PAK1 is a breast cancer oncogene that coordinately activates MAPK and MET signaling.

Science.gov (United States)

Shrestha, Y; Schafer, E J; Boehm, J S; Thomas, S R; He, F; Du, J; Wang, S; Barretina, J; Weir, B A; Zhao, J J; Polyak, K; Golub, T R; Beroukhim, R; Hahn, W C

2012-07-19

Activating mutations in the RAS family or BRAF frequently occur in many types of human cancers but are rarely detected in breast tumors. However, activation of the RAS-RAF-MEK-ERK MAPK pathway is commonly observed in human breast cancers, suggesting that other genetic alterations lead to activation of this signaling pathway. To identify breast cancer oncogenes that activate the MAPK pathway, we screened a library of human kinases for their ability to induce anchorage-independent growth in a derivative of immortalized human mammary epithelial cells (HMLE). We identified p21-activated kinase 1 (PAK1) as a kinase that permitted HMLE cells to form anchorage-independent colonies. PAK1 is amplified in several human cancer types, including 30--33% of breast tumor samples and cancer cell lines. The kinase activity of PAK1 is necessary for PAK1-induced transformation. Moreover, we show that PAK1 simultaneously activates MAPK and MET signaling; the latter via inhibition of merlin. Disruption of these activities inhibits PAK1-driven anchorage-independent growth. These observations establish PAK1 amplification as an alternative mechanism for MAPK activation in human breast cancer and credential PAK1 as a breast cancer oncogene that coordinately regulates multiple signaling pathways, the cooperation of which leads to malignant transformation.

1α,25(OH2D3 Induces Actin Depolymerization in Endometrial Carcinoma Cells by Targeting RAC1 and PAK1

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Ni Zeng

2016-12-01

Full Text Available Background: Cell proliferation and motility require actin reorganization, which is under control of various signalling pathways including ras-related C3 botulinum toxin substrate 1 (RAC1, p21 protein-activated kinase 1 (PAK1 and actin related protein 2 (ARP2. Tumour cell proliferation is modified by 1α,25-Dihydroxy-Vitamin D3 (1α,25(OH2D3, a steroid hormone predominantly known for its role in calcium and phosphorus metabolism. The present study explored whether 1α,25(OH2D3 modifies actin cytoskeleton in Ishikawa cells, a well differentiated endometrial carcinoma cell line. Methods: To this end, actin cytoskeleton was visualized by confocal microscopy. Globular over filamentous actin ratio was determined utilizing Western blotting and flow cytometry, transcript levels by qRT-PCR and protein abundance by immunoblotting. Results: A 24 hour treatment with 1α,25(OH2D3 (100 nM significantly decreased RAC1 and PAK1 transcript levels and activity, decreased ARP2 protein levels and depolymerized actin. The effect of 1α,25(OH2D3 on actin polymerization was mimicked by pharmacological inhibition of RAC1 and PAK1. Conclusions: 1α,25(OH2D3 leads to disruption of RAC1 and PAK1 activity with subsequent actin depolymerization of endometrial carcinoma cells.

Phosphorylation of Threonine 794 on Tie1 by Rac1/PAK1 Reveals a Novel Angiogenesis Regulatory Pathway.

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Jessica L Reinardy

Full Text Available The endothelial receptor tyrosine kinase (RTK Tie1 was discovered over 20 years ago, yet its precise function and mode of action remain enigmatic. To shed light on Tie1's role in endothelial cell biology, we investigated a potential threonine phosphorylation site within the juxtamembrane domain of Tie1. Expression of a non-phosphorylatable mutant of this site (T794A in zebrafish (Danio rerio significantly disrupted vascular development, resulting in fish with stunted and poorly branched intersomitic vessels. Similarly, T794A-expressing human umbilical vein endothelial cells formed significantly shorter tubes with fewer branches in three-dimensional Matrigel cultures. However, mutation of T794 did not alter Tie1 or Tie2 tyrosine phosphorylation or downstream signaling in any detectable way, suggesting that T794 phosphorylation may regulate a Tie1 function independent of its RTK properties. Although T794 is within a consensus Akt phosphorylation site, we were unable to identify a physiological activator of Akt that could induce T794 phosphorylation, suggesting that Akt is not the physiological Tie1-T794 kinase. However, the small GTPase Ras-related C3 botulinum toxin substrate 1 (Rac1, which is required for angiogenesis and capillary morphogenesis, was found to associate with phospho-T794 but not the non-phosphorylatable T794A mutant. Pharmacological activation of Rac1 induced downstream activation of p21-activated kinase (PAK1 and T794 phosphorylation in vitro, and inhibition of PAK1 abrogated T794 phosphorylation. Our results provide the first demonstration of a signaling pathway mediated by Tie1 in endothelial cells, and they suggest that a novel feedback loop involving Rac1/PAK1 mediated phosphorylation of Tie1 on T794 is required for proper angiogenesis.

Hair Growth Promoting and Anticancer Effects of p21-activated kinase 1 (PAK1 Inhibitors Isolated from Different Parts of Alpinia zerumbet

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Nozomi Taira

2017-01-01

Full Text Available PAK1 (p21-activated kinase 1 is an emerging target for the treatment of hair loss (alopecia and cancer; therefore, the search for PAK1 blockers to treat these PAK1-dependent disorders has received much attention. In this study, we evaluated the anti-alopecia and anticancer effects of PAK1 inhibitors isolated from Alpinia zerumbet (alpinia in cell culture. The bioactive compounds isolated from alpinia were found to markedly promote hair cell growth. Kaempferol-3-O-β-d-glucuronide (KOG and labdadiene, two of the isolated compounds, increased the proliferation of human follicle dermal papilla cells by approximately 117%–180% and 132%–226%, respectively, at 10–100 μM. MTD (2,5-bis(1E,3E,5E-6-methoxyhexa-1,3,5-trien-1-yl-2,5-dihydrofuran and TMOQ ((E-2,2,3,3-tetramethyl-8-methylene-7-(oct-6-en-1-yloctahydro-1H-quinolizine showed growth-promoting activity around 164% and 139% at 10 μM, respectively. The hair cell proliferation induced by these compounds was significantly higher than that of minoxidil, a commercially available treatment for hair loss. Furthermore, the isolated compounds from alpinia exhibited anticancer activity against A549 lung cancer cells with IC50 in the range of 67–99 μM. Regarding the mechanism underlying their action, we hypothesized that the anti-alopecia and anticancer activities of these compounds could be attributed to the inhibition of the oncogenic/aging kinase PAK1.

Potential role of p21 Activated Kinase 1 (PAK1) in the invasion and motility of oral cancer cells

International Nuclear Information System (INIS)

Parvathy, Muraleedharan; Sreeja, Sreeharshan; Kumar, Rakesh; Pillai, Madhavan Radhakrishna

2016-01-01

Oral cancer malignancy consists of uncontrolled division of cells primarily in and around the floor of the oral cavity, gingiva, oropharynx, lower lip and base of the tongue. According to GLOBOCAN 2012 report, oral cancer is one of the most common cancers among males and females in India. Even though significant advancements have been made in the field of oral cancer treatment modalities, the overall prognosis for the patients has not improved in the past few decades and hence, this demands a new thrust for the identification of novel therapeutic targets in oral cancer. p21 Activated Kinases (PAKs) are potential therapeutic targets that are involved in numerous physiological functions. PAKs are serine-threonine kinases and they serve as important regulators of cytoskeletal dynamics and cell motility, transcription through MAP kinase cascades, death and survival signalling, and cell-cycle progression. Although PAKs are known to play crucial roles in cancer progression, the role and clinical significance of PAKs in oral cancer remains poorly understood. Our results suggest that PAK1 is over-expressed in oral cancer cell lines. Stimulation of Oral Squamous Cell Carcinoma (OSCC) cells with serum growth factors leads to PAK1 re-localization and might cause a profound cytoskeletal remodelling. PAK1 was also found to be involved in the invasion, migration and cytoskeletal remodelling of OSCC cells. Our study revealed that PAK1 may play a crucial role in the progression of OSCC. Studying the role of PAK1 and its substrates is likely to enhance our understanding of oral carcinogenesis and potential therapeutic value of PAKs in oral cancer. The online version of this article (doi:10.1186/s12885-016-2263-8) contains supplementary material, which is available to authorized users

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

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Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

DEFF Research Database (Denmark)

Joseph, Giselle A; Lu, Min; Radu, Maria

2017-01-01

fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation and involves the cadherin coreceptor Cdo with its downstream effector, Cdc42. Individual genetic deletion of Pak1 and Pak2 in mice....... Furthermore, primary myoblasts lacking Pak1 and Pak2 display delayed expression of myogenic differentiation markers and myotube formation. These results identify Pak1 and Pak2 as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad/Cdo/Cdc42 signaling...

Increased Rac1 activity and Pak1 overexpression are associated with lymphovascular invasion and lymph node metastasis of upper urinary tract cancer

International Nuclear Information System (INIS)

Kamai, Takao; Shirataki, Hiromichi; Nakanishi, Kimihiro; Furuya, Nobutaka; Kambara, Tsunehito; Abe, Hideyuki; Oyama, Tetsunari; Yoshida, Ken-Ichiro

2010-01-01

Lymphovascular invasion (LVI) and lymph node metastasis are conventional pathological factors associated with an unfavorable prognosis of urothelial carcinoma of the upper urinary tract (UC-UUT), but little is known about the molecular mechanisms underlying LVI and nodal metastasis in this disease. Rac1 small GTPase (Rac1) is essential for tumor metastasis. Activated GTP-bound Rac1 (Rac1 activity) plays a key role in activating downstream effectors known as Pak (21-activated kinase), which are key regulators of cytoskeletal remolding, cell motility, and cell proliferation, and thus have a role in both carcinogenesis and tumor invasion. We analyzed Rac1 activity and Pak1 protein expression in matched sets of tumor tissue, non-tumor tissue, and metastatic lymph node tissue obtained from the surgical specimens of 108 Japanese patients with UC-UUT. Rac1 activity and Pak1 protein levels were higher in tumor tissue and metastatic lymph node tissue than in non-tumor tissue (both P < 0.0001). A high level of Rac1 activity and Pak1 protein expression in the primary tumor was related to poor differentiation (P < 0.05), muscle invasion (P < 0.01), LVI (P < 0.0001), and lymph node metastasis (P < 0.0001). Kaplan-Meier survival analysis showed that an increase of Rac1 activity and Pak1 protein was associated with a shorter disease-free survival time (P < 0.01) and shorter overall survival (P < 0.001). Cox proportional hazards analysis revealed that high Rac1 activity, Pak1 protein expression and LVI were independent prognostic factors for shorter overall and disease-free survival times (P < 0.01) on univariate analysis, although only Pak1 and LVI had an influence (P < 0.05) according to multivariate analysis. These findings suggest that Rac1 activity and Pak1 are involved in LVI and lymph node metastasis of UC-UUT, and may be prognostic markers for this disease

Development of a Hydronic Rooftop Unit-HyPak-MA

Energy Technology Data Exchange (ETDEWEB)

Lee, Eric; Berman, Mark

2009-11-14

The majority of U.S. commercial floor space is cooled by rooftop HVAC units (RTUs). RTU popularity derives chiefly from their low initial cost and relative ease of service access without disturbing building occupants. Unfortunately, current RTUs are inherently inefficient due to a combination of characteristics that unnecessarily increase cooling loads and energy use. 36% percent of annual U.S. energy, and two-thirds of electricity, is consumed in and by buildings. Commercial buildings consume approximately 4.2 quads of energy each year at a cost of $230 billion per year, with HVAC equipment consuming 1.2 quads of electricity. More than half of all U.S. commercial floor space is cooled by packaged HVAC units, most of which are rooftop units (RTUs). Inefficient RTUs create an estimated 3.5% of U.S. CO{sub 2} emissions, thus contributing significantly to global warming5. Also, RTUs often fail to maintain adequate ventilation air and air filtration, reducing indoor air quality. This is the second HyPak project to be supported by DOE through NETL. The prior project, referred to as HyPak-1 in this report, had two rounds of prototype fabrication and testing as well as computer modeling and market research. The HyPak-1 prototypes demonstrated the high performance capabilities of the HyPak concept, but made it clear that further development was required to reduce heat exchanger cost and improve system reliability before HyPak commercialization can commence. The HyPak-1 prototypes were limited to about 25% ventilation air fraction, limiting performance and marketability. The current project is intended to develop a 'mixed-air' product that is capable of full 0-100% modulation in ventilation air fraction, hence it was referred to as HyPak-MA in the proposal. (For simplicity, the -MA has been dropped when referencing the current project.) The objective of the HyPak Project is to design, develop and test a hydronic RTU that provides a quantum improvement over

AGNES - safety reassessment of Paks NPP

International Nuclear Information System (INIS)

Gado, J.

1995-01-01

The main goal of the AGNES (Advanced General and New Evaluation of Safety) project for the reassessment of the safety of Paks Nuclear Power Plant, Hungary, was to improve the safety culture of the technology at Paks. A report was prepared on the reassessment of the Paks NPP safety. The analysis was divided into four groups: systems analysis, analysis of design basis accidents, severe accident analysis, and level 1 probabilistic safety analysis. Proposed safety enhancement measures are discussed. (N.T.)

A βPIX-PAK2 complex confers protection against Scrib-dependent and cadherin-mediated apoptosis

DEFF Research Database (Denmark)

Frank, Scott R; Bell, Jennifer H; Frödin, Morten

2012-01-01

During epithelial morphogenesis, a complex comprising the βPIX (PAK-interacting exchange factor β) and class I PAKs (p21-activated kinases) is recruited to adherens junctions. Scrib, the mammalian ortholog of the Drosophila polarity determinant and tumor suppressor Scribble, binds βPIX directly. ...

Lentiviral Nef Proteins Utilize PAK2-Mediated Deregulation of Cofilin as a General Strategy To Interfere with Actin Remodeling▿ †

Science.gov (United States)

Stolp, Bettina; Abraham, Libin; Rudolph, Jochen M.; Fackler, Oliver T.

2010-01-01

Nef is an accessory protein and pathogenicity factor of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) which elevates virus replication in vivo. We recently described for HIV type 1SF2 (HIV-1SF2) the potent interference of Nef with T-lymphocyte chemotaxis via its association with the cellular kinase PAK2. Mechanistic analysis revealed that this interaction results in deregulation of the actin-severing factor cofilin and thus blocks the chemokine-mediated actin remodeling required for cell motility. However, the efficiency of PAK2 association is highly variable among Nef proteins from different lentiviruses, prompting us to evaluate the conservation of this actin-remodeling/cofilin-deregulating mechanism. Based on the analysis of a total of 17 HIV-1, HIV-2, and SIV Nef proteins, we report here that inhibition of chemokine-induced actin remodeling as well as inactivation of cofilin are strongly conserved activities of lentiviral Nef proteins. Of note, even for Nef variants that display only marginal PAK2 association in vitro, these activities require the integrity of a PAK2 recruitment motif and the presence of endogenous PAK2. Thus, reduced in vitro affinity to PAK2 does not indicate limited functionality of Nef-PAK2 complexes in intact HIV-1 host cells. These results establish hijacking of PAK2 for deregulation of cofilin and inhibition of triggered actin remodeling as a highly conserved function of lentiviral Nef proteins, supporting the notion that PAK2 association may be critical for Nef's activity in vivo. PMID:20147394

Nonautonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO, and PAK-1

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Lisa M. Kennedy

2013-09-01

Full Text Available Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to regulate the anterior migrations of the hermaphrodite-specific neurons (HSNs during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration; conversely, when signaling is enhanced, DAF-16 is inactivated, and migration is inhibited. We show that DAF-16 acts nonautonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of insulin/IGF-1-DAF-16 signaling in the nonautonomous control of HSN migration. Because a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are most likely conserved from C. elegans to higher organisms.

miR-155 Controls Lymphoproliferation in LAT Mutant Mice by Restraining T-Cell Apoptosis via SHIP-1/mTOR and PAK1/FOXO3/BIM Pathways.

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Alexandre K Rouquette-Jazdanian

Full Text Available Linker for Activation of T cells (LAT is an adapter protein that is essential for T cell function. Knock-in mice with a LAT mutation impairing calcium flux develop a fatal CD4+ lymphoproliferative disease. miR-155 is a microRNA that is correlated with hyperproliferation in a number of cancers including lymphomas and leukemias and is overexpressed in mutant LAT T cells. To test whether miR-155 was merely indicative of T cell activation or whether it contributes to lymphoproliferative disease in mutant LAT mice, we interbred LAT mutant and miR-155-deficient mice. miR-155 deficiency markedly inhibited lymphoproliferative disease by stimulating BIM-dependent CD4+ T cell apoptosis, even though ERK activation and T cell proliferation were increased in double mutant CD4+ T cells. Bim/Bcl2l11 expression is activated by the forkhead transcription factor FOXO3. Using miR-155-deficient, LAT mutant T cells as a discovery tool, we found two connected pathways that impact the nuclear translocation and activation of FOXO3 in T cells. One pathway is mediated by the inositide phosphatase SHIP-1 and the serine/threonine kinases AKT and PDK1. The other pathway involves PAK1 and JNK kinase activation. We define crosstalk between the two pathways via the kinase mTOR, which stabilizes PAK1. This study establishes a role for PAK1 in T cell apoptosis, which contrasts to its previously identified role in T cell proliferation. Furthermore, miR-155 regulates the delicate balance between PAK1-mediated proliferation and apoptosis in T cells impacting lymphoid organ size and function.

Non-autonomous Regulation of Neuronal Migration by Insulin Signaling, DAF-16/FOXO and PAK-1

Science.gov (United States)

Kennedy, Lisa M.; Pham, Steven C.D.L.; Grishok, Alla

2013-01-01

SUMMARY Neuronal migration is essential for nervous system development in all organisms and is regulated in the nematode, C. elegans, by signaling pathways that are conserved in humans. Here, we demonstrate that the Insulin/IGF-1-PI3K signaling pathway modulates the activity of the DAF-16/FOXO transcription factor to promote the anterior migrations of the hermaphrodite-specific neurons (HSNs) during embryogenesis of C. elegans. When signaling is reduced, DAF-16 is activated and promotes migration, conversely, when signaling is enhanced, DAF-16 is inactivated and migration is inhibited. We show that DAF-16 acts non-autonomously in the hypodermis to promote HSN migration. Furthermore, we identify PAK-1, a p21-activated kinase, as a downstream mediator of Insulin/IGF-1-DAF-16 signaling in the non-autonomous control of HSN migration. As a FOXO-Pak1 pathway was recently shown to regulate mammalian neuronal polarity, our findings indicate that the roles of FOXO and Pak1 in neuronal migration are likely conserved from C. elegans to higher organisms. PMID:23994474

Integral tightness measurements at the Paks-1 nuclear reactor

Energy Technology Data Exchange (ETDEWEB)

Taubner, R.; Techy, Z. (Villamosenergiaipari Kutato Intezet, Budapest (Hungary))

1983-01-01

The containment system experiments of the Paks-1 nuclear reactor are described. The integrated tightness measurements of the hermetic system were completed in 1982. The principles and methods and the evaluation of the results of the measurements are discussed. Some features of the filtration characteristics are demonstrated using relative values and a method enabling the description of the physical contents of the characteristics by flow technical functions is outlined.

Glucosinolates from pak choi and broccoli induce enzymes and inhibit inflammation and colon cancer differently.

Science.gov (United States)

Lippmann, Doris; Lehmann, Carsten; Florian, Simone; Barknowitz, Gitte; Haack, Michael; Mewis, Inga; Wiesner, Melanie; Schreiner, Monika; Glatt, Hansruedi; Brigelius-Flohé, Regina; Kipp, Anna P

2014-06-01

High consumption of Brassica vegetables is considered to prevent especially colon carcinogenesis. The content and pattern of glucosinolates (GSLs) can highly vary among different Brassica vegetables and may, thus, affect the outcome of Brassica intervention studies. Therefore, we aimed to feed mice with diets containing plant materials of the Brassica vegetables broccoli and pak choi. Further enrichment of the diets by adding GSL extracts allowed us to analyze the impact of different amounts (GSL-poor versus GSL-rich) and different patterns (broccoli versus pak choi) of GSLs on inflammation and tumor development in a model of inflammation-triggered colon carcinogenesis (AOM/DSS model). Serum albumin adducts were analyzed to confirm the up-take and bioactivation of GSLs after feeding the Brassica diets for four weeks. In agreement with their high glucoraphanin content, broccoli diets induced the formation of sulforaphane-lysine adducts. Levels of 1-methoxyindolyl-3-methyl-histidine adducts derived from neoglucobrassicin were the highest in the GSL-rich pak choi group. In the colon, the GSL-rich broccoli and the GSL-rich pak choi diet up-regulated the expression of different sets of typical Nrf2 target genes like Nqo1, Gstm1, Srxn1, and GPx2. GSL-rich pak choi induced the AhR target gene Cyp1a1 but did not affect Ugt1a1 expression. Both colitis and tumor number were drastically reduced after feeding the GSL-rich pak choi diet while the other three diets had no effect. GSLs can act anti-inflammatory and anti-carcinogenic but both effects depend on the specific amount and pattern of GSLs within a vegetable. Thus, a high Brassica consumption cannot be generally considered to be cancer-preventive.

PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2

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Laura Civiero

2017-12-01

Full Text Available Mutations in Leucine-rich repeat kinase 2 (LRRK2 are associated with Parkinson's disease (PD and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1 Activated Kinase 6 (PAK6. Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain.

Isolation and Functional Characterization of a Floral Repressor, BcMAF1, From Pak-choi (Brassica rapa ssp. Chinensis).

Science.gov (United States)

Huang, Feiyi; Liu, Tongkun; Hou, Xilin

2018-01-01

MADS-box genes form a large gene family in plants and are involved in multiple biological processes, such as flowering. However, the regulation mechanism of MADS-box genes in flowering remains unresolved, especially under short-term cold conditions. In the present study, we isolated BcMAF1 , a Pak-choi ( Brassica rapa ssp. Chinensis ) MADS AFFECTING FLOWERING ( MAF ), as a floral repressor and functionally characterized BcMAF1 in Arabidopsis and Pak-choi. Subcellular localization and sequence analysis indicated that BcMAF1 was a nuclear protein and contained a conserved MADS-box domain. Expression analysis revealed that BcMAF1 had higher expression levels in leaves, stems, and petals, and could be induced by short-term cold conditions in Pak-choi. Overexpressing BcMAF1 in Arabidopsis showed that BcMAF1 had a negative function in regulating flowering, which was further confirmed by silencing endogenous BcMAF1 in Pak-choi. In addition, qPCR results showed that AtAP3 expression was reduced and AtMAF2 expression was induced in BcMAF1 -overexpressing Arabidopsis . Meanwhile, BcAP3 transcript was up-regulated and BcMAF2 transcript was down-regulated in BcMAF1 -silencing Pak-choi. Yeast one-hybrid and dual luciferase transient assays showed that BcMAF1 could bind to the promoters of BcAP3 and BcMAF2 . These results indicated that BcAP3 and BcMAF2 might be the targets of BcMAF1. Taken together, our results suggested that BcMAF1 could negatively regulate flowering by directly activating BcMAF2 and repressing BcAP3 .

Autocrine VEGF and IL-8 Promote Migration via Src/Vav2/Rac1/PAK1 Signaling in Human Umbilical Vein Endothelial Cells.

Science.gov (United States)

Ju, Li; Zhou, Zhiwen; Jiang, Bo; Lou, Yue; Guo, Xirong

2017-01-01

Pro-angiogenic factors VEGF and IL-8 play a major role in modulating the migratory potential of endothelial cells. The goal of this study was to investigate the effect of autocrine VEGF and IL-8 in the form of self-conditioned medium (CM) on human umbilical vein endothelial cells (HUVECs). Enzyme-linked immunosorbent assay (ELISA) examined the automatic secretion of VEGF and IL-8 protein by HUVECs. Western blot, small interfering RNA (siRNA), pulldown and Transwell assays were used to explore the role and the mechanism of autocrine VEGF and IL-8 in migration of HUVECs. Neutralizing VEGF and IL-8 in CM significantly abrogated CM-induced migration of HUVECs. Autocrine VEGF and IL-8 increased Src phosphorylation, Rac1 activity and PAK1 phosphorylation in a time dependent manner. Additionally, blocking Rac1 activity with Rac1 siRNA largely abolished autocrine VEGF and IL-8-induced cell migration. Vav2 siRNA suppressed autocrine VEGF and IL-8-induced Rac1 activation and cell migration. Furthermore, blocking Src signaling with PP2, a specific inhibitor for Src, markedly prevented autocrine VEGF and IL-8-induced Vav2 and Rac1 activation as well as consequently cell migration. PAK1 siRNA also significantly abolished autocrine VEGF and IL-8-induced cell migration. We demonstrated for the first time that autocrine VEGF and IL-8 promoted endothelial cell migration via the Src/Vav2/Rac1/PAK1 signaling pathway. This finding reveals the molecular mechanism in the increase of endothelial cell migration induced by autocrine growth factors and cytokines, which is expected to provide a novel therapeutic target in vascular diseases. © 2017 The Author(s)Published by S. Karger AG, Basel.

GIT1/beta PIX signaling proteins and PAK1 kinase regulate microtubule nucleation

Czech Academy of Sciences Publication Activity Database

Černohorská, Markéta; Sulimenko, Vadym; Hájková, Zuzana; Sulimenko, Tetyana; Sládková, Vladimíra; Vinopal, Stanislav; Dráberová, Eduarda; Dráber, Pavel

2016-01-01

Roč. 1863, č. 6 (2016), s. 1282-1297 ISSN 0167-4889 R&D Projects: GA ČR GAP302/12/1673; GA ČR GA15-22194S; GA MŠk LH12050; GA MZd NT14467; GA ČR GA16-23702S Institutional support: RVO:68378050 Keywords : Centrosome * Microtubule nucleation * gamma-tubulin * GIT1/beta PIX signaling proteins * PAK1 kinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.521, year: 2016

p21-Activated kinase (PAK regulates cytoskeletal reorganization and directional migration in human neutrophils.

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Asako Itakura

Full Text Available Neutrophils serve as a first line of defense in innate immunity owing in part to their ability to rapidly migrate towards chemotactic factors derived from invading pathogens. As a migratory function, neutrophil chemotaxis is regulated by the Rho family of small GTPases. However, the mechanisms by which Rho GTPases orchestrate cytoskeletal dynamics in migrating neutrophils remain ill-defined. In this study, we characterized the role of p21-activated kinase (PAK downstream of Rho GTPases in cytoskeletal remodeling and chemotactic processes of human neutrophils. We found that PAK activation occurred upon stimulation of neutrophils with f-Met-Leu-Phe (fMLP, and PAK accumulated at the actin-rich leading edge of stimulated neutrophils, suggesting a role for PAK in Rac-dependent actin remodeling. Treatment with the pharmacological PAK inhibitor, PF3758309, abrogated the integrity of RhoA-mediated actomyosin contractility and surface adhesion. Moreover, inhibition of PAK activity impaired neutrophil morphological polarization and directional migration under a gradient of fMLP, and was associated with dysregulated Ca(2+ signaling. These results suggest that PAK serves as an important effector of Rho-family GTPases in neutrophil cytoskeletal reorganization, and plays a key role in driving efficient directional migration of human neutrophils.

Leveraging the Pre-DFG Residue Thr-406 To Obtain High Kinase Selectivity in an Aminopyrazole-Type PAK1 Inhibitor Series.

Science.gov (United States)

Rudolph, Joachim; Aliagas, Ignacio; Crawford, James J; Mathieu, Simon; Lee, Wendy; Chao, Qi; Dong, Ping; Rouge, Lionel; Wang, Weiru; Heise, Christopher; Murray, Lesley J; La, Hank; Liu, Yanzhou; Manning, Gerard; Diederich, François; Hoeflich, Klaus P

2015-06-11

To increase kinase selectivity in an aminopyrazole-based PAK1 inhibitor series, analogues were designed to interact with the PAK1 deep-front pocket pre-DFG residue Thr-406, a residue that is hydrophobic in most kinases. This goal was achieved by installing lactam head groups to the aminopyrazole hinge binding moiety. The corresponding analogues represent the most kinase selective ATP-competitive Group I PAK inhibitors described to date. Hydrogen bonding with the Thr-406 side chain was demonstrated by X-ray crystallography, and inhibitory activities, particularly against kinases with hydrophobic pre-DFG residues, were mitigated. Leveraging hydrogen bonding side chain interactions with polar pre-DFG residues is unprecedented, and similar strategies should be applicable to other appropriate kinases.

Increased expression of microRNA-221 inhibits PAK1 in endothelial progenitor cells and impairs its function via c-Raf/MEK/ERK pathway

International Nuclear Information System (INIS)

Zhang, Xiaoping; Mao, Haian; Chen, Jin-yuan; Wen, Shengjun; Li, Dan; Ye, Meng; Lv, Zhongwei

2013-01-01

Highlights: ► MicroRNA-221 is upregulated in the endothelial progenitor cells of atherosclerosis patients. ► PAK1 is a direct target of microRNA-221. ► MicroRNA-221 inhibits EPCs proliferation through c-Raf/MEK/ERK pathway. -- Abstract: Coronary artery disease (CAD) is associated with high mortality and occurs via endothelial injury. Endothelial progenitor cells (EPCs) restore the integrity of the endothelium and protect it from atherosclerosis. In this study, we compared the expression of microRNAs (miRNAs) in EPCs in atherosclerosis patients and normal controls. We found that miR-221 expression was significantly up-regulated in patients compared with controls. We predicted and identified p21/Cdc42/Rac1-activated kinase 1 (PAK1) as a novel target of miR-221 in EPCs. We also demonstrated that miR-221 targeted a putative binding site in the 3′UTR of PAK1, and absence of this site was inversely associated with miR-221 expression in EPCs. We confirmed this relationship using a luciferase reporter assay. Furthermore, overexpression of miR-221 in EPCs significantly decreased EPC proliferation, in accordance with the inhibitory effects induced by decreased PAK1. Overall, these findings demonstrate that miR-221 affects the MEK/ERK pathway by targeting PAK1 to inhibit the proliferation of EPCs

ASSET experience at Paks NPP

International Nuclear Information System (INIS)

Szabo, I.

1997-01-01

At Paks NPP special attention has been paid to international reviews since the very beginning of operation. Several international teams visited Paks in order to provide independent assessment of plant performance, conditions and safety. Paks NPP Management has the further intention to invite international reviews regularly (yearly) in the future as well. The experience gained during these reviews helped to establish a unified process of preparation for the reviews, performing them and handling the results. The Safety Department is in charge of organization of the whole process. All these reviews have their specific features and they are focused on different areas. The ASSET reviews provides the assessment of plant performance and safety through the analysis of safety significant events, which have occurred at the nuclear power plant. This approach makes this review specific and different from the other ones

ASSET experience at Paks NPP

Energy Technology Data Exchange (ETDEWEB)

Szabo, I [Operational Safety Dept., Paks NPP, Paks (Hungary)

1997-10-01

At Paks NPP special attention has been paid to international reviews since the very beginning of operation. Several international teams visited Paks in order to provide independent assessment of plant performance, conditions and safety. Paks NPP Management has the further intention to invite international reviews regularly (yearly) in the future as well. The experience gained during these reviews helped to establish a unified process of preparation for the reviews, performing them and handling the results. The Safety Department is in charge of organization of the whole process. All these reviews have their specific features and they are focused on different areas. The ASSET reviews provides the assessment of plant performance and safety through the analysis of safety significant events, which have occurred at the nuclear power plant. This approach makes this review specific and different from the other ones.

A Trio-Rac1-PAK1 signaling axis drives invadopodia disassembly

Science.gov (United States)

Moshfegh, Yasmin; Bravo-Cordero, Jose Javier; Miskolci, Veronika; Condeelis, John; Hodgson, Louis

2014-01-01

Rho family GTPases control cell migration and participate in the regulation of cancer metastasis. Invadopodia, associated with invasive tumor cells, are crucial for cellular invasion and metastasis. To study Rac1 GTPase in invadopodia dynamics, we developed a genetically-encoded, single-chain Rac1 Fluorescence Resonance Energy Transfer (FRET) biosensor. The biosensor shows Rac1 activity exclusion from the core of invadopodia, and higher activity when invadopodia disappear, suggesting that reduced Rac1 activity is necessary for their stability, and Rac1 activation is involved in disassembly. Photoactivating Rac1 at invadopodia confirmed this previously-unknown Rac1 function. We built an invadopodia disassembly model, where a signaling axis involving TrioGEF, Rac1, PAK1, and phosphorylation of cortactin, causing invadopodia dissolution. This mechanism is critical for the proper turnover of invasive structures during tumor cell invasion, where a balance of proteolytic activity and locomotory protrusions must be carefully coordinated to achieve a maximally invasive phenotype. PMID:24859002

Cerita Humor Pak Andir

Directory of Open Access Journals (Sweden)

Rohim Rohim

2014-06-01

Full Text Available This study attempts to describe the meaning of comic tale "Pak Andir" with the perspective of hermeneutics. This study is focused on exploring the main character with the theory of functional models and aktan, developed by Greimas. The source of data is the story of "Pak Andir" from the community of South Bengkulu. From the analysis, it is concluded that the behavior of the husband as the central character has made the wife a victim. The husband’s arrogance in strictly practicing the patriarchal tradition makes the wife have no courage to be herself. The wife’s claim at the end of the story is a positive thing, but it's too late. As a form of appreciation of literary work, the meaning of these stories need to be disseminated to the public, especially the residents in Bengkulu, that the husband and wife’s attitudes ares incorrect and need to be avoided. This study attempts to describe the meaning of comic tale "Pak Andir" with the perspective of hermeneutics. This study is focused on exploring the main character with the theory of functional models and aktan, developed by Greimas. The source of data is the story of "Pak Andir" from the community of South Bengkulu. From the analysis, it is concluded that the behavior of the husband as the central character has made the wife a victim. The husband’s arrogance in strictly practicing the patriarchal tradition makes the wife have no courage to be herself. The wife’s claim at the end of the story is a positive thing, but it's too late. As a form of appreciation of literary work, the meaning of these stories need to be disseminated to the public, especially the residents in Bengkulu, that the husband and wife’s attitudes ares incorrect and need to be avoided Key Words: comic tale; aktan model; functional model; hermeneutic Abstrak: Penelitian ini berusaha mendeskripsikan makna cerita humor “Pak Andir” dengan perspektif hermeneutika. Kajian ini difokuskan untuk mengeksplorasi tokoh utama

GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways

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Jian Zhang

2016-04-01

Full Text Available Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4 has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer.

Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.

Science.gov (United States)

Piccand, Julie; Meunier, Aline; Merle, Carole; Jia, Zhengping; Barnier, Jean-Vianney; Gradwohl, Gérard

2014-01-01

The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.

Pak1, adjuvant tamoxifen therapy, and breast cancer recurrence risk in a Danish population-based study

DEFF Research Database (Denmark)

Ahern, Thomas P; Cronin-Fenton, Deirdre P; Lash, Timothy L

2016-01-01

-/TAM - group. Pak1 cytoplasmic intensity was not associated with breast cancer recurrence in either group (ER+/TAM + ORadj for strong vs. no cytoplasmic staining = 0.91, 95% CI 0.57, 1.5; ER-/TAM - ORadj for strong vs. no cytoplasmic staining = 0.74, 95% CI 0.39, 1.4). Associations between Pak1 nuclear......Background Adjuvant tamoxifen therapy approximately halves the risk of estrogen receptor-positive (ER+) breast cancer recurrence, but many women do not respond to therapy. Observational studies nested in clinical trial populations suggest that overexpression or nuclear localization of p21-activated...... by immunohistochemical staining of primary breast tumors from recurrence cases and matched controls from two breast cancer populations; women diagnosed with ER-positive tumors who received at least one year of tamoxifen therapy (ER+/TAM+), and women diagnosed with ER-negative tumors who survived for at least one year...

Lifetime-management and lifetime-extension at PAKS nuclear power plant

International Nuclear Information System (INIS)

Katona, Tamas; Ratkai, Sandor; Janosi, Agnes Biro

2002-01-01

Paks Nuclear Power Plant provides 38-40% of domestic generation at lowest price. It has an important energy-policy role in Hungary. NPP Paks shall be a decisive and perspectively permanent element of the domestic electricity generation during the next two decades, which shall be ensured by plant safe operation, the lifetime extension and power uprating. Paks Nuclear Power Plant investigated the nuclear power plant's lifetime extension possibilities and alternatives, as well as technical and business feasibility of such alternatives. The feasibility study is based on the evaluation of a representative set of systems, structures and components, operational, test, in-service inspection and maintenance practice, experience and findings of the Periodic Safety Review. The most important results of this study showing the feasibility of 20 years lifetime extension is summarised in the paper. It was found that there are no technical or safety issues or limits, which may inhibit the operation of the Nuclear Power Plant Paks up to 50 years. In case of most systems and equipment the recent monitoring, maintenance and regular reconstruction practice of the NPP Paks allows the lifetime extension without outstanding cost. Replacement or reconstruction of a few equipment and systems requires significant investment costs. Material of reactor vessels of VVER/213 incorporated at Paks, compared to vessels of the similar units, is less sensitive to the embrittlement. At units 3-4 reactor vessels do not require any measure, consequently, any additional cost, even in case of a lifetime of 50 years. At unit 2 to extend the lifetime of the reactor vessel, only heating-up of emergency core cooling tanks is needed in order to decrease thermal stress levels caused by pressure thermal shock (PST) transients. For this purpose cost-effective technical solutions are available. At unit 1, beside the heating-up of the emergency core cooling tanks annealing of the welded joint No. 5/6 close to the

MODELACIÓN DEL PROCESO DE RECUPERACIÓN PARCIAL DE ENVASES DE TETRA PAK MODELAÇÃO DO PROCESSO DE RECUPERAÇÃO PARCIAL DE EMBALAGENS TETRA PAK MODELING THE PARTIAL RECOVERY PROCESS OF TETRA PAK PACKAGES

Directory of Open Access Journals (Sweden)

JORGE MARIO OBANDO

2009-07-01

Full Text Available En el presente artículo se estudian el patrón de consumo, las expectativas y satisfacción de la población de Medellín con los envases de Tetra Pak, el tratamiento que se les da cuando son descartados y la conducta que se seguiría, conociendo que el Tetra Pak es reciclable; luego, se modela el procedimiento para recuperar parcialmente esos desechos de Tetra Pak y comercializarlos como bienes intermedios, aptos para ser reintegrados dentro de diversos procesos productivos. Se estudian varias políticas de operación mediante un modelo de simulación de eventos discretos construido en Extend.No presente artigo se estudam o patrão de consumo, as expectativas e satisfação da população de M edellín com as embalagens Tetra Pak, o tratamento que se lhes dá quando são descartadas e a conduta que se seguiria, conhecendo que o Tetra Pak é reciclável; depois, se modela o procedimento para recuperar parcialmente esses resíduos de Tetra Pak e comercializá-los como bens intermédios, aptos para ser reintegrados dentro de diversos processos produtivos. Estudam-se várias políticas de operação mediante um modelo de simulação de eventos discretos construído em Extend.In this paper we study the consumption pattern, expectations and satisfaction of the population of Medellin with Tetra Pak packages, the treatment given to them now when they are discarded and the conduct to be followed, knowing that the Tetra Pak is recyclable, then the process to recover partially debris from Tetra Pak is modeled and marketed as intermediate goods, eligible to be reinstated within various production processes. Several operating policies through a discrete event simulation built in Extend are studied.

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3 and KIT driven Leukemogenesis

Science.gov (United States)

Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H.; Waskow, Emily R.; Visconte, Valeria; Tiu, Ramon V.; Smith, Catherine C.; Shah, Neil; Bunting, Kevin D.; Boswell, H. Scott; Liu, Yan; Chan, Rebecca J.; Kapur, Reuben

2015-01-01

SUMMARY Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN) and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK), whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. PMID:25456130

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis

Directory of Open Access Journals (Sweden)

Anindya Chatterjee

2014-11-01

Full Text Available Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML and myeloproliferative neoplasms (MPNs, and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis.

Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain

DEFF Research Database (Denmark)

Pandey, A.; Dan, I.; Kristiansen, T.Z.

2002-01-01

cloned a novel human PAK family kinase that has been designated as PAK5. PAK5 contains a CDC42/Rac1 interactive binding (CRIB) motif at the N-terminus and a Ste20-like kinase domain at the C-terminus. PAK5 is structurally most related to PAK4 and PAK6 to make up the PAK-II subfamily. We have shown...

Experience in modernization of safety I and C in VVER 440 nuclear power plants Bohunice V1 and Paks

International Nuclear Information System (INIS)

Martin, M.

2000-01-01

For nuclear power plants which have been in operation for more than 15 years, backfitting or even complete replacement of the instrumentation and control (I and C) equipment becomes an increasingly attractive option, motivated not only by the objective to reduce the cost of I and C system maintenance and repair but also to prolong or at least to safeguard the plant life-time: optimized spare-part management through use of standard equipment; reduction of number and variety of different items of equipment by implementing functions stepwise in application software; adding new functionality in the application software which was not possible in the old technology due to lack of space; safeguarding of long-term After-Sales-Service. Some years ago Bohunice V1 NPP, Slovak Republic and Paks NPP, Hungary intended to replace parts of their Safety I and C, mainly the Reactor Trip System, the Reactor Limitation System and the Neutron Flux Excore Instrumentation and Monitoring Systems. After a Basic Engineering Phase in Bohunice V1 and a Feasibility Study in Paks both plants decided to use the Siemens' Digital Safety I and C System TELEPERM XS to modernize their plants. Both Bohunice, Unit 2 and Paks, Unit 1 have been back on line for over six months with the new Digital Safety I and C. At the present time Bohunice, Unit 1 and within the next few months Paks, Unit 2 will be replaced. Trouble-free start-ups and no major problems under operation in the first two plants were based on: thorough understanding of the VVER 440 technology; comprehensive planning together with the plant operators and authorities; the possibility to adapt TELEPERM XS to every plant type; the execution of extensive pre-operational tests. Regarding these modernization measures Siemens, as well as the above Operators, have gained considerable experience in the field of I and C Modernization in VVER 440 NPPs. Important aspects of this experience are: how to transfer the VVER technology to TELEPERM XS; how to

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2

Science.gov (United States)

O’Hagan, Kyle L.; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru

2015-01-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. PMID:26519537

Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis.

Science.gov (United States)

Chatterjee, Anindya; Ghosh, Joydeep; Ramdas, Baskar; Mali, Raghuveer Singh; Martin, Holly; Kobayashi, Michihiro; Vemula, Sasidhar; Canela, Victor H; Waskow, Emily R; Visconte, Valeria; Tiu, Ramon V; Smith, Catherine C; Shah, Neil; Bunting, Kevin D; Boswell, H Scott; Liu, Yan; Chan, Rebecca J; Kapur, Reuben

2014-11-20

Oncogenic mutations of FLT3 and KIT receptors are associated with poor survival in patients with acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs), and currently available drugs are largely ineffective. Although Stat5 has been implicated in regulating several myeloid and lymphoid malignancies, how precisely Stat5 regulates leukemogenesis, including its nuclear translocation to induce gene transcription, is poorly understood. In leukemic cells, we show constitutive activation of focal adhesion kinase (FAK) whose inhibition represses leukemogenesis. Downstream of FAK, activation of Rac1 is regulated by RacGEF Tiam1, whose inhibition prolongs the survival of leukemic mice. Inhibition of the Rac1 effector PAK1 prolongs the survival of leukemic mice in part by inhibiting the nuclear translocation of Stat5. These results reveal a leukemic pathway involving FAK/Tiam1/Rac1/PAK1 and demonstrate an essential role for these signaling molecules in regulating the nuclear translocation of Stat5 in leukemogenesis. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Safety upgrading of the PAKS Nuclear Plant

International Nuclear Information System (INIS)

Vamos, G.; Vigassy, J.

1993-01-01

In the last several years the net electricity from the Paks NPP represents almost half of the Hungarian total. The 4 units of Paks belong to the latest generation of the VVER-440 units, the small-sized Russian designed PWRs. Reviewing the main design features of them, the safety merits and safety concerns are summarized. Due to the conservative design and the extensive operating experience the safety merits appear to be more significant than generally believed. The VVER-440 type has two models, the 230 and 213, which have a large number of distinctive safety features. These are highlighted in the section comparisons. A quality assurance program was initiated in Paks very early. A long-term safety upgrading program was also initiated, originating from vendor recommendations, regulatory decisions, in-house operating experience and safety concerns, and independent reviews. The main areas and some examples of the measures are described. This program, like all other activities related to nuclear safety, has been under regulatory control. The specific features of the Hungarian regulatory system are described. For advanced, general and new evaluation of the safety of the units in Paks in accordance with the internationally recommended criteria of the 90's, the project AGNES has been launched with international participation. The scope of this project is summarized. International efforts as the IAEA Regional Project on safety assessment of VVER-440/213 and VVER-440/230 units are underway. Since safety is not only a question of design, but it can be significantly influenced by operations and maintenance practices, the Paks NPP has invited LAEA's OSART and ASSET missions, WANO's Pilot Peer Review

Summary of IVO participation in Paks blast test analysis

International Nuclear Information System (INIS)

Varpasuo, P.

2001-01-01

The paper deals with the numerical simulation of the triple blast test performed at Paks NPP. A detailed background analysis was carried out to complete the geological and geotechnical properties and, consequently, special frequency dependent soil stiffnesses have been evaluated. The structural model (3D) allowed a very refined result presentation in terms of profiles of displacements and forces at different elevations, for direct comparison with the experimental output. (author)

Productive Entry of Foot-and-Mouth Disease Virus via Macropinocytosis Independent of Phosphatidylinositol 3-Kinase

Science.gov (United States)

Han, Shi-Chong; Guo, Hui-Chen; Sun, Shi-Qi; Jin, Ye; Wei, Yan-Quan; Feng, Xia; Yao, Xue-Ping; Cao, Sui-Zhong; Xiang Liu, Ding; Liu, Xiang-Tao

2016-01-01

Virus entry is an attractive target for therapeutic intervention. Here, using a combination of electron microscopy, immunofluorescence assay, siRNA interference, specific pharmacological inhibitors, and dominant negative mutation, we demonstrated that the entry of foot-and-mouth disease virus (FMDV) triggered a substantial amount of plasma membrane ruffling. We also found that the internalization of FMDV induced a robust increase in fluid-phase uptake, and virions internalized within macropinosomes colocalized with phase uptake marker dextran. During this stage, the Rac1-Pak1 signaling pathway was activated. After specific inhibition on actin, Na+/H+ exchanger, receptor tyrosine kinase, Rac1, Pak1, myosin II, and protein kinase C, the entry and infection of FMDV significantly decreased. However, inhibition of phosphatidylinositol 3-kinase (PI3K) did not reduce FMDV internalization but increased the viral entry and infection to a certain extent, implying that FMDV entry did not require PI3K activity. Results showed that internalization of FMDV exhibited the main hallmarks of macropinocytosis. Moreover, intracellular trafficking of FMDV involves EEA1/Rab5-positive vesicles. The present study demonstrated macropinocytosis as another endocytic pathway apart from the clathrin-mediated pathway. The findings greatly expand our understanding of the molecular mechanisms of FMDV entry into cells, as well as provide potential insights into the entry mechanisms of other picornaviruses. PMID:26757826

Pak2 Controls Acquisition of NKT Cell Fate by Regulating Expression of the Transcription Factors PLZF and Egr2.

Science.gov (United States)

O'Hagan, Kyle L; Zhao, Jie; Pryshchep, Olga; Wang, Chyung-Ru; Phee, Hyewon

2015-12-01

NKT cells constitute a small population of T cells developed in the thymus that produce large amounts of cytokines and chemokines in response to lipid Ags. Signaling through the Vα14-Jα18 TCR instructs commitment to the NKT cell lineage, but the precise signaling mechanisms that instruct their lineage choice are unclear. In this article, we report that the cytoskeletal remodeling protein, p21-activated kinase 2 (Pak2), was essential for NKT cell development. Loss of Pak2 in T cells reduced stage III NKT cells in the thymus and periphery. Among different NKT cell subsets, Pak2 was necessary for the generation and function of NKT1 and NKT2 cells, but not NKT17 cells. Mechanistically, expression of Egr2 and promyelocytic leukemia zinc finger (PLZF), two key transcription factors for acquiring the NKT cell fate, were markedly diminished in the absence of Pak2. Diminished expression of Egr2 and PLZF were not caused by aberrant TCR signaling, as determined using a Nur77-GFP reporter, but were likely due to impaired induction and maintenance of signaling lymphocyte activation molecule 6 expression, a TCR costimulatory receptor required for NKT cell development. These data suggest that Pak2 controls thymic NKT cell development by providing a signal that links Egr2 to induce PLZF, in part by regulating signaling lymphocyte activation molecule 6 expression. Copyright © 2015 by The American Association of Immunologists, Inc.

Simulation of the Paks-2 incident. The CODEX-CT-1 experiment

International Nuclear Information System (INIS)

Windberg, P.; Hozer, Z.; Nagy, I.; Vimi, A.

2006-01-01

The Paks-2 cleaning tank incident was simulated with an electrically heated fuel bundle in the CODEX facility. The test conditions included seven hours of oxidation in hydrogen rich steam and final water quenching of the brittle fuel rods. The final state of the bundle showed similar picture that was observed after the incident at the power plant in 2003. (author)

KRITIK SOSIAL DALAM KOMIK STRIP PAK BEI

Directory of Open Access Journals (Sweden)

Yudhi Novriansyah

2016-08-01

Full Text Available This research aimed to do interpret the marking which flange social criticism and know laboring ideology in story of Comic Strip Pak Bei. Research based on theory of structural semiotic according to Ferdinand De Saussure. Using analysis of Syntagmatic as first level of meaning to the text network and also picture, and analysis of Paradigmatic as second level of meaning or implicit meaning (connota-tion, myth, ideology Analysis done to six Comic choice edition of Strip Pak Bei period of November 2004 - Februari 2005 which tend to flange social criticism. At band of syntagmatic, result of research indicate that story theme lifted from social problems that happened in major society. The fact clear progressively when connected by Intertextual with information and texts which have preexisted. At band of Paradigmatic, social criticism tend to emerge dimly, is not transparent. Because of Comic Strip Pak Bei expand in the middle of Java cultural domination that developing myth of criticize as action menacing compatibility and orderliness of society. Story of Comic Strip Pak Bei also confirm dominant ideology in Java society culture, namely ideology of Patriarkhi and Feudalism which still go into effect until now. This prove ideology idea according to Louis Althusser which not again opposition between class, but have been owned and practiced by all social class.

Introduction of the SAT based training programs at Paks NPP

International Nuclear Information System (INIS)

Kiss, I.

1998-01-01

An introduction of the SAT based training programs at Paks nuclear power plant is described in detail, including framework of project operation; project implementation; process of SAT applied at Paks NPP and the needs of its introduction

Database for the OECD-IAEA Paks Fuel Project

International Nuclear Information System (INIS)

Szabo, Emese; Hozer, Zoltan; Gyori, Csaba; Hegyi, Gyoergy

2010-01-01

On 10 April 2003 severe damage of fuel assemblies took place during an incident at Unit 2 of Paks Nuclear Power Plant in Hungary. The assemblies were being cleaned in a special tank below the water level of the spent fuel storage pool in order to remove crud buildup. That afternoon, the chemical cleaning of assemblies was completed and the fuel rods were being cooled by circulation of storage pool water. The first sign of fuel failure was the detection of some fission gases released from the cleaning tank during that evening. The cleaning tank cover locks were released after midnight and this operation was followed by a sudden increase in activity concentrations. The visual inspection revealed that all 30 fuel assemblies were severely damaged. The first evaluation of the event showed that the severe fuel damage happened due to inadequate coolant circulation within the cleaning tank. The damaged fuel assemblies will be removed from the cleaning tank in 2005 and will be stored in special canisters in the spent fuel storage pool of the Paks NPP. Following several discussions between expert from different countries and international organisations the OECD-IAEA Paks Fuel Project was proposed. The project is envisaged in two phases. - Phase 1 is to cover organization of visual inspection of material, preparation of database, performance of analyses and preparatory work for fuel examination. - Phase 2 is to cover the fuel transport and the hot cell examination. The first meeting of the project was held in Budapest on 30-31 January 2006. Phase 1 of the Paks Fuel Project will focus on the numerical simulation of the most important aspects of the incident. This activity will help in the reconstruction of the accidental scenario. The first step of Phase 1 was the collection of a database necessary for the code calculations. The main objective of database collection was to provide input data for calculations. For this reason the collection was focused on such data that are

3ON PAK RUPEE EXCHANGE RATES: WHETHER STOCK OR FLOW MATTERS?

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Razzaque H Bhatti

2011-01-01

Full Text Available This paper examines whether the monetary model or the flow model of exchange rate explains the long-run movements in Pak rupee exchange rates vis-à-vis the four major currencies – the US dollar, British pound, Swiss franc and Japanese yen – over the period 1983q1-2009q4. Results obtained by employing the Johansen and Juselius (1990 technique of cointegration are supportive of the monetary model in two Pak rupee exchange rates vis-à-vis the US dollar and the Swiss franc when both short- and long-run interest rates are used and of the flow model in three exchange rates vis-à-vis the British pound, Swiss franc and Japanese yen when the short-run interest rate is used. These results show that both stock equilibrium in capital markets and flow equilibrium in foreign exchange markets determine Pak rupee exchange rates.

PTS assessment - The basis of life time evaluation at NPP Paks

International Nuclear Information System (INIS)

Elter, J.; Oszwald, F.; Ratkay, S.; Fekete, T.; Gillemot, F.; Marothy, L.

1997-01-01

Plant specific PTS analysis at NPP Paks was performed in the frame of the AGNES (Advanced General New Evaluation of Safety) project. NPP Paks belongs to the second generation of the WWER-440/213 NPP-s. To verify the safety during transient events and predict the lifetime of the RPV-s several transient cases have been analyzed. The paper summarizes: The general scheme elaborated for the assessment; the safety philosophy used; the applied and available codes and methods; the ongoing and planned developments. (author). 8 refs, 3 figs, 1 tab

PTS assessment - The basis of life time evaluation at NPP Paks

Energy Technology Data Exchange (ETDEWEB)

Elter, J; Oszwald, F; Ratkay, S [NPP Paks (Hungary); Fekete, T; Gillemot, F; Marothy, L [Atomic Energy Research Inst., Budapest (Hungary)

1997-09-01

Plant specific PTS analysis at NPP Paks was performed in the frame of the AGNES (Advanced General New Evaluation of Safety) project. NPP Paks belongs to the second generation of the WWER-440/213 NPP-s. To verify the safety during transient events and predict the lifetime of the RPV-s several transient cases have been analyzed. The paper summarizes: The general scheme elaborated for the assessment; the safety philosophy used; the applied and available codes and methods; the ongoing and planned developments. (author). 8 refs, 3 figs, 1 tab.

