sweden)

Allen C T Teng

Full Text Available Interferon regulatory factor 2 binding protein 2 (IRF2BP2 is a muscle-enriched transcription factor required to activate vascular endothelial growth factor-A (VEGFA expression in muscle. IRF2BP2 is found in the nucleus of cardiac and skeletal muscle cells. During the process of skeletal muscle differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the functional significance of this relocation and the mechanisms that control nucleocytoplasmic localization of IRF2BP2 are not yet known.Here, by fusing IRF2BP2 to green fluorescent protein and testing a series of deletion and site-directed mutagenesis constructs, we mapped the nuclear localization signal (NLS to an evolutionarily conserved sequence (354ARKRKPSP(361 in IRF2BP2. This sequence corresponds to a classical nuclear localization motif bearing positively charged arginine and lysine residues. Substitution of arginine and lysine with negatively charged aspartic acid residues blocked nuclear localization. However, these residues were not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation of serine 360 (S360. Many large-scale phosphopeptide proteomic studies had reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear localization in C(2C(12 myoblasts and CV1 cells. In contrast, substituting serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic redistribution in differentiated C(2C(12 muscle cells. As for the effects of these mutations on VEGFA promoter activity, the S360A mutation interfered with VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered with VEGFA activation, suggesting that this mutation, while enforcing nuclear entry, may disrupt an essential activation function of IRF2BP2.Nuclear localization of IRF2BP2 depends on phosphorylation near a conserved NLS. Changes in phosphorylation status

IRSN-ANCCLI partnership. Organizational and human factors in nuclear safety - April 2014

International Nuclear Information System (INIS)

Jeffroy, Francois; Garron, Joel; Mercel, Philippe; Compagnat, Gilles; Gaucher, Eric; Gaillard, Pierre; Fanchini, Henri; Jacquemont, Vincent

2013-06-01

The contributions (Power Point presentations) of this seminar first address the history of the taking into account of organizational and human factors until the Fukushima accident (history of their taking into account in nuclear safety expertise in France, history of the development of policy of organizational and human factors by an operator). The next contributions discuss the main issues regarding these factors after Fukushima: report by a work-group, work performed by the the Comite d'Orientation sur les Facteurs Sociaux, Organisationnels et Humains (Committee of orientation on social, organizational and human factors). The third session addresses the implication of stakeholders in expertise on these factors: analysis of organizational and human factors by a local information commission or by a CHSCT (committee of hygiene, safety and working conditions)

Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam®-Histoculture and Tumor-Sphere Models of Chemo-Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging.

Directory of Open Access Journals (Sweden)

Shuya Yano

Full Text Available Stomach cancer carcinomatosis peritonitis (SCCP is a recalcitrant disease. The goal of the present study was to establish an in vitro-in vivo-like imageable model of SCCP to develop cell-cycle-based therapeutics of SCCP. We established 3-D Gelfoam® histoculture and tumor-sphere models of SCCP. FUCCI-expressing MKN-45 stomach cancer cells were transferred to express the fluorescence ubiquinized cell-cycle indicator (FUCCI. FUCCI-expressing MKN-45 cells formed spheres on agarose or on Gelfoam® grew into tumor-like structures with G0/G1 cancer cells in the center and S/G2 cancer cells located in the surface as indicated by FUCCI imaging when the cells fluoresced red or green, respectively. We treated FUCCI-expressing cancer cells forming SCCP tumors in Gelfoam® histoculture with OBP-301, cisplatinum (CDDP, or paclitaxel. CDDP or paclitaxel killed only cycling cancer cells and were ineffective against G1/G2 MKN-45 cells in tumors growing on Gelfoam®. In contrast, the telomerase-dependent adenovirus OBP-301 decoyed the MKN-45 cells in tumors on Gelfoam® to cycle from G0/G1 phase to S/G2 phase and reduced their viability. CDDP- or paclitaxel-treated MKN-45 tumors remained quiescent and did not change in size. In contrast, OB-301 reduced the size of the MKN-45 tumors on Gelfoam®. We examined the cell cycle-related proteins using Western blotting. CDDP increased the expression of p53 and p21 indicating cell cycle arrest. In contrast, OBP-301 decreased the expression of p53 and p21 Furthermore, OBP-301 increased the expression of E2F and pAkt as further indication of cell cycle decoy. This 3-D Gelfoam® histoculture and FUCCI imaging are powerful tools to discover effective therapy of SCCP such as OBP-301.

Efficacy of a Cell-Cycle Decoying Killer Adenovirus on 3-D Gelfoam®-Histoculture and Tumor-Sphere Models of Chemo-Resistant Stomach Carcinomatosis Visualized by FUCCI Imaging

Science.gov (United States)

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2016-01-01

Stomach cancer carcinomatosis peritonitis (SCCP) is a recalcitrant disease. The goal of the present study was to establish an in vitro-in vivo-like imageable model of SCCP to develop cell-cycle-based therapeutics of SCCP. We established 3-D Gelfoam® histoculture and tumor-sphere models of SCCP. FUCCI-expressing MKN-45 stomach cancer cells were transferred to express the fluorescence ubiquinized cell-cycle indicator (FUCCI). FUCCI-expressing MKN-45 cells formed spheres on agarose or on Gelfoam® grew into tumor-like structures with G0/G1 cancer cells in the center and S/G2 cancer cells located in the surface as indicated by FUCCI imaging when the cells fluoresced red or green, respectively. We treated FUCCI-expressing cancer cells forming SCCP tumors in Gelfoam® histoculture with OBP-301, cisplatinum (CDDP), or paclitaxel. CDDP or paclitaxel killed only cycling cancer cells and were ineffective against G1/G2 MKN-45 cells in tumors growing on Gelfoam®. In contrast, the telomerase-dependent adenovirus OBP-301 decoyed the MKN-45 cells in tumors on Gelfoam® to cycle from G0/G1 phase to S/G2 phase and reduced their viability. CDDP- or paclitaxel-treated MKN-45 tumors remained quiescent and did not change in size. In contrast, OB-301 reduced the size of the MKN-45 tumors on Gelfoam®. We examined the cell cycle-related proteins using Western blotting. CDDP increased the expression of p53 and p21 indicating cell cycle arrest. In contrast, OBP-301 decreased the expression of p53 and p21 Furthermore, OBP-301 increased the expression of E2F and pAkt as further indication of cell cycle decoy. This 3-D Gelfoam® histoculture and FUCCI imaging are powerful tools to discover effective therapy of SCCP such as OBP-301. PMID:27673332

The Impact of Organizational Factors on Safety. The Perspective of Experts from the Spanish Nuclear Sector; El Impacto de los Factores Organizativos en la Seguridad. La Vision de los Expertos del Sector Nuclear Espanol

Energy Technology Data Exchange (ETDEWEB)

German, S.; Silla, I.; Navajas, J.

2014-07-01

Previous research supports the importance of organizational factors on safety in high reliability organizations. This study aims to determine the impact of those factors in the Spanish nuclear sector. Particularly, this study focuses on examining the role of performance indicators, organizational culture, organizational factors, and organizational context. With that purpose, an electronic survey addressed to experts from the Spanish nuclear sector was carried out. Results showed that performance indicators are well-known among industry experts and are perceived as useful for improving performance. Behavioural norms that influence safety and some relevant factors that promote problem identification were identified. Additionally, findings suggested that organizational context must be taken into account to better understand the role of organizational culture. Moreover, industry experts pointed out organizational factors to be improved: organizational communication processes within the organization, positive reinforcement, and field supervisors practices. Finally, findings supported the influence of organizational context on safety. It is noteworthy the role of the social impact of international events (e.g., Chernobyl...), the relationship with the regulator and the legislative and governmental framework. (Author)

How to implement decoy-state quantum key distribution for a satellite uplink with 50-dB channel loss

Science.gov (United States)

Meyer-Scott, Evan; Yan, Zhizhong; MacDonald, Allison; Bourgoin, Jean-Philippe; Hübel, Hannes; Jennewein, Thomas

2011-12-01

Quantum key distribution (QKD) takes advantage of fundamental properties of quantum physics to allow two distant parties to share a secret key; however, QKD is hampered by a distance limitation of a few hundred kilometers on Earth. The most immediate solution for global coverage is to use a satellite, which can receive separate QKD transmissions from two or more ground stations and act as a trusted node to link these ground stations. In this article we report on a system capable of performing QKD in the high loss regime expected in an uplink to a satellite using weak coherent pulses and decoy states. Such a scenario profits from the simplicity of its receiver payload, but has so far been considered to be infeasible due to very high transmission losses (40-50 dB). The high loss is overcome by implementing an innovative photon source and advanced timing analysis. Our system handles up to 57 dB photon loss in the infinite key limit, confirming the viability of the satellite uplink scenario. We emphasize that while this system was designed with a satellite uplink in mind, it could just as easily overcome high losses on any free space QKD link.

How to implement decoy-state quantum key distribution for a satellite uplink with 50-dB channel loss

International Nuclear Information System (INIS)

Meyer-Scott, Evan; Yan, Zhizhong; MacDonald, Allison; Bourgoin, Jean-Philippe; Huebel, Hannes; Jennewein, Thomas

2011-01-01

Quantum key distribution (QKD) takes advantage of fundamental properties of quantum physics to allow two distant parties to share a secret key; however, QKD is hampered by a distance limitation of a few hundred kilometers on Earth. The most immediate solution for global coverage is to use a satellite, which can receive separate QKD transmissions from two or more ground stations and act as a trusted node to link these ground stations. In this article we report on a system capable of performing QKD in the high loss regime expected in an uplink to a satellite using weak coherent pulses and decoy states. Such a scenario profits from the simplicity of its receiver payload, but has so far been considered to be infeasible due to very high transmission losses (40-50 dB). The high loss is overcome by implementing an innovative photon source and advanced timing analysis. Our system handles up to 57 dB photon loss in the infinite key limit, confirming the viability of the satellite uplink scenario. We emphasize that while this system was designed with a satellite uplink in mind, it could just as easily overcome high losses on any free space QKD link.

CSNI technical opinion papers no.10. The role of human and organisational factors in nuclear power plant modifications

International Nuclear Information System (INIS)

2009-01-01

Nuclear power plant modifications may be needed for a number of different reasons. These include physical ageing of plant systems, structures and components; obsolescence in hardware and software; feedback from operating experience; and opportunities for improved plant safety, reliability or capability. However, experience has also shown that weaknesses in the design and/or implementation of modifications can present significant challenges to plant safety. They can also have a considerable impact on the commercial performance of the plant. It is therefore important that the plant modification process reflect a recognition of the potential impact of human errors and that it incorporate suitable measures to minimise the potential for such errors. In this context, the NEA Committee on the Safety of Nuclear Installations (CSNI) and its Working Group on Human and Organisational Factors organised an international workshop in 2003 to discuss the role of human and organisational performance in the nuclear plant modification process. This technical opinion paper represents the consensus of specialists in human and organisational factors (HOF) in the NEA member countries on commendable practices and approaches to dealing with nuclear plant modifications. It considers factors that should be taken into account when developing a modification process and identifies some lessons learnt from application of the process. The paper should be of particular interest of nuclear safety regulators and nuclear power plant operators. (author)

The need and direction of a human factors research program for the nuclear power industry

International Nuclear Information System (INIS)

Blackman, H.S.; Meyer, O.R.; Nelson, W.R.

1986-01-01

It is axiomatic that the need for a human factors program in the nuclear power industry must be based upon an examination of the process of nuclear energy production and the role that the human plays in this process. It has been pointed out by others that a large number of incidents in technology based industries can be attributed to human error, thereby demonstrating the need to understand the human in interacting with complex processes. But an emphasis upon human ''error'' is a negative approach and can be non-productive, particularly when the ''correct'' human action has not been clearly defined prior to the incident. Some industries have expended great resources in a positive attempt to maximize the performance of the human in critical roles, e.g., the man-in-space program, the commercial airlines industry, deep-sea exploration. Central to this issue of human factors in nuclear power is the question of the role that the human plays in reducing the risk of the total system. If, as in other areas of application, the nuclear industry can make substantial improvements in the performance of humans, one needs to know how much risk is really reduced

DMPD: Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 17349209 Nuclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Carmody...uclear factor-kappaB: activation and regulation during toll-like receptorsignaling. Authors Carmody

A preliminary study on related factors of mental health in nuclear power plant operators

International Nuclear Information System (INIS)

Dai Tingting; Liu Yulong; Li Yuan; Liao Haihong; Qiu Mengyue; Bian Huahui; Chen Weibo; Liu Chunfeng

2012-01-01

Objective: To explore the status of nuclear power plant operators in mental health and its correlation with emotional stability, liveliness, anxiety and urgency. Methods: 255 male operators were randomly selected from three nuclear power bases, meanwhile 61 undergraduates were used as control group. The mental health and neurobehavioral evaluation system of Chinese nuclear power plant operators was developed by Second Affiliated Hospital of Soochow University, which was used to assess mental health of the subjects. The scores of mental health personality factors were recorded, together with four main personality factors including emotional stability, liveliness, anxiety and urgency. Results: The score of lie was lower than 8 which showed all inspected groups were normal. 1.57% (4/255) operators had psychological disorders, 3.92% (10/255) had poor mental health, 27.84% (71/255) had general mental health, 66.7% (170/255) had excellent mental health, whereas 9.84% (6/61) for control group had psychological disorders. Obvious difference was observed in the final scores between the nuclear power plant operators and control group. The former gained higher scores on mental health,emotional stability,and lower scores on anxiety and urgency (t=3.437, 4.423, -2.493, -2.093, P<0.05). Both groups aged over 27 years and with length of service over 5 years were awarded higher scores on mental health, emotional stability (t=2.585, 2.349; t=2.606, 2.947, P<0.05), lower scores on anxiety and urgency (t=-3.407, -2.138; t=- 2.941, -2.256, P<0.05). The mental health was positively correlated with emotional stability and liveliness (r=0.721, 0.650, P<0.05), but negatively correlated with anxiety and urgency (r=-0.809, -0.693, P<0.05). Conclusions: The majority of nuclear power plant operators had excellent psychological quality, but some factors should be paid more attention, such as different ages and length of service time. (authors)

Bone Canopies in Pediatric Renal Osteodystrophy

DEFF Research Database (Denmark)

Pereira, Renata C; Levin Andersen, Thomas; Friedman, Peter A

2016-01-01

Pediatric renal osteodystrophy (ROD) is characterized by changes in bone turnover, mineralization, and volume that are brought about by alterations in bone resorption and formation. The resorptive and formative surfaces on the cancellous bone are separated from the marrow cavity by canopies...... and their association with biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney disease (CKD) patients (stage 2-5) across the spectrum of ROD. Canopies in CKD patients often appeared as thickened multilayered canopies, similar to previous reports in patients with primary hyperparathyroidism....... This finding contrasts with the thin appearance reported in healthy individuals with normal kidney function. Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa-B ligand (RANKL). The number of surfaces...

Development of safety factors to be used for evaluation of cracked nuclear components

International Nuclear Information System (INIS)

Brickstad, B.; Bergman, M.

1996-10-01

A modified concept for safety evaluation is introduced which separately accounts for the failure mechanisms fracture and plastic collapse. For application on nuclear components a set of safety factors are also proposed that retain the safety margins expressed in ASME, section III and XI. By performing comparative studies of the acceptance levels for surface cracks in pipes and a pressure vessel, it is shown that some of the anomalies connected with the old safety procedures are removed. It is the authors belief that the outlined safety evaluation procedure has the capability of treating cracks in a consistent way and that the procedure together with the proposed safety factors fulfill the basic safety requirements for nuclear components. Hopefully, it is possible in the near future to develop a probabilistic safety assessment procedure in Sweden, which enables a systematic treatment of uncertainties in the involved data. 14 refs

Anti-Inflammatory Effect of ETAS®50 by Inhibiting Nuclear Factor-κB p65 Nuclear Import in Ultraviolet-B-Irradiated Normal Human Dermal Fibroblasts

Directory of Open Access Journals (Sweden)

Ken Shirato

2018-01-01

Full Text Available Ultraviolet (UV irradiation induces proinflammatory responses in skin cells, including dermal fibroblasts, accelerating premature skin aging (photoaging. ETAS 50, a standardized extract from the Asparagus officinalis stem, is a novel and unique functional food that suppresses proinflammatory responses of hydrogen peroxide-stimulated skin fibroblasts and interleukin- (IL- 1β-stimulated hepatocytes. To elucidate its antiphotoaging potencies, we examined whether ETAS 50 treatment after UV-B irradiation attenuates proinflammatory responses of normal human dermal fibroblasts (NHDFs. UV-B-irradiated NHDFs showed reduced levels of the cytosolic inhibitor of nuclear factor-κB α (IκBα protein and increased levels of nuclear p65 protein. The nuclear factor-κB nuclear translocation inhibitor JSH-23 abolished UV-B irradiation-induced IL-1β mRNA expression, indicating that p65 regulates transcriptional induction. ETAS 50 also markedly suppressed UV-B irradiation-induced increases in IL-1β mRNA levels. Immunofluorescence analysis revealed that ETAS 50 retained p65 in the cytosol after UV-B irradiation. Western blotting also showed that ETAS 50 suppressed the UV-B irradiation-induced increases in nuclear p65 protein. Moreover, ETAS 50 clearly suppressed UV-B irradiation-induced distribution of importin-α protein levels in the nucleus without recovering cytosolic IκBα protein levels. These results suggest that ETAS 50 exerts anti-inflammatory effects on UV-B-irradiated NHDFs by suppressing the nuclear import machinery of p65. Therefore, ETAS 50 may prevent photoaging by suppressing UV irradiation-induced proinflammatory responses of dermal fibroblasts.

Prescribing safety, negotiating expertise. Building of nuclear safety human factors expertise

International Nuclear Information System (INIS)

Rolina, Gregory

2008-01-01

This Ph.D thesis is dedicated to a specific type of expertise, the safety of nuclear installations in the field of human and organisational factors. Empirical work is at the foundation of this thesis: the monitoring of experts 'in action', allowed a detailed reconstruction of three cases they were examining. The analysis, at the core of which lies the definition of what an efficient expertise can be, emphasizes the incompleteness of the knowledge that links together the nuclear facilities' organisational characteristics and their safety. This leads us to identify the expert's three ranges of actions (rhetorical, cognitive, operative). Defined from objectives and constraints likely to influence the expert's behaviour, those three ranges each require specific skills. A conception of expertise based on these ranges seems adaptable to other sectors and allows an enrichment of models of expertise cited in literature. Historical elements from French institutions of nuclear safety are also called upon to take into consideration some of the determinants of the expertise; its efficiency relies on the upholding of a continuous dialogue between the regulators (the experts and the control authority) and the regulated (the operators). This type of historically inherited regulation makes up a specificity of the French system of external control of nuclear risks. (author) [fr

Assessment of job stress factors and organizational personality types for procedure-based jobs in nuclear power plants

International Nuclear Information System (INIS)

Kim, Dae-Ho; Lee, Yong-Hee; Lee, Jung-Woon

2008-01-01

The purpose of this study is to assess the organizational types and the job stress factors that affect procedure-based job performances in nuclear power plants. We derived 24 organizational factors affecting job stress level in nuclear power plants from the job stress analysis models developed by NIOSH, JDI, and IOR. Considering the safety characteristics in the operating tasks of nuclear power plants, we identified the job contents and characteristics through the analyses of job assignments that appeared in the organizational chart and the results of an activity-based costing. By using questionnaire surveys and structured interviews with the plant personnel and expert panels, we assessed 70 jobs among the 777 jobs managed officially in accordance with the procedures. They consist of the representative jobs of each department and are directly related to safety. We utilized the organizational personality type indicators to characterize the personality types of each organization in nuclear power plants. (author)

Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

International Nuclear Information System (INIS)

Faria, Jerusa A.Q.A.; Andrade, Carolina de; Goes, Alfredo M.; Rodrigues, Michele A.; Gomes, Dawidson A.

