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Sample records for protecting rb-e2f-1 complex

  1. Deregulation of Rb-E2F1 Axis Causes Chromosomal Instability by Engaging the Transactivation Function of Cdc20–Anaphase-Promoting Complex/Cyclosome

    PubMed Central

    Nath, Somsubhra; Chowdhury, Abhishek; Dey, Sanjib; Roychoudhury, Anirban; Ganguly, Abira; Bhattacharyya, Dibyendu

    2014-01-01

    The E2F family of transcription factors regulates genes involved in various aspects of the cell cycle. Beyond the well-documented role in G1/S transition, mitotic regulation by E2F has also been reported. Proper mitotic progression is monitored by the spindle assembly checkpoint (SAC). The SAC ensures bipolar separation of chromosomes and thus prevents aneuploidy. There are limited reports on the regulation of the SAC by E2F. Our previous work identified the SAC protein Cdc20 as a novel transcriptional regulator of the mitotic ubiquitin carrier protein UbcH10. However, none of the Cdc20 transcription complex proteins have any known DNA binding domain. Here we show that an E2F1-DP1 heterodimer is involved in recruitment of the Cdc20 transcription complex to the UBCH10 promoter and in transactivation of the gene. We further show that inactivation of Rb can facilitate this transactivation process. Moreover, this E2F1-mediated regulation of UbcH10 influences mitotic progression. Deregulation of this pathway results in premature anaphase, chromosomal abnormalities, and aneuploidy. We conclude that excess E2F1 due to Rb inactivation recruits the complex of Cdc20 and the anaphase-promoting complex/cyclosome (Cdc20-APC/C) to deregulate the expression of UBCH10, leading to chromosomal instability in cancer cells. PMID:25368385

  2. Disruption of RB/E2F-1 interaction by single point mutations in E2F-1 enhances S-phase entry and apoptosis.

    PubMed Central

    Shan, B; Durfee, T; Lee, W H

    1996-01-01

    The retinoblastoma protein (RB) has been proposed to function as a negative regulator of cell proliferation by complexing with cellular proteins such as the transcription factor E2F. To study the biological consequences of the RB/E2F-1 interaction, point mutants of E2F-1 which fail to bind to RB were isolated by using the yeast two-hybrid system. Sequence analysis revealed that within the minimal 18-amino acid peptide of E2F-1 required for RB binding, five residues, Tyr (position 411), Glu (419), and Asp-Leu-Phe (423-425), are critical. These amino acids are conserved among the known E2F family members. While mutation of any of these five amino acids abolished binding to RB, all mutants retained their full transactivation potential. Expression of mutated E2F-1, when compared with that of wild-type, significantly accelerated entry into S phase and subsequent apoptosis. These results provide direct genetic evidence for the biological significance of the RB/E2F interaction and strongly suggest that the interplay between RB and E2F is critical for proper cell cycle progression. Images Fig. 3 Fig. 4 PMID:8570615

  3. HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4(+) T cells.

    PubMed

    Kawatsuki, A; Yasunaga, J-I; Mitobe, Y; Green, P L; Matsuoka, M

    2016-08-25

    Human T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus that induces a fatal T-cell malignancy, adult T-cell leukemia (ATL). Among several regulatory/accessory genes in HTLV-1, HTLV-1 bZIP factor (HBZ) is the only viral gene constitutively expressed in infected cells. Our previous study showed that HBZ functions in two different molecular forms, HBZ protein and HBZ RNA. In this study, we show that HBZ protein targets retinoblastoma protein (Rb), which is a critical tumor suppressor in many types of cancers. HBZ protein interacts with the Rb/E2F-1 complex and activates the transcription of E2F-target genes associated with cell cycle progression and apoptosis. Mouse primary CD4(+) T cells transduced with HBZ show accelerated G1/S transition and apoptosis, and importantly, T cells from HBZ transgenic (HBZ-Tg) mice also demonstrate enhanced cell proliferation and apoptosis. To evaluate the functions of HBZ protein alone in vivo, we generated a new transgenic mouse strain that expresses HBZ mRNA altered by silent mutations but encoding intact protein. In these mice, the numbers of effector/memory and Foxp3(+) T cells were increased, and genes associated with proliferation and apoptosis were upregulated. This study shows that HBZ protein promotes cell proliferation and apoptosis in primary CD4(+) T cells through activation of the Rb/E2F pathway, and that HBZ protein also confers onto CD4(+) T-cell immunophenotype similar to those of ATL cells, suggesting that HBZ protein has important roles in dysregulation of CD4(+) T cells infected with HTLV-1. PMID:26804169

  4. CBX8 antagonizes the effect of Sirtinol on premature senescence through the AKT-RB-E2F1 pathway in K562 leukemia cells.

    PubMed

    Lee, Sang Hyup; Um, Soo-Jong; Kim, Eun-Joo

    2016-01-22

    Although tyrosine kinase inhibitor (TKI) therapies are highly effective in the treatment of chronic myeloid leukemia (CML), frequent recurrence limits their usage and demands new approaches for CML therapy. Stress-induced premature senescence (SIPS) is considered a potential anticancer treatment, but the underlying mechanism remains elusive. Here, we report that Sirtinol, a known SIRT1 inhibitor, induces premature senescence and growth arrest in K562 CML cells. Chromobox homolog 8 (CBX8) suppresses the Sirtinol-induced premature senescence, which is reversed by CBX8 knockdown. Upon Sirtinol treatment, the phosphorylation of AKT1, p27KIP1 and RB is severely downregulated. However, CBX8 overexpression enhances phosphorylation and, thereby, promotes the transcriptional activity of E2F1, both of which are impaired upon CBX depletion. These data suggest that CBX8 modulates SIPS through the RB-E2F1 pathway in CML cells and provide important insight into its application in CML treatment. PMID:26718407

  5. Attempted Cell Cycle Induction in Post-Mitotic Neurons Occurs in Early and Late Apoptotic Programs Through Rb, E2F1, and Caspase 3

    PubMed Central

    Chong, Zhao Zhong; Li, Faqi; Maiese, Kenneth

    2007-01-01

    Either the absence or dysfunction of a number of critical pathways, such as those that involve the nuclear retinoblastoma protein (Rb) and the transcription factor E2F1, may account for the aberrant induction of the cell cycle in post-mitotic neurons that can be responsible for oxidative stress-induced apoptotic cellular destruction. Yet, it is unclear whether early programs of apoptotic injury that involve membrane phosphatidylserine (PS) exposure and calreticulin expression as well as later phases of apoptotic injury with nuclear DNA injury require the critical modulation of Rb and E2F1. We demonstrate that both the post-translational of phosphorylation of Rb to prevent E2F1 transcription as well as the protein integrity of Rb are closely aligned with the modulation of cell cycle induction in post mitotic neurons during oxidative stress. More importantly, we illustrate that both the initial onset of apoptosis with either membrane PS exposure or calreticulin analysis as well as the more terminal phases of apoptosis that involve nuclear DNA degradation proceed concurrently in the same neuronal cells with cell cycle induction. Progression of attempted cell cycle induction is closely associated with the phosphorylation of Rb, its inability to bind to E2F1, and the degradation of the Rb protein. Inhibition of Rb phosphorylation using cyclin dependent kinase inhibitors maintains the integrity of the E2F1/Rb complex and is neuroprotective during free radical exposure. Furthermore, maintenance of the integrity of the Rb protein is specifically dependent upon caspase 3-like activity, since caspase 3 can cleave Rb during free radical activity and this degradation of Rb can be blocked during the inhibition of caspase 3 activity. Our studies not only highlight the critical role of attempted cell cycle induction during oxidative stress-induced neuronal apoptotic injury, but also bring to light the significant impact of the Rb and E2F1 pathways upon early apoptotic programs

  6. pRb/E2F-1-mediated caspase-dependent induction of Noxa amplifies the apoptotic effects of the Bcl-2/Bcl-xL inhibitor ABT-737

    PubMed Central

    Bertin-Ciftci, J; Barré, B; Le Pen, J; Maillet, L; Couriaud, C; Juin, P; Braun, F

    2013-01-01

    Although Bcl-2 family members control caspase activity by regulating mitochondrial permeability, caspases can, in turn, amplify the apoptotic process upstream of mitochondria by ill-characterized mechanisms. We herein show that treatment with a potent inhibitor of Bcl-2 and Bcl-xL, ABT-737, triggers caspase-dependent induction of the BH3-only protein, Mcl-1 inhibitor, Noxa. RNA interference experiments reveal that induction of Noxa, and subsequent cell death, rely not only on the transcription factor E2F-1 but also on its regulator pRb. In response to ABT-737, pRb is cleaved by caspases into a p68Rb form that still interacts with E2F-1. Moreover, pRb occupies the noxa promoter together with E2F-1, in a caspase-dependent manner upon ABT-737 treatment. Thus, caspases contribute to trigger the mitochondrial apoptotic pathway by coupling Bcl-2/Bcl-xL inhibition to that of Mcl-1, via the pRb/E2F-1-dependent induction of Noxa. PMID:23429261

  7. Periodic expression of Kv10.1 driven by pRb/E2F1 contributes to G2/M progression of cancer and non-transformed cells

    PubMed Central

    Urrego, Diana; Movsisyan, Naira; Ufartes, Roser; Pardo, Luis A.

    2016-01-01

    ABSTRACT Progression of cell cycle is associated with changes in K+ channel expression and activity. In this study, we report that Kv10.1, a K+ channel that increases cell proliferation and tumor growth, is regulated at the transcriptional level by the pRb/E2F1 pathway. De-repression of E2F1 by HPV-E7 oncoprotein leads to increased expression of Kv10.1. In proliferating cells, E2F1 transcription factor binds directly to the Kv10.1 promoter during (or close to) G2/M, resulting in transient expression of the channel. Importantly, this happens not only in cancer cells but also in non-transformed cells. Lack of Kv10.1 in both cancer and non-transformed cells resulted in prolonged G2/M phase, as indicated by phosphorylation of Cdk1 (Y15) and sustained pRb hyperphosphorylation. Our results strongly suggest that Kv10.1 expression is coupled to cell cycle progression and facilitates G2/M progression in both healthy and tumor cells. PMID:27029528

  8. Epithelial cell-derived periostin functions as a tumor suppressor in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14ARF/Mdm2 signaling pathway.

    PubMed

    Lv, Hongjun; Liu, Rui; Fu, Jiao; Yang, Qi; Shi, Jing; Chen, Pu; Ji, Meiju; Shi, Bingyin; Hou, Peng

    2014-01-01

    Periostin is usually considered as an oncogene in diverse human cancers, including breast, prostate, colon, esophagus, and pancreas cancers, whereas it acts as a tumor suppressor in bladder cancer. In gastric cancer, it has been demonstrated that periglandular periostin expression is decreased whereas stromal periostin expression is significantly increased as compared with normal gastric tissues. Moreover, periostin produced by stromal myofibroblasts markedly promotes gastric cancer cell growth. These observations suggest that periostin derived from different types of cells may play distinct biological roles in gastric tumorigenesis. The aim of this study was to explore the biological functions and related molecular mechanisms of epithelial cell-derived periostin in gastric cancer. Our data showed that periglandular periostin was significantly down-regulated in gastric cancer tissues as compared with matched normal gastric mucosa. In addition, its expression in metastatic lymph nodes was significantly lower than that in their primary cancer tissues. Our data also demonstrated that periglandular periostin expression was negatively associated with tumor stage. More importantly, restoration of periostin expression in gastric cancer cells dramatically suppressed cell growth and invasiveness. Elucidation of the mechanisms involved revealed that periostin restoration enhanced Rb phosphorylation and sequentially activated the transcription of E2F1 target gene p14(ARF), leading to Mdm2 inactivation and the stabilization of p53 and E-cadherin proteins. Strikingly, these effects of periostin were abolished upon Rb deletion. Collectively, we have for the first time demonstrated that epithelial cell-derived periostin exerts tumor-suppressor activities in gastric cancer through stabilizing p53 and E-cadherin proteins via the Rb/E2F1/p14(ARF)/Mdm2 signaling pathway. PMID:25486483

  9. Ritonavir-Mediated Induction of Apoptosis in Pancreatic Cancer Occurs via the RB/E2F-1 and AKT Pathways

    PubMed Central

    Batchu, Ramesh B.; Gruzdyn, Oksana V.; Bryant, Christopher S.; Qazi, Aamer M.; Kumar, Sanjeev; Chamala, Sreedhar; Kung, Shu T.; Sanka, Ramana S.; Puttagunta, Udaya S.; Weaver, Donald W.; Gruber, Scott A.

    2014-01-01

    Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks. PMID:24451403

  10. Cancer complexity and radiation protection.

    PubMed

    Mossman, Kenneth L

    2014-07-01

    Management of radiological risks typically encountered in environmental and occupational settings is challenging because of uncertainties in the magnitude of the risks and the benefits of risk reduction. In practice, radiation dose instead of risk is measured. However, the relationship between dose and risk is not straightforward because cancer (the major health effect of concern at low doses) is a disease of complexity. Risks at small doses (defined as less than 100 mSv) can never be known exactly because of the inherent uncertainties in cancer as a complex disease. Tumors are complex because of the nonlinear interactions that occur among tumor cells and between the tumor and its local tissue environment. This commentary reviews evidence for cancer complexity and what complexity means for radiation protection. A complexity view of cancer does not mean we must abandon our current system of protection. What it does mean is that complexity requires new ways of thinking about control of cancer-the ideas that cancers can occur without cause, cancers behave unpredictably, and calculated cancer risks following small doses of radiation are highly uncertain. PMID:24849905

  11. TNFα Modulates Fibroblast Growth Factor Receptor 2 Gene Expression through the pRB/E2F1 Pathway: Identification of a Non-Canonical E2F Binding Motif

    PubMed Central

    D’Amici, Sirio; Ceccarelli, Simona; Vescarelli, Enrica; Romano, Ferdinando; Frati, Luigi; Marchese, Cinzia; Angeloni, Antonio

    2013-01-01

    Interactions between epithelium and mesenchyme during wound healing are not fully understood, but Fibroblast Growth Factors (FGFs) and their receptors FGFRs are recognized as key elements. FGFR2 gene encodes for two splicing transcript variants, FGFR2-IIIb or Keratinocyte Growth Factor Receptor (KGFR) and FGFR2-IIIc, which differ for tissue localization and ligand specificity. Proinflammatory cytokines play an essential role in the regulation of epithelial-mesenchymal interactions, and have been indicated to stimulate FGFs production. Here we demonstrated that upregulation of FGFR2 mRNA and protein expression is induced by the proinflammatory cytokines Tumor Necrosis Factor-α, Interleukin-1β and Interleukin 2. Furthermore, we found that TNFα determines FGFR2 transcriptional induction through activation of pRb, mediated by Raf and/or p38 pathways, and subsequent release of the transcription factor E2F1. Experiments based on FGFR2 promoter serial deletions and site-directed mutagenesis allowed us to identify a minimal responsive element that retains the capacity to be activated by E2F1. Computational analysis indicated that this element is a non-canonical E2F responsive motif. Thus far, the molecular mechanisms of FGFR2 upregulation during wound healing or in pathological events are not known. Our data suggest that FGFR2 expression can be modulated by local recruitment of inflammatory cytokines. Furthermore, since alterations in FGFR2 expression have been linked to the pathogenesis of certain human cancers, these findings could also provide elements for diagnosis and potential targets for novel therapeutic approaches. PMID:23613863

  12. Evolutionary complexity for protection of critical assets.

    SciTech Connect

    Battaile, Corbett Chandler; Chandross, Michael Evan

    2005-01-01

    This report summarizes the work performed as part of a one-year LDRD project, 'Evolutionary Complexity for Protection of Critical Assets.' A brief introduction is given to the topics of genetic algorithms and genetic programming, followed by a discussion of relevant results obtained during the project's research, and finally the conclusions drawn from those results. The focus is on using genetic programming to evolve solutions for relatively simple algebraic equations as a prototype application for evolving complexity in computer codes. The results were obtained using the lil-gp genetic program, a C code for evolving solutions to user-defined problems and functions. These results suggest that genetic programs are not well-suited to evolving complexity for critical asset protection because they cannot efficiently evolve solutions to complex problems, and introduce unacceptable performance penalties into solutions for simple ones.

  13. Antenna complexes protect Photosystem I from Photoinhibition

    PubMed Central

    Alboresi, Alessandro; Ballottari, Matteo; Hienerwadel, Rainer; Giacometti, Giorgio M; Morosinotto, Tomas

    2009-01-01

    Background Photosystems are composed of two moieties, a reaction center and a peripheral antenna system. In photosynthetic eukaryotes the latter system is composed of proteins belonging to Lhc family. An increasing set of evidences demonstrated how these polypeptides play a relevant physiological function in both light harvesting and photoprotection. Despite the sequence similarity between antenna proteins associated with the two Photosystems, present knowledge on their physiological role is mostly limited to complexes associated to Photosystem II. Results In this work we analyzed the physiological role of Photosystem I antenna system in Arabidopsis thaliana both in vivo and in vitro. Plants depleted in individual antenna polypeptides showed a reduced capacity for photoprotection and an increased production of reactive oxygen species upon high light exposure. In vitro experiments on isolated complexes confirmed that depletion of antenna proteins reduced the resistance of isolated Photosystem I particles to high light and that the antenna is effective in photoprotection only upon the interaction with the core complex. Conclusion We show that antenna proteins play a dual role in Arabidopsis thaliana Photosystem I photoprotection: first, a Photosystem I with an intact antenna system is more resistant to high light because of a reduced production of reactive oxygen species and, second, antenna chlorophyll-proteins are the first target of high light damages. When photoprotection mechanisms become insufficient, the antenna chlorophyll proteins act as fuses: LHCI chlorophylls are degraded while the reaction center photochemical activity is maintained. Differences with respect to photoprotection strategy in Photosystem II, where the reaction center is the first target of photoinhibition, are discussed. PMID:19508723

  14. Flood protection for the Kansas City bannister federal complex

    SciTech Connect

    Nolan, J.J.; Williams, R.H.; Betzen, G.A.

    1995-08-01

    The Bannister Federal Complex is bordered on the east by the Blue River and on the south by Indian Creek. After a flood in 1961 and several near-miss floods, flood protection has been installed. The protection consists of 2,916 feet of concrete flood walls, 8,769 feet of levee, five rolling gates, four stoplog gaps, one hinged pedestrian gate, and one sandbag gap. The flood walls are over 14 feet tall. Construction was started on August 3, 1992 and was completed in early 1995. Architectural treatment was incorporated in the flood walls as well as landscaping to enhance the appearance of the flood protection.

  15. Physical protection technologies for the reconfigured weapons complex

    SciTech Connect

    Jaeger, C.D.

    1994-08-01

    Sandia National Laboratories was a memtier of the Weapons Complex Reconfiguration (WCR) Safeguards and Security (S&S) team providing assistance to the Department of Energy`s (DOE) Office of Weapons Complex Reconfigaration. New and improved S&S concepts, approaches and technologies were needed to support both new and upgraded facilities. Physical protection technologies used in these facilities were to use proven state-of-the-art systems in such areas as image processing, alarm communications and display, entry control, contraband detection, intrusion detection and video assessment, access delay, automation and robotics, and various insider protection systems. Factors considered in the selection of these technologies were protection against the design basis threat, reducing S&S life-cycle costs, automation of S&S functions to minimize operational costs, access to critical assets and exposure of people to hazardous environments, increasing the amount of delay to an outsider adversary and having reliable and maintainable systems. This paper will discuss the S&S issues, requirements, technology opportunities and needs. Physical protection technologies and systems considered in the design effort of the Weapons Complex Reconfiguration facilities will be reviewed.

  16. Protection of cooled blades of complex internal structure

    NASA Technical Reports Server (NTRS)

    Glamiche, P.

    1977-01-01

    The problem of general protection of cooled blades of complex internal structure was solved by a method called SF technique which makes possible the protection of both external and internal surfaces, as well as those of the orifices of cooling air, whatever their diameter. The SF method is most often applied in the case of pack process, at controlled or high activity; it can be of use on previously uncoated parts, but also on pieces already coated by a thermochemical, chemical or PVD method. The respective thickness of external and internal coatings may be precisely predetermined, no parasitic particle being liable to remain inside the parts after application of the protecting treatment. Results obtained to date by application of this method are illustrated by the presentation and examination of a various selection of advanced turbo engines.

  17. Assistance, protection, and governance networks in complex emergencies.

    PubMed

    Lautze, Sue; Leaning, Jennifer; Raven-Roberts, Angela; Kent, Randolph; Mazurana, Dyan

    This article presents an introduction to the causes and characteristics of armed conflicts. It reviews some of the key humanitarian crises that broke new ground in terms of the technologies and practices that developed at the field level in response to each new complex emergency, with particular focus on the health sector. It introduces the concept of humanitarian governance as a framework for addressing the consequences and implications of the failure of worldwide governance for the protection of civilians in armed conflict. Here, we term humanitarian governance to include the use of international humanitarian law and human rights instruments to govern the behaviour of state and non-state organisations in conflict zones in a way that protects the lives and livelihoods of affected populations. We note, however, that terrorist concerns appear to be replacing humanitarian logic in the network of worldwide governance. PMID:15589312

  18. Formation of glutathionyl dinitrosyl iron complexes protects against iron genotoxicity.

    PubMed

    Lewandowska, Hanna; Sadło, Jarosław; Męczyńska, Sylwia; Stępkowski, Tomasz M; Wójciuk, Grzegorz; Kruszewski, Marcin

    2015-07-28

    Dinitrosyl iron(i) complexes (DNICs), intracellular NO donors, are important factors in nitric oxide-dependent regulation of cellular metabolism and signal transduction. It has been shown that NO diminishes the toxicity of iron ions and vice versa. To gain insight into the possible role of DNIC in this phenomenon, we examined the effect of GS-DNIC formation on the ability of iron ions to mediate DNA damage, by treatment of the pUC19 plasmid with physiologically relevant concentrations of GS-DNIC. It was shown that GS-DNIC formation protects against the genotoxic effect of iron ions alone and iron ions in the presence of a naturally abundant antioxidant, GSH. This sheds new light on the iron-related protective effect of NO under the circumstances of oxidative stress. PMID:26079708

  19. Regulation for environmental protection: The Nanticoke industrial complex, Ontario, Canada

    NASA Astrophysics Data System (ADS)

    Nelson, J. G.; Day, J. C.; Jessen, Sabine

    1981-09-01

    This assessment of the environmental protection regulatory system for the 2.2 billion iron and steel plant, oil refinery, and thermal generating station composing the core of the greenfield Nanticoke industrial complex is based upon: the use of governmental and industrial research in project management; technology and institutional arrangements for environmental protection; evidence of environmental changes to date; analysis of government and industrial approval files; and interviews with government, industry, and interest group representatives. Planning, regulation, and management have been reasonably efficient and effective to the beginning of the operational stage for all three major industries as of spring 1980. Of major future concern, however, is management of the cumulative and synergistic impacts of the industries and associated development on air quality as well as the lands, waters, and sensitive ecosystems of the nearby Lake Erie coast. Continuous monitoring, more comprehensive research, and better overall coordination of government, industrial, and public interests are required if Nanticoke benefits are to be achieved without undue cost to pre-project resource users within and outside the Haldimand-Norfolk region.

  20. RNA protects a nucleoprotein complex against radiation damage.

    PubMed

    Bury, Charles S; McGeehan, John E; Antson, Alfred A; Carmichael, Ian; Gerstel, Markus; Shevtsov, Mikhail B; Garman, Elspeth F

    2016-05-01

    Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3-25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein-DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density. PMID:27139628

  1. RNA protects a nucleoprotein complex against radiation damage

    PubMed Central

    Bury, Charles S.; McGeehan, John E.; Antson, Alfred A.; Carmichael, Ian; Gerstel, Markus; Shevtsov, Mikhail B.; Garman, Elspeth F.

    2016-01-01

    Radiation damage during macromolecular X-ray crystallographic data collection is still the main impediment for many macromolecular structure determinations. Even when an eventual model results from the crystallographic pipeline, the manifestations of radiation-induced structural and conformation changes, the so-called specific damage, within crystalline macromolecules can lead to false interpretations of biological mechanisms. Although this has been well characterized within protein crystals, far less is known about specific damage effects within the larger class of nucleoprotein complexes. Here, a methodology has been developed whereby per-atom density changes could be quantified with increasing dose over a wide (1.3–25.0 MGy) range and at higher resolution (1.98 Å) than the previous systematic specific damage study on a protein–DNA complex. Specific damage manifestations were determined within the large trp RNA-binding attenuation protein (TRAP) bound to a single-stranded RNA that forms a belt around the protein. Over a large dose range, the RNA was found to be far less susceptible to radiation-induced chemical changes than the protein. The availability of two TRAP molecules in the asymmetric unit, of which only one contained bound RNA, allowed a controlled investigation into the exact role of RNA binding in protein specific damage susceptibility. The 11-fold symmetry within each TRAP ring permitted statistically significant analysis of the Glu and Asp damage patterns, with RNA binding unexpectedly being observed to protect these otherwise highly sensitive residues within the 11 RNA-binding pockets distributed around the outside of the protein molecule. Additionally, the method enabled a quantification of the reduction in radiation-induced Lys and Phe disordering upon RNA binding directly from the electron density. PMID:27139628

  2. TGF{beta}-mediated formation of pRb-E2F complexes in human myeloid leukemia cells

    SciTech Connect

    Hu Xiaotang

    2008-05-02

    TGF{beta} is well known for its inhibitory effect on cell cycle G1 checkpoint kinases. However, its role in the control of pRb-E2F complexes is not well established. TGF{beta} inhibits phosphorylation of pRb at several serine and threonine residues and regulates the association of E2F transcription factors with pRb family proteins. Recent studies found that predominantly E2F-4, p130, and histone deacetylase (HDAC) are found to bind to corresponding E2F-responsive promoters in G0/G1 phase. As cells progress through mid-G1, p130-E2F4 complex are replaced by p107-E2F4 followed by activators E2F1, 2, and 3. pRb was not detectable in the promoters containing the E2F-responsive site in cycling cells but was associated with E2F4-p130 complexes or E2F4-p107 complexes during G0/G1 phase. In human myeloid leukemia cell line, MV4-11, TGF{beta} upregulated pRb-E2F-4 and p130-E2F-4, and downregulated p107-E2F-4 complexes. However, pRB-E2F1 and pRb-E2F3 complexes were found in proliferating cells but not in TGF{beta} arrested G1 cells. In addition, electrophoretic gel mobility shift assay (EMSA) could not detect pRb-E2F DNA-binding activities either in S or G1 phase but exhibited the existence of p107-E2F4 in proliferating cells and p130-E2F4 complexes in TGF{beta}-arrested G1 cells, respectively. Our data suggest that p107 and p130, but not pRb, and the repressor E2F, but not activator E2Fs, play a critical role in regulating E2F-responsive gene expression in TGF{beta}-mediated cell cycle control in human myeloid leukemia cells.

  3. Exploring the complexity of the mechanism of cathodic protection

    SciTech Connect

    Thompson, N.G.; Lawson, K.M.; Beavers, J.A.

    1994-12-31

    The present understanding of the mechanism of cathodic protection is too simplistic to explain when, why, and under what conditions corrosion is mitigated for a buried pipeline. This paper presents a general framework which attempts to explain why cathodic protection is achieved and what factors are critical in determining the ability of cathodic protection to mitigate corrosion. It is speculated that the changes in the ``near-surface`` environment due to the reduction processes on the cathodically protected steel surface play a significant role in mitigating corrosion and in defining the level of polarization achieved. This is accomplished by contributing a concentration polarization term to the overall level of polarization. Furthermore, the concentration polarization term explains many field related observations not easily explained by activation polarization and mixed potential theory. 32 refs.

  4. Complexity analysis and control in joint channel protection system for wireless video communications

    NASA Astrophysics Data System (ADS)

    Jin, Xin; Zhu, Guangxi

    2007-02-01

    In wireless communications, channel coding and error control are essential to protect the video data from wireless interference. The power it consumed, which is determined by the protection method it used, will directly affect the system performance especially on the decoding side. In this paper, a channel coding and error control system, called joint channel protection (JCP) system here, is proposed as an improvement of the hybrid automatic repeat request (HARQ) system to integrate the complexity controllability. The complexity models of the encoder and decoder are established based on theoretical analysis and statistical data retrieval using the time complexity concept, and the relative variation in the computational complexity is carefully studied to provide a proportional variation reference for complexity control. Based on the models, strategies are designed to control the system complexity by adjusting the packet length, iterative decoding times and retransmission ratio according to the decoding quality and complexity level.

