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Sample records for unit iia congaree

  1. Widespread occurrence and potential for biodegradation of bioactive contaminants in Congaree National Park, USA

    Science.gov (United States)

    Bradley, Paul M.; Battaglin, William A.; Clark, Jimmy M.; Henning, Frank; Hladik, Michelle; Iwanowicz, Luke; Journey, Celeste; Riley, Jeffrey W.; Romanok, Kristin

    2017-01-01

    Organic contaminants with designed molecular bioactivity, such as pesticides and pharmaceuticals, originate from human and agricultural sources, occur frequently in surface waters, and threaten the structure and function of aquatic and terrestrial ecosystems. Congaree National Park in South Carolina (USA) is a vulnerable park unit due to its location downstream of multiple urban and agricultural contaminant sources and its hydrologic setting, being composed almost entirely of floodplain and aquatic environments. Seventy-two water and sediment samples were collected from 16 sites in Congaree National Park during 2013 to 2015, and analyzed for 199 and 81 targeted organic contaminants, respectively. More than half of these water and sediment analytes were not detected or potentially had natural sources. Pharmaceutical contaminants were detected (49 total) frequently in water throughout Congaree National Park, with higher detection frequencies and concentrations at Congaree and Wateree River sites, downstream from major urban areas. Forty-seven organic wastewater indicator chemicals were detected in water, and 36 were detected in sediment, of which approximately half are distinctly anthropogenic. Endogenous sterols and hormones, which may originate from humans or wildlife, were detected in water and sediment samples throughout Congaree National Park, but synthetic hormones were detected only once, suggesting a comparatively low risk of adverse impacts. Assessment of the biodegradation potentials of 8 14C-radiolabeled model contaminants indicated poor potentials for some contaminants, particularly under anaerobic sediments conditions.

  2. Comparison of Methylmercury Production and Accumulation in Sediments of the Congaree and Edisto River Basins, South Carolina, 2004-06

    Science.gov (United States)

    Bradley, Paul M.; Chapelle, Francis H.; Journey, Celeste

    2009-01-01

    Fish-tissue mercury concentrations (approximately 2 micrograms per gram) in the Edisto River basin of South Carolina are among the highest recorded in the United States. Substantially lower mercury concentrations (approximately 0.2 microgram per gram) are reported in fish from the adjacent (about 30 kilometer) Congaree River basin and the Congaree National Park. In contrast, concentrations of total mercury were statistically higher in sediments from the Congaree River compared with those in sediments from the Edisto River. Furthermore, no statistically significant difference was observed in concentrations of methylmercury or net methylation potential in sediments collected from various Edisto and Congaree hydrologic settings. In both systems, the net methylation potential was low (0-0.17 nanogram per gram per day) for in-stream sediments exposed to continuously flowing water but substantially higher (about 1.8 nanograms per gram per day) in wetland sediments exposed to standing water. These results are not consistent with the hypothesis that differences in fish-tissue mercury between the Edisto and Congaree basins reflect fundamental differences in the potential for each system to methylate mercury. Rather, the significantly higher ratios of methylmercury to total mercury observed in the Edisto system suggest that the net accumulation and(or) preservation of methylmercury are greater in the Edisto system. The marked differences in net methylation potential observed between the wetland and in-stream settings suggest the hypothesis that methylmercury transport from zones of production (wetlands) to points of entry into the food chain (channels) may contribute to the observed differences in fish-tissue mercury concentrations between the two river systems.

  3. Digital Geologic Map of Congaree National Park and Vicinity, South Carolina (NPS, GRD, GRI, CONG, CONG digital map)

    Data.gov (United States)

    National Park Service, Department of the Interior — The Digital Geologic Map of Congaree National Park and Vicinity, South Carolina is composed of GIS data layers complete with ArcMap 9.3 layer (.LYR) files, two...

  4. Issues in IIA Uplifting

    Energy Technology Data Exchange (ETDEWEB)

    Kallosh, Renata; Soroush, Masoud

    2006-12-12

    Moduli stabilization in the type IIA massive string theory so far was achieved only in the AdS vacua. The uplifting to dS vacua has not been performed as yet: neither the analogs of type IIB anti-D3 brane at the tip of the conifold, nor the appropriate D-terms have been identified. The hope was recently expressed that the F-term uplifting may work. We investigate this possibility in the context of a simplified version of the type IIA model developed in hep-th/0505160 and find that the F-term does not uplift the AdS vacua to dS vacua with positive CC. Thus it remains a challenging task to find phenomenologically acceptable vacua in the type IIA string theory.

  5. Analysis of tanshinone IIA induced cellular apoptosis in leukemia cells by genome-wide expression profiling

    Directory of Open Access Journals (Sweden)

    Liu Chang

    2012-01-01

    Full Text Available Abstract Background Tanshinone IIA (Tan IIA is a diterpene quinone extracted from the root of Salvia miltiorrhiza, a Chinese traditional herb. Although previous studies have reported the anti-tumor effects of Tan IIA on various human cancer cells, the underlying mechanisms are not clear. The current study was undertaken to investigate the molecular mechanisms of Tan IIA's apoptotic effects on leukemia cells in vitro. Methods The cytotoxicity of Tan IIA on different types of leukemia cell lines was evaluated by the 3-[4,5-dimethylthiazol-2,5]-diphenyl tetrazolium bromide (MTT assay on cells treated without or with Tan IIA at different concentrations for different time periods. Cellular apoptosis progression with and without Tan IIA treatment was analyzed by Annexin V and Caspase 3 assays. Gene expression profiling was used to identify the genes regulated after Tan IIA treatment and those differentially expressed among the five cell lines. Confirmation of these expression regulations was carried out using real-time quantitative PCR and ELISA. The antagonizing effect of a PXR inhibitor L-SFN on Tan IIA treatment was tested using Colony Forming Unit Assay. Results Our results revealed that Tan IIA had different cytotoxic activities on five types of leukemia cells, with the highest toxicity on U-937 cells. Tan IIA inhibited the growth of U-937 cells in a time- and dose-dependent manner. Annexin V and Caspase-3 assays showed that Tan IIA induced apoptosis in U-937 cells. Using gene expression profiling, 366 genes were found to be significantly regulated after Tan IIA treatment and differentially expressed among the five cell lines. Among these genes, CCL2 was highly expressed in untreated U-937 cells and down-regulated significantly after Tan IIA treatment in a dose-dependent manner. RT-qPCR analyses validated the expression regulation of 80% of genes. Addition of L- sulforaphane (L-SFN, an inhibitor of Pregnane × receptor (PXR significantly

  6. Tanshinone IIA stimulates erythrocyte phosphatidylserine exposure

    NARCIS (Netherlands)

    Zelenak, C.; Pasham, V.; Jilani, K.; Tripodi, P.M.; Rosaclerio, L.; Pathare, G.T.; Lupescu, A.; Faggio, C.; Qadri, S.M.; Lang, F.

    2012-01-01

    Tanshinone IIA, an antimicrobial, antioxidant, antianaphylactic, antifibrotic, vasodilating, antiatherosclerotic, organo-protective and antineoplastic component from the rhizome of Salvia miltiorrhiza, is known to trigger apoptosis of tumor cells. Tanshinone IIA is effective in part through mitochon

  7. Investigating Inflation in Type IIA

    Energy Technology Data Exchange (ETDEWEB)

    Hertzberg, Mark P.; /MIT; Kachru, Shamit; /Stanford U., Phys. Dept. /SLAC; Taylor, Washington; Tegmark, Max; /MIT, LNS

    2007-12-14

    We prove that inflation is forbidden in the most well understood class of semi-realistic type IIA string compactifications: Calabi-Yau compactifications with only standard NS-NS 3-form flux, R-R fluxes, D6-branes and O6-planes at large volume and small string coupling. With these ingredients, the first slow-roll parameter satisfies {epsilon} {ge} 27/13 whenever V > 0, ruling out both inflation (including brane/anti-brane inflation) and de Sitter vacua in this limit. Our proof is based on the dependence of the 4-dimensional potential on the volume and dilaton moduli in the presence of fluxes and branes. We also describe broader classes of IIA models which may include cosmologies with inflation and/or de Sitter vacua. The inclusion of extra ingredients, such as NS 5-branes and geometric or non-geometric NS-NS fluxes, evades the assumptions used in deriving the no-go theorem. We focus on NS 5-branes and outline how such ingredients may prove fruitful for cosmology, but we do not provide an explicit model. We contrast the results of our IIA analysis with the rather different situation in IIB.

  8. Isolation and Characterization of Plantaricin Produced by Lactobacillus plantarum Strains (IIA-1A5, IIA-1B1, IIA-2B2

    Directory of Open Access Journals (Sweden)

    I. I. Arief

    2013-08-01

    Full Text Available Bacteriocins produced by Indonesian lactic acid bacteria Lactobacillus plantarum IIA-1A5, IIA-1B1, IIA-2B2 were purified and characterized. Plantaricin W gene had been successfully amplified from all strains. This amplicon showed the expected 200 bp size of plantaricin W gene. This bacteriocins purified from L. plantarum IIA-1A5, IIA-1B1, and IIA-2B2 were named plantaricin IIA-1A5, IIA-1B1, and IIA-2B2. Purification by cation exchange chromatography increased the purity (fold and activity of plantaricins. Purity of plantaricin IIA-1A5 was increased by 3.13 fold with specific activity 13.40 AU/mg. Plantaricin IIA-1B1 had 2.98 fold purity with specific activity 5.12 AU/mg, while purity of plantaricin IIA-2B2 was 1.37 fold with specific activity 7.70 AU/mg. All plantaricins could inhibit the growth of pathogenic bacteria, such as Escherichia coli, Salmonella typhimurium, Bacillus cereus, and Staphylococcus aureus. Plantaricins could be digested by trypsin. Stability of plantaricins at 80 oC for 30 min and at 121 oC for 15 min were affected by type of plantaricin and species of pathogenic bacteria. Generally, plantaricin IIA-1A5 was better as antimicrobial agent than plantaricin IIA-1B1 and plantaricin IIA-2B2.

  9. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    Science.gov (United States)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; van Iperen, Erik P.A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J.W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M.A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, André G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N.M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C.M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A.A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Paré, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease. Background Higher circulating levels of sPLA2-IIA mass or sPLA2 enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA2 inhibitor (varespladib) was stopped prematurely for lack of efficacy. Methods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA2-IIA isoenzyme, as an instrumental variable. Results PLA2G2A rs11573156 C allele associated with lower circulating sPLA2-IIA mass (38% to 44%) and sPLA2 enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA2-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. Conclusions Reducing sPLA2-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events. PMID:23916927

  10. The Continuing Story of Class IIa Bacteriocins

    OpenAIRE

    Drider, Djamel; Fimland, Gunnar; Héchard, Yann; McMullen, Lynn M.; Prévost, Hervé

    2006-01-01

    Many bacteria produce antimicrobial peptides, which are also referred to as peptide bacteriocins. The class IIa bacteriocins, often designated pediocin-like bacteriocins, constitute the most dominant group of antimicrobial peptides produced by lactic acid bacteria. The bacteriocins that belong to this class are structurally related and kill target cells by membrane permeabilization. Despite their structural similarity, class IIa bacteriocins display different target cell specificities. In the...

  11. Class IIa Bacteriocins: Diversity and New Developments

    Directory of Open Access Journals (Sweden)

    Yanhua Cui

    2012-12-01

    Full Text Available Class IIa bacteriocins are heat-stable, unmodified peptides with a conserved amino acids sequence YGNGV on their N-terminal domains, and have received much attention due to their generally recognized as safe (GRAS status, their high biological activity, and their excellent heat stability. They are promising and attractive agents that could function as biopreservatives in the food industry. This review summarizes the new developments in the area of class IIa bacteriocins and aims to provide uptodate information that can be used in designing future research.

  12. Class IIa Bacteriocins: Current Knowledge and Perspectives

    Science.gov (United States)

    Belguesmia, Yanath; Naghmouchi, Karim; Chihib, Nour-Eddine; Drider, Djamel

    Lactic acid bacteria (LAB) are known to produce antibacterial peptides and small proteins called bacteriocins, which enable them to compete against other bacteria in the environment. Bacteriocins fall structurally and chemically into three different classes, I, II, and III. Bacteriocins are ribosomally synthesized peptides with antagonism against closely related bacteria. This late observation has evolved because bacteriocins active against Gram-negative bacteria have recently been reported. Members of class IIa bacteriocins, referred to as pediocin-like bacteriocins, are among the most studied bacteriocins. This chapter is aimed at providing an updated review on the biology of class IIa bacteriocins.

  13. Class IIa bacteriocins: diversity and new developments.

    Science.gov (United States)

    Cui, Yanhua; Zhang, Chao; Wang, Yunfeng; Shi, John; Zhang, Lanwei; Ding, Zhongqing; Qu, Xiaojun; Cui, Hongyu

    2012-12-06

    Class IIa bacteriocins are heat-stable, unmodified peptides with a conserved amino acids sequence YGNGV on their N-terminal domains, and have received much attention due to their generally recognized as safe (GRAS) status, their high biological activity, and their excellent heat stability. They are promising and attractive agents that could function as biopreservatives in the food industry. This review summarizes the new developments in the area of class IIa bacteriocins and aims to provide uptodate information that can be used in designing future research.

  14. Class IIa Bacteriocins: Diversity and New Developments

    Science.gov (United States)

    Cui, Yanhua; Zhang, Chao; Wang, Yunfeng; Shi, John; Zhang, Lanwei; Ding, Zhongqing; Qu, Xiaojun; Cui, Hongyu

    2012-01-01

    Class IIa bacteriocins are heat-stable, unmodified peptides with a conserved amino acids sequence YGNGV on their N-terminal domains, and have received much attention due to their generally recognized as safe (GRAS) status, their high biological activity, and their excellent heat stability. They are promising and attractive agents that could function as biopreservatives in the food industry. This review summarizes the new developments in the area of class IIa bacteriocins and aims to provide uptodate information that can be used in designing future research. PMID:23222636

  15. Characterization of groundwater flow and transport in the General Separations Area, Savannah River Plant: Effect of groundwater withdrawals on the Tuscaloosa-Congaree aquifer head reversal in H Area. Final report

    Energy Technology Data Exchange (ETDEWEB)

    Spalding, C.P.; Duffield, G.M.; Shaw, S.T. [GeoTrans, Inc., Herndon, VA (United States)

    1988-01-01

    The Savannah River Plant (SRP) has maintained a number of sites used for land disposal of various waste materials. The General Separations Area at SRP, located between the Upper Three Runs and Four Mile Creeks, has served as an active area for waste storage for about thirty years. The Tuscaloosa aquifer, which lies beneath the General Separations Area, is a water source for SRP and the surrounding area. The isolation of the Tuscaloosa aquifer has been maintained by an upward hydraulic gradient from the Tuscaloosa aquifer to the overlying Congaree aquifer. This upward gradient is referred to as a hydraulic head reversal in the General Separations Area, i.e., hydraulic heads in the upper Tuscaloosa are higher than hydraulic heads in the Congaree. This head reversal has declined in recent years due to increased groundwater pumping in the upper and lower Tuscaloosa formations. The objective of this investigation is to assess the effects of pumping within the General Separations Area on the Congaree/upper Tuscaloosa head reversal. Methods of maintaining future Tuscaloosa aquifer isolation through the optimization of groundwater withdrawal location and rate were studied. Steady-state and transient groundwater flow models were used to characterize past and potential future groundwater conditions. Future groundwater conditions were simulated for a variety of pumping scenarios.

  16. Phacomatosis pigmentovascularis type IIa - Case report*

    Science.gov (United States)

    Segatto, Majoriê Mergen; Schmitt, Eloísa Unfer; Hagemann, Laura Netto; da Silva, Roberta Castilhos; Cattani, Cristiane Almeida Soares

    2013-01-01

    Phacomatosis Pigmentovascularis is a rare syndrome characterized by capillary malformation and pigmentary nevus. A case of a 2-year-old patient is reported, who presented extensive nevus flammeus and an aberrant Mongolian spot, without systemic disease, manifestations that allow us to classify this case as type IIa Phacomatosis Pigmentovascularis, according to Hasegawa's classification. PMID:24346888

  17. High altitude balloon experiments at IIA

    Science.gov (United States)

    Nayak, Akshata; Sreejith, A. G.; Safonova, Margarita; Murthy, Jayant

    Recent advances in balloon experiments as well as in electronics have made it possible to fly scientific payloads at costs accessible to university departments. We have begun a program of high altitude ballooning at the Indian Institute of Astrophysics, Bengaluru. The primary purpose of this activity is to test low-cost ultraviolet (UV) payloads for eventual space flight, but we will also try scientific exploration of the phenomena occurring in the upper atmosphere, including sprites and meteorite impacts. We present the results of the initial experiments carried out at the CREST campus of IIA, Hosakote, and describe our plans for the future.

  18. Stage IIA and IIB testicular seminoma treated post-orchiectomy with radiation therapy versus other approaches: a population-based analysis of 241 patients

    Directory of Open Access Journals (Sweden)

    Kamran A. Ahmed

    2015-02-01

    Full Text Available Objectives To evaluate post-orchiectomy utilization of radiation therapy (RT versus other management approaches in stage IIA and IIB testicular seminoma patients. Materials and Methods Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER database. Results Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72% vs. 46%, respectively; P<0.001. There was no significant change in RT utilization for stage IIA or IIB disease between 1988 and 2003 (P = 0.89. Conclusions Between 1988 and 2003, stage IIA patients underwent RT more often than stage IIB patients in the United States. There was no significant change in RT utilization for stage IIA or IIB disease during this time period. Based on reports describing excellent progression-free survival with cisplatin-based chemotherapy, this approach has increased in popularity since 2003 and may eventually become the most popular treatment approach for both stage IIA and IIB testicular seminoma.

  19. Secretory Phospholipase A2-IIA and Cardiovascular Disease

    DEFF Research Database (Denmark)

    Holmes, Michael V; Simon, Tabassome; Exeter, Holly J

    2013-01-01

    This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease.......This study sought to investigate the role of secretory phospholipase A2 (sPLA2)-IIA in cardiovascular disease....

  20. The Kaluza-Klein monopole in a massive IIA background

    NARCIS (Netherlands)

    Eyras, E; Lozano, Y

    1999-01-01

    We construct the effective action of the KK monopole in a massive Spe IIA background. We follow two approaches. First we construct a massive M-theory KK monopole from which the IIA monopole is obtained by double dimensional reduction. This eleven-dimensional monopole contains two isometries: one und

  1. Secretory Phospholipase A(2)-IIA and Cardiovascular Disease

    NARCIS (Netherlands)

    Holmes, Michael V.; Simon, Tabassome; Exeter, Holly J.; Folkersen, Lasse; Asselbergs, Folkert W.; Guardiola, Montse; Cooper, Jackie A.; Palmen, Jutta; Hubacek, Jaroslav A.; Carruthers, Kathryn F.; Horne, Benjamin D.; Brunisholz, Kimberly D.; Mega, Jessica L.; Van Iperen, Erik P. A.; Li, Mingyao; Leusink, Maarten; Trompet, Stella; Verschuren, Jeffrey J. W.; Hovingh, G. Kees; Dehghan, Abbas; Nelson, Christopher P.; Kotti, Salma; Danchin, Nicolas; Scholz, Markus; Haase, Christiane L.; Rothenbacher, Dietrich; Swerdlow, Daniel I.; Kuchenbaecker, Karoline B.; Staines-Urias, Eleonora; Goel, Anuj; van 't Hooft, Ferdinand; Gertow, Karl; de Faire, Ulf; Panayiotou, Andrie G.; Tremoli, Elena; Baldassarre, Damiano; Veglia, Fabrizio; Holdt, Lesca M.; Beutner, Frank; Gansevoort, Ron T.; Navis, Gerjan J.; Mateo Leach, Irene; Breitling, Lutz P.; Brenner, Hermann; Thiery, Joachim; Dallmeier, Dhayana; Franco-Cereceda, Anders; Boer, Jolanda M. A.; Stephens, Jeffrey W.; Hofker, Marten H.; Tedgui, Alain; Hofman, Albert; Uitterlinden, Andre G.; Adamkova, Vera; Pitha, Jan; Onland-Moret, N. Charlotte; Cramer, Maarten J.; Nathoe, Hendrik M.; Spiering, Wilko; Klungel, Olaf H.; Kumari, Meena; Whincup, Peter H.; Morrow, David A.; Braund, Peter S.; Hall, Alistair S.; Olsson, Anders G.; Doevendans, Pieter A.; Trip, Mieke D.; Tobin, Martin D.; Hamsten, Anders; Watkins, Hugh; Koenig, Wolfgang; Nicolaides, Andrew N.; Teupser, Daniel; Day, Ian N. M.; Carlquist, John F.; Gaunt, Tom R.; Ford, Ian; Sattar, Naveed; Tsimikas, Sotirios; Schwartz, Gregory G.; Lawlor, Debbie A.; Morris, Richard W.; Sandhu, Manjinder S.; Poledne, Rudolf; Maitland-van der Zee, Anke H.; Khaw, Kay-Tee; Keating, Brendan J.; van der Harst, Pim; Price, Jackie F.; Mehta, Shamir R.; Yusuf, Salim; Witteman, Jaqueline C. M.; Franco, Oscar H.; Jukema, J. Wouter; de Knijff, Peter; Tybjaerg-Hansen, Anne; Rader, Daniel J.; Farrall, Martin; Samani, Nilesh J.; Kivimaki, Mika; Fox, Keith A. A.; Humphries, Steve E.; Anderson, Jeffrey L.; Boekholdt, S. Matthijs; Palmer, Tom M.; Eriksson, Per; Pare, Guillaume; Hingorani, Aroon D.; Sabatine, Marc S.; Mallat, Ziad; Casas, Juan P.; Talmud, Philippa J.

    2013-01-01

    Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. Background Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clea

  2. Position of nonmuscle myosin heavy chain IIA (NMMHC-IIA) mutations predicts the natural history of MYH9-related disease

    DEFF Research Database (Denmark)

    Pecci, A.; Panza, E.; Pujol-Moix, N.

    2008-01-01

    MYH9-related disease (MYH9-RD) is a rare autosomal-dominant disorder caused by mutations in MYH9, the gene for the heavy chain of nonmuscle myosin IIA (NMMHC-IIA). All patients present from birth with macrothrombocytopenia, but in infancy or adult life, some of them develop sensorineural deafness...

  3. Low-flow frequency and flow duration of selected South Carolina streams in the Saluda, Congaree, and Edisto River basins through March 2009

    Science.gov (United States)

    Feaster, Toby D.; Guimaraes, Wladmir B.