2016-01-01

The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. - Highlights: • EGF, HB-EGF, TGF-α, β-Cellulin are involved in the EGFR nuclear translocation. • Amphiregulin and epiregulin did not promote nuclear translocation of EGFR. • EGF, HB-EGF, TGF-α and β-Cellulin have a role in SkHep-1 cells migration. • EGFR ligands associated with better prognosis don't stimulate EGFR translocation.

Effects of different ligands on epidermal growth factor receptor (EGFR) nuclear translocation

Energy Technology Data Exchange (ETDEWEB)

Faria, Jerusa A.Q.A.; Andrade, Carolina de; Goes, Alfredo M. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Rodrigues, Michele A. [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Department of General Pathology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil); Gomes, Dawidson A., E-mail: dawidson@ufmg.br [Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, Belo Horizonte, MG, 31270-901 (Brazil)

2016-09-09

The epidermal growth factor receptor (EGFR) is activated through binding to specific ligands and generates signals for proliferation, differentiation, migration, and cell survival. Recent data show the role of nuclear EGFR in tumors. Although many EGFR ligands are upregulated in cancers, little is known about their effects on EGFR nuclear translocation. We have compared the effects of six EGFR ligands (EGF, HB-EGF, TGF-α, β-Cellulin, amphiregulin, and epiregulin) on nuclear translocation of EGFR, receptor phosphorylation, migration, and proliferation. Cell fractionation and confocal immunofluorescence detected EGFR in the nucleus after EGF, HB-EGF, TGF-α and β-Cellulin stimulation in a dose-dependent manner. In contrast, amphiregulin and epiregulin did not generate nuclear translocation of EGFR. EGF, HB-EGF, TGF-α and β-Cellulin showed correlations between a higher rate of wound closure and increased phosphorylation of residues in the carboxy-terminus of EGFR, compared to amphiregulin and epiregulin. The data indicate that EGFR is translocated to the nucleus after stimulation with EGF, HB-EGF, TGF-α and β-Cellulin, and that these ligands are related to increased phosphorylation of EGFR tyrosine residues, inducing migration of SkHep-1 cells. - Highlights: • EGF, HB-EGF, TGF-α, β-Cellulin are involved in the EGFR nuclear translocation. • Amphiregulin and epiregulin did not promote nuclear translocation of EGFR. • EGF, HB-EGF, TGF-α and β-Cellulin have a role in SkHep-1 cells migration. • EGFR ligands associated with better prognosis don't stimulate EGFR translocation.

Identification of potential nuclear reprogramming and differentiation factors by a novel selection method for cloning chromatin-binding proteins

International Nuclear Information System (INIS)

Wang Liu; Zheng Aihua; Yi Ling; Xu Chongren; Ding Mingxiao; Deng Hongkui

2004-01-01

Nuclear reprogramming is critical for animal cloning and stem cell creation through nuclear transfer, which requires extensive remodeling of chromosomal architecture involving dramatic changes in chromatin-binding proteins. To understand the mechanism of nuclear reprogramming, it is critical to identify chromatin-binding factors specify the reprogramming process. In this report, we have developed a high-throughput selection method, based on T7 phage display and chromatin immunoprecipitation, to isolate chromatin-binding factors expressed in mouse embryonic stem cells using primary mouse embryonic fibroblast chromatin. Seven chromatin-binding proteins have been isolated by this method. We have also isolated several chromatin-binding proteins involved in hepatocyte differentiation. Our method provides a powerful tool to rapidly and selectively identify chromatin-binding proteins. The method can be used to study epigenetic modification of chromatin during nuclear reprogramming, cell differentiation, and transdifferentiation

Human Milk Contains Novel Glycans That Are Potential Decoy Receptors for Neonatal Rotaviruses*

Science.gov (United States)

Yu, Ying; Lasanajak, Yi; Song, Xuezheng; Hu, Liya; Ramani, Sasirekha; Mickum, Megan L.; Ashline, David J.; Prasad, B. V. Venkataram; Estes, Mary K.; Reinhold, Vernon N.; Cummings, Richard D.; Smith, David F.

2014-01-01

Human milk contains a rich set of soluble, reducing glycans whose functions and bioactivities are not well understood. Because human milk glycans (HMGs) have been implicated as receptors for various pathogens, we explored the functional glycome of human milk using shotgun glycomics. The free glycans from pooled milk samples of donors with mixed Lewis and Secretor phenotypes were labeled with a fluorescent tag and separated via multidimensional HPLC to generate a tagged glycan library containing 247 HMG targets that were printed to generate the HMG shotgun glycan microarray (SGM). To investigate the potential role of HMGs as decoy receptors for rotavirus (RV), a leading cause of severe gastroenteritis in children, we interrogated the HMG SGM with recombinant forms of VP8* domains of the RV outer capsid spike protein VP4 from human neonatal strains N155(G10P[11]) and RV3(G3P[6]) and a bovine strain, B223(G10P[11]). Glycans that were bound by RV attachment proteins were selected for detailed structural analyses using metadata-assisted glycan sequencing, which compiles data on each glycan based on its binding by antibodies and lectins before and after exo- and endo-glycosidase digestion of the SGM, coupled with independent MSn analyses. These complementary structural approaches resulted in the identification of 32 glycans based on RV VP8* binding, many of which are novel HMGs, whose detailed structural assignments by MSn are described in a companion report. Although sialic acid has been thought to be important as a surface receptor for RVs, our studies indicated that sialic acid is not required for binding of glycans to individual VP8* domains. Remarkably, each VP8* recognized specific glycan determinants within a unique subset of related glycan structures where specificity differences arise from subtle differences in glycan structures. PMID:25048705

Land and Water Use, CO2 Emissions, and Worker Radiological Exposure Factors for the Nuclear Fuel Cycle

Energy Technology Data Exchange (ETDEWEB)

Brett W Carlsen; Brent W Dixon; Urairisa Pathanapirom; Eric Schneider; Bethany L. Smith; Timothy M. AUlt; Allen G. Croff; Steven L. Krahn

2013-08-01

The Department of Energy Office of Nuclear Energy’s Fuel Cycle Technologies program is preparing to evaluate several proposed nuclear fuel cycle options to help guide and prioritize Fuel Cycle Technology research and development. Metrics are being developed to assess performance against nine evaluation criteria that will be used to assess relevant impacts resulting from all phases of the fuel cycle. This report focuses on four specific environmental metrics. • land use • water use • CO2 emissions • radiological Dose to workers Impacts associated with the processes in the front-end of the nuclear fuel cycle, mining through enrichment and deconversion of DUF6 are summarized from FCRD-FCO-2012-000124, Revision 1. Impact estimates are developed within this report for the remaining phases of the nuclear fuel cycle. These phases include fuel fabrication, reactor construction and operations, fuel reprocessing, and storage, transport, and disposal of associated used fuel and radioactive wastes. Impact estimates for each of the phases of the nuclear fuel cycle are given as impact factors normalized per unit process throughput or output. These impact factors can then be re-scaled against the appropriate mass flows to provide estimates for a wide range of potential fuel cycles. A companion report, FCRD-FCO-2013-000213, applies the impact factors to estimate and provide a comparative evaluation of 40 fuel cycles under consideration relative to these four environmental metrics.

Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

International Nuclear Information System (INIS)

Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos

2009-01-01

Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

Safety, reliability, risk management and human factors: an integrated engineering approach applied to nuclear facilities

Energy Technology Data Exchange (ETDEWEB)

Vasconcelos, Vanderley de; Silva, Eliane Magalhaes Pereira da; Costa, Antonio Carlos Lopes da; Reis, Sergio Carneiro dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)], e-mail: vasconv@cdtn.br, e-mail: silvaem@cdtn.br, e-mail: aclc@cdtn.br, e-mail: reissc@cdtn.br

2009-07-01

Nuclear energy has an important engineering legacy to share with the conventional industry. Much of the development of the tools related to safety, reliability, risk management, and human factors are associated with nuclear plant processes, mainly because the public concern about nuclear power generation. Despite the close association between these subjects, there are some important different approaches. The reliability engineering approach uses several techniques to minimize the component failures that cause the failure of the complex systems. These techniques include, for instance, redundancy, diversity, standby sparing, safety factors, and reliability centered maintenance. On the other hand system safety is primarily concerned with hazard management, that is, the identification, evaluation and control of hazards. Rather than just look at failure rates or engineering strengths, system safety would examine the interactions among system components. The events that cause accidents may be complex combinations of component failures, faulty maintenance, design errors, human actions, or actuation of instrumentation and control. Then, system safety deals with a broader spectrum of risk management, including: ergonomics, legal requirements, quality control, public acceptance, political considerations, and many other non-technical influences. Taking care of these subjects individually can compromise the completeness of the analysis and the measures associated with both risk reduction, and safety and reliability increasing. Analyzing together the engineering systems and controls of a nuclear facility, their management systems and operational procedures, and the human factors engineering, many benefits can be realized. This paper proposes an integration of these issues based on the application of systems theory. (author)

The Regulatory Role of Nuclear Factor Kappa B in the Heart of Hereditary Hypertriglyceridemic Rat

Czech Academy of Sciences Publication Activity Database

Vranková, S.; Barta, A.; Klimentová, J.; Dovinová, I.; Líšková, Silvia; Dobešová, Zdenka; Pecháňová, O.; Kuneš, Jaroslav; Zicha, Josef

2016-01-01

Roč. 2016, č. 2016 (2016), s. 9814038 ISSN 1942-0900 R&D Projects: GA MZd(CZ) NV15-25396A Institutional support: RVO:67985823 Keywords : nuclear factor-kB * nitric oxide * reactive oxygen species * heart * hereditary hypertriglyceridemic rats Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 4.593, year: 2016

Human factors in nuclear power plants

International Nuclear Information System (INIS)

Bohr, E.; Hennig, J.; Preuss, W.; Thau, G.

1977-01-01

This report describes the results of a study on the functions of operating and maintenance personnel in nuclear power plants. Since an effective power plant design must take into systematic account the possibilities and limitations of the human element, the basic aim of the study was to identify what the human operators are required to do and how they achieve it. Information was acquired by direct observation and by interviews as well as by evaluation of written documents (e.g. incident reports, procedures manuals, work regulations) and of working conditions (e.g. equipment and workplace design). A literature search and evaluation carried out within the scope of this study has been published as a separate document. The main part of the report is devoted to discussions and conclusions on selected areas of potential improvements. The topics include control room design, factors of the physical environment including radiation, problems of maintainability, design of written documents, problems in communicating information, design and control of tasks, placement and training. A separate section deals with problems of recording human errors. (orig.) [de

Foot-and-mouth disease virus leader proteinase inhibits dsRNA-induced type I interferon transcription by decreasing interferon regulatory factor 3/7 in protein levels

Energy Technology Data Exchange (ETDEWEB)

Wang, Dang; Fang, Liurong; Luo, Rui; Ye, Rui; Fang, Ying; Xie, Lilan; Chen, Huanchun [Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China); Xiao, Shaobo, E-mail: shaoboxiao@yahoo.com [Division of Animal Infectious Diseases, State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070 (China)

2010-08-13

Research highlights: {yields} FMDV L{sup pro} inhibits poly(I:C)-induced IFN-{alpha}1/{beta} mRNA expression. {yields} L{sup pro} inhibits MDA5-mediated activation of the IFN-{alpha}1/{beta} promoter. {yields} L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes. {yields} L{sup pro} inhibits IFN-{alpha}1/{beta} promoter activation by decreasing IRF-3/7 in protein levels. {yields} The ability to process eIF-4G of L{sup pro} is not necessary to inhibit IFN-{alpha}1/{beta} activation. -- Abstract: The leader proteinase (L{sup pro}) of foot-and-mouth disease virus (FMDV) has been identified as an interferon-{beta} (IFN-{beta}) antagonist that disrupts the integrity of transcription factor nuclear factor {kappa}B (NF-{kappa}B). In this study, we showed that the reduction of double stranded RNA (dsRNA)-induced IFN-{alpha}1/{beta} expression caused by L{sup pro} was also associated with a decrease of interferon regulatory factor 3/7 (IRF-3/7) in protein levels, two critical transcription factors for activation of IFN-{alpha}/{beta}. Furthermore, overexpression of L{sup pro} significantly reduced the transcription of multiple IRF-responsive genes including 2',5'-OAS, ISG54, IP-10, and RANTES. Screening L{sup pro} mutants indicated that the ability to process eIF-4G of L{sup pro} is not required for suppressing dsRNA-induced activation of the IFN-{alpha}1/{beta} promoter and decreasing IRF-3/7 expression. Taken together, our results demonstrate that, in addition to disrupting NF-{kappa}B, L{sup pro} also decreases IRF-3/7 expression to suppress dsRNA-induced type I IFN production, suggesting multiple strategies used by FMDV to counteract the immune response to viral infection.

Nuclear accidents and safety measures of domestic nuclear power plants

International Nuclear Information System (INIS)

Song Zurong; Che Shuwei; Pan Xiang

2012-01-01

Based on the design standards for the safety of nuclear and radiation in nuclear power plants, the three accidents in the history of nuclear power are analyzed. And the main factors for these accidents are found out, that is, human factors and unpredicted natural calamity. By combining the design and operation parameters of domestic nuclear plants, the same accidents are studied and some necessary preventive schemes are put forward. In the security operation technology of domestic nuclear power plants nowadays, accidents caused by human factors can by prevented completely. But the safety standards have to be reconsidered for the unpredicted neutral disasters. How to reduce the hazard of nuclear radiation and leakage to the level that can be accepted by the government and public when accidents occur under extreme conditions during construction and operation of nuclear power plants must be considered adequately. (authors)

Explaining the ratification of nuclear waste disposal by the finnish parliament: political culture and contextual factors

International Nuclear Information System (INIS)

Ruostetsaari, I.

2002-01-01

According to the Nuclear Energy Act the government's Decision in Principle (DiP) on the nuclear waste disposal needs to be ratified by Parliament. The DiP was ratified by general consent (159-3) on 18 May 2001. How we can explain this parliamentary consensus taking account that the previous DiP concerning construction of a new nuclear power plant was overruled in 1993 and the public debate on nuclear power is still pronounced. The explanation can be sought, together with the institutional arrangements, from two sources; on one hand from the Finnish political culture, i.e., traditional and inherited ways of decision-makers to make decisions and citizens' ways to react to those decisions, and on the other hand, from current contextual factors linking to nuclear waste management. (authors)

Mutation in the factor VII hepatocyte nuclear factor 4α-binding site contributes to factor VII deficiency.

Science.gov (United States)

Zheng, Xing-Wu; Kudaravalli, Rama; Russell, Theresa T; DiMichele, Donna M; Gibb, Constance; Russell, J Eric; Margaritis, Paris; Pollak, Eleanor S

2011-10-01

Severe coagulant factor VII (FVII) deficiency in postpubertal dizygotic twin males results from two point mutations in the FVII gene, a promoter region T→C transition at -60 and a His-to-Arg substitution at amino acid 348; both mutations prevent persistence of plasma functional FVII. This report documents longitudinal laboratory measurements from infancy to adulthood of FVII coagulant activity (FVII:C) in the twin FVII-deficient patients; it also details specific biochemical analyses of the -60 T→C mutation. The results revealed FVII:C levels of less than 1% in infancy that remain severely decreased through puberty and into adulthood. In-vitro analyses utilizing hepatocyte nuclear factor 4α (HNF4α) co-transfection and a chromatin immunoprecipitation assay indicate that the -60 T→C mutation severely diminishes functional interaction between the FVII promoter and transcription factor HNF4α. The importance of interaction between the FVII gene and HNF4α in normal FVII expression provides an in-vivo illustration of the regulated expression of an autosomal gene encoding a coagulation protein. The constancy of FVII:C and peripubertal patient symptomatology reported here illustrates androgen-independent expression in contrast to expression with an analogous mutation in the promoter region of the gene encoding coagulation FIX.

An improvement of the applicability of human factors guidelines for coping with human factors issues in nuclear power plants

International Nuclear Information System (INIS)

Lee, Y. H.; Lee, J. Y.

2003-01-01

Human factors have been well known as one of the key factors to the system effectiveness as well as the efficiency and safety of nuclear power plants(NPPs). Human factors engineering(HFE) are included in periodic safety review(PSR) on the existing NPPs and the formal safety assessment for the new ones. However, HFE for NPPs is still neither popular in practice nor concrete in methodology. Especially, the human factors guidelines, which are the most frequent form of human factors engineering in practice, reveal the limitations in their applications. We discuss the limitations and their casual factors found in human factors guidelines in order to lesson the workload of HFE practitioners and to improve the applicability of human factors guidelines. According to the purposes and the phases of HFE for NPPs, more selective items and specified criteria should be prepared carefully in the human factors guidelines for the each HFE applications in practice. These finding on the human factors guidelines can be transferred to the other HFE application field, such as military, aviation, telecommunication, HCI, and product safety

Incorporating organizational factors into probabilistic safety assessment of nuclear power plants through canonical probabilistic models

Energy Technology Data Exchange (ETDEWEB)

Galan, S.F. [Dpto. de Inteligencia Artificial, E.T.S.I. Informatica (UNED), Juan del Rosal, 16, 28040 Madrid (Spain)]. E-mail: seve@dia.uned.es; Mosleh, A. [2100A Marie Mount Hall, Materials and Nuclear Engineering Department, University of Maryland, College Park, MD 20742 (United States)]. E-mail: mosleh@umd.edu; Izquierdo, J.M. [Area de Modelado y Simulacion, Consejo de Seguridad Nuclear, Justo Dorado, 11, 28040 Madrid (Spain)]. E-mail: jmir@csn.es

2007-08-15

The {omega}-factor approach is a method that explicitly incorporates organizational factors into Probabilistic safety assessment of nuclear power plants. Bayesian networks (BNs) are the underlying formalism used in this approach. They have a structural part formed by a graph whose nodes represent organizational variables, and a parametric part that consists of conditional probabilities, each of them quantifying organizational influences between one variable and its parents in the graph. The aim of this paper is twofold. First, we discuss some important limitations of current procedures in the {omega}-factor approach for either assessing conditional probabilities from experts or estimating them from data. We illustrate the discussion with an example that uses data from Licensee Events Reports of nuclear power plants for the estimation task. Second, we introduce significant improvements in the way BNs for the {omega}-factor approach can be constructed, so that parameter acquisition becomes easier and more intuitive. The improvements are based on the use of noisy-OR gates as model of multicausal interaction between each BN node and its parents.

Incorporating organizational factors into probabilistic safety assessment of nuclear power plants through canonical probabilistic models

International Nuclear Information System (INIS)

Galan, S.F.; Mosleh, A.; Izquierdo, J.M.