Reactor protection system refurbishment at Paks

International Nuclear Information System (INIS)

Hetzmann, A.; Turi, T.

1997-01-01

The history and the milestones of the reactor protection system refurbishment are outlined. During the preparation phase of the refurbishment project, detailed requirements have been set up and specific technical solutions developed. The structure of the project documents prepared during these activities is shown in a figure. The life cycle of the project was divided into four phases: the preparatory phase; the design and manufacturing phase; the installation and commissioning phase; and the operation phase. For all four Paks units a time schedule for implementation was set up. The licensing process is dealt with; the principal license was issued in June 1996. (A.K.)

OECD-IAEA Paks Fuel Project. Final Report

International Nuclear Information System (INIS)

2010-05-01

It is important for nuclear power plant designers, operators and regulators to effectively use lessons learned from events occurring at nuclear power plants since, in general, it is impossible to reproduce the event using experimental facilities. In particular, evaluation of the event using accident analysis codes is expected to contribute to improving understanding of phenomena during the events and to facilitate the validation of computer codes through simulation analyses. The information presented in this publication will be of use in future revisions of safety guides on accident analysis. During a fuel crud removal operation on the Paks-2 unit of the Paks nuclear power plant, Hungary on 10 April 2003, several fuel assemblies were severely damaged. The assemblies were being cleaned in a special tank under deep water in a service pit connected to the spent fuel storage pool. The first sign of fuel failures was the detection of some fission gases released from the cleaning tank. Later, visual inspection revealed that most of the 30 fuel assemblies suffered heavy oxidation and fragmentation. The first evaluation of the event showed that the severe fuel damage had been caused by inadequate cooling. The Paks-2 event was discussed in various committees of the OECD Nuclear Energy Agency (OECD/NEA) and of the International Atomic Energy Agency (IAEA). Recommendations were made to undertake actions to improve the understanding of the incident sequence and of the consequence this had on the fuel. It was considered that the Paks-2 event may constitute a useful case for a comparative exercise on safety codes, in particular for models devised to predict fuel damage and potential releases under abnormal cooling conditions and the analyses of the Paks-2 event may provide information which is relevant for in-reactor and spent fuel storage safety evaluations. The OECD-IAEA Paks Fuel Project was established in 2005 as a joint project between the IAEA and the OECD/NEA. The IAEA

Discovery of 2-(4-Substituted-piperidin/piperazine-1-yl-N-(5-cyclopropyl-1H-pyrazol-3-yl-quinazoline-2,4-diamines as PAK4 Inhibitors with Potent A549 Cell Proliferation, Migration, and Invasion Inhibition Activity

Directory of Open Access Journals (Sweden)

Tianxiao Wu

2018-02-01

Full Text Available A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4 inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC50 < 1 μM. Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC50 = 0.060 μM and 0.068 μM, respectively. Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity.

Reciprocally coupled residues crucial for protein kinase Pak2 activity calculated by statistical coupling analysis.

Directory of Open Access Journals (Sweden)

Yuan-Hao Hsu

2010-03-01

Full Text Available Regulation of Pak2 activity involves at least two mechanisms: (i phosphorylation of the conserved Thr(402 in the activation loop and (ii interaction of the autoinhibitory domain (AID with the catalytic domain. We collected 482 human protein kinase sequences from the kinome database and globally mapped the evolutionary interactions of the residues in the catalytic domain with Thr(402 by sequence-based statistical coupling analysis (SCA. Perturbation of Thr(402 (34.6% suggests a communication pathway between Thr(402 in the activation loop, and Phe(387 (DeltaDeltaE(387F,402T = 2.80 in the magnesium positioning loop, Trp(427 (DeltaDeltaE(427W,402T = 3.12 in the F-helix, and Val(404 (DeltaDeltaE(404V,402T = 4.43 and Gly(405 (DeltaDeltaE(405G,402T = 2.95 in the peptide positioning loop. When compared to the cAMP-dependent protein kinase (PKA and Src, the perturbation pattern of threonine phosphorylation in the activation loop of Pak2 is similar to that of PKA, and different from the tyrosine phosphorylation pattern of Src. Reciprocal coupling analysis by SCA showed the residues perturbed by Thr(402 and the reciprocal coupling pairs formed a network centered at Trp(427 in the F-helix. Nine pairs of reciprocal coupling residues crucial for enzymatic activity and structural stabilization were identified. Pak2, PKA and Src share four pairs. Reciprocal coupling residues exposed to the solvent line up as an activation groove. This is the inhibitor (PKI binding region in PKA and the activation groove for Pak2. This indicates these evolutionary conserved residues are crucial for the catalytic activity of PKA and Pak2.

Integrated solidity test measurement of the airtight compartment system at the Paks nuclear power plant

Energy Technology Data Exchange (ETDEWEB)

Osztheimer, M.; Taubner, R.; Techy, Zs. (Villamosenergiaipari Kutato Intezet, Budapest (Hungary))

1983-01-01

A brief report on the purpose of the integrated solidity test measurements of the airtight compartment system of the Paks nuclear power plant and on the applied measuring principles is given. The measuring system and the selected measuring methods are evaluated. The characteristic features of the airtight system of the Paks nuclear power plant's 1st block and their effects on the measurement are mentioned.

Analyses for licensing of new fuel types at Paks NPP

International Nuclear Information System (INIS)

Kereszturi, A.; Bogatyr, S.; Miko, S.; Nemes, I.

2003-01-01

In the last years Paks NPP initiated several projects aiming at the introduction of new fuel types and resulting in more economic fuel cycles. The motivations, the reasons, and the economic consequences of the above modifications are detailed. The application of a new fuel type requires the renewal of the relevant chapters of the Safety Analysis Report. The fulfilment of fuel design basis requirements, to be summarised briefly also in the paper, must be investigated during normal and accidental conditions. The characteristics of the different codes, the data transfer between them are detailed. After, the cases of the Normal Operation, Anticipated Operation Occurrence, and the Postulated Accidents, judged as the most relevant ones in case of fuel modifications, are overviewed. In the last part, selected examples of the licensing calculations, performed by the above tools are presented. In conclusion, modifications of the WWER fuel, namely increased enrichment, application of burnable fuel pins, modified geometry make more economic fuel cycles (larger discharge burnup, power up-rate, reduced pressure vessel fluence) are possible. The further step (increased enrichment, burnable poison) of the fuel modernisation at NPP Paks is necessary for more economic fuel cycles and fuel consuming. A sound basis of licensing methodology, safety analysis, and necessary computer codes for the WWER fuel modernisation is available

Rho Kinase (ROCK) collaborates with Pak to Regulate Actin Polymerization and Contraction in Airway Smooth Muscle.

Science.gov (United States)

Zhang, Wenwu; Bhetwal, Bhupal P; Gunst, Susan J

2018-05-10

. We find that ROCK regulates airway smooth muscle contraction by mediating activation of the serine-threonine kinase, Pak, to promote actin polymerization. Pak catalyzes paxillin phosphorylation on Ser273 and coupling of the GIT1-βPIX-Pak signaling module to paxillin, which activates the GEF activity βPIX towards cdc42. Cdc42 is required for the activation of Neuronal Wiskott-Aldrich Syndrome protein (N-WASp), which transmits signals from cdc42 to the Arp2/3 complex for the nucleation of actin filaments. Our results demonstrate a novel molecular function for ROCK in the regulation of Pak and cdc42 activation that is critical for the processes of actin polymerization and contractility in airway smooth muscle. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Methuosis: nonapoptotic cell death associated with vacuolization of macropinosome and endosome compartments.

Science.gov (United States)

Maltese, William A; Overmeyer, Jean H

2014-06-01

Apoptosis is the most widely recognized form of physiological programmed cell death. During the past three decades, various nonapoptotic forms of cell death have gained increasing attention, largely because of their potential importance in pathological processes, toxicology, and cancer therapy. A recent addition to the panoply of cell death phenotypes is methuosis. The neologism is derived from the Greek methuo (to drink to intoxication) because the hallmark of this form of cell death is displacement of the cytoplasm by large fluid-filled vacuoles derived from macropinosomes. The demise of the cell resembles many forms of necrosis, insofar as there is a loss of metabolic capacity and plasma membrane integrity, without the cell shrinkage and nuclear fragmentation associated with apoptosis. Methuosis was initially defined in glioblastoma cells after ectopic expression of activated Ras, but recent reports have described small molecules that can induce the features of methuosis in a broad spectrum of cancer cells, including those that are resistant to conventional apoptosis-inducing drugs. This review summarizes the available information about the distinguishing morphological characteristics and underlying mechanisms of methuosis. We compare and contrast methuosis with other cytopathological conditions in which accumulation of clear cytoplasmic vacuoles is a prominent feature. Finally, we highlight key questions that need to be answered to determine whether methuosis truly represents a unique form of regulated cell death. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Comparative evaluation of anoxomat and conventional anaerobic GasPak jar systems for the isolation of anaerobic bacteria.

Science.gov (United States)

Shahin, May; Jamal, Wafaa; Verghese, Tina; Rotimi, V O

2003-01-01

To evaluate the performance of the Anoxomat, in comparison with the conventional anaerobic GasPak jar system, for the isolation of obligate anaerobes. Anoxomat, model WS800, and anaerobic GasPak jar system (Oxoid) were evaluated. Anoxomat system utilized a gas mixture of 80% N(2), 10% CO(2) and 10% H(2), while the GasPak used a gas mixture of 90% H(2) and 10% CO(2). An anaerobic indicator within the jars monitored anaerobiosis. A total of 227 obligate anaerobic bacteria comprising 116 stock strains, 5 ATCC reference strains and 106 fresh strains, representing different genera, were investigated for growth on anaerobic agar plates and scored for density, colony sizes, susceptibility zones of antibiotic inhibition and the speed of anaerobiosis (reducing the indicator). The results demonstrate that the growth of anaerobic bacteria is faster inside the Anoxomat jar than in the anaerobic GasPak jar system. Of the 227 strains tested, the colonies of 152 (67%) were larger (by size range of 0.2-2.4 mm) in the Anoxomat at 48 h than in the GasPak jar compared with only 21% (range 0.1-0.3 mm) that were larger in the GasPak than in the Anoxomat. The remaining 12% were equal in their sizes. There was no measurable difference in the colony sizes of the reference strains. The Porphyromonas asaccharolytica strains failed to grow within the GasPak system but grew inside the Anoxomat. With the Anoxomat, anaerobiosis was achieved about 35 min faster than in the GasPak system. The density of growth recorded for 177 (78%) strains was heavier in the Anoxomat than in the GasPak jar. The zones of inhibition of the antibiotics tested were not different in the two systems. The Anoxomat system provided superior growth, in terms of density and colony size, and achieved anaerobiosis more rapidly. Evidently, the Anoxomat method is more reliable and appears to support the growth of strict anaerobes better. Copyright 2003 S. Karger AG, Basel

Seismic analyses of Paks RB. Progress report 1993-1994

Energy Technology Data Exchange (ETDEWEB)

David, M [David Consulting, Engineering and Design Office (Czech Republic)

1995-07-01

The dynamic analysis presented in this report refers to the seismic analysis of the main building of Paks NPP. The following tasks which have been completed are described: design of 3-dimensional model of the main building; calculation of frequencies and modes of free vibrations; determination of modal masses for all modes of vibrations; floor response spectra as response to seismic excitation assumed for the Paks site; relative response of seismic acceleration at the top of the condensing tower.

Safety reassessment of the Paks NPP (the AGNES project)

Energy Technology Data Exchange (ETDEWEB)

Gado, J [Hungarian Academy of Sciences, Budapest (Hungary). Central Research Inst. for Physics; Bajsz, J; Cserhati, A; Elter, J [Paksi Atomeroemue Vallalat, Paks (Hungary); Hollo, E [Energiagazdalkodasi Intezet, Budapest (Hungary); Kovacs, K [EROTERV Engineering and Contractor Co (Hungary); Maroti, L [Hungarian Academy of Sciences, Budapest (Hungary). Central Research Inst. for Physics; Miko, S [Paksi Atomeroemue Vallalat, Paks (Hungary); Techy, Z [Energiagazdalkodasi Intezet, Budapest (Hungary); Vidovszky, I [Hungarian Academy of Sciences, Budapest (Hungary). Central Research Inst. for Physics

1996-12-31

The reassessment of the Paks NPP safety according to internationally recognized criteria of the Advanced General and New Evaluation of Safety (AGNES) project is outlined. The Paks NPP consists of four WWER-440/V-213 units. The following groups of analysis have been performed: system analysis and description; analysis of design basis accidents; severe accidents analysis; level 1 probabilistic safety analysis. Postulated accidents (PA) and Anticipated Operational Occurrences (AOO) are estimated in detail for the following initiating events: increase/decrease in secondary heat removal; decrease in primary coolant inventory; increase/decrease of reactor coolant inventory; reactivity and power distribution anomalies; analysis of transients with the failure of reactor scram (ATWS); pressurized thermal shock analyses. Severe accident analysis was made for the accidents on in-vessel phase and containment phase, for radioactive release and for accident management.

Safety reassessment of the Paks NPP (the AGNES project)

International Nuclear Information System (INIS)

Gado, J.; Hollo, E.; Kovacs, K.; Maroti, L.; Techy, Z.; Vidovszky, I.

1995-01-01

The reassessment of the Paks NPP safety according to internationally recognized criteria of the Advanced General and New Evaluation of Safety (AGNES) project is outlined. The Paks NPP consists of four WWER-440/V-213 units. The following groups of analysis have been performed: system analysis and description; analysis of design basis accidents; severe accidents analysis; level 1 probabilistic safety analysis. Postulated accidents (PA) and Anticipated Operational Occurrences (AOO) are estimated in detail for the following initiating events: increase/decrease in secondary heat removal; decrease in primary coolant inventory; increase/decrease of reactor coolant inventory; reactivity and power distribution anomalies; analysis of transients with the failure of reactor scram (ATWS); pressurized thermal shock analyses. Severe accident analysis was made for the accidents on in-vessel phase and containment phase, for radioactive release and for accident management

Review of Paks outage results 1990

International Nuclear Information System (INIS)

Lukacs, P.; Zsoldos, F.; Kiss, Z.

1991-01-01

The year 1990 was not the most successful from an outage point of view at the Paks Nuclear Power Plant in Hungary -there were one or two long delays. Work at unit 4 had a delay of 10 days because of an error made during assembling the reactor vessel. While the outage of unit 3 was running, a feedwater pipe hanger problem was discovered - several hangers were found displaced from the right position. A general inspection of the affected system was required and this took about 11 days. Information about each outage is presented on diagrams, making comparison easier. These diagrams give information about deviations from the outage plan, about work hours performed during outages, and about collective exposure. (author)

PLEX at Paks: making a virtue out of necessity

International Nuclear Information System (INIS)

Katona, T.; Bajsz, J.

1992-01-01

There are four VVER-440 units in operation at Paks Nuclear plant in Hungary. The units are of the V-213 type, ie the design which approaches the current, demanding Western standards in many aspects. During construction a number of innovations were adopted in these units. In particular, the instrumentation and control system was thoroughly improved, but there were also some changes to the main components (eg the pressure vessel). Although the quality assurance carried out during construction and commissioning was not the same as in Western practice, it was effective and resulted in relatively well constructed and tested units. Due to this, Pak has a good foundation on which to build a life extension programme-high availability, quality upgrading, a high integrity pressure vessel and a careful operating policy. Although life extension, economically speaking, is a necessity and not an option for Paks, the programme in itself should bring other benefits which would pay for themselves within the plant's design lifetime. (author)

Fuel assembly leakage, unit 4, cycle 22, Paks NPP

International Nuclear Information System (INIS)

Szecsenyi, C.; Burjan, T.; Torma, B.; Bona, G.

2009-01-01

At the beginning of Cycle 22, Unit 4, Paks NPP the Iodine isotopes activity concentrations raised irregularly in the water of the primary circuit. Analysis supposed that from 1 to 10 fuel rods in one or more newly loaded follower assemblies had lost their integrity. Due to the fact it was not necessary to shut down the reactor, but at the end of the cycle sipping tests were performed for the entire core to find out the facts using a telescope sipping device supplied by H and B Co., Germany. This paper describes the circumstances of the emergence of the problem, the operational inspection and limitation rules in Paks NPP, the theoretical analysis to estimate the scope and kind of the problem, the sipping device and the measurement/evaluation methods applied for the practical tests, fulfilment the tests, the results and their evaluation and the conclusions regarding the event. (Authors)

Fuel assembly leakage, Unit 4, Cycle 22, Paks NPP

International Nuclear Information System (INIS)

Szecsenyi, Z.; Burjan, T.; Torma, B.; Bona, G.

2009-01-01

At the beginning of Cycle 22, Unit 4, Paks NPP the Iodine isotopes activity concentrations raised irregularly in the water of the primary circuit. Analysis supposed that from 1 to 10 fuel rods in one or more newly loaded follower assemblies had lost their integrity. Due to the fact it was not necessary to shut down the reactor, but at the end of the cycle sipping tests were performed for the entire core to find out the facts using a telescope sipping device supplied by H and B Co., Germany. This paper describes the circumstances of the emergence of the problem, the operational inspection and limitation rules in the Paks NPP, the theoretical analysis to estimate the scope and kind of the problem, the sipping device and the measurement/evaluation methods applied for the practical tests, fulfilment the tests, the results and their evaluation and the conclusions regarding the event. (authors)

PAH analysis in Leipzig allotment soils; Untersuchungen zum Gefaehrdungspotential polycyclischer aromatischer Kohlenwasserstoffe (PAK) in Leipziger Kleingartenboeden

Energy Technology Data Exchange (ETDEWEB)

Bittrich, R.; Butze, B.; Mueller, S.; Prawalsky, R.; Stoye, H. [Umwelt-Consult e.V., Leipzig (Germany)

2000-09-01

Soils in 29 allotments were analyzed systematically with a view to the following aspects: Concentration ratios of the 16 components analyzed. Occurrence and classification of so-called PAH patterns. Interdependences between PAH patterns and soil features. PAH concentrations and soil-immanent buffer characteristics (humus concentration, pH, clay concentration, sesquioxide concentrations, exchange capacity). [German] Die vorliegende Arbeit konzentriert sich auf die Untersuchung der PAK-Belastung kleingaertnerisch genutzter Boeden. Die hier vorgestellten Ergebnisse resultieren aus Probjekten von Umwelt-Consult e.V. aus den Jahren 1995 bis 1997 im Auftrag der Stadt Leipzig und dem unter fachlicher Begleitung des Referates Geochemie der Abt. Boden/Geochemie vom LfUG gefoerderten Forschungsvorhaben 'Untersuchungen zum Gefaehrdungspotential polycyclischer aromatischer Kohlenwasserstoffe (PAK) in Boeden der Stadt Leipzig'. Hierbei wurden systematisch Boeden in 29 Kleingartenanlagen untersucht. Folgende Fragestellungen sollten beantwortet werden: Stehen die PAK-Konzentrationen der 16 analysierten Einzelkomponenten in bestimmten Groessenverhaeltnissen zueinander? Sind sogenannte PAK-Muster zu erkennen und lassen sich diese klassifizieren? Welche Beziehungen gibt es zwischen PAK-Mustern und Bodenmerkmalen? Korrespondieren die PAK-Konzentrationen (Gesamt-PAK, Einzelkomponenten) im Boden und deren bodenhorizont-bezogene Abfolge mit der Auspraegung bodenimmanenter Puffermerkmale (Humusgehalt, pH-Wert, Tongehalt, Gehalt an Sesquioxiden, Austauschkapazitaet)? (orig.)

Corporate portal system at PAKS NPP, Hungary

International Nuclear Information System (INIS)

2009-01-01

The new Corporate Portal System (CPS) of Paks NPP was launched in November 2006. The portal is based on one of the latest technologies, Plumtree Enterprise WEB 5.0. The main purpose of the installation of the new technology was to serve the working culture change, to give a platform to access all information and applications including the integrated process model used at the NPP. The new technology also supports those goals which were defined in the organization development programme: e.g. to improve internal communication with the establishment of communities of practice. Installation of the CPS has provided a powerful tool for knowledge management; it is possible to share and find all information through a controlled access in documents from various sources, to have links to people, portlets and different communities. Document management of the Paks NPP is supported by the integration of the Document 5 application, as the new Electronic Data Management System (EDMS) and the CPS. Depending on their access rights, all users of the CPS, through Microsoft Internet Explorer, can access technical, economic and human resources documents which are stored anywhere on the internal network (file servers, EDMS, old INRANET). The CPS is also accessible from the internet through a secure connection. The main concept is the integration of all applications to one platform and to help users to find all information they need. An access control list specifies which users and groups have access to an object (and what kind of access privileges they have such as read, select, edit, admin)

An emerging role for p21-activated kinases (Paks) in viral infections

DEFF Research Database (Denmark)

Van den Broeke, Celine; Radu, Maria; Chernoff, Jonathan

2010-01-01

and motility, and abnormal Pak function is associated with a number of human diseases. Here, we discuss emerging evidence that these enzymes also play a major role in the entry, replication and spread of many important pathogenic human viruses, including HIV. Careful assessment of the potential role of Paks...

Review report on the dynamical study of the main building of the Paks NPP

International Nuclear Information System (INIS)

Gatti, F.

1995-01-01

The present report deals with the review of the report 'Dynamical Study of the main building of the Paks NPP', issued by Paks NPP (Hungary) on April, 1993, within the frame of the IAEA benchmark study for the seismic analysis and testing of an existing Nuclear Power Plant (M), and on behalf of ENEL DSR/VDN Rome, in the aims of the nuclear activities of ENEL DSR/VDN (Rome). After a foreword to define the aims of the job (Chapter 1) and the identification of the scope of the work (Chapter 2), a short list of references is given (Chapter 3). In Chapter 4, the criteria followed in the review activity are listed; in Chapter 5, the contents of the Paks NPP report are summarized. In Chapter 6 the results of the review are given, while the main conclusions of the review activities are summarized in the Chapter 7. (author)

PAK4 crystal structures suggest unusual kinase conformational movements.

Science.gov (United States)

Zhang, Eric Y; Ha, Byung Hak; Boggon, Titus J

2018-02-01

In order for protein kinases to exchange nucleotide they must open and close their catalytic cleft. These motions are associated with rotations of the N-lobe, predominantly around the 'hinge region'. We conducted an analysis of 28 crystal structures of the serine-threonine kinase, p21-activated kinase 4 (PAK4), including three newly determined structures in complex with staurosporine, FRAX486, and fasudil (HA-1077). We find an unusual motion between the N-lobe and C-lobe of PAK4 that manifests as a partial unwinding of helix αC. Principal component analysis of the crystal structures rationalizes these movements into three major states, and analysis of the kinase hydrophobic spines indicates concerted movements that create an accessible back pocket cavity. The conformational changes that we observe for PAK4 differ from previous descriptions of kinase motions, and although we observe these differences in crystal structures there is the possibility that the movements observed may suggest a diversity of kinase conformational changes associated with regulation. Protein kinases are key signaling proteins, and are important drug targets, therefore understanding their regulation is important for both basic research and clinical points of view. In this study, we observe unusual conformational 'hinging' for protein kinases. Hinging, the opening and closing of the kinase sub-domains to allow nucleotide binding and release, is critical for proper kinase regulation and for targeted drug discovery. We determine new crystal structures of PAK4, an important Rho-effector kinase, and conduct analyses of these and previously determined structures. We find that PAK4 crystal structures can be classified into specific conformational groups, and that these groups are associated with previously unobserved hinging motions and an unusual conformation for the kinase hydrophobic core. Our findings therefore indicate that there may be a diversity of kinase hinging motions, and that these may

The Hungarian model project: Strengthening training for operational safety at Paks nuclear power plant

International Nuclear Information System (INIS)

Mautner Markhof, F.

1998-01-01

The Hungarian Model project (HMP) reflects the commitment to constant increase of safety and reliability of the NPP Paks, the Government of Hungary and the IAEA. It includes some of the most important nuclear power objectives of Paks NPP, namely the strengthening of NPP personnel training and competence through the application of international best practice, the systematic approach to training (SAT), for training operation and maintenance personnel; setting up a state of-the-art maintenance training center (MTC) at Paks and enhancing safety culture at Paks NPP. The IAEA supported implementation of the HMP through fellowships and scientific visits, expert missions, provision of hardware and software for SAT application, and supply od major new uncontaminated items of actual WWER equipment for the MTC

Full scale dynamic testing of Paks nuclear power plant structures

International Nuclear Information System (INIS)

Da Rin, E.M.

1995-01-01

This report refers to the full-scale dynamic structural testing activities that have been performed in December 1994 at the Paks (H) Nuclear Power Plant, within the framework of: the IAEA Coordinated research Programme 'Benchmark Study for the Seismic Analysis and Testing of WWER-type Nuclear Power Plants, and the nuclear research activities of ENEL-WR/YDN, the Italian National Electricity Board in Rome. The specific objective of the conducted investigation was to obtain valid data on the dynamic behaviour of the plant's major constructions, under normal operating conditions, for enabling an assessment of their actual seismic safety to be made. As described in more detail hereafter, the Paks NPP site has been subjected to low level earthquake like ground shaking, through appropriately devised underground explosions, and the dynamic response of the plant's 1 st reactor unit important structures was appropriately measured and digitally recorded. In-situ free field response was measured concurrently and, moreover, site-specific geophysical and seismological data were simultaneously acquired too. The above-said experimental data is to provide basic information on the geophysical and seismological characteristics of the Paks NPP site, together with useful reference information on the true dynamic characteristics of its main structures and give some indications on the actual dynamic soil-structure interaction effects for the case of low level excitation

Calculation uncertainty of distribution-like parameters in NPP of PAKS

International Nuclear Information System (INIS)

Szecsenyi, Zsolt; Korpas, Layos

2000-01-01

In the reactor-physical point of view there were two important events in the Nuclear Power Plant of PAKS in this year. The Russian type profiled assemblies were loaded into the PAKS Unit 3, and new limitation system was introduced on the same Unit. It was required to solve a lot of problems because of these both events. One of these problems was the determination of uncertainty of quantities of the new limitation considering the fabrication uncertainties for the profiled assembly. The importance of determination of uncertainty is to guarantee on 99.9% level the avoidance of fuel failure. In this paper the principles of determination of calculation accuracy, applied methods and obtained results are presented in case of distribution-like parameters. A few elements of the method have been presented on earlier symposiums, so in this paper the whole method is just outlined. For example the GPT method was presented in the following paper: Uncertainty analysis of pin wise power distribution of WWER-440 assembly considering fabrication uncertainties. Finally in the summary of this paper additional intrinsic opportunities in the method are presented. (Authors)

Periodical safety review of units 1 and 2 of PAKS NPP. Examples from summary report

International Nuclear Information System (INIS)

Hammar, K.

1998-01-01

On the basis of American practice of qualification and relevant IAEA recommendations detailed guidelines of the qualification procedure were developed and executed on the Units 1 and 2 of the Paks NPP. Periodic safety supervision will be performed by evaluation of the following reports to be submitted by NPP: real technical conditions of the facility; existing practice and proposals for equipment qualification; evaluation of the existing safety reports estimating their validity up to the plant lifetime; ageing and ageing management; procedures of operation, maintenance, supervision; organisation and administration; safety impact of human factor, training, education, qualification of personnel

An AFLP marker linked to turnip mosaic virus resistance gene in pak ...

African Journals Online (AJOL)

An AFLP marker linked to turnip mosaic virus resistance gene in pak-choi. W Xinhua, C Huoying, Z Yuying, H Ruixian. Abstract. Pak-choi is one of the most important vegetable crops in China. Turnip mosaic virus (TuMV) is one of its main pathogen. Screening the molecular marker linked to the TuMV resistance gene is an ...

Stereoselective uptake and distribution of chiral neoniconoid insecticide paichongding in chinese pak choi (Brassica campestris ssp. Chinenesis)

International Nuclear Information System (INIS)

Wang Haiyan; Yang Zhen; Liu Ruyang; Fu Qiuguo; Zhang Sufen; Li Juying; Zhao Xiaojun; Ye Qingfu; Wang Wei; Li Zhong

2014-01-01

Paichongding, a neonicotinoid chiral insecticide containing two chiral centers, is a promising substitute for the widely used imidacloprid because it is effective against many imidacloprid-resistant insects. In this study, four optically-pure stereoisomers of Paichongding with 5R, 7R, 5S, 7S, 5S, 7R, and 5R, 7S were employed in both foliar and root of Chinese pak choi to investigate the stereoselective uptake and distribution of the insecticide in pak choi. The results showed, after foliar application, total absorption of individual "1"4C-Paichongding stereoisomers into pak-choi plants demonstrated no stereoselectivity between the enantiomers. The translocation of the four absorbed stereoisomers within pak choi occurred in both acropetal and basipetal directions and the transport of "1"4C from enantiomers 5R, 7R and 5S, 7S were significantly higher than enantiomers 5R, 7S and 5S, 7R. The statistically significant stereoselective translocation inside plants was observed between Paichongding epimers. Root treatment revealed that enantioselective and diastereoselective root uptake into pak-choi plants were both found between the four enantiomers. The enantiomers of 5R, 7S and 5S, 7R were more readily taken up by roots, and more readily accumulated in edible leaves than 5R, 7R and 5S, 7S. These results will help to develop an understanding of the proper application of Paichongding isomers in vegetables, and give useful information for food and environmental assessments of chiral pesticides. (authors)

Herpes simplex virus internalization into epithelial cells requires Na+/H+ exchangers and p21-activated kinases but neither clathrin- nor caveolin-mediated endocytosis.

Science.gov (United States)

Devadas, Deepika; Koithan, Thalea; Diestel, Randi; Prank, Ute; Sodeik, Beate; Döhner, Katinka

2014-11-01

Herpes simplex virus 1 (HSV-1) is an alphaherpesvirus that has been reported to infect some epithelial cell types by fusion at the plasma membrane but others by endocytosis. To determine the molecular mechanisms of productive HSV-1 cell entry, we perturbed key endocytosis host factors using specific inhibitors, RNA interference (RNAi), or overexpression of dominant negative proteins and investigated their effects on HSV-1 infection in the permissive epithelial cell lines Vero, HeLa, HEp-2, and PtK2. HSV-1 internalization required neither endosomal acidification nor clathrin- or caveolin-mediated endocytosis. In contrast, HSV-1 gene expression and internalization were significantly reduced after treatment with 5-(N-ethyl-N-isopropyl)amiloride (EIPA). EIPA blocks the activity of Na(+)/H(+) exchangers, which are plasma membrane proteins implicated in all forms of macropinocytosis. HSV-1 internalization furthermore required the function of p21-activated kinases that contribute to macropinosome formation. However, in contrast to some forms of macropinocytosis, HSV-1 did not enlist the activities of protein kinase C (PKC), tyrosine kinases, C-terminal binding protein 1, or dynamin to activate its internalization. These data suggest that HSV-1 depends on Na(+)/H(+) exchangers and p21-activated kinases either for macropinocytosis or for local actin rearrangements required for fusion at the plasma membrane or subsequent passage through the actin cortex underneath the plasma membrane. After initial replication in epithelial cells, herpes simplex viruses (HSVs) establish latent infections in neurons innervating these regions. Upon primary infection and reactivation from latency, HSVs cause many human skin and neurological diseases, particularly in immunocompromised hosts, despite the availability of effective antiviral drugs. Many viruses use macropinocytosis for virus internalization, and many host factors mediating this entry route have been identified, although the

Molecular evolution, characterization and expression analysis of SnRK2 gene family in Pak-choi (Brassica rapa ssp. chinensis

Directory of Open Access Journals (Sweden)

Zhinan eHuang

2015-10-01

Full Text Available Abstract: The sucrose non-fermenting 1-related protein kinase 2 (SnRK2 family members are plant-specific serine/threonine kinases that are involved in the plant response to abiotic stress and abscisic acid (ABA-dependent plant development. Further understanding of the evolutionary history and expression characteristics of these genes will help to elucidate the mechanisms of the stress tolerance in Pak-choi, an important green leafy vegetable in China. Thus, we investigated the evolutionary patterns, footprints and conservation of SnRK2 genes in selected plants and later cloned and analyzed SnRK2 genes in Pak-choi. We found that this gene family was preferentially retained in Brassicas after the Brassica-Arabidopsis thaliana split. Next, we cloned and sequenced 13 SnRK2 from both cDNA and DNA libraries of stress-induced Pak-choi, which were under conditions of ABA, salinity, cold, heat, and osmotic treatments. Most of the BcSnRK2s have eight exons and could be divided into three groups. The subcellular localization predictions suggested that the putative BcSnRK2 proteins were enriched in the nucleus. The results of an analysis of the expression patterns of the BcSnRK2 genes showed that BcSnRK2 group III genes were robustly induced by ABA treatments. Most of the BcSnRK2 genes were activated by low temperature, and the BcSnRK2.6 genes responded to both ABA and low temperature. In fact, most of the BcSnRK2 genes showed positive or negative regulation under ABA and low temperature treatments, suggesting that they may be global regulators that function at the intersection of multiple signaling pathways to play important roles in Pak-choi stress responses.

Radiation protection aspects of the repair work at Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Bujtas, T.; Nenyei, A.

2006-01-01

On the Unit 2 at Paks Nuclear Power Plant accident occurred on 10th April 2003. Thirty fuel assemblies damaged in the cleaning tank installed in the Pit No. 1. Due to the accident casing of the fuel elements and uranium-dioxide pellets inside them damaged. The scratched fuel assemblies and nuclear fuel fragments should be removed and safely deposited. In order to restore the operational condition of the Pit No. 1 a lot of complicated activities with radiation hazard should be implemented. These tasks bring up both technical difficulties and serious radiation protection problems, and it is essential to resolve them in order to reduce radiation exposure of the working personnel and to minimize the amount of off-site radioactive releases.There was a serious incident (An INES level 3 event) at Paks Nuclear Power plant in april 10, 2003. (TRA)

Summary of structural analysis and comparison with experimental results for Paks NPP

International Nuclear Information System (INIS)

Hauptenbuchner, B.; David, M.

2001-01-01

This contribution deals with the analysis and comparison of the dynamic response, calculated and measured by the explosion test in Nuclear Power Plant Paks, Hungary. Some details of the calculation model are also presented. The calculated and measured data of dynamic response are compared in selected points of the NPP Paks reactor building. Conclusions and recommendations are derived from this comparison. (author)

External hazards considered for Paks NPP

International Nuclear Information System (INIS)

Kiss, Tibor

2000-01-01

PAKS NPP was built according to Soviet construction standards which took into account meteorological aspects but no documents for other external hazards were available. Main activities concerning earthquakes cover reevaluation of the plant site, seismic safety technological concept, improving the seismic resistance, installation of seismic monitoring and protection system, and seismic PSA

Pertumbuhan Dan Produktivitas Sawi Pak Choy (Brasica Rapa L.) Pada Umur Transplanting Dan Pemberian Mulsa Organik

OpenAIRE

Pribadi, Gandhi Yudhistira; Roviq, Mochammad; Wardiyati, Tatik

2014-01-01

Potensi produksi tanaman pak choy belum optimal, rendahnya produksi pak choy dikarenakan pada teknik budidayanya petani cendrung tidak memperhatikan kondisi lingkungan mikro dan masih belum adanya standart transplanting yang tepat. Penelitian bertujuan untuk mendapatkan teknik budidaya pak choy dengan penggunaan mulsa dan saat transplanting yang tepat. Dilaksanakan pada bulan Mei - Juli 2013 di Desa Pandanrejo, Kecamatan Bumiaji - Batu. Penelitian menggunakan Ranca-ngan Acak Kelompok Faktoria...

Description of Website for the OECD-IAEA Paks Fuel Project

International Nuclear Information System (INIS)

Szabo, Emese; Hozer, Zoltan; Nagy, Imre

2010-01-01

The first version of the database for the OECD-IAEA PAKS FUEL PROJECT has been collected and it is available on the following password protected website: http://nagy.aeki.kfki.hu Several modifications have been made and new items added according to the minutes of the 1st meeting held in Budapest on 30-31 January 2005

miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

Energy Technology Data Exchange (ETDEWEB)

Zhai, Jian [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Shuping [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Li, Xiaowei; Zhong, Jiaming; Chen, Xiaoxia [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Qu, Zengqiang, E-mail: drquzengqiang@163.com [Department II of Interventional Radiology, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China); Wu, Dong, E-mail: wudongstc@126.com [Department II of Special Medical Care, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438 (China)

2015-08-14

Emerging evidence suggests that microRNAs (miRNAs) play important roles in regulating HCC development and progression; however, the mechanisms by which their specific functions and mechanisms remained to be further explored. miR-129 has been reported in gastric cancers, lung cancer and colon cancer. In this study, we disclosed a new tumor suppresser function of miR-129 in HCC. We also found the downregulation of miR-129 occurred in nearly 3/4 of the tumors examined (56/76) compared with adjacent nontumorous tissues, which was more importantly, correlated to the advanced stage and vascular invasion. We then demonstrated that miR-129 overexpression attenuated HCC cells proliferation and invasion, inducing apoptosis in vitro. Moreover, we used miR-129 antagonist and found that anti-miR-129 promoted HCC cells malignant phenotypes. Mechanistically, our further investigations revealed that miR-129 suppressed cell proliferation and invasion by targeting the 3’-untranslated region of PAK5, as well as miR-129 silencing up-regulated PAK5 expression. Moreover, miR-129 expression was inversely correlated with PAK5 expression in 76 cases of HCC samples. RNA interference of PAK5 attenuated anti-miR-129 mediated cell proliferation and invasion in HCC cells. Taken together, these results demonstrated that miR-129 suppressed tumorigenesis and progression by directly targeting PAK5, defining miR-129 as a potential treatment target for HCC. - Highlights: • Decreased of miR-129 is found in HCC and associated with advanced stage and metastasis. • miR-129 suppresses proliferation and invasion of HCC cells. • miR-129 directly targets the 3′ UTR of PAK5 and diminishes PAK5 expression. • PAK5 is involved in miR-129 mediated suppression functions.

Gfi1b controls integrin signaling-dependent cytoskeleton dynamics and organization in megakaryocytes.

Science.gov (United States)

Beauchemin, Hugues; Shooshtarizadeh, Peiman; Vadnais, Charles; Vassen, Lothar; Pastore, Yves D; Möröy, Tarik

2017-03-01

Mutations in GFI1B are associated with inherited bleeding disorders called GFI1B -related thrombocytopenias. We show here that mice with a megakaryocyte-specific Gfi1b deletion exhibit a macrothrombocytopenic phenotype along a megakaryocytic dysplasia reminiscent of GFI1B -related thrombocytopenia. GFI1B deficiency increases megakaryocyte proliferation and affects their ploidy, but also abrogates their responsiveness towards integrin signaling and their ability to spread and reorganize their cytoskeleton. Gfi1b -null megakaryocytes are also unable to form proplatelets, a process independent of integrin signaling. GFI1B-deficient megakaryocytes exhibit aberrant expression of several components of both the actin and microtubule cytoskeleton, with a dramatic reduction of α-tubulin. Inhibition of FAK or ROCK, both important for actin cytoskeleton organization and integrin signaling, only partially restored their response to integrin ligands, but the inhibition of PAK, a regulator of the actin cytoskeleton, completely rescued the responsiveness of Gfi1b -null megakaryocytes to ligands, but not their ability to form proplatelets. We conclude that Gfi1b controls major functions of megakaryocytes such as integrin-dependent cytoskeleton organization, spreading and migration through the regulation of PAK activity whereas the proplatelet formation defect in GFI1B-deficient megakaryocytes is due, at least partially, to an insufficient α-tubulin content. Copyright© Ferrata Storti Foundation.

Experience of Hungarian model project: 'Strengthening training for operational safety at Paks NPP'

International Nuclear Information System (INIS)

Kiss, I.

1998-01-01

Training of Operational Safety at Paks NPP is described including all the features of the project including namely: description of Paks NPP, its properties and performances; reasons for establishing Hungarian Model Project, its main goals, mentioning Hungarian and IAEA experts involved in the Project, its organization, operation, budget, current status together with its short term and long term impact

DESIGNAND EVALUATION OF TETRA-PAK CONTAINERS' RECYCLING PLANT ON A SMALLSCALE

OpenAIRE

Inche Mitma, Jorge; Vergiú Canto, Jorge|; Mavila Hinojoza, Daniel; Godoy Martínez, Manuel; Chung Pinzás, Alfonso

2014-01-01

This study deals about the design and evaluation of Tetra Pak containers' recycling plant on a small scale. The basic Plant Engineering was found from the information gathered. Some aspects included were: product design, process design, equipment design and costs evaluation, with the aim of determining its technical, economical and environmental capability for its implementation. El estudio trata sobre el diseño y evaluación de una planta de reciclaje de envases tetra pak a pequeña escala....

Strategi Pengembangan Usaha Ayam Potong Pak Imanto Di Pasar Tapiv Binjai

OpenAIRE

Meliala, Karina Octavina

2014-01-01

Chicken meat were popular among people. There are many reasons why people’s interest on buying chicken meat were high.Until this day, many people fond of chickend meat and that is what making this chicken meat business promising.Huge market makes this business promising in the future.One small scale enterpreneur who work in this business is Pak Imanto who opened Pak Imanto’s Chicken Meat retailer. In order to grow, this business needs to develop its streght, weakneses, opportunities and threa...

Safety assessment, safety performance indicators at the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Baji, C.; Vamos, G.; Toth, J.

2001-01-01

The Paks Nuclear Power Plant has been using different methods of safety assessment (event analysis, self-assessment, probabilistic safety analysis), including performance indicators characterizing both operational and safety performance since the early years of operation of the plant. Regarding the safety performance, the indicators include safety system performance, number of scrams, release of radioactive materials, number of safety significant events, industrial safety indicator, etc. The Paks NPP also reports a set of ten indicators to WANO Performance Indicator Programme which, among others, include safety related indicators as well. However, a more systematic approach to structuring and trending safety indicators is needed so that they can contribute to the enhancement of the operational safety. A more comprehensive set of indicators and a systematic evaluation process was introduced in 1996. The performance indicators framework proposed by the IAEA was adapted to Paks in this year to further improve the process. Safety culture assessment and characterizing safety culture is part of the assessment process. (author)

123I-Iodomethyl tyrosine radiochemical synthesis and quantification of residual impurities after SepPak purification

International Nuclear Information System (INIS)

Matte, G.; Abrams, D.; Kumar, P.; Mercer, J.

2002-01-01

[123-I]-Iodomethyl tyrosine, an analog of tyrosine, is used as a radiopharmaceutical to detect malignant tissue in vivo. Initial synthesis report removal of the starting material using HPLC reversed phase chromatography as well as a simple method using a C18-SepPak cartridge when an HPLC system is not available. Small amounts of residual starting material have not been reported to interfere with tumor uptake following biodistribution in vivo. However, in vitro tissue culture studies do require the final product to be free of un-reacted methyl tyrosine. Our goal was to quantify the amount of residual methyl tyrosine after C18-SepPak purification to confirm that 123 I methyl tyrosine purified in this manner would be suitable tissue culture studies. A preconditioned (rinsed with 2 ml Ethanol and 8 ml PBS) C18-SepPak cartridge is loaded with the 123 I-iodomethyl tyrosine reaction mixture and washed with 8 mL of PBS to remove the un-reacted methyl tyrosine and free 123 I-iodide. The cartridge is then eluted with a 20% alcohol/PBS mixture to recover the 123 I-iodomethyl tyrosine. Paper chromatography confirmed the removal of un-reacted 123 I-iodide. A parallel study with a methyl tyrosine standard was used to confirm the removal of the methyl tyrosine from the SepPak cartridge during the washing with 8 mL of PBS. Fractions were collected and UV absorbance was recorded. A standard curve was prepared using the UV absorbance of serial dilutions of methyl tyrosine. The detection limit was in the order of ng/mL. An elution profile of both 123 I methyl tyrosine and methyl tyrosine was obtained and shows that traces of methyl tyrosine can still be present after an 8 mL PBS wash

The maintenance training center of the paks nuclear power plant - past, present and future

International Nuclear Information System (INIS)

Kiss, I.

2001-01-01

The safety of the Paks nuclear power plant (Paks NPP) is a political-economic factor with general influence on the stability of the Hungarian economy. Since the beginning of the 1990s, the plant management has been taking significant efforts to learn about the factors that define plant safety and to reveal areas where safety can be further improved. Major emphasis is also placed on the provision of resources and creation of conditions necessary for the preservation of staff competence. In 1997 a separate, maintenance-specific facility was erected. The Maintenance Training Center of the Paks NPP is a worldwide major unique center. (orig.) [de

Interim storage of spent fuel elements in the Paks Nuclear Power Plant, Hungary

International Nuclear Information System (INIS)

Szabo, B.

1998-01-01

The interim storage of spent fuel cassettes of the Paks NPP provides storage for 50 years at the Paks NPP site. The modular dry storage technology is presented. The technological design and the licensing of the facility has been made by the GEC Alsthom ESL firm. This storage facility can accommodate 450 fuel cassettes until their final disposal. (R.P.)

Safety upgrading at PAKS Nuclear Power Plant

International Nuclear Information System (INIS)

Bajsz, J.; Elter, J.

2000-01-01

The operation of Paks NPP has reached its half time. Until this time the plant fulfilled expectations raised before its construction: the four units have produced safely and reliably more than 200 TWh electricity. The production of the plant has been at the stable level since its construction and has provided 43-38 % of electricity consumed in Hungary. The annual production is around 14 TWh, which means a load factor higher than 85 %. Safety upgrading activities [1] at Paks had started in the late eighties, when the commissioning work of units 3 and 4 were carried out. That time the main emphases were put to lessons learned of the TMI and Chernobyl accidents. The international reviews hosted by our plant widened our review's scope. To systematize our approach a complete safety review, the AGNES (Advanced General Safety and New Evaluation of Safety) project was started in 1991. The goal of the project was to evaluate to what extent Paks NPP satisfied the current international safety expectations and to help in determining the priorities for safety enhancement and upgrading measures. The project completed in 1994 ranked our safety upgrading measures by safety significance, which became a basis for technical design work and financial scheduling. The other important outcome of the AGNES project was the introduction the Periodical Safety Review regime by our nuclear authority. These periodical reviews held after 10 years of operation offer the possibility - and obligation for the licensee - to perform a comprehensive assessment of the safety of the plant, to evaluate the integral effects of changes of circumstances happened during the review period. The goal of these reviews is to deal with cumulative effects of NPP ageing, modifications, operating experience and technical developments aimed at ensuring a high level of safety throughout plant service life. The execution of our safety-upgrading program is well advancing. For the whole program from 1996 to 2002 250

Maintenance training centre at NPP Paks, Hungary

International Nuclear Information System (INIS)

Babos, K.

1996-01-01

The lecture shows the feature of WWER-440/213 units maintenance, the existing maintenance training system, the necessity of the change in maintenance training system at NPP Paks. The author introduces the would-be maintenance training centre, the training facilities and the main tasks related to the maintenance training. (author)

IAEA expert review mission completes assessment of fuel cleaning incident at Paks Nuclear Power Plant

International Nuclear Information System (INIS)

2003-01-01

. It also resulted in the issuance of a 'license in principal' which lacked the requirement for an expanded review and assessment. On the fuel cleaning operation in the course of the incident, the team found that the contractor worked without proper supervision of the Paks plant. In general, personnel involved did not receive adequate training in the safety aspects of this specific operation. Additionally, operating and emergency procedures were not sufficiently developed. On radiation protection, the IAEA team found that the Paks undertook appropriate monitoring and assessments of the radiation exposure to staff. Based upon the data or dose assessments provided by Paks and other authorities, the IAEA team found no indication that the annual dose limits for occupational exposure as specified in IAEA Basic Safety Standards have been exceeded. The team also agreed with the Paks and regulatory authority's assessment that the annual dose limits for the general public resulting from the release specified in IAEA Basic Safety Standards have not been exceeded. On transparency, the IAEA team was given total access to all information and personnel at Paks and at Hungarian Atomic Energy Authority. The team was allowed to independently verify any information that it believed was relevant to its review. Both Paks and the Hungarian Atomic Energy Authority said they would welcome further IAEA assistance as they continue to review and manage this incident and improve safety at the facility. The IAEA team also provided a number of recommendations for improvement in the above and in other areas. The team today turned over a draft of their findings and recommendations to the Hungarian Atomic Energy Authority in the form of 'Technical Notes' for factual comment only. This document will be reviewed at IAEA headquarters and submitted as a final report to the Hungarian Government within one month. The Hungarian Government intends to make the final report available to the public. (IAEA)

Training system enhancement for nuclear safety at PAKS NPP

International Nuclear Information System (INIS)

KIss, I.

2000-01-01

Paks Nuclear Power Plant is the only commercial nuclear facility in Hungary, which has been operational since 1982. The over 15 years operation of the plant can from all aspects be considered as a success, to which the well qualified, competent staff significantly contributes. Like other N-plants, Paks NPP is also exposed to major challenges due to plant ageing and changes in circumstances that affect the operation. The management focusing on maintaining nuclear safety launched an overall programme to upgrade quality of personnel training and to improve its infrastructure. Though this programme has successfully finished with visible proofs, further actions to develop a reconsidered human resource policy is needed so that the plant would successfully stand against the challenges of the 21. century. (author)

ABCB1 genetic variability and methadone dosage requirements in opioid-dependent individuals.

Science.gov (United States)

Coller, Janet K; Barratt, Daniel T; Dahlen, Karianne; Loennechen, Morten H; Somogyi, Andrew A

2006-12-01

The most common treatment for opioid dependence is substitution therapy with another opioid such as methadone. The methadone dosage is individualized but highly variable, and program retention rates are low due in part to nonoptimal dosing resulting in withdrawal symptoms and further heroin craving and use. Methadone is a substrate for the P-glycoprotein transporter, encoded by the ABCB1 gene, which regulates central nervous system exposure. This retrospective study aimed to investigate the influence of ABCB1 genetic variability on methadone dose requirements. Genomic deoxyribonucleic acid was isolated from opioid-dependent subjects (n = 60) and non-opioid-dependent control subjects (n = 60), and polymerase chain reaction-restriction fragment length polymorphism and allele-specific polymerase chain reaction were used to determine the presence of single nucleotide polymorphisms at positions 61, 1199, 1236, 2677, and 3435. ABCB1 haplotypes were inferred with PHASE software (version 2.1). There were no significant differences in the allele or genotype frequencies of the individual single nucleotide polymorphisms or haplotypes between the 2 populations. ABCB1 genetic variability influenced daily methadone dose requirements, such that subjects carrying 2 copies of the wild-type haplotype required higher doses compared with those with 1 copy and those with no copies (98.3 +/- 10.4, 58.6 +/- 20.9, and 55.4 +/- 26.1 mg/d, respectively; P = .029). In addition, carriers of the AGCTT haplotype required significantly lower doses than noncarriers (38.0 +/- 16.8 and 61.3 +/- 24.6 mg/d, respectively; P = .04). Although ABCB1 genetic variability is not related to the development of opioid dependence, identification of variant haplotypes may, after larger prospective studies have been performed, provide clinicians with a tool for methadone dosage individualization.

Evaluasi Konsumen di "RM. Pak Kardi" Pemalang dengan Analisis Diskriminan

Directory of Open Access Journals (Sweden)

Tuis Susanto

2017-02-01

Full Text Available Penelitian ini bertujuan mengetahui apakah ada perbedaan yang siqnifikan dalam variabel dependen (Y yang meliputi konsumen sering Beli (YO, Cukup (Y I dan Jarang Beli (Y2, serta bertujuan mengetahui perilaku konsumen yang benar-benar berbeda, perbedaan dalam  arti perilaku   mereka  sering  membeli, cukup dan jarang membeli. Metode analisis  yang digunakan adalah dengan Wilk's Lambda, Pairwise, F test. Canonical  corellation,   untuk  mencari ada dan tidak perbedaan antar group variabel dependen dan  menginterpretasikan     berdasarkan function at group centroid untuk mengetahui variabel independen mana yang   menjadi  faktor diskriminannya. Hasil yang didapat dari penelitian ini adalah  bahwa  variabel  menu  merupakan faktor pembeda (diskriminan.  Artinya konsumen grup (sering  beli,  cukup  dan jarang   beli  tidak terpengaruh   dengan  usia,  harga,  pendapatan,   dan pelayanan  yang  diberikan oleh RM. Pak Kardi ditunjukkan dengan tanda (+ padafunction I. Jadi  konsumen  yang  membeli  di RM. Pak  Kardi adalah  mereka  yang  benar-benar   menyukai menu  (masakan  khas kepiting RM. Pak Kardi.  Jarak antara  grup  Sering  Beli  dengan grup  Jarang   Beli  adalah yang  terbesar, yakni 7,350. Sedangkan jarak   terkecil   adalah antara grup  Cukup  dengan  grup  Jarang   Beli  (0.522. Dengan demikian dapat  dikatakan   bahwa  Konsumen   di grup  Sering  Beli paling berbeda  selera  Menu  masakannya. Sebaliknya   Menu yang  disukai  oleh  konsumen di RM. Pak Kardi yang termasuk konsumen Cukup mempunyai perbedaan yang  kecil dengan  mereka  yang jarang membeli

Achievements and challenges of Paks NPP

International Nuclear Information System (INIS)

Bajsz, J.; Katona, T.