    2012-01-01

    Part of the mission of the South Carolina Department of Health and Environmental Control and the South Carolina Department of Natural Resources is to protect and preserve South Carolina's water resources. Doing so requires an ongoing understanding of streamflow characteristics of the rivers and streams in South Carolina. A particular need is information concerning the low-flow characteristics of streams, which is especially important for effectively managing the State's water resources during critical flow periods, such as during periods of severe drought like South Carolina has experienced in the last decade or so. The U.S. Geological Survey, in cooperation with the South Carolina Department of Health and Environmental Control, initiated a study in 2008 to update low-flow statistics at continuous-record streamgaging stations operated by the U.S. Geological Survey in South Carolina. This report presents the low-flow statistics for 25 selected streamgaging stations in the Saluda, Congaree, and Edisto River basins in South Carolina, and includes flow durations for the 5-, 10-, 25-, 50-,75-, 90-, and 95-percent exceedances and the annual minimum 1-, 3-, 7-, 14-, 30-, 60-, and 90-day average flows with recurrence intervals of 2, 5, 10, 20, 30, and 50 years, depending on the length of record available at the streamgaging station. The low-flow statistics were computed from records available through March 31, 2009. Of the 25 streamgaging stations for which recurrence interval computations were made, 20 were compared to low-flow statistics that were published in previous U.S. Geological Survey reports. A comparison of the low-flow statistics for the annual minimum 7-day average streamflow with a 10-year recurrence interval (7Q10) from this study with the most recently published values indicates that 18 of the 20 streamgaging stations have values lower than the previous published values. The low-flow statistics are influenced by length of record, hydrologic regime under

  4. Plantaricin IIA-1A5 from Lactobacillus plantarum IIA-1A5 displays bactericidal activity against Staphylococcus aureus.

    Science.gov (United States)

    Arief, I Isnafia; Budiman, C; Jenie, B Sri Laksmi; Andreas, E; Yuneni, A

    2015-01-01

    Plantaricin IIA-1A5 is a bacteriocin produced by Lactobacillus plantarum IIA-1A5 isolated from Indonesian beef. This research aimed to identify the genes involved in plantaricin IIA-1A5 production and examine its mode of action against Staphylococcus aureus. It has been reported that a bacteriocin structural gene, plnW, is present in genome of L. plantarum IIA-1A5. Here, we reported the presence of additional genes responsible for plantaricin precursor (plnA and plnEF) and a gene encoding the quorum sensor of histidine kinase (plnB). It indicates that genes involved in production of plantaricin IIA-1A5 are organized in at least two bacteriocin operons (plnABCD, plnEFI) and a structural plnW gene. Purified plantaricin IIA-1A5 yielded a single band in SDS-PAGE with apparent size of 6.4 kDa. Amino acid composition of purified plantaricin IIA-1A5 was mainly composed of cationic glutamic acid and cysteine that allowed the formation of disulphide bonds, suggesting plantaricin IIA-1A5 belongs to the pediocin-subclass of class II bacteriocins. Plantaricin IIA-1A5 displayed remarkable antibacterial activity against S. aureus, which was initiated by the adsorption of plantaricin IIA-1A5 onto the cell membrane of S. aureus. The adsorption is hypothesised to be facilitated by non-ionic interactions as it is reduced by the presence of organic solvents or detergents. This adsorption promoted leakage of cellular metabolites through the cell membrane of S. aureus, as indicated by the release of genetic and proteinaceous material of S. aureus observed at 260 and 280 nm, respectively. The leakage also promoted the release of divalent (Ca(2+), Mg(2+)) and monovalent (K(+)) cations. The release of these intracellular components might be due to pores formed in the cell membrane of S. aureus by plantaricin IIA-1A5 as shown by scanning electron microscopy. Altogether, the mode of action of plantaricin IIA-1A5 against S. aureus seems to be bactericidal as indicated by lysis of the cell

  5. Inhibitory effect of tanshinone IIA on rat hepatic stellate cells.

    Directory of Open Access Journals (Sweden)

    Ya-Wei Liu

    Full Text Available Anti-inflammation via inhibition of NF-κB pathways in hepatic stellate cells (HSCs is one therapeutic approach to hepatic fibrosis. Tanshinone IIA (C19H18O3, Tan IIA is a lipophilic diterpene isolated from Salvia miltiorrhiza Bunge, with reported anti-inflammatory activity. We tested whether Tan IIA could inhibit HSC activation.The cell line of rat hepatic stellate cells (HSC-T6 was stimulated with lipopolysaccharide (LPS (100 ng/ml. Cytotoxicity was assessed by MTT assay. HSC-T6 cells were pretreated with Tan IIA (1, 3 and 10 µM, then induced by LPS (100 ng/ml. NF-κB activity was evaluated by the luciferase reporter gene assay. Western blotting analysis was performed to measure NF-κB-p65, and phosphorylations of MAPKs (ERK, JNK, p38. Cell chemotaxis was assessed by both wound-healing assay and trans-well invasion assay. Quantitative real-time PCR was used to detect gene expression in HSC-T6 cells.All concentrations of drugs showed no cytotoxicity against HSC-T6 cells. LPS stimulated NF-κB luciferase activities, nuclear translocation of NF-κB-p65, and phosphorylations of ERK, JNK and p38, all of which were suppressed by Tan IIA. In addition, Tan IIA significantly inhibited LPS-induced HSCs chemotaxis, in both wound-healing and trans-well invasion assays. Moreover, Tan IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS, and α-SMA in HSC-T6 cells.Our results demonstrated that Tan IIA decreased LPS-induced HSC activation.

  6. Epidemiology and genetic characterization of hepatitis A virus genotype IIA.

    Science.gov (United States)

    Desbois, Delphine; Couturier, Elisabeth; Mackiewicz, Vincent; Graube, Arielle; Letort, Marie-José; Dussaix, Elisabeth; Roque-Afonso, Anne-Marie

    2010-09-01

    Three hepatitis A virus (HAV) genotypes, I, II, and III, divided into subtypes A and B, infect humans. Genotype I is the most frequently reported, while genotype II is hardly ever isolated, and its genetic diversity is unknown. From 2002 to 2007, a French epidemiological survey of HAV identified 6 IIA isolates, mostly from patients who did not travel abroad. The possible African origin of IIA strains was investigated by screening the 2008 mandatory notification records of HAV infection: 171 HAV strains from travelers to West Africa and Morocco were identified. Genotyping was performed by sequencing of the VP1/2A junction in 68 available sera. Entire P1 and 5' untranslated regions of IIA strains were compared to reference sequences of other genotypes. The screening retrieved 5 imported IIA isolates. An additional autochthonous case and 2 more African cases were identified in 2008 and 2009, respectively. A total of 14 IIA isolates (8 African and 6 autochthonous) were analyzed. IIA sequences presented lower nucleotide and amino acid variability than other genotypes. The highest variability was observed in the N-terminal region of VP1, while for other genotypes the highest variability was observed at the VP1/2A junction. Phylogenetic analysis identified 2 clusters, one gathering all African and two autochthonous cases and a second including only autochthonous isolates. In conclusion, most IIA strains isolated in France are imported by travelers returning from West Africa. However, the unexplained contamination mode of autochthonous cases suggests another, still to be discovered geographical origin or a French reservoir to be explored.

  7. Massive IIA string theory and Matrix theory compactification

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, David A. E-mail: lowe@het.brown.edu; Nastase, Horatiu; Ramgoolam, Sanjaye

    2003-09-08

    We propose a Matrix theory approach to Romans' massive Type IIA supergravity. It is obtained by applying the procedure of Matrix theory compactifications to Hull's proposal of the massive Type IIA string theory as M-theory on a twisted torus. The resulting Matrix theory is a super-Yang-Mills theory on large N three-branes with a space-dependent noncommutativity parameter, which is also independently derived by a T-duality approach. We give evidence showing that the energies of a class of physical excitations of the super-Yang-Mills theory show the correct symmetry expected from massive Type IIA string theory in a lightcone quantization.

  8. Compactifications of IIA supergravity on SU(2)-structure manifolds

    Energy Technology Data Exchange (ETDEWEB)

    Spanjaard, B.

    2008-07-15

    In this thesis, we study compactifications of type IIA supergravity on six-dimensional manifolds with an SU(2)-structure. A general study of six-dimensional manifolds with SU(2)-structure shows that IIA supergravity compactified on such a manifold should yield a four-dimensional gauged N=4 supergravity. We explicitly derive the bosonic spectrum, gauge transformations and action for IIA supergravity compactified on two different manifolds with SU(2)-structure, one of which also has an H{sup (3)}{sub 10}-flux, and confirm that the resulting four-dimensional theories are indeed N=4 gauged supergravities. In the second chapter, we study an explicit construction of a set of SU(2)-structure manifolds. This construction involves a Scherk-Schwarz duality twist reduction of the half-maximal six-dimensional supergravity obtained by compactifying IIA supergravity on a K3. This reduction results in a gauged N=4 four-dimensional supergravity, where the gaugings can be divided into three classes of parameters. We relate two of the classes to parameters we found before, and argue that the third class of parameters could be interpreted as a mirror flux. (orig.)

  9. Orientifolds of type IIA strings on Calabi-Yau manifolds

    CERN Document Server

    Govindarajan, S; Govindarajan, Suresh; Majumder, Jaydeep

    2004-01-01

    We identify type IIA orientifolds that are dual to M-theory compactifications on manifolds with G_2-holonomy. We then discuss the construction of crosscap states in Gepner models. (Based on a talk presented by S.G. at PASCOS 2003 held at the Tata Institute of Fundamental Research, Mumbai during Jan. 3-8, 2003.)

  10. Puzzles on the duality between heterotic and type IIA strings

    CERN Document Server

    Abe, M; Abe, Mitsuko; Sato, Masamichi

    1999-01-01

    We discuss the possibility of the extension of the duality between the webs of heterotic string and the type IIA string to Calabi-Yau 3-folds with another K3 fiber by comparing the dual polyhedron of Calabi-Yau 3-folds given by Candelas, Perevalov and Rajesh.

  11. Characteristic of Lamb Sausages Fermented by Indonesian Meat-Derived Probiotic, Lactobacillus plantarum IIA-2C12 and Lactobacillus acidophilus IIA-2B4

    Directory of Open Access Journals (Sweden)

    Noraimah Binti Sulaiman

    2016-08-01

    Full Text Available Probiotic is a group of microorganism, mainly from lactic acid bacteria (LAB, widely used to increase functionality of various foodstuffs, including lamb which was limited by its goaty odor and short life issue. This study aimed to evaluate the characteristic of lamb sausages fermented by either Lactobacillus plantarum IIA-2C12 or L. acidophilus IIA-2B4 isolated from local cattle in Indonesia, and stored for 21 days at low temperature (4oC. Fermented lamb sausages were made with the addition of L. plantarum IIA-2C12 and L. acidophilus IIA-2B4 with three replications. The result showed that pH value, protein, and cholesterol contents of the sausages with addition of L. acidophilus IIA-2B4 were higher (P<0.05 than that of L. plantarum IIA-2C12. Meanwhile, the sausage fermented with L. plantarum IIA-2C12 had higher titratable acid (TA value, texture, and the content of fat, carbohydrate, tyrosine, lysine, myristoleic (C14:1, pentadecanoic (C15:0, heneicosanoic (C21:0 and cis-11-eicosatrienoic (C20:1 as compared to that of  L. acidophilus 2C12-2B4. Final population of LAB in the sausage fermented by L. plantarum IIA-2C12 was also higher than that of L. acidophilus IIA-2B4, yet both can be categorized as a probiotic. The differences between characteristics of the physicochemical traits and microbiological quality of the sausage fermentation associated with the addition of L. plantarum IIA-2C12 or L. acidophilus IIA-2B4. The 21 days of storage at cold temperatures with probiotics addition could extend shelf life and maintain quality of fermented sausage.

  12. Exceptional generalised geometry for massive IIA and consistent reductions

    CERN Document Server

    Cassani, Davide; Petrini, Michela; Strickland-Constable, Charles; Waldram, Daniel

    2016-01-01

    We develop an exceptional generalised geometry formalism for massive type IIA supergravity. In particular, we construct a deformation of the generalised Lie derivative, which generates the type IIA gauge transformations as modified by the Romans mass. We apply this new framework to consistent Kaluza-Klein reductions preserving maximal supersymmetry. We find a generalised parallelisation of the exceptional tangent bundle on S^6, and from this reproduce the consistent truncation ansatz and embedding tensor leading to dyonically gauged ISO(7) supergravity in four dimensions. We also discuss closely related hyperboloid reductions, yielding a dyonic ISO(p,7-p) gauging. Finally, while for vanishing Romans mass we find a generalised parallelisation on S^d, d=4,3,2, leading to a maximally supersymmetric reduction with gauge group SO(d+1) (or larger), we provide evidence that an analogous reduction does not exist in the massive theory.

  13. Exceptional generalised geometry for massive IIA and consistent reductions

    Science.gov (United States)

    Cassani, Davide; de Felice, Oscar; Petrini, Michela; Strickland-Constable, Charles; Waldram, Daniel

    2016-08-01

    We develop an exceptional generalised geometry formalism for massive type IIA supergravity. In particular, we construct a deformation of the generalised Lie derivative, which generates the type IIA gauge transformations as modified by the Romans mass. We apply this new framework to consistent Kaluza-Klein reductions preserving maximal supersymmetry. We find a generalised parallelisation of the exceptional tangent bundle on S 6, and from this reproduce the consistent truncation ansatz and embedding tensor leading to dyonically gauged ISO(7) supergravity in four dimensions. We also discuss closely related hyperboloid reductions, yielding a dyonic ISO( p, 7 - p) gauging. Finally, while for vanishing Romans mass we find a generalised parallelisation on S d , d = 4 , 3 , 2, leading to a maximally supersymmetric reduction with gauge group SO( d + 1) (or larger), we provide evidence that an analogous reduction does not exist in the massive theory.

  14. Pure Spinor Superstrings on Generic type IIA Supergravity Backgrounds

    CERN Document Server

    D'Auria, R; Grassi, P A; Trigiante, M

    2008-01-01

    We derive the Free Differential Algebra for type IIA supergravity in 10 dimensions in the string frame. We provide all fermionic terms for all curvatures. We derive the Green-Schwarz sigma model for type IIA superstring based on the FDA construction and we check its invariance under kappa-symmetry. Finally, we derive the pure spinor sigma model and we check the BRST invariance. The present derivation has the advantage that the resulting sigma model is constructed in terms of the superfields appearing in the FDA and therefore one can directly relate a supergravity background with the corresponding sigma model. The complete explicit form of the BRST transformations is given and some new pure spinor constraints are obtained. Finally, the explicit form of the action is given.

  15. Development of Class IIa Bacteriocins as Therapeutic Agents

    OpenAIRE

    Lohans, Christopher T.; Vederas, John C.

    2012-01-01

    Class IIa bacteriocins have been primarily explored as natural food preservatives, but there is much interest in exploring the application of these peptides as therapeutic antimicrobial agents. Bacteriocins of this class possess antimicrobial activity against several important human pathogens. Therefore, the therapeutic development of these bacteriocins will be reviewed. Biological and chemical modifications to both stabilize and increase the potency of bacteriocins are discussed, as well as ...

  16. Proteolytic Characterization of Trimmed Beef Fermented Sausages Inoculated by Indonesian Probiotics: Lactobacillus plantarum IIA-2C12 and Lactobacillus acidophilus IIA-2B4

    Directory of Open Access Journals (Sweden)

    Dyah Nurul Afiyah

    2015-05-01

    Full Text Available Proteolysis is one of the most important biochemical changes affecting proteins during the ripening and preservation of fermented beef sausages. In this study, proteolytic activities of two Indonesian probiotics, Lactobacillus plantarum IIA-2C12 and Lactobacillus acidophilus IIA-2B4 used as starters in trimmed beef are investigated. IIA-2B4 used as starters in trimmed beef are investigated. L. plantarum IIA-2C12 and L. acidophilus displayed remarkable proteolytic activities against milk casein substrate, in which the activity of L. plantarum IIA-2C12 is higher than that of L. acidophilus IIA-2B4. Similar evidences were observed when proteolytic activities of both strains were visualized by using SDS-Page against meat sarcoplasmic proteins. The differences in the number of proteases encoded by the genomes of both starters might account for these differences. The activities of both strains were slightly reduced upon storage at room temperature for 28 days due to decreasing of the amount of substrate and or stability of proteases. In addition, we found also that the sausage inoculated by L. acidophilus IIA-2B4 tends to produce more aromatic amino acids than that of L. plantarum IIA-2C12. This might differently contribute to flavor (especially aroma of both sausages. Altogether, this is, to our knowledge, first evidences for the proteolytic activity of L. acidophilus strain towards muscle proteins during sausage fermentation.

  17. Human group IIA secretory phospholipase A2 induces neuronal cell death via apoptosis.

    Science.gov (United States)

    Yagami, Tatsurou; Ueda, Keiichi; Asakura, Kenji; Hata, Satoshi; Kuroda, Takayuki; Sakaeda, Toshiyuki; Takasu, Nobuo; Tanaka, Kazushige; Gemba, Takefumi; Hori, Yozo

    2002-01-01

    Expression of group IIA secretory phospholipase A2 (sPLA2-IIA) is documented in the cerebral cortex (CTX) after ischemia, suggesting that sPLA2-IIA is associated with neurodegeneration. However, how sPLA2-IIA is involved in the neurodegeneration remains obscure. To clarify the pathologic role of sPLA2-IIA, we examined its neurotoxicity in rats that had the middle cerebral artery occluded and in primary cultures of cortical neurons. After occlusion, sPLA2 activity was increased in the CTX. An sPLA2 inhibitor, indoxam, significantly ameliorated not only the elevated activity of the sPLA2 but also the neurodegeneration in the CTX. The neuroprotective effect of indoxam was observed even when it was administered after occlusion. In primary cultures, sPLA2-IIA caused marked neuronal cell death. Morphologic and ultrastructural characteristics of neuronal cell death by sPLA2-IIA were apoptotic, as evidenced by condensed chromatin and fragmented DNA. Before apoptosis, sPLA2-IIA liberated arachidonic acid (AA) and generated prostaglandin D2 (PGD2), an AA metabolite, from neurons. Indoxam significantly suppressed not only AA release, but also PGD2 generation. Indoxam prevented neurons from sPLA2-IIA-induced neuronal cell death. The neuroprotective effect of indoxam was observed even when it was administered after sPLA2-IIA treatment. Furthermore, a cyclooxygenase-2 inhibitor significantly prevented neurons from sPLA2-IIA-induced PGD2 generation and neuronal cell death. In conclusion, sPLA2-IIA induces neuronal cell death via apoptosis, which might be associated with AA metabolites, especially PGD2. Furthermore, sPLA2 contributes to neurodegeneration in the ischemic brain, highlighting the therapeutic potential of sPLA2-IIA inhibitors for stroke.

  18. Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer's Disease Phase IIa and Expanded Access Trials.

    Science.gov (United States)

    Nelson, Thomas J; Sun, Miao-Kun; Lim, Chol; Sen, Abhik; Khan, Tapan; Chirila, Florin V; Alkon, Daniel L

    2017-01-01

    Bryostatin 1, a potent activator of protein kinase C epsilon (PKCɛ), has been shown to reverse synaptic loss and facilitate synaptic maturation in animal models of Alzheimer's disease (AD), Fragile X, stroke, and other neurological disorders. In a single-dose (25 μg/m2) randomized double-blind Phase IIa clinical trial, bryostatin levels reached a maximum at 1-2 h after the start of infusion. In close parallel with peak blood levels of bryostatin, an increase of PBMC PKCɛ was measured (p = 0.0185) within 1 h from the onset of infusion. Of 9 patients with a clinical diagnosis of AD, of which 6 received drug and 3 received vehicle within a double-blind protocol, bryostatin increased the Mini-Mental State Examination (MMSE) score by +1.83±0.70 unit at 3 h versus -1.00±1.53 unit for placebo. Bryostatin was well tolerated in these AD patients and no drug-related adverse events were reported. The 25 μg/m2 administered dose was based on prior clinical experience with three Expanded Access advanced AD patients treated with bryostatin, in which return of major functions such as swallowing, vocalization, and word recognition were noted. In one Expanded Access patient trial, elevated PKCɛ levels closely tracked cognitive benefits in the first 24 weeks as measured by MMSE and ADCS-ADL psychometrics. Pre-clinical mouse studies showed effective activation of PKCɛ and increased levels of BDNF and PSD-95. Together, these Phase IIa, Expanded Access, and pre-clinical results provide initial encouragement for bryostatin 1 as a potential treatment for AD.

  19. Tanshinone IIA Induces Apoptosis in Human Oral Cancer KB Cells through a Mitochondria-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Pao-Yu Tseng

    2014-01-01

    Full Text Available Tanshinone IIA (Tan IIA, an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.

  20. Exploiting N=2 in consistent coset reductions of type IIA

    CERN Document Server

    Cassani, Davide

    2009-01-01

    We study compactifications of type IIA supergravity on cosets exhibiting SU(3) structure. We establish the consistency of the truncation based on left-invariance, providing a justification for the choice of expansion forms which yields gauged N=2 supergravity in 4 dimensions. We explore N=1 solutions of these theories, emphasizing the requirements of flux quantization, as well as their non-supersymmetric companions. In particular, we obtain a no-go result for de Sitter solutions at string tree level, and, exploiting the enhanced leverage of the N=2 setup, provide a preliminary analysis of the existence of de Sitter vacua at all string loop order.

  1. On de Sitter vacua in type IIA orientifold compactifications

    Energy Technology Data Exchange (ETDEWEB)

    Saueressig, Frank [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, 3508 TD Utrecht (Netherlands)]. E-mail: f.s.saueressig@phys.uu.nl; Theis, Ulrich [Institute for Theoretical Physics, Friedrich-Schiller-University Jena, Max-Wien-Platz 1, D-07743 Jena (Germany)]. E-mail: ulrich.theis@uni-jena.de; Vandoren, Stefan [Institute for Theoretical Physics and Spinoza Institute, Utrecht University, 3508 TD Utrecht (Netherlands)]. E-mail: s.vandoren@phys.uu.nl

    2006-02-02

    This Letter discusses the orientifold projection of the quantum corrections to type IIA strings compactified on rigid Calabi-Yau threefolds. It is shown that N=2 membrane instanton effects give a holomorphic contribution to the superpotential, while the perturbative corrections enter into the Kahler potential. At the level of the scalar potential the corrections to the Kahler potential give rise to a positive energy contribution similar to adding anti-D3-branes in the KKLT scenario. This provides a natural mechanism to lift an AdS vacuum to a meta-stable dS vacuum.