  5. Targeting insect mitochondrial complex I for plant protection.

    PubMed

    Wu, Xiu-Ming; Yang, Chang-Qing; Mao, Ying-Bo; Wang, Ling-Jian; Shangguan, Xiao-Xia; Chen, Xiao-Ya

    2016-09-01

    Plant engineered to express double-stranded RNA (dsRNA) can target the herbivorous insect gene for silencing. Although mounting evidence has emerged to support feasibility of this new pest control technology, field application is slow largely due to lack of potent targets. Here, we show that suppression of the gene encoding NDUFV2, a subunit of mitochondrial complex I that catalyses NADH dehydrogenation in respiratory chain, was highly lethal to insects. Feeding cotton bollworm (Helicoverpa armigera) larvae with transgenic cotton tissues expressing NDUFV2 dsRNA led to mortality up to 80% within 5 days, and almost no larvae survived after 7 days of feeding, due to the altered mitochondrial structure and activity. Transcriptome comparisons showed a drastic repression of dopa decarboxylase genes. Reciprocal assays with Asian corn borer (Ostrinia furnacalis), another lepidopteran species, revealed the sequence-specific effect of NDUFV2 suppression. Furthermore, the hemipteran lugus Apolygus lucorum was also liable to NDUFV2 repression. These data demonstrate that the mitochondrial complex I is a promising target with both sequence specificity and wide applicability for the development of new-generation insect-proof crops. PMID:26914579

  6. Distribution Line Protection Relaying Scheme Based on Complex Number Operation

    NASA Astrophysics Data System (ADS)

    Tsuji, Kouichi

    In Japan, operational principles from the mechanical-type era, such as the directional ground relay (DG) and overcurrent relay (OC), are still used without modification for the protection of distribution lines. We are now facing various problems, such as ground faults with high fault resistance in systems isolated from the ground. A new operational principle to solve the above problems is summarized below. ·A fault is simulated by replacing a branched distribution line with a one-section single distribution line, in which loads are concentrated at its terminals. ·Lines with a one-line to ground fault are detected on the basis of the relationship between the fault-phase voltage E before the fault and the fault current using Ho and Thevenin's theorem. ·Faults are assumed to occur at both terminals in the section. If the signs of the obtained fault reactance Xf at the two terminals are opposite, it is judged that a fault point where Xf = 0 holds exists within the section. As a result of the simulation using the program we developed, it was confirmed that no errors in the detection of the internal and external ground faults with a high fault resistance of 0-30kΩ were observed.

  7. Immune complex-based vaccine for pig protection against parvovirus.

    PubMed

    Roić, B; Cajavec, S; Ergotić, N; Lipej, Z; Madić, J; Lojkić, M; Pokrić, B

    2006-02-01

    The insoluble immune complexes (ICs) were prepared under the conditions of double immunodiffusion in gel, using the suspension of the ultrasound treated PK-15 cell-line infected with porcine parvovirus (PPV) containing both viral particles and viral proteins, as well as pig or rabbit anti-PPV polyclonal immune sera. The immunodiffusion performed in an agarose gel allows only viral subunits with a molecular mass equal to or less than 1000 kDa, rather than the viral particles, to diffuse through the gel and reach the point where the immunoprecipitate is to be formed. The immunoprecipitation under the conditions of the diffusion ensures the optimal, i.e. equimolar ratio of both immunoprecipitating components, antibody/antigen in the IC. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Western blot analyses showed the ICs were composed of two proteins, a protein in which molecular mass corresponded to the VP2 of the PPV and a protein with a molecular mass of the IgG. This suggests that the ICs are mainly composed of the VP2 antigen and IgG class antibodies. The potency of the IC-vaccines prepared in the form of a water-in-oil-in-water emulsion was compared with that of a commercially available, inactivated oil vaccine. The vaccination of gilts, 6 weeks before mating, with the IC containing allogeneic pig antibodies, resulted in the development of high and long-lasting anti-PPV antibody titres, similar to those generated by the licenced vaccine (P > 0.01). The content of the virus material administered by the IC was twice lower than that in the licenced vaccine. Neither systemic nor local reactions were observed in the gilts during the period of the trial with the IC vaccine. The number of viable piglets per litter varied between 9 and 12 and no signs of the PPV infection were detected. Rabbits were used as one of the alternative laboratory animal models accepted for the testing of the vaccine against the PPV. The rabbit humoral immune response

  8. Preparation, stability, and photoreactivity of thiolato ruthenium polypyridyl complexes: Can cysteine derivatives protect ruthenium-based anticancer complexes?

    PubMed

    van Rixel, Vincent H S; Busemann, Anja; Göttle, Adrien J; Bonnet, Sylvestre

    2015-09-01

    Ruthenium polypyridyl complexes may act as light-activatable anticancer prodrugs provided that they are protected by well-coordinated ligands that i) prevent coordination of other biomolecules to the metal center in the dark and ii) can be removed by visible light irradiation. In this paper, the use of monodentate thiol ligands RSH as light-cleavable protecting groups for the ruthenium complex [Ru(tpy)(bpy)(OH2)](PF6)2 ([1](PF6)2; tpy=2,2';6',2″-terpyridine, bpy=2,2'-bypyridine), is investigated. The reaction of [1](2+) with RSH=H2Cys (L-cysteine), H2Acys (N-acetyl-L-cysteine), and HAcysMe (N-acetyl-L-cysteine methyl ester), is studied by UV-visible spectroscopy, NMR spectroscopy, and mass spectrometry. Coordination of the monodentate thiol ligands to the ruthenium complex takes place upon heating to 353 K, but full conversion to the protected complex [Ru(tpy)(bpy)(SR)]PF6 is only possible when a large excess of ligand is used. Isolation and characterization of the two new thiolato complexes [Ru(tpy)(bpy)(κS-HCys)]PF6 ([2]PF6) and [Ru(tpy)(bpy)(κS-HAcys)]PF6 ([3]PF6) is reported. [3]PF6 shows a metal-to-ligand charge-transfer absorption band that is red shifted (λmax=492 nm in water) compared to its methionine analogue [Ru(tpy)(bpy)(κS-HAmet)](Cl)2 ([5](Cl)2, λmax=452 nm; HAmet=N-acetyl-methionine). In the dark the thiolate ligand coordinated to ruthenium is oxidized even by traces of oxygen, which first leads to the sulfenato, sulfinato, and disulfide ruthenium complexes, and finally to the formation of the aqua complex [1](2+). [3]PF6 showed slow photosubstitution of the thiolate ligand by water under blue light irradiation, together with faster photooxidation of the thiolate ligand compared to dark conditions. The use of thiol vs. thioether monodentate ligands is discussed for the protection of anticancer ruthenium-based prodrugs. PMID:26187140

  9. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL: THEORETICAL BASIS AND PRELIMINARY EVALUATION

    EPA Science Inventory

    The theoretical basis, physical structure, and preliminary evaluation of the U.S. Environmental Protection Agency's Complex Terrain Dispersion Model (CTDM) are described. CTDM is a point-source plume model designed primarily to estimate windward-side surface concentrations on dis...

  10. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL DEVELOPMENT: THIRD MILESTONE REPORT 1983

    EPA Science Inventory

    The U.S. Environmental Protection Agency is sponsoring the Complex Terrain Model Development program, a multi-year integrated program to develop and validate practical plume dispersion models of known reliability and accuracy for simulating one-hour-average ground-level concentra...

  11. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL DEVELOPMENT. FOURTH MILESTONE REPORT - 1984

    EPA Science Inventory

    The U.S. Environmental Protection Agency is sponsoring the Complex Terrain Development program, a multi-year integrated program to develop, and validate practical plume dispersion models of known reliability and accuracy for simulating one-hour-average ground-level concentrations...

  12. Astrocyte-Specific Overexpression of Nrf2 Protects Striatal Neurons from Mitochondrial Complex II Inhibition

    PubMed Central

    Calkins, Marcus J.; Vargas, Marcelo R.; Johnson, Delinda A.; Johnson, Jeffrey A.

    2010-01-01

    Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that is known to regulate a variety of cytoprotective genes through the antioxidant response element (ARE). This endogenous response is one of the major pathways by which cells are protected from xenobiotic or innate oxidative insults. Furthermore, in neural systems, astrocyte-specific activation of Nrf2 is known to protect neurons. In previous work, our laboratory found that Nrf2 protects from intrastriatal injections of the mitochondrial complex II inhibitor malonate. Here, we extend these results to show that multiple methods of astrocyte-specific Nrf2 overexpression provide protection from neurotoxicity in vivo. GFAP-Nrf2 transgenic mice are significantly more resistant to malonate lesioning. This outcome is associated with an increased basal resistance, but more so, an enhanced Nrf2 response to lesioning that attenuated the ensuing neurotoxicity. Furthermore, striatal transplantation of neuroprogenitor cells overexpressing Nrf2 that differentiate into astrocytes after grafting also significantly reduced malonate toxicity. Overall, these data establish that enhanced astrocytic Nrf2 response and Nrf2 preconditioning are both sufficient to protect from acute lesions from mitochondrial complex II inhibition. PMID:20211941

  13. Iron-Scytonemin Complexes: DFT Calculations on New UV Protectants for Terrestrial Cyanobacteria and Astrobiological Implications

    NASA Astrophysics Data System (ADS)

    Varnali, Tereza; Edwards, Howell G. M.

    2010-09-01

    Cyanobacterial colonies produce the radiation-protectant biomolecule scytonemin as part of their response strategy for survival in environmentally stressed conditions in hot and cold deserts. These colonies frequently use sandstone rocks as host matrices for subsurface colonization, which is accompanied by a zone of depletion of iron and transportation of iron compounds to the mineral surface. It is suggested that an iron-scytonemin complex could feature in this survival strategy and facilitate the movement of iron through the rock. Calculations were as host matrices for subsurface colonization, which is accompanied by a zone of depletion of iron and transportation of iron compounds to the mineral surface. It is suggested that an iron-scytonemin complex could feature in this survival strategy and facilitate the movement of iron through the rock. Calculations were carried out on several hypothetical iron-scytonemin complexes to evaluate the most stable structure energetically and examine the effect of the complexation of the biomolecule upon the electronic absorption characteristics of the radiation-protectant species. The implications for extraterrestrial planetary detection and analytical monitoring of an iron-scytonemin complex are assessed.

  14. Protection against fire in the mountainous forests of Greece case study: forest complex of W. Nestos

    NASA Astrophysics Data System (ADS)

    Drosos, Vasileios C.; Giannoulas, Vasileios J.; Stergiadou, Anastasia; Karagiannis, Evaggelos; Doukas, Aristotelis-Kosmas G.

    2014-08-01

    Forest fires are an ancient phenomenon. Appear, however, with devastating frequency and intensity over the last 30 years. In our country, the climatic conditions in combination with the intense relief, favor their rapid spread. Considering the fact that environmental conditions provided for decades even worse (increased temperature, drought and vegetation), then the problem of forest fires in our country, is expected to become more intense. The work focuses on the optimization model of the opening up of the forest mountain areas taking into account the prevention and suppression of forest fires. Research area is the mountain forest complex of W. Nestos of Drama Prefecture. The percentage of forest protection area is examined under the light whether the total hose length corresponds to the actual operational capacity to reach a fire source. For this reason are decided to present a three case study concerning area of the forest being protected by fire extinguishing vehicles. The first one corresponds to a fire suppression bandwidth (buffer zone) with a capacity radius of 150m uphill and 250m downhill from the origin point where the fire extinguishing vehicle stands. The second one corresponds to a fire suppression capacity of 200m uphill and 400m downhill and the third one corresponds to a fire suppression capacity of 300m uphill and 500m downhill. The most important forest technical infrastructures to prevent fire are roads network (opening up) for fire protection and buffer zones. Patrols of small and agile 4 × 4 appropriately equipped (pipe length of 500 meters and putting pressure on uphill to 300 meters) for the first attack of the fire in the summer months coupled with early warning of fire observatories adequately cover the forest protection of W. Nestos complex. But spatial distribution needed improvements to a road density of the optimum economic Dec, both forest protection and for better management (skidding) of woody capital.

  15. Coronavirus genomic and subgenomic minus-strand RNAs copartition in membrane-protected replication complexes.

    PubMed Central

    Sethna, P B; Brian, D A

    1997-01-01

    The majority of porcine transmissible gastroenteritis coronavirus plus-strand RNAs (genome and subgenomic mRNAs), at the time of peak RNA synthesis (5 h postinfection), were not found in membrane-protected complexes in lysates of cells prepared by Dounce homogenization but were found to be susceptible to micrococcal nuclease (85%) or to sediment to a pellet in a cesium chloride gradient (61%). They therefore are probably free molecules in solution or components of easily dissociable complexes. By contrast, the majority of minus-strand RNAs (genome length and subgenomic mRNA length) were found to be resistant to micrococcal nuclease (69%) or to remain suspended in association with membrane-protected complexes following isopycnic sedimentation in a cesium chloride gradient (85%). Furthermore, 35% of the suspended minus strands were in a dense complex (1.20 to 1.24 g/ml) that contained an RNA plus-to-minus-strand molar ratio of approximately 8:1 and viral structural proteins S, M, and N, and 65% were in a light complex (1.15 to 1.17 g/ml) that contained nearly equimolar amounts of plus- and minus-strand RNAs and only trace amounts of proteins M and N. In no instance during fractionation were genome-length minus strands found segregated from sub-genome-length minus strands. These results indicate that all minus-strand species are components of similarly structured membrane-associated replication complexes and support the concept that all are active in the synthesis of plus-strand RNAs. PMID:9311859

  16. Architecture of the botulinum neurotoxin complex: a molecular machine for protection and delivery

    PubMed Central

    Lam, Kwok-Ho; Jin, Rongsheng

    2015-01-01

    Botulinum neurotoxins (BoNTs) are extremely poisonous protein toxins that cause the fatal paralytic disease botulism. They are naturally produced in bacteria with several nontoxic neurotoxin-associated proteins (NAPs) and together they form a progenitor toxin complex (PTC), the largest bacterial toxin complex known. In foodborne botulism, the PTC functions as a molecular machine that helps BoNT breach the host defense in the gut. Here, we discuss the substantial recent advance in elucidating the atomic structures and assembly of the 14-subunit PTC, including structures of BoNT and four NAPs. These structural studies shed light on the molecular mechanisms by which BoNT is protected against the acidic environment and proteolytic destruction in the gastrointestinal tract, and how it is delivered across the intestinal epithelial barrier. PMID:25889616

  17. Malin and laforin are essential components of a protein complex that protects cells from thermal stress.

    PubMed

    Sengupta, Sonali; Badhwar, Ishima; Upadhyay, Mamta; Singh, Sweta; Ganesh, Subramaniam

    2011-07-01

    The heat-shock response is a conserved cellular process characterized by the induction of a unique group of proteins known as heat-shock proteins. One of the primary triggers for this response, at least in mammals, is heat-shock factor 1 (HSF1)--a transcription factor that activates the transcription of heat-shock genes and confers protection against stress-induced cell death. In the present study, we investigated the role of the phosphatase laforin and the ubiquitin ligase malin in the HSF1-mediated heat-shock response. Laforin and malin are defective in Lafora disease (LD), a neurodegenerative disorder associated with epileptic seizures. Using cellular models, we demonstrate that these two proteins, as a functional complex with the co-chaperone CHIP, translocate to the nucleus upon heat shock and that all the three members of this complex are required for full protection against heat-shock-induced cell death. We show further that laforin and malin interact with HSF1 and contribute to its activation during stress by an unknown mechanism. HSF1 is also required for the heat-induced nuclear translocation of laforin and malin. This study demonstrates that laforin and malin are key regulators of HSF1 and that defects in the HSF1-mediated stress response pathway might underlie some of the pathological symptoms in LD. PMID:21652633

  18. Capillary Liquid Chromatography Mass Spectrometry Analysis of Intact Monolayer-Protected Gold Clusters in Complex Mixtures.

    PubMed

    Black, David M; Bach, Stephan B H; Whetten, Robert L

    2016-06-01

    In some respects, large noble-metal clusters protected by thiolate ligands behave as giant molecules of definite composition and structure; however, their rigorous analysis continues to be quite challenging. Analysis of complex mixtures of intact monolayer-protected clusters (MPCs) by liquid chromatography mass spectrometry (LC-MS) could provide quantitative identification of the various components present. This advance is critical for biomedical and toxicological research, as well as in fundamental studies that rely on the identification of selected compositions. This work expands upon the separate LC and MS results previously achieved, by interfacing the capillary liquid chromatograph directly to the electrospray source of the mass spectrometer, in order to provide an extremely sensitive, quantitative, and rapid means to characterize MPCs and their derivatives far beyond that of earlier reports. Here, we show that nonaqueous reversed-phase chromatography can be coupled to mass-spectrometry detection to resolve complex mixtures in minute (∼100 ng) samples of gold MPCs, of molecular masses up to ∼40 kDa, and with single-species sensitivity easily demonstrated for components on the level of sub-10 ng or picomole (1 pmol). PMID:27216373

  19. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation

    PubMed Central

    Smith, Joan T.; Gaidamakova, Elena K.; Matrosova, Vera Y.; Grichenko, Olga; Knollmann-Ritschel, Barbara; Daly, Michael J.; Kiang, Juliann G.

    2016-01-01

    The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex (MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was investigated in a mouse model of radiation injury. MDP was previously reported to be extraordinarily radioprotective of proteins in the setting of vaccine development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected from a group of synthetic peptides screened in vitro for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR). We show that the peptides accumulated in Jurkat T-cells and protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed to 60,000 Gy. In vivo, MDP was nontoxic and protected B6D2F1/J (female) mice from acute radiation syndrome. All irradiated mice treated with MDP survived exposure to 9.5 Gy (LD70/30) in comparison to the untreated mice, which displayed 63% lethality after 30 days. Our results show that MDP provides early protection of white blood cells, and attenuates IR-induced damage to bone marrow and hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated the immunomodulation of several cytokine concentrations in serum including G-CSF, GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary prelude for future efforts towards clinical application of MDP as a promising IR countermeasure. Further investigation of MDP as a pre-exposure prophylactic and post-exposure therapeutic in radiotherapy and radiation emergencies is warranted. PMID:27500529

  20. MDP: A Deinococcus Mn2+-Decapeptide Complex Protects Mice from Ionizing Radiation.

    PubMed

    Gupta, Paridhi; Gayen, Manoshi; Smith, Joan T; Gaidamakova, Elena K; Matrosova, Vera Y; Grichenko, Olga; Knollmann-Ritschel, Barbara; Daly, Michael J; Kiang, Juliann G; Maheshwari, Radha K

    2016-01-01

    The radioprotective capacity of a rationally-designed Mn2+-decapeptide complex (MDP), based on Mn antioxidants in the bacterium Deinococcus radiodurans, was investigated in a mouse model of radiation injury. MDP was previously reported to be extraordinarily radioprotective of proteins in the setting of vaccine development. The peptide-component (DEHGTAVMLK) of MDP applied here was selected from a group of synthetic peptides screened in vitro for their ability to protect cultured human cells and purified enzymes from extreme damage caused by ionizing radiation (IR). We show that the peptides accumulated in Jurkat T-cells and protected them from 100 Gy. MDP preserved the activity of T4 DNA ligase exposed to 60,000 Gy. In vivo, MDP was nontoxic and protected B6D2F1/J (female) mice from acute radiation syndrome. All irradiated mice treated with MDP survived exposure to 9.5 Gy (LD70/30) in comparison to the untreated mice, which displayed 63% lethality after 30 days. Our results show that MDP provides early protection of white blood cells, and attenuates IR-induced damage to bone marrow and hematopoietic stem cells via G-CSF and GM-CSF modulation. Moreover, MDP mediated the immunomodulation of several cytokine concentrations in serum including G-CSF, GM-CSF, IL-3 and IL-10 during early recovery. Our results present the necessary prelude for future efforts towards clinical application of MDP as a promising IR countermeasure. Further investigation of MDP as a pre-exposure prophylactic and post-exposure therapeutic in radiotherapy and radiation emergencies is warranted. PMID:27500529

  1. Vacuolar compartmentation of the cadmium-glutathione complex protects Saccharomyces cerevisiae from mutagenesis.

    PubMed

    Adamis, Paula D B; Panek, Anita D; Eleutherio, Elis C A

    2007-08-30

    In the yeast Saccharomyces cerevisiae, gamma-glutamyl transferase (gamma-GT; EC 2.3.2.2) is a vacuolar-membrane bound enzyme. In this work we verified that S. cerevisiae cells deficient in gamma-GT absorbed almost 2.5-fold as much cadmium as the wild-type (wt) cells, suggesting that this enzyme might be responsible for the recycle of cadmium-glutathione complex stored in the vacuole. The mutant strain showed difficulty in keeping constant levels of glutathione (GSH) during the stress, although the GSH-reductase activity was practically the same in both wt and mutant strains, before and after metal stress. This difficulty to maintain the GSH levels in the gamma-GT mutant strain led to high levels of lipid peroxidation and carbonyl proteins in response to cadmium, higher than in the wt, but lower than in a mutant deficient in GSH synthesis. Although the increased levels of oxidative stress, gamma-GT mutant strain showed to be tolerant to cadmium and showed similar mutation rates to the wt, indicating that the compartmentation of the GSH-cadmium complex in vacuole protects cells against the mutagenic action of the metal. Confirming this hypothesis, a mutant strain deficient in Ycf1, which present high concentrations of GSH-cadmium in cytoplasm due to its deficiency in transport the complex to vacuole, showed increased mutation rates. PMID:17644279

  2. Compromising the 19S proteasome complex protects cells from reduced flux through the proteasome

    PubMed Central

    Tsvetkov, Peter; Mendillo, Marc L; Zhao, Jinghui; Carette, Jan E; Merrill, Parker H; Cikes, Domagoj; Varadarajan, Malini; van Diemen, Ferdy R; Penninger, Josef M; Goldberg, Alfred L; Brummelkamp, Thijn R; Santagata, Sandro; Lindquist, Susan

    2015-01-01

    Proteasomes are central regulators of protein homeostasis in eukaryotes. Proteasome function is vulnerable to environmental insults, cellular protein imbalance and targeted pharmaceuticals. Yet, mechanisms that cells deploy to counteract inhibition of this central regulator are little understood. To find such mechanisms, we reduced flux through the proteasome to the point of toxicity with specific inhibitors and performed genome-wide screens for mutations that allowed cells to survive. Counter to expectation, reducing expression of individual subunits of the proteasome's 19S regulatory complex increased survival. Strong 19S reduction was cytotoxic but modest reduction protected cells from inhibitors. Protection was accompanied by an increased ratio of 20S to 26S proteasomes, preservation of protein degradation capacity and reduced proteotoxic stress. While compromise of 19S function can have a fitness cost under basal conditions, it provided a powerful survival advantage when proteasome function was impaired. This means of rebalancing proteostasis is conserved from yeast to humans. DOI: http://dx.doi.org/10.7554/eLife.08467.001 PMID:26327695

  3. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    SciTech Connect

    Wang Danher; Hevey, Michael; Juompan, Laure Y.; Trubey, Charles M.; Raja, Nicholas U.; Deitz, Stephen B.; Woraratanadharm, Jan; Luo Min; Yu Hong; Swain, Benjamin M.; Moore, Kevin M.; Dong, John Y. . E-mail: dongj@genphar.com

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10{sup 7} pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.

  4. Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage

    PubMed Central

    Völkers, Mirko; Konstandin, Mathias H.; Doroudgar, Shirin; Toko, Haruhiro; Quijada, Pearl; Din, Shabana; Joyo, Anya; Ornelas, Luis; Samse, Kaitleen; Thuerauf, Donna J.; Gude, Natalie; Glembotski, Christopher C.; Sussman, Mark A.

    2014-01-01

    Background The mechanistic target of rapamycin (mTOR) comprises 2 structurally distinct multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2). Deregulation of mTOR signaling occurs during and contributes to the severity of myocardial damage from ischemic heart disease. However, the relative roles of mTORC1 versus mTORC2 in the pathogenesis of ischemic damage are unknown. Methods and Results Combined pharmacological and molecular approaches were used to alter the balance of mTORC1 and mTORC2 signaling in cultured cardiac myocytes and in mouse hearts subjected to conditions that mimic ischemic heart disease. The importance of mTOR signaling in cardiac protection was demonstrated by pharmacological inhibition of both mTORC1 and mTORC2 with Torin1, which led to increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. Predominant mTORC1 signaling mediated by suppression of mTORC2 with Rictor similarly increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. In comparison, preferentially shifting toward mTORC2 signaling by inhibition of mTORC1 with PRAS40 led to decreased cardiomyocyte apoptosis and tissue damage after myocardial infarction. Conclusions These results suggest that selectively increasing mTORC2 while concurrently inhibiting mTORC1 signaling is a novel therapeutic approach for the treatment of ischemic heart disease. PMID:24008870

  5. Morphological characterisation of complex powder used for protective coatings for geothermal plant components

    NASA Astrophysics Data System (ADS)

    Csaki, I.; Karlsdottir, S. N.; Buzaianu, A.; Serghiuta, S.; Popescu, G.; Motoiu, V. A.; Ragnarstottir, K. R.; Guðlaugsson, S.

    2016-06-01

    This paper aims to review the morphological characteristics, microstructures, physical and chemical properties of two complex composite powders: Ni18Cr5Si2B and Ni21Cr11Al2.5Y. These powders will be used as an option for coating geothermal turbine blades to prevent corrosion. The corrosion process in the steam turbine results in damages being recognized as the leading cause of reduced availability in geothermal power plants and is depends on temperature, mechanical and vaporous carryover of impurities and water treatment. Thermal spraying is a suitable technique for coating layers with wear and corrosion resistance. Therefore this technique could be successfully used in geothermal applications for obtaining coatings layers from new complex composite powders protecting the turbine blades from corrosions and good control of steam chemistry. The composite powders were investigated using X-ray diffraction and electronic microscopy to provide detailed information about composites morphological modifications. The results obtained after morphological evaluation are encouraging for using these composite powders as an option for coating geothermal components using thermal spraying technique.

  6. Entangling the complexity of protected area management: the case of Wolong Biosphere Reserve, southwestern China.

    PubMed

    Fu, Bojie; Wang, Kelin; Lu, Yihe; Liu, Shiliang; Keming, Ma; Chen, Liding; Liu, Guohua

    2004-06-01

    Protected Area (PA) management is a complex issue that requires the consideration of many factors and relationships. A conceptual framework for the analysis of biodiversity change, local human communities, and PA management was put forward, accordingly. Under the framework, we investigated the economic status, livelihood activities, biodiversity use and perceptions of local communities, and the land use history in Wolong Biosphere Reserve, southwestern China through household survey and document review in order to gain a better understanding of the complexity of PA management. According to the land use history, the preservation of agro-biodiversity, and the raising of productivity, ecological rehabilitation and the regulation of the human pressures are indispensable in the management of the reserve. Livelihood activities and the perceptions of local communities were largely determined by the socioeconomic background, which has important implications in solving the conflicts or incompatibilities in the reserve. In Wolong Biosphere Reserve, it is beneficial to support local farmers in solving their socioeconomic problems such as the overabundance of labor force and the lack of livelihood alternatives. Without this, there will be scarcely any effective biodiversity conservation and successful reserve management in the long term. PMID:15517679

  7. Calculating the Lightning Protection System Downconductors' Grounding Resistance at Launch Complex 39B, Kennedy Space Center

    NASA Technical Reports Server (NTRS)

    Mata, Carlos T.; Mata, Angel G.

    2012-01-01

    A new Lightning Protection System (LPS) was designed and built at Launch Complex 39B (LC39B), at the Kennedy Space Center (KSC), Florida, which consists of a catenary wire system (at a height of about 181 meters above ground level) supported by three insulators installed atop three towers in a triangular configuration. Nine downconductors (each about 250 meters long) are connected to the catenary wire system. Each downconductor is connected to a 7.62-meter-radius circular counterpoise conductor with six equally spaced, 6-meter-long vertical grounding rods. Grounding requirements at LC39B call for all underground and aboveground metallic piping, enclosures, raceways, and cable trays, within 7.62 meters of the counterpoise, to be bonded to the counterpoise, which results in a complex interconnected grounding system, given the many metallic piping, raceways, and cable trays that run in multiple directions around LC39B. The complexity of this grounding system makes the fall-of-potential method, which uses multiple metallic rods or stakes, unsuitable for measuring the grounding impedances of the downconductors. To calculate the grounding impedance of the downconductors, an Earth Ground Clamp (EGC) (a stakeless device for measuring grounding impedance) and an Alternative Transient Program (ATP) model of the LPS are used. The EGC is used to measure the loop impedance plus the grounding impedance of each downconductor, and the ATP model is used to calculate the loop impedance of each downconductor circuit. The grounding resistance of the downconductors is then calculated by subtracting the ATP calculated loop impedances from the EGC measurements.

  8. The Protective Antigen Component of Anthrax Toxin Forms Functional Octameric Complexes

    PubMed Central

    Kintzer, Alexander F.; Thoren, Katie L.; Sterling, Harry J.; Dong, Ken C.; Feld, Geoffrey K.; Tang, Iok I.; Zhang, Teri T.; Williams, Evan R.; Berger, James M.; Krantz, Bryan A.