2002-01-01

As the six year long safety upgrading program at Paks NPP is approaching its final stage this year, it is a good opportunity to draw the conclusion: what have been done and how have measures influenced the safety of the plant. In its first part the paper gives an overview of the program's main issues, assesses the results from the point of view of safety, reliability and cost effectiveness as well. In the second part a survey of future tasks follows: (1) Hungary is joining to the EU. The accession process so far has not revealed any major problems concerning nuclear safety which could be seen as obstacles toward the membership. However the plant should be ready to meet the increasing level of safety regulations. Further safety upgrading measures are planned, mostly in the field of severe accident management. (2) The electricity market liberalisation in Hungary will start in 2003 and being a EU member state, the full market opening will happen within a few years. The plant has to take into account the specificity of market functioning. The most important thing is to preserve the present cost advantage of nuclear electricity generation within the market conditions. The paper presents measures performed and planned to keep the unit generation cost competitive. (3) The first unit at Paks will mark its 20't'h anniversary this year. Lifetime management issues are at the centre of the engineering activities. The work already started to prepare the lifetime extension for 20 years. The program for the license renewal, which was elaborated jointly with the nuclear regulatory body will be described.(author)

IAEA OSART/EXPERT follow-up review mission completes assessment of actions taken by Paks Nuclear Power Plant

International Nuclear Information System (INIS)

2004-01-01

On 28 February 2004 the IAEA completed its follow-up review mission to assess the actions taken by Paks nuclear power plant (NPP) in response to the Agency's recommendations and suggestions made during the 2001 Operational Safety Review Team (OSART) mission and the 2003 Expert mission that investigated the fuel cleaning incident at the Paks NPP in Hungary. The mission was requested by the Hungarian Government to provide an independent assessment of the actions taken by Paks NPP. The IAEA team determined that the actions taken by Paks have resulted in tangible progress and concluded that all issues were either fully resolved or progressing satisfactorily. In a press conference, the team's conclusions in five areas were highlighted: management, Regulatory Oversight/Interface, operations and maintenance, including operating experience, radiation protection, emergency planning and preparedness, and transparency

Pak pakub porgandi- ja peedipulbrit / Silja Lättemäe

Index Scriptorium Estoniae

Lättemäe, Silja, 1952-

2006-01-01

Harjumaa Kadarbiku köögiviljakasvatustalu peremees Ants Pak hakkab porgandi- ja peedimahla tootmisjääke pulbriks kuivatama. Uudistoodet on plaanis turustada kamalisandina ja ekspordiks arengumaadesse

Ecotoxicological and human toxicological risk assessment of PAH-contaminated soils before and after biological treatment; Oekotoxikologische und humantoxikologische Risikobewertung PAK-belasteter Boeden vor und nach biologischer Behandlung

Energy Technology Data Exchange (ETDEWEB)

Roos, P.H.; Hanstein, W.G. [Bochum Univ. (Germany). Inst. fuer Physiologische Chemie; Weissenfels, W.D. [RAG Umwelt Kommunal GmbH, Bottrop (Germany); Afferden, M. van [IMTA, Jiutepec, Mor. (Mexico); Pfeifer, F. [DMT-Gesellschaft fuer Forschung und Pruefung mbH, Essen (Germany)

2000-07-01

The goal of the present work is to assess the adverse effects of soil bound polycyclic aromatic hydrocarbons (PAH) which remain in soils after biological remediation. We focus on risk assessment for mammalian species with respect to the oral uptake of contaminated soil particles and compare the results of a biomarker test with those of an ecotoxicological assay, the bioluminescence inhibition test with Vibrio fischeri. As a biomarker effect in mammals, we determined the liver microsomal cytochrome P450 enzyme CYP1A1 which is induced by PAH in exposed rats. After biological soil treatment, different amounts of PAH remain in the soil depending on the soil properties and initial pollutant composition. Particularly, higher condensated PAH resists biological treatment due to its hydrophobicity. In addition, high amounts of organic carbon in the soils affect remediation efficiency. In the bioluminescence inhibition test, eluates of all biologically treated soils studied do not reveal any or only low inhibitory effects. In contrast, the oral uptake of biologically treated contaminated soils leads to induction levels for CYP1A1 similar to those in the untreated samples. A good correlation is obtained between CYP1A1 levels and the amount of 5 and 6-ring PAH in the soil samples. The main result is that the remediation efficiency determined by the luminescence test is not reflected by the biomarker test, a finding which indicates the high bioavailability of residual PAH in soils. Consequently, new criteria for human risk assessment can be delineated. (orig.) [German] Ziel dieser Arbeit ist es, moegliche toxische Wirkungen PAK-belasteter Boeden vor und nach biologischer Sanierung zu erfassen. Hierbei liegt der Schwerpunkt auf der Abschaetzung des Risikos fuer Saeugetiere nach oraler Aufnahme von Bodenpartikeln. Als Biomarker-Effekt fuer die PAK-Aufnahme haben wir in Ratten die Induktion des lebermikrosomalen P450-Enzyms CYP1A1 bestimmt, dessen Expression durch PAK moduliert

OECD-IAEA Paks Fuel Project. Detailed Description of the Results of Calculations

International Nuclear Information System (INIS)

2010-05-01

On 10 April 2003 severe damage of fuel assemblies took place during an incident at Unit 2 of Paks Nuclear Power Plant in Hungary. The assemblies were being cleaned in a special tank below the water level of the spent fuel storage pool in order to remove crud buildup. That afternoon, the chemical cleaning of assemblies was completed and the fuel rods were being cooled by circulation of storage pool water. The first sign of fuel failure was the detection of some fission gases released from the cleaning tank during that evening. The cleaning tank cover locks were released after midnight and this operation was followed by a sudden increase in activity concentrations. The visual inspection revealed that all 30 fuel assemblies were severely damaged. The first evaluation of the event showed that the severe fuel damage happened due to inadequate coolant circulation within the cleaning tank. The damaged fuel assemblies will be removed from the cleaning tank in 2005 and will be stored in special canisters in the spent fuel storage pool of the Paks NPP. Following several discussions between expert from different countries and international organisations the OECD-IAEA Paks Fuel Project was proposed. The project is envisaged in two phases. - Phase 1 is to cover organization of visual inspection of material, preparation of database, performance of analyses and preparatory work for fuel examination. - Phase 2 is to cover the fuel transport and the hot cell examination

Extension of the surveillance program at NPP Paks

International Nuclear Information System (INIS)

Gillemot, F.

1992-01-01

In WWER-440 reactors the surveillance specimens are located in accelerated irradiation positions. After five years all specimens are withdrawn and the operational changes are not monitored. At Paks NPP a new surveillance program extension is started to eliminate of this disadvantage of the original program. (author)

External Events PSA for the Paks NPP

International Nuclear Information System (INIS)

Bareith, Attila; Karsa, Zoltan; Siklossy, Tamas; Vida, Zoltan

2014-01-01

Initially, probabilistic safety assessment of external events was limited to the analysis of earthquakes for the Paks Nuclear Power Plant in Hungary. The level 1 seismic PSA was completed in 2002 showing a significant contribution of seismic failures to core damage risk. Although other external events of natural origin had previously been screened out from detailed plant PSA mostly on the basis of event frequencies, a review of recent experience on extreme weather phenomena made during the periodic safety review of the plant led to the initiation of PSA for external events other than earthquakes in 2009. In the meantime, the accident of the Fukushima Dai-ichi Nuclear Power Plant confirmed further the importance of such an analysis. The external event PSA for the Paks plant followed the commonly known steps: selection and screening of external hazards, hazard assessment for screened-in external events, analysis of plant response and fragility, PSA model development, and risk quantification and interpretation of results. As a result of event selection and screening the following weather related external hazards were subject to detailed analysis: extreme wind, extreme rainfall (precipitation), extreme snow, extremely high and extremely low temperatures, lightning, frost and ice formation. The analysis proved to be a significant challenge due to scarcity of data, lack of knowledge, as well as limitations of existing PSA methodologies. This paper presents an overview of the external events PSA performed for the Paks NPP. Important methodological aspects are summarised. Key analysis findings and unresolved issues that need further elaboration are highlighted. Development of external events PSA for the Paks NPP was completed by the end of 2012. The analysis followed the commonly known steps: selection and screening of external hazards, hazard assessment for screened-in external events, analysis of plant response and fragility, PSA model development, and risk

How to ensure the safety of extended operations: Practice and experience of Paks NPP

International Nuclear Information System (INIS)

Kovacs, J.

2005-01-01

The Paks Nuclear Power Plant strategy is to extend the operational lifetime of the plant and renew the operational license for 20 years over the designed and licensed lifetime. In the paper the preconditions of long-term operation are discussed and the basic findings and experience of the license renewal works are also presented. The further plans fo NPP Paks for ensuring safe operation in long-term are discussed. (author)

Structural response of Paks NPP WWER-440 MW main building complex to blast input motion. Final report

International Nuclear Information System (INIS)

1999-01-01

The Soviet standard design units WWER-440/213 type installed in Paks NPP were not originally designed for a Safe Shutdown Earthquake. At the time of selection of Paks site on the basis of historical earthquake data was supposed that the maximum earthquake is of grade V according MSK-64 scale. This seismicity level had not required any special measures to account for seismic event effects on the Main Building Complex Structure. Current site seismicity studies reveal that the seismic hazard for the site significantly exceeds the originally estimated. In addition the safety rules and seismic code requirements became more rugged. As a part of the activities to increase the seismic safety of the Paks NPP the study on dynamic behaviour of the Main Building Complex Structure has been performed with support of IAEA. The explosion full scale tests were carried out for determining the dynamic behaviour of the structure and for assessment of the Soil Structure Interaction (SSI) effects in the modelling and analysis procedures, used in the dynamic response analyses. The objective of the project was to evaluate the blast response of the WWER-440/213 Main Building Complex at Paks NPP, based on the data available for the soil properties, recorded free-field blast input motion, and structural design. The scope of EQE-Bulgaria study was to conduct a state-of-the-art SSI analysis with a multiple foundations supported model of the Main Building Complex to assess the structure blast response. The analysis was focused on a modelling technique that assess realistically the SSI effects on the dynamic response of a structure supported on multiple foundation instead of simplified, but more conservative techniques. The scope of research was covered splitting the study into the following steps: development of a twin units model for Main Building Complex structure; development of a Low Strain Soil Properties Model; development of SSI Parameters consisting of a Multiple Foundations System

Structural requirements for cub domain containing protein 1 (CDCP1 and Src dependent cell transformation.

Directory of Open Access Journals (Sweden)

Gwendlyn Kollmorgen

Full Text Available Cub domain containing protein 1 (CDCP1 is strongly expressed in tumors derived from lung, colon, ovary, or kidney. It is a membrane protein that is phosphorylated and then bound by Src family kinases. Although expression and phosphorylation of CDCP1 have been investigated in many tumor cell lines, the CDCP1 features responsible for transformation have not been fully evaluated. This is in part due to the lack of an experimental system in which cellular transformation depends on expression of exogenous CDCP1 and Src. Here we use retrovirus mediated co-overexpression of c-Src and CDCP1 to induce focus formation of NIH3T3 cells. Employing different mutants of CDCP1 we show that for a full transformation capacity, the intact amino- and carboxy-termini of CDCP1 are essential. Mutation of any of the core intracellular tyrosine residues (Y734, Y743, or Y762 abolished transformation, and mutation of a palmitoylation motif (C689,690G strongly reduced it. Src kinase binding to CDCP1 was not required since Src with a defective SH2 domain generated even more CDCP1 dependent foci whereas Src myristoylation was necessary. Taken together, the focus formation assay allowed us to define structural requirements of CDCP1/Src dependent transformation and to characterize the interaction of CDCP1 and Src.

Mobilization of PAH by synthetic gastrointestinal juice from contaminated soil of a former landfill area; Mobilisierung von PAK durch synthetische Verdauungssaefte aus dem kontaminierten Bodenmaterial einer Altlastenflaeche

Energy Technology Data Exchange (ETDEWEB)

Hack, A.; Selenka, F.; Wilhelm, M. [Bochum Univ. (Germany). Abt. fuer Hygiene, Sozial- und Umweltmedizin

1998-10-01

In the present study, the amount of polycyclic aromatic hydrocarbons (PAH) in contaminated soil material, which may be available for absorption in the gastrointestinal tract, is estimated by means of evaluating the PAH mobilization by synthetic gastric and intestinal juice in an in vitro test system. Five contaminated soil materials from a former landfill site are analysed in this gastrointestinal model for the PAH of the U.S.EPA-standard. For quantification, an HPLC method with reversed-phase chromatography and on line fluorescence detection is used. The PAH concentration of the contaminated soil materials ranged from 37 {mu}g/g up to 196 {mu}g/g in total. The mobilization of the PAH in the gastrointestinal model ranged from 0.3% up to 1.3% when gastrointestinal juice was used alone. In the presence of whole milk powder, however, the mobilization was enhanced to values from 10.8% up to 14.5%. Since the soil material was taken from different parts of the contaminated area, and since the mobilization of the PAH from the different materials shows only minor differences, the mobilization data evaluated may be considered as representative for the whole contaminated area. Compared to other contaminated soil materials, especially those from gas work areas or coke plants, the mobilization rate of PAH by the gastrointestinal model from the soil materials used in this study is low. The health risk caused, by ingestion of this soil material, as far as PAH are concerned, is actually smaller than the risk calculated from the total content of PAH of the contaminated soil. (orig.) [Deutsch] Im allgemeinen wird nur ein Teil der Schadstoffe aus oral aufgenommenem kontaminiertem Bodenmaterial im Gastrointestinaltrakt resorbiert. In der vorliegenden Studie wird der resorptionsverfuegbare Anteil der PAK aus dem real kontaminierten Bodenmaterial einer ehemaligen Deponie aus dem sueddeutschen Raum anhand der Mobilisierbarkeit der PAK durch die Verdauungssaefte des oberen

A population growth trend analysis for Neotricula aperta, the snail intermediate host of Schistosoma mekongi, after construction of the Pak-Mun dam.

Directory of Open Access Journals (Sweden)

Stephen W Attwood

2013-11-01

Full Text Available The Pak-Mun dam is a controversial hydro-power project on the Mun River in Northeast Thailand. The dam is sited in a habitat of the freshwater snail Neotricula aperta, which is the intermediate host for the parasitic blood-fluke Schistosoma mekongi causing Mekong schistosomiasis in humans in Cambodia and Laos. Few data are available which can be used to assess the effects of water resource development on N. aperta. The aim of this study was to obtain data and to analyze the possible impact of the dam on N. aperta population growth.Estimated population densities were recorded for an N. aperta population in the Mun River 27 km upstream of Pak-Mun, from 1990 to 2011. The Pak-Mul dam began to operate in 1994. Population growth was modeled using a linear mixed model expression of a modified Gompertz stochastic state-space exponential growth model. The N. aperta population was found to be quite stable, with the estimated growth parameter not significantly different from zero. Nevertheless, some marked changes in snail population density were observed which were coincident with changes in dam operation policy.The study found that there has been no marked increase in N. aperta population growth following operation of the Pak-Mun dam. The analysis did indicate a large and statistically significant increase in population density immediately after the dam came into operation; however, this increase was not persistent. The study has provided the first vital baseline data on N. aperta population behavior near to the Pak-Mun dam and suggests that the operation policy of the dam may have an impact on snail population density. Nevertheless, additional studies are required for other N. aperta populations in the Mun River and for an extended time series, to confirm or refine the findings of this work.

pix-1 controls early elongation in parallel with mel-11 and let-502 in Caenorhabditis elegans.

Science.gov (United States)

Martin, Emmanuel; Harel, Sharon; Nkengfac, Bernard; Hamiche, Karim; Neault, Mathieu; Jenna, Sarah

2014-01-01

Cell shape changes are crucial for metazoan development. During Caenorhabditis elegans embryogenesis, epidermal cell shape changes transform ovoid embryos into vermiform larvae. This process is divided into two phases: early and late elongation. Early elongation involves the contraction of filamentous actin bundles by phosphorylated non-muscle myosin in a subset of epidermal (hypodermal) cells. The genes controlling early elongation are associated with two parallel pathways. The first one involves the rho-1/RHOA-specific effector let-502/Rho-kinase and mel-11/myosin phosphatase regulatory subunit. The second pathway involves the CDC42/RAC-specific effector pak-1. Late elongation is driven by mechanotransduction in ventral and dorsal hypodermal cells in response to body-wall muscle contractions, and involves the CDC42/RAC-specific Guanine-nucleotide Exchange Factor (GEF) pix-1, the GTPase ced-10/RAC and pak-1. In this study, pix-1 is shown to control early elongation in parallel with let-502/mel-11, as previously shown for pak-1. We show that pix-1, pak-1 and let-502 control the rate of elongation, and the antero-posterior morphology of the embryos. In particular, pix-1 and pak-1 are shown to control head, but not tail width, while let-502 controls both head and tail width. This suggests that let-502 function is required throughout the antero-posterior axis of the embryo during early elongation, while pix-1/pak-1 function may be mostly required in the anterior part of the embryo. Supporting this hypothesis we show that low pix-1 expression level in the dorsal-posterior hypodermal cells is required to ensure high elongation rate during early elongation.

Iron deficiency anemia interfering the diagnosis of compound heterozygosity for Hb constant spring and Hb Paksé: The first case report.

Science.gov (United States)

Chiasakul, Thita; Uaprasert, Noppacharn

2018-01-01

Diagnosis of thalassemia or hemoglobinopathy concomitant with iron deficiency anemia (IDA) is challenging. We report a case of 43-year-old female whose diagnosis of compound heterozygosity for hemoglobin Constant Spring (HbCS) and Hb Paksé became apparent after the treatment of IDA. Prior to treatment, Hb analysis using isoelectric focusing (IEF) showed HbA 95.6%, HbA 2 2.7%, and HbCS 1.7% compatible with heterozygous HbCS. After 4 months of oral iron therapy resulting in an improved Hb level, her HbCS level was substantially increased to 8.7% on IEF suggesting homozygous HbCS. Subsequent DNA analysis using multiplex amplification refractory mutation system analysis revealed compound heterozygosity for HbCS and Hb Paksé. This case demonstrated that IDA can significantly reduce HbCS/Hb Paksé levels and probably mask the diagnosis of homozygous HbCS, homozygous Hb Paksé or the compound heterozygosity for both hemoglobinopathies by hemoblogin analysis. The test should be repeated after resolution of IDA, or molecular testing should be performed to confirm the diagnosis. © 2017 Wiley Periodicals, Inc.

Safer nuclear power. Strengthening training for operational safety at Paks nuclear power plant - Hungary

International Nuclear Information System (INIS)

2003-01-01

For a nuclear power plant, safety must always be paramount. There can be no compromise on safety to meet production targets or to reduce costs. For any reactor, and in particular where older type reactors are in place, their operational safety can be enhanced by upgrading the training of personnel responsible for operating and maintaining the plant. The Department of Technical Co-operation is sponsoring a programme with technical support from the Nuclear Energy and Nuclear Safety Departments to help improve facilities at the PAKS plant in Hungary and establish self sufficiency in training to the highest international standards for all levels of nuclear power plant manpower. The Model Project described will have a direct impact on the improvement of operational safety and performance at PAKS NPP. It will lead to a more efficient use of resources which in turn will result in lower electricity generation costs. The impact of the project is not expected to be limited to Hungary. WWER reactors are common in Eastern Europe and provide one third to one half of the electricity supply to the region. The training programmes and facilities at PAKS offer a possibility in the future to provide training to experts from other countries operating WWER units and serve as a model to be emulated. Slovakia and the Czech Republic have already expressed interest in using the PAKS experience

COMPARISON OF PAI AND PAK: AN OVERVIEW OF VALUES OF MULTICULTURAL EDUCATION

Directory of Open Access Journals (Sweden)

Ali Murfi

2015-06-01

Full Text Available This research to reveal comparative Islamic Education (PAI with Christian Education (PAK through a textbook’s lesson in terms of content values of multicultural education. The comparative’s analysis includes three aspects, differences, similarities, and common platform. The results showed that substance of values of multicultural education contained in the textbooks have much in similarities which eventually became common platform both than the differences that exist, so that PAI and PAK should move bind themselves to each other in one joint effort to raise the noble values of multicultural, where both scientific traditions stand firm through efforts integration and comprehension charge of teaching materials.

Development and installation of a new on-line plant safety monitoring system for the Paks VVER-440 units

International Nuclear Information System (INIS)

Vegh, J.; Major, C.; Buerger, L.; Lipcsei, S.; Horvath, C.; Kapocs, G.; Eiler, J.; Hornaes, A.; Hulsund, J.E.

2000-01-01

The paper describes the architecture, modules, algorithms and human-machine interface of a new operator support system (OSS), which is integrated into the new, reconstructed Paks NPP plant computers. The main task of the new OSS is to perform continuous plant safety monitoring and assessment, it has the following basic functions: on-line evaluation and presentation of critical safety function (CSF) status trees, continuous evaluation and presentation of the actual safety status of the plant, displaying and browsing the new symptom-oriented EOPs, automatic displaying of those process signals which are quoted in the EOPs. The first version of the new operator support system was connected to the Paks NPP full scope simulator in October 1999. This configuration was later successfully applied for the simulator testing of the new symptom-oriented EOP set for the Paks NPP in November 1999. The installation process was continued in 2000: the new system started its operation on Unit 2 (June) and on Unit 1 (August), together with the reconstructed, new PCS. (author)

Slit stimulation recruits Dock and Pak to the roundabout receptor and increases Rac activity to regulate axon repulsion at the CNS midline.

Science.gov (United States)

Fan, Xueping; Labrador, Juan Pablo; Hing, Huey; Bashaw, Greg J

2003-09-25

Drosophila Roundabout (Robo) is the founding member of a conserved family of repulsive axon guidance receptors that respond to secreted Slit proteins. Here we present evidence that the SH3-SH2 adaptor protein Dreadlocks (Dock), the p21-activated serine-threonine kinase (Pak), and the Rac1/Rac2/Mtl small GTPases can function during Robo repulsion. Loss-of-function and genetic interaction experiments suggest that limiting the function of Dock, Pak, or Rac partially disrupts Robo repulsion. In addition, Dock can directly bind to Robo's cytoplasmic domain, and the association of Dock and Robo is enhanced by stimulation with Slit. Furthermore, Slit stimulation can recruit a complex of Dock and Pak to the Robo receptor and trigger an increase in Rac1 activity. These results provide a direct physical link between the Robo receptor and an important cytoskeletal regulatory protein complex and suggest that Rac can function in both attractive and repulsive axon guidance.

Description of training activities and re-training system for nuclear professionals at the Paks Nuclear Power Plant, Hungary

International Nuclear Information System (INIS)

Jambrich, I.; Trampus, P.

1993-01-01

The nuclear power units of Paks, Hungary, have always been operated by Hungarian personnel, from the very beginning. The operator staff of unit 1 acquired its knowledge primarily outside of the country, but since 1983 the overall training process has been run entirely in Hungary, in Paks. This report gives details of present system of training programme in Hungary. The system of training for professionals builds up in vertically linked modules and is job oriented. It begins with theoretical training, followed by programmed on-the-job training which must successfully be finished before a release onto in-company or authority licensing exams for individual job performance

SparsePak: A Formatted Fiber Field Unit for the WIYN Telescope Bench Spectrograph. I. Design, Construction, and Calibration

NARCIS (Netherlands)

Bershady, Matthew A.; Andersen, David R.; Harker, Justin; Ramsey, Larry W.; Verheijen, Marc A. W.

2004-01-01

We describe the design and construction of a formatted fiber field unit, SparsePak, and characterize its optical and astrometric performance. This array is optimized for spectroscopy of low surface brightness extended sources in the visible and near-infrared. SparsePak contains 82, 4.7" fibers

Substance P induces rapid and transient membrane blebbing in U373MG cells in a p21-activated kinase-dependent manner.

Directory of Open Access Journals (Sweden)

John Meshki

Full Text Available U373MG astrocytoma cells endogenously express the full-length neurokinin 1 receptor (NK1R. Substance P (SP, the natural ligand for NK1R, triggers rapid and transient membrane blebbing and we report that these morphological changes have different dynamics and intracellular signaling as compared to the changes that we have previously described in HEK293-NK1R cells. In both cell lines, the SP-induced morphological changes are Gq-independent, and they require the Rho, Rho-associated coiled-coil kinase (ROCK signaling pathway. Using confocal microscopy we have demonstrated that tubulin is phosphorylated subsequent to cell stimulation with SP and that tubulin accumulates inside the blebs. Colchicine, a tubulin polymerization inhibitor, blocked SP-induced blebbing in U373MG but not in HEK293-NK1R cells. Although p21-activated kinase (PAK is expressed in both cell lines, SP induced rapid phosphorylation of PAK in U373MG, but failed to phosphorylate PAK in HEK293-NK1R cells. The cell-permeable Rho inhibitor C3 transferase inhibited SP-induced PAK phosphorylation, but the ROCK inhibitor Y27632 had no effect on PAK phosphorylation, suggesting that Rho activates PAK in a ROCK-independent manner. Our study demonstrates that SP triggers rapid changes in cell morphology mediated by distinct intracellular signaling mechanisms in U373MG versus HEK293-NK1R cells.

Stereoselective uptake and distribution of the chiral neonicotinoid insecticide, Paichongding, in Chinese pak choi (Brassica campestris ssp. chinenesis)

International Nuclear Information System (INIS)

Wang, Haiyan; Yang, Zhen; Liu, Ruyang; Fu, Qiuguo; Zhang, Sufen; Cai, Zhiqiang; Li, Juying; Zhao, Xiaojun; Ye, Qingfu; Wang, Wei; Li, Zhong

2013-01-01

Highlights: • Absorption of foliar applied Paichongding by pak choi was not stereoselective. • Foliar uptake and downward transport of Paichongding were both found in pak choi. • Enantioselective and epimer-selective root uptake were observed for Paichongding. • Foliage/root uptake showed diastereoselective transport of Paichongding epimers. • The SR and RS are more easily taken up by roots and accumulated in edible parts. -- Abstract: Neonicotinoid chiral insecticidal Paichongding is a promising substitute for the widely used imidacloprid. Four stereoisomers of Paichongding, 5R,7R, 5S,7S, 5S,7R and 5R,7S, were employed in both foliage and roots of Chinese pak choi to investigate their stereoselective uptake and distribution in pak choi. Results showed that after foliar application, no stereoselective absorption into pak-choi plants was observed among the enantiomers. Total absorptions were 35.40% of the applied amount for 5R,7R, 36.66% for 5S,7S, 36.80% for 5S,7R and 38.20% for 5R,7S at 96 HAT. The translocation of the four absorbed stereoisomers within pak choi occurred both acropetally and basipetally and the transport of 14 C from enantiomers 5R,7R and 5S,7S were significantly higher than for 5R,7S and 5S,7R. Significant stereoselective translocation inside plants was observed between Paichongding epimers. Total root uptake reached 16.49–19.85% for 5R,7R and 5S,7S, and 24.57–28.82% for 5S,7R and 5R,7S at 144 HAT. Both enantioselective and diastereoselective root uptake into pak-choi occurred between the four stereoisomers. The 5R,7S and 5S,7R enantiomers were more readily uptaken by the roots than 5R,7R and 5S,7S and accumulated in the edible leaves. These results will help to develop an understanding of Paichongding using only the target-active enantiomer of pesticides

Stereoselective uptake and distribution of the chiral neonicotinoid insecticide, Paichongding, in Chinese pak choi (Brassica campestris ssp. chinenesis)

Energy Technology Data Exchange (ETDEWEB)

Wang, Haiyan; Yang, Zhen; Liu, Ruyang; Fu, Qiuguo; Zhang, Sufen; Cai, Zhiqiang; Li, Juying; Zhao, Xiaojun [Institute of Nuclear Agricultural Sciences, Key Laboratory of Nuclear Agricultural Sciences of Ministry of Agriculture and Zhejiang Province, Zhejiang University, Hangzhou 310029 (China); Ye, Qingfu, E-mail: qfye@zju.edu.cn [Institute of Nuclear Agricultural Sciences, Key Laboratory of Nuclear Agricultural Sciences of Ministry of Agriculture and Zhejiang Province, Zhejiang University, Hangzhou 310029 (China); Wang, Wei [Institute of Nuclear Agricultural Sciences, Key Laboratory of Nuclear Agricultural Sciences of Ministry of Agriculture and Zhejiang Province, Zhejiang University, Hangzhou 310029 (China); Li, Zhong, E-mail: lizhong@ecust.edu.cn [School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 (China)

2013-11-15

Highlights: • Absorption of foliar applied Paichongding by pak choi was not stereoselective. • Foliar uptake and downward transport of Paichongding were both found in pak choi. • Enantioselective and epimer-selective root uptake were observed for Paichongding. • Foliage/root uptake showed diastereoselective transport of Paichongding epimers. • The SR and RS are more easily taken up by roots and accumulated in edible parts. -- Abstract: Neonicotinoid chiral insecticidal Paichongding is a promising substitute for the widely used imidacloprid. Four stereoisomers of Paichongding, 5R,7R, 5S,7S, 5S,7R and 5R,7S, were employed in both foliage and roots of Chinese pak choi to investigate their stereoselective uptake and distribution in pak choi. Results showed that after foliar application, no stereoselective absorption into pak-choi plants was observed among the enantiomers. Total absorptions were 35.40% of the applied amount for 5R,7R, 36.66% for 5S,7S, 36.80% for 5S,7R and 38.20% for 5R,7S at 96 HAT. The translocation of the four absorbed stereoisomers within pak choi occurred both acropetally and basipetally and the transport of {sup 14}C from enantiomers 5R,7R and 5S,7S were significantly higher than for 5R,7S and 5S,7R. Significant stereoselective translocation inside plants was observed between Paichongding epimers. Total root uptake reached 16.49–19.85% for 5R,7R and 5S,7S, and 24.57–28.82% for 5S,7R and 5R,7S at 144 HAT. Both enantioselective and diastereoselective root uptake into pak-choi occurred between the four stereoisomers. The 5R,7S and 5S,7R enantiomers were more readily uptaken by the roots than 5R,7R and 5S,7S and accumulated in the edible leaves. These results will help to develop an understanding of Paichongding using only the target-active enantiomer of pesticides.

Vertical Population Gradients in NGC 891. I. ∇Pak Instrumentation and Spectral Data

Science.gov (United States)

Eigenbrot, Arthur; Bershady, Matthew A.

2018-02-01

We have measured vertical and radial stellar population gradients in NGC 891. We compare these gradients to those known for the Milky Way from studies of resolved stars. Optical spectroscopic measurements extend spatially from the disk midplane up to 2.6 {kpc} in height and out to a radius of 12 {kpc} on both sides of the galaxy. Data were acquired with ∇Pak, a variable-pitch fiber integral field unit (IFU) on the WIYN telescope. We describe the laboratory and on-sky performance of ∇Pak, as well as modifications to the standard observational and analysis procedures necessary to calibrate data taken with this unique IFU. ∇Pak has a mean throughput of 80% at 5500 \\mathringA . To achieve an estimated precision of 10% in light-weighted mean age and metallicity, we define a set of spatial apertures in radius and height in which spectra are binned to achieve a signal-to-noise ratio of ∼20 Å‑1. We use spectral indices to measure age, metallicity, and abundance, indicating that NGC 891's stellar populations have 0.2 7 {Gyr}) stellar populations at 0.4 {kpc}, roughly the scale height of the thin disk. We also find a slight trend toward younger populations at larger radii, consistent with flaring in an inside-out disk formation scenario. The vertical age gradient in NGC 891 is in remarkable qualitative agreement with a model for disk heating tuned to studies of the Milk Way’s solar cylinder.

Automatic closed-loop stereo-photogrammetric system for the Nuclear Power Station Paks

International Nuclear Information System (INIS)

Eoery, K.; Szabados, J.; Szerovay, A.

1982-01-01

The geodesic work for the NPS Paks project required an extensive modernization of traditional measuring techniques, besides the development of measuring devices and methods encompassing the complete procedure of data processing. Stereo-photogrammetry based on three-dimensional measuring technique plays an outstanding role in 'bulk work' required for measuring as well as in efficient technical data supply. A detailed analysis of the technical parameters is given concerning the interactive graphic and digital data processing and data base organizing system. After the description of the main types of process equipment system organization problems are discussed. The paper outlines research and testing tasks related to the practical application of the technology system of world standard, representing a unique solution in Hungarian relation. Finally, fields of application for the system in power station design are presented. (author)

Energy policy, economic and engineering issues of the extension of Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Aszodi, Attila; Boros, Ildiko; Kovacs, Arnold

2014-01-01

The four operating blocks of the Paks Nuclear Power Plant are of Russian design. They entered into operation three decades ago, between 1982 and 1987. In 2013 they produced 15 TWh out of the 42 TWh energy consumption of Hungary, that is they produced 36% of the energy demand. In the beginning of 2014 the Hungarian and the Russian governments signed the agreement on the extension of Paks site with building two new blocks, producing 1200 MW each. The paper summarizes the energy policy, engineering, safety and economic aspects of the extension. (TRA)

Composition and activity variations in bulk gas of drum waste packages of Paks NPP

International Nuclear Information System (INIS)

Molnar, M.; Palcsu, L.; Svingor, E.; Szanto, Zs.; Futo, I.; Ormai, P.

2001-01-01

To obtain reliable estimates of the quantities and rates of the gas production a series of measurements was carried out in drum waste packages generated and temporarily stored at the site of Paks Nuclear Power Plant (Paks NPP). Ten drum waste packages were equipped with sampling valves for repeated sampling. Nine times between 04/02/2000 and 19/07/2001 qualitative gas component analyses of bulk gases of drums were executed. Gas samples were delivered to the laboratory of the ATOMKI for tritium and radiocarbon content measurements.(author)

MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

International Nuclear Information System (INIS)

Wang, Zhigang; Zhang, Xiaoping; Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun; Zheng, Qi

2012-01-01

Highlights: ► MiR-145 targets a putative binding site in the 3′UTR of PAK4. ► MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. ► MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3′UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response.

Science.gov (United States)

Wang, Manyu; Chen, Pei-Yi; Wang, Chien-Hsiang; Lai, Tzu-Ting; Tsai, Pei-I; Cheng, Ying-Ju; Kao, Hsiu-Hua; Chien, Cheng-Ting

2016-10-01

In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ). In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD) houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.

Migration of itx (Isopropyl Thioxantone from Tetra Pak Bricks into Food

Directory of Open Access Journals (Sweden)

Sonja Jamnicki

2010-01-01

Full Text Available At the beginning of September 2005, itx, a photoinitiator used in uv cured ink, has been identified to have migrated from packaging to food products. Tetra Pak has identified the source of migration to be uv cured offset printing ink.The presence of itx in food packed in Tetra Pak bricks is the result of the contamination of the inner polyethylene layer of the box walls. itx can either migrate through the packaging material or it can reach the food by contact, for example, as a result of the print set-off phenomenon. Most likely, the transfer of itx was due to the physical contact between the printed outer layer with the inner layer of the packaging, whereby the ink or ink substance transfers from the print to the reverse of the adjacent sheet.Tetra Pak has committed itself to move away from this technology immediately and to use alternative printing technologies to ensure that there is no or minimal migration of itx or other substances from its packages.itx is still not on the eu’s negative list of banned substances in food nor does the World Health Organization (who categorize it as being detrimental to human health. After an investigation in the health risks of itx following the incident, the European Food Safety Authority (efsa concluded that the levels found in foods, “while undesirable, do not give cause for health concern.”

Migration of ITX (Isopropyl Thioxantone from Tetra Pak Bricks into Food

Directory of Open Access Journals (Sweden)

Tatjana Jamnicki

2010-06-01

Full Text Available At the beginning of September 2005, ITX, a photoinitiator used in uv cured ink, has been identified to have migrated from packaging to food products. Tetra Pak has identified the source of migration to be uv cured offset printing ink.The presence of ITX in food packed in Tetra Pak bricks is the result of the contamination of the inner polyethylene layer of the box walls. ITX can either migrate through the packaging material or it can reach the food by contact, for example, as a result of the print set-off phenomenon. Most likely, the transfer of ITX was due to the physical contact between the printed outer layer with the inner layer of the packaging, whereby the ink or ink substance transfers from the print to the reverse of the adjacent sheet.Tetra Pak has committed itself to move away from this technology immediately and to use alternative printing technologies to ensure that there is no or minimal migration of ITX or other substances from its packages.ITX is still not on the eu’s negative list of banned substances in food nor does the World Health Organization (WHO categorize it as being detrimental to human health. After an investigation in the health risks of ITX following the incident, the European Food Safety Authority (EFSA concluded that the levels found in foods, “while undesirable, do not give cause for health concern.”

MiR-145 regulates PAK4 via the MAPK pathway and exhibits an antitumor effect in human colon cells

Energy Technology Data Exchange (ETDEWEB)

Wang, Zhigang [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zhang, Xiaoping [Department of Nuclear Medicine, Shanghai 10th People' s Hospital, Tongji University School of Medicine (China); Yang, Zhili; Du, Hangxiang; Wu, Zhenqian; Gong, Jianfeng; Yan, Jun [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China); Zheng, Qi, E-mail: zhengqi1957@yahoo.com.cn [Department of General Surgery, Shanghai Jiaotong University Affiliated 6th People' s Hospital, Shanghai (China)

2012-10-26

Highlights: Black-Right-Pointing-Pointer MiR-145 targets a putative binding site in the 3 Prime UTR of PAK4. Black-Right-Pointing-Pointer MiR-145 played an important role in inhibiting cell growth by directly targeting PAK4. Black-Right-Pointing-Pointer MiR-145 may function as tumor suppressors. -- Abstract: MicroRNAs (miRNAs) are regulators of numerous cellular events; accumulating evidence indicates that miRNAs play a key role in a wide range of biological functions, such as cellular proliferation, differentiation, and apoptosis in cancer. Down-regulated expression of miR-145 has been reported in colon cancer tissues and cell lines. The molecular mechanisms underlying miR-145 and the regulation of colon carcinogenesis remain unclear. In this study, we investigated the levels of miR-145 in human colon cancer cells using qRT-PCR and found markedly decreased levels compared to normal epithelial cells. We identified PAK4 as a novel target of miR-145 using informatics screening. Additionally, we demonstrated that miR-145 targets a putative binding site in the 3 Prime UTR of PAK4 and that its abundance is inversely associated with miR-145 expression in colon cancer cells; we confirmed this relationship using the luciferase reporter assay. Furthermore, restoration of miR-145 by mimics in SW620 cells significantly attenuated cell growth in vitro, in accordance with the inhibitory effects induced by siRNA mediated knockdown of PAK4. Taken together, these findings demonstrate that miR-145 downregulates P-ERK expression by targeting PAK4 and leads to inhibition of tumor growth.

Example of an application of systematic approach to training. Paks NPP Ltd

International Nuclear Information System (INIS)

Bajor, L.

1998-01-01

In order to show a practical example of how Hungarian Maintenance program works implementation of SAT based training of primary circuit field operator is described in detail as implemented at Paks NPP

Seismic safety of Paks nuclear power plant

International Nuclear Information System (INIS)

Katona, T.

1993-01-01

An extensive program is underway at Paks NPP for evaluation of the seismic safety and for development of the necessary safety increasing measures. This program includes the following five measures: investigation of methods, regulations and techniques utilized for reassessment of seismic safety of operating NPPs and promoting safety; investigation of earthquake hazards; development of concepts for creating the seismic safety location of earthquake warning system; determination of dynamic features of systems and facilities determined by the concept, and preliminary evaluation of the seismic safety

Controlled composting of waste wood contaminated with PAH; Untersuchungen zur gesteuerten Rotte von mit polyzyklischen aromatischen Kohlenwasserstoffen (PAK) kontaminiertem Altholz

Energy Technology Data Exchange (ETDEWEB)

Ulbricht, H.

2002-07-01

The author investigated the potential and limits of microbial pollutant degradation in PAH-polluted waste wood by composting. The conditions in which autochthonic micro-organisms are able to decomposite the PAH contained in wood by solid phase fermentation were investigated. The focus was on phenanthrene, anthracene and pyrene, all of which are used as protective materials (disinfestants) for wood. The results were verified on contaminated waste wood, including an analytical investigations of decomposition of PAH of the EPA catalogue. Boundary conditions for achieving high rates of PAH decomposition were investigated. [German] Generelles Ziel der Arbeit war die Untersuchung der Moeglichkeiten und Grenzen des mikrobiellen Schadstoffabbaus in PAK-belastetem Altholz durch Kompostierung und die Pruefung auf Anwendbarkeit der Erkenntnisse in technischen Verfahren. In der vorliegenden Arbeit wurde untersucht, unter welchen Bedingungen die autochthonen Mikroorganismen in der Lage sind, an das Holz gebundene PAK durch Feststofffermentation abzubauen. Als Schwerpunkt wurde zunaechst der Abbau der im zum Holzschutz verwendetem Teeroel vorkommenden PAK Phenanthren, Anthracen und Pyren untersucht. Eine Verifizierung der Ergebnisse erfolgte mit real kontaminiertem Altholz, dabei wurde der Abbau der PAK der EPA-Liste analytisch verfolgt. Es sollten geeignete Randbedingungen gefunden werden, um im Festphasensystem hohe Abbauraten der PAK zu erreichen. (orig.)

Dbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response.

Directory of Open Access Journals (Sweden)

Manyu Wang

2016-10-01

Full Text Available In response to environmental and physiological changes, the synapse manifests plasticity while simultaneously maintains homeostasis. Here, we analyzed mutant synapses of henji, also known as dbo, at the Drosophila neuromuscular junction (NMJ. In henji mutants, NMJ growth is defective with appearance of satellite boutons. Transmission electron microscopy analysis indicates that the synaptic membrane region is expanded. The postsynaptic density (PSD houses glutamate receptors GluRIIA and GluRIIB, which have distinct transmission properties. In henji mutants, GluRIIA abundance is upregulated but that of GluRIIB is not. Electrophysiological results also support a GluR compositional shift towards a higher IIA/IIB ratio at henji NMJs. Strikingly, dPAK, a positive regulator for GluRIIA synaptic localization, accumulates at the henji PSD. Reducing the dpak gene dosage suppresses satellite boutons and GluRIIA accumulation at henji NMJs. In addition, dPAK associated with Henji through the Kelch repeats which is the domain essential for Henji localization and function at postsynapses. We propose that Henji acts at postsynapses to restrict both presynaptic bouton growth and postsynaptic GluRIIA abundance by modulating dPAK.

Example of an application of systematic approach to training. Paks NPP Ltd

International Nuclear Information System (INIS)

Szabo, Z.

1998-01-01

In order to show a practical example of how Hungarian Maintenance program works implementation of SAT based training of primary circuit valve maintenance senior mechanic is described and explained in detail as done at Paks NPP

Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group by Methyl Jasmonate

Directory of Open Access Journals (Sweden)

Moo Jung Kim

2017-05-01

Full Text Available Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates, indole glucosinolate concentrations (153–229% and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in “Chinese cabbage” in the control group (32.5 µmol/g DW, but indole glucosinolates increased the greatest in “Asian” when treated with MeJA.

Activity release from damaged fuel during the Paks-2 cleaning tank incident in the spent fuel storage pool

International Nuclear Information System (INIS)

Hozer, Zoltan; Szabo, Emese; Pinter, Tamas; Varju, Ilona Baracska; Bujtas, Tibor; Farkas, Gabor; Vajda, Nora

2009-01-01

During crud removal operations the integrity of 30 fuel assemblies was lost at high temperature at the unit No. 2 of the Paks NPP. Part of the fission products was released from the damaged fuel into the coolant of the spent fuel storage pool. The gaseous fission products escaped through the chimney from the reactor hall. The volatile and non-volatile materials remained mainly in the coolant and were collected on the filters of water purification system. The activity release from damaged fuel rods during the Paks-2 cleaning tank incident was estimated on the basis of coolant activity concentration measurements and chimney activity data. The typical release rate of noble gases, iodine and caesium was 1-3%. The release of non-volatile fission products and actinides was also detected.

Activity release from damaged fuel during the Paks-2 cleaning tank incident in the spent fuel storage pool

Energy Technology Data Exchange (ETDEWEB)

Hozer, Zoltan, E-mail: hozer@aeki.kfki.h [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest 114, P.O. Box 49 (Hungary); Szabo, Emese [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest 114, P.O. Box 49 (Hungary); Pinter, Tamas; Varju, Ilona Baracska; Bujtas, Tibor; Farkas, Gabor [Nuclear Power Plant Paks, H-7031 Paks, P.O. Box 71 (Hungary); Vajda, Nora [Institute of Nuclear Techniques, Budapest University of Technology and Economics, H-1521 Budapest, Muegyetem rakpart 9 (Hungary)

2009-07-01

During crud removal operations the integrity of 30 fuel assemblies was lost at high temperature at the unit No. 2 of the Paks NPP. Part of the fission products was released from the damaged fuel into the coolant of the spent fuel storage pool. The gaseous fission products escaped through the chimney from the reactor hall. The volatile and non-volatile materials remained mainly in the coolant and were collected on the filters of water purification system. The activity release from damaged fuel rods during the Paks-2 cleaning tank incident was estimated on the basis of coolant activity concentration measurements and chimney activity data. The typical release rate of noble gases, iodine and caesium was 1-3%. The release of non-volatile fission products and actinides was also detected.

The Paks Nuclear Power Station

International Nuclear Information System (INIS)

Erdosi, N.; Szabo, L.

1978-01-01

As the first stage in the construction of the Paks Nuclear Power Station, two units of 440 MW(e) each will be built. They are operated with two coolant loops each. The reactor units are VVER 440 type water-moderated PWR type heterogeneous power reactors designed in the Soviet Union and manufactured in Czechoslovakia. Each unit operates two Soviet-made K-220-44 steam turbines and Hungarian-made generators of an effective output of 220 MW. The output of the transformer units - also of Hungarian made - is 270 MVA. The radiation protection system of the nuclear power station is described. Protection against system failures is accomplished by specially designed equipment and security measures especially within the primary circuit. Some data on the power station under construction are given. (R.P.)

Adhesion inhibition of F1C-fimbriated Escherichia coli and Pseudomonas aeruginosa PAK and PAO by multivalent carbohydrate ligands.

Science.gov (United States)

Autar, Reshma; Khan, A Salam; Schad, Matthias; Hacker, Jörg; Liskamp, Rob M J; Pieters, Roland J

2003-12-05

In order to evaluate their inhibition of bacterial adhesion, the carbohydrate sequences GalNAcbeta1-->4Gal and GalNAcbeta1-->4Galbeta1-->4Glc were synthesized. The disaccharide was conjugated to dendrons based on the 3,5-di-(2-aminoethoxy)-benzoic acid branching unit to yield di- and tetravalent versions of these compounds. A divalent compound was also prepared that had significantly longer spacer arms. Relevant monovalent compounds were prepared for comparison. Their anti-adhesion properties against F1C-fimbriated uropathogenic Escherichia coli were evaluated in an ELISA-type assay by using a recombinant strain and also by using Pseudomonas aeruginosa strains PAO and PAK. Adhesion inhibition was observed in all cases, and multivalency effects of up to one order of magnitude were observed. The combination of spacer and multivalency effects led to a 38-fold increase in the potency of a divalent inhibitor with long spacer arms towards the PAO strain when compared with the free carbohydrate.

A conceptual magnetic fabric development model for the Paks loess in Hungary

DEFF Research Database (Denmark)

Bradák, B.; Ujvari, Gabor; Seto, Y.

2018-01-01

We describe magnetic fabric and depositional environments of aeolian (loess) deposits from Paks, Hungary, and develop a novel, complex conceptual sedimentation model based on grain size and low-field magnetic susceptibility anisotropy data. A plot of shape factor (magnetic fabric parameter) and d...

Induced Production of 1-Methoxy-indol-3-ylmethyl Glucosinolate by Jasmonic Acid and Methyl Jasmonate in Sprouts and Leaves of Pak Choi (Brassica rapa ssp. chinensis

Directory of Open Access Journals (Sweden)

Hansruedi Glatt

2013-07-01

Full Text Available Pak choi plants (Brassica rapa ssp. chinensis were treated with different signaling molecules methyl jasmonate, jasmonic acid, linolenic acid, and methyl salicylate and were analyzed for specific changes in their glucosinolate profile. Glucosinolate levels were quantified using HPLC-DAD-UV, with focus on induction of indole glucosinolates and special emphasis on 1-methoxy-indol-3-ylmethyl glucosinolate. Furthermore, the effects of the different signaling molecules on indole glucosinolate accumulation were analyzed on the level of gene expression using semi-quantitative realtime RT-PCR of selected genes. The treatments with signaling molecules were performed on sprouts and mature leaves to determine ontogenetic differences in glucosinolate accumulation and related gene expression. The highest increase of indole glucosinolate levels, with considerable enhancement of the 1-methoxy-indol-3-ylmethyl glucosinolate content, was achieved with treatments of sprouts and mature leaves with methyl jasmonate and jasmonic acid. This increase was accompanied by increased expression of genes putatively involved in the indole glucosinolate biosynthetic pathway. The high levels of indole glucosinolates enabled the plant to preferentially produce the respective breakdown products after tissue damage. Thus, pak choi plants treated with methyl jasmonate or jasmonic acid, are a valuable tool to analyze the specific protection functions of 1-methoxy-indole-3-carbinole in the plants defense strategy in the future.

Essential oil of Pinus koraiensis inhibits cell proliferation and migration via inhibition of p21-activated kinase 1 pathway in HCT116 colorectal cancer cells.

Science.gov (United States)

Cho, Sun-Mi; Lee, Eun-Ok; Kim, Sung-Hoon; Lee, Hyo-Jeong

2014-07-30

The essential oil of Pinus koraiensis (EOPK) is biologically active compound obtained from the leaves of P. koraiensis. The goal of this study was to investigate the anti-cancer mechanism of EOPK in HCT116 colorectal cancer cells. HCT116 cell proliferation was assessed by conducting crystal violet and BrdU assays. To assess the effects of EOPK on cell migration, we performed a wound-healing assay. Further, the contribution of PAK1 to EOPK-induced AKT and extracellular signal-regulated kinase (ERK) suppression was assessed by siRNA-mediated PAK1 knockdown. Changes to the expression and phosphorylation of PAK1 and its effectors were determined by western blotting, and changes to the actin cytoskeleton were determined by performing an immunofluorescence assay. EOPK significantly decreased HCT116 cell proliferation and migration, and induced G1 arrest without affecting normal cells. Additionally, EOPK suppressed the expression of PAK1, and decreased ERK and AKT phosphorylation in HCT116 cells. Finally, EOPK suppressed β-catenin, cyclin D1, and CDK4/6 expression. Our studies indicate that EOPK significantly reduced proliferation and migration of colorectal cancer cells. Furthermore, EOPK suppressed PAK1 expression in a dose-dependent manner, and this suppression of PAK1 led to inhibition of ERK, AKT, and β-catenin activities. Our findings suggest that EOPK exerts its anticancer activity via the inhibition of PAK1 expression, suggesting it may be a potent chemotherapeutic agent for colorectal cancer.

Comparison of chromatography and Sep-pak methods for estimating the radiochemical purity of I-123 and I-131 labelled meta-iodobenzylguanidine (mIBG), synthesised in house

International Nuclear Information System (INIS)

Kumar, V.

1998-01-01

Full text: Radioiodine (I-123 or I-131) labelled mlBG has been prepared routinely in-house in a number of radiopharmacy laboratories. The radiochemical purity can be estimated by several methods. Available literature suggests that the results of chronatographic analysis are comparable with electrophoresis and high pressure liquid chromatography (HPLC) methods which are considered as gold-standard procedures. However, due to the cost involved with these equipments most of the radiopharmacy laboratories are not fortunate enough to have them. The present study compares the validity of reverse-phase Sep-pak cartridge method against chromatographic technique. We analysed twenty four preparations of mIBG by both Sep-pak and chromatography methods (20 batches of I-123 mD3G and 4 batches of I-131 mIBG). Chromatographic analysis, which takes >2hrs, was performed with Whatman No 1/ n-butanol: acetic acid: water (60:15:25 v/v) and the activity associated with the peaks for free iodine and I-123 mD3G were measured. Sep-pak cartridge method, which takes less than 10 min, was performed as follows: the cartridge was activated by injecting 5 mL ethanol (200% pure) followed by flushing with 5mL distilled water. A sample (0.1mL) of radioiodine labelled mD3G was applied to the column and was eluted with 5mL distilled water. Subsequently two aliquots of 5mL solution containing tetrahydrofuran: (0.1M) sodium dihydrogen phosphate (25:75v/v) were passed through and the activity in each elute was measured. Analysing the results by Student's paired t-test for I-123 mlBG using the Sep-pak method gave a mean + SD of 98.8+ 0.6 % which correlated well (r 2 = 0.780) with the results obtained by the chromatographic method 99.3+0.5% (p <0.05). The results obtained for free I-123 by the two methods were 1.09 + 0.56% and 0.6 + 0.5% (p <0.05) respectively. The parameters did not differ significantly when I-131, instead of I-123, was used to synthesise mIBG. The results clearly indicate that the Sep-pak

Waste Cellulose from Tetra Pak Packages as Reinforcement of Cement Concrete

Directory of Open Access Journals (Sweden)

Gonzalo Martínez-Barrera

2015-01-01

Full Text Available The development of the packaging industry has promoted indiscriminately the use of disposable packing as Tetra Pak, which after a very short useful life turns into garbage, helping to spoil the environment. One of the known processes that can be used for achievement of the compatibility between waste materials and the environment is the gamma radiation, which had proved to be a good tool for modification of physicochemical properties of materials. The aim of this work is to study the effects of waste cellulose from Tetra Pak packing and gamma radiation on the mechanical properties of cement concrete. Concrete specimens were elaborated with waste cellulose at concentrations of 3, 5, and 7 wt% and irradiated at 200, 250, and 300 kGy of gamma dose. The results show highest improvement on the mechanical properties for concrete with 3 wt% of waste cellulose and irradiated at 300 kGy; such improvements were related with the surface morphology of fracture zones of cement concrete observed by SEM microscopy.

Failed (leaking) spent fuel management and storage in the Paks NPP

International Nuclear Information System (INIS)

Burjan, T.

2011-01-01

At the cycle 22, unit 4, Paks NPP the fissile contents raised irregularly in the water of the primary circuit. At the end of the cycle sipping tests were performed for the entire core to find out the leaking fuel assembly primarily responsible for this phenomenon. The identified leaking assembly temporarily was placed in the Spent Fuel Relaxing Pool. For measuring environmental impact of leaking assemblies an investigation program was developed and implemented. The assessment covered the following: effects of the leaking fuel on the water of relaxing pool and on the gaseous emissions in case open storage; in case when the leaking cassette is in a special hermetical storage case, how much gas is collected in the locked case and what is its composition; how to change the measured sipping test signal depending on relaxing time of leaking fuel cassettes. Based on the evaluation of the investigation program results the NPP modified the operational instructions for the treatment and storage of failed fuel assemblies. (author)

Vimentin is involved in regulation of mitochondrial motility and membrane potential by Rac1

Directory of Open Access Journals (Sweden)

Elena A. Matveeva

2015-10-01

Full Text Available In this study we show that binding of mitochondria to vimentin intermediate filaments (VIF is regulated by GTPase Rac1. The activation of Rac1 leads to a redoubling of mitochondrial motility in murine fibroblasts. Using double-mutants Rac1(G12V, F37L and Rac1(G12V, Y40H that are capable to activate different effectors of Rac1, we show that mitochondrial movements are regulated through PAK1 kinase. The involvement of PAK1 kinase is also confirmed by the fact that expression of its auto inhibitory domain (PID blocks the effect of activated Rac1 on mitochondrial motility. The observed effect of Rac1 and PAK1 kinase on mitochondria depends on phosphorylation of the Ser-55 of vimentin. Besides the effect on motility Rac1 activation also decreases the mitochondrial membrane potential (MMP which is detected by ∼20% drop of the fluorescence intensity of mitochondria stained with the potential sensitive dye TMRM. One of important consequences of the discovered regulation of MMP by Rac1 and PAK1 is a spatial differentiation of mitochondria in polarized fibroblasts: at the front of the cell they are less energized (by ∼25% than at the rear part.