  2. Anti-Inflammatory and Immunomodulatory Mechanism of Tanshinone IIA for Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zhuo Chen

    2014-01-01

    Full Text Available Tanshinone IIA (Tan II A is widely used in the treatment of cardiovascular diseases as an active component of Salvia miltiorrhiza Bunge. It has been demonstrated to have pleiotropic effects for atherosclerosis. From the anti-inflammatory and immunomodulatory mechanism perspective, this paper reviewed major progresses of Tan IIA in antiatherosclerosis research, including immune cells, antigens, cytokines, and cell signaling pathways.

  3. Explore the Molecular Mechanism of Apoptosis Induced by Tanshinone IIA on Activated Rat Hepatic Stellate Cells

    Directory of Open Access Journals (Sweden)

    Tai-Long Pan

    2012-01-01

    Full Text Available Since the activated hepatic stellate cell (HSC is the predominant event in the progression of liver fibrosis, selective clearance of HSC should be a potential strategy in therapy. Salvia miltiorrhiza roots ethanol extract (SMEE remarkably ameliorates liver fibrogenesis in DMN-administrated rat model. Next, tanshinone IIA (Tan IIA, the major compound of SMEE, significantly inhibited rat HSC viability and led to cell apoptosis. Proteome tools elucidated that increased prohibitin is involved in cell cycle arrest under Tan IIA is the treatment while knockdown of prohibitin could attenuate Tan IIA-induced apoptosis. In addition, Tan IIA mediated translocation of C-Raf which interacted with prohibitin activating MAPK and inhibiting AKT signaling in HSC. MAPK antagonist suppressed ERK phosphorylation which was necessary for Tan IIA-induced expression of Bax and cytochrome c. PD98059 also abolished Tan IIA-modulated cleavage of PARP. Our findings suggested that Tan IIA could contribute to apoptosis of HSC by promoting ERK-Bax-caspase pathways through C-Raf/prohibitin complex.

  4. Secretory PLA2-IIA: a new inflammatory factor for Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Sun Albert Y

    2006-10-01

    Full Text Available Abstract Secretory phospholipase A2-IIA (sPLA2-IIA is an inflammatory protein known to play a role in the pathogenesis of many inflammatory diseases. Although this enzyme has also been implicated in the pathogenesis of neurodegenerative diseases, there has not been a direct demonstration of its expression in diseased human brain. In this study, we show that sPLA2-IIA mRNA is up-regulated in Alzheimer's disease (AD brains as compared to non-demented elderly brains (ND. We also report a higher percentage of sPLA2-IIA-immunoreactive astrocytes present in AD hippocampus and inferior temporal gyrus (ITG. In ITG, the majority of sPLA2-IIA-positive astrocytes were associated with amyloid β (Aβ-containing plaques. Studies with human astrocytes in culture demonstrated the ability of oligomeric Aβ1–42 and interleukin-1β (IL-1β to induce sPLA2-IIA mRNA expression, indicating that this gene is among those induced by inflammatory cytokines. Since exogenous sPLA2-IIA has been shown to cause neuronal injury, understanding the mechanism(s and physiological consequences of sPLA2-IIA upregulation in AD brain may facilitate the development of novel therapeutic strategies to inhibit the inflammatory responses and to retard the progression of the disease.

  5. Disruption of the Class IIa HDAC Corepressor Complex Increases Energy Expenditure and Lipid Oxidation

    Directory of Open Access Journals (Sweden)

    Vidhi Gaur

    2016-09-01

    Full Text Available Drugs that recapitulate aspects of the exercise adaptive response have the potential to provide better treatment for diseases associated with physical inactivity. We previously observed reduced skeletal muscle class IIa HDAC (histone deacetylase transcriptional repressive activity during exercise. Here, we find that exercise-like adaptations are induced by skeletal muscle expression of class IIa HDAC mutants that cannot form a corepressor complex. Adaptations include increased metabolic gene expression, mitochondrial capacity, and lipid oxidation. An existing HDAC inhibitor, Scriptaid, had similar phenotypic effects through disruption of the class IIa HDAC corepressor complex. Acute Scriptaid administration to mice increased the expression of metabolic genes, which required an intact class IIa HDAC corepressor complex. Chronic Scriptaid administration increased exercise capacity, whole-body energy expenditure and lipid oxidation, and reduced fasting blood lipids and glucose. Therefore, compounds that disrupt class IIa HDAC function could be used to enhance metabolic health in chronic diseases driven by physical inactivity.

  6. Purification and biochemical characterization of a secreted group IIA chicken intestinal phospholipase A2

    Directory of Open Access Journals (Sweden)

    Gargouri Youssef

    2011-02-01

    Full Text Available Abstract Background Secretory phospholipase A2 group IIA (IIA PLA2 is a protein shown to be highly expressed in the intestine of mammals. However, no study was reported in birds. Results Chicken intestinal group IIA phospholipase A2 (ChPLA2-IIA was obtained after an acidic treatment (pH.3.0, precipitation by ammonium sulphate, followed by sequential column chromatographies on Sephadex G-50 and mono-S ion exchanger. The enzyme was found to be a monomeric protein with a molecular mass of around 14 kDa. The purified enzyme showed a substrate preference for phosphatidylethanolamine and phosphatidylglycerol, and didn't hydrolyse phosphatidylcholine. Under optimal assay conditions, in the presence of 10 mM NaTDC and 10 mM CaCl2, a specific activity of 160 U.mg-1 for purified ChPLA2-IIA was measured using egg yolk as substrate. The fifteen NH2-terminal amino acid residues of ChPLA2-IIA were sequenced and showed a close homology with known intestinal secreted phospholipases A2. The gene encoding the mature ChPLA2-IIA was cloned and sequenced. To further investigate structure-activity relationship, a 3D model of ChPLA2-IIA was built using the human intestinal phospholipase A2 structure as template. Conclusion ChPLA2-IIA was purified to homogeneity using only two chromatographic colomns. Sequence analysis of the cloned cDNA indicates that the enzyme is highly basic with a pI of 9.0 and has a high degree of homology with mammalian intestinal PLA2-IIA.

  7. Worldsheet one-loop energy correction to IIA Giant Magnon

    CERN Document Server

    Bai, Xiaojian; Park, I Y

    2013-01-01

    We compute one-loop corrections to the energy of a IIA giant magnon solution in the $AdS_4 \\times CP^3$ background by using the standard quantum field theory (QFT) techniques. The string action is expanded around the solution to the quadratic order in the fluctuation fields. The resulting action has 2D coordinate dependent-coefficients, a feature that complicates the analysis. The solution contains a worldsheet velocity parameter $v$, and is expanded in terms of the parameter. A perturbative analysis is carried out by treating the $v$-dependent parts as vertices. The energy is computed by first putting the system in a box of length $L$ and Fourier-transforming the fields into the discrete momentum modes. We compare our result with the results obtained by the algebraic curve method.

  8. First Results from the DRIFT-IIa Dark Matter Detector

    CERN Document Server

    Burgos, S; Ghag, C; Gold, M; Kudryavtsev, V A; Lawson, T B; Loomba, D; Majewski, P; Muna, D; Murphy, A StJ; Nicklin, G G; Paling, S M; Petkov, A; Plank, S J S; Robinson, M; Sanghi, N; Smith, N J T; Snowden-Ifft, D P; Spooner, N J C; Sumner, T J; Turk, J; Tziaferi, E

    2007-01-01

    Data from the DRIFT-IIa directional dark matter experiment are presented, collected during a near continuous 6 month running period. A detailed calibration analysis comparing data from gamma-ray, x-ray and neutron sources to a GEANT4 Monte Carlo simulations reveals an efficiency for detection of neutron induced recoils of 94+/-2(stat.)+/-5(sys.)%. Software-based cuts, designed to remove non-nuclear recoil events, are shown to reject 60Co gamma-rays with a rejection factor of better than 8x10-6 for all energies above threshold. An unexpected event population has been discovered and is shown here to be due to the alpha-decay of 222Rn daughter nuclei that have attached to the central cathode. A limit on the flux of neutrons in the Boulby Underground Laboratory is derived from analysis of unshielded and shielded data.

  9. On the absence of BPS preonic solutions in IIA and IIB supergravities

    CERN Document Server

    Bandos, I A; de Azcárraga, J A; Azcarraga, Jose A. de; Bandos, Igor A.; Varela, Oscar

    2006-01-01

    We consider the present absence of 31 out of 32 supersymmetric solutions in supergravity i.e., of solutions describing BPS preons. A recent result indicates that (bosonic) BPS preonic solutions do not exist in type IIB supergravity. We reconsider this analysis by using the G-frame method, extend it to the IIA supergravity case, and show that there are no (bosonic) preonic solutions for type IIA either. For the classical D=11 supergravity no conclusion can be drawn yet, although the negative IIA results permit establishing the conditions that preonic solutions would have to satisfy. For supergravities with `stringy' corrections, the existence of BPS preonic solutions remains fully open.

  10. Study on inclusion complexes of hydroxypropyl-β-cyclodextrin with tanshinone IIA

    Institute of Scientific and Technical Information of China (English)

    YAN Jinhong; ZHANG Cuiping; YANG Pin

    2007-01-01

    The inclusion complex formation of tanshinone IIA(Tan IIA)with hydroxypropyl-β-cyclodextrin(HPCD)was studied by using phase solubility method,and the formation constant for tanshinone IIA-HPCD- dextrin was determined.The effect of temperature on the reaction was studied through thermodynamics,and the changes inentropy,enthalpy,and free energy of the reaction were calculated.The molecular modeling provided further evidence for the formation of the inclusion complexes.Stable inclusion complex in solid state was characterized by IR spectra.

  11. Regulation of myosin IIA and filamentous actin during insulin-stimulated glucose uptake in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Stall, Richard; Ramos, Joseph; Kent Fulcher, F.; Patel, Yashomati M., E-mail: ympatel@uncg.edu

    2014-03-10

    Insulin stimulated glucose uptake requires the colocalization of myosin IIA (MyoIIA) and the insulin-responsive glucose transporter 4 (GLUT4) at the plasma membrane for proper GLUT4 fusion. MyoIIA facilitates filamentous actin (F-actin) reorganization in various cell types. In adipocytes F-actin reorganization is required for insulin-stimulated glucose uptake. What is not known is whether MyoIIA interacts with F-actin to regulate insulin-induced GLUT4 fusion at the plasma membrane. To elucidate the relationship between MyoIIA and F-actin, we examined the colocalization of MyoIIA and F-actin at the plasma membrane upon insulin stimulation as well as the regulation of this interaction. Our findings demonstrated that MyoIIA and F-actin colocalized at the site of GLUT4 fusion with the plasma membrane upon insulin stimulation. Furthermore, inhibition of MyoII with blebbistatin impaired F-actin localization at the plasma membrane. Next we examined the regulatory role of calcium in MyoIIA-F-actin colocalization. Reduced calcium or calmodulin levels decreased colocalization of MyoIIA and F-actin at the plasma membrane. While calcium alone can translocate MyoIIA it did not stimulate F-actin accumulation at the plasma membrane. Taken together, we established that while MyoIIA activity is required for F-actin localization at the plasma membrane, it alone is insufficient to localize F-actin to the plasma membrane. - Highlights: • Insulin induces colocalization of MyoIIA and F-actin at the cortex in adipocytes. • MyoIIA is necessary but not sufficient to localize F-actin at the cell cortex. • MyoIIA-F-actin colocalization is regulated by calcium and calmodulin.

  12. Heterotic-type IIA duality and degenerations of K3 surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Braun, A.P. [Department of Mathematics, University of Oxford,Andrew Wiles Building, Woodstock Rd, Oxford OX2 6GG (United Kingdom); Watari, T. [Kavli Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwano-ha 5-1-5, 277-8583 (Japan)

    2016-08-04

    We study the duality between four-dimensional N=2 compactifications of heterotic and type IIA string theories. Via adiabatic fibration of the duality in six dimensions, type IIA string theory compactified on a K3-fibred Calabi-Yau threefold has a potential heterotic dual compactification. This adiabatic picture fails whenever the K3 fibre degenerates into multiple components over points in the base of the fibration. Guided by monodromy, we identify such degenerate K3 fibres as solitons generalizing the NS5-brane in heterotic string theory. The theory of degenerations of K3 surfaces can then be used to find which solitons can be present on the heterotic side. Similar to small instanton transitions, these solitons escort singular transitions between different Calabi-Yau threefolds. Starting from well-known examples of heterotic-type IIA duality, such transitions can take us to type IIA compactifications with unknown heterotic duals.

  13. Tanshinone IIA ameliorates dextran sulfate sodium-induced inflammatory bowel disease via the pregnane X receptor

    Directory of Open Access Journals (Sweden)

    Zhang X

    2015-12-01

    Full Text Available Xianxie Zhang,1 Yuguang Wang,2 Zengchun Ma,2 Qiande Liang,2 Xianglin Tang,2 Donghua Hu,2 Hongling Tan,2 Chengrong Xiao,2 Yue Gao2 1Air Force General Hospital of People’s Liberation Army, Beijing, People’s Republic of China; 2Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing, People’s Republic of China Abstract: Tanshinone IIA (Tan IIA (C19H18O3 is one of the major active lipophilic components in a conventional Chinese medicine called danshen, and it has long been used in the People’s Republic of China and other neighboring countries to treat patients suffering from inflammatory bowel disease (IBD. Previous experiments by many teams determined which mechanism of Tan IIA is relevant to the treatment of IBD associated with inflammation and the pregnane X receptor (PXR. The current study demonstrated that Tan IIA is an efficacious PXR agonist and its ability to induce CYP3A4 mRNA and protein expression was mediated by the transactivation of PXR, a known target of abrogating inflammation in IBD. Clinical symptoms in mice and histological assessment data suggested that administration of Tan IIA in mice demonstrated significant protection and showed that in DSS-induced IBD it acts in a concentration-dependent manner. PXR-silenced mice treated with Tan IIA demonstrated low protection against DSS-induced mouse IBD and exacerbated the severity of IBD compared with wild-type mice; PXR-silenced mice demonstrated the necessity for PXR in Tan IIA-mediated upregulation of xenobiotic metabolism genes. The IBD treatment effects of Tan IIA are partially due to PXR-mediated upregulation of xenobiotic metabolism and downregulation of inflammatory mediators. The novel findings reported here may contribute to the effective utilization of Tan IIA and its derivatives as a PXR ligand in the treatment of human IBD. This suggests that Tan IIA may have considerable clinical utility. Keywords: dashen, ulcerative colitis

  14. Low frequency solar radio astronomy at the Indian Institute of Astrophysics (IIA)

    Science.gov (United States)

    Ramesh, R.

    IIA is presently involved in the expansion of its existing radioheliograph operating in the frequency 120-40 MHz at the Gauribidanur radio observatory located about 80 km north of Bangalore. Once completed, the expanded array will have an angular resolution of ≈ 1' at a typical frequency of 100 MHz. This paper describes the development of solar radio astronomy activities at IIA since 1952 when the first observations were carried out.

  15. Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis

    Science.gov (United States)

    Liu, Nathan J.; Chapman, Robert; Lin, Yiyang; Mmesi, Jonas; Bentham, Andrew; Tyreman, Matthew; Abraham, Sonya; Stevens, Molly M.

    2016-02-01

    Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care.Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in-house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08423g

  16. Type IIA flux compactifications. Vacua, effective theories and cosmological challenges

    Energy Technology Data Exchange (ETDEWEB)

    Koers, Simon

    2009-07-30

    In this thesis, we studied a number of type IIA SU(3)-structure compactifications with 06-planes on nilmanifolds and cosets, which are tractable enough to allow for an explicit derivation of the low energy effective theory. In particular we calculated the mass spectrum of the light scalar modes, using N = 1 supergravity techniques. For the torus and the Iwasawa solution, we have also performed an explicit Kaluza-Klein reduction, which led to the same result. For the nilmanifold examples we have found that there are always three unstabilized moduli corresponding to axions in the RR sector. On the other hand, in the coset models, except for SU(2) x SU(2), all moduli are stabilized. We discussed the Kaluza-Klein decoupling for the supersymmetric AdS vacua and found that it requires going to the Nearly-Calabi Yau limited. We searched for non-trivial de Sitter minima in the original flux potential away from the AdS vacuum. Finally, in chapter 7, we focused on a family of three coset spaces and constructed non-supersymmetric vacua on them. (orig.)

  17. D6-brane Splitting on Type IIA Orientifolds

    CERN Document Server

    Cvetic, M; Li, T; Liu, T; Cvetic, Mirjam; Langacker, Paul; Li, Tianjun; Liu, Tao

    2004-01-01

    We address both the string and field theory aspects of D6-brane splitting on Type IIA orientifolds with supersymmetric intersecting D6-branes. We focus specifically on the Z_2 x Z_2 orientifolds and address the symmetry breaking pattern for D6-branes parallel with the orientifold 6-planes as well as those positioned at angles. We demonstrate that the string theory results, which have a beautiful geometric interpretation, are in one to one correspondence with the field theory results associated with vacuum expectation values (Higgsing) of moduli in the antisymmetric representation of Sp(2N) gauge symmetry (for branes parallel with orientifold planes) or adjoint representation of U(N) (for branes at general angles). In particular, moving branes away from the orientifold planes results in change of the chiral spectrum and may change the number of families. We also provide the first new examples of the supersymmetric Standard-like models with the electroweak symmetry arising from the branes parallel with the orie...

  18. Type IIA orientifolds on SU(2)-structure manifolds

    Energy Technology Data Exchange (ETDEWEB)

    Danckaert, Thomas

    2010-11-15

    We investigate the possible supersymmetry-preserving orientifold projections of type IIA string theory on a six-dimensional background with SU(2)-structure. We find two categories of projections which preserve half of the low-energy supersymmetry, reducing the effective theory from an N=4 supergravity theory, to an N=2 supergravity. For these two cases, we impose the projection on the low-energy spectrum and reduce the effective N=4 supergravity action accordingly. We can identify the resulting gauged N=2 supergravity theory and bring the action into canonical form. We compute the scalar moduli spaces and characterize the gauged symmetries in terms of the geometry of these moduli spaces. Due to their origin in N=4 supergravity, which is a highly constrained theory, the moduli spaces are of a very simple form. We find that, for suitable background manifolds, isometries in all scalar sectors can become gauged. The obtained gaugings share many features with those of N=2 supergravities obtained previously from other G-structure compactifications. (orig.)

  19. Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery

    Directory of Open Access Journals (Sweden)

    Melissa H. Jorrisch

    2013-02-01

    Cell motility is a cornerstone of embryogenesis, tissue remodeling and repair, and cancer cell invasion. It is generally thought that migrating cells grab and exert traction force onto the extracellular matrix in order to pull the cell body forward. While previous studies have shown that myosin II deficient cells migrate efficiently, whether these cells exert traction forces during cell migration in the absence of the major contractile machinery is currently unknown. Using an array of micron-sized pillars as a force sensor and shRNA specific to each myosin II isoform (A and B, we analyzed how myosin IIA and IIB individually regulate cell migration and traction force generation. Myosin IIA and IIB localized preferentially to the leading edge where traction force was greatest, and the trailing edge, respectively. When individual myosin II isoforms were depleted by shRNA, myosin IIA deficient cells lost actin stress fibers and focal adhesions, whereas myosin IIB deficient cells maintained similar actin organization and focal adhesions as wild-type cells. Interestingly, myosin IIA deficient cells migrated faster than wild-type or myosin IIB deficient cells on both a rigid surface and a pillar array, yet myosin IIA deficient cells exerted significantly less traction force at the leading edge than wild-type or myosin IIB deficient cells. These results suggest that, in the absence of myosin IIA mediated force-generating machinery, cells move with minimal traction forces at the cell periphery, thus demonstrating the remarkable ability of cells to adapt and migrate.

  20. Myosin IIA deficient cells migrate efficiently despite reduced traction forces at cell periphery.

    Science.gov (United States)

    Jorrisch, Melissa H; Shih, Wenting; Yamada, Soichiro

    2013-04-15

    Cell motility is a cornerstone of embryogenesis, tissue remodeling and repair, and cancer cell invasion. It is generally thought that migrating cells grab and exert traction force onto the extracellular matrix in order to pull the cell body forward. While previous studies have shown that myosin II deficient cells migrate efficiently, whether these cells exert traction forces during cell migration in the absence of the major contractile machinery is currently unknown. Using an array of micron-sized pillars as a force sensor and shRNA specific to each myosin II isoform (A and B), we analyzed how myosin IIA and IIB individually regulate cell migration and traction force generation. Myosin IIA and IIB localized preferentially to the leading edge where traction force was greatest, and the trailing edge, respectively. When individual myosin II isoforms were depleted by shRNA, myosin IIA deficient cells lost actin stress fibers and focal adhesions, whereas myosin IIB deficient cells maintained similar actin organization and focal adhesions as wild-type cells. Interestingly, myosin IIA deficient cells migrated faster than wild-type or myosin IIB deficient cells on both a rigid surface and a pillar array, yet myosin IIA deficient cells exerted significantly less traction force at the leading edge than wild-type or myosin IIB deficient cells. These results suggest that, in the absence of myosin IIA mediated force-generating machinery, cells move with minimal traction forces at the cell periphery, thus demonstrating the remarkable ability of cells to adapt and migrate.

  1. The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.

    Science.gov (United States)

    Pang, Hui; Han, Bing; Yu, Tao; Peng, Zhen

    2014-01-01

    Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH), the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32) were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day) or 5% glucose injection (GS). Sham-operated rats (n = 8) received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson's trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2) and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2) protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS) group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM) deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA) content and increased superoxide dismutase (SOD) activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM deposition

  2. The complex regulation of tanshinone IIA in rats with hypertension-induced left ventricular hypertrophy.

    Directory of Open Access Journals (Sweden)

    Hui Pang

    Full Text Available Tanshinone IIA has definite protective effects on various cardiovascular diseases. However, in hypertension-induced left ventricular hypertrophy (H-LVH, the signaling pathways of tanshinone IIA in inhibition of remodeling and cardiac dysfunction remain unclear. Two-kidney, one-clip induced hypertensive rats (n = 32 were randomized to receive tanshinone IIA (5, 10, 15 mg/kg per day or 5% glucose injection (GS. Sham-operated rats (n = 8 received 5%GS as control. Cardiac function and dimensions were assessed by using an echocardiography system. Histological determination of the fibrosis and apoptosis was performed using hematoxylin eosin, Masson's trichrome and TUNEL staining. Matrix metalloproteinase 2 (MMP2 and tissue inhibitor of matrix metalloproteinases type 2 (TIMP2 protein expressions in rat myocardial tissues were detected by immunohistochemistry. Rat cardiomyocytes were isolated by a Langendorff perfusion method. After 48 h culture, the supernatant and cardiomyocytes were collected to determine the potential related proteins impact on cardiac fibrosis and apoptosis. Compared with the sham rats, the heart tissues of H-LVH (5%GS group suffered severely from the oxidative damage, apoptosis of cardiomyocytes and extracellular matrix (ECM deposition. In the H-LVH group, tanshinone IIA treated decreased malondialdehyde (MDA content and increased superoxide dismutase (SOD activity. Tanshinone IIA inhibited cardiomyocytes apoptosis as confirmed by the reduction of TUNEL positive cardiomyocytes and the down-regulation of Caspase-3 activity and Bax/Bcl-2 ratio. Meanwhile, plasma apelin level increased with down-regulation of APJ receptor. Tanshinone IIA suppressed cardiac fibrosis through regulating the paracrine factors released by cardiomyocytes and the TGF-β/Smads signaling pathway activity. In conclusion, our in vivo study showed that tanshinone IIA could improve heart function by enhancing myocardial contractility, inhibiting ECM

  3. Bryostatin Effects on Cognitive Function and PKCɛ in Alzheimer’s Disease Phase IIa and Expanded Access Trials

    Science.gov (United States)

    Nelson, Thomas J.; Sun, Miao-Kun; Lim, Chol; Sen, Abhik; Khan, Tapan; Chirila, Florin V.; Alkon, Daniel L.