    2009-01-01

    The assembly of bacterial toxins and virulence factors is critical to their function, but the regulation of assembly during infection has not been studied. We begin to address this question using anthrax toxin as a model. The protective antigen (PA) component of the toxin assembles into ring-shaped homooligomers that bind the two other enzyme components of the toxin, lethal factor (LF) and edema factor (EF), to form toxic complexes. To disrupt the host, these toxic complexes are endocytosed, such that the PA oligomer forms a membrane-spanning channel that LF and EF translocate through to enter the cytosol. We show using single-channel electrophysiology that PA channels contain two populations of conductance states, which correspond with two different PA pre-channel oligomers observed by electron microscopy—the well-described heptamer and a novel octamer. Mass spectrometry demonstrates that the PA octamer binds four LFs, and assembly routes leading to the octamer are populated with even-numbered, dimeric and tetrameric, PA intermediates. Both heptameric and octameric PA complexes can translocate LF and EF with similar rates and efficiencies. Here we also report a 3.2-Å crystal structure of the PA octamer. The octamer comprises ∼20−30% of the oligomers on cells, but outside of the cell, the octamer is more stable than the heptamer under physiological pH. Thus the PA octamer is a physiological, stable, and active assembly state capable of forming lethal toxins that may withstand the hostile conditions encountered in the bloodstream. This assembly mechanism may provide a novel means to control cytotoxicity. PMID:19627991

  9. Mutations Causing Complex Disease May under Certain Circumstances Be Protective in an Epidemiological Sense.

    PubMed

    Siegert, Sabine; Wolf, Andreas; Cooper, David N; Krawczak, Michael; Nothnagel, Michael

    2015-01-01

    Guided by the practice of classical epidemiology, research into the genetic basis of complex disease has usually taken for granted the dictum that causative mutations are invariably over-represented among clinically affected as compared to unaffected individuals. However, we show that this supposition is not true and that a mutation contributing to the etiology of a complex disease can, under certain circumstances, be depleted among patients. Populations with defined disease prevalence were repeatedly simulated under a Wright-Fisher model, assuming various types of population history and genotype-phenotype relationship. For each simulation, the resulting mutation-specific population frequencies and odds ratios (ORs) were evaluated. In addition, the relationship between mutation frequency and OR was studied using real data from the NIH GWAS catalogue of reported phenotype associations of single-nucleotide polymorphisms (SNPs). While rare diseases (prevalence <1%) were found to be consistently caused by rare mutations with ORs>1, up to 20% of mutations causing a pandemic disease (prevalence 10-20%) had ORs<1, and their population frequency ranged from 0% to 100%. Moreover, simulation-based ORs exhibited a wide distribution, irrespective of mutation frequency. In conclusion, a substantial proportion of mutations causing common complex diseases may appear 'protective' in genetic epidemiological studies and hence would normally tend to be excluded, albeit erroneously, from further study. This apparently paradoxical result is explicable in terms of mutual confounding of the respective genotype-phenotype relationships due to a negative correlation between causal mutations induced by their common gene genealogy. As would be predicted by our findings, a significant negative correlation became apparent in published genome-wide association studies between the OR of genetic variants associated with a particular disease and the prevalence of that disease. PMID:26161957

  10. Building, characterising and catalytic activity testing of Co-C-protected amino acid complexes covalently grafted onto chloropropylated silica gel

    NASA Astrophysics Data System (ADS)

    Varga, G.; Timár, Z.; Csendes, Z.; Bajnóczi, É. G.; Carlson, S.; Canton, S. E.; Bagi, L.; Sipos, P.; Pálinkó, I.

    2015-06-01

    Co-C-protected amino acid (C-protected L-histidine, L-tyrosine, L-cysteine and L-cystine) complexes were covalently grafted onto chloropropylated silica gel, and the materials thus obtained were structurally characterised by mid/far IR and X-ray absorption spectroscopies. The superoxide dismutase-like activities of the substances were determined via the Beauchamp-Fridovich test reaction. It was found that covalent grafting and the preparation of the anchored complexes were successful in most cases. The coordinating groups varied upon changing the conditions of the syntheses. All materials displayed catalytic activity, although catalytic activities differed widely.

  11. Chiral copper(II) complex-catalyzed reactions of partially protected carbohydrates.

    PubMed

    Allen, C Liana; Miller, Scott J

    2013-12-20

    Catalyst-controlled regioselective functionalization of partially protected saccharide molecules is a highly important yet under-developed area of carbohydrate chemistry. Such reactions allow for the reduction of protecting group manipulation steps required in syntheses involving sugars. Herein, an approach to these processes using enantiopure copper-bis(oxazoline) catalysts to control couplings of electrophiles to various partially protected sugars is reported. In a number of cases, divergent regioselectivity was observed as a function of the enantiomer of catalyst that is used. PMID:24274325

  12. A Ribonucleoprotein Complex Protects the Interleukin-6 mRNA from Degradation by Distinct Herpesviral Endonucleases

    PubMed Central

    Muller, Mandy; Hutin, Stephanie; Marigold, Oliver; Li, Kathy H.; Burlingame, Al; Glaunsinger, Britt A.

    2015-01-01

    During lytic Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6), a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3’ untranslated region (UTR) that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Here, we pursued how this protective RNA element functions to maintain mRNA stability. Using affinity purification and mass spectrometry, we identified a set of proteins that associate specifically with the protective element. Although multiple proteins contributed to the escape mechanism, depletion of nucleolin (NCL) most severely impacted protection. NCL was re-localized out of the nucleolus during lytic KSHV infection, and its presence in the cytoplasm was required for protection. After loading onto the IL-6 3’ UTR, NCL differentially bound to the translation initiation factor eIF4H. Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the RNA, suggesting that interactions between proteins bound to distant regions of the mRNA are important for escape. Finally, we found that the IL-6 3’ UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX. These findings highlight how a multitude of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA. PMID:25965334

  13. A ribonucleoprotein complex protects the interleukin-6 mRNA from degradation by distinct herpesviral endonucleases.

    PubMed

    Muller, Mandy; Hutin, Stephanie; Marigold, Oliver; Li, Kathy H; Burlingame, Al; Glaunsinger, Britt A

    2015-05-01

    During lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection, the viral endonuclease SOX promotes widespread degradation of cytoplasmic messenger RNA (mRNA). However, select mRNAs escape SOX-induced cleavage and remain robustly expressed. Prominent among these is interleukin-6 (IL-6), a growth factor important for survival of KSHV infected B cells. IL-6 escape is notable because it contains a sequence within its 3' untranslated region (UTR) that can confer protection when transferred to a SOX-targeted mRNA, and thus overrides the endonuclease targeting mechanism. Here, we pursued how this protective RNA element functions to maintain mRNA stability. Using affinity purification and mass spectrometry, we identified a set of proteins that associate specifically with the protective element. Although multiple proteins contributed to the escape mechanism, depletion of nucleolin (NCL) most severely impacted protection. NCL was re-localized out of the nucleolus during lytic KSHV infection, and its presence in the cytoplasm was required for protection. After loading onto the IL-6 3' UTR, NCL differentially bound to the translation initiation factor eIF4H. Disrupting this interaction, or depleting eIF4H, reinstated SOX targeting of the RNA, suggesting that interactions between proteins bound to distant regions of the mRNA are important for escape. Finally, we found that the IL-6 3' UTR was also protected against mRNA degradation by the vhs endonuclease encoded by herpes simplex virus, despite the fact that its mechanism of mRNA targeting is distinct from SOX. These findings highlight how a multitude of RNA-protein interactions can impact endonuclease targeting, and identify new features underlying the regulation of the IL-6 mRNA. PMID:25965334

  14. Implementation of a complex of measures to fulfill the planetary protection requirements of the ExoMars-2016 mission

    NASA Astrophysics Data System (ADS)

    Khamidullina, Natalia; Novikova, Nataliya; Deshevaya, Elena; Orlov, Oleg; Guridov, Alexander; Zakharenko, Dmitry; Zaytseva, Olga

    2016-07-01

    The major purpose of the planetary protection program in the ExoMars-2016 mission is to forestall Mars contamination by terrestrial microorganisms. Since Martian descent module is not intended for biological experiments, ExoMars-2016 mission falls under COSPAR category IVa. Within the joint project co-sponsored by ESA and Roscosmos the European side holds full responsibility for ensuring a prescribed level of SC microbiological purity, while the Russian side is charged with compliance of the launch services provided on Baikonur technical complex with the planetary protection requirements that is, specifically, prevention of SC recontamination. To this end, a complex of measures was executed to control microbial contamination of cosmodrome facilities on the prescribed level which included: - regular decontamination of clean rooms using an effective disinfectant and impulse ultraviolet radiation that created favorable conditions for reliable functioning of the ESA clean tent, - replacement of airline filters in the Thermal Conditioning Unit (TCU) air duct for SC conditioning with pure air. The results of microbiological tests performed in the period of 2015 - 2016 lead to the conclusion that the Baikonur clean rooms (ISO class 8), TCU air ducts and Air Thermal Control System (ATCS) at launch site are ready for the launch campaign and that the Russian side fulfilled the planetary protection requirements of the ExoMars-2016 mission.

  15. [The health protection of Italian workers abroad: complex and varied but still guaranteed].

    PubMed

    Di Lorenzo, Luigi; Corfiati, Marisa; Cassano, Filippo

    2011-01-01

    The employment contracts for Italian working abroad are legally different. So many national laws, European Union (EU) directives and regulations should be applied concerning health and safety at work. This paper is aimed to clarify these features, focusing on their impact on workers' health surveillance. For originally transnational contracts the law applicable is chosen by the parties but in compliance with minimum standards of workers' health protection. An authorization by Italian Labour Minister is also needed for employment in non-EU countries requiring minimum protection conditions. Italian legislation is applied to temporary work abroad. Long-lasting or permanent abroad transfer is regulated as originally transnational work. Workers posted in a EU country should receive the same protection ensured by laws, regulations, collective agreements or arbitrations to resident workers. Health surveillance of workers hired or transferred to work abroad is performed by a occupational physician (OP) operating in the foreign country. Temporary abroad workers undergo health surveillance by the Italian OP. The workplace inspection could be conducted by the OP through audiovisual electronic systems, reserving the on-site visit to particular situations. The host employer is responsible for health surveillance of posted workers entrusted to a local OP. PMID:23393830

  16. Protection of polynucleotides against nuclease-mediated hydrolysis by complexation with schizophyllan.

    PubMed

    Mizu, Masami; Koumoto, Kazuya; Kimura, Taro; Sakurai, Kazuo; Shinkai, Seiji

    2004-07-01

    Schizophyllan is a beta-(1-->3)-D-glucan existing as a triple helix in water and as a single chain in dimethylsulfoxide (DMSO), respectively. As we already reported, when some homo-polynucleotide (for example, poly(dA) or poly(C)) is added to the schizophyllan/DMSO solution and subsequently DMSO is exchanged for water, the single chain of schizophyllan (s-SPG) forms a complex with the polynucleotide. The present work demonstrates that the polynucleotide bound in the complex is more stable to nuclease-mediated hydrolysis than the polynucleotide itself (i.e., naked polynucleotide), using high-performance liquid chromatography and ultraviolet absorbance technique. A kinetic study for the hydrolysis clarified that the simple Michaelis-Menten relation is held and the maximum velocity for the complex is one-sixth as small as that of the naked polynucleotide. This low hydrolysis rate for the complex suggests that s-SPG is applicable to a carrier for antisense oligonucleotides. PMID:14967545

  17. Calculating the Lightning Protection System Downconductors' Grounding Resistance at Launch Complex 39B, Kennedy Space Center, Florida

    NASA Technical Reports Server (NTRS)

    Mata, Carlos; Mata, Angel

    2011-01-01

    A new Lightning Protection System (LPS) was designed and built at Launch Complex 39B (LC39B), at the Kennedy Space Center (KSC). Florida, which consists of a catenary wire system (at a height of about 181 meters above ground level) supported by three insulation installed atop three towers in a triangular configuration. Nine downconductors (each about 250 meters long) are connected to the catenary wire system. Each downconductor is connected to a 7.62-meter-radius circular counterpoise conductor with six equally spaced. 6-meter-1ong vertical grounding rods. Grounding requirements at LC39B call for all underground and above ground metallic piping. enclosures, raceways. and. cable trays. within 7.62 meters of. counterpoise, to be bonded to the counterpoise, which results in a complex interconnected grounding system, given the many metallic piping, raceways and cable trays that run in multiple directions around LC39B.

  18. Molecular modeling of the human hemoglobin-haptoglobin complex sheds light on the protective mechanisms of haptoglobin.

    PubMed

    Nantasenamat, Chanin; Prachayasittikul, Virapong; Bulow, Leif

    2013-01-01

    Hemoglobin (Hb) plays a critical role in human physiological function by transporting O2. Hb is safe and inert within the confinement of the red blood cell but becomes reactive and toxic upon hemolysis. Haptoglobin (Hp) is an acute-phase serum protein that scavenges Hb and the resulting Hb-Hp complex is subjected to CD163-mediated endocytosis by macrophages. The interaction between Hb and Hp is extraordinarily strong and largely irreversible. As the structural details of the human Hb-Hp complex are not yet available, this study reports for the first time on insights of the binding modalities and molecular details of the human Hb-Hp interaction by means of protein-protein docking. Furthermore, residues that are pertinent for complex formation were identified by computational alanine scanning mutagenesis. Results revealed that the surface of the binding interface of Hb-Hp is not flat and protrudes into each binding partner. It was also observed that the secondary structures at the Hb-Hp interface are oriented as coils and α-helices. When dissecting the interface in more detail, it is obvious that several tyrosine residues of Hb, particularly β145Tyr, α42Tyr and α140Tyr, are buried in the complex and protected from further oxidative reactions. Such finding opens up new avenues for the design of Hp mimics which may be used as alternative clinical Hb scavengers. PMID:23638175

  19. Cattle with increased severity of bovine respiratory disease complex exhibit decreased capacity to protect against histone cytotoxicity.

    PubMed

    Matera, J A; Wilson, B K; Hernandez Gifford, J A; Step, D L; Krehbiel, C R; Gifford, C A

    2015-04-01

    Bovine respiratory disease complex (BRDC) is the leading cause of morbidity and mortality in feedlot cattle. Significant inflammation and lesions are often observed in lungs of infected cattle. During acute inflammatory responses, histones contribute to mortality in rodents and humans and serum proteins can protect against histone-induced cytotoxicity. We hypothesized that cattle experiencing chronic or fatal cases of BRDC have reduced ability to protect against cytotoxic effects of histones. Serum samples were collected from 66 bull calves at the time of normal feedlot processing procedures. Animals were retrospectively assigned to groups consisting of calves never treated for BRDC (control [CONT]; n = 10), calves treated with antimicrobials once for BRDC (1T; n = 16), calves treated twice for BRDC (2T; n = 13), calves treated 3 times for BRDC (3T; n = 14), or calves treated 4 times for BRDC (4T; n = 13). Samples were also collected each time animals received antimicrobial treatment; animals within a group were further sorted by calves that recovered and calves that died to test histone cytotoxicity. Bovine kidney cells were cultured in duplicate in 96-well plates and exposed to 0 or 50 μg/mL of total histones for 18 h with 1% serum from each animal. Cell viability was assessed by the addition of resazurin for 6 h followed by fluorescent quantification. Fluorescent values from serum alone were subtracted from values obtained for histone treatment for each animal. Serum from CONT, 1T, and 2T at initial processing all exhibited a similar (P > 0.10) response to histone treatment with fluorescent values of -312 ± 557, -1,059 ± 441, and -975 ± 489, respectively. However, 3T and 4T demonstrated an impaired capacity (P < 0.05) to protect against histones (-2,778 ± 471 and -3,026 ± 489) at initial processing when compared to the other groups. When sorted by mortality within group, calves that were treated twice and recovered (-847 ± 331) demonstrated a greater (P

  20. Critical Infrastructures as Complex Systems: A Multi-level Protection Architecture

    NASA Astrophysics Data System (ADS)

    Assogna, Pierluigi; Bertocchi, Glauco; Dicarlo, Antonio; Milicchio, Franco; Paoluzzi, Alberto; Scorzelli, Giorgio; Vicentino, Michele; Zollo, Roberto

    This paper describes a security platform as a complex system of holonic communities, that are hierarchically organized, but self-reconfigurable when some of them are detached or cannot otherwise operate. Furthermore, every possible subset of holons may work autonomously, while maintaining self-conscience of its own mission, action lines and goals. Each holonic unit, either elementary or composite, retains some capabilities for sensing (perception), transmissive apparatus (communication), computational processes (elaboration), authentication/authorization (information security), support for data exchange (visualization & interaction), actuators (mission), ambient representation (geometric reasoning), knowledge representation (logic reasoning), situation representation and forecasting (simulation), intelligent feedback (command & control). The higher the organizational level of the holonic unit, the more complex and sophisticated each of its characteristic features.

  1. Vitamin A Palmitate-β-cyclodextrin inclusion complexes: characterization, protection and emulsification properties.

    PubMed

    Vilanova, Neus; Solans, Conxita

    2015-05-15

    The interest in the production of foods enriched with vitamins, in order to prevent diseases related with their deficiency, has recently increased. However, the low stability and the low water solubility of certain vitamins make difficult their incorporation in foodstuff, especially in water-based formulations. This limitation is typically overcome by using encapsulating systems such as cyclodextrins. In this paper the formation of water-soluble inclusion complexes of Vitamin A Palmitate with β-cyclodextrins, without the use of organic solvents, is described. The objective was to increase the water solubility of Vitamin A Palmitate and its stability against different external factors to eventually enrich aqueous-based products. The stability of Vitamin A Palmitate in the complexes towards temperature, oxygen and UV light was investigated. All results showed a notably increase of Vitamin A Palmitate water solubility and stability in front of those variables when encapsulated. The surface activity of the complex suggests its possible use as stabilizer in emulsion formulations. PMID:25577116

  2. Functions that Protect Escherichia coli from Tightly Bound DNA-Protein Complexes Created by Mutant EcoRII Methyltransferase.

    PubMed

    Henderson, Morgan L; Kreuzer, Kenneth N

    2015-01-01

    Expression of mutant EcoRII methyltransferase protein (M.EcoRII-C186A) in Escherichia coli leads to tightly bound DNA-protein complexes (TBCs), located sporadically on the chromosome rather than in tandem arrays. The mechanisms behind the lethality induced by such sporadic TBCs are not well studied, nor is it clear whether very tight binding but non-covalent complexes are processed in the same way as covalent DNA-protein crosslinks (DPCs). Using 2D gel electrophoresis, we found that TBCs induced by M.EcoRII-C186A block replication forks in vivo. Specific bubble molecules were detected as spots on the 2D gel, only when M.EcoRII-C186A was induced, and a mutation that eliminates a specific EcoRII methylation site led to disappearance of the corresponding spot. We also performed a candidate gene screen for mutants that are hypersensitive to TBCs induced by M.EcoRII-C186A. We found several gene products necessary for protection against these TBCs that are known to also protect against DPCs induced with wild-type M.EcoRII (after 5-azacytidine incorporation): RecA, RecBC, RecG, RuvABC, UvrD, FtsK, XerCD and SsrA (tmRNA). In contrast, the RecFOR pathway and Rep helicase are needed for protection against TBCs but not DPCs induced by M.EcoRII. We propose that stalled fork processing by RecFOR and RecA promotes release of tightly bound (but non-covalent) blocking proteins, perhaps by licensing Rep helicase-driven dissociation of the blocking M.EcoRII-C186A. Our studies also argued against the involvement of several proteins that might be expected to protect against TBCs. We took the opportunity to directly compare the sensitivity of all tested mutants to two quinolone antibiotics, which target bacterial type II topoisomerases and induce a unique form of DPC. We uncovered rep, ftsK and xerCD as novel quinolone hypersensitive mutants, and also obtained evidence against the involvement of a number of functions that might be expected to protect against quinolones. PMID:25993347

  3. Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody.

    PubMed

    Dai, Lianpan; Song, Jian; Lu, Xishan; Deng, Yong-Qiang; Musyoki, Abednego Moki; Cheng, Huijun; Zhang, Yanfang; Yuan, Yuan; Song, Hao; Haywood, Joel; Xiao, Haixia; Yan, Jinghua; Shi, Yi; Qin, Cheng-Feng; Qi, Jianxun; Gao, George F

    2016-05-11

    Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.0 Å and in complex with a flavivirus broadly neutralizing murine antibody 2A10G6 at 3.0 Å. ZIKV-E resembles all the known flavivirus E structures but contains a unique, positively charged patch adjacent to the fusion loop region of the juxtaposed monomer, which may influence host attachment. The ZIKV-E-2A10G6 complex structure reveals antibody recognition of a highly conserved fusion loop. 2A10G6 binds to ZIKV-E with high affinity in vitro and neutralizes currently circulating ZIKV strains in vitro and in mice. The E protein fusion loop epitope represents a potential candidate for therapeutic antibodies against ZIKV. PMID:27158114

  4. Toxicity of cadmium and protective effect of bee honey, vitamins C and B complex.

    PubMed

    Abdelaziz, I; Elhabiby, M I; Ashour, A A

    2013-04-01

    The present work aimed to study the toxic effect of cadmium (Cd) on rabbits' blood indices, as well as the therapeutic effect of the antioxidant agents, vitamins C and B complex and bee honey on Cd intoxicated rabbits. Cadmium chloride (CdCl2) was injected subcutaneously at a dose of 3 mg/kg of body weight. The results showed a significant increase in serum glucose, triglycerides, cholesterol, total protein, albumin, globulin, urea and creatinine, compared to the control group. In addition, CdCl2 intoxication increased the levels of uric acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. Concerning haematological parameters, the more obvious changes were an increase in mean corpuscular volume and a decrease in white blood cells count, platelets, lymphocytes, heamatocrit, haemoglobin and red blood cells count. Treatment of CdCl2-intoxicated animals with vitamins C and B complex and bee honey showed a decrease in the harmful effects of Cd by restoring haematological and biochemical changes. Bee honey treatment was the most effective in providing recoveries in the altered blood parameters. PMID:23111883

  5. Effect of Metals in Biomimetic Dimetal Complexes on Affinity and Gas-Phase Protection of Phosphate Esters.

    PubMed

    Svane, Simon; Jørgensen, Thomas J D; McKenzie, Christine J; Kjeldsen, Frank

    2015-07-21

    Although the biomimetic dimetal complex [LGa2(OH)2(H2O)2](3+) [L = 2,6-bis((N,N'-bis(2-picolyl)amino)methyl)-4-tertbutylphenolate] provides efficient protection against phosphate loss in phosphopeptides upon collision-induced dissociation tandem mass spectrometry (CID MS/MS), the underlying mechanism remains unknown. Here, we explored the mechanism in detail and investigated the selective binding to phosphate groups in solution. Dimetal complexes containing combinations of Ga(3+), In(3+), Fe(3+), Co(3+), Zn(2+), Cu(2+), and V(2+) were reacted with HPO4(2-), phosphoserine, and a phosphopeptide (FQpSEEQQQTEDELQDK, abbreviated "βcas") and studied with isothermal titration calorimetry (ITC), CID MS/MS, and density functional theory (DFT). Ka for HPO4(2-) binding scaled with the metal charge and was 35-fold larger for [LGa2(OH)2(H2O)2](3+) (3.08 ± 0.31 × 10(6) M(-1)) than for [LZn2(HCOO)2](+). CID MS/MS of [LGa2(βcas)](n+) revealed protection against phosphate detachment (<3% of the total ion intensity). Phosphate detachment from βcas was 22-40% and increased to 42-71% when bound to dimetal complexes of lower charge than {LGa2}(5+). CID data suggests that facile metal-phosphate dissociation is associated with proton transfer from the intermediate oxazoline ring formed in the phosphopeptide to the metal-phosphate complex. The observed phosphate stabilization was attributed to a significant reduction in the gas-phase basicity (GB) of the phosphate group when bound to {LGa2}(5+)/{LIn2}(5+) complex cores. Absence of proton transfer results in formation of an ion-zwitterion intermediate with a greater dissociation threshold. This hypothesis is supported by DFT calculations for [LGa2(PO4)](2+), [LGaZn(PO4)](+), [LZn2(PO4)], and 2,4-dimethyl-3-oxazoline showing that [LGa2(PO4)](2+) is the only compound with a substantial lower GB (321 kJ/mol less) than 2,4-dimethyl-3-oxazoline. PMID:26068532

  6. Protection of Metal Artifacts with the Formation of Metal–Oxalates Complexes by Beauveria bassiana

    PubMed Central

    Joseph, Edith; Cario, Sylvie; Simon, Anaële; Wörle, Marie; Mazzeo, Rocco; Junier, Pilar; Job, Daniel

    2012-01-01

    Several fungi present high tolerance to toxic metals and some are able to transform metals into metal–oxalate complexes. In this study, the ability of Beauveria bassiana to produce copper oxalates was evaluated. Growth performance was tested on various copper-containing media. B. bassiana proved highly resistant to copper, tolerating concentrations of up to 20 g L−1, and precipitating copper oxalates on all media tested. Chromatographic analyses showed that this species produced oxalic acid as sole metal chelator. The production of metal–oxalates can be used in the restoration and conservation of archeological and modern metal artifacts. The production of copper oxalates was confirmed directly using metallic pieces (both archeological and modern). The conversion of corrosion products into copper oxalates was demonstrated as well. In order to assess whether the capability of B. bassiana to produce metal–oxalates could be applied to other metals, iron and silver were tested as well. Iron appears to be directly sequestered in the wall of the fungal hyphae forming oxalates. However, the formation of a homogeneous layer on the object is not yet optimal. On silver, a co-precipitation of copper and silver oxalates occurred. As this greenish patina would not be acceptable on silver objects, silver reduction was explored as a tarnishing remediation. First experiments showed the transformation of silver nitrate into nanoparticles of elemental silver by an unknown extracellular mechanism. The production of copper oxalates is immediately applicable for the conservation of copper-based artifacts. For iron and silver this is not yet the case. However, the vast ability of B. bassiana to transform toxic metals using different immobilization mechanisms seems to offer considerable possibilities for industrial applications, such as the bioremediation of contaminated soils or the green synthesis of chemicals. PMID:22291684

  7. Protection against lethal measles virus infection in mice by immune-stimulating complexes containing the hemagglutinin or fusion protein.

    PubMed Central

    Varsanyi, T M; Morein, B; Löve, A; Norrby, E

    1987-01-01

    The importance of each of the two surface glycoproteins of measles virus in active and passive immunization was examined in mice. Infected-cell lysates were depleted of either the hemagglutinin (H) or fusion (F) glycoprotein by using multiple cycles of immunoaffinity chromatography. The products were used to prepare immune-stimulating complexes (iscoms) containing either F or H glycoprotein. Such complexes are highly immunogenic, possibly as a result of effective presentation of viral proteins to the immune system [B. Morein, B. Sundquist, S. Höglund, K. Dalsgaard, and A. Osterhaus, Nature (London) 308:457-460, 1984]. Groups of 3-week-old BALB/c mice were inoculated with the iscom preparations. All animals developed hemolysis-inhibiting antibodies, whereas only sera of animals immunized with the iscoms containing the H glycoprotein had hemagglutination-inhibiting antibodies. Sera from animals immunized with the H or F preparation only precipitated the homologous glycoprotein in radioimmune precipitation assays. The immunized animals were challenged with a lethal dose of the hamster neurotropic variant of measles virus. Of the 7-week-old animals in the nonimmunized control group, 50% died within 10 days after challenge. No animals in the immunized groups showed symptoms of disease throughout the observation period of 3 months. Passive administration of anti-H monoclonal antibodies gave full protection against the 100% lethal acute infection with the hamster neurotropic variant of measles virus in newborn mice, whereas anti-F monoclonal antibodies failed to protect the animals. This study emphasizes that both H and F glycoproteins need to be considered in the development of measles virus subunit vaccines. Images PMID:2960833

  8. Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

    PubMed Central

    Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2014-01-01

    Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. PMID:25172947

  9. Evaluation of Grounding Impedance of a Complex Lightning Protective System Using Earth Ground Clamp Measurements and ATP Modeling

    NASA Technical Reports Server (NTRS)

    Mata, Carlos T.; Rakov, V. A.; Mata, Angel G.

    2010-01-01

    A new Lightning Protection System (LPS) was designed and built at Launch Complex 39B (LC39B), at the Kennedy Space Center (KSC), Florida, which consists of a catenary wire system (at a height of about 181 meters above ground level) supported by three insulators installed atop three towers in a triangular configuration. A total of nine downconductors (each about 250 meters long, on average) are connected to the catenary wire system. Each of the nine downconductors is connected to a 7.62-meter radius circular counterpoise conductor with six equally spaced 6-meter long vertical grounding rods. Grounding requirements at LC39B call for all underground and above ground metallic piping, enclosures, raceways, and cable trays, within 7.62 meters of the counterpoise, to be bounded to the counterpoise, which results in a complex interconnected grounding system, given the many metallic piping, raceways, and cable trays that run in multiple direction around LC39B. The complexity of this grounding system makes the fall of potential method, which uses multiple metallic rods or stakes, unsuitable for measuring the grounding impedances of the downconductors. To calculate the downconductors grounding impedance, an Earth Ground Clamp (a stakeless grounding resistance measuring device) and a LPS Alternative Transient Program (ATP) model are used. The Earth Ground Clamp is used to measure the loop impedance plus the grounding impedance of each downconductor and the ATP model is used to calculate the loop impedance of each downconductor circuit. The grounding impedance of the downconductors is then calculated by subtracting the ATP calculated loop impedances from the Earth Ground Clamp measurements.

  10. Cu(II)-disulfide complexes with superoxide dismutase- and catalase-like activities protect mitochondria and whole cells against oxidative stress.