Rapid synthesis of maleimide functionalized fluorine-18 labeled prosthetic group using "radio-fluorination on the Sep-Pak" method.

Science.gov (United States)

Basuli, Falguni; Zhang, Xiang; Jagoda, Elaine M; Choyke, Peter L; Swenson, Rolf E

2018-03-25

Following our recently published fluorine-18 labeling method, "Radio-fluorination on the Sep-Pak", we have successfully synthesized 6-[ 18 F]fluoronicotinaldehyde by passing a solution (1:4 acetonitrile: t-butanol) of its quaternary ammonium salt precursor, 6-(N,N,N-trimethylamino)nicotinaldehyde trifluoromethanesulfonate (2), through a fluorine-18 containing anion exchange cartridge (PS-HCO 3 ). Over 80% radiochemical conversion was observed using 10 mg of precursor within 1 minute. The [ 18 F]fluoronicotinaldehyde ([ 18 F]5) was then conjugated with 1-(6-(aminooxy)hexyl)-1H-pyrrole-2,5-dione to prepare the fluorine-18 labeled maleimide functionalized prosthetic group, 6-[ 18 F]fluoronicotinaldehyde O-(6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexyl) oxime, 6-[ 18 F]FPyMHO ([ 18 F]6). The current Sep-Pak method not only improves the overall radiochemical yield (50 ± 9%, decay-corrected, n = 9) but also significantly reduces the synthesis time (from 60-90 minutes to 30 minutes) when compared with literature methods for the synthesis of similar prosthetic groups. Published 2018. This article is a U.S. Government work and is in the public domain in the USA.

Paks shows the way towards good operating practices

International Nuclear Information System (INIS)

Anon.

1989-01-01

The Paks-3 unit in Hungary was the first VVER (Soviet designed Pressurized Water Reactor) to be scrutinized by an International Atomic Energy Agency Operational Safety Analysis Review Team. A number of examples of good operational practice were noted. Those reported here include the cleanliness of the plant, the management attitude to training, early detection of and action to correct problems as they arise, an accident avoidance policy, a back-up research and development programme, and the provision of computer-based assistance to the operator to present operational data in an easily comprehensible form. (U.K.)

Análise de crescimento e produtividade do pak choi cultivado sob diferentes doses de nitrogênio

Directory of Open Access Journals (Sweden)

Janaína Dartora

2013-08-01

Full Text Available O objetivo deste trabalho foi avaliar a influência de diferentes doses de nitrogênio no crescimento e produtividade do pak choi. O experimento foi conduzido, em cultivo protegido, de outubro a novembro de 2007, em Marechal Cândido Rondon, PR. O delineamento experimental foi de blocos casualizados, com cinco tratamentos (0, 60, 105, 150 e 195 kg ha-1 de N e quatro repetições. O nitrogênio foi aplicado em três diferentes épocas (transplantio, 7 e 14 dias após o transplantio. Foram realizadas cinco coletas das plantas, semanalmente, avaliando-se a produção de massa da matéria seca e área foliar, para obtenção das taxas de crescimento absoluto e relativo, taxa assimilatória líquida, razão de área foliar e área foliar específica. Na colheita, foram avaliados altura da planta, diâmetro e matéria fresca da parte aérea e produtividade. Incrementos na adubação nitrogenada até a dose de 195 kg ha-1 proporcionam incrementos no crescimento e produtividade do pak choi.

Impact of Heat-Shock Treatment on Yellowing of Pak Choy Leaves

Institute of Scientific and Technical Information of China (English)

WANG Xiang-yang; SHEN Lian-qing; YUAN Hai-na

2004-01-01

The physiological mechanism of maintaining the green colour of pak choy leaves (Brassica rapa var chinensis) with heat-shock treatment was studied. Chlorophyll in the outer leaves of pak choy degraded rapidly during storage at ambient temperature (20 ± 2℃), a slight yellow appeared. Heat-shock treatment (46- 50℃) had a mild effect on maintaining the green colour of outer leaves. Normal chlorophyll degradation was associated with a binding of chlorophyll with chlorophyll-binding-protein preceding chlorophyll breakdown.Heat-shock treatment was found to reduce the binding-capacity between chlorophyllbinding-protein and chlorophyll. In the chlorophyll degradation pathway, pheide dioxygenase was synthesized during leaf senescence which was considered to be a key enzyme in chlorophyll degradation. Activity of this enzyme was reduced following heat-shock treatment, which might explain the observed reduction in chlorophyll breakdown. Two groups of heat-shock proteins were detected in treated leaves, the first group containing proteins from 54KDa to 74 Kda, and the second group contained proteins from 15 KDa to 29KDa. Heat-shock treatment was also found to retard the decline of glucose and fructose (the main energy substrates) of outer leaves.

Pollution and pollution tolerance in the case of polycyclic aromatic hydrocarbons (PAH); Belastung durch Polyzyklische aromatische Kohlenwasserstoffe (PAK)

Energy Technology Data Exchange (ETDEWEB)

Renger, M.; Mekiffer, B. [Technische Univ. Berlin (Germany). Inst. fuer Oekologie-Bodenkunde

1997-12-31

The purpose of the present follow-up project was to examine the contamination with polycyclic aromatic hydrocarbons (PAH) of different anthropogenic urban soils including clay soils containing demolition waste, household waste, ash, and residues from a coking plant. A further task was to analyse, or infer from other part-projects, standard soil parameters such as organic carbon content, pH, and anion levels in order to clarify any relationships between PAH contamination and the more easily determinable soil characteristics. Furthermore, the sorption behaviour for PAH of selected anthropogenic urban soils was to be characterised by means of batch experiments. [Deutsch] Im Rahmen des Anschlussvorhabens sollte die Kontamination von anthropogenen Stadtboeden- darunter Truemmerschutt-, Hausmuell-, Asche- sowie Kokereilehmboden- durch polyzyklische aromatische Kohlenwasserstoffe (PAK) untersucht werden. Zusaetzlich sollten die bodenkundlichen Standardparameter Corg, pH-Wert, Anionengehalte und KAKpot analysiert bzw. von den anderen Teilvorhaben uebernommen werden, um Zusammenhaenge zwischen der PAK-Kontamination und relativ leicht zu bestimmenden bodenkundlichen Kennwerten klaeren zu koennen. Das Sorptionsverhalten ausgewaehlter anthropogener Stadtboeden fuer PAK sollte durch Batchversuche charakterisiert werden. (orig./SR)

Analysis of a buried pipeline at WWER-440/213 Paks NPP

International Nuclear Information System (INIS)

1999-01-01

According to regulations, all safety structures of a NPP must be designed to withstand loads induced by earthquakes. This applies to safety related underground piping systems. These structures are typically embedded in about 2-3 m of layered soil, and sometimes protected by concrete slabs resting on the ground surface. A rigorous solution for the dynamic response of such a structure would require accounting for nonlinear and three dimensional effects. A non-linear analysis is possible by using specialized computer codes and material models to account for non-linear behaviour of the soil. The aim of this paper was to reanalyze the pipeline of Paks NPP in order to demonstrate its dynamic behaviour interacting with the soil and the connected buildings as well as to determine the dynamic responses and the stresses in typical regions of the pipeline. To perform the numerical analysis a three dimensional finite element code (SSASSI/S) based on 'flexible volume method' was applied

Numerical analyses of an ex-core fuel incident: Results of the OECD-IAEA Paks Fuel Project

Energy Technology Data Exchange (ETDEWEB)

Hozer, Z., E-mail: hozer@aeki.kfki.h [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary); Aszodi, A. [BME NTI Budapest (Hungary); Barnak, M. [IVS, Trnava (Slovakia); Boros, I. [BME NTI Budapest (Hungary); Fogel, M. [VUJE, Trnava (Slovakia); Guillard, V. [IRSN, Cadarache (France); Gyori, Cs. [ITU, EU, Karlsruhe (Germany); Hegyi, G. [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary); Horvath, G.L. [VEIKI, Budapest (Hungary); Nagy, I. [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary); Junninen, P. [VTT, Espoo (Finland); Kobzar, V. [KI, Moscow (Russian Federation); Legradi, G. [BME NTI Budapest (Hungary); Molnar, A. [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary); Pietarinen, K. [VTT, Espoo (Finland); Perneczky, L. [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary); Makihara, Y. [ATMEA, Paris (France); Matejovic, P. [IVS, Trnava (Slovakia); Perez-Fero, E.; Slonszki, E. [Hungarian Academy of Sciences KFKI Atomic Energy Research Institute, H-1525 Budapest, P.O. Box 49 (Hungary)

2010-03-15

The OECD-IAEA Paks Fuel Project was developed to support the understanding of fuel behaviour in accident conditions on the basis of analyses of the Paks-2 incident. Numerical simulation of the most relevant aspects of the event and comparison of the calculation results with the available data from the incident was carried out between 2006 and 2007. A database was compiled to provide input for the code calculations. The activities covered the following three areas: (a) Thermal hydraulic calculations described the cooling conditions possibly established during the incident. (b) Simulation of fuel behaviour described the oxidation and degradation mechanisms of the fuel assemblies. (c) The release of fission products from the failed fuel rods was estimated and compared to available measured data. The applied used codes captured the most important events of the Paks-2 incident and the calculated results improved the understanding of the causes and mechanisms of fuel failure. The numerical analyses showed that the by-pass flow leading to insufficient cooling amounted to 75-90% of the inlet flow rate, the maximum temperature in the tank was between 1200 and 1400 deg. C, the degree of zirconium oxidation reached 4-12% and the mass of produced hydrogen was between 3 and 13 kg.

Theses on fundamental issues of Paks extension debate in Hungary

International Nuclear Information System (INIS)

Ujhelyi, Geza

2014-01-01

The paper analyzes the expected price of electric power generated by the new blocks of the Paks Nuclear Power Plant. Takes into account the investment, the loan repayment, the depreciation period and the nuclear fuel prices. Calls the readers attention to the closing down of the existing four reactor blocks when reaching the end of the extended lifetime between 2032 and 2037. Compares the parameters of electric power generated by nuclear reactors with those of renewables. (TRA)

Gas formation in drum waste packages of Paks NPP

International Nuclear Information System (INIS)

Molnar, M.; Palcsu, L.; Svingor, E.; Szanto, Z.; Futo, I.; Ormai, P.

2000-01-01

Gas composition measurements have been carried out by mass spectrometry analysis of samples taken from the headspace of ten drum waste packages generated and temporarily stored at Paks NPP. Four drums contained compacted solid waste, three drums were filled with grouted (solidified) sludge and three drums contained solid waste without compaction. The drums have been equipped with a special gas outlet system to make repeated sampling possible. Based on the first measurements significant differences in the gas composition and the rate of gas generation among the drums were found. (author)

Nuclear safety at the Paks Plant

International Nuclear Information System (INIS)

Bajsz, Jozsef; Vamos, Gabor

1991-01-01

The Paks Nuclear Power Plant is located on the Danube river 114 km south of Budapest. It consists of four PWR units of the Soviet VVER-440 design. These are of the second generation design VVER 440 (model 213) with safety features as of 1975. It should be emphasized that these are two different generations of VVER 440 units. This is not always clear, not only to the general public, but sometimes even to people working in the nuclear industry. The widespread criticism of the first generation type 230 reactors is often extended to model 213 reactors, as the differences between the two models are often not sufficiently emphasized. In this situation it is very important to provide balanced information about the advantages and disadvantages of this reactor type. This paper attempts to do that. (author)

Specifying Functional Requirements Dependency in the REWiki

OpenAIRE

ZHANG, ZHANG

2013-01-01

Most of the individual requirements cannot be treated in isolation. Requirements may affect each other in various ways. The dependency between requirements impacts a number of software development aspects and activities. How to classify and specify requirements dependency remains a classic research topic. This research aims at providing an approach of specifying functional requirements dependency. In this thesis we generalize a classification of functional requirements dependency. We also pro...

Unveiling the role of PAK2 in CD44 mediated inhibition of proliferation, differentiation and apoptosis in AML cells

KAUST Repository

Aldehaiman, Mansour M.

2018-04-01

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by the accumulation of immature nonfunctional highly proliferative hematopoietic cells in the blood, due to a blockage in myeloid differentiation at various stages. Since the success of the differentiation agent, All-trans retinoic acid (ATRA), in the treatment of acute promyelocytic leukemia (APL), much effort has gone into trying to find agents that are able to differentiate AML cells and specifically the leukemic stem cell (LSC). CD44 is a cell surface receptor that is over-expressed on AML cells. When bound to anti-CD44 monoclonal antibodies (mAbs), this differentiation block is relieved in AML cells and their proliferation is reduced. The molecular mechanisms that AML cells undergo to achieve this reversal of their apparent phenotype is not fully understood. To this end, we designed a study using quantitative phosphoproteomics approaches aimed at identifying differences in phosphorylation found on proteins involved in signaling pathways post-treatment with CD44-mAbs. The Rho family of GTPases emerged as one of the most transformed pathways following the treatment with CD44-mAbs. The P21 activated kinase 2(PAK2), a target of the Rho family of GTPases, was found to be differentially phosphorylated in AML cells post-treatment with CD44-mAbs. This protein has been found to possess a role similar to that of a switch that determines whether the cell survives or undergoes apoptosis. Beyond confirming these results by various biochemical approaches, our study aimed to determine the effect of knock down of PAK2 on AML cell proliferation and differentiation. In addition, over-expression of PAK2 mutants using plasmid cloning was also explored to fully understand how levels of PAK2 as well as the alteration of specific phospohorylation sites could alter AML cell responses to CD44-mAbs. Results from this study will be important in determining whether PAK2 could be used as a potential therapeutic target

Final evaluation report for Lockheed Idaho Technologies Company, ARROW-PAK packaging, Docket 95-40-7A, Type A container

International Nuclear Information System (INIS)

Kelly, D.L.

1995-11-01

The report documents the U.S. Department of Transportation Specification 7A Type A (DOT-7A) compliance test results of the ARROW-PAK packaging. The ARROW-PAK packaging system consists of Marlex M-8000 Driscopipe (Series 8000 [gas] or Series 8600 [industrial]) resin pipe, manufactured by Phillips-Driscopipe, Inc., and is sealed with two dome-shaped end caps manufactured from the same materials. The patented sealing process involves the use of electrical energy to heat opposing faces of the pipe and end caps, and hydraulic rams to press the heated surfaces together. This fusion process produces a homogeneous bonding of the end cap to the pipe. The packaging may be used with or without the two internal plywood spacers. This packaging was evaluated and tested in October 1995. The packaging configuration described in this report is designed to ship Type A quantities of solid radioactive materials, Form No. 1, Form No. 2, and Form No. 3

20 CFR 219.42 - When evidence of child's dependency is required.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false When evidence of child's dependency is required. 219.42 Section 219.42 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE... child's dependency is required. Evidence of a child's dependency on the employee is required when— (a...

Refuelling design and core calculations at NPP Paks: codes and methods

International Nuclear Information System (INIS)

Pos, I.; Nemes, I.; Javor, E.; Korpas, L.; Szecsenyi, Z.; Patai-Szabo, S.

2001-01-01

This article gives a brief review of the computer codes used in the fuel management practice at NPP Paks. The code package consist of the HELIOS neutron and gamma transport code for preparation of few-group cross section library, the CERBER code to determine the optimal core loading patterns and the C-PORCA code for detailed reactor physical analysis of different reactor states. The last two programs have been developed at the NPP Paks. HELIOS gives sturdy basis for our neutron physical calculation, CERBER and C-PORCA programs have been enhanced in great extent for last years. Methods and models have become more detailed and accurate as regards the calculated parameters and space resolution. Introduction of a more advanced data handling algorithm arbitrary move of fuel assemblies can be followed either in the reactor core or storage pool. The new interactive WINDOWS applications allow easier and more reliable use of codes. All these computer code developments made possible to handle and calculate new kind of fuels as profiled Russian and BNFL fuel with burnable poison or to support the reliable reuse of fuel assemblies stored in the storage pool. To extend thermo-hydraulic capability, with KFKI contribution the COBRA code will also be coupled to the system (Authors)

Evaluation of the CervidTB STAT-PAK for the detection of Mycobacterium bovis infection in wild deer in Great Britain.

Science.gov (United States)

Gowtage-Sequeira, S; Paterson, A; Lyashchenko, K P; Lesellier, S; Chambers, M A

2009-10-01

Deer are acknowledged as hosts of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and determining the prevalence of infection in deer species is one of the key steps in understanding the epidemiological role played by cervids in the transmission and maintenance of bTB in the United Kingdom. This study evaluated a rapid lateral-flow test for the detection of bTB in samples from wild deer species in the United Kingdom. Fallow deer (Dama dama), roe deer (Capreolus capreolus), and red deer (Cervus elaphus) from areas in Wales, the Cotswolds, and southwestern England were necropsied for a bTB survey. Serum samples from individual deer were tested with the CervidTB STAT-PAK, and the results were evaluated against the culture of M. bovis from tissues (n = 432). Sensitivity and specificity were 85.7% (95% confidence interval [CI], 42.1 to 99.6%) and 94.8% (95% CI, 92.3 to 96.7%), respectively, with an odds ratio of 109.9 (95% CI, 12.7 to 953.6%) for a positive STAT-PAK result among culture-positive deer. The low prevalence of infection (3.8%, n = 860) affected the confidence of the sensitivity estimate of the test, but all culture-positive fallow deer (n = 6) were detected by the test. In addition, antibodies to M. bovis could be detected in poor-quality serum samples. The results suggest that the CervidTB STAT-PAK could be deployed as a field test for further evaluation.

Analysis of Paks NPP Personnel Activity during Safety Related Event Sequences

International Nuclear Information System (INIS)

Bareith, A.; Hollo, Elod; Karsa, Z.; Nagy, S.

1998-01-01

Within the AGNES Project (Advanced Generic and New Evaluation of Safety) the Level-1 PSA model of the Paks NPP Unit 3 was developed in form of a detailed event tree/fault tree structure (53 initiating events, 580 event sequences, 6300 basic events are involved). This model gives a good basis for quantitative evaluation of potential consequences of actually occurred safety-related events, i.e. for precursor event studies. To make these studies possible and efficient, the current qualitative event analysis practice should be reviewed and a new additional quantitative analysis procedure and system should be developed and applied. The present paper gives an overview of the method outlined for both qualitative and quantitative analyses of the operator crew activity during off-normal situations. First, the operator performance experienced during past operational events is discussed. Sources of raw information, the qualitative evaluation process, the follow-up actions, as well as the documentation requirements are described. Second, the general concept of the proposed precursor event analysis is described. Types of modeled interactions and the considered performance influences are presented. The quantification of the potential consequences of the identified precursor events is based on the task-oriented, Level-1 PSA model of the plant unit. A precursor analysis system covering the evaluation of operator activities is now under development. Preliminary results gained during a case study evaluation of a past historical event are presented. (authors)

Assessment of Human Performance and Safety Culture at the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Toth, Janos; Hadnagy, Lajos

2002-01-01

Evaluation of human performance and safety culture of the personnel at a Nuclear Power Plant is a very important element of the self assessment process. At the Paks NPP a systematic approach to this problem started in the early 90's. The first comprehensive analysis of the human performance of the personnel was performed by the Hungarian Research Institute for Electric Power (VEIKI). The analysis of human failures is also a part of the investigation and analysis of safety related reported events. This human performance analysis of events is carried out by the Laboratory of Psychology of the plant and a supporting organisation namely the Department of Ergonomics and Psychology of the Budapest University of Technical and Economical Sciences. The analysis of safety culture at the Paks NPP has been in the focus of attention since the implementation of the INSAG-4 document started world-wide. In 1993 an IAEA model project namely 'Strengthening Training for Operational Safety' was initiated with a sub-project called 'Enhancement of Safety Culture'. Within this project the first step was the initial assessment of the safety culture level at the Paks NPP. It was followed by some corrective actions and safety culture improvement programme. In 1999 the second assessment was performed in order to evaluate the progress as a result of the improvement programme. A few indicators reflecting the elements of safety culture were defined and compared. The assessment of the safety culture with a survey among the managers was performed in September 2000 and the results are being evaluated at the moment. The intention of the plant management is to repeat the assessment every 2-3 years and evaluate the trend of the indicator. (authors)

“Liting it up”: Popular Culture, Indo-Pak Basketball, and South Asian American Institutions

Directory of Open Access Journals (Sweden)

Stanley Ilango Thangaraj

2010-08-01

Full Text Available South Asian American participants of a co-ethnic basketball league, known as Indo-Pak Basketball, utilized urban basketball vernacular through the phrase “liting it up” to identify individuals scoring points in great numbers. The person “liting it up” becomes visible and receives recognition. Accordingly, I want to “lite up” the scholarship on South Asian America whereby situating South Asian American religious sites and cultural centers as key arenas for “Americanization” through US popular culture. I situate sport as a key element of popular culture through which South Asian American communities work out, struggle through, and contest notions of self. Informed by an Anthropology of Sport, ethnography of South Asian American communities in Atlanta takes place alongside an examination of the North American Indo-Pak Basketball circuit. Accordingly, my findings indicate that such community formation has also taken shape at the intersections of institutions, gender, and sexuality whereby excluding queers, women, and other communities of color.

The RELAP5-Based NPA of the VVER Type Paks NPP

International Nuclear Information System (INIS)

Guba, A.; Toth, I.; Mandy, C.; Stubbe, E.

1999-01-01

NPA is a data driven interactive graphical tool for visualisation of different plant conditions. Data generated by the analysis code RELAP5/MOD3.2 are processed and displayed on a computer monitor. The NPA model of Paks NPP Unit 3 was developed with the aim to demonstrate the phenomena occurring in different transient/accident scenarios. This VVER-specific NPA development is a result of a cooperation between BELGATOM and KFKI-AEKI. (author)

Test Plan for Lockheed Idaho Technologies Company (LITCO), ARROW-PAK Packaging, Docket 95-40-7A, Type A Container

International Nuclear Information System (INIS)

Kelly, D.L.

1995-01-01

This report documents the U.S. Department of Transportation Specification 7A Type A (DOT-7A) compliance testing to be followed for qualification of the Lockheed Idaho Technologies Company, ARROW-PAK, for use as a Type A Packaging. The packaging configuration being tested is intended for transportation of radioactive solids, Form No. 1, Form No. 2, and Form No. 3

Identification of flavonoids and hydroxycinnamic acids in pak choi varieties (Brassica campestris L. ssp. chinensis var. communis) by HPLC-ESI-MSn and NMR and their quantification by HPLC-DAD.

Science.gov (United States)

Harbaum, Britta; Hubbermann, Eva Maria; Wolff, Christian; Herges, Rainer; Zhu, Zhujun; Schwarz, Karin

2007-10-03

Twenty-eight polyphenols (11 flavonoid derivatives and 17 hydroxycinnamic acid derivatives) were detected in different cultivars of the Chinese cabbage pak choi ( Brassica campestris L. ssp. chinensis var. communis) by HPLC-DAD-ESI-MS(n). Kaempferol was found to be the major flavonoid in pak choi, glycosylated and acylated with different compounds. Smaller amounts of isorhamnetin were also detected. A structural determination was carried out by (1)H and (13)C NMR spectroscopy for the main compound, kaempferol-3-O-hydroxyferuloylsophoroside-7-O-glucoside, for the first time. Hydroxycinnamic acid derivatives were identified as different esters of quinic acid, glycosides, and malic acid. The latter ones are described for the first time in cabbages. The content of polyphenols was determined in 11 cultivars of pak choi, with higher concentrations present in the leaf blade than in the leaf stem. Hydroxycinnamic acid esters, particularly malic acid derivatives, are present in both the leaf blade and leaf stem, whereas flavonoid levels were determined only in the leaf blade.

Seismic assessment and upgrading of Paks nuclear power plant

International Nuclear Information System (INIS)

Tamas, K.

2001-01-01

A comprehensive programme for seismic assessment and upgrading is currently in progress at Hungary's Paks NPP. The re-evaluation of the site seismic hazard had been already completed. The technology of safe shut down and heat removal is established and the systems and structures relevant for seismic safety are identified. A seismic instrumentation is installed. The pre-earthquake preparedness and post-earthquake actions are elaborated. The methods for seismic capacity assessment are selected. The seismic capacity evaluation and the design of upgrading measures are currently in progress. The easy to perform upgrading covering the most urgent measures had been already performed. (author)

Phytoavailability of Cadmium (Cd) to Pak Choi (Brassica chinensis L.) Grown in Chinese Soils: A Model to Evaluate the Impact of Soil Cd Pollution on Potential Dietary Toxicity

Science.gov (United States)

Yang, Xiaoe; Xiao, Wendan; Stoffella, Peter J.; Saghir, Aamir; Azam, Muhammad; Li, Tingqiang

2014-01-01

Food chain contamination by soil cadmium (Cd) through vegetable consumption poses a threat to human health. Therefore, an understanding is needed on the relationship between the phytoavailability of Cd in soils and its uptake in edible tissues of vegetables. The purpose of this study was to establish soil Cd thresholds of representative Chinese soils based on dietary toxicity to humans and develop a model to evaluate the phytoavailability of Cd to Pak choi (Brassica chinensis L.) based on soil properties. Mehlich-3 extractable Cd thresholds were more suitable for Stagnic Anthrosols, Calcareous, Ustic Cambosols, Typic Haplustalfs, Udic Ferrisols and Periudic Argosols with values of 0.30, 0.25, 0.18, 0.16, 0.15 and 0.03 mg kg−1, respectively, while total Cd is adequate threshold for Mollisols with a value of 0.86 mg kg−1. A stepwise regression model indicated that Cd phytoavailability to Pak choi was significantly influenced by soil pH, organic matter, total Zinc and Cd concentrations in soil. Therefore, since Cd accumulation in Pak choi varied with soil characteristics, they should be considered while assessing the environmental quality of soils to ensure the hygienically safe food production. PMID:25386790

Phytoavailability of cadmium (Cd) to Pak choi (Brassica chinensis L.) grown in Chinese soils: a model to evaluate the impact of soil Cd pollution on potential dietary toxicity.

Science.gov (United States)

Rafiq, Muhammad Tariq; Aziz, Rukhsanda; Yang, Xiaoe; Xiao, Wendan; Stoffella, Peter J; Saghir, Aamir; Azam, Muhammad; Li, Tingqiang

2014-01-01

Food chain contamination by soil cadmium (Cd) through vegetable consumption poses a threat to human health. Therefore, an understanding is needed on the relationship between the phytoavailability of Cd in soils and its uptake in edible tissues of vegetables. The purpose of this study was to establish soil Cd thresholds of representative Chinese soils based on dietary toxicity to humans and develop a model to evaluate the phytoavailability of Cd to Pak choi (Brassica chinensis L.) based on soil properties. Mehlich-3 extractable Cd thresholds were more suitable for Stagnic Anthrosols, Calcareous, Ustic Cambosols, Typic Haplustalfs, Udic Ferrisols and Periudic Argosols with values of 0.30, 0.25, 0.18, 0.16, 0.15 and 0.03 mg kg-1, respectively, while total Cd is adequate threshold for Mollisols with a value of 0.86 mg kg-1. A stepwise regression model indicated that Cd phytoavailability to Pak choi was significantly influenced by soil pH, organic matter, total Zinc and Cd concentrations in soil. Therefore, since Cd accumulation in Pak choi varied with soil characteristics, they should be considered while assessing the environmental quality of soils to ensure the hygienically safe food production.

Phytoavailability of cadmium (Cd to Pak choi (Brassica chinensis L. grown in Chinese soils: a model to evaluate the impact of soil Cd pollution on potential dietary toxicity.

Directory of Open Access Journals (Sweden)

Muhammad Tariq Rafiq

Full Text Available Food chain contamination by soil cadmium (Cd through vegetable consumption poses a threat to human health. Therefore, an understanding is needed on the relationship between the phytoavailability of Cd in soils and its uptake in edible tissues of vegetables. The purpose of this study was to establish soil Cd thresholds of representative Chinese soils based on dietary toxicity to humans and develop a model to evaluate the phytoavailability of Cd to Pak choi (Brassica chinensis L. based on soil properties. Mehlich-3 extractable Cd thresholds were more suitable for Stagnic Anthrosols, Calcareous, Ustic Cambosols, Typic Haplustalfs, Udic Ferrisols and Periudic Argosols with values of 0.30, 0.25, 0.18, 0.16, 0.15 and 0.03 mg kg-1, respectively, while total Cd is adequate threshold for Mollisols with a value of 0.86 mg kg-1. A stepwise regression model indicated that Cd phytoavailability to Pak choi was significantly influenced by soil pH, organic matter, total Zinc and Cd concentrations in soil. Therefore, since Cd accumulation in Pak choi varied with soil characteristics, they should be considered while assessing the environmental quality of soils to ensure the hygienically safe food production.

Comparing the influence of selenite (Se4+) and selenate (Se6+) on the inhibition of the mercury (Hg) phytotoxicity to pak choi.

Science.gov (United States)

Tran, Thi Anh Thu; Dinh, Quang Toan; Cui, Zeiwei; Huang, Jie; Wang, Dan; Wei, Tianjiao; Liang, Dongli; Sun, Xin; Ning, Ping

2018-01-01

Selenite (Se (IV)) and selenate (Se (IV)) have recently been demonstrated to be equally effective in inhibiting mercury (Hg) phytotoxicity to plants. This assertion is still unclear. In this study, we aimed to explore the potential effects of Se species (Se 4+ and Se 6+ ) on the inhibition of the mercury (Hg) bioavailability to pak choi in dry land. Pot experiments with exposure to different dosages of mercuric chloride (HgCl 2 ) and selenite (Na 2 SeO 3 ) or selenate (Na 2 SeO 4 ) were treated. To compare the influence of Se (IV) and Se (VI) on the bioaccumulation and bioavailability of Hg, the levels of total Hg in different pak choi (Brassica chinensis L.) tissues (roots and shoots) and the distribution changes of Hg fractions in soil before planting and after harvest were determined as well as the Hg I R values in soils (relative binding intensity) were analyzed. Results showed that application Se (IV) reduced the concentrations of Hg in pak choi roots more than Se (VI). Hg concentrations were also decreased in pak choi shoots in Se (IV) treatments, while which notably increased in Se (VI) treatments. Thus, Se (IV) plays a more important role than Se (VI) in limiting the absorption and bioaccumulation of Hg in pak choi. Moreover, this inhibition may only significantly occur when Se (IV) is at an appropriate level (2.5mg/kg). In addition, the good correlations between the proportions of mobile Hg fractions (soluble and exchangeable fractions), I R values with the Hg concentrations in plants were observed. This affirmed the importance of the Hg fractions transformation and the I R indicator of Hg in the assessment of their bioavailability. Our findings regarding the importance of Se (IV) influence in reducing Hg bioaccumulation not only provided the correct appraisal about the effect of Se species on the inhibition of the Hg phytotoxicity to pak choi in dry land, but also be a good reference for selecting Se fertilizer forms (Se 4+ or Se 6+ ). Copyright © 2017

Main building complex WWER 440/213 upper range design response spectra for soft soil site conditions (Paks)

International Nuclear Information System (INIS)

Krutzik, N.

1996-01-01

Within the Benchmark studies parallel investigation were prepared for the main building complex of the WWER-440/213 Paks NPP by several participating institutions. The investigations were based on various mathematical models and procedures but all had the same seismological data as input. The calculation methods as well as software tools were different. This report covers the enveloped response results which were the basis for the benchmark studies and which should be used for upgrading of mechanical and electrical components and systems which will follow. These response spectra which consider a certain conservatism namely neglecting the frequency independence of the stiffness and the cut-off of damping values are named 'Upper Range design Benchmark Response Spectra' for the main building of Paks NPP

Main building complex WWER 440/213 upper range design response spectra for soft soil site conditions (Paks)

Energy Technology Data Exchange (ETDEWEB)

Krutzik, N [Siemens AG, Power Generation Group (KWU) NDA2, Offenbach (Germany)

1996-07-01

Within the Benchmark studies parallel investigation were prepared for the main building complex of the WWER-440/213 Paks NPP by several participating institutions. The investigations were based on various mathematical models and procedures but all had the same seismological data as input. The calculation methods as well as software tools were different. This report covers the enveloped response results which were the basis for the benchmark studies and which should be used for upgrading of mechanical and electrical components and systems which will follow. These response spectra which consider a certain conservatism namely neglecting the frequency independence of the stiffness and the cut-off of damping values are named 'Upper Range design Benchmark Response Spectra' for the main building of Paks NPP.

Overlapping effector interfaces define the multiple functions of the HIV-1 Nef polyproline helix

Directory of Open Access Journals (Sweden)

Kuo Lillian S

2012-05-01

Full Text Available Abstract Background HIV-1 Nef is a multifunctional protein required for full pathogenicity of the virus. As Nef has no known enzymatic activity, it necessarily functions through protein-protein interaction interfaces. A critical Nef protein interaction interface is centered on its polyproline segment (P69VRPQVPLRP78 which contains the helical SH3 domain binding protein motif, PXXPXR. We hypothesized that any Nef-SH3 domain interactions would be lost upon mutation of the prolines or arginine of PXXPXR. Further, mutation of the non-motif “X” residues, (Q73, V74, and L75 would give altered patterns of inhibition for different Nef/SH3 domain protein interactions. Results We found that mutations of either of the prolines or the arginine of PXXPXR are defective for Nef-Hck binding, Nef/activated PAK2 complex formation and enhancement of virion infectivity (EVI. Mutation of the non-motif “X” residues (Q, V and L gave similar patterns of inhibition for Nef/activated PAK2 complex formation and EVI which were distinct from the pattern for Hck binding. These results implicate an SH3 domain containing protein other than Hck for Nef/activated PAK2 complex formation and EVI. We have also mutated Nef residues at the N-and C-terminal ends of the polyproline segment to explore interactions outside of PXXPXR. We discovered a new locus GFP/F (G67, F68, P69 and F90 that is required for Nef/activated PAK2 complex formation and EVI. MHC Class I (MHCI downregulation was only partially inhibited by mutating the PXXPXR motif residues, but was fully inhibited by mutating the C-terminal P78. Further, we observed that MHCI downregulation strictly requires G67 and F68. Our mutational analysis confirms the recently reported structure of the complex between Nef, AP-1 μ1 and the cytoplasmic tail of MHCI, but does not support involvement of an SH3 domain protein in MHCI downregulation. Conclusion Nef has evolved to be dependent on interactions with multiple SH3 domain

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4G. Paks NPP: Analysis and testing. Working material

International Nuclear Information System (INIS)

1999-01-01

related to different structures or systems of Paks NPP and Kozloduy NPP Unit 5/6 and experience data (previous laboratory results or earthquake experience) for WWER type NPPs. The reports from the CRP participants have been compiled in volumes of IAEA Working Material grouped under five broad categories. This volume covers the following subjects: structural response of Paks NPP; Evaluation of seismic resistance of low voltage switchgear, Bohunice V1 NPP; final report of the seismic investigations at Paks NPP; report on vibration test of the scale worm tank model; plan of shaking table test of worm tank model; dynamic response of the Paks NPP chimney; vibration analysis of the Paks NPP stacks; functionality of WWER electrical, instrumentation and control components; dynamic analysis of Paks reactor building structures; and computational-experimental examination and ensuring of equipment and pipelines seismic resistance at starting and operation WWER type NPPs

HydroPak: concept design and analysis of a packaged cross-flow turbine

International Nuclear Information System (INIS)

2004-01-01

This report summarises the findings of a project to complete the conceptual design and economic optimization of a modular standardised crossflow hydro-turbine. Details are given of the work to date, the comparison of HydroPak cost with conventional micro- and mini-hydro power costs, and the economic advantages of taking the ''packaged'' and ''standardised approaches'' to the design process. The market for mini-hydro turbines is discussed

Evaluation of the CervidTB STAT-PAK for the Detection of Mycobacterium bovis Infection in Wild Deer in Great Britain▿

Science.gov (United States)

Gowtage-Sequeira, S.; Paterson, A.; Lyashchenko, K. P.; Lesellier, S.; Chambers, M. A.

2009-01-01

Deer are acknowledged as hosts of Mycobacterium bovis, the causative agent of bovine tuberculosis (bTB), and determining the prevalence of infection in deer species is one of the key steps in understanding the epidemiological role played by cervids in the transmission and maintenance of bTB in the United Kingdom. This study evaluated a rapid lateral-flow test for the detection of bTB in samples from wild deer species in the United Kingdom. Fallow deer (Dama dama), roe deer (Capreolus capreolus), and red deer (Cervus elaphus) from areas in Wales, the Cotswolds, and southwestern England were necropsied for a bTB survey. Serum samples from individual deer were tested with the CervidTB STAT-PAK, and the results were evaluated against the culture of M. bovis from tissues (n = 432). Sensitivity and specificity were 85.7% (95% confidence interval [CI], 42.1 to 99.6%) and 94.8% (95% CI, 92.3 to 96.7%), respectively, with an odds ratio of 109.9 (95% CI, 12.7 to 953.6%) for a positive STAT-PAK result among culture-positive deer. The low prevalence of infection (3.8%, n = 860) affected the confidence of the sensitivity estimate of the test, but all culture-positive fallow deer (n = 6) were detected by the test. In addition, antibodies to M. bovis could be detected in poor-quality serum samples. The results suggest that the CervidTB STAT-PAK could be deployed as a field test for further evaluation. PMID:19656989

Vibration system identification of Paks and Kozloduy reactor buildings on the basis of the blast test results

International Nuclear Information System (INIS)

Varpasuo, P.

1999-01-01

System identification allows to build mathematical models of a dynamic system based on measured data. System identification is carried out by adjusting parameters within a given model until its output coincides as well as possible with the measured output. The aim of this study is to investigate and model the behavior of complex vibratory systems on the basis of measured excitation and response. The first part of the study describes the theory used in the analysis and the software tools used in the analysis. The second part of the study describes the investigation and modeling of the response of single degree of freedom oscillator excited by sinusoidal and blast excitation. In the third part of the study the system identification of the Kozloduy NPP unit 5 reactor building and Paks NPP unit 1 reactor building is studied and the models are estimated using the method of segmentation of excitation and response. System identification is carried out using MATLAB software by adjusting parameters within a given model until its output coincides as well as possible with the measured output. The types of models used for the were: l) ARX models; 2) ARMAX model; 3) Output-Error (OE) models; 4) Box-Jenkins (BJ) models; 5) State-space models. The model coefficients for different models were calculated using the least-squares and maximum likelihood estimation methods available in MATLAB system identification toolbox. Excitation was in both Paks and Kozloduy case the measured free-field excitation and responses were the vibration responses of the building on the foundation slab level and top of the building. By examining the established models the frequency characteristics of vibration systems were determined with 95 % accuracy and the amplitude response with 80 % accuracy. In case of the steady state response of sinusoidally excited single dof oscillator the modelling gave almost exact results. But in the case of the blast response of the reactor building the obtaining of the

Refraktīvā lēcas ķirurģija pie augstas pakāpes ametropijas

OpenAIRE

Šamajeva, Nataļja

2012-01-01

Ametropija ir patoloģisks redzes stāvoklis, kad gaismas stari, izejot cauri acs optiskajām vidēm, fokusējas nevis uz tīklenes, bet pirms vai aiz tās, tad apkārtējo pasauli cilvēks redz neasi. Ametropijas veidi ir miopija, hipermetropija, astigmatisms, kā arī presbopija. Izšķir vājas, vidējas un augstas pakāpes ametropiju. Pilnībā sekmīgi izārstēt augstas pakāpes ametropijas var ar dabīgās acu lēcas aizvietošanu ar multifokālo intraokulāro lēcu. Turklāt pacientiem jāņem vērā, ka šai operā...

Glutamine nitrogen and ammonium nitrogen supplied as a nitrogen source is not converted into nitrate nitrogen of plant tissues of hydroponically grown pak-choi (Brassica chinensis L.).

Science.gov (United States)

Wang, H-J; Wu, L-H; Tao, Q-N; Miller, D D; Welch, R M

2009-03-01

Many vegetables, especially leafy vegetables, accumulate NO(-) (3)-N in their edible portions. High nitrate levels in vegetables constitute a health hazard, such as cancers and blue baby syndrome. The aim of this study was to determine if (1) ammonium nitrogen (NH(+) (4)-N) and glutamine-nitrogen (Gln-N) absorbed by plant roots is converted into nitrate-nitrogen of pak-choi (Brassica chinensis L.) tissues, and (2) if nitrate-nitrogen (NO(-) (3)-N) accumulation and concentration of pak-choi tissues linearly increase with increasing NO(-) (3)-N supply when grown in nutrient solution. In experiment 1, 4 different nitrogen treatments (no nitrogen, NH(+) (4)-N, Gln-N, and NO(-) (3)-N) with equal total N concentrations in treatments with added N were applied under sterile nutrient medium culture conditions. In experiment 2, 5 concentrations of N (from 0 to 48 mM), supplied as NO(-) (3)-N in the nutrient solution, were tested. The results showed that Gln-N and NH(+) (4)-N added to the nutrient media were not converted into nitrate-nitrogen of plant tissues. Also, NO(-) (3)-N accumulation in the pak-choi tissues was the highest when plants were supplied 24 mM NO(-) (3)-N in the media. The NO(-) (3)-N concentration in plant tissues was quadratically correlated to the NO(-) (3)-N concentration supplied in the nutrient solution.

HydroPak: concept design and analysis of a packaged cross-flow turbine

Energy Technology Data Exchange (ETDEWEB)

NONE

2004-07-01

This report summarises the findings of a project to complete the conceptual design and economic optimization of a modular standardised crossflow hydro-turbine. Details are given of the work to date, the comparison of HydroPak cost with conventional micro- and mini-hydro power costs, and the economic advantages of taking the ''packaged'' and ''standardised approaches'' to the design process. The market for mini-hydro turbines is discussed.

Decontamination of PAH polluted soils by fungi. Subproject: PAH degradation balance and testing of the extended laboratory process. Final report; Dekontamination von PAK belasteten Boeden durch Pilze. Teilprojekt: Bilanzierung des PAK-Abbaus und Erprobung des erweiterten Laborverfahrens. Abschlussbericht

Energy Technology Data Exchange (ETDEWEB)

Martens, R.; Zadrazil, F.; Wolter, M.; Bahadir, M.

1997-09-01

The aim of the research project was first to select a fungus with a high potential for mineralization of polycyclic aromatic hydrocarbons (PAH) and a good ability to colonize different soils. The application of this fungus for a degradation of PAH in soil had to be tested. In a screening of 57 white rot fungi the fungus Pleurotus sp. Florida fulfilled these requirements best. In pure culture it was able to metabolize and mineralize highly condensed 4-6 ring PAH to a great extent. For instance, up to 50% of {sup 14}C-pyrene or 39% of {sup 14}C-benzo(a)pyrene was mineralized to {sup 14}CO{sub 2} within 15 weeks. If different carriers for {sup 14}C-pyrene were used the mineralization correlated with the bioavailability, which was characterized by the desorption of the compound from the carriers with water. The mineralization of {sup 14}C-pyrene, {sup 14}C-benz(a)anthracene; {sup 14}C-benzo(a)-pyrene and {sup 14}C-dibenz(a, h)anthracene in native soils showed that a colonization with Pl. sp Florida inhibited the degradation of the less recalcitrant {sup 14}C-pyrene by the indigenous soil microflora. However, the mineralization of the carcinogenic, very recalcitrant and high condensed {sup 14}C-PAH was considerably supported by the fungus. Therefore this capabilities of the fungus could not be proven in a joint medium-scale soil experiment (0.8 m{sup 3} soil) which had been conducted within a parmership with scientists in Jena and an industriell firm. Because of safety aspects only the low condensed less recalcitrant PAH could be applied in this experiment. (orig./MG) [Deutsch] Ziel der Untersuchungen war es, zunaechst aus einer groesseren Zahl von Weissfaeulepilzen Pilze zu selektieren, die ein hohes Abbaupotential fuer PAK besitzen. Fuer die effektive Bildung der fuer den Xenobiotika-Abbau wahrscheinlich verantwortlichen lignolytischen Enzyme sollten die Pilze auf Stroh mit einer Kontamination von {sup 14}C-Pyren angezogen werden. An Hand der Freisetzung von {sup 14

Implementation of safeguards at modular vault dry store at Paks NPP in Hungary

International Nuclear Information System (INIS)

Safar, J.; Czoch, I.; Szoellosi, E.F.; Janov, J.; Sannie, G.; Daniel, G.; Szabo, J.L.

1999-01-01

A safeguards system has been implemented at the GEC-Alsthom designed Modular Vault Dry Store at Paks NPP in Hungary without previous safeguards related experience for this type of spent fuel storage. C/S measures and sealing have primary importance. In addition. spent fuel attribute signatures are detected by a fuel transfer monitor at the cask load/unload port. These are complemented with the corresponding accounting measures. (author)

Closed-loop automatic photogrammetry-geodesy information system for the construction of the Paks nuclear power plant

International Nuclear Information System (INIS)

Detrekoei, Akos; Eoery, Karacson; Sarkoezy, Ferenc

1984-01-01

The stereo photogrammetric data collection, measurement and data processing system operating within the Geodesy Plan of the Paks nuclear power plant is described. The interactive graphic computer system, its functions and operation, together with plotters and displays for the generation of graphic output are presented. (R.P.)

Results and interpretation of noise measurements using in-core self powered neutron detector strings at Unit 2 of the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Gloeckler, O.; Por, G.; Valko, J.

1986-11-01

In-core neutron noise and fuel assembly outlet temperature noise measurements were performed at Unit 2 of Paks Nuclear Power Plant. Characteristics of the reactor and the noise measuring equipment are briefly described. The in-core Rhodium emitter selfpowered neutron detector strings positioned axially above the other show high coherence and linear phase at low frequencies indicating a marked transport effect, not regularly measured in PWRs. The coherence between horizontally placed neutron detectors is small and the phase is zero. A transport effect of different nature is obtained between neutron detectors (in-core and ex-core) and fuel assembly outlet thermocouples. The observed characteristics depend on reactor and fuel assembly power in a way supporting interpretation in terms of coolant density and void content changes and power feedback effects. During routine analysis vibration of 1.1 Hz appeared as a strong peak in the power spectra. The control assembly that was responsible for the observed behaviour could be localized with high certainty. (author)

Seismic safety programme at NPP Paks. Propositions for coordinated international activity in seismic safety of the WWER-440 V-213

International Nuclear Information System (INIS)

Katona, T.

1995-01-01

This paper presents the Paks NPP seismic safety program, highlighting the specifics of the WWER-440/213 type in operation, and the results of work obtained so far. It covers the following scope: establishment of the seismic safety program (original seismic design, current requirements, principles and structure of the seismic safety program); implementation of the seismic safety program (assessing the seismic hazard of the site, development of the new concept of seismic safety for the NPP, assessing the seismic resistance of the building and the technology); realization of the seismic safety of higher level (technical solutions, drawings, realization); ideas and propositions for coordinated international activity

Tests of the Bayesian evaluation of SPRT outcomes on Paks NPP data

International Nuclear Information System (INIS)

Kulacsy, K.

1997-01-01

Self-powered neutron detector signals measured at the Paks Nuclear Power Plant, Hungary, are processed by a simple Binary Sequential Probability Ratio (SPRT) test and an SPRT combined with the Bayesian probability updating method. Since this latter is too robust against changes in the character of the signal, a new version of the Bayesian probability updating method is suggested and tested on the signals. The new method is found to detect signal failures faster and more effectively than the simple SPRT. (R.P.)

Conversion of dependability deterministic requirements into probabilistic requirements

International Nuclear Information System (INIS)

Bourgade, E.; Le, P.

1993-02-01

This report concerns the on-going survey conducted jointly by the DAM/CCE and NRE/SR branches on the inclusion of dependability requirements in control and instrumentation projects. Its purpose is to enable a customer (the prime contractor) to convert into probabilistic terms dependability deterministic requirements expressed in the form ''a maximum permissible number of failures, of maximum duration d in a period t''. The customer shall select a confidence level for each previously defined undesirable event, by assigning a maximum probability of occurrence. Using the formulae we propose for two repair policies - constant rate or constant time - these probabilized requirements can then be transformed into equivalent failure rates. It is shown that the same formula can be used for both policies, providing certain realistic assumptions are confirmed, and that for a constant time repair policy, the correct result can always be obtained. The equivalent failure rates thus determined can be included in the specifications supplied to the contractors, who will then be able to proceed to their previsional justification. (author), 8 refs., 3 annexes

Establishment of a computerized occupational health system at the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Otos, M.

1990-01-01

An overall personnel health system has been under installation in the Paks Nuclear Power Plant Company, Hungary, for an automatic health monitoring and survey of the personnel exposed to radiation. The system will consist of nine modules when completed. The personnel fitness module is described in detail, and the periodical fitness examinations with computer control are presented. The examinations are using a personnel database system, and a statistical module is used to evaluate monitoring results. (R.P.)

The common project for completion of Bubbler Condenser Qualification (Bohunice, Mochovce, Dukovany and Paks NPPs)

International Nuclear Information System (INIS)

Jaroslav, H.; Pavol, B.

2003-01-01

Described is the common project for completion of bubbler condenser qualification for nuclear power plants in Bohunice, Mochovice, Dukovany and Paks. Functionality of the bubbler condenser was elaborated during the simulation of the main steam line brake, medium break and small break LOCA. On this basis the appropriate operation of bubbler condenser containment under accident conditions can be positively confirmed

Zebrafish diras1 Promoted Neurite Outgrowth in Neuro-2a Cells and Maintained Trigeminal Ganglion Neurons In Vivo via Rac1-Dependent Pathway.

Science.gov (United States)

Yeh, Chi-Wei; Hsu, Li-Sung

2016-12-01

The small GTPase Ras superfamily regulates several neuronal functions including neurite outgrowth and neuron proliferation. In this study, zebrafish diras1a and diras1b were identified and were found to be mainly expressed in the central nervous system and dorsal neuron ganglion. Overexpression of green fluorescent protein (GFP)-diras1a or GFP-diras1b triggered neurite outgrowth of Neuro-2a cells. The wild types, but not the C terminus truncated forms, of diras1a and diras1b elevated the protein level of Ras-related C3 botulinum toxin substrate 1 (Rac1) and downregulated Ras homologous member A (RhoA) expression. Glutathione S-transferase (GST) pull-down assay also revealed that diras1a and diras1b enhanced Rac1 activity. Interfering with Rac1, Pak1, or cyclin-dependent kinase 5 (CDK5) activity or with the Arp2/3 inhibitor prevented diras1a and diras1b from mediating the neurite outgrowth effects. In the zebrafish model, knockdown of diras1a and/or diras1b by morpholino antisense oligonucleotides not only reduced axon guidance but also caused the loss of trigeminal ganglion without affecting the precursor markers, such as ngn1 and neuroD. Co-injection with messenger RNA (mRNA) derived from mouse diras1 or constitutively active human Rac1 restored the population of trigeminal ganglion. In conclusion, we provided preliminary evidence that diras1 is involved in neurite outgrowth and maintains the number of trigeminal ganglions through the Rac1-dependent pathway.

Reactor safety instrumentation of Paks NPP (experience and perspective)

International Nuclear Information System (INIS)

Elo, S.; Hamar, K.

1993-01-01

The majority of the existing control and protection systems in nuclear power plants use old analog technology and design philosophy. Maintenance and the procurement of spare parts is becoming increasingly difficult. In general there is an age degradation concern. Aging degradation in nuclear power plants must be effectively managed to avoid a loss of vital safety function, shutdown of the station, a reduced power generation, or any failure leading to expensive repair. Even with the best efforts in developing reliable and long life instrumentation and control systems for nuclear power plants it is expected that these systems for most plants will require replacements during the life of the plants. The instrumentation and control system of the nuclear power plants designed during the 70's and constructed in the 80's went out-of-date since nuclear safety is not a static concept and the digital computer technology has undergone rapid improvements during the 70's and 80's. Simultaneously the operation and the maintenance of the I ampersand C system of those plants described above becomes more and more difficult and expensive. In this context the pure quality of the former Soviet designed process instrumentation system increases the needs of upgrading this system. The author reviews the main design characteristics of the reactor safety instrumentation of the Paks NPP. Further he attempts to convey the perspective on upgrading the reactor safety instrumentation as seen by the HAEC and its Nuclear Safety Inspectorate

ISOLAMENTO TÉRMICO DE RESIDÊNCIAS ATRAVÉS DA REUTILIZAÇÃO DE EMBALAGENS TETRA PAK

Directory of Open Access Journals (Sweden)

Jaquiel Salvi Fernandes

2014-09-01

Full Text Available A reciclagem está presente na atualidade, não apenas pelo aspecto econômico, mas também pela questão ambiental. Não faz sentido jogar junto com o lixo orgânico materiais que possam ser reaproveitados ou transformados. Neste contexto também se encontram as embalagens de leite e/ou suco longa vida (Tetra Pak®, amplamente utilizadas pela população. Tais embalagens têm baixo valor comercial, e sua reciclagem é difícil e de custo muito elevado. Este trabalho de extensão universitária reutilizou estas embalagens, montando painéis com as dimensões do forro de residências selecionadas na cidade de Videira-SC, com o intuito de isolá-las termicamente. As caixinhas Tetra Pak possuem uma face aluminizada, a qual impede que o calor seja transmitido para o interior (ou exterior no caso do inverno da residência pelo processo de radiação, refletindo mais de 95% do calor. Com esta característica a caixa de leite se mostra perfeita para exercer a função de manta térmica, como uma alternativa às mantas convencionais, com a vantagem de ser uma solução ecológica e barata. Após a instalação, as casas que antes não possuíam forro passaram a registrar temperaturas internas menores no verão e maiores no inverno, além da prevenção contra goteiras e respingos. As famílias atendidas expressaram unanimidade de opinião, mostrando-se muito satisfeitas com o ambiente após a instalação, relatando o aumento da temperatura em dias mais frios e sua diminuição em dias mais quentes. Palavras-chave: painéis térmicos, reutilização, embalagens longa vida, extensão universitária. Thermal isolation of residences through reuse of Tetra Pak packaging Abstract: Nowadays recycling is present not only in economic but also in environmental issues. It makes no sense mixing together with organic waste the materials that can be reused or processed. Milk and long life juice cartons (Tetra Pak®, widely used by the population, are also included

Land use changes in Pak Phanang Basin using satellite images and geographic information system

Directory of Open Access Journals (Sweden)

Yongchalermchai, C.