2007-01-01

The ω-factor approach is a method that explicitly incorporates organizational factors into Probabilistic safety assessment of nuclear power plants. Bayesian networks (BNs) are the underlying formalism used in this approach. They have a structural part formed by a graph whose nodes represent organizational variables, and a parametric part that consists of conditional probabilities, each of them quantifying organizational influences between one variable and its parents in the graph. The aim of this paper is twofold. First, we discuss some important limitations of current procedures in the ω-factor approach for either assessing conditional probabilities from experts or estimating them from data. We illustrate the discussion with an example that uses data from Licensee Events Reports of nuclear power plants for the estimation task. Second, we introduce significant improvements in the way BNs for the ω-factor approach can be constructed, so that parameter acquisition becomes easier and more intuitive. The improvements are based on the use of noisy-OR gates as model of multicausal interaction between each BN node and its parents

Testing collinear factorization and nuclear parton distributions with pA collisions at the LHC

Energy Technology Data Exchange (ETDEWEB)

Quiroga-Arias, Paloma [Departamento de Fisica de PartIculas and IGFAE, Universidade de Santiago de Compostela 15706 Santiago de Compostela (Spain); Milhano, Jose Guilherme [CENTRA, Departamento de Fisica, Instituto Superior Tecnico (IST), Av. Rovisco Pais 1, P-1049-001 Lisboa (Portugal); Wiedemann, Urs Achim, E-mail: pquiroga@fpaxpl.usc.es [Physics Department, Theory Unit, CERN, CH-1211 Geneve 23 (Switzerland)

2011-01-01

Global perturbative QCD analyses, based on large data sets from electron-proton and hadron collider experiments, provide tight constraints on the parton distribution function (PDF) in the proton. The extension of these analyses to nuclear parton distributions (nPDF) has attracted much interest in recent years. nPDFs are needed as benchmarks for the characterization of hot QCD matter in nucleus-nucleus collisions, and attract further interest since they may show novel signatures of non- linear density-dependent QCD evolution. However, it is not known from first principles whether the factorization of long-range phenomena into process-independent parton distribution, which underlies global PDF extractions for the proton, extends to nuclear effects. As a consequence, assessing the reliability of nPDFs for benchmark calculations goes beyond testing the numerical accuracy of their extraction and requires phenomenological tests of the factorization assumption. Here we argue that a proton-nucleus collision program at the LHC would provide a set of measurements allowing for unprecedented tests of the factorization assumption underlying global nPDF fits.

A formal design verification and validation on the human factors of a computerized information system in nuclear power plants

International Nuclear Information System (INIS)

Lee, Yong Hee; Park, Jae Chang; Cheon, Se Woo; Jung, Kwang Tae; Baek, Seung Min; Han, Seung; Park, Hee Suk; Son, Ki Chang; Kim, Jung Man; Jung Yung Woo

1999-11-01

This report describe a technical transfer under the title of ''A formal design verification and validation on the human factors of a computerized information system in nuclear power plants''. Human factors requirements for the information system designs are extracted from various regulatory and industrial standards and guidelines, and interpreted into a more specific procedures and checklists for verifying the satisfaction of those requirements. A formalized implementation plan is established for human factors verification and validation of a computerized information system in nuclear power plants. Additionally, a Computer support system, named as DIMS-web (design Issue Management System), is developed based upon web internet environment so as to enhance the implementation of the human factors activities. DIMS-Web has three maine functions: supporting requirements review, tracking design issues, and management if issues screening evaluation. DIMS-Web shows its benefits in practice through a trial application to the design review of CFMS for YGN nuclear unit 5 and 6. (author)

A formal design verification and validation on the human factors of a computerized information system in nuclear power plants

Energy Technology Data Exchange (ETDEWEB)

Lee, Yong Hee; Park, Jae Chang; Cheon, Se Woo; Jung, Kwang Tae; Baek, Seung Min; Han, Seung; Park, Hee Suk; Son, Ki Chang; Kim, Jung Man; Jung Yung Woo

1999-11-01

This report describe a technical transfer under the title of ''A formal design verification and validation on the human factors of a computerized information system in nuclear power plants''. Human factors requirements for the information system designs are extracted from various regulatory and industrial standards and guidelines, and interpreted into a more specific procedures and checklists for verifying the satisfaction of those requirements. A formalized implementation plan is established for human factors verification and validation of a computerized information system in nuclear power plants. Additionally, a Computer support system, named as DIMS-web (design Issue Management System), is developed based upon web internet environment so as to enhance the implementation of the human factors activities. DIMS-Web has three maine functions: supporting requirements review, tracking design issues, and management if issues screening evaluation. DIMS-Web shows its benefits in practice through a trial application to the design review of CFMS for YGN nuclear unit 5 and 6. (author)

Polymorphisms in NFkB, PXR, LXR and risk of colorectal cancer in a prospective study of Danes

DEFF Research Database (Denmark)

Andersen, Vibeke; Christensen, Jane; Overvad, Kim

2010-01-01

. There was no interaction between use of nonsteroid antiinflammatory drugs (NSAID) or smoking status and NFkB, PXR or LXR polymorphisms. Conclusions A polymorphism in NFkB was associated with CRC risk and there was interaction between this polymorphism and meat intake in relation to CRC risk. This study suggests a role......-B, pregnane X receptor, and liver X receptor were associated with risk of CRC, and to investigate possible interactions with lifestyle factors such as smoking, meat consumption, and NSAID use. Methods The polymorphisms nuclear factor kappa-B (NFkB, NFKB1) -94 insertion/deletion ATTG (rs28362491), pregnane X...... and Health study of 57,053 persons. Results Carriers of NFkB -94deletion were at 1.45-fold higher risk of CRC than homozygous carriers of the insertion allele (incidence rate ratio (IRR) = 1.45, 95% confidence interval (95% CI): 1.10-1.92). There was interaction between this polymorphism and intake of red...

The Impact of Organizational Factors on Safety. The Perspective of Experts from the Spanish Nuclear Sector

International Nuclear Information System (INIS)

German, S.; Silla, I.; Navajas, J.

2014-01-01

Previous research supports the importance of organizational factors on safety in high reliability organizations. This study aims to determine the impact of those factors in the Spanish nuclear sector. Particularly, this study focuses on examining the role of performance indicators, organizational culture, organizational factors, and organizational context. With that purpose, an electronic survey addressed to experts from the Spanish nuclear sector was carried out. Results showed that performance indicators are well-known among industry experts and are perceived as useful for improving performance. Behavioural norms that influence safety and some relevant factors that promote problem identification were identified. Additionally, findings suggested that organizational context must be taken into account to better understand the role of organizational culture. Moreover, industry experts pointed out organizational factors to be improved: organizational communication processes within the organization, positive reinforcement, and field supervisors practices. Finally, findings supported the influence of organizational context on safety. It is noteworthy the role of the social impact of international events (e.g., Chernobyl...), the relationship with the regulator and the legislative and governmental framework. (Author)

A nuclear free southeast Asia - the China factor

International Nuclear Information System (INIS)

Malik, J.M.

1989-01-01

It is estimated that the principal nuclear threat to Southeast Asia comes from nuclear weapons stored by the two superpowers in their respective bases and their targeting of each other's bases. Calls for the creation of a nuclear weapons free zone in Southeast Asia (SEANFZ) poses a number of problems to China because of the perceived negative impact of such zones on Chinese security interests, force deployment and strategic doctrine. Hence, it is argued that China is unlikely to support a nuclear free zone treaty which only embraces the Asean states because it would lead to unilateral disarmament on the part of pro-western countries while leaving Indochinese states and the Soviet Union. However, if the proposed SEANFZ treaty resembles the South Pacific Nuclear Free Zone treaty, which allow the transit of nuclear-armed vessels, China could be expected to support it. ills

Human factor analysis and preventive countermeasures of maintenance in nuclear power plant

International Nuclear Information System (INIS)

Zhang Li; Hu Chao

2008-01-01

Based on the human error analysis theory and the characteristics of maintenance in a nuclear power plant, human factors of maintenance in NPP are divided into three different areas: human, technology, and organization, in which human refers to the individual factors, mainly including psychological quality, physiological characteristic, state of health, knowledge, skill level, and interpersonal relationship. Technology includes the maintenance technology, maintenance strategy, maintenance tool, maintenance interface, maintenance regulation, and work environment. Organization includes task arrangement, information communication, training, personnel external environment, team construction, and leadership. The analysis also reveals that the organization factors, which can indirectly influence personnel performance, are the primary initiators of human error. Based on these, some countermeasures are brought forward in order to reduce human errors. (authors)

Factors relevant to the recycling or reuse of components arising from the decommissioning and refurbishment of nuclear facilities

International Nuclear Information System (INIS)

1988-01-01

The decommissioning and decontamination of nuclear facilities is a topic of great interest to many Member States of the International Atomic Energy Agency (IAEA) because of the large number of older nuclear facilities which are or soon will be retired from service. To assist in the development of the required decommissioning expertise, the IAEA is developing reports and recommendations which will eventually form an integrated information base covering in a systematic way the wide range of topics associated with decommissioning. This information is required so that Member States can decommission their nuclear facilities in a safe, timely and cost effective manner and the IAEA can effectively respond to requests for assistance. One area which warrants more detailed analyses is an assessment of the factors important to the recycling or reuse of components arising from the refurbishment or decommissioning of nuclear plants, the topic of the present report. The document provides an up to date review of the engineering, social, scientific and administrative factors relevant to the safe recycling or reuse of components arising from decommissioning or refurbishment of nuclear facilities. This report should be of interest to owners, operators, policy makers and regulators involved with nuclear facilities, especially those in developing countries. Refs, figs and tabs

Alternative Pathways of Cancer Cell Death by Rottlerin: Apoptosis versus Autophagy

Czech Academy of Sciences Publication Activity Database

Torricelli, C.; Salvadori, S.; Valacchi, G.; Souček, Karel; Slabáková, Eva; Muscettola, M.; Volpi, N.; Maioli, E.

2012-01-01

Roč. 2012, NOV (2012), s. 1-11 /AN 980658/ ISSN 1741-427X R&D Projects: GA ČR(CZ) GPP301/12/P407 Institutional support: RVO:68081707 Keywords : PKC-DELTA * KAPPA-B * CARCINOMA CELLS Subject RIV: BO - Biophysics Impact factor: 1.722, year: 2012

Testing collinear factorization and nuclear parton distributions with pA collisions at the LHC

CERN Document Server

Quiroga-Arias, Paloma; Wiedemann, Urs Achim

2011-01-01

Global perturbative QCD analyses, based on large data sets from electron-proton and hadron collider experiments, provide tight constraints on the parton distribution function (PDF) in the proton. The extension of these analyses to nuclear parton distributions (nPDF) has attracted much interest in recent years. nPDFs are needed as benchmarks for the characterization of hot QCD matter in nucleus-nucleus collisions, and attract further interest since they may show novel signatures of non- linear density-dependent QCD evolution. However, it is not known from first principles whether the factorization of long-range phenomena into process-independent parton distribution, which underlies global PDF extractions for the proton, extends to nuclear effects. As a consequence, assessing the reliability of nPDFs for benchmark calculations goes beyond testing the numerical accuracy of their extraction and requires phenomenological tests of the factorization assumption. Here we argue that a proton-nucleus collision program a...

Human Factors Considerations in New Nuclear Power Plants: Detailed Analysis.

Energy Technology Data Exchange (ETDEWEB)

OHara,J.; Higgins, J.; Brown, W.; Fink, R.

2008-02-14

This Nuclear Regulatory Commission (NRC) sponsored study has identified human-performance issues in new and advanced nuclear power plants. To identify the issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were organized into seven high-level HFE topic areas: Role of Personnel and Automation, Staffing and Training, Normal Operations Management, Disturbance and Emergency Management, Maintenance and Change Management, Plant Design and Construction, and HFE Methods and Tools. The issues where then prioritized into four categories using a 'Phenomena Identification and Ranking Table' methodology based on evaluations provided by 14 independent subject matter experts. The subject matter experts were knowledgeable in a variety of disciplines. Vendors, utilities, research organizations and regulators all participated. Twenty issues were categorized into the top priority category. This Brookhaven National Laboratory (BNL) technical report provides the detailed methodology, issue analysis, and results. A summary of the results of this study can be found in NUREG/CR-6947. The research performed for this project has identified a large number of human-performance issues for new control stations and new nuclear power plant designs. The information gathered in this project can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas through regulatory research. Addressing human-performance issues will provide the technical basis from which regulatory review guidance can be developed to meet these challenges. The availability of this review guidance will help set clear expectations for how the NRC staff will evaluate new designs, reduce regulatory uncertainty, and provide a well-defined path to new nuclear power plant

DMPD: Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-signalingcascades during intracellular Toxoplasma gondii infection. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 15361242 Manipulation of mitogen-activated protein kinase/nuclear factor-kappaB-sig...mmunol Rev. 2004 Oct;201:191-205. (.png) (.svg) (.html) (.csml) Show Manipulation of mitogen-activated prote... gondii infection. PubmedID 15361242 Title Manipulation of mitogen-activated protein kinase/nuclear factor-k

Platelet-derived growth factor induces phosphorylation of a 64-kDa nuclear protein

International Nuclear Information System (INIS)

Shawver, L.K.; Pierce, G.F.; Kawahara, R.S.; Deuel, T.F.

1989-01-01

The platelet-derived growth factor (PDGF) stimulated the phosphorylation of a nuclear protein of 64 kDa (pp64) in nuclei of nontransformed normal rat kidney (NRK) cells. Low levels of phosphorylation of pp64 were observed in nuclei of serum-starved NRK cells. Fetal calf serum (FCS), PDGF, and homodimeric v-sis and PDGF A-chain protein enhanced the incorporation of 32P into pp64 over 4-fold within 30 min and over 8-fold within 2 h of exposure of NRK cells to the growth factors. In contrast, constitutive phosphorylation of 32P-labeled pp64 in nuclei of NRK cells transformed by the simian sarcoma virus (SSV) was high and only minimally stimulated by PDGF and FCS. 32P-Labeled pp64 was isolated from nuclei of PDGF-stimulated nontransformed NRK cells; the 32P of pp64 was labile in 1 M KOH, and pp64 was not significantly recognized by anti-phosphotyrosine antisera, suggesting that the PDGF-induced phosphorylation of pp64 occurred on serine or on threonine residues. However, pp64 from SSV-transformed NRK cell nuclei was significantly stable to base hydrolysis and was immunoprecipitated with anti-phosphotyrosine antisera, suggesting that pp64 from SSV-transformed cell nuclei is phosphorylated also on tyrosine. FCS, PDGF, and PDGF A- and B-chain homodimers thus stimulate the rapid time-dependent phosphorylation of a 64-kDa nuclear protein shortly after stimulation of responsive cells. The growth factor-stimulated phosphorylation of pp64 and the constitutive high levels of pp64 phosphorylation in cells transformed by SSV suggest important roles for pp64 and perhaps regulated nuclear protein kinases and phosphatases in cell division and proliferation

Virtual reality technology as a tool for human factors requirements evaluation in design of the nuclear reactors control desks

International Nuclear Information System (INIS)

Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Mol, Antonio C.A.; Carvalho, Paulo V.R.; Silva, Antonio C.F.; Ferreira, Francisco J.O.; Dutra, Marco A.M.

2007-01-01

The Virtual Reality (VR) is an advanced computer interface technology that allows the user to internet or to explore a three-dimensional environment through the computer, as was part of the virtual world. This technology presents great applicability in the most diverse areas of the human knowledge. This paper presents a study on the use of the VR as tool for human factors requirements evaluation in design of the nuclear reactors control desks. Moreover, this paper presents a case study: a virtual model of the control desk, developed using virtual reality technology to be used in the human factors requirements evaluation. This case study was developed in the Virtual Reality Laboratory at IEN, and understands the stereo visualization of the Argonauta research nuclear reactor control desk for a static ergonomic evaluation using check-lists, in accordance to the standards and human factors nuclear international guides (IEC 1771, NUREG-0700). (author)

Virtual reality technology as a tool for human factors requirements evaluation in design of the nuclear reactors control desks

Energy Technology Data Exchange (ETDEWEB)

Grecco, Claudio H.S.; Santos, Isaac J.A.L.; Mol, Antonio C.A.; Carvalho, Paulo V.R.; Silva, Antonio C.F.; Ferreira, Francisco J.O.; Dutra, Marco A.M. [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)]. E-mail: grecco@ien.gov.br; luquetti@ien.gov.br; mol@ien.gov.br; paulov@ien.gov.br; tonico@ien.gov.br; fferreira@ien.gov.br; dutra@ien.gov.br

2007-07-01

The Virtual Reality (VR) is an advanced computer interface technology that allows the user to internet or to explore a three-dimensional environment through the computer, as was part of the virtual world. This technology presents great applicability in the most diverse areas of the human knowledge. This paper presents a study on the use of the VR as tool for human factors requirements evaluation in design of the nuclear reactors control desks. Moreover, this paper presents a case study: a virtual model of the control desk, developed using virtual reality technology to be used in the human factors requirements evaluation. This case study was developed in the Virtual Reality Laboratory at IEN, and understands the stereo visualization of the Argonauta research nuclear reactor control desk for a static ergonomic evaluation using check-lists, in accordance to the standards and human factors nuclear international guides (IEC 1771, NUREG-0700). (author)

Review of human factors R and D in the nuclear power industry

International Nuclear Information System (INIS)

Parris, H.L.

1986-01-01

The history of human factors (HF) R and D in the nuclear power industry can clearly be divided into two phases: pre- and post-Three Mile Island (TMI). Pre-TMI, most people in the industry were unfamiliar with the discipline and its contributions to military and space system designs, and the number of HF professionals involved with nuclear power could essentially be counted on the fingers of two hands. Consequently, there was little research into the improvement of plant man/machine interfaces. The picture changed dramatically in the aftermath of TMI as investigation after investigation pointed to deficiencies in the operator/control room interface, training, procedures, communications, and organizational effectiveness. This paper first outlines pre-TMI events, then examines the post-TMI scenario, and concludes with summary observations and suggestions for future efforts

Thyroid hormone and retinoic acid nuclear receptors: specific ligand-activated transcription factors

International Nuclear Information System (INIS)

Brtko, J.

1998-01-01

Transcriptional regulation by both the thyroid hormone and the vitamin A-derived 'retinoid hormones' is a critical component in controlling many aspects of higher vertebrate development and metabolism. Their functions are mediated by nuclear receptors, which comprise a large super-family of ligand-inducible transcription factors. Both the thyroid hormone and the retinoids are involved in a complex arrangement of physiological and development responses in many tissues of higher vertebrates. The functions of 3,5,3'-triiodothyronine (T 3 ), the thyromimetically active metabolite of thyroxine as well as all-trans retinoic acid, the biologically active vitamin A metabolite are mediated by nuclear receptor proteins that are members of the steroid/thyroid/retinoid hormone receptor family. The functions of all members of the receptor super family are discussed. (authors)

NF-{kappa}B p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Ming, Gao [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yeh, P Y [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Lu, Y -S [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan, ROC (China); Chang, W C [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Kuo, M -L [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Cheng, A -L [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China)], E-mail: alcheng@ntu.edu.tw

2008-11-14

Lung adenocarcinoma Cl1-5 cells were selected from parental Cl1-0 cells based on their high metastatic potential. In a previous study, CRMP-1, an invasion suppressor gene, was shown to be suppressed in Cl1-5 cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-{kappa}B controls CRMP-1 expression. The electromobility shift assay showed that while Cl1-0 cells exhibited low NF-{kappa}B activity in response to TNF-{alpha}, an abundance of basal and TNF-{alpha}-induced NF-{kappa}B-DNA complex was detected in Cl1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodimer in the complex. ChIP and EMSA demonstrated that p50 binds to a {kappa}B site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into Cl1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of Cl1-5 cells.

