Regulation of NF-κB activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

International Nuclear Information System (INIS)

Spilsbury, Alison; Vauzour, David; Spencer, Jeremy P.E.; Rattray, Marcus

2012-01-01

Highlights: ► We tested the hypothesis that low concentrations of flavonoids inhibit NF-κB in astrocytes. ► Primary cultured astrocytes possess a functional κB-system, measured using luciferase assays. ► Seven flavonoids (100 nM–1 μM) failed to reduce NF-κB activity in astrocytes. ► Four flavonoids (100 nM–1 μM) failed to reduce TNFa-stimulated NF-κB activity in astrocytes. ► (−)-Epicatechin did not regulate nuclear translocation of the NF-κB subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Sustained activation of nuclear transcription factor κB (NF-κB) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-κB signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNFα, 150 ng/ml) increased NF-κB-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative IκBα construct. In addition, TNFα increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-κB activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((−)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1–1 μM) for 18 h. None of the flavonoids modulated constitutive or TNFα-induced NF-κB activity. Therefore, we conclude that NF-κB signalling in astrocytes is not a major target for flavonoids.

Integrated management system: The integration of ISO 9001, ISO 14001, OHSAS 18001 and ISO 31000

Science.gov (United States)

Muzaimi, Hafizzudin; Chew, Boon Cheong; Hamid, Syaiful Rizal

2017-03-01

The implementation of integrated management system (IMS) for better quality management has become a preference for many organizations. This can be seen as many organizations used the combination of quality ISO 9001, an environment ISO 14001 and occupational health and safety management system OHSAS 18001 as a core for the IMS that largely implemented. Besides, the linked between quality management with risk management system need to be identified as the management system that enhance the effectiveness of IMS. Therefore, the risk management system ISO 31000 also presented as a part of integration. In nowadays competitive environment, the increasing pressure and needs from customer or stakeholders make it compulsory for the organization to propose the new system and standards. This paper presents and discusses about the benefit of integration, the management system components that can be converged and the implementation approach. A series of interview was conducted through in-depth interviews with 8 experts in this field, while data collected were analyzed qualitatively. The results consist of 16 factors of IMS implementation that have been identified and the use of PDCA approach for an effective implementation of IMS. As a conclusion, the paper proposes the integration of four management systems (ISO 9001, ISO 14001, OHSAS 18001 and ISO 31000) and on how the IMS can be used to structure the process of management for quality management towards sustainability practices in the organization.

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

International Nuclear Information System (INIS)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Science.gov (United States)

Kanduri, M; Tobin, G; Åleskog, A; Nilsson, K; Rosenquist, R

2011-01-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo. PMID:22829125

The novel NF-κB inhibitor IMD-0354 induces apoptosis in chronic lymphocytic leukemia

Energy Technology Data Exchange (ETDEWEB)

Kanduri, M; Tobin, G [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden); Åleskog, A [Department of Medical Sciences, Clinical Pharmacology, Uppsala University, Uppsala (Sweden); Nilsson, K; Rosenquist, R [Rudbeck Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala (Sweden)

2011-03-01

Nuclear factor-κB (NF-κB) is an important regulator of cell survival and has been shown to be constitutively active in chronic lymphocytic leukemia (CLL) cells. Recently, a novel NF-κB inhibitor, IMD-0354 (N-(3, 5-bis-trifluoromethyl-phenyl)-5-chloro-2-hydroxy-benzamide), was shown to specifically inhibit the phosphorylation of IκBα by IkB kinases, thus preventing NF-κB release. In this study, we investigated if IMD-0354 can inhibit NF-κB activation and induce apoptosis in CLL cells in vitro. The rate of increase in apoptosis, drug sensitivity and DNA-binding activity of NF-κB were studied using Annexin V stainings, the fluorometric microculture cytotoxicity assay and electrophoretic mobility shift assay, respectively. Finally, the impact of IMD-0354 treatment on the expression of a set of apoptosis-related genes was investigated. The results clearly show that IMD-0354 induced apoptosis (mean 26%, range 8–48%) in CLL cells, independent of immunoglobulin heavy variable (IGHV) gene mutational status, and showed a dose-dependent cytotoxic effect. IMD-0354 treatment also significantly lowered the DNA-binding activity of NF-κB in CLL cells. In addition, we identified differences in expression levels of pro- and antiapoptotic genes following IMD-0354 treatment. In summary, our novel findings show that IMD-0354 can induce apoptosis in CLL cells, and thus merits further investigation as an anticancer agent in vivo.

Regorafenib induces extrinsic and intrinsic apoptosis through inhibition of ERK/NF-κB activation in hepatocellular carcinoma cells.

Science.gov (United States)

Tsai, Jai-Jen; Pan, Po-Jung; Hsu, Fei-Ting

2017-02-01

The aim of the present study was to investigate the role of NF-κB inactivation in regorafenib-induced apoptosis in human hepatocellular carcinoma SK-HEP-1 cells. SK-HEP-1 cells were treated with different concentrations of the NF-κB inhibitor 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (QNZ) or regorafenib for different periods. The effects of QNZ and regorafenib on cell viability, expression of NF-κB-modulated anti-apoptotic proteins and apoptotic pathways were analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blotting, DNA gel electrophoresis, flow cytometry and NF-κB reporter gene assay. Inhibitors of various kinases including AKT, c-Jun N-terminal kinase (JNK), P38 and extracellular signal-regulated kinase (ERK) were used to evaluate the mechanism of regorafenib-induced NF-κB inactivation. The results demonstrated that both QNZ and regorafenib significantly inhibited the expression of anti-apoptotic proteins and triggered extrinsic and intrinsic apoptosis. We also demonstrated that regorafenib inhibited NF-κB activation through ERK dephosphorylation. Taken all together, our findings indicate that regorafenib triggers extrinsic and intrinsic apoptosis through suppression of ERK/NF-κB activation in SK-HEP-1 cells.

ISO27001 / ISO27002 a pocket guide

CERN Document Server

Calder, Alan

2013-01-01

Information is one of your organisation's most important resources. Keeping it secure is therefore vital to your business. This handy pocket guide is an essential overview of two key information security standards that cover the formal requirements (ISO27001:2013) for creating an Information Security Management System (ISMS), and the best-practice recommendations (ISO27002:2013) for those responsible for initiating, implementing or maintaining it.

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

Science.gov (United States)

Quan, Juan-Hua; Kang, Byung-Hun; Yang, Jung-Bo; Rhee, Yun-Ee; Noh, Heung-Tae; Choi, In-Wook; Cha, Guang-Ho; Yuk, Jae-Min

2017-01-01

Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS), and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5) for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC), reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway. PMID:29410962

Trichomonas vaginalis Induces SiHa Cell Apoptosis by NF-κB Inactivation via Reactive Oxygen Species

Directory of Open Access Journals (Sweden)

Juan-Hua Quan

2017-01-01

Full Text Available Trichomonas vaginalis induces apoptosis in host cells through various mechanisms; however, little is known about the relationship between apoptosis, reactive oxygen species (ROS, and NF-κB signaling pathways in the cervical mucosal epithelium. Here, we evaluated apoptotic events, ROS production, and NF-κB activity in T. vaginalis-treated cervical mucosal epithelial SiHa cells, with or without specific inhibitors, using fluorescence microscopy, DNA fragmentation assays, subcellular fractionation, western blotting, and luciferase reporter assay. SiHa cells treated with live T. vaginalis at a multiplicity of infection of 5 (MOI 5 for 4 h produced intracellular and mitochondrial ROS in a parasite-load-dependent manner. Incubation with T. vaginalis caused DNA fragmentation, cleavage of caspase 3 and PARP, and release of cytochrome c into the cytoplasm. T. vaginalis-treated SiHa cells showed transient early NF-κB p65 nuclear translocation, which dramatically dropped at 4 h after treatment. Suppression of NF-κB activity was dependent on parasite burden. However, treatment with the ROS scavenger, N-acetyl-C-cysteine (NAC, reversed the effect of T. vaginalis on apoptosis and NF-κB inactivation in SiHa cells. Taken together, T. vaginalis induces apoptosis in human cervical mucosal epithelial cells by parasite-dose-dependent ROS production through an NF-κB-regulated, mitochondria-mediated pathway.

Regulation of NF-{kappa}B activity in astrocytes: effects of flavonoids at dietary-relevant concentrations

Energy Technology Data Exchange (ETDEWEB)

Spilsbury, Alison [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom); Vauzour, David; Spencer, Jeremy P.E. [Molecular Nutrition Group, Centre for Integrative Neuroscience and Neurodynamics, School of Chemistry, Food and Pharmacy, University of Reading, Reading RG6 6AP (United Kingdom); Rattray, Marcus, E-mail: m.a.n.rattray@reading.ac.uk [Reading School of Pharmacy, University of Reading, Reading RG6 6UB (United Kingdom)

2012-02-17

Highlights: Black-Right-Pointing-Pointer We tested the hypothesis that low concentrations of flavonoids inhibit NF-{kappa}B in astrocytes. Black-Right-Pointing-Pointer Primary cultured astrocytes possess a functional {kappa}B-system, measured using luciferase assays. Black-Right-Pointing-Pointer Seven flavonoids (100 nM-1 {mu}M) failed to reduce NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer Four flavonoids (100 nM-1 {mu}M) failed to reduce TNFa-stimulated NF-{kappa}B activity in astrocytes. Black-Right-Pointing-Pointer (-)-Epicatechin did not regulate nuclear translocation of the NF-{kappa}B subunit, p65. -- Abstract: Neuroinflammation plays an important role in the progression of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Sustained activation of nuclear transcription factor {kappa}B (NF-{kappa}B) is thought to play an important role in the pathogenesis of neurodegenerative disorders. Flavonoids have been shown to possess antioxidant and anti-inflammatory properties and we investigated whether flavonoids, at submicromolar concentrations relevant to their bioavailability from the diet, were able to modulate NF-{kappa}B signalling in astrocytes. Using luciferase reporter assays, we found that tumour necrosis factor (TNF{alpha}, 150 ng/ml) increased NF-{kappa}B-mediated transcription in primary cultures of mouse cortical astrocytes, which was abolished on co-transfection of a dominant-negative I{kappa}B{alpha} construct. In addition, TNF{alpha} increased nuclear localisation of p65 as shown by immunocytochemistry. To investigate potential flavonoid modulation of NF-{kappa}B activity, astrocytes were treated with flavonoids from different classes; flavan-3-ols ((-)-epicatechin and (+)-catechin), flavones (luteolin and chrysin), a flavonol (kaempferol) or the flavanones (naringenin and hesperetin) at dietary-relevant concentrations (0.1-1 {mu}M) for 18 h. None of the flavonoids modulated constitutive or

IsoBank workshop held at IsoEcol10 - University of Tokyo 2016

OpenAIRE

Hayden, Brian

2016-01-01

IsoBank is a repository for stable isotope values and relevant metadata. These slides were presented at a workshop held during IsoEcol10 to refine and design the IsoBank for the needs of a diverse group of researchers.

Characterization of the enhanced apoptotic response to azidothymidine by pharmacological inhibition of NF-kB.

Science.gov (United States)

Matteucci, Claudia; Minutolo, Antonella; Marino-Merlo, Francesca; Grelli, Sandro; Frezza, Caterina; Mastino, Antonio; Macchi, Beatrice

2015-04-15

The present study addresses the issue of enhanced apoptotic response to AZT following co-treatment with an NF-kB inhibitor. To investigate this issue, different cell lines were assayed for susceptibility to AZT-mediated apoptosis without or with the addition of the NF-kB inhibitor Bay-11-7085. For further investigation, U937 cells were selected as good-responder cells to the combination treatment with 32 or 128 μM AZT, and 1 μM Bay-11-7085. Inhibition of NF-kB activation by Bay-11-7085 in cells treated with AZT was assayed through Western blot analysis of p65 expression and by EMSA. Involvement of the mitochondrial pathway of apoptosis in mechanisms underlying the improved effect of AZT following Bay-11-7085 co-treatment, was evaluated by assaying the cytochrome c release and the mitochondrial membrane potential (MMP) status using the JC-1 dye. Moreover, the transcriptional activity of both anti- and pro-apoptotic genes in U937 cells after combination treatment was quantitatively evaluated through real-time PCR. We found that the combined treatment induced high levels of cytochrome c release and of MMP collapse in association with evident changes in the expression of both anti- and pro-apoptotic genes of the Bcl-2 family. Overexpression of Bcl-2 significantly suppressed the sensitization of U937 cells to an enhanced apoptotic response to AZT following co-treatment with the NF-kB inhibitor. The new findings suggest that a combination regimen based on AZT plus an NF-kB inhibitor could represent a new chemotherapeutic tool for retrovirus-related pathologies.

TRIM45 negatively regulates NF-κB-mediated transcription and suppresses cell proliferation

International Nuclear Information System (INIS)

Shibata, Mio; Sato, Tomonobu; Nukiwa, Ryota; Ariga, Tadashi; Hatakeyama, Shigetsugu

2012-01-01

Highlights: ► NF-κB plays an important role in cell survival and carcinogenesis. ► TRIM45 negatively regulates TNFα-induced NF-κB-mediated transcription. ► TRIM45 overexpression suppresses cell growth. ► TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth. -- Abstract: The NF-κB signaling pathway plays an important role in cell survival, immunity, inflammation, carcinogenesis, and organogenesis. Activation of NF-κB is regulated by several posttranslational modifications including phosphorylation, neddylation and ubiquitination. The NF-κB signaling pathway is activated by two distinct signaling mechanisms and is strictly modulated by the ubiquitin–proteasome system. It has been reported that overexpression of TRIM45, one of the TRIM family ubiquitin ligases, suppresses transcriptional activities of Elk-1 and AP-1, which are targets of the MAPK signaling pathway. In this study, we showed that TRIM45 also negatively regulates TNFα-induced NF-κB-mediated transcription by a luciferase reporter assay and that TRIM45 lacking a RING domain also has an activity to inhibit the NF-κB signal. Moreover, we found that TRIM45 overexpression suppresses cell growth. These findings suggest that TRIM45 acts as a repressor for the NF-κB signal and regulates cell growth.

Colorectal cancer: can nutrients modulate NF-kappaB and apoptosis?

Science.gov (United States)

Ravasco, Paula; Aranha, Márcia M; Borralho, Pedro M; Moreira da Silva, Isabel B; Correia, Luís; Fernandes, Afonso; Rodrigues, Cecília M P; Camilo, Maria

2010-02-01

NF-kappaB may promote carcinogenesis by altering cell cycle, inflammatory responses and apoptosis-related gene expression, though cell mechanisms relating diet and colorectal cancer (CRC) remain unveiled in humans. This study in patients with CRC aimed to explore potential interactions between the dietary pattern, nutrient intake, expression of NF-kappaB, apoptosis and tumour histological aggressiveness. Usual diet was assessed by diet history; nutrient composition was determined by DIETPLAN software. Histologically classified patient tissue samples (adenoma, adenocarcinoma and normal surrounding mucosa) were obtained via biopsies during colonoscopy (n=16) or surgery (n=8). NF-kappaB expression was determined by immunohistochemistry and apoptosis by TUNEL assay. NF-kappaB expression and apoptosis were higher in tumours (p<0.01), greater along with histological aggressiveness (p<0.01). Highest intake terciles of animal protein, refined carbohydrates, saturated fat, n-6 fatty acids and alcohol were associated with higher NF-kappaB, apoptosis and histological aggressiveness (p<0.01); the opposite tissue characteristics were associated with highest intake terciles of n-3 fatty acids, fibre, vitamin E, flavonoids, isoflavones, beta-carotene and selenium (p<0.002). Additionally, higher n-6:n-3 fatty acids ratio (median 26:1) was associated with higher NF-kappaB (p<0.006) and apoptosis (p<0.01), and more aggressive histology (p<0.01). Conversely, lower n-6:n-3 fatty acids ratio (median 6:1) was associated with lower NF-kappaB (p<0.002) and apoptosis (p<0.002), and less aggressive histology (p<0.002). NF-kappaB expression and apoptosis increased from adenoma to poorly differentiated adenocarcinoma. This degenerative transition, recognized as key in carcinogenesis, appear to have been influenced by a diet promoting a pro-inflammatory milieu that can trigger NF-kappaB. Copyright 2009 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Andrographolide inhibits multiple myeloma cells by inhibiting the TLR4/NF-κB signaling pathway.

Science.gov (United States)

Gao, Hui; Wang, Jianrong

2016-02-01

Andrographolide is an active component from the extract of Andrographis paniculata [(Burm.f) Nees], a medicinal plant from the Acanthaceae family. Pharmacological studies have revealed that andrographolide possesses anti-bacterial, anti-inflammatory, anti-viral, immune regulatory and hepatoprotective properties, and is efficacious in the treatment of cardiovascular diseases, while exhibiting low toxicity and low cost. The present study aimed to determine the inhibitory effects of andrographolide on the growth of multiple myeloma (MM) cells and its possible impact on the Toll-like receptor (TLR)4/nuclear factor (NF)-κB signaling pathway. Cell proliferation was detected using an MTT assay, cellular apoptosis was measured using flow cytometry, and caspase-9/3 activation were assessed using colorimetric assay kits. Furthermore, TLR4 and NF-κB protein expression was determined by western blot analysis. The results revealed that andrographolide reduced the proliferation, while increasing cellular apoptosis and caspase-9/3 activation of MM cells, in addition to downregulating the expression of TLR4 and NF-κB protein. Of note, TLR4- or NF-κB-targeting small-interfering (si)RNA enhanced the andrographolide-induced inhibition of cell proliferation and induction of apoptosis of MM cells. The results of the present study therefore suggested that andrographolide inhibited multiple myeloma cells via the TLR4/NF-κB signaling pathway.

ISO radiation protection standards

International Nuclear Information System (INIS)

Becker, K.; West, N.

1981-01-01

After a brief description of the International Organization for Standardization (ISO) and its Technical Committee (TC) 85 ''Nuclear Energy'', the work of its Sub-Committee (SC) 2 ''Radiation Protection'' is described in some detail. Several international standards on subjects closely related to radiation protection have already been published, for example ISO-361 (Basic radiation protection symbol), ISO-1757 (Photographic dosimeters), ISO-1758 and 1759 (Direct and indirect-reading pocket exposure meters), ISO-2889 (Sampling of airborne radioactive materials), ISO-4037 (X and gamma reference radiations for calibration) and ISO-4071 (Testing of exposure meters and dosimeters). TC 85/SC 2 has currently eight active Working Groups (WG) dealing with 14 standards projects, mostly in advanced stages, in such fields as neutron and beta reference radiations, and X and gamma radiations of high and low dose-rates and high energies for calibration purposes, reference radiations for surface contamination apparatus, ejection systems for gamma radiography apparatus, industrial and laboratory irradiators, lead shielding units, protective clothing, thermoluminescence dosemeters, radioelement gauges, and surface contamination and decontamination. (author)

Plasma 8-iso-Prostaglandin F2α concentrations and outcomes after acute intracerebral hemorrhage.

Science.gov (United States)

Du, Quan; Yu, Wen-Hua; Dong, Xiao-Qiao; Yang, Ding-Bo; Shen, Yong-Feng; Wang, Hao; Jiang, Li; Du, Yuan-Feng; Zhang, Zu-Yong; Zhu, Qiang; Che, Zhi-Hao; Liu, Qun-Jie

2014-11-01

Higher plasma 8-iso-Prostaglandin F2α concentrations have been associated with poor outcome of severe traumatic brain injury. We further investigated the relationships between plasma 8-iso-Prostaglandin F2α concentrations and clinical outcomes in patients with acute intracerebral hemorrhage. Plasma 8-iso-Prostaglandin F2α concentrations of 128 consecutive patients and 128 sex- and gender-matched healthy subjects were measured by enzyme-linked immunosorbent assay. We assessed their relationships with disease severity and clinical outcomes including 1-week mortality, 6-month mortality and unfavorable outcome (modified Rankin Scale score>2). Plasma 8-iso-Prostaglandin F2α concentrations were substantially higher in patients than in healthy controls. Plasma 8-iso-Prostaglandin F2α concentrations were positively associated with National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume using a multivariate linear regression. It emerged as an independent predictor for clinical outcomes of patients using a forward stepwise logistic regression. ROC curves identified the predictive values of plasma 8-iso-Prostaglandin F2α concentrations, and found its predictive value was similar to NIHSS scores and hematoma volumes. However, it just numerically added the predictive values of NIHSS score and hematoma volume. Increased plasma 8-iso-Prostaglandin F2α concentrations are associated with disease severity and clinical outcome after acute intracerebral hemorrhage. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation of NF-κB signal pathway with tumor metastasis of human head and neck squamous cell carcinoma

International Nuclear Information System (INIS)

Yan, Ming; Xu, Qin; Zhang, Ping; Zhou, Xiao-jian; Zhang, Zhi-yuan; Chen, Wan-tao

2010-01-01

Nuclear factor-kappa B (NF-κB) signaling constitutes a key event in the multistep process of carcinogenesis, progression and treatment in many cancer types. However, the significance of NF-κB pathway for complex and tissue-specific aspects of head and neck cancer progression, such as invasion and metastasis, is less understood. The expression of NF-κB p65 in squamous cell carcinoma of the head and neck (SCCHN) clinical specimens by immunohistochemistry. The role of NF-κB activity in head and neck squamous cell carcinoma was determined by western blot, reporter assay and EMSA analysis in vitro and metastasis assays in vivo in different metastatic potential tumor cells. Furthermore, the apoptosis rate and expression of metastasis-related protein such as MMP9 and VEGF were examined by Annexin V/PI staining and Western blot, respectively. A higher level of active nuclear-localized NF-κB was observed in the metastatic SCCHN specimens group (p < 0.01). The NF-κB activities of SCCHN cell lines with different metastatic potentials were then determined and in excellent agreement with results found in SCCHN specimens, highly metastatic SCCHN cell lines expressed high level of NF-κB activity. The treatment of highly metastatic SCCHN cells with NF-κB inhibitors reduced the in vitro cell invasion capacity of the cells without affecting the apoptotic rate. Additionally, the NF-κB inhibitors significantly inhibited the experimental lung metastasis of Tb cells and lymph node metastasis of TL cells in nude mice. Furthermore, the expression of metastasis-related proteins, such as matrix metalloproteinase 9 and vascular endothelial growth factor, was inhibited by pyrrolidine dithiocarbonate. This study suggests that NF-κB activity significantly contributes to tumor hematologic and lymphatic metastases and may aid in the development of early detection methods or therapies targeting non-conventional molecular targets

ISO radiation sterilization standards

International Nuclear Information System (INIS)

Lambert, Byron J.; Hansen, Joyce M.

1998-01-01

This presentation provides an overview of the current status of the ISO radiation sterilization standards. The ISO standards are voluntary standards which detail both the validation and routine control of the sterilization process. ISO 11137 was approved in 1994 and published in 1995. When reviewing the standard you will note that less than 20% of the standard is devoted to requirements and the remainder is guidance on how to comply with the requirements. Future standards developments in radiation sterilization are being focused on providing additional guidance. The guidance that is currently provided in informative annexes of ISO 11137 includes: device/packaging materials, dose setting methods, and dosimeters and dose measurement, currently, there are four Technical Reports being developed to provide additional guidance: 1. AAMI Draft TIR, 'Radiation Sterilization Material Qualification' 2. ISO TR 13409-1996, 'Sterilization of health care products - Radiation sterilization - Substantiation of 25 kGy as a sterilization dose for small or infrequent production batches' 3. ISO Draft TR, 'Sterilization of health care products - Radiation sterilization Selection of a sterilization dose for a single production batch' 4. ISO Draft TR, 'Sterilization of health care products - Radiation sterilization-Product Families, Plans for Sampling and Frequency of Dose Audits'

Mycobacterium leprae induces NF-κB-dependent transcription repression in human Schwann cells

International Nuclear Information System (INIS)

Pereira, Renata M.S.; Calegari-Silva, Teresa Cristina; Hernandez, Maristela O.; Saliba, Alessandra M.; Redner, Paulo; Pessolani, Maria Cristina V.; Sarno, Euzenir N.; Sampaio, Elizabeth P.; Lopes, Ulisses G.

2005-01-01

Mycobacterium leprae, the causative agent of leprosy, invades peripheral nerve Schwann cells, resulting in deformities associated with this disease. NF-κB is an important transcription factor involved in the regulation of host immune antimicrobial responses. We aimed in this work to investigate NF-κB signaling pathways in the human ST88-14 Schwannoma cell line infected with M. leprae. Gel shift and supershift assays indicate that two NF-κB dimers, p65/p50 and p50/p50, translocate to the nucleus in Schwann cells treated with lethally irradiated M. leprae. Consistent with p65/p50 and p50/p50 activation, we observed IκB-α degradation and reduction of p105 levels. The nuclear translocation of p50/p50 complex due to M. leprae treatment correlated with repression of NF-κB-driven transcription induced by TNF-α. Moreover, thalidomide inhibited p50 homodimer nuclear translocation induced by M. leprae and consequently rescues Schwann cells from NF-κB-dependent transcriptional repression. Here, we report for the first time that M. leprae induces NF-κB activation in Schwann cells and thalidomide is able to modulate this activation

Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

Energy Technology Data Exchange (ETDEWEB)

Kao, Shang-Jyh [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Su, Jen-Liang [Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan (China); Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan (China); Department of Biotechnology, Asia University, Taichung, Taiwan (China); Chen, Chi-Kuan [Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua [Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Bien, Mauo-Ying [School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Yang, Shun-Fa [Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chien, Ming-Hsien, E-mail: mhchien1976@gmail.com [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China)

2012-05-15

The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

Accreditation - ISO/IEC 17025

Science.gov (United States)

Kaus, Rüdiger

This chapter gives the background on the accreditation of testing and calibration laboratories according to ISO/IEC 17025 and sets out the requirements of this international standard. ISO 15189 describes similar requirements especially tailored for medical laboratories. Because of these similarities ISO 15189 is not separately mentioned throughout this lecture.

Iso-suillin isolated from Suillus luteus, induces G1 phase arrest and apoptosis in human hepatoma SMMC-7721 cells.

Science.gov (United States)

Jia, Zhi-Qiang; Chen, Ying; Yan, Yong-Xin; Zhao, Jun-Xia

2014-01-01

Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of G1 phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced G1 phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.

Internal Audit Status For ISO 9001 And ISO/ IEC 17025 In Malaysian Nuclear Agency

International Nuclear Information System (INIS)

Fazila Said; Nurul Huda Mudri; Nik Arlina Ali

2012-01-01

The development of MS ISO 9001 and MS ISO/ IEC 17025 in Malaysian Nuclear Agency is the basic step to enhance and improve the Quality Management System (QMS) for processes and laboratories that involve customers and suppliers in delivering products and services. The effectiveness of QMS is monitored by Research and Innovation Management Centre (RIMC) to ensure that all activities related to audit such as Internal Audit are well organized and implemented as documented in quality manual and procedure. This paper will discuss the status of internal audit for processes that implement MS ISO 9001 and laboratories that accredited with MS/ ISO IEC 17025 in year 2008, 2009 and 2010. The total of non-conformance (nc) and opportunity for improvement (ofi) for processes and laboratories and their numbers as per clause in MS ISO 9001 and MS ISO/ IEC 17025 are the indicators that reflects the effectiveness of QMS. Then, the total effectiveness of QMS for MS 9001 and MS ISO/ IEC 17025 is also determined via the number of conformance clause versus non-conformance clause for those three years. (author)

Food service compliance with ISO 14001 and ISO 22000

Directory of Open Access Journals (Sweden)

Laura Lyra Santos

2012-06-01

Full Text Available OBJECTIVE: The objective of this study was to assess food service environmental and food safety management systems according to two checklists based on ABNT ISO 22000 and 14001. METHODS: This exploratory and descriptive study investigated a-la-carte food services of the Federal District, Brazil. Two checklists were developed to investigate ISO 14001 and 22000 compliance. A total of 37 food services were selected from the list of the Brazilian Association of Bars and Restaurants by simple random sampling. Checklist results were analyzed according to ANVISA resolution nº 275/2002. RESULTS: Only five food services employed dietitians to supervise meal production. These establishments achieved the highest ISO compliance. However, no establishment had more than 50% ISO 14001 or 22000 compliance. Restaurants showed little concern for the environment and disobeyed waste disposal laws by not separating recyclables from non-recyclables. CONCLUSION: The study food services do not have safe meal production systems, evidenced by non-conformity with the reference standards. Additionally, they do not attempt to reduce the environmental impact of their wastes. Food services supervised by dietitians are better prepared to produce safe foods.

Involvement of activation of the Nrf2/ARE pathway in protection against 6-OHDA-induced SH-SY5Y cell death by α-iso-cubebenol.

Science.gov (United States)

Park, Sun Young; Kim, Do Yeon; Kang, Jong-Koo; Park, Geuntae; Choi, Young-Whan

2014-09-01

Free radical-mediated neurodegeneration is one of the many causes of Parkinson's disease (PD). As part of our ongoing studies on the identification of biologically active Schisandra chinensis components, we have isolated and structurally elucidated α-iso-cubebenol. This study was carried out in an attempt to clarify the neuroprotective effect of α-iso-cubebenol on toxin-insulted dopaminergic neuronal death using 6-hydroxy-dopamine (6-OHDA)-induced dopaminergic SH-SY5Y cells. α-iso-cubebenol significantly attenuated the loss of mitochondrial function (MTT assay) and membrane integrity (lactate dehydrogenase assay) associated with 6-OHDA-induced neurotoxicity. Pretreatment of the cells with α-iso-cubebenol diminished the intracellular accumulation of reactive oxygen species (ROS) and calcium in response to 6-OHDA. Moreover, α-iso-cubebenol protected against 6-OHDA-induced neurotoxicity through inhibition of SH-SY5Y cell apoptosis. In addition, JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with α-iso-cubebenol. Notably, α-iso-cubebenol inhibited the release of mitochondrial flavoprotein apoptosis inducing factor (AIF) from the mitochondria to the cytosol and nucleus following 6-OHDA treatment. In addition, α-iso-cubebenol reduced the 6-OHDA-induced phosphorylation of ERK and induced the phosphorylation of PKA, PKB, and CREB in a dose-dependent manner. Moreover, α-iso-cubebenol stimulated the activation of Nrf2, a downstream target of CREB. Furthermore, α-iso-cubebenol stimulated the expression of multiple antioxidant response genes (NQO-1 and HO-1). Finally, CREB and Nrf2 siRNA transfection diminished α-iso-cubebenol-mediated neuroprotection. Copyright © 2014 Elsevier Inc. All rights reserved.

Increased expression of NF-AT3 and NF-AT4 in the atria correlates with procollagen I carboxyl terminal peptide and TGF-β1 levels in serum of patients with atrial fibrillation.

Science.gov (United States)

Zhao, Fei; Zhang, ShiJiang; Chen, YiJiang; Gu, WeiDong; Ni, BuQing; Shao, YongFeng; Wu, YanHu; Qin, JianWei

2014-11-25

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice. Unfortunately, the precise mechanisms and sensitive serum biomarkers of atrial remodeling in AF remain unclear. The aim of this study was to determine whether the expression of the transcription factors NF-AT3 and NF-AT4 correlate with atrial structural remodeling of atrial fibrillation and serum markers for collagen I and III synthesis. Right and left atrial specimens were obtained from 90 patients undergoing valve replacement surgery. The patients were divided into sinus rhythm (n = 30), paroxysmal atrial fibrillation (n = 30), and persistent atrial fibrillation (n = 30) groups. NF-AT3, NF-AT4, and collagen I and III mRNA and protein expression in atria were measured. We also tested the levels of the carboxyl-terminal peptide from pro-collagen I, the N-terminal type I procollagen propeptides, the N-terminal type III procollagen propeptides, and TGF-β1 in serum using an enzyme immunosorbent assay. NF-AT3 and NF-AT4 mRNA and protein expression were increased in the AF groups, especially in the left atrium. NF-AT3 and NF-AT4 expression in the right atrium was increased in the persistent atrial fibrillation group compared the sinus rhythm group with similar valvular disease. In patients with AF, the expression levels of nuclear NF-AT3 and NF-AT4 correlated with those of collagens I and III in the atria and with PICP and TGF-β1 in blood. These data support the hypothesis that nuclear NF-AT3 and NF-AT4 participates in atrial structural remodeling, and that PICP and TGF-β1 levels may be sensitive serum biomarkers to estimate atrial structural remodeling with atrial fibrillation.

Quantitative method for the determination of Iso-fludelone (KOS-1803) in human plasma by LC-MS/MS

Science.gov (United States)

Christner, Susan M.; Parise, Robert A.; Levine, Erica D.; Rizvi, Naiyer A.; Gounder, Mrinal M.; Beumer, Jan H.

2014-01-01

Epothilones are relatively new tubulin-poison anticancer drugs. Iso-fludelone (KOS-1803) is a synthetic third generation epothilone drug discovered at Memorial Sloan Kettering Cancer Center, and currently in Phase I clinical trials. We report an LC-MS/MS assay for the sensitive, accurate and precise quantitation of Iso-fludelone in 0.2 mL of human plasma. Validation was performed according to FDA guidance. The assay comprised of KOS-1724 as the internal standard and an MTBE liquid-liquid extraction with a water wash step. Separation was achieved with an YMC-Pack ODS-AQ column and an isocratic mobile phase of 0.1% formic acid in acetonitrile and water (70:30, v/v) at 0.3 mL/min for 4 min. Chromatographic separation was followed by electrospray, positive-mode ionization tandem mass spectrometric detection in the multiple reaction monitoring (MRM) mode. The assay was linear from 0.1– 300 ng/mL and was accurate (−9.41–7.07%) and precise (1.03–13.7%) which fulfilled FDA criteria for validation. Recovery from plasma was 73.9–79.7% and ion suppression was negligible (−22.8 to −31.3%). Plasma freeze thaw stability (99.97–105.7%), stability for 11 months at −80 °C (94.93–107.9%), and stability for 6 h at room temperature (94.75–105.5%) were all acceptable. This assay is currently being applied to quantitate Iso-fludelone in clinical samples. PMID:25168219

Quantitative method for the determination of iso-fludelone (KOS-1803) in human plasma by LC-MS/MS.

Science.gov (United States)

Christner, Susan M; Parise, Robert A; Levine, Erica D; Rizvi, Naiyer A; Gounder, Mrinal M; Beumer, Jan H

2014-11-01

Epothilones are relatively new tubulin-poison anticancer drugs. Iso-fludelone (KOS-1803) is a synthetic third generation epothilone drug discovered at Memorial Sloan Kettering Cancer Center, and currently in phase I clinical trials. We report an LC-MS/MS assay for the sensitive, accurate and precise quantitation of iso-fludelone in 0.2mL of human plasma. Validation was performed according to FDA guidance. The assay comprised of KOS-1724 as the internal standard and an MTBE liquid-liquid extraction with a water wash step. Separation was achieved with an YMC-Pack ODS-AQ column and an isocratic mobile phase of 0.1% formic acid in acetonitrile and water (70:30, v/v) at 0.3mL/min for 4min. Chromatographic separation was followed by electrospray, positive-mode ionization tandem mass spectrometric detection in the multiple reaction monitoring (MRM) mode. The assay was linear from 0.1 to 300ng/mL and was accurate (-9.41 to -7.07%) and precise (1.03-13.7%) which fulfilled FDA criteria for validation. Recovery from plasma was 73.9-79.7% and ion suppression was negligible (-22.8 to -31.3%). Plasma freeze-thaw stability (99.97-105.7%), stability for 11 months at -80°C (94.93-107.9%), and stability for 6h at room temperature (94.75-105.5%) were all acceptable. This assay is currently being applied to quantitate iso-fludelone in clinical samples. Copyright © 2014 Elsevier B.V. All rights reserved.

The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

International Nuclear Information System (INIS)

He, Di; Chen, Wantao; Xu, Qin; Yan, Ming; Zhang, Ping; Zhou, Xiaojian; Zhang, Zhiyuan; Duan, Wenhu; Zhong, Laiping; Ye, Dongxia

2009-01-01

Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated. Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) in vitro. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA. The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased. The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The

ISO 9000

International Nuclear Information System (INIS)

Graham, J.F.

1992-01-01

The European Community has adopted the Single European Act. The act states that in order to do business in Europe after 1992, a supplied is expected to be ISO 9000 registered. This paper reports on ISO 9000, which is a systematic approach to implementing a quality system. It is not in the category of technical or product standards, but a standard relating to management of quality in that sector of a company seeking registration. If a company is already systematically practicing quality improvement, these efforts will be applicable to the ISO 9000 certification process. A company will need to refine and update procedures and develop a quality manual. An internal auditing and a corrective action system will also have to be established. The latter addresses audit results, customer complaints, quality system problems, and internal quality improvement suggestions

Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro-Inflammatory Response in RAW 264 Cells.

Science.gov (United States)

Yamamoto, Shunsuke; Ohta, Noriyuki; Matsumoto, Atsuhiro; Horiguchi, Yu; Koide, Moe; Fujino, Yuji

2016-02-04

BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-κB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL)-1β, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-κB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-κB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1β, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor.

Activation of NF-κB is involved in 6-hydroxydopamine-but not MPP+-induced dopaminergic neuronal cell death: its potential role as a survival determinant

International Nuclear Information System (INIS)

Park, Seong H.; Choi, Won-Seok; Yoon, So-Young; Ahn, Young Soo; Oh, Young J.

2004-01-01

The nuclear factor-kappaB (NF-κB) family plays an important role in the control of the apoptotic response. Its activation has been demonstrated in both neurons and glial cells in many neurological disorders. In the present study, we specifically examined whether and to what extent NF-κB activation is involved in culture models of Parkinson's disease following exposure of MN9D dopaminergic neuronal cells to 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-4-phenylpyridinium ion (MPP + ). Both analysis by immunocytochemistry and of immunoblots revealed that NF-κB-p65 was translocated into the nuclei following 6-OHDA but not MPP + -treatment. A time-dependent activation of NF-κB induced by 6-OHDA but not MPP + was also demonstrated by an electrophoretic mobility shift assay. A competition assay indicated that not only NF-κB-p65 but also -p50 is involved in 6-OHDA-induced NF-κB activity. Co-treatment with an antioxidant, N-acetyl-L-cysteine, blocked 6-OHDA-induced activation of NF-κB signaling. In the presence of an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), 6-OHDA-induced cell death was accelerated while PDTC did not affect MPP + -induced cell death. Our data may point to a drug-specific activation of NF-κB as a survival determinant for dopaminergic neurons

Tinjauan Kritis Terhadap Implementasi Iso 9000

OpenAIRE

Purnama, Nursya’bani

2005-01-01

ISO 9000 telah diterima secara luas sebagai acuan sistem manajemen kualitas dan penjaminan kualitas. Perusahaan-Perusahaan yang memperoleh sertifikasi ISO dari tahun ke ke tahun mengalami pertumbu¬han yang pesat. Dengan implementasi dan memperoleh sertifikasi ISO 9000, banyak Perusahaan di dunia mem¬peroleh peningkatan kinerja. Meskipun demikian, implementasi ISO 9000 juga dihadapkan pada sejumlah ham¬batan. Implementasi ISO 9000 seringkali dikaitkan dengan Total Quality Management (TQM). Ban...

Pentacyclic Triterpenoids Inhibit IKKβ Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences.

Directory of Open Access Journals (Sweden)

Kalpesh R Patil

Full Text Available Pentacyclic Triterpenoids (PTs and their analogues as well as derivatives are emerging as important drug leads for various diseases. They act through a variety of mechanisms and a majority of them inhibit the nuclear factor kappa-beta (NF-κB signaling pathway. In this study, we examined the effects of the naturally occurring PTs on IκB kinase-β (IKKβ, which has great scientific relevance in the NF-κB signaling pathway. On virtual screening, 109 PTs were screened through the PASS (prediction of activity spectra of substances software for prediction of NF-κB inhibitory activity followed by docking on the NEMO/IKKβ association complex (PDB: 3BRV and testing for compliance with the softened Lipinski's Rule of Five using Schrodinger (LLC, New York, USA. Out of the projected 45 druggable PTs, Corosolic Acid (CA, Asiatic Acid (AA and Ursolic Acid (UA were assayed for IKKβ kinase activity in the cell free medium. The UA exhibited a potent IKKβ inhibitory effect on the hotspot kinase assay with IC50 of 69 μM. Whereas, CA at 50 μM concentration markedly reduced the NF-κB luciferase activity and phospho-IKKβ protein expressions. The PTs tested, attenuated the expression of the NF-κB cascade proteins in the LPS-stimulated RAW 264.7 cells, prevented the phosphorylation of the IKKα/β and blocked the activation of the Interferon-gamma (IFN-γ. The results suggest that the IKKβ inhibition is the major mechanism of the PTs-induced NF-κB inhibition. PASS predictions along with in-silico docking against the NEMO/IKKβ can be successfully applied in the selection of the prospective NF-κB inhibitory downregulators of IKKβ phosphorylation.

The stability of iso-α-acids and reduced iso-α-acids in stored blood specimens.

Science.gov (United States)

Rodda, Luke N; Gerostamoulos, Dimitri; Drummer, Olaf H

2014-06-01

The long-term stability of the iso-α-acids, and three structurally similar but chemically altered iso-α-acids (known as 'reduced iso-α-acids' and consisting of the rho-, tetrahydro- and hexahydro-iso-α-acid groups) were investigated in whole blood. Pools of blank blood spiked with the four beer-specific ingredient congener groups at two different concentration levels were stored at 20°C, 4°C and -20°C; and extracted in duplicate in weeks 1, 3, 5 and 8, using a previously published method. A loss of 15% of the initial concentration was considered to indicate possible instability and losses greater than 30% demonstrated significant losses. The individual analytes within the four iso-α-acid groups were also measured to determine which iso-α-acids were subject to greater degradation and were responsible for the overall group instability. All four iso-α-acid groups showed significant losses after 8 weeks of storage under room temperature conditions in particularly the natural iso-α-acid group where major losses were observed (96% and 85% losses for low and high concentrations, respectively). Some degradation in all iso-α-acid groups were seen at 4°C samples predominantly due to the 'n' analogs of the groups showing an increased instability in blood. The -20°C storage conditions resulted in minimal changes in concentrations of all analytes. Higher than frozen storage temperatures can result in substantial changes on the stability of the iso-α-acid type groups in blood. The aim of this study was to highlight the stabilities of the IAA analytes in order to assist in the interpretation of IAA in stored blood specimens. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Effects of returning NF concentrate on the MBR-NF process treating antibiotic production wastewater.

Science.gov (United States)

Li, Kun; Cheng, Yutao; Wang, Jianxing; Zhang, Junya; Liu, Jibao; Yu, Dawei; Li, Mingyue; Wei, Yuansong

2016-07-01

The optimization of the nanofiltration (NF) concentrate backflow ratio (R cb) and the influence of the NF concentrate on the performance of membrane bioreactor-nanofiltration (MBR-NF) process treating antibiotic production wastewater were investigated on a laboratory scale. The R cb was optimized at 60 % based on the removal rates of chemical oxygen demand (COD) and NH4 (+)-N by MBR. Data analyses indicated that salinity brought by NF concentrate is the major driver leading to the decrease of sludge activity, especially at a high R cb. EPS analysis showed that electric conductivity (EC), proteins in soluble microbial products (SMP), and SMP brought by NF concentrate are the dominant factors causing the severe membrane fouling in MBR. Furthermore, undegradable substances including fulvic acid-like and humic acid-like compounds accumulated in NF concentrate showed significant influence on fouling of NF. MBR could well degrade small MW compounds in NF concentrate, which confirmed the enhancement of organic removal efficiency by recycling the NF concentrate to MBR. The MBR-NF process showed a relatively stable performance at the R cb of 60 % (volume reduction factor (VRF) = 5), and the NF permeate could satisfy the water quality standard for fermentation process with a water recovery rate of 90.9 %.

Inhibition of NF-κB activity in rabbit vascular smooth muscle cells by lovastatin

International Nuclear Information System (INIS)

Luan Zhaoxia; Lan Xiaoli

2003-01-01

Nuclear factor NF-κB is believed to play an important role in regulating the production of matrix metalloproteinase (MMPs), which induce atherosclerosis, restenosis and plaque rupture. We incubated rabbit vascular smooth muscle cells (RVSMCs) with 5 μmol/L lovastatin in the presence of IL-1-α and PDGF BB (20 μg/L, respectively) to study whether lovastatin inhibited NF-κB binding activity induced by IL-1 and PDGF. The NF-κB activity was detected by electrophoretic mobility shift assay (EMSA); MMP-1 and MMP-3 were measured by western blotting; and MMP-9 was detected by zymography. The result showed that lovastatin strongly reduced NF-κB activity upregulated by IL-1 combined with PDGF, and lovastatin also dose-dependently inhibited the expression of MMP-1, -3 and -9 induced by IL-1 and PDGF. It suggested that the beneficial effects of statins may extend to mechanisms beyond cholesterol reduction

ISO 14000 : environmental management systems

International Nuclear Information System (INIS)

Boutin, C.; Emard, C.; Lalonde, G.; Levesque, A.; Robitaille, R.; Rollin, A.L.; Thibeault, I.

1996-01-01

This book is addressed to the managers, professionals, and government agents which wish to know the philosophy of the step as well as the stages to be followed for the establishment of a system of environmental management in conformity with the standards of the series ISO 14000. This work locates ISO 14000 in the historical context of its development by describing the bonds with other standards in place of which those of the series ISO 9000. This book answers questions that arise regarding a companies step toward accreditation to ISO 14000

NDT technical assessment for ISO 17025 and ISO 17020 certification

International Nuclear Information System (INIS)

Mohamad Pauzi Ismail

2011-01-01

ISO 17025 is an international standard that states the requirement criteria for testing and calibration laboratory, while ISO 17020 is for inspection body. Standard Malaysia is the accreditation body for both standards. The author involved in the technical assessment for both standards both in Nuclear Malaysia and outside. The experience in performing NDT assessment activity is explained and discussed. The comparison between both standards is also discussed. (author)

Explanation and practice on ISO 9000

International Nuclear Information System (INIS)

Kwon, Dong Myeong

2001-01-01

This book reveals introduction on revision of ISO 9000:2000 with full account and contents of revision and change method change into ISO 9001:2000, the basic principle on ISO 9000:2000 and improvement and aim, definition on explanation, method for detail term, demand for ISO/KS A 9001:2000, quality management system development and transition way, standardization for quality management, manual of quality and making procedure and guide, case of quality manual and procedure and guide and ISO 9001:2000 / KS A 9001:2001 an English-Korean translation.

Laadun- ja riskienhallinta johtamisjärjestelmässä ISO 9001:2015 ja ISO 31000:2009 mukaisesti

OpenAIRE

Reinvall, Niko; Karhunen, Joonas

2015-01-01

Tämän opinnäytetyön tarkoituksena on tarkastella riskienhallinnan ja laadunhallintajärjestelmien suhdetta ISO 9001:2015 ja ISO 31000:2009-standardien viitekehyksessä, tutkimuskysymyksen ollessa ”miten ja miksi integroida ISO 9001 mukaista laadunhallintaa ja ISO 31000 mukaista riskienhallintaa organisaation johtamisjärjestelmään”. Lisäksi työssä tarkastellaan standardien välisiä yhtymäkohtia ja riskienhallinnan merkitystä ISO 9001:2015 mukaisessa laadunhallintajärjestelmässä. Työn tilaaja...

p55PIK regulates alpha-fetoprotein expression through the NF-κB signaling pathway.

Science.gov (United States)

Ye, Guoguo; Sun, Ge; Cheng, Zhikui; Zhang, Lei; Hu, Kanghong; Xia, Xianmin; Zhou, Yin

2017-12-15

Alpha-fetoprotein (AFP) is regarded as a diagnostic and prognostic biomarker and a potential therapeutic target for hepatocellular carcinoma (HCC). However, the regulation of AFP expression in HCC remains poorly understood. This study aimed to investigate the mechanism by which AFP expression is regulated by p55PIK, an isoform of PI3K. Human HCC cell lines (HepG2 and Huh-7) were treated with p55PIK specific competitive inhibitor or shRNA, or p55PIK overexpression vector, in the absence or presence of NF-κB inhibitor PDTC. AFP expression was detected by quantitative real-time PCR and Western blotting. NF-κB responsive elements in AFP enhancer region were characterized by luciferase reporter assay. p55PIK significantly stimulated the expression of AFP by activating NF-κB signaling pathway in HCC cells. Furthermore, two NF-κB binding sites in AFP enhancer region were identified to be primarily responsible for p55PIK mediated upregulation of AFP expression. p55PIK/NF-κB signaling plays an important role in the upregulation of AFP expression in HCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Veronicastrum axillare Alleviates Ethanol-Induced Injury on Gastric Epithelial Cells via Downregulation of the NF-kB Signaling Pathway

Directory of Open Access Journals (Sweden)

Wei-chun Zhao

2017-01-01

Full Text Available We used human gastric epithelial cells (GES-1 line in an ethanol-induced cell damage model to study the protective effect of Veronicastrum axillare and its modulation to NF-κB signal pathway. The goal was to probe the molecular mechanism of V. axillare decoction in the prevention of gastric ulcer and therefore provide guidance in the clinical application of V. axillare on treating injuries from chronic nephritis, pleural effusion, gastric ulcer, and other ailments. The effects of V. axillare-loaded serums on cell viability were detected by MTT assays. Enzyme-linked immunosorbent assay (ELISA and Real-Time PCR methods were used to analyze the protein and mRNA expression of TNF-α, NF-κB, IκBα, and IKKβ. The results showed that V. axillare-loaded serum partially reversed the damaging effects of ethanol and NF-κB activator (phorbol-12-myristate-13-acetate: PMA and increased cell viability. The protein and mRNA expressions of TNF-α, NF-κB, IκBα, and IKKβ were significantly upregulated by ethanol and PMA while they were downregulated by V. axillare-loaded serum. In summary, V. axillare-loaded serum has significantly protective effect on GES-1 against ethanol-induced injury. The protective effect was likely linked to downregulation of TNF-α based NF-κB signal pathway.

75 FR 7581 - RTO/ISO Performance Metrics; Notice Requesting Comments on RTO/ISO Performance Metrics

Science.gov (United States)

2010-02-22

... performance communicate about the benefits of RTOs and, where appropriate, (2) changes that need to be made to... of staff from all the jurisdictional ISOs/RTOs to develop a set of performance metrics that the ISOs/RTOs will use to report annually to the Commission. Commission staff and representatives from the ISOs...

The PRR11-SKA2 Bidirectional Transcription Unit Is Negatively Regulated by p53 through NF-Y in Lung Cancer Cells

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Yitao Wang

2017-03-01

Full Text Available We previously identified proline-rich protein 11 (PRR11 as a novel cancer-related gene that is implicated in the regulation of cell cycle and tumorigenesis. Our recent study demonstrated that PRR11 and its adjacent gene, kinetochore associated 2 (SKA2, constitute a classic head-to-head gene pair that is coordinately regulated by nuclear factor Y (NF-Y. In the present study, we further show that the PRR11-SKA2 bidirectional transcription unit is an indirect target of the tumor suppressor p53. A luciferase reporter assay revealed that overexpression of wild type p53, but not mutant p53, significantly represses the basal activity and NF-Y mediated transactivation of the PRR11-SKA2 bidirectional promoter. Deletion and mutation analysis of the PRR11-SKA2 promoter revealed that p53-mediated PRR11-SKA2 repression is dependent on the presence of functional NF-Y binding sites. Furthermore, a co-immunoprecipitation assay revealed that p53 associates with NF-Y in lung cancer cells, and a chromatin immunoprecipitation assay showed that p53 represses PRR11-SKA2 transcription by reducing the binding amount of NF-Y in the PRR11-SKA2 promoter region. Consistently, the ability of p53 to downregulate PRR11-SKA2 transcription was significantly attenuated upon siRNA-mediated depletion of nuclear factor Y subunit beta (NF-YB. Notably, lung cancer patients with lower expression of either PRR11 or SKA2 along with wild type p53 exhibited the best overall survival compared with others with p53 mutation and/or higher expression of either PRR11 or SKA2. Taken together, our results demonstrate that p53 negatively regulates the expression of the PRR11-SKA2 bidirectional transcription unit through NF-Y, suggesting that the inability to repress the PRR11-SKA2 bidirectional transcription unit after loss of p53 might contribute to tumorigenesis.

Methylation-Dependent Activation of CDX1 through NF-κB

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Rau, Tilman T.; Rogler, Anja; Frischauf, Myrjam; Jung, Andreas; Konturek, Peter C.; Dimmler, Arno; Faller, Gerhard; Sehnert, Bettina; El-Rifai, Wael; Hartmann, Arndt; Voll, Reinhard E.; Schneider-Stock, Regine

2013-01-01

The caudal homeobox factor 1 (CDX1) is an essential transcription factor for intestinal differentiation. Its aberrant expression in intestinal metaplasia of the upper gastrointestinal tract is a hallmark within the gastritis-metaplasia-carcinoma sequence. CDX1 expression is influenced by certain pathways, such as Wnt, Ras, or NF-κB signaling; however, these pathways alone cannot explain the transient expression of CDX1 in intestinal metaplasia or the molecular inactivation mechanism of its loss in cases of advanced gastric cancer. In this study, we investigated the epigenetic inactivation of CDX1 by promoter methylation, as well as the functional link of CDX1 promoter methylation to the inflammatory NF-κB signaling pathway. We identified methylation-dependent NF-κB binding to the CDX1 promoter and quantified it using competitive electrophoretic mobility shift assays and chromatin immunoprecipitation. A methylated CDX1 promoter was associated with closed chromatin structure, reduced NF-κB binding, and transcriptional silencing. Along the gastritis-metaplasia-carcinoma sequence, we observed a biphasic pattern of tumor necrosis factor-α (TNF-α) protein expression and an inverse biphasic pattern of CDX1 promoter methylation; both are highly consistent with CDX1 protein expression. The stages of hyper-, hypo-, and hyper-methylation patterns of the CDX1 promoter were inversely correlated with the NF-κB signaling activity along this sequence. In conclusion, these functionally interacting events drive CDX1 expression and contribute to intestinal metaplasia, epithelial dedifferentiation, and carcinogenesis in the human stomach. PMID:22749770

Inhibitory effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation

International Nuclear Information System (INIS)

Shi Jianhui; Niu Yuhong; Ge Junbo; Xu Xiaoping; Cheng Wenying; Feng Xiao; Zhang Zongliang

2002-01-01

Objective: To explore effects of glucocorticoid on apoptosis and activation of NF-κB in P388 cells induced by radiation. Methods: Apoptosis in P388 cells induced by radiation treatment was detected by TUNEL assay. EMSA was used to detect the activation of NF-κB . Results: The apoptosis and activation of NF-κB in P388 cells could be induced by radiation. Dexamethasone (DXM) which could suppress activation of NF-κB of P388 cells increased significantly the apoptosis induced by radiation. Apoptosis rates in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure increased by 60%, 100%, 129% and 67%, respectively. Activation rates of NF-κB in DXM-treated P388 cells after 2, 4, 6 and 8 Gy exposure decreased by 25%, 45%, 52% and 40%, respectively. Conclusion: Radiation induces apoptosis and activation of NF-κB in P388 cells simultaneously. Glucocorticoid enhances apoptosis in leukemic cells, which may be by means of suppressing activation of NF-κB

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

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Kim, Ji H; Gupta, Subash C; Park, Byoungduck; Yadav, Vivek R; Aggarwal, Bharat B

2012-03-01

The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Generation and quenching of NF(a) and NF(b) molecules

International Nuclear Information System (INIS)

Setser, D.W.; Cha, H.; Quinones, E.; Du, K.

1987-01-01

The Ar( 3 Po,2) + NF 2 and 2F + HN 3 reactions have been developed as sources of NF(b 1 Σ + ) and NF(a 1 Δ) molecules, respectively, in a flow reactor. The decay kinetics for these molecules in the presence of added reagent can be studied using standard flow reactor techniques. Room temperature quenching rate constants for both molecules are reported for several reagents and compared to results for the isoelectronic O 2 (a) and O 2 (b) molecules

OsNF-YC2 and OsNF-YC4 proteins inhibit flowering under long-day conditions in rice

KAUST Repository

Kim, SoonKap

2015-11-05

OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response through the modulation of three flowering-time genes ( Ehd1, Hd3a , and RFT1 ) in rice. Plant NUCLEAR FACTOR Y (NF-Y) transcription factors control numerous developmental processes by forming heterotrimeric complexes, but little is known about their roles in flowering in rice. In this study, it is shown that some subunits of OsNF-YB and OsNF-YC interact with each other, and among them, OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response of rice. Protein interaction studies showed that the physical interactions occurred between the three OsNF-YC proteins (OsNF-YC2, OsNF-YC4 and OsNF-YC6) and three OsNF-YB proteins (OsNF-YB8, OsNF-YB10 and OsNF-YB11). Repression and overexpression of the OsNF-YC2 and OsNF-YC4 genes revealed that they act as inhibitors of flowering only under long-day (LD) conditions. Overexpression of OsNF-YC6, however, promoted flowering only under LD conditions, suggesting it could function as a flowering promoter. These phenotypes correlated with the changes in the expression of three rice flowering-time genes [Early heading date 1 (Ehd1), Heading date 3a (Hd3a) and RICE FLOWERING LOCUS T1 (RFT1)]. The diurnal and tissue-specific expression patterns of the subsets of OsNF-YB and OsNF-YC genes were similar to those of CCT domain encoding genes such as OsCO3, Heading date 1 (Hd1) and Ghd7. We propose that OsNF-YC2 and OsNF-YC4 proteins regulate the photoperiodic flowering response by interacting directly with OsNF-YB8, OsNF-YB10 or OsNF-YB11 proteins in rice.

Lycopene acts through inhibition of IκB kinase to suppress NF-κB signaling in human prostate and breast cancer cells.

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Assar, Emelia A; Vidalle, Magdalena Castellano; Chopra, Mridula; Hafizi, Sassan

2016-07-01

We studied the effect of the potent dietary antioxidant lycopene on multiple points along the nuclear factor kappa B (NF-κB) signaling pathway in prostate and breast cancer cells. Lycopene significantly inhibited prostate and breast cancer cell growth at physiologically relevant concentrations of ≥1.25 μM. Similar concentrations also caused a 30-40 % reduction in inhibitor of kappa B (IκB) phosphorylation in the cells, as determined by western blotting. Furthermore, the same degree of inhibition by lycopene was observed for NF-κB transcriptional activity, as determined by reporter gene assay. Concomitant with this, immunofluorescence staining of lycopene-treated cells showed a significant suppression (≥25 %) of TNF-induced NF-κB p65 subunit nuclear translocation. Further probing of lycopene's effects on upstream elements of the NF-κB pathway showed a 25 % inhibition of both activity of recombinant IκB kinase β (IKKβ) kinase in a cell-free in vitro assay, as well as activity of IKKβ immunoprecipitated from MDA-MB-231 cells treated with lycopene. In conclusion, the anticancer properties of lycopene may occur through inhibition of the NF-κB signaling pathway, beginning at the early stage of cytoplasmic IKK kinase activity, which then leads to reduced NF-κB-responsive gene regulation. Furthermore, these effects in cancer cells were observed at concentrations of lycopene that are relevant and achievable in vivo.

PAMPA--a drug absorption in vitro model. 5. Unstirred water layer in iso-pH mapping assays and pKa(flux)--optimized design (pOD-PAMPA).

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Ruell, Jeffrey A; Tsinman, Konstantin L; Avdeef, Alex

2003-12-01

Iso-pH mapping unstirred parallel artificial membrane permeability assay (PAMPA) was used to measure the effective permeability, P(e), as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, P(o), the unstirred water layer (UWL) permeability, P(u), and the apparent pK(a) (pK(a)(flux)) were determined from the pH dependence of logP(e). The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases and ampholytes. The average thickness of the unstirred water layer on each side of the membrane was estimated to be nearly 2000 microm, somewhat larger than that found in Caco-2 permeability assays (unstirred). Since the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g. pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially-selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log P(e)-pH plots, a method to improve the selection of the assay pH, called pK(a)(flux)-optimized design (pOD-PAMPA), was described and tested. From an optimally-selected assay pH, it is possible to estimate P(o), as well as the entire membrane permeability-pH profile.

Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression

International Nuclear Information System (INIS)

Woodfield, Sarah E.; Zhang, Linna; Scorsone, Kathleen A.; Liu, Yin; Zage, Peter E.

2016-01-01

Novel therapies are needed for children with high-risk and relapsed neuroblastoma. We hypothesized that MAPK/ERK kinase (MEK) inhibition with the novel MEK1/2 inhibitor binimetinib would be effective in neuroblastoma preclinical models. Levels of total and phosphorylated MEK and extracellular signal-regulated kinase (ERK) were examined in primary neuroblastoma tumor samples and in neuroblastoma cell lines by Western blot. A panel of established neuroblastoma tumor cell lines was treated with increasing concentrations of binimetinib, and their viability was determined using MTT assays. Western blot analyses were performed to examine changes in total and phosphorylated MEK and ERK and to measure apoptosis in neuroblastoma tumor cells after binimetinib treatment. NF1 protein levels in neuroblastoma cell lines were determined using Western blot assays. Gene expression of NF1 and MEK1 was examined in relationship to neuroblastoma patient outcomes. Both primary neuroblastoma tumor samples and cell lines showed detectable levels of total and phosphorylated MEK and ERK. IC 50 values for cells sensitive to binimetinib ranged from 8 nM to 1.16 μM, while resistant cells did not demonstrate any significant reduction in cell viability with doses exceeding 15 μM. Sensitive cells showed higher endogenous expression of phosphorylated MEK and ERK. Gene expression of NF1, but not MEK1, correlated with patient outcomes in neuroblastoma, and NF1 protein expression also correlated with responses to binimetinib. Neuroblastoma tumor cells show a range of sensitivities to the novel MEK inhibitor binimetinib. In response to binimetinib, sensitive cells demonstrated complete loss of phosphorylated ERK, while resistant cells demonstrated either incomplete loss of ERK phosphorylation or minimal effects on MEK phosphorylation, suggesting alternative mechanisms of resistance. NF1 protein expression correlated with responses to binimetinib, supporting the use of NF1 as a biomarker to identify

ISO 639-1 and ISO 639-2: International Standards for Language Codes. ISO 15924: International Standard for Names of Scripts.

Science.gov (United States)

Byrum, John D.

This paper describes two international standards for the representation of the names of languages. The first (ISO 639-1), published in 1988, provides two-letter codes for 136 languages and was produced primarily to meet terminological needs. The second (ISO 639-2) appeared in late 1998 and includes three-letter codes for 460 languages. This list…

Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

KAUST Repository

Hwang, Yoon-Hyung; Kim, SoonKap; Lee, Keh Chien; Chung, Young Soo; Lee, Jeong Hwan; Kim, Jeong-Kook

2016-01-01

Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

Functional conservation of rice OsNF-YB/YC and Arabidopsis AtNF-YB/YC proteins in the regulation of flowering time

KAUST Repository

Hwang, Yoon-Hyung

2016-01-11

Plant NUCLEAR FACTOR Y (NF-Y) transcription factors play important roles in plant development and abiotic stress. In Arabidopsis thaliana, two NF-YB (AtNF-YB2 and AtNF-YB3) and five NF-YC (AtNF-YC1, AtNF-YC2, AtNF-YC3, AtNF-YC4, and AtNF-YC9) genes regulate photoperiodic flowering by interacting with other AtNF-Y subunit proteins. Three rice NF-YB (OsNF-YB8, OsNF-YB10, and OsNF-YB11) and five rice OsNF-YC (OsNF-YC1, OsNF-YC2, OsNF-YC4, OsNF-YC6, and OsNF-YC7) genes are clustered with two AtNF-YB and five AtNF-YC genes, respectively. To investigate the functional conservation of these NF-YB and NF-YC genes in rice and Arabidopsis, we analyzed the flowering phenotypes of transgenic plants overexpressing the respective OsNF-YB and OsNF-YC genes in Arabidopsis mutants. Overexpression of OsNF-YB8/10/11 and OsNF-YC2 complemented the late flowering phenotype of Arabidopsis nf-yb2 nf-yb3 and nf-yc3 nf-yc4 nf-yc9 mutants, respectively. The rescued phenotype of 35S::OsNF-YC2 nf-yc3 nf-yc4 nf-yc9 plants was attributed to the upregulation of FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1). In vitro and in planta protein–protein analyses revealed that OsNF-YB8/10/11 and OsNF-YC1/2/4/6/7 interact with AtNF-YC3/4/9 and AtNF-YB2/3, respectively. Our data indicate that some OsNF-YB and OsNF-YC genes are functional equivalents of AtNF-YB2/3 and AtNF-YC3/4/9 genes, respectively, and suggest functional conservation of Arabidopsis and rice NF-Y genes in the control of flowering time.

NF-κB Signaling Regulates Epstein–Barr Virus BamHI-Q-Driven EBNA1 Expression

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Rob J. A. Verhoeven

2018-04-01

Full Text Available Epstein–Barr virus (EBV nuclear antigen 1 (EBNA1 is one of the few viral proteins expressed by EBV in nasopharyngeal carcinoma (NPC, most likely because of its essential role in maintaining the viral genome in EBV-infected cells. In NPC, EBNA1 expression is driven by the BamHI-Q promoter (Qp, which is regulated by both cellular and viral factors. We previously determined that the expression of another group of EBV transcripts, BamHI-A rightward transcripts (BARTs, is associated with constitutively activated nuclear factor-κB (NF-κB signaling in NPC cells. Here, we show that, like the EBV BART promoter, the EBV Qp also responds to NF-κB signaling. NF-κB p65, but not p50, can activate Qp in vitro, and NF-κB signaling regulates Qp-EBNA1 expression in NPC cells, as well as in other EBV-infected epithelial cells. The introduction of mutations in the putative NF-κB site reduced Qp activation by the NF-κB p65 subunit. Binding of p65 to Qp was shown by chromatin immunoprecipitation (ChIP analysis, while electrophoretic mobility shift assays (EMSAs demonstrated that p50 can also bind to Qp. Inhibition of NF-κB signaling by the IκB kinase inhibitor PS-1145 resulted in the downregulation of Qp-EBNA1 expression in C666-1 NPC cells. Since EBNA1 has been reported to block p65 activation by inhibiting IKKα/β through an unknown mechanism, we suggest that, in NPC, NF-κB signaling and EBNA1 may form a regulatory loop which supports EBV latent gene expression, while also limiting NF-κB activity. These findings emphasize the role of NF-κB signaling in the regulation of EBV latency in EBV-associated tumors.

Persistent activation of NF-kappaB related to IkappaB's degradation profiles during early chemical hepatocarcinogenesis

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García-Román Rebeca

2007-04-01

Full Text Available Abstract Background To define the NF-kappaB activation in early stages of hepatocarcinogenesis and its IkappaB's degradation profiles in comparison to sole liver regeneration. Methods Western-blot and EMSA analyses were performed for the NF-kappaB activation. The transcriptional activity of NF-kappaB was determined by RT-PCR of the IkappaB-α mRNA. The IkappaB's degradation proteins were determined by Western-blot assay. Results We demonstrated the persistent activation of NF-kappaB during early stages of hepatocarcinogenesis, which reached maximal level 30 min after partial hepatectomy. The DNA binding and transcriptional activity of NF-kappaB, were sustained during early steps of hepatocarcinogenesis in comparison to only partial hepatectomy, which displayed a transitory NF-kappaB activation. In early stages of hepatocarconogenesis, the IkappaB-α degradation turned out to be acute and transitory, but the low levels of IkappaB-β persisted even 15 days after partial hepatectomy. Interestingly, IkappaB-β degradation is not induced after sole partial hepatectomy. Conclusion We propose that during liver regeneration, the transitory stimulation of the transcription factor response, assures blockade of NF-kappaB until recovery of the total mass of the liver and the persistent NF-kappaB activation in early hepatocarcinogenesis may be due to IkappaB-β and IkappaB-α degradation, mainly IkappaB-β degradation, which contributes to gene transcription related to proliferation required for neoplasic progression.

Anti-proliferative, Cytotoxic and NF-ĸB Inhibitory Properties of Spiro(Lactone-Cyclohexanone) Compounds in Human Leukemia.

Science.gov (United States)

Bouhenna, Mustapha M; Orlikova, Barbora; Talhi, Oualid; Schram, Ben; Pinto, Diana C G A; Taibi, Nadia; Bachari, Khaldoun; Diederich, Marc; Silva, Artur M S; Mameri, Nabil

2017-09-01

NF-ĸB affects most aspects of cellular physiology. Deregulation of NF-ĸB signaling is associated with inflammatory diseases and cancer. In this study, we evaluated the cytotoxic and NF-ĸB inhibition potential of new spiro(lactone-cyclohexanone) compounds in two different human leukemia cell lines (U937 and K562). The anti-proliferative effects of the spiro(lactone-cyclohexanone) compounds on human K562 and U937 cell lines was evaluated by trypan blue staining, as well as their involvement in NF-kB regulation were analyzed by luciferase reporter gene assay, Caspase-3/7 activities were evaluated to analyze apoptosis induction. Both spiro(coumarin-cyclohexanone) 4 and spiro(6- methyllactone-cyclohexanone) 9 down-regulated cancer cell viability and proliferation. Compound 4 inhibited TNF-α-induced NF-ĸB activation in a dose-dependent manner and induced caspase-dependent apoptosis in both leukemia cell lines. Results show that compound 4 and compound 9 have potential as anti-cancer agents. In addition, compound 4 exerted NF-kB inhibition activity in leukemia cancer cells. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

The Arabidopsis NF-YA3 and NF-YA8 genes are functionally redundant and are required in early embryogenesis.

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Monica Fornari

Full Text Available Nuclear factor Y (NF-Y is a trimeric transcription factor composed of three distinct subunits called NF-YA, NF-YB and NF-YC. In Arabidopsis thaliana, NF-Y subunits are known to play roles in many processes, such as gametogenesis, embryogenesis, seed development, drought resistance, ABA signaling, flowering time, primary root elongation, Endoplasmic Reticulum (ER stress response and blue light responses. Here, we report that the closely related NF-YA3 and NF-YA8 genes control early embryogenesis. Detailed GUS and in situ analyses showed that NF-YA3 and NF-YA8 are expressed in vegetative and reproductive tissues with the highest expression being during embryo development from the globular to the torpedo embryo stage. Plants from the nf-ya3 and nf-ya8 single mutants do not display any obvious phenotypic alteration, whereas nf-ya3 nf-ya8 double mutants are embryo lethal. Morphological analyses showed that the nf-ya3 nf-ya8 embryos fail to undergo to the heart stage and develop into abnormal globular embryos with both proembryo and suspensor characterized by a disordered cell cluster with an irregular shape, suggesting defects in embryo development. The suppression of both NF-YA3 and NF-YA8 gene expression by RNAi experiments resulted in defective embryos that phenocopied the nf-ya3 nf-ya8 double mutants, whereas complementation experiments partially rescued the abnormal globular nf-ya3 nf-ya8 embryos, confirming that NF-YA3 and NF-YA8 are required in early embryogenesis. Finally, the lack of GFP expression of the auxin responsive DR5rev::GFP marker line in double mutant embryos suggested that mutations in both NF-YA3 and NF-YA8 affect auxin response in early developing embryos. Our findings indicate that NF-YA3 and NF-YA8 are functionally redundant genes required in early embryogenesis of Arabidopsis thaliana.

Neuronal RING finger protein 11 (RNF11 regulates canonical NF-κB signaling

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Pranski Elaine L

2012-04-01

Full Text Available Abstract Background The RING domain-containing protein RING finger protein 11 (RNF11 is a member of the A20 ubiquitin-editing protein complex and modulates peripheral NF-κB signaling. RNF11 is robustly expressed in neurons and colocalizes with a population of α-synuclein-positive Lewy bodies and neurites in Parkinson disease patients. The NF-κB pathway has an important role in the vertebrate nervous system, where the absence of NF-κB activity during development can result in learning and memory deficits, whereas chronic NF-κB activation is associated with persistent neuroinflammation. We examined the functional role of RNF11 with respect to canonical NF-κB signaling in neurons to gain understanding of the tight association of inflammatory pathways, including NF-κB, with the pathogenesis of neurodegenerative diseases. Methods and results Luciferase assays were employed to assess NF-κB activity under targeted short hairpin RNA (shRNA knockdown of RNF11 in human neuroblastoma cells and murine primary neurons, which suggested that RNF11 acts as a negative regulator of canonical neuronal NF-κB signaling. These results were further supported by analyses of p65 translocation to the nucleus following depletion of RNF11. Coimmunoprecipitation experiments indicated that RNF11 associates with members of the A20 ubiquitin-editing protein complex in neurons. Site-directed mutagenesis of the myristoylation domain, which is necessary for endosomal targeting of RNF11, altered the impact of RNF11 on NF-κB signaling and abrogated RNF11’s association with the A20 ubiquitin-editing protein complex. A partial effect on canonical NF-κB signaling and an association with the A20 ubiquitin-editing protein complex was observed with mutagenesis of the PPxY motif, a proline-rich region involved in Nedd4-like protein interactions. Last, shRNA-mediated reduction of RNF11 in neurons and neuronal cell lines elevated levels of monocyte chemoattractant protein 1 and

Isorhapontigenin (ISO) inhibited cell transformation by inducing G0/G1 phase arrest via increasing MKP-1 mRNA Stability.

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Gao, Guangxun; Chen, Liang; Li, Jingxia; Zhang, Dongyun; Fang, Yong; Huang, Haishan; Chen, Xiequn; Huang, Chuanshu

2014-05-15

The cancer chemopreventive property of Chinese herb new isolate isorhapontigenin (ISO) and mechanisms underlying its activity have never been explored. Here we demonstrated that ISO treatment with various concentrations for 3 weeks could dramatically inhibit TPA/EGF-induced cell transformation of Cl41 cells in Soft Agar assay, whereas co-incubation of cells with ISO at the same concentrations could elicit G0/G1 cell-cycle arrest without redundant cytotoxic effects on non-transformed cells. Further studies showed that ISO treatment resulted in cyclin D1 downregulation in dose- and time-dependent manner. Our results indicated that ISO regulated cyclin D1 at transcription level via targeting JNK/C-Jun/AP-1 activation. Moreover, we found that ISO-inhibited JNK/C-Jun/AP-1 activation was mediated by both upregulation of MKP-1 expression through increasing its mRNA stability and deactivating MKK7. Most importantly, MKP-1 knockdown could attenuate ISO-mediated suppression of JNK/C-Jun activation and cyclin D1 expression, as well as G0/G1 cell cycle arrest and cell transformation inhibition, while ectopic expression of FLAG-cyclin D1 T286A mutant also reversed ISO-induced G0/G1 cell-cycle arrest and inhibition of cell transformation. Our results demonstrated that ISO is a promising chemopreventive agent via upregulating mkp-1 mRNA stability, which is distinct from its cancer therapeutic effect with downregulation of XIAP and cyclin D1 expression.

Control: the effects of ISO

NARCIS (Netherlands)

Laura Ilzarbe; PhD Everard van Kemenade; Maria-Jezus Alvarez

2007-01-01

De effecten van ISO-certificering zoals gerapporteerd in wetenschappelijk onderzoek. Met speciale aandacht voor de resultaten in het onderwijs. ISO 9000:2000 doet het nadrukkelijk beter dan haar vorige versies.

Reconstitution of the NF1 GAP-related domain in NF1-deficient human Schwann cells

International Nuclear Information System (INIS)

Thomas, Stacey L.; Deadwyler, Gail D.; Tang, Jun; Stubbs, Evan B.; Muir, David; Hiatt, Kelly K.; Clapp, D. Wade; De Vries, George H.

2006-01-01

Schwann cells derived from peripheral nerve sheath tumors from individuals with Neurofibromatosis Type 1 (NF1) are deficient for the protein neurofibromin, which contains a GAP-related domain (NF1-GRD). Neurofibromin-deficient Schwann cells have increased Ras activation, increased proliferation in response to certain growth stimuli, increased angiogenic potential, and altered cell morphology. This study examined whether expression of functional NF1-GRD can reverse the transformed phenotype of neurofibromin-deficient Schwann cells from both benign and malignant peripheral nerve sheath tumors. We reconstituted the NF1-GRD using retroviral transduction and examined the effects on cell morphology, growth potential, and angiogenic potential. NF1-GRD reconstitution resulted in morphologic changes, a 16-33% reduction in Ras activation, and a 53% decrease in proliferation in neurofibromin-deficient Schwann cells. However, NF1-GRD reconstitution was not sufficient to decrease the in vitro angiogenic potential of the cells. This study demonstrates that reconstitution of the NF1-GRD can at least partially reverse the transformation of human NF1 tumor-derived Schwann cells

International Organization for Standardization (ISO) 15189.

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Schneider, Frank; Maurer, Caroline; Friedberg, Richard C

2017-09-01

The College of American Pathologists (CAP) offers a suite of laboratory accreditation programs, including one specific to accreditation to the international organization for standardization (ISO) 15189 standard for quality management specific to medical laboratories. CAP leaders offer an overview of ISO 15189 including its components, internal audits, occurrence management, document control, and risk management. The authors provide a comparison of its own ISO 15189 program, CAP 15189, to the CAP Laboratory Accreditation Program. The authors conclude with why laboratories should use ISO 15189. © The Korean Society for Laboratory Medicine.

A practical synthesis of long-chain iso-fatty acids (iso-C12–C19 and related natural products

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Mark B. Richardson

2013-09-01

Full Text Available A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12–C19 was developed commencing with methyl undec-10-enoate (methyl undecylenate (for iso-C12–C14 or the C15 and C16 lactones pentadecanolide (for iso-C15–C17 and hexadecanolide (for iso-C18–C19. Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13–C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S-2,15-dimethylpalmitic acid, (S-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.

Iso-suillin from Suillus flavus Induces Apoptosis in Human Small Cell Lung Cancer H446 Cell Line.

Science.gov (United States)

Zhao, Jun-Xia; Zhang, Qing-Shuang; Chen, Ying; Yao, Sheng-Jie; Yan, Yong-Xin; Wang, Ying; Zhang, Jin-Xiu; Wang, Li-An

2016-05-20

The suillin isoform iso-suillin is a natural substance isolated from a petroleum ether extract of the fruiting bodies of the mushroom Suillus flavus. Previous studies have found its inhibition effect on some cancer cells, and we aimed to study its effects on human small cell lung cancer H446 cell line. Cell viability was measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Cellular morphological changes (apoptosis and necrosis) were evaluated using an electron microscope and Hoechst 33258 staining detected by the inverted microscope. Flow cytometry was used to detect cell apoptosis, cell cycle distribution, and mitochondrial membrane potential. Protein expression was determined by Western blotting analysis. Here, we describe the ability of iso-suillin to inhibit the growth of H446 cells in time- and dose-dependent way. Iso-suillin had no obvious impact on normal human lymphocyte proliferation at low concentrations (9.09, 18.17, or 36.35 μmol/L) but promoted lymphocyte proliferation at a high concentration (72.70 μmol/L). After treatment of different concentrations of iso-suillin (6.82, 13.63, or 20.45 μmol/L), the apoptosis rate of H446 cells increased with increasing concentrations of iso-suillin (16.70%, 35.54%, and 49.20%, respectively, all P iso-suillin could induce H446 cell apoptosis through the mitochondrial pathway and the death-receptor pathway. Therefore, iso-suillin might have a potential application as a novel drug for lung cancer treatment.

ISO 9000 Quality Management System

Science.gov (United States)

Hadjicostas, Evsevios

The ISO 9000 series describes a quality management system applicable to any organization. In this chapter we present the requirements of the standard in a way that is as close as possible to the needs of analytical laboratories. The sequence of the requirements follows that in the ISO 9001:2008 standard. In addition, the guidelines for performance improvement set out in the ISO 9004 are reviewed. Both standards should be used as a reference as well as the basis for further elaboration.

Targeting the NF-κB Pathway as a Combination Therapy for Advanced Thyroid Cancer.

Directory of Open Access Journals (Sweden)

Nikita Pozdeyev

Full Text Available NF-κB signaling plays an important role in tumor cell proliferation, cell survival, angiogenesis, invasion, metastasis and drug/radiation resistance. Combination therapy involving NF-κB pathway inhibition is an attractive strategy for the treatment of advanced forms of thyroid cancer. This study was designed to test the efficacy of NF-κB pathway inhibition in combination with cytotoxic chemotherapy, using docetaxel and ionizing radiation in in vitro models of thyroid cancer. We found that while both docetaxel and ionizing radiation activated NF-κB signaling in thyroid cancer cells, there was no synergistic effect on cell proliferation and/or programmed cell death with either genetic (transduction of a dominant negative mutant form of IκBα or pharmacologic (proteasome inhibitor bortezomib and IKKβ inhibitor GO-Y030 inhibition of the NF-κB pathway in thyroid cancer cell lines BCPAP, 8505C, THJ16T and SW1736. Docetaxel plus bortezomib synergistically decreased in vitro invasion of 8505C cells, but not in the other cell lines. Screening of a panel of clinically relevant targeted therapies for synergy with genetic NF-κB inhibition in a proliferation/cytotoxicity assay identified the histone deacetylase (HDAC inhibitor suberoylanilide hydroxamic acid (SAHA as a potential candidate. However, the synergistic effect was confirmed only in the BCPAP cells. These results indicate that NF-κB inhibitors are unlikely to be beneficial as combination therapy with taxane cytotoxic chemotherapy, external radiation therapy or radioiodine therapy. There may be unique circumstances where NF-κB inhibitors may be considered in combination with docetaxel to reduce tumor invasion or in combination with HDAC inhibitors to reduce tumor growth, but this does not appear to be a combination therapy that could be broadly applied to patients with advanced thyroid cancer. Further research may identify which subsets of patients/tumors may respond to this therapeutic

The European Large Area ISO Survey

DEFF Research Database (Denmark)

Oliver, S.; Rowan-Robinson, M.; Alexander, D.M.

2000-01-01

We describe the European Large Area ISO Survey (ELAIS). ELAIS was the largest single Open Time project conducted by ISO, mapping an area of 12 deg(2) at 15 mu m with ISOCAM and at 90 mu m with ISOPHOT. Secondary surveys in other ISO bands were undertaken by the ELAIS team within the fields of the...

Prevalence of bortezomib-resistant constitutive NF-kappaB activity in mantle cell lymphoma

Directory of Open Access Journals (Sweden)

Kahl Brad S

2008-05-01

Full Text Available Abstract Background The proteasome inhibitor bortezomib can inhibit activation of the transcription factor NF-κB, a mechanism implicated in its anti-neoplastic effects observed in mantle cell lymphoma (MCL. However, NF-κB can be activated through many distinct mechanisms, including proteasome independent pathways. While MCL cells have been shown to harbor constitutive NF-κB activity, what fraction of this activity in primary MCL samples is sensitive or resistant to inhibition by bortezomib remains unclear. Results Proteasome activity in the EBV-negative MCL cell lines Jeko-1 and Rec-1 is inhibited by greater than 80% after exposure to 20 nM bortezomib for 4 hours. This treatment decreased NF-κB activity in Jeko-1 cells, but failed to do so in Rec-1 cells when assessed by electrophoretic mobility shift assay (EMSA. Concurrently, Rec-1 cells were more resistant to the cytotoxic effects of bortezomib than Jeko-1 cells. Consistent with a proteasome inhibitor resistant pathway of activation described in mouse B-lymphoma cells (WEHI231 and a breast carcinoma cell line (MDA-MB-468, the bortezomib-resistant NF-κB activity in Rec-1 cells is inhibited by calcium chelators, calmodulin inhibitors, and perillyl alcohol, a monoterpene capable of blocking L-type calcium channels. Importantly, the combination of perillyl alcohol and bortezomib is synergistic in eliciting Rec-1 cell cytotoxicity. The relevance of these results is illuminated by the additional finding that a considerable fraction of primary MCL samples (8 out of 10 displayed bortezomib-resistant constitutive NF-κB activity. Conclusion Our findings show that bortezomib-resistant NF-κB activity is frequently observed in MCL samples and suggest that this activity may be relevant to MCL biology as well as serve as a potential therapeutic target.

Mednarodni standardi - veličine in enote (ISO 31-0 do 31-13): International standards - quantities and units (ISO 31-0 to 31-13):

OpenAIRE

Glavič, Peter

2002-01-01

In this paper the international standards ISO 31 (Quantities and units) are presented with the following parts: ISO 31-0 (General principles), ISO 31-1 (Space and time), ISO 31-2 (Periodic and related phenomena), ISO 31-3 (Mechanics), ISO 31-4 (Heat), ISO 31-5 (Electricity and magnetism), ISO 31-8 (Physical chemistry and molecular physics), ISO 31-12 (Characteristic numbers)and others. The emphasis is given on the basic principles, which is important for writing of reports, presentations, art...

ISO27001 in a Windows Environment

CERN Document Server

Honan, Brian

2010-01-01

Ideal for project managers, IT and security staff, this book plugs the gap in current guidance literature for ISO27001. ISO27001, the information security management standard (ISMS), is providing a significant challenge for many organisations. One of the key areas of confusion is the relationship between the ISO27001 ISMS project manager and those responsible for implementing the technical controls.

Certification of ISO 9001: SSDL experiences

International Nuclear Information System (INIS)

Noriah Mod Ali

2005-01-01

Efforts given to maintain the quality management based on the ISO 9000 requirement able to improved the existing system, strengthen the customer confidence and to satisfied the worker needs. It gives direct impact on the harmonization of the Radiation Protection Program in the country. SSDL experiences towards obtaining the the ISO 9002/ISO 9001 certification and its maintenance are discussed in details. (Author)

NF1, Sp1 and HSF1 are synergistically involved in sulfide-induced sqr activation in echiuran worm Urechis unicinctus

Energy Technology Data Exchange (ETDEWEB)

Liu, Xiaolong; Qin, Zhenkui; Li, Xueyu; Ma, Xiaoyu; Gao, Beibei; Zhang, Zhifeng, E-mail: zzfp107@ouc.edu.cn

2016-06-15

Highlights: • Sulfide activates sqr transcription against respiratory toxicity in Urechis unicinctus. • Sulfide increases expressions and activities of NF1, Sp1 and HSF1 in a time-dependent manner. • NF1 and Sp1 participate in both basal and early sulfide-induced sqr transcription. • HSF1 functions more significantly than NF1 and Sp1 in sulfide-induced sqr transcription. • Transcription factors NF1, Sp1 and HSF1 enhance sqr promoter activity synergistically. - Abstract: Background: Sulfide is a well-known environmental toxic substance. Mitochondrial sulfide oxidation is a main mechanism of sulfide detoxification in organisms, and sulfide: quinone oxidoreductase (SQR) is a key enzyme which is involved in transferring electrons from sulfide to ubiquinone and converting sulfide into thiosulfate. Previous studies have revealed the SQR-mediated mitochondrial sulfide oxidation exists in the echiuran worm Urechis unicinctus, and its sqr mRNA level increased significantly when the worm is exposed to sulfide. In this study, we attempt to reveal the synergistic regulation of transcription factors on sulfide-induced sqr transcription in U. unicinctus. Methods: ChIP and EMSA were used to identify the interactions between sqr proximal promoter (from −391 to +194 bp) and transcription factors NF1 (nuclear factor 1) and Sp1 (specificity protein 1). Site-directed mutation and transfection assays further revealed their binding sites and synergistic roles of HSF1, NF1 and Sp1 in the sqr transcription. When U. unicinctus were exposed to 150 μM sulfide, the expression levels and nuclear contents of NF1 and Sp1 were examined by Western blotting, and the binding contents between NF1 or Sp1 and the sqr promoter were also detected by ChIP. Results: Transcription factors NF1 and Sp1 were confirmed to interact with the sqr proximal promoter, and their binding sites were identified in −75 to −69 bp for NF1 and −210 to −201 bp for Sp1. Transfection assays showed mutation

NF-kappa B activity in T cells stably expressing the Tax protein of human T cell lymphotropic virus type I

International Nuclear Information System (INIS)

Lacoste, J.; Cohen, L.; Hiscott, J.

1991-01-01

The effect of constitutive Tax expression on the interaction of NF-κ B with its recognition sequence and on NF-κ B-dependent gene expression was examined in T lymphoid Jurkat cell lines (19D and 9J) stably transformed with a Tax expression vector. Tax expressing T cell lines contained a constitutive level of NF-κ B binding activity, detectable by mobility shift assay and uv cross-linking using a palindromic NF-κ B probe homologous to the interferon beta PRDII site. In Jurkat and NC2.10 induction with phorbol esters resulted in the appearance of new DNA binding proteins of 85, 75, and 54 kDa, whereas in Tax expressing cells the 85-kDa protein and a 92-kDa DNA binding protein were constitutively induced. Expression of Tax protein in 19D and 9J resulted in transcription of the endogenous NF-kappa B-dependent granulocyte-macrophage colony stimulating factor gene and increased basal level expression of transfected NF-kappa B-regulated promoters. Nonetheless transcription of both the endogenous and the transfected gene was inducible by PMA treatment. Tax expression in Jurkat T cells may alter the stoichiometry of NF-kappa B DNA binding proteins and thus change the expression of NF-kappa B-regulated promoters

From ISO 9001:2008 to ISO 9001:2015: Significant changes and their impacts to aspiring organizations

Science.gov (United States)

Sari, Y.; Wibisono, E.; Wahyudi, R. D.; Lio, Y.

2017-11-01

ISO 9001:2015 is the latest version of ISO Quality Management System standard that has been updated recently from ISO 9001:2008. It is necessary for all organizations that have implemented and been certified with ISO 9001:2008 to prepare the transition and upgrade their Quality Management System because the certification will expire by September 2018. This paper attempts to provide knowledge on the significant changes from ISO 9001:2008 to ISO 9001:2015, what new requirements are added, and how they would impact the organizations. An exploratory and applied research was chosen as the research approach and aimed to explore what transition designs are needed to anticipate the changes as well as their impacts. The research applied a methodology of Plan-Do-Check-Action (PDCA) cycle into four organizations and their results were compared and discussed to explain the transition designs. Some qualitative methods such as observation and interview were used to collect the data. By addressing the new requirements, three transition designs that should be prepared are: (i) identifying needs from interested parties, (ii) analyzing internal and external factors of the organizations to formulate relevant strategies and quality objectives, and (iii) registering risks associated to business processes as well as organizational strategies.

A Smac-mimetic sensitizes prostate cancer cells to TRAIL-induced apoptosis via modulating both IAPs and NF-kappaB

International Nuclear Information System (INIS)

Dai, Yao; Liu, Meilan; Tang, Wenhua; Li, Yongming; Lian, Jiqin; Lawrence, Theodore S; Xu, Liang

2009-01-01

Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for human cancer therapy, prostate cancer still remains resistant to TRAIL. Both X-linked inhibitor of apoptosis (XIAP) and nuclear factor-kappaB function as key negative regulators of TRAIL signaling. In this study, we evaluated the effect of SH122, a small molecule mimetic of the second mitochondria-derived activator of caspases (Smac), on TRAIL-induced apoptosis in prostate cancer cells. The potential of Smac-mimetics to bind XIAP or cIAP-1 was examined by pull-down assay. Cytotoxicity of TRAIL and/or Smac-mimetics was determined by a standard cell growth assay. Silencing of XIAP or cIAP-1 was achieved by transient transfection of short hairpin RNA. Apoptosis was detected by Annexin V-PI staining followed by flow cytometry and by Western Blot analysis of caspases, PARP and Bid. NF-kappaB activation was determined by subcellular fractionation, real time RT-PCR and reporter assay. SH122, but not its inactive analog, binds to XIAP and cIAP-1. SH122 significantly sensitized prostate cancer cells to TRAIL-mediated cell death. Moreover, SH122 enhanced TRAIL-induced apoptosis via both the death receptor and the mitochondrial pathway. Knockdown of both XIAP and cIAP-1 sensitized cellular response to TRAIL. XIAP-knockdown attenuated sensitivity of SH122 to TRAIL-induced cytotoxicity, confirming that XIAP is an important target for IAP-inhibitor-mediated TRAIL sensitization. SH122 also suppressed TRAIL-induced NF-kappaB activation by preventing cytosolic IkappaB-alpha degradation and RelA nuclear translocation, as well as by suppressing NF-kappaB target gene expression. These results demonstrate that SH122 sensitizes human prostate cancer cells to TRAIL-induced apoptosis by mimicking Smac and blocking both IAPs and NF-kappaB. Modulating IAPs may represent a promising approach to overcoming TRAIL-resistance in human prostate cancer with constitutively active NF-kappaB signaling

Postoperative plasma 8-iso-prostaglandin F2α levels are associated with delirium and cognitive dysfunction in elderly patients after hip fracture surgery.

Science.gov (United States)

Zheng, Yuan-Bo; Ruan, Guo-Mo; Fu, Jia-Xing; Su, Zhong-Liang; Cheng, Peng; Lu, Jian-Zuo

2016-04-01

Oxidative stress may be involved in occurrence of postoperative delirium (POD) and cognitive dysfunction (POCD). 8-iso-Prostaglandin F2α (8-iso-PGF2α), an isoprostane derived from arachidonic acid via lipid peroxidation, is considered a gold standard for measuring oxidative stress. The present study aimed to investigate the ability of postoperative plasma 8-iso-PGF2α levels to predict POD and POCD in elderly patients undergoing hip fracture surgery. Postoperative plasma 8-iso-PGF2α levels of 182 patients were measured by an enzyme-linked immunosorbent assay. We assessed the relationships between plasma 8-iso-PGF2α levels and the risk of POD and POCD using a multivariate analysis. Plasma 8-iso-PGF2α levels and age were identified as the independent predictors for POD and POCD. Based on areas under receiver operating characteristic curve, the predictive values of 8-iso-PGF2α were obviously higher than those of age for POD and POCD. In a combined logistic-regression model, 8-iso-PGF2α significantly enhanced the areas under curve of age for prediction of POD and POCD. Postoperative plasma 8-iso-PGF2α levels may have the potential to predict POD and POCD in elder patients undergoing hip fracture surgery. Copyright © 2016 Elsevier B.V. All rights reserved.

ISO specifications and unclear energy quality certification

Energy Technology Data Exchange (ETDEWEB)

Lee, Tae Hun

2011-12-15

This book indicates necessity of quality management and change of company environment, basic conception of quality management and thinking way, role of each class for quality management, necessity and purpose of introduction of ISO9000 family, authentication process and construct method of ISO9000 family, authentication effect of ISO9000 family, present condition of ISO9000 family, standard of quality certification and quality management and explanation of 2001 requirement of KSA9000.

ISO specifications and unclear energy quality certification

International Nuclear Information System (INIS)

Lee, Tae Hun

2011-12-01

This book indicates necessity of quality management and change of company environment, basic conception of quality management and thinking way, role of each class for quality management, necessity and purpose of introduction of ISO9000 family, authentication process and construct method of ISO9000 family, authentication effect of ISO9000 family, present condition of ISO9000 family, standard of quality certification and quality management and explanation of 2001 requirement of KSA9000.

Adopting ISO 9712:2005 and ISO/IEC 17024:2003 as Philippine national standard for NDT for global competitiveness

International Nuclear Information System (INIS)

Banaga, Renato T.; Mateo, Alejandro J.

2005-01-01

This paper describes and promotes the adoption of ISO 9712: 2005 edition and the ISO/IEC 17024: 2003 edition by the Philippines to be globally competitive. ISO 9712 is a standard for qualifications and certification of nondestructive testing (NDT) personnel while ISO/IEC 17024 is conformity assessment-general requirements for bodies operating certification of persons. ISO 9712 defies that the effectiveness of an application of nondestructive testing depends on the capabilities and qualifications of personnel performing the NDT test. The Philippines through the national certifying body (NCB) implements the certification of proficiency of NDT personnel in accordance with the Philippine National Standards (PNS-146: 1998) This standard (formerly PNS-146: 1987) was originally based from the draft ISO/TC-135/SC7N35.3 and was later revised to conform to the latest ISO FDIS 9712: 1997 and rename PNS-146: 1998. Now with the issuance of the latest ISO 9712:2005 edition and to keep abreast with the current trends of NDT technology, present time and conditions dictates for us to revise our NDT personnel certification to the latest edition of ISO 9712. The International Atomic Energy Agency (IAEA) supports the establishment of a common NDT standard. The IAEA is promoting af financially supporting the establishment in developing countries of only one NDT standard. The IAEA through the Regional Cooperative Agreement (RCA) has initiated the harmonization of the NDT qualification and certification of personnel in the RCA member states. In October 2001, the IAEA sponsored the Dhaka meeting where the International Committee for Nondestructive Testing (ICNDT), Asia-Pacific Committee (APCNDT) and RCA member states representatives drafted a Mutual Recognition Agreement (MRA) for the Asia-Pacific NDT (APCNDT) personnel certification schemes acording to ISO 9712. Last August 2005, IAEA/RCA sponsored the Colombo meeting for the harmonization of regional NDT applying ISO 9712 and ISO

Promoting Strong ISO 50001 Outcomes with Supportive National Infrastructure

Energy Technology Data Exchange (ETDEWEB)

McKane, Aimee, T.; Siciliano, Graziella; de los Reyes, Pamela

2015-08-04

The ISO 50001 standard is a key mechanism for reducing greenhouse gas emissions and improving energy efficiency globally. An increasing number of companies are seeking certification, creating the need for personnel that are competent to conduct ISO 50001 certification audits. The growth of ISO 50001 is expected to accelerate as more companies integrate ISO 50001 into their corporate sustainability strategies and supplier requirements. Robust implementation of ISO 50001 represents an important tool for countries with climate change mitigation goals. Because of its dual focus on continual improvement of an organization’s energy management system (EnMS) and its energy performance improvement, ISO 50001 requires skills of both implementers and certification auditors that are not well-supported by current credentials and training. This paper describes an effort to address skill gaps of certification auditors, a critical factor to ensure that ISO 50001 implementations are robust and result in continued energy performance improvement. A collaboration of governments through the Energy Management Working Group (EMWG), formerly under Global Superior Energy Performance (GSEP), has formed to build workforce capacity for ISO 50001 certification audits. The EMWG is leading the development of an internationally-relevant certification scheme for ISO 50001 Lead Auditor that meets requirements for ISO/IEC 17024 accreditation and ISO 50003 for defining ISO 50001 Lead Auditor competency. Wider availability of competent ISO 50001 Lead Auditors will ultimately increase the impact and market value of ISO 50001 certification and improve consistency of ISO 50001 certification outcomes by establishing a standardized and high level of knowledge and skills globally.

Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.

Directory of Open Access Journals (Sweden)

Qian-Wen Wang

Full Text Available Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.

Complex formation of p65/RelA with nuclear Akt1 for enhanced transcriptional activation of NF-κB

International Nuclear Information System (INIS)

Kwon, Osong; Kim, Kyung A; He, Long; Jung, Mira; Jeong, Sook Jung; Ahn, Jong Seog; Kim, Bo Yeon

2008-01-01

Akt1 was revealed to interact with Ki-Ras in the cytoplasm of Ki-Ras-transformed human prostate epithelial cells, 267B1/K-ras. Moreover, p65/RelA in the nucleus was found to interact with both Ki-Ras and Akt1, suggesting the nuclear translocation of Akt1:Ki-Ras complex for NF- κB activation. In support of this, compared with wild type Akt1, the dominant negative Akt1 mutant was decreased in its nuclear expression, reducing the Ki-Ras-induced NF-κB transcriptional activation. Moreover, inhibitors of Ras (sulindac sulfide and farnesyltransferase inhibitor I) or PI3K/Akt (wortmannin), reduced the amounts of Akt1 and Ki-Ras in the nucleus as well as partial NF-κB activity. The complete inhibition of Ki-Ras-induced NF-κB activation, however, could only be obtained by combined treatment with wortmannin and proteasome inhibitor-1. Accordingly, clonogenic assay showed Akt1 contribution to IκBα-mediated NF-κB activation for oncogenic cell growth by Ki-Ras. Our data suggest a crucial role of Ki-Ras:Akt1 complex in NF-κB transcriptional activation and enhancement of cell survival

Improving Earth Science Metadata: Modernizing ncISO

Science.gov (United States)

O'Brien, K.; Schweitzer, R.; Neufeld, D.; Burger, E. F.; Signell, R. P.; Arms, S. C.; Wilcox, K.

2016-12-01

ncISO is a package of tools developed at NOAA's National Center for Environmental Information (NCEI) that facilitates the generation of ISO 19115-2 metadata from NetCDF data sources. The tool currently exists in two iterations: a command line utility and a web-accessible service within the THREDDS Data Server (TDS). Several projects, including NOAA's Unified Access Framework (UAF), depend upon ncISO to generate the ISO-compliant metadata from their data holdings and use the resulting information to populate discovery tools such as NCEI's ESRI Geoportal and NOAA's data.noaa.gov CKAN system. In addition to generating ISO 19115-2 metadata, the tool calculates a rubric score based on how well the dataset follows the Attribute Conventions for Dataset Discovery (ACDD). The result of this rubric calculation, along with information about what has been included and what is missing is displayed in an HTML document generated by the ncISO software package. Recently ncISO has fallen behind in terms of supporting updates to conventions such updates to the ACDD. With the blessing of the original programmer, NOAA's UAF has been working to modernize the ncISO software base. In addition to upgrading ncISO to utilize version1.3 of the ACDD, we have been working with partners at Unidata and IOOS to unify the tool's code base. In essence, we are merging the command line capabilities into the same software that will now be used by the TDS service, allowing easier updates when conventions such as ACDD are updated in the future. In this presentation, we will discuss the work the UAF project has done to support updated conventions within ncISO, as well as describe how the updated tool is helping to improve metadata throughout the earth and ocean sciences.

Foxtail millet NF-Y families: genome-wide survey and evolution analyses identified two functional genes important in abiotic stresses

Directory of Open Access Journals (Sweden)

Zhi-Juan eFeng

2015-12-01

Full Text Available It was reported that Nuclear Factor Y (NF-Y genes were involved in abiotic stress in plants. Foxtail millet (Setaria italica, an elite stress tolerant crop, provided an impetus for the investigation of the NF-Y families in abiotic responses. In the present study, a total of 39 NF-Y genes were identified in foxtail millet. Synteny analyses suggested that foxtail millet NF-Y genes had experienced rapid expansion and strong purifying selection during the process of plant evolution. De novo transcriptome assembly of foxtail millet revealed 11 drought up-regulated NF-Y genes. SiNF-YA1 and SiNF-YB8 were highly activated in leaves and/or roots by drought and salt stresses. Abscisic acid (ABA and H2O2 played positive roles in the induction of SiNF-YA1 and SiNF-YB8 under stress treatments. Transient luciferase (LUC expression assays revealed that SiNF-YA1 and SiNF-YB8 could activate the LUC gene driven by the tobacco (Nicotiana tobacam NtERD10, NtLEA5, NtCAT, NtSOD or NtPOD promoter under normal or stress conditions. Overexpression of SiNF-YA1 enhanced drought and salt tolerance by activating stress-related genes NtERD10 and NtCAT1 and by maintaining relatively stable relative water content (RWC and contents of chlorophyll, superoxide dismutase (SOD, peroxidase (POD, catalase (CAT and malondialdehyde (MDA in transgenic lines under stresses. SiNF-YB8 regulated expression of NtSOD, NtPOD, NtLEA5 and NtERD10 and conferred relatively high RWC and chlorophyll contents and low MDA content, resulting in drought and osmotic tolerance in transgenic lines under stresses. Therefore, SiNF-YA1 and SiNF-YB8 could activate stress-related genes and improve physiological traits, resulting in tolerance to abiotic stresses in plants. All these results will facilitate functional characterization of foxtail millet NF-Ys in future studies.

NF-kappa B modulation is involved in celastrol induced human multiple myeloma cell apoptosis.

Directory of Open Access Journals (Sweden)

Haiwen Ni

Full Text Available Celastrol is an active compound extracted from the root bark of the traditional Chinese medicine Tripterygium wilfordii Hook F. To investigate the effect of celastrol on human multiple myeloma cell cycle arrest and apoptosis and explore its molecular mechanism of action. The activity of celastrol on LP-1 cell proliferation was detected by WST-8 assay. The celastrol-induced cell cycle arrest was analyzed by flow cytometry after propidium iodide staining. Nuclear translocation of the nuclear factor kappa B (NF-κB was observed by fluorescence microscope. Celastrol inhibited cell proliferation of LP-1 myeloma cell in a dose-dependent manner with IC50 values of 0.8817 µM, which was mediated through G1 cell cycle arrest and p27 induction. Celastrol induced apoptosis in LP-1 and RPMI 8226 myeloma cells in a time and dose dependent manner, and it involved Caspase-3 activation and NF-κB pathway. Celastrol down-modulated antiapoptotic proteins including Bcl-2 and survivin expression. The expression of NF-κB and IKKa were decreased after celastrol treatment. Celastrol effectively blocked the nuclear translocation of the p65 subunit and induced human multiple myeloma cell cycle arrest and apoptosis by p27 upregulation and NF-kB modulation. It has been demonstrated that the effect of celastrol on NF-kB was HO-1-independent by using zinc protoporphyrin-9 (ZnPPIX, a selective heme oxygenase inhibitor. From the results, it could be inferred that celastrol may be used as a NF-kB inhibitor to inhibit myeloma cell proliferation.

Complexing properties of α-iso-saccharinate: thorium

International Nuclear Information System (INIS)

Allard, S.; Ekberg, C.

2005-01-01

Full text of publication follows: In the alkaline conditions of the intended Swedish repository for long-lived, low to intermediate level waste, SFL3-5, cellulose based items will degrade with iso-saccharinate being the dominant end-product. Iso-saccharinate is a strong complexing agent for tetravalent actinides, as well as for trivalent lanthanides, and its complexation properties are of interest for the long-term repository assessment. In the presented study, the complexation of 234 Th-α-iso-saccharinate is examined using liquid-liquid- extraction and radioanalytical techniques. An organic phase consisting of 0.1 M acetylacetone in toluene was used with a 1.0 M NaClO 4 aqueous phase kept at pH 8 in a thermostated AKUFVE unit. Since the α-iso-saccharinic system consists of three species - the carboxylic α-iso-saccharinic acid, α-iso-saccharinate and α-D-iso-saccharino-1,4-lactone - care must be taken when choosing the operational pH. Keeping the aqueous phase at pH 8 results in negligible concentrations of all but the α-iso-saccharinate form while at the same time being an excellent pH for the 234 Th-acetylacetone complexation with very limited hydrolysis effect. The α- iso-saccharinate concentration was incrementally increased, and samples of equal volumes were taken from the two phases and analyzed in a liquid scintillation detector once the radioactive equilibrium between 234 Th and 234 Pa had been reached. Two complexation constants were used to fit a distribution equation to the experimental data. (authors)

ISO standards on the evaluation of contamination

International Nuclear Information System (INIS)

Swinth, K.L.; Tamberg, T.A.

1993-01-01

The International Organization for Standardization (ISO) develops radiation calibration standards through Subcommittee 2 (titled ''Radiation Protection'') of Technical Committee 85 (ISO/TC85/SC2). The subcommittee has also developed standards providing guidance on the performance of measurements. ISO/TC85/SC2 consists of international technical experts who represent their countries through the international consensus process in providing guidance in several radiation protection areas. The purpose of this paper is to summarize ISO's is guidance provided in the area of contamination measurements

PENGENDALIAN KUALITAS PT AHM DENGAN MENGGUNAKAN ISO/TS 16949: 2002 UNTUK MENCEGAH KOMPONEN VALVE INLET BENGKOK PADA MOTOR SUPRA KHUSUSNYA MESIN NF100 (Studi Kasus Valve Inlet Bengkok di PT Astra Honda Motor

Directory of Open Access Journals (Sweden)

Naniek Utami Handayani

2012-02-01

Full Text Available Untuk memenuhi keinginan konsumen dalam hal mutu dan jumlah, PT AHM telah menerapkan ISO 9001:2000 (International Standard Organization versi tahun 2000, SIX SIGMA dan ISO/TS 16949:2002 untuk menangani customer claim dan memperbaiki mutu supplier yang ada. Sebelum penerapan ISO/TS 16949:2002, untuk keharmonisan kualitas supplier/penyalur tersebut, PT AHM telah menggunakan QS-9000 dalam mengendalikan kualitas produknya. Berhubung QS-9000 tidak diperbaharui lagi dan hanya akan berlaku sampai tahun 2006, maka sebagai gantinya perusahaan mengambil kebijakan untuk menerapkan ISO/TS 16949:2002 dan menyertakan dalam keseluruhannya kebutuhan ISO 9001:2000. Dari beberapa jenis motor yang diproduksi pada pabrik II dari PT AHM, jenis motor yang diproduksi adalah Legenda, Tiger, GL Max, Mega Pro dan Supra. Diantara kelima motor tersebut, Supra mempunyai prosentase permintaan yang paling tinggi dan juga sekaligus market claim tertingggi (periode Agustus s/d Desember 2004, yaitu sebesar 2,7%, sedangkan berdasarkan penelitian terhadap banyaknya claim customer terhadap komponen motor Supra periode Agustus s/d Desember 2004, claim terhadap komponen  terbesar mencapai 337 claim dari total 1440 claim. Komponen  motor Supra yang dimaksud disini adalah Valve Inlet. Dalam penelitian ini, dievaluasi hasil dari pelaksanaan persiapan penerapan ISO/TS 16949:2002 sebagai teknik pengendalian kualitas terbaru yang telah dipilih dengan menggunakan tools dari ISO/TS 16949:2002 yaitu SPC, FMEA dan Corrective Action. Hasil penelitian ini menunjukkan bahwa penyebab Valve Inlet bengkok bukan hanya berasal dari Valve inlet itu sendiri, melainkan juga sebagai akibat dari adanya ketidaksesuaian pada Guide Valve Inlet dan Cylinder head. Dari penelitian penerapan ISO/TS 16949:2002 di PT AHM dapat diketahui beberapa manfaat ISO/TS 16949:2002 dalam mengendalikan kualitas produk dan memenuhi kebutuhan customer. Kata Kunci: Market Claim, Customer Claim, ISO/TS 16949:2002, SPC, FMEA dan

Role of NF-κB and cytokine in experimental cancer cachexia

Institute of Scientific and Technical Information of China (English)

Wei Zhou; Zhi-Wei Jiang; Jie Tian; Jun Jiang; Ning Li; Jie-Shou Li

2003-01-01

AIM: To assess the putative involvement of NF-κB and proinflammatory cytokines in the pathogenesis of cancer cachexia and the therapeutic efficacy of indomethacin (IND)on cachexia.METHODS: Thirty young male BABL/c mice were divided randomly into five groups: (a) control, (b) tumor-bearing murine were inoculated subcutaneously to induce cachexia.Saline and IND were given intraperitoneally daily for 7 days from the onset of cachexia to sacrifice. Food intake and body composition were documented, serum levels of TNFα and IL-6 and activity of NF-κB in the spleen were investigated in all animals.RESULTS: Weight loss was observed in all tumor-bearing mice. By day 16, body weights of non-tumor mice were about 72 % of healthy controls (P＜0.01), and the weight of gastrocnemius was decreased by 28.7 % (P＜0.01). No difference was found between groups in food intake (P＞0.05).Gastrocnemius weight was increased markedly (P＜0.01)body weights were not significantly elevated. Tumor-bearing caused a 2-3 fold increase in serum levels of both TNF-αand IL-6 (P＜0.01). The concentration of TNF-α (P＜0.05)and IL-6 (P＜0.01) in tumor-bearing mice was reduced after of IL-6 was slightly elevated following treatment of IND 2.0tumor-bearing mice in comparison with controls in electrophoretic mobility shift assay (ENSA). NF-κB activity a higher NF-κB activity was observed in mice treated with CONCLUSION: Colon 26 adenocarcinoma cells can induce severe cancer cachexia experimentally, and the mechanism may be partially due to the enhanced TNF-αand IL-6 in tumor-bearing animals, which is controlled by NF-κB. Low dose of indomethacin alleviates the cachexia,decreases the activation of NF-κB and the serum levels of TNF-α and IL-6, and prevents body weight loss and muscle atrophy, while no further effect is gained by a higher dosage.

Usability evaluation of mobile applications using ISO 9241 and ISO 25062 standards.

Science.gov (United States)

Moumane, Karima; Idri, Ali; Abran, Alain

2016-01-01

This paper presents an empirical study based on a set of measures to evaluate the usability of mobile applications running on different mobile operating systems, including Android, iOS and Symbian. The aim is to evaluate empirically a framework that we have developed on the use of the Software Quality Standard ISO 9126 in mobile environments, especially the usability characteristic. To do that, 32 users had participated in the experiment and we have used ISO 25062 and ISO 9241 standards for objective measures by working with two widely used mobile applications: Google Apps and Google Maps. The QUIS 7.0 questionnaire have been used to collect measures assessing the users' level of satisfaction when using these two mobile applications. By analyzing the results we highlighted a set of mobile usability issues that are related to the hardware as well as to the software and that need to be taken into account by designers and developers in order to improve the usability of mobile applications.

[ISO 15189 medical laboratory accreditation].

Science.gov (United States)

Aoyagi, Tsutomu

2004-10-01

This International Standard, based upon ISO/IEC 17025 and ISO 9001, provides requirements for competence and quality that are particular to medical laboratories. While this International Standard is intended for use throughout the currently recognized disciplines of medical laboratory services, those working in other services and disciplines will also find it useful and appropriate. In addition, bodies engaged in the recognition of the competence of medical laboratories will be able to use this International Standard as the basis for their activities. The Japan Accreditation Board for Conformity Assessment (AB) and the Japanese Committee for Clinical Laboratory Standards (CCLS) are jointly developing the program of accreditation of medical laboratories. ISO 15189 requirements consist of two parts, one is management requirements and the other is technical requirements. The former includes the requirements of all parts of ISO 9001, moreover it includes the requirement of conformity assessment body, for example, impartiality and independence from any other party. The latter includes the requirements of laboratory competence (e.g. personnel, facility, instrument, and examination methods), moreover it requires that laboratories shall participate proficiency testing(s) and laboratories' examination results shall have traceability of measurements and implement uncertainty of measurement. Implementation of ISO 15189 will result in a significant improvement in medical laboratories management system and their technical competence. The accreditation of medical laboratory will improve medical laboratory service and be useful for patients.

C26 cancer-induced muscle wasting is IKKβ-dependent and NF-kappaB-independent.

Directory of Open Access Journals (Sweden)

Evangeline W Cornwell

Full Text Available Existing data suggest that NF-kappaB signaling is a key regulator of cancer-induced skeletal muscle wasting. However, identification of the components of this signaling pathway and of the NF-κB transcription factors that regulate wasting is far from complete. In muscles of C26 tumor bearing mice, overexpression of dominant negative (d.n. IKKβ blocked muscle wasting by 69% and the IκBα-super repressor blocked wasting by 41%. In contrast, overexpression of d.n. IKKα or d.n. NIK did not block C26-induced wasting. Surprisingly, overexpression of d.n. p65 or d.n. c-Rel did not significantly affect muscle wasting. Genome-wide mRNA expression arrays showed upregulation of many genes previously implicated in muscle atrophy. To test if these upregulated genes were direct targets of NF-κB transcription factors, we compared genome-wide p65 binding to DNA in control and cachectic muscle using ChIP-sequencing. Bioinformatic analysis of ChIP-sequencing data from control and C26 muscles showed very little p65 binding to genes in cachexia and little to suggest that upregulated p65 binding influences the gene expression associated with muscle based cachexia. The p65 ChIP-seq data are consistent with our finding of no significant change in protein binding to an NF-κB oligonucleotide in a gel shift assay, no activation of a NF-κB-dependent reporter, and no effect of d.n.p65 overexpression in muscles of tumor bearing mice. Taken together, these data support the idea that although inhibition of IκBα, and particularly IKKβ, blocks cancer-induced wasting, the alternative NF-κB signaling pathway is not required. In addition, the downstream NF-κB transcription factors, p65 and c-Rel do not appear to regulate the transcriptional changes induced by the C26 tumor. These data are consistent with the growing body of literature showing that there are NF-κB-independent substrates of IKKβ and IκBα that regulate physiological processes.

Intermediate species measurement during iso-butanol auto-ignition

KAUST Repository

Ji, Weiqi

2015-10-01

© 2015 The Combustion Institute.Published by Elsevier Inc. All rights reserved. This work presents the time histories of intermediate species during the auto-ignition of iso-butanol at high pressure and intermediate temperature conditions obtained using a rapid compression machine and recently developed fast sampling system. Iso-butanol ignition delays were acquired for iso-butanol/O2 mixture with an inert/O2 ratio of 7.26, equivalence ratio of 0.4, in the temperature range of 840-950 K and at pressure of 25 bar. Fast sampling and gas chromatography were used to acquire and quantify the intermediate species during the ignition delay of the same mixture at P = 25.3 bar and T = 905 K. The ignition delay times and quantitative measurements of the mole fraction time histories of methane, ethene, propene, iso-butene, iso-butyraldehyde, iso-butanol, and carbon monoxide were compared with predictions from the detailed mechanisms developed by Sarathy et al., Merchant et al., and Cai et al. It is shown that while the Sarathy mechanism well predicts the overall ignition delay time, it overpredicts ethene by a factor of 6-10, underpredicts iso-butene by a factor of 2, and overpredicts iso-butyraldehyde by a factor of 2. Reaction path and sensitivity analyses were carried out to identify the reactions responsible for the observed inadequacy. The rates of iso-butanol hydrogen atom abstraction by OH radical and the beta-scission reactions of hydroxybutyl radicals were updated based on recently published quantum calculation results. Significant improvements were achieved in predicting ignition delay at high pressures (25 and 30 bar) and the species concentrations of ethene and iso-butene. However, the updated mechanism still overpredicts iso-butyraldehyde concentrations. Also, the updated mechanism degrades the prediction in ignition delay at lower pressure (15 bar) compared to the original mechanism developed by Sarathy et al.

Intermediate species measurement during iso-butanol auto-ignition

KAUST Repository

Ji, Weiqi; Zhang, Peng; He, Tanjin; Wang, Zhi; Tao, Ling; He, Xin; Law, Chung K.

2015-01-01

© 2015 The Combustion Institute.Published by Elsevier Inc. All rights reserved. This work presents the time histories of intermediate species during the auto-ignition of iso-butanol at high pressure and intermediate temperature conditions obtained using a rapid compression machine and recently developed fast sampling system. Iso-butanol ignition delays were acquired for iso-butanol/O2 mixture with an inert/O2 ratio of 7.26, equivalence ratio of 0.4, in the temperature range of 840-950 K and at pressure of 25 bar. Fast sampling and gas chromatography were used to acquire and quantify the intermediate species during the ignition delay of the same mixture at P = 25.3 bar and T = 905 K. The ignition delay times and quantitative measurements of the mole fraction time histories of methane, ethene, propene, iso-butene, iso-butyraldehyde, iso-butanol, and carbon monoxide were compared with predictions from the detailed mechanisms developed by Sarathy et al., Merchant et al., and Cai et al. It is shown that while the Sarathy mechanism well predicts the overall ignition delay time, it overpredicts ethene by a factor of 6-10, underpredicts iso-butene by a factor of 2, and overpredicts iso-butyraldehyde by a factor of 2. Reaction path and sensitivity analyses were carried out to identify the reactions responsible for the observed inadequacy. The rates of iso-butanol hydrogen atom abstraction by OH radical and the beta-scission reactions of hydroxybutyl radicals were updated based on recently published quantum calculation results. Significant improvements were achieved in predicting ignition delay at high pressures (25 and 30 bar) and the species concentrations of ethene and iso-butene. However, the updated mechanism still overpredicts iso-butyraldehyde concentrations. Also, the updated mechanism degrades the prediction in ignition delay at lower pressure (15 bar) compared to the original mechanism developed by Sarathy et al.