2004-01-01

Full Text Available This study defined major changes in land use in Pak Phanang Basin, Nakhon Si Thammarat Province by using remote sensing and geographic information system techniques. The land use map conducted by Department of Land Development in 1988 was compared with the land use map interpreted from satelliteimages of Landsat-5 TM acquired in 1995 and 1999. The results revealed that between 1988 to 1999, forest area in the basin decreased by a total of 98.08 km2, a drastic decline of 60% that was changed to rubber plantation area. The rubber area increased about 181.7 km2 or 41%. Shrimp farm area increased by 184.87 km2, equivalent to a high increase of 886% while paddy field area decreased by 248.7 km2, or 16% that was converted to shrimp farm and rubber land. A decline in forest area caused soil erosion. The severe expansion of shrimp farm area caused the salinity and affected nearby paddy field and water source areas, that resulted in degradation of the environment. Application of remote sensing and geographic information system was utilized as a tool for monitoring the land use change and planning proper resource utilization for sustainable development in Pak Phanang Basin.

A growth factor signaling cascade confined to circular ruffles in macrophages

Directory of Open Access Journals (Sweden)

Timothy P. Welliver

2012-06-01

The formation of macropinosomes requires large-scale movements of membranes and the actin cytoskeleton. Over several minutes, actin-rich surface ruffles transform into 1–5 µm diameter circular ruffles, which close at their distal margins, creating endocytic vesicles. Previous studies using fluorescent reporters of phosphoinositides and Rho-family GTPases showed that signals generated by macrophages in response to the growth factor Macrophage Colony-Stimulating Factor (M-CSF appeared transiently in domains of plasma membrane circumscribed by circular ruffles. To address the question of how signaling molecules are coordinated in such large domains of plasma membrane, this study analyzed the relative timing of growth factor-dependent signals as ruffles transformed into macropinosomes. Fluorescent protein chimeras expressed in macrophages were imaged by microscopy and quantified relative to circular ruffle formation and cup closure. The large size of macropinocytic cups allowed temporal resolution of the transitions in phosphoinositides and associated enzyme activities that organize cup closure. Circular ruffles contained transient and sequential spikes of phosphatidylinositol (4,5-bisphosphate (PI(4,5P2, phosphatidylinositol (3,4,5-trisphosphate (PIP3, diacylglycerol, PI(3,4P2, PI(3P and the activities of protein kinase C-α, Rac1, Ras and Rab5. The confinement of this signal cascade to circular ruffles indicated that diffusion barriers present in these transient structures focus feedback activation and deactivation of essential enzyme activities into restricted domains of plasma membrane.

Degradation Behavior and Accelerated Weathering of Composite Boards Produced from Waste Tetra Pak® Packaging Materials

Science.gov (United States)

Nural Yilgor; Coskun Kose; Evren Terzi; Aysel Kanturk Figen; Rebecca Ibach; S. Nami Kartal; Sabriye Piskin

2014-01-01

Manufacturing panels from Tetra Pak® (TP) packaging material might be an alternative to conventional wood-based panels. This study evaluated some chemical and physical properties as well as biological, weathering, and fire performance of panels with and without zinc borate (ZnB) by using shredded TP packaging cartons. Such packaging material, a worldwide well-known...

Research and higher education background of the Paks Nuclear Power Plant, Hungary. Past and present

International Nuclear Information System (INIS)

Csom, Gy.

2002-01-01

The connection of the Paks Nuclear Power Plant, Hungary, with research and development as well as with higher education is discussed. The main research areas include reactor physics, thermohydraulics, radiochemistry and radiochemical analysis, electronics and nuclear instruments, computers, materials science. The evolution of relations with higher education in Hungary and the PNPP is presented, before and after the installation of the various units. (R.P.)

Safety improvement of Paks nuclear power plant

International Nuclear Information System (INIS)

Vamos, G.

1999-01-01

Safety upgrading completed in the early nineties at the Paks NPP include: replacement of steam generator safety valves and control valves; reliability improvement of the electrical supply system; modification of protection logic; enhancement of the fire protection; construction of full scope Training Simulator. Design safety upgrading measures achieved in recent years were concerned with: relocation of steam generator emergency feed-water supply; emergency gas removal from the primary coolant system; hydrogen management in the containment; protection against sumps; preventing of emergency core cooling system tanks from refilling. Increasing seismic resistance, containment assessment, refurbishment of reactor protection system, improving reliability of emergency electrical supply, analysis of internal hazards are now being implemented. Safety upgrading measures which are being prepared include: bleed and feed procedures; reactor over-pressurisation protection in cold state; treatment of steam generator primary to secondary leak accidents. Operational safety improvements are dealing with safety culture, training measures and facilities; symptom based emergency operating procedures; in-service inspection; fire protection. The significance of international cooperation is emphasised in view of achieving nuclear safety standards recognised in EU

Radiation protection measurements at Paks and its surroundings after the accident of the Chernobylsk nuclear power plant from 28 Apr 1986

International Nuclear Information System (INIS)

German, Endre; Kemenes, Laszlo; Rosa, Geza; Szabo, I.C.; Ormai, Peter; Ronaky, Jozsef; Divos, Ferenc; Varju, Bela; Horvath, Etelka.

1986-08-01

Experimental data on the contaminantion measured within a radius of 30 km from the Paks Nuclear Power Plant due to the accident of the Chernobylsk-4 reactor are given for the period between 28 Apr and 13 Jun 1986. Measurements on airborne and fallout activities, surface contamination of the ground, dose rates of γ radiation, activity concentration of the Danube, of milk, plant and food samples and the activity of human thyroid gland were carried out in the environmental control lab of the Paks NPP. According to the preliminary dose calculations the increment of the radiation exposure of the population is regarded to mount up to the average dose burden for half a year due to natural environmental radiation. (V.N.)

Review of studies pertaining to the seismic input at Paks NPP

International Nuclear Information System (INIS)

Muzzi, F.

1995-01-01

This report refers to the examination performed on the available material relevant for the seismic input estimate for the Paks NPP, within the frame of the IAEA benchmark study for the seismic analysis and testing of the existing NPPs. The aim of the report is to provide an expert judgement about the quantity and quality of the data and studies performed. The first chapter describes the sources of the data set examined, the second involves the criteria followed in the judgment. The third chapter contains the detailed opinion on the content of the data set, the conclusion and suggestions are reported in chapter four

Discovery and characterization of small molecule Rac1 inhibitors.

Science.gov (United States)

Arnst, Jamie L; Hein, Ashley L; Taylor, Margaret A; Palermo, Nick Y; Contreras, Jacob I; Sonawane, Yogesh A; Wahl, Andrew O; Ouellette, Michel M; Natarajan, Amarnath; Yan, Ying

2017-05-23

Aberrant activation of Rho GTPase Rac1 has been observed in various tumor types, including pancreatic cancer. Rac1 activates multiple signaling pathways that lead to uncontrolled proliferation, invasion and metastasis. Thus, inhibition of Rac1 activity is a viable therapeutic strategy for proliferative disorders such as cancer. Here we identified small molecule inhibitors that target the nucleotide-binding site of Rac1 through in silico screening. Follow up in vitro studies demonstrated that two compounds blocked active Rac1 from binding to its effector PAK1. Fluorescence polarization studies indicate that these compounds target the nucleotide-binding site of Rac1. In cells, both compounds blocked Rac1 binding to its effector PAK1 following EGF-induced Rac1 activation in a dose-dependent manner, while showing no inhibition of the closely related Cdc42 and RhoA activity. Furthermore, functional studies indicate that both compounds reduced cell proliferation and migration in a dose-dependent manner in multiple pancreatic cancer cell lines. Additionally, the two compounds suppressed the clonogenic survival of pancreatic cancer cells, while they had no effect on the survival of normal pancreatic ductal cells. These compounds do not share the core structure of the known Rac1 inhibitors and could serve as additional lead compounds to target pancreatic cancers with high Rac1 activity.

Proteomic analysis of HIV-1 Nef cellular binding partners reveals a role for exocyst complex proteins in mediating enhancement of intercellular nanotube formation

Directory of Open Access Journals (Sweden)

Mukerji Joya

2012-06-01

Full Text Available Abstract Background HIV-1 Nef protein contributes to pathogenesis via multiple functions that include enhancement of viral replication and infectivity, alteration of intracellular trafficking, and modulation of cellular signaling pathways. Nef stimulates formation of tunneling nanotubes and virological synapses, and is transferred to bystander cells via these intercellular contacts and secreted microvesicles. Nef associates with and activates Pak2, a kinase that regulates T-cell signaling and actin cytoskeleton dynamics, but how Nef promotes nanotube formation is unknown. Results To identify Nef binding partners involved in Pak2-association dependent Nef functions, we employed tandem mass spectrometry analysis of Nef immunocomplexes from Jurkat cells expressing wild-type Nef or Nef mutants defective for the ability to associate with Pak2 (F85L, F89H, H191F and A72P, A75P in NL4-3. We report that wild-type, but not mutant Nef, was associated with 5 components of the exocyst complex (EXOC1, EXOC2, EXOC3, EXOC4, and EXOC6, an octameric complex that tethers vesicles at the plasma membrane, regulates polarized exocytosis, and recruits membranes and proteins required for nanotube formation. Additionally, Pak2 kinase was associated exclusively with wild-type Nef. Association of EXOC1, EXOC2, EXOC3, and EXOC4 with wild-type, but not mutant Nef, was verified by co-immunoprecipitation assays in Jurkat cells. Furthermore, shRNA-mediated depletion of EXOC2 in Jurkat cells abrogated Nef-mediated enhancement of nanotube formation. Using bioinformatic tools, we visualized protein interaction networks that reveal functional linkages between Nef, the exocyst complex, and the cellular endocytic and exocytic trafficking machinery. Conclusions Exocyst complex proteins are likely a key effector of Nef-mediated enhancement of nanotube formation, and possibly microvesicle secretion. Linkages revealed between Nef and the exocyst complex suggest a new paradigm of

Nodal-dependent mesendoderm specification requires the combinatorial activities of FoxH1 and Eomesodermin.

Directory of Open Access Journals (Sweden)

Christopher E Slagle

2011-05-01

Full Text Available Vertebrate mesendoderm specification requires the Nodal signaling pathway and its transcriptional effector FoxH1. However, loss of FoxH1 in several species does not reliably cause the full range of loss-of-Nodal phenotypes, indicating that Nodal signals through additional transcription factors during early development. We investigated the FoxH1-dependent and -independent roles of Nodal signaling during mesendoderm patterning using a novel recessive zebrafish FoxH1 mutation called midway, which produces a C-terminally truncated FoxH1 protein lacking the Smad-interaction domain but retaining DNA-binding capability. Using a combination of gel shift assays, Nodal overexpression experiments, and genetic epistasis analyses, we demonstrate that midway more accurately represents a complete loss of FoxH1-dependent Nodal signaling than the existing zebrafish FoxH1 mutant schmalspur. Maternal-zygotic midway mutants lack notochords, in agreement with FoxH1 loss in other organisms, but retain near wild-type expression of markers of endoderm and various nonaxial mesoderm fates, including paraxial and intermediate mesoderm and blood precursors. We found that the activity of the T-box transcription factor Eomesodermin accounts for specification of these tissues in midway embryos. Inhibition of Eomesodermin in midway mutants severely reduces the specification of these tissues and effectively phenocopies the defects seen upon complete loss of Nodal signaling. Our results indicate that the specific combinations of transcription factors available for signal transduction play critical and separable roles in determining Nodal pathway output during mesendoderm patterning. Our findings also offer novel insights into the co-evolution of the Nodal signaling pathway, the notochord specification program, and the chordate branch of the deuterostome family of animals.

“Liting it up”: Popular Culture, Indo-Pak Basketball, and South Asian American Institutions

OpenAIRE

Stanley Ilango Thangaraj

2010-01-01

South Asian American participants of a co-ethnic basketball league, known as Indo-Pak Basketball, utilized urban basketball vernacular through the phrase “liting it up” to identify individuals scoring points in great numbers. The person “liting it up” becomes visible and receives recognition. Accordingly, I want to “lite up” the scholarship on South Asian America whereby situating South Asian American religious sites and cultural centers as key arenas for “Americanization” through US popula...

A modernized and versatile startup reactivity measuring system installed at NPP Paks and its application for subcritical systems

International Nuclear Information System (INIS)

Czibok, T.; Dezso, Z.; Horvath, Cs.; Lipcsei, S.; Vegh, J.; Pos, I.

2006-01-01

In 2004 the Hungarian Paks NPP completed a project for upgrading the reactivity measuring system applied during reactor startup experiments. Almost all components of the previous system were replaced, only ex-core ionisation chambers remained unaltered. New hardware and software components were introduced for neutron flux signal handling, for data acquisition, as well as for measurement evaluation and data presentation. High-precision picoamper meters were installed at each reactor unit, current signals are handled by a portable signal processing unit. The system applies an accurate on-line reactivity calculation algorithm based on the point-kinetic model with six delayed neutron groups. Detailed off-line evaluation and analysis of startup measurements can be performed on the portable unit, as well. The paper describes the architecture, data acquisition modules, services and man-machine interface of the new system. Functions and results are illustrated with measured data recorded during a startup of Unit 3. In 2003 and 2004 the RMR was installed and tested at all Paks NPP units successfully and now it is in regular use during unit startups. The second part of the paper illustrates an extension of the new system to perform reactivity measurements using the well-known Rossi-α and Feynman-α statistical methods. The modified system was needed to estimate the reactivity of a subcritical system formed by damaged fuel assemblies stored at the fuel service pit of Paks Unit 2. Theoretical background of the applied algorithms is outlined, then results of validation tests and on site measurements are treated. The measurements have shown that the subcriticality of the damaged fuel was sufficiently deep if the high boron concentration in the fuel service pit was maintained

MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis

Directory of Open Access Journals (Sweden)

Yingmei Wang

2016-10-01

Full Text Available Abstract Background Endometrial carcinoma (EC is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. Methods Immunohistochemistry was used to measure MIIP expression in normal and EC tissue. Both gain-of-function (infection and loss-of-function (siRNA assays were used to alter MIIP expression levels. The effect of MIIP on cell migration and invasion was measured by transwell assay. F-actin immunofluorescence staining was used to observe the cell morphology. The activation of GTP-loaded Rac1 was evaluated by Rac activity assay kit. Immunoprecipitation/WB was used to measure the interaction between MIIP and PAK1. Results We demonstrate that MIIP expression was significantly decreased in EC patients comparing to the normal ones, and decreased MIIP expression in EC tissues is associated with deep myometrial invasion, advanced stage, and the presence of lymph node metastasis. Using both gain-of-function (infection and loss-of-function (siRNA assays, we show that MIIP markedly blocked EC cell migration, whereas loss of MIIP led to increase in EC cell migration. We demonstrate that elevated expression of MIIP resulted in cytoskeleton reorganization with decreased formation of lamellipodia. We also provide evidence that MIIP is a key molecule in directing Rac1 signaling cascades in EC. Ectopically expressed MIIP consistently competed with Rac1-GTP for binding with the PAK1 p21-binding domain. Our data show that MIIP and PAK1 bind each other and that a C-terminal polyproline domain of MIIP is required for PAK1 binding. Deletion of the PAK1-binding domain of MIIP reduced cell migration-inhibiting activity. Conclusions MIIP may function as a tumor

MIIP remodels Rac1-mediated cytoskeleton structure in suppression of endometrial cancer metastasis.

Science.gov (United States)

Wang, Yingmei; Hu, Limei; Ji, Ping; Teng, Fei; Tian, Wenyan; Liu, Yuexin; Cogdell, David; Liu, Jinsong; Sood, Anil K; Broaddus, Russell; Xue, Fengxia; Zhang, Wei

2016-10-19

Endometrial carcinoma (EC) is one of the most common malignancies of the female reproductive system. Migration and invasion inhibitory protein (MIIP) gene was recently discovered candidate tumor suppress gene which located at chromosome 1p36.22. 1p36 deletion was found in many types of tumor including EC. In the present study, we will determine the role and mechanism of MIIP in EC metastasis. Immunohistochemistry was used to measure MIIP expression in normal and EC tissue. Both gain-of-function (infection) and loss-of-function (siRNA) assays were used to alter MIIP expression levels. The effect of MIIP on cell migration and invasion was measured by transwell assay. F-actin immunofluorescence staining was used to observe the cell morphology. The activation of GTP-loaded Rac1 was evaluated by Rac activity assay kit. Immunoprecipitation/WB was used to measure the interaction between MIIP and PAK1. We demonstrate that MIIP expression was significantly decreased in EC patients comparing to the normal ones, and decreased MIIP expression in EC tissues is associated with deep myometrial invasion, advanced stage, and the presence of lymph node metastasis. Using both gain-of-function (infection) and loss-of-function (siRNA) assays, we show that MIIP markedly blocked EC cell migration, whereas loss of MIIP led to increase in EC cell migration. We demonstrate that elevated expression of MIIP resulted in cytoskeleton reorganization with decreased formation of lamellipodia. We also provide evidence that MIIP is a key molecule in directing Rac1 signaling cascades in EC. Ectopically expressed MIIP consistently competed with Rac1-GTP for binding with the PAK1 p21-binding domain. Our data show that MIIP and PAK1 bind each other and that a C-terminal polyproline domain of MIIP is required for PAK1 binding. Deletion of the PAK1-binding domain of MIIP reduced cell migration-inhibiting activity. MIIP may function as a tumor suppressor gene for endometrial carcinoma. MIIP attenuates Rac1

The nuclear immune receptor RPS4 is required for RRS1SLH1-dependent constitutive defense activation in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Kee Hoon Sohn

2014-10-01

Full Text Available Plant nucleotide-binding leucine-rich repeat (NB-LRR disease resistance (R proteins recognize specific "avirulent" pathogen effectors and activate immune responses. NB-LRR proteins structurally and functionally resemble mammalian Nod-like receptors (NLRs. How NB-LRR and NLR proteins activate defense is poorly understood. The divergently transcribed Arabidopsis R genes, RPS4 (resistance to Pseudomonas syringae 4 and RRS1 (resistance to Ralstonia solanacearum 1, function together to confer recognition of Pseudomonas AvrRps4 and Ralstonia PopP2. RRS1 is the only known recessive NB-LRR R gene and encodes a WRKY DNA binding domain, prompting suggestions that it acts downstream of RPS4 for transcriptional activation of defense genes. We define here the early RRS1-dependent transcriptional changes upon delivery of PopP2 via Pseudomonas type III secretion. The Arabidopsis slh1 (sensitive to low humidity 1 mutant encodes an RRS1 allele (RRS1SLH1 with a single amino acid (leucine insertion in the WRKY DNA-binding domain. Its poor growth due to constitutive defense activation is rescued at higher temperature. Transcription profiling data indicate that RRS1SLH1-mediated defense activation overlaps substantially with AvrRps4- and PopP2-regulated responses. To better understand the genetic basis of RPS4/RRS1-dependent immunity, we performed a genetic screen to identify suppressor of slh1 immunity (sushi mutants. We show that many sushi mutants carry mutations in RPS4, suggesting that RPS4 acts downstream or in a complex with RRS1. Interestingly, several mutations were identified in a domain C-terminal to the RPS4 LRR domain. Using an Agrobacterium-mediated transient assay system, we demonstrate that the P-loop motif of RPS4 but not of RRS1SLH1 is required for RRS1SLH1 function. We also recapitulate the dominant suppression of RRS1SLH1 defense activation by wild type RRS1 and show this suppression requires an intact RRS1 P-loop. These analyses of RRS1SLH1 shed

Test and evaluation report for Lockheed Idaho Technologies Company, arrow-pak packaging, docket 95-40-7A, type A container

International Nuclear Information System (INIS)

Kelly, D.L.

1996-01-01

This report incorporates the U.S. Department of Energy, Office of Facility Safety Analysis (DOE/EH-32) approval letter for packaging use. This report documents the U.S. Department of Transportation Specification 7A Type A (DOT-7A) compliance test results of the Arrow-Pak packaging. The Arrow-Pak packaging system consists of Marlex M-8000 Driscopipe, manufactured by Phillips-Driscopipe, Inc., and is sealed with two dome-shaped end caps manufactured from the same materials. The patented sealing process involves the use of electrical energy to heat opposing faces of the pipe and end caps, and hydraulic rams to press the heated surfaces together. This fusion process produces a homogeneous bonding of the end cap to the pipe. The packaging may be used with or without the two internal plywood spacers. This packaging configuration described in this report is designed to ship Type A quantities of solid radioactive materials

Novel radiosynthesis of PET HSV-tk gene reporter probes [18F]FHPG and [18F]FHBG employing dual Sep-Pak SPE techniques.

Science.gov (United States)

Wang, Ji-Quan; Zheng, Qi-Huang; Fei, Xiangshu; Mock, Bruce H; Hutchins, Gary D

2003-11-17

Positron emission tomography (PET) herpes simplex virus thymidine kinase (HSV-tk) gene reporter probes 9-[(3-[(18)F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([(18)F]FHPG) and 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl)guanine ([(18)F]FHBG) were prepared by nucleophilic substitution of the appropriate tosylated precursors with [(18)F]KF/Kryptofix 2.2.2 followed by a quick deprotection reaction and purification with a simplified dual Silica Sep-Pak solid-phase extraction (SPE) method in 15-30% radiochemical yield.

Diagnostic system and diagnostic experiences at the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Katona, Tamas

1986-01-01

The major functions of the diagnostic system of the first two units of the Paks Nuclear Power Plant are as follows: monitoring the mechanical integrity of the reactor and the primary coolant circuit by means of vibration diagnostics; leakage detection of the primary coolant circuit by means of high frequency sonic analysis; loose parts monitoring based on the analysis of high frequency signals of acceleration detectors; and monitoring the vibration state of the turbines and rotary machines by the latter method or by a procedure based on the detection of mechanical vibrations. Up-to-date vibration diagnostics is based on the information supplied by either acceleration detectors or pressure fluctuation detectors, or in-core and ex-core neutron detectors. (V.N.)

Diagnostics of the boiling state of coolant based on neutron fluctuation at the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Por, G.; Gloeckler, O.; Izsak, E.; Valko, J.

1985-09-01

A short summary of theory and early experiments on the effect of propagating perturbation on neutron fluctuations in nuclear reactors is given. Boiling noise was examined in the Rheisenberg reactor of 70 MWe. Comparing the results of measurements with those carried out in the Paks nuclear power plant it seems possible that a small subcooled boiling took place during the 2nd fuel cycle. (author)

Renewal of the operation licence for Paks NPP

International Nuclear Information System (INIS)

Toth, Andras

2002-01-01

Full text: 1. Current situation - Hungarian legislation does not exclude Lr of the units; There are no detailed instructions how to renew the current licence after 'design lifetime'; There is only one type of Time Limited ageing Analyses in Final Safety Analysis Report: Rp embrittlement; Fatigue analyses, equipment qualification or other TLAA's are not included in the Far; There are a lot of statements without background documentation about the operability of certain equipment for 30 years; Ageing is managed as part of maintenance, test and ISI activities; FSAR has been elaborated on the basis of NRC Reg. Guide 1.70 and has to be updated yearly, but there are big gaps in the design bases information in comparison with R-G 1.70 requirements; Periodic Safety Review complies with guide 50-SG-O12 of the IAEA; it is to be submitted to RB every 10 years. 2. Preparatory activities, performed by HAEA - Studying IAEA documents related to ageing; Studying US NRC documents related to ageing and LR; Listing equipment, which needs ageing management; Identification of scope and structure of ageing analyses; Ageing analysis of selected equipment (provided by TSO VEIKI); Preparation of guides on ageing management in accordance with Hungarian regulations' structure; Studying NRC Reg. Guide 1.70 on FSAR and IAEA safety guide 50-SG-O12 on PSR (identification of gaps and overlaps in these documents); Comparison of international experience with Hungarian opportunities (identification of gaps in input information). 3. Lessons learned from preparatory activities - Design basis documentation of Paks NPP needs completion and re-evaluation; The ageing Management Program should cover all SSCs important to safety in consistent and auditable manner; Equipment qualification was not included in initial design basis therefore the EQ documentation is not complete and part of equipment does not comply with EQ requirements; Effective maintenance of technical condition of safety related equipment has

Experimental investigation and numerical modelling of tritium wash-out by precipitation in the area of the nuclear power plant of Paks, Hungary

International Nuclear Information System (INIS)

Koelloe, Z.; Palcsu, L.; Major, Z.; Papp, L.; Molnar, M.

2009-01-01

Complete text of publication follows. Tritium is an important radioactive isotope because its natural occurrence in the air and precipitation due to natural and artificial sources. In order to investigate the natural changes in tritium concentration, the artificial component has to be known. Some field experiments were carried out before to investigate the washout of tritium by precipitation emitted from artificial sources, but none of them were carried out around a real power plant, measuring the deposition pattern. We collected rainwater around the nuclear power plant of Paks (Paks NPP), and analyzed them for tritium. The rainwater samplers were constructed at ATOMKI. Their structure consists of a funnel, support parts and a long tube, acting as the storage vessel for the rainwater. One end of the tube is connected to the funnel, the other end is open. This way when 'new' rainwater falls, it pushes out the 'old' water, causing that always the last rainwater is in the tube (if enough rain is falling). In total 54 samplers were placed out around the Paks NPP in two half circles, with radiuses 400 and 800 m, pointing east. We collected samples after a rain period on 7-8 June 2009. They were prepared and measured with liquid scintillation counting (LSC) for tritium. We measured some samples also with the 3 He-ingrowth method, to ensure better accuracy. The measurement results in Fig. 1 clearly show the trace of the tritium plume emitted from the plant. However, the highest values are not very high, compared to environmental levels, and considering the fact that all the samples were collected from the area of the plant. A numerical model was coded to calculate the washout of tritium theoretically from the meteorological and emission data, and to estimate the effect of the plant in larger distances. In Fig. 1 it is apparent that the model, however does not describe the data precisely, but gives reasonable results, especially for the outer circle. The calculations also

Refurbishment of the reactor protection system at Paks NPP. The refurbishment process

International Nuclear Information System (INIS)

Turi, T.; Katics, B.

1998-01-01

The Reactor Protection System Refurbishment Project had an extensive preparation period in Paks started in 1992. During this preparation a large volume of the basic engineering tasks has been performed and as a result a contract for implementation of a three-train digital RPS on the four Units was concluded with Siemens in September, 1996. According to that contract the first refurbished Unit will be commissioned in 1999 followed by a further Unit in each succeeding year. This paper introduces the process of the refurbishment, overview of the V and V activities, introduce the architecture, summarize the main design principles and outlines the additional tasks to be performed together with the RPS design. (author)

Time versus frequency domain calculation of the main building complex of the VVER 440/213 NPP PAKS

International Nuclear Information System (INIS)

Katona, T.; Ratkai, S.; Halbritter, A.; Krutzik, N.J.; Schuetz, W.

1995-01-01

Various dynamic analyses were conducted for the main building complex of the VVER 440/213 PAKS in order to determine the dynamic response and assess the aseismic capacity of this nuclear power plant. Different types of mathematical models for idealizing the soil and the building structures were used. The main goal of the study presented here was to demonstrate the effects of different procedures for consideration of soil-structure interaction on the dynamic response of the structures mentioned above. The analyses were based on appropriate mathematical models of the coupled vibration structures (reactor building, turbine hall, intermediate building structures) and the layered soil. On the basis of this study, it can be concluded that substructure models using frequency-independent impedances and cut-off of modal damping usually provide conservative results. Complex models which allow the soil-soil and the structure or by frequency-dependent impedances) provide more accurate results. The latter approach results in more efficient designs which are not only safe but also economical. (author). 7 refs., 15 figs

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 1. Data related to sites and plants: Paks NPP, Kozloduy NPP. Working material

International Nuclear Information System (INIS)

1995-01-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on data related to sites and NPPs Paks and Kozloduy

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 1. Data related to sites and plants: Paks NPP, Kozloduy NPP. Working material

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-07-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on data related to sites and NPPs Paks and Kozloduy.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

Energy Technology Data Exchange (ETDEWEB)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Junko Y., E-mail: yama_jun@aoni.waseda.jp [Faculty of Science and Engineering, Waseda University, Wakamatsu-cho 2-2, Shinjuku-ku, Tokyo 162-8480 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Toshima, Jiro, E-mail: jtosiscb@rs.noda.tus.ac.jp [Department of Biological Science and Technology, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan); Research Center for RNA Science, RIST, Tokyo University of Science, Niijuku 6-3-1, Katsushika-ku, Tokyo 125-8585 (Japan)

2014-01-10

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V{sub o} subunit of vacuolar-type H{sup +}-ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling.

V-ATPase-dependent luminal acidification is required for endocytic recycling of a yeast cell wall stress sensor, Wsc1p

International Nuclear Information System (INIS)

Ueno, Kazuma; Saito, Mayu; Nagashima, Makiko; Kojima, Ai; Nishinoaki, Show; Toshima, Junko Y.; Toshima, Jiro

2014-01-01

Highlights: •A targeted genome screen identified 5 gene groups affecting Wsc1p recycling. •V-ATPase-dependent luminal acidification is required for Wsc1p recycling. •Activity of V-ATPase might be required for cargo recognition by the retromer complex. -- Abstract: Wsc1p is a major cell wall sensor protein localized at the polarized cell surface. The localization of Wsc1p is maintained by endocytosis and recycling from endosomes back to the cell surface, but changes to the vacuole when cells are subjected to heat stress. Exploiting this unique property of Wsc1p, we screened for yeast single-gene deletion mutants exhibiting defects in Wsc1p trafficking. By expressing 3GFP-tagged Wsc1p in mutants with deleted genes whose function is related to intracellular trafficking, we identified 5 gene groups affecting Wsc1p trafficking, impaired respectively in endocytic internalization, multivesicular body sorting, the GARP complex, endosomal maturation/vacuolar fusion, and V-ATPase. Interestingly, deletion of the VPH1 gene, encoding the V o subunit of vacuolar-type H + -ATPase (V-ATPase), led to mis-localization of Wsc1p from the plasma membrane to the vacuole. In addition, disruption of other V-ATPase subunits (vma mutants) also caused defects of Wsc1p trafficking and vacuolar acidification similar to those seen in the vph1Δ mutant. Moreover, we found that deletion of the VPS26 gene, encoding a subunit of the retromer complex, also caused a defect in Wsc1p recycling and mis-localization of Wsc1p to the vacuole. These findings clarified the previously unidentified Wsc1p recycling pathway and requirement of V-ATPase-dependent luminal acidification for Wsc1p recycling

Increased Circulating Endothelial Microparticles Associated with PAK4 Play a Key Role in Ventilation-Induced Lung Injury Process

Directory of Open Access Journals (Sweden)

Shuming Pan

2017-01-01

Full Text Available Inappropriate mechanical ventilation (MV can result in ventilator-induced lung injury (VILI. Probing mechanisms of VILI and searching for effective methods are current areas of research focus on VILI. The present study aimed to probe into mechanisms of endothelial microparticles (EMPs in VILI and the protective effects of Tetramethylpyrazine (TMP against VILI. In this study, C57BL/6 and TLR4KO mouse MV models were used to explore the function of EMPs associated with p21 activated kinases-4 (PAK-4 in VILI. Both the C57BL/6 and TLR4 KO groups were subdivided into a mechanical ventilation (MV group, a TMP + MV group, and a control group. After four hours of high tidal volume (20 ml/kg MV, the degree of lung injury and the protective effects of TMP were assessed. VILI inhibited the cytoskeleton-regulating protein of PAK4 and was accompanied by an increased circulating EMP level. The intercellular junction protein of β-catenin was also decreased accompanied by a thickening alveolar wall, increased lung W/D values, and neutrophil infiltration. TMP alleviated VILI via decreasing circulating EMPs, stabilizing intercellular junctions, and alleviating neutrophil infiltration.

Full-scale dynamic structural testing of Paks nuclear power plant

International Nuclear Information System (INIS)

Da Rin, E.M.; Muzzi, F.P.

1995-01-01

Within the framework of the IAEA coordinated 'Benchmark Study for the seismic analysis and testing of WWER-type NPPs', in-situ dynamic structural testing activities have been performed at the Paks Nuclear Power Plant in Hungary. The specific objective of the investigation was to obtain experimental data on the actual dynamic structural behaviour of the plant's major constructions and equipment under normal operating conditions, for enabling a valid seismic safety review to be made. This paper gives a synthetic description of the conducted experiments and presents some results, regarding in particular the free-field excitations produced during the earthquake-simulation experiments and an experiment of the dynamic soil-structure interaction global effects at the base of the reactor containment structure. Moreover, a method which can be used for inferring dynamic structural characteristics from the recorded time-histories is briefly described and a simple illustrative example given. (author)

Upgrading the reactor noise diagnostic systems at the Paks NPP

International Nuclear Information System (INIS)

Czibok, T.; Dezsoe, Z.; Kiss, K.; Krinizs, K.; Lipcsei, S.

2002-01-01

The paper reports on the actual step in upgrading process of the reactor noise diagnostic systems at Paks NPP. This step has mainly a technical character. Renewal of facilities for signal conditioning and for data acquisition is going on. Autonomous systems at each of the four reactor units will be able to acquire a set of data series which can be arbitrarily chosen from the whole set of several hundred in-core neutron and other signals. The autonomous systems can be remotely controlled by a central computer through the local network. Modularity and extensibility are important features of the new systems: the size of the set of available signals can be extended and new modules for more advanced evaluations can be installed later. Present plans for system hardware upgrading are outlined, together with some technical details of measurement control, data acquisition moduls and network communication.(abstract)

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4F. Paks NPP: Analysis and testing. Working material

International Nuclear Information System (INIS)

1999-01-01

In August 1991, following the SMiRT-11 Conference in Tokyo, a Technical Committee Meeting was held on the 'Seismic safety issues relating to existing NPPs'. The Proceedings of this TCM was subsequently compiled in an IAEA Working Material. One of the main recommendations of this TCM, called for the harmonization of criteria and methods used in Member States in seismic reassessment and upgrading of existing NPPs. Twenty four institutions from thirteen countries participated in the CRP named 'Benchmark study for the seismic analysis and testing of WWER type NPPs'. Two types of WWER reactors (WWER-1000 and WWER-440/213) selected for benchmarking. Kozloduy NPP Units 5/6 and Paks NPP represented these respectively as prototypes. Consistent with the recommendations of the TCM and the working paper prepared by the subsequent Consultants' Meeting, the focal activity of the CRP was the benchmarking exercises. A similar methodology was followed both for Paks NPP and Kozloduy NPP Unit 5. Firstly, the NPP (mainly the reactor building) was tested using a blast loading generated by a series of explosions from buried TNT charges. Records from this test were obtained at several free field locations (both downhole and surface), foundation mat, various elevations of structures as well as some tanks and the stack. Then the benchmark participants were provided with structural drawings, soil data and the free field record of the blast experiment. Their task was to make a blind prediction of the response at preselected locations. The analytical results from these participants were then compared with the results from the test. Although the benchmarking exercises constituted the focus of the CRP, there were many other interesting problems related to the seismic safety of WWER type NPPs which were addressed by the participants. These involved generic studies, i.e. codes and standards used in original WWER designs and their comparison with current international practice; seismic analysis

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4B. Paks NPP: Analysis/testing. Working material

International Nuclear Information System (INIS)

1995-01-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on dynamic study of the main building of the Paks NPP; shake table investigation at Paks NPP and the Final report of the Co-ordinated Research Programme

Knowledge Management Applications at the Paks NPP Ltd

International Nuclear Information System (INIS)

Buza, K.

2006-01-01

The objective of the human resource policy at the Paks NPP Ltd. is to make available personnel in optimal quantity, either employed or contracted, that are properly selected, trained and equipped with all knowledge, skills and attitudes required for the long term safe, competitive and reliable operation of the plant. The plant's service time extension has been approved as a consequence of which significant efforts must be turned to ensure properly prepared labor force for the long term plant operation. This is only achievable if - using knowledge related to the corporate recruitment needs and the job-specific requirements/expectations - personnel are selected from internal or external resources that can be prepared through expedient, targeted development programs to fill in positions specified as necessary for plant operations. A decisive factor of the achievements of the plant is the staff properly prepared and performing jobs with professionalism. The accumulated collective knowledge and experience of the long years are assets which, - when the future of the plant is planned - can and must be used as a firm foundation. What value does this knowledge represent, how can it be preserved and transferred to the next generation and what steps have been taken already by the plant to achieve this goal? - these are the questions that the paper is to provide a concise response for. The concise program has set the ultimate goal of - while keeping the best of traditional tools such as the spontaneous knowledge management - evolving to address KM in a planned, conscious manner, making use of the achievements of dedicated projects already terminated or on-going (like the Safety Upgrading Program, the Training Reconstruction Project or the Final Safety Report) and introducing a complex, needs-driven career and succession planning system. Planned to run on three main tracks: the selection and development of leaders in frame of the Management Pool of Talents; the selection and

Influence of tensides and lipophilic substrates on the biological availability of polycyclic aromatic hydrocarbons (PAHs); Ueber dem Einfluss von Tensiden und lipophilen Substraten auf die Bioverfuegbarkeit von polyzyklischen aromatischen Kohlenwasserstoffen (PAK)

Energy Technology Data Exchange (ETDEWEB)

Soeder, C.J. von; Kleespies, M; Eschner, C; Webb, L; Groeneweg, J [Forschungszentrum Juelich GmbH (Germany). IBT-3/ICG-6

1998-12-31

The objects of the study were as follows: isolation and characterization of PAH-degrading micro-organisms from lysimeters; tests relating to the experimental simulation of the conditions permitting pollutant degradation in soil; investigation of the influence of tensides and other dissolved organic compounds on the biological availability and degradation of PAHs. (orig./SR) [Deutsch] - Isolierung und Charakterisierung PAK-abbauender Mikroorganismen aus Lysimetern; Versuche zur experimentellen Simulation der Bedingungen, unter denen der Abbau von Schadstoffen im Boden erfolgt. - Untersuchung des Einflusses von Tensiden und anderen geloesten organischen Verbindungen auf Bioverfuegbarkeit und Abbau von PAK. (orig./SR)

Influence of tensides and lipophilic substrates on the biological availability of polycyclic aromatic hydrocarbons (PAHs); Ueber dem Einfluss von Tensiden und lipophilen Substraten auf die Bioverfuegbarkeit von polyzyklischen aromatischen Kohlenwasserstoffen (PAK)

Energy Technology Data Exchange (ETDEWEB)

Soeder, C.J. von; Kleespies, M.; Eschner, C.; Webb, L.; Groeneweg, J. [Forschungszentrum Juelich GmbH (Germany). IBT-3/ICG-6

1997-12-31

The objects of the study were as follows: isolation and characterization of PAH-degrading micro-organisms from lysimeters; tests relating to the experimental simulation of the conditions permitting pollutant degradation in soil; investigation of the influence of tensides and other dissolved organic compounds on the biological availability and degradation of PAHs. (orig./SR) [Deutsch] - Isolierung und Charakterisierung PAK-abbauender Mikroorganismen aus Lysimetern; Versuche zur experimentellen Simulation der Bedingungen, unter denen der Abbau von Schadstoffen im Boden erfolgt. - Untersuchung des Einflusses von Tensiden und anderen geloesten organischen Verbindungen auf Bioverfuegbarkeit und Abbau von PAK. (orig./SR)

The scaffold protein MEK Partner 1 is required for the survival of estrogen receptor positive breast cancer cells

Directory of Open Access Journals (Sweden)

Marina Mihaela

2012-07-01

Full Text Available Abstract MEK Partner 1 (MP1 or MAPKSP1 is a scaffold protein that has been reported to function in multiple signaling pathways, including the ERK, PAK and mTORC pathways. Several of these pathways influence the biology of breast cancer, but MP1’s functional significance in breast cancer cells has not been investigated. In this report, we demonstrate a requirement for MP1 expression in estrogen receptor (ER positive breast cancer cells. MP1 is widely expressed in both ER-positive and negative breast cancer cell lines, and in non-tumorigenic mammary epithelial cell lines. However, inhibition of its expression using siRNA duplexes resulted in detachment and apoptosis of several ER-positive breast cancer cell lines, but not ER-negative breast cancer cells or non-tumorigenic mammary epithelial cells. Inhibition of MP1 expression in ER-positive MCF-7 cells did not affect ERK activity, but resulted in reduced Akt1 activity and reduced ER expression and activity. Inhibition of ER expression did not result in cell death, suggesting that decreased ER expression is not the cause of cell death. In contrast, pharmacological inhibition of PI3K signaling did induce cell death in MCF-7 cells, and expression of a constitutively active form of Akt1 partially rescued the cell death observed when the MP1 gene was silenced in these cells. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3K/Akt pathway in ER-positive breast cancer cells.

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

Science.gov (United States)

Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S

1996-06-01

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Regulatory Approach To and Lessons Learned with Licensing of Service Life Extension at PAKS NPP

International Nuclear Information System (INIS)

Petofi, G.

2012-01-01

Paks Nuclear Power Plant of Hungary decided to extend the original design lifetime of the plant by 20 years, which expires on December 31, 2012 concerning unit 1. The Hungarian Atomic Energy Authority established the legal environments in order to license the extension using an approach similar to that followed in the United States. The regulation specifies the pre-conditions for the extension, defines the scoping and screening process for the passive and long lived systems, structures and components to be involved in the licensing and the respective methods of treatment and also determines how the active components shall be dealt with during the extended lifetime. The regulatory procedure is a two-step process including the oversight of the preparatory programme of the operator for the extension that started 4 years before the expiry of the lifetime and the licensing process itself, which is currently under way for unit 1 after the submittal of the licensee's application at the end of 2011. The first experiences with the regulatory assessment of the application are available yet and presented in this paper. (author)

RMR. A new portable Reactivity Measuring System installed at NPP Paks

International Nuclear Information System (INIS)

Czibok, T.; Horvath, C.; Bara, P.; Dezsoe, Z.; Laz, J.; Vegh, J.; Pos, I.

2003-01-01

The Hungarian Paks NPP is conducting a two year project for upgrading the reactivity measuring system applied during reactor startup experiments. The NPP has decided to replace almost all components of the previous system, only ionisation chambers remain unaltered. Devices for measuring neutron flux by means of ionisation chambers, for data acquisition and for measurement evaluation were completely renewed: new hardware-software components were introduced. Autonomous, high-precision current measuring systems (picoampere meters) are applied at each reactor unit, the converted picoampere signals are handled by a portable processing unit. The portable unit - based on a notebook PC - handles measured signals by using a high-precision A/D converter card, the scan time is 0.10 sec. In addition to handling three ionisation chamber signals the portable unit collects control rod position measurements through a serial line. The portable unit is able to receive additional measured data (e.g. core inlet temperature and boron concentration) from the process computer via local area network. Archiving of all measured and calculated data is performed in a redundant manner: data are stored locally and in the process computer, as well. The new system applies an accurate on-line reactivity calculation algorithm based on the point-kinetic model with 6 delayed neutron groups. Input data (effective delayed neutron fraction and other delayed neutron parameters) to the on-line calculation are taken from the off-line core design calculation. Detailed evaluation and analysis of startup measurements can be performed also on the portable unit. The user interface of the system is tailored to support various startup measurement tasks effectively: measured and calculated data are displayed on trends and on dedicated pictures. A user-friendly trending and listing graphic tool facilitates visualisation of archived data. The paper describes the architecture, data acquisition modules, algorithms and

Optimal organization of structural analysis and site inspection for the seismic requalification of Paks NPP

International Nuclear Information System (INIS)

Contri, P.

1996-01-01

The analysis described in this report deals with a numerical procedure aimed for the assessment of a methodology for the optimal organization of data collection, in the context of seismic requalification of structures and components of existing nuclear power plants. The presented procedure has quite a general application and an example was chosen for the Paks NPP where seismic requalification is in progress. The assessment was carried out in reference to the following main tasks: structure and soil data analysis; numerical model generation; deterministic dynamic analysis description; reliability analysis framework discussion; transfer function calculation via response surface approach; and the sensitivity evaluation

Physical, mechanical and hydration kinetics of particleboards manufactured with woody biomass (Cupressus lusitanica, Gmelina arborea, Tectona grandis), agricultural resources, and Tetra Pak packages.

Science.gov (United States)

Moya, Róger; Camacho, Diego; Oporto, Gloria S; Soto, Roy F; Mata, Julio S

2014-02-01

Lignocellulosic wastes resulting from agricultural activities as well as Tetra Pak residues from urban centres can cause significant levels of pollution. A possible action to minimize this problem is to use them in the production of particleboards. The purpose of this study was to evaluate the physical, mechanical, and hydration properties of particleboards manufactured with the mixture of woody biomass (Cupressus lusitanica, Gmelina arborea, and Tectona grandis) and either agricultural wastes [pineapple leaves (Ananas comosus) and palm residues (Elaeis guineensis)] or Tetra Pak residues (TP). The results show that the particleboards prepared with TP and woody biomass can reduce the swelling and water absorption in up to 40% and 50% compared with particleboards without TP. Also, these particleboards had increased flexure resistance and shear stress (up to 100%) compared with those without TP. On the contrary, particleboards prepared with pineapple leaves in combination with woody biomass showed the lowest mechanical properties, particularly for tensile strength, hardness, glue-line shear, and nail and screw evaluation.

Continuous analysis of radioiodine isotopes in the primary coolant of NPP Paks, Hungary

International Nuclear Information System (INIS)

Erdoes, E.; Soos, J.; Vincze, A.; Zsille, O.; Gujgiczer, A.; Solymosi, J.; Pinter, T.

1998-01-01

The radioiodine analyser has been installed at the Paks-3 reactor unit. The analyser is based on an efficient and simple method of radioiodine separation: the iodine compound is converted to elementary iodine quantitatively by oxidation with potassium iodate in acid medium. Owing to its volatility, iodine is evaporated quantitatively from the primary coolant (desorption) using air flow. The air is bubbled through a solution of a reducer, and iodine is absorbed in a form which is ready for measurement. A simple NaI(Tl) detector is used for the measurement of gamma spectra. The system is controlled and data are processed by a computer. The analyser displays activity concentration data of the five iodine isotopes periodically every 15 minutes. (M.D.)

Experiences with the upgraded SKP system during refuelling Paks nuclear power plant

International Nuclear Information System (INIS)

Baranyai, A.; Hetzmann, A.

1997-01-01

In order to control the neutron flux during the refueling period, new measuring chains were developed and put into operation by the experts of KFKI-RegTron Co., Ltd. and the Paks Nuclear Power Plant with the purpose of partially substituting the original Refuelling Neutron Monitoring system (SKP) of WWER-440 reactor units. The modified monitoring system processes the signals of detectors located in channels outside the core. The outputs of measurement amplifiers equipped with up-to-date electronics fit in the original system perfectly. Use of the out-of-core measuring technique confirmed the preliminary expectations: interference sensitivity has decreased, the neutron/gamma ration increased and refueling time has become shorter by one to one-and-a-half day. The paper details the reasons for upgrading, the essence of utilized solutions and the operational experience. (author)

Proposal of In-vessel corium retention concept for Paks NPP

International Nuclear Information System (INIS)

Elter, J.; Toth, E.; Matejovic, P.

2011-01-01

The in-vessel corium retention (IVR) via external reactor vessel cooling (ERVC) seems to be a promising severe accident management strategy not only for new generation of advanced PWRs, but also for VVER-440/V213 reactors, which were designed several years ago. The basic idea of in-vessel retention of corium is to prevent RPV failure by flooding the reactor cavity so that the reactor pressure vessel is submerged in water up to its support structures, and thus the decay heat can be transferred from the corium pool through the vessel wall and into the water surrounding the vessel. An IVR concept with simple ECVR loop based only on minor modifications of existing plant technology was proposed for the Paks Nuclear Power Plant. 2 severe accident (LB and SB LOCA) without availability of HP and LP safety injection in power upgrade (108%) conditions were simulated using the ASTEC code. The analyses show that the proposed solution is effective in preserving RPV integrity in the case of severe accident. Possible uncertainties in code predictions are covered by the applied conservative assumptions

Primary water chemistry control at units of Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Schunk, J.; Patek, G.; Pinter, T.; Tilky, P.; Doma, A.; Osz, J.

2010-01-01

The primary water chemistry of the four identical units of Paks Nuclear Power Plant has been developed based on Western-type PWR units, taking into consideration some Soviet-Russian modifications. The political changes in 90s have also influenced the water chemistry specifications and directions. At PWR units the transition operational modes have been developed while in case of VVER units - in lack of central uniform regulation - this question has become the competence and responsibility of each individual plant. This problem has resulted in separate water chemistry developments with a considerable time delay. The needs for life-time extensions all over the World have made the development of start-up and shut-down chemistry procedures extremely important, since they considerably influence the long term and safe operation of plants. The uniformly structured limit value system, the principles applied for the system development, and the logic schemes for actions to be taken are discussed in the paper, both for normal operation and transition modes. (author)

Primary Water Chemistry Control at Units of Paks Nuclear Power Plant

Energy Technology Data Exchange (ETDEWEB)

Schunk, J.; Pinter, G. Patek T.; Tilky, P.; Doma, A. [Paks Nuclear Power Plant Co. Ltd., Paks (Hungary); Osz, J. [Budapest University of Technology and Economics, Budapest (Hungary)

2013-03-15

The primary water chemistry of the four identical units of Paks Nuclear Power Plant has been developed based on Western type PWR units, taking into consideration some Russian modifications. The political changes in the 1990s have also influenced the water chemistry specifications and directions. At PWR units the transition operational modes have been developed while in case of WWER units - in lack of central uniform regulation - this question has become the competence and responsibility of each individual plant. This problem has resulted in separate water chemistry developments with a considerable time delay. The need for lifetime extensions worldwide has made the development of startup and shutdown chemistry procedures extremely important, since they considerably influence the long term and safe operation of plants. The uniformly structured limit value system, the principles applied for the system development, and the logic schemes for actions to be taken are discussed in the paper, both for normal operation and transition modes. (author)

Automation of the electromagnetic filter applied for condensation water treatment in the secondary cooling system of the Paks Nuclear Power Plant

International Nuclear Information System (INIS)

Szilagyi, Gyoergy

1989-01-01

A full-flow condensation water purification system is applied in the secondary cooling circuit of the Paks NPP. The electromagnetic filter of the filtering system eliminates ferromagnetic impurities. The filter consists of a high current coil and an automatic control unit. During the improvement of this unit, a FESTO FPC-404 type controller based on an extended capability PLC was installed. (R.P.) 5 figs

Results of secondary side water regime modification in Nuclear Power Plant Paks

International Nuclear Information System (INIS)

Oesz, J.; Salamon, T.; Nagy, O.; Tilky, P.

2001-01-01

In order to extend the lifetime of Paks NPP, and for a possible power increase it is more and more evident that steam generators may be the limit. For the wear-out of the SG, it is decisive that at the end of the planned lifetime (after 25-30 reactor years) the number of plugged tubes should be as far as possible from the heat capacity limit. The modification of the secondary side water regime was started in 1997. It has been completed in the summer of year 2000, each of the four units has been operating using the new water regime. The results of this modification were evaluated on the basis of data obtained from six reactor years. The new water regime - after the overhaul check of the SG tubes - significantly decrease the number of tubes to plugged in the future. (R.P.)

Evaluation of Historic Indo-Pak Relations, Water Resource Issues and Its impact on Contemporary Bilateral Affairs

Directory of Open Access Journals (Sweden)

Muhammad Tayyab Sohail

2015-02-01

Full Text Available Being developed countries both Pakistan and India are striving for the economic development. Pakistan and India share a 1610 km long border. They share same language, dress and culture and also six watercourses, namely the Indus, Jhelum, Chenab, Ravi, Sutlej and Beas, along with their numerous tributaries. Pakistan, like other countries of the region depends heavily on agriculture, with the greater part of the population relying on it for livelihood. As a result, water is not only vital for everyday needs, but a critical source for economic development. Water is a resource on which there is dependency of economy and no substitute. Pakistan and India are close neighbors and lied in South East of Asia. Apart from sharing border and history both the countries have various same customs and traditions.Both countries gained independence in 1947 from British Government, from the day of independence Pakistan has been facing lots of internal and external challenges. Apart from other conflicts, water issues also exist between Pakistan and India. After the nine years negotiation with the help of World Bank, they solved this issue but after some time it started again. Some kind of historical issues including water issues has been discussed in this paper. To judge the public opinion of the both countries, an interview survey was conducted by some international expert and from the people who are directly involved in these kind of profession of Indo-Pak relation. Analyses of interview with some statistic information and on the behalf of history some conclusions and suggestions were including at the end of this study.

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

Science.gov (United States)

Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

2016-12-01

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Metagenomes of complex microbial consortia derived from different soils as sources for novel genes conferring formation of carbonyls from short-chain polyols on Escherichia coli.

Science.gov (United States)

Knietsch, Anja; Waschkowitz, Tanja; Bowien, Susanne; Henne, Anke; Daniel, Rolf

2003-01-01

Metagenomic DNA libraries from three different soil samples (meadow, sugar beet field, cropland) were constructed. The three unamplified libraries comprised approximately 1267000 independent clones and harbored approximately 4.05 Gbp of environmental DNA. Approximately 300000 recombinant Escherichia coli strains of each library per test substrate were screened for the production of carbonyls from short-chain (C2 to C4) polyols such as 1,2-ethanediol, 2,3-butanediol, and a mixture of glycerol and 1,2-propanediol on indicator agar. Twenty-four positive E. COLI clones were obtained during the initial screen. Fifteen of them contained recombinant plasmids, designated pAK201-215, which conferred a stable carbonyl-forming phenotype on E. coli Sequencing revealed that the inserts of pAK201-215 encoded 26 complete and 14 incomplete predicted protein-encoding genes. Most of these genes were similar to genes with unknown functions from other microorganisms or unrelated to any other known gene. The further analysis was focused on the 7 plasmids (pAK204, pAK206, pAK208, and pAK210-213) recovered from the positive clones, which exhibited an NAD(H)-dependent alcohol oxidoreductase activity with polyols or the correlating carbonyls as substrates in crude extracts. Three genes (ORF6, ORF24, and ORF25) conferring this activity were identified during subcloning of the inserts of pAK204, pAK211, and pAK212. The sequences of the three deduced gene products revealed no significant similarities to known alcohol oxidoreductases, but contained putative glycine-rich regions, which are characteristic for binding of nicotinamide cofactors. Copyright 2003 S. Karger AG, Basel

ARF1 recruits RAC1 to leading edge in neutrophil chemotaxis.