Quality factors quantification/assurance for software related to safety in nuclear power plants

International Nuclear Information System (INIS)

Nunez McLeod, J.E.; Rivera, S.S.

1997-01-01

Quality assurance plan is needed to guarantee the software quality. The use of such a plan involves activities that should take place all along the life cycle, and which can be evaluated using the so called quality factors. This is due to the fact that the quality itself cannot be measured, but some of its manifestations can be used for this purpose. In the present work, a methodology to quantify a set of quality factors is proposed, for software based systems to be used in safety related areas in nuclear power plants. (author) [es

Zinc or copper deficiency-induced impaired inflammatory response to brain trauma may be caused by the concomitant metallothionein changes

DEFF Research Database (Denmark)

Penkowa, Milena; Giralt, M.; Thomsen, Pernille Sjølin

2001-01-01

, and this response was significantly blunted by zinc deficiency. The MT-III isoform was moderately increased by both TBI and zinc deficiency. TBI strongly increased oxidative stress levels, as demonstrated by malondialdehyde (MDA), protein tyrosine nitration (NITT), and nuclear factor kappaB (NF-kappaB) levels irs......, all of which were potentiated by zinc deficiency. Further analysis revealed unbalanced expression of prooxidant and antioxidant proteins besides MT, since the levels of inducible nitric oxide synthase (iNOS) and Cu,Zn-SOD were increased and decreased, respectively, by zinc deficiency. All......The role of zinc- and copper-deficient diets on the inflammatory response to traumatic brain injury (TBI) has been evaluated in adult rats. As expected, zinc deficiency decreased food intake and body weight gain, and the latter effect was higher than that observed in pair-fed rats. In noninjured...

Inflammation and insulin resistance induced by trans-10, cis-12 conjugated linoleic acid depend on intracellular calcium levels in primary cultures of human adipocytes

DEFF Research Database (Denmark)

Kennedy, Arion; Martinez, Kristina; Chung, Soonkyu

2010-01-01

We previously demonstrated that trans-10, cis-12 (10,12) conjugated linoleic acid (CLA) induced inflammation and insulin resistance in primary human adipocytes by activating nuclear factor kappaB (NFkappaB) and extracellular signal-related kinase (ERK) signaling. In this study, we demonstrated...... that the initial increase in intracellular calcium ([Ca2+]i) mediated by 10,12 CLA was attenuated by TMB-8, an inhibitor of calcium release from the endoplasmic reticulum (ER), by BAPTA, an intracellular calcium chelator, and by D609, a phospholipase C (PLC) inhibitor. Moreover, BAPTA, TMB-8, and D609 attenuated......, and suppression of peroxisome proliferator activated receptor gamma protein levels and insulin-stimulated glucose uptake. These data suggest that 10,12 CLA increases inflammation and insulin resistance in human adipocytes, in part by increasing [Ca2+]i levels, particularly calcium from the ER....

FTZ-Factor1 and Fushi tarazu interact via conserved nuclear receptor and coactivator motifs

Science.gov (United States)

Schwartz, Carol J.E.; Sampson, Heidi M.; Hlousek, Daniela; Percival-Smith, Anthony; Copeland, John W.R.; Simmonds, Andrew J.; Krause, Henry M.

2001-01-01

To activate transcription, most nuclear receptor proteins require coactivators that bind to their ligand-binding domains (LBDs). The Drosophila FTZ-Factor1 (FTZ-F1) protein is a conserved member of the nuclear receptor superfamily, but was previously thought to lack an AF2 motif, a motif that is required for ligand and coactivator binding. Here we show that FTZ-F1 does have an AF2 motif and that it is required to bind a coactivator, the homeodomain-containing protein Fushi tarazu (FTZ). We also show that FTZ contains an AF2-interacting nuclear receptor box, the first to be found in a homeodomain protein. Both interaction motifs are shown to be necessary for physical interactions in vitro and for functional interactions in developing embryos. These unexpected findings have important implications for the conserved homologs of the two proteins. PMID:11157757

Global Developmental Gene Programing Involves a Nuclear Form of Fibroblast Growth Factor Receptor-1 (FGFR1.

Directory of Open Access Journals (Sweden)

Christopher Terranova

Full Text Available Genetic studies have placed the Fgfr1 gene at the top of major ontogenic pathways that enable gastrulation, tissue development and organogenesis. Using genome-wide sequencing and loss and gain of function experiments the present investigation reveals a mechanism that underlies global and direct gene regulation by the nuclear form of FGFR1, ensuring that pluripotent Embryonic Stem Cells differentiate into Neuronal Cells in response to Retinoic Acid. Nuclear FGFR1, both alone and with its partner nuclear receptors RXR and Nur77, targets thousands of active genes and controls the expression of pluripotency, homeobox, neuronal and mesodermal genes. Nuclear FGFR1 targets genes in developmental pathways represented by Wnt/β-catenin, CREB, BMP, the cell cycle and cancer-related TP53 pathway, neuroectodermal and mesodermal programing networks, axonal growth and synaptic plasticity pathways. Nuclear FGFR1 targets the consensus sequences of transcription factors known to engage CREB-binding protein, a common coregulator of transcription and established binding partner of nuclear FGFR1. This investigation reveals the role of nuclear FGFR1 as a global genomic programmer of cell, neural and muscle development.

Experimental realization of Shor's quantum factoring algorithm using nuclear magnetic resonance.

Science.gov (United States)

Vandersypen, L M; Steffen, M; Breyta, G; Yannoni, C S; Sherwood, M H; Chuang, I L

The number of steps any classical computer requires in order to find the prime factors of an l-digit integer N increases exponentially with l, at least using algorithms known at present. Factoring large integers is therefore conjectured to be intractable classically, an observation underlying the security of widely used cryptographic codes. Quantum computers, however, could factor integers in only polynomial time, using Shor's quantum factoring algorithm. Although important for the study of quantum computers, experimental demonstration of this algorithm has proved elusive. Here we report an implementation of the simplest instance of Shor's algorithm: factorization of N = 15 (whose prime factors are 3 and 5). We use seven spin-1/2 nuclei in a molecule as quantum bits, which can be manipulated with room temperature liquid-state nuclear magnetic resonance techniques. This method of using nuclei to store quantum information is in principle scalable to systems containing many quantum bits, but such scalability is not implied by the present work. The significance of our work lies in the demonstration of experimental and theoretical techniques for precise control and modelling of complex quantum computers. In particular, we present a simple, parameter-free but predictive model of decoherence effects in our system.

Human and social factors in the transportation of nuclear wastes

International Nuclear Information System (INIS)

Freudenburg, W.R.

1991-01-01

The main body of this report is a broad-based examination of human and social factors in the transportation of nuclear wastes. It deals with pair interested problems that, while familiar to the social science community, appear to have received little attention from the risk assessment community to data: The human and social attenuation of risk estimates, and the organizational amplification of risks. Second, given the special opportunities for learning that are presented by the recent Alaska oil spill, in particular, the Appendix to this report examines the issue of organizational foresight in the context of the Exxon oil spill

GATA transcription factors associate with a novel class of nuclear bodies in erythroblasts and megakaryocytes.

NARCIS (Netherlands)

A.G. Elefanty (Andrew); M. Antoniou (Michael); N. Custodio; M. Carmo-Fonseca; F.G. Grosveld (Frank)

1996-01-01

textabstractThe nuclear distribution of GATA transcription factors in murine haemopoietic cells was examined by indirect immunofluorescence. Specific bright foci of GATA-1 fluorescence were observed in erythroleukaemia cells and primary murine erythroblasts and megakaryocytes, in addition to diffuse

Nuclear issues in the Asia-Pacific region: socio-political factors

International Nuclear Information System (INIS)

Tanaka, Y.

1984-01-01

This paper explores the prospect of peaceful use of nuclear power in the Asia-Pacific region, criteria for judging the acceptability of nuclear electric power in the region, and alternative worldviews on the basis of which a regional nuclear order should be established. First, current nuclear power issues in Japan are discussed. Secondly, the Asia-Pacific countries are classified according to their stages of civil nuclear development, Thirdly, the acceptability of civil nuclear power in the region is discussed, using nuclear nonproliferation, safety, and public acceptance as three major criteria. Fourthly, conflicts of interest that cut across North/South, East/West, nuclear/non-nuclear, and nuclear weapons states/non-nuclear weapons states boundaries are discussed. Lastly,it is proposed that an international forum be convened of all the countries concerned with nuclear issues in the region. Several major objectives of this forum are suggested, including construction of a rational model for a solution for non-zero-sum gain to everyone regarding use of nuclear power in the region. (author)

An Adenovirus DNA Replication Factor, but Not Incoming Genome Complexes, Targets PML Nuclear Bodies.

Science.gov (United States)

Komatsu, Tetsuro; Nagata, Kyosuke; Wodrich, Harald

2016-02-01

Promyelocytic leukemia protein nuclear bodies (PML-NBs) are subnuclear domains implicated in cellular antiviral responses. Despite the antiviral activity, several nuclear replicating DNA viruses use the domains as deposition sites for the incoming viral genomes and/or as sites for viral DNA replication, suggesting that PML-NBs are functionally relevant during early viral infection to establish productive replication. Although PML-NBs and their components have also been implicated in the adenoviral life cycle, it remains unclear whether incoming adenoviral genome complexes target PML-NBs. Here we show using immunofluorescence and live-cell imaging analyses that incoming adenovirus genome complexes neither localize at nor recruit components of PML-NBs during early phases of infection. We further show that the viral DNA binding protein (DBP), an early expressed viral gene and essential DNA replication factor, independently targets PML-NBs. We show that DBP oligomerization is required to selectively recruit the PML-NB components Sp100 and USP7. Depletion experiments suggest that the absence of one PML-NB component might not affect the recruitment of other components toward DBP oligomers. Thus, our findings suggest a model in which an adenoviral DNA replication factor, but not incoming viral genome complexes, targets and modulates PML-NBs to support a conducive state for viral DNA replication and argue against a generalized concept that PML-NBs target incoming viral genomes. The immediate fate upon nuclear delivery of genomes of incoming DNA viruses is largely unclear. Early reports suggested that incoming genomes of herpesviruses are targeted and repressed by PML-NBs immediately upon nuclear import. Genome localization and/or viral DNA replication has also been observed at PML-NBs for other DNA viruses. Thus, it was suggested that PML-NBs may immediately sense and target nuclear viral genomes and hence serve as sites for deposition of incoming viral genomes and

The Security of Russia's Nuclear Arsenal: The Human Factor

International Nuclear Information System (INIS)

Ball, D.Y.

1999-01-01

Assertions by the Russian military that all of their nuclear weapons are secure against theft and that nuclear units within the military are somehow insulated from the problems plaguing the Russian military should not be accepted uncritically. Accordingly, we should not give unwarranted credence to the pronouncements of military figures like Cal.-Gen. Igor Valynkin, Chief of the Defense Ministry's 12th Main Directorate, which oversees the country's nuclear arsenal. He contends that ''Russian nuclear weapons are under reliable supervision'' and that ''talk about the unreliability of our control over nuclear weapons has only one pragmatic goal--to convince international society that the country is incapable of maintaining nuclear safety and to introduce international oversight over those weapons, as it is done, for example, in Iraq.'' While the comparison to Iraq is preposterous, many analysts might agree with Valynkin's sanguine appraisal of the security of Russia's nuclear weapons. In contrast, I argue that the numerous difficulties confronting the military as a whole should cause concern in the West over the security of the Russian nuclear arsenal

Nuclear Modification Factor RpA of b jets in pPb collisions

CERN Document Server

CMS Collaboration

2014-01-01

We present a measurement of the nuclear modification factor $R_{\\mathrm{pA}}^{\\mathrm{PYTHIA}}$ of b jets in proton-lead collisions from CMS. Jets from b-quark fragmentations are found by exploiting the long lifetime of the b-quark through tagging methods using distributions of the secondary vertex displacement. From these, b-jet cross-sections are calculated and compared to a pp cross-section obtained from a PYTHIA simulation. The $R_{\\mathrm{pA}}^{\\mathrm{PYTHIA}}$ is consistent with unity within systematic uncertainties and may show slight enhancement due to cold nuclear matter effects for a wide range in pseudorapidity. These effects are qualitatively consistent with the observed value for the inclusive jet $R_{\\mathrm{pA}}$. We use 35 nb$^{-1}$ of proton-lead data collected during the 2013 heavy-ion run at the LHC.

Factors in public perception of nuclear energy

International Nuclear Information System (INIS)

Hore-Lacy, I.

1999-01-01

Public communication about nuclear energy needs to relate to the cultural undercurrents which determine how people perceive the environment. The paper discusses some of these and suggests ways of responding to them. It also outlines major ethical considerations relevant to uranium mining and nuclear energy and communication about both and shows that competent discourse about values is fundamental

RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

Science.gov (United States)

Shen, Chao; Ma, Yingjuan; Zeng, Ziling; Yin, Qingqing; Hong, Yan; Hou, Xunyao; Liu, Xueping

2017-10-01

Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aβ-induced inflammatory response by blocking the ligation of Aβ to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

Potential human factors deficiencies in the design of local control stations and operator interfaces in nuclear power plants

International Nuclear Information System (INIS)

Hartley, C.S.; Levy, I.S.; Fecht, B.A.

1984-04-01

The Pacific Northwest Laboratory has completed a project to identify human factors deficiencies in safety-significant control stations outside the control room of a nuclear power plant and to determine whether NUREG-0700, Guidelines for Control Room Design Reviews, would be sufficient for reviewing those local control stations (LCSs). The project accomplished this task by first, reviewing existing data pertaining to human factors deficiencies in LCSs involved in significant safety actions; second, surveying LCSs environments and design features at several operating nuclear power plants; and third, assessing the results of that survey relative to the contents of NUREG-0700

A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

International Nuclear Information System (INIS)

Kim, Jiyoung; Cha, Young-Nam; Surh, Young-Joon

2010-01-01

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

Greenhouse gas emission factor for coal power chain in China and the comparison with nuclear power chain

International Nuclear Information System (INIS)

Ma Zhonghai; Pan Ziqiang; He Huimin

1999-01-01

The Greenhouse Gas Emission for coal power chain in China is analyzed in detail and comprehensively by using the Life Cycle Analysis method. The Greenhouse Gas Emission Factors (GGEF) in each link and for the total power chain are calculated. The total GGEF for coal power chain is 1302.3 gCO 2 /kWh, about 40 times more than that for nuclear power chain. And consequently greenhouse effect could not be aggravated further by nuclear power. The energy strategy for nuclear power development is one of reality ways to retard the greenhouse effect, put resources into rational use and protect environment

Inhibition of CRM1-mediated nuclear export of transcription factors by leukemogenic NUP98 fusion proteins.

Science.gov (United States)

Takeda, Akiko; Sarma, Nayan J; Abdul-Nabi, Anmaar M; Yaseen, Nabeel R

2010-05-21

NUP98 is a nucleoporin that plays complex roles in the nucleocytoplasmic trafficking of macromolecules. Rearrangements of the NUP98 gene in human leukemia result in the expression of numerous fusion oncoproteins whose effect on nucleocytoplasmic trafficking is poorly understood. The present study was undertaken to determine the effects of leukemogenic NUP98 fusion proteins on CRM1-mediated nuclear export. NUP98-HOXA9, a prototypic NUP98 fusion, inhibited the nuclear export of two known CRM1 substrates: mutated cytoplasmic nucleophosmin and HIV-1 Rev. In vitro binding assays revealed that NUP98-HOXA9 binds CRM1 through the FG repeat motif in a Ran-GTP-dependent manner similar to but stronger than the interaction between CRM1 and its export substrates. Two NUP98 fusions, NUP98-HOXA9 and NUP98-DDX10, whose fusion partners are structurally and functionally unrelated, interacted with endogenous CRM1 in myeloid cells as shown by co-immunoprecipitation. These leukemogenic NUP98 fusion proteins interacted with CRM1, Ran, and the nucleoporin NUP214 in a manner fundamentally different from that of wild-type NUP98. NUP98-HOXA9 and NUP98-DDX10 formed characteristic aggregates within the nuclei of a myeloid cell line and primary human CD34+ cells and caused aberrant localization of CRM1 to these aggregates. These NUP98 fusions caused nuclear accumulation of two transcription factors, NFAT and NFkappaB, that are regulated by CRM1-mediated export. The nuclear entrapment of NFAT and NFkappaB correlated with enhanced transcription from promoters responsive to these transcription factors. Taken together, the results suggest a new mechanism by which NUP98 fusions dysregulate transcription and cause leukemia, namely, inhibition of CRM1-mediated nuclear export with aberrant nuclear retention of transcriptional regulators.

The human factor data management system of Daya Bay Nuclear Power Station

International Nuclear Information System (INIS)

Zhang Li; Zhang Ning; Guo Jianbing; Huang Weigang; Zhu Minhong; Wang Jin

1999-12-01

The collection, analysis and quantification of human factor data are very important parts of human reliability analysis and probabilistic risk assessment. Therefore various human databases have been created. But a human data management system with the functions of data collection, classification, analysis, computation and forecast is scarcely seen at home and abroad. So the authors have developed the human data management system of Daya Bay Nuclear Power Station. The system includes three modules and four databases. The authors firstly set forth some basic problems on the human factor data, which are concerned during the development of the system. Then the structure and function of the system are described. In view of the important role of human factor databases in the system, the authors also discuss the structure problems of the data in the databases in detail

Zyxin regulates migration of renal epithelial cells through activation of hepatocyte nuclear factor-1β.

Science.gov (United States)

Choi, Yun-Hee; McNally, Brian T; Igarashi, Peter

2013-07-01

Hepatocyte nuclear factor-1β (HNF-1β) is an epithelial tissue-specific transcription factor that regulates gene expression in the kidney, liver, pancreas, intestine, and other organs. Mutations of HNF-1β in humans produce renal cysts and congenital kidney anomalies. Here, we identify the LIM-domain protein zyxin as a novel binding partner of HNF-1β in renal epithelial cells. Zyxin shuttles to the nucleus where it colocalizes with HNF-1β. Immunoprecipitation of zyxin in leptomycin B-treated cells results in coprecipitation of HNF-1β. The protein interaction requires the second LIM domain of zyxin and two distinct domains of HNF-1β. Overexpression of zyxin stimulates the transcriptional activity of HNF-1β, whereas small interfering RNA silencing of zyxin inhibits HNF-1β-dependent transcription. Epidermal growth factor (EGF) induces translocation of zyxin into the nucleus and stimulates HNF-1β-dependent promoter activity. The EGF-mediated nuclear translocation of zyxin requires activation of Akt. Expression of dominant-negative mutant HNF-1β, knockdown of zyxin, or inhibition of Akt inhibits EGF-stimulated cell migration. These findings reveal a novel pathway by which extracellular signals are transmitted to the nucleus to regulate the activity of a transcription factor that is essential for renal epithelial differentiation.

Nuclear insulin-like growth factor 1 receptor phosphorylates proliferating cell nuclear antigen and rescues stalled replication forks after DNA damage.