    2017-01-01

    Bryostatin 1, a potent activator of protein kinase C epsilon (PKCɛ), has been shown to reverse synaptic loss and facilitate synaptic maturation in animal models of Alzheimer’s disease (AD), Fragile X, stroke, and other neurological disorders. In a single-dose (25 μg/m2) randomized double-blind Phase IIa clinical trial, bryostatin levels reached a maximum at 1-2 h after the start of infusion. In close parallel with peak blood levels of bryostatin, an increase of PBMC PKCɛ was measured (p = 0.0185) within 1 h from the onset of infusion. Of 9 patients with a clinical diagnosis of AD, of which 6 received drug and 3 received vehicle within a double-blind protocol, bryostatin increased the Mini-Mental State Examination (MMSE) score by +1.83±0.70 unit at 3 h versus –1.00±1.53 unit for placebo. Bryostatin was well tolerated in these AD patients and no drug-related adverse events were reported. The 25 μg/m2 administered dose was based on prior clinical experience with three Expanded Access advanced AD patients treated with bryostatin, in which return of major functions such as swallowing, vocalization, and word recognition were noted. In one Expanded Access patient trial, elevated PKCɛ levels closely tracked cognitive benefits in the first 24 weeks as measured by MMSE and ADCS-ADL psychometrics. Pre-clinical mouse studies showed effective activation of PKCɛ and increased levels of BDNF and PSD-95. Together, these Phase IIa, Expanded Access, and pre-clinical results provide initial encouragement for bryostatin 1 as a potential treatment for AD. PMID:28482641

  4. Tanshinone IIA exerts protective effects in a LCA-induced cholestatic liver model associated with participation of pregnane X receptor.

    Science.gov (United States)

    Zhang, Xianxie; Ma, Zengchun; Liang, Qiande; Tang, Xianglin; Hu, Donghua; Liu, Canglong; Tan, Hongling; Xiao, Chengrong; Zhang, Boli; Wang, Yuguang; Gao, Yue

    2015-04-22

    Tanshinone IIA (Tan IIA) is one of the main natural active ingredients purified from Salvia miltiorrhiza radix, which has long been used in clinical practice in China to treat diseases including liver fibrosis, Alzheimer׳s disease, and cardiovascular diseases. Tan IIA has hepatoprotective properties, and is an efficacious PXR agonist. Our study was designed to observe the function and mechanism of the hepatoprotective properties of Tan IIA. HepG2 cells were used to investigate the vitrol effects of Tan IIA on PXR and CYP3A4. Gut-formed LCA is hepatotoxic, and has been implicated in the pathogenesis of cholestatic diseases. To further investigate the hepatoprotective mechanisms of Tan IIA against LCA-induced cholestasis in vivo, we choose the normal mice and siRNA-treated mice. The in vitro study demonstrated that the effect of Tan IIA on CYP3A4 was mediated by transactivation of PXR in a dose- and time-dependent manner. The in vivo experiments using PXR siRNA revealed that Tan IIA could protect against LCA-induced hepatotoxicity and cholestasis in a dose-dependent manner. These effects were partially caused by the upregulation of PXR, as well as Cyp3a11, Cyp3a13, and Mdr1, which are the enzymes responsible for LCA metabolism. This is the first report showing that the hepatoprotective effects of Tan IIA are partly mediated by PXR.

  5. Tanshinone IIA induces intrinsic apoptosis in osteosarcoma cells both in vivo and in vitro associated with mitochondrial dysfunction

    Science.gov (United States)

    Huang, Sheng-Teng; Huang, Chao-Chun; Huang, Wen-Liang; Lin, Tsu-Kung; Liao, Pei-Lin; Wang, Pei-Wen; Liou, Chia-Wei; Chuang, Jiin-Haur

    2017-01-01

    Tanshinone IIA (Tan IIA), a phytochemical derived from the roots of Salvia miltiorrhiza, has been shown to inhibit growth and induce apoptosis in various cancer cells. The association of its inhibitory effect on the primary malignant bone tumor, osteosarcoma, with mitochondrial dysfunction remains unclear. This study aimed to investigate the anti-proliferative effects of Tan IIA on human osteosarcoma 143B cells both in vitro and in vivo. Administration of Tan IIA to NOD-SCID mice implanted with 143B cells led to significant inhibition of tumor development. The inhibition of proliferation, migration, and invasion was observed in 143B cells treated with Tan IIA. The tumor proliferation markers, Ki67 and PCNA, were suppressed and apoptosis by TUNEL assay was activated respectively. Apoptosis in the Tan IIA-treated 143B cells and xerograft mice was associated with the activation of caspase cascade via the modulation of Bcl-2 family. The CD31 was inhibited in Tan IIA-treated xenografts to indicate anti-neovasculization. Tan IIA administration resulted in a significant decrease in the mitochondrial fusion proteins, Mfn1/2 and Opa1, as well as an increase in the fission protein Drp1. We concluded that mitochondrial dysfunction associated with dynamic change was involved in apoptosis and anti-angiogenesis elicited by Tan IIA. PMID:28106052

  6. A Case Report of Multiple Endocrine Neoplasia Type IIa Associated with Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2013-10-01

    Full Text Available Introduction: Multiple endocrine neoplasia type IIa (MEN IIa is an autosomal dominant syn-drome characterized bypheochromocytoma ,medullary thyroid carcinoma and hyperparathy-roidism. Pheochromocytoma approximately occurs in 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and becomes manifest like Cushing syndrome,although it is very rare. Case Report: We report a 26-year-old woman patient with severe muscle weakness, skin le-sions in extremity, hypertension, new onset diabetes and in the laboratory data hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. Conclusion: In the patients with hypertension, new onset diabetes and hypokalemia Cushing syndrome and pheochromocytoma should always be ruled out. (Sci J Hamadan Univ Med Sci 2013; 20 (3:260-265

  7. Tanshinone IIA Protects against Dextran Sulfate Sodium- (DSS-) Induced Colitis in Mice by Modulation of Neutrophil Infiltration and Activation.

    Science.gov (United States)

    Liu, Xiaowei; He, Haiyue; Huang, Tingting; Lei, Zhen; Liu, Fuquan; An, Guangyu; Wen, Tao

    2016-01-01

    Neutrophils play a critical role in the initiation and maintenance of intestinal inflammation. However, conventional neutrophil-targeted therapies can impair normal host defense. Tanshinone IIA has been recently revealed to act directly on neutrophils. Hence, we aimed at investigating whether Tanshinone IIA can protect against experimental colitis through modulation of neutrophils. We induced colitis in C57BL/6 mice by giving 3% dextran sulfate sodium (DSS) orally, and meanwhile, we treated mice daily with Tanshinone IIA intraperitoneally. The severity of colitis was evaluated by calculating disease activity index (DAI) and histological parameters. Neutrophil infiltration and activation in the colons of mice were measured. Moreover, whether Tanshinone IIA has direct effects on neutrophil migration and activation was determined in vitro. Our data showed that Tanshinone IIA significantly ameliorated the severity of DSS-induced colitis in mice, evidenced by the reduced DAI and improved colonic inflammation. In addition, Tanshinone IIA decreased neutrophil infiltration of intestinal mucosa and activation and reduced colonic inflammatory cytokines in DSS-treated mice. Furthermore, Tanshinone IIA was demonstrated to significantly suppress neutrophil migration and activation. These results provide compelling evidence that Tanshinone IIA has a therapeutic potential for alleviating inflammatory colitis in mice, which is possibly mediated by the immunomodulation of neutrophils.

  8. Tanshinone IIA Prevents Leu27IGF-II-Induced Cardiomyocyte Hypertrophy Mediated by Estrogen Receptor and Subsequent Akt Activation.

    Science.gov (United States)

    Weng, Yueh-Shan; Wang, Hsueh-Fang; Pai, Pei-Ying; Jong, Gwo-Ping; Lai, Chao-Hung; Chung, Li-Chin; Hsieh, Dennis Jine-Yuan; HsuanDay, Cecilia; Kuo, Wei-Wen; Huang, Chih-Yang

    2015-01-01

    IGF-IIR plays important roles as a key regulator in myocardial pathological hypertrophy and apoptosis, which subsequently lead to heart failure. Salvia miltiorrhiza Bunge (Danshen) is a traditional Chinese medicinal herb used to treat cardiovascular diseases. Tanshinone IIA is an active compound in Danshen and is structurally similar to 17[Formula: see text]-estradiol (E[Formula: see text]. However, whether tanshinone IIA improves cardiomyocyte survival in pathological hypertrophy through estrogen receptor (ER) regulation remains unclear. This study investigates the role of ER signaling in mediating the protective effects of tanshinone IIA on IGF-IIR-induced myocardial hypertrophy. Leu27IGF-II (IGF-II analog) was shown in this study to specifically activate IGF-IIR expression and ICI 182,780 (ICI), an ER antagonist used to investigate tanshinone IIA estrogenic activity. We demonstrated that tanshinone IIA significantly enhanced Akt phosphorylation through ER activation to inhibit Leu27IGF-II-induced calcineurin expression and subsequent NFATc3 nuclear translocation to suppress myocardial hypertrophy. Tanshinone IIA reduced the cell size and suppressed ANP and BNP, inhibiting antihypertrophic effects induced by Leu27IGF-II. The cardioprotective properties of tanshinone IIA that inhibit Leu27IGF-II-induced cell hypertrophy and promote cell survival were reversed by ICI. Furthermore, ICI significantly reduced phospho-Akt, Ly294002 (PI3K inhibitor), and PI3K siRNA significantly reduced the tanshinone IIA-induced protective effect. The above results suggest that tanshinone IIA inhibited cardiomyocyte hypertrophy, which was mediated through ER, by activating the PI3K/Akt pathway and inhibiting Leu27IGF-II-induced calcineurin and NFATC3. Tanshinone IIA exerted strong estrogenic activity and therefore represented a novel selective ER modulator that inhibits IGF-IIR signaling to block cardiac hypertrophy.

  9. Production and immunogenicity of Actinobacillus pleuropneumoniae ApxIIA protein in transgenic rice callus.

    Science.gov (United States)

    Kim, Mi-Young; Kim, Tae-Geum; Yang, Moon-Sik

    2017-04-01

    Actinobacillus pleuropneumoniae is a major etiological agent that is responsible for swine pleuropneumonia, a highly contagious respiratory infection that causes severe economic losses in the swine production industry. ApxIIA is one of the virulence factors in A. pleuropneumoniae and has been considered as a candidate for developing a vaccine against the bacterial infection. A gene encoding an ApxIIA fragment (amino acids 439-801) was modified based on a plant-optimized codon and constructed into a plant expression vector under the control of a promoter and the 3' UTR of the rice amylase 3D gene. The plant expression vector was introduced into rice embryogenic callus (Oryza sativa L. cv. Dongjin) via particle bombardment-mediated transformation. The integration and transcription of the ApxIIA439-801 gene were confirmed by using genomic DNA PCR amplification and Northern blot analysis, respectively. The synthesis of ApxIIA439-801 antigen protein in transgenic rice callus was confirmed by western blot analysis. The concentration of antigen protein in lyophilized samples of transgenic rice callus was 250 μg/g. Immunizing mice with protein extracts from transgenic plants intranasally elicited secretory IgA. These results demonstrate the feasibility of using a transgenic plant to elicit immune responses against A. pleuropneumoniae. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. D-branes in Type IIA and Type IIB theories from tachyon condensation

    CERN Document Server

    Kluson, J

    2000-01-01

    In this paper we will construct all D-branes in Type IIA and Type IIB theories via tachyon condensation. We also propose form of Wess-Zumino term for non-BPS D-brane and we will show that tachyon condensation in this term leads to standard Wess-Zumino term for BPS D-brane.

  11. Bactericidal properties of group IIA and group V phospholipases A2

    NARCIS (Netherlands)

    Grönroos, J.O.; Laine, V.J.O.; Janssen, M.J.W.; Egmond, M.R.; Nevalainen, T.J.

    2010-01-01

    Group V phospholipase A2 (PLA2) is a recently characterized 14-kDa secretory PLA2 of mammalian heart and macrophage-derived cells. Group IIA PLA2, which is structurally close to group V PLA2, has been shown to kill Gram-positive bacteria in vitro and to prevent symptoms of Gram-positive infection in

  12. Purification and characterization of a phospholipase A2-IIA from common stingray (Dasyatis pastinaca) intestine.

    Science.gov (United States)

    Ben Bacha, Abir; Daihan, Sooad K; Moubayed, Nadine M S; Mejdoub, Hafedh

    2013-06-01

    A phospholipase A2 belonging to IIA group secretory PLA2 was isolated and purified to homogeneity from the intestine of common stingray (Dasyatis pastinaca) using acidic treatment (pH 1.5) and ammonium sulphate precipitation methods combined with single-column ion-exchange chromatography. The purified enzyme was found to be a glycosylated monomeric protein with a molecular mass of about 14 kDa. The stingray sPLA2-IIA had optimum activity at 45 degrees C, unlike known mammalian PLA2-IIAs, which show optimum activity at 37 degrees C. The purified enzyme exhibited a specific activity of 290 U/mg at optimal conditions (pH 9.5 and 45 degrees C) in the presence of 6 mM NaDC and 8 mM CaCl2 with egg yolk as substrate. The NH2-terminal sequence of the enzyme and some protein fragments obtained from its tryptic digestion were also determined. All sequences obtained were similar to those of sPLA2-IIA. The enzyme also showed good stability in the presence of organic solvents, acidic and alkaline pH media and high temperature conditions. Thus, the purified enzyme exhibited a number of unique and promising properties, making it a potential possible candidate for future applications in the treatment of phospholipid-rich industrial effluents and synthesis of useful preparations for the food production and processing industry.

  13. Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System

    Directory of Open Access Journals (Sweden)

    Qing-Qing Xu

    2016-01-01

    Full Text Available Sodium Tanshinone IIA sulfonate (STS is a derivative of Tanshinone IIA (Tan IIA. Tan IIA has been reported to possess neuroprotective effects against Alzheimer’s disease (AD. However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP- induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE and increased the activity of choline acetyltransferase (ChAT in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD and decreased the levels of malondialdehyde (MDA and reactive oxygen species (ROS in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3. STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

  14. Consistent ${\\cal N}=8$ truncation of massive IIA on $S^6$

    CERN Document Server

    Guarino, Adolfo

    2015-01-01

    Massive type IIA supergravity is shown to admit a consistent truncation on the six-sphere to maximal supergravity in four dimensions with a dyonic ISO(7) gauging. We obtain the complete, non-linear embedding of all the $D=4$ fields into the IIA metric and form potentials, and show its consistency. We first rewrite the IIA theory in an $\\textrm{SO}(1,3) \\times \\textrm{SL}(7)$--covariant way. Then, we employ an ${\\cal N}=8$ SL(7)--covariant restriction of the $D=4$ tensor hierarchy in order to find the full embedding. The redundant $D=4$ degrees of freedom introduced by the tensor hierarchy can be eliminated by writing the embedding in terms of the field strengths and exploiting the restricted duality hierarchy. In particular, closed expressions for the Freund-Rubin term are found using this technique which reveal a pattern valid for other truncations. Finally, we show that the present ${\\cal N}=8$ truncation of massive IIA on $S^6$ and the ${\\cal N}=2$ truncation obtained when $S^6$ is equipped with its nearly...

  15. Class IIa histone deacetylases are hormone-activated regulators of FOXO and mammalian glucose homeostasis

    DEFF Research Database (Denmark)

    Mihaylova, Maria M; Vasquez, Debbie S; Ravnskjær, Kim;

    2011-01-01

    . In response to the fasting hormone glucagon, class IIa HDACs are rapidly dephosphorylated and translocated to the nucleus where they associate with the promoters of gluconeogenic enzymes such as G6Pase. In turn, HDAC4/5 recruit HDAC3, which results in the acute transcriptional induction of these genes via...

  16. 30 CFR 57.22603 - Blasting from the surface (II-A mines).

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Blasting from the surface (II-A mines). 57.22603 Section 57.22603 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... MINES Safety Standards for Methane in Metal and Nonmetal Mines Explosives § 57.22603 Blasting from...

  17. Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.

    Science.gov (United States)

    Smith, T J; Soderlund, D M

    1998-12-01

    Pyrethroid insecticides bind to a unique site on voltage-dependent sodium channels and prolong sodium currents, leading to repetitive bursts of action potentials or use-dependent nerve block. To further characterize the site and mode of action of pyrethroids on sodium channels, we injected synthetic mRNA encoding the rat brain IIa sodium channel alpha subunit, either alone or in combination with synthetic mRNA encoding the rat sodium channel beta1 subunit, into oocytes of the frog Xenopus laevis and assessed the actions of the pyrethroid insecticide [1R,cis,alphaS]-cypermethrin on expressed sodium currents by two-electrode voltage clamp. In oocytes expressing only the rat brain IIa alpha subunit, cypermethrin produced a slowly-decaying sodium tail current following a depolarizing pulse. In parallel experiments using oocytes expressing the rat brain IIa alpha subunit in combination with the rat beta1 subunit, cypermethrin produced qualitatively similar tail currents following a depolarizing pulse and also induced a sustained component of the sodium current measured during a step depolarization of the oocyte membrane. The voltage dependence of activation and steady-state inactivation of the cypermethrin-dependent sustained current were identical to those of the peak transient sodium current measured in the absence of cypermethrin. Concentration-response curves obtained using normalized tail current amplitude as an index of the extent of sodium channel modification by cypermethrin revealed that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit increased the apparent affinity of the sodium channel binding site for cypermethrin by more than 20-fold. These results confirm that the pyrethroid binding site is intrinsic to the sodium channel alpha subunit and demonstrate that coexpression of the rat brain IIa alpha subunit with the rat beta1 subunit alters the apparent affinity of this site for pyrethroids.

  18. Effects of starch synthase IIa gene dosage on grain, protein and starch in endosperm of wheat.

    Science.gov (United States)

    Konik-Rose, Christine; Thistleton, Jenny; Chanvrier, Helene; Tan, Ihwa; Halley, Peter; Gidley, Michael; Kosar-Hashemi, Behjat; Wang, Hong; Larroque, Oscar; Ikea, Joseph; McMaugh, Steve; Regina, Ahmed; Rahman, Sadequr; Morell, Matthew; Li, Zhongyi

    2007-11-01

    Starch synthases (SS) are responsible for elongating the alpha-1,4 glucan chains of starch. A doubled haploid population was generated by crossing a line of wheat, which lacks functional ssIIa genes on each genome (abd), and an Australian wheat cultivar, Sunco, with wild type ssIIa alleles on each genome (ABD). Evidence has been presented previously indicating that the SGP-1 (starch granule protein-1) proteins present in the starch granule in wheat are products of the ssIIa genes. Analysis of 100 progeny lines demonstrated co-segregation of the ssIIa alleles from the three genomes with the SGP-1 proteins, providing further evidence that the SGP-1 proteins are the products of the ssIIa genes. From the progeny lines, 40 doubled haploid lines representing the eight possible genotypes for SSIIa (ABD, aBD, AbD, ABd, abD, aBd, Abd, abd) were characterized for their grain weight, protein content, total starch content and starch properties. For some properties (chain length distribution, pasting properties, swelling power, and gelatinization properties), a progressive change was observed across the four classes of genotypes (wild type, single nulls, double nulls and triple nulls). However, for other grain properties (seed weight and protein content) and starch properties (total starch content, granule morphology and crystallinity, granule size distribution, amylose content, amylose-lipid dissociation properties), a statistically significant change only occurred for the triple nulls, indicating that all three genes had to be missing or inactive for a change to occur. These results illustrate the importance of SSIIa in controlling grain and starch properties and the importance of amylopectin fine structure in controlling starch granule properties in wheat.

  19. Mapping the interfacial binding surface of human secretory group IIa phospholipase A2.

    Science.gov (United States)

    Snitko, Y; Koduri, R S; Han, S K; Othman, R; Baker, S F; Molini, B J; Wilton, D C; Gelb, M H; Cho, W

    1997-11-25

    Human secretory group IIa phospholipase A2 (hIIa-PLA2) contains a large number of prominent cationic patches on its molecular surface and has exceptionally high affinity for anionic surfaces, including anionic membranes. To identify the cationic amino acid residues that support binding of hIIa-PLA2 to anionic membranes, we have performed extensive site-directed mutagenesis of this protein and measured vesicle binding and interfacial kinetic properties of the mutants using polymerized liposomes and nonpolymerized anionic vesicles. Unlike other secretory PLA2s, which have a few cationic residues that support binding of enzyme to anionic membranes, interfacial binding of hIIa-PLA2 is driven in part by electrostatic interactions involving a number of cationic residues forming patches on the putative interfacial binding surface. Among these residues, the amino-terminal patch composed of Arg-7, Lys-10, and Lys-16 makes the most significant contribution to interfacial adsorption, and this is supplemented by contributions from other patches, most notably Lys-74/Lys-87/Arg-92 and Lys-124/Arg-127. For these mutants, complete vesicle binding occurs in the presence of high vesicle concentrations, and under these conditions the mutants display specific activities comparable to that of wild-type enzyme. These studies indicate that electrostatic interactions between surface lysine and arginine residues and the interface contribute to interfacial binding of hIIa-PLA2 to anionic vesicles and that cationic residues closest to the opening of the active-site slot make the most important interactions with the membrane. However, because the wild type binds extremely tightly to anionic vesicles, it was not possible to exactly determine what fraction of the total interfacial binding energy is due to electrostatics.