    PubMed

    Aliaga, Margarita E; Sandoval-Acuña, Cristián; López-Alarcón, Camilo; Fuentes, Jocelyn; Speisky, Hernan

    2014-10-01

    Mitochondria are a major subcellular site of superoxide (O2(-)) formation. Conditions leading to an uncontrolled production, accumulation and/or conversion of O2(-) into hydrogen peroxide result in an increment in the intramitochondrial oxidative tone which, ultimately leads to the loss of cell viability. Recently, we reported on the ability of a series of Cu(II)-disulfide complexes to act simultaneously as SOD- and catalase-like molecules. In the present study, we addressed the potential of such compounds to protect mitochondria and cells against the oxidative stress and the cytolytic damage induced by diclofenac. Exposure of Caco-2 cells to diclofenac (250µM, 20min) led to a near 80% inhibition of mitochondrial complex I activity and almost doubled the rate of mitochondrial O2(-) production (assessed by Mitosox). A comparable increment was seen in whole cells when the oxidative tone was assessed through the largely hydrogen peroxide-dependent dichlorofluorescein (DCFH) oxidation. The increment in mitochondrial O2(-) production was totally and concentration-dependently prevented by the addition of the complexes formed between Cu(II) and the disulfides of glutathione, homocysteine, or a-dehydro-lipoic acid (20µM each); comparatively, the Cu(II)-cystine complex exerted a weaker protection. A comparable protection pattern was seen at the whole cell level, as these complexes were also effective in preventing the increment in DCFH oxidation. The mitochondrial and whole cell antioxidant protection also translated into a full protection against the cytolytic effects of diclofenac (45min). Results from the present study indicate that the here-tested Cu(II)-disulfides complexes are able to effectively protect cells against the oxidative and the lytic effects of O2(-)-overproducing mitochondria, suggesting a potential for these type of compounds to act as SOD- and catalase-like molecules under oxidative-stress conditions. Supported by FONDECYT #1110018. PMID:26461399

  11. Phase Retrieval from Modulus Using Homeomorphic Signal Processing and the Complex Cepstrum: An Algorithm for Lightning Protection Systems

    SciTech Connect

    Clark, G A

    2004-06-08

    In general, the Phase Retrieval from Modulus problem is very difficult. In this report, we solve the difficult, but somewhat more tractable case in which we constrain the solution to a minimum phase reconstruction. We exploit the real-and imaginary part sufficiency properties of the Fourier and Hilbert Transforms of causal sequences to develop an algorithm for reconstructing spectral phase given only spectral modulus. The algorithm uses homeomorphic signal processing methods with the complex cepstrum. The formal problem of interest is: Given measurements of only the modulus {vert_bar}H(k){vert_bar} (no phase) of the Discrete Fourier Transform (DFT) of a real, finite-length, stable, causal time domain signal h(n), compute a minimum phase reconstruction {cflx h}(n) of the signal. Then compute the phase of {cflx h}(n) using a DFT, and exploit the result as an estimate of the phase of h(n). The development of the algorithm is quite involved, but the final algorithm and its implementation are very simple. This work was motivated by a Phase Retrieval from Modulus Problem that arose in LLNL Defense Sciences Engineering Division (DSED) projects in lightning protection for buildings. The measurements are limited to modulus-only spectra from a spectrum analyzer. However, it is desired to perform system identification on the building to compute impulse responses and transfer functions that describe the amount of lightning energy that will be transferred from the outside of the building to the inside. This calculation requires knowledge of the entire signals (both modulus and phase). The algorithm and software described in this report are proposed as an approach to phase retrieval that can be used for programmatic needs. This report presents a brief tutorial description of the mathematical problem and the derivation of the phase retrieval algorithm. The efficacy of the theory is demonstrated using simulated signals that meet the assumptions of the algorithm. We see that for

  12. Vaccinia virus entry/fusion complex subunit A28 is a target of neutralizing and protective antibodies

    SciTech Connect

    Nelson, Gretchen E.; Sisler, Jerry R.; Chandran, Dev; Moss, Bernard

    2008-10-25

    The vaccinia virus entry/fusion complex (EFC) is comprised of at least eight transmembrane proteins that are conserved in all poxviruses. However, neither the physical structure of the EFC nor the immunogenicity of the individual components has been determined. We prepared soluble forms of two EFC components, A28 and H2, by replacing the transmembrane domain with a signal peptide and adding a polyhistidine tail. The proteins were expressed by baculoviruses, secreted from insect cells, purified by affinity chromatography and used to raise antibodies in rabbits. The antibodies recognized the viral proteins but only the antibody to recombinant A28 bound intact virions and neutralized infectivity. Analyses with a set of overlapping peptides revealed a neutralizing epitope between residues 73 and 92 of A28. Passive immunization of mice with IgG purified from the anti-A28 serum provided partial protection against a vaccinia virus intranasal challenge, whereas IgG from the anti-H2 serum did not.

  13. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL DEVELOPMENT DESCRIPTION OF A COMPUTER DATA BASE FROM SMALL HILL IMPACTION STUDY NO. 1, CINDER CONE BUTTE, IDAHO

    EPA Science Inventory

    As part of the U.S. Environmental Protection Agency's effort to develop and demonstrate a reliable model of atmospheric dispersion for pollutant emissions in irregular mountainous terrain, the Complex Terrain Model Development Program was initiated. The first phase, a comprehensi...

  14. Hydroxychloroquine protects melanocytes from autoantibody-induced injury by reducing the binding of antigen-antibody complexes.

    PubMed

    Li, Dong-Guang; Hu, Wen-Zhi; Ma, Hui-Jun; Liu, Wen; Yang, Qing-Qi; Zhao, Guang

    2016-08-01

    Vitiligo is a polygenic autoimmune disorder characterized by loss of pigmentation due to melanocyte destruction. Hydroxychloroquine (HCQ) is an effective immunosuppressant widely used in the treatment of autoimmune disorders. As generalized vitiligo (GV) is commonly considered to be a T cell and autoantibody-induced immune disorder, the present study aimed to determine whether HCQ protects melanocytes from autoantibody‑induced disruption. Anti‑melanocyte antibodies were obtained from the serum of patients with progressive GV and the effects of HCQ on prevent the autoantibody‑induced disruption of melanocytes was observed. Cell‑based ELISA, indirect immunofluorescence and western blotting were used to analyze the autoantibody content of sera samples obtained from 32 patients with progressive GV. The cytotoxicity of HCQ was detected by MTT assay, and 1 µg/ml HCQ was applied to human primary melanocytes (HMCs) to examine whether it could exert protective effects against autoantibody‑induced immune injury. Flow cytometry was used to measure autoantibody binding to the surface of HMCs. Complement‑dependent cytotoxicity (CDC) and antibody‑dependent cell‑mediated cytotoxicity (ADCC) were monitored by MTT and lactate dehydrogenase‑releasing assays. The concentration of autoantibodies in sera samples taken from GV patients was significantly higher than in controls, particularly in patients who had >10% of their body surface affected by vitiligo. The majority of the autoantibodies presented in the HMCs and human keratinocytes (HKCs) and were predominantly localized to the cell surface and cytoplasm. The molecular weights of the autoantigens were identified as 30, 37‑39, 42, 53, 60‑75, 90, 100, 110, and 126 kDa; the 30 kDa protein was observed only in HMCs. The addition of HCQ at a concentration of 1 µg/ml produced no significant cytotoxicity in HMCs and was demonstrated to reduce the binding of GV immunoglobulin G (IgG) to the surface of HMCs

  15. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-01

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense. PMID:26643168

  16. Inhibition of mitochondrial complex I by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action.

    PubMed

    Sandoval-Acuña, Cristian; Lopez-Alarcón, Camilo; Aliaga, Margarita E; Speisky, Hernán

    2012-07-30

    Mitochondrial dysfunction plays a major role in the development of oxidative stress and cytotoxicity induced by non-steroidal anti-inflammatory drugs (NSAIDs). A major objective of the present study was to investigate whether in vitro the NSAIDs, aspirin, indomethacin, diclofenac, piroxicam and ibuprofen, which feature different chemical structures, are able to inhibit mitochondrial complex I. All NSAIDs were effective inhibitors when added both, directly to mitochondria isolated from rat duodenum epithelium (50 μM) or to Caco-2 cells (250 μM). In the former system, complex I inhibition was concentration-dependent and susceptible to competition and reversion by the addition of coenzyme Q (32.5-520 μM). Based on reports suggesting a potential gastro-protective activity of quercetin, the ability of this flavonoid to protect isolated mitochondria against NSAIDs-induced complex I inhibition was evaluated. Low micromolar concentrations of quercetin (1-20 μM) protected against such inhibition, in a concentration dependent manner. In the case of aspirin, quercetin (5 μM) increased the IC50 by 10-fold. In addition, the present study shows that quercetin (5-10 μM) can behave as a "coenzyme Q-mimetic" molecule, allowing a normal electron flow along the whole electron transporting chain (complexes I, II, III and IV). The exposed findings reveal that complex I inhibition is a common deleterious effect of NSAIDs at the mitochondrial level, and that such effect is, for all tested agents, susceptible to be prevented by quercetin. Data provided here supports the contention that the protective action of quercetin resides on its, here for first time-shown, ability to behave as a coenzyme Q-like molecule. PMID:22652335

  17. Experimental and theoretical study of organometallic radiation-protective materials adapted to radiation sources with a complex isotopic composition

    NASA Astrophysics Data System (ADS)

    Russkikh, I. M.; Seleznev, E. N.; Tashlykov, O. L.; Shcheklein, S. E.

    2015-12-01

    The significance of optimizing the content of components of a radiation-protective material, which is determined by the isotopic composition of radioactive contamination, depending on the reactor type, operating time, and other factors is demonstrated. The results of computational and experimental investigation of the gamma-radiation attenuation capacity of homogenous radiation-protective materials with different fillers are reported.

  18. Child Protective Services: Complex Challenges Require New Strategies. Report to the to the Honorable Nydia Velazquez, House of Representatives.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC. Health, Education, and Human Services Div.

    At the request of the U.S. House of Representatives, this study identified problems confronting child protective service (CPS) units, which affect the system's capacity to protect children from abuse and neglect. State and local responses to these problems, and opportunities for the federal government to assist in improving the system's capacity…

  19. Experimental and theoretical study of organometallic radiation-protective materials adapted to radiation sources with a complex isotopic composition

    SciTech Connect

    Russkikh, I. M.; Seleznev, E. N.; Tashlykov, O. L. Shcheklein, S. E.

    2015-12-15

    The significance of optimizing the content of components of a radiation-protective material, which is determined by the isotopic composition of radioactive contamination, depending on the reactor type, operating time, and other factors is demonstrated. The results of computational and experimental investigation of the gamma-radiation attenuation capacity of homogenous radiation-protective materials with different fillers are reported.

  20. Synthesis and structural characterization of dioxomolybdenum and dioxotungsten hydroxamato complexes and their function in the protection of radiation induced DNA damage.

    PubMed

    Paul, Shiv Shankar; Selim, Md; Saha, Abhijit; Mukherjea, Kalyan K

    2014-02-21

    The synthesis and structural characterization of two novel dioxomolybdenum(VI) (1) and dioxotungsten(VI) (2) complexes with 2-phenylacetylhydroxamic acid (PAHH) [M(O)2(PAH)2] [M = Mo, W] have been accomplished. The dioxomolybdenum(VI) and dioxotungsten(VI) moiety is coordinated by the hydroxamate group (-CONHO(-)) of the 2-phenylacetylhydroxamate (PAH) ligand in a bi-dentate fashion. In both the complexes the PAHH ligand is coordinated through oxygen atoms forming a five membered chelate. The hydrogen atom of N-H of the hydroxamate group is engaged in intermolecular H-bonding with the carbonyl oxygen of another coordinated hydroxamate ligand, thereby forming an extended 1D chain. The ligand as well as both the complexes exhibit the ability to protect from radiation induced damage both in CTDNA as well as in pUC19 plasmid DNA. As the damage to DNA is caused by the radicals generated during radiolysis, its scavenging imparts protection from the damage to DNA. To understand the mechanism of protection, binding affinities of the ligand and the complex with DNA were determined using absorption and emission spectral studies and viscosity measurements, whereby the results indicate that both the complexes and the hydroxamate ligand interact with calf thymus DNA in the minor groove. The intrinsic binding constants, obtained from UV-vis studies, are 7.2 × 10(3) M(-1), 5.2 × 10(4) M(-1) and 1.2 × 10(4) M(-1) for the ligand and complexes 1 and 2 respectively. The Stern-Volmer quenching constants obtained from a luminescence study for both the complexes are 5.6 × 10(4) M(-1) and 1.6 × 10(4) M(-1) respectively. The dioxomolybdenum(VI) complex is found to be a more potent radioprotector compared to the dioxotungsten(VI) complex and the ligand. Radical scavenging chemical studies suggest that the complexes have a greater ability to scavenge both the hydroxyl as well as the superoxide radicals compared to the ligand. The free radical scavenging ability of the ligand and the

  1. An AIE-active boron-difluoride complex: multi-stimuli-responsive fluorescence and application in data security protection.

    PubMed

    Zhu, Xiaolin; Liu, Rui; Li, Yuhao; Huang, Hai; Wang, Qiang; Wang, Danfeng; Zhu, Xuan; Liu, Shishen; Zhu, Hongjun

    2014-11-01

    A novel AIE-active boron-difluoride complex (PTZ) was synthesized which exhibits multi-stimuli responsive characteristics. Its colours and emissions can be switched by mechanical grinding, organic solvent vapours and acid/base vapours. This complex can be utilized in data encryption and decryption based on the protonation-deprotonation effect. PMID:25220502

  2. Limitations of plasmid vaccines to complex viruses: selected myxoma virus antigens as DNA vaccines were not protective.

    PubMed

    Adams, Mathew M; van Leeuwen, Barbara H; Kerr, Peter J

    2004-11-25

    Myxoma virus, a poxvirus of the genus Leporipoxvirus, is the causative agent of the disease myxomatosis which is highly lethal in European rabbits (Oryctolagus cuniculus). Current vaccines to protect against myxomatosis are either attenuated live strains of the virus or the antigenically related rabbit fibroma virus. We examined the immune response of outbred domestic rabbits to the individual myxoma virus antigens M055R, M073R, M115L and M121R, delivered as DNA vaccines co-expressing rabbit interleukin-2 or interleukin-4. M115L and M121R were also delivered simultaneously. None of the vaccine constructs were able to protect the rabbits from disease or reduce mortality after challenge with virulent myxoma virus, despite induction of antigen-specific cell-mediated and humoral immune responses. PMID:15531037

  3. Multi-antigen vaccines based on complex adenovirus vectors induce protective immune responses against H5N1 avian influenza viruses.

    PubMed

    Holman, David H; Wang, Danher; Raja, Nicholas U; Luo, Min; Moore, Kevin M; Woraratanadharm, Jan; Mytle, Nutan; Dong, John Y

    2008-05-19

    There are legitimate concerns that the highly pathogenic H5N1 avian influenza virus could adapt for human-to-human transmission and cause a pandemic similar to the 1918 "Spanish flu" that killed 50 million people worldwide. We have developed pandemic influenza vaccines by incorporating multiple antigens from both avian and Spanish influenza viruses into complex recombinant adenovirus vectors. In vaccinated mice, these vaccines induced strong humoral and cellular immune responses against pandemic influenza virus antigens, and protected vaccinated mice against lethal H5N1 virus challenge. These results indicate that this multi-antigen, broadly protective vaccine may serve as a safer and more effective approach than traditional methods for development of a pandemic influenza vaccine. PMID:18395306

  4. A sensitive aptasensor for colorimetric detection of adenosine triphosphate based on the protective effect of ATP-aptamer complexes on unmodified gold nanoparticles.

    PubMed

    Huo, Yuan; Qi, Liang; Lv, Xiao-Jun; Lai, Ting; Zhang, Jing; Zhang, Zhi-Qi

    2016-04-15

    Adenosine triphosphate (ATP) is the most direct source of energy in organisms. This study is the first to demonstrate that ATP-aptamer complexes provide greater protection for unmodified gold nanoparticles (AuNPs) against salt-induced aggregation than either aptamer or ATP alone. This protective effect was confirmed using transmission electron microscopy, dynamic light scattering, Zeta potential measurement, and fluorescence polarization techniques. Utilizing controlled particle aggregation/dispersion as a gauge, a sensitive and selective aptasensor for colorimetric detection of ATP was developed using ATP-binding aptamers as the identification element and unmodified AuNPs as the probe. This aptasensor exhibited a good linear relationship between the absorbance and the logarithm concentration of ATP within a 50-1000 nM range. ATP analogs such as guanosine triphosphate, uridine triphosphate and cytidine triphosphate resulted in little or no interference in the determination of ATP. PMID:26638040

  5. TYK2 protein-coding variants protect against rheumatoid arthritis and autoimmunity, with no evidence of major pleiotropic effects on non-autoimmune complex traits.

    PubMed

    Diogo, Dorothée; Bastarache, Lisa; Liao, Katherine P; Graham, Robert R; Fulton, Robert S; Greenberg, Jeffrey D; Eyre, Steve; Bowes, John; Cui, Jing; Lee, Annette; Pappas, Dimitrios A; Kremer, Joel M; Barton, Anne; Coenen, Marieke J H; Franke, Barbara; Kiemeney, Lambertus A; Mariette, Xavier; Richard-Miceli, Corrine; Canhão, Helena; Fonseca, João E; de Vries, Niek; Tak, Paul P; Crusius, J Bart A; Nurmohamed, Michael T; Kurreeman, Fina; Mikuls, Ted R; Okada, Yukinori; Stahl, Eli A; Larson, David E; Deluca, Tracie L; O'Laughlin, Michelle; Fronick, Catrina C; Fulton, Lucinda L; Kosoy, Roman; Ransom, Michael; Bhangale, Tushar R; Ortmann, Ward; Cagan, Andrew; Gainer, Vivian; Karlson, Elizabeth W; Kohane, Isaac; Murphy, Shawn N; Martin, Javier; Zhernakova, Alexandra; Klareskog, Lars; Padyukov, Leonid; Worthington, Jane; Mardis, Elaine R; Seldin, Michael F; Gregersen, Peter K; Behrens, Timothy; Raychaudhuri, Soumya; Denny, Joshua C; Plenge, Robert M

    2015-01-01

    Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3 x 10(-21)), A928V (rs35018800, OR = 0.53, P = 1.2 x 10(-9)), and I684S (rs12720356, OR = 0.86, P = 4.6 x 10(-7)). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6 x 10(-18)), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; P(omnibus) = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases. PMID:25849893

  6. TYK2 Protein-Coding Variants Protect against Rheumatoid Arthritis and Autoimmunity, with No Evidence of Major Pleiotropic Effects on Non-Autoimmune Complex Traits

    PubMed Central

    Diogo, Dorothée; Bastarache, Lisa; Liao, Katherine P.; Graham, Robert R.; Fulton, Robert S.; Greenberg, Jeffrey D.; Eyre, Steve; Bowes, John; Cui, Jing; Lee, Annette; Pappas, Dimitrios A.; Kremer, Joel M.; Barton, Anne; Coenen, Marieke J. H.; Franke, Barbara; Kiemeney, Lambertus A.; Mariette, Xavier; Richard-Miceli, Corrine; Canhão, Helena; Fonseca, João E.; de Vries, Niek; Tak, Paul P.; Crusius, J. Bart A.; Nurmohamed, Michael T.; Kurreeman, Fina; Mikuls, Ted R.; Okada, Yukinori; Stahl, Eli A.; Larson, David E.; Deluca, Tracie L.; O'Laughlin, Michelle; Fronick, Catrina C.; Fulton, Lucinda L.; Kosoy, Roman; Ransom, Michael; Bhangale, Tushar R.; Ortmann, Ward; Cagan, Andrew; Gainer, Vivian; Karlson, Elizabeth W.; Kohane, Isaac; Murphy, Shawn N.; Martin, Javier; Zhernakova, Alexandra; Klareskog, Lars; Padyukov, Leonid; Worthington, Jane; Mardis, Elaine R.; Seldin, Michael F.; Gregersen, Peter K.; Behrens, Timothy; Raychaudhuri, Soumya; Denny, Joshua C.; Plenge, Robert M.

    2015-01-01

    Despite the success of genome-wide association studies (GWAS) in detecting a large number of loci for complex phenotypes such as rheumatoid arthritis (RA) susceptibility, the lack of information on the causal genes leaves important challenges to interpret GWAS results in the context of the disease biology. Here, we genetically fine-map the RA risk locus at 19p13 to define causal variants, and explore the pleiotropic effects of these same variants in other complex traits. First, we combined Immunochip dense genotyping (n = 23,092 case/control samples), Exomechip genotyping (n = 18,409 case/control samples) and targeted exon-sequencing (n = 2,236 case/controls samples) to demonstrate that three protein-coding variants in TYK2 (tyrosine kinase 2) independently protect against RA: P1104A (rs34536443, OR = 0.66, P = 2.3x10-21), A928V (rs35018800, OR = 0.53, P = 1.2x10-9), and I684S (rs12720356, OR = 0.86, P = 4.6x10-7). Second, we show that the same three TYK2 variants protect against systemic lupus erythematosus (SLE, Pomnibus = 6x10-18), and provide suggestive evidence that two of the TYK2 variants (P1104A and A928V) may also protect against inflammatory bowel disease (IBD; Pomnibus = 0.005). Finally, in a phenome-wide association study (PheWAS) assessing >500 phenotypes using electronic medical records (EMR) in >29,000 subjects, we found no convincing evidence for association of P1104A and A928V with complex phenotypes other than autoimmune diseases such as RA, SLE and IBD. Together, our results demonstrate the role of TYK2 in the pathogenesis of RA, SLE and IBD, and provide supporting evidence for TYK2 as a promising drug target for the treatment of autoimmune diseases. PMID:25849893

  7. Development of quercetin-phospholipid complex to improve the bioavailability and protection effects against carbon tetrachloride-induced hepatotoxicity in SD rats.

    PubMed

    Zhang, Kexia; Zhang, Meiyu; Liu, Ziying; Zhang, Yuanyuan; Gu, Liqiang; Hu, Gaosheng; Chen, Xiaohui; Jia, Jingming

    2016-09-01

    Quercetin (QT) is a natural flavonoid with various biological activities and pharmacological actions. However, the bioavailability of QT is relatively low due to its low solubility which severely limits its use. In this study, we intended to improve the bioavailability of QT by preparing quercetin-phospholipid complex (QT-PC) and investigate the protective effect of QT-PC against carbon tetrachloride (CCl4) induced acute liver damage in Sprague-Dawley (SD) rats. The physicochemical properties of QT-PC were characterized in terms of infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (XRPD) and water/n-octanol solubility. FTIR, DSC and XRPD data confirmed the formation of QT-PC. The water solubility of QT was improved significantly in the prepared complex, indicating its increased hydrophilicity. Oral bioavailability of QT and QT-PC was evaluated in SD rats, and the plasma QT was estimated by HPLC-MS. QT-PC exhibited higher Cmax (1.58±0.11 vs. 0.67±0.08μg/mL), increased AUC0-∞ (8.60±1.25 vs. 2.41±0.51mg/Lh) and t1/2z (7.76±1.09 vs. 4.81±0.87h) when compared to free QT. The greater absorption of QT-PC group suggested the improved bioavailability. Moreover, biochemical changes and histopathological observations revealed that QT-PC provided better protection to rat liver than free QT at the same dose. Thus, phospholipid complexation might be one of the suitable approaches to improve the oral bioavailability of QT and obtain better protective effects against CCl4 induced acute liver damage in SD rats than free QT at the same dose level. PMID:27431774

  8. Y-12 Groundwater Protection Program CY 2009 Triennial Report Of The Monitoring Well Inspection And Maintenance Program, Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2013-06-01

    This document is the triennial report for the Well Inspection and Maintenance Program of the Y- 12 Groundwater Protection Program (GWPP), at the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12). This report formally documents well inspection events conducted on active and inactive wells at Y-12 during calendar years (CY) 2007 through 2009; it documents well maintenance and plugging and abandonment activities completed since the last triennial inspection event (CY 2006); and provides summary tables of well inspection events, well maintenance events, and well plugging and abandonment events during the reference time period.

  9. Environmental assessment and finding of no significant impact for completion of flood protection works, Bannister Road Federal Complex, Kansas City, Missouri

    SciTech Connect

    Not Available

    1991-09-18

    The Department of Energy (DOE) proposes to provide partial funding to the Corps of Engineers (COE) for the completion of the flood protection works at the Bannister Road Federal Complex in Kansas City, Missouri. The DOE Kansas City Plant is a major tenant of the Complex. COE has prepared an environmental assessment (EA) for the project which includes the construction of levees, floodwalls, and drainage ditches. DOE has adopted the EA prepared by COE (DOE/EA-0509), this report. Based on the analyses in this EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969, 42 USC 4321 et seq. Therefore, the preparation of an environmental impact statement is not required, and DOE is issuing this Finding of No Significant Impact (FONSI).

  10. A tomato lycopene complex protects the kidney from cisplatin-induced injury via affecting oxidative stress as well as Bax, Bcl-2, and HSPs expression.

    PubMed

    Dogukan, Ayhan; Tuzcu, Mehmet; Agca, Can Ali; Gencoglu, Hasan; Sahin, Nurhan; Onderci, Muhittin; Ozercan, Ibrahim Hanifi; Ilhan, Necip; Kucuk, Omer; Sahin, Kazim

    2011-01-01

    complex has protective effects against cisplatin-induced nephrotoxicity and lipid peroxidation in rats. PMID:21391123

  11. Protective activity of Cynara scolymus L. leaf extract against chemically induced complex genomic alterations in CHO cells.

    PubMed

    Jacociunas, Laura Vicedo; de Andrade, Heloisa Helena Rodrigues; Lehmann, Mauricio; Pedersini, Larissa Wölfle; Ferraz, Alexandre de Barros Falcão; da Silva, Juliana; Dihl, Rafael Rodrigues

    2013-09-15

    Cynara scolymus L., popularly known as artichoke, has been widely used in traditional medicine as an herbal medicament for therapeutic purposes. The study aimed at assessing the protective activity of Cynara scolymus leaf extract (LE) against DNA lesions induced by the alkylating agent ethylmethnesulphonate (EMS) in Chinese hamster ovary cells (CHO). The ability of C. scolymus L. LE to modulate the mutagenicity of EMS was examined using the cytokinesis block micronucleus (CBMN) cytome assay in three antigenotoxic protocols, pre- post- and simultaneous treatments. In the pre-treatment, C. scolymus L. LE reduced the frequencies of MNi and NBUDs induced by EMS in the lower concentration. In contrast, at the highest concentration (5 mg/ml) artichoke enhanced the frequency of MNi, potentiating EMS genotoxicity. In the simultaneous treatment only the induction of MNi was repressed by the exposure of cells to C. scolymus L. LE. No modification in genotoxicity was observed in LE post-treatment. The results obtained in this study suggest that lower concentrations of artichoke prevent chemically induced genomic damage in mammalian cells. In this context, the protective activity of C. scolymus L. could be associated to its constitutive antioxidants compounds. PMID:23830816

  12. Evolution and Conservation on Top of the World: Phylogeography of the Marbled Water Frog (Telmatobius marmoratus Species Complex; Anura, Telmatobiidae) in Protected Areas of Chile.

    PubMed

    Victoriano, Pedro F; Muñoz-Mendoza, Carla; Sáez, Paola A; Salinas, Hugo F; Muñoz-Ramírez, Carlos; Sallaberry, Michel; Fibla, Pablo; Méndez, Marco A

    2015-01-01

    The Andean Altiplano has served as a complex setting throughout its history, driving dynamic processes of diversification in several taxa. We investigated phylogeographic processes in the Telmatobius marmoratus species complex occurring in this region by studying the geographic patterns of genetic variability, genealogies, and historical migration, using the cytochrome b (cyt-b) gene as a marker. DNA sequences from Telmatobius gigas and Telmatobius culeus, Bolivian species with an uncertain taxonomic status, were also included. Additionally, we evaluated the phylogenetic diversity (PD) represented within Chilean protected areas and the complementary contribution from unprotected populations. Phylogenetic reconstructions from 148 cyt-b sequences revealed 4 main clades, one of which corresponded to T. culeus. T. gigas was part of T. marmoratus clade indicating paraphyletic relationships. Haplotypes from Chilean and Bolivian sites were not reciprocally monophyletic. Geographic distribution of lineages, spatial Bayesian analysis, and migration patterns indicated that T. marmoratus displays a weaker geographic structure than expected based on habitat distribution and physiological requirements. Demographic and statistical phylogeography analyses pointed out to a scenario of recent population expansion and high connectivity events of a more recent age than the post Last Glacial Maximum, probably associated to more humid events in Altiplano. PD of T. marmoratus populations within protected areas represents 55.6% of the total estimated PD. The unprotected populations that would contribute the most to PD are Caquena and Quebe (21%). Recent evolutionary processes and paleoclimatic changes, potentially driving shifts in habitat connectivity levels and population sizes, could explain the phylogeographic patterns recovered herein. PMID:26245789

  13. Evaluation of soil corrosivity and aquifer protective capacity using geoelectrical investigation in Bwari basement complex area, Abuja

    NASA Astrophysics Data System (ADS)

    Adeniji, A. E.; Omonona, O. V.; Obiora, D. N.; Chukudebelu, J. U.

    2014-04-01

    Bwari is one of the six municipal area councils of the Federal Capital Territory (FCT), Abuja with its attendant growing population and infrastructural developments. Groundwater is the main source of water supply in the area, and urbanization and industrialization are the predominant contributors of contaminants to the hydrological systems. In order to guarantee a continuous supply of potable water, there is a need to investigate the vulnerability of the aquifers to contaminants emanating from domestic and industrial wastes. A total of 20 vertical electrical soundings using Schlumberger electrode array with a maximum half current electrodes separation of 300 m was employed. The results show that the area is characterized by 3-6 geoelectric subsurface layers. The measured overburden thickness ranges from 1.0 to 24.3 m, with a mean value of 7.4 m. The resistivity and longitudinal conductance of the overburden units range from 18 to 11,908 Ωm and 0.047 to 0.875 mhos, respectively. Areas considered as high corrosivity are the central parts with ρ < 180 Ωm. The characteristic longitudinal unit conductance was used to classify the area into zones of good (0.7-4.49 mhos), moderate (0.2-0.69 mhos), weak (0.1-0.19 mhos), and poor (<0.1) aquifer protective capacity. Zones characterized by materials of moderate to good protective capacity serve as sealing potential for the underlying hydrogeological system in the area. This study is aimed at delineating zones that are very prone to groundwater contamination from surface contaminants and subsurface soils that are corrosive to utility pipes buried underground. Hence the findings of this work will constitute part of the tools for groundwater development and management and structural/infrastructural development planning of the area.

  14. Y-12 Groundwater Protection Program Extent Of The Primary Groundwater Contaminants At The Y-12 National Security Complex

    SciTech Connect

    2013-12-01

    This report presents data summary tables and maps used to define and illustrate the approximate lateral extent of groundwater contamination at the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee. The data tables and maps address the primary (i.e., most widespread and mobile) organic, inorganic, and radiological contaminants in the groundwater. The sampling locations, calculated contaminant concentrations, plume boundary values, and paired map format used to define, quantify, delineate, and illustrate the approximate extent of the primary organic, inorganic, and radiological contaminants in groundwater at Y-12 are described.