Science.gov (United States)

Mazaki, Yuichi; Onodera, Yasuhito; Higashi, Tsunehito; Horinouchi, Takahiro; Oikawa, Tsukasa; Sabe, Hisataka

2017-10-02

The small GTPase ARF1 mediates membrane trafficking mostly from the Golgi, and is essential for the G protein-coupled receptor (GPCR)-mediated chemotaxis of neutrophils. In this process, ARF1 is activated by the guanine nucleotide exchanger GBF1, and is inactivated by the GTPase-activating protein GIT2. Neutrophils generate the Gβγ-PAK1-αPIX-GIT2 linear complex during GPCR-induced chemotaxis, in which αPIX activates RAC1/CDC42, which then employs PAK1. However, it has remained unclear as to why GIT2 is included in this complex. We investigated the association between ARF1 and RAC1/CDC42 during the fMLP-stimulated chemotaxis of HL60 cells. We found that the silencing of GBF1 significantly impaired the recruitment of RAC1 to the leading edges, but not PAK1, αPIX, RAC2, or CDC42. A significant population of RAC1 colocalized with ARF1 at the leading edges in stimulated cells, whereas fMLP activated both ARF1 and ARF5. Consistently, the silencing of ARF1, but not ARF5, impaired the recruitment of RAC1, whereas the silencing of RAC1 did not affect the recruitment of ARF1 to the leading edges. Our results indicated that the activation of ARF1 triggers the plasma membrane recruitment of RAC1 in GPCR-mediated chemotaxis, which is essential for cortical actin remodeling. Thus, membrane remodeling at the leading edges appears to precede actin remodeling in chemotaxis. Together with the fact that GIT2, which inactivates ARF1, is an integral component of the machinery activating RAC1, we proposed a model in which the ARF1-RAC1 linkage enables the regulation of ARF1 by repetitive on/off cycles during GPCR-mediated neutrophil chemotaxis.

Active ras triggers death in glioblastoma cells through hyperstimulation of macropinocytosis.

Science.gov (United States)

Overmeyer, Jean H; Kaul, Aparna; Johnson, Erin E; Maltese, William A

2008-06-01

Expression of activated Ras in glioblastoma cells induces accumulation of large phase-lucent cytoplasmic vacuoles, followed by cell death. This was previously described as autophagic cell death. However, unlike autophagosomes, the Ras-induced vacuoles are not bounded by a double membrane and do not sequester organelles or cytoplasm. Moreover, they are not acidic and do not contain the autophagosomal membrane protein LC3-II. Here we show that the vacuoles are enlarged macropinosomes. They rapidly incorporate extracellular fluid-phase tracers but do not sequester transferrin or the endosomal protein EEA1. Ultimately, the cells expressing activated Ras detach from the substratum and rupture, coincident with the displacement of cytoplasm with huge macropinosome-derived vacuoles. These changes are accompanied by caspase activation, but the broad-spectrum caspase inhibitor carbobenzoxy-Val-Ala-Asp-fluoromethylketone does not prevent cell death. Moreover, the majority of degenerating cells do not exhibit chromatin condensation typical of apoptosis. These observations provide evidence for a necrosis-like form of cell death initiated by dysregulation of macropinocytosis, which we have dubbed "methuosis." An activated form of the Rac1 GTPase induces a similar form of cell death, suggesting that Ras acts through Rac-dependent signaling pathways to hyperstimulate macropinocytosis in glioblastoma. Further study of these signaling pathways may lead to the identification of other chemical and physiologic triggers for this unusual form of cell death.

Optimal organization of structural analysis and site inspection for the seismic requalification of the nuclear power plant of Paks, Hungary

International Nuclear Information System (INIS)

Fregonese, R.

1995-01-01

The analysis described in this report deals with a numerical procedure aimed at the assessment of a methodology for the optimal organization of data collection, in a contest of seismic requalification of structures and components of existing nuclear power stations (NPPs). The activity has been carried out in the frame of IAEA benchmark study for the seismic analysis of existing Nuclear Power Plants. This study starts from the assumption that seismic qualification of existing NPPs usually has to be carried out even in lack of sufficient data on structural behaviour and site conditions. In this framework, the organization of the analysis possibly requires a special approach, based on reliability analysis, able to give the distributions of dependent structural variables. This result can in fact be used in iterative updating of the analysis, leading at last at a required uncertainty target level for the structural evaluation. Therefore, the global uncertainty can be reduced by the reduction of the uncertainties of the variables that affect most the structural behaviour: the proposed procedure is able to drive this process in an optimal way. The analysis manager can therefore organize additional experimental inspections (for example in geotechnics, geophysics, structural behaviour)and data collections with the confidence of a minimum effort required for the prescribed target in terms of seismic safety. The procedure presented in this report has quite a general application following the general description is provided; therefore the example test has been chosen for the Paks NPP in Hungary, where a seismic requalification is in progress. To this aim, in the following specific reference will be made to the variables of interest for the on going job, namely: the probability distribution of some structural parameters, such as acceleration or shear force in critical points, giving a global overview on the reliability of structural calculations; the sensitivity coefficient

Design and implementation experience of seismic upgrades at Kozloduy and Paks NPPs

Energy Technology Data Exchange (ETDEWEB)

Borov, V; Trichkov, V; Alexandrov, A; Jordanov, M [EQE-Bulgaria, Sofia (Bulgaria)

1995-07-01

Series of upgrades have been designed and implemented by EQE-Bulgaria at Kozloduy NPP and as a subcontractor of EQE-International - at Paks NPP. Wide variety of facilities have been upgraded, including Electrical Equipment, Control and Instrumentation Equipment, Technological Equipment, Brick Walls and Building Structures. Different design approaches and concepts have been applied in compliance with the specific technological and structural conditions. The effect of the excitation intensity as well as the presence of specific floor response spectra over the upgrading concept and cost is discussed. Specific problems of supporting heavy technological equipment are noted. A practical approach for seismic upgrading of Brick Walls, as well as a tendency for unification of the engineering design is shown. The first completely upgraded Building Structure at Kozloduy NPP is the structure of the Electrical Control Building to the Diesel Generator of the River-bank Pump Station. Specific problems of the implementation of the final upgrading design of the Diesel Generator Building are outlined. (author)

Ex-core fuel damage event at paks causes, consequences and lessons learned

International Nuclear Information System (INIS)

Bajsz, J.; Gado, J.

2004-01-01

On April 10, 2003 Paks NPP experienced a loss of decay-heat removal to 30 irradiated fuel assemblies undergoing a cleaning process in a fuel service pit near the unit 2 spent fuel pool. Following chemical cleaning of high decay-heat fuel, a delay in removing the cleaning vessel's lid left the cleaning system in such a condition that did not provide adequate cooling to the fuel. After several hours of the fuel being under-cooled, a steam bubble developed in the vessel, essentially uncovering the fuel. When the lid of the vessel was removed, the sudden introduction of cool water thermally shocked the fuel causing significant structural damage and a release of fission product gases to the reactor building. The paper will discuss the causes of the event as well as the contributing factors to it. Detailed information will be given about the planning and preparation of the recovery actions. The in-depth analyses of the consequences and lessons learned complete the lecture. (author)

Design and implementation experience of seismic upgrades at Kozloduy and Paks NPPs

International Nuclear Information System (INIS)

Borov, V.; Trichkov, V.; Alexandrov, A.; Jordanov, M.

1995-01-01

Series of upgrades have been designed and implemented by EQE-Bulgaria at Kozloduy NPP and as a subcontractor of EQE-International - at Paks NPP. Wide variety of facilities have been upgraded, including Electrical Equipment, Control and Instrumentation Equipment, Technological Equipment, Brick Walls and Building Structures. Different design approaches and concepts have been applied in compliance with the specific technological and structural conditions. The effect of the excitation intensity as well as the presence of specific floor response spectra over the upgrading concept and cost is discussed. Specific problems of supporting heavy technological equipment are noted. A practical approach for seismic upgrading of Brick Walls, as well as a tendency for unification of the engineering design is shown. The first completely upgraded Building Structure at Kozloduy NPP is the structure of the Electrical Control Building to the Diesel Generator of the River-bank Pump Station. Specific problems of the implementation of the final upgrading design of the Diesel Generator Building are outlined. (author)

Inspections of CRDM Nozzle Penetrations in Paks NPP

International Nuclear Information System (INIS)

Doszpod, B.; Doczi, M.

2008-01-01

During the maintenance outage of Unit 2 of Paks Nuclear Power Plant in 2002, performing the regular drop-test of Control Rod Driving Mechanisms (CRDM) reduced drop-speed was observed in case of one CRDM. In spite of the measured value of speed was inside the acceptance limit, so it was still satisfactory, decision was made to disassemble the CRDM to clarify the cause of the speed-anomaly. After removal of the CRDM, by means of visual inspection deformation (bulge) was observed on the inside surface of the heat protection tube of the CRDM nozzle penetration. Deformation was big enough to obstruct the free movement of CRDM. After the deformed heat protection tube was removed, significant bulge was observed also on the corrosion protection tube, at the same elevation. As the root cause of these deformations, presence of water in the space between the CRDM nozzle and the corrosion protection tube was assumed. Non destructive inspection procedures were worked out and utilized to detect the presence of water in the space in question and to find the possible way of water inlet. Performed inspections successfully localized the place of water inlet. Developed inspection program of CRDM nozzles has to be performed during each outage on each unit. Paper deals with introduction of the phenomenon, the cause of damage, inspection the procedures which were worked out and applied, summarize the results of inspections performed.(author)

SIMPL enhancement of tumor necrosis factor-α dependent p65-MED1 complex formation is required for mammalian hematopoietic stem and progenitor cell function.

Directory of Open Access Journals (Sweden)

Weina Zhao

Full Text Available Significant insight into the signaling pathways leading to activation of the Rel transcription factor family, collectively termed NF-κB, has been gained. Less well understood is how subsets of NF-κB-dependent genes are regulated in a signal specific manner. The SIMPL protein (signaling molecule that interacts with mouse pelle-like kinase is required for full Tumor Necrosis Factor-α (TNFα induced NF-κB activity. We show that SIMPL is required for steady-state hematopoiesis and the expression of a subset of TNFα induced genes whose products regulate hematopoietic cell activity. To gain insight into the mechanism through which SIMPL modulates gene expression we focused on the Tnf gene, an immune response regulator required for steady-state hematopoiesis. In response to TNFα SIMPL localizes to the Tnf gene promoter where it modulates the initiation of Tnf gene transcription. SIMPL binding partners identified by mass spectrometry include proteins involved in transcription and the interaction between SIMPL and MED1 was characterized in more detail. In response to TNFα, SIMPL is found in p65-MED1 complexes where SIMPL enhances p65/MED1/SIMPL complex formation. Together our results indicate that SIMPL functions as a TNFα-dependent p65 co-activator by facilitating the recruitment of MED1 to p65 containing transcriptional complexes to control the expression of a subset of TNFα-induced genes.

A review of cancer mortality data of radiation workers of Nuclear Power Plant, Paks, Hungary, in the light the international radiation epidemiology study

International Nuclear Information System (INIS)

Turai, I.; Kerekes, A.; Otos, M.; Veress, K.

2007-01-01

Complete text of publication follows. Objective: To give a review of cancer mortality data among Hungarian radiation workers in nuclear industry in comparison with the results of the international nuclear workers' study prevailing the size of the study group of all former studies. Methods: Retrospective cohort study including 598,068 workers of 154 nuclear establishments in 15 countries (AUS, BEL, CAN, FIN, FRA, GER, HUN, JAP, LIT, ROK, SLK, SPA, SWE, UK, USA) coordinated by the International Agency for Research on Cancer (IARC, Lyon, France). The national study was extended for an additional 4-year period. Results: In the international study 407,391 persons in 13 years of average employment received 19.4 mSv mean cumulative dose, while in the national study 3322 radiation workers of Nuclear Power Plant (NPP) Paks, Hungary, in 14 years of follow-up period accumulated in average 5.13 mSv, only. There were 5233 cancer deaths registered in the international study, associated with an estimated ERR of 0.97 per Sv. Thus, 19.4 mSv recorded cumulative dose can explain 1 to 2% of cancer death cases. In radiation workers of NPP, Paks, during the period of 1985-1998 there were 40 cancer deaths observed against the expected 58.8 cases. In a further four year period (1999-2002) 29 cancer death cases were identified vs. the expected 65.5 cases. The SMR for the cancer death cases registered in recent and former radiation workers of NPP, Paks in the 18-year follow-up period is 56%. The SMR from all causes was even lower, 40% only. Conclusions: In the international study the mean accumulated radiation dose received by nuclear workers in 13 years is below of the recent annual dose limit (20 mSv/yr of the effective dose). The average value for the whole of radiation workers in 15 countries is almost 4-times higher of that registered in Hungary. The 'healthy worker effect' in the nuclear industry, and particularly in Hungary has been proven, once again. Nevertheless, the results

Method for investigation of various iodine species in the primary coolant of the nuclear power plant in Paks

International Nuclear Information System (INIS)

Volent, G.; Gimesi, O.; Solymosi, J.

1996-01-01

Iodine isotopes formed in the course of fission in nuclear reactors may be present in the primary coolant in different oxidation states, i.e., in different chemical forms. It is important to know the chemical forms and their proportions in order to asses the environmental effect of the emitted iodine and the performance of air filters used in the primary circuit for binding iodine, species, since both depend on the chemical forms in which it is present. Volatile components were separated from water samples taken separately from each block of the nuclear power station by purging with inert gas, then the aerosol, iodine vapour and alkyl iodides were selectively bound on the filter system of the 'KOMBI' sampler. I 3 - , I - , IO - , IO 3 - and IO 4 - left in the aqueous phase after purging were separated by consecutive physical and chemical procedures (extraction, isotope exchange, reduction). The results of the investigations have shown that the water technology used in the Nuclear Power Plant in Paks is appropriate with respect to the radioiodine balance. Iodine was found to be predominant species, and no volatile iodine species were found to be present in the primary coolant. Volatile iodine species sometimes appearing in emissions may be formed from leaching waters due to secondary effects. (author)

Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes.

Directory of Open Access Journals (Sweden)

Mohammad F Saeed

2010-09-01

Full Text Available Zaire ebolavirus (ZEBOV, a highly pathogenic zoonotic virus, poses serious public health, ecological and potential bioterrorism threats. Currently no specific therapy or vaccine is available. Virus entry is an attractive target for therapeutic intervention. However, current knowledge of the ZEBOV entry mechanism is limited. While it is known that ZEBOV enters cells through endocytosis, which of the cellular endocytic mechanisms used remains unclear. Previous studies have produced differing outcomes, indicating potential involvement of multiple routes but many of these studies were performed using noninfectious surrogate systems such as pseudotyped retroviral particles, which may not accurately recapitulate the entry characteristics of the morphologically distinct wild type virus. Here we used replication-competent infectious ZEBOV as well as morphologically similar virus-like particles in specific infection and entry assays to demonstrate that in HEK293T and Vero cells internalization of ZEBOV is independent of clathrin, caveolae, and dynamin. Instead the uptake mechanism has features of macropinocytosis. The binding of virus to cells appears to directly stimulate fluid phase uptake as well as localized actin polymerization. Inhibition of key regulators of macropinocytosis including Pak1 and CtBP/BARS as well as treatment with the drug EIPA, which affects macropinosome formation, resulted in significant reduction in ZEBOV entry and infection. It is also shown that following internalization, the virus enters the endolysosomal pathway and is trafficked through early and late endosomes, but the exact site of membrane fusion and nucleocapsid penetration in the cytoplasm remains unclear. This study identifies the route for ZEBOV entry and identifies the key cellular factors required for the uptake of this filamentous virus. The findings greatly expand our understanding of the ZEBOV entry mechanism that can be applied to development of new

Voltage-Dependent Gating: Novel Insights from KCNQ1 Channels

Science.gov (United States)

Cui, Jianmin

2016-01-01

Gating of voltage-dependent cation channels involves three general molecular processes: voltage sensor activation, sensor-pore coupling, and pore opening. KCNQ1 is a voltage-gated potassium (Kv) channel whose distinctive properties have provided novel insights on fundamental principles of voltage-dependent gating. 1) Similar to other Kv channels, KCNQ1 voltage sensor activation undergoes two resolvable steps; but, unique to KCNQ1, the pore opens at both the intermediate and activated state of voltage sensor activation. The voltage sensor-pore coupling differs in the intermediate-open and the activated-open states, resulting in changes of open pore properties during voltage sensor activation. 2) The voltage sensor-pore coupling and pore opening require the membrane lipid PIP2 and intracellular ATP, respectively, as cofactors, thus voltage-dependent gating is dependent on multiple stimuli, including the binding of intracellular signaling molecules. These mechanisms underlie the extraordinary KCNE1 subunit modification of the KCNQ1 channel and have significant physiological implications. PMID:26745405

Rapid purification of radioiodinated peptides with Sep-Pak reversed phase cartridges and HPLC

International Nuclear Information System (INIS)

Miller, J.J.; Schultz, G.S.; Levy, R.S.

1984-01-01

A simple, rapid method is described for the purification of radioiodinated peptides for use in radioimmuno- and in radioreceptor assays. Iodinated reaction mixtures are applied directly onto Sep-Pak disposable, reversed phase cartridges equilibrated with phosphate buffer. Unreacted 125-iodide and other non-peptide reaction components are eluted with buffer. The peptide fraction is then eluted with 70% buffer:30% acetonitrile. The peptide fraction is further purified by reversed phase high pressure liquid chromatography to separate the native peptide and the mono- and diiodo-derivatives. In this study the method is used to prepare 125-iodide-labeled monoiodo-leucine enkephalin and monoiodo-angiotensin II, which are free of the parent peptides and diiodo-derivatives and are of maximum obtainable specific radioactivity. The usefulness of these labeled peptides in radioimmuno- and radioreceptor assays is demonstrated by their binding to specific antibodies and receptors, respectively. (author)

Task-dependent inhibition of slow-twitch soleus and excitation of fast-twitch gastrocnemius do not require high movement speed and velocity-dependent sensory feedback

Directory of Open Access Journals (Sweden)

Ricky eMehta

2014-10-01

Full Text Available Although individual heads of triceps surae, soleus (SO and medial gastrocnemius (MG muscles, are often considered close functional synergists, previous studies have shown distinct activity patterns between them in some motor behaviors. The goal of this study was to test two hypotheses explaining inhibition of slow SO with respect to fast MG: (1 inhibition occurs at high movement velocities and mediated by velocity-dependent sensory feedback and (2 inhibition depends on the ankle-knee joint moment combination and does not require high movement velocities. The hypotheses were tested by comparing the SO EMG/MG EMG ratio during fast and slow motor behaviors (cat paw shake responses vs. back, straight leg load lifting in humans, which had the same ankle extension-knee flexion moment combination; and during fast and slow behaviors with the ankle extension-knee extension moment combination (human vertical jumping and stance phase of walking in cats and leg load lifting in humans. In addition, SO EMG/MG EMG ratio was determined during cat paw shake responses and walking before and after removal of stretch velocity-dependent sensory feedback by self-reinnervating SO and/or gastrocnemius. We found the ratio SO EMG/MG EMG below 1 (p<0.05 during fast paw shake responses and slow back load lifting, requiring the ankle extension-knee flexion moment combination; whereas the ratio SO EMG/MG EMG was above 1 (p<0.05 during fast vertical jumping and slow tasks of walking and leg load lifting, requiring ankle extension-knee extension moments. Removal of velocity-dependent sensory feedback did not affect the SO EMG/MG EMG ratio in cats. We concluded that the relative inhibition of SO does not require high muscle velocities, depends on ankle-knee moment combinations, and is mechanically advantageous for allowing a greater MG contribution to ankle extension and knee flexion moments.

p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1 chemokine-induced vascular smooth muscle cell migration and proliferation.

Science.gov (United States)

Singh, Nikhlesh K; Janjanam, Jagadeesh; Rao, Gadiparthi N

2017-08-25

Although the involvement of Rho proteins in the pathogenesis of vascular diseases is well studied, little is known about the role of their upstream regulators, the Rho guanine nucleotide exchange factors (RhoGEFs). Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1)-induced vascular wall remodeling. We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs). Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migration and proliferation. Consistent with these observations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid arteries, and siRNA-mediated down-regulation of its levels substantially attenuated BI-induced smooth muscle cell migration and proliferation, resulting in reduced neointima formation. Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling, which, as we reported previously, is involved in vascular wall remodeling. Our findings also show that protein kinase N1 (PKN1) downstream of Rac1-cyclin D1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling axis is involved in the modulation of vascular wall remodeling. Of note, we also observed that CCR2-G i/o -Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation. These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and proliferation in vitro and for injury-induced neointima formation in vivo by modulating Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signaling. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Resolving the issues arisen during the development of License Renewal Application at PAKS NPP

International Nuclear Information System (INIS)

Ratkai, Sandor; Katona, Tamas Janos

2012-01-01

Operational license of the four VVER-440/213 units at Paks NPP, Hungary is limited to the design lifetime of 30 years. Extension by an additional 20 years of the original license is one of the main goals of the plant owner. In 2008 a programme for long-term operation (LTO) was developed and submitted to the Hungarian Atomic Energy Authority. The LTO Programme defines the activities for ensuring the extension of the operational lifetime and contains the justification of the safe LTO. The LTO Programme has to be implemented and comprehensive justification of the safe LTO has to be provided in the formal License Renewal Applications unit by unit. This work has been completed by the end of 2011, and the application has been submitted for approval for the Unit 1. The authority review and the approval of the License Renewal Application for Unit 1 should be finished before the expiration of the original design lifetime in 2012. In line with the regulations and supporting the License Renewal Application, a large number of engineering tasks have been performed. In this paper the entire project will be reported. The issues will be discussed, which have been arisen during the development of the application. The difficulties caused by the Hungarian technical and regulatory peculiarities will be presented. (author)

Effect of gamma rays on M1 generation in basmati rice

International Nuclear Information System (INIS)

Ashraf, M.; Cheema, A.A.; Rashid, M.; Zia-ul-Qamar

2003-01-01

To estimate the sensitivity to gamma rays in Basmati rice, five varieties namely Basmati 370, Basmati Pak, Basmati 385, Super Basmati and Basmati 2000were exposed to different doses of gamma rays ranging 150- 350 Gy with an increment of 50 Gy among the doses. Plant growth parameters such as seedling shoot and root lengths were measured in the laboratory. Highly significant differences were observed among the varieties for seedling shoot and root lengths. Radiations showed highly significant negative correlations with seedling shoot length (-0.998), seedling root length (-0.941) showing dose dependent responses. Highly significant negative correlations with panicle fertility (-0.941) and grain yield (-0.971), and significant negative correlation for seedling emergence (-0.941) showed detrimental dose dependent responses.Seedling emergence, panicle fertility and grain yield declined with increasing dose level in all the varieties. The dose at which panicle fertility halved was 260.37 Gy. Basmati 2000 was observed to be the most sensitive followed by Basmati 370, Super Basmati and Basmati Pak, but Basmati 385 was found to be the least sensitive variety to gamma rays

Lessons from the PAKS NPP case study

International Nuclear Information System (INIS)

Ronaky, J.

2007-01-01

A serious fuel cleaning incident happened in 2003 at the Hungarian Paks Nuclear Power Plant resulting in 30 damaged fuel bundles. The event was thoroughly investigated by the national authorities and reviewed by an IAFA team. Recovery operations have been successfully finished recently. The event attracted wide political and media coverage. Regulatory aspects of the event and the preparation for and realisation of the recovery operations will be presented with special emphasis on transparency and openness. Communication of the event itself and the national and international review process was challenging, but openness resulted in reconciliation of the Hungarian public. Recovery operations were accomplished after a careful preparation that took about three years. The situation was further complicated by the fact that the plant decided to start the operation or the reactor next to the cleaning tank before the recovery action. Some changes had to be licensed by the Regulatory Body in order to start the operation of the reactor. It attracted quite a big media interest. Detailed communication plans were prepared and followed both by the Regulatory Body and the Operator. Stakeholders were regularly invited to the plant to witness the operations and milestones of the process. NGOs requested the Regulatory Body to make public all technical data of both the operation of the reactor and the recovery process. Legal procedures in the court are going on to determine the extent and nature of data publicity associated with the recovery operations, while the Operator claims that technical details are proprietary information and not fully public. In the meantime lifetime extension of the plant and the construction of a low and intermediate level radioactive waste repository were debated and approved by the Hungarian Parliament. Good communication and open debate resulted in a wide political consensus and high public support in Hungary on the future of nuclear energy. (author)

CRM1-mediated nuclear export is required for 26 S proteasome-dependent degradation of the TRIP-Br2 proto-oncoprotein.

Science.gov (United States)

Cheong, Jit Kong; Gunaratnam, Lakshman; Hsu, Stephen I-Hong

2008-04-25

Overexpression of the proto-oncogene TRIP-Br2 (SERTAD2) has been shown to induce E2F activity and promote tumorigenesis, whereas ablation of TRIP-Br2 arrests cell proliferation. Timely degradation of many cell cycle regulators is fundamental to the maintenance of proper cell cycle progression. Here we report novel mechanism(s) that govern the tight regulation of TRIP-Br2 levels during cell cycle progression. TRIP-Br2 was observed to be a short-lived protein in which the expression level peaks at the G(1)/S boundary. TRIP-Br2 accumulated in cells treated with 26 S proteasome inhibitors. Co-immunoprecipitation studies revealed that TRIP-Br2 forms ubiquitin conjugates. In silico analysis identified a putative leucine-rich nuclear export signal (NES) motif that overlaps with the PHD-Bromo interaction domain in the acidic C-terminal transactivation domain (TAD) of TRIP-Br2. This NES motif is highly conserved in widely divergent species and in all TRIP-Br family members. TRIP-Br2 was shown to be stabilized in G(2)/M phase cells through nuclear entrapment, either by deletion of the acidic C-terminal TAD, which includes the NES motif, or by leptomycin B-mediated inhibition of the CRM1-dependent nuclear export machinery. Mutation of leucine residue 238 of this NES motif abolished the interaction between CRM1 and TRIP-Br2, as well as the nuclear export of TRIP-Br2 and its subsequent 26 S proteasome-dependent degradation. These data suggest that CRM1-mediated nuclear export may be required for the proper execution of ubiquitin-proteasome-dependent degradation of TRIP-Br2.

ATR-Chk1-APC/C-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress

DEFF Research Database (Denmark)

Yamada, M.; Watanabe, K.; Mistrik, M.

2013-01-01

replication. Stalled DNA replication evoked stabilization of the Cdc7-ASK (Dbf4) complex in a manner dependent on ATR-Chk1-mediated checkpoint signaling and its interplay with the anaphase-promoting complex/cyclosomeCdh1 (APC/C) ubiquitin ligase. Mechanistically, Chk1 kinase inactivates APC/C through...... degradation of Cdh1 upon replication block, thereby stabilizing APC/C substrates, including Cdc7-ASK (Dbf4). Furthermore, motif C of ASK (Dbf4) interacts with the N-terminal region of RAD18 ubiquitin ligase, and this interaction is required for chromatin binding of RAD18. Impaired interaction of ASK (Dbf4...

Protein kinase C activation decreases cell surface expression of the GLT-1 subtype of glutamate transporter. Requirement of a carboxyl-terminal domain and partial dependence on serine 486.

Science.gov (United States)

Kalandadze, Avtandil; Wu, Ying; Robinson, Michael B

2002-11-29

Na(+)-dependent glutamate transporters are required for the clearance of extracellular glutamate and influence both physiological and pathological effects of this excitatory amino acid. In the present study, the effects of a protein kinase C (PKC) activator on the cell surface expression and activity of the GLT-1 subtype of glutamate transporter were examined in two model systems, primary co-cultures of neurons and astrocytes that endogenously express GLT-1 and C6 glioma cells transfected with GLT-1. In both systems, activation of PKC with phorbol ester caused a decrease in GLT-1 cell surface expression. This effect is opposite to the one observed for the EAAC1 subtype of glutamate transporter (Davis, K. E., Straff, D. J., Weinstein, E. A., Bannerman, P. G., Correale, D. M., Rothstein, J. D., and Robinson, M. B. (1998) J. Neurosci. 18, 2475-2485). Several recombinant chimeric proteins between GLT-1 and EAAC1 transporter subtypes were generated to identify domains required for the subtype-specific redistribution of GLT-1. We identified a carboxyl-terminal domain consisting of 43 amino acids (amino acids 475-517) that is required for PKC-induced GLT-1 redistribution. Mutation of a non-conserved serine residue at position 486 partially attenuated but did not completely abolish the PKC-dependent redistribution of GLT-1. Although we observed a phorbol ester-dependent incorporation of (32)P into immunoprecipitable GLT-1, mutation of serine 486 did not reduce this signal. We also found that chimeras containing the first 446 amino acids of GLT-1 were not functional unless amino acids 475-517 of GLT-1 were also present. These non-functional transporters were not as efficiently expressed on the cell surface and migrated to a smaller molecular weight, suggesting that a subtype-specific interaction is required for the formation of functional transporters. These studies demonstrate a novel effect of PKC on GLT-1 activity and define a unique carboxyl-terminal domain as an

WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

KAUST Repository

Abdallah, Abdallah

2018-04-09

The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates in pathogenic mycobacteria.

KAUST Repository

Abdallah, Abdallah; Weerdenburg, Eveline; Guan, Qingtian; Ummels, Roy; Borggreve, S; Adroub, Sabir; Malas, Tareq; Naeem, Raeece; Zhang, Huoming; Otto, Thomas; Bitter, Wilbert; Pain, Arnab

2018-01-01

The mycobacterial type VII secretion system ESX-1 is responsible for the secretion of a number of proteins that play important roles during host infection. The regulation of the expression of secreted proteins is often essential to establish successful infection. Using transcriptome sequencing, we found that the abrogation of ESX-1 function in Mycobacterium marinum leads to a pronounced increase in gene expression levels of the espA operon during the infection of macrophages, suggesting an important role in ESX-1-mediated virulence during the early phase of infection. In addition, the disruption of ESX-1-mediated protein secretion also leads to a specific down-regulation of the ESX-1 substrates, but not of the structural components of this system, during growth in culture medium. This effect is observed in both M. marinum and M. tuberculosis. We established that down-regulation of ESX-1 substrates is the result of a regulatory process that is influenced by the putative transcriptional regulator whib6, which is located adjacent to the esx-1 locus. In addition, the overexpression of the ESX-1-associated PE35/PPE68 protein pair resulted in a significantly increased secretion of the ESX-1 substrate EsxA, demonstrating a functional link between these proteins. Taken together, these data show that WhiB6 is required for the secretion-dependent regulation of ESX-1 substrates and that ESX-1 substrates are regulated independently from the structural components, both during infection and as a result of active secretion.

Update of the tectonic model for the Pannonian basin: a contribution to the seismic hazard reassessment of the Paks NPP (Hungary)

Science.gov (United States)

Horváth, Ferenc; Tóth, Tamás; Wórum, Géza; Koroknai, Balázs; Kádi, Zoltán; Kovács, Gábor; Balázs, Attila; Visnovitz, Ferenc

2015-04-01

The planned construction of two new units at the site of the Paks NPP requires a comprehensive site investigation including complete reassessment of the seismic hazard according to the Hungarian as well as international standards. Following the regulations of the Specific Safety Guide no. 9 (IAEA 2010), the approved Hungarian Geological Investigation Program (HGIP) includes integrated geological-geophysical studies at different scales. The regional study aims at to elaborate a new synthesis of all published data for the whole Pannonian basin. This task is nearly completed and the main outcomes have already been published (Horváth et al. 2015). The near regional study is in progress and addresses the construction of a new tectonic model for the circular area with 50 km radius around the NPP using a wealth of unpublished oil company seismic and borehole data. The site vicinity study has also been started with a core activity of 300 km² 3D seismic data acquisition, processing and interpretation assisted by a series of additional geophysical surveys, new drillings and geological mapping. This lecture will present a few important results of the near regional study, which sheds new light on the intricate tectonic evolution of the Mid-Hungarian Fault Zone (MHFZ), which is a strongly deformed belt between the Alcapa and Tisza-Dacia megatectonic units. The nuclear power plant is located at the margin of the Tisza unit near to the southern edge of the MHFZ. Reassessment of seismic hazard at the site of the NPP requires better understanding of the Miocene to Recent tectonic evolution of this region in the central part of the Pannonian basin. Early to Middle Miocene was a period of rifting with formation of 1 to 3 km deep half-grabens filled with terrestrial to marine deposits and large amount of rift-related volcanic material. Graben fill became strongly deformed as a consequence of juxtaposition of the two megatectonic units leading to strong compression and development of

VERONA V6.22 – An enhanced reactor analysis tool applied for continuous core parameter monitoring at Paks NPP

Energy Technology Data Exchange (ETDEWEB)

Végh, J., E-mail: janos.vegh@ec.europa.eu [Institute for Energy and Transport of the Joint Research Centre of the European Commission, Postbus 2, NL-1755 ZG Petten (Netherlands); Pós, I., E-mail: pos@npp.hu [Paks Nuclear Power Plant Ltd., H-7031 Paks, P.O. Box 71 (Hungary); Horváth, Cs., E-mail: csaba.horvath@energia.mta.hu [Centre for Energy Research, Hungarian Academy of Sciences, H-1525 Budapest 114, P.O. Box 49 (Hungary); Kálya, Z., E-mail: kalyaz@npp.hu [Paks Nuclear Power Plant Ltd., H-7031 Paks, P.O. Box 71 (Hungary); Parkó, T., E-mail: parkot@npp.hu [Paks Nuclear Power Plant Ltd., H-7031 Paks, P.O. Box 71 (Hungary); Ignits, M., E-mail: ignits@npp.hu [Paks Nuclear Power Plant Ltd., H-7031 Paks, P.O. Box 71 (Hungary)

2015-10-15

Between 2003 and 2007 the Hungarian Paks NPP performed a large modernization project to upgrade its VERONA core monitoring system. The modernization work resulted in a state-of-the-art system that was able to support the reactor thermal power increase to 108% by more accurate and more frequent core analysis. Details of the new system are given in Végh et al. (2008), the most important improvements were as follows: complete replacement of the hardware and the local area network; application of a new operating system and porting a large fraction of the original application software to the new environment; implementation of a new human-system interface; and last but not least, introduction of new reactor physics calculations. Basic novelty of the modernized core analysis was the introduction of an on-line core-follow module based on the standard Paks NPP core design code HELIOS/C-PORCA. New calculations also provided much finer spatial resolution, both in terms of axial node numbers and within the fuel assemblies. The new system was able to calculate the fuel applied during the first phase of power increase accurately, but it was not tailored to determine the effects of burnable absorbers as gadolinium. However, in the second phase of the power increase process the application of fuel assemblies containing three fuel rods with gadolinium content was intended (in order to optimize fuel economy), therefore off-line and on-line VERONA reactor physics models had to be further modified, to be able to handle the new fuel according to the accuracy requirements. In the present paper first a brief overview of the system version (V6.0) commissioned after the first modernization step is outlined; then details of the modified off-line and on-line reactor physics calculations are described. Validation results for new modules are treated extensively, in order to illustrate the extent and complexity of the V&V procedure associated with the development and licensing of the new

Estudo do centro de massa e estabilidade de quatro posturas básicas do Kung-fu Pak Hok

OpenAIRE

Miranda,Pedro Jeferson; Brinatti,André Maurício; Silva,Silvio Luiz Rutz da; Godoy,Marino Luiz Michelin

2016-01-01

Este trabalho trata da análise dos centros de massa e do cálculo da estabilidade das quatro posturas básicas do Kung Fu Pak Hok. Embora a biomecânica tenha surgido em 1960, a sua aplicação em artes marciais, como no Kung Fu ainda é pouco frequente. Apesar de haver estudos de movimentos do Kung Fu, não há trabalhos sobre o centro de massa e a estabilidade para as posturas mais básicas. Este trabalho como objetivo descrever o centro de massa e a estabilidade das quatro posturas mais básicas do ...

Practice of fuel management and outage strategy at Paks NPP

International Nuclear Information System (INIS)

Farago, P.; Hamvas, I.; Szecsenyi, Zs.; Nemes, I.; Javor, E.

2000-01-01

The Paks Nuclear Power Plant generates almost 40% of Hungarian electricity production at lowest price. In spite of this fact the reduction of operational and maintenance costs is one of the most important goal of the plant management. The proper fuel management and outage strategy can give a considerable influence for this cost reduction. The aim of loading pattern planning is to get the required cycle length with available fuel cassettes and to keep all key parameters of safety analysis under safety limits. Another important point is production at profit, where both the fuel and spent fuel cost are determining. Earlier the conditions given by our only fuel supplier restricted our possibilities, so at the beginning the fuel arrangement changing was the only way to improve efficiency of fuel using. As first step we introduced the low leakage core design. The next step was the 4 years cycle using of some cassettes. By this way nearly half of 3 years cycle old cassettes remained in the core for fourth cycle. In the immediate future we want to use profiled cassettes developed by Russian supplier. Simultaneously we will load new type of WWER cassettes with burnable poison developed by BNFL Company. Hereby we can apply more BNFL cassettes for four years cycle even more. Both cost of fuel and number of spent fuel can be reduced besides keeping parameters under safety limits. The Hungarian in service inspection rules determine that every four year we have to make a complete inspection of reactor vessel. Therefore earlier we had two types of outages. Every 4 years we planned a long outage with 55-65 days duration and normal ones with about 30-35 days duration between the long ones. During the normal outages this way did not give us enough room to utilise the shortest possible critical path determined by works on reactor. Some years ago we changed our outage strategy. Now we plan every 4 years a long outage, and between them one normal and two short ones. As a result the

Investigation of radioisotopes in different organisms around Paks NPP

International Nuclear Information System (INIS)

Janovics, R.; Bihari, A.; Major, Z.; Palcsu, L.; Papp, L.; Veres, M.

2010-01-01

Complete text of publication follows. The Paks Nuclear Power Plant is a pressurised water reactor, therefore, it requires a large amount of cooling water. Cooling water is pumped from the Danube, and used water is also discharged back to the river through the warm-water channel. In the study Danube water and various aquatic organisms (a snail, Viviparus Acerosus, a mussel Unio Tumidus, a predatory fish Stizostedion lucioperca and a non-predatory fish Leuciscus idus) were collected upstream and downstream of the inlet of the channel. After freeze-drying both from the interstitial water and the dry matter of the aquatic organisms collected, tritium measurements were performed by the T- 3 He method to gain information about the ratio of the tritium concentration of the organically bound and the not-bound hydrogen, as well. The activity of the organically bound tritium reflects the mean activity of the environment of the organism, while the tritium activity of the interstitial water shows the actual activity of the aquatic environment. The activity of gamma emitters in the dry matter was also measured by gamma spectrometry. In case of the mussel and snail samples gamma spectrometry measurements were performed separately from the calciferous skeleton and the tissues. Besides the aquatic organisms, soil and plant samples (Scots Pine Pinus sylvestris, Common Milkweed Asclepias syriaca L., giant goldenrod Solidago gigantea) were collected in the vicinity of the nuclear power plant and in a background site, as well. These samples were analysed by gamma spectrometry and for tritium concentration, and the results were compared with a background site. On the basis of the gamma spectrometry results significant amount of artificial gamma emitter isotopes do not get to the Danube through the warm-water channel. Only 60 Co occurred in certain mussel, snail and sludge in a measurable activity concentration, however, it is not of power plant origin, as it was present even in the

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4E. Paks NPP: Analysis and testing. Working material

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-07-01

In August 1991, following the SMiRT-11 Conference in Tokyo, a Technical Committee Meeting was held on the 'Seismic safety issues relating to existing NPPs'. The Proceedings of this TCM was subsequently compiled in an IAEA Working Material. One of the main recommendations of this TCM, called for the harmonization of criteria and methods used in Member States in seismic reassessment and upgrading of existing NPPs. Twenty four institutions from thirteen countries participated in the CRP named 'Benchmark study for the seismic analysis and testing of WWER type NPPs'. Two types of WWER reactors (WWER-1000 and WWER-440/213) selected for benchmarking. Kozloduy NPP Units 5/6 and Paks NPP represented these respectively as prototypes. Consistent with the recommendations of the TCM and the working paper prepared by the subsequent Consultants' Meeting, the focal activity of the CRP was the benchmarking exercises. A similar methodology was followed both for Paks NPP and Kozloduy NPP Unit 5. Firstly, the NPP (mainly the reactor building) was tested using a blast loading generated by a series of explosions from buried TNT charges. Records from this test were obtained at several free field locations (both downhole and surface), foundation mat, various elevations of structures as well as some tanks and the stack. Then the benchmark participants were provided with structural drawings, soil data and the free field record of the blast experiment. Their task was to make a blind prediction of the response at preselected locations. The analytical results from these participants were then compared with the results from the test. Although the benchmarking exercises constituted the focus of the CRP, there were many other interesting problems related to the seismic safety of WWER type NPPs which were addressed by the participants. These involved generic studies, i.e. codes and standards used in original WWER designs and their comparison with current international practice; seismic analysis

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4E. Paks NPP: Analysis and testing. Working material

International Nuclear Information System (INIS)

1995-01-01

In August 1991, following the SMiRT-11 Conference in Tokyo, a Technical Committee Meeting was held on the 'Seismic safety issues relating to existing NPPs'. The Proceedings of this TCM was subsequently compiled in an IAEA Working Material. One of the main recommendations of this TCM, called for the harmonization of criteria and methods used in Member States in seismic reassessment and upgrading of existing NPPs. Twenty four institutions from thirteen countries participated in the CRP named 'Benchmark study for the seismic analysis and testing of WWER type NPPs'. Two types of WWER reactors (WWER-1000 and WWER-440/213) selected for benchmarking. Kozloduy NPP Units 5/6 and Paks NPP represented these respectively as prototypes. Consistent with the recommendations of the TCM and the working paper prepared by the subsequent Consultants' Meeting, the focal activity of the CRP was the benchmarking exercises. A similar methodology was followed both for Paks NPP and Kozloduy NPP Unit 5. Firstly, the NPP (mainly the reactor building) was tested using a blast loading generated by a series of explosions from buried TNT charges. Records from this test were obtained at several free field locations (both downhole and surface), foundation mat, various elevations of structures as well as some tanks and the stack. Then the benchmark participants were provided with structural drawings, soil data and the free field record of the blast experiment. Their task was to make a blind prediction of the response at preselected locations. The analytical results from these participants were then compared with the results from the test. Although the benchmarking exercises constituted the focus of the CRP, there were many other interesting problems related to the seismic safety of WWER type NPPs which were addressed by the participants. These involved generic studies, i.e. codes and standards used in original WWER designs and their comparison with current international practice; seismic analysis

The requirements for herpes simplex virus type 1 cell-cell spread via nectin-1 parallel those for virus entry.

Science.gov (United States)

Even, Deborah L; Henley, Allison M; Geraghty, Robert J

2006-08-01

Herpes simplex virus type 1 (HSV-1) spreads from an infected cell to an uninfected cell by virus entry, virus-induced cell fusion, and cell-cell spread. The three forms of virus spread require the viral proteins gB, gD, and gH-gL, as well as a cellular gD receptor. The mutual requirement for the fusion glycoproteins and gD receptor suggests that virus entry, cell fusion, and cell-cell spread occur by a similar mechanism. The goals of this study were to examine the role of the nectin-1alpha transmembrane domain and cytoplasmic tail in cell-cell spread and to obtain a better understanding of the receptor-dependent events occurring at the plasma membrane during cell-cell spread. We determined that an intact nectin-1alpha V-like domain was required for cell-cell spread, while a membrane-spanning domain and cytoplasmic tail were not. Chimeric forms of nectin-1 that were non-functional for virus entry did not mediate cell-cell spread regardless of whether they could mediate cell fusion. Also, cell-cell spread of syncytial isolates was dependent upon nectin-1alpha expression and occurred through a nectin-1-dependent mechanism. Taken together, our results indicate that nectin-1-dependent events occurring at the plasma membrane during cell-cell spread were equivalent to those for virus entry.

Reactor Dosimetry Aspects of the Service Life Extension of the Hungarian Paks NPP

Directory of Open Access Journals (Sweden)

Zsolnay Eva M.

2016-01-01

Full Text Available The service life of the Hungarian Paks Nuclear Power Plant (NPP will be extended from the originally planned 30 years to 50 years. To improve the reliability of the results obtained in frame of the old reactor pressure vessel (RPV surveillance programme, new methods have been developed, and based on them, the old exposition data have been re-evaluated for all the four reactor units. At the same time, a new RPV surveillance programme has been developed and introduced, and long term irradiations have been performed to determine the radiation damage of the surveillance specimens due to the high fast neutron exposition. Neutron transport calculations have been performed with a validated neutron transport code system to determine the fast neutron exposition of the RPVs during the extended service life. The cavity dosimetry is in the introductory phase. This paper presents the new developments in the field of the RPV surveillance dosimetry and summarises the results obtained. According to the results the service life of the NPP can safely be extended for the planned 50 years.

Reading the Af-Pak Narrative, from the US Disengagement to Russian Re-Engagement

Directory of Open Access Journals (Sweden)

A. Dhaka

2017-01-01

Full Text Available The US has prolonged its stay in Afghanistan with the security situation remaining far from improving. The indefatigable demand for resources to maintain counter-insurgency operations was a major debate in 2016 US Presidential elections with a demand for an earlier withdrawal from America’s trillion dollars plus war effort. Russians having sensed the weakening of the US infl uence warmed upto the idea of new Afghan situation involving Taliban and their masters, the Pakistan army. Russia had experienced vulnerabilities of Islamisation in Central Asia and Caucasus, and the ISIS brand radicalisation added to the fear of political destabilisation of Central Asian states. The Islamic State showed up in Afghanistan and Pakistan as ISIS-Khorasan branch. Russia needed Pakistan as an ally to fi ght Daesh’s presence on its southern periphery. However, there remained many intertwined security challenges that complicate the South Asian geopolitics, especially, the Af-Pak region. Russia’s Taliban policy might be the hitherto unused leverage that it might be using in order to strike balance all along the shatter belt.

Extinction of Contextual Cocaine Memories Requires Cav1.2 within D1R-Expressing Cells and Recruits Hippocampal Cav1.2-Dependent Signaling Mechanisms.

Science.gov (United States)

Burgdorf, Caitlin E; Schierberl, Kathryn C; Lee, Anni S; Fischer, Delaney K; Van Kempen, Tracey A; Mudragel, Vladimir; Huganir, Richard L; Milner, Teresa A; Glass, Michael J; Rajadhyaksha, Anjali M

2017-12-06

Exposure to cocaine-associated contextual cues contributes significantly to relapse. Extinction of these contextual associations, which involves a new form of learning, reduces cocaine-seeking behavior; however, the molecular mechanisms underlying this process remain largely unknown. We report that extinction, but not acquisition, of cocaine conditioned place preference (CPP) in male mice increased Ca v 1.2 L-type Ca 2+ channel mRNA and protein in postsynaptic density (PSD) fractions of the hippocampus, a brain region involved in drug-context associations. Moreover, viral-mediated deletion of Ca v 1.2 in the dorsal hippocampus attenuated extinction of cocaine CPP. Molecular studies examining downstream Ca v 1.2 targets revealed that extinction recruited calcium/calmodulin (Ca 2+ /CaMK)-dependent protein kinase II (CaMKII) to the hippocampal PSD. This occurred in parallel with an increase in phosphorylation of the AMPA GluA1 receptor subunit at serine 831 (S831), a CaMKII site, along with an increase in total PSD GluA1. The necessity of S831 GluA1 was further demonstrated by the lack of extinction in S831A GluA1 phosphomutant mice. Of note hippocampal GluA1 levels remained unaltered at the PSD, but were reduced near the PSD and at perisynaptic sites of dendritic spines in extinction-resistant S831A mutant mice. Finally, conditional knock-out of Ca v 1.2 in dopamine D1 receptor (D1R)-expressing cells resulted in attenuation of cocaine CPP extinction and lack of extinction-dependent changes in hippocampal PSD CaMKII expression and S831 GluA1 phosphorylation. In summary, we demonstrate an essential role for the hippocampal Ca v 1.2/CaMKII/S831 GluA1 pathway in cocaine CPP extinction, with data supporting contribution of hippocampal D1R-expressing cells in this process. These findings demonstrate a novel role for Ca v 1.2 channels in extinction of contextual cocaine-associated memories. SIGNIFICANCE STATEMENT Continued drug-seeking behavior, a defining characteristic of

Återvinning av dryckeskartonger : En studie som syftar till att öka återvinningsgraden av Tetra Paks förpackningar i Indonesien

OpenAIRE

Backlund, Per

2014-01-01

People of the modern world consume more than they ever used to do. Because of the close correlation between consumption and the amount of waste, the waste volume is also expected to increase. The purpose of this study is to examine if some measures in the recycling process from Sweden could be implemented in Indonesia. In fact, Indonesia is one of the countries in which the waste management system is struggling. Tetra Pak, one of the world leading producer of food packaging, is studied in thi...

Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

Science.gov (United States)

Harris, Julia M; Nguyen, Phil P; Patel, Milan J; Sporn, Zachary A; Hines, Justin K

2014-07-01

Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have

Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology.

Science.gov (United States)

Albin, Stephanie D; Davis, Graeme W

2004-08-04

Here, we show that postsynaptic p21-activated kinase (Pak) signaling diverges into two genetically separable pathways at the Drosophila neuromuscular junction. One pathway controls glutamate receptor abundance. Pak signaling within this pathway is specified by a required interaction with the adaptor protein Dreadlocks (Dock). We demonstrate that Dock is localized to the synapse via an Src homology 2-mediated protein interaction. Dock is not necessary for Pak localization but is necessary to restrict Pak signaling to control glutamate receptor abundance. A second genetically separable function of Pak kinase signaling controls muscle membrane specialization through the regulation of synaptic Discs-large. In this pathway, Dock is dispensable. We present a model in which divergent Pak signaling is able to coordinate two different features of postsynaptic maturation, receptor abundance, and muscle membrane specialization.

The Mincle-activating adjuvant TDB induces MyD88-dependent Th1 and Th17 responses through IL-1R signaling.

Directory of Open Access Journals (Sweden)

Christiane Desel

Full Text Available Successful vaccination against intracellular pathogens requires the generation of cellular immune responses. Trehalose-6,6-dibehenate (TDB, the synthetic analog of the mycobacterial cord factor trehalose-6,6-dimycolate (TDM, is a potent adjuvant inducing strong Th1 and Th17 immune responses. We previously identified the C-type lectin Mincle as receptor for these glycolipids that triggers the FcRγ-Syk-Card9 pathway for APC activation and adjuvanticity. Interestingly, in vivo data revealed that the adjuvant effect was not solely Mincle-dependent but also required MyD88. Therefore, we dissected which MyD88-dependent pathways are essential for successful immunization with a tuberculosis subunit vaccine. We show here that antigen-specific Th1/Th17 immune responses required IL-1 receptor-mediated signals independent of IL-18 and IL-33-signaling. ASC-deficient mice had impaired IL-17 but intact IFNγ responses, indicating partial independence of TDB adjuvanticity from inflammasome activation. Our data suggest that the glycolipid adjuvant TDB triggers Mincle-dependent IL-1 production to induce MyD88-dependent Th1/Th17 responses in vivo.

Coastal erosion and accretion in Pak Phanang, Thailand by GIS analysis of maps and satellite imagery

Directory of Open Access Journals (Sweden)

Sayedur Rahman Chowdhury

2013-12-01

Full Text Available Coastal erosion and accretion in Pak Phanang of southern Thailand between 1973 and 2003 was measured using multi-temporal topographic maps and Landsat satellite imageries. Within a GIS environment landward and seaward movements of shoreline was estimated by a transect-based analysis, and amounts of land accretion and erosion were estimated by a parcel-based geoprocessing. The whole longitudinal extent of the 58 kilometer coast was classified based on the erosion and accretion trends during this period using agglomerative hierarchical clustering approach. Erosion and accretion were found variable over time and space, and periodic reversal of status was also noticed in many places. Estimates of erosion were evaluated against field-survey based data, and found reasonably accurate where the rates were relatively great. Smoothing of shoreline datasets was found desirable as its impacts on the estimates remained within tolerable limits.

1 CFR 10.1 - Publication required.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication required. 10.1 Section 10.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER PRESIDENTIAL PAPERS Regular Publication § 10.1 Publication required. The Director publishes a special edition...

1 CFR 9.1 - Publication required.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication required. 9.1 Section 9.1 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER THE UNITED STATES GOVERNMENT MANUAL § 9.1 Publication required. The Director of the Federal Register shall...

Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development.

Science.gov (United States)

Luo, Ting; Xu, Yanhua; Hoffman, Trevor L; Zhang, Tailin; Schilling, Thomas; Sargent, Thomas D

2007-04-01

Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC). Knockdown experiments in frog and fish using antisense morpholinos reveal essential functions for Inca in a subset of NC cells that form craniofacial cartilage. Cells lacking Inca migrate successfully but fail to condense into skeletal primordia. Overexpression of Inca disrupts cortical actin and prevents formation of actin "purse strings", which are required for wound healing in Xenopus embryos. We show that Inca physically interacts with p21-activated kinase 5 (PAK5), a known regulator of the actin cytoskeleton that is co-expressed with Inca in embryonic ectoderm, including in the NC. These results suggest that Inca and PAK5 cooperate in restructuring cytoskeletal organization and in the regulation of cell adhesion in the early embryo and in NC cells during craniofacial development.

Separation properties of aluminium-plastic laminates in post-consumer Tetra Pak with mixed organic solvent.

Science.gov (United States)

Zhang, S F; Zhang, L L; Luo, K; Sun, Z X; Mei, X X

2014-04-01

The separation properties of the aluminium-plastic laminates in postconsumer Tetra Pak structure were studied in this present work. The organic solvent blend of benzene-ethyl alcohol-water was used as the separation reagent. Then triangle coordinate figure analysis was taken to optimize the volume proportion of various components in the separating agent and separation process. And the separation temperature of aluminium-plastic laminates was determined by the separation time, efficiency, and total mass loss of products. The results show that cost-efficient separations perform best with low usage of solvents at certain temperatures, for certain times, and within a certain range of volume proportions of the three components in the solvent agent. It is also found that similar solubility parameters of solvents and polyethylene adhesives (range 26.06-34.85) are a key factor for the separation of the aluminium-plastic laminates. Such multisolvent processes based on the combined-system concept will be vital to applications in the recycling industry.