Aplikace ISO norem v oblasti vývoje softwaru

OpenAIRE

Ullrich, Jan

2007-01-01

Thesis evaluates ISO standars used for software developement and their relationship to methodologies. It also describes processes according to international standard ISO/IEC 12207 and quality management systems according to ISO 9000. It evaluates also mothodlogy RUP and agile methodollogies. The goal of the thesis to tailor processes related to ISO 9001 to be compliant to the ISO/IEC 12207 in a small company.

Collagen gel protects L929 cells from TNFα-induced death by activating NF-κB.

Science.gov (United States)

Wang, Hong-Ju; Li, Meng-Qi; Liu, Wei-Wei; Hayashi, Toshihiko; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2017-09-01

Type I collagen is one of the most abundant components of extracellular matrix. We previously illustrated that murine fibrosarcoma L929 cells grew well on type I collagen gel and escaped from TNFα-induced cell death. In this study, we investigated the mechanism underlying the protective effect of collagen gel. We used western blot, confocal microscopy, MTT assay and flow cytometry by introducing fluorescence staining to determine the expression levels of nuclear factor kappa B (NF-κB), inhibitory ratio and autophagy. L929 cells on collagen gel showed higher expression of NF-κB in the nucleus. Inhibition of NF-κB with pyrrolidine dithiocarbamate hydrochloride (PDTC) or knockdown by NF-κB-siRNA canceled the protective effect of collagen gel on L929 cells from TNFα-induced death, suggesting for the role of NF-κB in the protection from cell death. We found a new aspect of the effect of PDTC on L929 cells cultured on collagen gel. PDTC alone without TNFα induced apoptosis in the L929 cells cultured on collagen gel but not the cells on plastic dish. The apoptosis induction of the L929 cells cultured on collagen gel with PDTC was repressed by inhibiting autophagy with chloroquine, an autophagy inhibitor, suggesting that autophagy contributes to the death induced by the treatment with PDTC. Possible underlying mechanism of this finding is discussed. NF-κB played an important role in protecting the L929 cells cultured on collagen gel from TNFα-induced death.

[NF-κB signaling pathways and the future perspectives of bone disease therapy using selective inhibitors of NF-κB].

Science.gov (United States)

Jimi, Eijiro; Fukushima, Hidefumi

2016-02-01

The transcriptional factor nuclear factor κB(NF-κB)regulates the expression of a wide variety of genes that are involved in immune and inflammatory responses, proliferation, and tumorigenesis. NF-κB consists of five members, such as p65(RelA), RelB, c-Rel, p50/p105(NF-κB1), and p52/p100(NF-κB2). There are two distinct NF-κB activation pathways, termed the classical and alternative NF-κB signaling pathways. Since mice lacking both p50 and p52 subunits developed typical osteopetrosis, due to total lack of osteoclasts, NF-κB is also important osteoclast differentiation. A selective NF-κB inhibitor blocked receptor activator of NF-κB ligand(RANKL)-induced osteoclastogenesis both in vitro and in vivo. Recent findings have shown that inactivation of NF-κB enhances osteoblast differentiation in vitro and bone formation in vivo. NF-κB is constitutively activated in many cancers including oral squamous cell carcinoma(OSCC), and is involved in the invasive characteristics of OSCC. A selective NF-κB inhibitor also prevented jaw bone destruction by OSCC by reduced osteoclast numbers in animal model. Thus the inhibition of NF-κB might useful for the treatment of bone diseases, such as arthritis, osteoporosis, periodontitis, and bone invasion by OSCC by inhibiting bone resorption and by stimulating bone formation.

The clinical significance of HER-2 and NF-KB expression in gastric cancer.

Science.gov (United States)

Li, Xiaogai; Tu, Jiancheng; Zhang, Di; Xu, Zhigao; Yang, Guifang; Gong, Lingling; Yu, Mingxia

2013-09-01

To investigate the expression of human epidermal growth factor 2 (HER-2) and Nuclear factor-Kb (NF-KB) in gastric cancer, and the relation of these two parameters with stage, grade and metastasis of gastric cancer. The serum level of HER-2 in 75 gastric cancer patients and control participants were determined by enzyme-linked immunosorbent assay (ELISA) kits. Expression of HER-2 and NF-KB protein were detected by immunohistochemical staining (SP method) of paraffin-embedded tissues in 75 tumors (observed group) and 22 normal gastric specimens. The clinical pathological data was statistically analyzed. Serum HER-2 level were significantly increased in study group compared with those in the control group (pKB in the observed group was 24.00% (18/75) and 62.67% (47/75) respectively. The expression of HER-2 and NF-KB were not correlated with age and gender, but with stage, grade and metastasis (pKB was correlated with tumor size (pKB had a positive rate of 94.44% (17/18), but a positive rate of 52.63% (30/57) when HER-2 was negative. Expression of NF-KB in gastric cancer tissue was correlated with HER-2 expression (X2 = 8.514, pKB in gastric cancer tissue is correlated with HER-2 expression, and they may play a very important role in the progress of gastric cancer.

[Fisetin alleviates hypoxia/reoxygenation injury in rat hepatocytes via modulation of TLR4/NF-κB signaling pathway].

Science.gov (United States)

Pu, Junliang; Wan, Lei; Zheng, Daofeng; Wei, Xufu; Wu, Zhongjun; Tang, Chengyong

2017-07-01

Objective To investigate the protective effect of fisetin (FIS) against hypoxia/reoxygenation (H/R) injury in rat hepatocytes and its mechanism. Methods H/R injury model of BRL-3A cells was established and the cells were pretreated with FIS. Survival rate was detected by CCK-8 assay. Cell apoptosis was measured by flow cytometry. The levels of ALT and AST were determined by microplate assay. The production of TNF-α and IL-1β were detected by ELISA. The mRNA and protein levels of TLR4 and NF-κBp65 were analyzed by quantitative real-time PCR and Western blotting, respectively. Results After subjected to H/R, cell survival rate decreased and the apoptosis level increased. The levels of ALT and AST in cell supernatant were elevated, so were the production of TNF-α and IL-1β. FIS pretreatment increased the cell survival rate and inhibited apoptosis. The levels of ALT, AST and the production of TNF-α and IL-1β were reduced significantly. Moreover, FIS inhibited the increasing expression levels of TLR4 and NF-κBp65 induced by H/R. Conclusion FIS alleviates the hepatocyte injury induced by H/R via modulation of TLR4/NF-κB signaling pathway.

Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway.

Science.gov (United States)

Li, Yu; He, Shengnan; Tang, Jishun; Ding, Nana; Chu, Xiaoyan; Cheng, Lianping; Ding, Xuedong; Liang, Ting; Feng, Shibin; Rahman, Sajid Ur; Wang, Xichun; Wu, Jinjie

2017-01-01

Andrographolide, the main active component extracted from Andrographis paniculata (Burm.f.) Wall. ex Nees, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the molecular mechanisms of Andrographolide in modifying lipopolysaccharide- (LPS-) induced signaling pathway in RAW264.7 cells. An in vitro model of inflammation was induced by LPS in mouse RAW264.7 cells in the presence of Andrographolide. The concentration and expression levels of proinflammatory cytokines were determined by an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The nuclear level of NF- κ B was measured by an electrophoretic mobility shift assay (EMSA). The expression levels of NF- κ B, p38, ERK, and JNK were determined by western blot. Andrographolide dose-dependently inhibited the release and mRNA expression of TNF- α , IL-6, and IL-1 β in LPS-stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in Andrographolide treatment group. Western blot analysis showed that Andrographolide suppressed LPS-induced NF- κ B activation and the phosphorylation of IkBa, ERK1/2, JNK, and p38. These results suggest that Andrographolide exerts an anti-inflammatory effect by inhibiting the activation of NF- κ B/MAPK signaling pathway and the induction of proinflammatory cytokines.

Andrographolide Inhibits Inflammatory Cytokines Secretion in LPS-Stimulated RAW264.7 Cells through Suppression of NF-κB/MAPK Signaling Pathway

Directory of Open Access Journals (Sweden)

Yu Li

2017-01-01

Full Text Available Andrographolide, the main active component extracted from Andrographis paniculata (Burm.f. Wall. ex Nees, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear. The objective of this study was to investigate the molecular mechanisms of Andrographolide in modifying lipopolysaccharide- (LPS- induced signaling pathway in RAW264.7 cells. An in vitro model of inflammation was induced by LPS in mouse RAW264.7 cells in the presence of Andrographolide. The concentration and expression levels of proinflammatory cytokines were determined by an enzyme-linked immunosorbent assay (ELISA and quantitative real-time polymerase chain reaction (qRT-PCR, respectively. The nuclear level of NF-κB was measured by an electrophoretic mobility shift assay (EMSA. The expression levels of NF-κB, p38, ERK, and JNK were determined by western blot. Andrographolide dose-dependently inhibited the release and mRNA expression of TNF-α, IL-6, and IL-1β in LPS-stimulated RAW264.7 cells. The nuclear level of p65 protein was decreased in Andrographolide treatment group. Western blot analysis showed that Andrographolide suppressed LPS-induced NF-κB activation and the phosphorylation of IkBa, ERK1/2, JNK, and p38. These results suggest that Andrographolide exerts an anti-inflammatory effect by inhibiting the activation of NF-κB/MAPK signaling pathway and the induction of proinflammatory cytokines.

Benazepril inhibited the NF-κB and TGF-β networking on LV hypertrophy in rats.

Science.gov (United States)

Yan, Shi-Hai; Zhao, Ning-Wei; Zhu, Xuan-Xuan; Wang, Qiong; Wang, Hai-Dan; Fu, Rui; Sun, Yuan; Li, Qi-Yi

2013-05-01

Benazepril, an angiotensin-converting enzyme (ACE) inhibitor, has been used to treat hypertension, congestive heart failure, and chronic renal failure. However, its biological activity and mechanism of action in inflammation are not fully identified. The present study was designed to determine the in vivo anti-inflammatory effects of benazepril on LV hypertrophy in rats. LV hypertrophy was produced in rats by abdominal aortic coarctation. They were then divided into the following groups: sham operation; LV hypertrophy; LV hypertrophy+benazepril (1mg/kg in a gavage, once a day for 4 weeks). Both morphological assays (hemodynamic and hemorheological measurement; LV hypertrophy assessment), and molecular assays (protein levels of Collagen type I/III, TNF-α and VCAM-1; TGF-β gene expression; NF-κB or Smad activation; intracellular ROS production) were performed. The following effects were observed in rats treated with benazepril: (1) marked improvements in hemodynamic and hemorheological parameters; (2) significant reductions in LV hypertrophy, dilatation and fibrosis; (3) significantly attenuated protein levels of Collagen type I/III, TGF-β, TNF-α and VCAM-1, NF-κB or Smad activation, as well as intracellular ROS production. These results suggest that the anti-inflammatory properties of benazepril may be ascribed to their down-regulation of both NF-κB and TGF-β signaling pathways by acting on the intracellular ROS production in rats with LV hypertrophy, thus supporting the use of benazepril as an anti-inflammatory agent. Copyright © 2013 Elsevier B.V. All rights reserved.

RIP1 regulates TNF-α-mediated lymphangiogenesis and lymphatic metastasis in gallbladder cancer by modulating the NF-κB-VEGF-C pathway.

Science.gov (United States)

Li, Cheng-Zong; Jiang, Xiao-Jie; Lin, Bin; Hong, Hai-Jie; Zhu, Si-Yuan; Jiang, Lei; Wang, Xiao-Qian; Tang, Nan-Hong; She, Fei-Fei; Chen, Yan-Ling

2018-01-01

Tumor necrosis factor alpha (TNF-α) enhances lymphangiogenesis in gallbladder carcinoma (GBC) via activation of nuclear factor (NF-κB)-dependent vascular endothelial growth factor-C (VEGF-C). Receptor-interacting protein 1 (RIP1) is a multifunctional protein in the TNF-α signaling pathway and is highly expressed in GBC. However, whether RIP1 participates in the signaling pathway of TNF-α-mediated VEGF-C expression that enhances lymphangiogenesis in GBC remains unclear. The RIP1 protein levels in the GBC-SD and NOZ cells upon stimulation with increasing concentrations of TNF-α as indicated was examined using Western blot. Lentiviral RIP1 shRNA and siIκBα were constructed and transduced respectively them into NOZ and GBC-SD cells, and then PcDNA3.1-RIP1 vectors was transduced into siRIP1 cell lines to reverse RIP1 expression. The protein expression of RIP1, inhibitor of NF-κB alpha (IκBα), p-IκBα, TAK1, NF-κB essential modulator were examined through immunoblotting or immunoprecipitation. Moreover, VEGF-C mRNA levels were measured by quantitative real-time polymerase chain reaction, VEGF-C protein levels were measured by immunoblotting and enzyme-linked immunosorbent assay, and VEGF-C promoter and NF-κB activities were quantified using a dual luciferase reporter assay. The association of NF-κB with the VEGF-C promoter was analysed by chromatin immunoprecipitation assay. A three-dimensional coculture method and orthotopic transplantation nude mice model were used to evaluate lymphatic tube-forming and metastasis ability in GBC cells. The expression of RIP1 protein, TNF-α protein and lymphatic vessels in human GBC tissues was examined by immunohistochemistry, and the dependence between RIP1 protein with TNF-α protein and lymphatic vessel density was analysed. TNF-α dose- and time-dependently increased RIP1 protein expression in the GBC-SD and NOZ cells of GBC, and the strongest effect was observed with a concentration of 50 ng/ml. RIP1 is fundamental

Analysis of JC virus DNA replication using a quantitative and high-throughput assay

International Nuclear Information System (INIS)

Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.

2014-01-01

Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication

Analysis of JC virus DNA replication using a quantitative and high-throughput assay

Energy Technology Data Exchange (ETDEWEB)

Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States); Gagnon, David [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Gjoerup, Ole [Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA 02111 (United States); Archambault, Jacques [Institut de Recherches Cliniques de Montreal (IRCM), 110 Pine Avenue West, Montreal, Quebec, Canada H2W 1R7 (Canada); Department of Biochemistry and Molecular Medicine, Université de Montréal, Montréal, Quebec (Canada); Bullock, Peter A., E-mail: Peter.Bullock@tufts.edu [Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA 02111 (United States)

2014-11-15

Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. - Highlights: • Development of a high-throughput screening assay for JCV DNA replication using C33A cells. • Evidence that T-ag fails to accumulate in the nuclei of established glioma cell lines. • Evidence that NF-1 directly promotes JCV DNA replication in C33A cells. • Proof-of-concept that the HTS assay can be used to identify pharmacological inhibitor of JCV DNA replication.

ANKRD1 modulates inflammatory responses in C2C12 myoblasts through feedback inhibition of NF-κB signaling activity

Energy Technology Data Exchange (ETDEWEB)

Liu, Xin-Hua [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Bauman, William A. [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Cardozo, Christopher, E-mail: chris.cardozo@va.gov [National Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Rehabilitation Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States); Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029 (United States)

2015-08-14

Transcription factors of the nuclear factor-kappa B (NF-κB) family play a pivotal role in inflammation, immunity and cell survival responses. Recent studies revealed that NF-κB also regulates the processes of muscle atrophy. NF-κB activity is regulated by various factors, including ankyrin repeat domain 2 (AnkrD2), which belongs to the muscle ankyrin repeat protein family. Another member of this family, AnkrD1 is also a transcriptional effector. The expression levels of AnkrD1 are highly upregulated in denervated skeletal muscle, suggesting an involvement of AnkrD1 in NF-κB mediated cellular responses to paralysis. However, the molecular mechanism underlying the interactive role of AnkrD1 in NF-κB mediated cellular responses is not well understood. In the current study, we examined the effect of AnkrD1 on NF-κB activity and determined the interactions between AnkrD1 expression and NF-κB signaling induced by TNFα in differentiating C2C12 myoblasts. TNFα upregulated AnkrD1 mRNA and protein levels. AnkrD1-siRNA significantly increased TNFα-induced transcriptional activation of NF-κB, whereas overexpression of AnkrD1 inhibited TNFα-induced NF-κB activity. Co-immunoprecipitation studies demonstrated that AnkrD1 was able to bind p50 subunit of NF-κB and vice versa. Finally, CHIP assays revealed that AnkrD1 bound chromatin at a NF-κB binding site in the AnrkD2 promoter and required NF-κB to do so. These results provide evidence of signaling integration between AnkrD1 and NF-κB pathways, and suggest a novel anti-inflammatory role of AnkrD1 through feedback inhibition of NF-κB transcriptional activity by which AnkrD1 modulates the balance between physiological and pathological inflammatory responses in skeletal muscle. - Highlights: • AnkrD1 is upregulated by TNFα and represses NF-κB-induced transcriptional activity. • AnkrD1 binds to p50 subunit of NF-κB and is recruited to NF-κB bound to chromatin. • AnkrD1 mediates a feed-back inhibitory loop

Peningkatan Mutu Proses Perguruan Tinggi Melalui Sistem Mutu Iso 9000

Directory of Open Access Journals (Sweden)

Th. Widia Soerjaningsih

2004-09-01

Full Text Available Article was made to answer these several questions;  what is acreditation and the application in the college; what is ISO 9000 quality system; why is ISO 9000 needed by the college; how ISO 9000 can support the achievement of the defined quality level; how ISO  9000 guarantee the achievement of BAN target including quality, efficiency, and relevance; what is the difference between BAN Acreditation and ISO 9000 Certification; ISO 9000 Consultant: why it is necessary, how to choose it, the line of the contract; ISO 9000 Assessor and the achieve certification: SGS and etc.; and ISO 9000 Certification Proccess Cost Aspect.   

ISO science - observations of dusty discs.

Science.gov (United States)

Heske, A.

1992-12-01

ISO, the Infrared Space Observatory, will be an infrared observing facility in space. Via submission of observing proposals, use of this facility will be open to the astronomical community. The scientific payload consists of two spectrometers, a camera and a photo-polarimeter. Following an overview of the ISO mission, this paper describes the highlights of the Central Programme - proposals which are being prepared by the instrument groups, the mission scientists and the astronomers of the ISO Science Operations Team - with special emphasis on the proposals concerned with dusty discs.

Launching the chaotic realm of iso-fractals: A short remark

Energy Technology Data Exchange (ETDEWEB)

O' Schmidt, Nathan [Department of Mathematics, Boise State University, 1910 University Drive, Boise, ID 83725 (United States); Katebi, Reza [Department of Physics, California State University in Fullerton, 800 North State College Boulevard, Fullerton, CA 92831 (United States); Corda, Christian [Institute for Theoretical Physics and Advanced Mathematics Einstein-Galilei (IFM), Via Santa Gonda 14, 59100 Prato (Italy)

2015-03-10

In this brief note, we introduce the new, emerging sub-discipline of iso-fractals by highlighting and discussing the preliminary results of recent works. First, we note the abundance of fractal, chaotic, non-linear, and self-similar structures in nature while emphasizing the importance of studying such systems because fractal geometry is the language of chaos. Second, we outline the iso-fractal generalization of the Mandelbrot set to exemplify the newly generated Mandelbrot iso-sets. Third, we present the cutting-edge notion of dynamic iso-spaces and explain how a mathematical space can be iso-topically lifted with iso-unit functions that (continuously or discretely) change; in the discrete case examples, we mention that iteratively generated sequences like Fibonacci’s numbers and (the complex moduli of) Mandelbrot’s numbers can supply a deterministic chain of iso-units to construct an ordered series of (magnified and/or de-magnified) iso-spaces that are locally iso-morphic. Fourth, we consider the initiation of iso-fractals with Inopin’s holographic ring (IHR) topology and fractional statistics for 2D and 3D iso-spaces. In total, the reviewed iso-fractal results are a significant improvement over traditional fractals because the application of Santilli’s iso-mathematics arms us an extra degree of freedom for attacking problems in chaos. Finally, we conclude by proposing some questions and ideas for future research work.

Blockage of NOX2/MAPK/NF-κB Pathway Protects Photoreceptors against Glucose Deprivation-Induced Cell Death

Directory of Open Access Journals (Sweden)

Bin Fan

2017-01-01

Full Text Available Acute energy failure is one of the critical factors contributing to the pathogenic mechanisms of retinal ischemia. Our previous study demonstrated that glucose deprivation can lead to a caspase-dependent cell death of photoreceptors. The aim of this study was to decipher the upstream signal pathway in glucose deprivation- (GD- induced cell death. We mimicked acute energy failure by using glucose deprivation in photoreceptor cells (661W cells. GD-induced oxidative stress was evaluated by measuring ROS with the DCFH-DA assay and HO-1 expression by Western blot analysis. The activation of NOX2/MAPK/NF-κB signal was assessed by Western blot and immunohistochemical assays. The roles of these signals in GD-induced cell death were measured by using their specific inhibitors. Inhibition of Rac-1 and NOX2 suppressed GD-induced oxidative stress and protected photoreceptors against GD-induced cell death. NOX2 was an upstream signal in the caspase-dependent cell death cascade, yet the downstream MAPK pathways were activated and blocking MAPK signals rescued 661W cells from GD-induced death. In addition, GD caused the activation of NF-κB signal and inhibiting NF-κB significantly protected 661W cells. These observations may provide insights for treating retinal ischemic diseases and protecting retinal neurons from ischemia-induced cell death.

Lessons learned with ISO 14001 at DOE sites

Energy Technology Data Exchange (ETDEWEB)

Wilkinson, C. H., LLNL

1998-03-01

ISO 14001 is the international standard for environmental management systems (EMS). The standard applies the `plan, do, check, act` management system model to assure that the environmental impacts of operations are fully considered in planning and facility operations. ISO 14001 has grown in popularity in both the public and the private sector and has seen increasing utility within the U.S. Department of Energy (DOE). While there is no final DOE policy or requirement for ISO 14001 EMS implementation, ISO 14001 commands an active presence at many DOE sites. In general, the impetus for ISO 14001 in the DOE complex has been either an initiative by site management contractors to improve performance, or an actual requirement in the new management contracts for the sites. Several DOE sites now are committed to implement EMS`s in conformance with ISO 14001: Brookhaven National Laboratory (BNL), Hanford, Idaho National Engineering and Environmental Laboratory (INEEL), Kansas City Plant, Nevada Test Site, Savannah River Site (SRS), Waste Isolation Pilot Project (WIPP), West Valley. Several other DOE sites are expected to proceed in the near future with an EMS consistent with ISO 14001. However, not all sites are proceeding with an ISO 14001 EMS based on individual site business considerations. This paper describes the status of EMS implementation at these sites and identifies lessons learned that may be of use to other DOE sites.

Profile of NF-κBp(65/NFκBp50) among prostate specific antigen sera levels in prostatic pathologies.

Science.gov (United States)

Bouraoui, Y; Ben Jemaa, A; Rodriguez, G; Ben Rais, N; Fraile, B; Paniagua, R; Sellemi, S; Royuela, M; Oueslati, R

2012-10-01

The aim of this work was to characterise the immunoexpression of NF-κB (p50/p65) in human prostatic pathologies and to study its profiles of activation among sera prostate specific antigen antigen (PSA) according the three groups: 0-4ng/mL, 4-20ng/mL and >20ng/mL. Twenty-four men with benign prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with normal prostates (NP). Immunohistochemical and western blot analysis was performed. Serum levels of PSA were assayed by immulite autoanalyser. In BPH and PC samples, immunoexpressions were observed for NF-κBp65 and NF-κBp50; while in NP samples, only were detected NF-κBp50. PC samples showed immunoreactions to NF-κBp65 and NF-κBp50 more intense (respectively 24.18±0.67 and 28.23±2.01) than that observed in BPH samples (respectively18.46±2.04 and 18.66±1.59) with special localisation in the nucleus. Different profiles of NF-κBp65 immunoexpressions were observed and BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and >20ng/mL. No immunoreactions to NF-κBp65 were observed in PC patients with sera PSA levels between 4-20ng/mL. The sensibility of both NF-κB and PSA to inflammation allowed confirming the relationship between these two molecules and its involvement in prostatic diseases progression (inflammatory and neoplasic). Copyright © 2011 Elsevier Masson SAS. All rights reserved.

The international ISOE programme. ISOE IAEA technical centre activities

International Nuclear Information System (INIS)

Gustafsson, M.

1996-01-01

The objective of the sub-programme on Occupational Radiation Protection in the International Atomic Energy Agency, IAEA, is to promote a harmonized approach to optimizing occupational radiation protection by developing guidelines for controlling radiation doses in the workplace and on current occupational radiation protection techniques. A significant part of this programme is the provision of assistance to developing member states to bring their radiation safety infrastructure to an appropriate level for the usage of radiation in the state. In consistence with these objectives the IAEA has been involved with the ISOE programme from its inception and has contributed actively to its growth. In 1993 an arrangement was agreed between the IAEA and the Nuclear Energy Agency, NEA, by which the IAEA co-sponsors ISOE inviting those IAEA member states which are not members of the NEA to participate cost-free in the programme. (author)

Transgenic Brassica rapa plants over-expressing eIF(iso)4E variants show broad-spectrum Turnip mosaic virus (TuMV) resistance.

Science.gov (United States)

Kim, Jinhee; Kang, Won-Hee; Hwang, Jeena; Yang, Hee-Bum; Dosun, Kim; Oh, Chang-Sik; Kang, Byoung-Cheorl

2014-08-01

The protein-protein interaction between VPg (viral protein genome-linked) of potyviruses and eIF4E (eukaryotic initiation factor 4E) or eIF(iso)4E of their host plants is a critical step in determining viral virulence. In this study, we evaluated the approach of engineering broad-spectrum resistance in Chinese cabbage (Brassica rapa) to Turnip mosaic virus (TuMV), which is one of the most important potyviruses, by a systematic knowledge-based approach to interrupt the interaction between TuMV VPg and B. rapa eIF(iso)4E. The seven amino acids in the cap-binding pocket of eIF(iso)4E were selected on the basis of other previous results and comparison of protein models of cap-binding pockets, and mutated. Yeast two-hybrid assay and co-immunoprecipitation analysis demonstrated that W95L, K150L and W95L/K150E amino acid mutations of B. rapa eIF(iso)4E interrupted its interaction with TuMV VPg. All eIF(iso)4E mutants were able to complement an eIF4E-knockout yeast strain, indicating that the mutated eIF(iso)4E proteins retained their function as a translational initiation factor. To determine whether these mutations could confer resistance, eIF(iso)4E W95L, W95L/K150E and eIF(iso)4E wild-type were over-expressed in a susceptible Chinese cabbage cultivar. Evaluation of the TuMV resistance of T1 and T2 transformants demonstrated that the over-expression of the eIF(iso)4E mutant forms can confer resistance to multiple TuMV strains. These data demonstrate the utility of knowledge-based approaches for the engineering of broad-spectrum resistance in Chinese cabbage. © 2014 BSPP AND JOHN WILEY & SONS LTD.

A graded approach to ISO 9000 implementation for records managers

Energy Technology Data Exchange (ETDEWEB)

Pasterczyk, C.E.

1994-08-01

ISO 9000 is a series of quality system standards developed by Technical Committee 176 of the International Standards Organization. The series includes three standards, ISO 9001 `Quality systems--Model for quality assurance in design/development, production, installation and serving,` ISO 9002 `Quality systems--Model for quality assurance in production and installation,` ISO 9003 `Quality systems--Model for quality assurance in final inspection and test,` and two guidelines, ISO 9000 `Quality management and quality assurance standards` and ISO 9004 `Quality management and quality system elements--Guidelines.` In companies with quality programs already in place, the structure of the ISO series lends itself to augmenting those policies, procedures, and instructions where problems exist or where the risks of failure are greater. The objectives of this paper are to provide a basic familiarity to ISO 9000 and quality assurance concepts; provide a higher level of familiarity to the records management and document control portions of the ISO 9000 series; and to discuss a graded approach to meeting the intent of ISO 9000.

UPP mediated Diabetic Retinopathy via ROS/PARP and NF-κB inflammatory factor pathways.

Science.gov (United States)

Luo, D-W; Zheng, Z; Wang, H; Fan, Y; Chen, F; Sun, Y; Wang, W-J; Sun, T; Xu, X

2015-01-01

Diabetic retinopathy (DR) is a leading cause of blindness in adults at working age. Human diabetic retinopathy is characterized by the basement membrane thick, pericytes loss, microaneurysms formation, retina neovascularization and vitreous hemorrhage. To investigate whether UPP activated ROS/PARP and NF-κB inflammatory factor pathways in Diabetic Retinopathy, human retinal endothelial cells (HRECs) and rats with streptozotocin-induced diabetes were used to determine the effect of UPP on ROS generation, cell apoptosis, mitochondrial membrane potential (ΔΨm) and inflammatory factor protein expression, through flow cytometry assay, immunohistochemistry, Real-time PCR, Western blot analysis and ELISA. The levels of ROS and apoptosis and the expressions of UPP (Ub and E3) and inflammatory factor protein were increased in high glucose-induced HRECs and retina of diabetic rats, while ΔΨm was decreased. The UPP inhibitor and UbshRNA could attenuate these effects through inhibiting the pathway of ROS/PARP and the expression of NF-κB inflammatory factors, and the increased UPP was a result of high glucose-induced increase of ROS generation and NF-κBp65 expression, accompanied with the decrease of ΔΨm. Clinical study showed the overexpression of UPP and detachment of epiretinal membranes in proliferative DR (PDR) patients. It has been indicated that the pathogenic effect of UPP on DR was involved in the increase of ROS generation and NF-κB expression, which associated with the ROS/PARP and NF-κB inflammatory factor pathways. Our study supports a new insight for further application of UPP inhibitor in DR treatment.

The C-terminal domains of NF-H and NF-M subunits maintain axonal neurofilament content by blocking turnover of the stationary neurofilament network.

Directory of Open Access Journals (Sweden)

Mala V Rao

Full Text Available Newly synthesized neurofilaments or protofilaments are incorporated into a highly stable stationary cytoskeleton network as they are transported along axons. Although the heavily phosphorylated carboxyl-terminal tail domains of the heavy and medium neurofilament (NF subunits have been proposed to contribute to this process and particularly to stability of this structure, their function is still obscure. Here we show in NF-H/M tail deletion [NF-(H/M(tailΔ] mice that the deletion of both of these domains selectively lowers NF levels 3-6 fold along optic axons without altering either rates of subunit synthesis or the rate of slow axonal transport of NF. Pulse labeling studies carried out over 90 days revealed a significantly faster rate of disappearance of NF from the stationary NF network of optic axons in NF-(H/M(tailΔ mice. Faster NF disappearance was accompanied by elevated levels of NF-L proteolytic fragments in NF-(H/M(tailΔ axons. We conclude that NF-H and NF-M C-terminal domains do not normally regulate NF transport rates as previously proposed, but instead increase the proteolytic resistance of NF, thereby stabilizing the stationary neurofilament cytoskeleton along axons.

ISO 14001

DEFF Research Database (Denmark)

Jørgensen, Tine Herreborg

2004-01-01

The aim of this paper is to discuss a number of issues related to ISO 14001, the international standard for environmental management systems (EMS). The standard is a process standard that leaves room for interpretation at company level as well as among lead auditors from certifying bodies...

Antagonism of bradykinin B2 receptor prevents inflammatory responses in human endothelial cells by quenching the NF-kB pathway activation.

Directory of Open Access Journals (Sweden)

Erika Terzuoli

Full Text Available Bradykinin (BK induces angiogenesis by promoting vessel permeability, growth and remodeling. This study aimed to demonstrate that the B2R antagonist, fasitibant, inhibits the BK pro-angiogenic effects.We assesed the ability of fasibitant to antagonize the BK stimulation of cultured human cells (HUVEC and circulating pro-angiogenic cells (PACs, in producing cell permeability (paracellular flux, migration and pseocapillary formation. The latter parameter was studied in vitro (matrigel assay and in vivo in mice (matrigel plug and in rat model of experimental osteoarthritis (OA. We also evaluated NF-κB activation in cultured cells by measuring its nuclear translocation and its downstream effectors such as the proangiogenic ciclooxygenase-2 (COX-2, prostaglandin E-2 and vascular endothelial growth factor (VEGF.HUVEC, exposed to BK (1-10 µM, showed increased permeability, disassembly of adherens and tight-junction, increased cell migration, and pseudocapillaries formation. We observed a significant increase of vessel density in the matrigel assay in mice and in rats OA model. Importantly, B2R stimulation elicited, both in HUVEC and PACs, NF-κB activation, leading to COX-2 overexpression, enhanced prostaglandin E-2 production. and VEGF output. The BK/NF-κB axis, and the ensuing amplification of inflammatory/angiogenic responses were fully prevented by fasitibant as well as by IKK VII, an NF-κB. Inhibitor.This work illustrates the role of the endothelium in the inflammation provoked by the BK/NF-κB axis. It also demonstates that B2R blockade by the antaogonist fasibitant, abolishes both the initial stimulus and its amplification, strongly attenuating the propagation of inflammation.

Risk in Management Systems according to ISO standard

Directory of Open Access Journals (Sweden)

P. Królas

2010-07-01

Full Text Available The purpose of this article was to present selected management standards in context of risk management. It presents main ISOmanagement standards (ISO 9001, ISO 14001, OHSAS 18001, ISO 27001, BS 25999, ISO 31000 that apply to polish enterprises. In thefirst part of this article there are analyzed management standards regarding quality, environment, occupational health and safety,information security, as well as business continuity management and risk management. The second part of the article discusses the processof dealing with risk based on chosen management standard.

Implementation and Impact of ISO 9001

NARCIS (Netherlands)

B. Manders (Basak)

2015-01-01

markdownabstract__Abstract __ The ISO 9001 quality management standard has been implemented by more than one million organizations in 187 countries since its introduction in 1987. A newer version of ISO 9001 is planned to be introduced in 2015. Even though it is widely used by organizations to

cAMP-response Element-binding Protein (CREB) and NF-κB Transcription Factors Are Activated during Prolonged Hypoxia and Cooperatively Regulate the Induction of Matrix Metalloproteinase MMP1*

Science.gov (United States)

Nakayama, Koh

2013-01-01

Responses to low levels of oxygen (hypoxia) are essential to maintain homeostasis. During the hypoxic response, gene expression is altered by various transcription factors. The transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxic response. The α subunit of HIF, which is actively degraded during normoxia, becomes stabilized during hypoxia, which leads to HIF activation. A microarray analysis of HeLa cells showed that expression of matrix metalloproteinase 1 (MMP1) was markedly induced during prolonged hypoxia. CREB and NF-κB binding sites were identified in the MMP1 promoter region between 1945 and 1896 nucleotides upstream of the transcription start site. Assays with luciferase reporters demonstrated that HIF activity was induced during the early phase of hypoxia, whereas CREB and NF-κB were activated during the later (prolonged) phase. Depletion of CREB and/or NF-κB reduced MMP1 induction during prolonged hypoxia both at the mRNA and protein levels. A chromatin immunoprecipitation assay demonstrated binding of CREB and NF-κB to the MMP1 promoter. Finally, cell migration and invasion on a collagen matrix and pulmonary metastasis in nude mice were inhibited after depletion of CREB and NF-κB in MDA-MB-231 cells. Taken together, these results suggest that the cooperative action of CREB and NF-κB plays an important role to induce MMP1 expression during prolonged hypoxia and regulates cell migration and invasion in cancer cells. PMID:23775082

Synergistic activation of the CMV promoter by NF-κB P50 and PKG

International Nuclear Information System (INIS)

He Bin; Weber, Georg F.

2004-01-01

Several DNA binding NF-κB subunits are substrates for cGMP-dependent kinase (PKG) and their transactivation from cognate sites is induced by phosphorylation. This includes p50, which does not have a transcriptional activation domain and therefore needs to bind to other proteins to mediate gene expression. Here, we describe the synergistic transactivation by p50 and PKG from the CMV promoter. This is caused not only by phosphorylation of p50, leading to increased DNA binding, but also by PKG-dependent activation of CRE sites in the promoter. One of the CRE sites is located directly adjacent to a NF-κB site and is essential for p50-mediated induction of transcription. According to the binding of CREB to p50 in pull-down assays and according to the inhibition of p50-dependent transactivation by dominant-negative CREB, this reflects the formation of a transcription factor complex containing CREB and p50. The nuclear translocation of NF-κB is insufficient to distinguish among the multitude of promoters that harbor cognate recognition sites. The phosphorylation of multiple transcription factors by an upstream kinase, such as PKG, can lead to the formation of transcription factor complexes and differential transactivation from a subset of NF-κB sites. These interactions may be relevant for the activation of viral gene expression

The preservative polyquaternium-1 increases cytoxicity and NF-kappaB linked inflammation in human corneal epithelial cells

Science.gov (United States)

Paimela, Tuomas; Ryhänen, Tuomas; Kauppinen, Anu; Marttila, Liisa; Salminen, Antero

2012-01-01

Purpose In numerous clinical and experimental studies, preservatives present in eye drops have had detrimental effects on ocular epithelial cells. The aim of this study was to compare the cytotoxic and inflammatory effects of the preservative polyquaternium-1 (PQ-1) containing Travatan (travoprost 0.004%) and Systane Ultra eye drops with benzalkonium chloride (BAK) alone or BAK-preserved Xalatan (0.005% latanoprost) eye drops in HCE-2 human corneal epithelial cell culture. Methods HCE-2 cells were exposed to the commercial eye drops Travatan, Systane Ultra, Xalatan, and the preservative BAK. Cell viability was determined using colorimetric MTT (3-(4,5-dimethyldiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and by release of lactate dehydrogenase (LDH). Induction of apoptosis was measured with a using a colorimetric caspase-3 assay kit. DNA binding of the nuclear factor kappa B (NF-κB) transcription factor, and productions of the proinflammatory cytokines, interleukins IL-6 and IL-8, were determined using an enzyme-linked immunosorbent assay (ELISA) method. Results Cell viability, as measured by the MTT assay, declined by up to 50% after exposure to Travatan or Systane Ultra solutions which contain 0.001% PQ-1. BAK at 0.02% rather than at 0.001% concentration evoked total cell death signs on HCE-2 cells. In addition, cell membrane permeability, as measured by LDH release, was elevated by sixfold with Travatan and by a maximum threefold with Systane Ultra. Interestingly, Travatan and Systane Ultra activated NF-κB and elevated the secretion of inflammation markers IL-6 by 3 to eightfold and IL-8 by 1.5 to 3.5 fold, respectively, as analyzed with ELISA. Conclusions Eye drops containing PQ-1 evoke cytotoxicity and enhance the NF-κB driven inflammation reaction in cultured HCE-2 cells. Our results indicate that these harmful effects of ocular solutions preserved with PQ-1 should be further evaluated in vitro and in vivo. PMID:22605930

NF-κB is involved in the LPS-mediated proliferation and apoptosis of MAC-T epithelial cells as part of the subacute ruminal acidosis response in cows.

Science.gov (United States)

Fan, Wen-Jie; Li, He-Ping; Zhu, He-Shui; Sui, Shi-Ping; Chen, Pei-Ge; Deng, Yue; Sui, Tong-Ming; Wang, Yue-Ying

2016-11-01

To determine the effect of NF-κB on cell proliferation and apoptosis, we investigate the expression of inflammation and apoptosis-related factors in the bovine mammary epithelial cell line, MAC-T. MAC-T cells were cultured in vitro and MTT and LDH assays used to determine the effects of lipopolysaccharide (LPS) on proliferation and cytotoxicity respectively. RT-PCR and western blotting were used to evaluate the effect of LPS and NF-κB inhibition [pyrrolidine dithiocarbamate (PDTC) treatment] on the expression of inflammation and apoptosis-related factors. LPS significantly inhibited MAC-T cell proliferation in a dose- and time-dependent manner. Furthermore, LPS promoted apoptosis while the NF-кB inhibitor PDTC attenuated this effect. After LPS treatment, the NF-кB signaling pathway was activated, and the expression of inflammation and apoptosis-related factors increased. When PDTC blocked NF-кB signaling, the expression of inflammation and apoptosis-related factors were decreased in MAC-T cells. LPS activates the TLR4/NF-κB signaling pathway, inhibits proliferation and promotes apoptosis in MAC-T cells. NF-кB inhibition attenuates MAC-T cell apoptosis and TLR4/NF-κB signaling pathway. NF-кB inhibitor alleviating MAC-T cell apoptosis is presumably modulated by NF-кB.

URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway

International Nuclear Information System (INIS)

Xing, Sizhong; Zhang, Bing; Hua, Ruixi; Tai, William Chi-shing; Zeng, Zhirong; Xie, Binhui; Huang, Chenghui; Xue, Jisu; Xiong, Shiqiu; Yang, Jianyong; Liu, Side; Li, Heping

2015-01-01

Angiogenesis is essential for tumor growth. Hepatocellular carcinoma (HCC) is characterized by hypervascularity; high levels of angiogenesis are associated with poor prognosis and a highly invasive phenotype in HCC. Up-regulated gene-4 (URG4), also known as upregulator of cell proliferation (URGCP), is overexpressed in multiple tumor types and has been suggested to act as an oncogene. This study aimed to elucidate the effect of URG4/URGCP on the angiogenic capacity of HCC cells in vitro. Expression of URG4/URGCP in HCC cell lines and normal liver epithelial cell lines was examined by Western blotting and quantitative real-time PCR. URG4/URGCP was stably overexpressed or transiently knocked down using a shRNA in two HCC cell lines. The human umbilical vein endothelial cell (HUVEC) tubule formation and Transwell migration assays and chicken chorioallantoic membrane (CAM) assay were used to examine the angiogenic capacity of conditioned media from URG4/URGCP-overexpressing and knockdown cells. A luciferase reporter assay was used to examine the transcriptional activity of nuclear factor kappa – light – chain - enhancer of activated B cells (NF-κB). NF-κB was inhibited by overexpressing degradation-resistant mutant inhibitor of κB (IκB)-α. Expression of vascular endothelial growth factor C (VEGFC), tumor necrosis factor-α (TNFα), interleukin (IL)-6, IL-8 and v-myc avian myelocytomatosis viral oncogene homolog (MYC) were examined by quantitative real-time PCR; VEGFC protein expression was analyzed using an ELISA. URG4/URGCP protein and mRNA expression were significantly upregulated in HCC cell lines. Overexpressing URG4/URGCP enhanced - while silencing URG4/URGCP decreased - the capacity of HCC cell conditioned media to induce HUVEC tubule formation and migration and neovascularization in the CAM assay. Furthermore, overexpressing URG4/URGCP increased - whereas knockdown of URG4/URGCP decreased - VEGFC expression, NF-κB transcriptional activity, the levels

The new international standard ISO 14001: 2004 environmental management system

International Nuclear Information System (INIS)

Oheba, Jamal Basher

2006-01-01

ISO 14001 is one standard in the ISO 14000 series of standards developed by International Organization of Standardization (ISO). Since it was published in 19096, it has rapidly become the most important environmental standard in the world. ISO 14001 is an environmental management system (EMS) that can be classified into environmental technologies provides a systematic procedure to all kind of organizations to prevent pollutions, protect environment and to improve their overall environmental performance. This new standard ISO 14001 2004 was published on November 15, 2004. It cancels and replaced the old ISO 14001-1996. Because the important of the previous standard for our local industries, firms, ...etc, this paper presents ISO 14001 concepts, issues, benefits and focuses on the stages of implementation to achieve ISO 14001-2004 certification which includes general requirements environmental policy, planning (objectives, targets ..), implementation and operations, checking and management review ...etc and presents how to apply isotop time saver software to design records, and to save time to implement ISO 14001 2004 and finally a conclusion is provided.(Author)

The Regulation of NF-κB Subunits by Phosphorylation

Directory of Open Access Journals (Sweden)

Frank Christian

2016-03-01

Full Text Available The NF-κB transcription factor is the master regulator of the inflammatory response and is essential for the homeostasis of the immune system. NF-κB regulates the transcription of genes that control inflammation, immune cell development, cell cycle, proliferation, and cell death. The fundamental role that NF-κB plays in key physiological processes makes it an important factor in determining health and disease. The importance of NF-κB in tissue homeostasis and immunity has frustrated therapeutic approaches aimed at inhibiting NF-κB activation. However, significant research efforts have revealed the crucial contribution of NF-κB phosphorylation to controlling NF-κB directed transactivation. Importantly, NF-κB phosphorylation controls transcription in a gene-specific manner, offering new opportunities to selectively target NF-κB for therapeutic benefit. This review will focus on the phosphorylation of the NF-κB subunits and the impact on NF-κB function.

Application Security in the ISO27001 Environment

CERN Document Server

Vinod, Vasudevan; Firosh, Ummer

2008-01-01

Application Security in the ISO27001 Environment demonstrates how to secure software applications within a best practice ISO/IEC 27001 environment and supports implementation of the PCI DSS Payment Application Security Standard.

Tietoturvallisuusauditointi ISO 27000-viitekehyksessä

OpenAIRE

Luoma, Ilmari

2015-01-01

Tiedon olemassaolo eri olomuodoissa muodostaa vaikeasti hallittavan uhkakentän, jonka käsittelyyn kansainvälisesti hyväksytty ISO 27000 -standardi on hyvä väline. Työn tarkoitus on perehtyä ISO/IEC 27000 -standardisarjaan, soveltaa standardin vaatimuksia laatimalla tietoturvallisuuden auditointiaineisto ja -menetelmä, sekä toteuttaa tietoturvallisuusauditointi käytännössä. Työssä esitellään tietoturvallisuuden kytkeytyminen yritysturvallisuuteen, tietoturvallisuuden osa-alueittainen ...

PENGGABUNGAN PENERAPAN SISTEM JAMINAN MUTU ISO 9001:2008 DAN SISTEM HACCP KE DALAM SISTEM MANAJEMEN KEAMANAN PANGAN ISO 22000:2009 (STUDI KASUS DI PT INDOKOM SAMUDRA PERSADA [The Merger of Quality Assurance System ISO 9001:2008 and HACCP system into Food

Directory of Open Access Journals (Sweden)

Novri Ilmiawan

2014-10-01

Full Text Available The object of this research was to merge the application of HACCP system and ISO 9001:2008 in ISP company into ISO 22000:2009. The  research method used was case study method. The study was conducted on three stages. The first was the arrangement gap analysis conducted by comparing the conditions of the company with ISO 22000:2009 standards. The second was by observing sanitation and pre requisite programs. The third was by observing traceability system. The data in this research were reported descriptively, consisted of ISO 9001:2008 and HACCP application in the company and the gaps of principles in ISO 22000:2009 toward ISO 9001:2008 and HACCP. The result showed that ISP company has applied 12 steps which covered in HACCP system, and also the ISO 9001 system were appropriate with ISO 9001:2008 standards in every clauses. Pre requisite program (GMP and SSOP have been effectively applied. GMP in ISP company is categorized on the first spot (excellent. The eight keys of SSOP have been fulfilled. ISP company has been fulfilling 54 from 57 (94.74% criteria in ISO 22000:2009 standards, yet there still several things needed to be improved, which are the quality manual content  and HACCP table plan and its monitoring. The  traceability system has been applied well in ISP. Keywords : HACCP, ISO 9001, ISO 22000, GMP, SSOP.

Recombinant Human Endostatin Suppresses Mouse Osteoclast Formation by Inhibiting the NF-κB and MAPKs Signaling Pathways

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Non eChen

2016-06-01

Full Text Available Rheumatoid arthritis is an autoimmune disease characterized by synovial hyperplasia and progressive joint destruction. As reported previously, recombinant human endostatin (rhEndostatin is associated with inhibition of joint bone destruction present in rat adjuvant-induced arthritis; however, the effect of rhEndostatin on bone destruction is not known. This study was designed to assess the inhibitory effect and mechanisms of rhEndostatin on formation and function of osteoclasts in vitro, and to gain insight into the mechanism underlying the inhibitory effect of bone destruction. Bone marrow-derived macrophages isolated from BALB/c mice were stimulated with receptor activator of NF-κB ligand (RANKL and macrophage colony-stimulating factor to establish osteoclast formation. Osteoclast formation was determined by TRAP staining. Cell viability of BMMs affected by rhEndostatin was determined using a MTT assay. Bone resorption was examined with a bone resorption pits assay. The expression of osteoclast-specific markers was analyzed using quantitative real-time PCR. The related signaling pathways were examined using a Luciferase reporter assay and western blot analysis. Indeed, rhEndostatin showed a significant reduction in the number of osteoclast-like cells and early-stage bone resorption. Moreover, molecular analysis demonstrated that rhEndostatin attenuated RANKL-induced NF-κB signaling by inhibiting the phosphorylation of IκBα and NF-κB p65 nuclear translocation. Furthermore, rhEndostatin significantly inhibited the activation of RANKL-dependent mitogen-activated protein kinases (MAPKs, such as ERK1/2, JNK, and p38. Hence, we demonstrated for the first time that preventing the formation and function of osteoclasts is an important anti-bone destruction mechanism of rhEndostatin, which might be useful in the prevention and treatment of bone destruction in RA.

ADOPTION OF ISO 9001 QUALITY MANAGEMENT STANDARD IN AFRICA

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Erlantz Allur

2014-03-01

Full Text Available This article analyzes the dissemination of ISO 9001, the main global management standards, within Africa. The work refers to the diffusion of ISO 9001 standard in terms of its certification intensity. In this article, the dissemination of ISO 9001 in Africa has been analyzed. The findings reveal that the diffusion of the standard in this continent is not very relevant, what might be seen as an indicator of the process of Africa's trade marginalization in the age of globalization. The general certification intensity of the continet is of 0.18; in other words, the proportion of the contribution of Africa to the global GDP of the world is more than five times superior to the proportion of ISO 9001 certificates located in Africa. By means of the logistic model the dissemination of ISO 9001 is forecasted, and it has been observed that the diffusion of ISO 9001 in Africa is in an 85% of its saturation point. Taking into account this model, it's expected that the dissemination of ISO 9001 will be growing until 2020.

A new structural class of proteasome inhibitors that prevent NF-kappa B activation.

Science.gov (United States)

Lum, R T; Kerwar, S S; Meyer, S M; Nelson, M G; Schow, S R; Shiffman, D; Wick, M M; Joly, A

1998-05-01

The multicatalytic proteinase or proteasome is a highly conserved cellular structure that is responsible for the ATP-dependent proteolysis of many proteins involved in important regulatory cellular processes. We have identified a novel class of inhibitors of the chymotrypsin-like proteolytic activity of the 20S proteasome that exhibit IC50 values ranging from 0.1 to 0.5 microgram/mL (0.1 to 1 microM). In cell proliferation assays, these compounds inhibit growth with an IC50 ranging from 5 to 10 micrograms/mL (10-20 microM). A representative member of this class of inhibitors was tested in other biological assays. CVT-634 (5-methoxy-1-indanone-3-acetyl-leu-D-leu-1-indanylamide) prevented lipopolysaccharide (LPS), tumor necrosis factor (TNF)-, and phorbol ester-induced activation of nuclear factor kappa B (NF-kappa B) in vitro by preventing signal-induced degradation of I kappa B-alpha. In these studies, the I kappa B-alpha that accumulated was hyperphosphorylated, indicating that CVT-634 did not inhibit I kappa B-alpha kinase, the enzyme responsible for signal-induced phosphorylation of I kappa B-alpha. In vivo studies indicated that CVT-634 prevented LPS-induced TNF synthesis in a murine macrophage cell line. In addition, in mice pretreated with CVT-634 at 25 and 50 mg/kg and subsequently treated with LPS, serum TNF levels were significantly lower (225 +/- 59 and 83 +/- 41 pg/mL, respectively) than in those mice that were treated only with LPS (865 +/- 282 pg/mL). These studies suggest that specific inhibition of the chymotrypsin-like activity of the proteasome is sufficient to prevent signal-induced NF-kappa B activation and that the proteasome is a novel target for the identification of agents that may be useful in the treatment of diseases whose etiology is dependent upon the activation of NF-kappa B.

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

Science.gov (United States)

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

2017-07-01

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

Verification the 25-kgy dose using the iso standard iso/tr 13409 for the production of bone grafts

International Nuclear Information System (INIS)

Otero, I.; Barrera, L.; Diaz, A.; Napoles, D.; Sanchez, E

2001-01-01

The purpose of this work was to verify the 25 Gy dose using the ISO standard ISO/TR 13409 for the production of bone grafts from the Tissue Bank ORTOP of the Complejo Cientifico Ortopedico Internacional Frank Pais. We performed two principal microbiological activities: bioburden estimate, pre-sterilization count plus a compensation for the efficiency of the recovery method, by ISO 11737-1 and test of sterility by ISO 11737-2. The techniques for Bioburden estimation could be direct or indirect. Choice of direct vs. indirect depends on number of contaminating micro-organisms, product configuration, ability to remove microbial contamination, effect of removal method on microbial viability, types and location of micro-organisms, nature of product and culture conditions. For a test of sterility, he product unit or SIP putted direct immersion in educated culture medium and incubate. Keep precaution to minimize level to the false positives is necessary

Cirhin up-regulates a canonical NF-{kappa}B element through strong interaction with Cirip/HIVEP1

Energy Technology Data Exchange (ETDEWEB)

Yu, Bin; Mitchell, Grant A. [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada); Richter, Andrea, E-mail: andrea.richter@umontreal.ca [Genetique Medicale, Centre de Recherche CHU Sainte-Justine, Departement de Pediatrie, Universite de Montreal, Montreal, QC (Canada)

2009-11-01

North American Indian childhood cirrhosis (NAIC/CIRH1A) is a severe autosomal recessive intrahepatic cholestasis. All NAIC patients have a homozygous mutation in CIRH1A that changes conserved Arg565 to Trp (R565W) in Cirhin, a nucleolar protein of unknown function. Subcellular localization is unaffected by the mutation. Yeast two-hybrid screening identified Cirip (Cirhin interaction protein) and found that interaction between Cirip and R565W-Cirhin was weakened. Co-immunoprecipitation of the two proteins from nuclear extracts of HeLa cells strongly supports the yeast two hybrid results. Cirip has essentially the same sequence as the C-terminal of HIVEP1, a regulator of a canonical NF-{kappa}B sequence. Since Cirip has the zinc fingers required for this interaction, we developed an in vitro assay based on this element in mammalian cells to demonstrate functional Cirhin-Cirip interaction. The strong positive effect of Cirip on the NF-{kappa}B sequence was further increased by both Cirhin and R565W-Cirhin. Importantly, the effect of R565W-Cirhin was weaker than that of the wild type protein. We observed increased levels of Cirhin-Cirip complex in nuclear extracts in the presence of this NF-{kappa}B sequence. Our hypothesis is that Cirhin is a transcriptional regulatory factor of this NF-{kappa}B sequence and could be a participant in the regulation of other genes with NF-{kappa}B responsive elements. Since the activities of genes regulated through NF-{kappa}B responsive elements are especially important during development, this interaction may be a key to explain the perinatal appearance of NAIC.

Cirhin up-regulates a canonical NF-κB element through strong interaction with Cirip/HIVEP1

International Nuclear Information System (INIS)

Yu, Bin; Mitchell, Grant A.; Richter, Andrea

2009-01-01

North American Indian childhood cirrhosis (NAIC/CIRH1A) is a severe autosomal recessive intrahepatic cholestasis. All NAIC patients have a homozygous mutation in CIRH1A that changes conserved Arg565 to Trp (R565W) in Cirhin, a nucleolar protein of unknown function. Subcellular localization is unaffected by the mutation. Yeast two-hybrid screening identified Cirip (Cirhin interaction protein) and found that interaction between Cirip and R565W-Cirhin was weakened. Co-immunoprecipitation of the two proteins from nuclear extracts of HeLa cells strongly supports the yeast two hybrid results. Cirip has essentially the same sequence as the C-terminal of HIVEP1, a regulator of a canonical NF-κB sequence. Since Cirip has the zinc fingers required for this interaction, we developed an in vitro assay based on this element in mammalian cells to demonstrate functional Cirhin-Cirip interaction. The strong positive effect of Cirip on the NF-κB sequence was further increased by both Cirhin and R565W-Cirhin. Importantly, the effect of R565W-Cirhin was weaker than that of the wild type protein. We observed increased levels of Cirhin-Cirip complex in nuclear extracts in the presence of this NF-κB sequence. Our hypothesis is that Cirhin is a transcriptional regulatory factor of this NF-κB sequence and could be a participant in the regulation of other genes with NF-κB responsive elements. Since the activities of genes regulated through NF-κB responsive elements are especially important during development, this interaction may be a key to explain the perinatal appearance of NAIC.

Genotyping of PCR-based polymorphisms and linkage-disequilibrium analysis at the NF1 locus

Energy Technology Data Exchange (ETDEWEB)

Purandare, S.M.; Viskochil, D.H.; Cawthon, R. [Univ. of Utah, Salt Lake City, UT (United States)] [and others

1996-07-01

Six polymorphism across the NF1 gene have been adapted for genotyping through application of PCR-based assays. Three exon-based polymorphisms - at positions 702, 2034, and 10647 in the NF1 cDNA - were genotyped by mutagenically separated PCR (MS-PCR). A fourth polymorphism, DV1.9, is an L1 insertion element in intron 30, and the other two polymorphisms, GXAlu and EVI-20, are short tandem repeats in intron 27b. All the polymorphisms were evaluated in a cohort of 110 CEPH individuals who previously had been analyzed by use of eight RFLPs at the NF1 locus. Pairwise linkage-disequilibrium analyses with the six PCR-based polymorphisms and their flanking markers demonstrated disequilibrium between all tested loci. Genotypes of the four diallelic polymorphisms (702, 2034, 10647, and DV1.9) were also evaluated in cohorts from the CEPH, African, and Japanese populations. The CEPH and Japanese cohorts showed similar heterozygosities and linkage-disequilibrium coefficients. The African cohort showed a higher degree of heterozygosity and lower linkage-disequilibrium values, compared with the CEPH and Japanese cohorts. 36 refs., 2 figs., 3 tabs.

Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

LENUS (Irish Health Repository)

Killeen, S D

2009-05-19

Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.

ISO 9001 quality management systems

CERN Document Server

Natarajan, Dhanasekharan

2017-01-01

This book explains the requirements of ISO 9001 for establishing quality management system (QMS) for an organization. The requirements are illustrated with examples from industries for understanding the requirements and preparing the documents of QMS with high clarity. Methods of integrating ISO 9001 requirements with enterprise resource planning (ERP) software are presented. The software integrated approach enables process owners to focus on their core tasks of achieving the planned outputs of processes and the software generates quality records automatically.

Lean principles adoption in environmental management system (EMS - ISO 14001

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Perumal Puvanasvaran

2012-12-01

Full Text Available Purpose: The purpose of this study is to examine the characteristic of the lean principles into ISO 14001 and to propose linkage of the lean principles and ISO 14001.Design/methodology/approach: To achieve the objective of the study, literature survey and quantitative research method using questionnaires survey are used.Findings and Originality/value: The findings of this study confirm that ISO 14001 certified company adopted lean production practices.  The study also proves that lean principles have positive and significant relationship with ISO 14001 EMS and the linkage can be made between lean principles and ISO 14001 to achieve Continual Improvement.Research limitations/implications: The small sizes of the sample of the participating companies are the main limitations of this study and this research mainly focuses on the manufacturing environment and services industry.Practical implications: This research show that all ISO 14001 companies do adopt at least one lean production practices and the main findings are lean principles has positive and highly significant relationship with ISO 14001 requirements.  This is because the integration of lean principles into ISO 14001 will serve practical methods for ISO14001 EMS to achieve the continual improvement.Originality/value: This research is amongst the first to study the combined lean principles with ISO 1400.  Based on the current situation, there is no integration within this two management system. 