  20. Prevalence of aac(3-IIa gene among clinical isolates of uropathogenic Escherichia coli in Delfan, Lorestan

    Directory of Open Access Journals (Sweden)

    Somayeh Momeni Mofrad

    2013-09-01

    Full Text Available Backgrounds: Uropathogenic Escherichia coli strains are the predominant causative organisms of urinary tract infections (UTIs. Aminoglycosides are clinically useful antibiotics with bactericidal activity against this bacterium. The most common mechanism for resistance to these antibiotics are mediated through production of aminoglycoside modifying enzymes (AMEs. The most common of these enzymes are Aminoglycoside Acetyltransferases (AACs. The epidemiology of the dominant type of these enzymes, AAC(3-II, varies from region to region. The aim of this study was to determine the antimicrobial susceptibility pattern with a focus on aminoglycosides and the prevalence of aac(3-IIa gene among clinical isolates of uropathogenic Escherichia coli obtained from Delfan, Lorestan, Iran. Materials and Methods: In this descriptive study, a total of 100 uropathogenic Escherichia coli isolates were collected from BoAli hospital in Delfan city, Lorestan, from July to November 2010. Antibiotic susceptibility patterns of the isolates were determined using disk diffusion method according to Clinical and Laboratory Standards Institute CLSI guidelines. Prevalence of aac(3-IIa gene was determined by PCR and the relationship between resistance phenotypes to aminoglycosides and presence of aac(3-IIa gene was evaluated. Results: Among the 100 tested isolates, maximal resistance was seen to ampicillin (85%; whereas, no resistance to imipenem was found. Sixty percent of the isolates demonstrated resistance to at least one of the tested aminoglycosides. Resistance rate towards these agents were as followed: gentamicin 39%, kanamycin 26%, neomycin 31% and amikacin 1%. Forty–four isolates (44% harbored the aac(3-IIa gene. The maximal rate of gene presence (36 isolates, 92.3% was detected in strains with gentamicin resistant phenotype (39 isolates, 39%. Conclusion: On the basis of our findings, use of antibiotics such as nitrofurantoin, amikacin or imipenem are recommended for

  1. Concurrent chemoradiotherapy with nedaplatin in patients with stage IIA to IVA cervical carcinoma.

    Science.gov (United States)

    Fujioka, Toru; Yasuoka, Toshiaki; Koizumi, Masae; Tanaka, Hiroki; Hashimoto, Hisashi; Nabeta, Motoo; Koizumi, Koji; Matsubara, Yuko; Hamada, Katsuyuki; Matsubara, Keiichi; Katayama, Tomihiro; Nawa, Akihiro

    2013-01-01

    The present study aimed to evaluate the efficacy and toxicities of nadaplatin-based concurrent chemoradiotherapy (CCRT) in patients with stage IIA to IVA cervical carcinoma. Patients with an International Federation of Gynecology and Obstetrics (FIGO) stage IIA to IVA cervical carcinoma were treated with nadaplatin-based CCRT, using high-dose rate intracavitary brachytherapy (HDR-ICBT) or radiotherapy (RT) alone, in patients with FIGO stage IIA to IVA cervical carcinoma. CCRT with nedaplatin (80 mg/m(2)) was administered on Days 1 and 29. The records of 17 women treated either with nadaplatin-based CCRT using HSR-ICBT (n=8) or RT alone (n=9), for stage IIA to IVA cervical carcinoma were retrospectively reviewed. The activity and toxicity were compared in the two treatment groups. Progression-free survival (PFS) and overall survival (OS) were the main endpoints. The 5-year overall survival rates in the CCRT and RT groups were 68.6 and 77.8%, respectively. The median OS of the CCRT and RT groups was 38.5 and 27.3 months, respectively. There was no significant difference in either PFS (P=0.618) or OS (P= 0.231). The most common grade 3-4 or higher toxicities in the CCRT groups were leuko-/neutropenia (37.5%). The frequency of acute grade 3-4 toxicity was higher in the CCRT compared to the RT group. However, no statistically significant difference was observed. Nedaplatin-based CCRT was safely performed. Although the prognosis of patients with FIGO stage IIA to IVA cervical carcinoma was not significantly improved, fewer distant relapses were observed in this treatment. Consequently, nedaplatin-based CCRT may be considered as a potential alternative to cisplatin-based CCRT in this patient population.

  2. Industrial Maintenance, Volume II-A. Post Secondary Curriculum Guide.

    Science.gov (United States)

    Butler, Raymond H.; And Others

    This volume is the second of four volumes that comprise a curriculum guide for a postsecondary industrial maintenance program. It contains part of section 3 of the guide which contains the unit guides for two of the 12 duties included in the course. Each of the 197 tasks included in these two duties is presented on a separate page and contains the…

  3. Tanshinone IIA Inhibits Epithelial-Mesenchymal Transition in Bladder Cancer Cells via Modulation of STAT3-CCL2 Signaling

    Directory of Open Access Journals (Sweden)

    Sung-Ying Huang

    2017-07-01

    Full Text Available Tanshinone IIA (Tan-IIA is an extract from the widely used traditional Chinese medicine (TCM Danshen (Salvia miltiorrhiza, and has been found to attenuate the proliferation of bladder cancer (BCa cells (The IC50 were: 5637, 2.6 μg/mL; BFTC, 2 μg/mL; T24, 2.7 μg/mL, respectively.. However, the mechanism of the effect of Tan-IIA on migration inhibition of BCa cells remains unclear. This study investigates the anti-metastatic effect of Tan-IIA in human BCa cells and clarifies its molecular mechanism. Three human BCa cell lines, 5637, BFTC and T24, were used for subsequent experiments. Cell migration and invasion were evaluated by transwell assays. Real-time RT-PCR and western blotting were performed to detect epithelial-mesenchymal transition (EMT-related gene expression. The enzymatic activity of matrix metalloproteinases (MMP was evaluated by zymography assay. Tan-IIA inhibited the migration and invasion of human BCa cells. Tan-IIA suppressed both the protein expression and enzymatic activity of MMP-9/-2 in human BCa cells. Tan-IIA up-regulated the epithelial marker E-cadherin and down-regulated mesenchymal markers such as N-cadherin and Vimentin, along with transcription regulators such as Snail and Slug in BCa cells in a time- and dose-dependent manner. Mechanism dissection revealed that Tan-IIA-inhibited BCa cell invasion could function via suppressed chemokine (C-C motif ligand 2 (CCL2 expression, which could be reversed by the addition of CCL2 recombinant protein. Furthermore, Tan-IIA could inhibit the phosphorylation of the signal transducer and activator of transcription 3 (STAT3 (Tyr705, which cannot be restored by the CCL2 recombinant protein addition. These data implicated that Tan-IIA might suppress EMT on BCa cells through STAT3-CCL2 signaling inhibition. Tan-IIA inhibits EMT of BCa cells via modulation of STAT3-CCL2 signaling. Our findings suggest that Tan-IIA can serve as a potential anti-metastatic agent in BCa therapy.

  4. Anti-inflammatory effects of tanshinone IIA on radiation-induced microglia BV-2 cells inflammatory response

    DEFF Research Database (Denmark)

    Dong, Xiaorong; Dong, Jihua; Zhang, Ruiguang

    2009-01-01

    that Tanshinone II(A) exerts anti-inflammatory properties by suppressing the transcription of proinflammatory cytokine genes that might be associated with the NF-kappabeta signaling pathway. It is postulated that irradiation causes immediate cellular reaction, and that double-strand breaks trigger the molecular......AIM: The aim of this study was to explore the inhibitory effects of Tanshinone II(A) on the production of proinflammation cytokines in radiation-stimulated microglia. METHODS: Microglia cells were treated with 2, 4, 8, 16, and 32 Gy of irradiation or sham-irradiated in the presence or absence of 1.......0 microg/mL of Tanshinone II(A). The effects of Tanshinone II(A) on radiation-induced proinflammatory cytokines were evaluated by real-time polymerase chain reaction; the expression level of nuclear factor (NF-kappabeta) p65 in cytoplasm and nucleus was measured by Western blot. Immunofluorescence staining...

  5. Expression of mptC of Listeria monocytogenes induces sensitivity to class IIa bacteriocins in Lactococcus lactis

    National Research Council Canada - National Science Library

    Ramnath, Manilduth; Arous, Safia; Gravesen, Anne; Hastings, John W; Hechard, Yann

    2004-01-01

    ..., Rolighedsvej 30, DK-1958 Frederiksberg C, Denmark Correspondence Yann Héchard yann.hechard{at}univ-poitiers.fr Sensitivity to class IIa bacteriocins from lactic acid bacteria was recently associated with the mannose phosphotransferase system...

  6. Deformed N = 8 supergravity from IIA strings and its Chern-Simons duals

    Energy Technology Data Exchange (ETDEWEB)

    Guarino, Adolfo [Nikhef Theory Group, Amsterdam (Netherlands); Jafferis, Daniel L. [Center for the Fundamental Laws of Nature, Harvard University, Cambridge, MA (United States); Varela, Oscar [Center for the Fundamental Laws of Nature, Harvard University, Cambridge, MA (United States); Centre de Physique Theorique, Ecole Polytechnique, CNRS UMR 7644, Palaiseau (France)

    2016-04-15

    Do electric/magnetic deformations of N = 8 supergravity enjoy a string/M-theory origin, or are they just a fourdimensional artefact? We address this question for the gauging of a group closely related to SO(8): its contraction ISO(7). We argue that the deformed ISO(7) supergravity arises from consistent truncation of massive IIA supergravity on S{sup 6}, and its electric/magnetic deformation parameter descends directly from the Romans mass. The critical points of the supergravity uplift to AdS{sub 4} massive type IIA vacua and the corresponding CFT{sub 3} duals are identified as super-Chern-Simons-matter theories with gauge group SU(N) and level k given also by the Romans mass. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  7. AdS{sub 4} solutions of massive IIA from dyonic ISO(7) supergravity

    Energy Technology Data Exchange (ETDEWEB)

    Varela, Oscar [Center for the Fundamental Laws of Nature,Harvard University, Cambridge, MA 02138 (United States)

    2016-03-14

    Explicit formulae are given for the consistent truncation of massive type IIA supergravity on the six-sphere to the SU(3)–invariant sector of D=4N=8 supergravity with dyonic ISO(7) gauging. These formulae are then used to construct AdS{sub 4} solutions of massive type IIA via uplift on S{sup 6} of the critical points of the D=4 supergravity with at least SU(3) symmetry. We find a new N=1 solution with SU(3) symmetry, a new non-supersymmetric solution with SO(6) symmetry, and recover previously known solutions. We quantise the fluxes, calculate the gravitational free energies of the solutions and discuss the stability of the non-supersymmetric ones. Among these, a (previously known) G{sub 2}-invariant solution is found to be stable.

  8. Rational sphere valued supercocycles in M-theory and type IIA string theory

    Science.gov (United States)

    Fiorenza, Domenico; Sati, Hisham; Schreiber, Urs

    2017-04-01

    We show that supercocycles on super L∞-algebras capture, at the rational level, the twisted cohomological charge structure of the fields of M-theory and of type IIA string theory. We show that rational 4-sphere-valued supercocycles for M-branes in M-theory descend to supercocycles in type IIA string theory with coefficients in the free loop space of the 4-sphere, to yield the Ramond-Ramond fields in the rational image of twisted K-theory, with the twist given by the B-field. In particular, we derive the M2/M5 ↔ F1/Dp/NS5 correspondence via dimensional reduction of sphere-valued super-L∞-cocycles.

  9. Fabrication of High Quality Broadband Type IIA Chirped Fiber Bragg Gratings

    Institute of Scientific and Technical Information of China (English)

    SANG Xin-zhu; YU Chong-xiu; YAN Bin-bin; MA Jian-xin; LU Nai-guang

    2006-01-01

    Chirped fiber Bragg gratings have found many applications in optical communication and sensing systems. High quality filters based on chirped fiber Bragg gratings with reflection bandwidth of 2.6 and 32nm and high reflectivity are demonstrated experimentally with 2 and 4cm long phase masks, respectively. These filters with flat reflection band and high reflectivity are achieved by writing type IIA chirped Bragg gratings.

  10. 10D massive type IIA supergravities as the uplift of parabolic M2-brane torus bundles

    Energy Technology Data Exchange (ETDEWEB)

    Garcia del Moral, Maria Pilar [Universidad de Antofagasta (Chile). Dept. de Fisica; Restuccia, Alvaro [Universidad de Antofagasta (Chile). Dept. de Fisica; Universidad Simon Bolivar, Caracas (Venezuela, Bolivarian Republic of). Dept. de Fisica

    2016-04-15

    We remark that the two 10D massive deformations of the N = 2 maximal type IIA supergravity (Romans and HLW supergravity) are associated to the low energy limit of the uplift to 10D of M2-brane torus bundles with parabolic monodromy linearly and non-linearly realized respectively. Romans supergravity corresponds to M2-brane compactified on a twice-punctured torus bundle. (copyright 2015 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  11. 30 CFR 57.22101 - Smoking (I-A, II-A, III, and V-A mines).

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Smoking (I-A, II-A, III, and V-A mines). 57.22101 Section 57.22101 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... Smoking (I-A, II-A, III, and V-A mines). Persons shall not smoke or carry smoking materials, matches,...

  12. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

    Directory of Open Access Journals (Sweden)

    Wang Wen-Quan

    2012-11-01

    Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

  13. 30 CFR 57.22212 - Air flow (I-C, II-A, and V-A mines).

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Air flow (I-C, II-A, and V-A mines). 57.22212... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22212 Air flow (I-C, II-A, and V-A mines). Air flow across each working face shall be sufficient to carry away any accumulation of methane,...

  14. A dangerous liaison: Leptin and sPLA2-IIA join forces to induce proliferation and migration of astrocytoma cells

    Science.gov (United States)

    Martín, Rubén; Cordova, Claudia; Gutiérrez, Beatriz; Hernández, Marita; Nieto, María L.

    2017-01-01

    Glioblastoma, the most aggressive type of primary brain tumour, shows worse prognosis linked to diabetes or obesity persistence. These pathologies are chronic inflammatory conditions characterized by altered profiles of inflammatory mediators, including leptin and secreted phospholipase A2-IIA (sPLA2-IIA). Both proteins, in turn, display diverse pro-cancer properties in different cell types, including astrocytes. Herein, to understand the underlying relationship between obesity and brain tumors, we investigated the effect of leptin, alone or in combination with sPLA2-IIA on astrocytoma cell functions. sPLA2-IIA induced up-regulation of leptin receptors in 1321N1 human astrocytoma cells. Leptin, as well as sPLA2-IIA, increased growth and migration in these cells, through activation/phosphorylation of key proteins of survival cascades. Leptin, at concentrations with minimal or no activating effects on astrocytoma cells, enhanced growth and migration promoted by low doses of sPLA2-IIA. sPLA2-IIA alone induced a transient phosphorylation pattern in the Src/ERK/Akt/mTOR/p70S6K/rS6 pathway through EGFR transactivation, and co-addition of leptin resulted in a sustained phosphorylation of these signaling regulators. Mechanistically, EGFR transactivation and tyrosine- and serine/threonine-protein phosphatases revealed a key role in this leptin-sPLA2-IIA cross-talk. This cooperative partnership between both proteins was also found in primary astrocytes. These findings thus indicate that the adipokine leptin, by increasing the susceptibility of cells to inflammatory mediators, could contribute to worsen the prognosis of tumoral and neurodegenerative processes, being a potential mediator of some obesity-related medical complications. PMID:28249041

  15. 30 CFR 57.22608 - Secondary blasting (I-A, II-A, and V-A mines).

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Secondary blasting (I-A, II-A, and V-A mines... blasting (I-A, II-A, and V-A mines). Prior to secondary blasting, tests for methane shall be made in the mine atmosphere at blast sites by a competent person. Secondary blasting shall not be done when...

  16. Focal cortical dysplasia type IIa and IIb: MRI aspects in 118 cases proven by histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Colombo, Nadia; Citterio, Alberto [Ospedale Ca Granda Niguarda, Department of Neuroradiology, Milano (Italy); Tassi, Laura; Mai, Roberto; Sartori, Ivana; Cardinale, Francesco; Lo Russo, Giorgio [Ospedale Niguarda, Claudio Munari Epilepsy Surgery Center, Milano (Italy); Deleo, Francesco; Spreafico, Roberto [IRCCS Foundation Neurological Institute ' ' C. Besta' ' , Department of Epilepsy Clinic and Experimental Neurophysiology, Milano (Italy); Bramerio, Manuela [Ospedale Niguarda, Department of Pathology, Milano (Italy)

    2012-10-15

    This study aims to review the magnetic resonance imaging (MRI) aspects of a large series of patients with focal cortical dysplasia type II (FCD II) and attempt to identify distinctive features in the two histopathological subtypes IIa and IIb. We retrospectively reviewed the MRI scans of 118 patients with histological proven FCD IIa (n = 37) or IIb (n = 81) who were surgically treated for intractable epilepsy. MRI was abnormal in 93 patients (79 %) and unremarkable in 25 (21 %). A dysplastic lesion was identified in 90 cases (97 %) and classified as FCD II in 83 and FCD non-II in seven cases. In three cases, the MRI diagnosis was other than FCD. There was a significant association between the presence of cortical thickening (p = 0.002) and the ''transmantle sign'' (p < 0.001) and a correct MRI diagnosis of FCD II. MRI positivity was more frequent in the patients with FCD IIb than in those with FCD IIa (91 % vs. 51 %), and the detection rate of FCD II was also better in the patients with type IIb (88 % vs. 32 %). The transmantle sign was significantly more frequent in the IIb subgroup (p = 0.003). The rates of abnormal MRI results and correct MRI diagnoses of FCD II were significantly higher in the IIb subgroup. Although other MRI stigmata may contribute to the diagnosis, the only significant correlation was between the transmantle sign and FCD IIb. (orig.)

  17. Anti-bactericidal properties of stingray Dasyatis pastinaca groups V, IIA, and IB phospholipases A2: a comparative study.

    Science.gov (United States)

    Bacha, Abir Ben

    2014-10-01

    Group IIA secreted phospholipase A2 (group IIA sPLA2) is known to display potent Gram-positive bactericidal activity in vitro and in vivo. We have analyzed the bactericidal activity of the full set of native stingray and dromedary groups V, IIA, and IB sPLA2s on several Gram-positive and Gram-negative strains. The rank order potency among both marine and mammal sPLA2s against Gram-positive bacteria is group IIA > V > IB, whereas Gram-negative bacteria exhibited a much higher resistance. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2.The bactericidal efficiency of groups V and IIA sPLA2s was shown to be dependent upon the presence of calcium ions and to a less extent Mg(2+) ions and then a correlation could be made to its hydrolytic activity of membrane phospholipids. Importantly, we showed that stingray and dromedary groups V, IIA, and IB sPLA2s present no cytotoxicity after their incubation with MDA-MB-231cells. stingray groups V and IIA sPLA2s, like mammal ones, may be considered as future therapeutic agents against bacterial infections.

  18. Tanshinone IIA Inhibits Growth of Keratinocytes through Cell Cycle Arrest and Apoptosis: Underlying Treatment Mechanism of Psoriasis

    Directory of Open Access Journals (Sweden)

    Fu-Lun Li

    2012-01-01

    Full Text Available The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE, and flow cytometry methods. Apoptosis was partially blocked by the caspase-3 inhibitor Ac-DEVD-CHO. Mitochondrial regulation of apoptosis further downstream was investigated, showing changes in the mitochondrial membrane potential, cytochrome c release into the cytoplasm, and enhanced activation of cleaved caspase-3 and Poly ADP-ribose polymerase (PARP. There was also no translocation of apoptosis-inducing factor (AIF from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. Our findings provide the molecular mechanisms by which Tan IIA can be used to treat psoriasis and support the traditional use of Salvia miltiorrhiza Bungee (Labiatae for psoriasis and related skin diseases.

  19. Application of Antimicrobial Agents Produced by Lactobacillus plantarum IIA-1A5 as Natural Preservative on Beef during Room Temperature Storage

    Directory of Open Access Journals (Sweden)

    Dewi Elfrida Sihombing

    2015-05-01

    Full Text Available Lactobacillus plantarum IIA-1A5 is indigenous lactic acid bacteria isolated from Indonesian beef. Lactobacillus plantarum IIA-1A5 was reported could produce bacteriocin, called plantaricin IIA-1A5. The aims of this research was to analyze application of plantaricin IIA-1A5 as a natural preservative on beef. Based on antagonistic test, plantaricin IIA-1A5 had good moderate antimicrobial activity against pathogenic bacteria isolated from human’s feces that cause diarrhea such as Salmonella 38, Enteropathogenic Escherichia coli K11 and Shigella A33. Application of plantaricin IIA-1A5 was effective as a natural preservative on beef stored at room temperature by inhibiting the growth of Escherichia coli and Staphylococcus aureus. Plantaricin IIA-1A5 could kill all of the Escherichia coli after 5 h storage. Plantaricin IIA-1A5 could reduce the population of Staphylococcus aureus in beef during room temperature storage. Interestingly, plantaricin produced by Lactobacillus plantarum IIA-1A5 was effective against gram negative and positive bacteria. According to physichochemichal and microbiology quality, plantaricin IIA-1A5 was recommended as biopreservative agents for beef.

  20. Effects of Statins and Xuezhikang on the Expression of Secretory Phospholipase A2, Group IIA in Rat Vascular Smooth Muscle Cells.

    Science.gov (United States)

    Xie, Qiang; Zhang, Dan

    2017-02-07

    Atherosclerosis is a multifactorial vascular disease characterized by formation of inflammatory lesions. Secretory phospholipase A2, group IIA (sPLA2-IIA) is involved in this process and plays a critical role. However, the exact role of sPLA2-IIA in cardiovascular inflammation is more complicated and remains unclear. Furthermore, both statins and Xuezhikang (XZK) are widely used in the prevention and treatment of cardiovascular disease risk because of their pleiotropic effects on the cardiovascular system. However, their effects on sPLA2-IIA are still controversial. We investigated the regulation of sPLA2-IIA by rat thoracic aorta smooth muscle cells (VSMCs) in culture. Cells were first incubated with IL-1β alone to induce expression of sPLA2-IIA and then treated with several concentrations of statins or XZK for different times in the absence or presence of IL-1β. We tested the expression of sPLA2-IIA, including sPLA2-IIA mRNA, protein, as well as activity. We found that statins or IL-1β increase the expression of sPLA2-IIA in VSMCs and the effect is based on a synergetic relationship between them. However, for the first time, we observed that XZK effectively reduces sPLA2-IIA expression in IL-1β-treated VSMCs. Our findings may shine a new light on the clinical use of XZK and statins in the prevention and treatment of atherosclerosis-related thrombosis.