  15. Immunostimulatory complexes containing Eimeria tenella antigens and low toxicity plant saponins induce antibody response and provide protection from challenge in broiler chickens.

    PubMed

    Berezin, V E; Bogoyavlenskyi, A P; Khudiakova, S S; Alexuk, P G; Omirtaeva, E S; Zaitceva, I A; Tustikbaeva, G B; Barfield, R C; Fetterer, R H

    2010-01-20

    Immunostimulating complexes (ISCOMs) are unique multimolecular structures formed by encapsulating antigens, lipids and triterpene saponins and are one of the most successful antigen delivery systems for microbial antigens. In the current study, both the route of administration and the antigen concentration of ISCOMs, containing Eimeria tenella antigens and saponins from native plants, were evaluated in their ability to stimulate humoral immunity and to protect chickens against a challenge infection with E. tenella. Broiler chickens were immunized with ISCOM preparations containing E. tenella antigens and the purified saponins Gg6, Ah6 and Gp7 isolated from Glycyrrhiza glabra, Aesculus hippocastanum and Gipsophila paniculata, respectively. The effects of the route of administration, dose of antigen and type of saponin used for construction of ISCOMs were evaluated for ability to stimulate serum IgG and IgM and to protect chickens against a homologous challenge. A single intranasal immunization was the most effective route for administering ISCOMs although the in ovo route was also quite effective. Dose titration experiments demonstrated efficacy after single immunization with various ISCOM doses but maximum effects were observed when ISCOMs contain 5-10mug antigen. Immunization of birds by any of the three routes with E. tenella antigens alone or antigens mixed with alum hydroxide adjuvant resulted in lower serum antibody and reduced protection to challenge relative to immunization with ISCOMs. Overall the results of this study confirm that significant immunostimulation and protection to challenge are achieved by immunization of chickens with ISCOMs containing purified saponins and native E. tenella antigens and suggest that ISCOMs may be successfully used to develop a safe and effective vaccine for prevention of avian coccidiosis. PMID:19879050

  16. Protection of gingival epithelium against complement-mediated damage by strong expression of the membrane attack complex inhibitor protectin (CD59).

    PubMed

    Rautemaa, R; Meri, S

    1996-01-01

    Adult periodontitis (AP) is a chronic inflammatory disease of the tooth-supporting apparatus. Activation products of the inflammation-inducing complement system have been detected in the gingival crevicular fluid at the site of gingival inflammation. In the present study, we examined whether evidence for ongoing complement activation in gingival tissues of patients with AP can be obtained. In light of the potential tissue-damaging effects of the complement system, we also examined how the gingival tissue is protected against the cytolytic activity of complement. Surgical and autopsy samples of AP (n = 18) and healthy (n = 11) gingiva were analyzed for the expression or deposition of the complement regulators protectin (CD59) and vitronectin (S-protein) and complement components C3d and C9 by indirect immunofluorescence microscopy with specific antibodies. In healthy gingiva, protection was strongly expressed on the membranes of epithelial cells and on the vascular endothelia of the underlying connective tissue. In AP, protectin was also strongly expressed by endothelial cells, but in the epithelia the expression was granular and weaker than in the healthy gingiva. Coarse granular deposits of complement components were seen in the subepithelial tissues of 61% (C3d), 39% (C9), and 33% (vitronectin) of AP patients, compared with 9% (one case in 11) in healthy controls. In addition, deposits of C3d, C9, and vitronectin were observed on the basement membranes of both pocket and oral epithelium of healthy and AP gingiva but not at sites of protectin expression. The results suggest an increased turnover of the complement system in the gingival tissues of AP patients. The gingival epithelium and connective tissue endothelia are well-protected against damage by the membrane attack complex of complement (MAC). Protection of the underlying connective tissue is insufficient, however, and may allow for deposition of MAC and autologous tissue damage in AP. PMID:8655761

  17. A System Dynamic Analysis approach to deal with complexity in water resources management: the case of groundwater protection in the Apulia region (Southern Italy)

    NASA Astrophysics Data System (ADS)

    Giordano, Raffaele; Pluchinotta, Irene; Brugnach, Marcela; Pagano, Alessandro

    2015-04-01

    The increasing complexity and uncertainty of water resources management is claiming changes in the role of tools and methods aiming to support decision makers. Complexity due to the densely interconnected networks in which decision-actors operate. Uncertainty arises because of the fact that whatever action other decision agents involved in the network are going to do is largely unknown. In these complex and uncertain environments, it is very difficult to determine how effective a policy will be. Part of the difficulty resides in the fact that any action choice will influence and be influenced by the actions choices of the other actors. While these interactions among a diversity of actors may contribute to the development of beneficial adaptive behaviours, they can also result in dysfunctional dynamics, often leading to policy resistance. Action choices are not neutral, but commensurate with the problem frames held by the actors making the decisions. Our research hypothesis is that neglecting differences in problem framings leads decision makers to oversimplify the complexity of the interactions within the system to be managed, and to act as if the system is as simple as the decision makers presume it to be. Therefore, decision tools and methodologies should support the decision makers to become aware of the complexity of the interaction space, to disclose and analyse the existing interconnections, and to govern those interactions. In these circumstances, decision makers could take advantage from the interactional nature of the knowledge creation process. In order to demonstrate the research hypothesis, a methodology based on System Dynamic Modelling (SDM) was implemented in the Apulia Region (Southern Italy) to support the implementation of the groundwater (GW) protection policy. Due to the increasing of GW withdrawal for irrigation purposes, several phenomena are drastically reducing the quality of the GW resources. In order to protect the quality of GW, the

  18. Supplementary chromium(III) propionate complex does not protect against insulin resistance in high-fat-fed rats.

    PubMed

    Król, Ewelina; Krejpcio, Zbigniew; Iwanik, Katarzyna

    2014-02-01

    Improper eating habits such as high-fat or high-carbohydrate diets are responsible for metabolic changes resulting in impaired glucose tolerance, hyperinsulinemia, insulin resistance, and ultimately diabetes. Although the essentiality of trivalent chromium for humans has been recently questioned by researchers, pharmacological dosages of this element can improve insulin sensitivity in experimental animals and diabetic subjects. The aim of the study was to assess the preventive potential of the supplementary chromium(III) propionate complex (CrProp) in rats fed a high-fat diet. The experiment was conducted on 32 male Wistar rats divided into four groups and fed the following diets: the control (C, AIN-93G), high-fat diets (HF, 40% energy from fat), and a high-fat diet supplemented with CrProp at dosages of 10 and 50 mg Cr/kg diet (HF + Cr10 and HF + Cr50, respectively). After 8 weeks, high-fat feeding led to an increased body mass, hyperinsulinemia, insulin resistance, a decreased serum urea concentration, accumulation of lipid droplets in hepatocytes, and increased renal Fe and splenic Cu contents. Supplementary CrProp in both dosages did not alleviate these changes but increased renal Cr content and normalized splenic Cu content in high-fat-fed rats. Supplementary CrProp does not prevent the development of insulin resistance in rats fed a high-fat diet. PMID:24415067

  19. Groundwater Protection Program Management Plan for the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2001-06-01

    This document presents the Groundwater Protection Program (GWPP) management plan for the U.S. Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12). The Y-12 GWPP functions as the primary point-of-contact for groundwater-related issues at Y-12, provides stewardship of the extensive network of groundwater monitoring wells at Y-12, and serves as a resource for technical expertise, support, and historical data for groundwater-related activities at Y-12. These organizational functions each serve the primary programmatic purpose of the GWPP, which is to ensure that groundwater monitoring activities within areas under Y-12 administrative control provide representative data in compliance with the multiple purposes of applicable state and federal regulations, DOE orders, and the corporate policies of BWXT Y-12, L.L.C. (hereafter referenced as BWXT Y-12), the Y-12 management and operations (M and O) subcontractor for DOE.

  20. Membrane attack complex (MAC)-mediated damage to spermatozoa: protection of the cells by the presence on their membranes of MAC inhibitory proteins.

    PubMed Central

    Rooney, I A; Davies, A; Morgan, B P

    1992-01-01

    Although antibody and complement are known to cause immobilization and killing of spermatozoa in vitro the components of the complement system mediating these effects remain undefined. Here we have examined the effects of the membrane attack complex (MAC) on spermatozoa and demonstrate that spermatotoxic effects are dependent on assembly of the complete MAC. We subsequently examined the presence and functional significance of the complement regulatory proteins decay accelerating factor (DAF), MAC-inhibiting protein (MIP) and CD59 antigen on spermatozoa. Both DAF and CD59 antigen were present on the membranes of these cells. Neutralization of CD59 antigen with specific antibodies increased the susceptibility of the cells to MAC-mediated damage, suggesting a role for this molecule in the protection of spermatozoa from complement-mediated damage in the female reproductive tract. Images Figure 2 Figure 4 PMID:1374057

  1. Y-12 Groundwater Protection Program CY2012 Triennial Report Of The Monitoring Well Inspection And Maintenance Program Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2013-09-01

    This document is the triennial report for the Well Inspection and Maintenance Program of the Y- 12 Groundwater Protection Program (GWPP), at the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12). This report formally documents well inspections completed by the GWPP on active and inactive wells at Y-12 during calendar years (CY) 2010 through 2012. In addition, this report also documents well inspections performed under the Y-12 Water Resources Restoration Program, which is administered by URS|CH2M Oak Ridge (UCOR). This report documents well maintenance activities completed since the last triennial inspection event (CY 2009); and provides summary tables of well inspections and well maintenance activities during the reference time period.

  2. Integration of numerical models and geoinformatic techniques in the delimitation of a protection zone for the MGB 319 complex multi-aquifer system in southwest Poland

    NASA Astrophysics Data System (ADS)

    Gurwin, Jacek

    2015-09-01

    The study area, situated near the city of Wrocław in southwest Poland, is part of the hydrogeological system of the Quaternary/Neogene MGB 319, inclusive of a buried valley of high water potential, named the Bogdaszowice structure. This structure is an alternative source of water supply for the Wrocław city area. Numerical modelling is the most effective tool in establishing a groundwater protection strategy for Major Groundwater Basins (MGBs) in complex aquifer systems. In the present study, the first step was to assess the hydrodynamic conditions of the Radakowice groundwater intake by analyses of head contours, pathlines, average flow times and capture zones of particular wells. Subsequently, these results were used in combination with other data and compiled as GIS layers. The spatial distribution of hydraulic conductivity was based on the lithology of surface sediments. Other data sets such as the thickness of the unsaturated zone, average soil moisture and infiltration rate were taken either directly from the model or were calculated. Based on the input data obtained, vertical flow time calculations for every model cell were made. The final outcome is a map of the protection zone for the aquifer system of the MGB 319.

  3. HspB5/αB-crystallin increases dendritic complexity and protects the dendritic arbor during heat shock in cultured rat hippocampal neurons.

    PubMed

    Bartelt-Kirbach, Britta; Moron, Margarethe; Glomb, Maximilian; Beck, Clara-Maria; Weller, Marie-Pascale; Golenhofen, Nikola

    2016-10-01

    The small heat shock protein ΗspΒ5 (αB-crystallin) exhibits generally cytoprotective functions and possesses powerful neuroprotective capacity in the brain. However, little is known about the mode of action of ΗspΒ5 or other members of the HspB family particularly in neurons. To get clues of the neuronal function of HspBs, we overexpressed several HspBs in cultured rat hippocampal neurons and investigated their effect on neuronal morphology and stress resistance. Whereas axon length and synapse density were not affected by any HspB, dendritic complexity was enhanced by HspB5 and, to a lesser extent, by HspB6. Furthermore, we could show that this process was dependent on phosphorylation, since a non-phosphorylatable mutant of HspB5 did not show this effect. Rarefaction of the dendritic arbor is one hallmark of several neurodegenerative diseases. To investigate if HspB5, which is upregulated at pathophysiological conditions, might be able to protect dendrites during such situations, we exposed HspB5 overexpressing neuronal cultures to heat shock. HspB5 prevented heat shock-induced rarefaction of dendrites. In conclusion, we identified regulation of dendritic complexity as a new function of HspB5 in hippocampal neurons. PMID:27085702

  4. Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity.

    PubMed

    Blaney, J E; Nobusawa, E; Brehm, M A; Bonneau, R H; Mylin, L M; Fu, T M; Kawaoka, Y; Tevethia, S S

    1998-12-01

    We have evaluated the potential of conferring protective immunity to herpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-specific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a single major histocompatibility complex class I-restricted CTL recognition epitope. We generated a recombinant vaccinia virus (rVV-ES-gB498-505) which expresses the H-2Kb-restricted, HSV-1/2-cross-reactive CTL recognition epitope, HSV glycoprotein B residues 498 to 505 (SSIEFARL) (gB498-505), fused to the adenovirus type 5 E3/19K endoplasmic reticulum insertion sequence (ES). Mucosal immunization of C57BL/6 mice with this recombinant vaccinia virus induced both a primary CTL response in the draining lymph nodes and a splenic memory CTL response directed against HSV gB498-505. To determine the ability of the gB498-505-specific memory CTL response to provide protection from HSV infection, immunized mice were challenged with a lethal dose of HSV-2 strain 186 by the intranasal (i.n.) route. Development of the gB498-505-specific CTL response conferred resistance in 60 to 75% of mice challenged with a lethal dose of HSV-2 and significantly reduced the levels of infectious virus in the brains and trigeminal ganglia of challenged mice. Finally, i.n. immunization of C57BL/6 mice with either a recombinant influenza virus or a recombinant vaccinia virus expressing HSV gB498-505 without the ES was also demonstrated to induce an HSV-specific CTL response and provide protection from HSV infection. This finding confirms that the induction of an HSV-specific CTL response directed against a single epitope is sufficient for conferring protective immunity to HSV. Our findings support the role of CD8(+) T cells in the control of HSV infection of the central nervous system and suggest the potential importance of eliciting HSV-specific mucosal CD8(+) CTL in HSV vaccine design. PMID:9811690

  5. Groundwater Protection Program Management Plan for the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    Elvado Environmental LLC; Environmental Compliance Department Environment, Safety, and Health Division Y-12 National Security Complex

    2004-03-31

    This document presents the Groundwater Protection Program (GWPP) management plan for the U.S. Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12). The Y-12 GWPP functions as the primary point-of-contact for groundwater-related issues at Y-12, provides stewardship of the extensive network of groundwater monitoring wells at Y-12, and serves as a resource for technical expertise, support, and historical data for groundwater-related activities at Y-12. These organizational functions each serve the primary programmatic purpose of the GWPP, which is to ensure that groundwater monitoring activities within areas under Y-12 administrative control provide representative data in compliance with the multiple purposes of applicable state and federal regulations, DOE orders, and the corporate policies of BWXT Y-12, L.L.C. (hereafter referenced as BWXT), the Y-12 management and operations (M&O) contractor for DOE. This GWPP management plan addresses the requirements of DOE Order 450.1 (BWXT Y12 S/RID) regarding the implementation of a site-wide approach for groundwater protection at each DOE facility. Additionally, this plan is a ''living'' document that is reviewed annually, revised and reissued every three years, and is formatted to provide for updating individual sections independent of the rest of the document. Section 2 includes a short description of the groundwater system at Y-12, the history of groundwater monitoring at Y-12 and the corresponding evolution of the GWPP, and an overview of ongoing Y-12 groundwater monitoring activities. Section 3 describes the key elements of the GWPP management strategy. Organizational roles and responsibilities of GWPP personnel are outlined in Section 4. Section 5 presents an overview of the GWPP project plans for applicable programmatic elements. Section 6 lists the reports, plans, and documents that are referenced for technical and administrative details.

  6. Groundwater Protection Program Management Plan For The U.S. Department Of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    Elvado Environmental, LLC

    2009-09-01

    This document presents the Groundwater Protection Program (GWPP) management plan for the U.S. Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12). The Y-12 GWPP functions as the primary point-of-contact for groundwater-related issues at Y-12, provides stewardship of the extensive network of groundwater monitoring wells at Y-12, and serves as a resource for technical expertise, support, and historical data for groundwater-related activities at Y-12. These organizational functions each serve the primary programmatic purpose of the GWPP, which is to ensure that groundwater monitoring activities within areas under Y-12 administrative control provide representative data in compliance with the multiple purposes of applicable state and federal regulations, DOE orders, and the corporate policies of Babcock & Wilcox Technical Services Y-12 LLC (hereafter referenced as B&W Y-12), the Y-12 management and operations (M&O) contractor for DOE. B&W Y-12 is a new corporate name, assumed in January 2007, for the company formerly known as BWXT Y-12, L.L.C., hereafter referenced as BWXT. This GWPP management plan addresses the requirements of DOE Order 450.1A Environmental Protection Program (hereafter referenced as DOE O 450.1A), which emphasize a site-wide approach for groundwater protection at each DOE facility through implementation of groundwater surveillance monitoring. Additionally, this plan addresses the relevant and applicable GWPP elements and goals described in the DOE O 450.1A technical guidance documents issued in June 2004 (DOE 2004) and May 2005 (DOE 2005). This GWPP management plan is a 'living' document that is reviewed annually, revised and reissued every three years, and is formatted to provide for updating individual sections independent of the rest of the document. Section 2 includes a short description of the groundwater system at Y-12, the history of groundwater monitoring at Y-12 and the corresponding evolution of the GWPP

  7. Y-12 Groundwater Protection Program Monitoring Optimization Plan For Groundwater Monitoring Wells At The U.S. Department Of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    none,

    2013-09-01

    This document is the monitoring optimization plan for groundwater monitoring wells associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee. The plan describes the technical approach that is implemented under the Y-12 Groundwater Protection Program (GWPP) to focus available resources on the monitoring wells at Y-12 that provide the most useful hydrologic and groundwater quality monitoring data. The technical approach is based on the GWPP status designation for each well. Under this approach, wells granted "active" status are used by the GWPP for hydrologic monitoring and/or groundwater quality sampling, whereas wells granted "inactive" status are not used for either purpose. The status designation also defines the frequency at which the GWPP will inspect applicable wells, the scope of these well inspections, and extent of any maintenance actions initiated by the GWPP. Details regarding the ancillary activities associated with implementation of this plan (e.g., well inspection) are deferred to the referenced GWPP plans. This plan applies to groundwater wells associated with Y-12 and related waste management areas and facilities located within three hydrogeologic regimes.

  8. Ten Weeks of Infection with a Tissue-Invasive Helminth Protects against Local Immune Complex-Mediated Inflammation, but Not Cutaneous Type I Hypersensitivity, in Previously Sensitized Mice.

    PubMed

    Evans, Holly; Killoran, Kristin E; Mitre, Blima K; Morris, C Paul; Kim, So-Young; Mitre, Edward

    2015-10-01

    In this study, we evaluated the effect chronic helminth infection has on allergic disease in mice previously sensitized to OVA. Ten weeks of infection with Litomosoides sigmodontis reduced immunological markers of type I hypersensitivity, including OVA-specific IgE, basophil activation, and mast cell degranulation. Despite these reductions, there was no protection against immediate clinical hypersensitivity following intradermal OVA challenge. However, late-phase ear swelling, due to type III hypersensitivity, was significantly reduced in chronically infected animals. Levels of total IgG2a, OVA-specific IgG2a, and OVA-specific IgG1 were reduced in the setting of infection. These reductions were most likely due to increased Ab catabolism as ELISPOT assays demonstrated that infected animals do not have suppressed Ab production. Ear histology 24 h after challenge showed infected animals have reduced cellular infiltration in the ear, with significant decreases in numbers of neutrophils and macrophages. Consistent with this, infected animals had less neutrophil-specific chemokines CXCL-1 and CXCL-2 in the ear following challenge. Additionally, in vitro stimulation with immune complexes resulted in significantly less CXCL-1 and CXCL-2 production by eosinophils from chronically infected mice. Expression of FcγRI was also significantly reduced on eosinophils from infected animals. These data indicate that chronic filarial infection suppresses eosinophilic responses to Ab-mediated activation and has the potential to be used as a therapeutic for pre-existing hypersensitivity diseases. PMID:26324775

  9. Naringin and Sertraline Ameliorate Doxorubicin-Induced Behavioral Deficits Through Modulation of Serotonin Level and Mitochondrial Complexes Protection Pathway in Rat Hippocampus.

    PubMed

    Kwatra, Mohit; Jangra, Ashok; Mishra, Murli; Sharma, Yogita; Ahmed, Sahabuddin; Ghosh, Pinaki; Kumar, Vikas; Vohora, Divya; Khanam, Razia

    2016-09-01

    The present study was designed to investigate the neuroprotective effect of naringin (NR) alone as well as its combination with sertraline (SRT) against doxorubicin (DOX)-induced neurobehavioral and neurochemical anomalies. DOX (15 mg/kg; i.p.) administration caused behavioral alterations, oxidative stress, neuroinflammation, mitochondrial dysfunction and monoamines alteration in male Wistar rats. NR (50 and 100 mg/kg; i.p.) and SRT (5 mg/kg; i.p.) treatment significantly attenuated DOX-induced anxiety and depressive-like behavior as evident from elevated plus maze (EPM) and modified forced swimming test (mFST), respectively. NR treatment significantly attenuated DOX-induced raised plasma corticosterone (CORT), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in the hippocampus (HC). Furthermore, we found that combination of NR and SRT regimen ameliorated DOX-induced behavioral anomalies through modulation of the 5-HT level and mitochondrial complexes protection pathway along with alleviation of oxidative stress in the HC region. Therefore, NR treatment alone or in combination with SRT could be beneficial against DOX-induced neurotoxicity. PMID:27209303

  10. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria

    PubMed Central

    Weaver, Rupert; Reiling, Linda; Feng, Gaoqian; Drew, Damien R.; Mueller, Ivo; Siba, Peter M.; Tsuboi, Takafumi; Richards, Jack S.; Fowkes, Freya J. I.; Beeson, James G.

    2016-01-01

    Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity. PMID:27604417

  11. Costimulation of CD3/TcR complex with either integrin or nonintegrin ligands protects CD4+ allergen-specific T-cell clones from programmed cell death.

    PubMed

    Agea, E; Bistoni, O; Bini, P; Migliorati, G; Nicoletti, I; Bassotti, G; Riccardi, C; Bertotto, A; Spinozzi, F

    1995-08-01

    An optimal stimulation of CD4+ cells in an immune response requires not only signals transduced via the TcR/CD3 complex, but also costimulatory signals delivered as a consequence of interactions between T-cell surface-associated costimulatory receptors and their counterparts on antigen-presenting cells (APC). The intercellular adhesion molecule-1 (ICAM-1, CD54) efficiently costimulates proliferation of resting, but not antigen-specific, T cells. In contrast, CD28 and CD2 support interleukin (IL)-2 synthesis and proliferation of antigen-specific T cells more efficiently than those of resting T cells. The molecular basis for this differential costimulation of T cells is poorly understood. Cypress-specific T-cell clones (TCC) were generated from four allergic subjects during in vivo seasonal exposure to the allergen. Purified cypress extract was produced directly from fresh collected pollen and incubated with the patients' mononuclear cells. Repeated allergen stimulation was performed in T-cell cultures supplemented with purified extract and autologous APC. The limiting-dilution technique was then adopted to generate allergen-specific TCC, which were also characterized by their cytokine secretion pattern as Th0 (IL-4 plus interferon-gamma) or Th2 (IL-4). Costimulation-induced proliferation or apoptosis was measured by propidium iodide cytofluorometric assay. By cross-linking cypress-specific CD4+ and CD8+ T-cell clones with either anti-CD3 or anti-CD2, anti-CD28, and anti-CD54 monoclonal antibodies, we demonstrated that CD4+ clones (with Th0- or Th2-type cytokine production pattern) undergo programmed cell death only after anti-CD3 stimulation, whereas costimulation with either anti-CD54 or anti-CD28 protects target cells from apoptosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7503404

  12. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria.

    PubMed

    Weaver, Rupert; Reiling, Linda; Feng, Gaoqian; Drew, Damien R; Mueller, Ivo; Siba, Peter M; Tsuboi, Takafumi; Richards, Jack S; Fowkes, Freya J I; Beeson, James G

    2016-01-01

    Understanding the targets and mechanisms of human immunity to malaria is important for advancing the development of highly efficacious vaccines and serological tools for malaria surveillance. The PfRH5 and PfRipr proteins form a complex on the surface of P. falciparum merozoites that is essential for invasion of erythrocytes and are vaccine candidates. We determined IgG subclass responses to these proteins among malaria-exposed individuals in Papua New Guinea and their association with protection from malaria in a longitudinal cohort of children. Cytophilic subclasses, IgG1 and IgG3, were predominant with limited IgG2 and IgG4, and IgG subclass-specific responses were higher in older children and those with active infection. High IgG3 to PfRH5 and PfRipr were significantly and strongly associated with reduced risk of malaria after adjusting for potential confounding factors, whereas associations for IgG1 responses were generally weaker and not statistically significant. Results further indicated that malaria exposure leads to the co-acquisition of IgG1 and IgG3 to PfRH5 and PfRipr, as well as to other PfRH invasion ligands, PfRH2 and PfRH4. These findings suggest that IgG3 responses to PfRH5 and PfRipr may play a significant role in mediating naturally-acquired immunity and support their potential as vaccine candidates and their use as antibody biomarkers of immunity. PMID:27604417

  13. Y-12 Groundwater Protection Program Monitoring Optimization Plan For Groundwater Monitoring Wells At The U.S. Department Of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    Elvado Environmental LLC

    2009-12-01

    This document is the monitoring optimization plan for groundwater monitoring wells associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee (Figure A.1). The plan describes the technical approach that will be implemented under the Y-12 Groundwater Protection Program (GWPP) to focus available resources on the monitoring wells at Y-12 that provide the most useful hydrologic and groundwater quality monitoring data. The technical approach is based on the GWPP status designation for each well (Section 2.0). Under this approach, wells granted 'active' status are used by the GWPP for hydrologic monitoring and/or groundwater quality sampling (Section 3.0), whereas wells granted 'inactive' status are not used for either purpose. The status designation also defines the frequency at which the GWPP will inspect applicable wells, the scope of these well inspections, and extent of any maintenance actions initiated by the GWPP (Section 3.0). Details regarding the ancillary activities associated with implementation of this plan (e.g., well inspection) are deferred to the referenced GWPP plans and procedures (Section 4.0). This plan applies to groundwater wells associated with Y-12 and related waste management areas and facilities located within three hydrogeologic regimes (Figure A.1): the Bear Creek Hydrogeologic Regime (Bear Creek Regime), the Upper East Fork Poplar Creek Hydrogeologic Regime (East Fork Regime), and the Chestnut Ridge Hydrogeologic Regime (Chestnut Ridge Regime). The Bear Creek Regime encompasses a section of Bear Creek Valley (BCV) immediately west of Y-12. The East Fork Regime encompasses most of the Y-12 process, operations, and support facilities in BCV and, for the purposes of this plan, includes a section of Union Valley east of the DOE Oak Ridge Reservation (ORR) boundary along Scarboro Road. The Chestnut Ridge Regime encompasses a section of Chestnut Ridge directly south of Y-12 that is bound on

  14. Complete Protection of Mice against Lethal Murine Cytomegalovirus Challenge by Immunization with DNA Vaccines Encoding Envelope Glycoprotein Complex III Antigens gH, gL and gO

    PubMed Central

    Wang, Huadong; Huang, Chaoyang; Dong, Jinrong; Yao, Yanfeng; Xie, Zhenyuan; Liu, Xueying; Zhang, Wenjie; Fang, Fang; Chen, Ze

    2015-01-01

    Human cytomegalovirus infects the majority of humanity which may lead to severe morbidity and mortality in newborns and immunocompromised adults. Humoral and cellular immunity are critical for controlling CMV infection. HCMV envelope glycoprotein complexes (gC I, II, III) represent major antigenic targets of antiviral immune responses. The gCIII complex is comprised of three glycoproteins, gH, gL, and gO. In the present study, DNA vaccines expressing the murine cytomegalovirus homologs of the gH, gL, and gO proteins were evaluated for protection against lethal MCMV infection in the mouse model. The results demonstrated that gH, gL, or gO single gene immunization could not yet offer good protection, whereas co-vaccination strategy apparently showed effects superior to separate immunization. Twice immunization with gH/gL/gO pDNAs could provide mice complete protection against lethal salivary gland-derived MCMV (SG-MCMV) challenge, while thrice immunization with pgH/pgL, pgH/pgO or pgL/pgO could not provide full protection. Co-vaccination with gH, gL and gO pDNAs elicited robust neutralizing antibody and cellular immune responses. Moreover, full protection was also achieved by simply passive immunization with anti-gH/gL/gO sera. These data demonstrated that gCIII complex antigens had fine immunogenicity and might be a promising candidate for the development of HCMV vaccines. PMID:25803721

  15. Y-12 Groundwater Protection Program Monitoring Optimization Plan for Groundwater Monitoring Wells at the U.S. Department of Energy Y-12 National Security Complex

    SciTech Connect

    2006-12-01

    This document is the monitoring optimization plan for groundwater monitoring wells associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee (Figure A.1). The plan describes the technical approach that will be implemented under the Y-12 Groundwater Protection Program (GWPP) to focus available resources on the monitoring wells at Y-12 that provide the most useful hydrologic and water-quality monitoring data. The technical approach is based on the GWPP status designation for each well (Section 2.0). Under this approach, wells granted ''active'' status are used by the GWPP for hydrologic monitoring and/or groundwater quality sampling (Section 3.0), whereas wells granted ''inactive'' status are not used for either purpose. The status designation also defines the frequency at which the GWPP will inspect applicable wells, the scope of these well inspections, and extent of any maintenance actions initiated by the GWPP (Section 3.0). Details regarding the ancillary activities associated with implementation of this plan (e.g., well inspection) are deferred to the referenced GWPP plans and procedures (Section 4.0). This plan applies to groundwater wells associated with Y-12 and related waste management areas and facilities located within three hydrogeologic regimes (Figure A.1): the Bear Creek Hydrogeologic Regime (Bear Creek Regime), the Upper East Fork Poplar Creek Hydrogeologic Regime (East Fork Regime), and the Chestnut Ridge Hydrogeologic Regime (Chestnut Ridge Regime). The Bear Creek Regime encompasses a section of Bear Creek Valley (BCV) immediately west of Y-12. The East Fork Regime encompasses most of the Y-12 process, operations, and support facilities in BCV and, for the purposes of this plan, includes a section of Union Valley east of the DOE Oak Ridge Reservation (ORR) boundary along Scarboro Road. The Chestnut Ridge Regime encompasses a section of Chestnut Ridge directly south of Y-12 that is bound on the

  16. Y-12 Groundwater Protection Program Monitoring Optimization Plan for Groundwater Monitoring Wells at the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2003-09-30

    This document is the monitoring optimization plan for groundwater monitoring wells associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (Y-12) in Oak Ridge, Tennessee (Figure 1). The plan describes the technical approach that will be implemented under the Y-12 Groundwater Protection Program (GWPP) to focus available resources on the monitoring wells at Y-12 which provide the most useful hydrologic and water-quality monitoring data. The technical approach is based on the GWPP status designation for each well (Section 2.0). Under this approach, wells granted ''active'' status are used by the GWPP for hydrologic monitoring and/or groundwater sampling (Section 3.0), whereas well granted ''inactive'' status are not used for either purpose. The status designation also determines the frequency at which the GWPP will inspect applicable wells, the scope of these well inspections, and extent of any maintenance actions initiated by the GWPP (Section 4.0). Details regarding the ancillary activities associated with implementation of this plan (e.g., well inspection) are deferred to the referenced GWPP plans and procedures (Section 5.0). This plan applies to groundwater monitoring wells associated with Y-12 and related waste management facilities located within three hydrogeologic regimes (Figure 1): the Bear Creek Hydrogeologic Regime (Bear Creek Regime), the Upper East Fork Poplar Creek Hydrogeologic Regime (East Fork Regime), and the Chestnut Ridge Hydrogeologic Regime (Chestnut Ridge Regime). The Bear Creek Regime encompasses a section of Bear Creek Valley (BCV) immediately west of Y-12. The East Fork Regime encompasses most of the Y-12 process, operations, and support facilities in BCV and, for the purposes of this plan, includes a section of Union Valley east of the DOE Oak Ridge Reservation (ORR) boundary along Scarboro Road. The Chestnut Ridge Regime is directly south of Y-12 and encompasses a section of Chestnut Ridge that is bound to the

  17. Dectin-1 targeting delivery of TNF-α antisense ODNs complexed with β-1,3-glucan protects mice from LPS-induced hepatitis.