Enabling Requirements-Based Programming for Highly-Dependable Complex Parallel and Distributed Systems

Science.gov (United States)

Hinchey, Michael G.; Rash, James L.; Rouff, Christopher A.

2005-01-01

The manual application of formal methods in system specification has produced successes, but in the end, despite any claims and assertions by practitioners, there is no provable relationship between a manually derived system specification or formal model and the customer's original requirements. Complex parallel and distributed system present the worst case implications for today s dearth of viable approaches for achieving system dependability. No avenue other than formal methods constitutes a serious contender for resolving the problem, and so recognition of requirements-based programming has come at a critical juncture. We describe a new, NASA-developed automated requirement-based programming method that can be applied to certain classes of systems, including complex parallel and distributed systems, to achieve a high degree of dependability.

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4A. Paks NPP: Analysis/testing. Working material

International Nuclear Information System (INIS)

1995-01-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on data related to seismic analyses of structures of Paks and Kozloduy reactor buildings and WWER-440/213 primary coolant loops with different antiseismic devices

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4A. Paks NPP: Analysis/testing. Working material

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-07-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on data related to seismic analyses of structures of Paks and Kozloduy reactor buildings and WWER-440/213 primary coolant loops with different antiseismic devices.

Tumor cell invasion of collagen matrices requires coordinate lipid agonist-induced G-protein and membrane-type matrix metalloproteinase-1-dependent signaling

Directory of Open Access Journals (Sweden)

Anthis Nicholas J

2006-12-01

fundamental regulator of MT1-MMP-dependent tumor cell invasion of 3D collagen matrices. In contrast, S1P appears to act as an inhibitory stimulus in most cases, while stimulating only select tumor lines. MT1-MMP is required only when tumor cells navigate 3D barriers and not when cells migrate on 2D substrata. We demonstrate that tumor cells require coordinate regulation of LPA/S1P receptors and Rho GTPases to migrate, and additionally, require MT1-MMP in order to invade collagen matrices during neoplastic progression.

End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1.

Science.gov (United States)

Lescasse, Rachel; Pobiega, Sabrina; Callebaut, Isabelle; Marcand, Stéphane

2013-03-20

In eukaryotes, permanent inhibition of the non-homologous end joining (NHEJ) repair pathway at telomeres ensures that chromosome ends do not fuse. In budding yeast, binding of Rap1 to telomere repeats establishes NHEJ inhibition. Here, we show that the Uls1 protein is required for the maintenance of NHEJ inhibition at telomeres. Uls1 protein is a non-essential Swi2/Snf2-related translocase and a Small Ubiquitin-related Modifier (SUMO)-Targeted Ubiquitin Ligase (STUbL) with unknown targets. Loss of Uls1 results in telomere-telomere fusions. Uls1 requirement is alleviated by the absence of poly-SUMO chains and by rap1 alleles lacking SUMOylation sites. Furthermore, Uls1 limits the accumulation of Rap1 poly-SUMO conjugates. We propose that one of Uls1 functions is to clear non-functional poly-SUMOylated Rap1 molecules from telomeres to ensure the continuous efficiency of NHEJ inhibition. Since Uls1 is the only known STUbL with a translocase activity, it can be the general molecular sweeper for the clearance of poly-SUMOylated proteins on DNA in eukaryotes.

Bmi1 Is Required for Hedgehog Pathway-Driven Medulloblastoma Expansion

Directory of Open Access Journals (Sweden)

Lowell Evan Michael

2008-12-01

Full Text Available Inappropriate Hedgehog (Hh signaling underlies development of a subset of medulloblastomas, and tumors with elevated HH signaling activity express the stem cell self-renewal gene BMI1. To test whether Bmi1 is required for Hh-driven medulloblastoma development, we varied Bmi1 gene dosage in transgenic mice expressing an oncogenic Hh effector, SmoA1, driven by a glial fibrillary acidic protein (GFAP promoter. Whereas 100% of SmoA1; Bmi1+/+ or SmoA1;Bmi1+/- mice examined between postnatal (P days 14 and 26 had typical medulloblastomas (N = 29, tumors were not detected in any of the SmoA1;Bmi1-/- animals examined (N = 6. Instead, small ectopic collections of cells were present in the region of greatest tumor load in SmoA1 animals, suggesting that medulloblastomas were initiated but failed to undergo expansion into frank tumors. Cells within these Bmi1-/- lesions expressed SmoA1 but were largely nonproliferative, in contrast to cells in Bmi1+/+ tumors (6.2% vs 81.9% PCNA-positive, respectively. Ectopic cells were negative for the progenitor marker nestin, strongly GFAP-positive, and highly apoptotic, relative to Bmi1+/+ tumor cells (29.6% vs 6.3% TUNEL-positive. The alterations in proliferation and apoptosis in SmoA1;Bmi1-/- ectopic cells are associated with reduced levels of Cyclin D1 and elevated expression of cyclin-dependent kinase inhibitor p19Arf, two inversely regulated downstream targets of Bmi1. These data provide the first demonstration that Bmi1 is required for spontaneous de novo development of a solid tumor arising in the brain, suggest a crucial role for Bmi1-dependent, nestin-expressing progenitor cells in medulloblastoma expansion, and implicate Bmi1 as a key factor required for Hh pathway-driven tumorigenesis.

26 CFR 301.6723-1 - Failure to comply with other information reporting requirements.

Science.gov (United States)

2010-04-01

... under section 6050K(c)(1) (relating to the requirement that a transferor notify the partnership of an exchange of a partnership interest); (ii) Any requirement contained in the regulations under section 6109.... The Form 1040 requires him to provide the TINs of his two dependents, which A fails to do. Because A...

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4C. Paks NPP: Analysis and testing. Working material

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-07-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material involves comparative analysis of the seismic analysis results of the reactor building for soft soil conditions, derivation of design response spectra for components and systems; and upper range design response spectra for soft soil site conditions at Paks NPP.

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4C. Paks NPP: Analysis and testing. Working material

International Nuclear Information System (INIS)

1996-01-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material involves comparative analysis of the seismic analysis results of the reactor building for soft soil conditions, derivation of design response spectra for components and systems; and upper range design response spectra for soft soil site conditions at Paks NPP

Identification of a highly conserved valine-glycine-phenylalanine amino acid triplet required for HIV-1 Nef function

Directory of Open Access Journals (Sweden)

Meuwissen Pieter J

2012-04-01

Full Text Available Abstract Background The Nef protein of HIV facilitates virus replication and disease progression in infected patients. This role as pathogenesis factor depends on several genetically separable Nef functions that are mediated by interactions of highly conserved protein-protein interaction motifs with different host cell proteins. By studying the functionality of a series of nef alleles from clinical isolates, we identified a dysfunctional HIV group O Nef in which a highly conserved valine-glycine-phenylalanine (VGF region, which links a preceding acidic cluster with the following proline-rich motif into an amphipathic surface was deleted. In this study, we aimed to study the functional importance of this VGF region. Results The dysfunctional HIV group O8 nef allele was restored to the consensus sequence, and mutants of canonical (NL4.3, NA-7, SF2 and non-canonical (B2 and C1422 HIV-1 group M nef alleles were generated in which the amino acids of the VGF region were changed into alanines (VGF→AAA and tested for their capacity to interfere with surface receptor trafficking, signal transduction and enhancement of viral replication and infectivity. We found the VGF motif, and each individual amino acid of this motif, to be critical for downregulation of MHC-I and CXCR4. Moreover, Nef’s association with the cellular p21-activated kinase 2 (PAK2, the resulting deregulation of cofilin and inhibition of host cell actin remodeling, and targeting of Lck kinase to the trans-golgi-network (TGN were affected as well. Of particular interest, VGF integrity was essential for Nef-mediated enhancement of HIV virion infectivity and HIV replication in peripheral blood lymphocytes. For targeting of Lck kinase to the TGN and viral infectivity, especially the phenylalanine of the triplet was essential. At the molecular level, the VGF motif was required for the physical interaction of the adjacent proline-rich motif with Hck. Conclusion Based on these findings, we

Results of a benchmark study for the seismic analysis and testing of WWER type NPPs: Overview and general comparison for Paks NPP

International Nuclear Information System (INIS)

Guerpinar, A.; Zola, M.

2001-01-01

Within the framework of the IAEA coordinated 'Benchmark Study for the seismic analysis and testing of WWER-type NPPs', in-situ dynamic structural testing activities have been performed at the Paks Nuclear Power Plant in Hungary. The specific objective of the investigation was to obtain experimental data on the actual dynamic structural behaviour of the plant's major constructions and equipment under normal operating conditions, for enabling a valid seismic safety review to be made. This paper refers on the comparison of the results obtained from the experimental activities performed by ISMES with those coming from analytical studies performed for the Coordinated Research Programme (CRP) by Siemens (Germany), EQE (Bulgaria), Central Laboratory (Bulgaria), M. David Consulting (Czech Republic), IVO (Finland). This paper gives a synthetic description of the conducted experiments and presents some results, regarding in particular the free-field excitations produced during the earthquake-simulation experiments and an experiment of the dynamic soil-structure interaction global effects at the base of the reactor containment structure. The specific objective of the experimental investigation was to obtain valid data on the dynamic behaviour of the plant's major constructions, under normal operating conditions, to support the analytical assessment of their actual seismic safety. The full-scale dynamic structural testing activities have been performed in December 1994 at the Paks (H) Nuclear Power Plant. The Paks NPP site has been subjected to low level earthquake-like ground shaking, through appropriately devised underground explosions, and the dynamic response of the plant's 1st reactor unit important structures was appropriately measured and digitally recorded, with the whole nuclear power plant under normal operating conditions. In-situ free field response was measured concurrently and, moreover, site-specific geophysical and seismological data were simultaneously

A Conserved GPG-Motif in the HIV-1 Nef Core Is Required for Principal Nef-Activities.

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Marta Martínez-Bonet

Full Text Available To find out new determinants required for Nef activity we performed a functional alanine scanning analysis along a discrete but highly conserved region at the core of HIV-1 Nef. We identified the GPG-motif, located at the 121-137 region of HIV-1 NL4.3 Nef, as a novel protein signature strictly required for the p56Lck dependent Nef-induced CD4-downregulation in T-cells. Since the Nef-GPG motif was dispensable for CD4-downregulation in HeLa-CD4 cells, Nef/AP-1 interaction and Nef-dependent effects on Tf-R trafficking, the observed effects on CD4 downregulation cannot be attributed to structure constraints or to alterations on general protein trafficking. Besides, we found that the GPG-motif was also required for Nef-dependent inhibition of ring actin re-organization upon TCR triggering and MHCI downregulation, suggesting that the GPG-motif could actively cooperate with the Nef PxxP motif for these HIV-1 Nef-related effects. Finally, we observed that the Nef-GPG motif was required for optimal infectivity of those viruses produced in T-cells. According to these findings, we propose the conserved GPG-motif in HIV-1 Nef as functional region required for HIV-1 infectivity and therefore with a potential interest for the interference of Nef activity during HIV-1 infection.

Myosin-1C uses a novel phosphoinositide-dependent pathway for nuclear localization.

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Nevzorov, Ilja; Sidorenko, Ekaterina; Wang, Weihuan; Zhao, Hongxia; Vartiainen, Maria K

2018-02-01

Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding. Nuclear import of Myo1C is preceded by its interaction with the endoplasmic reticulum, and phosphoinositide binding is specifically required for nuclear import, but not nuclear retention, of Myo1C. Our results therefore demonstrate, for the first time, that membrane association and binding to nuclear partners is sufficient to drive nuclear localization of also soluble proteins, opening new perspectives to evolution of cellular protein sorting mechanisms. © 2018 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

Morphogenesis checkpoint kinase Swe1 is the executor of lipolysis-dependent cell-cycle progression.

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Chauhan, Neha; Visram, Myriam; Cristobal-Sarramian, Alvaro; Sarkleti, Florian; Kohlwein, Sepp D

2015-03-10

Cell growth and division requires the precise duplication of cellular DNA content but also of membranes and organelles. Knowledge about the cell-cycle-dependent regulation of membrane and storage lipid homeostasis is only rudimentary. Previous work from our laboratory has shown that the breakdown of triacylglycerols (TGs) is regulated in a cell-cycle-dependent manner, by activation of the Tgl4 lipase by the major cyclin-dependent kinase Cdc28. The lipases Tgl3 and Tgl4 are required for efficient cell-cycle progression during the G1/S (Gap1/replication phase) transition, at the onset of bud formation, and their absence leads to a cell-cycle delay. We now show that defective lipolysis activates the Swe1 morphogenesis checkpoint kinase that halts cell-cycle progression by phosphorylation of Cdc28 at tyrosine residue 19. Saturated long-chain fatty acids and phytosphingosine supplementation rescue the cell-cycle delay in the Tgl3/Tgl4 lipase-deficient strain, suggesting that Swe1 activity responds to imbalanced sphingolipid metabolism, in the absence of TG degradation. We propose a model by which TG-derived sphingolipids are required to activate the protein phosphatase 2A (PP2A(Cdc55)) to attenuate Swe1 phosphorylation and its inhibitory effect on Cdc28 at the G1/S transition of the cell cycle.

Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

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Wu, Weibin; Sun, Zhichao; Wu, Jingwen; Peng, Xiaomin; Gan, Huacheng; Zhang, Chunyi; Ji, Lingling; Xie, Jianhui; Zhu, Haiyan; Ren, Shifang

2012-01-01

c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src. PMID:22238675

The discovery and the structural basis of an imidazo[4,5-b]pyridine-based p21-activated kinase 4 inhibitor.

Science.gov (United States)

Park, Jeung Kuk; Kim, Sunmin; Han, Yu Jin; Kim, Seong Hwan; Kang, Nam Sook; Lee, Hyuk; Park, SangYoun

2016-06-01

p21-Activated kinases (PAKs) which belong to the family of ste20 serine/threonine protein kinases regulate cytoskeletal reorganization, cell motility, cell proliferation, and oncogenic transformation which are all related to the cellular functions during cancer induction and metastasis. The fact that PAK mutations are detected in multiple tumor tissues makes PAKs a novel therapeutic drug target. In this study, an imidazo[4,5-b]pyridine-based PAK4 inhibitor, KY-04045 (6-Bromo-2-(3-isopropyl-1-methyl-1H-pyrazol-4-yl)-1H-imidazo[4,5-b]pyridine), was discovered using a virtual site-directed fragment-based drug design and was validated using an inhibition assay. Although PAK4 affinity to KY-04045 seems much weaker than that of the reported PAK4 inhibitors, the location of KY-04045 is clearly defined in the structure of PAK4 co-crystallized with KY-04045. The crystal structure illustrates that the pyrazole and imidazopyridine rings of KY-04045 are sufficient for mediating PAK4 hinge loop interaction. Hence, we believe that KY-04045 can be exploited as a basic building block in designing novel imidazo[4,5-b]pyridine-based PAK4 inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Rac1-stimulated macropinocytosis enhances Gβγ activation of PI3Kβ.

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Erami, Zahra; Khalil, Bassem D; Salloum, Gilbert; Yao, Yanhua; LoPiccolo, Jaclyn; Shymanets, Aliaksei; Nürnberg, Bernd; Bresnick, Anne R; Backer, Jonathan M

2017-11-16

Phosphoinositide 3-kinases (PI 3-kinases) are regulated by a diverse range of upstream activators, including receptor tyrosine kinases (RTKs), G-protein-coupled receptors (GPCRs), and small GTPases from the Ras, Rho and Rab families. For the Class IA PI 3-kinase PI3Kβ, two mechanisms for GPCR-mediated regulation have been described: direct binding of Gβγ subunits to the C2-helical domain linker of p110β, and Dock180/Elmo1-mediated activation of Rac1, which binds to the Ras-Binding Domain of p110β. We now show that the integration of these dual pathways is unexpectedly complex. In breast cancer cells, expression of constitutively activated Rac1 (CA-Rac1) along with either GPCR stimulation or expression of Gβγ led to an additive PI3Kβ-dependent activation of Akt. Whereas CA-Rac1-mediated activation of Akt was blocked in cells expressing a mutated PI3Kβ that cannot bind Gβγ, Gβγ and GPCR-mediated activation of Akt was preserved when Rac1 binding to PI3Kβ was blocked. Surprisingly, PI3Kβ-dependent CA-Rac1 signaling to Akt was still seen in cells expressing a mutant p110β that cannot bind Rac1. Instead of directly binding to PI3Kβ, CA-Rac1 acts by enhancing Gβγ coupling to PI3Kβ, as CA-Rac1-mediated Akt activation was blocked by inhibitors of Gβγ. Cells expressing CA-Rac1 exhibited a robust induction of macropinocytosis, and inhibitors of macropinocytosis blocked the activation of Akt by CA-Rac1 or lysophosphatidic acid. Our data suggest that Rac1 can potentiate the activation of PI3Kβ by GPCRs through an indirect mechanism, by driving the formation of macropinosomes that serve as signaling platforms for Gβγ coupling to PI3Kβ. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The Xenopus laevis morphogenetic factor, tumorhead, causes defects in polarized growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe

International Nuclear Information System (INIS)

Wu, Chuan Fen; Yang, Peirong; Traverso, Edwin E.; Etkin, Laurence D.; Marcus, Stevan

2004-01-01

Tumorhead (TH) is a maternally expressed gene product that regulates neural tube morphogenesis in the amphibian, Xenopus laevis. Here we describe the effects of TH expression in the rod-shaped fission yeast, Schizosaccharomyces pombe. Expression of TH in S. pombe resulted in severe morphological defects, including ovoid, bottle-shaped, and enlarged cells. Multi-septated cells were also observed in TH expressing cultures, indicating that TH is inhibitory to a process required for the completion of cytokinesis. TH expression caused significant actin and microtubule cytoskeletal defects, including depolarization of the cortical F-actin cytoskeleton and increased microtubule formation. Immunostaining experiments showed that TH is localized to the cell cortex, cell tips, and septum in S. pombe cells. Localization of TH to the cell cortex was dependent on the S. pombe PAK homolog, Shk1. Moreover, TH expression was inhibitory to the growth of a mutant defective in Shk1 function, suggesting that TH may interact with a component(s) of a PAK-mediated morphogenetic regulatory pathway in S. pombe. Taken together, our findings demonstrate that S. pombe may be a useful model organism for identifying potential TH interacting factors

Structural basis for the differential effects of CaBP1 and calmodulin on CaV1.2 calcium-dependent inactivation

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Findeisen, Felix; Minor, Daniel L.

2010-01-01

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (CaVs) with unusual properties. CaBP1 inhibits CaV1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit CaV1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF-hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the CaV1.2 IQ domain at a site that overlaps with the Ca2+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates CaVs. PMID:21134641

Structural basis for the differential effects of CaBP1 and calmodulin on Ca(V)1.2 calcium-dependent inactivation.

Science.gov (United States)

Findeisen, Felix; Minor, Daniel L

2010-12-08

Calcium-binding protein 1 (CaBP1), a calmodulin (CaM) homolog, endows certain voltage-gated calcium channels (Ca(V)s) with unusual properties. CaBP1 inhibits Ca(V)1.2 calcium-dependent inactivation (CDI) and introduces calcium-dependent facilitation (CDF). Here, we show that the ability of CaBP1 to inhibit Ca(V)1.2 CDI and induce CDF arises from interaction between the CaBP1 N-lobe and interlobe linker residue Glu94. Unlike CaM, where functional EF hands are essential for channel modulation, CDI inhibition does not require functional CaBP1 EF hands. Furthermore, CaBP1-mediated CDF has different molecular requirements than CaM-mediated CDF. Overall, the data show that CaBP1 comprises two structural modules having separate functions: similar to CaM, the CaBP1 C-lobe serves as a high-affinity anchor that binds the Ca(V)1.2 IQ domain at a site that overlaps with the Ca²+/CaM C-lobe site, whereas the N-lobe/linker module houses the elements required for channel modulation. Discovery of this division provides the framework for understanding how CaBP1 regulates Ca(V)s. Copyright © 2010 Elsevier Ltd. All rights reserved.

MYR1-Dependent Effectors Are the Major Drivers of a Host Cell’s Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects

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Adit Naor

2018-04-01

Full Text Available The obligate intracellular parasite Toxoplasma gondii controls its host cell from within the parasitophorous vacuole (PV by using a number of diverse effector proteins, a subset of which require the aspartyl protease 5 enzyme (ASP5 and/or the recently discovered MYR1 protein to cross the PV membrane. To examine the impact these effectors have in the context of the entirety of the host response to Toxoplasma, we used RNA-Seq to analyze the transcriptome expression profiles of human foreskin fibroblasts infected with wild-type RH (RH-WT, RHΔmyr1, and RHΔasp5 tachyzoites. Interestingly, the majority of the differentially regulated genes responding to Toxoplasma infection are MYR1 dependent. A subset of MYR1 responses were ASP5 independent, and MYR1 function did not require ASP5 cleavage, suggesting the export of some effectors requires only MYR1. Gene set enrichment analysis of MYR1-dependent host responses suggests an upregulation of E2F transcription factors and the cell cycle and a downregulation related to interferon signaling, among numerous others. Most surprisingly, “hidden” responses arising in RHΔmyr1- but not RH-WT-infected host cells indicate counterbalancing actions of MYR1-dependent and -independent activities. The host genes and gene sets revealed here to be MYR1 dependent provide new insight into the parasite’s ability to co-opt host cell functions.

NPM1 directs PIDDosome-dependent caspase-2 activation in the nucleolus.

Science.gov (United States)

Ando, Kiyohiro; Parsons, Melissa J; Shah, Richa B; Charendoff, Chloé I; Paris, Sheré L; Liu, Peter H; Fassio, Sara R; Rohrman, Brittany A; Thompson, Ruth; Oberst, Andrew; Sidi, Samuel; Bouchier-Hayes, Lisa

2017-06-05

The PIDDosome (PIDD-RAIDD-caspase-2 complex) is considered to be the primary signaling platform for caspase-2 activation in response to genotoxic stress. Yet studies of PIDD-deficient mice show that caspase-2 activation can proceed in the absence of PIDD. Here we show that DNA damage induces the assembly of at least two distinct activation platforms for caspase-2: a cytoplasmic platform that is RAIDD dependent but PIDD independent, and a nucleolar platform that requires both PIDD and RAIDD. Furthermore, the nucleolar phosphoprotein nucleophosmin (NPM1) acts as a scaffold for PIDD and is essential for PIDDosome assembly in the nucleolus after DNA damage. Inhibition of NPM1 impairs caspase-2 processing, apoptosis, and caspase-2-dependent inhibition of cell growth, demonstrating that the NPM1-dependent nucleolar PIDDosome is a key initiator of the caspase-2 activation cascade. Thus we have identified the nucleolus as a novel site for caspase-2 activation and function. © 2017 Ando et al.

UnPAKing RUNX3 functions-Both sides of the coin.

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Kumar, Arun; Sundaram, Sandhya; Rayala, Suresh K; Venkatraman, Ganesh

2017-06-19

Post translational modifications of RUNX3 have been shown to play an important role in directing RUNX3 functions. In this review we highlight the phosphorylation dependent functions of RUNX3 as regulated by PAK1 and its implications on tumorigenesis.

LeCPK1, a Calcium-Dependent Protein Kinase from Tomato. Plasma Membrane Targeting and Biochemical Characterization1

Science.gov (United States)

Rutschmann, Frank; Stalder, Urs; Piotrowski, Markus; Oecking, Claudia; Schaller, Andreas

2002-01-01

The cDNA of LeCPK1, a calcium-dependent protein kinase, was cloned from tomato (Lycopersicon esculentum Mill.). LeCPK1 was expressed in Escherichia coli and purified from bacterial extracts. The recombinant protein was shown to be a functional protein kinase using a synthetic peptide as the substrate (syntide-2, Km = 85 μm). Autophosphorylation of LeCPK1 was observed on threonine and serine residues, one of which was identified as serine-439. Kinase activity was shown to be Ca2+ dependent and required the C-terminal, calmodulin-like domain of LeCPK1. Two classes of high- and low-affinity Ca2+-binding sites were observed, exhibiting dissociation constants of 0.6 and 55 μm, respectively. LeCPK1 was found to phosphorylate the regulatory C-terminal domain of the plasma membrane H+-ATPase in vitro. A potential role in the regulation of proton pump activity is corroborated by the apparent colocalization of the plasma membrane H+-ATPase and LeCPK1 in vivo. Upon transient expression in suspension-cultured cells, a C-terminal fusion of LeCPK1 with the green fluorescent protein was targeted to the plasma membrane. Myristoylation of the LeCPK1 N terminus was found to be required for plasma membrane targeting. PMID:12011347

FAK/src-family dependent activation of the Ste20-like kinase SLK is required for microtubule-dependent focal adhesion turnover and cell migration.

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Simona Wagner

2008-04-01

Full Text Available Cell migration involves a multitude of signals that converge on cytoskeletal reorganization, essential for development, immune responses and tissue repair. Using knockdown and dominant negative approaches, we show that the microtubule-associated Ste20-like kinase SLK is required for focal adhesion turnover and cell migration downstream of the FAK/c-src complex. Our results show that SLK co-localizes with paxillin, Rac1 and the microtubules at the leading edge of migrating cells and is activated by scratch wounding. SLK activation is dependent on FAK/c-src/MAPK signaling, whereas SLK recruitment to the leading edge is src-dependent but FAK independent. Our results show that SLK represents a novel focal adhesion disassembly signal.

An assessment of the parameters and experimental data of the continuous water activity monitors operating in the upstream and downstream channels of the Paks nuclear power plant

International Nuclear Information System (INIS)

Nagy, Gy.; Feher, I.

1986-03-01

A NaI(Tl) scintillator was placed into a measuring vessel of 8 msup(3) volume for monitoring the effluents in the upstream and downstream channels of the Paks nuclear power plant. The effects of radioactivity, meteorological parameters, and the atmospheric pressure on the counting rates, and their daily and monthly average values in both channels were analyzed. The short-term increases of the monitor signals could be attributed to rainy weather. The sup(222)Rn countent of water was also evaluated. (author)

Cytotaxonomy of Eurypyga helias (Gruiformes, Eurypygidae): First Karyotypic Description and Phylogenetic Proximity with Rynochetidae

Science.gov (United States)

dos Santos, Michelly da Silva; Tagliarini, Marcella Mergulhão; O´Brien, Patricia C. M.; Ferguson-Smith, Malcolm A.; de Oliveira, Edivaldo H. C.

2015-01-01

The sunbittern (Eurypyga helias) is a South American Gruiformes, the only member of Family Eurypigidae. In most phylogenetic proposals, it is placed in a more distant position than other families of the so-called “core Gruiformes”. Different studies based on molecular, morphological and biogeographical data suggest that the Eurypigidae is closely related to the kagu (Rhynochetos jubatus), the only species in Rynochetidae, another family not included in the core Gruiformes. Here, the karyotype of the sunbittern is described for the first time, by classical and molecular cytogenetics, using whole chromosome probes derived from Gallus gallus and Leucopternis albicollis. We found a diploid number of 80, with only one pair of biarmed autosomal macrochromosomes, similar to that observed in the kagu. Chromosome painting revealed that most syntenies found in the avian putative ancestral karyotype (PAK) were conserved in the sunbittern. However, PAK1, PAK2, and PAK5 corresponded to two chromosome pairs each. Probes derived from L. albicollis confirm that fissions in PAK1 and PAK2 were centric, whereas in PAK5 the fission is interstitial. In addition, there is fusion of segments homologous to PAK2q and PAK5. From a phylogenetic point of view, comparisons of our results with two other Gruiformes belonging to family Rallidae suggest that the PAK5q fission might be a synapomorphy for Gruiformes. Fissions in PAK1 and PAK2 are found only in Eurypigidae, and might also occur in Rynochetidae, in view of the similar chromosomal morphology between the sunbittern and the kagu. This suggests a close phylogenetic relationship between Eurypigidae and Rynochetidae, whose common ancestor was separated by the Gondwana vicariancy in South America and New Caledonia, respectively. PMID:26624624

An assesment of the characteristics of the GM detectors and iodine remote detectors of the Paks environmental monitoring system based on the data measured from 1982 to 1985

International Nuclear Information System (INIS)

Nagy, Gy.; Lang, Edit; Deme, S.; Feher, I.

1986-03-01

Measurements performed at the GM detectors and iodine remote detectors of the continuous environmental monitoring system of the Paks NPP can be used for estimating the effect of atmospheric releases. Based on the investigations carried out from Sep. 1982 to July 1985, a good correlation between the signals and the background radioactivity levels could be established. It was further stated that radon fallout during raining was responsible for significant signal changes of both types of detectors. (V.N.)

Monitoring and assessment of health issues at energy plant and gas station Pak steel bin Qasim Karachi

International Nuclear Information System (INIS)

Memon, Z.

2005-01-01

No doubt Environmental and health safety issues in big cities of Pakistan are developing havoc problems due to mechanized operations by emitting flue gases, effluent and acoustic noise, which it is my topic to discuss in detail. Acoustic noise is one of the major environmental problems in Industrial Plants. The noise study under taken in detail at feed pumps, super heater, exhausters and accumulators of Energy plant (E.P) as the regulators, control room etc. of Gas station (G.S) Pak Steel Bin Qasim Karachi. In light of permissible occupational noise exposure limits, as allowed by the ISO,EEC and other National Standards, some recommendations have been made to provide safety measures for workers against high level noise health hazards like head ache, hearing problem, Irritation, accidents at work, tension, disturbance to work and so many physiological and psychological effects, along with guidelines to overcome the break downs an improve efficiency of the plants. (Orig./A.B.)

GTSE1 is a microtubule plus-end tracking protein that regulates EB1-dependent cell migration.

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Massimilano Scolz

Full Text Available The regulation of cell migration is a highly complex process that is often compromised when cancer cells become metastatic. The microtubule cytoskeleton is necessary for cell migration, but how microtubules and microtubule-associated proteins regulate multiple pathways promoting cell migration remains unclear. Microtubule plus-end binding proteins (+TIPs are emerging as important players in many cellular functions, including cell migration. Here we identify a +TIP, GTSE1, that promotes cell migration. GTSE1 accumulates at growing microtubule plus ends through interaction with the EB1+TIP. The EB1-dependent +TIP activity of GTSE1 is required for cell migration, as well as for microtubule-dependent disassembly of focal adhesions. GTSE1 protein levels determine the migratory capacity of both nontransformed and breast cancer cell lines. In breast cancers, increased GTSE1 expression correlates with invasive potential, tumor stage, and time to distant metastasis, suggesting that misregulation of GTSE1 expression could be associated with increased invasive potential.

Status of safety analysis reports

Energy Technology Data Exchange (ETDEWEB)

Cserhati, A

1999-06-01

The safety regulation connected to both of the Atomic Acts from 1980 and 1996 requires preparation of the Preliminary Safety Analysis Report (PSAR) as well as Final SAR (FSAR). In this respect the licensing procedure for the construction and commissioning of Paks NPP did not formally deviate from the standards applied in developed countries; this is particularly true if comparison is made with the standards applied for commissioning NPPs in the second half of the seventies. By the time the overall development of internationally accepted safety standards and some existing deficiencies of earlier SAR made necessary a general reassessment of the plant safety (AGNES project). The carried out PSR for Paks-1 and 2 also added a valuable contribution to the SAR content, however a formal update of SAR is not made yet. A Hungarian nuclear authority decree from 1997 obligates the licensee to prepare and submit a major upgrade of FSAR until the mid of 2000, after finishing the PSR for Paks-3 and 4. From this date a periodic update of FSAR is required every year. The operational license renewal affects only the PSR but not the FSAR updating. The new Nuclear Safety Code outlines the contents of PSAR and FSAR, based on US NRC Reg. Guide 1. 70. Rev. 3. Hungary by now can fulfill the upgrading of SAR without major external technical or financial help. The AGNES project covered the safety analysis chapters of SAR. It was financed mainly by the country. In the project there have been involved in limited cases as performers the VTT (Finland), Belgatom (Belgium), GRS (Germany), etc., the IVO (Finland) fulfilled tasks of an independent reviewer for safety analysis. The AGNES had certain interconnection with the similar IAEA RER safety reassessment project for WWER-440/213. The PSR for Paks-1 and 2 have been carried out by the Paks staff from the resources of the plant. During the evaluation of several parts of Paks-3 and 4 PSR documentation the authority intends to use certain

GEMC1 is a TopBP1 interacting protein required for chromosomal DNA replication

Science.gov (United States)

Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

2010-01-01

Many factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication in complex multicellular organisms is poorly understood. Here, we report the identification of GEMC1, a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus egg extract we show that Xenopus GEMC1 (xGEMC1) binds to checkpoint and replication factor TopBP1, which promotes xGEMC1 binding to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 directly interacts with replication factors such as Cdc45 and Cdk2-CyclinE by which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication whereas depletion of xGEMC1 prevents DNA replication onset due to impairment of Cdc45 loading onto chromatin. Likewise, inhibition of GEMC1 expression by morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in higher eukaryotes by mediating TopBP1 and Cdk2 dependent recruitment of Cdc45 onto replication origins. PMID:20383140

Degradation Behavior and Accelerated Weathering of Composite Boards Produced from Waste Tetra Pak® Packaging Materials

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Nural Yilgo

2014-06-01

Full Text Available Manufacturing panels from Tetra Pak® (TP packaging material might be an alternative to conventional wood-based panels. This study evaluated some chemical and physical properties as well as biological, weathering, and fire performance of panels with and without zinc borate (ZnB by using shredded TP packaging cartons. Such packaging material, a worldwide well-known multilayer beverage packaging system, is composed of cellulose, low-density polyethylene (LDPE, and aluminum (Al. Panels produced from waste TP packaging material were also examined by FT-IR to understand the fungal deterioration and extent of degradation after accelerated weathering. Before FT-IR investigations, panel specimens were ground under nitrogen atmosphere due to non-uniformity of the composite material. The FT-IR results showed that fungal degradation occurred in the natural polymer of the panel matrix. Although the natural polymer is mostly composed of cellulose, there were also small amounts of polyoses and lignin. It was seen that especially polyose and lignin bands in FT-IR spectra were affected more than cellulose bands by fungal attack. No changes were observed by the fungi in the plastic component (LDPE of the matrix; however, LDPE seemed more sensitive to weathering than cellulose. Incorporation of ZnB at loading level of 1% (w/w did not contribute fire performance of the panels when compared to control panel specimens, while a loading level of 10% improved fire performance considering test parameters such as mass loss, ignition time and peak heat release rate.

MYR1-Dependent Effectors Are the Major Drivers of a Host Cell's Early Response to Toxoplasma, Including Counteracting MYR1-Independent Effects.

Science.gov (United States)

Naor, Adit; Panas, Michael W; Marino, Nicole; Coffey, Michael J; Tonkin, Christopher J; Boothroyd, John C

2018-04-03

The obligate intracellular parasite Toxoplasma gondii controls its host cell from within the parasitophorous vacuole (PV) by using a number of diverse effector proteins, a subset of which require the aspartyl protease 5 enzyme (ASP5) and/or the recently discovered MYR1 protein to cross the PV membrane. To examine the impact these effectors have in the context of the entirety of the host response to Toxoplasma , we used RNA-Seq to analyze the transcriptome expression profiles of human foreskin fibroblasts infected with wild-type RH (RH-WT), RHΔ myr1 , and RHΔ asp5 tachyzoites. Interestingly, the majority of the differentially regulated genes responding to Toxoplasma infection are MYR1 dependent. A subset of MYR1 responses were ASP5 independent, and MYR1 function did not require ASP5 cleavage, suggesting the export of some effectors requires only MYR1. Gene set enrichment analysis of MYR1-dependent host responses suggests an upregulation of E2F transcription factors and the cell cycle and a downregulation related to interferon signaling, among numerous others. Most surprisingly, "hidden" responses arising in RHΔ myr1 - but not RH-WT-infected host cells indicate counterbalancing actions of MYR1-dependent and -independent activities. The host genes and gene sets revealed here to be MYR1 dependent provide new insight into the parasite's ability to co-opt host cell functions. IMPORTANCE Toxoplasma gondii is unique in its ability to successfully invade and replicate in a broad range of host species and cells within those hosts. The complex interplay of effector proteins exported by Toxoplasma is key to its success in co-opting the host cell to create a favorable replicative niche. Here we show that a majority of the transcriptomic effects in tachyzoite-infected cells depend on the activity of a novel translocation system involving MYR1 and that the effectors delivered by this system are part of an intricate interplay of activators and suppressors. Removal of all MYR1

RNASEK is required for internalization of diverse acid-dependent viruses.

Science.gov (United States)

Hackett, Brent A; Yasunaga, Ari; Panda, Debasis; Tartell, Michael A; Hopkins, Kaycie C; Hensley, Scott E; Cherry, Sara

2015-06-23

Viruses must gain entry into cells to establish infection. In general, viruses enter either at the plasma membrane or from intracellular endosomal compartments. Viruses that use endosomal pathways are dependent on the cellular factors that control this process; however, these genes have proven to be essential for endogenous cargo uptake, and thus are of limited value for therapeutic intervention. The identification of genes that are selectively required for viral uptake would make appealing drug targets, as their inhibition would block an early step in the life cycle of diverse viruses. At this time, we lack pan-antiviral therapeutics, in part because of our lack of knowledge of such cellular factors. RNAi screening has begun to reveal previously unknown genes that play roles in viral infection. We identified dRNASEK in two genome-wide RNAi screens performed in Drosophila cells against West Nile and Rift Valley Fever viruses. Here we found that ribonuclease kappa (RNASEK) is essential for the infection of human cells by divergent and unrelated positive- and negative-strand-enveloped viruses from the Flaviviridae, Togaviridae, Bunyaviridae, and Orthomyxoviridae families that all enter cells from endosomal compartments. In contrast, RNASEK was dispensable for viruses, including parainfluenza virus 5 and Coxsackie B virus, that enter at the plasma membrane. RNASEK is dispensable for attachment but is required for uptake of these acid-dependent viruses. Furthermore, this requirement appears specific, as general endocytic uptake of transferrin is unaffected in RNASEK-depleted cells. Therefore, RNASEK is a potential host cell Achilles' heel for viral infection.

Nitrogen requirements of cassava in selected soils of Thailand

Directory of Open Access Journals (Sweden)

Jakchaiwat Kaweewong

2013-08-01

Full Text Available Cassava (Manihot esculenta is one of the most important export crops in Thailand, yet the nitrogen requirement is unknown and not considered by growers and producers. Cassava requirements for N were determined in field experiments during a period of four years and four sites on the Satuk (Suk, Don Chedi (Dc, Pak Chong (Pc,and Ban Beung (BBg soil series in Lopburi, Supanburi, Nakhon Ratchasima, and Chonburi sites, respectively. The fertilizer treatment structure comprised 0, 62.5, 125, 187.5, 250 and 312.5 kg N ha^(-1 as urea. At each site cassava was harvested at nine months and yield parameters and the minimum datasets were taken. The fertilizer rate which resulted in maximum yield ranged from 187.5 kg N ha^(-1 in Supanburi and Chonburi (fresh weight yield of 47,500 and 30,000 kg ha^(-1 respectively to 250 kg N ha^(-1 in Lopburi and Nakhon Ratchasima (fresh weight yield of 64,100 and 46,700 kg ha^(-1 respectively. Yield appeared to decrease at the higher, 312 kg ha^(-1, at Supanburi and Lopburi, and 250 kg ha^(-1 (Chonburi fertilizer N rates. Net revenue was 70.4 and 72.9 % higher than where no N was appliedLopburi and Nakhon Ratchasima sites. Net revenue at the Supanburi and Chonburi sites were 53.8 and 211.0 % higher than that where no N was applied. This study suggests that at all sites improved cassava production and net revenue could be obtained with the judicious application of higher quantities of N. The results provide needed guidance to nitrogen fertilization of the important industrial crop cassava in Thailand.

Reliability analysis of protection systems in NPP applying fault-tree analysis method

International Nuclear Information System (INIS)

Bokor, J.; Gaspar, P.; Hetthessy, J.; Szabo, G.

1998-01-01

This paper demonstrates the applicability and limits of dependability analysis in nuclear power plants (NPPS) based on the reactor protection refurbishment project (RRP) in NPP Paks. This paper illustrates case studies from the reliability analysis for NPP Paks. It also investigates the solutions for the connection between the data acquisition and subsystem control units (TSs) and the voter units (VTs), it analyzes the influence of the voting in the VT computer level, it studies the effects of the testing procedures to the dependability parameters. (author)

Handling requirements dependencies in agile projects: A focus group with agile software development practitioners

NARCIS (Netherlands)

Martakis, Aias; Daneva, Maia; Wieringa, Roelf J.; Jean-Louis Cavarero, S.; Rolland, C; Cavarero, J.L.

2013-01-01

Agile practices on requirements dependencies are a relatively unexplored topic in literature. Empirical studies on it are scarce. This research sets out to uncover concepts that practitioners in companies of various sizes across the globe and in various industries, use for dealing with requirements

Activation-induced cytidine deaminase (AID)-dependent somatic hypermutation requires a splice isoform of the serine/arginine-rich (SR) protein SRSF1.

Science.gov (United States)

Kanehiro, Yuichi; Todo, Kagefumi; Negishi, Misaki; Fukuoka, Junji; Gan, Wenjian; Hikasa, Takuya; Kaga, Yoshiaki; Takemoto, Masayuki; Magari, Masaki; Li, Xialu; Manley, James L; Ohmori, Hitoshi; Kanayama, Naoki

2012-01-24

Somatic hypermutation (SHM) of Ig variable region (IgV) genes requires both IgV transcription and the enzyme activation-induced cytidine deaminase (AID). Identification of a cofactor responsible for the fact that IgV genes are much more sensitive to AID-induced mutagenesis than other genes is a key question in immunology. Here, we describe an essential role for a splice isoform of the prototypical serine/arginine-rich (SR) protein SRSF1, termed SRSF1-3, in AID-induced SHM in a DT40 chicken B-cell line. Unexpectedly, we found that SHM does not occur in a DT40 line lacking SRSF1-3 (DT40-ASF), although it is readily detectable in parental DT40 cells. Strikingly, overexpression of AID in DT40-ASF cells led to a large increase in nonspecific (off-target) mutations. In contrast, introduction of SRSF1-3, but not SRSF1, into these cells specifically restored SHM without increasing off-target mutations. Furthermore, we found that SRSF1-3 binds preferentially to the IgV gene and inhibits processing of the Ig transcript, providing a mechanism by which SRSF1-3 makes the IgV gene available for AID-dependent SHM. SRSF1 not only acts as an essential splicing factor but also regulates diverse aspects of mRNA metabolism and maintains genome stability. Our findings, thus, define an unexpected and important role for SRSF1, particularly for its splice variant, in enabling AID to function specifically on its natural substrate during SHM.

Co-ordinated research programme on benchmark study for the seismic analysis and testing of WWER-type nuclear power plants. V. 4D. Paks NPP: Analysis and testing. Working material

International Nuclear Information System (INIS)

1996-01-01

The Co-ordinated research programme on the benchmark study for the seismic analysis and testing of WWER-type nuclear power plants was initiated subsequent to the request from representatives of Member States. The conclusions adopted at the Technical Committee Meeting on Seismic Issues related to existing nuclear power plants held in Tokyo in 1991 called for the harmonization of methods and criteria used in Member States in issues related to seismic safety. The Consulltants' Meeting which followed resulted in producing a working document for CRP. It was decided that a benchmark study is the most effective way to achieve the principal objective. Two types of WWER reactors (WWER-440/213 and WWER-1000) were selected as prototypes for the benchmark exercise to be tested on a full scale using explosions and/or vibration generators. The two prototypes are Kozloduy Units 5/6 for WWER-1000 and Paks for WWER-440/213 nuclear power plants. This volume of Working material contains reports on seismic margin assessment and earthquake experience based methods for WWER-440/213 type NPPs; structural analysis and site inspection for site requalification; structural response of Paks NPP reactor building; analysis and testing of model worm type tanks on shaking table; vibration test of a worm tank model; evaluation of potential hazard for operating WWER control rods under seismic excitation

GEMC1 is a TopBP1-interacting protein required for chromosomal DNA replication.

Science.gov (United States)

Balestrini, Alessia; Cosentino, Claudia; Errico, Alessia; Garner, Elizabeth; Costanzo, Vincenzo

2010-05-01

Many of the factors required for chromosomal DNA replication have been identified in unicellular eukaryotes. However, DNA replication is poorly understood in multicellular organisms. Here, we report the identification of GEMC1 (geminin coiled-coil containing protein 1), a novel vertebrate protein required for chromosomal DNA replication. GEMC1 is highly conserved in vertebrates and is preferentially expressed in proliferating cells. Using Xenopus laevis egg extract we show that Xenopus GEMC1 (xGEMC1) binds to the checkpoint and replication factor TopBP1, which promotes binding of xGEMC1 to chromatin during pre-replication complex (pre-RC) formation. We demonstrate that xGEMC1 interacts directly with replication factors such as Cdc45 and the kinase Cdk2-CyclinE, through which it is heavily phosphorylated. Phosphorylated xGEMC1 stimulates initiation of DNA replication, whereas depletion of xGEMC1 prevents the onset of DNA replication owing to the impairment of Cdc45 loading onto chromatin. Similarly, inhibition of GEMC1 expression with morpholino and siRNA oligos prevents DNA replication in embryonic and somatic vertebrate cells. These data suggest that GEMC1 promotes initiation of chromosomal DNA replication in multicellular organisms by mediating TopBP1- and Cdk2-dependent recruitment of Cdc45 onto replication origins.

The carboxy-terminal tail or the intracellular loop 3 is required for β-arrestin-dependent internalization of a mammalian type II GnRH receptor.

Science.gov (United States)

Madziva, Michael T; Mkhize, Nonhlanhla N; Flanagan, Colleen A; Katz, Arieh A

2015-08-15

The type II GnRH receptor (GnRH-R2) in contrast to mammalian type I GnRH receptor (GnRH-R1) has a cytosolic carboxy-terminal tail. We investigated the role of β-arrestin 1 in GnRH-R2-mediated signalling and mapped the regions in GnRH-R2 required for recruitment of β-arrestin, employing internalization assays. We show that GnRH-R2 activation of ERK is dependent on β-arrestin and protein kinase C. Appending the tail of GnRH-R2 to GnRH-R1 enabled GRK- and β-arrestin-dependent internalization of the chimaeric receptor. Surprisingly, carboxy-terminally truncated GnRH-R2 retained β-arrestin and GRK-dependent internalization, suggesting that β-arrestin interacts with additional elements of GnRH-R2. Mutating serine and threonine or basic residues of intracellular loop 3 did not abolish β-arrestin 1-dependent internalization but a receptor lacking these basic residues and the carboxy-terminus showed no β-arrestin 1-dependent internalization. Our results suggest that basic residues at the amino-terminal end of intracellular loop 3 or the carboxy-terminal tail are required for β-arrestin dependent internalization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Status of safety analysis reports

International Nuclear Information System (INIS)

Cserhati, A.

1999-01-01

The safety regulation connected to both of the Atomic Acts from 1980 and 1996 requires preparation of the Preliminary Safety Analysis Report (PSAR) as well as Final SAR (FSAR). In this respect the licensing procedure for the construction and commissioning of Paks NPP did not formally deviate from the standards applied in developed countries; this is particularly true if comparison is made with the standards applied for commissioning NPPs in the second half of the seventies. By the time the overall development of internationally accepted safety standards and some existing deficiencies of earlier SAR made necessary a general reassessment of the plant safety (AGNES project). The carried out PSR for Paks-1 and 2 also added a valuable contribution to the SAR content, however a formal update of SAR is not made yet. A Hungarian nuclear authority decree from 1997 obligates the licensee to prepare and submit a major upgrade of FSAR until the mid of 2000, after finishing the PSR for Paks-3 and 4. From this date a periodic update of FSAR is required every year. The operational license renewal affects only the PSR but not the FSAR updating. The new Nuclear Safety Code outlines the contents of PSAR and FSAR, based on US NRC Reg. Guide 1. 70. Rev. 3. Hungary by now can fulfill the upgrading of SAR without major external technical or financial help. The AGNES project covered the safety analysis chapters of SAR. It was financed mainly by the country. In the project there have been involved in limited cases as performers the VTT (Finland), Belgatom (Belgium), GRS (Germany), etc., the IVO (Finland) fulfilled tasks of an independent reviewer for safety analysis. The AGNES had certain interconnection with the similar IAEA RER safety reassessment project for WWER-440/213. The PSR for Paks-1 and 2 have been carried out by the Paks staff from the resources of the plant. During the evaluation of several parts of Paks-3 and 4 PSR documentation the authority intends to use certain

Steroids in porcine follicular fluid: analysis by HPLC, capillary CG and capillary CG/MS after purification on SEP-PAK C18 and ion exchange chromatography.

Science.gov (United States)

Khalil, M W; Lawson, V

1983-04-01

Steroids in porcine follicular fluid have been concentrated by reverse phase chromatography in SEP-PAK C18 and purified further on the cation exchanger SP-Sephadex C-25. Fractionation into unconjugated neutral and phenolic steroids, glucuronides and sulfates was carried out on triethylaminohydroxypropyl Sephadex LH-20 (TEAP-LH-20). The unconjugated neutral fraction was analysed by high pressure liquid chromatography (HPLC) on a C18 radial cartridge 5 mm I.D.; 10 mu, or on a C18 5 mu RESOLVE column, and by capillary gas chromatography (GC) on a 12 M OV-1 cross linked fused silica column. Testosterone, progesterone and androstenedione were the major steroids detected by HPLC monitored at 254 nm, although 17- hydroxy-, 20 alpha-dihydro- and 20 beta-dihydroprogesterone were also present. Pregnenolone, pregnanediol, dehydroepiandrosterone, 17-hydroxypregnenolone and androsterone were detected by capillary CG as their 0-methyloxime trimethylsilyether derivatives. Further confirmation of structure was provided by complete mass spectral data or by selective ion monitoring (SIM).

Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

OpenAIRE

Trabbic, Christopher J.; Overmeyer, Jean H.; Alexander, Evan M.; Crissman, Emily J.; Kvale, Heather M.; Smith, Marcie A.; Erhardt, Paul W.; Maltese, William A.

2015-01-01

Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1...

Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations.

Science.gov (United States)

Lee, Ju-Hyun; Yu, W Haung; Kumar, Asok; Lee, Sooyeon; Mohan, Panaiyur S; Peterhoff, Corrinne M; Wolfe, Devin M; Martinez-Vicente, Marta; Massey, Ashish C; Sovak, Guy; Uchiyama, Yasuo; Westaway, David; Cuervo, Ana Maria; Nixon, Ralph A

2010-06-25

Macroautophagy is a lysosomal degradative pathway essential for neuron survival. Here, we show that macroautophagy requires the Alzheimer's disease (AD)-related protein presenilin-1 (PS1). In PS1 null blastocysts, neurons from mice hypomorphic for PS1 or conditionally depleted of PS1, substrate proteolysis and autophagosome clearance during macroautophagy are prevented as a result of a selective impairment of autolysosome acidification and cathepsin activation. These deficits are caused by failed PS1-dependent targeting of the v-ATPase V0a1 subunit to lysosomes. N-glycosylation of the V0a1 subunit, essential for its efficient ER-to-lysosome delivery, requires the selective binding of PS1 holoprotein to the unglycosylated subunit and the Sec61alpha/oligosaccharyltransferase complex. PS1 mutations causing early-onset AD produce a similar lysosomal/autophagy phenotype in fibroblasts from AD patients. PS1 is therefore essential for v-ATPase targeting to lysosomes, lysosome acidification, and proteolysis during autophagy. Defective lysosomal proteolysis represents a basis for pathogenic protein accumulations and neuronal cell death in AD and suggests previously unidentified therapeutic targets.

Sea urchin akt activity is Runx-dependent and required for post-cleavage stage cell division

KAUST Repository

Robertson, Anthony J.

2013-03-25

In animal development following the initial cleavage stage of embryogenesis, the cell cycle becomes dependent on intercellular signaling and controlled by the genomically encoded ontogenetic program. Runx transcription factors are critical regulators of metazoan developmental signaling, and we have shown that the sea urchin Runx gene runt-1, which is globally expressed during early embryogenesis, functions in support of blastula stage cell proliferation and expression of the mitogenic genes pkc1, cyclinD, and several wnts. To obtain a more comprehensive list of early runt-1 regulatory targets, we screened a Strongylocentrotus purpuratus microarray to identify genes mis-expressed in mid-blastula stage runt-1 morphants. This analysis showed that loss of Runx function perturbs the expression of multiple genes involved in cell division, including the pro-growth and survival kinase Akt (PKB), which is significantly underexpressed in runt-1 morphants. Further genomic analysis revealed that Akt is encoded by two genes in the S. purpuratus genome, akt-1 and akt-2, both of which contain numerous canonical Runx target sequences. The transcripts of both genes accumulate several fold during blastula stage, contingent on runt-1 expression. Inhibiting Akt expression or activity causes blastula stage cell cycle arrest, whereas overexpression of akt-1 mRNA rescues cell proliferation in runt-1 morphants. These results indicate that post-cleavage stage cell division requires Runx-dependent expression of akt.

Sea urchin akt activity is Runx-dependent and required for post-cleavage stage cell division

KAUST Repository

Robertson, Anthony J.; Coluccio, Alison; Jensen, Sarah; Rydlizky, Katarina; Coffman, James A.

2013-01-01

In animal development following the initial cleavage stage of embryogenesis, the cell cycle becomes dependent on intercellular signaling and controlled by the genomically encoded ontogenetic program. Runx transcription factors are critical regulators of metazoan developmental signaling, and we have shown that the sea urchin Runx gene runt-1, which is globally expressed during early embryogenesis, functions in support of blastula stage cell proliferation and expression of the mitogenic genes pkc1, cyclinD, and several wnts. To obtain a more comprehensive list of early runt-1 regulatory targets, we screened a Strongylocentrotus purpuratus microarray to identify genes mis-expressed in mid-blastula stage runt-1 morphants. This analysis showed that loss of Runx function perturbs the expression of multiple genes involved in cell division, including the pro-growth and survival kinase Akt (PKB), which is significantly underexpressed in runt-1 morphants. Further genomic analysis revealed that Akt is encoded by two genes in the S. purpuratus genome, akt-1 and akt-2, both of which contain numerous canonical Runx target sequences. The transcripts of both genes accumulate several fold during blastula stage, contingent on runt-1 expression. Inhibiting Akt expression or activity causes blastula stage cell cycle arrest, whereas overexpression of akt-1 mRNA rescues cell proliferation in runt-1 morphants. These results indicate that post-cleavage stage cell division requires Runx-dependent expression of akt.