  1. Tolerance and efficacy of preoperative intracavitary HDR brachytherapy in IB and IIA cervical cancer

    Science.gov (United States)

    Bialas, Brygida; Fijalkowski, Marek; Raczek-Zwierzycka, Katarzyna

    2009-01-01

    Purpose The aim of this work is to analyze the efficacy and tolerance of preoperative intracavitary HDR brachytherapy (HDR-BT) in patients with IB and IIA cervical cancer. Material and methods 139 patients with cervical cancer IB-IIA with preoperative HDR-BT, out of which 60 patients with cervical cancer IB (43.2%) and 79 with IIA (56.8%) were treated since 1996 to 2002. In preoperative BT total dose to point A ranged from 30-45 Gy in 6-9 fractions twice a week. The fraction dose was 4-5 Gy at point A. Six weeks after BT all patients underwent radical Wertheim-Meigs hysterectomy. Patients with disadvantageous risk factors or with positive specimen histology had a complementary therapy: external-beam radiotherapy (EBRT) given to the whole pelvic volume in daily fractions of 2 Gy up to total dose of 36-52 Gy (20 patients) or EBRT with cisplatin-based chemotherapy with the dose of 30-40 mg/m2 in 5-7 fractions given weekly (7 patients) or chemotherapy (6 patients). Acute and late radiation toxicity was evaluated according to EORTC/RTOG. Results In postoperative specimen histopathology the number of 114 women (82%) had tumor-free specimen within brachytherapy target (in cervix and cavity), 96 women (60.1%) had tumor-free specimen both in and outside brachytherapy target (lymph nodes, parametra, adnexis). The 5-year and 10-year DFS were 93.8% and 88% for IB and 89.7% and 64.7% for IIA respectively. 7.9% of patients developed acute toxicity both in rectum and bladder (only in I and II grade of EORTC/RTOG). Late severe complication occurred in rectum in 2.2% of patients and in bladder 1.4%. Conclusions 1. Preoperative HDR-BT in patients with IB and IIA cervical cancer is an effective and well tolerated therapy with acceptable rate of side effects. 2. Preoperative HDR-BT followed by surgery in a group without risk factors is a sufficient treatment option with no additional adjuvant therapy requirement.

  2. Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells

    Science.gov (United States)

    Lin, C-Y; Chang, T-W; Hsieh, W-H; Hung, M-C; Lin, I-H; Lai, S-C; Tzeng, Y-J

    2016-01-01

    Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIPS) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIPS is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIPS, consequently causes FLIPS to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIPS levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIPS regulation-mediated apoptosis/necroptosis, which has not been previously documented

  3. The effects of Tanshinone IIA on blood-brain barrier and brain edema after transient middle cerebral artery occlusion in rats.

    Science.gov (United States)

    Tang, Chao; Xue, Hongli; Bai, Changlin; Fu, Rong; Wu, Anhua

    2010-12-01

    Disruption of blood-brain barrier (BBB) and edema formation play a key role in the development of neurological dysfunction after cerebral ischemia. In this study, the effects of Tanshinone IIA (Tan IIA), one of the active ingredients of Salvia miltiorrhiza root, on the BBB and brain edema after transient middle cerebral artery occlusion in rats were examined. Our study demonstrated that Tan IIA reduced brain infarct area, water content in the ischemic hemisphere. Furthermore, Tan IIA significantly decreased BBB permeability to Evans blue, suppressed the expression of intercellular adhesion molecule-1 (ICAM-1), matrix metalloproteinase-9 (MMP-9), inhibited the degradation of tight junction proteins zonula occludens-1 (ZO-1) and Occludin. These results demonstrated that Tan IIA was effective for attenuating the extent of brain edema formation in response to ischemia injury in rats, partly by Tan IIA's protective effect on the BBB. Our results may have implications in the treatment of brain edema in cerebral ischemia.

  4. Tanshinone IIA induced cell death via miR30b-p53-PTPN11/SHP2 signaling pathway in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Ren, Xuanqi; Wang, Cui; Xie, Binbin; Hu, Linfeng; Chai, Hui; Ding, Lei; Tang, Lihua; Xia, Yongliang; Dou, Xiaobing

    2017-02-05

    Tanshinone IIA, a multi-pharmaceutical compound from traditional Chinese herb, has been reported to have anti-hepatocarcinomic (HCC) properties through cell death induction. Apart from the typical p53-dependent pathway, mechanisms of the anti-carcinogenic role of Tanshinone remain scarce. In an effort to explore the mechanism behind Tanshinone IIA, we detected the upstream of the p53 and the potential novel pathway. Tanshinone IIA dose-dependently initiated HepG2 cell apoptosis and cell cycle arrest at the G1 checkpoint. In the miR30 family, only the transcription of miR30b was downregulated by Tanshinone IIA, which subsequently upregulated both the genomic and protein levels of p53. Further, we screened that PTPN11 and Tp53 are the two critical genomes involved in the pharmacology of Tanshinone IIA. Building upon LASAGNA-search and kinetics binding assay, p53 was found to be a potential transcription factor for PTPN11. Concomitant with the expression of p53, Tanshinone IIA stimulated both PTPN11 and its encoded protein SHP2. Inhibition miR30b attenuated the Tanshinone IIA-induced cytotoxicity, level of p53 and PTPN11 in HepG2 cells. Finally, the apoptotic molecules such as Bax/Bcl2, cleavage caspase 3 and the cell cycle regulation factors including p21, cyclin D1, and CDK6 were changed by Tanshinone IIA. Several cytotoxic endpoints induced by Tanshinone IIA were also checked in Hep3B cells. This study confirmed that Tanshinone IIA may induce hepatoma cell death through the miR30b-p53- PTPN11/SHP2 pathway. With regard to the complicated tumorigenesis of HCC and the multi-targets of Tanshinone IIA, our results propose developing Tanshinone IIA for clinic therapy and the interference of HCC.

  5. Stage IIA and IIB testicular seminoma treated postorchiectomy with radiation therapy versus other approaches: a population-based analysis of 241 patients.

    Science.gov (United States)

    Ahmed, Kamran A; Wilder, Richard B

    2015-01-01

    To evaluate post-orchiectomy utilization of radiation therapy (RT) versus other management approaches in stage IIA and IIB testicular seminoma patients. Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72 % vs. 46 %, respectively; P seminoma.

  6. Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk

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    Solange Torchia Carvalho

    2011-01-01

    Full Text Available Breast tumors exhibit extensive molecular and clinical heterogeneity. One of the most utilized breast carcinoma classifications is based on its molecular aspects and subdivides breast cancer into five major groups based on the expression of certain genes. In this study, we evaluated which factors are important in determining a prognosis after 5 years of follow-up for patients with clinical stage IIA breast tumors. We took into consideration the different phenotypes (luminal A luminal B HER-2 overexpression, basal and triple-negative, various epithelial-mesenchymal (EMT molecular markers and adhesion molecules (E-cadherin, P-cadherin, N-cadherin, vimentin, twist snail and slug and NOS-2, in addition to clinical and demographic data, tumor characteristics and treatment types. METHODS: The study population consisted of 82 patients with breast cancer. We analyzed eight molecular markers by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with ten years of follow-up, and we classified each tumor according to its estrogen receptor, progesterone receptor and HER-2 expression. We then placed the tumor into one of the above categories. RESULTS: The presence of several clinical and demographic factors, various histopathologies, treatment forms and several immunohistochemical markers were not associated with a worse prognosis for group IIA patients. The factors that were associated with a mortality risk were the triple-negative (odds ratio (OR = 11.8, 95% confident interval (CI = 2.0-70.3, P = 0.007 and basal (OR =18.4, 95% CI = 1.8-184.7, P= 0.013 phenotypic patterns. CONCLUSIONS: The EMT markers and NOS-2 were not mortality risk factors. Basal and triple-negative phenotypic patterns were related to a higher mortality risk in patients with stage IIA tumors.

  7. Energetics, molecular electronic structure, and spectroscopy of forming Group IIA dihalide complexes

    Science.gov (United States)

    Devore, T. C.; Gole, J. L.

    1999-02-01

    Multiple-collision relaxed (helium) chemiluminescence and laser-induced fluorescent spectroscopy have been used to demonstrate the highly efficient collisional stabilization of electronically excited Group IIA dihalide collision complexes formed in M (Ca,Sr)+X 2 (XY) (Cl 2, Br 2, ICl, IBr, I 2) reactive encounters. The first discrete emission spectra for the CaCl 2, CaBr 2, SrCl 2, SrBr 2, and SrICl dihalides are observed and evaluated; however, the low-pressure `continuous' chemiluminescent emission observed for forming barium dihalide (BaX 2) complexes is quenched under these experimental conditions. The reactions of the Group IIA metals with molecular fluorine do not readily produce the corresponding dihalide. While the lowest-lying observed dihalide visible transition is, as predicted, found to result in an extended progression in a dihalide complex bending mode (SrCl 2), the observed progression suggests the presence of a residual halogen (Cl-Cl) bond. Two higher-lying transitions are dominated by a vibrational mode structure corresponding to progressions in the symmetric stretching mode or, for nominally forbidden electronic transitions, odd quanta of the asymmetric stretching mode. Some evidence for sequence structure associated with the dihalide bending mode is also obtained. These observations are consistent with complex formation as it is coupled with a modified valence electron structure (correlation diagram) associated with the highly ionic nature of the dihalides. The bonding in the Group IIA dihalides (and their complexes), whose atomization energies are more than twice the metal monohalide bond energy, strongly influences the evaluation of energetics and the determination of monohalide bond energies from chemiluminescent processes. Discrepancies between those bond strengths determined by mass spectrometry and chemiluminescence are discussed with a focus on energy partitioning in dihalide complex formation and its influence on chemical vapor

  8. General N=1 supersymmetric flux vacua of massive type IIA string theory.

    Science.gov (United States)

    Behrndt, Klaus; Cvetic, Mirjam

    2005-07-08

    We derive conditions for the existence of four-dimensional N=1 supersymmetric flux vacua of massive type IIA string theory with general supergravity fluxes turned on. For an SU(3) singlet Killing spinor, we show that such flux vacua exist when the internal geometry is nearly Kähler. The geometry is not warped, all the allowed fluxes are proportional to the mass parameter, and the dilaton is fixed by a ratio of (quantized) fluxes. The four-dimensional cosmological constant, while negative, becomes small in the vacuum with the weak string coupling.

  9. New industrial heat pump applications to a synthetic rubber plant. Final report, Phase IIA

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1993-12-31

    This report summarizes the results of the Phase IIA of the DOE sponsored study titled, Advanced Industrial Heat Pump Application and Evaluation. The scope of this phase of the study was to finalize the process design of the heat pump scheme, develop a process and instrumentation diagram, and a detailed cost estimate for the project. This information is essential for the site management to evaluate the economic viability and operability of the proposed heat pump design, prior to the next phase of installation and testing.

  10. Expression of mptC of Listeria monocytogenes induces sensitivity to class IIa bacteriocins in Lactococcus lactis.

    Science.gov (United States)

    Ramnath, Manilduth; Arous, Safia; Gravesen, Anne; Hastings, John W; Héchard, Yann

    2004-08-01

    Sensitivity to class IIa bacteriocins from lactic acid bacteria was recently associated with the mannose phosphotransferase system (PTS) permease, in Listeria monocytogenes. To assess the involvement of this protein complex in class IIa bacteriocin activity, the mptACD operon, encoding, was heterologously expressed in an insensitive species, namely Lactococcus lactis, using the NICE double plasmid system. Upon induction of the cloned operon, the recombinant Lc. lactis became sensitive to leucocin A. Pediocin PA-1 and enterocin A also showed inhibitory activity against Lc. lactis cultures expressing mptACD. Furthermore, the role of the three genes of the mptACD operon was investigated. Derivative plasmids containing various combinations of these three genes were made from the parental mptACD plasmid by divergent PCR. The results showed that expression of mptC alone is sufficient to confer sensitivity to class IIa bacteriocins in Lc. lactis.

  11. Brane/antibrane Configurations in Type IIA and M-Theory

    Science.gov (United States)

    Marsano, Joseph

    We investigate the relation between large N duality applied to systems of D5's and /lineD5's wrapping vanishing cycles of local CY in type IIB and M-theory lifts of the NS5/D4//lineD4 systems in type IIA to which they are related by T-duality. Through a simple example based on a local CY constructed using an A2 singularity, we review this well-known correspondence in the supersymmetric setting and describe the manner in which it generalizes when antibranes are added. Agreement between the IIB and IIA pictures, which supports the assertion that {N}=2 supersymmetry is spontaneously broken in these systems at string tree level, is demonstrated when gs ≪ 1. Novel nonholomorphic features can arise away from this regime and their physical origin is discussed. This note is based on talks given at KITP, Harvard University, TIFR, the University of Tokyo at Hongo, the 2007 Les Houches Summer School, and the 2007 Simons Workshop, is based on work done in collaboration with K. Papadodimas and M. Shigemori, and contains some previously unpublished results.

  12. Radiotherapy and surgery in the management of stage IB and IIA carcinoma of the cervix

    Energy Technology Data Exchange (ETDEWEB)

    Rabin, S.; Browde, S.; Nissenbaum, M.; Koller, A.B.; De Moor, N.G.

    1984-03-10

    Ninety-two consecutive patients with stages IB and IIA carcinoma of the cervix were treated by one of two regimens: pre-operative intracavitary caesium-137 followed by a Wertheim hysterectomy (group 1) or staging laparotomy with biopsy of suspicious lymph nodes (group 2) (if there was no evidence of tumour on examination of a frozen section of the lymph nodes a Wertheim hysterectomy was performed, but if a tumour was present the abdomen was closed and a course of radical irradiation given). When there was evidence of extracervical spread on examination of the specimen after the Wertheim hysterectomy, postoperative irradiation was given. It was found that clinical staging had been incorrect in 38.5% of patients thought to have stage IB disease and in 71.4% of those thought to have stage IIA disease. The actuarial survival curves showed no significant statistical difference between group 1 and group 2. When examination of the operative specimen showed tumour invasion of the parametrium only, the disease was well controlled by postoperative irradiation (all 7 such patients survived). On the other hand, when there was evidence of tumour invasion of pelvic lymph nodes the 4-year survival rate fell to 31% (4 out of 13 patients), despite the use of postoperative irradiation.

  13. PENGGUNAAN BAHAN AJAR TEMATIK PEMBAGIAN UNTUK MENINGKATKAN HASIL BELAJAR DI KELAS IIA MI AHLIYAH II PALEMBANG

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    Luvi Antari

    2015-12-01

    Full Text Available This study aims to look at improving student learning outcomes in the materials division using a thematic approach based teaching materials. This research is a classroom action research (Claassroom Action Research with a research subject graders IIA MI Ahliyah 2 Palembang, the second semester of 2014/2015 the number of students 28 people, consisting of 14 male students and 14 female students. This study was conducted by two cycles following the model of a Class Action Research & McTaggart Kemmis models which consists of four stages: planning, implementation, observation, and reflection. The process of collecting data by using observation and tests. Based on this research, the data obtained in the first cycle who scored ≥ 70 there were 17 students with learning completeness percentage amounted to 60.71% of students had reached the indicators of success and the second cycle there are 23 students who reached a value ≥ 70 on the percentage of students learning completeness by 82 , 14% had reached an indicator of success. With the student response rate reached 76.56% in the first cycle and the second cycle reaches 81.25%. It can be concluded that learning by using a thematic approach based teaching materials division performed in this research was effective, because it can improve student learning outcomes in the distribution of matter in class IIA MI Ahliyah II Palembang Keywords: a thematic approach, materials division

  14. Down-Regulation of the Na+-Coupled Phosphate Transporter NaPi-IIa by AMP-Activated Protein Kinase

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    Miribane Dërmaku-Sopjani

    2013-11-01

    Full Text Available Background/Aims: The Na+-coupled phosphate transporter NaPi-IIa is the main carrier accomplishing renal tubular phosphate reabsorption. It is driven by the electrochemical Na+ gradient across the apical cell membrane, which is maintained by Na+ extrusion across the basolateral cell membrane through the Na+/K+ ATPase. The operation of NaPi-IIa thus requires energy in order to avoid cellular Na+ accumulation and K+ loss with eventual decrease of cell membrane potential, Cl- entry and cell swelling. Upon energy depletion, early inhibition of Na+-coupled transport processes may delay cell swelling and thus foster cell survival. Energy depletion is sensed by the AMP-activated protein kinase (AMPK, a serine/threonine kinase stimulating several cellular mechanisms increasing energy production and limiting energy utilization. The present study explored whether AMPK influences the activity of NAPi-IIa. Methods: cRNA encoding NAPi-IIa was injected into Xenopus oocytes with or without additional expression of wild-type AMPK (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1-HA, of inactive AMPKαK45R (AMPKα1K45R+AMPKβ1-Flag+AMPKγ1-HA or of constitutively active AMPKγR70Q (AMPKα1-HA+AMPKβ1-Flag+AMPKγ1R70Q. NaPi-IIa activity was estimated from phosphate-induced current in dual electrode voltage clamp experiments. Results: In NaPi-IIa-expressing, but not in water-injected Xenopus oocytes, the addition of phosphate (1 mM to the extracellular bath solution generated a current (Ip, which was significantly decreased by coexpression of wild-type AMPK and of AMPKγR70Q but not of AMPKαK45R. The phosphate-induced current in NaPi-IIa- and AMPK-expressing Xenopus ooocytes was significantly increased by AMPK inhibitor Compound C (20 µM. Kinetic analysis revealed that AMPK significantly decreased the maximal transport rate. Conclusion: The AMP-activated protein kinase AMPK is a powerful regulator of NaPi-IIa and thus of renal tubular phosphate transport.

  15. Prevention and Therapeutic Effects and Mechanisms of Tanshinone IIA Sodium Sulfonate on Acute Liver Injury Mice Model

    Directory of Open Access Journals (Sweden)

    Lunjie Lu

    2016-01-01

    Full Text Available Tanshinone IIA sodium sulfonate (TSS is a water-soluble derivative of tanshinone IIA, which is the main pharmacologically active component of Salvia miltiorrhiza. This study aimed to verify the preventive and therapeutic effects of TSS and its combined therapeutic effects with magnesium isoglycyrrhizinate (MI in D-galactosamine- (D-Gal- induced acute liver injury (ALI in mice. The potential regulatory mechanisms of TSS on ALI were also examined. Our results may provide a basis for the development of novel therapeutics for ALI.

  16. Domain-induced activation of human phospholipase A2 type IIA: Local versus global lipid composition

    DEFF Research Database (Denmark)

    Leidy, C.; Linderoth, L.; Andresen, T.L.

    2006-01-01

    , we show that local enrichment of anionic lipids into fluid domains triggers PLA(2)-IIA activity. In addition, the compositional range of enzyme activity is shown to be related to the underlying lipid phase diagram. A comparison is done between PLA(2)-IIA and snake venom PLA(2), which in contrast...

  17. Enhanced antigen uptake by dendritic cells induced by the B pentamer of the type II heat-labile enterotoxin LT-IIa requires engagement of TLR2.

    Science.gov (United States)

    Lee, Chang Hoon; Nawar, Hesham F; Mandell, Lorrie; Liang, Shuang; Hajishengallis, George; Connell, Terry D

    2010-05-07

    The potent mucosal adjuvant properties of the type II heat-labile enterotoxin LT-IIa of Escherichia coli are dependent upon binding of the B pentamer of the enterotoxin (LT-IIa-B(5)) to ganglioside receptors on immunocompetent cells. To evaluate the immunomodulatory activities of LT-IIa-B(5), in vitro experiments employing bone marrow-derived dendritic cells (BMDC) were performed. Uptake of OVA-FITC, a model antigen (Ag), was enhanced by treatment of BMDC with LT-IIa-B5, but not by treatment of cells with the B pentamer of cholera toxin (CTB). Expression of co-stimulatory molecules (CD40, CD80, CD86, and MHC-II) and cytokines (IL-12p40, TNF-alpha, and IFN-gamma) was increased in BMDC treated with LT-IIa-B(5). The capacity of LT-IIa-B(5) to enhance Ag uptake and to induce expression of co-stimulatory receptors and cytokines by BMDC was dependent upon expression of TLR2 by the cell. Increased Ag uptake induced by LT-IIa-B(5) was correlated with increased Ag-specific proliferation of CD4(+) T cells in an in vitro syngeneic DO11.10 CD4(+) T cell proliferation assay. These experiments confirm that LT-IIa-B(5) exhibits potent immunomodulatory properties which may be exploitable as a non-toxic mucosal adjuvant.