Standardization of Image Quality Analysis – ISO 19264

DEFF Research Database (Denmark)

Wüller, Dietmar; Kejser, Ulla Bøgvad

2016-01-01

There are a variety of image quality analysis tools available for the archiving world, which are based on different test charts and analysis algorithms. ISO has formed a working group in 2012 to harmonize these approaches and create a standard way of analyzing the image quality for archiving...... systems. This has resulted in three documents that have been or are going to be published soon. ISO 19262 defines the terms used in the area of image capture to unify the language. ISO 19263 describes the workflow issues and provides detailed information on how the measurements are done. Last...... but not least ISO 19264 describes the measurements in detail and provides aims and tolerance levels for the different aspects. This paper will present the new ISO 19264 technical specification to analyze image quality based on a single capture of a multi-pattern test chart, and discuss the reasoning behind its...

Twenty new ISO standards on dosimetry for radiation processing

International Nuclear Information System (INIS)

Farrar IV, H.

2000-01-01

Twenty standards on essentially all aspects of dosimetry for radiation processing were published as new ISO standards in December 1998. The standards are based on 20 standard practices and guides developed over the past 14 years by Subcommittee E10.01 of the American Society for Testing and Materials (ASTM). The transformation to ISO standards using the 'fast track' process under ISO Technical Committee 85 (ISO/TC85) commenced in 1995 and resulted in some overlap of technical information between three of the new standards and the existing ISO Standard 11137 Sterilization of health care products - Requirements for validation and routine control - Radiation sterilization. Although the technical information in these four standards was consistent, compromise wording in the scopes of the three new ISO standards to establish precedence for use were adopted. Two of the new ISO standards are specifically for food irradiation applications, but the majority apply to all forms of gamma, X-ray, and electron beam radiation processing, including dosimetry for sterilization of health care products and the radiation processing of fruit, vegetables, meats, spices, processed foods, plastics, inks, medical wastes, and paper. Most of the standards provide exact procedures for using individual dosimetry systems or for characterizing various types of irradiation facilities, but one covers the selection and calibration of dosimetry systems, and another covers the treatment of uncertainties using the new ISO Type A and Type B evaluations. Unfortunately, nine of the 20 standards just adopted by the ISO are not the most recent versions of these standards and are therefore already out of date. To help solve this problem, efforts are being made to develop procedures to coordinate the ASTM and ISO development and revision processes for these and future ASTM-originating dosimetry standards. In the meantime, an additional four dosimetry standards have recently been published by the ASTM but have

A Stepwise ISO-Based TQM Implementation Approach Using ISO 9001:2015

Directory of Open Access Journals (Sweden)

Chen Chi-kuang

2016-12-01

Full Text Available The lack of an implementation roadmap always deters enterprises from choosing Total Quality Management (TQM as its major management approach. This paper proposes a stepwise ISO-based TQM implementation approach which is based on the notion of the new three-dimensional overall business excellence framework developed by Dahlgaard et al. [1]. The proposed approach consists of nine steps comprising three categories: “TQM faith building”, “TQM tools and techniques learning”, and “system development”. The steps in each of the three categories are arranged to span across the proposed nine-step approach. The ISO 9001:2015 standard is used as a case study to demonstrate the proposed approach. The ideas and benefits of the proposed approach are further discussed in relation to this illustration.

New ISO standard - personnel photographic film dosemeters

International Nuclear Information System (INIS)

Brabec, D.

1980-01-01

The ISO Standard 1757 ''Personnel Photographic Film Dosemeters'', issued in June 1980, is briefly described. UVVVR's own dosemeter developed for use in the national film dosimetry service in Czechoslovakia is evaluated in relation to this ISO Standard. (author)

Effect of bisphosphonates on NFATc1 and correlators p-NF-κB and p-c-Jun in osteoclast differentiation

Directory of Open Access Journals (Sweden)

Wei DONG

2015-11-01

Full Text Available Objective　To study the effect of alendronate (ALN on NFATc1 and correlated signaling factors p-NF-κB and p-c-Jun in osteoclast differentiation. Methods　Osteoclasts were inductively cultivated with mouse mononuclear macrophage RAW264.7, and they were divided into 2 groups: group A (control group and group B (ALN-treated group. The protein expressions of NFATc1, p-NF-κB and p-c-Jun were determined with Western blotting at the 2nd day of cultivation; the expression of NFATc1 was assessed by immunofluorescent assay on the 4th day; and the osteoclast formation was examined on the 7th day of cultivation. RAW264.7 cells were inoculated on abrasive dentine disk, and divided into 2 groups and treated as mentioned above. The resorption function of osteoclast was observed on the 9th day of inoculation. Results　TRAP positive multinuclear osteoclasts were observed, and resorption lacunaes formed in the abrasive dentine disks of the 2 groups. More TRAP positive multinuclear cells and resorption lacunaes in large size were found in group A than those in group B. Immunofluorescence assay showed the expression of NFATc1 was higher in group A than in group B. The gene expressions of NFATc1, p-NF-κB and p-c-Jun were lower in group B than in group A(P<0.01 as determined with Western blotting. Conclusion　By down-regulating the expressions of p-NF-κB and p-c-Jun, ALN may strongly inhibit the osteoclast formation and its resorption function, thus inhibiting NFATc1 expression. DOI: 10.11855/j.issn.0577-7402.2015.10.02

The garlic NF-YC gene, AsNF-YC8, positively regulates non-ionic hyperosmotic stress tolerance in tobacco.

Science.gov (United States)

Sun, Xiudong; Lian, Haifeng; Liu, Xingchen; Zhou, Shumei; Liu, Shiqi

2017-05-01

To investigate the relationship between nuclear factor Y (NF-Y) and stress tolerance in garlic, we cloned a NF-Y family gene AsNF-YC8 from garlic, which was largely upregulated at dehydrate stage. Expression pattern analyses in garlic revealed that AsNF-YC8 is induced through abscisic acid (ABA) and abiotic stresses, such as NaCl and PEG. Compared with wild-type plants, the overexpressing-AsNF-YC8 transgenic tobacco plants showed higher seed germination rates, longer root length and better plant growth under salt and drought stresses. Under drought stress, the transgenic plants maintained higher relative water content (RWC), net photosynthesis, lower levels of malondialdehyde (MDA), and less ion leakage (IL) than wild-type control plants. These results indicate the high tolerance of the transgenic plants to drought stress compared to the WT. The transgenic tobacco lines accumulated less reactive oxygen species (ROS) and exhibited higher antioxidative enzyme activities compared with wild-type (WT) plants under drought stress, which suggested that the overexpression of AsNF-YC8 improves the antioxidant defense system by regulating the activities of these antioxidant enzymes, which in turn protect transgenic lines against drought stress. These results suggest that AsNF-YC8 plays an important role in tolerance to drought and salt stresses.

Evaluation of the role of 8-iso-PGF levels at multiple sites during intracranial hemorrhage in pediatric patients.

Science.gov (United States)

Qi, B-X; Yao, H; Shang, L; Sheng, L-P; Wang, X-C; Zhu, L; Zhang, X-X; Wang, J-P; Fang, D-H

2017-09-01

The present study was planned to explore the role of 8-isomeric-prostaglandinF2α (8-iso-PGF2α) levels at the multiple sites of cerebrospinal fluid in children with intracranial hemorrhage. 90 children with intracranial hemorrhage were admitted to Surgery Intensive Care Unit (SICU) of our hospital from January to December 2013 and were selected as study subjects. They were divided into group A (n=30), group B (n=30) and group C (n=30). The group A was given conventional treatment, the group B was treated with minimally invasive puncture and the group C was treated with cerebrospinal fluid decompression. After 1 d, 2 d, 3 d, and 7 d of hospitalization, enzyme-linked immunosorbent assay (ELISA) was used to detect the 8-iso-PGF2α levels in peripheral blood of children in all groups. On the day of admission and 10 d after treatment, 3 groups of children were implemented with brain nuclear magnetic resonance spectroscopy for metabolite analyses. On the day of admission there were no significant differences in the 8-iso-PGF2α levels among group A, B and C. Further, after 1 d, 3 d, 7 d of hospital stay, the 8-iso-PGF2α levels in peripheral blood showed a gradual downward trend, and decline range of the group C was greater than that of group A and B (p iso-PGF2α in peripheral blood (r = 0.546, p iso-PGF2α plays an important role in the pathogenesis of intracranial hemorrhage, and could be utilized as a biomarker of oxidative stress in children with intracranial hemorrhage. Further, cerebrospinal fluid decompression is a better method of treatment for intracranial hemorrhage.

SINERGI ISO 9001:2000 - CMMI PADA INDUSTRI PENGEMBANG PERANGKAT LUNAK

Directory of Open Access Journals (Sweden)

Leo Willyanto Santoso

2005-01-01

Full Text Available All sectors of society including softwere industry, have a big concern about quality, both of product quality and service quality. The need to manage risk, has a strong relation with quality and increases system complexity. Standarization in determining quality, ISO is a must for all software developer. If we study further, ISO 9001:2000 still has some weakness especially for implementation in software product. This paper presents a comparative analysis of quality approaches to risk management. This paper also provide a general overview of all the risks aspects treated in ISO 9001:2000 standards and CMMI model version 1.1. In this research, we obtain a strategy to implement ISO 9001:2000 and CMMI together when we make a planing to increase software process. Besides it produces analysis how to change position from ISO 9001:2000 to CMMI. In the implementation on software industry PT 'X', obtain get various benefits that has never been obtained before. Abstract in Bahasa Indonesia : Semua hal dalam hidup ini selalu memperhatikan masalah kualitas, baik itu berupa kualitas produk ataupun kualitas layanan. Pada industri perangkat lunak, hal ini tidak dibedakan, kebutuhan untuk menghasilkan produk yang berkualitas akan meningkatkan kekompleksan dari sebuah sistem. Standarisasi dalam penentuan kualitas, ISO sudah menjadi keharusan bagi para pengembang perangkat lunak. Apabila diteliti lebih lanjut, ISO 9001:2000 masih mempunyai banyak kekurangan, khususnya untuk diaplikasikan dalam produk perangkat lunak.Pada penelitian ini, akan dibahas analisis perbandingan dengan melakukan pendekatan kualitas untuk meningkatkan proses perangkat lunak dengan melakukan mapping antara ISO 9001:2000 dengan CMMI. Hal-hal yang dibahas berupa aspek-aspek dari standard ISO dan CMMI versi 1.1. Pada penelitian ini, dapat diperoleh strategi untuk menerapkan ISO 9001:2000 dan CMMI secara sinergi ketika merencanakan untuk melakukan peningkatan proses perangkat lunak. Selain itu

Helper component proteinase of the genus Potyvirus is an interaction partner of translation initiation factors eIF(iso)4E and eIF4E and contains a 4E binding motif.

Science.gov (United States)

Ala-Poikela, Marjo; Goytia, Elisa; Haikonen, Tuuli; Rajamäki, Minna-Liisa; Valkonen, Jari P T

2011-07-01

The multifunctional helper component proteinase (HCpro) of potyviruses (genus Potyvirus; Potyviridae) shows self-interaction and interacts with other potyviral and host plant proteins. Host proteins that are pivotal to potyvirus infection include the eukaryotic translation initiation factor eIF4E and the isoform eIF(iso)4E, which interact with viral genome-linked protein (VPg). Here we show that HCpro of Potato virus A (PVA) interacts with both eIF4E and eIF(iso)4E, with interactions with eIF(iso)4E being stronger, as judged by the data of a yeast two-hybrid system assay. A bimolecular fluorescence complementation assay on leaves of Nicotiana benthamiana showed that HCpro from three potyviruses (PVA, Potato virus Y, and Tobacco etch virus) interacted with the eIF(iso)4E and eIF4E of tobacco (Nicotiana tabacum); interactions with eIF(iso)4E and eIF4E of potato (Solanum tuberosum) were weaker. In PVA-infected cells, interactions between HCpro and tobacco eIF(iso)4E were confined to round structures that colocalized with 6K2-induced vesicles. Point mutations introduced to a 4E binding motif identified in the C-terminal region of HCpro debilitated interactions of HCpro with translation initiation factors and were detrimental to the virulence of PVA in plants. The 4E binding motif conserved in HCpro of potyviruses and HCpro-initiation factor interactions suggest new roles for HCpro and/or translation factors in the potyvirus infection cycle.

An introduction to information security and ISO27001:2013

CERN Document Server

Watkins, Steve

2013-01-01

Up to date with the latest version of the Standard (ISO27001:2013), An Introduction to information security and ISO27001:2013 is the perfect solution for anyone wanting an accurate, fast, easy-to-read primer on information security from an acknowledged expert on ISO27001.

Blocking NF-κB: an inflammatory issue.

Science.gov (United States)

Rahman, Arshad; Fazal, Fabeha

2011-11-01

The nuclear factor (NF)-κB is considered the master regulator of inflammatory responses. Studies in mouse models have established this transcription factor as an important mediator of many inflammatory disease states, including pulmonary diseases such as acute lung injury and acute respiratory distress syndrome. Endothelial cells provide the first barrier for leukocytes migrating to the inflamed sites and hence offer an attractive cellular context for targeting NF-κB for treatment of these diseases. However, recent studies showing that NF-κB also plays an important role in resolution phase of inflammation and in tissue repair and homeostasis have challenged the view of therapeutic inhibition of NF-κB. This article reviews the regulation of NF-κB in the context of endothelial cell signaling and provides a perspective on why "dampening" rather than "abolishing" NF-κB activation may be a safe and effective treatment strategy for inflammation-associated pulmonary and other inflammatory diseases.

Application of the dual-luciferase reporter assay to the analysis of promoter activity in Zebrafish embryos

Directory of Open Access Journals (Sweden)

Mulero Victoriano

2008-10-01

Full Text Available Abstract Background The dual-luciferase assay has been widely used in cell lines to determine rapidly but accurately the activity of a given promoter. Although this strategy has proved very useful, it does not allow the promoter and gene function to be analyzed in the context of the whole organism. Results Here, we present a rapid and sensitive assay based on the classical dual-luciferase reporter technique which can be used as a new tool to characterize the minimum promoter region of a gene as well as the in vivo response of inducible promoters to different stimuli. We illustrate the usefulness of this system for studying both constitutive (telomerase and inducible (NF-κB-dependent promoters. The flexibility of this assay is demonstrated by induction of the NF-κB-dependent promoters using simultaneous microinjection of different pathogen-associated molecular patterns as well as with the use of morpholino-gene mediated knockdown. Conclusion This assay has several advantages compared with the classical in vitro (cell lines and in vivo (transgenic mice approaches. Among others, the assay allows a rapid and quantitative measurement of the effects of particular genes or drugs in a given promoter in the context of a whole organism and it can also be used in high throughput screening experiments.

Andrographolide suppresses proliferation of human colon cancer SW620 cells through the TLR4/NF-κB/MMP-9 signaling pathway.

Science.gov (United States)

Zhang, Rui; Zhao, Jian; Xu, Jian; Jiao, De-Xin; Wang, Jian; Gong, Zhi-Qiang; Jia, Jian-Hui

2017-10-01

Modern pharmacological research has revealed that andrographolide has various functions, including anti-bacterial, anti-inflammatory and anti-viral effects, immunoregulation, treating cardiovascular and cerebrovascular diseases, and prevention and treatment of alcoholic liver injury. The present study investigated whether andrographolide suppresses the proliferation of human colon cancer cell through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB/matrix metalloproteinase-9 (MMP-9) signaling pathway. The MTT assay and lactate dehydrogenase assay were used to evaluate the anticancer effects of andrographolide on cell proliferation and cytotoxicity in human colon cancer SW620 cells. Flow cytometry was used to analyze the anticancer effects of andrographolide on apoptosis by Annexin V-fluorescein isothiocyanate/propidium iodide kit. The effects of andrographolide on the activity of caspase-3/9 were measured using ELISA. Western blot analysis was also used to analyze the protein expression of TLR4, myeloid differentiation primary response gene 88 (MyD88), NF-κB-p65 and MMP-9. In the present study, it was found that andrographolide suppressed the cell proliferation, augmented cytotoxicity, evoked cell apoptosis and activated caspase-3/9 activities in human colon cancer SW620 cells. The results revealed that the anti-proliferation effects of andrographolide on the SW620 cells was associated with the inhibition of TLR4, MyD88, NF-κB-p65 and MMP-9 signaling activation. The results suggest that andrographolide is a promising drug for treatment of human colon cancer via suppression of the TLR4/NF-κB/MMP-9 signaling pathway.

Information security risk management for ISO27001/ISO27002

CERN Document Server

Calder, A; Watkins, S

2010-01-01

Drawing on international best practice, including ISO/IEC 27005, NIST SP800-30 and BS7799-3, the book explains in practical detail how to carry out an information security risk assessment. It covers key topics, such as risk scales, threats and vulnerabilities, selection of controls, and roles and responsibilities, and includes advice on choosing risk assessment software.

A noncanonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia.

Science.gov (United States)

Shanmugam, Rajasubramaniam; Gade, Padmaja; Wilson-Weekes, Annique; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A; Baghdadi, Tareq Al; Sargent, Katie J; Cripe, Larry D; Kalvakolanu, Dhananjaya V; Boswell, H Scott

2012-01-15

Death-associated protein kinase 1 (DAPK1), a tumor suppressor, is a rate-limiting effector in an endoplasmic reticulum (ER) stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of acute myeloid leukemia (AML) with poor prognosis, which lacked ER stress-induced apoptosis. Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB-and c-Jun-responsive genes, was studied. RNA interference knockdown studies were carried out in an Flt3ITD(+) cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were carried out to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. AMLs characterized by normal karyotype with Flt3ITD were found to have 10- to 100-fold lower DAPK1 transcripts normalized to the expression of c-Jun, a transcriptional activator of DAPK1, as compared with a heterogeneous cytogenetic category. In addition, Meis1, a c-Jun-responsive adverse AML prognostic gene signature was measured as control. These Flt3ITD(+) AMLs overexpress relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter together with histone deacetylase 2 (HDAC2) and HDAC6 in the Flt3ITD(+) human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NF-κB-inducing kinase (NIK), de-repressed DAPK1. DAPK1-repressed primary Flt3ITD(+) AMLs had selective nuclear activation of p52NF-κB. Flt3ITD promotes a noncanonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD(+) AML. ©2011 AACR.

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

Science.gov (United States)

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

Rs4705342 polymorphism is involved in the tumorigenesis of HBV positive HCC by altering the binding affinity of HBV induced NF-kB with the promoter region of microRNA-143.

Science.gov (United States)

Yin, Xiuli; Sun, Shiying; Zhao, Junyan; Yang, Jing; Lei, Xiaofei; Xu, Changqing; Li, Kun

2017-12-13

The objective of this study was to explore the role of rs4705342 located in the miR-143 promoter in relation to the control of HBV positive HCC and the underlying molecular mechanism. A luciferase assay was performed to explore the factors which influenced miR-143 transcription activity and the target gene of miR-143. This would further be confirmed by ChIP assay. Western blot and real-time PCR were performed to identify the relationship between miR-143 and ORP8. Luciferase activity of miR-143 SNP was increased with the presence of C allele. The presence of T allele partially restored the transcription ability. NF-κB displayed a much higher degree of luciferase activity in relation to the cells transfected with vectors containing either T or C allele rather than control cells with a greater extent in C allele group than T allele group. At the same time, ChIP assay indicated that the affinity of NF-ΚB in the miR-143 promoter was higher in C/C cells. The over-expression of HBX promotes NF-kB expression thus increasing the extent of binding of NF-kB on the CC allele of the miR-143 promoter. The binding is also abolished by NF-kB siRNA. ORP8 was proven to be a target gene of miR-143 using bioinformatics algorithm analysis. It was further confirmed by the luciferase assay that miR-143 substantially inhibited luciferase activities of wild-type ORP8. However, it did not affect the mutant ORP8. HBx induced by HBV infection up-regulated miR-143 expression. NF- kB can partially abolish the promotion effect of HBx on the miR-143 level in cells genotyped as CC but not in cells genotyped as TT. Tissues derived from participants genotyped as CC exhibited a higher level of miR-143, but a lower level of ORP8. The presence of the minor allele of rs4705342 in the promoter of miR-143 attenuated the transcription ability. This promoted ORP8 expression and could be a factor contributing to the oncogenesis in HBV positive HCC. © 2017 Wiley Periodicals, Inc.

10−7 m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway

Science.gov (United States)

Wang, Y; Zheng, Y; Wang, Z; Li, J; Wang, Z; Zhang, G; Yu, J

2013-01-01

Objectives Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs). Materials and methods In this study, human DPSCs were isolated and treated with 10−7 m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed. Results Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation. Conclusion These findings provide evidence that 10−7 m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway. PMID:24152244

ISO 9001 2000 : the quality management process

CERN Document Server

Tricker, Ray

2006-01-01

With the publication of ISO 9001:2000, there is now a single quality management ?requirements? standard that is applicable to all organisations, products and services. ISO 9001:2000 is the only standard that can be used for the certification of a QMS and its generic requirements can be used by any organisation.ISO 9001:2000 applies to all types or organisations. It is the quality standard which specifies the requirements of quality management systems for use where organisations need to demonstrate their capability to provide products and services which meet both customer needs and relevant reg

[ISO 9001:2015 Certification in Quality Management].

Science.gov (United States)

Enders, Christian; Lang, Gabriele E; Lang, Gerhard K; Werner, Jens Ulrich

2017-07-01

Quality management improves the structures, processes and results of organizations of all kinds. Many practices and clinics have their existing quality management system certified according to ISO 9001, (e.g., to check their own quality management system or to obtain a testimonial against third parties). The latest version ISO 9001:2015 contains some changes, both structurally and in terms of content. These changes can be met with reasonable efforts. An ISO 9001:2015 certification represents a value for your organization, but these advantages are often not directly measurable. Georg Thieme Verlag KG Stuttgart · New York.

ISO 9001 and ISO 14001: An Integrated Quality Management System for an MTR Facility SAFARI-1 Research Reactor

International Nuclear Information System (INIS)

Du Bruyn, J.F.; Piani, C.S.B.

2005-01-01

The SAFARI-1 research reactor, owned and operated by the South African Nuclear Energy Corporation (Necsa), initially obtained ISO 9001 accreditation of its Quality, Health, Safety and Environmental (QHSE) management system via international affiliation from the South African Bureau of Standards (SABS) during 1998 and re-certification according to ISO 9001 (2000) in 2003. With ever-increasing demands on nuclear facilities to demonstrate conformance to environmental policies, SAFARI-1 has now developed an Environmental Management System (EMS) that is compliant with ISO 14001 (1996) and is fully integrated with the SAFARI-1 Quality Management System (QMS). The dynamic involvement of SAFARI-1 in commercial applications demanded that any transition of the original QMS to a fully incorporated QHSE system had to be done in a way that would ensure sustained delivery of a safe and reliable service with continuous quality. At the same time, the primary vision of operating a facility under an efficient financial management programme was essential. The criteria established by the original ISO 9001 compliant QMS were appraised against the additional requirements of ISO 14001 and a suitable superstructure derived for generation and implementation of an inclusive EMS. The transitional integration of this system was planned so as to produce a QMS suitable to quality, environmental and other management related issues for application to the unique function of a nuclear research reactor. (author)

Sertifikatõ ISO - mafioznaja struktura so znakom pljuss / Olesja Bõkova

Index Scriptorium Estoniae

Bõkova, Olesja

2005-01-01

Esimesed ISO sertifikaadid, mille aluseks on briti kvaliteedi standardite süsteem, anti Euroopa Liidus välja 1987. a. ISO sertifikaadid Eestis. Diagramm: Välja antud ISO 9000 sertifikaadid 1994-2004

Metrological management evaluation based on ISO10012: an empirical study in ISO-14001-certified Spanish companies

International Nuclear Information System (INIS)

Beltran, Jaime; Rivas, Miguel; Munuzuri, Jesus; Gonzalez, Cristina

2010-01-01

Environmental management systems based on the ISO 14001 standard rely strongly on metrological measurement and confirmation processes to certify the extent to which organizations monitor and improve their environmental behavior. Nevertheless, the literature lacks in studies that assess the influence of these metrological processes on the performance of environmental management in organizations, even now that the international standard ISO 10012 is already available to establish requisites and guidelines for the development of a metrological management system that is compatible with any other standardized management system. This work seeks to assess that influence through the development of an evaluation model for metrological management, which is then validated through an experimental analysis of the results obtained from the application of an audit process in 11 Spanish companies, all ISO-14001-certified and operating in different industrial sectors. (author)

Significance of ISO 9000 Quality Management System for ...

African Journals Online (AJOL)

Significance of ISO 9000 Quality Management System for Performance ... of ISO 9000 Quality Management System implementation for performance improvement. ... to find out the relationship between certification and process variability.

Neuroprotective effects of α-iso-cubebenol on glutamate-induced neurotoxicity.

Science.gov (United States)

Park, Sun Young; Choi, Yung Hyun; Park, Geuntae; Choi, Young-Whan

2015-09-01

α-Iso-cubebenol is a natural compound isolated from Schisandra chinensis, and is reported to have beneficial bioactivity including anti-inflammatory and anti-tumor activities. Glutamate-induced oxidative neuronal damage has been implicated in a variety of neurodegenerative disorders. Here we investigated the mechanisms of α-iso-cubebenol protection of mouse hippocampus-derived neuronal cells (HT22 cells) from apoptotic cell death induced by the major excitatory neurotransmitter, glutamate. Pretreatment with α-iso-cubebenol markedly attenuated glutamate-induced loss of cell viability and release of lactate dehydrogenase), in a dose-dependent manner. α-Iso-cubebenol significantly reduced glutamate-induced intracellular reactive oxygen species and calcium accumulation. Strikingly, α-iso-cubebenol inhibited glutamate-induced mitochondrial depolarization, which releases apoptosis-inducing factor from mitochondria. α-Iso-cubebenol also suppressed glutamate-induced phosphorylation of extracellular-signal-regulated kinases. Furthermore, α-iso-cubebenol induced CREB phosphorylation and Nrf-2 nuclear accumulation and increased the promoter activity of ARE and CREB in HT22 cells. α-Iso-cubebenol also upregulated the expression of phase-II detoxifying/antioxidant enzymes such as HO-1 and NQO1. Subsequent studies revealed that the inhibitory effects of α-iso-cubebenol on glutamate-induced apoptosis were abolished by small interfering RNA-mediated knockdown of CREB and Nrf-2. These findings suggest that α-iso-cubebenol prevents excitotoxin-induced oxidative damage to neurons by inhibiting apoptotic cell death, and might be a potential preventive or therapeutic agent for neurodegenerative disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

SISTEM HACCP KE DALAM SISTEM MANAJEMEN KEAMANAN PANGAN ISO 22000:2009 (STUDI KASUS DI PT INDOKOM SAMUDRA PERSADA [The Merger of Quality Assurance System ISO 9001:2008 and HACCP system into Food Safety Management SystemISO 22000:2009 (Case Study at Indoko

Directory of Open Access Journals (Sweden)

Novri Ilmiawan

2014-12-01

Full Text Available The object of this research was to merge the application of HACCP system and ISO 9001:2008 in ISP company into ISO 22000:2009. The  research method used was case study method. The study was conducted on three stages. The first was the arrangement gap analysis conducted by comparing the conditions of the company with ISO 22000:2009 standards. The second was by observing sanitation and pre requisite programs. The third was by observing traceability system. The data in this research were reported descriptively, consisted of ISO 9001:2008 and HACCP application in the company and the gaps of principles in ISO 22000:2009 toward ISO 9001:2008 and HACCP. The result showed that ISP company has applied 12 steps which covered in HACCP system, and also the ISO 9001 system were appropriate with ISO 9001:2008 standards in every clauses. Pre requisite program (GMP and SSOP have been effectively applied. GMP in ISP company is categorized on the first spot (excellent. The eight keys of SSOP have been fulfilled. ISP company has been fulfilling 54 from 57 (94.74% criteria in ISO 22000:2009 standards, yet there still several things needed to be improved, which are the quality manual content  and HACCP table plan and its monitoring. The  traceability system has been applied well in ISP .   Key words : HACCP, ISO 9001, ISO 22000, GMP, SSOP.

[Accreditation of clinical laboratories based on ISO standards].

Science.gov (United States)

Kawai, Tadashi

2004-11-01

International Organization for Standardization (ISO) have published two international standards (IS) to be used for accreditation of clinical laboratories; ISO/IEC 17025:1999 and ISO 15189:2003. Any laboratory accreditation body must satisfy the requirements stated in ISO/IEC Guide 58. In order to maintain the quality of the laboratory accreditation bodies worldwide, the International Laboratory Accreditation Cooperation (ILAC) has established the mutual recognition arrangement (MRA). In Japan, the International Accreditation Japan (IAJapan) and the Japan Accreditation Board for Conformity Assessment (JAB) are the members of the ILAC/MRA group. In 2003, the Japanese Committee for Clinical Laboratory Standards (JCCLS) and the JAB have established the Development Committee of Clinical Laboratory Accreditation Program (CLAP), in order to establish the CLAP, probably starting in 2005.

Environmental Management System ISO 14001

CERN Document Server

Haider, Syed

2010-01-01

This is a must-have tool for any company in the process of adopting and incorporating the ISO 14001:2004 requirements, this book and accompanying CD-ROM provides the latest updates and amendments and translates the ISO language into actionable strategy. Offering administrative solutions to managers of all sorts, it includes practical examples of policies with objectives, targets, and action plans applicable to any process related industry or an ordinary organization. With template formats and hands-on flow charts to describe step-by-step system development, documentation, and implementation ph

Evaluation of the PetrifilmTM EB and TEMPO® EB systems with ISO 21528-2:2004 method for the count of Enterobacteriaceae in milk

Directory of Open Access Journals (Sweden)

Andréia Cirolini

2013-09-01

Full Text Available The development of alternative microbiological techniques is driven by the necessity to meet the current needs to deliver rapid results in the manufacturing process of foods, but it is important that these methods be evaluated for each application. The objective of the present study was to assess the PetrifilmTM EB and the TEMPO® EB systems with ISO 21528-2:2004 for the count of Enterobacteriaceae in pasteurized and UHT milk samples. We analyzed the microflora of 141 pasteurized milk samples, 15 samples of artificially contaminated pasteurized milk and 15 samples of artificially contaminated UHT milk. Investigation of the method PetrifilmTM EB and ISO 21528:2 regression analysis showed a high correlation in the samples, r = 0.90 for the microflora of pasteurized milk, r = 0.98 for artificially contaminated pasteurized milk and r = 0.99 for the artificially contaminated UHT milk. In evaluating the system TEMPO EB ® method and ISO 21528:2 correlation was also significant in the analyzed samples, with r = 0.86 for the microflora of pasteurized milk, r = 0.96 for artificially contaminated pasteurized milk and r = 0.99 for artificially contaminated UHT milk. No statistically significant differences were observed between the three methods conducted to analyze artificially contaminated pasteurized and UHT milk at three inoculum levels. In conclusion, the PetrifilmTM EB system and the TEMPO® EB system may be an alternative to the ISO 21528-2:2004 for the Enterobacteriaceae assay for milk as because of the ease-of-operation and the time reduction achieved for conducting the microbiological assay using these systems.

Acrolein inhibits cytokine gene expression by alkylating cysteine and arginine residues in the NF-kappaB1 DNA binding domain.

Science.gov (United States)

Lambert, Cherie; Li, Jimei; Jonscher, Karen; Yang, Teng-Chieh; Reigan, Philip; Quintana, Megan; Harvey, Jean; Freed, Brian M

2007-07-06

Cigarette smoke is a potent inhibitor of pulmonary T cell responses, resulting in decreased immune surveillance and an increased incidence of respiratory tract infections. The alpha,beta-unsaturated aldehydes in cigarette smoke (acrolein and crotonaldehyde) inhibited production of interleukin-2 (IL-2), IL-10, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha by human T cells but did not inhibit production of IL-8. The saturated aldehydes (acetaldehyde, propionaldehyde, and butyraldehyde) in cigarette smoke were inactive. Acrolein inhibited induction of NF-kappaB DNA binding activity after mitogenic stimulation of T cells but had no effect on induction of NFAT or AP-1. Acrolein inhibited NF-kappaB1 (p50) binding to the IL-2 promoter in a chromatin immunoprecipitation assay by >99%. Using purified recombinant p50 in an electrophoretic mobility shift assay, we demonstrated that acrolein was 2000-fold more potent than crotonaldehyde in blocking DNA binding to an NF-kappaB consensus sequence. Matrix-assisted laser desorption/ionization time-of-flight and tandem mass spectrometry demonstrated that acrolein alkylated two amino acids (Cys-61 and Arg-307) in the DNA binding domain. Crotonaldehyde reacted with Cys-61, but not Arg-307, whereas the saturated aldehydes in cigarette smoke did not react with p50. These experiments demonstrate that aldehydes in cigarette smoke can regulate gene expression by direct modification of a transcription factor.

Synthesis and Biological Activity of 2',3'-iso-Aryl-abscisic Acid Analogs.

Science.gov (United States)

Wan, Chuan; Wang, Mingan; Yang, Dongyan; Han, Xiaoqiang; Che, Chuanliang; Ding, Shanshan; Xiao, Yumei; Qin, Zhaohai

2017-12-15

2',3'- iso -Benzoabscisic acid ( iso -PhABA), an excellent selective abscisic acid (ABA) analog, was developed in our previous work. In order to find its more structure-activity information, some structural modifications were completed in this paper, including the substitution of phenyl ring and replacing the ring with heterocycles. Thus, 16 novel analogs of iso -PhABA were synthesized and screened with three bioassays, Arabidopsis and lettuce seed germination and rice seedling elongation. Some of them, i.e., 2',3'- iso -pyridoabscisic acid ( iso -PyABA) and 2',3'- iso -franoabscisic acid ( iso -FrABA), displayed good bioactivities that closed to iso -PhABA and natural (+)-ABA. Some others, for instance, substituted- iso -PhABA, exhibited certain selectivity to different physiological process when compared to iso -PhABA or (+)-ABA. These analogs not only provided new candidates of ABA-like synthetic plant growth regulators (PGRs) for practical application, but also new potential selective agonist/antagonist for probing the specific function of ABA receptors.

Ethanol extract of Portulaca Oleracea L. reduced the carbon tetrachloride induced liver injury in mice involving enhancement of NF-κB activity

Science.gov (United States)

Shi, Hongguang; Liu, Xuefeng; Tang, Gusheng; Liu, Haiyan; Zhang, Yinghui; Zhang, Bo; Zhao, Xuezhi; Wang, Wanyin

2014-01-01

Acute hepatic injury causes high morbidity and mortality world-wide. Management of severe acute hepatic failure continues to be one of the most challenging problems in clinical medicine. In present study, carbon tetrachloride (CCl4) was used to induce acute liver damage in mice and the protective effects of ethanol extract of Portulaca Oleracea L. (PO) were examined. The aminotransferase activities were biochemical estimated and the liver damage was tested by morphological histological analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. The role of PO on the activity of NF-κB was determined by luciferase reporter gene assay and immunohistochemistry. The level of p-p65 was tested by western blot. Our results showed that PO administration on mice would decrease the serum aminotransferase level and reduced the liver histological damage. We also found that nuclear translocation of p65 was enhanced in liver tissues of mice treated with PO compared with control animals. In addition, in cultured hepatic cells, PO increased the NF-κB luciferase reporter gene activity and upregulated the level of phosphorylation of p65, but had no effects on mice liver SOD activity and MDA level. Collectively, PO attenuated CCl4 induced mice liver damage by enhancement of NF-κB activity. PMID:25628785

Novel Mechanism of Attenuation of LPS-Induced NF-κB Activation by the Heat Shock Protein 90 Inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in Human Lung Microvascular Endothelial Cells

Science.gov (United States)

Thangjam, Gagan S.; Dimitropoulou, Chistiana; Joshi, Atul D.; Barabutis, Nektarios; Shaw, Mary C.; Kovalenkov, Yevgeniy; Wallace, Chistopher M.; Fulton, David J.; Patel, Vijay

2014-01-01

Heat shock protein (hsp) 90 inhibition attenuates NF-κB activation and blocks inflammation. However, the precise mechanism of NF-κB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-κB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-κB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein–protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG–induced degradation of IKBα was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-κB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the κB elements of the IKBα (an NF-κB–responsive gene) promoter. The effect of LPS on IKBα mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-κB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells. PMID:24303801

Casticin Inhibits A375.S2 Human Melanoma Cell Migration/Invasion through Downregulating NF-κB and Matrix Metalloproteinase-2 and -1

Directory of Open Access Journals (Sweden)

Zih-Yun Wu

2016-03-01

Full Text Available Casticin is one of the main components from Fructus Viticis, which is widely used as an anti-inflammatory agent. The mechanism of how casticin affects melanoma cell migration and invasion is still not well known. Here we studied the anti-metastasis effects of casticin on A375.S2 melanoma cells by using a non-lethal concentration. First; we used an adhesion assay to test the A375.S2 cells’ adhesion ability after treatment with casticin. We next investigated the cell migration ability after casticin treatment by using a wound healing assay to prove that the migration of A375.S2 cells can be inhibited by casticin and double checked the results using the transwell-migration assay. The suppressive effects on matrix metalloproteinase-2; and -9 (MMP-2; and -9 activities were examined by gelatin zymography. Furthermore, western blotting was used to investigate the protein level changes in A375.S2 cells. We found that p-EGFR; Ras and p-ERK1/2 are decreased by casticin, indicating that casticin can down-regulate the migration and invasion ability of A375.S2 cells via the p-EGFR/Ras/p-ERK pathway. The NF-κB p65 and p-ERK levels in nuclear proteins are also decreased by treatment with casticin. An EMSA assay also discovered that the NF-κB p65 and DNA interaction is decreased. NF-κB p65 protein level was examined by immunofluorescence staining and also decreased. Our findings suggest that casticin has anti-metastatic potential by decreasing the invasiveness of A375.S2 cells. We also found that casticin suppressed A375.S2 cell proliferation and cell adhesion ability, but did not affect cell death, as examined using cytometry and a collagen adhesion assay. Based on these observations, casticin could be used as an inhibitor of migration and invasion of human melanoma cells in the future.

Information security in accordance with ISO/IEC 27000

OpenAIRE

Košćak , Damjan

2011-01-01

The diploma assignment discusses Information Technology Security according to standards ISO/IEC 27001 and ISO/IEC 27002. Diploma consists of two parts. In the first part of the diploma a theoretical bases of information security are presented. The second part presents the introduction of ISO/IEC 27001 security standard in the company »X« in wich I performed a practical training. In the closure my diploma work is upgraded with results of my research work and their analysis as well as wit...

Cancer Cell Growth Inhibitory Effect of Bee Venom via Increase of Death Receptor 3 Expression and Inactivation of NF-kappa B in NSCLC Cells

Directory of Open Access Journals (Sweden)

Kyung Eun Choi

2014-07-01

Full Text Available Our previous findings have demonstrated that bee venom (BV has anti-cancer activity in several cancer cells. However, the effects of BV on lung cancer cell growth have not been reported. Cell viability was determined with trypan blue uptake, soft agar formation as well as DAPI and TUNEL assay. Cell death related protein expression was determined with Western blotting. An EMSA was used for nuclear factor kappaB (NF-κB activity assay. BV (1–5 μg/mL inhibited growth of lung cancer cells by induction of apoptosis in a dose dependent manner in lung cancer cell lines A549 and NCI-H460. Consistent with apoptotic cell death, expression of DR3 and DR6 was significantly increased. However, deletion of DRs by small interfering RNA significantly reversed BV induced cell growth inhibitory effects. Expression of pro-apoptotic proteins (caspase-3 and Bax was concomitantly increased, but the NF-κB activity and expression of Bcl-2 were inhibited. A combination treatment of tumor necrosis factor (TNF-like weak inducer of apoptosis, TNF-related apoptosis-inducing ligand, docetaxel and cisplatin, with BV synergistically inhibited both A549 and NCI-H460 lung cancer cell growth with further down regulation of NF-κB activity. These results show that BV induces apoptotic cell death in lung cancer cells through the enhancement of DR3 expression and inhibition of NF-κB pathway.

ISO sertifikaat kuulutab tootja mainet üle maailma / Ain Alvela

Index Scriptorium Estoniae

Alvela, Ain, 1967-

2006-01-01

Ilmunud ka: Delovõje Vedomosti 12. apr. lk. 24-25. ISO standardi rakendamine tagab toodangu kvaliteedi ja annab firmale usaldusväärsuse. Kommenteerib Ain Noormägi. Vt. samas: ISO 9001; ISO 14 001; Universaalne standard kohandub ettevõtte vajadustega

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

Science.gov (United States)

Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

An in-vitro approach for water quality determination: activation of NF-κB as marker for cancer-related stress responses induced by anthropogenic pollutants of drinking water.

Science.gov (United States)

Spitta, Luis F; Diegeler, Sebastian; Baumstark-Khan, Christa; Hellweg, Christine E

2018-02-01

Epidemiological studies show that there is a link between urban water pollution and increase in human morbidity and mortality. With the increase in number of new substances arising from the chemical, pharmaceutical, and agricultural industries, there is an urgent need to develop biological test systems for fast evaluation of potential risks to humans and the environmental ecosystems. Here, a combined cellular reporter assay based on the cellular survival and the stress-induced activation of the survival-promoting factor nuclear factor κB (NF-κB) and its use for the detection of cytotoxicity and cancer-related stress responses is presented. A total of 14 chemicals that may be found in trace-amounts in ground water levels are applied and tested with the presented assay. The project is embedded within the joint research project TOX-BOX which aims to develop a harmonized testing strategy for risk management of anthropogenic trace substances in potable water. The assay identified carbendazim as a NF-κB-activating agent in mammalian cells.

Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine

Directory of Open Access Journals (Sweden)

Rivelilson Mendes de Freitas

2011-06-01

Full Text Available The aim of this study was to evaluate the in vitro antioxidant effects of 12-[(2R,5R,6R-5-hydroxy-6-methylpiperidin-2-yl]dodecan-2-one (iso-6-cassine; ISO and the anticonvulsant effects of ISO on pilocarpine-induced seizures in rats. Wistar rats were treated with 0.9% saline (i.p., control group, pilocarpine (400 mg/kg, i.p., pilocarpine group, and the association of ISO (1.0 mg/kg, i.p. plus pilocarpine (400 mg/kg, i.p., 30 min after administration of ISO (ISO plus pilocarpine group. After the treatments all groups were observed for 1h. The antioxidant effect of ISO on the pilocarpine model was assessed by determining the activity of glutathione peroxidase (GPx, glutathione-S-transferase (GST and catalase (CAT as well as the levels of reactive species (RS and lipid peroxidation (LP. In vitro, ISO (5 μM reduced RS and LP. ISO (1.0 mg/kg and abolished seizures and death induced by pilocarpine in rats. ISO protected against the increase in the RS and LP levels, GST activity as well as the inhibition of GPx activity caused by pilocarpine. In addition, ISO increased the catalase activity in hippocampus of seized rats. In conclusion, the dta suggest that ISO can present anticonvulsant and antioxidant properties in the pilocarpine model of seizures in rats.

ISO developments in the United States

International Nuclear Information System (INIS)

Hogan, William W.

1998-01-01

An important feature of the restructuring process in the United States is the creation of independent system operators (ISOs) to coordinate dispatch and access to transmission grids. A number of ISOs have been proposed and are summarized here. Perhaps the greatest challenge is the pricing of transmission to give proper economic signals to market participants, and the locational pricing scheme now operating in the PJM system offers the best hope for efficient pricing. (author)

ISO 9001 in a neonatal intensive care unit (NICU).

Science.gov (United States)

Vitner, Gad; Nadir, Erez; Feldman, Michael; Yurman, Shmuel

2011-01-01

The aim of this paper is to present the process for approving and certifying a neonatal intensive care unit to ISO 9001 standards. The process started with the department head's decision to improve services quality before deciding to achieve ISO 9001 certification. Department processes were mapped and quality management mechanisms were developed. Process control and performance measurements were defined and implemented to monitor the daily work. A service satisfaction review was conducted to get feedback from families. In total, 28 processes and related work instructions were defined. Process yields showed service improvements. Family satisfaction improved. The paper is based on preparing only one neonatal intensive care unit to the ISO 9001 standard. The case study should act as an incentive for hospital managers aiming to improve service quality based on the ISO 9001 standard. ISO 9001 is becoming a recommended tool to improve clinical service quality.

Allium cepa L. and Quercetin Inhibit RANKL/Porphyromonas gingivalis LPS-Induced Osteoclastogenesis by Downregulating NF-κB Signaling Pathway

Directory of Open Access Journals (Sweden)

Tatiane Oliveira

2015-01-01

Full Text Available Objectives. We evaluated the in vitro modulatory effects of Allium cepa L. extract (AcE and quercetin (Qt on osteoclastogenesis under inflammatory conditions (LPS-induced. Methods. RAW 264.7 cells were differentiated with 30 ng/mL of RANKL, costimulated with PgLPS (1 µg/mL, and treated with AcE (50–1000 µg/mL or Qt (1.25, 2.5, or 5 µM. Cell viability was determined by alamarBlue and protein assays. Nuclei morphology was analysed by DAPI staining. TRAP assays were performed as follows: p-nitrophenyl phosphate was used to determine the acid phosphatase activity of the osteoclasts and TRAP staining was used to evaluate the number and size of TRAP-positive multinucleated osteoclast cells. Von Kossa staining was used to measure osteoclast resorptive activity. Cytokine levels were measured on osteoclast precursor cell culture supernatants. Using western blot analysis, p-IκBα and IκBα degradation, inhibitor of NF-kappaB, were evaluated. Results. Both AcE and Qt did not affect cell viability and significantly reduced osteoclastogenesis compared to control. We observed lower production of IL-6 and IL-1α and an increased production of IL-3 and IL-4. AcE and Qt downregulated NF-κB pathway. Conclusion. AcE and Qt may be inhibitors of osteoclastogenesis under inflammatory conditions (LPS-induced via attenuation of RANKL/PgLPS-induced NF-κB activation.

Exploratory Research of ISO 14001:2015 Transition among Portuguese Organizations

Directory of Open Access Journals (Sweden)

Luis Miguel Fonseca

2018-03-01

Full Text Available The purpose of this paper is the assessment of the ISO 14001:2015 transition process among Portuguese ISO 14001 certified organizations, including those that successfully have already achieved ISO 14001:2015 certification. A considerable number of the surveyed companies proceeded with the transition to the ISO 14001:2015 by introducing slight adjustments and were supported by external consultants. Nearly all of the respondent companies (97% intend to transition until 15th September 2018. The highest ranked reported benefit is the “integrated approach with other management sub-systems” with a well-consolidated perception from the surveyed companies. This is aligned with the ISO 14001:2015 goal of improving the compatibility of management standards supported on the Annex SL. “Alignment with business strategy”, “improved top management commitment” and “improved internal and external communication” are also perceived to obtain significant benefits from ISO 14001:2015. The statistical tests carried out (Kruskal–Wallis confirmed that the perception of some achieved ISO 14001:2015 certification benefits is dependent on the size of the organization. Concerning the motivations to proceed with certification, results suggest that there is not a particular company profile that is compelled to certify their EMS based on a specific type of motivation (Internal or External. Due to ISO 14001:2015 novelty, these exploratory results should be subjected to additional research confirmation.

Boiling Patterns of Iso-asymmetric Nuclear Matter

International Nuclear Information System (INIS)

Tõke, Jan

2013-01-01

Limits of thermodynamic metastability of self-bound neutron-rich nuclear matter are explored within the framework of microcanonical thermodynamics of interacting Fermi Gas model in Thomas-Fermi approximation. It is found that as the excitation energy per nucleon of the system is increased beyond a certain limiting value, the system loses metastability and becomes unstable with respect to joint fluctuations in excitation energy per nucleon and in isospin per nucleon. As a result, part of the system is forced to boil off in a form of iso-rich non-equilibrated vapors. Left behind in such a process, identifiable with distillation, is a more iso-symmetric metastable residue at a temperature characteristic of its residual isospin content. With a progressing increase in the initial excitation energy per nucleon, more neutron-rich matter is boiled off and a more iso-symmetric residue is left behind with progressively increasing characteristic temperature. Eventually, when all excess neutrons are shed, the system boils uniformly with a further supply of excitation energy, leaving behind a smaller and smaller residue at a characteristic boiling-point temperature of iso-symmetric matter.

Attenuation of liver pro-inflammatory responses by Zingiber officinale via inhibition of NF-kappa B activation in high-fat diet-fed rats.

Science.gov (United States)

Li, Xiao-Hong; McGrath, Kristine C-Y; Nammi, Srinivas; Heather, Alison K; Roufogalis, Basil D

2012-03-01

The aim of this study was to investigate whether treatment with a ginger (Zingiber officinale) extract of high-fat diet (HFD)-fed rats suppresses Nuclear factor-kappa B (NF-κB)-driven hepatic inflammation and to subsequently explore the molecular mechanisms in vitro. Adult male Sprague-Dawley rats were treated with an ethanolic extract of Zingiber officinale (400 mg/kg) along with a HFD for 6 weeks. Hepatic cytokine mRNA levels, cytokine protein levels and NF-κB activation were measured by real-time PCR, Western blot and an NF-κB nuclear translocation assay, respectively. In vitro, cell culture studies were carried out in human hepatocyte (HuH-7) cells by treatment with Zingiber officinale (100 μg/mL) for 24 hr prior to interleukin-1β (IL-1β, 8 ng/mL)-induced inflammation. We showed that Zingiber officinale treatment decreased cytokine gene TNFα and IL-6 expression in HFD-fed rats, which was associated with suppression of NF-κB activation. In vitro, Zingiber officinale treatment decreased NF-κB-target inflammatory gene expression of IL-6, IL-8 and serum amyloid A1 (SAA1), while it suppressed NF-κB activity, IκBα degradation and IκB kinase (IKK) activity. In conclusion, Zingiber officinale suppressed markers of hepatic inflammation in HFD-fed rats, as demonstrated by decreased hepatic cytokine gene expression and decreased NF-κB activation. The study demonstrates that the anti-inflammatory effect of Zingiber officinale occurs at least in part through the NF-κB signalling pathway. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

Evidence of correlation between TGFBR2 gene expression mediated by NF-kB signaling pathways and Kawasaki disease in children.

Science.gov (United States)

Gao, Qinling; Yuan, Shuhua; Yuan, Dawei

2017-09-15

We explored the correlation between the TGFBR2 gene that is mediated by NF-kb signaling pathways and the pathogenesis of Kawasaki disease in children. In this study, 43 children with Kawasaki disease from April 2014 to January 2016 at our hospital were selected as the observation group, and 42 healthy children were selected as the control group. The mRNA expression levels of NF-kb gene and TGFBR2 gene in different groups were detected using fluorescence quantitative PCR. The protein expression levels of the NF-kb and TGFBR2 were detected using enzyme-linked immunosorbent assay (ELISA) in different groups. The expression levels of NF-kb and TGFBR2 in the observation group and the control group were detected using immunohistochemistry. Compared to the control group, the mRNA expression levels of NF-kb and TGFBR2 were 12.3 times and 27.5 times as high as those in the control group respectively and there were significant differences between the two groups (pkb and TGFBR2 in the control group (0.87±0.12, 1.25±0.18) ug/l and those in the observation group (3.27±0.17, 8.16±0.22) ug/l (pkB and TGFBR2 in children with Kawasaki disease were significantly higher than those in healthy subjects (pkB signaling pathways.

Fucofuroeckol-A from Eisenia bicyclis Inhibits Inflammation in Lipopolysaccharide-Induced Mouse Macrophages via Downregulation of the MAPK/NF-κB Signaling Pathway

Directory of Open Access Journals (Sweden)

Sang-Hoon Lee

2016-01-01

Full Text Available Fucofuroeckol-A (FF isolated from an edible perennial brown seaweed Eisenia bicyclis was shown to be potent anti-inflammatory agents. FF suppressed the production of nitric oxide (NO and prostaglandin E2 (PGE2 and the expression of inducible nitric oxide synthase and cyclooxygenase-2 dose dependently in lipopolysaccharide- (LPS- induced RAW 264.7 mouse macrophages. An enzyme-linked immunosorbent assay and cytometric bead array assay demonstrated that FF significantly reduced the production of proinflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α, and that of the monocyte chemoattractant protein-1. Moreover, FF reduced the activation of nuclear factor κB (NF-κB and mitogen-activated protein kinases (MAPKs. These results strongly suggest that the inhibitory effects of fucofuroeckol-A from E. bicyclis on LPS-induced NO and PGE2 production might be due to the suppression of the NF-κB and MAPK signaling pathway.

10(-7)  m 17β-oestradiol enhances odonto/osteogenic potency of human dental pulp stem cells by activation of the NF-κB pathway.

Science.gov (United States)

Wang, Y; Zheng, Y; Wang, Z; Li, J; Wang, Z; Zhang, G; Yu, J

2013-12-01

Oestrogen has been proven to significantly enhance osteogenic potency, while oestrogen deficiency usually leads to impaired osteogenic differentiation of mesenchymal stem cells. However, little is known concerning direct effects of oestrogen on differentiation of human dental pulp stem cells (DPSCs). In this study, human DPSCs were isolated and treated with 10(-7)  m 17β-oestradiol (E2). Alkaline phosphatase (ALP) assay and alizarin red staining were performed. Alkaline phosphatase and alizarin red showed that E2 treatment significantly enhanced ALP activity and mineralization ability of DPSCs, but had no effect on cell proliferation. Real-time RT-PCR and western blot assay demonstrated that odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN and DSPP/DSP) were significantly upregulated in the cells after E2 treatment. Moreover, phosphorylation of cytoplasmic IκBα/P65 and expression of nuclear P65 were enhanced in a time-dependent manner following E2 treatment, suggesting activation of NF-κB signaling. Conversely, inhibition of the NF-κB pathway suppressed E2-mediated upregulation of odonto/osteogenic markers, indicating that the NF-κB pathway was pivotal for E2-mediated differentiation. These findings provide evidence that 10(-7)  m 17β-oestradiol promoted odonto/osteogenic differentiation of human DPSCs via activation of the NF-κB signaling pathway. © 2013 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.

Anesthetic propofol reduces endotoxic inflammation by inhibiting reactive oxygen species-regulated Akt/IKKβ/NF-κB signaling.

Directory of Open Access Journals (Sweden)

Chung-Hsi Hsing

Full Text Available BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS induces inflammation through toll-like receptor (TLR 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α, interleukin (IL-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180 and nuclear factor (NF-κB (Ser536; the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473 partly by reducing reactive oxygen species (ROS generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways.

Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling

Science.gov (United States)

Hsing, Chung-Hsi; Lin, Ming-Chung; Choi, Pui-Ching; Huang, Wei-Ching; Kai, Jui-In; Tsai, Cheng-Chieh; Cheng, Yi-Lin; Hsieh, Chia-Yuan; Wang, Chi-Yun; Chang, Yu-Ping; Chen, Yu-Hong; Chen, Chia-Ling; Lin, Chiou-Feng

2011-01-01

Background Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. Methodology/Principal Findings Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. Conclusions/Significance These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways. PMID:21408125

PRAPI: post-transcriptional regulation analysis pipeline for Iso-Seq.

Science.gov (United States)

Gao, Yubang; Wang, Huiyuan; Zhang, Hangxiao; Wang, Yongsheng; Chen, Jinfeng; Gu, Lianfeng

2018-05-01

The single-molecule real-time (SMRT) isoform sequencing (Iso-Seq) based on Pacific Bioscience (PacBio) platform has received increasing attention for its ability to explore full-length isoforms. Thus, comprehensive tools for Iso-Seq bioinformatics analysis are extremely useful. Here, we present a one-stop solution for Iso-Seq analysis, called PRAPI to analyze alternative transcription initiation (ATI), alternative splicing (AS), alternative cleavage and polyadenylation (APA), natural antisense transcripts (NAT), and circular RNAs (circRNAs) comprehensively. PRAPI is capable of combining Iso-Seq full-length isoforms with short read data, such as RNA-Seq or polyadenylation site sequencing (PAS-seq) for differential expression analysis of NAT, AS, APA and circRNAs. Furthermore, PRAPI can annotate new genes and correct mis-annotated genes when gene annotation is available. Finally, PRAPI generates high-quality vector graphics to visualize and highlight the Iso-Seq results. The Dockerfile of PRAPI is available at http://www.bioinfor.org/tool/PRAPI. lfgu@fafu.edu.cn.

Dissociation of NF3 in shock waves

International Nuclear Information System (INIS)

Breshears, W.D.; Bird, P.F.

1978-01-01

The thermal dissociation rate of NF 3 in mixtures of 5% and 10%NF 3 in Ar has been measured behind incident shock waves over the temperature range 1330-2000 K. Dissociation rates were determined from postshock density gradients measured by laser beam deflection. The second order rate coefficient determined for NF 3 -Ar collisions is k/sub d/=2.31 x 10 15 exp(-20500/T) cm 3 mole sec

ISO's analysis of Comet Hale-Bopp

Science.gov (United States)

1997-03-01

The European Space Agency's Infrared Space Observatory ISO inspected Comet Hall-Bopp during the spring and autumn of 1996. The need to keep ISO's telescope extremely cold restricts the spacecraft's pointing in relation to the Sun and the Earth and it ruled out observations at other times. The analyses of the 1996 observations are not yet complete, but already they give new insight into the nature of comets. Comet Hale-Bopp is believed to be a large comet with a nucleus up to 40 kilometres wide. It was discovered in July 1995 by two American astronomers working independently, Alan Hale and Thomas Bopp. At that time, the comet was a billion kilometres away from the Sun, but 200 times brighter than Halley's Comet was, when at a comparable distance. Comet Hale-Bopp will make its closest approach to the Earth on 22 March, and its closest approach to the Sun (perihelion) on 1 April 1997. Some scientific results from ISO The discovery of Comet Hale-Bopp occurred before ISO's launch in November 1995. When first observed by ISO in March and April 1996, the comet was still 700 million kilometres from the Sun, and almost as far from the Earth and ISO. With its privileged view of infrared wavebands inaccessible from the Earth's surface, ISO's photometer ISOPHOT discovered that carbon dioxide was an important constituent of the comet's emissions of vapour.ISOPHOT measured the temperature of the dust cloud around Comet Hale-Bopp. In March 1996, when the comet was still more than 700 million kilometres from the Sun, the dust cloud was at minus 120 degrees C. When ISOPHOT made similar observations in October 1996, the comet was 420 million kilometres from the Sun, and the dust cloud had warmed to about minus 50 degrees C. Intensive observations of Comet Hale-Bopp were also made by ISO's Short-Wave Spectrometer SWS, the Long-Wave Spectrometer LWS, and the ISOPHOT spectrometer PHOT-S. Results are due for publication at the end of March. They will give details about the composition

CNEN, IAEA and ISO normative requirements for measurement management

International Nuclear Information System (INIS)

Kibrit, Eduardo

2009-01-01

International standard ISO 10012:2003 establishes requirements for measurement management systems, including requirements for measurement processes and measuring equipment. ISO 9001:2008 presents requirements for quality management systems, including requirements for the control of monitoring and measuring equipment. ISO 17025:2005 presents general requirements for the competence of testing and calibration laboratories. In the nuclear field the requirements for measurement management are established by standards published by the International Atomic Energy Agency (IAEA), and in Brazil, by the National Nuclear Energy Commission (CNEN). The present paper presents and discusses the normative requirements for measurement management, considering requirements established by National Nuclear Energy Commission (CNEN), International Atomic Energy Agency (IAEA), and International Organisation for Standardisation (ISO). (author)

Die bestuur en opleiding van SABS ISO 9000 reeks

OpenAIRE

2014-01-01

With the lifting of sanctions, South African businesses are faced with a new challenge to compete against their international counterparts on the international and domestic markets. Competing on the international markets is dependant on conforming to a recognised quality management system standard such as ISO 9000 (ISO International Standards Organisation). The South African equivalent for this standard is SABS ISO 9000. (SABS - South African Bureau of Standards). It is thus important for Sou...

Determination of Interference During In Vitro Pyrogen Detection: Development and Characterization of a Cell-Based Assay.