Light exposure before learning improves memory consolidation at night

Science.gov (United States)

Shan, Li-Li; Guo, Hao; Song, Ning-Ning; Jia, Zheng-Ping; Hu, Xin-Tian; Huang, Jing-Fei; Ding, Yu-Qiang; Richter-Levine, Gal; Zhou, Qi-Xin; Xu, Lin

2015-01-01

Light is recently recognized as a modulator able to activate the hippocampus and modulate memory processing, but little is known about the molecular mechanisms. Here, we report that in mice, a short pulse of white light before learning dramatically improves consolidation of contextual fear memory during the night. The light exposure increases hippocampal active p21-activated kinase 1 (PAK1) and CA1 long-term potentiation (LTP). These light effects are abolished in PAK1 knockout and dominant-negative transgenic mice, but preserved by expression of constitutively active PAK1 in the hippocampus. Our results indicate that light can act as a switch of PAK1 activity that modulate CA1 LTP and thereby memory consolidation without affecting learning and short-term memory. PMID:26493375

The HIV1 protein Vpr acts to enhance constitutive DCAF1-dependent UNG2 turnover.

Directory of Open Access Journals (Sweden)

Xiaoyun Wen

Full Text Available The HIV1 protein Vpr assembles with and acts through an ubiquitin ligase complex that includes DDB1 and cullin 4 (CRL4 to cause G2 cell cycle arrest and to promote degradation of both uracil DNA glycosylase 2 (UNG2 and single-strand selective mono-functional uracil DNA glycosylase 1 (SMUG1. DCAF1, an adaptor protein, is required for Vpr-mediated G2 arrest through the ubiquitin ligase complex. In work described here, we used UNG2 as a model substrate to study how Vpr acts through the ubiquitin ligase complex. We examined whether DCAF1 is essential for Vpr-mediated degradation of UNG2 and SMUG1. We further investigated whether Vpr is required for recruiting substrates to the ubiquitin ligase or acts to enhance its function and whether this parallels Vpr-mediated G2 arrest.We found that DCAF1 plays an important role in Vpr-independent UNG2 and SMUG1 depletion. UNG2 assembled with the ubiquitin ligase complex in the absence of Vpr, but Vpr enhanced this interaction. Further, Vpr-mediated enhancement of UNG2 degradation correlated with low Vpr expression levels. Vpr concentrations exceeding a threshold blocked UNG2 depletion and enhanced its accumulation in the cell nucleus. A similar dose-dependent trend was seen for Vpr-mediated cell cycle arrest.This work identifies UNG2 and SMUG1 as novel targets for CRL4(DCAF1-mediated degradation. It further shows that Vpr enhances rather than enables the interaction between UNG2 and the ubiquitin ligase. Vpr augments CRL4(DCAF1-mediated UNG2 degradation at low concentrations but antagonizes it at high concentrations, allowing nuclear accumulation of UNG2. Further, the protein that is targeted to cause G2 arrest behaves much like UNG2. Our findings provide the basis for determining whether the CRL4(DCAF1 complex is alone responsible for cell cycle-dependent UNG2 turnover and will also aid in establishing conditions necessary for the identification of additional targets of Vpr-enhanced degradation.

Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of non-apoptotic cell death

OpenAIRE

Robinson, Michael W.; Overmeyer, Jean H.; Young, Ashley M.; Erhardt, Paul W.; Maltese, William A.

2012-01-01

Methuosis is a novel caspase-independent form of cell death in which massive accumulation of vacuoles derived from macropinosomes ultimately causes cells to detach from the substratum and rupture. We recently described a chalcone-like compound, 3-(2-methyl-1H indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (i.e. MIPP), which can induce methuosis in glioblastoma and other types of cancer cells. Herein we describe the synthesis and structure-activity relationships of a directed library of related co...

A chalcone-related small molecule that induces methuosis, a novel form of non-apoptotic cell death, in glioblastoma cells

OpenAIRE

Overmeyer, Jean H; Young, Ashley M; Bhanot, Haymanti; Maltese, William A

2011-01-01

Abstract Background Methuosis is a unique form of non-apoptotic cell death triggered by alterations in the trafficking of clathrin-independent endosomes, ultimately leading to extreme vacuolization and rupture of the cell. Results Here we describe a novel chalcone-like molecule, 3-(2-methyl-1H- indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MIPP) that induces cell death with the hallmarks of methuosis. MIPP causes rapid accumulation of vacuoles derived from macropinosomes, based on time-lapse mi...

Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

International Nuclear Information System (INIS)

Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

2010-01-01

Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1 - low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2 - the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3 - knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

8 CFR 312.1 - Literacy requirements.

Science.gov (United States)

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Literacy requirements. 312.1 Section 312.1... FOR NATURALIZATION § 312.1 Literacy requirements. (a) General. Except as otherwise provided in... determining English proficiency, as outlined in paragraph(c) of this section. (c) Literacy examination—(1...

Ecological Smorgasbord: A Balanced Reading Diet. [Project ECOLogy ELE Pak, Lorain & Backman Pak].

Science.gov (United States)

Lorain, Sue; Backman, Judi

This is one of a series of units for environmental education developed by the Highline Public Schools. This material was basically designed to be used as an individualized reading kit for the intermediate grade student. The books in this kit readily lend themselves to a supplementary reading program as part of a science unit. Depending on a…

skn-1 is required for interneuron sensory integration and foraging behavior in Caenorhabditis elegans.

Science.gov (United States)

Wilson, Mark A; Iser, Wendy B; Son, Tae Gen; Logie, Anne; Cabral-Costa, Joao V; Mattson, Mark P; Camandola, Simonetta

2017-01-01

Nrf2/skn-1, a transcription factor known to mediate adaptive responses of cells to stress, also regulates energy metabolism in response to changes in nutrient availability. The ability to locate food sources depends upon chemosensation. Here we show that Nrf2/skn-1 is expressed in olfactory interneurons, and is required for proper integration of multiple food-related sensory cues in Caenorhabditis elegans. Compared to wild type worms, skn-1 mutants fail to perceive that food density is limiting, and display altered chemo- and thermotactic responses. These behavioral deficits are associated with aberrant AIY interneuron morphology and migration in skn-1 mutants. Both skn-1-dependent AIY autonomous and non-autonomous mechanisms regulate the neural circuitry underlying multisensory integration of environmental cues related to energy acquisition.

Impact of different feedstocks derived biochar amendment with cadmium low uptake affinity cultivar of pak choi (Brassica rapa ssb. chinensis L.) on phytoavoidation of Cd to reduce potential dietary toxicity.

Science.gov (United States)

Yasmin Khan, Kiran; Ali, Barkat; Cui, Xiaoqiang; Feng, Ying; Yang, Xiaoe; Joseph Stoffella, Peter

2017-07-01

Biochar has become eco-friendly amendment used for phytoavoidation with low cadmium (Cd) accumulating cultivars of crops to ensure food safety in Cd contaminated soils. In this study, biochar with different waste feedstock material were evaluated for their effectiveness on essential trace metals mobility, Cd bioavailability and its accumulation in two contrasting Cd accumulating cultivars of pak choi (Brassica rapa ssp. chinensis L.) grown in Cd contaminated Mollisol soil. A greenhouse experiment was conducted with plants grown in Cd contaminated soil that had been amended with biochar derived from barley straw, tomato green waste, chicken manure, duck manure and swine manure at application rate of 0%, 2.5% and 5.0% (w/w). The results showed that soil pH was significantly increased by all treatments. Biochar increased plant dry biomass, micronutrients bioavailability with significant differences in the Cd sorption capacity, with the effectiveness higher with increasing biochar application rate. However, tomato green waste (TGW) and chicken manure (CM) derived biochar were more effective than the other biochar in reducing Cd mobilization in soil by 35-54% and 26-43% and reduced its accumulation in shoots of pak choi cultivars by 34-76% and 33-72% in low Cd accumulator cultivar and 64-85% and 55-80% in high Cd accumulator cultivar than the control. Overall, results indicate that TGW and CM biochar can efficiently immobilize Cd, thereby reducing bioavailability in Cd contaminated Mollisol soil to ensure food safety. Copyright © 2017 Elsevier Inc. All rights reserved.

The F-BAR domain protein PACSIN2 associates with Rac1 and regulates cell spreading and migration

NARCIS (Netherlands)

de Kreuk, Bart-Jan; Nethe, Micha; Fernandez-Borja, Mar; Anthony, Eloise C.; Hensbergen, Paul J.; Deelder, Andre M.; Plomann, Markus; Hordijk, Peter L.

2011-01-01

The Rac1 GTPase controls cytoskeletal dynamics and is a key regulator of cell spreading and migration mediated by signaling through effector proteins, such as the PAK kinases and the Scar and WAVE proteins. We previously identified a series of regulatory proteins that associate with Rac1 through its

Deletion of the GluA1 AMPA receptor subunit impairs recency-dependent object recognition memory

Science.gov (United States)

Sanderson, David J.; Hindley, Emma; Smeaton, Emily; Denny, Nick; Taylor, Amy; Barkus, Chris; Sprengel, Rolf; Seeburg, Peter H.; Bannerman, David M.

2011-01-01

Deletion of the GluA1 AMPA receptor subunit impairs short-term spatial recognition memory. It has been suggested that short-term recognition depends upon memory caused by the recent presentation of a stimulus that is independent of contextual–retrieval processes. The aim of the present set of experiments was to test whether the role of GluA1 extends to nonspatial recognition memory. Wild-type and GluA1 knockout mice were tested on the standard object recognition task and a context-independent recognition task that required recency-dependent memory. In a first set of experiments it was found that GluA1 deletion failed to impair performance on either of the object recognition or recency-dependent tasks. However, GluA1 knockout mice displayed increased levels of exploration of the objects in both the sample and test phases compared to controls. In contrast, when the time that GluA1 knockout mice spent exploring the objects was yoked to control mice during the sample phase, it was found that GluA1 deletion now impaired performance on both the object recognition and the recency-dependent tasks. GluA1 deletion failed to impair performance on a context-dependent recognition task regardless of whether object exposure in knockout mice was yoked to controls or not. These results demonstrate that GluA1 is necessary for nonspatial as well as spatial recognition memory and plays an important role in recency-dependent memory processes. PMID:21378100

Dma1-dependent degradation of SIN proteins during meiosis in Schizosaccharomyces pombe.

Science.gov (United States)

Krapp, Andrea; Simanis, Viesturs

2014-07-15

The Schizosaccharomyces pombe septation initiation network (SIN) is required for cytokinesis during vegetative growth and for spore formation during meiosis. Regulation of the SIN during mitosis has been studied extensively, but less is known about its meiotic regulation. Here, we show that several aspects of SIN regulation differ between mitosis and meiosis. First, the presence of GTP-bound Spg1p is not the main determinant of the timing of Cdc7p and Sid1p association with the spindle pole body (SPB) during meiosis. Second, the localisation dependencies of SIN proteins differ from those in mitotic cells, suggesting a modified functional organisation of the SIN during meiosis. Third, there is stage-specific degradation of SIN components in meiosis; Byr4p is degraded after meiosis I, whereas the degradation of Cdc7p, Cdc11p and Sid4p occurs after the second meiotic division and depends upon the ubiquitin ligase Dma1p. Finally, Dma1p-dependent degradation is not restricted to the SIN, as we show that Dma1p is needed for the degradation of Mcp6p (also known as Hrs1p) during meiosis I. Taken together, these data suggest that stage-specific targeted proteolysis plays an important role in regulating meiotic progression. © 2014. Published by The Company of Biologists Ltd.

SUV2, which encodes an ATR-related cell cycle checkpoint and putative plant ATRIP, is required for aluminium-dependent root growth inhibition in Arabidopsis.

Science.gov (United States)

Sjogren, Caroline A; Larsen, Paul B

2017-09-01

A suppressor mutagenesis screen was conducted in order to identify second site mutations that could reverse the extreme hypersensitivity to aluminium (Al) seen for the Arabidopsis mutant, als3-1. From this screen, it was found that a loss-of-function mutation in the previously described SUV2 (SENSITIVE TO UV 2), which encodes a putative plant ATRIP homologue that is a component of the ATR-dependent cell checkpoint response, reversed the als3-1 phenotype. This included prevention of hallmarks associated with als3-1 including Al-dependent terminal differentiation of the root tip and transition to endoreduplication. From this analysis, SUV2 was determined to be required for halting cell cycle progression and triggering loss of the quiescent centre (QC) following exposure to Al. In conjunction with this, SUV2 was found to have a similar role as ATR, ALT2 and SOG1 in Al-dependent stoppage of root growth, all of which are required for promotion of expression of a suite of genes that likely are part of an Al-dependent DNA damage transcriptional response. This work argues that these Al response factors work together to detect Al-dependent damage and subsequently activate a DNA damage response pathway that halts the cell cycle and subsequently promotes QC differentiation and entrance into endocycling. © 2017 John Wiley & Sons Ltd.

The Diaphanous-related Formin FHOD1 associates with ROCK1 and promotes Src-dependent plasma membrane blebbing.

Science.gov (United States)

Hannemann, Sebastian; Madrid, Ricardo; Stastna, Jana; Kitzing, Thomas; Gasteier, Judith; Schönichen, André; Bouchet, Jerome; Jimenez, Alberto; Geyer, Matthias; Grosse, Robert; Benichou, Serge; Fackler, Oliver T

2008-10-10

Diaphanous-related formins (DRFs) mediate GTPase-triggered actin rearrangements to regulate central cellular processes, such as cell motility and cytokinesis. The DRF FHOD1 interacts with the Rho-GTPase Rac1 and mediates formation of actin stress fibers in its deregulated form; the physiologically relevant activities and molecular mechanisms of endogenous FHOD1, however, are still unknown. Here we report that FHOD1 physically associates via the N-terminal part of its FH2 domain with the central domain of ROCK1. Although FHOD1 does not affect the kinase activity of ROCK1, the DRF is an efficient substrate for phosphorylation by ROCK1. Co-expression of FHOD1 and ROCK1 results in the generation of nonapoptotic plasma membrane (PM) blebs, to which the DRF is efficiently recruited. Blebbing induced by FHOD1 and ROCK1 depends on F-actin integrity, the Rho-ROCK cascade, and Src activity and is reminiscent of the recently described PM blebs triggered by expression of Src homology 4 (SH4) domain PM targeting signals. Consistently, endogenous FHOD1 is required in SH4 domain expressing cells for efficient PM blebbing and rounded cell morphology in two-dimensional cultures or three-dimensional matrices, respectively. Efficient association of FHOD1 with ROCK1, as well as recruitment of the DRF to blebs, depends on Src activity, suggesting that the functional interaction between both proteins is regulated by Src. These results define a role for endogenous FHOD1 in SH4 domain-induced blebbing and suggest that its activity is regulated by ROCK1 in a Src-dependent manner.

20 CFR 219.43 - Evidence of child's dependency.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Evidence of child's dependency. 219.43... EVIDENCE REQUIRED FOR PAYMENT Evidence of Relationship § 219.43 Evidence of child's dependency. (a) When the dependency requirement must be met. Usually the dependency requirement must be met at one of the...

Chronic cerebral hypoperfusion-induced impairment of Aβ clearance requires HB-EGF-dependent sequential activation of HIF1α and MMP9.

Science.gov (United States)

Ashok, Anushruti; Rai, Nagendra Kumar; Raza, Waseem; Pandey, Rukmani; Bandyopadhyay, Sanghamitra

2016-11-01

Chronic cerebral hypoperfusion (CCH) manifests Alzheimer's Disease (AD) neuropathology, marked by increased amyloid beta (Aβ). Besides, hypoxia stimulates Heparin-binding EGF-like growth factor (HB-EGF) mRNA expression in the hippocampus. However, involvement of HB-EGF in CCH-induced Aβ pathology remains unidentified. Here, using Bilateral Common Carotid Artery Occlusion mouse model, we explored the mechanism of HB-EGF regulated Aβ induction in CCH. We found that HB-EGF inhibition suppressed, while exogenous-HB-EGF triggered hippocampal Aβ, proving HB-EGF-dependent Aβ increase. We also detected that HB-EGF affected the expression of primary Aβ transporters, receptor for advanced glycation end-products (RAGE) and lipoprotein receptor-related protein-1 (LRP-1), indicating impaired Aβ clearance across the blood-brain barrier (BBB). An HB-EGF-dependent loss in BBB integrity supported impaired Aβ clearance. The effect of HB-EGF on Amyloid Precursor Protein pathway was relatively insignificant, suggesting a lesser effect on Aβ generation. Delving into BBB disruption mechanism demonstrated HB-EGF-mediated stimulation of Matrix metalloprotease-9 (MMP9), which affected BBB via HB-EGF-ectodomain shedding and epidermal growth factor receptor activation. Examining the intersection of HB-EGF-regulated pathway and hypoxia revealed HB-EGF-dependent increase in transcription factor, Hypoxia-inducible factor-1alpha (HIF1α). Further, via binding to hypoxia-responsive elements in MMP9 gene, HIF1α stimulated MMP9 expression, and therefore appeared as a prominent intermediary in HB-EGF-induced BBB damage. Overall, our study reveals the essential role of HB-EGF in triggering CCH-mediated Aβ accumulation. The proposed mechanism involves an HB-EGF-dependent HIF1α increase, generating MMP9 that stimulates soluble-HB-EGF/EGFR-induced BBB disintegration. Consequently, CCH-mediated hippocampal RAGE and LRP-1 deregulation together with BBB damage impair Aβ transport and clearance

Proton channel HVCN1 is required for effector functions of mouse eosinophils

Science.gov (United States)

2013-01-01

Background Proton currents are required for optimal respiratory burst in phagocytes. Recently, HVCN1 was identified as the molecule required for the voltage-gated proton channel activity associated with the respiratory burst in neutrophils. Although there are similarities between eosinophils and neutrophils regarding their mechanism for respiratory burst, the role of proton channels in eosinophil functions has not been fully understood. Results In the present study, we first identified the expression of the proton channel HVCN1 in mouse eosinophils. Furthermore, using HVCN1-deficient eosinophils, we demonstrated important cell-specific effector functions for HVCN1. Similar to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils produced significantly less reactive oxygen species (ROS) upon phorbol myristate acetate (PMA) stimulation compared with WT eosinophils. In contrast to HVCN1-deficient neutrophils, HVCN1-deficient eosinophils did not show impaired calcium mobilization or migration ability compared with wild-type (WT) cells. Uniquely, HVCN1-deficient eosinophils underwent significantly increased cell death induced by PMA stimulation compared with WT eosinophils. The increased cell death was dependent on NADPH oxidase activation, and correlated with the failure of HVCN1-deficient cells to maintain membrane polarization and intracellular pH in the physiological range upon activation. Conclusions Eosinophils require proton channel HVCN1 for optimal ROS generation and prevention of activation-induced cell death. PMID:23705768

skn-1 is required for interneuron sensory integration and foraging behavior in Caenorhabditis elegans.

Directory of Open Access Journals (Sweden)

Mark A Wilson

Full Text Available Nrf2/skn-1, a transcription factor known to mediate adaptive responses of cells to stress, also regulates energy metabolism in response to changes in nutrient availability. The ability to locate food sources depends upon chemosensation. Here we show that Nrf2/skn-1 is expressed in olfactory interneurons, and is required for proper integration of multiple food-related sensory cues in Caenorhabditis elegans. Compared to wild type worms, skn-1 mutants fail to perceive that food density is limiting, and display altered chemo- and thermotactic responses. These behavioral deficits are associated with aberrant AIY interneuron morphology and migration in skn-1 mutants. Both skn-1-dependent AIY autonomous and non-autonomous mechanisms regulate the neural circuitry underlying multisensory integration of environmental cues related to energy acquisition.

Disruption of endolysosomal trafficking pathways in glioma cells by methuosis-inducing indole-based chalcones.

Science.gov (United States)

Mbah, Nneka E; Overmeyer, Jean H; Maltese, William A

2017-06-01

Methuosis is a form of non-apoptotic cell death involving massive vacuolization of macropinosome-derived endocytic compartments, followed by a decline in metabolic activity and loss of membrane integrity. To explore the induction of methuosis as a potential therapeutic strategy for killing cancer cells, we have developed small molecules (indole-based chalcones) that trigger this form of cell death in glioblastoma and other cancer cell lines. Here, we report that in addition to causing fusion and expansion of macropinosome compartments, the lead compound, 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), disrupts vesicular trafficking at the lysosomal nexus, manifested by impaired degradation of EGF and LDL receptors, defective processing of procathepsins, and accumulation of autophagosomes. In contrast, secretion of the ectodomain derived from a prototypical type-I membrane glycoprotein, β-amyloid precursor protein, is increased rather than diminished. A closely related MOMIPP analog, which causes substantial vacuolization without reducing cell viability, also impedes cathepsin processing and autophagic flux, but has more modest effects on receptor degradation. A third analog, which causes neither vacuolization nor loss of viability, has no effect on endolysosomal trafficking. The results suggest that differential cytotoxicity of structurally similar indole-based chalcones is related, at least in part, to the severity of their effects on endolysosomal trafficking pathways.

Radionuclide dispersion calculation in environmental radiation monitoring system of the PAKS NPP

International Nuclear Information System (INIS)

Deme, S.; Janosy, J. S.; Lang, E.; Szabo, I. C.

2003-01-01

The new Environmental Radiation Monitoring System of the Paks NPP in Hungary consists of three radiation release measurement posts (placed into the two ventilation stacks of the four units and into the ventilation stack of the spent fuel intermediate storage building), 9 radiation monitoring stations and 11 gamma-radiation measurement posts placed more or less evenly around the plant. The basic goal of the Environmental Radiation Monitoring System is to provide complex and reliable information about the releases in all operating modes to facilitate the adequate estimation of the situation and to promote the decision making. Thanks to the astonishing development in the digital technology and to the state-of-the-art, up-to-date measurement techniques, a new level of confidence can be reached. Unpredictable radioactive leakage of the containment can be detected and the radiological situation of a relatively large area can be calculated and predicted. A very reliable system can be constructed withstanding earthquake and protected against single failure. Based on reliable and detailed measurement data, advanced simulation methodology and well-designed graphical user interface, an easy-to-use operator advisory system can be created to help the decision making in the very first and most difficult period of a nuclear accident. It is very important that the same system is used with the same features during the normal operation of the nuclear power plant, too; this means that the operators are able to get the necessary 'hands-on' training in order to be able to use the system during extreme stress and very unusual situations, too. Shaping the system in close cooperation with plant engineers and operators is indispensable in order to achieve the aforementioned goals. (authors)

ASIC-dependent LTP at multiple glutamatergic synapses in amygdala network is required for fear memory.

Science.gov (United States)

Chiang, Po-Han; Chien, Ta-Chun; Chen, Chih-Cheng; Yanagawa, Yuchio; Lien, Cheng-Chang

2015-05-19

Genetic variants in the human ortholog of acid-sensing ion channel-1a subunit (ASIC1a) gene are associated with panic disorder and amygdala dysfunction. Both fear learning and activity-induced long-term potentiation (LTP) of cortico-basolateral amygdala (BLA) synapses are impaired in ASIC1a-null mice, suggesting a critical role of ASICs in fear memory formation. In this study, we found that ASICs were differentially expressed within the amygdala neuronal population, and the extent of LTP at various glutamatergic synapses correlated with the level of ASIC expression in postsynaptic neurons. Importantly, selective deletion of ASIC1a in GABAergic cells, including amygdala output neurons, eliminated LTP in these cells and reduced fear learning to the same extent as that found when ASIC1a was selectively abolished in BLA glutamatergic neurons. Thus, fear learning requires ASIC-dependent LTP at multiple amygdala synapses, including both cortico-BLA input synapses and intra-amygdala synapses on output neurons.

A role for the retinoblastoma protein as a regulator of mouse osteoblast cell adhesion: implications for osteogenesis and osteosarcoma formation.

Directory of Open Access Journals (Sweden)

Bernadette Sosa-García

2010-11-01

Full Text Available The retinoblastoma protein (pRb is a cell cycle regulator inactivated in most human cancers. Loss of pRb function results from mutations in the gene coding for pRb or for any of its upstream regulators. Although pRb is predominantly known as a cell cycle repressor, our data point to additional pRb functions in cell adhesion. Our data show that pRb regulates the expression of a wide repertoire of cell adhesion genes and regulates the assembly of the adherens junctions required for cell adhesion. We conducted our studies in osteoblasts, which depend on both pRb and on cell-to-cell contacts for their differentiation and function. We generated knockout mice in which the RB gene was excised specifically in osteoblasts using the cre-lox P system and found that osteoblasts from pRb knockout mice did not assemble adherens junction at their membranes. pRb depletion in wild type osteoblasts using RNAi also disrupted adherens junctions. Microarrays comparing pRb-expressing and pRb-deficient osteoblasts showed that pRb controls the expression of a number of cell adhesion genes, including cadherins. Furthermore, pRb knockout mice showed bone abnormalities consistent with osteoblast adhesion defects. We also found that pRb controls the function of merlin, a well-known regulator of adherens junction assembly, by repressing Rac1 and its effector Pak1. Using qRT-PCR, immunoblots, co-immunoprecipitation assays, and immunofluorescent labeling, we observed that pRb loss resulted in Rac1 and Pak1 overexpression concomitant with merlin inactivation by Pak1, merlin detachment from the membrane, and adherens junction loss. Our data support a pRb function in cell adhesion while elucidating the mechanism for this function. Our work suggests that in some tumor types pRb inactivation results in both a loss of cell cycle control that promotes initial tumor growth as well as in a loss of cell-to-cell contacts, which contributes to later stages of metastasis.

Abscisic acid-dependent multisite phosphorylation regulates the activity of a transcription activator AREB1

OpenAIRE

Furihata, Takashi; Maruyama, Kyonoshin; Fujita, Yasunari; Umezawa, Taishi; Yoshida, Riichiro; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

2006-01-01

bZIP-type transcription factors AREBs/ABFs bind an abscisic acid (ABA)-responsive cis-acting element named ABRE and transactivate downstream gene expression in Arabidopsis. Because AREB1 overexpression could not induce downstream gene expression, activation of AREB1 requires ABA-dependent posttranscriptional modification. We confirmed that ABA activated 42-kDa kinase activity, which, in turn, phosphorylated Ser/Thr residues of R-X-X-S/T sites in the conserved regions of AREB1. Amino acid subs...

48 CFR 9903.202-1 - General requirements.

Science.gov (United States)

2010-10-01

... ACCOUNTING STANDARDS CONTRACT COVERAGE CAS Program Requirements 9903.202-1 General requirements. (a) A... subcontract is of the type or value exempted by 9903.201-1 or (ii) In the most recently completed cost... of Germany. (3) United Kingdom. (f) Educational institutions—disclosure requirements. (1) Educational...

1 CFR 10.10 - Publication required.

Science.gov (United States)

2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Publication required. 10.10 Section 10.10 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER SPECIAL EDITIONS OF THE FEDERAL REGISTER PRESIDENTIAL PAPERS Annual Publication § 10.10 Publication required. The Director of the Federal...

Crosstalk between Rac1-mediated actin regulation and ROS production.

Science.gov (United States)

Acevedo, Alejandro; González-Billault, Christian

2018-02-20

The small RhoGTPase Rac1 is implicated in a variety of events related to actin cytoskeleton rearrangement. Remarkably, another event that is completely different from those related to actin regulation has the same relevance; the Rac1-mediated production of reactive oxygen species (ROS) through NADPH oxidases (NOX). Each outcome involves different Rac1 downstream effectors; on one hand, events related to the actin cytoskeleton require Rac1 to bind to WAVEs proteins and PAKs that ultimately promote actin branching and turnover, on the other, NOX-derived ROS production demands active Rac1 to be bound to a cytosolic activator of NOX. How Rac1-mediated signaling ends up promoting actin-related events, NOX-derived ROS, or both is poorly understood. Rac1 regulators, including scaffold proteins, are known to exert tight control over its functions. Hence, evidence of Rac1 regulatory events leading to both actin remodeling and NOX-mediated ROS generation are discussed. Moreover, cellular functions linked to physiological and pathological conditions that exhibit crosstalk between Rac1 outcomes are analyzed, while plausible roles in neuronal functions (and dysfunctions) are highlighted. Together, discussed evidence shed light on cellular mechanisms which requires Rac1 to direct either actin- and/or ROS-related events, helping to understand crucial roles of Rac1 dual functionality. Copyright © 2018 Elsevier Inc. All rights reserved.

Endothelial-Rac1 is not required for tumor angiogenesis unless alphavbeta3-integrin is absent.

Directory of Open Access Journals (Sweden)

Gabriela D'Amico

2010-03-01

Full Text Available Endothelial cell migration is an essential aspect of tumor angiogenesis. Rac1 activity is needed for cell migration in vitro implying a requirement for this molecule in angiogenesis in vivo. However, a precise role for Rac1 in tumor angiogenesis has never been addressed. Here we show that depletion of endothelial Rac1 expression in adult mice, unexpectedly, has no effect on tumor growth or tumor angiogenesis. In addition, repression of Rac1 expression does not inhibit VEGF-mediated angiogenesis in vivo or ex vivo, nor does it affect chemotactic migratory responses to VEGF in 3-dimensions. In contrast, the requirement for Rac1 in tumor growth and angiogenesis becomes important when endothelial beta3-integrin levels are reduced or absent: the enhanced tumor growth, tumor angiogenesis and VEGF-mediated responses in beta3-null mice are all Rac1-dependent. These data indicate that in the presence of alphavbeta3-integrin Rac1 is not required for tumor angiogenesis.

Critical infrastructure dependencies 1-0-1

NARCIS (Netherlands)

Luiijf, H.A.M.; Nieuwenhuijs, A.H.; Klaver, M.H.A.

2008-01-01

Most of our critical infrastructures consist of complex systems-of-systems that provide services or products. The coupling mechanism between the chained systems in such complex systems of systems is dependencies. Dependencies may propagate cascading failures. Most studies on dependencies in

1 CFR 18.1 - Original and copies required.

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2010-01-01

... 1 General Provisions 1 2010-01-01 2010-01-01 false Original and copies required. 18.1 Section 18.1... PROCESSING OF DOCUMENTS PREPARATION AND TRANSMITTAL OF DOCUMENTS GENERALLY § 18.1 Original and copies... agency submitting a document to be filed and published in the Federal Register shall send an original and...

Postirradiation recovery dependent on the uvr-1 Locus in Bacillus subtilis

International Nuclear Information System (INIS)

Hadden, C.T.

1976-01-01

A mutant (uvr-1) of Bacillus subtilis that is deficient in excision of ultraviolet (uv)-induced pyrimidine dimers from deoxyribonucleic acid (DNA) shows a marked increase in ability to survive uv irradiation when plated on amino acid-supplemented agar medium compared with its survival ability when plated on nutrient agar. Since the extent of killing depends on the richness of the plating medium, the effect is considered to be one of growth-dependent lethality. Irradiated stationary phase uvr-1 cells, incubated in liquid medium lacking amino acids required for growth, recover from this sensitivity to rich medium within 3 to 4 h after irradiation. Recovery is greatly reduced in the absence of glucose or in the presence of NaCN, athough it is not completely eliminated. Exponentially growing cells have a limited ability to recover from sensitivity to rich medium. Growth-dependent lethality can also occur in liquid medium. In nutrient broth the ability of irradiated stationary-phase uvr-1 cells to form colonies on defined agar medium decreases during postirradiation incubation, but treatment with chloramphenicol inhibits the loss of colony-forming ability. Recovery from sensitivity to rich media is inhibited by caffeine but not by 6-(p-hydroxyphenylazo)-uracil, an inhibitor of DNA replication. Alkaline sucrose gradient profiles show that conditions allowing recovery also favor maintaining intact DNA strands, whereas DNA strand breakage or degradation is associated with loss of viability

Molecular dissection of the APC/C inhibitor Rca1 shows a novel F-box-dependent function.

Science.gov (United States)

Zielke, Norman; Querings, Silvia; Grosskortenhaus, Ruth; Reis, Tânia; Sprenger, Frank

2006-12-01

Rca1 (regulator of Cyclin A)/Emi (early mitotic inhibitor) proteins are essential inhibitors of the anaphase-promoting complex/cyclosome (APC/C). In Drosophila, Rca1 is required during G2 to prevent premature cyclin degradation by the Fizzy-related (Fzr)-dependent APC/C activity. Here, we present a structure and function analysis of Rca1 showing that a carboxy-terminal fragment is sufficient for APC/C inhibition. Rca1/Emi proteins contain a conserved F-box and interact with components of the Skp-Cullin-F-box (SCF) complex. So far, no function has been ascribed to this domain. We find that the F-box of Rca1 is dispensable for APC/C-Fzr inhibition during G2. Nevertheless, we show that Rca1 has an additional function at the G1-S transition, which requires the F-box. Overexpression of Rca1 accelerates the G1-S transition in an F-box-dependent manner. Conversely, S-phase entry is delayed in cells in which endogenous Rca1 is replaced by a transgene lacking the F-box. We propose that Rca1 acts as an F-box protein in an as yet uncharacterized SCF complex, which promotes S-phase entry.

Spred1 is required for synaptic plasticity and hippocampus-dependent learning

NARCIS (Netherlands)

E. Denayer (Ellen); T. Ahmed (Tariq); H. Brems (Hilde); G.M. van Woerden (Geeske); N.Z. Borgesius; Z. Callaerts-Vegh (Zsuzsanna); A. Yoshimura (Akihiko); D. Hartmann (Dieter); Y. Elgersma (Ype); R. D'Hooge (Rudi); E. Legius (Eric); D. Balschun (Detlef)

2008-01-01

textabstractGermline mutations in SPRED1, a negative regulator of Ras, have been described in a neurofibromatosis type 1 (NF1)-like syndrome (NFLS) that included learning difficulties in some affected individuals. NFLS belongs to the group of phenotypically overlapping neurocardio-facial-cutaneous

Cyclin D1 represses p300 transactivation through a cyclin-dependent kinase-independent mechanism.

Science.gov (United States)

Fu, Maofu; Wang, Chenguang; Rao, Mahadev; Wu, Xiaofang; Bouras, Toula; Zhang, Xueping; Li, Zhiping; Jiao, Xuanmao; Yang, Jianguo; Li, Anping; Perkins, Neil D; Thimmapaya, Bayar; Kung, Andrew L; Munoz, Alberto; Giordano, Antonio; Lisanti, Michael P; Pestell, Richard G

2005-08-19

Cyclin D1 encodes a regulatory subunit, which with its cyclin-dependent kinase (Cdk)-binding partner forms a holoenzyme that phosphorylates and inactivates the retinoblastoma protein. In addition to its Cdk binding-dependent functions, cyclin D1 regulates cellular differentiation in part by modifying several transcription factors and nuclear receptors. The molecular mechanism through which cyclin D1 regulates the function of transcription factors involved in cellular differentiation remains to be clarified. The histone acetyltransferase protein p300 is a co-integrator required for regulation of multiple transcription factors. Here we show that cyclin D1 physically interacts with p300 and represses p300 transactivation. We demonstrated further that the interaction of the two proteins occurs at the peroxisome proliferator-activated receptor gamma-responsive element of the lipoprotein lipase promoter in the context of the local chromatin structure. We have mapped the domains in p300 and cyclin D1 involved in this interaction. The bromo domain and cysteine- and histidine-rich domains of p300 were required for repression by cyclin D1. Cyclin D1 repression of p300 was independent of the Cdk- and retinoblastoma protein-binding domains of cyclin D1. Cyclin D1 inhibits histone acetyltransferase activity of p300 in vitro. Microarray analysis identified a signature of genes repressed by cyclin D1 and induced by p300 that promotes cellular differentiation and induces cell cycle arrest. Together, our results suggest that cyclin D1 plays an important role in cellular proliferation and differentiation through regulation of p300.

Late Protein Synthesis-Dependent Phases in CTA Long-Term Memory: BDNF Requirement

OpenAIRE

Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F.; Escobar, Martha L.

2011-01-01

It has been proposed that long-term memory persistence requires a late protein synthesis-dependent phase, even many hours after memory acquisition. Brain-derived neurotrophic factor (BDNF) is an essential protein synthesis product that has emerged as one of the most potent molecular mediators for long-term synaptic plasticity. Studies in the rat hippocampus have been shown that BDNF is capable to rescue the late-phase of long-term potentiation as well as the hippocampus-related long-term memo...

Fluxes of Ca2+ and K+ are required for the listeriolysin O-dependent internalization pathway of Listeria monocytogenes.

Science.gov (United States)

Vadia, Stephen; Seveau, Stephanie

2014-03-01

Listeria monocytogenes is responsible for the life-threatening food-borne disease listeriosis. This disease mainly affects elderly and immunocompromised individuals, causing bacteremia and meningoencephalitis. In pregnant women, L. monocytogenes infection leads to abortion and severe infection of the fetus or newborn. The L. monocytogenes intracellular life cycle is critical for pathogenesis. Previous studies have established that the major virulence factor of L. monocytogenes, the pore-forming toxin listeriolysin O (LLO), is sufficient to induce L. monocytogenes internalization into human epithelial cell lines. This internalization pathway strictly requires the formation of LLO pores in the plasma membrane and can be stimulated by the heterologous pore-forming toxin pneumolysin, suggesting that LLO acts nonspecifically by forming transmembrane pores. The present work tested the hypothesis that Ca2+ and K+ fluxes subsequent to perforation by LLO control L. monocytogenes internalization. We report that L. monocytogenes perforates the host cell plasma membrane in an LLO-dependent fashion at the early stage of invasion. In response to perforation, host cells undergo Ca2+ -dependent but K+ -independent resealing of their plasma membrane. In contrast to the plasma membrane resealing process, LLO-induced L. monocytogenes internalization requires both Ca2+ and K+ fluxes. Further linking ion fluxes to bacterial internalization, treating cells with a combination of Ca2+ and K+ ionophores but not with individual ionophores is sufficient to induce efficient internalization of large cargoes, such as 1-μm polystyrene beads and bacteria. We propose that LLO-induced L. monocytogenes internalization requires a Ca2+ - and K+ -dependent internalization pathway that is mechanistically distinct from the process of plasma membrane resealing.

Caffeine Induces Cell Death via Activation of Apoptotic Signal and Inactivation of Survival Signal in Human Osteoblasts

Directory of Open Access Journals (Sweden)

Wen-Hsiung Chan

2008-05-01

Full Text Available Caffeine consumption is a risk factor for osteoporosis, but the precise regulatory mechanisms are currently unknown. Here, we show that cell viability decreases in osteoblasts treated with caffeine in a dose-dependent manner. This cell death is attributed primarily to apoptosis and to a smaller extent, necrosis. Moreover, caffeine directly stimulates intracellular oxidative stress. Our data support caffeine-induced apoptosis in osteoblasts via a mitochondria-dependent pathway. The apoptotic biochemical changes were effectively prevented upon pretreatment with ROS scavengers, indicating that ROS plays a critical role as an upstream controller in the caffeine-induced apoptotic cascade. Additionally, p21-activated protein kinase 2 (PAK2 and c-Jun N-terminal kinase (JNK were activated in caffeine-treated osteoblasts. Experiments further found that PAK2 activity is required for caffeine-induced JNK activation and apoptosis. Importantly, our data also show that caffeine triggers cell death via inactivation of the survival signal, including the ERK- and Akt-mediated anti-apoptotic pathways. Finally, exposure of rats to dietary water containing 10~20 μM caffeine led to bone mineral density loss. These results demonstrate for the first time that caffeine triggers apoptosis in osteoblasts via activation of mitochondria-dependent cell death signaling and inactivation of the survival signal, and causes bone mineral density loss in vivo.

Unitary relation for the time-dependent SU(1,1) systems

International Nuclear Information System (INIS)

Song, Dae-Yup

2003-01-01

The system whose Hamiltonian is a linear combination of the generators of SU(1,1) group with time-dependent coefficients is studied. It is shown that there is a unitary relation between the system and a system whose Hamiltonian is simply proportional to the generator of the compact subgroup of SU(1,1). The unitary relation is described by the classical solutions of a time-dependent (harmonic) oscillator. Making use of the relation, the wave functions satisfying the Schroedinger equation are given, for a general unitary representation, in terms of the matrix elements of a finite group transformation (Bargmann function). The wave functions of the harmonic oscillator with an inverse-square potential is studied in detail, and it is shown that through an integral, the model provides a way of deriving the Bargmann function for the representation of positive discrete series of SU(1,1)

Adaptor Protein Complex-2 (AP-2) and Epsin-1 Mediate Protease-activated Receptor-1 Internalization via Phosphorylation- and Ubiquitination-dependent Sorting Signals*

Science.gov (United States)

Chen, Buxin; Dores, Michael R.; Grimsey, Neil; Canto, Isabel; Barker, Breann L.; Trejo, JoAnn

2011-01-01

Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by β-arrestins, like most classic GPCRs. In contrast, internalization of PAR1 occurs through a clathrin- and dynamin-dependent pathway independent of β-arrestins. PAR1 displays two modes of internalization. Constitutive internalization of unactivated PAR1 is mediated by the clathrin adaptor protein complex-2 (AP-2), where the μ2-adaptin subunit binds directly to a tyrosine-based motif localized within the receptor C-tail domain. However, AP-2 depletion only partially inhibits agonist-induced internalization of PAR1, suggesting a function for other clathrin adaptors in this process. Here, we now report that AP-2 and epsin-1 are both critical mediators of agonist-stimulated PAR1 internalization. We show that ubiquitination of PAR1 and the ubiquitin-interacting motifs of epsin-1 are required for epsin-1-dependent internalization of activated PAR1. In addition, activation of PAR1 promotes epsin-1 de-ubiquitination, which may increase its endocytic adaptor activity to facilitate receptor internalization. AP-2 also regulates activated PAR1 internalization via recognition of distal C-tail phosphorylation sites rather than the canonical tyrosine-based motif. Thus, AP-2 and epsin-1 are both required to promote efficient internalization of activated PAR1 and recognize discrete receptor sorting signals. This study defines a new pathway for internalization of mammalian GPCRs. PMID:21965661

Requirements for superoxide-dependent tyrosine hydroperoxide formation in peptides

DEFF Research Database (Denmark)

Winterbourn, Christine C; Parsons-Mair, Helena N; Gebicki, Silvia

2004-01-01

Superoxide reacts rapidly with other radicals, but these reactions have received little attention in the context of oxidative stress. For tyrosyl radicals, reaction with superoxide is 3-fold faster than dimerization, and forms the addition product tyrosine hydroperoxide. We have explored structural...... requirements for hydroperoxide formation using tyrosine analogues and di- and tri-peptides. Superoxide and phenoxyl radicals were generated using xanthine oxidase, peroxidase and the respective tyrosine derivative, or by gamma-radiation. Peroxides were measured using FeSO4/Xylenol Orange. Tyrosine and tyramine...... formed stable hydroperoxides, but N-acetyltyrosine and p-hydroxyphenylacetic acid did not, demonstrating a requirement for a free amino group. Using [14C]tyrosine, the hydroperoxide and dityrosine were formed at a molar ratio of 1.8:1. Studies with pre-formed hydroperoxides, and measurements of substrate...

HIV-1 Infection of T Cells and Macrophages Are Differentially Modulated by Virion-Associated Hck: A Nef-Dependent Phenomenon

Directory of Open Access Journals (Sweden)

Gilda Tachedjian

2013-09-01

Full Text Available The proline repeat motif (PxxP of Nef is required for interaction with the SH3 domains of macrophage-specific Src kinase Hck. However, the implication of this interaction for viral replication and infectivity in macrophages and T lymphocytes remains unclear. Experiments in HIV-1 infected macrophages confirmed the presence of a Nef:Hck complex which was dependent on the Nef proline repeat motif. The proline repeat motif of Nef also enhanced both HIV-1 infection and replication in macrophages, and was required for incorporation of Hck into viral particles. Unexpectedly, wild-type Hck inhibited infection of macrophages, but Hck was shown to enhance infection of primary T lymphocytes. These results indicate that the interaction between Nef and Hck is important for Nef-dependent modulation of viral infectivity. Hck-dependent enhancement of HIV-1 infection of T cells suggests that Nef-Hck interaction may contribute to the spread of HIV-1 infection from macrophages to T cells by modulating events in the producer cell, virion and target cell.

Biochemical composition of zooplankton from the northern Arabian Sea

Digital Repository Service at National Institute of Oceanography (India)

Bhat, K.L.; Sreepada, R.A; Ansari, Z.A

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Respiratory metabolism in Oreochromis mossambicus, Peters under different environmentl conditions

Digital Repository Service at National Institute of Oceanography (India)

Thampi, R.; Rattan, P; Chatterji, A.

stream_size 5 stream_content_type text/plain stream_name Pak_J_Mar_Sci_3_9.pdf.txt stream_source_info Pak_J_Mar_Sci_3_9.pdf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 ...

Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation.

Science.gov (United States)

Conde, Carlos; Osswald, Mariana; Barbosa, João; Moutinho-Santos, Tatiana; Pinheiro, Diana; Guimarães, Sofia; Matos, Irina; Maiato, Helder; Sunkel, Claudio E

2013-06-12

Maintenance of genomic stability during eukaryotic cell division relies on the spindle assembly checkpoint (SAC) that prevents mitotic exit until all chromosomes are properly attached to the spindle. Polo is a mitotic kinase proposed to be involved in SAC function, but its role has remained elusive. We demonstrate that Polo and Aurora B functional interdependency comprises a positive feedback loop that promotes Mps1 kinetochore localization and activity. Expression of constitutively active Polo restores normal Mps1 kinetochore levels even after Aurora B inhibition, highlighting a role for Polo in Mps1 recruitment to unattached kinetochores downstream of Aurora B. We also show that Mps1 kinetochore localization is required for BubR1 hyperphosphorylation and formation of the 3F3/2 phosphoepitope. This is essential to allow recruitment of Cdc20 to unattached kinetochores and the assembly of anaphase-promoting complex/cyclosome-inhibitory complexes to levels that ensure long-term SAC activity. We propose a model in which Polo controls Mps1-dependent BubR1 phosphorylation to promote Cdc20 kinetochore recruitment and sustained SAC function.

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

8 CFR 333.1 - Description of required photographs.

Science.gov (United States)

2010-01-01

... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Description of required photographs. 333.1 Section 333.1 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS PHOTOGRAPHS § 333.1 Description of required photographs. (a) Every applicant required to furnish photographs of...

Induction of non-apoptotic programmed cell death by oncogenic RAS in human epithelial cells and its suppression by MYC overexpression.

Science.gov (United States)

Dendo, Kasumi; Yugawa, Takashi; Nakahara, Tomomi; Ohno, Shin-Ichi; Goshima, Naoki; Arakawa, Hirofumi; Kiyono, Tohru

2018-02-09

Oncogenic mutations of RAS genes, found in about 30% of human cancers, are considered to play important roles in cancer development. However, oncogenic RAS can also induce senescence in mouse and human normal fibroblasts. In some cell lines, oncogenic RAS has been reported to induce non-apoptotic programed cell death (PCD). Here, we investigated effects of oncogenic RAS expression in several types of normal human epithelial cells. Oncogenic RAS but not wild-type RAS stimulated macropinocytosis with accumulation of large-phase lucent vacuoles in the cytoplasm, subsequently leading to cell death which was indistinguishable from a recently proposed new type of PCD, methuosis. A RAC1 inhibitor suppressed accumulation of macropinosomes and overexpression of MYC attenuated oncogenic RAS-induced such accumulation, cell cycle arrest and cell death. MYC suppression or rapamycin treatment in some cancer cell lines harbouring oncogenic mutations in RAS genes induced cell death with accumulation of macropinosomes. These results suggest that this type of non-apoptotic PCD is a tumour-suppressing mechanism acting against oncogenic RAS mutations in normal human epithelial cells, which can be overcome by MYC overexpression, raising the possibility that its induction might be a novel approach to treatment of RAS-mutated human cancers. © The Author(s) 2017. Published by Oxford University Press.

Transportin-1-dependent YB-1 nuclear import

International Nuclear Information System (INIS)

Mordovkina, Daria A.; Kim, Ekaterina R.; Buldakov, Ilya A.; Sorokin, Alexey V.; Eliseeva, Irina A.; Lyabin, Dmitry N.; Ovchinnikov, Lev P.

2016-01-01

The DNA/RNA-binding protein YB-1 (Y-box binding protein 1) performs multiple functions both in the cytoplasm and the nucleus of the cell. Generally localized to the cytoplasm, under certain conditions YB-1 is translocated to the nucleus. Here we report for the first time a transport factor that mediates YB-1 nuclear import – transportin-1. The YB-1/transportin-1 complex can be isolated from HeLa cell extract. Nuclear import of YB-1 and its truncated form YB-1 (1-219) in in vitro transport assay was diminished in the presence of a competitor substrate and ceased in the presence of transportin-1 inhibitor M9M. Inhibitors of importin β1 had no effect on YB-1 transport. Furthermore, transport of YB-1 (P201A/Y202A) and YB-1 (1–219) (P201A/Y202A) bearing inactivating mutations in the transportin-1-dependent nuclear localization signal was practically abolished. Together, these results indicate that transportin-1 mediates YB-1 nuclear translocation. - Highlights: • Transportin-1 mediates YB-1 nuclear import. • YB-1 nuclear translocation is diminished in the presence of transportin-1 inhibitors. • Mutations in the PY motif of YB-1 NLS prevent its translocation to the nucleus.

26 CFR 1.382-11 - Reporting requirements.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 4 2010-04-01 2010-04-01 false Reporting requirements. 1.382-11 Section 1.382-11 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Insolvency Reorganizations § 1.382-11 Reporting requirements. (a) Information...

Dependencies among Architectural Views Got from Software Requirements Based on a Formal Model

Directory of Open Access Journals (Sweden)

Osis Janis

2014-12-01

Full Text Available A system architect has software requirements and some unspecified knowledge about a problem domain (e.g., an enterprise as source information for assessment and evaluation of possible solutions and getting the target point, a preliminary software design. The solving factor is architect’s experience and expertise in the problem domain (“AS-IS”. A proposed approach is dedicated to assist a system architect in making an appropriate decision on the solution (“TO-BE”. It is based on a formal mathematical model, Topological Functioning Model (TFM. Compliant TFMs can be transformed into software architectural views. The paper demonstrates and discusses tracing dependency links from the requirements to and between the architectural views.

PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner

Directory of Open Access Journals (Sweden)

Jin Wenying

2010-12-01

Full Text Available Abstract Background Acid-sensing ion channel 1a (ASIC1a is the major ASIC subunit determining acid-activated currents in brain neurons. Recent studies show that ASIC1a play critical roles in acid-induced cell toxicity. While these studies raise the importance of ASIC1a in diseases, mechanisms for ASIC1a trafficking are not well understood. Interestingly, ASIC1a interacts with PICK1 (protein interacting with C-kinase 1, an intracellular protein that regulates trafficking of several membrane proteins. However, whether PICK1 regulates ASIC1a surface expression remains unknown. Results Here, we show that PICK1 overexpression increases ASIC1a surface level. A BAR domain mutant of PICK1, which impairs its lipid binding capability, blocks this increase. Lipid binding of PICK1 is also required for PICK1-induced clustering of ASIC1a. Consistent with the effect on ASIC1a surface levels, PICK1 increases ASIC1a-mediated acidotoxicity and this effect requires both the PDZ and BAR domains of PICK1. Conclusions Taken together, our results indicate that PICK1 regulates trafficking and function of ASIC1a in a lipid binding-dependent manner.

Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage

Science.gov (United States)

Flott, Sonja; Rouse, John

2005-01-01

Members of the RecQ family of DNA helicases, mutated in several syndromes associated with cancer predisposition, are key regulators of genome stability. The Saccharomyces cerevisiae SLX4 gene is required for cell viability in the absence of Sgs1, the only yeast RecQ helicase. SLX4 encodes one subunit of the heterodimeric Slx1–Slx4 endonuclease, although its cellular function is not clear. Slx1–Slx4 was reported to preferentially cleave replication fork-like structures in vitro, and cells lacking SLX4 are hypersensitive to DNA alkylation damage. Here we report that Slx4 becomes phosphorylated in cells exposed to a wide range of genotoxins. Even though it has been proposed that the role of Slx4 is restricted to S-phase, Slx4 phosphorylation is observed in cells arrested in G1 or G2 phases of the cell cycle, but not during an unperturbed cell cycle. Slx4 phosphorylation is completely abolished in cells lacking the Mec1 and Tel1 protein kinases, critical regulators of genome stability, but is barely affected in the absence of both Rad53 and Chk1 kinases. Finally we show that, whereas both Slx1 and Slx4 are dispensable for activation of cell-cycle checkpoints, Slx4, but not Slx1, is required for repair of DNA alkylation damage in both aynchronously growing cells and in G2-phase-arrested cells. These results reveal Slx4 as a new target of the Mec1/Tel1 kinases, with a crucial role in DNA repair that is not restricted to the processing of stalled replisomes. PMID:15975089

DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.

Science.gov (United States)

Qin, Weihua; Wolf, Patricia; Liu, Nan; Link, Stephanie; Smets, Martha; La Mastra, Federica; Forné, Ignasi; Pichler, Garwin; Hörl, David; Fellinger, Karin; Spada, Fabio; Bonapace, Ian Marc; Imhof, Axel; Harz, Hartmann; Leonhardt, Heinrich

2015-08-01

DNMT1 is recruited by PCNA and UHRF1 to maintain DNA methylation after replication. UHRF1 recognizes hemimethylated DNA substrates via the SRA domain, but also repressive H3K9me3 histone marks with its TTD. With systematic mutagenesis and functional assays, we could show that chromatin binding further involved UHRF1 PHD binding to unmodified H3R2. These complementation assays clearly demonstrated that the ubiquitin ligase activity of the UHRF1 RING domain is required for maintenance DNA methylation. Mass spectrometry of UHRF1-deficient cells revealed H3K18 as a novel ubiquitination target of UHRF1 in mammalian cells. With bioinformatics and mutational analyses, we identified a ubiquitin interacting motif (UIM) in the N-terminal regulatory domain of DNMT1 that binds to ubiquitinated H3 tails and is essential for DNA methylation in vivo. H3 ubiquitination and subsequent DNA methylation required UHRF1 PHD binding to H3R2. These results show the manifold regulatory mechanisms controlling DNMT1 activity that require the reading and writing of epigenetic marks by UHRF1 and illustrate the multifaceted interplay between DNA and histone modifications. The identification and functional characterization of the DNMT1 UIM suggests a novel regulatory principle and we speculate that histone H2AK119 ubiquitination might also lead to UIM-dependent recruitment of DNMT1 and DNA methylation beyond classic maintenance.