Science.gov (United States)

Waraky, Ahmed; Lin, Yingbo; Warsito, Dudi; Haglund, Felix; Aleem, Eiman; Larsson, Olle

2017-11-03

We have previously shown that the insulin-like growth factor 1 receptor (IGF-1R) translocates to the cell nucleus, where it binds to enhancer-like regions and increases gene transcription. Further studies have demonstrated that nuclear IGF-1R (nIGF-1R) physically and functionally interacts with some nuclear proteins, i.e. the lymphoid enhancer-binding factor 1 (Lef1), histone H3, and Brahma-related gene-1 proteins. In this study, we identified the proliferating cell nuclear antigen (PCNA) as a nIGF-1R-binding partner. PCNA is a pivotal component of the replication fork machinery and a main regulator of the DNA damage tolerance (DDT) pathway. We found that IGF-1R interacts with and phosphorylates PCNA in human embryonic stem cells and other cell lines. In vitro MS analysis of PCNA co-incubated with the IGF-1R kinase indicated tyrosine residues 60, 133, and 250 in PCNA as IGF-1R targets, and PCNA phosphorylation was followed by mono- and polyubiquitination. Co-immunoprecipitation experiments suggested that these ubiquitination events may be mediated by DDT-dependent E2/E3 ligases ( e.g. RAD18 and SHPRH/HLTF). Absence of IGF-1R or mutation of Tyr-60, Tyr-133, or Tyr-250 in PCNA abrogated its ubiquitination. Unlike in cells expressing IGF-1R, externally induced DNA damage in IGF-1R-negative cells caused G 1 cell cycle arrest and S phase fork stalling. Taken together, our results suggest a role of IGF-1R in DDT. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Organizational/institutional factors affecting performance in the nuclear power industry

International Nuclear Information System (INIS)

Benson, J.L.

1992-01-01

The dramatic macro experiences occurring at Three Mile Island and Chernobyl as well as the cumulative micro experiences represented by sky-rocketing costs and public concerns have demonstrated how the institutionally and organizationally related aspects of the nuclear power industry have dominated and shaped the technical ones. Further, given the relatively stable or evolutionary nature of the technology as it is currently applied, these institutional and organizational factors contain the roots of most of the complications/problems associated with the industry relative to achieving any or all of its future performance objectives (technical, economic, and safety). Some technology transfer was attempted by the author from the field of general systems/cybernetics, which was explicitly aimed at dealing with the organizational/institutional factors, i.e., the problems and issues were approached using principles and methodology substantially different from that typically seen from applications based on the more traditional paradigmic engineering/industrial management orientation

Training and other conditioning factors in nuclear medicine in a developing country

International Nuclear Information System (INIS)

Touya, E.

1986-01-01

The aim of the paper is to discuss the validity of nuclear medicine in 1985, in a developing region, on the basis of certain knowledge of the area and with 20 years' experience of the problem in a small country belonging to that region. An attempt is made to identify the factors which have most significance and the action to take so as to arrive at proposals which would be useful in planning this special field. The effect of the difficult economic situation at the present time in the developing regions on health programmes and policies is discussed. The vital need for promoting and giving impetus to primary medical care is recognized and the obligation to provide secondary and tertiary medical care in the same manner in order to restore health standards is pointed out. It is understood that nuclear medicine may have an impact at the three levels of medical care, and that only those studies which strictly valorize the effectiveness and the cost/benefit and risk/benefit ratios should be encouraged. It is believed that criteria of centralization and critical mass should be met when organizing a nuclear medicine programme. The main items of multipurpose nuclear medicine equipment are determined and there is discussion of the problems involved in training for the nuclear physician, radiopharmacist, hospital physicist, electronics engineer, technician and nurse. Mention is made of the most critical aspects of equipment maintenance, availability of spares, supply of radioisotopes and radiopharmaceuticals, quality control and the individual effectiveness of each service. Reasons are given for the advantage of intervening mainly at the level on instruction and through continuous training courses so as to correct deviations and introduce new policies making for greater effectiveness in utilizing the limited economic resources available. (author)

Nuclear factor kappa B: a pro-inflammatory, transcription factor-mediated signalling pathway in lung carcinogenesis and its inhibition by nonsteroidal anti-inflammatory drugs.

Science.gov (United States)

Setia, Shruti; Sanyal, Sankar Nath

2012-01-01

9,10-Dimethyl benz(a)anthracene (DMBA), when injected intratracheally once at a dose of 20 mg/kg body weight, is found to induce lung cancer in rats. Two nonsteroidal anti-inflammatory drugs (NSAIDs), indomethacin and etoricoxib, are given orally daily as chemopreventive agents at a dose of 0.6 mg/kg body weight and 2 mg/kg body weight, respectively, along with DMBA. Morphologic and histologic analysis revealed the occurence of tumors and intense cellular proliferation in the DMBA-treated animals, whereas no such features were observed in the other groups. Nuclear factor κB, a nuclear transcription factor, and proliferating cell nuclear antigen, a cell proliferation antigen, were studied by immunoblotting and immunohistochemistry and their levels were markedly elevated in the DMBA group compared with the others. Oxidative stress parameters, as studied by the inducible nitric oxide synthase activity, and the levels of reactive oxygen and nitrogen species were found to be suppressed in the DMBA group. Furthermore, fluorescent staining of the isolated lung cells from bronchoalveolar lavage was performed to study apoptosis and alterations in the mitochondrial membrane potential, and the DMBA-induced lung cancer was found to be associated with high inner mitochondrial membrane potential and a suppressed level of apoptosis.

Nuclear TK1 expression is an independent prognostic factor for survival in pre-malignant and malignant lesions of the cervix

International Nuclear Information System (INIS)

Chen, Gang; He, Cheng; Li, Ling; Lin, An; Zheng, Xiongwei; He, Ellen; Skog, Sven

2013-01-01

Thymidine kinase 1 (TK1) is a proliferation biomarker that has been found useful for prognostication in cancer patients. Here we investigate for the first time the use of TK1 expression as a prognostic factor for patients with premalignant and malignant lesions of the uterine cervix. TK1 expression was determined by immunohistochemistry in cervical lesions (cervical intraepithelial neoplasia (CIN), n = 216; invasive cervical carcinoma, n = 84). TK1 and Ki-67 expressions and pathological/FIGO stages and age were correlated with 5-year survival by Kaplan-Meier, log rank and COX hazard uni- and multivariate analyses. TK1 labeling index (LI) was significantly correlated with CIN grades and invasive cervical carcinoma stages, while TK1 labeling intensity was only correlated to CIN grades. TK1 LI was significantly higher compared with Ki-67 LI. TK1 LI correlated significantly to 5-year survival in patients with invasive cervical carcinoma, particularly nuclear TK1 LI. In a multivariate analysis, nuclear TK1 expression was independent prognostic factor in patients with in situ/invasive cervical carcinoma or in invasive cervical carcinoma alone. Interestingly, in invasive cervical carcinoma patients with advanced tumors, nuclear TK1 expression could identify patients with significantly better survival rates (80%), while Ki-67 could not. Nuclear TK1 expression in early grade CIN predicts risk for progression to malignancy. Nuclear TK1 expression is also a prognostic factor for treatment outcome, particularly in patients with advanced cervical carcinomas. Nuclear TK1 expression is more useful than Ki-67 and pathological/FIGO stages

Ultraviolet B Radiation Stimulates the Interaction between Nuclear Factor of Activated T Cells 5 (NFAT5) and Nuclear Factor-Kappa B (NF-κB) in Human Lens Epithelial Cells.

Science.gov (United States)

Chung, Inyoung; Hah, Young-Sool; Ju, SunMi; Kim, Ji-Hye; Yoo, Woong-Sun; Cho, Hee-Young; Yoo, Ji-Myong; Seo, Seong-Wook; Choi, Wan-Sung; Kim, Seong-Jae

2017-07-01

Nuclear factor-kappa B (NF-κB) has been proposed as a therapeutic target for the treatment of cataracts. The authors investigated the relationship between nuclear factor of activated T cells 5 (NFAT5) and NF-κB in ultraviolet B (UVB)-irradiated human lens epithelial (HLE) cells. Human lens epithelial B-3 (HLE-B3) cells were exposed to UVB light at a dose of 10 mJ/cm 2 and then incubated for 24 h. Cell viability was assessed by using the Cell Counting Kit-8 (CCK-8) assay. Gene expression level of NFAT5 was determined using real-time quantitative polymerase chain reaction (qPCR). Protein expression levels of NFAT5, NF-κB p65, and α-smooth muscle actin (α-SMA) and the association of NFAT5 with the NF-κB p65 subunit were measured by Western blot analysis and a co-immunoprecipitation assay, respectively. The cellular distribution of NFAT5 and NF-κB p65 was examined by triple immunofluorescence staining. At 24 h after UVB exposure, cell viability significantly decreased in a dose-dependent manner, and UVB light (15 and 20 mJ/cm 2 ) significantly increased the ROS generation. UVB irradiation increased NFAT5 mRNA and protein levels and increased phosphorylation of NF-κB in HLE-B3 cells. α-SMA protein levels were increased in the irradiated cells. In addition, NFAT5 and NF-κB translocated from the cytoplasm to the nucleus, and binding between the p65 subunit and NFAT5 was increased. Exposure to UVB radiation induces nuclear translocation and stimulates binding between NFAT5 and NF-κB proteins in HLE-B3 cells. These interactions may form part of the biochemical mechanism of cataractogenesis in UVB-irradiated HLECs.

Role of apoptosis-inducing factor (AIF in programmed nuclear death during conjugation in Tetrahymena thermophila

Directory of Open Access Journals (Sweden)

Endoh Hiroshi

2010-02-01

Full Text Available Abstract Background Programmed nuclear death (PND, which is also referred to as nuclear apoptosis, is a remarkable process that occurs in ciliates during sexual reproduction (conjugation. In Tetrahymena thermophila, when the new macronucleus differentiates, the parental macronucleus is selectively eliminated from the cytoplasm of the progeny, concomitant with apoptotic nuclear events. However, the molecular mechanisms underlying these events are not well understood. The parental macronucleus is engulfed by a large autophagosome, which contains numerous mitochondria that have lost their membrane potential. In animals, mitochondrial depolarization precedes apoptotic cell death, which involves DNA fragmentation and subsequent nuclear degradation. Results We focused on the role of mitochondrial apoptosis-inducing factor (AIF during PND in Tetrahymena. The disruption of AIF delays the normal progression of PND, specifically, nuclear condensation and kilobase-size DNA fragmentation. AIF is localized in Tetrahymena mitochondria and is released into the macronucleus prior to nuclear condensation. In addition, AIF associates and co-operates with the mitochondrial DNase to facilitate the degradation of kilobase-size DNA, which is followed by oligonucleosome-size DNA laddering. Conclusions Our results suggest that Tetrahymena AIF plays an important role in the degradation of DNA at an early stage of PND, which supports the notion that the mitochondrion-initiated apoptotic DNA degradation pathway is widely conserved among eukaryotes.

Effects of Nuclear Factor-E2-related factor 2/Heme Oxygenase 1 on splanchnic hemodynamics in experimental cirrhosis with portal hypertension.

Science.gov (United States)

Qin, Jun; He, Yue; Duan, Ming; Luo, Meng

2017-05-01

We explored the effects of Nuclear Factor-E2-related factor 2 (Nrf2) and Heme Oxygenase 1 (HO-1) on splanchnic hemodynamics in portal hypertensive rats. Experimental cirrhosis with portal hypertension was induced by intraperitoneal injection of carbon tetrachloride. The expression of proteins was examined by immunoblotting. Hemodynamic studies were performed by radioactive microspheres. The vascular perfusion system was used to measure the contractile response of mesentery arterioles in rats. Nrf2 expression in the nucleus and HO-1 expression in cytoplasm was significantly enhanced in portal hypertensive rats. Portal pressure, as well as regional blood flow, increased significantly in portal hypertension and can be blocked by tin protoporphyrin IX. The expression of endogenous nitric oxide synthase and vascular endothelial growth factors increased significantly compared to normal rats, while HO-1 inhibition decreased the expression of these proteins significantly. The contractile response of mesenteric arteries decreased in portal hypertension, but can be partially recovered through tin protoporphyrin IX treatment. The expression of Nrf2/HO-1 increased in mesenteric arteries of portal hypertensive rats, which was related to oxidative stress. HO-1was involved in increased portal pressure and anomaly splanchnic hemodynamics in portal hypertensive rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Main influence factors on the final energy generation cost of a nuclear power plant in comparison with other energy sources

International Nuclear Information System (INIS)

Souza, J.A.M. de; Glardon, C.; Schmidt, R.M.

1981-01-01

The main factors in the construction and in the operation of nuclear power plants that affect the final energy generation cost are presented. The structure of the energy generation cost, of the nuclear fuel cost and the total investment are studied. (E.G.) [pt

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

International Nuclear Information System (INIS)

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

1994-01-01

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

Two intestinal specific nuclear factors binding to the lactase-phlorizin hydrolase and sucrase-isomaltase promoters are functionally related oligomeric molecules

DEFF Research Database (Denmark)

Troelsen, J T; Mitchelmore, C; Sjöström, H

1994-01-01

Lactase-phlorizin hydrolase (LPH) and sucrase-isomaltase (SI) are enterocyte-specific gene products. The identification of regulatory cis-elements in the promoter of these two genes has enabled us to carry out comparative studies of the corresponding intestinal-specific nuclear factors (NF-LPH1...... and SIF1-BP). Electrophoretic mobility shift assays demonstrated that the two nuclear factors compete for binding on the same cis-elements. The molecular size of the DNA binding polypeptide is estimated to be approximately 50 kDa for both factors. In the native form the factors are found as 250 k......Da oligomeric complexes. Based on these results NF-LPH1 and SIF1-BP are suggested to be either identical or closely related molecules....

Model calculating annual mean atmospheric dispersion factor for coastal site of nuclear power plant

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

This paper describes an atmospheric dispersion field experiment performed on the coastal site of nuclear power plant in the east part of China during 1995 to 1996. The three-dimension joint frequency are obtained by hourly observation of wind and temperature on a 100m high tower; the frequency of the “event day of land and sea breezes” are given by observation of surface wind and land and sea breezes; the diffusion parameters are got from measurements of turbulent and wind tunnel simulation test.A new model calculating the annual mean atmospheric dispersion factor for coastal site of nuclear power plant is developed and established.This model considers not only the effect from mixing release and mixed layer but also the effect from the internal boundary layer and variation of diffusion parameters due to the distance from coast.The comparison between results obtained by the new model and current model shows that the ratio of annual mean atmospheric dispersion factor gained by the new model and the current one is about 2.0.

Nuclear translocation of phospholipase C-zeta, an egg-activating factor, during early embryonic development

International Nuclear Information System (INIS)

Sone, Yoshie; Ito, Masahiko; Shirakawa, Hideki; Shikano, Tomohide; Takeuchi, Hiroyuki; Kinoshita, Katsuyuki; Miyazaki, Shunichi

2005-01-01

Phospholipase C-zeta (PLCζ), a strong candidate of the egg-activating sperm factor, causes intracellular Ca 2+ oscillations and egg activation, and is subsequently accumulated into the pronucleus (PN), when expressed in mouse eggs by injection of RNA encoding PLCζ. Changes in the localization of expressed PLCζ were investigated by tagging with a fluorescent protein. PLCζ began to translocate into the PN formed at 5-6 h after RNA injection and increased there. Observation in the same embryo revealed that PLCζ in the PN dispersed to the cytoplasm upon nuclear envelope breakdown and translocated again into the nucleus after cleavage. The dynamics was found in the second mitosis as well. When RNA was injected into fertilization-originated 1-cell embryos or blastomere(s) of 2-8-cell embryos, the nuclear localization of expressed PLCζ was recognized in every embryo up to blastocyst. Thus, PLCζ exhibited alternative cytoplasm/nucleus localization during development. This supports the view that the sperm factor could control cell cycle-dependent generation of Ca 2+ oscillations in early embryogenesis

Development of a Pilot Program for Human Factors Management in Operating Nuclear Power plants

International Nuclear Information System (INIS)

Lee, Jung-Woon; Lee, Yong-Hee; Jang, Tong-Il; Kim, Dae-Ho

2007-01-01

The human factors of operating NPPs have been reviewed as a part of Periodic Safety Reviews (PSRs). This human factors PSR covers a wide range of human factors including control room man-machine interfaces (MMIs), procedures, working conditions, qualification, training, information requirements and workload. Korea Atomic Energy Research Institute (KAERI) has performed human factors PSRs from the first PSR for Kori 1. It was determined in 2005 that for a Continuous Operation of the Korean NPPs an enhanced PSR should be performed and issues raised from the PSRs should be resolved. From the results of the PSR for Kori 1, several safety enhancement issues related to human factors were raised. KAERI is working on a resolution of some of the human factors issues for the Korea Hydro and Nuclear Power Co. (KHNP). As a part of the resolution, we are developing a human factors management program (HFMP) for Kori 1. This paper introduces the status of our development of HFMP

Implementation and test of proposals to integrate human factors in reporting and causal analysis in nuclear power plants

International Nuclear Information System (INIS)

Wilpert; Maimer, H.; Miller, R.; Fahlbruch, B.; Leiber, I.; Szameitat, S.; Baggen, R.; Gans, A.; Becker, G.

1998-01-01

The research project 'Implementation and Test of Proposals to integrate Human Factors in Reporting and Causal Analysis in Nuclear Power Plants' ('Implementation and Test', SR 2039/8) is based on two antecedent projects: 'Reporting System' (SR 2039/1) and 'Causal Analysis' (SR 2039/2). The project 'Implementation and Test' conducted various tests and introductory programs in cooperation with different target groups concerning the event analysis methodology 'SOL - Safety through Organizational Learning': Regulators, consultant organizations, union/works councillors and utilities. Thus, SOL was concurrently optimized and [apted for the practice in the German nuclear power industry. SOL was also validated in a German nuclear power plant using a concrete event. Results of the 'Implementation and Test' project demonstrate that SOL is fit to conduct event analyses practicably and economically with appropriate comprehensiveness and depth. SOL facilitates the identification of relevant contributing factors of events. This report concludes with various concrete proposals for the further development of the Program of the Federal Ministry of Environment, Nature Protection and Reactor Safety (BMU) and the Federal Agency of R[iation Protection (BfS) concerning 'The Contribution of Humans to Safety of Nuclear Power Plants'. (orig.) [de

Research on review technology for three key safety factors of periodic safety review (PSR) and its application to Qinshan Nuclear Power Plant

International Nuclear Information System (INIS)

Xu Shoulv; Yao Weida; Dou Yikang; Lin Shaoxuan; Cao Yenan; Zhou Quanfu; Zheng Jiong; Zhang Ming

2009-04-01

In 2001, after 10 years' operation, Qinshan Nuclear Power Plant (Q1) started to carry out periodic safety review (PSR) based on a nuclear safety guideline, Periodic Safety Review for Operational Nuclear Power Plants (HAF0312), issued by National Nuclear Safety Administration of China (NNSA). Entrusted by the owner of Q1, Shanghai Nuclear Engineering Research and Design Institute (SNERDI) implemented reviews of three key safety factors including safety analysis, equipment qualification and ageing. PSR was a challenging work in China at that time and through three years' research and practice, SNERDI summarized a systematic achievement for the review including review methodology, scoping, review contents and implementation steps, etc.. During the process of review for the three safety factors, totally 148 review reports and 341 recommendations for corrections were submitted to Q1. These reports and recommendations have provided guidance for correction actions as follow-up of PSR. This paper focuses on technical aspects to carry out PSR for the above-mentioned three safety factors, including review scoping, contents, methodology and main steps. The review technology and relevant experience can be taken for reference for other NPPs to carry out PSR. (authors)

Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

Energy Technology Data Exchange (ETDEWEB)

Oh, Se Jeong [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Gu, Dong Ryun [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Jin, Su Hyun [Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Park, Keun Ha [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Lee, Seoung Hoon, E-mail: leesh2@wku.ac.kr [Department of Oral Microbiology and Immunology, College of Dentistry, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Center for Metabolic Function Regulation (CMFR), School of Medicine, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of); Wonkwang Institute of Biomaterials and Implant, Wonkwang University, Iksan, Jeonbuk 54538 (Korea, Republic of)

2016-06-17

Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.