Science.gov (United States)

Palma, Linda; Rossetti, Francesca; Dominici, Sabrina; Buondelmonte, Costantina; Rocchi, Marco B L; Rizzardi, Gian P; Vallanti, Giuliana; Magnani, Mauro

Contamination of pharmaceutical products and medical devices with pyrogens such as endotoxins is the most common cause of systemic inflammation and, in worst cases, of septic shock. Thus, quantification of pyrogens is crucial. The limulus amebocyte lysate (LAL)-based assays are the reference tests for in vitro endotoxin detection, in association with the in vivo rabbit pyrogen test (RPT), according to European Pharmacopoeia (EP 2.6.14), and U.S. Pharmacopoeia (USP ). However, several substances interfere with LAL assay, while RPT is not accurate, not quantitative, and raises ethical limits. Biological assays, as monocyte activation tests, have been developed and included in European Pharmacopoeia (EP 7.0; 04/2010:20630) guidelines as an alternative to RPT and proved relevant to the febrile reaction in vivo. Because this reaction is carried out by endogenous mediators under the transcriptional control of nuclear factor-kappaB (NF-kappaB), we sought to determine whether a NF-kappaB reporter-gene assay, based on MonoMac-6 (MM6) cells, could reconcile the basic mechanism of innate immune response with the relevance of monocytoid cell lines to the organism reaction to endotoxins. This article describes both optimization and characterization of the reporter cells-based assay, which overall proved the linearity, accuracy, and precision of the test, and demonstrated the sensitivity of the assay to 0.24 EU/mL endotoxin, close to the pyrogenic threshold in humans. Moreover, the assay was experimentally compared to the LAL test in the evaluation of selected interfering samples. The good performance of the MM6 reporter test demonstrates the suitability of this assay to evaluate interfering or false-positive samples.

Application of ISO 9001:2000 in a Nuclear Medicine Department

International Nuclear Information System (INIS)

Rayo, J.I.; Serrano, J.; Martin, R.; Corral, C.

2002-01-01

Since 1947 ISO has been developing voluntary technical standards over almost all sectors of business, industry, and technology. The ISO 9000 standards were published in 1987, and new versions of the standards saw daylight in 1994 and 2000. The highlights of ISO 9001:2000 are: quality management system, management responsibility, resource management, product realization and measurement, analysis and improvement. Aim: Application of ISO 9001:2000 to a Nuclear Medicine Department for provides the organization with a model to follow, customer focus, people will understand the goals of the organization and are motivated to work for objectives and lower costs and shorter cycle times through effective use of resources. Conclusion: ISO 9001:2000 focuses on continual improvement of business processes that should be a permanent objective of the Nuclear Medicine Department

Gloss uniformity measurement update for ISO/IEC 19751

Science.gov (United States)

Ng, Yee S.; Cui, Chengwu; Kuo, Chunghui; Maggard, Eric; Mashtare, Dale; Morris, Peter

2005-01-01

To address the standardization issues of perceptually based image quality for printing systems, ISO/IEC JTC1/SC28, the standardization committee for office equipment chartered the W1.1 project with the responsibility of drafting a proposal for an international standard for the evaluation of printed image quality1. An ISO draft Standard2, ISO/WD 19751-1, Office Equipment - Appearance-based image quality standards for printers - Part 1: Overview, Procedure and Common Methods, 2004 describes the overview of this multi-part appearance-based image quality standard. One of the ISO 19751 multi-part Standard"s tasks is to address the appearance-based gloss and gloss uniformity issues (in ISO 19751-2). This paper summarizes the current status and technical progress since the last two updates3, 4. In particular, we will be discussion our attempt to include 75 degree gloss (G75) objective measurement5 in differential gloss and within-page gloss uniformity. The result for a round-robin experiment involving objective measurement of differential gloss using G60 and G75 gloss measurement geometry is described. The results for two perceptual-based round-robin experiments relating to haze effect on the perception of gloss, and gloss artifacts (gloss streaks/bands, gloss graininess/mottle) are discussed.

Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells from inflammatory dental pulps via NF-κB pathway.

Science.gov (United States)

Wang, Y; Yan, M; Fan, Z; Ma, L; Yu, Y; Yu, J

2014-10-01

This study was designed to investigate the effects of mineral trioxide aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). inflammatory DPSCs were isolated from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned medium. MTT assay and flow cytometry were performed to evaluate the proliferation of iDPSCs. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time RT-PCR, and Western blot assay were used to investigate the differentiation capacity as well as the involvement of NF-κB pathway in iDPSCs. Mineral trioxide aggregate-treated iDPSCs demonstrated the higher ALP activity and formed more mineralized nodules than the untreated group. The odonto/osteoblastic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP, respectively) in MTA-treated iDPSCs were significantly upregulated as compared with untreated iDPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in MTA-treated iDPSCs were significantly increased in a time-dependent manner. Moreover, the inhibition of NF-κB pathway suppressed the MTA-induced odonto/osteoblastic differentiation of iDPSCs, as indicated by decreased ALP levels, weakened mineralization capacity and downregulated levels of odonto/osteoblastic genes (Osx, Ocn, and Dspp). Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Relationship between the Training Function and ISO-9000 Registration.

Science.gov (United States)

Maxwell, Randy C.; Jost, Karen L.

ISO 9000 is one of a series of international standards providing guidelines and governing quality of products and services. The ISO 9000 certification demonstrates the capability of a supplier to control the processes that determine the acceptability of the product or service being supplied. This paper focuses on the training aspects of ISO 9000…

API and ISO standards can be combined

International Nuclear Information System (INIS)

Weightman, R.T.; Warnack, M.F.

1992-01-01

This paper reports that oil field equipment and product manufacturers can maintain a competitive advantage and minimize costs by integrating American Petroleum Institute (API) licensing programs with International Standards Organization (ISO) 9001 standards under one quality system. A combined quality system approach can position a company for quality system certification under ISO 9001 while maintaining API specifications. Furthermore, only one quality system manual is needed for API licensing and ISO certification, avoiding duplication of effort. The benefits of a documented quality program include the flowing: Job descriptions and personnel qualification requirements are documented; The improved documentation allows direct tracing of specific production activities; Laboratory test methods and calibration of test equipment follow accepted standards for more reliable and reproducible test data; Quality control becomes proactive, not reactive, through internal process controls previously not implemented; Employee attitudes improve through appreciation for the overall goals of the company; Ambiguous quality issues, such as documenting special customer requirements, are easily resolved; and The company image improves with customers, particularly for those that require API Specification Q1 or ISO 9001 compliance or those having their own quality performance standards

Demethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-κB Pathways.

Science.gov (United States)

Lin, Chin-Chung; Kuo, Chao-Lin; Huang, Yi-Ping; Chen, Cheng-Yen; Hsu, Ming-Jie; Chu, Yung Lin; Chueh, Fu-Shin; Chung, Jing-Gung

2018-05-01

Demethoxycurcumin (DMC), one of the curcuminoids present in turmeric, has been shown to induce cell death in many human cancer cell lines, however, there has not been any investigation on whether DMC inhibits metastatic activity in human cervical cancer cells in vitro. In the present study, DMC at 2.5-15 μM decreased cell number, thus, we used IC 20 (7.5 μM) for further investigation of its anti-metastatic activity in human cervical cancer HeLa cells. The wound healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of DMC on HeLa cells. The wound healing assay was used to show that DMC suppressed cell movement of HeLa cells. Furthermore, the trans-well chamber assay was used to show that DMC suppressed HeLa cell migration and invasion. Gelatin zymography assay did not show any significant effects of DMC on the gelatinolytic activity (MMP-2 and -9) in conditioned media of HeLa cells treated by DMC. Western blotting showed that DMC significantly reduced protein levels of GRB2, MMP-2, ERK1/2, N-cadherin and Ras but increased the levels of E-cadherin and NF-κB in HeLa cells. Confocal laser microscopy indicated that DMC increased NF-κB in HeLa cells confirming the results from Western blotting. DMC may be used as a novel anti-metastatic agent for the treatment of human cervical cancer in the future. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Experience with ISO quality control in assisted reproductive technology.

Science.gov (United States)

Alper, Michael M

2013-12-01

Assisted reproductive technology (ART) programs are complex organizations requiring the integration of multiple disciplines. ISO 9001:2008 is a quality management system that is readily adaptable to an ART program. The value that ISO brings to the entire organization includes control of documents, clear delineation of responsibilities of staff members, documentation of the numerous processes and procedures, improvement in tracking and reducing errors, and overall better control of systems. A quality ART program sets quality objectives and monitors their progress. ISO provides a sense of transparency within the organization and clearer understanding of how service is provided to patients. Most importantly, ISO provides the framework to allow for continual improvement. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Effects of vitamin E on the NF-κB pathway in rats treated with the peroxisome proliferator, ciprofibrate

International Nuclear Information System (INIS)

Calfee-Mason, Karen G.; Spear, Brett T.; Glauert, Howard P.

2004-01-01

Peroxisome proliferators (PPs) are a diverse group of nongenotoxic compounds, which induce hepatic tumors in rodents. The mechanisms leading to hepatic tumors have not been elucidated, but oxidative stress may play a role in the process. Previous studies in our laboratory have shown that peroxisome proliferators activate the transcription factor nuclear factor-kappa B (NF-κB) and that this activation is mediated at least in part by oxidative stress. We therefore hypothesized that increased dietary vitamin E would decrease NF-κB DNA binding in rodents treated with ciprofibrate (CIP). In this study, 36 male Sprague-Dawley rats were fed a purified diet containing varying levels of vitamin E (10, 50, 250 ppm α-tocopherol acetate). After 28 days on the purified diet, seven animals per vitamin E group received 0.01% CIP in the diet for 10 days. Electrophoretic mobility shift assays (EMSAs) showed that CIP treatment increased DNA binding of NF-κB. Increased dietary α-tocopherol acetate inhibited CIP-induced NF-κB DNA binding. Because NF-κB translocates to the nucleus upon the phosphorylation and degradation of inhibitor of IκB, we also used Western blots to measure cytosolic protein levels of IκBα and IκBβ, and the IκB kinases, IKKα and IKKβ. IκBα protein levels were decreased in all three CIP-treated groups, with the 10 ppm vitamin E diet also decreasing IκBα levels in control rats. No difference in IκBβ protein levels was observed among any of the groups. The CIP-treated rats generally had lower protein levels of IKKα and IKKβ. This study supports our working hypothesis that an increased antioxidant environment can inhibit CIP-mediated NF-κB induction

Identification and characterization of NF-YB family genes in tung tree.

Science.gov (United States)

Yang, Susu; Wang, Yangdong; Yin, Hengfu; Guo, Haobo; Gao, Ming; Zhu, Huiping; Chen, Yicun

2015-12-01

The NF-YB transcription factor gene family encodes a subunit of the CCAAT box-binding factor (CBF), a highly conserved trimeric activator that strongly binds to the CCAAT box promoter element. Studies on model plants have shown that NF-YB proteins participate in important developmental and physiological processes, but little is known about NF-YB proteins in trees. Here, we identified seven NF-YB transcription factor-encoding genes in Vernicia fordii, an important oilseed tree in China. A phylogenetic analysis separated the genes into two groups; non-LEC1 type (VfNF-YB1, 5, 7, 9, 11, 13) and LEC1-type (VfNF-YB 14). A gene structure analysis showed that VfNF-YB 5 has three introns and the other genes have no introns. The seven VfNF-YB sequences contain highly conserved domains, a disordered region at the N terminus, and two long helix structures at the C terminus. Phylogenetic analyses showed that VfNF-YB family genes are highly homologous to GmNF-YB genes, and many of them are closely related to functionally characterized NF-YBs. In expression analyses of various tissues (root, stem, leaf, and kernel) and the root during pathogen infection, VfNF-YB1, 5, and 11 were dominantly expressed in kernels, and VfNF-YB7 and 9 were expressed only in the root. Different VfNF-YB family genes showed different responses to pathogen infection, suggesting that they play different roles in the pathogen response. Together, these findings represent the first extensive evaluation of the NF-YB family in tung tree and provide a foundation for dissecting the functions of VfNF-YB genes in seed development, stress adaption, fatty acid synthesis, and pathogen response.

Autoantibodies Targeting AT1 Receptor from Patients with Acute Coronary Syndrome Upregulate Proinflammatory Cytokines Expression in Endothelial Cells Involving NF-κB Pathway

Directory of Open Access Journals (Sweden)

Weijuan Li

2014-01-01

Full Text Available Our study intended to prove whether agonistic autoantibodies to angiotensin II type 1 receptor (AT1-AAs exist in patients with coronary heart disease (CHD and affect the human endothelial cell (HEC by upregulating proinflammatory cytokines expression involved in NF-κB pathway. Antibodies were determined by chronotropic responses of cultured neonatal rat cardiomyocytes coupled with receptor-specific antagonists (valsartan and AT1-EC2 as described previously. Interleukin-6 (IL-6, vascular cell adhesion molecule-1 (VCAM-1, and monocyte chemotactic protein-1 (MCP-1 expression were improved at both mRNA and protein levels in HEC, while NF-κB in the DNA level was improved detected by electrophoretic mobility shift assays (EMSA. These improvements could be inhibited by specific AT1 receptor blocker valsartan, NF-κB blocker pyrrolidine dithiocarbamate (PDTC, and specific short peptides from the second extracellular loop of AT1 receptor. These results suggested that AT1-AAs, via the AT1 receptor, induce expression of proinflammatory cytokines involved in the activation of NF-κB. AT1-AAs may play a great role in the pathogenesis of the acute coronary syndrome by mediating vascular inflammatory effects involved in the NF-κB pathway.

Double-edged swords as cancer therapeutics: novel, orally active, small molecules simultaneously inhibit p53-MDM2 interaction and the NF-κB pathway.

Science.gov (United States)

Zhuang, Chunlin; Miao, Zhenyuan; Wu, Yuelin; Guo, Zizhao; Li, Jin; Yao, Jianzhong; Xing, Chengguo; Sheng, Chunquan; Zhang, Wannian

2014-02-13

Simultaneous inactivation of p53 and hyperactivation of nuclear factor-κB (NF-κB) is a common occurrence in human cancer. Currently, antitumor agents are being designed to selectively activate p53 or inhibit NF-κB. However, there is no concerted effort yet to deliberately design inhibitors that can simultaneously do both. This paper provided a proof-of-concept study that p53-MDM2 interaction and NF-κB pathway can be simultaneously targeted by a small-molecule inhibitor. A series of pyrrolo[3,4-c]pyrazole derivatives were rationally designed and synthesized as the first-in-class inhibitors of p53-MDM2 interaction and NF-κB pathway. Most of the compounds were identified to possess nanomolar p53-MDM2 inhibitory activity. Compounds 5q and 5s suppressed NF-κB activation through inhibition of IκBα phosphorylation and elevation of the cytoplasmic levels of p65 and phosphorylated IKKα/β. Biochemical assay for the kinases also supported the fact that pyrrolo[3,4-c]pyrazole compounds directly targeted the NF-κB pathway. In addition, four compounds (5j, 5q, 5s, and 5u) effectively inhibited tumor growth in the A549 xenograft model. Further pharmacokinetic study revealed that compound 5q exhibited excellent oral bioavailability (72.9%).

NF-kappaB in Lung Tumorigenesis

International Nuclear Information System (INIS)

Cai, Zhenjian; Tchou-Wong, Kam-Meng; Rom, William N.

2011-01-01

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis

NF-kappaB in Lung Tumorigenesis

Energy Technology Data Exchange (ETDEWEB)

Cai, Zhenjian [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, New York University School of Medicine, 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

2011-12-14

The development of lung cancer in humans can be divided into three steps initiation, promotion and progression. This process is driven by alterations in related signal transduction pathways. These pathways signal the aberrant activation of NF-kappaB, a transcription factor that regulates the expression of genes important for lung tumorigenesis. Our current knowledge about the role of the NF-kappaB signaling pathway in the development of lung cancer has been bolstered by animal models demonstrating the connection between K-ras and tobacco induced lung transformation with NF-kappaB. Activation of downstream genes leads to cell proliferation, inhibition of apoptosis, angiogenesis, inflammation, invasion, and metastasis.

NF-kappaB: Two Sides of the Same Coin.

Science.gov (United States)

Pires, Bruno R B; Silva, Rafael C M C; Ferreira, Gerson M; Abdelhay, Eliana

2018-01-09

Nuclear Factor-kappa B (NF-κB) is a transcription factor family that regulates a large number of genes that are involved in important physiological processes, including survival, inflammation, and immune responses. More recently, constitutive expression of NF-κB has been associated with several types of cancer. In addition, microorganisms, such as viruses and bacteria, cooperate in the activation of NF-κB in tumors, confirming the multifactorial role of this transcription factor as a cancer driver. Recent reports have shown that the NF-κB signaling pathway should receive attention for the development of therapies. In addition to the direct effects of NF-κB in cancer cells, it might also impact immune cells that can both promote or prevent tumor development. Currently, with the rise of cancer immunotherapy, the link among immune cells, inflammation, and cancer is a major focus, and NF-κB could be an important regulator for the success of these therapies. This review discusses the contrasting roles of NF-κB as a regulator of pro- and antitumor processes and its potential as a therapeutic target.

RNA interference suppression of A100A4 reduces the growth and metastatic phenotype of human renal cancer cells via NF-kB-dependent MMP-2 and bcl-2 pathway.

Science.gov (United States)

Yang, X-C; Wang, X; Luo, L; Dong, D-H; Yu, Q-C; Wang, X-S; Zhao, K

2013-06-01

S100A4 is a well established marker and mediator of metastatic disease, but the exact mechanisms responsible for the metastasis promoting effects are less well defined. We tested a hypothesis that the S100A4 gene plays a role in the proliferation and invasiveness of human renal cancer cells (RCC) and may be associated with its metastatic spread. The small interference RNA vector pcDNA3.1-S100A4 siRNA was transfected in to the human renal cancer cell lines ACHN, Ketr-3, OS-RC-2, CaKi-2 and HTB-47, then treated with ABT-737 or BB94. Cell apoptosis and cell viability was detected by flow cytometry and MTT assay. Matrigel was used for cell motility and invasion assay. MMP-2, bcl-2 and S100A4 was detected by RT-PCR and western blot assay. NF-kB subunit p65 activity was detected by confocal microscopy assay. We then determine the effect S100A4 sliencing on tumor growth, lung metastasis development in vivo. Immunohistochemistry was used to detected the expression of S100A4, bcl-2, MMP-2, p65 and CD31. S100A4 silencing in ACHN cells by RNA interference significantly inhibited NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and cellular migration, proliferation, and promoted apoptosis. Furthermore, re-expression of S100A4 in S100A4-siRNA-transfected ACHN cells by transient S100A4 cDNA transfection restored the NF-kB and NF-kB-mediated MMP-2 and bcl-2 activation and their high migratory and cellular proliferative ability. An inhibitor ABT-737 (the Bcl-2 antagonist targets Bcl-2) against Bcl-2 suppressed cellular proliferation and promoted apoptosis induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. A inhibitor BB94 against MMPs to neutralize MMP-2 protein suppressed cellular invasion and migration induced by S100A4 re-expression in S100A4-siRNA-transfected ACHN cells. In the prevention model, S100A4 silencing inhibited primary tumor growth by (tumor weight) (76 ± 8%) and (tumor volum) (78 ± 4%) respectively and promoted apoptosis and the formation

On the composition of ISO 25964 hierarchical relations (BTG, BTP, BTI)

NARCIS (Netherlands)

Alexiev, A; Isaac, A.H.J.C.A.; Lindenthal, J

2015-01-01

Knowledge organization systems (KOS) can use different types of hierarchical relations: broader generic (BTG), broader partitive (BTP), and broader instantial (BTI). The latest ISO standard on thesauri (ISO 25964) has formalized these relations in a corresponding OWL ontology (De Smedt et al., ISO

ERK inhibition enhances TSA-induced gastric cancer cell apoptosis via NF-κB-dependent and Notch-independent mechanism.

Science.gov (United States)

Yao, Jun; Qian, Cui-Juan; Ye, Bei; Zhang, Xin; Liang, Yong

2012-09-04

To analyze the combined impact of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) and the extracellular-signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on gastric cancer (GC) cell line SGC7901 growth. SGC7901 cells were treated with TSA, PD98059 or with a TSA-PD98059 combination. Effects of drug treatment on tumor cell proliferation, apoptosis, cell cycle progression, and cell signaling pathways were investigated by MTS assay, flow cytometry, Western blotting, chromatin immunoprecipitation (ChIP) assay, electrophoretic mobility shift assay (EMSA), and luciferase reporter assay, respectively. PD98059 enhanced TSA-induced cell growth arrest, apoptosis and activation of p21(WAF1/CIP1), but reversed TSA-induced activation of ERK1/2 and nuclear factor-κB (NF-κB). TSA alone up-regulated Notch1 and Hes1, and down-regulated Notch2, but PD98059 did not affect the trends of Notch1 and Notch2 induced by TSA. Particularly, PD98059 did potentiate the ability of TSA to down-regulate phospho-histone H3 protein, but increased levels of the acetylated forms of histone H3 bound to the p21(WAF1/CIP1) promoter, leading to enhanced expression of p21(WAF1/CIP1) in SGC7901 cells. PD98059 synergistically potentiates TSA-induced GC growth arrest and apoptosis by manipulating NF-κB and p21(WAF1/CIP1) independent of Notch. Therefore, concomitant administration of HDACIs and ERK1/2 inhibitors may be a promising treatment strategy for individuals with GC. Copyright © 2012 Elsevier Inc. All rights reserved.

Phorbol-ester-induced activation of the NF-κB transcription factor involves dissociation of an apparently cytoplasmic NF-κB/inhibitor complex

International Nuclear Information System (INIS)

Baeuerle, P.A.; Lenardo, M.; Pierce, J.W.; Baltimore, D.

1988-01-01

There is increasing evidence that inducible transcription of genes is mediated through the induction of the activity of trans-acting protein factors. The NF-κB transcription factor provides a model system to study the posttranslational activation of a phorbol-ester-inducible transcription factor. The finding that NF-κB activity is undectable in subcellular fractions from unstimulated cells suggests that NF-κB exists as an inactive precursor. The authors showed that NF-κB is detectable in two different forms. After selective removal of endogenous NF-κB, they demonstrate the existence of a protein inhibitor in cytosolic fractions of unstimulated cells that is able in vitro to convert NF-κB into an inactive desoxycholate-dependent form. The data are consistent with a molecular mechanism of inducible gene expression by which an apparently cytoplasmic transcription factor-inhibitor complex is dissociated by the action of TPA-activated protein kinase C

ISO 14000 information platform. Quarterly report, January 1--March 31, 1998

Energy Technology Data Exchange (ETDEWEB)

NONE

1998-09-01

GETE, through its ISO 14000 Information Platform, globeNet{trademark} (www.iso14000.net), seeks to provide FETC and the US Department of Energy (DOE) with a timely, accurate, and reliable information resource on the issue of environmental management standards. This resource allows FETC to keep track of the latest developments in the ISO 14000 arena, in DOE as well as throughout the federal complex and industry. Utilizing this information, FETC and DOE can make critical decisions on their own use and implementation of the ISO 14000 standards. The information platform also provides FETC with a forum to present information on its activities, such as the DOE ISO 14000 Pilot Projects, and as an information gathering and dissemination resource for its publications. GETE works with an array of national and international contacts and content sources to gather information and provide daily updates on ISO 14000 and related environmental management issues.

"Life-like" assessment of antimicrobial surfaces by a new touch transfer assay displays strong superiority of a copper alloy compared to silver containing surfaces.

Directory of Open Access Journals (Sweden)

Johannes Karl-Mark Knobloch

Full Text Available Transmission of bacteria from inanimate surfaces in healthcare associated environments is an important source of hospital acquired infections. A number of commercially available medical devices promise to fulfill antibacterial activity to reduce environmental contamination. In this study we developed a touch transfer assay modeling fingerprint transmission to investigate the antibacterial activity of surfaces, with confirmed antibacterial activity by a modified ISO 22196 (JIS Z 2801 assay to test such surfaces under more realistic conditions. Bacteria were taken up from a dry standardized primary contaminated surface (PCS with disinfected fingers or fingers covered with sterile and moistened cotton gloves. Subsequently, bacteria were transferred by pressing on secondary contaminated surfaces (SCS with or without potential antibacterial activity and the relative reduction rate was determined after 24 h. A stable transmission rate between PCS and SCS was observed using moistened sterile gloves. A copper containing alloy displayed at least a tenfold reduction of the bacterial load consistently reaching less than 2.5 cfu/cm2. In contrast, no significant reduction of bacterial contamination by silver containing surfaces and matured pure silver was observed in the touch transfer assay. With the touch transfer assay we successfully established a new reproducible method modeling cross contamination. Using the new method we were able to demonstrate that several surfaces with confirmed antimicrobial activity in a modified ISO 22196 (JIS Z 2801 assay lacked effectiveness under defined ambient conditions. This data indicate that liquid based assays like the ISO 22196 should be critically reviewed before claiming antibacterial activity for surfaces in the setting of contamination of dry surfaces by contact to the human skin. We suggest the newly developed touch transfer assay as a new additional tool for the assessment of potential antimicrobial surfaces

ISO 9001 certification for hospitals in Bulgaria: does it help service?

Science.gov (United States)

Stoimenova, Assena; Stoilova, Ani; Petrova, Guenka

2014-03-04

The aim of our study is to review the published literature on establishment and implementation of ISO 9001 QMS in European hospitals, to study the availability of International Organization for Standardization (ISO) quality management systems (QMS) in Bulgarian hospitals and to outline the main advantages of ISO implementation in the hospitals in Bulgaria. The information on availability of ISO QMS in the hospitals in Bulgaria was gathered via Bulgarian certification register, the registries of various quality associations, websites of hospitals and certification companies presented in Bulgaria. A total number of 312 hospitals in Bulgaria were screened for the availability of QMS certified against the ISO 9001 requirements. The experience of European hospitals that implemented QMS is positive and the used approaches to improve the processes and the demonstrated effects from ISO implementation are analysed by the researchers. Unlike other European Union member states, the establishment of quality management systems in Bulgaria is not compulsory. However, our study revealed that 14.42% of the hospitals in Bulgaria have implemented and have certified quality systems against the requirements of ISO 9001. Our study confirmed that a quality management system using the ISO 9001 standard is useful for the hospitals as it can help to increase the operational efficiencies, to reduce errors, improve patient safety and produce a more preventive approach instead of a reactive environment.

Inter ISO Market Coordination by Calculating Border Locational Marginal Prices

Directory of Open Access Journals (Sweden)

BABIC, A. B.

2013-05-01

Full Text Available In this paper the methodology for solving Locational Marginal Price (LMP differences (inconsistency of LMPs that arise at the boundary buses between separate power markets is proposed. The algorithm developed enables us to obtain consistent LMP values at the boundary buses between interconnected ISOs. A Primal-Dual Interior Point based optimal power flow (OPF is applied, with complete set of power system physical limit constraints, to solve a regional spot market. The OPF is implemented such that producer and consumer behaviors are modeled simultaneously, while the welfare is maximized. In this paper a generalized methodology for multiple ISOs case is proposed and later it is practically applied on two interconnected independent entities. The algorithm for approximation of cost coefficients of generators and dispatchable loads for neighboring ISOs is proposed. The developed algorithm enables participating ISOs to obtain LMPs at the boundary buses with other interconnected ISOs. By controlling interchange of electric power at the scheduled level, regional spot markets are resolved eliminating possible exercise of market power by individual interconnected ISOs. Results of proposed methodology are tested on the IEEE 118-bus power system.

The dark side of ISO 14001: The symbolic environmental behavior

Directory of Open Access Journals (Sweden)

Vera Ferrón Vílchez

2017-01-01

Full Text Available Some of the academic research on ISO 14001 has focused on analyzing the benefits of its adoption. However, this international standard has also received some criticism, particularly in respect of the adoption of ISO 14001 when not accompanied by significant improvements in environmental performance. This study analyzes the relationship between the symbolic environmental behavior and the adoption of ISO 14001. In so doing, it uses binary logistic regression to analyze an international sample of 1961 manufacturing facilities that each employs more than 50 people. The results indicate that the higher the symbolic environmental performance of the firm, the greater the probability of adopting ISO 14001.

ISO certification pays off in quality improvement

International Nuclear Information System (INIS)

Vermeer, F.J.G.

1992-01-01

This paper reports that by obtaining and maintaining International Standards Organization (ISO) 9001 certification, a company can improve its quality control system, cut waste, and motivate its employees. In so doing it improves its competitive position in both international and domestic markets. The success of a number of countries (notably Japan) in the world markets has focused the attention of the industrialized countries on improving quality levels and striving for a unified, worldwide quality standard. This has been particularly true in Europe; with several countries competing in a single market, a common quality standard has been a highly desirable goal for decades. One of the first multinational quality standards evolved in the European Community, which is estimated to become a single market with a gross national product of $4.5 trillion by 1992. As a consequence, in 1987 the International Standards Organization created ISO 9000, a single standard to ensure uniform quality in products and services offered with this growing market. U.S. petroleum and natural gas companies must recognize and implement the ISO 9000 standards or possibly lose international markets. If the present worldwide trend towards ISO 9000 continues (and there is no reason to believe that it will not), the standards will be just as important in the domestic market

CREB, NF-Y and MEIS1 conserved binding sites are essential to balance Myostatin promoter/enhancer activity during early myogenesis.

Science.gov (United States)

Grade, Carla Vermeulen Carvalho; Mantovani, Carolina Stefano; Fontoura, Marina Alves; Yusuf, Faisal; Brand-Saberi, Beate; Alvares, Lúcia Elvira

2017-10-01

Myostatin (MSTN) is a strong inhibitor of skeletal muscle growth in human and other vertebrates. Its transcription is controlled by a proximal promoter/enhancer (Mstn P/E) containing a TATA box besides CREB, NF-Y, MEIS1 and FXR transcription factor binding sites (TFBSs), which are conserved throughout evolution. The aim of this work was to investigate the role of these TFBSs on Mstn P/E activity and evaluate the potential of their putative ligands as Mstn trans regulators. Mstn P/E mutant constructs were used to establish the role of conserved TFBSs using dual-luciferase assays. Expression analyses were performed by RT-PCR and in situ hybridization in C2C12 myoblasts and E10.5 mouse embryos, respectively. Our results revealed that CREB, NF-Y and MEIS1 sites are required to balance Mstn P/E activity, keeping Mstn transcription within basal levels during myoblast proliferation. Furthermore, our data showed that NF-Y site is essential, although not sufficient, to mediate Mstn P/E transcriptional activity. In turn, CREB and MEIS1 binding sites seem to depend on the presence of NF-Y site to induce Mstn P/E. FXR appears not to confer any effect on Mstn P/E activity, except in the absence of all other conserved TFBS. Accordingly, expression studies pointed to CREB, NF-Y and MEIS1 but not to FXR factors as possible regulators of Mstn transcription in the myogenic context. Altogether, our findings indicated that CREB, NF-Y and MEIS1 conserved sites are essential to control basal Mstn transcription during early myogenesis, possibly by interacting with these or other related factors.

The impact of ISO 14000 on developing world businesses

International Nuclear Information System (INIS)

Mohamed, S.T.

2001-01-01

ISO 14000 has attracted interest from industry, international organizations and governments around the globe. Policy-makers and industry both appear to be looking to the standards as a key component of a new paradigm for cooperation between regulators and industry. This realization seems to have resulted from a growing awareness that the fragmented, reactive approach to environmental management in the past has not produced optimal results. Businesses are realizing the value of integrating their compliance procedures for each regulation into a broader system. Compliance problems can often be linked to system problems such as inadequate training, lack of responsibility at the right level, inadequate data, and other related causes. An effective Environmental Management System (EMS) eliminates these pitfalls. The evolution of the EMS is being shaped by market forces, ISO 9000, regulatory shifts, public awareness, and cost implications for ISO certifications. The transformation of these management practices is not limited to industrialized countries. In anticipation of the non-tariff trade barriers that could be erected as a result of these standards, many developing countries are seeking avenues of compliance with ISO 14000's requirements. Egypt should be concerned with the implementation of this system, for firms in countries of the European Community (EC) have been given explicit instructions by the three prevalent European standard-setting organizations to ''familiarize'' themselves with the requirements of ISO 14000. This paper will focus primarily on the expected effects of ISO 14001. (author)

Effect of X-irradiation on DNA binding activity of NF-kB in EL-4 cells

International Nuclear Information System (INIS)

He Shujie; Jin Shunzi; Liu Shuzheng

2002-01-01

Changes in time course of the DNA-binding activity of NF-κB as well as the subcellular localization of p65 subunit and expression of IκBα in EL-4 cells after irradiation with 2 Gy and 0.075 Gy X-rays were examined using electrophoresis mobility shift assay (EMSA) and immunohistochemistry (IHC), respectively. Results showed that the increases in DNA-binding activity of NF-κB p50/p50 and p50/p65 were induced by both 0.075 Gy and 2 Gy X-rays. However, the amplitude of the increase in activity of the two dimers was different after irradiation with the two doses of X-rays. After irradiation with 0.075 Gy, the increase in p50/p65 activity was higher than that of p50/p50 activity. After irradiation with 2 Gy, the situation was reversed. Irradiation with both 2 Gy and 0.075 Gy induced an increase in the rate of p65 nuclear translocation and the degradation of IκBα before the increase of its expression, but the degree of these changes after different dose irradiation was different. These results suggest that the transcriptional regulation of NF-κB changes with irradiation dose, resulted in the difference in responses of cells

Fisetin Imparts Neuroprotection in Experimental Diabetic Neuropathy by Modulating Nrf2 and NF-κB Pathways.

Science.gov (United States)

Sandireddy, Reddemma; Yerra, Veera Ganesh; Komirishetti, Prashanth; Areti, Aparna; Kumar, Ashutosh

2016-08-01

The current study is aimed to assess the therapeutic potential of fisetin, a phytoflavonoid in streptozotocin (STZ)-induced experimental diabetic neuropathy (DN) in rats. Fisetin was administered (5 and 10 mg/kg) for 2 weeks (7th and 8th week) post STZ administration. Thermal and mechanical hyperalgesia were assessed by measuring tactile sensitivity to thermal and mechanical stimuli, respectively. Motor nerve conduction velocity (MNCV) was determined using power lab system and sciatic nerve blood flow (NBF) was determined using laser Doppler system. Nerve sections were processed for TUNEL assay and NF-κB, COX-2 immunohistochemical staining. Sciatic nerve homogenate was used for biochemical and Western blotting analysis. MNCV and sciatic NBF deficits associated with DN were ameliorated in fisetin administered rats. Fisetin treatment reduced the interleukin-6 and tumour necrosis factor-alpha in sciatic nerves of diabetic rats (p < 0.001). Protein expression studies have identified that the therapeutic benefit of fisetin might be through regulation of redox sensitive transcription factors such as nuclear erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB). Our study provides an evidence for the therapeutic potential of fisetin in DN through simultaneous targeting of NF-κB and Nrf2.

Iso-α-acids, bitter components of beer, prevent obesity-induced cognitive decline.

Science.gov (United States)

Ayabe, Tatsuhiro; Ohya, Rena; Kondo, Keiji; Ano, Yasuhisa

2018-03-19

Dementia and cognitive decline have become worldwide public health problems, and it was recently reported that life-style related diseases and obesity are key risk factors in dementia. Iso-α-acids, hop-derived bitter components of beer, have been reported to have various physiological functions via activation of peroxisome proliferator-activated receptor γ. In this report, we demonstrated that daily intake of iso-α-acids suppresses inflammations in the hippocampus and improves cognitive decline induced by high fat diet (HFD). Body weight, epididymal fat weight, and plasma triglyceride levels were increased in HFD-fed mice, and significantly decreased in iso-α-acids supplemented HFD-fed mice. HFD feeding enhances the production of inflammatory cytokines and chemokines, such as TNF-α, which was significantly suppressed by iso-α-acids administration. HFD-induced neuroinflammation caused lipid peroxidation, neuronal loss, and atrophy in hippocampus, and those were not observed in iso-α-acids-treated mice. Furthermore, iso-α-acids intake significantly improved cognitive decline induced by HFD-feeding. Iso-α-acids are food derived components that suppressing both lipid accumulation and brain inflammation, thus iso-α-acids might be beneficial for the risk of dementia increased by obesity and lifestyle-related diseases.

New water and remote galaxies complete ISO's observations

Science.gov (United States)

ISO's operational teams at ESA's ground station at Villafranca near Madrid have been hurrying to provide the world's astronomers with as many observations as possible. They have long anticipated the exhaustion of ISO's vital supply of liquid helium, which cooled the infrared telescope and its instruments to their operating temperatures, close to absolute zero. Two weeks after ISO was put into orbit on 17 November 1995 by an Ariane 44P launcher, the external parts of the cooling system had settled to the operating temperature. The specification required that ISO should then operate for at least 18 months -- implying that operations might have to end in May 1997. Thanks to superb engineering by European industry, which built the spacecraft and its super-cool telescope, ISO has given astronomers almost a year longer than that. During the extra time the count of ISO's observations of cosmic objects has risen from 16,000 to about 26,000. Among the benefits of ISO's longevity has been the chance to examine an important region of the sky, in and around the constellation of Orion. This was not accessible in the nominal mission but has now been observed in two periods. Four inter national teams, supported by national funding agencies, supplied the instruments to analyse the infrared rays received by ISO's telescope. The principal investigators leading the teams are Dietrich Lemke (Heidelberg, Germany) for the versatile photometer ISOPHOT, Catherine Cesarsky (Saclay, France) for the camera ISOCAM, Thijs de Graauw (Groningen, the Netherlands) for the Short Wavelength Spectrometer SWS, and Peter Clegg (London, UK) for the Long Wavelength Spectrometer LWS. Water vapour on Titan A big difference between ISO and the only previous infrared astronomy satellite (IRAS 1983) has been its ability to examine individual objects across a wide range of accurately defined infrared wavelengths. Many spectra showing patterns of intensities at the different wavelengths have enabled astronomers

The ISO 50001 Impact Estimator Tool (IET 50001 V1.1.4) - User Guide and Introduction to the ISO 50001 Impacts Methodology

Energy Technology Data Exchange (ETDEWEB)

Therkelsen, Peter L. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rao, Prakash [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Aghajanzadeh, Arian [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); McKane, Aimee T. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2016-08-01

ISO 50001-Energy management systems – Requirements with guidance for use, is an internationally developed standard that provides organizations with a flexible framework for implementing an energy management system (EnMS) with the goal of continual energy performance improvement. The ISO 50001 standard was first published in 2011 and has since seen growth in the number of certificates issued around the world, primarily in the industrial (agriculture, manufacturing, and mining) and service (commercial) sectors. Policy makers in many regions and countries are looking to or are already using ISO 50001 as a basis for energy efficiency, carbon reduction, and other energy performance improvement schemes. The Impact Estimator Tool 50001 (IET 50001 Tool) is a computational model developed to assist researchers and policy makers determine the potential impact of ISO 50001 implementation in the industrial and service (commercial) sectors for a given region or country. The IET 50001 Tool is based upon a methodology initially developed by the Lawrence Berkeley National Laboratory that has been improved upon and vetted by a group of international researchers. By using a commonly accepted and transparent methodology, users of the IET 50001 Tool can easily and clearly communicate the potential impact of ISO 50001 for a region or country.

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

International Nuclear Information System (INIS)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena

2017-01-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by 60 Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found to be

Downregulation of NF-ΚB1 enhances the radiosensitivity of renal cell carcinoma

Energy Technology Data Exchange (ETDEWEB)

Ikegami, Amanda; Silva, Luiz Felipe Teixeira da; Bellini, Maria Helena [Instituto De Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-07-01

Full text: Introduction: Clear cell renal cell carcinoma (ccRCC) accounts for ∼80% of all renal cell carcinomas (RCC) and has the Von Hippel-Lindau (VHL) tumor suppressor gene mutated. The lack of VHL protein leads to a constitutionally active Hypoxia Inducible Factor (HIF) pathway that confers both chemoresistance and radioresistance for renal tumor. HIF pathway is known to interact with the transcription factor nuclear factor kappa B (NF-kB). Increased NF-κB activity is associated with the development and progression of RCC (IKEGAMI A, TEIXEIRA LF. BRAGA MS et al. The American Society for Cell Biology 2016; 26: 3948-3955). Objective: Evaluate the synergistic effect of NF-kB1 knockdown and ionizing radiation in murine renal adenocarcinoma cell line. Methods: The murine renal adenocarcinoma cell line (Renca cells) (ATCC, USA) was cultured in RPMI 1640 supplemented with 10% FBS and penicillin/streptomycin. Lentiviral shRNA vector was used to knockdown of NF-KB1 gene in Renca cells, as described previously (1). In the clonogenic cell survival assay, the cells were irradiated by {sup 60}Co source in the range from 0 to 10 Gy, using the GammaCell 220 – Irradiation Unit of Canadian-Atomic Energy Commision Ltd. (CTR-IPEN). After 10-14 days of culture, cell colonies were fixed and stained with formaldehyde 4% and rhodamine B 2% and counted. To assess cell viability, tetrazolium [3-(4,5-dimethylthiazol-2-yl)-5- (3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-MTS] was performed within 24 hours after irradiation at a dose of 10Gy. The survival variables α e β were fitted according to the linear quadratic equation (SF=exp[-αD-βD2]); SF=survival fraction, D=dose of irradiation and P value was determined by F test. Multiple comparisons were assessed by One-way ANOVA followed by Bonferroni´s tests with GraphPad Prism version 6.0 software. P< 0.05 was considered statistically significant. Data are shown as the mean ± SD. Results: The Renca-shRNA-NF-kB1 cells were found

ISO 50001 and SEP Faster and Cheaper - Exploring the Enterprise-Wide Approach

Energy Technology Data Exchange (ETDEWEB)

Liu, Jingjing [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Rao, Prakash [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Therkelsen, Peter [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sheaffer, Paul [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Scheihing, Paul [USDOE, Washington, DC (United States); Tamm, Yannick [Energetics, Inc. (United States)

2017-06-01

ISO 50001 and other management systems (e.g., ISO 9001 and ISO 14001) allow for implementation and certification at the enterprise level. The "Central Office" concept, which allows a small group of employees to manage and facilitate the organization’s energy management system (EnMS) at the enterprise level, was introduced within the ISO 50003 standard to provide guidance to ISO 50001 certification bodies. Four industrial companies have partnered with the United States Department of Energy to pilot the enterprise-wide ISO 50001/SEP concept under the Better Buildings Superior Energy Performance (SEP) Enterprise-wide Accelerator. Each organization developed a Central Office to host their EnMS while implementing ISO 50001/SEP at multiple physically separated sites. The four corporate partners tailored their Central Office implementation model to meet their own specific circumstances and needs. This paper reviews the commonalities, differences, and benefits of each of these enterprise-wide implementation models, including organizational structures, Central Office staff responsibilities, and key strategies. The cost savings and benefits of using the enterprise-wide approach were assessed, including the cost per site compared with that of a conventional, single-site ISO 50001/SEP implementation approach. This paper also discusses the drivers for the cost reductions realized through these enterprise-wide approaches. The four partner companies worked with 30 total sites. On average, these 30 sites improved energy performance by 5% annually over their SEP achievement periods, saved more than $600,000 annually in energy costs and reduced implementation cost for ISO 50001 and SEP by $19,000 and 0.8 Full Time Equivalent × years (FTE-yr) of staff time per site. The results can inform other organizations seeking to implement enterprise-wide ISO 50001/SEP, as well as energy efficiency organizations seeking to promote wider adoption of ISO 50001 implementation.

Implementation of ISO guide 25 in a medical dosimetry secondary standards calibration laboratory

International Nuclear Information System (INIS)

DeWerd, L.A.

1995-01-01

Currently, there is a great deal of discussion among industry and government agencies about ISO 9000 accreditation. U.S. manufacturers with ISO 9000 accreditation are regarded more favorably by European countries. The principles behind the ISO 9000 accreditation are based on the Total Quality Management (TQM) principles that are being implemented in many U.S. industries. This paper will deal only with the calibration issue. There is a difference in the areas covered by ISO 9000 and ISO Guide 25 documents. ISO 9000, in particular ISO 9001 - ISO 9003, cover the open-quotes calibrationclose quotes of inspection, measuring and test equipment. This equipment is basically used for open-quotes factory calibrationsclose quotes to determine that equipment is performing within manufacturer specifications. ISO Guide 25 is specifically for open-quotes calibration and testing laboratories,close quotes generally laboratories that have painstaking procedures to reduce uncertainties and establish high accuracy of the transfer of calibration. The experience of the University of Wisconsin Accredited Dosimetry Calibration Laboratory in conforming to ISO Guide 25 will be outlined. The entire laboratory staff must become familiar with the process and an individual with direct authority must become the one to maintain the quality of equipment and calibrations in the role of open-quotes quality-assurance manager.close quotes

Perancangan SMKI Berdasarkan SNI ISO/IEC27001:2013 dan SNI ISO/IEC27005:2013 (Studi Kasus DPTSI-ITS

Directory of Open Access Journals (Sweden)

Furqon Mauladani

2018-03-01

Full Text Available Institut Teknologi Sepuluh Nopember (ITS adalah salah satu universitas di Surabaya. ITS telah menggunakan TIK untuk keperluan operasional bisnisnya (contohnya isi kartu program studi, proses absensi, pembaharuan informasi, dan lainnya. Penggunaan TIK tidak dapat dipisahkan dari ancaman yang dapat mengganggu operasional TIK. Ancaman terdiri dari ancaman yang berasal dari luar (penyebaran malware, aktifitas social engineering, orang dalam (sengaja, tidak sengaja, kegagalan teknis (kesalahan penggunaan, kegagalan perangkat keras/lunak ataupun bencana alam (kebakaran, gempa, banjir. Metode yang digunakan pada penelitian ini adalah melakukan manajemen resiko keamanan informasi berdasarkan SNI ISO/IEC 27005 dan perancangan dokumen SMKI berdasarkan SNI ISO/IEC 27001. Hasil penelitian ini adalah 60 resiko yang tidak diterima dari total 228 resiko yang telah teridentifikasi. Dari 60 resiko tersebut, terdapat 58 risk modification, 1 risk avoidance, dan 1 risk sharing. Tata kelola keamanan informasi yang dirancang berdasarkan SNI ISO/IEC 27001 adalah ruang lingkup SMKI, kebijakan SMKI, proses penilaian resiko, proses penanganan resiko, statement of applicability, dan sasaran keamanan informasi.

Standardization by ISO to Ensure the Sustainability of Space Activities

Science.gov (United States)

Kato, A.; Lazare, B.; Oltrogge, D.; Stokes, H.

2013-08-01

The ISO / Technical Committee 20 / Sub-committee 14 develops debris-related standards and technical reports to mitigate debris and help ensure mission and space sustainability. While UN Guidelines and the IADC Guidelines encourage national governments and agencies to promote debris mitigation design and operation, the ISO standards will help the global space industry promote and sustain its space-related business. In this paper the scope and status of each ISO standard is discussed within an overall framework. A comparison with international guidelines is also provided to demonstrate the level of consistency. Finally, as a case study, the ISO standards are applied to a CubeSat mission, thus demonstrating their usability on a relatively recent and popular class of satellite.

Isoe - information system on occupational exposure. Ten years of experience

International Nuclear Information System (INIS)

2002-01-01

The information System on Occupational Exposure (ISOE) was created in 1992 to provide a forum for radiation protection experts from both utilities and national regulatory authorities to discuss, promote and co-ordinate international co-operative undertakings in the area of worker protection at nuclear power plants. The ISOE System is jointly managed by the OECD Nuclear Energy Agency (NEA) and the International Atomic Energy Agency (IAEA). This report provides an overview of the experience gained from, and benefits provided by, the ISOE System over the past ten years. Active participation of a large number of utilities in ISOE has contributed to a reduction in occupational exposure at nuclear power plants worldwide. (authors)

A non-canonical Flt3ITD/NF-κB signaling pathway represses DAPK1 in acute myeloid leukemia (AML)

Science.gov (United States)

Shanmugam, Rajasubramaniam; Sayar, Hamid; Suvannasankha, Attaya; Goswami, Chirayu; Li, Lang; Gupta, Sushil; Cardoso, Angelo A.; Baghdadi, Tareq Al; Sargent, Katie J.; Cripe, Larry D.; Kalvakolanu, Dhananjaya V.; Boswell, H. Scott

2014-01-01

Purpose DAPK1, a tumor suppressor, is a rate-limiting effector in an ER stress-dependent apoptotic pathway. Its expression is epigenetically suppressed in several tumors. A mechanistic basis for epigenetic/transcriptional repression of DAPK1 was investigated in certain forms of AML with poor prognosis, which lacked ER stress-induced apoptosis. Experimental Design Heterogeneous primary AMLs were screened to identify a subgroup with Flt3ITD in which repression of DAPK1, among NF-κB- and c- jun-responsive genes, was studied. RNAi knockdown studies were performed in Flt3ITD+ve cell line, MV-4-11, to establish genetic epistasis in the pathway Flt3ITD-TAK1-DAPK1 repression, and chromatin immunoprecipitations were performed to identify proximate effector proteins, including TAK1-activated p52NF-κB, at the DAPK1 locus. Results AMLs characterized by normal karyotype with Flt3ITD were found to have 10-100-fold lower DAPK1 transcripts normalized to the expression of c-jun, a transcriptional activator of DAPK1, as compared to a heterogeneous cytogenetic category. Meis1, a c-jun-responsive adverse AML prognostic gene signature was also measured as control. These Flt3ITD+ve AMLs over-express relB, a transcriptional repressor, which forms active heterodimers with p52NF-κB. Chromatin immunoprecipitation assays identified p52NF-κB binding to the DAPK1 promoter along with HDAC2 and HDAC6 in the Flt3ITD+ve human AML cell line MV-4-11. Knockdown of p52NF-κB or its upstream regulator, NIK, de-repressed DAPK1. DAPK1-repressed primary Flt3ITD+ve AMLs had selective nuclear activation of p52NF-κB. Conclusions Flt3ITD promotes a non-canonical pathway via TAK1 and p52NF-κB to suppress DAPK1 in association with HDACs, which explains DAPK1 repression in Flt3ITD+ve AML. PMID:22096027

[Efforts to achieve and effects of acquiring ISO 15189 in Tokushima University Hospital].

Science.gov (United States)

Shono, Kazuko; Kishi, Misako; Satou, Mituyo; Nagamine, Yasunori; Doi, Tosio

2009-12-01

The medical laboratory of Tokushima University Hospital acquired ISO 15189, an international standard for medical laboratories, on July 6th, 2007, resulting in it achieving the 24th place in Japan and 5th place among national university hospitals. The first surveillance was just performed on October 6th, 2008. Tokushima University Hospital, in which our medical laboratory is included as one section, already succeeded in acquiring ISO 9001, PrivacyMark System, and Quality Health Care ver. 5 before accomplishing ISO 15189. To achieve ISO 15189, we prepared documents based on ISO 9001 without any consultation, resulting in a review of the difference between ISO 9001 and ISO 15189 after the preliminary survey. Although achieving ISO 15189 resulted in an improvement in the reliability of laboratory results and accuracy, leading to the development of our technical skills and awareness, and sharing of knowledge, we consider that the considerable investment of time to prepare the requirements remains to be overcome.

IL-15 up-regulates the MMP-9 expression levels and induces inflammatory infiltration of macrophages in polymyositis through regulating the NF-kB pathway.

Science.gov (United States)

Yan, Wang; Fan, Weinv; Chen, Caijing; Wu, Yunqin; Fan, Zhenyi; Chen, Jiaqi; Chen, Zhaoying; Chen, Huimin

2016-10-10

This study was aimed to research the effects of IL-15 on inducing inflammatory infiltration of macrophages in polymyositis (PM) through the NF-kB pathway, and whether IL-15 was able to further regulate MMP-9 expression levels. Prepared PM cells, collected from the patients suffering from PM, were administered to SD rats. Also, a group of healthy SD rats was undergoing the same treatment as the control group. The test animals were treated with either anti-IL-15, IL-15, MMP-9 siRNA or ERK1/2 inhibitor. The blood toxicological parameters creatine kinase (CK) and CD163 were tested by using ELISA and immunohistochemistry assay. In addition, NF-kB expression in macrophages was measured by immunocytochemical assay. To measure the degree of cell infiltration the Transwell assay was performed. Lastly, western blot and zymography were carried out to compare MMP-9 and ERK expression levels between the two groups, both in vivo and in vitro. The results showed that S-CK, IL-15 and IL-15Rα levels increased rapidly after the conventional treatment was introduced to the PM infected SD rats. The PM model establishment and IL-15 treatment significantly increased the expressions of IL-15Rα, MMP-9, p-ERK and p-IKBα. However, the same effect can be suppressed by using anti-IL-15, MMP-9 siRNA or ERK1/2 inhibitor (P kB in the macrophages. IL-15 is able to significantly regulate the inflammatory infiltration of macrophages in PM patients through affecting the NF-kB pathway and MMP-9 expression levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature-dependent interaction potential between NF3 molecules and thermophysical properties of gaseous NF3

International Nuclear Information System (INIS)

Damyanova, M; Balabanova, E; Hohm, U

2014-01-01

A temperature-dependent effective intermolecular interaction potential is applied to describe the interaction between two nitrogen fluoride (NF 3 ) molecules in gas phase. To this end, a spherically-symmetric (n-6) Lennard-Jones temperature-dependent potential (LJTDP) is used. The (n-6) LJTDP takes into account the influence of vibrational excitation of the molecules on the potential parameters, namely, the equilibrium distance r m and the potential well depth ε. The potential parameters at T = 0 K were obtained from the very small amount of existing thermophysical equilibrium and transport properties of low-density NF 3 gas. Fitting formulae are tabulated for a fast and reliable prediction of the thermophysical properties and potential parameters in the temperature range between 200 K and 1200 K. A comparison is also presented between our estimates for some thermophysical properties of the NF 3 gas with the available experimental and calculated data.

77 FR 11532 - Notice of Attendance at ISO New England and NEPOOL Meetings

Science.gov (United States)

2012-02-27

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Notice of Attendance at ISO New England... members of the Commission and Commission staff may attend upcoming ISO New England Inc. (ISO-NE) and New..., the Commission and Commission staff may monitor the various meetings posted on the ISO-NE Web site...

ISO 14001 ENVIRONMENTL MANAGEMENT SYSTEMS IN GOVERNMENT AND INDUSTRY

Science.gov (United States)

Two new USEPA documents address environmental management systems (EMS) from the perspectives of government and industry and are offered as tools for understanding the process of the ISO 14000 Standards development and usefulness of an EMS approach. The first document, ISO 14001 -...

IS ISO 9000 CERTIFICATION LOSING ITS CREDIBILITY?

Directory of Open Access Journals (Sweden)

P.R. Ramesh

2013-03-01

Full Text Available ISO certification was a great hope for many stakeholders in India for making the country strong in terms of quality practices. It was a blessing in disguise when in early nineties; buyers were imposing conditions that you should be ISO compliant to do business with them. ISO was a great system to bring in improvements in the way an organization functions. But unfortunately some have adopted a short cut approach in getting the certification done. It is only just before the audit team comes for re-inspection that firms start removing dust from the quality manual files so that they can pretend that that they follow those systems. But a real commitment to adhering to these systems is missing. The paper describes such scenario existing in some quarters in India and warns against such practices for the overall good of the system.

Bee venom suppresses PMA-mediated MMP-9 gene activation via JNK/p38 and NF-kappaB-dependent mechanisms.

Science.gov (United States)

Cho, Hyun-Ji; Jeong, Yun-Jeong; Park, Kwan-Kyu; Park, Yoon-Yub; Chung, Il-Kyung; Lee, Kwang-Gill; Yeo, Joo-Hong; Han, Sang-Mi; Bae, Young-Seuk; Chang, Young-Chae

2010-02-17

Bee venom has been used for the treatment of inflammatory diseases such as rheumatoid arthritis and for the relief of pain in traditional oriental medicine. The purpose of this study is to elucidate the effects of bee venom on MMP-9 expression and determine possible mechanisms by which bee venom relieves or prevents the expression of MMP-9 during invasion and metastasis of breast cancer cells. We examined the expression and activity of MMP-9 and possible signaling pathway affected in PMA-induced MCF-7 cells. Bee venom was obtained from the National Institute of Agricultural Science and Technology of Korea. Matrigel invasion assay, wound-healing assay, zymography assay, western blot assay, electrophoretic mobility shift assay and luciferase gene assay were used for assessment. Bee venom inhibited cell invasion and migration, and also suppressed MMP-9 activity and expression, processes related to tumor invasion and metastasis, in PMA-induced MCF-7 cells. Bee venom specifically suppressed the phosphorylation of p38/JNK and at the same time, suppressed the protein expression, DNA binding and promoter activity of NF-kappaB. The levels of phosphorylated ERK1/2 and c-Jun did not change. We also investigated MMP-9 inhibition by melittin, apamin and PLA(2), representative single component of bee venom. We confirmed that PMA-induced MMP-9 activity was significantly decreased by melittin, but not by apamin and phospholipase A(2). These data demonstrated that the expression of MMP-9 was abolished by melittin, the main component of bee venom. Bee venom inhibits PMA-induced MMP-9 expression and activity by inhibition of NF-kappaB via p38 MAPK and JNK signaling pathways in MCF-7 cells. These results indicate that bee venom can be a potential anti-metastatic and anti-invasive agent. This useful effect may lead to future clinical research on the anti-cancer properties of bee venom. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

ISO Results Presented at International Astronomical Union

Science.gov (United States)

1997-08-01

Some of the work being presented is collected in the attached ESA Information Note N 25-97, ISO illuminates our cosmic ancestry. A set of six colour images illustrating various aspects have also been released and are available at http://www.estec.esa.nl/spdwww/iso1808.htm or in hard copy from ESA Public Relations Paris (fax:+33.1.5369.7690). These pictures cover: 1. Distant but powerful infrared galaxies 2. A scan across the milky way 3. Helix nebula: the shroud of a dead star 4. Supernova remnant Cassiopeia A 5. Trifid nebula: a dusty birthplace of stars 6. Precursors of stars and planets The International Astronomical Union provides a forum where astronomers from all over the world can develop astronomy in all its aspects through international co-operation. General Assemblies are held every three years. It is expected that over 1600 astronomers will attend this year's meeting, which is being held in Kyoto, Japan from 18-30 August. Further information on the meeting can be found at: www.tenmon.or.jp/iau97/ . ISO illuminates our cosmic ancestry The European Space Agency's Infrared Space Observatory, ISO, is unmatched in its ability to explore and analyse many of the universal processes that made our existence possible. We are children of the stars. Every atom in our bodies was created in cosmic space and delivered to the Sun's vicinity in time for the Earth's formation, during a ceaseless cycle of birth, death and rebirth among the stars. The most creative places in the sky are cool and dusty, and opaque even to the Hubble Space Telescope. Infrared rays penetrating the dust reveal to ISO hidden objects, and the atoms and molecules of cosmic chemistry. "ISO is reading Nature's recipe book," says Roger Bonnet, ESA's director of science. "As the world's only telescope capable of observing the Universe over a wide range of infrared wavelengths, ISO plays an indispensable part in astronomical discoveries that help to explain how we came to exist." This Information Note

Revision of the ISO and EN radiation sterilization standards

DEFF Research Database (Denmark)

Miller, A.; Hansen, J.

2002-01-01

The radiation sterilization standards, ISO 11137 and EN 552, are now being revised under "ISO lead", with the aim of producing only one international standard, although in four parts: (1) requirements. (2) dose-setting methods, (3) dose-substantiation methods and (4) dosimetry. Several aspects...

Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB.