    PubMed

    Mochizuki, Shinichi; Sakurai, Kazuo

    2011-04-30

    Antisense therapy, the first concept of oligonucleotide therapeutics, was proposed more than two decades ago. However, the lack of suitable delivering carriers continues to be a major obstacle to practical therapy. In this study, we present a novel complex consisting of β-1,3-glucan and antisense oligonucleotide (AS-ODN) as a new candidate of the carriers. We used schizophyllan (SPG) as a β-1,3-glucan and an AS-ODN sequence to suppress tumor necrosis factor alpha (TNF-α), where the AS-ODN has a (dA)(60) tail to induce complex with SPG. When the complexes were applied to peritoneal macrophages, they were incorporated into the cells via dectin-1 (a β-1,3-glucan receptor expressed on antigen presenting cells) and suppressed lipopolysaccharide (LPS)-induced TNF-α secretion. In-vivo, AS-ODN/SPG decreased the secretion of TNF-α in serum and drastically reduced the inflammation of LPS-induced hepatitis. This new complex could overcome the long outstanding problem for antisense therapy because of its complexation ability, non-toxicity and high target specificity. PMID:21281680

  18. Gastrin-releasing peptide receptor antagonist or N-acetylcysteine combined with omeprazol protect against mitochondrial complex II inhibition in a rat model of gastritis.

    PubMed

    Rezin, Gislaine T; Petronilho, Fabricia C; Araújo, João H; Gonçalves, Cinara L; Daufenbach, Juliana F; Cardoso, Mariane R; Roesler, Rafael; Schwartsmann, Gilberto; Dal-Pizzol, Felipe; Streck, Emilio L

    2011-03-01

    The pathophysiology of gastritis involves an imbalance between gastric acid attack and mucosal defence. In addition, the gastric mucosal injury results in adenosine triphosphate (ATP) depletion leading to mitochondrial dysfunction. Several studies have shown the association of mitochondrial disorders with gastrointestinal dysfunction. In the present study, we investigated the activity of mitochondrial respiratory chain complexes activity in the stomach of rats with gastritis induced by indomethacin (IDM) and treated with omeprazole (OM), N-acetylcysteine (NAC) and the gastrin-releasing peptide receptor (GRPR) antagonist RC-3095. Adult male Wistar rats were pre-treated for 7 days with OM, NAC, RC-3095, combination of OM plus RC-3095, OM plus NAC and water (control). The animals were then submitted to fasting for 24 hr; IDM was administered. The rats were killed 6 hr later, and the stomachs were used for evaluation of macroscopic damage and respiratory chain activity. Our results showed that complex I and IV activities were not affected by administration of IDM. On the other hand, complex II and III activities were inhibited. In addition, OM plus RC-3095 and OM plus NAC did not reverse complex II activity inhibition. However, the complex III activity inhibition was reversed only with the combined use of OM plus RC-3095 and OM plus NAC. Our results are in agreement with previous studies indicating mitochondrial dysfunction in the pathophysiology of gastrointestinal tract disease and we suggest that GRPR antagonism might be a novel therapeutic strategy in gastritis. PMID:21138529

  19. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL DEVELOPMENT: DESCRIPTION OF A COMPUTER DATA BASE FROM SMALL HILL IMPACTION STUDY NO. 2, HOGBACK RIDGE, NEW MEXICO

    EPA Science Inventory

    The second field study of EPA's Complex Terrain Model Development Program, Small Hill Impaction Study No. 2, was conducted along a 1.5-km section of the Hogback Ridge near Farmington, New Mexico in October 1982. Eleven quantative tracer experiments were performed, each lasting 8 ...

  20. EPA (ENVIRONMENTAL PROTECTION AGENCY) COMPLEX TERRAIN MODEL DEVELOPMENT: DESCRIPTION OF A COMPUTER DATA BASE FROM THE FULL SCALE PLUME STUDY, TRACY POWER PLANT, NEVADA

    EPA Science Inventory

    As part of the EPA's Complex Terrain Model Development Program, the Full Scale Study was conducted at the Tracy Power Plant near Reno, Nevada. SO6 tracer gas and oil-fog particles were injected into the base of a 91.4 smokestack, and CF3Br tracer was released from one of three le...

  1. Immunostimulatory complexes containing Eimeria tenella antigens and low toxicity plant saponins induce antibody response and provide protection from challenge in broiler chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunostimulating complexes (ISCOMs) are unique multimolecular structures formed by encapsulating antigens, lipids and triterpene saponins and are one of the most successful antigen delivery systems for microbial antigens. In the current study, both the route of administration and the antigen conce...

  2. Lipoxin A4-Induced Heme Oxygenase-1 Protects Cardiomyocytes against Hypoxia/Reoxygenation Injury via p38 MAPK Activation and Nrf2/ARE Complex

    PubMed Central

    Chen, Xiao-Qing; Wu, Sheng-Hua; Zhou, Yu; Tang, Yan-Rong

    2013-01-01

    Objective To investigate whether lipoxin A4 (LXA4) increases expression of heme oxygenase-1(HO-1) in cardiomyocytes, whether LXA4-induced HO-1 protects cardiomyocytes against hypoxia/reoxygenation (H/R) injury, and what are the mechanisms involved in the LXA4-induced HO-1 induction. Methods Rat cardiomyocytes were exposed to H/R injury with or without preincubation with LXA4 or HO-1 inhibitor ZnPP-IX or various signal molecule inhibitors. Expressions of HO-1 protein and mRNA were analyzed by using Western blot and RT-PCR respectively. Activity of nuclear factor E2-related factor 2 (Nrf2) binding to the HO-1 E1 enhancer was assessed by chromatin immunoprecipitation. Nrf2 binding to the HO-1 antioxidant responsive element (ARE) were measured by using electrophoretic mobility shift assay. Results Pretreatment of the cells undergoing H/R lesion with LXA4 significantly reduced the lactate dehydrogenase and creatine kinase productions, increased the cell viability, and increased the expressions of HO-1 protein and mRNA and HO-1 promoter activity. HO-1 inhibition abolished the protective role of LXA4 on the cells undergoing H/R lesion. LXA4 increased p38 mitogen-activated protein kinase (p38 MAPK) activation, nuclear translocation of Nrf2, Nrf2 binding to the HO-1 ARE and E1 enhancer in cardiomyocytes with or without H/R exposure. Conclusion The protection role of LXA4 against H/R injury of cardiomyocytes is related to upregulation of HO-1, via activation of p38 MAPK pathway and nuclear translocation of Nrf2 and Nrf2 binding to the HO-1 ARE and E1 enhancer, but not via activation of phosphatidyinositol-3-kinase or extracellular signal-regulated kinase pathway. PMID:23826208

  3. Affinity purification and characterization of a fibrinogen-binding protein complex which protects mice against lethal challenge with Streptococcus equi subsp. equi.

    PubMed

    Meehan, M; Nowlan, P; Owen, P

    1998-04-01

    Cell-wall-associated proteins from Streptococcus equi subsp. equi, the causative agent of strangles, were analysed with a view to identifying a potential protective antigen. Preparations of these proteins, isolated from mutanolysin extracts of cell walls, were shown to contain one major high-M(r) protein species (apparent M(r) 220,000 and 550,000 when analysed by SDS-PAGE and gel-filtration chromatography, respectively). The high-M(r) protein bound horse fibrinogen and was purified under non-denaturing conditions using fibrinogen affinity chromatography. The fibrinogen-binding protein (FgBP) reacted with serum taken from horses recovering from strangles and protected mice against lethal challenge from S. equi subsp. equi. The sequence of the corresponding gene (fbp) was determined and shown to encode a mature protein (M(r) 54,597) with predicted coiled-coil structure. An FgBP truncate, lacking the C-terminal cell wall/membrane anchor domain, was overexpressed in and purified from Escherichia coli and was shown to behave in an analogous fashion to the wild-type product in terms of M(r) estimation, fibrinogen binding and seroreactivity. PMID:9579073

  4. A cationic liposome-DNA complexes adjuvant (JVRS-100) enhances the immunogenicity and cross-protective efficacy of pre-pandemic influenza A (H5N1) vaccine in ferrets.

    PubMed

    Liu, Feng; Sun, Xiangjie; Fairman, Jeffery; Lewis, David B; Katz, Jacqueline M; Levine, Min; Tumpey, Terrence M; Lu, Xiuhua

    2016-05-01

    Influenza A (H5N1) viruses continue to pose a public health threat. As inactivated H5N1 vaccines are poorly immunogenic, adjuvants are needed to improve the immunogenicity of H5N1 vaccine in humans. Here, we investigated the immunogenicity and cross-protective efficacy in ferrets of a clade 2.2-derived vaccine with addition of JVRS-100, an adjuvant consisting of cationic liposome-DNA complexes (CLDC). After the first vaccination, significantly higher levels of hemagglutination-inhibition (HAI) and neutralizing antibody titers were detected in ferrets immunized with adjuvanted vaccine compared to unadjuvanted vaccine. Following a second dose of adjuvanted vaccine, HAI antibody titers of ≥ 40 were detected against viruses from multiple H5N1 clades. HAI antibodies against newly isolated H5N2 and H5N8 viruses were also augmented by JVRS-100. Ferrets were challenged with a heterologous H5N1 virus. All ferrets that received two doses of adjuvanted vaccine exhibited mild illness, significantly reduced nasal wash virus titers and protection from lethal challenge. In contrast, ferrets that received unadjuvanted vaccine showed greater weight loss, high viral titers and 3 of 6 animals succumbed to the lethal challenge. Our results indicate that the addition of JVRS-100 to H5N1 vaccine enhanced immunogenicity and cross-protection against lethal H5N1 virus disease in ferrets. JVRS-100 warrants further investigation as a potential adjuvant for influenza vaccines. PMID:26967975

  5. Materials and Fuels Complex Hazardous Waste Management Act/Resource Conservation and Recovery Act Storage and Treatment Permit Reapplication, Environmental Protection Agency Number ID4890008952

    SciTech Connect

    Holzemer, Michael J.; Hart, Edward

    2015-04-01

    Hazardous Waste Management Act/Resource Conservation and Recovery Act Storage and Treatment Permit Reapplication for the Idaho National Laboratory Materials and Fuels Complex Hazardous Waste Management Act/Resource Conservation and Recovery Act Partial Permit, PER-116. This Permit Reapplication is required by the PER-116 Permit Conditions I.G. and I.H., and must be submitted to the Idaho Department of Environmental Quality in accordance with IDAPA 58.01.05.012 [40 CFR §§ 270.10 and 270.13 through 270.29].

  6. Genome Protection by the 9-1-1 Complex Subunit HUS1 Requires Clamp Formation, DNA Contacts, and ATR Signaling-independent Effector Functions.

    PubMed

    Lim, Pei Xin; Patel, Darshil R; Poisson, Kelsey E; Basuita, Manpreet; Tsai, Charlton; Lyndaker, Amy M; Hwang, Bor-Jang; Lu, A-Lien; Weiss, Robert S

    2015-06-12

    The RAD9A-HUS1-RAD1 (9-1-1) complex is a heterotrimeric clamp that promotes checkpoint signaling and repair at DNA damage sites. In this study, we elucidated HUS1 functional residues that drive clamp assembly, DNA interactions, and downstream effector functions. First, we mapped a HUS1-RAD9A interface residue that was critical for 9-1-1 assembly and DNA loading. Next, we identified multiple positively charged residues in the inner ring of HUS1 that were crucial for genotoxin-induced 9-1-1 chromatin localization and ATR signaling. Finally, we found two hydrophobic pockets on the HUS1 outer surface that were important for cell survival after DNA damage. Interestingly, these pockets were not required for 9-1-1 chromatin localization or ATR-mediated CHK1 activation but were necessary for interactions between HUS1 and its binding partner MYH, suggesting that they serve as interaction domains for the recruitment and coordination of downstream effectors at damage sites. Together, these results indicate that, once properly loaded onto damaged DNA, the 9-1-1 complex executes multiple, separable functions that promote genome maintenance. PMID:25911100

  7. Genome Protection by the 9-1-1 Complex Subunit HUS1 Requires Clamp Formation, DNA Contacts, and ATR Signaling-independent Effector Functions*

    PubMed Central

    Lim, Pei Xin; Patel, Darshil R.; Poisson, Kelsey E.; Basuita, Manpreet; Tsai, Charlton; Lyndaker, Amy M.; Hwang, Bor-Jang; Lu, A-Lien; Weiss, Robert S.

    2015-01-01

    The RAD9A-HUS1-RAD1 (9-1-1) complex is a heterotrimeric clamp that promotes checkpoint signaling and repair at DNA damage sites. In this study, we elucidated HUS1 functional residues that drive clamp assembly, DNA interactions, and downstream effector functions. First, we mapped a HUS1-RAD9A interface residue that was critical for 9-1-1 assembly and DNA loading. Next, we identified multiple positively charged residues in the inner ring of HUS1 that were crucial for genotoxin-induced 9-1-1 chromatin localization and ATR signaling. Finally, we found two hydrophobic pockets on the HUS1 outer surface that were important for cell survival after DNA damage. Interestingly, these pockets were not required for 9-1-1 chromatin localization or ATR-mediated CHK1 activation but were necessary for interactions between HUS1 and its binding partner MYH, suggesting that they serve as interaction domains for the recruitment and coordination of downstream effectors at damage sites. Together, these results indicate that, once properly loaded onto damaged DNA, the 9-1-1 complex executes multiple, separable functions that promote genome maintenance. PMID:25911100

  8. Sun protection

    MedlinePlus

    ... age spots are caused by exposure to the sun. The two types of sun rays that can injure the skin are ultraviolet ... changes is to protect your skin from the sun. This includes using sunscreen and other protective measures. ...

  9. Mena/VASP and αII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy

    PubMed Central

    2013-01-01

    Background In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities. PMID:23937664

  10. Y-12 Groundwater Protection Program Calendar Year 2000 Groundwater Monitoring Data Evaluation Report for the Chestnut Ridge Hydrogeologic Regime at the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2001-09-01

    This report presents an evaluation of the groundwater and surface water monitoring data obtained during calendar year (CY) 2000 from sampling locations in the Chestnut Ridge Hydrogeologic Regime (Chestnut Ridge Regime). The Chestnut Ridge Regime encompasses several hazardous and nonhazardous waste management facilities associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12) southeast of Oak Ridge, Tennessee (Figure A.1). Prepared by the Y-12 Groundwater Protection Program (GWPP), this monitoring data evaluation report addresses applicable provisions of DOE Order 5400.1 -- General Environmental Protection Program -- that require: (1) an evaluation of the quantity and quality of groundwater in areas that are, or could be, impacted by Y-12 operations, (2) an evaluation of the quality of surface water and groundwater where contaminants from Y-12 facilities are most likely to migrate beyond the DOE Oak Ridge Reservation (ORR) property line, and (3) an evaluation of long-term trends in groundwater quality at Y-12. The following sections of this report contain relevant background information (Section 2.0); describe the results of the respective data evaluations required under DOE Order 5400.1 (Section 3.0); summarize significant findings of each evaluation (Section 4.0); and list the technical reports and regulatory documents cited for more detailed information (Section 5.0). Illustrations (maps and trend graphs) and data summary tables referenced in each section are presented in Appendix A and Appendix B, respectively.

  11. Insider protection

    SciTech Connect

    Waddoups, I.G.

    1993-07-01

    The government community is broadly addressing the insider threat. The first section of this paper defines protection approaches and the latter sections present various applicable technology developments. The bulk of the paper discusses technology developments applied to (1) personnel and material tracking and inventory, (2) classified document protection, and (3) protecting security systems. The personnel and material tracking system uses a PC based-host to (1) collect information from proximity tags and material movement sensors, (2) apply rules to this input to assure that the ongoing activity meets the site selectable rules and, (3) forward the results to either an automated inventory system or an alarm system. The document protection system uses a PC network to efficiently and securely control classified material which is stored on write-once-read-mostly optical media. The protection of sensor to multiplexer communications in a security system is emphasized in the discussion of protecting security systems.

  12. Tomboy as protective identity.

    PubMed

    Craig, Traci; Lacroix, Jessica

    2011-01-01

    The tomboy in contemporary U.S. culture is a complex identity, providing meaning to many girls and women. In this article, we argue tomboy as a gendered social identity also provides temporary "protections" to girls and women in three main ways. First, tomboy identity can excuse masculine-typed behavior in girls and women and, in doing so, protect women from presumptions about sexual reputation and sexual orientation. Second, tomboy identities can provide some protection for lesbian girls and women who prefer to not divulge their sexual orientation. And, third, tomboy identity can gain women limited privilege to spaces for which masculinity is an unspoken requirement. The temporary nature of the protections provided to tomboys undermines the ability of tomboys to truly transcend the binary gender system. PMID:21973066

  13. Cathodic protection: Theory and practice

    SciTech Connect

    Ashworth, V.; Booker, C.J.L.

    1986-01-01

    This book presents an account of cathodic protection. It covers the advances made over the past decade, both in terms of understanding the complexity of the systems to which cathodic protection has been applied and assuring the reliability of the designs which have evolved. It shows how computer-validated design is superseding empirical design. The use of field gradient measurements for current output, acoustic transmission of potential data, and monitoring and surveying of cathodic protection systems are included.

  14. Micrometeorological principles of protected cultivation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protected cultivation is a broad term commonly used among producers of specialty crops. Techniques can range from complex fixed structures to field site selection, to straightforward cultural practices in the field. This introduction to the ASHS workshop "Protected cultivation for fruit crops" consi...

  15. Y-12 Groundwater Protection Program Calendar Year 2000 Groundwater Monitoring Data Evaluation Report for the Bear Creek Hydrogeologic Regime at the U.S. Department of Energy Y-12 National Security Complex, Oak Ridge, Tennessee

    SciTech Connect

    2001-09-01

    This report presents an evaluation of the groundwater and surface water monitoring data obtained during calendar year (CY) 2000 in the Bear Creek Hydrogeologic Regime (Bear Creek Regime). The Bear Creek Regime encompasses many confirmed and potential sources of groundwater and surface water contamination associated with the U.S. Department of Energy (DOE) Y-12 National Security Complex (hereafter referenced as Y-12) in Oak Ridge, Tennessee (Figure A.1). Prepared by the Y-12 Groundwater Protection Program (GWPP), this report addresses applicable provisions of DOE Order 5400.1 (General Environmental Protection Program) that require: (1) an evaluation of the quantity and quality of groundwater and surface water in areas that are, or could be, affected by Y-12 operations, (2) an evaluation of groundwater and surface water quality in areas where contaminants from Y-12 operations are most likely to migrate beyond the DOE Oak Ridge Reservation (ORR) property line, and (3) an evaluation of long-term trends in groundwater quality at Y-12. The following sections of this report contain relevant background information (Section 2.0); describe the results of the respective data evaluations required under DOE Order 5400.1 (Section 3.0); summarize significant findings of each evaluation (Section 4.0); and list the technical reports and regulatory documents cited for more detailed information (Section 5.0). Illustrations (maps and trend graphs) are presented in Appendix A. Brief data summary tables referenced in each section are contained within the sections. Supplemental information and extensive data tables are provided in Appendix B.

  16. Memory protection

    NASA Technical Reports Server (NTRS)

    Denning, Peter J.

    1988-01-01

    Accidental overwriting of files or of memory regions belonging to other programs, browsing of personal files by superusers, Trojan horses, and viruses are examples of breakdowns in workstations and personal computers that would be significantly reduced by memory protection. Memory protection is the capability of an operating system and supporting hardware to delimit segments of memory, to control whether segments can be read from or written into, and to confine accesses of a program to its segments alone. The absence of memory protection in many operating systems today is the result of a bias toward a narrow definition of performance as maximum instruction-execution rate. A broader definition, including the time to get the job done, makes clear that cost of recovery from memory interference errors reduces expected performance. The mechanisms of memory protection are well understood, powerful, efficient, and elegant. They add to performance in the broad sense without reducing instruction execution rate.

  17. Protective Eyewear

    MedlinePlus

    ... Whether you’re on the basketball court, in chemistry class, or sitting by the pool, wearing protective ... remember to wear safety goggles. Using chemicals in chemistry class? Look like a real scientist by wearing ...

  18. Corrosion protection

    DOEpatents

    Brown, Donald W.; Wagh, Arun S.

    2003-05-27

    There has been invented a chemically bonded phosphate corrosion protection material and process for application of the corrosion protection material for corrosion prevention. A slurry of iron oxide and phosphoric acid is used to contact a warm surface of iron, steel or other metal to be treated. In the presence of ferrous ions from the iron, steel or other metal, the slurry reacts to form iron phosphates which form grains chemically bonded onto the surface of the steel.

  19. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1994-01-01

    Kit-built airplanes are more affordable because they are assembled by the owner and do not require Federal Aviation Administration (FAA) certification. The Glasair III, is an advanced technology homebuilt, constructed of a fiberglass and graphite fiber composite material, and equipped with digital instruments. Both technologies make the airplane more susceptible to lightning effects. When Glasair manufacturer, Stoddard-Hamilton, decided that lightning protection would enable more extensive instrument flight and make the plane more marketable, they proposed a joint development program to NASA Langley Research Center (LAR). Under a Small Business Innovation Research (SBIR) contract, Langley contractors designed and tested a lightning protection system, and the Glasair III-LP became the first kit-built composite aircraft to be lightning tested and protection-verified under FAA guidelines for general aviation aircraft.

  20. Noise Protection

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Environmental Health Systems puts forth an increasing effort in the U.S. to develop ways of controlling noise, particularly in industrial environments due to Federal and State laws, labor union insistence and new findings relative to noise pollution impact on human health. NASA's Apollo guidance control system aided in the development of a noise protection product, SMART. The basis of all SMART products is SMART compound a liquid plastic mixture with exceptional energy/sound absorbing qualities. The basic compound was later refined for noise protection use.

  1. Lightning Protection

    NASA Technical Reports Server (NTRS)

    1991-01-01

    Lightning Technologies, Inc., Pittsfield, MA, - a spinoff company founded by president J. Anderson Plumer, a former NASA contractor employee who developed his expertise with General Electric Company's High Voltage Laboratory - was a key player in Langley Research Center's Storm Hazards Research Program. Lightning Technologies used its NASA acquired experience to develop protective measures for electronic systems and composite structures on aircraft, both of which are particularly susceptible to lightning damage. The company also provides protection design and verification testing services for complete aircraft systems or individual components. Most aircraft component manufacturers are among Lightning Technologies' clients.

  2. Protecting Privacy.

    ERIC Educational Resources Information Center

    Coyle, Karen

    2001-01-01

    Discusses privacy issues related to use of the Internet. Topics include data gathering functions that are built into applications of the World Wide Web; cookies that identify Web site visitors; personal identity information; libraries and privacy, including the need for privacy policies; protecting your privacy; and developing privacy literacy.…

  3. Protective Clothing

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Beta Glass material, originating from the Apollo program is supplied to Fyrepel by Owens-Corning and incorporated into Fyrepel's Fyretex and Beta-Mex aluminized fabrics. Fabrics are used in fire entry suits, several other types of protective suits for wear in hot industrial environments and such accessory items as heat-reflecting curtains for industrial applications.

  4. Protect thyself

    SciTech Connect

    Sullivan, A.M.

    1982-06-01

    The article considers items of personal protection for miners: Self-rescuers, respirators, hard hats and cap lamps. A table provides a comparison between five types of self-contained self-rescuer. Details are also given of hard hat cap lamp and respirator manufacturers.

  5. Protective Coating

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Inorganic Coatings, Inc.'s K-Zinc 531 protective coating is water-based non-toxic, non-flammable and has no organic emissions. High ratio silicate formula bonds to steel, and in 30 minutes, creates a very hard ceramic finish with superior adhesion and abrasion resistance. Improved technology allows application over a minimal commercial sandblast, fast drying in high humidity conditions and compatibility with both solvent and water-based topcoats. Coating is easy to apply and provides long term protection with a single application. Zinc rich coating with water-based potassium silicate binder offers cost advantages in materials, labor hours per application, and fewer applications over a given time span.

  6. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks.

    PubMed

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A

    2016-07-27

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. PMID:27280975

  7. Uncovering the role of APC-Cdh1 in generating the dynamics of S-phase onset

    PubMed Central

    Yuan, Xi; Srividhya, Jeyaraman; De Luca, Thomas; Lee, Ju-hyong E.; Pomerening, Joseph R.

    2014-01-01

    Cdh1, a coactivator of the anaphase-promoting complex (APC), is a potential tumor suppressor. Cdh1 ablation promotes precocious S-phase entry, but it was unclear how this affects DNA replication dynamics while contributing to genomic instability and tumorigenesis. We find that Cdh1 depletion causes early S-phase onset in conjunction with increase in Rb/E2F1-mediated cyclin E1 expression, but reduced levels of cyclin E1 protein promote this transition. We hypothesize that this is due to a weakened cyclin-dependent kinase inhibitor (CKI)–cyclin-dependent kinase 2 positive-feedback loop, normally generated by APC-Cdh1–mediated proteolysis of Skp2. Indeed, Cdh1 depletion increases Skp2 abundance while diminishing levels of the CKI p27. This lowers the level of cyclin E1 needed for S-phase entry and delays cyclin E1 proteolysis during S-phase progression while corresponding to slowed replication fork movement and reduced frequency of termination events. In summary, using both experimental and computational approaches, we show that APC-Cdh1 establishes a stimulus–response relationship that promotes S phase by ensuring that proper levels of p27 accumulate during G1 phase, and defects in its activation accelerate the timing of S-phase onset while prolonging its progression. PMID:24356446

  8. Integration of TP53, DREAM, MMB-FOXM1 and RB-E2F target gene analyses identifies cell cycle gene regulatory networks

    PubMed Central

    Fischer, Martin; Grossmann, Patrick; Padi, Megha; DeCaprio, James A.