Cytosolic malate dehydrogenase regulates RANKL-mediated osteoclastogenesis via AMPK/c-Fos/NFATc1 signaling

International Nuclear Information System (INIS)

Oh, Se Jeong; Gu, Dong Ryun; Jin, Su Hyun; Park, Keun Ha; Lee, Seoung Hoon

2016-01-01

Cytosolic malate dehydrogenase (malate dehydrogenase 1, MDH1) plays pivotal roles in the malate/aspartate shuttle that might modulate metabolism between the cytosol and mitochondria. In this study, we investigated the role of MDH1 in osteoclast differentiation and formation. MDH1 expression was induced by receptor activator of nuclear factor kappa-B ligand (RANKL) treatment. Knockdown of MDH1 by infection with retrovirus containing MDH1-specific shRNA (shMDH1) reduced mature osteoclast formation and bone resorption activity. Moreover, the expression of marker genes associated with osteoclast differentiation was downregulated by shMDH1 treatment, suggesting a role of MDH1 in osteoclast differentiation. In addition, intracellular ATP production was reduced following the activation of adenosine 5′ monophosphate-activated protein kinase (AMPK), a cellular energy sensor and negative regulator of RANKL-induced osteoclast differentiation, in shMDH1-infected osteoclasts compared to control cells. In addition, the expression of c-Fos and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), a critical transcription factor of osteoclastogenesis, was decreased with MDH1 knockdown during RANKL-mediated osteoclast differentiation. These findings provide strong evidence that MDH1 plays a critical role in osteoclast differentiation and function via modulation of the intracellular energy status, which might affect AMPK activity and NFATc1 expression.

Human factors evaluation of man-machine interface for periodic safety review of nuclear power plants

International Nuclear Information System (INIS)

Lee, Yong Hee; Lee, Jung Woon; Park, Jae Chang; Hwang, In Koo; Lee, Hyun Cheol; Jang, Tong Il; Ku, Jin Young; Kim, Soo Jin

2004-12-01

This report describes the research results of human factors assessment on the MMI(Man Machine Interface) equipment as part of Periodic Safety Review(PSR) of Nuclear Power Plants(NPPs). As MMI is a key factor among human factors to be reviewed in PSR, we reviewed the MMI components of nuclear power plants in aspect of human factors engineering. The availability, suitability, and effectiveness of the MMI devices were chosen to be reviewed. The MMI devices were investigated through the review of design documents related to the MMI, survey of control panels, evaluation of experts, and experimental assessment. Checklists were used to perform this assessment and record the review results. The items mentioned by the expert comments to review in detail in relation with task procedures were tested by experiments with operators' participation. For some questionable issues arisen during this MMI review, operator workload and possibility of errors in operator actions were analysed. The reviewed MMI devices contain MCR(Main Control Room), SPDS(Safety Parameter Display System), RSP(Remote Shutdown Panel), and the selected LCBs(Local Control Boards) importantly related to safety. As results of the assessments, any significant problem challenging the safety was not found on human factors in the MMI devices. However, several small items to be changed and improved in suitability of MMI devices were discovered. An action plan is recommended to accommodate the suggestions and review comments. It will enhance the plant safety on MMI area

Human factors survey of advanced instrumentation and controls technologies in nuclear plants

International Nuclear Information System (INIS)

Carter, R.J.

1992-01-01

A survey of advanced instrumentation and controls (I ampersand C) technologies and associated human factors issues in the US and Canadian nuclear industries was carried out by a team from Oak Ridge national laboratory to provide background for the development of regulatory policy, criteria, and guides for review of advanced I ampersand C systems as well as human engineering guidelines for evaluating these systems. The survey found those components of the US nuclear industry surveyed to be quite interested in advanced I ampersand C, but very cautious in implementing such systems in nuclear facilities and power plants. The trend in the facilities surveyed is to experiment cautiously when there is an intuitive advantage or short-term payoff. In the control room, the usual practice is direct substitution of digital and microprocessor-based instruments or systems that are functionally identical to the analog instruments or systems being replaced. The most advanced I ampersand C systems were found in the Canadian CANDU plants, where the newest plant has digital system in almost 100% of its control systems and in over 70% of its plant protection system. The hypothesis that properly 'introducing digital systems increases safety' is supported by the Canadian experience. The performance of these digital systems was achieved using an appropriate quality assurance program for the software development. The ability of digital systems to detect impending failures and initiate a fail-safe action, is a significant safety issue that should be of special interest to every US utility as well as to the US Nuclear Regulatory Commission. (orig.)

Importin α-importin β complex mediated nuclear translocation of insulin-like growth factor binding protein-5.

Science.gov (United States)

Sun, Min; Long, Juan; Yi, Yuxin; Xia, Wei

2017-10-28

Insulin-like growth factor-binding protein (IGFBP)-5 is a secreted protein that binds to IGFs and modulates IGF actions, as well as regulates cell proliferation, migration, and apoptosis independent of IGF. Proper cellular localization is critical for the effective function of most signaling molecules. In previous studies, we have shown that the nuclear IGFBP-5 comes from ER-cytosol retro-translocation. In this study, we further investigated the pathway mediating IGFBP-5 nuclear import after it retro-translocation. Importin-α5 was identified as an IGFBP-5-interacting protein with a yeast two-hybrid system, and its interaction with IGFBP-5 was further confirmed by GST pull down and co-immunoprecipitation. Binding affinity of IGFBP-5 and importins were determined by surface plasmon resonance (IGFBP-5/importin-β: K D =2.44e-7, IGFBP-5/importin-α5: K D =3.4e-7). Blocking the importin-α5/importin-β nuclear import pathway using SiRNA or dominant negative impotin-β dramatically inhibited IGFBP-5-EGFP nuclear import, though importin-α5 overexpress does not affect IGFBP-5 nuclear import. Furthermore, nuclear IGFBP-5 was quantified using luciferase report assay. When deleted the IGFBP-5 nuclear localization sequence (NLS), IGFBP-5 ΔNLS loss the ability to translocate into the nucleus and accumulation of IGFBP-5 ΔNLS was visualized in the cytosol. Altogether, our findings provide a substantially evidence showed that the IGFBP-5 nuclear import is mediated by importin-α/importin-β complex, and NLS is critical domain in IGFBP-5 nuclear translocation.

Extracellular Matrix Remodeling and Modulation of Inflammation and Oxidative Stress by Sulforaphane in Experimental Diabetic Peripheral Neuropathy.

Science.gov (United States)

Moustafa, Passant E; Abdelkader, Noha F; El Awdan, Sally A; El-Shabrawy, Osama A; Zaki, Hala F

2018-04-27

The peripheral nervous system is one of many organ systems that can be profoundly impacted in diabetes mellitus. Diabetic peripheral neuropathy has a significant negative effect on patients' quality of life as it begins with loss of limbs' sensation and may result in lower limb amputation. This investigation aimed at exploring the effect of sulforaphane on peripheral neuropathy in diabetic rats. Experimental diabetes was induced through single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Rats were divided into five groups. Two groups were treated with saline or sulforaphane (1 mg/kg, p.o.). Three diabetic groups were either untreated or given sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). Two weeks after drugs' administration, biochemical, behavioral, histopathological, and immunohistochemical investigations were carried out. Treatment with sulforaphane restored animals' body weight, reduced blood glucose, glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of tail flick test, increased the latency withdrawal time of cold allodynia test, and ameliorated histopathological changes. Treatment of sulforaphane, likewise, decreased sciatic nerve malondialdehyde, nitric oxide, interleukin-6, and matrix metalloproteinase-2 and -9 contents. Similarly, it reduced sciatic nerve DNA fragmentation and expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, it increased sciatic nerve superoxide dismutase and interleukin-10 contents. These results reveal the neuroprotective effect of sulforaphane against peripheral neuropathy in diabetic rats possibly through modulating oxidative stress, inflammation, and extracellular matrix remodeling. Graphical Abstract Diagram that illustrates the effects of sulforaphane in treating experimental diabetic peripheral neuropathy. In NA-STZ model of diabetes mellitus, sulforaphane, restored

A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders

Energy Technology Data Exchange (ETDEWEB)

Kim, Jiyoung [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cha, Young-Nam [Inha University College of Medicine, Incheon 382-751 (Korea, Republic of); Surh, Young-Joon, E-mail: surh@plaza.snu.ac.kr [National Research Laboratory, College of Pharmacy, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 151-742 (Korea, Republic of); Cancer Research Institute, Seoul National University, Seoul 110-799 (Korea, Republic of)

2010-08-07

Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a key transcription factor that plays a central role in cellular defense against oxidative and electrophilic insults by timely induction of antioxidative and phase-2 detoxifying enzymes and related stress-response proteins. The 5'-flanking regions of genes encoding these cytoprotective proteins contain a specific consensus sequence termed antioxidant response element (ARE) to which Nrf2 binds. Recent studies have demonstrated that Nrf2-ARE signaling is also involved in attenuating inflammation-associated pathogenesis, such as autoimmune diseases, rheumatoid arthritis, asthma, emphysema, gastritis, colitis and atherosclerosis. Thus, disruption or loss of Nrf2 signaling causes enhanced susceptibility not only to oxidative and electrophilic stresses but also to inflammatory tissue injuries. During the early-phase of inflammation-mediated tissue damage, activation of Nrf2-ARE might inhibit the production or expression of pro-inflammatory mediators including cytokines, chemokines, cell adhesion molecules, matrix metalloproteinases, cyclooxygenase-2 and inducible nitric oxide synthase. It is likely that the cytoprotective function of genes targeted by Nrf2 may cooperatively regulate the innate immune response and also repress the induction of pro-inflammatory genes. This review highlights the protective role of Nrf2 in inflammation-mediated disorders with special focus on the inflammatory signaling modulated by this redox-regulated transcription factor.

Regulation of Gene Expression with Double-Stranded Phosphorothioate Oligonucleotides

Science.gov (United States)

Bielinska, Anna; Shivdasani, Ramesh A.; Zhang, Liquan; Nabel, Gary J.

1990-11-01

Alteration of gene transcription by inhibition of specific transcriptional regulatory proteins is necessary for determining how these factors participate in cellular differentiation. The functions of these proteins can be antagonized by several methods, each with specific limitations. Inhibition of sequence-specific DNA-binding proteins was achieved with double-stranded (ds) phosphorothioate oligonucleotides that contained octamer or kappaB consensus sequences. The phosphorothioate oligonucleotides specifically bound either octamer transcription factor or nuclear factor (NF)-kappaB. The modified oligonucleotides accumulated in cells more effectively than standard ds oligonucleotides and modulated gene expression in a specific manner. Octamer-dependent activation of a reporter plasmid or NF-kappaB-dependent activation of the human immunodeficiency virus (HIV) enhancer was inhibited when the appropriate phosphorothioate oligonucleotide was added to a transiently transfected B cell line. Addition of phosphorothioate oligonucleotides that contained the octamer consensus to Jurkat T leukemia cells inhibited interleukin-2 (IL-2) secretion to a degree similar to that observed with a mutated octamer site in the IL-2 enhancer. The ds phosphorothioate oligonucleotides probably compete for binding of specific transcription factors and may provide anti-viral, immunosuppressive, or other therapeutic effects.

Factor analysis on hazards for safety assessment in decommissioning workplace of nuclear facilities using a semantic differential method

Energy Technology Data Exchange (ETDEWEB)

Jeong, Kwan-Seong [Korea Atomic Energy Research Institute, 1045 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)], E-mail: ksjeongl@kaeri.re.kr; Lim, Hyeon-Kyo [Chungbuk National University, 410 Sungbong-ro, Heungduk-gu, Cheongju, Chungbuk 361-763 (Korea, Republic of)

2009-10-15

The decommissioning of nuclear facilities must be accomplished according to its structural conditions and radiological characteristics. An effective risk analysis requires basic knowledge about possible risks, characteristics of potential hazards, and comprehensive understanding of the associated cause-effect relationships within a decommissioning for nuclear facilities. The hazards associated with a decommissioning plan are important not only because they may be a direct cause of harm to workers but also because their occurrence may, indirectly, result in increased radiological and non-radiological hazards. Workers need to be protected by eliminating or reducing the radiological and non-radiological hazards that may arise during routine decommissioning activities as well as during accidents. Therefore, to prepare the safety assessment for decommissioning of nuclear facilities, the radiological and non-radiological hazards should be systematically identified and classified. With a semantic differential method of screening factor and risk perception factor, the radiological and non-radiological hazards are screened and identified.

Radiation factors and smoking interaction at lung cancer incidence for workers at a nuclear enterprise

International Nuclear Information System (INIS)

Tokarskaya, Z.B.; Khokhryakov, V.T.; Okladnikova, N.D.; Belyaeva, Z.D.; Zhuntova, G.V.; Fleck, C.M.; Schollnberger, H.; Drozhko, E.G.

1998-01-01

A study is reported which is a continuation of a previous investigation of lung cancer incidence in workers at a nuclear enterprise and its relation to three basic etiological factors: the body burden due to 239 Pu, chronic external gamma irradiation, and smoking. Whereas previously each of the factors was assessed separately, in the present study the attempt was made to assess the interaction of the factors. A statistical analysis of the data revealed that for the following pairs of factors a superposition effect could be seen: external gamma irradiation and 239 Pu body burden; external gamma irradiation and a medium level of smoking; and 239 Pu body burden and a medium level of smoking. (A.K.)

Nuclear energy 1985: Nuclear power as an economic factor of growing importance

International Nuclear Information System (INIS)

Anon.

1985-01-01

Summary of the results of the Technical Sessions and Poster Sessions of the ten Technical Sections: Reactor physics; thermodynamics and fluid dynamics; safety of nuclear facilities; fuel cycle and waste management; fuel elements and fuel element materials; components and component materials; quality assurance; construction and operation of nuclear facilities; fusion technology; energy systems - energy industry; atomic law, radiation protection law, law on the protection against misances, related fields of law. Separate records are available for each paper. (HP) [de

Assessment of theoretical and experimental results in the calculation of atmospheric dilution factors in the Atucha I nuclear power plant

International Nuclear Information System (INIS)

Quintana, E.E.; Tossi, M.H.; Telleria, D.M.

1990-01-01

Collective doses produced during the normal working of the Atucha I Nuclear Power Plant are calculated using annual atmospheric factors. This work studies the behaviour of the dilution factors in different periods of the year in order to fit the calculated dose model applying factors from seasonal, monthly or weekly periods. The Radiation Protection Group of the C.N.E.A. have carried out continuous environmental monitoring in the surroundings of the Atucha I Nuclear Power Plant. These studies include the measurement of air tritium concentration, radionuclide that is found principally as tritiated water vapour. This isotope, normally released by the nuclear power plant was used as a tracer to assess the atmospheric dilution factors. Factors were calculated by two methods: an experimental one, based on environmental measurements of the tritium concentration in the surroundings of the nuclear power plant and another one by applying a theoretical model based on information from the micrometeorological tower located in the mentioned place. To carry out the environmental monitoring, four monitoring stations in the surroundings of the power plant were chosen. Three of them are approximately one kilometer from the plant and the fourth is 7.5 km away, near the city of Lima. To condense and collect the atmospheric water vapour, an overcooling system was used. The measurement was performed by liquid scintillation counting, previous alkaline electrolytical enrichment of the samples. The theoretical model uses hourly values of direction and wind intensity, as well as the atmospheric dispersive properties. Values obtained during the period 1976 to 1988 allowed, applying statistical tests, to validate the theoretical model and to observe seasonal variation of the dilution factors throughout the same year and between different years. Finally, results and graphics are presented showing that the behaviour of the dilution factors in different periods of the year. It is recommended to

Nuclear factor erythroid 2-related factor-2 activity controls 4-hydroxynonenal metabolism and activity in prostate cancer cells.

Science.gov (United States)

Pettazzoni, Piergiorgio; Ciamporcero, Eric; Medana, Claudio; Pizzimenti, Stefania; Dal Bello, Federica; Minero, Valerio Giacomo; Toaldo, Cristina; Minelli, Rosalba; Uchida, Koji; Dianzani, Mario Umberto; Pili, Roberto; Barrera, Giuseppina

2011-10-15

4-Hydroxynonenal (HNE) is an end product of lipoperoxidation with antiproliferative and proapoptotic properties in various tumors. Here we report a greater sensitivity to HNE in PC3 and LNCaP cells compared to DU145 cells. In contrast to PC3 and LNCaP cells, HNE-treated DU145 cells showed a smaller reduction in growth and did not undergo apoptosis. In DU145 cells, HNE did not induce ROS production and DNA damage and generated a lower amount of HNE-protein adducts. DU145 cells had a greater GSH and GST A4 content and GSH/GST-mediated HNE detoxification. Nuclear factor erythroid 2-related factor-2 (Nrf2) is a regulator of the antioxidant response. Nrf2 protein content and nuclear accumulation were higher in DU145 cells compared to PC3 and LNCaP cells, whereas the expression of KEAP1, the main negative regulator of Nrf2 activity, was lower. Inhibition of Nrf2 expression with specific siRNA resulted in a reduction in GST A4 expression and GS-HNE formation, indicating that Nrf2 controls HNE metabolism. In addition, Nrf2 knockdown sensitized DU145 cells to HNE-mediated antiproliferative and proapoptotic activity. In conclusion, we demonstrated that increased Nrf2 activity resulted in a reduction in HNE sensitivity in prostate cancer cells, suggesting a potential mechanism of resistance to pro-oxidant therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Influence factors on etching rate of PET nuclear pore membrane

International Nuclear Information System (INIS)

Zuo Zhenzhong; Wu Zhendong; Liang Haiying; Ju Wei; Chen Dongfeng; Fu Yuanyong; Qu Guopu

2014-01-01

Background: The nuclear pore membrane is a kind of liquid filtration material manufactured by irradiation and chemical etching. Various conditions in etch process have a great influence on etch rate. Purpose: The influence factors of concentration and temperature of etch solution and the irradiation energy of heavy ions on etch rate was studied. Methods: Four layers of PET (polyethylene terephthalate) films were stacked together and were irradiated with 140-MeV 32 S ions at room temperature under vacuum conditions. Utilizing conductivity measurement technique, the electrical current changes through the u:radiated PET film were monitored during etching, from which the breakthrough time and therefore the track etching rate was calculated. Results: The results show that there is an exponential correlation between etch rate and temperature, and a linear correlation between etch rate and concentration. The track etching rate increases linearly with energy loss rate. Empirical formula for the bulk etching rate as a function of etchant concentration and temperature was also established via fitting of measurements. Conclusion: It is concluded that by using 1.6-MeV·u -1 32 S ions, PET nuclear pore membrane with cylindrical pore shape can be prepared at 85℃ with etchant concentration of l mol·L -1 . (authors)

Ethanol Inhibits High-Affinity Immunoglobulin E Receptor (Fc epsilon RI) Signaling in Mast Cells by Suppressing the Function of Fc epsilon RI-Cholesterol Signalosome

Czech Academy of Sciences Publication Activity Database

Dráberová, Lubica; Paulenda, Tomáš; Hálová, Ivana; Potůčková, Lucie; Bugajev, Viktor; Bambousková, Monika; Tůmová, Magda; Dráber, Petr

2015-01-01

Roč. 10, č. 12 (2015), e0144596-e0144596 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GBP302/12/G101; GA MŠk LD12073 Institutional support: RVO:68378050 Keywords : KAPPA-B Activation * Lipid rafts * Nadph oxidase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

Analysis of chemical factors affecting marine ecosystem around nuclear power plant

International Nuclear Information System (INIS)

Chun, Kwan Sik; Choi, Yoon Dong; Chun, Ki Jeong; Kim, Jin Kyu; Jung, Kyeong Chai; Lee, Yeong Keun; Park, Hyo Kook

1994-06-01

The ecological data of the coastal area of Youngkwang nuclear power plant from 1987 to 1993 were comprehensively analyzed, and various physical and chemical properties of sea water and sediments were measured. Major factors affecting phytoplankton standing crops were suspended substances, nitrate, and silicate. The contents of iron, chromium, copper, and sulfur in sediments sampled from the discharge channel were slightly higher than those in the other areas. In order to qantify the chemical impacts on marine ecosystem, it is desirable that a systematic survey be made through the whole year cycle to assure the consistency and confidence of the related data. (Author)

Characterization of germ cell-specific expression of the orphan nuclear receptor, germ cell nuclear factor.