Science.gov (United States)

Park, Mi Hee; Choi, Myoung Suk; Kwak, Dong Hoon; Oh, Ki-Wan; Yoon, Do Young; Han, Sang Bae; Song, Ho Sueb; Song, Min Jong; Hong, Jin Tae

2011-06-01

Bee venom has been used as a traditional medicine to treat arthritis, rheumatism, back pain, cancerous tumors, and skin diseases. However, the effects of bee venom on the prostate cancer and their action mechanisms have not been reported yet. To determine the effect of bee venom and its major component, melittin on the prostate cancer cells, apoptosis is analyzed by tunnel assay and apoptotic gene expression. For xenograft studies, bee venom was administrated intraperitoneally twice per week for 4 weeks, and the tumor growth was measured and the tumor were analyzed by immunohistochemistry. To investigate whether bee venom and melittin can inactivate nuclear factor kappa B (NF-κB), we assessed NF-κB activity in vitro and in vivo. Bee venom (1-10 µg/ml) and melittin (0.5-2.5 µg/ml) inhibited cancer cell growth through induction of apoptotic cell death in LNCaP, DU145, and PC-3 human prostate cancer cells. These effects were mediated by the suppression of constitutively activated NF-κB. Bee venom and melittin decreased anti-apoptotic proteins but induced pro-apoptotic proteins. However, pan caspase inhibitor abolished bee venom and melittin-induced apoptotic cell death and NF-κB inactivation. Bee venom (3-6 mg/kg) administration to nude mice implanted with PC-3 cells resulted in inhibition of tumor growth and activity of NF-κB accompanied with apoptotic cell death. Therefore, these results indicated that bee venom and melittin could inhibit prostate cancer in in vitro and in vivo, and these effects may be related to NF-κB/caspase signal mediated induction of apoptotic cell death. Copyright © 2010 Wiley-Liss, Inc.

Antitumor Activity of Tenacissoside H on Esophageal Cancer through Arresting Cell Cycle and Regulating PI3K/Akt-NF-κB Transduction Cascade

Directory of Open Access Journals (Sweden)

Yong-sen Jia

2015-01-01

Full Text Available Objective. The purpose of the study was to elucidate the molecular mechanism of tenacissoside H (TDH inhibiting esophageal carcinoma infiltration and proliferation. Methods. In vitro, EC9706 cells were treated with TDH. Cells proliferation and cell cycle were assayed. PI3K and NF-κB mRNAs expression were determined by real time PCR. In vivo, model of nude mice with tumor was established. Mice were treated with TDH. Inhibition ratio of tumor volume was calculated. PCNA expression was examined. Protein expression in PI3K/Akt-NF-κB signaling pathway was determined. Results. In vitro, TDH significantly inhibited cells proliferation in a time-and-dose-dependent manner. TDH arrested the cell cycle in S phase and significantly inhibited PI3K and NF-κB mRNA expression, compared with blank controlled group (P<0.05. In vivo, TDH strongly inhibits tumor growth and volume. PCNA expression was significantly decreased after treatment of TDH. TDH downregulated proteins expression in PI3K/Akt-NF-κB transduction cascade (P<0.05. Conclusion. TDH inhibited esophageal carcinoma infiltration and proliferation both in vitro and in vivo. The anticancer activity has relation to arresting the cell cycle at the S phase, inhibited the PCNA expression of transplanted tumors in nude mice, and regulated the protein expression in the PI3K/Akt-NF-κB transduction cascade.

Measuring the Software Product Quality during the Software Development Life-Cycle: An ISO Standards Perspective

OpenAIRE

Rafa E. Al-Qutaish

2009-01-01

Problem statement: The International Organization for Standardization (ISO) published a set of international standards related to the software engineering, such as ISO 12207 and ISO 9126. However, there is a set of cross-references between the two standards. Approach: The ISO 9126 on software product quality and ISO 12207 on software life cycle processes had been analyzed to invistigate the relationships between them and to make a mapping from the ISO 9126 quality characteristics to the ISO 1...

Haloperidol Abrogates Matrix Metalloproteinase-9 Expression by Inhibition of NF-κB Activation in Stimulated Human Monocytic Cells

Directory of Open Access Journals (Sweden)

Yueh-Lun Lee

2018-01-01

Full Text Available Much evidence has indicated that matrix metalloproteinases (MMPs participate in the progression of neuroinflammatory disorders. The present study was undertaken to investigate the inhibitory effect and mechanism of the antipsychotic haloperidol on MMP activation in the stimulated THP-1 monocytic cells. Haloperidol exerted a strong inhibition on tumor necrosis factor- (TNF- α-induced MMP-9 gelatinolysis of THP-1 cells. A concentration-dependent inhibitory effect of haloperidol was observed in TNF-α-induced protein and mRNA expression of MMP-9. On the other hand, haloperidol slightly affected cell viability and tissue inhibition of metalloproteinase-1 levels. It significantly inhibited the degradation of inhibitor-κB-α (IκBα in activated cells. Moreover, it suppressed activated nuclear factor-κB (NF-κB detected by a mobility shift assay, NF-κB reporter gene, and chromatin immunoprecipitation analyses. Consistent with NF-κB inhibition, haloperidol exerted a strong inhibition of lipopolysaccharide- (LPS- induced MMP-9 gelatinolysis but not of transforming growth factor-β1-induced MMP-2. In in vivo studies, administration of haloperidol significantly attenuated LPS-induced intracerebral MMP-9 activation of the brain homogenate and the in situ in C57BL/6 mice. In conclusion, the selective anti-MMP-9 activation of haloperidol could possibly involve the inhibition of the NF-κB signal pathway. Hence, it was found that haloperidol treatment may represent a bystander of anti-MMP actions for its conventional psychotherapy.

USGIN ISO metadata profile

Science.gov (United States)

Richard, S. M.

2011-12-01

The USGIN project has drafted and is using a specification for use of ISO 19115/19/39 metadata, recommendations for simple metadata content, and a proposal for a URI scheme to identify resources using resolvable http URI's(see http://lab.usgin.org/usgin-profiles). The principal target use case is a catalog in which resources can be registered and described by data providers for discovery by users. We are currently using the ESRI Geoportal (Open Source), with configuration files for the USGIN profile. The metadata offered by the catalog must provide sufficient content to guide search engines to locate requested resources, to describe the resource content, provenance, and quality so users can determine if the resource will serve for intended usage, and finally to enable human users and sofware clients to obtain or access the resource. In order to achieve an operational federated catalog system, provisions in the ISO specification must be restricted and usage clarified to reduce the heterogeneity of 'standard' metadata and service implementations such that a single client can search against different catalogs, and the metadata returned by catalogs can be parsed reliably to locate required information. Usage of the complex ISO 19139 XML schema allows for a great deal of structured metadata content, but the heterogenity in approaches to content encoding has hampered development of sophisticated client software that can take advantage of the rich metadata; the lack of such clients in turn reduces motivation for metadata producers to produce content-rich metadata. If the only significant use of the detailed, structured metadata is to format into text for people to read, then the detailed information could be put in free text elements and be just as useful. In order for complex metadata encoding and content to be useful, there must be clear and unambiguous conventions on the encoding that are utilized by the community that wishes to take advantage of advanced metadata

Evaluation of Virological Microparticle Enzyme Immunoassay According to the ISO 15189: Real-Life Experience in a University Hospital.

Science.gov (United States)

Lafontaine, Sophie; Prin-Mathieu, Christine; Velay, Aurélie; Agulles, Odette; Schvoerer, Evelyne; Jeulin, Hélène

2016-01-01

The International Standard ISO 15189 based on the ISO 9001:2008 emphasizes specific requirements for quality and ability of medical laboratories. The accreditation of medical laboratories according to ISO 15189 includes the validation of biological methods, which depends on collection of bibliographic data and experimental proofs. Moreover, these results must be compared to provider data sheets and independent scientific data. In the immunodiagnostic field, independent published data are deeply lacking. The aim of our work was to share experience of method validation for virological immune markers on the widely used Architect i2000sr. After risk analysis, intra- and inter-assay variability, and inter-sample contamination were evaluated for each method, and sensitivity was investigated for antigen detection tests. A comparison between the two Architect i2000sr available in our laboratory was also performed. All tested methods were consistent with the manufacturer data (from the data sheet). No inter-sample contamination was observed. Both devices are broadly equivalent and can be used indifferently or as a backup solution of the other. To our knowledge, those results are the first independent complete data on the reliability of the Architect i2000sr in real-life experience. These data are needed to the accreditation of our platform and potentially useful for the accreditation of other laboratories using the same equipment.

ISO CD 14492

DEFF Research Database (Denmark)

Martins, Bo; Kossentini, F.; Arps, R.

1998-01-01

This Recommendation | International Standard, informally called JBIG2, defines a coding method for bilevel images, that is, images consisting of a single rectangular bit plane, with each pixel taking on one of just two possible colors. Itis being drafted by the Joint Bi-level Image Experts Group ...... (JBIG), a "Collaborative team" that reports both to ISO/IEC JTC1/SC29/WG1 and to ITU-T/SG8....

Implications of ISO 9000 for personnel dosimetry

International Nuclear Information System (INIS)

Yoder, R.C.

1995-01-01

Landauer, Inc. has gained approval to provide personnel dosimetry services in several countries. Each experiene reflects the different concerns adopted by national approval agencies. None have adopted ISO 9000 registration as evidence of a suitable quality system of management. Instead, each organization has prepared its own set of requirements with no provisions for recognizing the results of performance tests or audits conducted by other approval organizations. As ISO 9000 has become a communication symbol for commercial organizations dealing with each other, it has not been similarly viewed by radiation regulation bodies. A key reason arises from a tradition to regulate bodies. A key reason arises from a tradition to regulate, not promote, international trade, not encourage innovation, nor foster economic competition. A second reason is the inability to separate the technical requirements from quality assurance. ISO 9000 may become useful once the national technical organizations learn to trust those of other countries

IMPLEMENTASI SISTEM MANAJEMEN MUTU BERBASIS ISO 9001:2000 PADA SEKOLAH MENENGAH KEJURUAN

Directory of Open Access Journals (Sweden)

Mardi Wiyono

2012-09-01

Full Text Available Abstract: The implementation of ISO 9001:2000 quality management system in vocational school. The needs of quality products and services is largerly expanded in various organizations including education. Recently, the vocational schools also realize how important the quality product and service is. For achieving the quality product or service, some organizations implement the concept of ISO 9001:2000 quality management system. In 2006/2007 it is reported that there are some vocational schools have been certified with ISO 9001:2000. ISO 9001 is a serial document consists of Quality Management System Standard which has been refised from its previous standard. ISO 9001:2000 gives a number of prerequisites for organizations having business initialized by design and development, production, installations, and services. The vocational schools which have been certified with ISO 9001:2000, have to be re-accredited after three years of implementation.

Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells.

Science.gov (United States)

Yang, Po-Min; Wu, Zhi-Zhen; Zhang, Yu-Qi; Wung, Being-Sun

2016-06-15

Age-related macular degeneration (AMD) is one of the most common diseases leading to blindness in elderly people. The progression of AMD may be prevented through anti-inflammation and antioxidation in retinal pigment epithelium (RPE) cells. Lycopene, a carotenoid, has been shown to possess both antioxidative and anti-inflammatory properties. This research was conducted to detail the mechanisms of these effects of lycopene-treated RPE cells. We exposed ARPE-19 cells to TNFα after pretreatment with lycopene, and measured monocyte adhesion, ICAM-1 expression, NF-κB nuclear translocation, and transcriptional activity. Cell viability was assayed with Alamar Blue. The cell redox state was tested by glutathione (GSH) and reactive oxygen species (ROS) levels. The importance of the Nrf2 pathway was tested in nuclear translocation, promoter reporter assay, and siRNA. Lycopene could reduce TNF-α-induced monocyte adhesion and H2O2- induced cell damage in RPE cells. Furthermore, lycopene inhibits ICAM-1 expression and abolishes NF-κB activation for up to 12h in TNFα-treated RPE cells. Lycopene upregulates Nrf2 levels in nuclear extracts and increases the transactivity of antioxidant response elements. The use of Nrf2 siRNA blocks the inhibitory effect of lycopene in TNF-α-induced ICAM-1 expression and NF-κB activation. Glutamate-cysteine ligase (GCL) is the rate-limiting enzyme in the de novo synthesis of GSH. We found that lycopene increases intracellular GSH levels and GCL expression. Following lycopene treatment, TNF-α-induced ROS production was abolished. The Nrf2-regulated antioxidant property plays a pivotal role in the anti-inflammatory mechanism underlying the inhibition of NF-κB activation in lycopene-treated ARPE-19 cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Formulation and drug-content assay of microencapsulated antisense oligonucleotide to NF-κB using ATR-FTIR

International Nuclear Information System (INIS)

Siwale, Rodney; Meadows, Fred; Mody, Vicky V; Shah, Samit

2013-01-01

Antisense oligonucleotide to NF-κB sequence: 5′-GGA AAC ACA TCC TCC ATG-3′, was microencapsulated in an albumin matrix by the method of spray drying TM . Spectral analysis was performed on varying drug loading formulations of both drugs by mid-IR attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An out of plane O–H bending vibration at 948 cm −1 , unique to both the native and microencapsulated drugs was identified. The calculated peak areas corresponded to the drug loadings in the microsphere formulations. A standard curve could then be used to determine the drug content of an unknown microsphere formulation. Accuracy and precision were determined to be comparable to other analytical techniques such as HPLC. (paper)

Modelovanje georeferenciranih podataka u katastru nepokretnosti primenom ISO 19100 serije standarda / Spatial data modeling in the real estate cadastre using ISO 19100 series of standards

Directory of Open Access Journals (Sweden)

Mirko N. Petrović

2010-01-01

Full Text Available Potreba za standardizacijom u oblasti geografskih informacionih sistema odavno postoji. Međunarodne aktivnosti na ovom polju rezultirale su uspostavljanjem ISO 19100 serije standarda, kojima se regulišu različiti aspekti na polju geoinformatike. U članku su opisane mogućnosti primene relevantnih standarda iz serije ISO 19100 u modelovanju georeferenciranih podataka za katastar nepokretnosti. / Introduction Standardization in geo-information technologies contributes to the establishment of efficient information functions, their greater stability and easier transition. Application of international, national and internal standards in the process of developing software products in the field of geo-information technology creates conditions for the development of efficient, low cost, reliable and secure software products. Spatial data modeling basics for real estate cadastre In terms of modeling, the spatial information of real estate cadastre is based on the vector data model which is suitable for modeling objects with a smaller number of properties with emphasis on the position. The vector spatial data model consists of two components: spatial and descriptive. The basis of the spatial one is geometry that contains metric data usually given in coordinates of a reference system. Geometry and Topology uniquely determine the shape, size and position of the object model in space, i.e. they represent its spatial component. Merging the spatial component with the descriptive one results in a completely defined object from the real world. Elements of spatial data quality Spatial data quality can be reviewed through a set of the following elements: origin, positional accuracy, attribute accuracy, completeness, logical consistency, semantic accuracy and the time information. The elements of spatial data quality listed above are provided using ISO 19100 series of standards. Application of ISO19100 series of standards in spatial data modeling for real

Reasons to Adopt ISO 50001 Energy Management System

Directory of Open Access Journals (Sweden)

Frederic Marimon

2017-09-01

Full Text Available Purpose: The main aim of this paper is to analyze the relationships between the corporate motivations that lead organizations to establish the ISO 50001 Energy Management System (EnMS standard, and the difficulties and benefits derived from its adoption. Design/methodology/approach: Three independent exploratory factor analyses (EFA were conducted in order to identify (i sources of motivation: social requirements, ecology drivers, and competitive advantage; (ii the difficulties of an ISO 50001 adoption: operational difficulties and organizational difficulty; and (iii types of benefits: ecological benefits and operational benefits. In a second step, an exploratory path analysis, performed through Structural Equation Modeling (SEM, was used to analyze the relations among motivation, difficulties, and benefits related to the adoption of the ISO 50001 standard. Findings: Social requirements explain operational difficulties, which in turn impacts on operational benefits. Ecology drivers are directly related to ecological benefits. Organizational difficulties have an inverse relationship with operational and ecological benefits. Operational difficulties are related to operational benefits and ecological benefits. Research limitations/implications: The questionnaire was disseminated to 87 Spanish companies with ISO 50001 certification. Managers and other practitioners such as consultants, auditing companies, and official organizations in charge of developing standards might find useful implications. Originality/value: The standard was published in 2011 by the International Organization for Standardization (ISO. This paper contributes to assessment of the benefits of the standard by collecting information directly from the pioneer organizations that have adopted it, and provides clues on how to implement the standard and improve it in future.

Nuclear NF-κB p65 in peripheral blood mononuclear cells correlates with urinary MCP-1, RANTES and the severity of type 2 diabetic nephropathy.

Directory of Open Access Journals (Sweden)

Bin Yi

Full Text Available AIMS: To investigate if nuclear NF-κB p65 expression in ex vivo isolated peripheral blood mononuclear cells correlates with urinary MCP-1 or RANTES and the severity of type 2 diabetic nephropathy. METHODS: According to their urinary albumin-to-creatinine ratio (uACR, 107 patients with type 2 diabetes (eGFR >60 ml/min were divided into normal albuminuria group (DN0 group, 38 cases, microalbuminuria group (DN1 group, 38 cases, and macroalbuminuria group (DN2 group, 31 cases, compared with matched healthy normal control group (NC group, 30 cases. Nuclear NF-κB p65 protein expression levels in peripheral blood mononuclear cells were detected by western blotting. Real-time quantitative polymerase chain reaction was used to detect NF-κB p65 mRNA expression and ELISA assay was used to detect the levels of urinary MCP-1 and RANTES. RESULTS: Nuclear NF-κB p65 protein and NF-κB p65 mRNA expression levels in peripheral blood mononuclear cells, urinary MCP-1/Cr and RANTES/Cr were all significantly higher in all diabetes groups as compared with NC group. In particular, the increase of nuclear NF-κB p65 protein and NF-κB p65 mRNA expressions, urinary MCP-1/Cr and RANTES/Cr all correlated with the severity of type 2 diabetic nephropathy as indicated by the increase in uACR. Pearson correlation analysis indicated that both urinary MCP-1/Cr and RANTES/Cr were positively correlated with nuclear NF-κB p65 protein or NF-κB p65 mRNA levels. Stepwise multiple regression analysis showed that nuclear NF-κB p65 protein or NF-κB p65 mRNA was an independent variable for urinary MCP-1/Cr, and MCP-1/Cr and RANTES/Cr were two independent variables for uACR. CONCLUSION: Our research demonstrates that nuclear NF-κB p65 protein and mRNA expressions in ex vivo isolated peripheral blood mononuclear cells well correlate with urinary MCP-1/Cr, RANTES/Cr and the severity of type 2 diabetic nephropathy.

Energy care in relation to your management system. Linking lists between the Reference Energy Care and ISO 14001, ISO 9001 and HACCP; Energiezorg in relatie tot uw zorgsysteem. Linking lists tussen de Referentie Energiezorg en ISO 14001, ISO 9001 en HACCP

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

Several so-called care systems are in use at institutes and companies. For efficiency reasons it makes sense to integrate an energy care system to the existing care system. For the so-called Reference Energy Care, developed by the Netherlands Agency for Energy and the Environment (Novem) links to three of the most important care systems have been elaborated: environmental care according to ISO 14001, the quality care system ISO 9001:2000 and the food safety system Hazard Analysis Critical Control Points (HACCP). The elaboration resulted in three tables, indicating the connections ('linking lists') between each of those care systems and the Reference Energy Care system and how energy care can be integrated into those systems. [Dutch] Bij instellingen en bedrijven zijn diverse zorgsystemen in gebruik. Het is zinvol om energiezorg - waar mogelijk - in een dergelijk bestaand systeem op te nemen. Meerdere zorgsystemen naast elkaar in stand houden is minder efficient dan de systemen integreren tot een systeem. Novem heeft daarom voor haar Referentie Energiezorg de link laten uitwerken naar drie van de meest voorkomende systemen: milieuzorg volgens ISO 14001, het kwaliteitszorgsysteem ISO 9001:2000 en het voedselveiligheidssysteem HACCP (Hazard Analysis Critical Control Points). Hieruit zijn drie tabellen voortgekomen, die aangeven welke verbanden er zijn tussen elk van deze zorgsystemen en de Referentie Energiezorg en hoe u energiezorg kunt integreren in elk van deze systemen. Deze tabellen worden aangeduid als 'linking lists' en u kunt ze gebruiken als hulpmiddel bij het integreren van energiezorg in uw eigen zorgsysteem. U vindt ze in deze brochure.

Energy care in relation to your management system. Linking lists between the Reference Energy Care and ISO 14001, ISO 9001 and HACCP; Energiezorg in relatie tot uw zorgsysteem. Linking lists tussen de Referentie Energiezorg en ISO 14001, ISO 9001 en HACCP

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-07-01

Several so-called care systems are in use at institutes and companies. For efficiency reasons it makes sense to integrate an energy care system to the existing care system. For the so-called Reference Energy Care, developed by the Netherlands Agency for Energy and the Environment (Novem) links to three of the most important care systems have been elaborated: environmental care according to ISO 14001, the quality care system ISO 9001:2000 and the food safety system Hazard Analysis Critical Control Points (HACCP). The elaboration resulted in three tables, indicating the connections ('linking lists') between each of those care systems and the Reference Energy Care system and how energy care can be integrated into those systems. [Dutch] Bij instellingen en bedrijven zijn diverse zorgsystemen in gebruik. Het is zinvol om energiezorg - waar mogelijk - in een dergelijk bestaand systeem op te nemen. Meerdere zorgsystemen naast elkaar in stand houden is minder efficient dan de systemen integreren tot een systeem. Novem heeft daarom voor haar Referentie Energiezorg de link laten uitwerken naar drie van de meest voorkomende systemen: milieuzorg volgens ISO 14001, het kwaliteitszorgsysteem ISO 9001:2000 en het voedselveiligheidssysteem HACCP (Hazard Analysis Critical Control Points). Hieruit zijn drie tabellen voortgekomen, die aangeven welke verbanden er zijn tussen elk van deze zorgsystemen en de Referentie Energiezorg en hoe u energiezorg kunt integreren in elk van deze systemen. Deze tabellen worden aangeduid als 'linking lists' en u kunt ze gebruiken als hulpmiddel bij het integreren van energiezorg in uw eigen zorgsysteem. U vindt ze in deze brochure.

21 CFR 184.1165 - n-Butane and iso-butane.

Science.gov (United States)

2010-04-01

... FOR HUMAN CONSUMPTION (CONTINUED) DIRECT FOOD SUBSTANCES AFFIRMED AS GENERALLY RECOGNIZED AS SAFE Listing of Specific Substances Affirmed as GRAS § 184.1165 n-Butane and iso-butane. (a) n-Butane and iso..., odorless, flammable gases at normal temperatures and pressures. They are easily liquefied under pressure at...

Juhtimissüsteemide selgroog. Lean ning ISO - terviklahendused tootmise haldamiseks / Anton Ovsjankin

Index Scriptorium Estoniae

Ovsjankin, Anton

2011-01-01

Kasvanud on juurutatavate Lean ja ISO süsteemide arv, kuid on kasvanud ka nende juurutamise ja arendamisega seotud ebaõnnestumiste arv. Põhjustest, miks jäävad paljud Leani ja ISO juurutanud ettevõtted ilma lubatud tulemusteta. Leani ja ISO haldamiseks vajalikest teguritest

Valproic acid inhibits neural progenitor cell death by activation of NF-κB signaling pathway and up-regulation of Bcl-XL

Directory of Open Access Journals (Sweden)

Han Seol

2011-07-01

Full Text Available Abstract Background At the beginning of neurogenesis, massive brain cell death occurs and more than 50% of cells are eliminated by apoptosis along with neuronal differentiation. However, few studies were conducted so far regarding the regulation of neural progenitor cells (NPCs death during development. Because of the physiological role of cell death during development, aberration of normal apoptotic cell death is detrimental to normal organogenesis. Apoptosis occurs in not only neuron but also in NPCs and neuroblast. When growth and survival signals such as EGF or LIF are removed, apoptosis is activated as well as the induction of differentiation. To investigate the regulation of cell death during developmental stage, it is essential to investigate the regulation of apoptosis of NPCs. Methods Neural progenitor cells were cultured from E14 embryonic brains of Sprague-Dawley rats. For in vivo VPA animal model, pregnant rats were treated with VPA (400 mg/kg S.C. diluted with normal saline at E12. To analyze the cell death, we performed PI staining and PARP and caspase-3 cleavage assay. Expression level of proteins was investigated by Western blot and immunocytochemical assays. The level of mRNA expression was investigated by RT-PCR. Interaction of Bcl-XL gene promoter and NF-κB p65 was investigated by ChIP assay. Results In this study, FACS analysis, PI staining and PARP and caspase-3 cleavage assay showed that VPA protects cultured NPCs from cell death after growth factor withdrawal both in basal and staurosporine- or hydrogen peroxide-stimulated conditions. The protective effect of prenatally injected VPA was also observed in E16 embryonic brain. Treatment of VPA decreased the level of IκBα and increased the nuclear translocation of NF-κB, which subsequently enhanced expression of anti-apoptotic protein Bcl-XL. Conclusion To the best of our knowledge, this is the first report to indicate the reduced death of NPCs by VPA at developmentally

ISO 14000: Review and guidelines for the photovoltaic industry

Energy Technology Data Exchange (ETDEWEB)

DePhillips, M.P.

1997-08-01

The International Organization for Standardization (ISO) has released and is in the process of ratifying a new set of environmental management system standards, ISO 14000. These voluntary international standards will have a significant impact on how companies throughout the international community manage their environmental programs. Initially this impact will result in increased international trade opportunities due to the anticipated customer requirement for suppliers to demonstrate certification. Other potential impacts will benefit both companies engaged in international commerce and companies with a domestic focus. These would include installing a cohesive system to manage environmental matters, participation within a new regulatory paradigm, and adhering to a potentially new set of legal standards. The wide range of potential environmental, commercial, legal and regulatory benefits offered by ISO 14000 offer most companies significant reason to explore the possibilities of implementing an environmental management system. Organizations will be able to anticipate and meet growing environmental expectations and to ensure ongoing compliance with national and international requirements as well as satisfy the growing demands of customers, stakeholders and the interested public. As an emerging industry with significant international ties, the photovoltaic (PV) community will be effected from these standards if they do become globally adopted. In fact some major players in the PV industry have recently received certification to ISO 9000. This again demonstrates a trend within the industry to move toward a uniform system approach to management. This paper will expose interested parties within the PV industry to the details of ISO 14000 and will assist decision makers assess the various possibilities for implementation certification of ISO 14000 for an individual facility.

Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

Directory of Open Access Journals (Sweden)

Yao Fong

2012-05-01

Full Text Available Caffeic acid (CA, a natural phenolic compound, is abundant in medicinal plants. CA possesses multiple biological effects such as anti-bacterial and anti-cancer growth. CA was also reported to induce fore stomach and kidney tumors in a mouse model. Here we used two human lung cancer cell lines, A549 and H1299, to clarify the role of CA in cancer cell proliferation. The growth assay showed that CA moderately promoted the proliferation of the lung cancer cells. Furthermore, pre-treatment of CA rescues the proliferation inhibition induced by a sub-IC₅₀ dose of paclitaxel (PTX, an anticancer drug. Western blot showed that CA up-regulated the pro-survival proteins survivin and Bcl-2, the down-stream targets of NF-κB. This is consistent with the observation that CA induced nuclear translocation of NF-κB p65. Our study suggested that the pro-survival effect of CA on PTX-treated lung cancer cells is mediated through a NF-κB signaling pathway. This may provide mechanistic insights into the chemoresistance of cancer calls.

Mesenchymal stem cells attenuate adriamycin-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of the NF-kB.

Science.gov (United States)

Song, In-Hwan; Jung, Kyong-Jin; Lee, Tae-Jin; Kim, Joo-Young; Sung, Eon-Gi; Bae, Young Chul; Park, Yong Hoon

2018-05-01

This study aimed to evaluate the molecular mechanism mitigating progress of chronic nephropathy by mesenchymal stem cells (MSCs). Rats were divided into normal control (Normal), adriamycin (ADR)+vehicle (CON), and ADR+MSC (MSC) groups. Nephropathy was induced by ADR (4 mg/kg) and MSCs (2 × 10 6 ) were injected. Rats were euthanized 1 or 6 weeks after ADR injection. NF-kB, MAPKs, inflammation, oxidative stress, profibrotic molecules, and nephrin expression were evaluated. Electron and light microscopy were used for structural analysis. MSCs were co-cultured with renal tubular epithelial cells or splenocytes to evaluate relation with oxidative stress and inflammatory molecules RESULTS: Adriamycin treatment upregulated inflammation, oxidative stress, and profibrotic molecules; this was mitigated by MSCs. Glomerulosclerosis and interstitial fibrosis were observed in ADR-treated groups, and were more prominent in the CON group than in the MSC group. Fusion of foot processes and loss of slit diaphragms were also more prominent in the CON group than in the MSC group. In vitro, MSCs reduced oxidative stress related molecules, inflammatory cytokines, and NF-kB transcription. MSC- or ADR-induced regulation of NF-kB transcriptional activity was confirmed by a luciferase reporter assay. Mesenchymal stem cells attenuate ADR-induced nephropathy by diminishing oxidative stress and inflammation via downregulation of NF-kB. © 2017 Asian Pacific Society of Nephrology.

ISO 9000. Guidelines to increased costs and reduced product quality

International Nuclear Information System (INIS)

Reedy, R.F.

1994-01-01

Many US companies are considering being registered to the provisions of ISO 9000, International Standards for Quality Management. One important problem with the document is that ISO 9000 is not focused on control of product quality. The quality assurance rules established in ISO 9000 have been used in the US for more than 25 years with disastrous financial consequences and little, if any, improvement in quality and safety. These rules are so reliant on documentation and strict compliance that ensuring products comply with specifications has become a secondary issues. That is not what was intended, but it is the result. ISO 9000 program can work effectively only when the top executive responsible for engineering or production takes full responsibility for interpretation and implementation of the quality assurance program. 3 refs., 1 tab

Anthocyanins from black rice (Oryza sativa L.) demonstrate antimetastatic properties by reducing MMPs and NF-κB expressions in human oral cancer CAL 27 cells.

Science.gov (United States)

Fan, Ming-Jen; Wang, I-Chen; Hsiao, Yung-Ting; Lin, Hui-Yi; Tang, Nou-Ying; Hung, Tzu-Chieh; Quan, Christine; Lien, Jin-Cherng; Chung, Jing-Gung

2015-01-01

Aside from the commonly known white rice lines, colored varieties also exist. These varieties have historically been used in Chinese medicine. Anthocyanins, a large group of natural polyphenols existing in a variety of daily fruits and vegetables, have been widely recognized as cancer chemopreventive agents. The primary objective of cancer treatment strategies has traditionally focused on preventing the occurrence of metastasis. In this research the antimetastatic mechanism of anthocyanins on the invasion/migration of human oral CAL 27 cells was performed using a transwell to quantify the migratory potential of CAL 27 cells and the results show that anthocyanins can inhibit the in vitro migration and invasion of CAL 27 cancer cells. In addition, the gelatin zymography assay indicated that anthocyanins inhibited the activity of matrix metalloproteinases-2 (MMP-2). Western blotting assay also demonstrated that anthocyanins inhibited the associated protein expression of migration/invasion of CAL 27 cell. Immunofluorescence staining proved that anthocyanins inhibited nuclear factor kappa B p65 (NF-κB p65) expressions. These results demonstrated that anthocyanins from a species of black rice (selected purple glutinous indica rice cultivated at Asia University) could suppress CAL 27 cell metastasis by reduction of MMP-2, MMP-9, and NF-κB p65 expression through the suppression of PI3K/Akt pathway and inhibition of NF-κB levels.

Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-κB/MMP-9 Pathway

Science.gov (United States)

Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

2015-01-01

Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-κB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-κB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells. PMID:26115086

Hibiscus sabdariffa Leaf Extract Inhibits Human Prostate Cancer Cell Invasion via Down-Regulation of Akt/NF-kB/MMP-9 Pathway.

Science.gov (United States)

Chiu, Chun-Tang; Chen, Jing-Hsien; Chou, Fen-Pi; Lin, Hui-Hsuan

2015-06-24

Hibiscus sabdariffa leaf has been previously shown to possess hypoglycemic, hypolipidemic, and antioxidant effects, and induce tumor cell apoptosis. However, the molecular mechanisms involved in the anticancer activity of H. sabdariffa leaf extract (HLE) are poorly understood. The object of the study was to examine the anti-invasive potential of HLE. First, HLE was demonstrated to be rich in polyphenols. The results of wound-healing assay and in vitro transwell assay revealed that HLE dose-dependently inhibited the migration and invasion of human prostate cancer LNCaP (lymph node carcinoma of the prostate) cells under non-cytotoxic concentrations. Our results further showed that HLE exerted an inhibitory effect on the activity and expressions of matrix metalloproteinase-9 (MMP-9). The HLE-inhibited MMP-9 expression appeared to be a consequence of nuclear factor-kappaB (NF-κB) inactivation because its DNA-binding activity was suppressed by HLE. Molecular data showed all these influences of HLE might be mediated via inhibition of protein kinase B (PKB, also known as Akt)/NF-kB/MMP-9 cascade pathway, as demonstrated by the transfection of Akt1 overexpression vector. Finally, the inhibitory effect of HLE was proven by its inhibition on the growth of LNCaP cells and the expressions of metastasis-related molecular proteins in vivo. These findings suggested that the inhibition of MMP-9 expression by HLE may act through the suppression of the Akt/NF-kB signaling pathway, which in turn led to the reduced invasiveness of the cancer cells.

OntoCR: A CEN/ISO-13606 clinical repository based on ontologies.

Science.gov (United States)

Lozano-Rubí, Raimundo; Muñoz Carrero, Adolfo; Serrano Balazote, Pablo; Pastor, Xavier

2016-04-01

To design a new semantically interoperable clinical repository, based on ontologies, conforming to CEN/ISO 13606 standard. The approach followed is to extend OntoCRF, a framework for the development of clinical repositories based on ontologies. The meta-model of OntoCRF has been extended by incorporating an OWL model integrating CEN/ISO 13606, ISO 21090 and SNOMED CT structure. This approach has demonstrated a complete evaluation cycle involving the creation of the meta-model in OWL format, the creation of a simple test application, and the communication of standardized extracts to another organization. Using a CEN/ISO 13606 based system, an indefinite number of archetypes can be merged (and reused) to build new applications. Our approach, based on the use of ontologies, maintains data storage independent of content specification. With this approach, relational technology can be used for storage, maintaining extensibility capabilities. The present work demonstrates that it is possible to build a native CEN/ISO 13606 repository for the storage of clinical data. We have demonstrated semantic interoperability of clinical information using CEN/ISO 13606 extracts. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 51996 - Notice of Commission Staff Attendance at Midwest ISO Meetings

Science.gov (United States)

2010-08-24

... Midwest ISO Meetings August 16, 2010. The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and Commission staff may attend the following Midwest ISO-related meetings...., St. Paul, MN) [cir] September 15 [cir] October 20 [cir] November 17 [cir] December 1 Midwest ISO...

ISO celebrates its prolonged life with a video of Jupiter

Science.gov (United States)

1997-07-01

This is excellent news for astronomers and especially for the multinational teams, with leaders in France, Germany, the Netherlands and the United Kingdom, who spent many years devising the four instruments served by ISO's telescope. The camera ISOCAM, the photometer ISOPHOT, the Short Wavelength Spectrometer and the Long Wavelength Spectrometer span between them an unprecedented range of infrared wavelengths from 2 to 200 microns. The atmosphere of Jupiter is one of the cool and cloudy places attracting ISO's attention, and ESA today releases a video of unprecedented images of Jupiter. The planet changes its appearance drastically as the camera ISOCAM scans a range of 90 different infrared wavelengths. Picture by picture, ISOCAM picks out different features of the atmosphere's composition and behaviour. These and other results from ISO will enable scientists to sharpen their ideas about how Jupiter's weather works. "ISO is giving us a new impression of the giant planets of the Solar System," comments Roger Bonnet, ESA's director of science. "Not just Jupiter, but Saturn, Uranus and Neptune too. By observing the planets across its very wide range of infrared wavelengths, ISO can see features overlooked even by spacecraft visiting the planets. The remarkable movie of Jupiter released today represents only a few per cent of ISO's wavelength range, yet every image tells its own story." More information about the Jupiter video appears later in this Information Note. How ISO's cold telescope beat the calendar The need to keep ISO's telescope and instruments chilled to a very low temperature sets a limit to their useful operating life. ISO was supplied with more than 2000 litres of superfluid helium to cool it. Slow evaporation maintains key parts of the spacecraft at temperatures close to absolute zero, below minus 271 degrees C. The rate of loss of helium was expected to be about 3 litres a day, but the cryogenic system could not be tested in exactly the conditions

[Effect of NF-κB on the expression of interleukin-6 induced by lipopolysaccharides of Porphyromonas endodontalis in MC3T3-E1 cells].

Science.gov (United States)

Yu, Ya-qiong; Guo, Jia-jie; Qiu, Li-hong; Lv, You; Jia, Ge; Guo, Yan

2013-08-01

To investigate the effect of NF-κB signaling on the expression of interleukin-6(IL-6) induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e) in MC3T3-El cells. MC3T3-E1 cells were pretreated with BAY-117082 for 1 h, and then were treated with 10 mg/L P.e-LPS for different times. The translocation of NF-κB was observed by immunofluorescence. The expression of IL-6 was detected by reverse transcription polymerse chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). Statistical analysis was performed using multi-way ANOVA and Dunnett's t test with SPSS 13.0 software package. The staining of NF-κB was mostly in cytoplasm in untreated cells. Rapid translocation of NF-κB into nucleus was observed in the cells stimulated for 30 min and mostly relocalization of NF-κB from nucleus to cytoplasm was observed after 60 min. Pretreatment with 10 μmol/L BAY-117082 for 1h significantly inhibited P.e-LPS-induced translocation of NF-κB .The mRNA and proteins of IL-6 decreased significantly after pretreatment with 10 μmol/L BAY-117082 and the expression of IL-6 proteins was reduced from (774.983±6.585) ng/L to (377.384±14.620) ng/L (P<0.01). The group of treatment with BAY-117082 alone had no significant difference from the blank control group. P.e-LPS can induce translocation of NF-κB in mouse osteoblast MC3T3-El, and P.e-LPS may induce the expression of IL-6 in mouse osteoblast through the signaling of NF-κB.

Expression and significance of TRAIL and NF-kB in osteosarcoma

International Nuclear Information System (INIS)

Du Xiumin; You Murong; Qi Falian; Hu Chengjin

2005-01-01

To investigate the relationship between expressions of TRAIL, NF-kB and cell proliferation in human osteosarcomas, the expressions of TRAIL and NF-kB in 16 cases of osteosarcoma, 5 cases of giant cell tumor of bone and 6 cases of chondrosarcoma were studied by flow cytometry. The expressions of TRAIL and NF-kB in osteosarcomas of different differentiation states were higher than those in other two kinds of tumors significantly in our study(P 0.05). The expressions of TRAIL and NF-kB in chondrosarcoma and giant cell tumor of bone were not different significantly(P>0.05). The higher expression of TRAIL in osteosarcoma with different differentiation states could not induce apoptosis because of the higher expression of NF-kB. NF-kB may restrain the apoptosis of tumor cells by regulating the NF-kB- induced apoptosis path way in osteosarcoma. (authors)

NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

Directory of Open Access Journals (Sweden)

McCarthy Brian A

2012-05-01

Full Text Available Abstract Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.

Direct non transcriptional role of NF-Y in DNA replication.

Science.gov (United States)

Benatti, Paolo; Belluti, Silvia; Miotto, Benoit; Neusiedler, Julia; Dolfini, Diletta; Drac, Marjorie; Basile, Valentina; Schwob, Etienne; Mantovani, Roberto; Blow, J Julian; Imbriano, Carol

2016-04-01

NF-Y is a heterotrimeric transcription factor, which plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation, apoptosis and DNA damage response. The knock-down of the sequence-specific subunit NF-YA triggers defects in S-phase progression, which lead to apoptotic cell death. Here, we report that NF-Y has a critical function in DNA replication progression, independent from its transcriptional activity. NF-YA colocalizes with early DNA replication factories, its depletion affects the loading of replisome proteins to DNA, among which Cdc45, and delays the passage from early to middle-late S phase. Molecular combing experiments are consistent with a role for NF-Y in the control of fork progression. Finally, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication, specifically in the DNA elongation process, using a Xenopus cell-free system. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific TFs required for proper and efficient DNA replication. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

ISO standardization in nuclear technology

Energy Technology Data Exchange (ETDEWEB)

Brabec, D [Ustav pro Vyzkum, Vyrobu a Vyuziti Radioisotopu, Prague (Czechoslovakia); Cermak, O [Urad pro Normalizaci a Mereni, Prague (Czechoslovakia)

1984-10-01

The activity is described of the technical commission ISO/TC 85 which is currently divided into 4 subcommissions (SC) and 24 working groups. SC 1 ''Terminology, definitions, units, abbreviations'' has one working group. The most important document of this SC is ISO 921-1972 (Dictionary of nuclear technology). SC 2 ''Radiation protection'' has 9 working groups and has processed standards in dosimetry. SC 3 ''Technology of power reactors'' has 6 working groups and its work is related to IAEA activities within the NUSS program. SC 4 ''Technology of nuclear fuels'' has 8 working groups. SC 4 has compiled the basic standards for sealed sources and methods of testing their tightness. The results of the work of this group have been reflected into the standardization work of CMEA. A list is given of published international standards within TC 85.

Pressure-dependent kinetics of initial reactions in iso-octane pyrolysis.

Science.gov (United States)

Ning, HongBo; Gong, ChunMing; Li, ZeRong; Li, XiangYuan

2015-05-07

This study focuses on the studies of the main pressure-dependent reaction types of iso-octane (iso-C8H18) pyrolysis, including initial C-C bond fission of iso-octane, isomerization, and β-scission reactions of the alkyl radicals produced by the C-C bond fission of iso-octane. For the C-C bond fission of iso-octane, the minimum energy potentials are calculated at the CASPT2(2e,2o)/6-31+G(d,p)//CAS(2e,2o)/6-31+G(d,p) level of theory. For the isomerization and the β-scission reactions of the alkyl radicals, the optimization of the geometries and the vibrational frequencies of the reactants, transition states, and products are performed at the B3LYP/CBSB7 level, and their single point energies are calculated by using the composite CBS-QB3 method. Variable reaction coordinate transition state theory (VRC-TST) is used for the high-pressure limit rate constant calculation and Rice-Ramsperger-Kassel-Marcus/master equation (RRKM/ME) is used to calculate the pressure-dependent rate constants of these channels with pressure varying from 0.01-100 atm. The rate constants obtained in this work are in good agreement with those available from literatures. We have updated the rate constants and thermodynamic parameters for species involved in these reactions into a current chemical kinetic mechanism and also have improved the concentration profiles of main products such as C3H6 and C4H6 in the shock tube pyrolysis of iso-octane. The results of this study provide insight into the pyrolysis of iso-octane and will be helpful in the future development of branched paraffin kinetic mechanisms.

Energy management systems in the practice. ISO 50001. A guideline for companies and institutions; Energiemanagementsysteme in der Praxis. ISO 50001. Leitfaden fuer Unternehmen und Organisationen

Energy Technology Data Exchange (ETDEWEB)

Kohlenborn, Walter; Kabisch, Sibylle; Klein, Johanna; Richter, Ina; Schuermann, Silas

2012-06-15

The guideline under consideration is an updated version of the guideline to the regulation EN 16001 and amended to ISO 50001. This contribution supports institutes in the implementation of an energy management system according to ISO 50001. The differences and commonalities to the European environment management system EMAS as well as to the regulation ISO 14001 are described. EMAS certified companies fulfil regularly all conditions of an energy management system. A practised energy management system is an excellent platform for the implementation of EMAS.

76 FR 4104 - Notice of Commission Staff Attendance at Midwest ISO Meetings

Science.gov (United States)

2011-01-24

... Midwest ISO Meetings January 13, 2011. The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and Commission staff may attend the following Midwest ISO-related meetings...] September 14 [cir] October 19 [cir] November 16 [cir] December 6 Midwest ISO Informational Forum (3 p.m.-5 p...

75 FR 3228 - Notice of Commission Staff Attendance at Midwest ISO Meetings

Science.gov (United States)

2010-01-20

... Midwest ISO Meetings January 12, 2010. The Federal Energy Regulatory Commission hereby gives notice that members of the Commission and Commission staff may attend the following Midwest ISO-related meetings...] November 17 [cir] December 1 Midwest ISO Informational Forum (3 p.m.-5 p.m., ET) [cir] January 19 [cir...

KSC Center Director Bridges accepts an ISO 9001 certificate from DNV

Science.gov (United States)

1998-01-01

Center Director Roy Bridges displays the ISO 9001 certificate he was awarded by Det Norske Veritas (DNV), Inc., an international ISO certification organization, at a ceremony at KSC. Dalton Lyon of DNV made the presentation, which included a 2000th ISO Certificate Plaque. ISO 9001 comprises the most detailed, comprehensive set of standard requirements for quality programs established by the International Standards Organization. The presentation followed a successful independent audit by DNV of the KSC Management System in May of this year. The third-party auditors examined about 20 elements of KSC's system, including management responsibility, design control, documentation, test and inspection, and corrective action procedures. DNV found that KSC met or exceeded the stringent quality standards in all areas. KSC will use this certification as a tool to improve an already world-class team. All NASA centers are required by NASA Administrator Daniel S. Goldin to be ISO 9001 registered by September 1999. NASA is the first federal agency to seek the quality certification.

Competence Requirements of ISO/IEC Standards for Information Security Professionals

Directory of Open Access Journals (Sweden)

Natalia G. Miloslavskaya

2017-11-01

Full Text Available The rapid progress in the filed of information security (IS puts one in a need of periodic revision of professional competencies (formulated in the federal state educational standards –FSESs and working functions (formulated in the professional standards – PSs. Under these conditions, a timely reaction to everything new that emerges or will appear in modern regulatory documents (primarily in standards is extremely important. We make a forecast for the content of the ISO/IEC 27021 and ISO/IEC 19896 standards drafted by the International Organization for Standardization (ISO, which should contain the requirements for the competencies of IS management system professionals and the competence of IS testers and evaluators. Our forecast takes into account the requirements of the ISO/IEC 27000 standard group and the recommendations of the European e-Competence Framework e-CF 3.0.

Migración de un SGSI basado en ISO/IEC 27001:2005 a la versión ISO/IEC 27001:2013

OpenAIRE

Espol; Rendón Freire, María José

2015-01-01

Este proyecto tiene como objetivo identificar los cambios en los requisitos de la norma ISO/IEC 27001:2013 respecto a la versión 2005, para lograr la actualización de un sistema de gestión de seguridad de la información basado en ISO/IEC 27001:2005 acorde a lo establecido en el nuevo estándar. Guayaquil Magíster en Seguridad Informática Aplicada

Sifting through the ISO 9000 maze

International Nuclear Information System (INIS)

Abraham, K.S.

1993-01-01

Various forces in the global upstream market are more frequently pressuring equipment and services firms to be certified according to the latest international standards in order to do business. However, understanding and completing the registration process can appear confusing and intimidating at first glance. This paper reviews the ISO's 9000 series of generic standards that provide quality assurance requirements and management guidance. It describes its applicability to the oil and gas industry which often found itself cut out of international markets because they were not recognized as registered ISO participants. It then describes the registration process, evaluation process, and time tables involved. It also describes the difference performance standards of the 9000 series

NF45/ILF2 tissue expression, promoter analysis, and interleukin-2 transactivating function

International Nuclear Information System (INIS)

Zhao Guohua; Shi Lingfang; Qiu Daoming; Hu Hong; Kao, Peter N.

2005-01-01

NF45/ILF2 associates with NF90/ILF3 in the nucleus and regulates IL-2 gene transcription at the antigen receptor response element (ARRE)/NF-AT DNA target sequence (P.N. Kao, L. Chen, G. Brock, J. Ng, A.J. Smith, B. Corthesy, J. Biol. Chem. 269 (1994) 20691-20699). NF45 is widely expressed in normal tissues, especially testis, brain, and kidney, with a predominantly nuclear distribution. NF45 mRNA expression is increased in lymphoma and leukemia cell lines. The human and murine NF45 proteins differ only by substitution of valine by isoleucine at amino acid 142. Fluorescence in situ hybridization localized the human NF45 gene to chromosome 1q21.3, and mouse NF45 gene to chromosome 3F1. Promoter analysis of 2.5 kB of the murine NF45 gene reveals that significant activation is conferred by factors, possible including NF-Y, that bind to the CCAAT-box sequence. The function of human NF45 in regulating IL-2 gene expression was characterized in Jurkat T-cells stably transfected with plasmids directing expression of NF45 cDNA in sense or antisense orientations. NF45 sense expression increased IL-2 luciferase reporter gene activity 120-fold, and IL-2 protein expression 2-fold compared to control cells. NF45 is a highly conserved, regulated transcriptional activator, and one target gene is IL-2

IMPLEMENTING AN ISO 10001-BASED PROMISE IN INPATIENTS CARE

Directory of Open Access Journals (Sweden)

Mohammad Ashiqur Rahman Khan

2013-09-01

Full Text Available This paper presents the implementation of a Customer Satisfaction Promise (CSP that requires nurses to introduce themselves and explain the care plan to the patients of a hospital unit in Canada. The CSP implementation, maintenance and improvement activities were based on ISO 10001:2007. Qualitative and quantitative performance data were collected from nurses, the unit manager and patients, and improvement suggestions were made. During the implementation, nurses introduced themselves 95% of the time and explained the care plan 86% of the time. When interviewed, some nurses stated that the CSP was a good reinforcement of a practice already expected of them, which made patients happy, satisfied and more comfortable. Data from a small sample of patients was not adequate in clearly indicating the CSP's performance or improvement, but was useful in validating the survey and the feedback form. To our knowledge, applications of ISO 10001:2007 in health care have not been studied. Furthermore, this paper may be the first example of the integrated use of ISO 10001 and ISO 10002 in health care.

Repression of MHC class I transcription by HPV16E7 through interaction with a putative RXRβ motif and NF-κB cytoplasmic sequestration

International Nuclear Information System (INIS)

Li, Hui; Zhan, TaiLan; Li, Chang; Liu, Mugen; Wang, Qing K.

2009-01-01

Down-regulation of transcription of the MHC class I genes in HPV16 tumorigenic cells is partly due to HPV16E7 associated with the MHC class I promoter and repressed chromatin activation. In this study, we further demonstrated that HPV16E7 is physically associated with a putative RXRβ binding motif (GGTCA) of the proximal promoter of the MHC class I genes by using reporter transcriptional assays and chromatin immunoprecipitation assays. Our data also provide evidence that HPV16E7 inhibits TNF-α-induced up-regulation of MHC class I transcription by impaired nuclear translocation of NF-κB. More importantly, CaSki tumor cells treated with TSA and transfected with the constitutively active mutant form of IKK-α (which can activate NF-κB directly) showed a maximal level of up-regulation of MHC-I expression. Taken together, our results suggest that HPV16E7 may employ two independent mechanisms to ensure that either the constitutive or inducible transcription of MHC class I genes is down-regulated.

Towards better GHG emissions savings with use of ISO GHG standards

International Nuclear Information System (INIS)

Chan Kook Weng

2010-01-01

The 15th Conference of Parties (COP 15) at Copenhagen, Denmark in December 2009 highlighted the need to combat climate change by facing the challenge of committing to reducing our emissions at all three levels with locally appropriate mitigation actions (LAMAs) at the local level to be linked to the nationally appropriate mitigation actions (NAMAs) and then contribute onwards to globally appropriate mitigation actions (GAMAs). The aim is to find solutions for both adaptation and mitigation by ensuring sufficient means are made available to support such efforts. This is because the world in entering a new phase that will be characterised by green growth in business. Thus be it agriculture that uses local knowledge of specific crop and livestock varieties to help in secure food supply, bio-energy, transport, industries, there must be policies to understand ecosystem-based to link people, biodiversity, energy, water and carbon so as to be more resilient and adaptable to the need for a low carbon economy in todays society.Climate change therefore affects organisations in many areas and they include legal compliance, carbon market, corporate social responsibility and sustainable development. Promoting sustainability requires making efficient use of energy, water and natural resources, decrease in waste load through recycling and streamlining the processes leading to everything that decreases their CO 2 and water footprints. Currently there are many GHG schemes and programmes and the issues centres around compatibility, costs and most importantly credibility. Achieving real GHG emissions reduction requires controlled and verified emissions reductions and quantification that are sound and verifiable. Thanks to the development of the ISO suite of standards on GHG and related matters, the use of these harmonised standards has given the assurance that a tonne of carbon is a tonne of carbon be it in Malaysia, Mali or Mongolia.The use of these standards like ISO 14064 Part 1

Evaluating Education Quality in Terms of ISO9000 Standards

Science.gov (United States)

Fengchun, Cheng; Vogel, Linda R.; Zhaoyu, Zheng

2014-01-01

While nations measure the quality of educational systems by different standards, many nations, such as China, have adopted the ISO9000 quality standards to assess the quality of schools. This article explores the various elements of the the ISO9000 standards and how each element relates to the various groups that are consumers or stakeholders in…

Homeostatic regulatory role of Pokemon in NF-κB signaling: stimulating both p65 and IκBα expression in human hepatocellular carcinoma cells.

Science.gov (United States)

Zhang, Nan-Nan; Sun, Qin-Sheng; Chen, Zhe; Liu, Feng; Jiang, Yu-Yang

2013-01-01

NF-κB consists of p50, p65 (RelA), p52, c-Rel, and RelB, and among them p65 is a representative protein to investigate the regulation and function of this signaling. NF-κB integrates inflammation and carcinogenesis and regulates the expression of a variety of genes in response to immunity, inflammation, and apoptosis. IκBα acts as an inhibitor of NF-κB through forming an inactive NF-κB/IκBα complex. Pokemon is a ubiquitous transcription factor involved in different signaling pathways, playing a pivotal role in cell proliferation, anti-apoptosis, embryonic development, and maintenance. In this study, we found that p65 and IκBα are both novel regulatory targets of Pokemon. Ectopic expression of Pokemon in immortalized liver cells HL7702 enhanced p65 and IκBα expression, whereas silencing of Pokemon in hepatocellular carcinoma cells QGY7703 reduced cellular p65 levels. ChIP assay and targeted mutagenesis revealed that Pokemon directly binds to the element of -434 to -430 bp in p65 promoter and of -453 to -448 bp in IκBα promoter and stimulates luciferase reporter gene expression. Co-transfection of Pokemon with p65 or IκBα promoter-reporter notably enhanced their promoter activity. These data suggest that Pokemon activates the expression of both p65 and IκBα by sequence-specific binding to their promoters and plays a dual role in regulating NF-κB signaling.

Establishing an ISO 10001-based promise in inpatients care.

Science.gov (United States)

Khan, Mohammad Ashiqur Rahman; Karapetrovic, Stanislav

2015-01-01

The purpose of this paper is to explore ISO 10001:2007 in planning, designing and developing a customer satisfaction promise (CSP) intended for inpatients care. Through meetings and interviews with research participants, who included a program manager, unit managers and registered nurses, information about potential promises and their implementation was obtained and analyzed. A number of promises were drafted and one was finally selected to be developed as a CSP. Applying the standard required adaptation and novel interpretation. Additionally, ISO 10002:2004 (Clause 7) was used to design the feedback handling activities. A promise initially chosen for development turned out to be difficult to implement, experience that helped in selecting and developing the final promise. Research participants found the ISO 10001-based method useful and comprehensible. This paper presents a specific health care example of how to adapt a standard's guideline in establishing customer promises. The authors show how a promise can be used in alleviating an existing issue (i.e. communication between carers and patients). The learning can be beneficial in various health care settings. To the knowledge, this paper shows the first example of applying ISO 10001:2007 in a health care case. A few activities suggested by the standard are further detailed, and a new activity is introduced. The integrated use of ISO 10001:2007 and 10002:2004 is presented and how one can be "augmented" by the other is demonstrated.

Correspondence of ISO 9001:2008 with IAEA GS-R-3

International Nuclear Information System (INIS)

Kibrit, Eduardo

2009-01-01

This article identifies, characterises and analyses International Organisation for Standardisation (ISO) and International Atomic Energy Agency (IAEA) normative requirements for the development and implementation of quality management systems in nuclear organisations. The structures of the applicable standards, ISO 9001:2008 and IAEA GS-R-3, are characterised. The differences and similarities of objective, focus, scope, level of application, structure, vocabulary, management system, management responsibility, resource management, process implementation, measurement, assessment and improvement verified in the applicable standards are deeply reviewed. A correspondence of the applicable standards' requirements is presented topic by topic. A correlation of the applicable standards' requirements is made, showing IAEA GS-R-3 topics that have no correlation with ISO 9001:2008 and ISO 9001:2008 topics that have no correlation with IAEA GS-R-3. Conclusive remarks advise the pros and cons of using one of the applicable standards or the other. (author)

The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription

International Nuclear Information System (INIS)

Simon, Priscilla S.; Sharman, Sarah K.; Lu, Chunwan; Yang, Dafeng; Paschall, Amy V.; Tulachan, Sidhartha S.; Liu, Kebin

2015-01-01

Inducible nitric oxide synthase (iNOS) metabolizes L-arginine to produce nitric oxide (NO) which was originally identified in myeloid cells as a host defense mechanism against pathogens. Recent studies, however, have revealed that iNOS is often induced in tumor cells and myeloid cells in the tumor microenvironment. Compelling experimental data have shown that iNOS promotes tumor development in certain cellular context and suppresses tumor development in other cellular conditions. The molecular mechanisms underlying these contrasting functions of iNOS is unknown. Because iNOS is often induced by inflammatory signals, it is therefore likely that these contrasting functions of iNOS could be controlled by the inflammatory signaling pathways, which remains to be determined. iNOS is expressed in colon carcinoma and myeloid cells in the tumor microenvironment. Colon carcinoma and myeloid cell lines were used to elucidate the molecular mechanisms underlying iNOS expression. Chromatin immunoprecipitation and electrophoretic mobility shift assay were used to determine the IFNγ-activated pSTAT1 and NF-κB association with the chromatin DNA of the nos2 promoter. We show here that iNOS is dramatically up-regulated in inflammed human colon tissues and in human colon carcinoma as compared to normal colon tissue. iNOS is expressed in either the colon carcinoma cells or immune cells within the tumor microenvironment. On the molecular level, the proinflammatory IFNγ and NF-κB signals induce iNOS expression in human colon cancer cells. We further demonstrate that NF-κB directly binds to the NOS2 promoter to regulate iNOS expression. Although neither the IFNγ signaling pathway nor the NF-κB signaling pathway alone is sufficient to induce iNOS expression in myeloid cells, IFNγ and NF-κB synergistically induce iNOS expression in myeloid cells. Furthermore, we determine that IFNγ up-regulates IRF8 expression to augment NF-κB induction of iNOS expression. More interestingly, we

Porcine arterivirus activates the NF-κB pathway through IκB degradation

International Nuclear Information System (INIS)

Lee, Sang-Myeong; Kleiboeker, Steven B.