    2016-01-01

    Cell cycle (CC) and TP53 regulatory networks are frequently deregulated in cancer. While numerous genome-wide studies of TP53 and CC-regulated genes have been performed, significant variation between studies has made it difficult to assess regulation of any given gene of interest. To overcome the limitation of individual studies, we developed a meta-analysis approach to identify high confidence target genes that reflect their frequency of identification in independent datasets. Gene regulatory networks were generated by comparing differential expression of TP53 and CC-regulated genes with chromatin immunoprecipitation studies for TP53, RB1, E2F, DREAM, B-MYB, FOXM1 and MuvB. RNA-seq data from p21-null cells revealed that gene downregulation by TP53 generally requires p21 (CDKN1A). Genes downregulated by TP53 were also identified as CC genes bound by the DREAM complex. The transcription factors RB, E2F1 and E2F7 bind to a subset of DREAM target genes that function in G1/S of the CC while B-MYB, FOXM1 and MuvB control G2/M gene expression. Our approach yields high confidence ranked target gene maps for TP53, DREAM, MMB-FOXM1 and RB-E2F and enables prediction and distinction of CC regulation. A web-based atlas at www.targetgenereg.org enables assessing the regulation of any human gene of interest. PMID:27280975

  9. Radiation-induced microrna-622 causes radioresistance in colorectal cancer cells by down-regulating Rb

    PubMed Central

    Liang, Li; Zhang, Yan; Ding, Yi; Lin, Xiaoshan; Li, Guoxin; Ding, Yanqing

    2015-01-01

    The standard treatment for patients with locally advanced rectal cancer is preoperative 5-fluorouracil-based chemoradiotherapy followed by total mesorectal excision. However, tumor response to standard dose radiation varies. In this study, we found that miR-622 was increased significantly in ionizing radiation-treated colorectal cancer (CRC) cells compared to the cells cultured with irradiated medium, and persisted stably in surviving cells treated with continuous low-dose radiation. Overexpression of miR-622 induced the radioresistance in vitro. In addition, miR-622 inhibited Rb expression by directly targeting RB1-3′UTR. Overexpression of Rb reversed miR-622-induced radioresistance in vitro. In response to ionizing radiation, the Rb-E2F1-P/CAF complex activated proapoptotic genes. Importantly, miR-622 was highly expressed in tumors of rectal cancer patients with non-regression after standard dose radiotherapy. In conclusion, miR-622 overexpressing cells are induced or selected by radiotherapy, causing in turn radioresistance and poor response to further therapy. MiR-622 is a potential biomarker of responders for radiotherapy and a potential therapeutic target. PMID:25961730

  10. Protecting Antarctica

    NASA Astrophysics Data System (ADS)

    Carlowicz, Michael

    House Science Committee Chairman Robert Walker (R-Pa.) has introduced a bill into Congress to give the United States the legislative authority to implement the 1991 Environmental Protocol to the Antarctic Treaty. That protocol established rules and principles to shield the Antarctic environment from human spoilage—placing limits on the discharge of pollutants, protecting plant and animal life, and requiring environmental impact assessments before new activities and programs are launched. The protocol also forbids prospecting or developing of mineral resources except for scientific research.

  11. Protective Coatings

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Ameron International Protective Coatings Group developed a special coating for NASA that would withstand the high temperatures generated by the Space Shuttle rocket engines. The coating remains intact for at least 10 minutes, and insulates the launch pad so that it does not exceed 150 degrees and buckle. The NASA formulation was from Ameron's Engineered Siloxane (PSX) chemistry, which employs an inorganic silicon-oxygen structure which the company states is stronger and more reliable than organic polymers. Some of Ameron's PSX product line is based on the NASA technology, used for everything from industrial equipment to bridges.

  12. Protective Coatings

    NASA Technical Reports Server (NTRS)

    1980-01-01

    General Magnaplate Corporation's pharmaceutical machine is used in the industry for high speed pressing of pills and capsules. Machine is automatic system for molding glycerine suppositories. These machines are typical of many types of drug production and packaging equipment whose metal parts are treated with space spinoff coatings that promote general machine efficiency and contribute to compliance with stringent federal sanitation codes for pharmaceutical manufacture. Collectively known as "synergistic" coatings, these dry lubricants are bonded to a variety of metals to form an extremely hard slippery surface with long lasting self lubrication. The coatings offer multiple advantages; they cannot chip, peel or be rubbed off. They protect machine parts from corrosion and wear longer, lowering maintenance cost and reduce undesired heat caused by power-robbing friction.

  13. Protection from clinical disease against three highly virulent strains of Newcastle disease virus after in ovo application of an antibody-antigen complex vaccine in maternal antibody-positive chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Worldwide, Newcastle disease virus (NDV) remains one of the most economically important diseases of poultry. Current vaccination strategies for commercial poultry include the use of inactivated and live NDV vaccines that typically induce protection against less virulent field viruses. The value of...

  14. On the protection of "protected areas".

    PubMed

    Joppa, Lucas N; Loarie, Scott R; Pimm, Stuart L

    2008-05-01

    Tropical moist forests contain the majority of terrestrial species. Human actions destroy between 1 and 2 million km(2) of such forests per decade, with concomitant carbon release into the atmosphere. Within these forests, protected areas are the principle defense against forest loss and species extinctions. Four regions-the Amazon, Congo, South American Atlantic Coast, and West Africa-once constituted about half the world's tropical moist forest. We measure forest cover at progressively larger distances inside and outside of protected areas within these four regions, using datasets on protected areas and land-cover. We find important geographical differences. In the Amazon and Congo, protected areas are generally large and retain high levels of forest cover, as do their surroundings. These areas are protected de facto by being inaccessible and will likely remain protected if they continue to be so. Deciding whether they are also protected de jure-that is, whether effective laws also protect them-is statistically difficult, for there are few controls. In contrast, protected areas in the Atlantic Coast forest and West Africa show sharp boundaries in forest cover at their edges. This effective protection of forest cover is partially offset by their very small size: little area is deep inside protected area boundaries. Lands outside protected areas in the Atlantic Coast forest are unusually fragmented. Finally, we ask whether global databases on protected areas are biased toward highly protected areas and ignore "paper parks." Analysis of a Brazilian database does not support this presumption. PMID:18451028

  15. Synthesis, spectroscopic and thermal studies of Mg(II), Ca(II), Sr(II) and Ba(II) diclofenac sodium complexes as anti-inflammatory drug and their protective effects on renal functions impairment and oxidative stress

    NASA Astrophysics Data System (ADS)

    El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

    2015-01-01

    The main task of our present study is the preparation of newly complexes of Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac which succeeded to great extent in alleviating the side effects of diclofenac alone and ameliorating the kidney function parameters and antioxidant capacities with respect to diclofenac treated group alone. The Mg(II), Ca(II), Sr(II) and Ba(II) with diclofenac have been synthesized and characterized using infrared, electronic and 1H NMR spectral, thermogravimetric and conductivity measurements. The diclofenac ligand has been found to act as bidentate chelating agent. Diclofenac complexes coordinate through the oxygen's of the carboxyl group. The molar ratio chelation is 1:2 (M2+-dic) with general formula [M(dic)2(H2O)2]ṡnH2O. Antibacterial screening of the alkaline earth metal complexes against Escherichia coli (Gram - ve), Bacillus subtilis (Gram + ve) and anti-fungal (Asperagillus oryzae, Asperagillus niger, Asperagillus flavus) were investigated. The kidney functions in male albino rats were ameliorated upon treatment with metal complexes of dic, which are represented by decreasing the levels of urea and uric acid to be located within normal values. The other looks bright spot in this article is the assessment of antioxidant defense system including SOD, CAT and MDA with the help of Sr2+, Mg2+ and Ca2+-dic complexes. The hormones related to kidney functions and stresses have been greatly ameliorated in groups treated with dic complexes in comparable with dic treated group.

  16. Complexity Survey.

    ERIC Educational Resources Information Center

    Gordon, Sandra L.; Anderson, Beth C.

    To determine whether consensus existed among teachers about the complexity of common classroom materials, a survey was administered to 66 pre-service and in-service kindergarten and prekindergarten teachers. Participants were asked to rate 14 common classroom materials as simple, complex, or super-complex. Simple materials have one obvious part,…

  17. Occupant Protection Project

    NASA Technical Reports Server (NTRS)

    Bopp, Genie; Somers, Jeff; Granderson, Brad; Gernhardt, Mike; Currie, Nancy; Lawrence, Chuck

    2010-01-01

    Topics include occupant protection overview with a focus on crew protection during dynamic phases of flight; occupant protection collaboration; modeling occupant protection; occupant protection considerations; project approach encompassing analysis tools, injury criteria, and testing program development; injury criteria update methodology, unique effects of pressure suits and other factors; and a summary.

  18. Communication complexity and information complexity

    NASA Astrophysics Data System (ADS)

    Pankratov, Denis

    Information complexity enables the use of information-theoretic tools in communication complexity theory. Prior to the results presented in this thesis, information complexity was mainly used for proving lower bounds and direct-sum theorems in the setting of communication complexity. We present three results that demonstrate new connections between information complexity and communication complexity. In the first contribution we thoroughly study the information complexity of the smallest nontrivial two-party function: the AND function. While computing the communication complexity of AND is trivial, computing its exact information complexity presents a major technical challenge. In overcoming this challenge, we reveal that information complexity gives rise to rich geometrical structures. Our analysis of information complexity relies on new analytic techniques and new characterizations of communication protocols. We also uncover a connection of information complexity to the theory of elliptic partial differential equations. Once we compute the exact information complexity of AND, we can compute exact communication complexity of several related functions on n-bit inputs with some additional technical work. Previous combinatorial and algebraic techniques could only prove bounds of the form theta( n). Interestingly, this level of precision is typical in the area of information theory, so our result demonstrates that this meta-property of precise bounds carries over to information complexity and in certain cases even to communication complexity. Our result does not only strengthen the lower bound on communication complexity of disjointness by making it more exact, but it also shows that information complexity provides the exact upper bound on communication complexity. In fact, this result is more general and applies to a whole class of communication problems. In the second contribution, we use self-reduction methods to prove strong lower bounds on the information

  19. COMMUNITY BASED ENVIRONMENTAL PROTECTION

    EPA Science Inventory

    Community Based Environmental Protection intends to make environmental protection spring from the needs and values of the community of interest. Real community involvement in protecting the environment requires a process in which the environmental needs of communities and ecosyst...

  20. Subunit composition determines E2F DNA-binding site specificity.

    PubMed Central

    Tao, Y; Kassatly, R F; Cress, W D; Horowitz, J M

    1997-01-01

    The product of the retinoblastoma (Rb) susceptibility gene, Rb-1, regulates the activity of a wide variety of transcription factors, such as E2F, in a cell cycle-dependent fashion. E2F is a heterodimeric transcription factor composed of two subunits each encoded by one of two related gene families, denoted E2F and DP. Five E2F genes, E2F-1 through E2F-5, and two DP genes, DP-1 and DP-2, have been isolated from mammals, and heterodimeric complexes of these proteins are expressed in most, if not all, vertebrate cells. It is not yet clear whether E2F/DP complexes regulate overlapping and/or specific cellular genes. Moreover, little is known about whether Rb regulates all or a subset of E2F-dependent genes. Using recombinant E2F, DP, and Rb proteins prepared in baculovirus-infected cells and a repetitive immunoprecipitation-PCR procedure (CASTing), we have identified consensus DNA-binding sites for E2F-1/DP-1, E2F-1/DP-2, E2F-4/DP-1, and E2F-4/DP-2 complexes as well as an Rb/E2F-1/DP-1 trimeric complex. Our data indicate that (i) E2F, DP, and Rb proteins each influence the selection of E2F-binding sites; (ii) E2F sites differ with respect to their intrinsic DNA-bending properties; (iii) E2F/DP complexes induce distinct degrees of DNA bending; and (iv) complex-specific E2F sites selected in vitro function distinctly as regulators of cell cycle-dependent transcription in vivo. These data indicate that the specific sequence of an E2F site may determine its role in transcriptional regulation and suggest that Rb/E2F complexes may regulate subsets of E2F-dependent cellular genes. PMID:9372931

  1. 40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... metal complex. 721.4596 Section 721.4596 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.4596 Diazo substituted carbomonocyclic metal complex. (a) Chemical... as a diazo substituted carbomonocyclic metal complex (PMN P-94-1039) is subject to reporting...

  2. 40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... metal complex. 721.4596 Section 721.4596 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.4596 Diazo substituted carbomonocyclic metal complex. (a) Chemical... as a diazo substituted carbomonocyclic metal complex (PMN P-94-1039) is subject to reporting...

  3. 40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... metal complex. 721.4596 Section 721.4596 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.4596 Diazo substituted carbomonocyclic metal complex. (a) Chemical... as a diazo substituted carbomonocyclic metal complex (PMN P-94-1039) is subject to reporting...

  4. 40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... metal complex. 721.4596 Section 721.4596 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.4596 Diazo substituted carbomonocyclic metal complex. (a) Chemical... as a diazo substituted carbomonocyclic metal complex (PMN P-94-1039) is subject to reporting...

  5. 40 CFR 721.10003 - Manganese heterocyclic tetraamine complex (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... complex (generic). 721.10003 Section 721.10003 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.10003 Manganese heterocyclic tetraamine complex (generic). (a) Chemical... as manganese heterocyclic tetraamine complex (PMNs P-98-625/626/627/628/629 and P-00-614/617)...

  6. Complex derivatives

    NASA Astrophysics Data System (ADS)

    Battiston, Stefano; Caldarelli, Guido; Georg, Co-Pierre; May, Robert; Stiglitz, Joseph

    2013-03-01

    The intrinsic complexity of the financial derivatives market has emerged as both an incentive to engage in it, and a key source of its inherent instability. Regulators now faced with the challenge of taming this beast may find inspiration in the budding science of complex systems.

  7. Designing Complexity

    ERIC Educational Resources Information Center

    Glanville, Ranulph

    2007-01-01

    This article considers the nature of complexity and design, as well as relationships between the two, and suggests that design may have much potential as an approach to improving human performance in situations seen as complex. It is developed against two backgrounds. The first is a world view that derives from second order cybernetics and radical…

  8. Supramolecular complexations of natural products.

    PubMed

    Schneider, Hans-Jörg; Agrawal, Pawan; Yatsimirsky, Anatoly K

    2013-08-21

    Complexations of natural products with synthetic receptors as well as the use of natural products as host compounds are reviewed, with an emphasis on possible practical uses or on biomedical significance. Applications such as separation, sensing, enzyme monitoring, and protection of natural drugs are first outlined. We then discuss examples of complexes with all important classes of natural compounds, such as amino acids, peptides, nucleosides/nucleotides, carbohydrates, catecholamines, flavonoids, terpenoids/steroids, alkaloids, antibiotics and toxins. PMID:23703643

  9. Complex of vitamins and antioxidants protects low-density lipoproteins in blood plasma from free radical oxidation and activates antioxidants enzymes in erythrocytes from patients with coronary heart disease.

    PubMed

    Konovalova, G G; Lankin, V Z; Tikhaze, A K; Nezhdanova, I B; Lisina, M O; Kukharchuk, V V

    2003-08-01

    We studied the effect of a complex containing antioxidant vitamins C and E, provitamin A, and antioxidant element selenium on the contents of primary (lipid peroxides) and secondary products (malonic dialdehyde) of free radical lipid oxidation in low-density lipoproteins isolated from the plasma of patients with coronary heart disease and hypercholesterolemia by means of preparative ultracentrifugation. Activity of key antioxidant enzymes in the blood was measured during treatment with the antioxidant preparation. Combination treatment with antioxidant vitamins and antioxidant element selenium sharply decreased the contents of primary and secondary free radical oxidation products in circulating low-density lipoproteins and increased activity of antioxidant enzymes in erythrocytes. Activities of superoxide dismutase and selenium-containing glutathione peroxidase increased 1 and 2 months after the start of therapy, respectively. PMID:14631494

  10. Carney Complex

    MedlinePlus

    ... Screening guidelines may change over time as new technologies are developed and more is learned about Carney complex. It is important to talk with your doctor about appropriate screening tests. Learn more about what to expect when having ...

  11. [Radiation protection in interventional cardiology].

    PubMed

    Durán, Ariel

    2015-01-01

    INTERVENTIONAL: cardiology progress makes each year a greater number of procedures and increasing complexity with a very good success rate. The problem is that this progress brings greater dose of radiation not only for the patient but to occupationally exposed workers as well. Simple methods for reducing or minimizing occupational radiation dose include: minimizing fluoroscopy time and the number of acquired images; using available patient dose reduction technologies; using good imaging-chain geometry; collimating; avoiding high-scatter areas; using protective shielding; using imaging equipment whose performance is controlled through a quality assurance programme; and wearing personal dosimeters so that you know your dose. Effective use of these methods requires both appropriate education and training in radiation protection for all interventional cardiology personnel, and the availability and use of appropriate protective tools and equipment. Regular review and investigation of personnel monitoring results, accompanied as appropriate by changes in how procedures are performed and equipment used, will ensure continual improvement in the practice of radiation protection in the interventional suite. PMID:26169040

  12. Complex networks: Patterns of complexity

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2010-07-01

    The Turing mechanism provides a paradigm for the spontaneous generation of patterns in reaction-diffusion systems. A framework that describes Turing-pattern formation in the context of complex networks should provide a new basis for studying the phenomenon.

  13. GENERAL PERSPECTIVE VIEW OF THE COMPLEX, VIEW LOOKING EAST AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL PERSPECTIVE VIEW OF THE COMPLEX, VIEW LOOKING EAST AT THE FOREST PROTECTION BUILDING, THE MOTORPOOL, AND THE AUTOMOTIVE SHOP (FROM LEFT TO RIGHT). - Oregon State Forester's Office Complex, 2600 State Street, Salem, Marion, OR

  14. GENERAL PERSPECTIVE VIEW OF THE COMPLEX, VIEW LOOKING WEST AT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    GENERAL PERSPECTIVE VIEW OF THE COMPLEX, VIEW LOOKING WEST AT THE MOTORPOOL, AUTOMOTIVE SHOP AND FOREST PROTECTION BUILDING (FROM LEFT TO RIGHT). - Oregon State Forester's Office Complex, 2600 State Street, Salem, Marion, OR

  15. MSFC Respiratory Protection Services

    NASA Technical Reports Server (NTRS)

    CoVan, James P.

    1999-01-01

    An overview of the Marshall Space Flight Center Respiratory Protection program is provided in this poster display. Respiratory protection personnel, building, facilities, equipment, customers, maintenance and operational activities, and Dynatech fit testing details are described and illustrated.

  16. Personal protective equipment

    MedlinePlus

    ... protective equipment. Available at: www.cdc.gov/niosh/ppe . Accessed October 27, 2015. Holland MG, Cawthon D. Personal protective equipment and decontamination of adults and children. Emerg Med Clin N ...

  17. Medicare Rights and Protections

    MedlinePlus

    CENTERS for MEDICARE & MEDICAID SERVICES Medicare Rights & Protections This official government booklet has important information about: Your rights & protections in: ■ ■ Original Medicare ■ ■ Medicare Advantage Plan or other Medicare health ...

  18. Protecting Children's Online Privacy.

    ERIC Educational Resources Information Center

    Kresses, Mamie

    2001-01-01

    Discuss provisions of new federal Children's Online Privacy Protection Act that principals should know to protect student privacy on the Internet. Also discusses relevant provisions of the Family Educational Rights and Privacy Act. (PKP)

  19. Corium protection assembly

    DOEpatents

    Gou, Perng-Fei; Townsend, Harold E.; Barbanti, Giancarlo

    1994-01-01

    A corium protection assembly includes a perforated base grid disposed below a pressure vessel containing a nuclear reactor core and spaced vertically above a containment vessel floor to define a sump therebetween. A plurality of layers of protective blocks are disposed on the grid for protecting the containment vessel floor from the corium.

  20. Careers in Environmental Protection.

    ERIC Educational Resources Information Center

    Millard, Reed

    The book presents concerns of our society in protecting our environment and the challenges involved in meaningful careers in environmental protection and management. "Estimates by the Environmental Protection Agency indicate that, compared with their numbers in the mid-'70's, the need for environmental professionals will triple by 1980.'" In a…

  1. Abrasion protection in process piping

    SciTech Connect

    Accetta, J.

    1996-07-01

    Process piping often is subjected to failure from abrasion or a combination of abrasion and corrosion. Abrasion is a complex phenomenon, with many factors involved to varying degrees. Hard, mineral based alumina ceramic and basalt materials are used to provide protection against abrasion in many piping systems. Successful life extension examples are presented from many different industries. Lined piping components require special attention with regard to operating conditions as well as design and engineering considerations. Economic justification involves direct cost comparisons and avoided costs.

  2. Complex interactions

    NASA Astrophysics Data System (ADS)

    de Régules, Sergio

    2016-04-01

    Complexity science – which describes phenomena such as collective and emergent behaviour – is the focus of a new centre where researchers are examining everything from the spread of influenza to what a healthy heartbeat looks like. Sergio de Régules reports.

  3. Researching Complexity.

    ERIC Educational Resources Information Center

    Sumara, Dennis J.

    2000-01-01

    Discusses what Complexity Theory (presented as a rubric that collects theoretical understandings from a number of domains such as ecology, biology, neurology, and education) suggests about mind, selfhood, intelligence, and practices of reading, and the import of these reconceptualizations to reader-response researchers. Concludes that developing…

  4. Complex Clouds

    Atmospheric Science Data Center

    2013-04-16

    ...     View Larger Image The complex structure and beauty of polar clouds are highlighted by these images acquired ... Multi-angle Imaging SpectroRadiometer observes the daylit Earth continuously from pole to pole, and every 9 days views the entire globe ...

  5. Amorphic complexity

    NASA Astrophysics Data System (ADS)

    Fuhrmann, G.; Gröger, M.; Jäger, T.

    2016-02-01

    We introduce amorphic complexity as a new topological invariant that measures the complexity of dynamical systems in the regime of zero entropy. Its main purpose is to detect the very onset of disorder in the asymptotic behaviour. For instance, it gives positive value to Denjoy examples on the circle and Sturmian subshifts, while being zero for all isometries and Morse-Smale systems. After discussing basic properties and examples, we show that amorphic complexity and the underlying asymptotic separation numbers can be used to distinguish almost automorphic minimal systems from equicontinuous ones. For symbolic systems, amorphic complexity equals the box dimension of the associated Besicovitch space. In this context, we concentrate on regular Toeplitz flows and give a detailed description of the relation to the scaling behaviour of the densities of the p-skeletons. Finally, we take a look at strange non-chaotic attractors appearing in so-called pinched skew product systems. Continuous-time systems, more general group actions and the application to cut and project quasicrystals will be treated in subsequent work.

  6. Fire Protection Program Manual

    SciTech Connect

    Sharry, J A

    2012-05-18

    This manual documents the Lawrence Livermore National Laboratory (LLNL) Fire Protection Program. Department of Energy (DOE) Orders 420.1B, Facility Safety, requires LLNL to have a comprehensive and effective fire protection program that protects LLNL personnel and property, the public and the environment. The manual provides LLNL and its facilities with general information and guidance for meeting DOE 420.1B requirements. The recommended readers for this manual are: fire protection officers, fire protection engineers, fire fighters, facility managers, directorage assurance managers, facility coordinators, and ES and H team members.

  7. Office for Human Research Protections

    MedlinePlus

    ... Office for Human Research Protections The Office for Human Research Protections (OHRP) provides leadership in the protection of the rights, welfare, and wellbeing of human subjects involved in ...

  8. Burnout Stress Syndrome in Child Protection.

    ERIC Educational Resources Information Center

    Verstraete, Patricia A.

    1994-01-01

    Burnout stress syndrome is a complex concept reflecting a failure in both the individual's defense mechanism and in the work environment. Since child protection agencies cannot afford the costs of staff burnout, time and money spent by the organization to reduce employee stress is an investment in better service delivery. (TJQ)

  9. Antibodies: Protective, destructive and regulatory role

    SciTech Connect

    Milgrom, F.; Abeyounis, C.J.; Albini, B.

    1985-01-01

    This book contains papers under 10 subject headings. The headings are: Production and Function of Antibodies, Protective Role of Antibodies, Antibodies to Foreign and Neoplastic Cells, Autoantibodies, Regulatory Mechanisms, Allergy, Immune Complexes, Antibodies in Pregnancy and Aging, Administration of Antibodies for Prevention and Therapy, and Abstracts of Poster Presentations.

  10. Managing Complexity

    SciTech Connect

    Chassin, David P.; Posse, Christian; Malard, Joel M.

    2004-08-01

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today’s most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically-based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This paper explores the state of the art in the use physical analogs for understanding the behavior of some econophysical systems and to deriving stable and robust control strategies for them. In particular we review and discussion applications of some analytic methods based on the thermodynamic metaphor according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood.

  11. Resilience from coastal protection.

    PubMed

    Ewing, Lesley C

    2015-10-28

    Coastal areas are important residential, commercial and industrial areas; but coastal hazards can pose significant threats to these areas. Shoreline/coastal protection elements, both built structures such as breakwaters, seawalls and revetments, as well as natural features such as beaches, reefs and wetlands, are regular features of a coastal community and are important for community safety and development. These protection structures provide a range of resilience to coastal communities. During and after disasters, they help to minimize damages and support recovery; during non-disaster times, the values from shoreline elements shift from the narrow focus on protection. Most coastal communities have limited land and resources and few can dedicate scarce resources solely for protection. Values from shore protection can and should expand to include environmental, economic and social/cultural values. This paper discusses the key aspects of shoreline protection that influence effective community resilience and protection from disasters. This paper also presents ways that the economic, environmental and social/cultural values of shore protection can be evaluated and quantified. It presents the Coastal Community Hazard Protection Resilience (CCHPR) Index for evaluating the resilience capacity to coastal communities from various protection schemes and demonstrates the use of this Index for an urban beach in San Francisco, CA, USA. PMID:26392613

  12. 40 CFR 721.4596 - Diazo substituted carbomonocyclic metal complex.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... metal complex. 721.4596 Section 721.4596 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4596 Diazo substituted carbomonocyclic metal complex. (a)...

  13. Multiwall thermal protection system

    NASA Technical Reports Server (NTRS)

    Jackson, L. R. (Inventor)

    1982-01-01

    Multiwall insulating sandwich panels are provided for thermal protection of hypervelocity vehicles and other enclosures. In one embodiment, the multiwall panels are formed of alternate layers of dimpled and flat metal (titanium alloy) foil sheets and beaded scarfed edge seals to provide enclosure thermal protection up to 1000 F. An additional embodiment employs an intermediate fibrous insulation for the sandwich panel to provide thermal protection up to 2000 F. A third embodiment employs a silicide coated columbium waffle as the outer panel skin and fibrous layered intermediate protection for thermal environment protection up to 2500 F. The use of multiple panels on an enclosure facilitate repair and refurbishment of the thermal protection system due to the simple support provided by the tab and clip attachment for the panels.

  14. Emergency Protection from Aerosols

    SciTech Connect

    Cristy, G.A.

    2001-11-13

    Expedient methods were developed that could be used by an average person, using only materials readily available, to protect himself and his family from injury by toxic (e.g., radioactive) aerosols. The most effective means of protection was the use of a household vacuum cleaner to maintain a small positive pressure on a closed house during passage of the aerosol cloud. Protection factors of 800 and above were achieved.

  15. An EBV recombinant deleted for residues 130-159 in EBNA3C can deregulate p53/Mdm2 and Cyclin D1/CDK6 which results in apoptosis and reduced cell proliferation

    PubMed Central

    El-Naccache, Darine W.; Robertson, Erle S.

    2016-01-01

    Epstein-Barr virus (EBV), a gamma herpes virus is associated with B-cell malignancies. EBNA-3C is critical for in vitro primary B-cell transformation. Interestingly, the N terminal domain of EBNA3C which contains residues 130–159, interacts with various cellular proteins, such as p53, Mdm2, CyclinD1/Cdk6 complex, and E2F1. In the current reverse genetics study, we deleted the residues 130-159 aa within EBNA3C open reading frame (ORF) by BACmid recombinant engineering methodology. Our experiments demonstrated that deletion of the 130-159 aa showed a reduction in cell proliferation. Also, this recombinant virus showed with higher infectivity of human peripheral blood mononuclear cells (PBMCs) compared to wild type EBV. PBMCs- infected with recombinant EBV deleted for 130-159 residues have differential expression patterns for the p53/Mdm2, CyclinD1/Cdk6 and pRb/E2F1 pathways compared to wild type EBV-infected PBMCs. PBMCs infected with recombinant virus showed increased apoptotic cell death which further resulted in activation of polymerase 1 (PARP1), an important contributor to apoptotic signaling. Interestingly, cells infected with this recombinant virus showed a dramatic decrease in chromosomal instability, indicated by the presence of increased multinucleation and micronucleation. In addition infection with recombinant virus have increased cells in G0/G1 phase and decreased cells in S-G2M phase when compared to wild type infected cells. Thus, these differences in signaling activities due to 29 amino acid residues of EBNA3C is of particular significance in deregulation of cell proliferation in EBV-infected cells. PMID:26908453

  16. MicroRNA-155 controls RB phosphorylation in normal and malignant B lymphocytes via the noncanonical TGF-β1/SMAD5 signaling module.

    PubMed

    Jiang, Daifeng; Aguiar, Ricardo C T

    2014-01-01

    MicroRNA-155 (miR-155) plays pleiotropic roles in the biology of normal and malignant B lymphocytes, including the modulation of the transforming growth factor β (TGF-β) pathway via the targeting of SMAD5. However, the extent of the miR-155-mediated disruption of the TGF-β1/SMAD5 axis remains to be elucidated. To address this issue, we used the miR-155 knockout (KO) mouse and diffuse large B-cell lymphoma (DLBCL) cell lines ectopically expressing miR-155. In the DLBCL models, expression of miR-155 blocked TGF-β1-mediated activation of the retinoblastoma protein (RB), decreasing the abundance of the inhibitory pRB-E2F1 complex and limiting G0/G1 arrest. Genetic knockdown of SMAD5, p15, or p21 recapitulated these effects, establishing a circuitry whereby the targeting of SMAD5 by miR-155 blunts the TGF-β1-induced transcription of p15 and p21, thus sustaining RB phosphorylation and inactivity. Next, we demonstrated that SMAD5 levels are elevated in mature B lymphocytes from the miR-155 KO mice, which display a heightened sensitivity to TGF-β1 characterized by suppression of RB phosphorylation and more pronounced G0/G1 cell cycle arrest. Our findings suggest that a miR-155-mediated perturbation of the RB/E2F axis may play a role in DLBCL pathogenesis, and contribute to the reduced number of germinal center B cells and impaired T cell-dependent antibody response found in the miR-155 KO mice. PMID:24136167

  17. Pro-apoptotic function of the retinoblastoma tumor suppressor protein

    PubMed Central

    Ianari, Alessandra; Natale, Tiziana; Calo, Eliezer; Ferretti, Elisabetta; Alesse, Edoardo; Screpanti, Isabella; Haigis, Kevin; Gulino, Alberto; Lees, Jacqueline A.