  18. Radiation therapy for stage IIA and IIB testicular seminoma: peripheral dose calculations and risk assessments

    Science.gov (United States)

    Mazonakis, Michalis; Berris, Theocharris; Lyraraki, Efrossyni; Damilakis, John

    2015-03-01

    This study was conducted to calculate the peripheral dose to critical structures and assess the radiation risks from modern radiotherapy for stage IIA/IIB testicular seminoma. A Monte Carlo code was used for treatment simulation on a computational phantom representing an average adult. The initial treatment phase involved anteroposterior and posteroanaterior modified dog-leg fields exposing para-aortic and ipsilateral iliac lymph nodes followed by a cone-down phase for nodal mass irradiation. Peripheral doses were calculated using different modified dog-leg field dimensions and an extended conventional dog-leg portal. The risk models of the BEIR-VII report and ICRP-103 were combined with dosimetric calculations to estimate the probability of developing stochastic effects. Radiotherapy for stage IIA seminoma with a target dose of 30 Gy resulted in a range of 23.0-603.7 mGy to non-targeted peripheral tissues and organs. The corresponding range for treatment of stage IIB disease to a cumulative dose of 36 Gy was 24.2-633.9 mGy. A dose variation of less than 13% was found by altering the field dimensions. Radiotherapy with the conventional instead of the modern modified dog-leg field increased the peripheral dose up to 8.2 times. The calculated heart doses of 589.0-632.9 mGy may increase the risk for developing cardiovascular diseases whereas the testicular dose of more than 231.9 mGy may lead to a temporary infertility. The probability of birth abnormalities in the offspring of cancer survivors was below 0.13% which is much lower than the spontaneous mutation rate. Abdominoplevic irradiation may increase the lifetime intrinsic risk for the induction of secondary malignancies by 0.6-3.9% depending upon the site of interest, patient’s age and tumor dose. Radiotherapy for stage IIA/IIB seminoma with restricted fields and low doses is associated with an increased morbidity. These data may allow the definition of a risk-adapted follow-up scheme for long

  19. Effect of Tanshinone IIA on cardiac function and inflammatory cytokines in patients with acute myocardial infarction

    Institute of Scientific and Technical Information of China (English)

    Yan Li

    2016-01-01

    Objective:To explore the effect of Tanshinone IIA on the cardiac function and inflammatory cytokines in patients with acute myocardial infarction (AMI).Methods:A total of 70 patients with AMI who were admitted in our hospital from March, 2015 to March, 2016 were included in the study and randomized into the observation group and the control group. On the basis of routine treatments, the patients in the control group were given urokinase 1-1.5 million U + 0.5% NaCl 100 mL, iv drip, 30-45min, aspirin from the initial dosage of 300 mg/d to 100 mg/d on the second day, and low molecular weight heparin sodium, 7 500-1 000 IU/time, twice/d, subcutaneous injection. Seven-day treatment was regarded as one course. On the above basis, the patients in the observation group were given Tanshinone IIA 60 mg + 5% glucose 250 mL, iv drip, 1 time/d. Seven-day treatment was regarded as one course. The efficacy was evaluated after seven-day treatment. ELISA was used to detect hs-CRP, TNF-α, and IL-6 levels before and after treatment. The color Doppler ultrasound diagnostic apparatus was used to monitor LVEF, LVESD, LVEDD, and IVST. The occurrence of adverse cardiac events was observed. Results:After treatment, LVEF in the two groups was significantly elevated, LVESD, LVEDD, and IVST were significantly reduced when compared with before treatment (P<0.05), and those in the observation group were significantly superior to those in the control group (P<0.05). After treatment, the serum hs-CRP, TNF-α, and IL-6 levels in the two groups were significantly reduced when compared with before treatment (P<0.05), and the reduced degree in the observation group was significantly superior to that in the control group (P<0.05). The occurrence rate of arrhythmia, cardiogenic shock, and heart rate in the observation group was significantly lower than that in the control group (P<0.05).Conclusions:Tanshinone IIA in the treatment of AMI can effectively improve the cardiac function after thrombolysis

  20. On WZ and RR couplings of BPS branes and their all order α‧ corrections in IIB, IIA

    Science.gov (United States)

    Hatefi, Ehsan

    2017-03-01

    We compute all three and four point couplings of BPS Dp-branes for all different nonzero p-values on the entire world volume and transverse directions. We start finding out all four point function supersymmetric Wess-Zumino (WZ) actions of one closed string Ramond-Ramond (RR) field with two fermions, either with the same (IIB) or different chirality (IIA) as well as their all order α‧ corrections. The closed form of S-matrices of two closed string RR in both IIB, IIA, including their all order α‧ corrections have also been addressed. Our results confirm that, not only the structures of α‧ corrections but also their coefficients of IIB are quite different from their IIA ones. The S-matrix of an RR and two gauge (scalar) fields and their all order corrections in antisymmetric picture of RR have been carried out as well. Various remarks on the restricted Bianchi identities as well as all order α‧ corrections to all different supersymmetric WZ couplings in both type IIA and IIB superstring theory are also released. Lastly, different singularity structures as well as all order contact terms for all non-vanishing traces in type II have also been constructed.

  1. Silicon Phthalocyanine 4 and Photodynamic Therapy in Stage IA-IIA Cutaneous T-Cell Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-12-03

    Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IA Mycosis Fungoides/Sezary Syndrome; Stage IB Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IIA Mycosis Fungoides/Sezary Syndrome

  2. On WZ and RR Couplings of BPS Branes and their all order $\\alpha'$ Corrections in IIB, IIA

    CERN Document Server

    Hatefi, Ehsan

    2016-01-01

    We compute all three and four point couplings of BPS $D_{p}$-branes for all different nonzero $p$-values on the entire world volume and transverse directions. We start finding out all four point function supersymmetric Wess-Zumino (WZ) actions of one closed string Ramond-Ramond (RR) field with two fermions, either with the same (IIB) or different chirality (IIA) as well as their all order $\\alpha'$ corrections. The closed form of S-matrices of two closed string RR in both IIB, IIA, including their all order $\\alpha'$ corrections have also been addressed. Our results confirm that, not only the structures of $\\alpha'$ corrections but also their coefficients of IIB are quite different from their IIA ones. The S-matrix of an RR and two gauge (scalar) fields and their all order corrections in antisymmetric picture of RR have been carried out as well. Various remarks on the restricted Bianchi identities as well as all order $\\alpha'$ corrections to all different supersymmetric WZ couplings in both type IIA and IIB ...

  3. Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma.

    Science.gov (United States)

    Conti, Mary Anne; Saleh, Anthony D; Brinster, Lauren R; Cheng, Hui; Chen, Zhong; Cornelius, Shaleeka; Liu, Chengyu; Ma, Xuefei; Van Waes, Carter; Adelstein, Robert S

    2015-09-15

    To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (A(Nkx)/A(Nkx)) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 A(Nkx)/A(Nkx)) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In A(Nkx)/A(Nkx) mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.

  4. Increased type IIA secretory phospholipase A(2) expression contributes to oxidative stress in end-stage renal disease

    NARCIS (Netherlands)

    van der Giet, Markus; Toelle, Markus; Pratico, Domenico; Lufft, Volkmar; Schuchardt, Mirjam; Hoerl, Matthias P.; Zidek, Walter; Tietge, Uwe J. F.

    2010-01-01

    End-stage renal disease (ESRD) patients exhibit increased in vivo oxidative stress conceivably contributing to cardiovascular mortality. The type IIA secretory phospholipase A(2) (sPLA(2)) has proatherogenic activity. We explored the hypothesis that sPLA(2) contributes to oxidative stress generation

  5. U2 toggles iteratively between the stem IIa and stem IIc conformations to promote pre-mRNA splicing.

    Science.gov (United States)

    Hilliker, Angela K; Mefford, Melissa A; Staley, Jonathan P

    2007-04-01

    To ligate exons in pre-messenger RNA (pre-mRNA) splicing, the spliceosome must reposition the substrate after cleaving the 5' splice site. Because spliceosomal small nuclear RNAs (snRNAs) bind the substrate, snRNA structures may rearrange to reposition the substrate. However, such rearrangements have remained undefined. Although U2 stem IIc inhibits binding of U2 snRNP to pre-mRNA during assembly, we found that weakening U2 stem IIc suppressed a mutation in prp16, a DExD/H box ATPase that promotes splicing after 5' splice site cleavage. The prp16 mutation was also suppressed by mutations flanking stem IIc, suggesting that Prp16p facilitates a switch from stem IIc to the mutually exclusive U2 stem IIa, which activates binding of U2 to pre-mRNA during assembly. Providing evidence that stem IIa switches back to stem IIc before exon ligation, disrupting stem IIa suppressed 3' splice site mutations, and disrupting stem IIc impaired exon ligation. Disrupting stem IIc also exacerbated the 5' splice site cleavage defects of certain substrate mutations, suggesting a parallel role for stem IIc at both catalytic stages. We propose that U2, much like the ribosome, toggles between two conformations--a closed stem IIc conformation that promotes catalysis and an open stem IIa conformation that promotes substrate binding and release.

  6. High-level resistance to class IIa bacteriocins is associated with one general mechanism in Listeria monocytogenes.

    Science.gov (United States)

    Gravesen, Anne; Ramnath, Manilduth; Rechinger, K Björn; Andersen, Natalie; Jänsch, Lothar; Héchard, Yann; Hastings, John W; Knøchel, Susanne

    2002-08-01

    Class IIa bacteriocins may be used as natural food preservatives, yet resistance development in the target organisms is still poorly understood. In this study, the understanding of class IIa resistance development in Listeria monocytogenes is extended, linking the seemingly diverging results previously reported. Eight resistant mutants having a high resistance level (at least a 10(3)-fold increase in MIC), originating from five wild-type listerial strains, were independently isolated following exposure to four different class IIa bacteriocin-producing lactic acid bacteria (including pediocin PA-1 and leucocin A producers). Two of the mutants were isolated from food model systems (a saveloy-type sausage at 10 degrees C, and salmon juice at 5 degrees C). Northern blot analysis showed that the eight mutants all had increased expression of EII(Bgl) and a phospho-beta-glucosidase homologue, both originating from putative beta-glucoside-specific phosphoenolpyruvate-dependent phosphotransferase systems (PTSs). However, disruption of these genes in a resistant mutant did not confer pediocin sensitivity. Comparative two-dimensional gel analysis of proteins isolated from mutant and wild-type strains showed that one spot was consistently missing in the gels from mutant strains. This spot corresponded to the MptA subunit of the mannose-specific PTS, found only in the gels of wild-type strains. The mptACD operon was recently shown to be regulated by the sigma(54) transcription factor in conjunction with the activator ManR. Class IIa bacteriocin-resistant mutants having defined mutations in mpt or manR also exhibited the two diverging PTS expression changes. It is suggested here that high-level class IIa resistance in L. monocytogenes and at least some other Gram-positive bacteria is developed by one prevalent mechanism, irrespective of wild-type strain, class IIa bacteriocin, or the tested environmental conditions. The changes in expression of the beta-glucoside-specific and

  7. Structural characterization of the PTS IIA and IIB proteins associated with pneumococcal fucose utilization.

    Science.gov (United States)

    Higgins, Melanie A; Hamilton, Aileen M; Boraston, Alisdair B

    2017-05-01

    Streptococcus pneumoniae harbors a significant number of transporters, including phosphotransferase (PTS) systems, allowing the bacterium to utilize a number of different carbohydrates for metabolic and other purposes. The genes encoding for one PTS transport system in particular (EII(fuc) ) are found within a fucose utilization operon in S. pneumoniae TIGR4. Here, we report the three-dimensional structures of IIA(fuc) and IIB(fuc) providing evidence that this PTS system belongs to the EII(man) family. Additionally, the predicted metabolic pathway for this distinctive fucose utilization system suggests that EII(fuc) transports the H-disaccharide blood group antigen, which would represent a novel PTS transporter specificity. Proteins 2017; 85:963-968. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  8. Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A).

    Science.gov (United States)

    Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2004-10-21

    The streptogramins are antibiotics which act by binding two different components at separate nearby sites on the bacterial 50S ribosome, inhibiting protein synthesis. The first component, a macrolactone, is common to many of the streptogramin antibiotics and, thus, is referred to by many names including virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X-Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating enzyme show a different conformation to that of VM1 in chloroform solution. We now report the results of high resolution 2D NMR experiments that show that the conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in chloroform solution and in the bound form. The 3D structure and the 1H NMR and 13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

  9. Effects of homoeologous wheat starch synthase IIa genes on starch properties.

    Science.gov (United States)

    Shimbata, Tomoya; Ai, Yongfeng; Fujita, Masaya; Inokuma, Takayuki; Vrinten, Patricia; Sunohara, Ai; Saito, Mika; Takiya, Toshiyuki; Jane, Jay-lin; Nakamura, Toshiki

    2012-12-05

    Near-isogenic lines (NILs) of the eight haplotypes of starch synthase IIa (SSIIa) were used to analyze the effects of SSIIa gene dosage on branch chain length, gelatinization, pasting, retrogradation, and enzymatic hydrolysis of starches. Compared to wild-type, the amylopectin of lines missing one or more active SSIIa enzymes had increases in the proportion of short branch chains (DP6-10) and decreases in midlength chains (DP11-24), and the size of these differences depended on the dosage of active SSIIa enzymes. Of the three loci, SSIIa-A1 had the smallest contribution to amylopectin structure and SSIIa-B1 the largest. The different effects of the three SSIIa enzymes on starch properties were also seen in gelatinization, retrogradation, pasting, and enzymatic hydrolysis properties. Such differences in starch properties might be useful in influencing the texture and shelf life of food products.

  10. Standard Model Compactifications of IIA Z3 x Z3 Orientifolds from Intersecting D6-branes

    CERN Document Server

    Kokorelis, C E

    2004-01-01

    We discuss the construction of chiral four dimensional T^6/(Z3 x Z3) orientifold compactifications of IIA theory, using D6-branes intersecting at angles and not aligned with the orientifold O6 planes. Cancellation of mixed U(1) anomalies requires the presence of a generalized Green-Schwarz mechanism mediated by RR partners of closed string untwisted moduli. As expected all complex moduli fields get stabilized naturally in these constructions by the orbifold symmetry. In this respect we describe the appearance of three quark and lepton family SU(3)_C x SU(2)_L x U(1)_Y non-supersymmetric orientifold models with only the massless spectrum of the SM at low energy that can have either no exotics present and three families of $\

  11. Class IIA ring avulsion injuries: an absolute indication for microvascular repair.

    Science.gov (United States)

    Nissenbaum, M

    1984-11-01

    The class II ring avulsion category, includes those patients in whom only digital arteries are damaged but all other structures are intact and functional (here labeled class IIA). Current literature suggests this is a rare lesion. Seven patients with this specific injury in whom the affected digits were nonviable are reported. Four of the seven were misdiagnosed on initial emergency room evaluation. Two did not seek additional medical attention and the condition progressed to necrosis and amputation. The other two, who sought additional treatment because of progressive ischemia, and three additional patients who were correctly diagnosed on initial examination underwent simple digital arterial repair. All digits operated on survived and demonstrated near normal function. Since failure to operate results in digital loss, this is an absolute indication for microvascular repair.

  12. On Black Attractors in 8D and Heterotic/Type IIA Duality

    CERN Document Server

    Saidi, El Hassan

    2010-01-01

    Motivated by the study of black attractors in 8D supergravity with 16 supersymmetries, we use the field theory approach and 8D supersymmetry with non trivial central charges to shed light on the exact duality between heterotic string on T^2 and type IIA on real connected and compact surfaces {\\Sigma}2. We investigate the two constraints that should be obeyed by {\\Sigma}2 and give their solutions in terms of intersecting 2-cycles as well their classification using Dynkin diagrams of affine Kac-Moody algebras. It is shown as well that the moduli space of these dual theories is given by SO(1,1)x((SO(2,r+2))/(SO(2)xSO(r+2))) where r stands for the rank of the gauge symmetry G_{r} of the 10D heterotic string on T^2. The remarkable cases r=-2,-1,0 as well as other features are also investigated.

  13. Involvement of aph(3‘-IIa in the formation of mosaic aminoglycoside resistance genes in natural environments

    Directory of Open Access Journals (Sweden)

    Markus eWoegerbauer

    2015-05-01

    Full Text Available Intragenic recombination leading to mosaic gene formation is known to alter resistance profiles for particular genes and bacterial species. Few studies have examined to what extent aminoglycoside resistance genes undergo intragenic recombination.We screened the GenBank database for mosaic gene formation in homologs of the aph(3’-IIa (nptII gene. APH(3’-IIa inactivates important aminoglycoside antibiotics. The gene is widely used as a selectable marker in biotechnology and enters the environment via laboratory discharges and the release of transgenic organisms. Such releases may provide opportunities for recombination in competent environmental bacteria.The retrieved GenBank sequences were grouped in 3 datasets comprising river water samples, duck pathogens and full-length variants from various bacterial genomes and plasmids. Analysis for recombination in these datasets was performed with the Recombination Detection Program, RDP4, and the Genetic Algorithm for Recombination Detection, GARD.From a total of 89 homologous sequences, 83% showed 99% - 100% sequence identity with aph(3’-IIa originally described as part of transposon Tn5. Fifty one were unique sequence variants eligible for recombination analysis. Only a single recombination event was identified with high confidence and indicated the involvement of aph(3’-IIa in the formation of a mosaic gene located on a plasmid of environmental origin in the multi-resistant isolate Pseudomonas aeruginosa PA96. The available data suggest that aph(3’-IIa is not an archetypical mosaic gene as the divergence between the described sequence variants and the number of detectable recombination events is low. This is in contrast to the numerous mosaic alleles reported for certain penicillin or tetracycline resistance determinants.

  14. The secretory phospholipase A2 group IIA: a missing link between inflammation, activated renin-angiotensin system, and atherogenesis?

    Directory of Open Access Journals (Sweden)

    Dimitar Divchev

    2008-06-01

    Full Text Available Dimitar Divchev, Bernhard SchiefferDepartment of Cardiology and Angiology, Medizinische Hochschule Hannover, GermanyAbstract: Inflammation, lipid peroxidation and chronic activation of the renin–angiotensin system (RAS are hallmarks of the development of atherosclerosis. Recent studies have suggested the involvement of the pro-inflammatory secretory phospholipase A2 (sPLA2-IIA in atherogenesis. This enzyme is produced by different cell types through stimulation by proinflammatory cytokines. It is detectable in the intima and in media smooth muscle cells, not only in atherosclerotic lesions but also in the very early stages of atherogenesis. sPLA2-IIA can hydrolyse the phospholipid monolayers of low density lipoproteins (LDL. Such modified LDL show increased affinity to proteoglycans. The modified particles have a greater tendency to aggregate and an enhanced ability to insert cholesterol into cells. This modification may promote macrophage LDL uptake leading to the formation of foam cells. Furthermore, sPLA2-IIA is not only a mediator for localized inflammation but may be also used as an independent predictor of adverse outcomes in patients with stable coronary artery disease or acute coronary syndromes. An interaction between activated RAS and phospholipases has been indicated by observations showing that inhibitors of sPLA2 decrease angiotensin (Ang II-induced macrophage lipid peroxidation. Meanwhile, various interactions between Ang II and oxLDL have been demonstrated suggesting a central role of sPLA2-IIA in these processes and offering a possible target for treatment. The role of sPLA2-IIA in the perpetuation of atherosclerosis appears to be the missing link between inflammation, activated RAS and lipidperoxidation.Keywords: secretory phospholipase A2, lipoproteins, renin-angiotensin system, inflammation, atherosclerosis

  15. Inhibition of sPLA₂-IIA prevents LPS-induced neuroinflammation by suppressing ERK1/2-cPLA₂α pathway in mice cerebral cortex.

    Directory of Open Access Journals (Sweden)

    Yanxiao Xiang

    Full Text Available Neuroinflammation is involved in various central nervous system (CNS disorders, including brain infections, ischemia, trauma, stroke, and degenerative CNS diseases. In the CNS inflammation, secretory phospholipase A₂-IIA (sPLA₂-IIA acts as a mediator, resulting in the generation of the precursors of pro-inflammatory lipid mediators, such as prostaglandins (PGs and leukotrienes (LTs. However, the role of sPLA₂-IIA in neuroinflammation is more complicated and remains unclear yet. In the present study, we investigated the effect of sPLA₂-IIA inhibition by specific inhibitor SC-215 on the inflammation in LPS-induced mice cerebral cortex and primary astrocytes. Our results showed that the inhibition of sPLA₂-IIA alleviated the release of PGE₂ by suppressing the activation of ERK1/2, cPLA₂α, COX-2 and mPGES-1. These findings demonstrated that sPLA₂-IIA showed the potential to regulate the neuroinflammation in vivo and in vitro, indicating that sPLA₂-IIA might be a novel target for the treatment of acute neuroinflammation.

  16. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

    Science.gov (United States)

    Xiao, Jianyong; Zhang, Guangxian; Qiu, Pengxiang; Liu, Xijuan; Wu, Yingya; Du, Biaoyan; Li, Jiefen; Zhou, Jing; Li, Jingjing; Tan, Yuhui

    2013-01-01

    The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV). This effect is reported to be mediated by gap junctional intercellular communication (GJIC), and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA), a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  17. Tanshinone IIA increases the bystander effect of herpes simplex virus thymidine kinase/ganciclovir gene therapy via enhanced gap junctional intercellular communication.

    Directory of Open Access Journals (Sweden)

    Jianyong Xiao

    Full Text Available The bystander effect is an intriguing phenomenon by which adjacent cells become sensitized to drug treatment during gene therapy with herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV. This effect is reported to be mediated by gap junctional intercellular communication (GJIC, and therefore, we postulated that upregulation of genes that facilitate GJIC may enhance the HSV-tk/GCV bystander effect. Previous findings have shown Tanshinone IIA (Tan IIA, a chemical substance derived from a Chinese medicine herb, promotes the upregulation of the connexins Cx26 and Cx43 in B16 cells. Because gap junctions are formed by connexins, we hypothesized that Tan IIA might increase GJIC. Our results show that Tan IIA increased GJIC in B16 melanoma cells, leading to more efficient GCV-induced bystander killing in cells stably expressing HSV-tk. Additionally, in vivo experiments demonstrated that tumors in mice with 10% HSV-tk positive B16 cells and 90% wild-type B16 cells became smaller following treatment with the combination of GCV and Tan IIA as compared to GCV or Tan IIA alone. These data demonstrate that Tan IIA can augment the bystander effect of HSV-tk/GCV system through increased gap junction coupling, which adds strength to the promising strategy that develops connexins inducer to potentiate the effects of suicide gene therapy.

  18. Stage IIA and IIB testicular seminoma treated post-orchiectomy with radiation therapy versus other approaches: a population-based analysis of 241 patients

    Science.gov (United States)

    Ahmed, Kamran A.; Wilder, Richard B.