2005-01-01

Nuclear factor-kappaB (NF-κB) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-κB in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-κB activation was characterized by translocation of NF-κB from the cytoplasm to the nucleus, increased DNA binding activity, and NF-κB-regulated gene expression. NF-κB activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-κB activation. Degradation of IκB protein was detected late in PRRSV infection, and overexpression of the dominant negative form of IκBα (IκBαDN) significantly suppressed NF-κB activation induced by PRRSV. However, IκBαDN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-κB DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-κB was activated by PRRSV infection. Moreover, NF-κB-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-κB activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV

Tumor necrosis factor α triggers proliferation of adult neural stem cells via IKK/NF-κB signaling

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Kaltschmidt Christian

2006-09-01

Full Text Available Abstract Background Brain inflammation has been recognized as a complex phenomenon with numerous related aspects. In addition to the very well-described neurodegenerative effect of inflammation, several studies suggest that inflammatory signals exert a potentially positive influence on neural stem cell proliferation, migration and differentiation. Tumor necrosis factor alpha (TNF-α is one of the best-characterized mediators of inflammation. To date, conclusions about the action of TNF on neural stem or progenitor cells (NSCs, NPCs have been conflicting. TNF seems to activate NSC proliferation and to inhibit their differentiation into NPCs. The purpose of the present study was to analyze the molecular signal transduction mechanisms induced by TNF and resulting in NSC proliferation. Results Here we describe for the first time the TNF-mediated signal transduction cascade in neural stem cells (NSCs that results in increased proliferation. Moreover, we demonstrate IKK-α/β-dependent proliferation and markedly up-regulated cyclin D1 expression after TNF treatment. The significant increase in proliferation in TNF-treated cells was indicated by increased neurosphere volume, increased bromodeoxyuridin (BrdU incorporation and a higher total cell number. Furthermore, TNF strongly activated nuclear factor-kappa B (NF-κB as measured by reporter gene assays and by an activity-specific antibody. Proliferation of control and TNF-treated NSCs was strongly inhibited by expression of the NF-κB super-repressor IκB-AA1. Pharmacological blockade of IκB ubiquitin ligase activity led to comparable decreases in NF-κB activity and proliferation. In addition, IKK-β gene product knock-down via siRNA led to diminished NF-κB activity, attenuated cyclin D1 expression and finally decreased proliferation. In contrast, TGFβ-activated kinase 1 (TAK-1 is partially dispensable for TNF-mediated and endogenous proliferation. Understanding stem cell proliferation is crucial

PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities.

Science.gov (United States)

Hossen, Muhammad Jahangir; Cho, Jae Youl; Kim, Daewon

2016-08-22

Xanthium strumarium L. (Asteraceae) has traditionally been used to treat bacterial infections, nasal sinusitis, urticaria, arthritis, chronic bronchitis and rhinitis, allergic rhinitis, edema, lumbago, and other ailments. However, the molecular mechanisms by which this plant exerts its anti-inflammatory effects are poorly characterized. Here we studied the immunopharmacological activities of the methanolic extract of the aerial parts of this plant (Xs-ME) and validated its pharmacological targets. To evaluate the anti-inflammatory activity of Xs-ME, we employed lipopolysaccharide (LPS)-treated macrophages and an HCl/EtOH-induced mouse model of gastritis. We also used HPLC to identify the potentially active anti-inflammatory components of this extract. The molecular mechanisms of its anti-inflammatory activity were studied by kinase assays, reporter gene assays, immunoprecipitation analysis, and overexpression of target enzymes. The production of nitric oxide (NO) and prostaglandin E2 (PGE2) were both suppressed by Xs-ME. Moreover, orally administered Xs-ME ameliorated HCl/EtOH-induced gastric lesions. Furthermore, this extract downregulated the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 and reduced the nuclear levels of NF-κB. Signaling events upstream of NF-κB translocation, such as phosphorylation of AKT and the formation of PDK1-AKT signaling complexes, were also inhibited by Xs-ME. Moreover, Xs-ME suppressed the enzymatic activity of PDK1. Additionally, PDK1-induced luciferase activity and Akt phosphorylation were both inhibited by Xs-ME. We also identified the polyphenol resveratrol as a likely active anti-inflammatory component in Xs-ME that targets PDK1. Xs-ME exerts anti-inflammatory activity in vitro and in vivo by inhibiting PDK1 kinase activity and blocking signaling to its downstream transcription factor, NF-κB. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Approval of ISO/IEC 17025 and quality control of laboratory testing].

Science.gov (United States)

Yamamoto, Shigeki; Asakura, Hiroshi; Machii, Kenji; Igimi, Shizunobu

2010-01-01

First section of Division of Biomedical Food Research, National Institute of Health Sciences (NIHS) was approved by ISO/IEC 17025 as a laboratory having an appropriate laboratory testing technique. NIHS is the first national laboratory approved by ISO/IEC 17025. NIHS has also been accepted the appropriate technique and facility for the BSL3 level pathogens by ISO/IEC 17025. NIHS is necessary to take an external audit almost every year. This approval is renewed every 4 years.

ISO 9000 IMPLEMENTATION AND PERCEIVED ORGANISATIONAL OUTCOME: THE CASE OF A SERVICE ORGANISATION

Directory of Open Access Journals (Sweden)

Jasni Abdul Latif

2003-01-01

Full Text Available The study examines the relationship between the perceptions of the employees about ISO 9000 implementation and perceived organisational outcomes. A conceptual framework linking the level of employee influence and involvement, their perception of ISO 9000 and the perceived impact on their work and the organisational outcomes is posited. Data was collected from a random sample of 64 employees of a service organisation. Contrary to expectations, the work impact of ISO 9000 was not correlated with the efficiency and market outcomes of ISO 9000 certification but the employee involvement, influence and perception of ISO 9000 were. The conceptualization of the influence path of ISO 9000 implementation on the organisational outcomes may require rethinking as perception may have a direct effect on the outcomes without the mediation of the impact on work. In short, employees may report benefits or positive outcomes even though no change is reported in their work.

Fluocinolone acetonide partially restores the mineralization of LPS-stimulated dental pulp cells through inhibition of NF-κB pathway and activation of AP-1 pathway

Science.gov (United States)

Liu, Zhongning; Jiang, Ting; Wang, Xinzhi; Wang, Yixiang

2013-01-01

BACKGROUND AND PURPOSE Fluocinolone acetonide (FA) is commonly used as a steroidal anti-inflammatory drug. We recently found that in dental pulp cells (DPCs) FA has osteo-/odonto-inductive as well as anti-inflammatory effects. However, the mechanism by which FA induces these effects in DPCs is poorly understood. EXPERIMENTAL APPROACH The effect of FA on the mineralization of DPCs during inflammatory conditions and the underlying mechanism were investigated by real-time PCR, Western blot, EMSA, histochemical staining, immunostaining and pathway blockade assays. KEY RESULTS FA significantly inhibited the inflammatory response in LPS-treated DPCs not only by down-regulating the expression of pro–inflammation-related genes, but also by up-regulating the expression of the anti-inflammatory gene PPAR-γ and mineralization-related genes. Moreover, histochemical staining and immunostaining showed that FA could partially restore the expressions of alkaline phosphatase, osteocalcin and dentin sialophosphoprotein (DSPP) and mineralization in LPS-stimulated DPCs. Real-time PCR and Western blot analysis revealed that FA up-regulated DSPP and runt-related transcription factor 2 expression by inhibiting the expression of phosphorylated-NF-κB P65 and activating activator protein-1 (AP-1) (p-c-Jun and Fra-1). These results were further confirmed through EMSA, by detection of NF-κB DNA-binding activity and pathway blockade assays using a NF-κB pathway inhibitor, AP-1 pathway inhibitor and glucocorticoid receptor antagonist. CONCLUSIONS AND IMPLICATIONS Inflammation induced by LPS suppresses the mineralization process in DPCs. FA partially restored this osteo-/odonto-genesis process in LPS-treated DPCs and had an anti-inflammatory effect through inhibition of the NF-κB pathway and activation of the AP-1 pathway. Hence, FA is a potential new treatment for inflammation-associated bone/teeth diseases. PMID:24024985

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL

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Karacay Bahri

2010-10-01

Full Text Available Abstract Background Lung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL and IKK inhibition (AdIKKβKA to overcome TRAIL resistance in lung cancer cells. Methods Fluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding. Results Neither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression. Conclusions Combination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer.

NF-κB targeting by way of IKK inhibition sensitizes lung cancer cells to adenovirus delivery of TRAIL

International Nuclear Information System (INIS)

Aydin, Cigdem; Sanlioglu, Ahter D; Bisgin, Atil; Yoldas, Burcak; Dertsiz, Levent; Karacay, Bahri; Griffith, Thomas S; Sanlioglu, Salih

2010-01-01

Lung cancer causes the highest rate of cancer-related deaths both in men and women. As many current treatment modalities are inadequate in increasing patient survival, new therapeutic strategies are required. TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells but not in normal cells, prompting its current evaluation in a number of clinical trials. The successful therapeutic employment of TRAIL is restricted by the fact that many tumor cells are resistant to TRAIL. The goal of the present study was to test a novel combinatorial gene therapy modality involving adenoviral delivery of TRAIL (Ad5hTRAIL) and IKK inhibition (AdIKKβKA) to overcome TRAIL resistance in lung cancer cells. Fluorescent microscopy and flow cytometry were used to detect optimum doses of adenovirus vectors to transduce lung cancer cells. Cell viability was assessed via a live/dead cell viability assay. Luciferase assays were employed to monitor cellular NF-κB activity. Apoptosis was confirmed using Annexin V binding. Neither Ad5hTRAIL nor AdIKKβKA infection alone induced apoptosis in A549 lung cancer cells, but the combined use of Ad5hTRAIL and AdIKKβKA significantly increased the amount of A549 apoptosis. Luciferase assays demonstrated that both endogenous and TRAIL-induced NF-κB activity was down-regulated by AdIKKβKA expression. Combination treatment with Ad5hTRAIL and AdIKKβKA induced significant apoptosis of TRAIL-resistant A549 cells, suggesting that dual gene therapy strategy involving exogenous TRAIL gene expression with concurrent IKK inhibition may be a promising novel gene therapy modality to treat lung cancer

ISO 14000 and the nuclear licensing

International Nuclear Information System (INIS)

Martins, Nadia Soido Falcao

1999-01-01

As concern grows for maintaining and improving the quality of the environment and protecting human health, all the world is turning its attention to the potential environmental in pact of their industrial activities. One of the most important contribution in that way is the International Standard ISO 14000 series. In the utilization of nuclear energy, right from the inception, the safety of personnel, environment and the population has been the basic consideration. Over the years well established licenses criteria have been proposed to limit and control the environmental impact of the plant operation and emergencies situation. In this paper are discussed some specific requirements for implementation of the environmental management system specified by ISO 14000 compared to the environmental requirements for nuclear licensing. (author)

Definition of a CDI metadata profile and its ISO 19139 based encoding

Science.gov (United States)

Boldrini, Enrico; de Korte, Arjen; Santoro, Mattia; Schaap, Dick M. A.; Nativi, Stefano; Manzella, Giuseppe

2010-05-01

The Common Data Index (CDI) is the middleware service adopted by SeaDataNet for discovery and query. The primary goal of the EU funded project SeaDataNet is to develop a system which provides transparent access to marine data sets and data products from 36 countries in and around Europe. The European context of SeaDataNet requires that the developed system complies with European Directive INSPIRE. In order to assure the required conformity a GI-cat based solution is proposed. GI-cat is a broker service able to mediate from different metadata sources and publish them through a consistent and unified interface. In this case GI-cat is used as a front end to the SeaDataNet portal publishing the original data, based on CDI v.1 XML schema, through an ISO 19139 application profile catalog interface (OGC CSW AP ISO). The choice of ISO 19139 is supported and driven by INSPIRE Implementing Rules, that have been used as a reference through the whole development process. A mapping from the CDI data model to the ISO 19139 was hence to be implemented in GI-cat and a first draft quickly developed, as both CDI v.1 and ISO 19139 happen to be XML implementations based on the same abstract data model (standard ISO 19115 - metadata about geographic information). This first draft mapping pointed out the CDI metadata model differences with respect to ISO 19115, as it was not possible to accommodate all the information contained in CDI v.1 into ISO 19139. Moreover some modifications were needed in order to reach INSPIRE compliance. The consequent work consisted in the definition of the CDI metadata model as a profile of ISO 19115. This included checking of all the metadata elements present in CDI and their cardinality. A comparison was made with respect to ISO 19115 and possible extensions were individuated. ISO 19139 was then chosen as a natural XML implementation of this new CDI metadata profile. The mapping and the profile definition processes were iteratively refined leading up to a

BiBTeX styl pro ČSN ISO 690 a ČSN ISO 690-2

OpenAIRE

Pyšný, Radek

2009-01-01

Tato práce popisuje průběh vytváření bibliografického stylu pro nástroj BibTeX, pomocí něhož lze v LaTeXu sázet bibliografické citace v souladu s normou ČSN ISO 690. V úvodu práce je proveden rozbor ČSN ISO 690. Následuje popis spolupráce mezi systémem LaTeX a nástrojem BibTeX. Podstatná část práce je věnována popisu struktury souborů, které BibTeX potřebuje pro svou funkci, tj. bibliografická databáze a bibliografický styl. Závěr této práce je věnovaný popisu vlastností vytvořeného bibliogra...

[ISO 9001-2000 certification for refractive laser treatment].

Science.gov (United States)

Lebuisson, D A; Arson, B; Abenhaïm, A; Albou-Ganem, C; Assouline, M; Chong Sit, D; Danan, A; Montefiore, G; Montin, J-F; Nguyen-Khoa, J-L; Pietrini, D; Saragoussi, J-J; Trong, Th; Amar, R

2005-05-01

To obtain ISO 9001-2000 certification for laser corneal refractive treatment, never before sought in Europe. The consulting firm Veritas led the certification process with the clinic's staff manager. This ISO norm is dedicated to the implementation of a quality management system. We assessed and optimized all necessary resources, evaluating customer satisfaction using patient and referring-physician surveys. We started quality rounds including surgeons, nurses, and technicians. Based on this preparation, we redefined and explained all processes including staff responsibilities and necessary resources in the quality manual. The procedure lasted 14 months with substantial involvement on the part of the management. Unconditional ISO 9001-2000 certification was granted by the independent audit firm, BVQI, in december 2003 for refractive laser treatment. The 2000 version of the new ISO 9001-2000 seeks to meet the demand for improving health care delivery in this field, most particularly by establishing a clear procedural orientation. Such certification enhances team work, stabilizes methodologies, and reinforces cohesion and self-audit. Patients notice that the center follows a consistent quality policy and are assured that the clinic respects rules and regulations. Certification is an advantageous alternative when accreditation cannot be considered. Our article discusses the steps taken in upper management, quality management, procedural guidance, as well as customer and staff counselling. It also discusses the project's cost/benefit ratio for the organization.

Instanton dominance over αs at low momenta from lattice QCD simulations at Nf = 0, Nf = 2 + 1 and Nf = 2 + 1 + 1

Science.gov (United States)

Athenodorou, Andreas; Boucaud, Philippe; de Soto, Feliciano; Rodríguez-Quintero, José; Zafeiropoulos, Savvas

2018-03-01

We report on an instanton-based analysis of the gluon Green functions in the Landau gauge for low momenta; in particular we use lattice results for αs in the symmetric momentum subtraction scheme (MOM) for large-volume lattice simulations. We have exploited quenched gauge field configurations, Nf = 0, with both Wilson and tree-level Symanzik improved actions, and unquenched ones with Nf = 2 + 1 and Nf = 2 + 1 + 1 dynamical flavors (domain wall and twisted-mass fermions, respectively). We show that the dominance of instanton correlations on the low-momenta gluon Green functions can be applied to the determination of phenomenological parameters of the instanton liquid and, eventually, to a determination of the lattice spacing. We furthermore apply the Gradient Flow to remove short-distance fluctuations. The Gradient Flow gets rid of the QCD scale, ΛQCD, and reveals that the instanton prediction extents to large momenta. For those gauge field configurations free of quantum fluctuations, the direct study of topological charge density shows the appearance of large-scale lumps that can be identified as instantons, giving access to a direct study of the instanton density and size distribution that is compatible with those extracted from the analysis of the Green functions.

FK506 Binding Protein Mediates Glioma Cell Growth and Sensitivity to Rapamycin Treatment by Regulating NF-κB Signaling Pathway

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Wei Jiang

2008-03-01

Full Text Available FK506 binding protein 5 (FKBP5 belongs to a family of immunophilins named for their ability to bind immunosuppressive drugs, also known as peptidyl-prolyl cis-trans isomerases, and also with chaperones to help protein folding. Using glioma cDNA microarray analysis, we found that FKBP5 was overexpressed in glioma tumors. This finding was further validated by real-time reverse transcription-polymerase chain reaction and Western blot analysis. The roles of FKBP5 in glioma cells were then examined. We found that cell growth was suppressed after FKBP5 expression was inhibited by short interfering RNA transfection and enhanced by FKBP5 overexpression. Electrophoretic mobility shift assay showed that nuclear factor-kappa B (NF-κB and DNA binding was enhanced by FKBP5 overexpression. The expression level of I-kappa B alpha and phosphorylated NF-κB was regulated by the expression of FKBP5. These data suggest that FKBP5 is involved in NF-κB pathway activation in glioma cells. In addition, FKBP5 overexpression in rapamycin-sensitive U87 cells blocked the cells' response to rapamycin treatment, whereas rapamycin-resistant glioma cells, both PTEN-positive and -negative, were synergistically sensitive to rapamycin after FKBP5 was knocked down, suggesting that the FKBP5 regulates glioma cell response to rapamycin treatment. In conclusion, our study demonstrates that FKBP5 plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-κB pathway.

Transcription Factor NF-κB: An Update on Intervention Strategies.

Science.gov (United States)

Panday, Arvind; Inda, Maria Eugenia; Bagam, Prathyusha; Sahoo, Malaya K; Osorio, Diana; Batra, Sanjay

2016-12-01

The nuclear factor (NF)-κB family of transcription factors are ubiquitous and pleiotropic molecules that regulate the expression of more than 150 genes involved in a broad range of processes including inflammation, immunity, cell proliferation, differentiation, and survival. The chronic activation or dysregulation of NF-κB signaling is the central cause of pathogenesis in many disease conditions and, therefore, NF-κB is a major focus of therapeutic intervention. Because of this, understanding the relationship between NF-κB and the induction of various downstream signaling molecules is imperative. In this review, we provide an updated synopsis of the role of NF-κB in DNA repair and in various ailments including cardiovascular diseases, HIV infection, asthma, herpes simplex virus infection, chronic obstructive pulmonary disease, and cancer. Furthermore, we also discuss the specific targets for selective inhibitors and future therapeutic strategies.

Framework for establishing records control in hospitals as an ISO 9001 requirement.

Science.gov (United States)

Al-Qatawneh, Lina

2017-02-13

Purpose The purpose of this paper is to present the process followed to control records in a Jordanian private community hospital as an ISO 9001:2008 standard requirement. Design/methodology/approach Under the hospital quality council's supervision, the quality management and development office staff were responsible for designing, planning and implementing the quality management system (QMS) using the ISO 9001:2008 standard. A policy for records control was established. An action plan for establishing the records control was developed and implemented. On completion, a coding system for records was specified to be used by hospital staff. Finally, an internal audit was performed to verify conformity to the ISO 9001:2008 standard requirements. Findings Successful certification by a neutral body ascertained that the hospital's QMS conformed to the ISO 9001:2008 requirements. A framework was developed that describes the records controlling process, which can be used by staff in any healthcare organization wanting to achieve ISO 9001:2008 accreditation. Originality/value Given the increased interest among healthcare organizations to achieve the ISO 9001 certification, the proposed framework for establishing records control is developed and is expected to be a valuable management tool to improve and sustain healthcare quality.

Human xenospecific T suppressor cells inhibit T helper cell proliferation to porcine aortic endothelial cells, and NF-kappaB activity in porcine APC.

Science.gov (United States)

Ciubotariu, R; Li, J; Colovai, A I; Platt, J L; Cortesini, R; Suciu Foca Cortesini, N

2001-05-01

Human T suppressor cells (Ts), capable of preventing autologous T helper cells (Th) from reacting against xenogeneic pig endothelial cells and pig APC can be generated in vitro. Ts derive from a population of CD3(+)CD8(+)CD28(-) T lymphocytes and specifically recognize the MHC class I antigens of the APC used for in vitro immunization. To study the mechanism that underlies suppression, we investigated whether Ts inhibit the expression of costimulatory molecules in xenogeneic professional and semiprofessional APC. We found that Ts down-regulate Th-induced expression of CD86 in pig APC, and that this effect occurs at the level of transcription, as indicated by nuclear run-on and Northern blot assays. EMSA results revealed that inhibition of CD86 expression is mediated by inactivation of transcription factor NF-kappaB. Furthermore, transfection of pig APC with a vector expressing NF-kappaB p65 partially rescued Th-induced expression of the CD86 molecule. These results strongly support the concept that xenospecific Ts inhibit the APC function of xenogeneic cells by preventing activation of NF-kappaB.

Klotho ameliorates cyclosporine A-induced nephropathy via PDLIM2/NF-kB p65 signaling pathway.

Science.gov (United States)

Jin, Meihua; Lv, Pengfei; Chen, Guanyu; Wang, Peng; Zuo, Zhongfu; Ren, Lili; Bi, Jing; Yang, Chul-Woo; Mei, Xifan; Han, Donghe

2017-04-29

Klotho, an antiaging protein, can extend the lifespan and modulate cellular responses to inflammation and oxidative stress which can ameliorate chronic kidney diseases (CKD). To investigate the molecular mechanism of Klotho on inflammation in cyclosporine A (CsA) induced nephropathy, the mice were transfected with adenovirus mediated Klotho gene and treated with cyclosporine A (CsA; 30 mg/kg/day) for 4 weeks. Also, primary human renal proximal tubule epithelial cells (RPTECs) were treated with soluble Klotho protein and LPS. The results showed that Ad-klotho significantly reduced serum creatinine (Scr) and blood urea nitrogen (BUN) caused by CsA, and significantly increased creatinine clearance. Tubule interstitial fibrosis score (TIF), renal 8-OHdG excretion, macrophage infiltration and MCP-1 were decreased after Ad-klotho gene transfer. In addition, the overexpression of Klotho led to increase in the expression of PDLIM2, decreased in the amount of NF-kB p65, and inhibited the production of inflammatory cytokines (TNFα, IL-6, IL-12) and iNOS. Accordingly, in vitro results showed, Klotho enhanced PDLIM2 expression and reduced NF-kB p65 expression, while PDLIM2 siRNA could block the inhibitory effects of Klotho on expression of NF-kB p65. Secretion of inflammatory cytokines was also inhibited by Klotho treatment, and PDLIM2 siRNA hindered regulatory effects of Klotho on the cytokines. Real-time PCR and Luciferase assay showed that Klotho markedly increased expression of PDLIM2 mRNA and PDLIM2 reporter activity in a dose-dependent manner. These findings suggest that Klotho can modulate inflammation via PDLIM2/NF-kB p65 pathway in CsA-induced nephropathy. Copyright © 2017 Elsevier Inc. All rights reserved.

Vocational High School Effectiveness Standard ISO 9001: 2008 for Achievement Content Standards, Standard Process and Competency Standards Graduates

Directory of Open Access Journals (Sweden)

Yeni Ratih Pratiwi

2014-06-01

Full Text Available Efektivitas Sekolah Menengah Kejuruan Berstandar ISO 9001:2008 terhadap Pencapaian Standar Isi, Standar Proses dan Standar Kompetensi Lulusan Abstract: The purpose of this study was to determine differences in the effectiveness of the achievement of the content standards, process standards, and competency standards in vocational already standard ISO 9001: 2008 with CMS that has not been standardized ISO 9001: 2008 both in public schools and private schools. Data collection using the questionnaire enclosed Likert scale models. Analysis of data using one-way ANOVA using SPSS. The results showed: (1 there is no difference in effectiveness between public SMK ISO standard ISO standards with private SMK (P = 0.001; (2 there are differences in the effectiveness of public SMK SMK ISO standards with ISO standards have not (P = 0.000; (3 there are differences in the effectiveness of public SMK ISO standards with private vocational yet ISO standards (P = 0.000; (4 there are differences in the effectiveness of the private vocational school with vocational standard ISO standard ISO country has not (P = 0.015; (5 there are differences in the effectiveness of the private vocational bertandar ISO with private vocational yet standardized ISO (P = 0.000; (6 there was no difference in the effectiveness of public SMK has not been standardized by the ISO standard ISO private SMK yet. Key Words: vocational high school standards ISO 9001: 2008, the standard content, process standards, competency standards Abstrak: Tujuan penelitian ini untuk mengetahui perbedaan efektivitas pencapaian standar isi, standar proses, dan standar kompetensi lulusan pada SMK yang sudah berstandar ISO 9001:2008 dengan SMK yang belum berstandar ISO 9001:2008 baik pada sekolah negeri maupun sekolah swasta. Pengumpulan data menggunakan kuisioner tertutup model skala likert. Analisis data menggunakan ANOVA one way menggunakan program SPSS. Hasil penelitian menunjukkan: (1 ada perbedaan

Analysis of JC virus DNA replication using a quantitative and high-throughput assay

Science.gov (United States)

Shin, Jong; Phelan, Paul J.; Chhum, Panharith; Bashkenova, Nazym; Yim, Sung; Parker, Robert; Gagnon, David; Gjoerup, Ole; Archambault, Jacques; Bullock, Peter A.

2015-01-01

Progressive Multifocal Leukoencephalopathy (PML) is caused by lytic replication of JC virus (JCV) in specific cells of the central nervous system. Like other polyomaviruses, JCV encodes a large T-antigen helicase needed for replication of the viral DNA. Here, we report the development of a luciferase-based, quantitative and high-throughput assay of JCV DNA replication in C33A cells, which, unlike the glial cell lines Hs 683 and U87, accumulate high levels of nuclear T-ag needed for robust replication. Using this assay, we investigated the requirement for different domains of T-ag, and for specific sequences within and flanking the viral origin, in JCV DNA replication. Beyond providing validation of the assay, these studies revealed an important stimulatory role of the transcription factor NF1 in JCV DNA replication. Finally, we show that the assay can be used for inhibitor testing, highlighting its value for the identification of antiviral drugs targeting JCV DNA replication. PMID:25155200

Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells

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Saikali Melody

2012-07-01

Full Text Available Abstract Background Sesquiterpene lactones (SL are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-β-methoxy-iso-seco-tanapartholide (β-tan isolated from Achillea falcata and salograviolide A (Sal A isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how β-tan and Sal A modulate their signaling pathways in JB6P + cells. Methods The effects of β-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. Results β-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. Conclusions These results highlight the anti-tumor promoting properties of β-tan and Sal A. These SL molecules isolated from two plant species native to

Sesquiterpene lactones isolated from indigenous Middle Eastern plants inhibit tumor promoter-induced transformation of JB6 cells.

Science.gov (United States)

Saikali, Melody; Ghantous, Akram; Halawi, Racha; Talhouk, Salma N; Saliba, Najat A; Darwiche, Nadine

2012-07-09

Sesquiterpene lactones (SL) are plant secondary metabolites that are known for their anti-fungal, anti-bacterial, anti-inflammatory, and anti-tumor properties. Considering that several SL-derived drugs are currently in cancer clinical trials, we have tested two SL molecules, 3-β-methoxy-iso-seco-tanapartholide (β-tan) isolated from Achillea falcata and salograviolide A (Sal A) isolated from Centaurea ainetensis, for their anti-tumor properties. We used the mouse epidermal JB6P + cells as a model for tumor promotion and cellular transformation. Key players that are involved in cellular transformation and tumorigenesis are the AP-1 and NF-κB transcription factors; therefore, we assessed how β-tan and Sal A modulate their signaling pathways in JB6P + cells. The effects of β-tan and Sal A on the growth of normal and neoplastic keratinocytes and on the tumor promotion-responsive JB6P + cells were determined using the MTT assay. Anchorage-independent cell growth transformation assays were used to evaluate the anti-tumor promoting properties of these SL molecules in JB6P + cells and dual luciferase reporter assays and western blot analysis were used to investigate their effects on tumor promoter-induced AP-1 and NF-κB activities and protein levels of key AP-1 and NF-кB target genes. β-tan and Sal A selectively inhibited tumor promoter-induced cell growth and transformation of JB6P + cells at concentrations that do not affect JB6P + and primary keratinocytes basal cell growth. In addition, both molecules reduced basal and tumor promoter-induced NF-κB transcriptional activities, differentially regulated basal and tumor promoter-induced AP-1 transcriptional activities, and modulated key players of the AP-1 and NF-κB signaling pathways. These results highlight the anti-tumor promoting properties of β-tan and Sal A. These SL molecules isolated from two plant species native to the Middle East may provide opportunities for complementary

Analysis of ISO 26262 Compliant Techniques for the Automotive Domain

NARCIS (Netherlands)

M. S. Kannan; Y. Dajsuren (Yanjindulam); Y. Luo; I. Barosan

2015-01-01

htmlabstractThe ISO 26262 standard denes functional safety for automotive E/E systems. Since the publication of the rst edition of this standard in 2011, many dierent safety techniques complying to the ISO 26262 have been developed. However, it is not clear which parts and (sub-) phases of the

Analysis of ISO 26262 compliant techniques for the automotive domain

NARCIS (Netherlands)

S., Manoj Kannan; Dajsuren, Y.; Luo, Y.; Barosan, I.; Antkiewicz, M.; Atlee, J.; Dingel, J.; S, R.

2015-01-01

The ISO 26262 standard defines functional safety for automotive E/E systems. Since the publication of the first edition of this standard in 2011, many different safety techniques complying to the ISO 26262 have been developed. However, it is not clear which parts and (sub-) phases of the standard

Diagnóstico da integração dos sistemas de gestão ISO 9001, ISO 14001 e OHSAS 18001

Directory of Open Access Journals (Sweden)

Samuel Vinícius Bonato

2015-09-01

Full Text Available Este artigo apresenta os resultados de uma pesquisa que teve por finalidade o diagnóstico do nível de integração de sistemas de gestão baseados nas normas ISO 9001, ISO 14001 e OHSAS 18001 em empresas do ramo metal-mecânico. Inicialmente foi descrito o método de diagnóstico e posteriormente realizada a sua aplicação em uma empresa já certificada nas três normas, mas que possui dois sistemas de gestão distintos: o Sistema de Gestão da Qualidade (SGQ baseado na norma ISO 9001 e o Sistema de Gestão de Saúde, Segurança e Meio Ambiente (SSM baseado nas normas ISO 14001 e OHSAS 18001. Entre os principais resultados, destaca-se a aceitação favorável do diagnóstico da integração na empresa estudada. Com a realização do diagnóstico, verificou-se que a organização não atende totalmente a integração de nenhum dos requisitos avaliados. Foram sugeridas oportunidades de melhoria para integração dos requisitos normativos comuns, reduzindo custos e recursos para manutenção do sistema de gestão da empresa.

Discussion on the compilation of document of iso quality management system for radiation sterilization enterprises

International Nuclear Information System (INIS)

Li Chunhong; Ha Yiming; Zhou Hongjie; Feng Zhiguo; Wang Feng

2006-01-01

According to the character of cooperation of radiation sterilization, and association with request of ISO9001, ISO13485 and ISO11137, compilation of document in quality manual, procedure document and technological document during certification of ISO quality management system of cooperation of radiation sterilization was discussed. (authors)

Motor dysfunction in NF1: Mediated by attention deficit or inherent to the disorder?

Science.gov (United States)

Haas-Lude, Karin; Heimgärtner, Magdalena; Winter, Sarah; Mautner, Victor-Felix; Krägeloh-Mann, Ingeborg; Lidzba, Karen

2018-01-01

Attention deficit and compromised motor skills are both prevalent in Neurofibromatosis type 1 (NF1), but the relationship is unclear. We investigated motor function in children with NF1 and in children with Attention Deficit/Hyperactivity Disorder (ADHD), and explored if, in patients with NF1, attention deficit influences motor performance. Motor performance was measured using the Movement Assessment Battery for Children (M-ABC) in 71 children (26 with NF1 plus ADHD, 14 with NF1 without ADHD, and 31 with ADHD without NF1) aged 6-12 years. There was a significant effect of group on motor performance. Both NF1 groups scored below children with ADHD without NF1. Attention performance mediated motor performance in children with ADHD without NF1, but not in children with NF1. Motor function is not mediated by attention performance in children with NF1. While in ADHD, attention deficit influences motor performance, motor problems in NF1 seem to be independent from attention deficit. This argues for different pathomechanisms in these two groups of developmental disorders. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Interim Report on ISO TC 163 Working Group 3. Annual progress report

Energy Technology Data Exchange (ETDEWEB)

Fairey, Philip [Florida Solar Energy Center, Cocoa, FL (United States)

2009-04-02

This reports cover the initial year efforts of the International Standards Organization (ISO) to develop international standards for rating the energy performance of buildings. The author of this report is a participant in this effort. This report summarizes the activities of the ISO Working Group charged with development of these standards and makes recommendations to the sponsors for future U.S. involvement in this ISO effort.

Progress report on the management of the NEA ISOE system

Energy Technology Data Exchange (ETDEWEB)

Lazo, E. [OECD Nuclear Energy Agency, Issy-les-Moulineaux (France)

1995-03-01

The Information System on Occupational Exposure (ISOE) was launched by the Organization for Economic Cooperation and Development (OECD), Nuclear Energy Agency (NEA) on 1 January, 1992, to facilitate the communication of dosimetric and ALARA implementation data among nuclear utilities around the world. After two years of operation the System has become a mature interactive network for transfer of data and experience. Currently, 37 utilities from 12 countries, representing 289 power plants, and 12 national regulatory authorities participate in ISOE. Agreements for cooperation also exist between the NEA and the Commission of the European Communities (CEC), and the Paris Center of the WOrld Association of Nuclear Operators (WANO-PC). In addition, the International Atomic Energy Agency (IAEA) is acting as a co-sponsor of ISOE for the participation of non-NEA member countries. Three Regional Technical Centres, Europe, Asia, and Non-NEA member countries, serve to administer the system. The ISOE Network is comprised of three data bases and a communications network at several levels. The three ISOE data bases include the following types of information: NEA1 - annual plant dosimetric information; NEA2 - plant operational characteristics for dose and dose rate reduction; and NEA3 - job specific ALARA practices and experiences. The ISOE communications network has matured greatly during 1992 and 1993. In addition to having access to the above mentioned data bases, participants may now solicit information on new subjects, through the Technical Centres, from all other participants on a real-time basis. Information Sheets on these studies are produced for distribution to all participants. In addition, Topical Reports on areas of interest are produced, and Topical Meetings are held annually.

Progress report on the management of the NEA ISOE system

International Nuclear Information System (INIS)

Lazo, E.

1995-01-01

The Information System on Occupational Exposure (ISOE) was launched by the Organization for Economic Cooperation and Development (OECD), Nuclear Energy Agency (NEA) on 1 January, 1992, to facilitate the communication of dosimetric and ALARA implementation data among nuclear utilities around the world. After two years of operation the System has become a mature interactive network for transfer of data and experience. Currently, 37 utilities from 12 countries, representing 289 power plants, and 12 national regulatory authorities participate in ISOE. Agreements for cooperation also exist between the NEA and the Commission of the European Communities (CEC), and the Paris Center of the WOrld Association of Nuclear Operators (WANO-PC). In addition, the International Atomic Energy Agency (IAEA) is acting as a co-sponsor of ISOE for the participation of non-NEA member countries. Three Regional Technical Centres, Europe, Asia, and Non-NEA member countries, serve to administer the system. The ISOE Network is comprised of three data bases and a communications network at several levels. The three ISOE data bases include the following types of information: NEA1 - annual plant dosimetric information; NEA2 - plant operational characteristics for dose and dose rate reduction; and NEA3 - job specific ALARA practices and experiences. The ISOE communications network has matured greatly during 1992 and 1993. In addition to having access to the above mentioned data bases, participants may now solicit information on new subjects, through the Technical Centres, from all other participants on a real-time basis. Information Sheets on these studies are produced for distribution to all participants. In addition, Topical Reports on areas of interest are produced, and Topical Meetings are held annually

ISO standardization in nuclear technology

Energy Technology Data Exchange (ETDEWEB)

Brabec, D. (Ustav pro Vyzkum, Vyrobu a Vyuziti Radioisotopu, Prague (Czechoslovakia)); Cermak, O. (Urad pro Normalizaci a Mereni, Prague (Czechoslovakia))

1984-10-01

The activity is described of the technical commission ISO/TC 85 which is currently divided into 4 subcommissions (SC) and 24 working groups. SC 1 ''Terminology, definitions, units, abbreviations'' has one working group. The most important document of this SC is ISO 921-1972 (Dictionary of nuclear technology). SC 2 ''Radiation protection'' has 9 working groups and has processed standards in dosimetry. SC 3 ''Technology of power reactors'' has 6 working groups and its work is related to IAEA activities within the NUSS program. SC 4 ''Technology of nuclear fuels'' has 8 working groups. SC 4 has compiled the basic standards for sealed sources and methods of testing their tightness. The results of the work of this group have been reflected into the standardization work of CMEA. A list is given of published international standards within TC 85.

IMPLEMENTASI ISO 9001: 2000 PADA PEMBELAJARAN PRODUKTIF BIDANG KEAHLIAN BANGUNAN DI SEKOLAH MENENGAH KEJURUAN

Directory of Open Access Journals (Sweden)

Riban Riban

2012-08-01

Full Text Available The implementation of ISO 9001: 2000 in productive learning of building engineering sector in vocational education. The objtective of this study was to uncover the barriers to implementation of ISO 9001:2000 in productive learning. The study was designed using multisite study design. Tecniques of collecting the data were interview, observation to partici­pants, and documentation test. The result of the study are: (1 Implementation of the ISO 9001: 2000 in productive learning of  building engineering sector relates to the implementation of the concept of P-D-C-A in the ISO quality management system; (2 the barriers in implementation of ISO 9001:2000 in pro­ductive learning include low awareness level, inconsistencies, and disobedience; and (3 efforts to overcome the barriers to implementation of ISO 9001:2000 in produc­tive learning involve building the shared commitment, socialization in order to create together awareness, supervising, and doing the preventive action. Implementasi ISO 9001: 2000 pada Pembelajaran Produktif Bidang Keahlian Bangunan di Sekolah Menengah Kejuruan. Penelitian ini bermaksud meng­ungkap lebih mendalam tentang, imple­men­­­tasi, hambatan-hambatan, dan upaya-upaya dalam mengatasi ham­batan penerap­an ISO 9001: 2000 pada pembelajaran produktif. Penelitian ini diran­cang dengan menggunakan rancangan studi multisitus. Teknik pengum­pulan data meliputi wawan­cara, observasi partisipan, dan studi dokumentasi. Temuan penelitian adalah: (1 Penerapan ISO 9001: 2000 pada pem­belajaran pro­duktif teknik bangunan mengacu pada konsep P-D-C-A ke dalam sistem manajemen mutu ISO; (2 hambatan implementasi ISO 9001: 2000 pada pem­bel­ajaran produktif meliputi tingkat kesadaran rendah, inkonsistensi, dan ketidak­taatasasan; dan (3 upaya mengatasi hambatan dalam implementasi ISO 9001: 2000 pada pembelajar­an produk­tif meliputi membangun komitmen bersama, sosialisasi dalam rangka me­num­buhkan kesadaran bersama

NF-κB suppresses HIF-1α response by competing for P300 binding

International Nuclear Information System (INIS)

Mendonca, Daniela B.S.; Mendonca, Gustavo; Aragao, Francisco J.L.; Cooper, Lyndon F.

2011-01-01

Research highlights: → p65 completely blocked HIF-1α activity at the HRE on different cell lines. → p65 caused minor changes in HIF-1α and HIF-1α target genes mRNA expression. → p65 reduced transcription of VEGF promoter. → p65 competes with HIF-1α for p300. -- Abstract: Hypoxia has emerged as a key determinant of osteogenesis. HIF-1α is the transcription factor mediating hypoxia responses that include induction of VEGF and related bone induction. Inflammatory signals antagonize bone repair via the NF-κB pathway. The present investigation explored the functional relationship of hypoxia (HIF-1α function) and inflammatory signaling (NF-κB) in stem like and osteoprogenitor cell lines. The potential interaction between HIF-1α and NF-κB signaling was explored by co-transfection studies in hFOB with p65, HIF-1α and 9x-HRE-luc or HIF-1α target genes reporter plasmids. Nuclear cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and confirmed by co-immunoprecipitation/western blotting assays. The results show that inflammatory stimulation (TNF-α treatment) causes a marked inhibition of HIF-1α function at the HRE in all cell lines studied. Also, co-transfection with p65 expression vector leads to reduced hVEGFp transcription after DFO-induced hypoxia. However, TNF-α treatment had little effect on HIF-1α mRNA levels. The functional interaction of Gal4-HIF-1α and VP16-p300 fusion proteins is effectively blocked by expression of p65 in a dose dependent manner. It was concluded that NF-κB-mediated inflammatory signaling is able to block HIF-1α transactivation at HRE-encoding genes by direct competition for p300 binding at the promoter. Inflammation may influence the stem cell niche and tissue regeneration by influencing cellular responses to hypoxia.

ISO 26000 – An Integrative Approach of Corporate Social Responsibility

Directory of Open Access Journals (Sweden)

Herciu Mihaela

2016-04-01

Full Text Available ISO 26000 represents a guidance on corporate social responsibility and it is, at the present time, one of the most important document on CSR in the world. Without being mandatory or regulated, ISO 26000 is focus on seven core subjects that have to be approached synergistic – governance, human right, labor, environment, business practices, consumer, and community – in order to achieve its goal. The present paper intends to present and analyze the seven core subjects of ISO 26000 from tow perspectives: by emphasizing the benefits of implementing the standard into the business strategy and by revealing the correlation between corporate social responsibility and sustainable development.

Age, colors and ISO standards

NARCIS (Netherlands)

Nes, van F.L.; Eschbach, R; Marcu, G.G.; Tominaga, S.; Rizzi, A.

2010-01-01

Age influences all bodily functions, also vision. Therefore, the effects of age on vision should be mirrored in ergonomic requirements laid down in display standards such as ISO 9241-300/307, 'Electronic visual display requirements'. However, this is only true to a limited extent - just as is the

ISO 14001: time for improvements?

DEFF Research Database (Denmark)

Jørgensen, Tine Herreborg

2007-01-01

The aim of this paper is to discuss a number of issues related to ISO 14001:2004, the international standard for Environmental Management Systems (EMS) with the purpose of improving the next edition in order to recognise and reflect new recognitions in approaches to pollution prevention. A case...

Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

Energy Technology Data Exchange (ETDEWEB)

Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

2014-02-28

Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

Specification of Energy Assessment Methodologies to Satisfy ISO 50001 Energy Management Standard

Science.gov (United States)

Kanneganti, Harish

Energy management has become more crucial for industrial sector as a way to lower their cost of production and in reducing their carbon footprint. Environmental regulations also force the industrial sector to increase the efficiency of their energy usage. Hence industrial sector started relying on energy management consultancies for improvements in energy efficiency. With the development of ISO 50001 standard, the entire energy management took a new dimension involving top level management and getting their commitment on energy efficiency. One of the key requirements of ISO 50001 is to demonstrate continual improvement in their (industry) energy efficiency. The major aim of this work is to develop an energy assessment methodology and reporting format to tailor the needs of ISO 50001. The developed methodology integrates the energy reduction aspect of an energy assessment with the requirements of sections 4.4.3 (Energy Review) to 4.4.6 (Objectives, Targets and Action Plans) in ISO 50001 and thus helping the facilities in easy implementation of ISO 50001.

Implementation of ISO 10110 optics drawing standards for the National Ignition Facility

International Nuclear Information System (INIS)

Aikens, D. M.; English, R. E.; Wang, D. Y.

1999-01-01

The National Ignition Facility (NIF) project elected to implement ISO 10110 standard for the specifications of NIF optics drawings in 1996. More than 7,000 NIF large optics and 20,000 NIF small optics will be manufactured based on ISO 10110 indications. ISO 10110 standard meets many of the needs of the NIF optics specifications. It allows the optical engineer to quantify and clearly communicate the desired optical specifications. While no single drawing standard specifies all the requirements of high energy laser system, a combination of ISO 10110 standard with detailed notes make it possible to apply international drawing standards to the NIF laser system. This paper will briefly describe LLNL's interpretation and implementation of the ISO 10110 drawing standard, present some examples of NIF optics drawings, and discuss pros and cons of the indications from the perspective of this application. Emphasis will be given to the surface imperfection specifications, known as 5/, for the NIF optics

Implementation of ISO 10110 optics drawing standards for the National Ignition Facility

Science.gov (United States)

Wang, David Y.; English, R. Edward, Jr.; Aikens, David M.

1999-11-01

The National Ignition Facility (NIF) project elected to implement ISO 10110 standard for the specifications of NIF optics drawings in 1996. More than 7,000 NIF large optics and 20,000 NIF small optics will be manufactured based on ISO 10110 indications. ISO 10110 standard meets many of the needs of the NIF optics specifications. It allows the optical engineer to quantify and clearly communicate the desired optical specifications. While no single drawing standard specifies all the requirements of high energy laser system, a combination of ISO 10110 standard with detailed notes make it possible to apply international drawing standards to the NIF laser system. This paper will briefly describe LLNL's interpretation and implementation of the ISO 10110 drawing standard, present some examples of NIF optics drawings, and discuss pros and cons of the indications from the perspective of this application. Emphasis will be given to the surface imperfection specifications, known as 5/, for the NIF optics.

Plasma 8-iso-Prostaglandin F2α, a possible prognostic marker in aneurysmal subarachnoid hemorrhage.

Science.gov (United States)

Pan, De-Sheng; Yan, Min; Hassan, Muhammad; Fang, Ze-Bin; Chen, Man-Tao

2017-06-01

8-iso-Prostaglandin F2α (8-iso-PGF2α) is a potential biomarker of oxidative stress. This study clarified whether plasma 8-iso-PGF2α concentrations were affected and its underlying relevance to prognosis in aneurysmal subarachnoid hemorrhage (aSAH). In this prospective, observational study, a total of 170 controls and 170 aSAH patients were enrolled. Plasma 8-iso-PGF2α concentrations were detected using an ELISA. Severity was assessed by World Federation of Neurological Surgeons (WFNS) scale and modified Fisher grading scale. Clinical outcomes included 6-month mortality and poor outcome referred to as Glasgow outcome scale score of 1-3. As compared to controls, admission plasma 8-iso-PGF2α concentrations were significantly enhanced. Increased concentrations of plasma 8-iso-PGF2α correlated with WFNS scores and modified Fisher scores. 8-iso-PGF2α in plasma was an independent predictor for clinical outcomes. Under ROC curve, the predictive values of 8-iso-PGF2α concentrations resembled those of WFNS scores and modified Fisher scores for clinical outcomes. An elevation in plasma 8-iso-PGF2α concentrations is associated with the severity and poor outcome after aSAH, substantializing 8-iso-PGF2α as a potential prognostic biomarker of aSAH. Copyright © 2017. Published by Elsevier B.V.

75 FR 5779 - Notice Providing Agenda for Technical Conference on RTO/ISO Responsiveness

Science.gov (United States)

2010-02-04

... Conference on RTO/ISO Responsiveness January 27, 2010. California Independent System Operator Docket No. ER09.... Southwest Power Pool, Inc Docket Nos. ER09-1050-000, ER09- 1192-000. ISO New England, Inc. and New England.... Agenda--Technical Conference on RTO/ISO Responsiveness February 4, 2010 12:30 Panel 1--Stakeholder...

ISO 9000 Series Certification Over Time: what have we learnt?

NARCIS (Netherlands)

A. van der Wiele (Ton); A.M. Brown (Alan)

2002-01-01

textabstractThe ISO 9000 experiences of the same sample of organisations over a five year time period is examined in this paper. The responses to a questionnaire sent out at the end of 1999 to companies which had a reasonably long term experience with the ISO 9000 series quality system are analysed.

Quality standards: Comparison between IAEA 50-C/SG-Q and ISO 9001:2000

International Nuclear Information System (INIS)

2002-01-01

The International Atomic Energy Agency (IAEA) has the statutory mandate to seek to accelerate and enlarge the contribution of atomic energy to peace, health and prosperity throughout the world. As part of the activities to achieve its objectives, the IAEA is authorized to establish standards of safety for the protection of health and the minimization of danger to life and property. The standards of safety developed by the IAEA are recommendations for use by its Member States in the framework of national regulations for the safe utilization of nuclear energy. Such standards should be considered as nuclear safety regulatory documents. The standards developed by the International Organization for Standardization (ISO) are complementary technical documents emphasizing industrial application and contractual aspects. Regarding the quality assurance topic, the IAEA developed the publication Safety Series No. 50-C/SG-Q, Quality Assurance for Safety in Nuclear Power Plants and other Nuclear Installations, which is mostly used directly or indirectly to establish the nuclear safety requirements at the nuclear utility-regulator interface. The ISO 9001:2000 standard, Quality Management Systems Requirements, is often used to define the quality management system requirements at the utility-supplier interface. The relationship between the IAEA and ISO quality standards is growing in significance owing to their increasing impact upon utilities (owners/operators of nuclear facilities) and their contractors/suppliers. The relationship between the IAEA and ISO standards is considered critical in particular with respect to contractors/suppliers with a small range of nuclear supplies. These contractors-suppliers are not always willing to prepare special quality assurance programmes based on nuclear safety standards. On the other hand, these contractors/suppliers may be qualified on the basis of the ISO quality standard. In any case, for delivering nuclear items and services the

Regulation of Neph3 gene in podocytes - key roles of transcription factors NF-kappaB and Sp1

LENUS (Irish Health Repository)

Ristola, Mervi

2009-08-24

Abstract Background Neph3 (filtrin) is expressed in the glomerular podocytes where it localizes at the specialized cell adhesion structures of the foot processes called slit diaphragms which form the outermost layer of the glomerular filtration barrier. Neph3 protein shows homology and structural similarity to Neph1, Neph2 and nephrin, which all are crucial for maintaining the normal glomerular ultrafiltration function. The exact function of Neph3 in the kidney is not known but we have previously shown that the level of Neph3 mRNA is decreased in proteinuric diseases. This suggests that Neph3 may play a role in the pathogenesis of kidney damage, and emphasizes the need to analyze the regulatory mechanisms of Neph3 gene. In this study we investigated the transcriptional regulation of Neph3 gene by identifying transcription factors that control Neph3 expression. Results We cloned and characterized approximately 5 kb fragment upstream of the Neph3 gene. Neph3 proximal promoter near the transcription start site was found to be devoid of TATA and CAAT boxes, but to contain a highly GC-rich area. Using promoter reporter gene constructs, we localized the main activating regulatory region of Neph3 gene in its proximal promoter region from -105 to -57. Within this region, putative transcription factor binding sites for NF-κB and Sp1 were found by computational analysis. Mutational screening indicated that NF-κB and Sp1 response elements are essential for the basal transcriptional activity of the Neph3 promoter. Co-transfection studies further showed that NF-κB and Sp1 regulate Neph3 promoter activity. In addition, overexpression of NF-κB increased endogenous Neph3 gene expression. Chromatin immunoprecipitation assay using cultured human podocytes demonstrated that both NF-κB and Sp1 interact with the Neph3 promoter. Conclusion Our results show that NF-κB and Sp1 are key regulators of Neph3 expression at the basal level in podocytes, therefore providing new insight

The handwriting performance of children with NF1.

Science.gov (United States)

Gilboa, Yafit; Josman, Naomi; Fattal-Valevski, Aviva; Toledano-Alhadef, Hagit; Rosenblum, Sara

2010-01-01

The objective of this study was to analyze the process and product of handwriting among children with Neurofibromatosis Type 1 (NF1) in comparison to those of Typically Developing (TD) children. Children with NF1 are at risk for some cognitive deficits, a wide range of deficits in perceptual skills and, motor and visual-motor integration skills which may interfere with handwriting competency, which is an essential ingredient for success at school. Participants were 30 NF1 children and 30 age and gender matched TD children, between the ages 8 and 16.08. The handwriting performance of children with NF1 was evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration (VMI), for copying text and free style writing tasks, using: (1) Computerized Penmanship Evaluation Tool (ComPET) to assess mechanical aspects of the writing process. (2) The Hebrew Handwriting Evaluation (HHE) to examine product legibility. (3) The Six-Trait Writing Model to judge the quality of the written product. Significant differences between the NF1 children and the control group were found in the process and product measures. Significant correlations were found between the VMI, the ComPET, the HHE and the Six-Trait Writing Model variables for both groups. We suggest a possible relationship between executive dysfunction and poor performance in handwriting.

NF1 Signal Transduction and Vascular Dysfunction

Science.gov (United States)

2015-05-01

microenvironment that promotes much of the pathology associated with the disease . Moreover we hypothesize that a mechanistic consequence of the loss...obliteration of the normal red pulp architecture. In addition, we found significant peri-aveolar and peri-vascular inflammatory infiltrates in the lung...the mouse model of NF1 disease in the endothelium we proposed and have done experiments investigating the loss of endothelial NF1 in the adult

ISO 14001: implementar ou não? Uma proposta para a tomada de decisão ISO 14001: adopt it or not? A proposal for the decision making process

Directory of Open Access Journals (Sweden)

Giuliano Nacarato Moretti

2008-12-01

Full Text Available Entre as vantagens e desvantagens oferecidas pela implementação da norma ISO 14001, o empresário, muitas vezes, não encontra subsídios suficientes para a tomada de decisão pela adoção ou não da referida norma. Este trabalho apresenta uma ferramenta de auxílio à tomada de decisão empresarial, promovendo um estudo sobre a real necessidade e viabilidade da implementação da norma ISO 14001 e a respectiva certificação. Trata-se de uma análise multicriterial, em que se verifica a compatibilidade entre o perfil organizacional e a norma ISO 14001. Busca-se facilitar a decisão das organizações em adotar ou não a ISO 14001, por meio de uma recomendação que aumente sua probabilidade de atingir os objetivos almejados. A ferramenta demonstrou sua forte aplicabilidade quando implementada em duas empresas.One of the difficulties of the decision making process, is that many entrepreneurs may find themselves incapable of finding enough subsidies for the decision of adopting or not the ISO 14001 standard. This work presents a tool that facilitates corporate decision making, providing a thorough analysis of the real necessity and feasibility of the implementation of the ISO 14001 standard and its certification. This tool consists of a multicriterial analysis, in which is possible to verify the compatibility between the organizational profile and the ISO 14001 standard. This recommendation of adopting or not the ISO 14001 standard seeks to facilitate the organization decision making; and, as a result, it also enhances the probability of the organization attaining its objectives. This tool presented a strong applicability when implemented in two companies.

PERBANDINGAN IMPLEMENTASI ISO DAN PELUNCURAN ENTERPRISE RESOURCES PLANNING TERHADAP INDEKS KINERJA KEUANGAN

Directory of Open Access Journals (Sweden)

Sautma Ronni Basana

2017-03-01

Full Text Available Recently, companies implemented projects which applied on companies’ overall system. These recent bestpractices of pursuing companies’ effectiveness and efficiency would be implementation of ISO 9000 and ERP.Previous research showed that these two projects could bring benefits for these companies which implementedit. However, it had not been compared which project would bring more benefits to these companies. Thisresearch observed 35 companies which consisted of 15 companies in food and beverages industry, 9 companiesin pharmaceutical industry, 4 companies in cigarettes industry, 4 companies in cosmetics industry, and 3companies in household appliances industry. The data were taken by observing and recording the valueswhich related to COGS (cost of goods sold, total inventory, net income, gross income, operating income, pretaxincome, cash flow operation, total liabilities, and total asset after ISO and ERP implementation. The resultsshowed that there was no significant difference of the ISO and ERP implementation on the factors of inventoryturnover, and weeks of supply. While the other factors showed significant differences between the implementationof ERP and ISO. Net profit margin, gross profit margin, and operating profit margin showed better resulton ERP launching. On the other hand, pretax margin showed better than ISO 9000 implementation. Overall,ERP implementation showed better results compared with ISO 9000.

Iso-vector form factors of the delta and nucleon in QCD sum rules

International Nuclear Information System (INIS)

Ozpineci, A.

2012-01-01

Form factors are important non-perturbative properties of hadrons. They give information about the internal structure of the hadrons. In this work, iso-vector axial-vector and iso-vector tensor form factors of the nucleon and the iso-vector axial-vector Δ→N transition form factor calculations in QCD Sum Rules are presented.

Analytical method for the identification and assay of 12 phthalates in cosmetic products: application of the ISO 12787 international standard "Cosmetics-Analytical methods-Validation criteria for analytical results using chromatographic techniques".

Science.gov (United States)

Gimeno, Pascal; Maggio, Annie-Françoise; Bousquet, Claudine; Quoirez, Audrey; Civade, Corinne; Bonnet, Pierre-Antoine

2012-08-31

Esters of phthalic acid, more commonly named phthalates, may be present in cosmetic products as ingredients or contaminants. Their presence as contaminant can be due to the manufacturing process, to raw materials used or to the migration of phthalates from packaging when plastic (polyvinyl chloride--PVC) is used. 8 phthalates (DBP, DEHP, BBP, DMEP, DnPP, DiPP, DPP, and DiBP), classified H360 or H361, are forbidden in cosmetics according to the European regulation on cosmetics 1223/2009. A GC/MS method was developed for the assay of 12 phthalates in cosmetics, including the 8 phthalates regulated. Analyses are carried out on a GC/MS system with electron impact ionization mode (EI). The separation of phthalates is obtained on a cross-linked 5%-phenyl/95%-dimethylpolysiloxane capillary column 30 m × 0.25 mm (i.d.) × 0.25 mm film thickness using a temperature gradient. Phthalate quantification is performed by external calibration using an internal standard. Validation elements obtained on standard solutions, highlight a satisfactory system conformity (resolution>1.5), a common quantification limit at 0.25 ng injected, an acceptable linearity between 0.5 μg mL⁻¹ and 5.0 μg mL⁻¹ as well as a precision and an accuracy in agreement with in-house specifications. Cosmetic samples ready for analytical injection are analyzed after a dilution in ethanol whereas more complex cosmetic matrices, like milks and creams, are assayed after a liquid/liquid extraction using ter-butyl methyl ether (TBME). Depending on the type of cosmetics analyzed, the common limits of quantification for the 12 phthalates were set at 0.5 or 2.5 μg g⁻¹. All samples were assayed using the analytical approach described in the ISO 12787 international standard "Cosmetics-Analytical methods-Validation criteria for analytical results using chromatographic techniques". This analytical protocol is particularly adapted when it is not possible to make reconstituted sample matrices. Copyright © 2012

The Fruits of Wampee Inhibit H2O2-Induced Apoptosis in PC12 Cells via the NF-κB Pathway and Regulation of Cellular Redox Status

Directory of Open Access Journals (Sweden)

Xiaobin Zeng

2014-06-01

Full Text Available Wampee (Clausena lansium fruits (CLS, whose pulp can be used to prepare fruit cups, desserts, jam, or jelly, can be eaten along with the peel. In this study, a PC12 cell model was built to observe the protective effect of CLS against H2O2-induced oxidative stress. We found that pretreatment with CLS increased cell viability and inhibited cytotoxicity, caspase-3 activity and DNA condensation. CLS also attenuated the increase in ROS production and MMP reduction. Moreover, we attempted to determine whether CLS suppressed the expression and phosphorylation of NF-κB. Western blot and immunostaining assay revealed that CLS inhibited H2O2-induced up-regulation of NF-κB p65 and pNF-κB p65. And CLS significantly suppressed the translocation of NF-κB p65 and pNF-κB p65 from cytoplasm to nuclear. Also, seven major compounds including a new flavanoid, luteolin-4'-O-β-d-gluco-pyranoside (3 and six known compounds 1,2, 4–7 were isolated and identified from CLS. Their antioxidative and H2O2-induced PC12 cell apoptosis-reversing activity were determined. These findings suggest that CLS and its major constituents (flavanoids may be potential antioxidant agents and should encourage further research into their use as a functional food for neurodegenerative diseases.

Involvement of NF-κBIZ and related cytokines in age-associated renal fibrosis.