    2009-01-01

    SUMMARY The retinoblastoma protein (pRB) tumor suppressor blocks cell proliferation by repressing the E2F transcription factors. This inhibition is relieved through mitogen-induced phosphorylation of pRB, triggering E2F release and activation of cell cycle genes. E2F1 can also activate pro-apoptotic genes in response to genotoxic or oncogenic stress. However, pRB’s role in this context has not been established. Here we show that DNA damage and E1A-induced oncogenic stress promotes formation of a pRB-E2F1 complex even in proliferating cells. Moreover, pRB is bound to pro-apoptotic promoters that are transcriptional active and pRB is required for maximal apoptotic response in vitro and in vivo. Together, these data reveal a direct role for pRB in the induction of apoptosis in response to genotoxic or oncogenic stress. SIGNIFICANCE pRB function is disrupted in many human tumors through either inactivation of the Rb gene or alterations in its upstream regulators. pRB’s tumor suppressive activity is at least partially dependent upon its ability to arrest cells through E2F inhibition. Our data now establish a second role for pRB as a stress-induced activator of apoptosis. Notably, pRB’s ability to promote either arrest versus apoptosis seems to be context dependent, with apoptosis being favored in proliferating cells. This finding has the potential to explain why cells are typically more resistant to apoptosis when in the arrested state. Most importantly, our observations suggest that Rb status will influence tumor response to chemotherapy by impairing both the arrest and apoptotic checkpoint responses. PMID:19249677

  18. Copyright protection for GIS vector data production

    NASA Astrophysics Data System (ADS)

    Li, A.; Zhou, W.; Lin, B.; Chen, Y.

    2008-10-01

    Limited by the characters of GIS vector data, such as variety and complexity of expression, universality, mass, disorder and pretty good privacy, etc., the traditional copyright protection methods for image and audio productions cannot be applied into GIS vector data productions directly. In this paper, a solution to copyright protection of GIS vector data productions is proposed. Firstly, information characteristics, data organization and storage characteristics and attack characteristics of GIS vector data are comprehensively analyzed. Secondly, based on hash, file filter driver, dynamic encryption and decryption, the key techniques including zero-watermarking generation, access control, and data content protection are described. Finally, a copyright protection frame of GIS vector data is put forward.

  19. 28. GENERAL VIEW OF ELECTRICAL EQUIPMENT PROTECTED BY CONCRETE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    28. GENERAL VIEW OF ELECTRICAL EQUIPMENT PROTECTED BY CONCRETE AND EARTH BLAST BERM; VIEW TO NORTHEAST. - Cape Canaveral Air Station, Launch Complex 17, Facility 28402, East end of Lighthouse Road, Cape Canaveral, Brevard County, FL

  20. 29. GENERAL VIEW OF ELECTRICAL EQUIPMENT PROTECTED BY CONCRETE AND ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    29. GENERAL VIEW OF ELECTRICAL EQUIPMENT PROTECTED BY CONCRETE AND EARTH BLAST BERM; VIEW TO SOUTHEAST. - Cape Canaveral Air Station, Launch Complex 17, Facility 28402, East end of Lighthouse Road, Cape Canaveral, Brevard County, FL

  1. NASA Fire Protection

    NASA Technical Reports Server (NTRS)

    Clark, Theodore

    2001-01-01

    This viewgraph presentation provides information on fire protection operations and administration at Stennis Space Center (SSC). The presentation also lists innovative practices and recent improvements.

  2. Protection - Principles and practice.

    NASA Technical Reports Server (NTRS)

    Graham, G. S.; Denning, P. J.

    1972-01-01

    The protection mechanisms of computer systems control the access to objects, especially information objects. The principles of protection system design are formalized as a model (theory) of protection. Each process has a unique identification number which is attached by the system to each access attempted by the process. Details of system implementation are discussed, taking into account the storing of the access matrix, aspects of efficiency, and the selection of subjects and objects. Two systems which have protection features incorporating all the elements of the model are described.

  3. Complex Systems

    PubMed Central

    Goldberger, Ary L.

    2006-01-01

    Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and “chaos theory,” is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease. PMID:16921107

  4. [Carney complex].

    PubMed

    Kacerovská, D; Michal, M; Síma, R; Grossmann, P; Kazakov, D V

    2011-10-01

    Carney complex is a clinically and genetically heterogeneous disease, with at least two genetic loci including the PRKAR1A gene located on chromosome 17 and the CNC2 locus mapped to chromosome 2. Clinically this syndrome is characterized by multiple myxomas occurring in different anatomic sites, mucocutaneous pigmentary lesions, and a variety of non-endocrine and endocrine tumors, often causing endocrine abnormalities, involving various organs. Knowledge of morphological findings in CNC patients with their typical locations is necessary to raise suspicion of this syndrome by pathologists. Confirmation of the diagnosis allows regular clinical check-ups and early treatment of these patients. PMID:22145222

  5. Carney complex.

    PubMed

    Espiard, Stéphanie; Bertherat, Jérôme

    2013-01-01

    Carney complex is a rare, dominantly inherited multiple endocrine neoplasia syndrome, affecting endocrine glands as the adrenal cortex (causing Cushing's syndrome), the pituitary and the thyroid. It is associated with many other nonendocrine tumors, including cardiac myxomas, testicular tumors, melanotic schwannoma, breast myxomatosis, and abnormal pigmentation (lentiginosis) or myxomas of the skin. The gene located on the CNC1 locus was identified 12 years ago as the regulatory subunit 1A (R1A) of the protein kinase A (PRKAR1A) located at 17q22-24. Inactivating heterozygous germline mutations of PRKAR1A are observed in about two thirds of Carney complex patients with some genotype-phenotype correlation useful for follow-up and prognosis. More rarely, mutations of phosphodiesterase genes have been reported in patients presenting mainly with Cushing's syndrome. In vitro and in vivo studies help to understand how R1A inactivation leads to tumorigenesis. PRKAR1A appears to be a relatively weak tumorigenic signal which can cooperate with other signaling pathways and tumor suppressors. PMID:23652670

  6. Consumer Protection in HE: Complacency and Complaints, Compliance and Complexities

    ERIC Educational Resources Information Center

    Palfreyman, David

    2012-01-01

    The author argues that a Higher Education Bill will be lacking in the future, as promised in the 2011 White Paper on HE; and hence the regulatory framework for English HE will, for the immediate future at least, have to evolve within the law as it is rather than via new legal powers. The essential issue is how to extract the benefits of market…

  7. The REST remodeling complex protects genomic integrity during embryonic neurogenesis

    PubMed Central

    Nechiporuk, Tamilla; McGann, James; Mullendorff, Karin; Hsieh, Jenny; Wurst, Wolfgang; Floss, Thomas; Mandel, Gail

    2016-01-01

    The timely transition from neural progenitor to post-mitotic neuron requires down-regulation and loss of the neuronal transcriptional repressor, REST. Here, we have used mice containing a gene trap in the Rest gene, eliminating transcription from all coding exons, to remove REST prematurely from neural progenitors. We find that catastrophic DNA damage occurs during S-phase of the cell cycle, with long-term consequences including abnormal chromosome separation, apoptosis, and smaller brains. Persistent effects are evident by latent appearance of proneural glioblastoma in adult mice deleted additionally for the tumor suppressor p53 protein (p53). A previous line of mice deleted for REST in progenitors by conventional gene targeting does not exhibit these phenotypes, likely due to a remaining C-terminal peptide that still binds chromatin and recruits co-repressors. Our results suggest that REST-mediated chromatin remodeling is required in neural progenitors for proper S-phase dynamics, as part of its well-established role in repressing neuronal genes until terminal differentiation. DOI: http://dx.doi.org/10.7554/eLife.09584.001 PMID:26745185

  8. Micrometeorological principles of protected cultivation for fruit crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Protected cultivation is a broad term commonly used among producers of specialty crops. Techniques can range from complex fixed structures to field site selection, to straightforward cultural practices in the field. This introduction to the ASHS workshop "Protected cultivation for fruit crops" consi...

  9. A new method testing the orthogonality of different protecting groups.

    PubMed

    Ágoston, Károly; Ágoston, Ágnes; Dorgan, Colin R; Fügedi, Péter

    2015-12-11

    A new test was elaborated to identify a new set of orthogonal protecting groups. With the developed method eight different protecting groups were tested under various deprotection conditions and the complex reaction mixtures were analysed by HPLC. The developed method allows for quick identification of orthogonality using simple model structures. PMID:26580711

  10. Measuring the Impact of Child Protection through Activation States

    ERIC Educational Resources Information Center

    Brackenridge, Celia H.; Pawlaczek, Zofia; Bringer, Joy D.; Cockburn, Claudi; Nutt, Gareth; Pitchford, Andy; Russell, Kate

    2005-01-01

    Child protection (CP) has risen to the top of the UK sports policy agenda in the past four years and the Football Association has invested in this major strategy as part of its commitment to "use the power of football to build a better future" (Football Association, 2000a). Evidencing the impact of child protection is, however, a complex task,…

  11. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  12. Cosmic Complexity

    NASA Technical Reports Server (NTRS)

    Mather, John C.

    2012-01-01

    What explains the extraordinary complexity of the observed universe, on all scales from quarks to the accelerating universe? My favorite explanation (which I certainty did not invent) ls that the fundamental laws of physics produce natural instability, energy flows, and chaos. Some call the result the Life Force, some note that the Earth is a living system itself (Gaia, a "tough bitch" according to Margulis), and some conclude that the observed complexity requires a supernatural explanation (of which we have many). But my dad was a statistician (of dairy cows) and he told me about cells and genes and evolution and chance when I was very small. So a scientist must look for me explanation of how nature's laws and statistics brought us into conscious existence. And how is that seemll"!gly Improbable events are actually happening a!1 the time? Well, the physicists have countless examples of natural instability, in which energy is released to power change from simplicity to complexity. One of the most common to see is that cooling water vapor below the freezing point produces snowflakes, no two alike, and all complex and beautiful. We see it often so we are not amazed. But physlc!sts have observed so many kinds of these changes from one structure to another (we call them phase transitions) that the Nobel Prize in 1992 could be awarded for understanding the mathematics of their common features. Now for a few examples of how the laws of nature produce the instabilities that lead to our own existence. First, the Big Bang (what an insufficient name!) apparently came from an instability, in which the "false vacuum" eventually decayed into the ordinary vacuum we have today, plus the most fundamental particles we know, the quarks and leptons. So the universe as a whole started with an instability. Then, a great expansion and cooling happened, and the loose quarks, finding themselves unstable too, bound themselves together into today's less elementary particles like protons and

  13. Protecting the Crown Jewels.

    ERIC Educational Resources Information Center

    Andrus, Cecil

    1979-01-01

    The National Park Service seeks to set the standard for environmental protection in the federally-owned lands which it administers. Often pollution from sources outside park boundaries creates adverse impacts within the parks. Innovative approaches and cooperative efforts are then required to protect the parks. (RE)

  14. Protective Garment Ensemble

    NASA Technical Reports Server (NTRS)

    Wakefield, M. E.

    1982-01-01

    Protective garment ensemble with internally-mounted environmental- control unit contains its own air supply. Alternatively, a remote-environmental control unit or an air line is attached at the umbilical quick disconnect. Unit uses liquid air that is vaporized to provide both breathing air and cooling. Totally enclosed garment protects against toxic substances.

  15. Electroplating offers embrittlement protection

    NASA Technical Reports Server (NTRS)

    Daniels, C. M., Jr.

    1970-01-01

    Thin copper electrodeposited layer protects metal parts in environments with which they may be incompatible. Originally developed for main engine of Space Shuttle where high strength nickle alloy bellows must operate in high-pressure hydrogen, technique protects nickel and is unaffected by forming process or subsequent heat treatment and preinstallation processing.

  16. Environmental protection Implementation Plan

    SciTech Connect

    R. C. Holland

    1999-12-01

    This ``Environmental Protection Implementation Plan'' is intended to ensure that the environmental program objectives of Department of Energy Order 5400.1 are achieved at SNL/California. This document states SNL/California's commitment to conduct its operations in an environmentally safe and responsible manner. The ``Environmental Protection Implementation Plan'' helps management and staff comply with applicable environmental responsibilities.

  17. A Duty to Protect

    ERIC Educational Resources Information Center

    Lee, James

    2009-01-01

    Asylum is a value. At its most basic, it is about the importance of protecting someone's life from persecution. The 1951 Refugee Convention seeks to achieve this--by ensuring that those people with a well-founded fear of persecution should be able to find protection within a state that has signed up to the Convention. The UK's commitments under…

  18. Protection of multimaterial assemblies

    NASA Astrophysics Data System (ADS)

    Mikhail, L. Zheludkevich; Silvar, Kallip; Maria, Serdechnova

    2016-01-01

    The light-weight design calls for broader utilization of multimaterial mixes (M3) in different engineering structures, especially in the transportation area. Together with joining technologies for hybrid structures, the optimization of the life cycle of such systems is an issue of prime importance. Multimaterial structures are often prone to faster degradation under service conditions because of galvanically forced electrochemical corrosion. The protection technologies traditionally used for single-material structures are not always applicable for multimaterial design because of compatibility issues and a stronger thermodynamic driving force for degradation. In this chapter different strategies for protection of multimaterials structures are briefly overviewed. The main focus is on new alternative protection systems based on combination of synergistic inhibiting mixtures introduced into protective coatings. A road map which can be followed in order to create an efficient active protection coating for hybrid structures is suggested.

  19. Wake Shield Target Protection

    SciTech Connect

    Valmianski, Emanuil I.; Petzoldt, Ronald W.; Alexander, Neil B.

    2003-05-15

    The heat flux from both gas convection and chamber radiation on a direct drive target must be limited to avoid target damage from excessive D-T temperature increase. One of the possibilities of protecting the target is a wake shield flying in front of the target. A shield will also reduce drag force on the target, thereby facilitating target tracking and position prediction. A Direct Simulation Monte Carlo (DSMC) code was used to calculate convection heat loads as boundary conditions input into ANSYS thermal calculations. These were used for studying the quality of target protection depending on various shapes of shields, target-shield distance, and protective properties of the shield moving relative to the target. The results show that the shield can reduce the convective heat flux by a factor of 2 to 5 depending on pressure, temperature, and velocity. The protective effect of a shield moving relative to the target is greater than the protective properties of a fixed shield. However, the protective effect of a shield moving under the drag force is not sufficient for bringing the heat load on the target down to the necessary limit. Some other ways of diminishing heat flux using a protective shield are discussed.

  20. Radiation protection in space.

    PubMed

    Reitz, G; Facius, R; Sandler, H

    1995-01-01

    Radiation environment, basic concepts of radiation protection, and specific aspects of the space radiation field are reviewed. The discussion of physico-chemical and subcellular radiation effects includes mechanisms of radiation action and cellular consequences. The discussion of radiobiological effects includes unique aspects of HZE particle effects, space flight findings, terrestrial findings, analysis of somatic radiation effects and effects on critical organs, and early and delayed effects. Other topics include the impact of the space flight environment, measurement of radiation exposure, establishing radiation protection limits, limitations in establishing space-based radiation exposure limits, radiation protection measures, and recommendations. PMID:11541474

  1. Optimization of radiation protection

    SciTech Connect

    Lochard, J.

    1981-07-01

    The practical and theoretical problems raised by the optimization of radiological protection merit a review of decision-making methods, their relevance, and the way in which they are used in order to better determine what role they should play in the decision-making process. Following a brief summary of the theoretical background of the cost-benefit analysis, we examine the methodological choices implicit in the model presented in the International Commission on Radiological Protection Publication No. 26 and, particularly, the consequences of the theory that the level of radiation protection, the benefits, and the production costs of an activity can be treated separately.

  2. Fire protection design criteria

    SciTech Connect

    1997-03-01

    This Standard provides supplemental fire protection guidance applicable to the design and construction of DOE facilities and site features (such as water distribution systems) that are also provided for fire protection. It is intended to be used in conjunction with the applicable building code, national Fire Protection Association Codes and Standards, and any other applicable DOE construction criteria. This Standard, along with other delineated criteria, constitutes the basic criteria for satisfying DOE fire and life safety objectives for the design and construction or renovation of DOE facilities.

  3. Protected areas and poverty

    PubMed Central

    Brockington, Daniel; Wilkie, David

    2015-01-01

    Protected areas are controversial because they are so important for conservation and because they distribute fortune and misfortune unevenly. The nature of that distribution, as well as the terrain of protected areas themselves, have been vigorously contested. In particular, the relationship between protected areas and poverty is a long-running debate in academic and policy circles. We review the origins of this debate and chart its key moments. We then outline the continuing flashpoints and ways in which further evaluation studies could improve the evidence base for policy-making and conservation practice. PMID:26460124

  4. 40 CFR Appendix B to Part 414 - Complexed Metal-Bearing Waste Streams

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 28 2010-07-01 2010-07-01 true Complexed Metal-Bearing Waste Streams B Appendix B to Part 414 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Pt. 414, App. B Appendix B to Part 414—Complexed Metal-Bearing...

  5. 40 CFR Appendix B to Part 414 - Complexed Metal-Bearing Waste Streams

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 30 2012-07-01 2012-07-01 false Complexed Metal-Bearing Waste Streams B Appendix B to Part 414 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORGANIC CHEMICALS, PLASTICS, AND SYNTHETIC FIBERS Pt. 414, App. B Appendix B to Part 414—Complexed Metal-Bearing...

  6. 40 CFR 80.48 - Augmentation of the complex emission model by vehicle testing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 16 2010-07-01 2010-07-01 false Augmentation of the complex emission model by vehicle testing. 80.48 Section 80.48 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Reformulated Gasoline § 80.48 Augmentation of the complex...

  7. Optimal shield mass distribution for space radiation protection

    NASA Technical Reports Server (NTRS)

    Billings, M. P.

    1972-01-01

    Computational methods have been developed and successfully used for determining the optimum distribution of space radiation shielding on geometrically complex space vehicles. These methods have been incorporated in computer program SWORD for dose evaluation in complex geometry, and iteratively calculating the optimum distribution for (minimum) shield mass satisfying multiple acute and protected dose constraints associated with each of several body organs.

  8. Protecting Against Faults in JPL Spacecraft

    NASA Technical Reports Server (NTRS)

    Morgan, Paula

    2007-01-01

    A paper discusses techniques for protecting against faults in spacecraft designed and operated by NASA s Jet Propulsion Laboratory (JPL). The paper addresses, more specifically, fault-protection requirements and techniques common to most JPL spacecraft (in contradistinction to unique, mission specific techniques), standard practices in the implementation of these techniques, and fault-protection software architectures. Common requirements include those to protect onboard command, data-processing, and control computers; protect against loss of Earth/spacecraft radio communication; maintain safe temperatures; and recover from power overloads. The paper describes fault-protection techniques as part of a fault-management strategy that also includes functional redundancy, redundant hardware, and autonomous monitoring of (1) the operational and health statuses of spacecraft components, (2) temperatures inside and outside the spacecraft, and (3) allocation of power. The strategy also provides for preprogrammed automated responses to anomalous conditions. In addition, the software running in almost every JPL spacecraft incorporates a general-purpose "Safe Mode" response algorithm that configures the spacecraft in a lower-power state that is safe and predictable, thereby facilitating diagnosis of more complex faults by a team of human experts on Earth.

  9. Protective Face Mask

    NASA Technical Reports Server (NTRS)

    1981-01-01

    Mask to protect the physically impaired from injuries to the face and head has been developed by Langley Research Center. It is made of composite materials, usually graphite or boron fibers woven into a matrix. Weighs less than three ounces.

  10. Protective relaying performance reporting

    SciTech Connect

    Taylor, R.P.; Ingelson, J.W.; Arnold, P.F.; Babcock, G.; Burzese, A.A.; Cornelison, J.R.; Drum, P.R.; Hasenwinkle, I.; Johnson, R.; Marsh, W. J. Jr.

    1992-10-01

    This paper reports on the performance of protective relaying systems which is an issue within the electric power industry which has received inadequate attention. The wide variations in relaying types and styles and applications, as well as differences in company structures and industry terminology, have hindered the adoption of a standardized system for the evaluation of protective relaying system performance. Such a system, if adopted by a significant portion of the industry, would provide suppliers and users better information with which to improve the product and its application and operation. The Protective Relaying Performance Criteria Working Group of the IEEE Power System Relaying Committee has generated this paper for the purpose of defining a standardized protective relaying performance reporting system.

  11. Fire Protection Materials

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Avco has drawn upon its heat shield experience to develop a number of widely-accepted commercial fire protection materials. Originating from NASA's space shuttle thermal protection system, one such material is Chartek 59 fireproofing, an intumescent epoxy coating specifically designed for outdoor use by industrial facilities dealing with highly flammable products such as oil refineries and chemical plants. The coating is applied usually by spray gun to exterior structural steel conduits, pipes and valves, offshore platforms and liquefied petroleum gas tanks. Fireproofing provides two types of protection: ablation or dissipation of heat by burn-off and "intumescence" or swelling; the coating swells to about five times its original size, forming a protective blanket of char which retards transfer of heat to the metal structure preventing loss of structural strength and possible collapse which would compound the fire fighting problem.

  12. Protect Yourself: Respirators

    MedlinePlus

    ... worn whenever you are working in a hazardous atmosphere. The appropriate respi- rator will depend on the ... must not be used to protect from hazardous atmospheres. However, they may be useful in providing comfort ...

  13. Protect Your Fertility

    MedlinePlus

    ... lead to infertility. To protect your chances of conceiving, maintain a healthy weight through proper nutrition and ... decreased sperm production. To improve your chances of conceiving in the future, avoid drugs now. For more ...

  14. Health protection well inventory

    SciTech Connect

    Janssen, J.

    1989-03-01

    This report is an inventory of the wells contained in Health Protection (HP) documents since the startup of the Savannah River Plan (SRP) and includes wells monitored by special request and SRL research wells.

  15. Radiation Protection Handbook

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A handbook which sets forth the Kennedy Space Center radiation protection policy is presented. The book also covers administrative direction and guidance on organizational and procedural requirements of the program. Only ionizing radiation is covered.

  16. Wired for Protection.

    ERIC Educational Resources Information Center

    Kennedy, Mike

    2002-01-01

    Describes how growing acceptance of security measures such as access-control cards, video surveillance, and biometric devices is allowing colleges to protect students and their belongings more effectively. (EV)

  17. [Carney complex].

    PubMed

    Losada Grande, Eladio José; Al Kassam Martínez, Daniel; González Boillos, Margarita

    2011-01-01

    Carney complex (CNC) is an autosomal dominantly inherited syndrome characterized by spotty skin pigmentation, cardiac and cutaneous myxoma, and endocrine overactivity. Skin pigmentation includes lentigines and blue nevi. Myxomas may occur in breast, skin and heart. Cardiac myxomas may be multiple and occur in any cardiac chamber, and are more prone to recurrence. The most common endocrine gland manifestation is an ACTH-independent Cushing's syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). PPNAD may occur isolated, with no other signs of CNC. Pituitary and thyroid glands and gonads are also involved. The PRKAR1A gene, located in 17 q22-24, encodes type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of patients with CNC. PRKAR1A is a key component of the c-AMP signaling pathway that has been implicated in endocrine tumorigenesis. Many different mutations have been reported in the PRKAR1A gene. In almost all cases the sequence change was predicted to lead to a premature stop codon and the resultant mutant mRNA was subject to nonsense-mediated mRNA decay. There is no clear genotype-phenotype correlation in patients with CNC. Genetic analysis should be performed in all CNC index cases. All affected patients should be monitored for clinical signs of CNC at least once a year. Genetic diagnosis allows for more effective preparation of more appropriate and effective therapeutic strategies and genetic counseling for patients and gene carriers, and to avoid unnecessary tests to relatives not carrying the gene. PMID:21536508

  18. Advanced worker protection system

    SciTech Connect

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-12-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project will result in the development of an Advanced Worker Protection System (AWPS). The AWPS will be built around a life support backpack that uses liquid air to provide cooling as well as breathing gas to the worker. The backpack will be combined with advanced protective garments, advanced liquid cooling garment, respirator, communications, and support equipment to provide improved worker protection, simplified system maintenance, and dramatically improve worker productivity through longer duration work cycles. Phase I of the project has resulted in a full scale prototype Advanced Worker Protection Ensemble (AWPE, everything the worker will wear), with sub-scale support equipment, suitable for integrated testing and preliminary evaluation. Phase II will culminate in a full scale, certified, pre-production AWPS and a site demonstration.

  19. REDUCED PROTECTIVE CLOTHING DETERMINATIONS

    SciTech Connect

    BROWN, R.L.

    2003-06-13

    This technical basis document defines conditions where reduced protective clothing can be allowed, defines reduced protective clothing, and documents the regulatory review that determines the process is compliant with the Tank Farm Radiological Control Manual (TFRCM) and Title 10, Part 835, of the Code of Federal Regulations (10CFR835). The criteria, standards, and requirements contained in this document apply only to Tank Farm Contractor (TFC) facilities.

  20. Maintaining radiation protection records

    SciTech Connect

    Not Available

    1992-11-30

    This Report is part of a series prepared under the auspices of Scientific Committee 46 on Operational Radiation Safety. It provides guidance on maintaining radiation protection records. Record keeping is an essential element of every radiation protection program. This Report describes the elements that should enter into the design of a program for the maintenance of operational radiation safety records. The problems of the length of time for retention of records for operational, regulatory, epidemiologic and legal uses are discussed in detail.

  1. Lightweight Protective Garments

    NASA Technical Reports Server (NTRS)

    Du Fresne, E. R.

    1986-01-01

    Proposed garment material protects wearer from poisonous chemicals, bacteria, and radioactive particulates. Garment allows heat, moisture, and carbon dioxide to pass from inside to outside so wearer remains comfortable. Garment made of cotton fabric on which thin layer of polyacrylate rubber is deposited by calendering or spraying. Lighter and cooler than existing protective garments. Polyacrylate rubber selected for garment material because it transmits water vapor and carbon dioxide at high rates.

  2. Advanced worker protection system

    SciTech Connect

    Caldwell, B.; Duncan, P.; Myers, J.

    1995-10-01

    The Department of Energy (DOE) is in the process of defining the magnitude and diversity of Decontamination and Decommissioning (D&D) obligations at its numerous sites. The DOE believes that existing technologies are inadequate to solve many challenging problems such as how to decontaminate structures and equipment cost effectively, what to do with materials and wastes generated, and how to adequately protect workers and the environment. Preliminary estimates show a tremendous need for effective use of resources over a relatively long period (over 30 years). Several technologies are being investigated which can potentially reduce D&D costs while providing appropriate protection to DOE workers. The DOE recognizes that traditional methods used by the EPA in hazardous waste site clean up activities are insufficient to provide the needed protection and worker productivity demanded by DOE D&D programs. As a consequence, new clothing and equipment which can adequately protect workers while providing increases in worker productivity are being sought for implementation at DOE sites. This project describes the development of an Advanced Worker Protection System (AWPS) which will include a life-support backpack with liquid air for cooling and as a supply of breathing gas, protective clothing, respirators, communications, and support equipment.

  3. 40 CFR 721.10460 - Azo nickel complex (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Azo nickel complex (generic). 721... Substances § 721.10460 Azo nickel complex (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as azo nickel complex (PMN...

  4. 40 CFR 721.5325 - Nickel acrylate complex.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Nickel acrylate complex. 721.5325... Substances § 721.5325 Nickel acrylate complex. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nickel acrylate complex (PMN P-85-1034) is subject to reporting...

  5. 40 CFR 721.5325 - Nickel acrylate complex.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Nickel acrylate complex. 721.5325... Substances § 721.5325 Nickel acrylate complex. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nickel acrylate complex (PMN P-85-1034) is subject to reporting...

  6. 40 CFR 721.10388 - Bisphospite nickel cyanoalkyl complex (generic).

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Bisphospite nickel cyanoalkyl complex... Specific Chemical Substances § 721.10388 Bisphospite nickel cyanoalkyl complex (generic). (a) Chemical... as bisphospite nickel cyanoalkyl complex (PMN P-10-364) is subject to reporting under this...

  7. 40 CFR 721.5325 - Nickel acrylate complex.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Nickel acrylate complex. 721.5325... Substances § 721.5325 Nickel acrylate complex. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance nickel acrylate complex (PMN P-85-1034) is subject to reporting...

  8. 40 CFR 721.5325 - Nickel acrylate complex.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Nickel acrylate complex. 721.5325... Substances § 721.5325 Nickel acrylate complex. Link to an amendment published at 79 FR 34637, June 18, 2014... nickel acrylate complex (PMN P-85-1034) is subject to reporting under this section for the...

  9. 40 CFR 721.10388 - Bisphospite nickel cyanoalkyl complex (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Bisphospite nickel cyanoalkyl complex... Specific Chemical Substances § 721.10388 Bisphospite nickel cyanoalkyl complex (generic). (a) Chemical... as bisphospite nickel cyanoalkyl complex (PMN P-10-364) is subject to reporting under this...

  10. 40 CFR 721.10388 - Bisphospite nickel cyanoalkyl complex (generic).

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Bisphospite nickel cyanoalkyl complex... Specific Chemical Substances § 721.10388 Bisphospite nickel cyanoalkyl complex (generic). (a) Chemical... as bisphospite nickel cyanoalkyl complex (PMN P-10-364) is subject to reporting under this...