Science.gov (United States)

Katz, D; Niederberger, C; Slaughter, G R; Cooney, A J

1997-10-01

Nuclear receptors, such as those for androgens, estrogens, and progesterones, control many reproductive processes. Proteins with structures similar to these receptors, but for which ligands have not yet been identified, have been termed orphan nuclear receptors. One of these orphans, germ cell nuclear factor (GCNF), has been shown to be germ cell specific in the adult and, therefore, may also participate in the regulation of reproductive functions. In this paper, we examine more closely the expression patterns of GCNF in germ cells to begin to define spatio-temporal domains of its activity. In situ hybridization showed that GCNF messenger RNA (mRNA) is lacking in the testis of hypogonadal mutant mice, which lack developed spermatids, but is present in the wild-type testis. Thus, GCNF is, indeed, germ cell specific in the adult male. Quantitation of the specific in situ hybridization signal in wild-type testis reveals that GCNF mRNA is most abundant in stage VII round spermatids. Similarly, Northern analysis and specific in situ hybridization show that GCNF expression first occurs in testis of 20-day-old mice, when round spermatids first emerge. Therefore, in the male, GCNF expression occurs postmeiotically and may participate in the morphological changes of the maturing spermatids. In contrast, female expression of GCNF is shown in growing oocytes that have not completed the first meiotic division. Thus, GCNF in the female is expressed before the completion of meiosis. Finally, the nature of the two different mRNAs that hybridize to the GCNF complementary DNA was studied. Although both messages contain the DNA binding domain, only the larger message is recognized by a probe from the extreme 3' untranslated region. In situ hybridization with these differential probes demonstrates that both messages are present in growing oocytes. In addition, the coding region and portions of the 3' untranslated region of the GCNF complementary DNA are conserved in the rat.

Lessons Learned from Human Factor Technical Support for Nuclear Power Plants

International Nuclear Information System (INIS)

Jung, Yeon Sub; Song, Tae Young

2011-01-01

NETEC is on the frontier to support Korean nuclear power plants. Requests of service are distributed through web based system. Human factor requests are occasionally posted. This paper analyzes interesting human factors requests/responses serviced, and summarizes the lesson learned. Subjects of the service include man machine interface, equipment label, procedure writing, procedure adherence, BISI, hand switch and alarm tile. Specifically the man machine interface is related to control command generated by acknowledge button, arrangement of switches. Procedure writing is about how to write contingency actions with proper numbering scheme. BISI is analyzed in view of automation level. Alarm tile is about how to handle the common alarm tile originated from local alarm boards. These topics seem to be legacies of past technology. Even though there are still human engineering discrepancies, these have been less evaluated because the topics need knowledge of other field domains

Applying Human Factors Evaluation and Design Guidance to a Nuclear Power Plant Digital Control System

Energy Technology Data Exchange (ETDEWEB)

Thomas Ulrich; Ronald Boring; William Phoenix; Emily Dehority; Tim Whiting; Jonathan Morrell; Rhett Backstrom

2012-08-01

The United States (U.S.) nuclear industry, like similar process control industries, has moved toward upgrading its control rooms. The upgraded control rooms typically feature digital control system (DCS) displays embedded in the panels. These displays gather information from the system and represent that information on a single display surface. In this manner, the DCS combines many previously separate analog indicators and controls into a single digital display, whereby the operators can toggle between multiple windows to monitor and control different aspects of the plant. The design of the DCS depends on the function of the system it monitors, but revolves around presenting the information most germane to an operator at any point in time. DCSs require a carefully designed human system interface. This report centers on redesigning existing DCS displays for an example chemical volume control system (CVCS) at a U.S. nuclear power plant. The crucial nature of the CVCS, which controls coolant levels and boration in the primary system, requires a thorough human factors evaluation of its supporting DCS. The initial digital controls being developed for the DCSs tend to directly mimic the former analog controls. There are, however, unique operator interactions with a digital vs. analog interface, and the differences have not always been carefully factored in the translation of an analog interface to a replacement DCS. To ensure safety, efficiency, and usability of the emerging DCSs, a human factors usability evaluation was conducted on a CVCS DCS currently being used and refined at an existing U.S. nuclear power plant. Subject matter experts from process control engineering, software development, and human factors evaluated the DCS displays to document potential usability issues and propose design recommendations. The evaluation yielded 167 potential usability issues with the DCS. These issues should not be considered operator performance problems but rather opportunities

The obscure factor analysis on the vibration reliability of the internals of nuclear power plant reactor and anti-vibration measures

International Nuclear Information System (INIS)

Fu Geyan; Zhu Qirong

1998-11-01

It is pointed out that the main reason making nuclear power plants reactors leak is the vibration of internals of reactors. The factors which lead the vibration all have randomness and obscureness. The obscure reliability theory is introduced to the vibration system of internals of nuclear power reactor. Based on a quantity of designing and moving data, the obscure factors effecting the vibration reliability of the internals of nuclear power plant reactor are analyzed and the anti-vibration reliability criteria and the evaluating model are given. And the anti-vibration reliability measures are advanced from different quarters of the machine design and building, the thermohydraulics design, the control of reactivity, etc.. They may benefit the theory and practice for building and perfecting the vibration obscure reliability model of the reactor internals

A new contribution to the nuclear modification factor of non-photonic electrons in Au + Au collisions at √sNN = 200 GeV

International Nuclear Information System (INIS)

Martinez-Garcia, G.; Gadrat, S.; Crochet, P.

2007-02-01

We investigate the effect of the so-called anomalous baryon/meson enhancement to the nuclear modification factor of non-photonic electrons in Au+Au collisions at √s NN = 200 GeV. It is demonstrated that an enhancement of the charm baryon/meson ratio, as it is observed for non-strange and strange hadrons, can be responsible for a part of the amplitude of the nuclear modification factor of non-photonic electrons. About half of the measured suppression of non-photonic electrons in the 2 - 4 GeV/c p t range can be explained by a charm baryon/meson enhancement of 5. This contribution to the non-photonic electron nuclear modification factor has nothing to do with heavy quark energy loss. (authors)

Knowledge Sharing Through Virtual Mode: The Influenced Factors for KM Development Among the Researchers in Nuclear Malaysia

International Nuclear Information System (INIS)

Adnan, H.; Sulaiman, M.S.; Yusof, M.H.; Ali, I.

2014-01-01

Conclusion: • The primary contribution of this study is to assess the influence of virtual mode as a KM medium in Nuclear Malaysia. • Direct relationship between the researchers and the used of virtual mode in the knowledge sharing process. • Finding reveals that virtual mode contributes significant factors in influencing researchers’ knowledge sharing behaviour. • The findings from the study may be used by the management of Nuclear Malaysia to improve or enhance the capacity of virtual mode provided by the organisation

Human factors and nuclear space technology in long-term exploration

International Nuclear Information System (INIS)

Brown-VanHoozer, S.A.; VanHoozer, W.R.

2000-01-01

Allocation of manual versus automated tasks for operation and maintenance of nuclear power systems in space will be crucial at the onset and at the return of a space flight. Such factors as space adaptation syndrome (SAS), a temporary space motion sickness that has affected 40 to 50% of crew members on past space flights, can result in lost effort ranging from a few hours to a full day. This could have a significant impact on manual performance where high levels of execution are likely to be required in the very early stages of the mission. Other considerations involving higher-level behavioral phenomena such as interpersonal and group processes, individual belief systems, social and motivational factors, and (subjective) cognitive function have received little attention; nevertheless these will be essential elements for success in long-term exploration. Understanding that long-term space flight missions may create groups that become unique societies distinct unto themselves will test current ethical, moral, and social belief systems, requiring one to examine the amalgamation as well as organizational structures for the safety and balance of the crew

Evaluation of response factors for seismic probabilistic safety assessment of nuclear power plants

International Nuclear Information System (INIS)

Ebisawa, K.; Abe, K.; Muramatsu, K.; Itoh, M.; Kohno, K.; Tanaka, T.

1994-01-01

This paper presents a method for evaluating 'response factors' of components in nuclear power plants for use in a seismic probabilistic safety assessment (PSA). The response factor here is a measure of conservatism included in response calculations in seismic design analysis of components and is defined as a ratio of conservative design resonse to actual response. This method has the following characteristic features: (1) The components are classified into several groups based on the differences in their location and in the vibration models used in design response analyses; (2) the response factors are decomposed into subfactors corresponding to the stages of the seismic response analyses in the design practices; (3) the response factors for components are calculated as products of subfactors; (4) the subfactors are expressed either as a single value or as a function of parameters that influence the response of components. This paper describes the outline of this method and results from an application to a sample problem in which response factors were quantified for examples of components selected from the groups. (orig.)

A Human Factors Study on an Information Visualization System for Nuclear Power Plants Decommissioning Engineering

Energy Technology Data Exchange (ETDEWEB)

Yang, Chih Wei; Yang, Li Chen [Institute of Nuclear Energy Research, Atomic Energy Council, Longtan (China)

2014-08-15

Most nuclear power plants (NPPs) in the world have an operating life of up to 40 years. The utility should prepare a comprehensive decommissioning plan with purpose to document and to display how decommissioning activities can be safely performed. In the past, most studies related to NPPs decommissioning planning put emphasis on technical issues, little attention have been given to human factors in decommissioning activities. In fact, human factors are a critical factor to successful NPPs decommissioning. NPPs decommissioning will face potential risks. These risks include not only dismantling and moving large equipment but also treating with the radioactive materials. Using information visualization system, such as virtual reality (VR) technology, for staff training can improve decommissioning work safety and economy. Therefore, this study presents a study using VR to solve real world problems in the nuclear plant decommissioning. Then appropriate cases for introducing VR systems are summarized and future prospects are given. This study assesses availability and performance of the work training system by using heuristic evaluation and actual experiment. In the result, block type of radiation visibility was found relatively better both in performance and person's preference than other types. The results presented in this paper illustrate the VR applications a NPP decommissioning perspective.

A Human Factors Study on an Information Visualization System for Nuclear Power Plants Decommissioning Engineering

International Nuclear Information System (INIS)

Yang, Chih Wei; Yang, Li Chen

2014-01-01

Most nuclear power plants (NPPs) in the world have an operating life of up to 40 years. The utility should prepare a comprehensive decommissioning plan with purpose to document and to display how decommissioning activities can be safely performed. In the past, most studies related to NPPs decommissioning planning put emphasis on technical issues, little attention have been given to human factors in decommissioning activities. In fact, human factors are a critical factor to successful NPPs decommissioning. NPPs decommissioning will face potential risks. These risks include not only dismantling and moving large equipment but also treating with the radioactive materials. Using information visualization system, such as virtual reality (VR) technology, for staff training can improve decommissioning work safety and economy. Therefore, this study presents a study using VR to solve real world problems in the nuclear plant decommissioning. Then appropriate cases for introducing VR systems are summarized and future prospects are given. This study assesses availability and performance of the work training system by using heuristic evaluation and actual experiment. In the result, block type of radiation visibility was found relatively better both in performance and person's preference than other types. The results presented in this paper illustrate the VR applications a NPP decommissioning perspective

Nuclear energy an introduction to the concepts, systems, and applications of nuclear processes

CERN Document Server

Murray, Raymond

2001-01-01

Nuclear Energy, Fifth Edition provides nuclear engineers, plant designers and radiation physicists with a comprehensive overview of nuclear energy and its uses, discusses potential problems and provides an outlook for the futureNew and important trends are discussed including probabilistic safety analysis (PSA), deregulation of the electric power industry to permit competition in the supply of electricity; improvements in performance characteristics of nuclear power plants, such as capacity factor, production costs, and safety factors; storage and disposal of all types of radioactive w

Nuclear energy and nuclear weapons proliferation

International Nuclear Information System (INIS)

1989-01-01

A summary of the report dispatched in the middle of 1978 by the Atlantic Council of United States, organized by North American citizens, is presented. The report considers the relation between the production of nucleoelectric energy and the capacity of proliferation of nuclear weapons. The factors which affect the grade of proliferation risk represented by the use of nuclear energy in the world comparing this risk with the proliferation risks independently of nuclear energy, are examined. (M.C.K.) [pt

Highlights on distinctive structural and functional properties of HTLV Tax proteins

Science.gov (United States)

Romanelli, Maria Grazia; Diani, Erica; Bergamo, Elisa; Casoli, Claudio; Ciminale, Vincenzo; Bex, Françoise; Bertazzoni, Umberto

2013-01-01

Human T cell leukemia viruses (HTLVs) are complex human retroviruses of the Deltaretrovirus genus. Four types have been identified thus far, with HTLV-1 and HTLV-2 much more prevalent than HTLV-3 or HTLV-4. HTLV-1 and HTLV-2 possess strictly related genomic structures, but differ significantly in pathogenicity, as HTLV-1 is the causative agent of adult T cell leukemia and of HTLV-associated myelopathy/tropical spastic paraparesis, whereas HTLV-2 is not associated with neoplasia. HTLVs code for a protein named Tax that is responsible for enhancing viral expression and drives cell transformation. Much effort has been invested to dissect the impact of Tax on signal transduction pathways and to identify functional differences between the HTLV Tax proteins that may explain the distinct oncogenic potential of HTLV-1 and HTLV-2. This review summarizes our current knowledge of Tax-1 and Tax-2 with emphasis on their structure, role in activation of the NF-κB (nuclear factor kappa-B) pathway, and interactions with host factors. PMID:24058363

Fanconi anemia FANCD2 and FANCI proteins regulate the nuclear dynamics of splicing factors.

Science.gov (United States)

Moriel-Carretero, María; Ovejero, Sara; Gérus-Durand, Marie; Vryzas, Dimos; Constantinou, Angelos

2017-12-04

Proteins disabled in the cancer-prone disorder Fanconi anemia (FA) ensure the maintenance of chromosomal stability during DNA replication. FA proteins regulate replication dynamics, coordinate replication-coupled repair of interstrand DNA cross-links, and mitigate conflicts between replication and transcription. Here we show that FANCI and FANCD2 associate with splicing factor 3B1 (SF3B1), a key spliceosomal protein of the U2 small nuclear ribonucleoprotein (U2 snRNP). FANCI is in close proximity to SF3B1 in the nucleoplasm of interphase and mitotic cells. Furthermore, we find that DNA replication stress induces the release of SF3B1 from nuclear speckles in a manner that depends on FANCI and on the activity of the checkpoint kinase ATR. In chromatin, both FANCD2 and FANCI associate with SF3B1, prevent accumulation of postcatalytic intron lariats, and contribute to the timely eviction of splicing factors. We propose that FANCD2 and FANCI contribute to the organization of functional domains in chromatin, ensuring the coordination of DNA replication and cotranscriptional processes. © 2017 Moriel-Carretero et al.

Human Factors Engineering Incorporated into the Carolina Power and Light company's nuclear power plant control panel modifications

International Nuclear Information System (INIS)

Beith, D.M.; Shoemaker, E.M.; Horn, K.; Boush, D.

1988-01-01

Maintaining human factors conventions/practices that were established during the Detailed Control Design Review (DCRDR), is difficult if Human Factors Engineering (HFE) is not incorporated into the plant modification process. This paper presents the approach used at Carolina Power and Light's nuclear power plants that has successfully incorporated human factors engineering into their plant modification process. An HFE Design Guide or HFE Specification was developed which is used by the design engineers or plant engineering support groups in the preparation of plant modifications

Perindopril, fosinopril and losartan inhibited the progression of diethylnitrosamine-induced hepatocellular carcinoma in mice via the inactivation of nuclear transcription factor kappa-B.

Science.gov (United States)

Saber, Sameh; Mahmoud, Amr A A; Goda, Reham; Helal, Noha S; El-Ahwany, Eman; Abdelghany, Rasha H

2018-05-31

Hepatocellular carcinoma (HCC) is a major global health problem. Therapeutic interventions of HCC are still limited because of its complicated molecular pathogenesis. Many reports showed that renin-angiotensin system (RAS) contributes to the development of different types of malignancies. Therefore, the present study aimed to examine the effect of RAS inhibition using perindopril (1 mg/kg), fosinopril (2 mg/kg), or losartan (10 mg/kg) on diethylnitrosamine-induced HCC compared to sorafenib (30 mg/kg). The administration of RAS inhibitors resulted in improved liver function and histologic picture with a reduction in AFP levels. These effects found to be mediated through inactivation of NFкB pathway by the inhibition of NFĸB p65 phosphorylation at the Ser536 residue and inhibition of the phosphorylation-induced degradation of NFĸBia. Consequently, expression levels of cyclin D1 mRNA were significantly lowered. In addition, NFкB-induced TNF-α and TGF-β1 levels were reduced leading to lower levels of MMP-2 and VEGF. We concluded that RAS inhibition either through inhibiting the ACE or the blockade of AT1R has the same therapeutic benefit and that the tissue affinity of the ACEIs has no impact on its anti-tumor activity. These results suggest that ACEIs and ARBs can serve as promising candidates for further clinical trials in the management of HCC. Copyright © 2018 Elsevier B.V. All rights reserved.