Science.gov (United States)

Chung, Ki Wung; Jeong, Hyeong Oh; Lee, Bonggi; Park, Daeui; Kim, Dae Hyun; Choi, Yeun Ja; Lee, Eun Kyeong; Kim, Kyung Mok; Park, June Whoun; Yu, Byung Pal; Chung, Hae Young

2017-01-31

Chronic inflammation is a major contributor to age-related nephropathic changes, including renal fibrosis. In this study, various experimental paradigms were designed to delineate the role played by NF-κBIZ (also known as IκBζ) in age-associated renal fibrosis. Analyses based on RNA-sequencing findings obtained by next generation sequencing (NGS) revealed the upregulations of NF-κBIZ and of IL-6 and MCP-1 (both known to be regulated by NF-κBIZ) during aging. The up-regulation of NF-κBIZ in aged rat kidneys coincided with increased macrophage infiltration. In LPS-treated macrophages, oxidative stress was found to play a pivotal role in NF-κBIZ expression, suggesting age-related oxidative stress is associated with NF-κBIZ activation. Furthermore, these in vitro findings were confirmed in LPS-treated old rats, which showed higher levels of oxidative stress and NF-κBIZ in kidneys than LPS-treated young rats. Additional in vitro experiments using macrophages and kidney fibroblasts demonstrated NF-κBIZ and related cytokines participate in fibrosis. In particular, increased levels of NF-κBIZ-associated cytokines in macrophages significantly up-regulated TGF-β induced kidney fibroblast activation. Moreover, experiments with NF-κBIZ knocked down macrophages showed reduced TGF-β-induced kidney fibroblast activation. The findings of the present study provide evidence regarding an involvement of NF-κBIZ in age-associated progressive renal fibrosis and provides potential targets for its prevention.

A search for PAHs in the ISO spectra of comet Hale-Bopp

Science.gov (United States)

Crovisier, J.; Bockelée-Morvan, D.

2007-12-01

From a new analysis of a spectrum of comet C/1995 O1 (Hale-Bopp) obtained with the Infrared Space Observatory (ISO), Lisse et al. (2007) claimed the identification of many new dust species. Among them are PAHs, which were not found in our first analysis of the ISO spectra. We present a re-examination of the ISO observations of comet Hale-Bopp, which does not confirm the conclusion of Lisse et al.

U-value measurements on ISO round Robin window

DEFF Research Database (Denmark)

Duer, Karsten

1997-01-01

9 laboratories in 6 european and 2 north american countries have participated in a round robin U-value test of a standard facade window. The objective of the round robin test was to verify that the ISO/CEN proposals for U-value measurement standard is robust.......9 laboratories in 6 european and 2 north american countries have participated in a round robin U-value test of a standard facade window. The objective of the round robin test was to verify that the ISO/CEN proposals for U-value measurement standard is robust....

The new ISO 6579-1: A real horizontal standard for detection of Salmonella, at last!

Science.gov (United States)

Mooijman, Kirsten A

2018-05-01

Up to 2016, three international standard methods existed for the detection of Salmonella spp. in food, animal feed and samples from the primary production stage: ISO 6785:2001 for milk and milk products, ISO 6579:2002 for (other) food and animal feed and Annex D of ISO 6579:2007 for samples from the primary production stage. In 2009, an ISO/CEN working group started with the revision of ISO 6579:2002 with two main aims: combining the three aforementioned standards in one document and improving the information in ISO 6579:2002. Additionally it was decided to split ISO 6579 into three parts, where part 1 describes the detection, part 2 the enumeration by mini-MPN (published in 2012) and part 3 the serotyping of Salmonella (published in 2014). This paper describes the experiments and choices made for improving the part on detection of Salmonella (ISO 6579-1). The final voting stage on (draft) ISO 6579-1 was finished by the end of December 2016, with a positive outcome. Finally, a real horizontal standard became available for detection of Salmonella in food, animal feed, environmental samples in the area of food production and food handling and in samples from the primary production stage in 2017. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonlethal Levels of Zeaxanthin Inhibit Cell Migration, Invasion, and Secretion of MMP-2 via NF-κB Pathway in Cultured Human Uveal Melanoma Cells

Directory of Open Access Journals (Sweden)

Ming-Chao Bi

2016-01-01

Full Text Available Zeaxanthin at nonlethal dosages (3–10 μM significantly inhibited the cell migration of cultured uveal melanoma cells (C918 cell line as determined by wound healing assay and Boyden chamber assay. Matrigel invasion assay showed that cell invasion of uveal melanoma cells could be significantly inhibited by zeaxanthin. Secretion of MMP-2 by melanoma cells was significantly inhibited by zeaxanthin in a dose-dependent manner as measured by ELISA kit. Zeaxanthin also significantly inhibited the NF-κB levels in nuclear extracts of the UM cells, which is the upstream of the MMP-2 secretion. These results suggest that zeaxanthin might be a potentially therapeutic approach in the prevention of metastasis in uveal melanoma.

ISO sertifikaat aitab otsustada / Toomas Udu

Index Scriptorium Estoniae

Udu, Toomas

2005-01-01

Ilmunud ka: Delovõje Vedomosti : Transport i logistika 25. mai lk. 8. Teenuse kvaliteedi näitajad logistikafirmas ISO standardi alusel. Vt. samas: Eestis kasutatakse kolme kvaliteedistandardit; Kuidas mõjutada kvaliteeti läbi juhtimissüsteemi

Gaining competitive advantage in personal dosimetry services through ISO 9001 certification

International Nuclear Information System (INIS)

Noriah, M.A.

2005-01-01

Full text: In Malaysia, the harmonization of dose monitoring for almost 12,000 radiation workers is assigned to the Secondary Standard Dosimetry Laboratory of Malaysian Institute for Nuclear Technology Research, SSDL-MINT. Established in 1980, SSDL-MINT is responsible for improving personal and workplace safety by providing high quality personal dosimetry services. It is important to demonstrate that the performance of personal dosimetry meets recognized standards, to ensure radiation doses to individual workers are within the safe limits and to verify compliance with dose limits. Concern on the quality of personal dosimetry service began to be expressed in 2000. The concern led to the ISO certification, which brought an unprecedented effort characterized by high degree coordination, proper documentation and well trained of personal dosimetry operators. These huge efforts resulted with certification ISO 9002:1994 by the SIRIM International QAS Sdn. Bhd. in January 2002. The adoption of these requirements for the ISO 9002 standard makes routine handling of the process easier, and increases the reliability and effectiveness of the services. This helps to increase the quality and uniformity of personal dosimetry. The revision of the ISO 9002:1994 to ISO 9001:2000 necessitated SSDL-MINT revising its quality management system. The work began in middle 2002, and by May 2003, SSDL-MINT has been upgraded to ISO 9001:2000. Certification to the ISO 9001:2000 demonstrates our ability to consistency provide service that meets the requirements of the customer and the regulatory authority. These includes: improved consistency of service / product performance and therefore higher customer satisfaction levels; uniformity in work processes across organizations; simplified and more uniform structure for quality documents; improved customer perception of the organizations image, culture and performance; reduced number of product and process non-conformances; greater employee

PYME y cooperativas ante el reto de la RSE: la nueva ISO 26000 (SMEs and cooperatives confront the challenge of CSR: the new ISO 26000

Directory of Open Access Journals (Sweden)

Juan Pablo Landa

2012-05-01

Full Text Available Corporate Social Responsibility is a central issue in modern business and a main factor of companies strategies for competitiveness in a global economy . The recent approval of ISO26000 shows this general tendency to introduce social and environmental principles in global governance and organizational behaviour in all kinds of firms, organizations and multinational corporations. This paper offers a critical approach to the effects of ISO 26000 in the small and medium companies, and cooperatives, too. This norm is not focussed on the particularities of this kind of companies and shows some problems when implementing it in SME & social economy organizations. The question which comes up is if there is a necessity to adapt the implementation of ISO 26000 to these particular firms: in which cases and to what limits. La Responsabilidad Social Corporativa es una cuestión central en la economía moderna, y un factor fundamental en las estrategias competitivas de las empresas, en el marco de una economía globalizada. La reciente aprobación de la norma ISO 26000 recoge la tendencia general de introducir principios sociales y medioambientales en el gobierno global y en la organización de todo tipo de empresas, organizaciones y corporaciones multinacionales. Este artículo ofrece un acercamiento crítico a los efectos de la norma ISO 26000 en las PYMEs y cooperativas. Esta norma no contempla las particularidades de este tipo de compañías, y muestra algunos problemas al implantarlas en PYMEs y organizaciones de la economía social. Se cuestiona la necesidad de adaptar la implementación de la norma ISO 26000 a este tipo de organizaciones, en qué casos, y con qué limites.DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2049865

Rosmarinic acid inhibits inflammation and angiogenesis of hepatocellular carcinoma by suppression of NF-κB signaling in H22 tumor-bearing mice

Directory of Open Access Journals (Sweden)

Wen Cao

2016-10-01

Full Text Available The aim of this study was to explore the anti-tumor effect and therapeutic potential of rosmarinic acid (RA in the treatment of hepatocellular carcinoma (HCC. RA at 75, 150 and 300 mg/kg was given to H22 tumor-bearing mice by intragastric administration once daily for 10 consecutive days. Levels of inflammatory and angiogenic factors, including interleukin-1β (IL-1β, interleukin-6 (IL-6, tumor necrosis factor-α (TNF-α, vascular endothelial growth factor (VEGF, and transforming growth factor-β (TGF-β were measured by enzyme linked immunosorbent assays (ELISA. Protein levels of phosphorylated NF-κB p65 and p65 were detected by western blot. mRNA level of NF-κB p65 was analyzed by qRT-PCR. The results showed that RA could effectively suppress tumor growth with fewer toxic effects by regulating the secretion of cytokines associated with inflammation and angiogenesis, and suppressing the expression of NF-κB p65 in the xenograft microenvironment. Our findings unveil the possible anti-tumor mechanisms of RA and support RA as a potential drug for the treatment of HCC.

Occupational exposures at nuclear power plants. Twelfth annual report of the Isoe programme, 2002

International Nuclear Information System (INIS)

2004-01-01

The Information System on Occupational Exposure (ISOE) was created by the OECD Nuclear Energy Agency in 1992 to promote and co-ordinate international co-operative undertakings in the area of worker protection at nuclear power plants. The ISOE Programme provides experts in occupational radiation protection with a forum for communication and exchange of experience. The ISOE databases enable the analysis of occupational exposure data from the 465 commercial nuclear power plants participating in the Programme (representing some 90 per cent of the world's total operating commercial reactors). The Twelfth Annual Report of the ISOE Programme summarises achievements made during 2002 and compares annual occupational exposure data. Principal developments in ISOE participating countries are also described. (author)

TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

Energy Technology Data Exchange (ETDEWEB)

Zhang, Wanlu [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Tang, Zhuqi; Zhu, Xiaohui [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Xia, Nana; Zhao, Yun; Wang, Suxin [Department of Pathogen Biology, Medical College, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, 19 Qixiu Road, Nantong 226001, Jiangsu Province (China); Cui, Shiwei, E-mail: neifenmicui@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China); Wang, Cuifang, E-mail: binghuodinghuo@163.com [Department of Endocrinology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong 226001, Jiangsu Province (China)

2015-11-20

High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

TRAF1 knockdown alleviates palmitate-induced insulin resistance in HepG2 cells through NF-κB pathway

International Nuclear Information System (INIS)

Zhang, Wanlu; Tang, Zhuqi; Zhu, Xiaohui; Xia, Nana; Zhao, Yun; Wang, Suxin; Cui, Shiwei; Wang, Cuifang

2015-01-01

High-fat diet (HFD) and inflammation are key contributors to insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). With HFD, plasma free fatty acids (FFAs) can activate the nuclear factor-κB (NF-κB) in target tissues, then initiate negative crosstalk between FFAs and insulin signaling. However, the molecular link between IR and inflammation remains to be identified. We here reported that tumor necrosis factor receptor-associated factor 1 (TRAF1), an adapter in signal transduction, was involved in the onset of IR in hepatocytes. TRAF1 was significantly up-regulated in insulin-resistant liver tissues and palmitate (PA)-treated HepG2 cells. In addition, we showed that depletion of TRAF1 led to inhibition of the activity of NF-κB. Given the fact that the activation of NF-κB played a facilitating role in IR, the phosphorylation of Akt and GSK3β was also analyzed. We found that depletion of TRAF1 markedly reversed PA-induced attenuation of the phosphorylation of Akt and GSK3β in the cells. The accumulation of lipid droplets in hepatocyte and expression of two key gluconeogenic enzymes, PEPCK and G6Pase, were also determined and found to display a similar tendency with the phosphorylation of Akt and GSK3β. Glucose uptake assay indicated that knocking down TRAF1 blocked the effect of PA on the suppression of glucose uptake. These data implicated that TRAF1 knockdown might alleviate PA-induced IR in HepG2 cells through NF-κB pathway. - Highlights: • TRAF1 accelerated PA-induced IR in HepG2 cells mediated through NF-κB signaling. • Knockdown of TRAF1 alleviated PA-induced IR in HepG2 cells. • Knockdown of TRAF1 alleviated PA-induced lipid accumulation in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced suppression of glucose uptake in HepG2 cells. • Knockdown of TRAF1 reversed PA-induced gluconeogenesis in HepG2 cells.

Stimulation of interleukin-13 expression by human T-cell leukemia virus type 1 oncoprotein Tax via a dually active promoter element responsive to NF-kappaB and NFAT.

Science.gov (United States)

Silbermann, Katrin; Schneider, Grit; Grassmann, Ralph

2008-11-01

The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein transforms human lymphocytes and is critical for the pathogenesis of HTLV-1-induced adult T-cell leukaemia. In HTLV-transformed cells, Tax upregulates interleukin (IL)-13, a cytokine with proliferative and anti-apoptotic functions that is linked to leukaemogenesis. Tax-stimulated IL-13 is thought to result in autocrine stimulation of HTLV-infected cells and thus may be relevant to their growth. The causal transactivation of the IL-13 promoter by Tax is predominantly dependent on a nuclear factor of activated T cells (NFAT)-binding P element. Here, it was shown that the isolated IL-13 Tax-responsive element (IL13TaxRE) was sufficient to mediate IL-13 transactivation by Tax and NFAT1. However, cyclosporin A, a specific NFAT inhibitor, revealed that Tax transactivation of IL13TaxRE or wild-type IL-13 promoter was independent of NFAT and that NFAT did not contribute to IL-13 upregulation in HTLV-transformed cells. By contrast, Tax stimulation was repressible by an efficient nuclear factor (NF)-kappaB inhibitor (IkBaDN), indicating the requirement for NF-kappaB. The capacity of NF-kappaB to stimulate IL13TaxRE was demonstrated by a strong response to NF-kappaB in reporter assays and by direct binding of NF-kappaB to IL13TaxRE. Thus, IL13TaxRE in the IL-13 promoter represents a dually active promoter element responsive to NF-kappaB and NFAT. Together, these results indicate that Tax causes IL-13 upregulation in HTLV-1-infected cells via NF-kappaB.

NF-1 Dependent Gene Regulation in Drosophila Melanogaster

Science.gov (United States)

2004-04-01

standard cornmeal medium at 25oC in a humidified incubator. Flies were collected and frozen in liquid nitrogen at the same time of day to minimize...melanogaster media, strains and heat-shock conditions Flies were raised at room temperature (22–248C) on standard cornmeal medium. The Nf1 mutants Nf1P1 and

ISO 50001 for US Commercial Buildings - Current Status and Opportunities

Energy Technology Data Exchange (ETDEWEB)

Liu, Jingjing; Sheaffer, Paul

2017-12-01

''ISO 50001: 2011 Energy management systems – Requirements with guidance for use'' is a voluntary International Standard which provides organizations a proven framework to manage energy and continuously improve their energy performance. Implementing ISO 50001 in the commercial building sector has its unique opportunities and challenges in comparison with the industrial sector. The energy footprint of a portfolio of commercial buildings can be just as significant as a large industrial facility in comparison. There are many energy-saving opportunities in commercial buildings that can be addressed without capital investments, and the perceived risks for making energy improvements can be lower than in the industrial sector. In addition, the energy-consuming systems in commercial buildings are limited in types and have many similarities across buildings, which makes it much easier to standardize many ISO 50001 required processes, 5 procedures and documents to simplify implementation. There are also some sector-unique challenges, such as less familiar with ISO systems and the certification process. Another challenge arises from the complexity in some buildings’ ownership, tenancy, and O&M responsibilities. This whitepaper discusses these opportunities and issues in detail. The paper also recommends the characteristics of organizations in the commercial building sector that can benefit the most from adopting the ISO 50001 standard – namely the “suitable market”. Eight segments (education, food sales, retail, inpatient health care, hospitality, office buildings, laboratories and data centers) within the commercial building sector are highlighted.

The ISO9000 standard in electrical research

Energy Technology Data Exchange (ETDEWEB)

Rodriguez-Ortiz, G.; Davila-Nunez, G.; Gonzalez-Sustaeta, J. [Inst. de Investigaciones Electricas, Cuernavaca (Mexico). Unidad de Sistemas Informaticos

1999-11-01

In this article, the main aspects that are considered important upon applying the ISO9000 standard [ISO 94] in a research institution, company, or group, are described. The 20 sections of the standard are discussed emphasizing the concepts and definitions that can be differently interpreted in the process of elaboration of a quality manual for a group devoted to research, than when they are applied in the elaboration of a manual for a factory that produces material goods. The exposed reasoning was used in the elaboration of the quality manual in the Information Systems Unit of the Electrical Research Institute in Mexico, and it is being used in the installation and operation of the quality system.

How the projection domains of NF-L and alpha-internexin determine the conformations of NF-M and NF-H in neurofilaments

NARCIS (Netherlands)

Leermakers, F.A.M.; Zhulina, E.B.

2010-01-01

Making use of a numerical self-consistent field method and polymer brush concepts, we model the solvated corona of neurofilaments (NF) composed of projection domains (unstructured tails) of constituent proteins. Projections are modeled with amino acid resolution. We focus on the importance of the

Sustainable development induction in organizations: a convergence analysis of ISO standards management tools' parameters.

Science.gov (United States)

Merlin, Fabrício Kurman; Pereira, Vera Lúciaduarte do Valle; Pacheco, Waldemar

2012-01-01

Organizations are part of an environment in which they are pressured to meet society's demands and acting in a sustainable way. In an attempt to meet such demands, organizations make use of various management tools, among which, ISO standards are used. Although there are evidences of contributions provided by these standards, it is questionable whether its parameters converge for a possible induction for sustainable development in organizations. This work presents a theoretical study, designed on structuralism world view, descriptive and deductive method, which aims to analyze the convergence of management tools' parameters in ISO standards. In order to support the analysis, a generic framework for possible convergence was developed, based on systems approach, linking five ISO standards (ISO 9001, ISO 14001, OHSAS 18001, ISO 31000 and ISO 26000) with sustainable development and positioning them according to organization levels (strategic, tactical and operational). The structure was designed based on Brundtland report concept. The analysis was performed exploring the generic framework for possible convergence based on Nadler and Tushman model. The results found the standards can contribute to a possible sustainable development induction in organizations, as long as they meet certain minimum conditions related to its strategic alignment.

Down-regulation of NF-κB DNA binding activity by Angelica Sinensis to ameliorate radiation-induced pulmonary injury in mouse model

International Nuclear Information System (INIS)

Cao Zhen; Xie Conghua; Zhou Fuxiang; Luo Zhiguo; Zhou Yunfeng; Hang Guang

2008-01-01

Objective: To study the trend of NF-kB binding activity during the course of radiation-induced pulmonary injury (RPI), and to evaluate the intervention effect of Angelica Sinensis on it. Methods: Adult female C57BL/6J mice were randomly divided into 4 groups: blank control group (N group), Angelica Sinensis control group (A group), irradiation group (NX group) and irradiation group with Angelica Sinensis intervention (AX group). All mice from the NX and AX groups underwent single fraction of 12 Gy γ-ray delivered to the whole thorax. All mice were intraperitoneally injected 25% Angelica Sinensis injection (20 ml/kg) or identical volume Normal Sodiumdaily injection initiated 1 week before irradiation, lasted till 2 weeks after irradiation. Mice were sacrificed at designated time points (1, 24, 72 h, 1, 2, 4, 8, 16 and 24 weeks), and the whole lungs were removed freshly. HE and Masson staining were performed to provide histopathologic evidence and to evaluate the collagen deposit situation respectively. The immunohistochemical staining of NF-κB P65 protein was performed to identify the location as well as the relative content of P65 protein. The DNA binding activity of NF-κB was detected by TransAM TM ELISA assay. Results: HE and Masson staining manifested that visible pathological alterations began at 2 weeks, typical interstitial pneumonitis were showed at 4 and 8 weeks, collagen deposition was visible from 16 weeks. The NF-κB binding activity detection and the immunohistochemical half-quantity analysis showed two-phase elevation, at 24 h and 8 weeks. Preventive application of Angelica Sinensis revealed prominently ameliorative effect for RPI, with pathological improvement, decreased immunohistochemical staining and lower NF-κB binding activity in both peaks. Conclusions: During the development process of RPI, NF-κB binding activity shows two-phase elevation. Chinese medicine Angelica Sinensis can down-regulate the elevation, showing noted ameliorative effect

KSC Center Director Bridges accepts an ISO 9001 certification plaque from DNV

Science.gov (United States)

1998-01-01

Center Director Roy Bridges (right) displays the 2000th ISO Certificate Plaque he was given by Dalton Lyon (left) of Det Norske Veritas (DNV), Inc., an international ISO certification organization, at a ceremony at KSC. The plaque is a representation of the ISO 9001 certification awarded to KSC by DNV. ISO 9001 comprises the most detailed, comprehensive set of standard requirements for quality programs established by the International Standards Organization. The presentation followed a successful independent audit by DNV of the KSC Management System in May of this year. The third-party auditors examined about 20 elements of KSC's system, including management responsibility, design control, documentation, test and inspection, and corrective action procedures. DNV found that KSC met or exceeded the stringent quality standards in all areas. KSC will use this certification as a tool to improve an already world- class team. All NASA centers are required by NASA Administrator Daniel S. Goldin to be ISO 9001 registered by September 1999. NASA is the first federal agency to seek the quality certification.

Step of quality assurance preparation on ISO 9001:2000 toward certification

International Nuclear Information System (INIS)

Agustiar

2007-01-01

ISO 9001:2000 is the International Standard for the quality management system that stipulate requirement and recommendation provided for design until product. The standard is also regulated the implementation and evaluation from management system point of view the objective to assure organization will meet specified requirement product. To propose ISO 9001:2000 certification, many steps of action should be carried out. There are 5 primary sections of the quality management system requirements of ISO 9001:2000. Quality Management system, Management responsibility, Resource management, Product realization and Measurement, Analysis and improvement, in which all will be begun with training until evaluation (author)

Predicting the quantifiable impacts of ISO 50001 on climate change mitigation

Energy Technology Data Exchange (ETDEWEB)

McKane, Aimee; Therkelsen, Peter; Scodel, Anna; Rao, Prakash; Aghajanzadeh, Arian; Hirzel, Simon; Zhang, Ruiqin; Prem, Richard; Fossa, Alberto; Lazarevska, Ana M.; Matteini, Marco; Schreck, Bettina; Allard, Fabian; Villegal Alcántar, Noé; Steyn, Karel; Hürdoğan, Ertaç; Björkman, Thomas; O' Sullivan, John

2017-08-01

The ISO 50001-Energy management standard provides a continual improvement framework for organizations to reduce their energy consumption, which in the industrial and commercial (service) sectors, accounts for nearly 40% of global greenhouse gas emissions. Reducing this energy consumption will be critical for countries to achieve their national greenhouse gas reduction commitments. Several national policies already support ISO 50001; however, there is no transparent, consistent process to estimate the potential impacts of its implementation. This paper presents the ISO 50001 Impacts Methodology, an internationally-developed methodology to calculate these impacts at a national, regional, or global scale suitable for use by policymakers. The recently-formed ISO 50001 Global Impacts Research Network provides a forum for policymakers to refine and encourage use of the methodology. Using this methodology, a scenario with 50% of projected global industrial and service sector energy consumption under ISO 50001 management by 2030 would generate cumulative primary energy savings of approximately 105 EJ, cost savings of nearly US $700 billion (discounted to 2016 net present value), and 6500 million metric tons (Mt) of avoided CO₂ emissions. The avoided annual CO₂ emissions in 2030 alone are equivalent to removing 210 million passenger vehicles from the road.

Towards continuous global measurements and optimal emission estimates of NF3

Science.gov (United States)

Arnold, T.; Muhle, J.; Salameh, P.; Harth, C.; Ivy, D. J.; Weiss, R. F.

2011-12-01

We present an analytical method for the continuous in situ measurement of nitrogen trifluoride (NF3) - an anthropogenic gas with a global warming potential of ~16800 over a 100 year time horizon. NF3 is not included in national reporting emissions inventories under the United Nations Framework Convention on Climate Change (UNFCCC). However, it is a rapidly emerging greenhouse gas due to emission from a growing number of manufacturing facilities with increasing output and modern end-use applications, namely in microcircuit etching, and in production of flat panel displays and thin-film photovoltaic cells. Despite success in measuring the most volatile long lived halogenated species such as CF4, the Medusa preconcentration GC/MS system of Miller et al. (2008) is unable to detect NF3 under remote operation. Using altered techniques of gas separation and chromatography after initial preconcentration, we are now able to make continuous atmospheric measurements of NF3 with average precisions NF3 produced. Emission factors are shown to have reduced over the last decade; however, rising production and end-use have caused the average global atmospheric concentration to double between 2005 and 2011 i.e. half the atmospheric NF3 present today originates from emissions after 2005. Finally we show the first continuous in situ measurements from La Jolla, California, illustrating how global deployment of our technique could improve the temporal and spatial scale of NF3 'top-down' emission estimates over the coming years. These measurements will be important for independent verification of emissions should NF3 be regulated under a new climate treaty.

Human Papillomavirus type 16 E6 and E 7 proteins alter NF-kB in cultured cervical epithelial cells and inhibition of NF-kB promotes cell growth and immortalization

Science.gov (United States)

Vandermark, Erik R.; Deluca, Krysta A.; Gardner, Courtney R.; Marker, Daniel F.; Schreiner, Cynthia N.; Strickland, David A.; Wilton, Katelynn M.; Mondal, Sumona; Woodworth, Craig D.

2012-01-01

The NF-kB family of transcription factors regulates important biological functions including cell growth, survival and the immune response. We found that Human Papillomavirus type 16 (HPV-16) E7 and E6/E7 proteins inhibited basal and TNF-alpha-inducible NF-kB activity in human epithelial cells cultured from the cervical transformation zone, the anatomic region where most cervical cancers develop. In contrast, HPV-16 E6 regulated NF-kB in a cell type- and cell growth-dependent manner. NF-kB influenced immortalization of cervical cells by HPV16. Inhibition of NF-kB by an IkB alpha repressor mutant increased colony formation and immortalization by HPV-16. In contrast, activation of NF-kB by constitutive expression of p65 inhibited proliferation and immortalization. Our results suggest that inhibition of NF-kB by HPV-16 E6/E7 contributes to immortalization of cells from the cervical transformation zone. PMID:22284893

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

Science.gov (United States)

Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

2015-12-01

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

The Role of ISO 9000 Certification on Waste Management of Leather Industry

International Nuclear Information System (INIS)

Susetyo Hario Putero; Dhani Astuti

2008-01-01

State of industry in an area could increase economy of this area. On the other hand, industry may be produce the waste. There are many factor influencing the success of industrial waste management. At present, ISO 14000 is known as an international environmental management standard. Practically, several matter required for ISO 14000 are similar with ISO 9000. So, the role of ISO 9000 certification on supporting waste management program of leather industry has been studied. Study has been pursued by comparing the environmental management systems of 2 leather industries in Sitimulyo, Piyungan, Bantul. Staff working way has been observed to know the suitability with working procedures and implementation of safety aspect on daily working. Observation of waste treatment facility and measurement of Chrome concentration also has been done. Samples were analysed using AAS method in Department of Chemistry, Faculty of Mathematics and Natural Science, Gadjah Mada University. Decontamination Factor (DF) was calculated by comparing the Chrome concentrations on outside plant and in waste treatment facility. Commitment of management and orderliness of system as required on ISO 9000 certification could push the industry to well execute waste management program as a part of environmental management system. ISO 9000 certification is convinced to make awareness of industry grow for continually improving their capability, including their capacity of waste treatment facility. (author)

Nanotechnology Standardization Activities – Support of U.S. Representation on ISO/TC 229 Nanotechnologies

Energy Technology Data Exchange (ETDEWEB)

Benko, Heather [American National Standards Inst. (ANSI), Washington, DC (United States)

2017-03-14

In carrying out its responsibilities on behalf of the United States, ANSI provides comprehensive, administrative support and expertise on international protocols and procedures to: (1) the U.S. Technical Advisory Group (TAG) to the International Organization for Standardization’s (ISO) Technical Committee (TC) 229 Nanotechnologies, and (2) the corresponding U.S. TAG Working Groups tasked with formulating U.S. positions on topics relevant to nanotechnology standardization. Additionally, secretariat and procedural support is provided for the ISO/TC 229 WG 3 on health, safety and environment, for which the United States was assigned leadership by the participating national body members of ISO/TC 229. As the official entity that serves as the U.S. representative to ISO, ANSI provides not only expert coordination of U.S. positions and representation at ISO but also strategic direction, advice and procedural expertise to facilitate navigation of international issues to promote U.S. positions for incorporation into the ISO/TC 229 program of work necessary to support U.S. objectives.

Blood and urine 8-iso-PGF2α levels in babies of different gestational ages.

Science.gov (United States)

Li, Sitao; Hao, Hu; Zhou, Ping; Gao, Ping Ming; Xiao, Xin

2014-01-01

We measured cord blood and urine 8-iso-prostaglandin F2α (8-iso-PGF2α) levels in babies of different gestational ages to determine lipid peroxidation status. Babies at gestational ages of 28-43 weeks were divided into group A (28-32 weeks), group B (33-36 weeks), group C (37-41 weeks), and group D (42-43 weeks). 8-iso-PGF2α in umbilical cord blood (UCB) at birth and urine at 6 hours after birth was and tested by ELISA. UCB and urine 8-iso-PGF2α levels in group C were 130.09 ± 31.73 pg/ml and 27.14 ± 6.73 pg/ml, respectively. UCB 8-iso-PGF2α levels in group A and B were 188.42 ± 59.34 pg/ml and 189.37 ± 68.46 pg/ml, and urine 8-iso-PGF2α were 32.14 ± 7.32 pg/ml and 30.46 ± 8.83 pg/ml, respectively. Blood and urine 8-iso-PGF2α levels in group D (post-term) were 252.01 ± 46.42 pg/ml and 44.00 ± 8.50 pg/ml. For all babies, UCB and urine iso-PGF2α levels were significantly correlated (r = 0.65, P iso-PGF2α levels in normal full-term babies. Urine 8-iso-PGF2α levels may reflect the extent of lipid peroxidation in babies. In pre-term and post-term babies, there was evidence for increased lipid peroxidation.

Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows.

Science.gov (United States)

Schwartz-Zimmermann, Heidi E; Hametner, Christian; Nagl, Veronika; Fiby, Iris; Macheiner, Lukas; Winkler, Janine; Dänicke, Sven; Clark, Erica; Pestka, James J; Berthiller, Franz

2017-12-01

The Fusarium mycotoxin deoxynivalenol (DON) is a frequent contaminant of cereal-based food and feed. Mammals metabolize DON by conjugation to glucuronic acid (GlcAc), the extent and regioselectivity of which is species-dependent. So far, only DON-3-glucuronide (DON-3-GlcAc) and DON-15-GlcAc have been unequivocally identified as mammalian DON glucuronides, and DON-7-GlcAc has been proposed as further DON metabolite. In the present work, qualitative HPLC-MS/MS analysis of urine samples of animals treated with DON (rats: 2 mg/kg bw, single bolus, gavage; mice: 1 mg/kg bw, single i.p. injection; pigs: 74 µg/kg bw, single bolus, gavage; cows: 5.2 mg DON/kg dry mass, oral for 13 weeks) revealed additional DON and deepoxy-DON (DOM) glucuronides. To elucidate their structures, DON and DOM were incubated with human (HLM) and rat liver microsomes (RLM). Besides the expected DON/DOM-3- and 15-GlcAc, minor amounts of four DON- and four DOM glucuronides were formed. Isolation and enzymatic hydrolysis of four of these compounds yielded iso-DON and iso-DOM, the identities of which were eventually confirmed by NMR. Incubation of iso-DON and iso-DOM with RLM and HLM yielded two main glucuronides for each parent compound, which were isolated and identified as iso-DON/DOM-3-GlcAc and iso-DON/DOM-8-GlcAc by NMR. Iso-DON-3-GlcAc, most likely misidentified as DON-7-GlcAc in the literature, proved to be a major DON metabolite in rats and a minor metabolite in pigs. In addition, iso-DON-8-GlcAc turned out to be one of the major DON metabolites in mice. DOM-3-GlcAc was the dominant DON metabolite in urine of cows and an important DON metabolite in rat urine. Iso-DOM-3-GlcAc was detected in urine of DON-treated rats and cows. Finally, DON-8,15-hemiketal-8-glucuronide, a previously described by-product of DON-3-GlcAc production by RLM, was identified in urine of DON-exposed mice and rats. The discovery of several novel DON-derived glucuronides in animal urine requires adaptation of

MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway.

Science.gov (United States)

Liu, Ai-Hua; Wu, Ya-Ting; Wang, Yu-Ping

2017-06-01

The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE-related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics+HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded. Neuronal injuries in the hippocampus regions were detected using HE, Nissl and FJB staining methods 24h following model establishment. Microglial cells were detected by OX-42 immunohistochemistry. Expressions of miR-129-5p, HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by qRT-PCR. Protein expressions of HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by Western blotting. Dual luciferase reporter gene assay showed that miR-129-5p was negatively targeting HMGB1. Neurons of hippocampal tissues in rats were heavily injured by an injection of lithium chloride. Compared with the model and control groups, neuronal injury of the hippocampus and AE-related epilepsy decreased and microglial cells increased in the miR-129-5p mimics, HMGB1 shRNA and TLR4/NF-kB groups; however, in the miR-129-5p inhibitor group, miR-129-5p expression decreased, HMGB1 expression increased, TLR4/NF-kB signaling pathway was activated, latency to a first epilepsy seizure attack was shortened, and neuronal injury increased. This study provides evidence that miR-129-5p inhibits the development of AE-related epilepsy by suppressing HMGB1 expression and inhibiting TLR4/NF-kB signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

Beneficios de la aplicación de normas internacionales ISO en procesos electorales

Directory of Open Access Journals (Sweden)

Jeffrey Badí Quinteros Basantes

2017-01-01

Full Text Available En este artículo se presentarán los beneficios de la aplicabilidad de las normas internacionales ISO en los procesos electorales, con el fin de poder elevar los niveles de percepción positiva de los ciudadanos. Se verificará la aplicación de normas ISO/TS 17582:2014, Sistemas de Gestión de la Calidad y la norma ISO/IEC 27001:2013, para todas las fases de un proceso electoral. Se expondrán los dominios que forman parte de la norma ISO/TS 17582:2014 , los cuales permiten un proceso de mejoramiento continuo a fin de garantizar la calidad de las metodologías que soportan la organización, administración, gestión, seguimiento y auditorías de un proceso electoral. La norma ISO/IEC 27001:2013 se alinea con la norma ISO9001:2008 para la gestión de seguridad de la información. La aplicación de esta normativa permitirá asegurar la integridad, confidencialidad y disponibilidad de la información durante los procesos electorales.

TEffect of nf-kappa B on diabetic retinopathy%NF-κB对糖尿病视网膜病变的影响

Institute of Scientific and Technical Information of China (English)

王爽; 宋子宣

2015-01-01

目的 研究和探讨核因子κB (NF-κ B)在糖尿病视网膜病变中的作用.方法 首先建立糖尿病视网膜病变(DR,diabetic retinopathy)动物模型,雄性SD大鼠,链脲佐菌素(streptozotocin,STZ) 60 mg/kg腹腔注射形成糖尿病模型,1.5个月后SD大鼠玻璃体内行血管内皮生长因子(VEGF)注射造成增殖型的糖尿病视网膜病变模型.视网膜铺片使用ADP酶染色视网膜血管,实时定量PCR检测NF-κ B表达量的变化,以及凋亡信号的检测.结果 视网膜血管染色的增殖面积造模给水组为(12.0±4.1)％,而视网膜血管染色的无灌注区面积造模给NF-κ B拮抗剂组为(37.9±3.9)％.正常组大鼠的NF-κ B蛋白的灰度值为(194.2890±3.8900),而造模给水组的NF-κB蛋白的灰度值为(74.4300±4.4900),凋亡实验结果显示正常组大鼠的凋亡信号个数平均为(32.2±3.1),而造模给水组的凋亡信号个数平均为(7.4±4.2).结论 NF-κB主要是通过引起细胞凋亡而减少糖尿病视网膜病变患者视网膜血管的增殖.%Objective To study the effect of nuclear factor kappa B (nf-kappa B) on diabetic retinopathy.Methods Diabetic retinopathy (DR,diabetic retinopathy) animal models were established.The SD rats intraperitoneal injected 60 cephalosporins (STZ streptozotocin) mg/kg to form diabetes models; 1.5 months from then,the SD rats were vitreously injected vascular endothelial growth factor (VEGF) to build models of proliferative diabetic retinopathy[l].Retinal blood vessels stained by ADP enzyme were used as retinal pave pieces.Real-time quantitative PCR was used to detect the e change of nf-kappa B expression quantity and apoptosis signal.Results The proliferation area of dyed retinal vessels of the model-buildingwith-water group was (12.0±4.1)％.The area without perfusion of dyed retinal blood vessels of the modelbuilding-with-nf-kappa-B-antagonist group was (37.9 ± 3.9)％.The gray value of nf-kappa B protein was (194.2890 ± 3.8900) in the

An iso-erodent map Imo state of Nigeria | Madubuike | International ...

African Journals Online (AJOL)

Among inputs/resources often needed for erosion risk assessment of a region is the iso-erodent map of the region. This is a map showing areas of equal erosion potentials in the region. As Imo and Abia states of Nigeria lie in a high erosion region of the country, it was decided in this work to produce an iso-erodent map of ...

Programación de las normas ISO 12217-1 (2011) e ISO 12217-3 (2011) para el estudio de la estabilidad y flotabilidad de embarcaciones de recreo

OpenAIRE

Gallardo Martínez, Antonio

2013-01-01

Las embarcaciones de recreo para operar dentro de la Comunidad Europea deben de obtener el marcado CE. Para ello se evalúa y clasifica su estabilidad y flotabilidad según la normativa ISO 12217 y se asigna una categoría de diseño (A, B, C o D) adecuada a su diseño y a su carga total máxima. El presente proyecto tiene como objetivo la programación de las normas ISO 12217-1 referente a embarcaciones no propulsadas a vela de eslora igual o superior a 6 m y la norma ISO 12217-3 ...

EPA STANDARDS NETWORK FACT SHEET: ISO 14000: INTERNATIONAL ENVIRONMENTAL MANAGEMENT STANDARDS

Science.gov (United States)

This flyer provides an overview of the ISO 14000 series of International standards, supplying a brief history, structure of the Technical Committee (TC) 207, structure of the U.S. Technical Advisory Group (TAG) to ISO TC-207, status of the Standards development as of June 1997, w...

Biochanin A induces anticancer effects in SK-Mel-28 human malignant melanoma cells via induction of apoptosis, inhibition of cell invasion and modulation of NF-κB and MAPK signaling pathways.

Science.gov (United States)

Xiao, Peng; Zheng, Bowen; Sun, Jiaming; Yang, Jia

2017-11-01

The present study aimed to investigate the antitumor activity of Biochanin A in SK-Mel-28 human malignant melanoma cells. An MTT assay was used to study the cytotoxic effects of Biochanin A. In vitro wound healing and invasion assays were used to investigate the effects on cell migration and invasion. Fluorescence microscopy using acridine orange/propidium iodide was used to study effects on cell morphology and apoptosis. Nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) protein expression levels were determined by western blot analysis. The results indicated that Biochanin A significantly inhibited the growth of SK-Mel-28 cells in a dose and time dependent manner. Treatment of the cells with Biochanin A induced apoptosis in a dose dependent manner. Additionally, Biochanin A led to inhibition of cell migration and invasion in a dose-dependent manner and upregulated the expression of key proteins in the NF-κB and MAPK signaling pathways.

Cellular Hsp27 interacts with classical swine fever virus NS5A protein and negatively regulates viral replication by the NF-κB signaling pathway.

Science.gov (United States)

Ling, Shifeng; Luo, Mingyang; Jiang, Shengnan; Liu, Jiayu; Ding, Chunying; Zhang, Qinghuan; Guo, Huancheng; Gong, Wenjie; Tu, Changchun; Sun, Jinfu

2018-05-01

Classical swine fever virus (CSFV) nonstructural protein NS5A is a multifunctional protein functioning in regulation of viral genome replication, protein translation and assembly by interaction with viral or host proteins. Here, heat shock protein 27 (Hsp27) has been identified as a novel binding partner of NS5A by using His tag "pull down" coupled with shotgun LC-MS/MS, with interaction of both proteins further confirmed by co-immunoprecipitation and laser confocal assays. In PK-15 cells, silencing of Hsp27 expression by siRNA enhanced CSFV replication, and upregulation of Hsp27 inhibited viral proliferation. Additionally, we have shown that overexpression of Hsp27 increased NF-κB signaling induced by TNFα. Blocking NF-κB signaling in PK-15 cells overexpressing Hsp27 by ammonium pyrrolidinedithiocarbamate (PDTC) eliminated the inhibition of CSFV replication by Hsp27. These findings clearly demonstrate that the inhibition of CSFV replication by Hsp27 is mediated via the NF-κB signaling pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

A requirement for NF-κB in developmental and plasticity-associated synaptogenesis

Science.gov (United States)

Boersma, Matthew C. H.; Dresselhaus, Erica C.; De Biase, Lindsay M.; Mihalas, Anca B.; Bergles, Dwight E.

2011-01-01

Structural plasticity of dendritic spines and synapses is a fundamental mechanism governing neuronal circuits and may form an enduring basis for information storage in the brain. We find that the p65 subunit of the NF-κB transcription factor, which is required for learning and memory, controls excitatory synapse and dendritic spine formation and morphology in murine hippocampal neurons. Endogenous NF-κB activity is elevated by excitatory transmission during periods of rapid spine and synapse development. During in-vitro synaptogenesis, NF-κB enhances dendritic spine and excitatory synapse density and loss of endogenous p65 decreases spine density and spine head volume. Cell-autonomous function of NF-κB within the postsynaptic neuron is sufficient to regulate the formation of both pre- and post-synaptic elements. During synapse development in-vivo, loss of NF-κB similarly reduces spine density and also diminishes the amplitude of synaptic responses. In contrast, after developmental synaptogenesis has plateaued, endogenous NF-κB activity is low and p65-deficiency no longer attenuates basal spine density. Instead, NF-κB in mature neurons is activated by stimuli that induce demand for new synapses, including estrogen and short-term bicuculline, and is essential for upregulating spine density in response to these stimuli. p65 is enriched in dendritic spines making local protein-protein interactions possible; however, the effects of NF-κB on spine density require transcription and the NF-κB-dependent regulation of PSD-95, a critical postsynaptic component. Collectively, our data define a distinct role for NF-κB in imparting transcriptional regulation required for the induction of changes to, but not maintenance of, excitatory synapse and spine density. PMID:21471377

[6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

Directory of Open Access Journals (Sweden)

Sung Ok Kim

2013-01-01

Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

PENGARUH CSR BERDASAR ISO 26000 TERHADAP NILAI PERUSAHAAN DENGAN KARAKTERSITIK PERUSAHAAN SEBAGAI VARIABEL MODERATING

Directory of Open Access Journals (Sweden)

Sri Wahjuni Latifah

2015-01-01

Full Text Available Research of the influence of ISO 26000 CSR toward the company’s value as a moderating variable which is done on companies listed in Indonesia Stock Exchange. The Company’s characteristics are measured by firm age, size, leverage and profitability. The data analysis was done by using double linear regression models, the first is to see the effect based on the ISO 26000 CSR and firm characteristics on value, and the second is to see the effect of interaction with the ISO 26000 corporate characteristics. The results of the study showed that there was no influence of ISO 26000, the characteristics of the company toward the value of the company. However, moderated ISO 26000 by firm characteristics affect the value of the company.

NF EN ISO 11137-1, July 2006. Sterilization of health care products - Irradiation - Part 1: Requirements for development, validation and routine control of a sterilization process for medical devices

International Nuclear Information System (INIS)

2006-01-01

This part of the ISO 11137 standard specifies requirements for the development, validation and routine control of a radiation sterilization process for medical devices. Although the scope of this part of the ISO 11137 standard is limited to medical devices, it specifies requirements and provides guidance that may be applicable to other products and equipment. This part of the international standard covers radiation processes employing irradiators using the radionuclide 60 Co or 137 Cs, a beam from an electron generator or a beam from an X-ray generator. This part of the international standard does not: - specify requirements for development, validation and routine control of a process for inactivating the causative agents of spongiform encephalopathies such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease; - detail specified requirements for designating a medical device as sterile; - specify a quality management system for the control of all stages of production of medical devices; - specify requirements for occupational safety associated with the design and operation of irradiation facilities; - specify requirements for the sterilization of used or reprocessed devices

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells

Directory of Open Access Journals (Sweden)

Chunwa Jiang

2017-02-01

Full Text Available Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB and signal transducer and activator of transcription 3 (STAT3 play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.

Providing for transmission in times of scarcity: an ISO cannot do it all

International Nuclear Information System (INIS)

Allen, E.; Ilic, M.; Younes, Z.

1999-01-01

The main purpose of this paper is to point out issues critical for establishing a good transmission strategy in an energy market. First, it is suggested that a transmission strategy must be discussed in the context of a specific market structure. Responsibilities of a transmission system provider differ fundamentally, depending on the type of energy market it is supposed to serve. To show this, a summary of information assumed to be known to an Independent System Operator (ISO) in three energy market structures is given, i.e., (1) a mandatory ISO, (2) an entirely multilateral market and (3) a voluntary ISO. The differences between these three proposals concerning an ISO's responsibility for achieving systemwide efficiency and fair charges for transmission service, particularly at times of scarcity, are analyzed. It is shown that an ISO equipped with the present types of optimization tools for both reliability and efficiency is generally 'blind' to questions of fairness with respect to the individual market participants when providing transmission system support. In order to get around this problem, much more work will have to he done by the technical and regulatory communities. The only tools at an ISO's disposal at present are used for systemwide objectives, such as systemwide reliability. While some of this work is under way, it will take some time to develop the actual ISO tools necessary for implementing the fairness criterion metrics ('standards'), whichever ones the community arrives at. (Developing metrics of fair reliability contributions for the individual market participants is a nonunique process, and it may be very difficult to actually agree upon). Meanwhile, in order to have an ISO actively help energy markets in a fair and efficient way in realistic markets, which are likely to be voluntary ISOs, a system user must become an active part of decision making, indicating how much it wishes to use the system at times of scarcity and at which price. One

ISO-PC Version 1.98: User`s guide

Energy Technology Data Exchange (ETDEWEB)

Rittmann, P.D.

1995-05-02

This document describes how to use Version 1.98 of the shielding program named ISO-PC. Version 1.98 corrects all known errors in ISOSHLD-II. In addition, a few numeric problems have been eliminated. There are three new namelist variables, 25 additional shielding materials, and 5 more energy groups. The two major differences with the original ISOSHLD-II are the removal of RIBD(radioisotope buildup and decay) source generator, and the removal of the non-uniform source distribution parameter, SSV1. This version of ISO-PC works with photon energies from 10 KeV to 10 MeV using 30 energy groups.

RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway

International Nuclear Information System (INIS)

Shimada, Kana; Saeki, Makio; Egusa, Hiroshi; Fukuyasu, Sho; Yura, Yoshiaki; Iwai, Kazuhiro; Kamisaki, Yoshinori

2011-01-01

Research highlights: → RNA polymerase II-associated protein 3 (RPAP3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO. → RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. → RPAP3 is a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents. -- Abstract: Activation of anti-apoptotic gene transcription by NF-κB (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-κB essential modulator) interacts with a number of proteins and modulates the activity of NF-κB pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. These results indicate that RPAP3 may be a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents.

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2008-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

A Functional Genomic Analysis of NF1-Associated Learning Disabilities

National Research Council Canada - National Science Library

Tang, Shao-Jun

2007-01-01

Learning disabilities severely deteriorate the life of many NF1 patients. However, the pathogenic process for NF1-associated learning disabilities has not been fully understood and an effective therapy is not available...

Comparative advantage: the impact of ISO 14001 environmental certification on exports.

Science.gov (United States)

Bellesi, Florencia; Lehrer, David; Tal, Alon

2005-04-01

Relative to the enormous acceptance of the ISO 9000 quality standard, the ISO 14001 environmental management certification has been met with only moderate enthusiasm among industrial facilities. The literature on corporate motivation for ISO 14001 participation is relatively modest considering the enormous number of publications reviewing other aspects of its adoption and implementation. It would seem that the present "marketing" package supporting ISO environmental commitments does not seem to offer sufficiently persuasive incentives for increased sales, either domestically or internationally. While researchers assume that a higher export rate of companies is positively associated with higher ISO participation rates, there have been very few empirical studies that support this inference, and conclusions have not been based on data taken from importing countries orfrom a systematic evaluation of expressed corporate preference for products sold by ISO 14001 certified companies. The present study reports the results of a survey to firms in six countries that are Israel's leading trade partners, importing chemicals, textiles, and produce. The survey results confirm that while the international market still considers price and quality as the paramount factors in selection of suppliers, environmental management systems (EMS) are an important feature that is frequently taken into consideration. EMS certification appears to signify a supplier who is managing the business well and exhibiting ethical responsibility. The European market proved to be more environmentally conscious than those in other industrialized parts of the world. EMS offer a particularly valuable advantage for producers wishing to reach European markets. As policy-makers seek to expand the voluntary adoption of EMS, a clear advantage for exporters should be highlighted among national industries.

IMPLEMENTASI QUALITY MANAGEMENT SYSTEM ISO 9001:2008 DALAM PEMBELAJARAN PRODUKTIF KEAHLIAN TEKNIK MESIN DAN OTOMOTIF SMK

Directory of Open Access Journals (Sweden)

Mochammad Ariful Ulfi

2013-07-01

Full Text Available The implementation of ISO 9001:2008 quality management system in the productive learning on the mechanical engineering and automotive in vocational high school. This research uses qualitative approach in term of a case study. The research is conducted at SMKN I Purwosari. The results of this research show that (1 the reason of the ISO imple­mentation is to obtain community trust, to improve compe­titiveness, and to increase the quality of the graduates; (2 the implementation of the quality management system in the learning process refers to the concept of PDCA of the ISO system; (3 the obstacles occured during the implementation of ISO is due to the lack of teachers’ awareness on the ISO system; and (4 some efforts to overcome those obstacles include developing commitment among all elements, socialization, supervision, and doing some preventive efforts. Penelitian ini menggunakan pendekatan kualitatif dengan rancangan studi kasus. Penelitian dilaksanakan di SMK Negeri 1 Purwosari. Adapun fokus penelitian adalah alasan penerapan ISO, implementasi dalam pembelajaran, hambatan, dan upaya mengatasi hambatan pelaksanaan ISO 9001:2008. Hasil penelitian menunjukkan   (1 alasan penerapan ISO adalah agar sekolah dipercaya masyarakat, meningkatkan daya saing, dan mening­kat­kan mutu lulusan; (2 implementasi dalam pembelajaran mengacu  pada konsep PDCA ke dalam sistem manajemen mutu ISO; (3 hambat­an implementasi ISO adalah tingkat kesadaran guru terhadap ISO yang rendah; (4 upaya mengatasi hambatan adalah membangun komitmen bersama, sosiali­sasi, supervisi, dan melakukan usaha pencegahan.

Interactions among oscillatory pathways in NF-kappa B signaling

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White Michael RH

2011-02-01

Full Text Available Abstract Background Sustained stimulation with tumour necrosis factor alpha (TNF-alpha induces substantial oscillations—observed at both the single cell and population levels—in the nuclear factor kappa B (NF-kappa B system. Although the mechanism has not yet been elucidated fully, a core system has been identified consisting of a negative feedback loop involving NF-kappa B (RelA:p50 hetero-dimer and its inhibitor I-kappa B-alpha. Many authors have suggested that this core oscillator should couple to other oscillatory pathways. Results First we analyse single-cell data from experiments in which the NF-kappa B system is forced by short trains of strong pulses of TNF-alpha. Power spectra of the ratio of nuclear-to-cytoplasmic concentration of NF-kappa B suggest that the cells' responses are entrained by the pulsing frequency. Using a recent model of the NF-kappa B system due to Caroline Horton, we carried out extensive numerical simulations to analyze the response frequencies induced by trains of pulses of TNF-alpha stimulation having a wide range of frequencies and amplitudes. These studies suggest that for sufficiently weak stimulation, various nonlinear resonances should be observable. To explore further the possibility of probing alternative feedback mechanisms, we also coupled the model to sinusoidal signals with a wide range of strengths and frequencies. Our results show that, at least in simulation, frequencies other than those of the forcing and the main NF-kappa B oscillator can be excited via sub- and superharmonic resonance, producing quasiperiodic and even chaotic dynamics. Conclusions Our numerical results suggest that the entrainment phenomena observed in pulse-stimulated experiments is a consequence of the high intensity of the stimulation. Computational studies based on current models suggest that resonant interactions between periodic pulsatile forcing and the system's natural frequencies may become evident for sufficiently

Organizational leadership: A study on the affects of certification to International Organization for Standardization (ISO)

Science.gov (United States)

Cowart, Jewel S.

Compliance to requirements of ISO is an important leadership problem for the International Aerospace Quality Group (IAQG) and the Aviation, Space and Defense (AS&D) companies. Furthermore, the IAQG seeks to understand the valuation of ISO/AS9100 requirements (2009), audit practices, management functions, business performance, customer satisfaction, and potential future concepts for the standard to assure quality. Since the release of the AS9100C total certification growth surpassed 1,100,000 organizations in 2010 with ISO 9001 series adoption and implementation governing business operations (ASQ, 2012b; ISO, 2011; Bernardo, Llach, & Marimon, 2011). Historians such as Crosby, Juran, Deming, and others established the foundation for quality assurance. Several researchers explored the issues which complicate overall benefits of ISO certification (Iwaro & Mwasha, 2012; Karthi et al., 2012; Sampaio et al., 2009). This study examined the effects on AS&D industries from ISO compliance to identify the implications (of ever-changing requirements) through an online survey of 15,000 practitioners. The research illuminated how ISO affects AS&D industries with current and future requirements for certification. The data showed that 75% of survey respondents report implementation of the AS9100C requirements still has benefits that outweigh the cost. Findings suggest that AS&D industries perceive significant value in the AS9100C document as part of the overall ISO 9000 series. In general, the comments from the survey can provide insight into the affects of ISO certification. The study concludes by recommending continued research to learn of further impacts from ISO certification within AS&D industries to improve the AS9100 document requirements for quality management systems.

ISO 15189 Accreditation: Navigation Between Quality Management and Patient Safety

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Plebani Mario

2017-09-01

Full Text Available Accreditation is a valuable resource for clinical laboratories and the development of an International Standard for their accreditation represented a milestone on the path towards improved quality and safety in laboratory medicine. The recent revision of the International Standard, ISO 15189, has further strengthened its value not only for improving the quality system of a clinical laboratory but also for better answering the request for competence, focus on customers’ needs and ultimate value of laboratory services. Although in some countries more general standards such as ISO 9001 for quality systems or ISO 17025 for testing laboratories are still used, there is increasing recognition of the value of ISO 15189 as the most appropriate and useful standard for the accreditation of medical laboratories. In fact, only this International Standard recognizes the importance of all steps of the total testing process, namely extra-analytical phases, the need to focus on technical competence in addition to quality systems, and the focus on customers’ needs. However, the number of accredited laboratories largely varies between European countries and also major differences affect the approaches to accreditation promoted by the national bodies. In particular, some national accreditation bodies perpetuate the use of fixed scopes, while the European co-operation for accreditation (EA and the European Federation of Laboratory Medicine (EFLM Working Group promote the use of flexible scopes. Major issues in clinical laboratory accreditation are the verification of examination procedures for imprecision, trueness and diagnostic accuracy and for estimating measurement uncertainty. In addition, quality indicators (QIs are a fundamental requirement of the ISO 15189 International Standard.

A role for NF-κB–dependent gene transactivation in sunburn

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Abeyama, Kazuhiro; Eng, William; Jester, James V.; Vink, Arie A.; Edelbaum, Dale; Cockerell, Clay J.; Bergstresser, Paul R.; Takashima, Akira

2000-01-01

Exposure of skin to ultraviolet (UV) radiation is known to induce NF-κB activation, but the functional role for this pathway in UV-induced cutaneous inflammation remains uncertain. In this study, we examined whether experimentally induced sunburn reactions in mice could be prevented by blocking UV-induced, NF-κB–dependent gene transactivation with oligodeoxynucleotides (ODNs) containing the NF-κB cis element (NF-κB decoy ODNs). UV-induced secretion of IL-1, IL-6, TNF-α, and VEGF by skin-derived cell lines was inhibited by the decoy ODNs, but not by the scrambled control ODNs. Systemic or local injection of NF-κB decoy ODNs also inhibited cutaneous swelling responses to UV irradiation. Moreover, local UV-induced inflammatory changes (swelling, leukocyte infiltration, epidermal hyperplasia, and accumulation of proinflammatory cytokines) were all inhibited specifically by topically applied decoy ODNs. Importantly, these ODNs had no effect on alternative types of cutaneous inflammation caused by irritant or allergic chemicals. These results indicate that sunburn reactions culminate from inflammatory events that are triggered by UV-activated transcription of NF-κB target genes, rather than from nonspecific changes associated with tissue damage. PMID:10862790

Incorporating an ISO 8583-Service into an Unreliable Application

OpenAIRE

Funcke, Alexander

2008-01-01

If an existing service is to be made available to a broader audience, via for instance the Internet. The implementation of the service may thereby get many new requirements, such as support for a different access method or stricter authorisation and security policies. This thesis discusses the implementation of an ISO 8583 to XML proxy. ISO 8583 is a widely used financial protocol, and was in this project used to communicate with the backing financial server in order to implement a complete w...

Evaluation of ISO EN 13606 as a result of its implementation in XML.

Science.gov (United States)

Austin, Tony; Sun, Shanghua; Hassan, Taher; Kalra, Dipak

2013-12-01

The five parts of the ISO EN 13606 standard define a means by which health-care records can be exchanged between computer systems. Starting within the European standardisation process, it has now become internationally ratified in ISO. However, ISO standards do not require that a reference implementation be provided, and in order for ISO EN 13606 to deliver the expected benefits, it must be provided not as a document, but as an operational system that is not vendor specific. This article describes the evolution of an Extensible Markup Language (XML) Schema through three iterations, each of which emphasised one particular approach to delivering an executable equivalent to the printed standard. Developing these operational versions and incorporating feedback from users of these demonstrated where implementation compromises were needed and exposed defects in the standard. These are discussed herein. They may require a future technical revision to ISO EN 13606 to resolve the issues identified.

Approaches to the ISO/IEC 17025 accreditation for Pu and U accountancy analysis

International Nuclear Information System (INIS)

Okazaki, Hiro; Sumi, Mika; Abe, Katsuo; Sato, Mitsuhiro; Kageyama, Tomio

2013-01-01

The quality control section of Plutonium Fuel Development Center (PFDC) of Japan Atomic Energy Agency has been analyzing isotopic compositions by Mass Spectrometry as well as content by Isotope Dilution Mass Spectrometry (IDMS) of plutonium and uranium in nuclear materials. Along with establishing and managing the quality assurance system, ensuring the reliability of the analysis data is important. PFDC has been establishing the quality management system with ISO9001. ISO9001 consists of management requirements for quality system of organizations. While ISO/IEC 17025 consists of technical requirements for the competence of testing and calibration laboratories in addition to the management requirements. The quality control section addressed technical improvement to improve further reliability of analysis quality and we have accredited for ISO/IEC 17025 of isotopic compositions and content of plutonium and uranium in nuclear materials in March 2010. In this presentation, we report our approaches to the ISO/IEC 17025 accreditation and operation status. (author)