Choosing the nuclear power option: Factors to be considered

International Nuclear Information System (INIS)

1998-01-01

A need was expressed by Member States for guidance on policy issues to be addressed by decision makers considering the introduction of nuclear power programmes. This publication has been prepared by the IAEA, on the basis of past experience with nuclear power programmes in Member States and the current realities of the world nuclear regime, to provide information on political, governmental, economic, financial, technical and safety issues associated with planning and implementing a nuclear power programme. It highlights the main areas in which policies must be developed as well as the roles and responsibilities of the government, the plant owner and the national industry. For those interested in examining some of the issues in more depth, a list of related IAEA publications is provided in the bibliography. It is hoped that this guide will serve a useful purpose in assisting decision makers and governments in Member States considering the introduction of nuclear power programmes

Colon-targeted delivery of piceatannol enhances anti-colitic effects of the natural product: potential molecular mechanisms for therapeutic enhancement

Directory of Open Access Journals (Sweden)

Yum S

2015-08-01

Full Text Available Soohwan Yum, Seongkeun Jeong, Sunyoung Lee, Joon Nam, Wooseong Kim, Jin-Wook Yoo, Min-Soo Kim, Bok Luel Lee, Yunjin Jung College of Pharmacy, Pusan National University, Busan, Republic of Korea Abstract: Piceatannol (PCT, an anti-colitic natural product, undergoes extensive Phase II hepatic metabolism, resulting in very low bioavailability. We investigated whether colon-targeted delivery of PCT could enhance anti-colitic effects and how therapeutic enhancement occurred at the molecular level. Molecular effects of PCT were examined in human colon carcinoma cells and inflamed colons. The anti-colitic effects of PCT in a colon-targeted capsule (colon-targeted PCT were compared with PCT in a gelatin capsule (conventional PCT in a trinitrobenzene sulfonic acid-induced rat colitis model. Colon-targeted PCT elicited greatly enhanced recovery of the colonic inflammation. In HCT116 cells, PCT inhibited nuclear factor kappaB while activating anti-colitic transcription factors, nuclear factor-erythroid 2 (NF-E2 p45-related factor 2, and hypoxia-inducible factor-1. Colon-targeted PCT, but not conventional PCT, modulated production of the target gene products of the transcription factors in the inflamed colonic tissues. Rectal administration of PCT, which simulates the therapeutic action of colon-targeted PCT, also ameliorated rat colitis and reproduced the molecular effects in the inflamed colonic tissues. Colon-targeted delivery increased therapeutic efficacy of PCT against colitis, likely resulting from multitargeted effects exerted by colon-targeted PCT. The drug delivery technique may be useful for therapeutic optimization of anti-colitic lead compounds including natural products. Keywords: piceatannol, colitis, colon-targeted delivery, multitarget, polypharmacology

Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

Energy Technology Data Exchange (ETDEWEB)

Bhattarai, Govinda; Lee, Young-Hee [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Lee, Min-Ho [Department of Dental Materials, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of); Park, Il-Song [Division of Advanced Materials Engineering, Research Center for Advanced Materials, Development and Institute of Biodegradable Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Yi, Ho-Keun, E-mail: yihokn@chonbuk.ac.kr [Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju (Korea, Republic of)

2015-10-01

Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology. �

Insulin-like growth factor binding protein-3 affects osteogenic efficacy on dental implants in rat mandible

International Nuclear Information System (INIS)

Bhattarai, Govinda; Lee, Young-Hee; Lee, Min-Ho; Park, Il-Song; Yi, Ho-Keun

2015-01-01

Insulin like growth factor binding protein-3 (IGFBP-3) in bone cells and its utilization in dental implants have not been well studied. The aim of this study was to determine the osteogenic efficacy of chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 coated titanium (Ti) implants. Ch-GNPs were conjugated with IGFBP-3 plasmid DNA through a coacervation process. Conjugation was cast over Ti surfaces, and cells were seeded on coated surfaces. For in vitro analysis the expression of different proteins was analyzed by immunoblotting. For in vivo analysis, Ch-GNP/IGFBP-3 coated implants were installed in rat mandibles. Four weeks post-implantation, mandibles were examined by microcomputed tomography (μCT), immunohistochemistry, hematoxylin & eosin and tartrate resistance acid phosphatase staining. In vitro overexpressed Ch-GNP/IGFBP-3 coated Ti surfaces was associated with activation of extracellular signal related kinase (ERK), inhibition of the stress activated protein c-Jun N-terminal kinase (JNK) and enhanced bone morphogenetic protein (BMP)-2 and 7 compared to control. Further, in vivo, Ch-GNP/IGFBP-3 coated implants were associated with inhibition of implant induced osteoclastogenesis molecules, receptor activator of nuclear factor kappa-B ligand (RANKL) and enhanced expression of osteogenic molecules including BMP2/7 and osteopontin (OPN). The μCT analysis demonstrated that IGFBP-3 increased the volume of newly formed bone surrounding the implants compared to control (n = 5; p < 0.05). These results support the view that IGFBP-3 overexpression diminishes osteoclastogenesis and enhances osteogenesis of Ti implants, and can serve as a potent molecule for the development of good implantation. - Highlights: • Chitosan gold nanoparticles were conjugated with IGFBP-3 and coated onto surface of the titanium implants for gene delivery to bone. • Implants were inserted in rat mandible for 4 weeks. • Parameters studied: histopathology and radiology. �

Regulation of stem cell factor expression in inflammation and asthma

Directory of Open Access Journals (Sweden)

Carla A Da Silva

2005-03-01

Full Text Available Stem cell factor (SCF is a major mast cell growth factor, which could be involved in the local increase of mast cell number in the asthmatic airways. In vivo, SCF expression increases in asthmatic patients and this is reversed after treatment with glucocorticoids. In vitro in human lung fibroblasts in culture, IL-1beta, a pro-inflammatory cytokine, confirms this increased SCF mRNA and protein expression implying the MAP kinases p38 and ERK1/2 very early post-treatment, and glucocorticoids confirm this decrease. Surprisingly, glucocorticoids potentiate the IL-1beta-enhanced SCF expression at short term treatment, implying increased SCF mRNA stability and SCF gene transcription rate. This potentiation involves p38 and ERK1/2. Transfection experiments with the SCF promoter including intron1 also confirm this increase and decrease of SCF expression by IL-1beta and glucocorticoids, and the potentiation by glucocorticoids of the IL-1beta-induced SCF expression. Deletion of the GRE or kappaB sites abolishes this potentiation, and the effect of IL-1beta or glucocorticoids alone. DNA binding of GR and NF-kappaB are also demonstrated for these effects. In conclusion, this review concerns new mechanisms of regulation of SCF expression in inflammation that could lead to potential therapeutic strategy allowing to control mast cell number in the asthmatic airways.

Improvements of the Regulatory Framework for Nuclear Installations in the Areas of Human and Organizational Factors and Safety Culture

International Nuclear Information System (INIS)

Tronea, M.; Ciurea, C.

2016-01-01

The paper presents the development of regulatory requirements in the area of human and organizational factors taking account of the lessons learned from major accidents in the nuclear industry and in particular of the factors that contributed to the Fukushima Daiichi accident and the improvement of the regulatory oversight of nuclear safety culture. New requirements have been elaborated by the National Commission for Nuclear Activities Control (CNCAN) on the nuclear safety policy of licencees for nuclear installations, on independent nuclear safety oversight, on safety conscious work environment and on the assessment of nuclear safety culture. The regulatory process for the oversight of nuclear safety culture within licencees’ organizations operating nuclear installations and the associated procedure and guidelines, based on the IAEA Safety Standards, have been developed in 2010-2011. CNCAN has used the 37 IAEA attributes for a strong safety culture, grouped into five areas corresponding to safety culture characteristics, as the basis for its regulatory guidelines providing support to the reviewers and inspectors, in their routine activities, for recognising and gathering information relevant to safety culture. The safety culture oversight process, procedure and guidelines are in process of being reviewed and revised to improve their effectiveness and to align with the current international practices, using lessons learned from the Fukushima Daiichi accident. Starting with July 2014, Romania has a National Strategy for Nuclear Safety and Security, which includes strategic objectives, associated directions for action and concrete actions for promoting nuclear safety culture in all the organizations in the nuclear sector. The progress with the implementation of this strategy with regard to nuclear safety culture is described in the paper. CNCAN started to define its own organizational culture model and identifying the elements that promote and support safety

Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

Energy Technology Data Exchange (ETDEWEB)

Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

2005-01-20

Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cells revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.

Andrographolide interferes with binding of nuclear factor-κB to DNA in HL-60-derived neutrophilic cells

Science.gov (United States)

Hidalgo, María A; Romero, Alex; Figueroa, Jaime; Cortés, Patricia; Concha, Ilona I; Hancke, Juan L; Burgos, Rafael A

2005-01-01

Andrographolide, the major active component from Andrographis paniculata, has shown to possess anti-inflammatory activity. Andrographolide inhibits the expression of several proinflammatory proteins that exhibit a nuclear factor kappa B (NF-κB) binding site in their gene. In the present study, we analyzed the effect of andrographolide on the activation of NF-κB induced by platelet-activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine (fMLP) in HL-60 cells differentiated to neutrophils. PAF (100 nM) and fMLP (100 nM) induced activation of NF-κB as determined by degradation of inhibitory factor B α (IκBα) using Western blotting in cytosolic extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA) in nuclear extracts. Andrographolide (5 and 50 μM) inhibited the NF-κB-luciferase activity induced by PAF. However, andrographolide did not reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IκBα degradation induced by PAF and fMLP. Andrographolide reduced the DNA binding of NF-κB in whole cells and in nuclear extracts induced by PAF and fMLP. Andrographolide reduced cyclooxygenase-2 (COX-2) expression induced by PAF and fMLP in HL-60/neutrophils. It is concluded that andrographolide exerts its anti-inflammatory effects by inhibiting NF-κB binding to DNA, and thus reducing the expression of proinflammatory proteins, such as COX-2. PMID:15678086

Multilateral nuclear approaches (MNAs), factors and issues lessons from IAEA study to regional cooperation

International Nuclear Information System (INIS)

Hwang, Yong Soo

2005-01-01

In response to the increasing emphasis being placed on the importance of international cooperation as part of global efforts to cope with growing non proliferation, and security concerns in the nuclear field, the Director General of the International Atomic Energy Agency (IAEA), Mohammed Elbaradei, appointed an international group of experts to consider possible multilateral approaches to the nuclear fuel cycle. The mandate of the Expert Group was three fold: · To identify and provide an analysis of issues and options relevant to multilateral approaches to the front and back ends of the nuclear fuel cycle; · To provide an overview of the policy, legal, security, economic, institutional and technological incentives and disincentives for cooperation in multilateral arrangements for the front and back ends of the nuclear fuel cycle; and · To provide a brief review of the historical and current experiences and analyses relating to multilateral fuel cycle arrangements relevant to the work of the Expert Group. The overall purpose was to assess MNAs in the framework of a double objective: strengthening the international nuclear non proliferation regime and making the peaceful uses of nuclear energy more economical and attractive. The Group identifies options for MNAs - options in terms of policy, institutional and legal factors - for those parts of the nuclear fuel cycle of greatest sensitivity from the point of view of proliferation risk. It also reflects the Groups deliberations on the corresponding benefits and disadvantages (pros and cons) of the various options and approaches. Although the Expert Group was able to agree to forward the resulting report to the Director General, it is important to note that the report does not reflect agreement by all of the experts on any of the options, nor a consensus assessment of their respective value. It is intended only to present options for MNAs, and to reflect on the range of considerations which could impact on the

Nuclear power

International Nuclear Information System (INIS)

Anon.

1980-01-01

The committee concludes that the nature of the proliferation problem is such that even stopping nuclear power completely could not stop proliferation completely. Countries can acquire nuclear weapons by means independent of commercial nuclear power. It is reasonable to suppose if a country is strongly motivated to acquire nuclear weapons, it will have them by 2010, or soon thereafter, no matter how nuclear power is managed in the meantime. Unilateral and international diplomatic measures to reduce the motivations that lead to proliferation should be high on the foreign policy agenda of the United States. A mimimum antiproliferation prescription for the management of nuclear power is to try to raise the political barriers against proliferation through misuse of nuclear power by strengthening the Non-Proliferation Treaty, and to seek to raise the technological barriers by placing fuel-cycle operations involving weapons-usable material under international control. Any such measures should be considered tactics to slow the spread of nuclear weapons and thus earn time for the exercise of statesmanship. The committee concludes the following about technical factors that should be considered in formulating nuclear policy: (1) rate of growth of electricity use is a primary factor; (2) growth of conventional nuclear power will be limited by producibility of domestic uranium sources; (3) greater contribution of nuclear power beyond 400 GWe past the year 2000 can only be supported by advanced reactor systems; and (4) several different breeder reactors could serve in principle as candidates for an indefinitely sustainable source of energy

The role of the form factor and short-range correlation in the relativistic Hartree-Fock model for nuclear matter

Science.gov (United States)

Hu, J.; Toki, H.; Wen, W.; Shen, H.

2010-03-01

The role of the form factor and short-range correlation in nuclear matter is studied within the relativistic Hartree-Fock approximation. We take, first, the mean-field approximation for meson fields and obtain the fluctuation terms of mesons to be used for the Fock energies. We introduce form factors in the meson-nucleon coupling vertices to take into account the finite-size effect of the nucleon. We use further the unitary correlation operator method for the treatment of the short-range correlation. The form factors of the size ( Λ ˜ 1.0 -2.0GeV) of the nucleon-nucleon interaction cut down largely the contribution of the ρ -meson in the Fock term. The short-range correlation effect is not large but has a significant effect on the pion and ρ -meson energies in the relativistic Hartree-Fock approximation for nuclear matter.

Quality factors in the life cycle of software oriented to safety systems in nuclear power plants

International Nuclear Information System (INIS)

Nunez McLeod, J.E.; Rivera, S.S.

1997-01-01

The inclusion of software in safety related systems for nuclear power plants, makes it necessary to include the software quality assurance concept. The software quality can be defined as the adjustment degree between the software and the specified requirements and user expectations. To guarantee a certain software quality level it is necessary to make a systematic and planned set of tasks, that constitute a software quality guaranty plan. The application of such a plan involves activities that should be performed all along the software life cycle, and that can be evaluated through the so called quality factors, due to the fact that the quality itself cannot be directly measured, but indirectly as some of it manifestations. In this work, a software life cycle model is proposed, for nuclear power plant safety related systems. A set os software quality factors is also proposed , with its corresponding classification according to the proposed model. (author) [es

Biogen water of the Irtysh river - the principal population health factor suffered from the nuclear test on the Semipalatinsk test site

International Nuclear Information System (INIS)

Inyushin, V.M.; Yurenkov, V.V.

2001-01-01

Authors notes, that Semipalatinsk test site activity together with other factors changes a water quality. The principal consequence of nuclear tests is build up in new cells by the 'pathogenous' water in plants, animals and human . 'Pathogenous water' is generating at steady changes of electronic strictures (spin performances) at ionizing radiation effect, radionuclides and other factors of nuclear explosions. These factors were did not known to a world-wide science. The second of very important phenomenon of nuclear explosions consequences at the Semipalatinsk test site is reduce of the hydro-plasma in the water sources the Irtysh River basin. This was proved with direct studies microcurrents density in the water as well as analysis of electronic and ionic structures with the plasma-graphic help. The water having the pathogenous memory - building up in the cells - reduces the immune status, negatively reflects on the vital functions, decreasing the resistance to unfavorable effects. It is offered for remediation of the 'pathogenous water' to use the bio-genized water as most adequate one to endogenous water of living cells. Mass usage of the bio-genized water takes out genetic consequences of nuclear explosions and increase of an immunity level. The 'Bio-genization' of the Irtysh River water is concludes a few stages

Measurement and evaluation of human factor training in nuclear power plants

International Nuclear Information System (INIS)

Hamasaki, Kenichi

2006-01-01

The purpose of this study is to measure and evaluate the effectiveness of human factor training aimed at awareness and behavioral changes, conducted by electric power company for the nuclear power plant staff. As the first step, the researcher investigated recent trends in training measurement and evaluation methods in the United States. It was found that many instances of training measurement/evaluation had been reported, and that the ROI model was the mainstream method for such measurement and evaluation. However, there had been no instances reported in which the effectiveness of human factor training for plant staff had been measured. The researcher therefore developed a new questionnaire-type of effectiveness measurement/evaluation method, based on the framework of the ROI model. Two-years of research was then conducted, in which the effectiveness of a human factor training program was measured using the newly developed method. This research revealed that participants' overall satisfaction and knowledge/skill acquisition levels were high. The percentage of participants who demonstrated awareness/behavioral change after returning to the workplace increased from 50% at first measurement to 81% at second measurement. It can therefore be concluded that the effectiveness of the second training is greater than that of the first training. Use of the new effectiveness measurement/evaluation method will enable quantification of human factor training effectiveness and help improve training quality. (author)

Factors affecting the future of nuclear power in OECD Europe

International Nuclear Information System (INIS)

Thompson, S.

1997-01-01

This report provides a brief review of nuclear power in OECD Europe and addresses the prospects for its future over, say, the next quarter century. Most of the data and findings are drawn from studies published by the Nuclear Energy Agency (NEA) of the Organisation for Economic Co-operation and Development (OECD). The NEA is a small agency with a rather modest budget whose 27 members are industrialized countries from North America, Asia and Europe. The Agency works to pool the expertise of our member countries to produce technical, economic and legal work of considerable depth and quality addressing issues of common interest to those countries. Our work covers such fields as nuclear science, nuclear power economics, nuclear safety, radiation protection, waste management and nuclear liability. The studies carried out in the framework of the Agency require fewer resources than would be needed by our member countries if they were to pursue them individually, which is especially important at a time of cut-backs in national programmes in such critical areas as nuclear safety research. (author)

A Study on Human Factors in Maintenance of a Nuclear Power Plant (NPP)

International Nuclear Information System (INIS)

Park, Young Ho; Seong, Poong Hyun

2006-01-01

In human factors research, more attention has been devoted to the operation of a nuclear power plant (NPP) than to their maintenance. However, more NPP incidents are caused by inadequate maintenance rather than by faulty operation. There is a trend in NPP toward introducing digital technology into safety and non-safety systems. This lead to changes of maintenance, and support systems such as diagnosis system, augmentation system and handy terminal will be developed. In this context, it is important to identify tasks of human related to each phase of maintenance and their relation in order to apply those to maintenance. However, there are few researches of human factors in maintenance. This paper studies on framework of cognitive task analysis for developing maintenance support systems

A Review on the Regulatory Strategy of Human Factors Engineering Consideration in Pakistan Nuclear Facilities

Energy Technology Data Exchange (ETDEWEB)

Sohail, Sabir [Korea Advanced Institute of Science and Technology, Daejeon (Korea, Republic of); Choi, Seong Nam [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2013-10-15

In this paper, the legal and regulatory infrastructure available in Pakistan for HFE requirements is assessed, and the methodology for strengthening of legal infrastructure is presented. The regulatory strategy on evaluation of HFE consideration should provide reviewers with guidance on review process. Therefore, the suggested methodology is based on preparation of guidance documents such as checklist, working procedures, S and Gs etc.; incorporation of PRM elements in regulatory system; and finally the development of PRM implementation criteria. Altogether, the scheme provide the enhancement in regulatory infrastructure and also the effective and efficient review process. The Three Mile Island (TMI) accident brought the general consensus among the nuclear community on the integration of human factors engineering (HFE) principles in all phases of nuclear power. This notion has further strengthened after the recent Fukushima nuclear accident. Much effort has been put over to incorporate the lesson learned and continuous technical evolution on HFE to device different standards. The total of 174 ergonomics standards are alone identified by Dul et al. (2004) published by International Organization for Standardization (ISO) and the European Committee for Standardization (CEN) and number of standards and HFE guidelines (S and Gs) are also published by organizations like Institute for Electrical and Electronics Engineering (IEEE), International Electrotechnical Commission (IEC), International Atomic Energy Agency (IAEA), United States Nuclear Regulatory Commission (USNRC), etc. The ambition of effective review on HFE integration in nuclear facility might be accomplished through the development of methodology for systematic implementation of S and Gs. Such kind of methodology would also be beneficial for strengthening the regulatory framework and practices for countries new in the nuclear arena and with small scale nuclear program. The objective of paper is to review the