    2015-01-01

    Objectives To evaluate post-orchiectomy utilization of radiation therapy (RT) versus other management approaches in stage IIA and IIB testicular seminoma patients. Materials and Methods Two hundred and forty-one patients with stage IIA and IIB testicular seminoma were identified between 1988 and 2003 using the Surveillance, Epidemiology, and End Results (SEER) database. Results Median follow-up was 10 years. Patients with stage IIA disease underwent RT more frequently than those with stage IIB disease (72% vs. 46%, respectively; Pseminoma. PMID:25928512

  19. Crosstalk between Beclin-1-dependent autophagy and caspase-dependent apoptosis induced by tanshinone IIA in human osteosarcoma MG-63 cells

    Science.gov (United States)

    Ma, Kun; Zhang, Chuan; Huang, Man-Yu; Guo, Yan-Xing; Hu, Guo-Qiang

    2016-01-01

    The aim of the present study was to ascertain whether or not autophagy is induced by tanshinone IIA (TanIIA), and to explore the crosstalk between autophagy and apoptosis in regards to the antitumor effects of TanIIA on MG-63 cells and the potential mechanism. MG-63 cells were cultured in vitro with various concentrations of TanIIA (0, 2.5, 5, 10 and 20 mg/l) for 0, 24, 48 and 72 h, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay was used to evaluate the inhibition of the proliferation of osteosarcoma MG-63 cells by TanIIA or in the presence/absence of chloroquine (CQ). Autophagic vacuoles and characteristic autophagosomes were observed by transmission electron microscopy (TEM). TanIIA-induced autophagy in MG-63 cells was confirmed by GFP-LC3 punctate fluorescence. The expression levels of apoptosis-related proteins caspase-3, caspase-8, caspase-9 and cleaved-PARP and autophagy-related proteins LC3II/LC3I and Beclin-1 were detected by western blotting. FITC-Annexin V/propidium iodide (PI) staining, flow cytometry and Hoechst 33258 staining were used to analyze the apoptotic rate. Fluorescence intensity of reactive oxygen species (ROS) was examined under a fluorescence microscope using an analysis software system. Cell proliferation was obviously inhibited by TanIIA in a dose- and time-dependent manner. Generation of autophagy was triggered by TanIIA (0–20 mg/l) treatment, and in a Beclin-1-dependent manner. Compared with the control group, the apoptosis ratio following treatment with 2.5 mg/l TanIIA failed to achieve statistical significance. Expression of caspase-3, -8 and -9, and cleaved-PARP in the other groups was gradually enhanced in dose-dependent manner. Our analysis also suggested that the influence of autophagy on TanIIA cytotoxicity had a phase effect; with low-dose drugs and shorter treatment periods, autophagy functioned as a damage repair mechanism. In conrast, when the cells were treated with higher doses of TanIIA

  20. Management and outcomes of clinical stage IIA/B seminoma: Results from the National Cancer Data Base 1998-2012.

    Science.gov (United States)

    Paly, Jonathan J; Lin, Chun Chieh; Gray, Phillip J; Hallemeier, Christopher L; Beard, Clair; Sineshaw, Helmneh; Jemal, Ahmedin; Efstathiou, Jason A

    Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease. Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed. A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P < .01) and community treatment setting (OR, 1.81-2.76; P < .01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P < .01), more recent year of diagnosis (continuous OR, 0.93; P < .01), and primary pathologic tumor 3/4 stage (OR, 0.47; P < .01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P < .01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P < .01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08). Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were

  1. Geology and mineral resources of central Antioquia Department (Zone IIA), Colombia

    Science.gov (United States)

    Hall, R.B.; Alvarez A., Jairo; Rico H., Hector

    1973-01-01

    Antioquian batholith. Displacement along the great Romeral wrench fault may have begun in the Cretaceous. Plutonism continued into the Cenozoic, exemplified by the hornblende-diorite Sabanalarga pluton. Intermontane basins were filled with molasse derived from the erosion of adjacent highlands; Tertiary sedimentation in marshy areas included organic carboniferous matter subsequently converted to lignite or subbituminous coal. The Sabanalarga fault system originated in the Late Tertiary; intermittent displacement continued on the older wrench faults such as the Romeral. Epeirogenic uplift, which probably began in the Pliocene and continued through the Pleistocene and Holocene, brought on renewed erosion which has sculptured the mountains into their present form. Mineral resources in subzone IIA are varied but not of outstanding importance. Gold and silver mining, significant in past centuries, is minor today. Ferruginous laterite on serpentinite once considered as a potential source of iron ore is not economically exploitable. IMN has explored nickeliferous laterite at the extreme northwest corner of subzone IIA; this is a potential resource, exploitable only after exhaustion of the larger and richer nickel laterite deposit at Cerro Matoso, farther to the north and outside the boundaries of Zone If. Known deposits of mercury, chromium, manganese, and copper are small, with limited economic potential. Nonmetallic resources include raw materials for cement, including portland cement. Saprolite clay is widely used in making common red brick and tile, still a dominant construction material in all but the most modern multistory buildings. Aggregate materials are varied and abundant. Kaolin of good quality near La Union is important as a ceramic raw mineral filler. Tertiary subbituminous coal beds are an important energy resource in western subzone IIA, and have a good potential for greater development. Deposits of sodic feldspar, talc, decorative stone, and silica a

  2. Presence of Cryptosporidium scrofarum, C. suis and C. parvum subtypes IIaA16G2R1 and IIaA13G1R1 in Eurasian wild boars (Sus scrofa).

    Science.gov (United States)

    García-Presedo, Ignacio; Pedraza-Díaz, Susana; González-Warleta, Marta; Mezo, Mercedes; Gómez-Bautista, Mercedes; Ortega-Mora, Luis Miguel; Castro-Hermida, José Antonio

    2013-09-23

    The aim of the present study was to identify the species of Cryptosporidium infecting Eurasian wild boars (Sus scrofa) in Galicia (NW, Spain). A sampling of 209 wild boars shot in different game preserves was carried out during the hunting season in 2009-2010. All samples were examined for Cryptosporidium infection, using both immunological and molecular tools. Cryptosporidium oocysts in faecal samples were identified using a direct immunofluorescence technique with monoclonal antibodies (DFA). The presence of Cryptosporidium DNA was determined using nested PCR involving amplification of a fragment of the small-subunit (SSU) ribosomal RNA gene (SSU rRNA). A total of 35 (16.7%) samples tested positive with both techniques. However, sequencing was only possible in 27 samples. Cryptosporidium scrofarum, Cryptosporidium suis and Cryptosporidium parvum oocysts were identified in 19, 5 and 3 of the samples, respectively. Moreover, C. scrofarum was detected as a dominant species infecting all age groups (juveniles, sub adults and adults). Sequence analyses of the glycoprotein (GP60) gene revealed the presence of C. parvum subtypes IIaA16G2R1 in 2 juveniles and IIaA13G1R1 in 1 sub adult wild boar. These species and subtypes have previously been described in human patients, indicating that isolates from asymptomatic wild boars might have zoonotic potential. This is the first report of the presence of C. scrofarum, C. suis and C. parvum subtypes IIaA16G2R1 and IIaA13G1R1 in wild boars (S. scrofa) in Spain.

  3. Preparation, characterization, and in vivo evaluation of tanshinone IIA solid dispersions with silica nanoparticles

    Directory of Open Access Journals (Sweden)

    Jiang YR

    2013-06-01

    Full Text Available Yan-rong Jiang,1,2 Zhen-hai Zhang,1 Qi-yuan Liu,1,2 Shao-ying Hu,1,2 Xiao-yun Chen,1,2 Xiao-bin Jia11Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 2College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of ChinaAbstract: We prepared solid dispersions (SDs of tanshinone IIA (TSIIA with silica nanoparticles, which function as dispersing carriers, using a spray-drying method and evaluated their in vitro dissolution and in vivo performance. The extent of TSIIA dissolution in the silica nanoparticles/TSIIA system (weight ratio, 5:1 was approximately 92% higher than that of the pure drug after 60 minutes. However, increasing the content of silica nanoparticles from 5:1 to 7:1 in this system did not significantly increase the rate or extent of TSIIA dissolution. The physicochemical properties of SDs were investigated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and Fourier transforms infrared spectroscopy. Studying the stability of the SDs of TSIIA revealed that the drug content of the formulation and dissolution behavior was unchanged under the applied storage conditions. In vivo tests showed that SDs of the silica nanoparticles/TSIIA had a significantly larger area under the concentration-time curve, which was 1.27 times more than that of TSIIA (P < 0.01. Additionally, the values of maximum plasma concentration and the time to reach maximum plasma concentration of the SDs were higher than those of TSIIA and the physical mixing system. Based on these results, we conclude that the silica nanoparticle based SDs achieved complete dissolution, increased absorption rate, maintained drug stability, and showed improved oral bioavailability compared to TSIIA alone.Keywords: tanshinone IIA, solid dispersions, silica nanoparticles, in vitro

  4. Cell-surface alterations in class IIa bacteriocin-resistant Listeria monocytogenes strains.

    Science.gov (United States)

    Vadyvaloo, Viveka; Arous, Safia; Gravesen, Anne; Héchard, Yann; Chauhan-Haubrock, Ramola; Hastings, John W; Rautenbach, Marina

    2004-09-01

    Strains of the food-borne pathogen Listeria monocytogenes, showing either intermediate or high-level resistance to class IIa bacteriocins, were investigated to determine characteristics that correlated with their sensitivity levels. Two intermediate and one highly resistant spontaneous mutant of L. monocytogenes B73, a highly resistant mutant of L. monocytogenes 412, and a highly resistant, defined (mptA) mutant of L. monocytogenes EGDe were compared with their respective wild-type strains in order to investigate the contribution of different factors to resistance. Decreased mannose-specific phosphotransferase system gene expression (mptA, EIIAB(Man) component) was implicated in all levels of resistance, confirming previous studies by the authors' group. However, a clear correlation between d-alanine content in teichoic acid (TA), in particular the alanine : phosphorus ratio, and a more positive cell surface, as determined by cytochrome c binding, were found for the highly resistant strains. Furthermore, two of the three highly resistant strains showed a significant increase in sensitivity towards d-cycloserine (DCS). However, real-time PCR of the dltA (d-alanine esterification), and dal and ddlA genes (peptidoglycan biosynthesis) showed no change in transcriptional levels. The link between DCS sensitivity and increased d-alanine esterification of TA may be that DCS competes with alanine for transport via the alanine transporter. A possible tendency towards increased lysinylation of membrane phospholipid in the highly resistant strains was also found. A previous study reported that cell membranes of all the resistant strains, including the intermediate resistant strains, contained more unsaturated phosphatidylglycerol, which is an indication of a more fluid cell membrane. The results of that study correlate with the possible lysinylation, decreased mptA expression, d-alanine esterification of TA and more positive cell surface charge found in this study for

  5. Remarks on non-BPS string amplitudes and their all order α' contact interactions in IIB, IIA

    Science.gov (United States)

    Hatefi, Ehsan

    2017-03-01

    We explore the entire form of S-Matrix elements of a potential C n-1 Ramond-Ramond (RR) form field, a tachyon and two transverse scalar fields on both world volume and transverse directions of type IIB and IIA superstring theories. Apart from string theory can be re-verified in an Effective Field Theory (EFT) by pull-back of branes. To construct the rest of S-matrix elements one needs to first derive restricted world volume (or bulk) Bianchi identities and then discover new EFT couplings in both type IIB and IIA. Finally the presence of commutator of scalar fields inside the exponential of Wess-Zumino action for non-BPS branes has been confirmed as well.

  6. Hydrogen adsorption on Be, Mg, Ca and Sr doped graphenes: The role of the dopant in the IIA main group

    Science.gov (United States)

    Luo, Huijuan; Li, Hejun; Fu, Qiangang

    2017-02-01

    Hydrogen (H2) adsorption on the IIA elements doped double-vacancy graphenes (BeG, MgG, CaG and SrG) was studied by using dispersion-corrected density functional theory calculations. Through investigation of different numbers of hydrogen dockings from two directions, it is found that 1H2/BeG, 1H2/MgG, 8H2/CaG and 8H2/SrG are the most stable adsorption configurations for Be, Mg, Ca and Sr doped graphenes, respectively. Atomic radius, electronegativity and ionization potential of the IIA dopant contribute to the dominating adsorption mechanism under specific H2 concentration. The study would facilitate exploration of high performance graphene-related supports for hydrogen storage.

  7. Multiple Authorisation: The Legal Complexity of Desentralisasi in Indonesia and the Potential Contribution of IIAs in Reducing Confusion

    Directory of Open Access Journals (Sweden)

    Michael Ewing-Chow

    2015-12-01

    Full Text Available Decentralisation system in Indonesia was introduced after the fall of the former President Soeharto with the objective of ensuring good governance and equitable development across all regions in the country. Unfortunately, the implementation of desentralisasi has been complicated. Some scholars have suggested that the model was flawed as it did not consider Indonesia’s context of less developed administrative institutions in the regions. Not only did desentralisasi cause headaches for the government, it also created confusion for foreign investors. Consequently, it affects the investment climate in the country and undermines the perception of Indonesia as an attractive place to invest in. In certain cases, desentralisasi has also led to claims by foreign investors for investor-State arbitration under Indonesia’s international investment agreements (IIAs. This paper analyses the problems of desentralisasi in Indonesia, its effects to foreign investors and suggests ways to alleviate the problems by modifying and using Indonesia’s IIAs effectively.

  8. Action of human group IIa secreted phospholipase A2 on cell membranes. Vesicle but not heparinoid binding determines rate of fatty acid release by exogenously added enzyme.

    Science.gov (United States)

    Koduri, R S; Baker, S F; Snitko, Y; Han, S K; Cho, W; Wilton, D C; Gelb, M H

    1998-11-27

    Human group IIa phospholipase A2 (hIIa-PLA2) is a highly basic protein that is secreted from a number of cells during inflammation and may play a role in arachidonate liberation and in destruction of invading bacteria. It has been proposed that rodent group IIa PLA2 is anchored to cell surfaces via attachment to heparan sulfate proteoglycan and that this interaction facilitates lipolysis. hIIa-PLA2 contains 13 lysines, 2 histidines, and 10 arginines that fall into 10 clusters. A panel of 26 hIIa-PLA2 mutants were prepared in which 1-4 basic residues in each cluster were changed to glutamate or aspartate (charge reversal). A detailed analysis of the affinities of these mutants for anionic vesicles and for heparin and heparan sulfate in vitro and of the specific activities of these proteins for hydrolysis of vesicles in vitro and of living cell membranes reveal the following trends: 1) the affinity of hIIa-PLA2 for heparin and heparan sulfate is modulated not by a highly localized site of basic residues but by diffuse sites that partially overlap with the interfacial binding site. In contrast, only those residues on the interfacial binding site of hIIa-PLA2 are involved in binding to membranes; 2) the relative ability of these mutants to hydrolyze cellular phospholipids when enzymes were added exogenously to CHO-K1, NIH-3T3, and RAW 264.7 cells correlates with their relative in vitro affinity for vesicles and not with their affinity for heparin and heparan sulfate. 3) The rates of exogenous hIIa-PLA2-catalyzed fatty acid release from wild type CHO-K1 cells and two mutant lines, one lacking glycosaminoglycan and one lacking heparan sulfate, were similar. Thus basic residues that modulate interfacial binding are important for plasma membrane fatty acid release by exogenously added hIIa-PLA2. Binding of hIIa-PLA2 to cell surface heparan sulfate does not modulate plasma membrane phospholipid hydrolysis by exogenously added hIIa-PLA2.

  9. Enzymatic properties of stingray Dasyatis pastinaca group V, IIA and IB phospholipases A(2): a comparative study.

    Science.gov (United States)

    Ben Bacha, Abir; Abid, Islem; Horchani, Habib; Mejdoub, Hafedh

    2013-11-01

    In the present study, we have purified the group V phospholipase from the heart of cartilaginous fish stingray Dasyatis pastinaca and compared its biochemical properties with group IIA (sPLA2-IIA) and IB (sPLA2-IB) phospholipases previously purified from pancreas and intestine, respectively. Group V phospholipase (sPLA2-V) was purified to homogeneity by heat treatment, ammonium sulphate precipitation and RP-HPLC. The N-terminal sequence of the purified sPLA2-V exhibits a high degree of homology with those of mammal. The enzyme was found to be monomeric with a molecular mass estimation of 14 kDa. The specific activity of the purified enzyme, measured at pH 8 and 37 °C was 52 U/mg. Like sPLA2-IB and sPLA2-IIA, the sPLA2-V is found to be stable between pH 3 and 11 after 30 min of incubation. The purified sPLA2-V retained 65% of its activity after 10 min of incubation at 70 °C and it absolutely requires Ca(2+) for enzymatic activity. In addition it displayed high tolerance to organic solvents. Kinetic parameters Kmapp, kcat and the deduced catalytic efficiency (kcat/Kmapp) of the purified group-V, -IB and -IIA PLA2s were determined using phosphatidylethanolamine (PE), phosphatidylcholine (PC) or phosphatidylserine (PS) as substrate. The three enzymes hydrolyze the zwiterionic PE and PC substrates more efficiently than anionic PS substrate.

  10. Non-perturbative black holes in Type-IIA String Theory vs. the No-Hair conjecture

    CERN Document Server

    Bueno, Pablo

    2013-01-01

    We obtain the first black hole solution to Type-IIA String Theory compactified on an arbitrary self-mirror Calabi Yau manifold in the presence of non-perturbative quantum corrections. Remarkably enough, the solution involves multivalued functions, which could lead to a violation of the No-Hair conjecture. We discuss how String Theory forbids such secenario. However the possibility still remains open in the context of four-dimensional ungauged Supergravity.

  11. Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro

    OpenAIRE

    Jian-Ping Dai; Dan-Xia Zhu; Jiang-Tao Sheng; Xiao-Xuan Chen; Wei-Zhong Li; Ge-Fei Wang; Kang-Sheng Li; Yun Su

    2015-01-01

    Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, q...

  12. Spatial Vegetation Data for Congaree National Park Vegetation Mapping Project

    Data.gov (United States)

    National Park Service, Department of the Interior — The National Park Service (NPS), in conjunction with the Biological Resources Division (BRD) of the U.S. Geological Survey (USGS), has implemented a program to...

  13. Human HDAC7 Harbors a Class IIa Histone Deacetylase-specific Zinc Binding Motif and Cryptic Deacetylase Activity

    Energy Technology Data Exchange (ETDEWEB)

    Schuetz, Anja; Min, Jinrong; Allali-Hassani, Abdellah; Schapira, Matthieu; Shuen, Michael; Loppnau, Peter; Mazitschek, Ralph; Kwiatkowski, Nick P.; Lewis, Timothy A.; Maglathin, Rebecca L.; McLean, Thomas H.; Bochkarev, Alexey; Plotnikov, Alexander N.; Vedadi, Masoud; Arrowsmith, Cheryl H. (MIT); (Toronto)

    2010-10-18

    Histone deacetylases (HDACs) are protein deacetylases that play a role in repression of gene transcription and are emerging targets in cancer therapy. Here, we characterize the structure and enzymatic activity of the catalytic domain of human HDAC7 (cdHDAC7). Although HDAC7 normally exists as part of a multiprotein complex, we show that cdHDAC7 has a low level of deacetylase activity which can be inhibited by known HDAC inhibitors. The crystal structures of human cdHDAC7 and its complexes with two hydroxamate inhibitors are the first structures of the catalytic domain of class IIa HDACs and demonstrate significant differences with previously reported class I and class IIb-like HDAC structures. We show that cdHDAC7 has an additional class IIa HDAC-specific zinc binding motif adjacent to the active site which is likely to participate in substrate recognition and protein-protein interaction and may provide a site for modulation of activity. Furthermore, a different active site topology results in modified catalytic properties and in an enlarged active site pocket. Our studies provide mechanistic insights into class IIa HDACs and facilitate the design of specific modulators.

  14. Value of diffusion-weighted imaging in predicting parametrial invasion in stage IA2-IIA cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jung Jae; Kim, Chan Kyo; Park, Sung Yoon; Park, Byung Kwan [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Bohyun [Mayo Clinic College of Medicine, Department of Radiology, Rochester, MN (United States)

    2014-05-15

    To investigate the value of diffusion-weighted imaging (DWI) in evaluating parametrial invasion (PMI) in stage IA2-IIA cervical cancer. A total of 117 patients with stage IA2-IIA cervical cancer who underwent preoperative MRI and radical hysterectomy were included in this study. Preoperative clinical variables and MRI variables were analysed and compared between the groups with and without pathologically proven PMI. All variables except age were significantly different between patients with and without pathologic PMI (P < 0.05). All variables except squamous cell carcinoma (SCC) antigen were also significantly correlated with pathologic PMI on univariate analysis (P < 0.05). Multivariate analysis indicated that PMI on MRI (P < 0.001) and tumour apparent diffusion coefficient (ADC) (P = 0.029) were independent predictors of pathologic PMI. Area under the curve of PMI on MRI increased significantly from 0.793 to 0.872 when combined with tumour ADC (P = 0.002). When PMI on MRI was further stratified by tumour ADC, the false negative rate was 2.0 % (1/49). In stage IA2-IIA cervical cancer, tumour ADC and PMI on MRI seem to be independent predictors of pathologic PMI. Combining the two predictors improved the diagnostic performance of identifying patients at low risk of pathologic PMI. (orig.)

  15. Targeting topoisomerase IIa in endometrial adenocarcinoma: a combined chromogenic in situ hybridization and immunohistochemistry study based on tissue microarrays.

    Science.gov (United States)

    Tsiambas, E; Alexopoulou, D; Lambropoulou, S; Gerontopoulos, K; Karakitsos, P; Karameris, A

    2006-01-01

    Topoisomerase IIa is a nucleic enzyme that affects the topological structure of DNA and also is a target for chemotherapy (ie, anthracyclines). In this study, we coevaluated its protein expression with chromosome 17 and gene status. Using tissue microarrays, 40 cases of sporadic, primary endometrial adenocarcinomas, 5 cases of atypical hyperplasia, and 5 cases of benign hyperplasia were obtained and reembedded into two paraffin blocks with a core diameter of 1 mm. Immunohistochemistry combined with chromogenic in situ hybridization was performed in 2 and 5 microm sections, respectively. Finally using a semiautomated Image Analysis System, we evaluated the levels of Nuclear labeling index of topoisomerase IIa expression. Statistical analysis was performed by SPSS version 11.0 software. The results indicate that chromosome 17 instability (aneuploidy in 7/40 cases) and Topo IIa gene deregulation (amplification in 3/40 and deletion in 1/40 cases) are significant genetic events correlated with biologic behavior in endometrial adenocarcinoma. Because protein overexpression was observed in a significant proportion of the tumors (18/40), detection of the specific gene deregulation mechanism is a crucial process for application of targeted chemotherapies, which are characterized by different levels of cardiotoxicity and other serious effects.

  16. Cryptosporidium parvum genotype IIa and Giardia duodenalis assemblage A in Mytilus galloprovincialis on sale at local food markets.

    Science.gov (United States)

    Giangaspero, Annunziata; Papini, Roberto; Marangi, Marianna; Koehler, Anson V; Gasser, Robin B

    2014-02-03

    To date, there has been no study to establish the genotypic or subgenotypic identities of Cryptosporidium and Giardia in edible shellfish. Here, we explored the genetic composition of these protists in Mytilus galloprovincialis (Mediterranean mussel) purchased from three markets in the city of Foggia, Italy, from May to December 2012. Samples from the digestive glands, gills and haemolymph were tested by nested PCR, targeting DNA regions within the 60 kDa glycoprotein (gp60) gene of Cryptosporidium, and the triose-phosphate isomerase (tpi) and β-giardin genes of Giardia. In total, Cryptosporidium and Giardia were detected in 66.7% of mussels (M. galloprovincialis) tested. Cryptosporidium was detected mostly between May and September 2012. Sequencing of amplicons showed that 60% of mussels contained Cryptosporidium parvum genotype IIa (including subgenotypes A15G2R1, IIaA15G2 and IIaA14G3R1), 23.3% Giardia duodenalis assemblage A, and 6.6% had both genetic types. This is the first report of these types in fresh, edible shellfish, particularly the very commonly consumed M. galloprovincialis from highly frequented fish markets. These genetic types of Cryptosporidium and Giardia are known to infect humans and thus likely to represent a significant public health risk. The poor observance of hygiene rules by vendors, coupled to the large numbers of M. galloprovincialis sold and the eating habits of consumers in Italy, call for more effective sanitary measures pertaining to the selling of fresh shellfish in street markets.

  17. Ubiquitin Ligase, MuRF-1 regulates myosin heavy chain type IIa transcripts during muscle atrophy under microgravity conditions

    Science.gov (United States)

    Kagawa, Sachiko

    Skeletal muscles are vulnerable to marked atrophy under microgravity conditions. We previously reported that gastrocnemius muscle atrophy by spaceflight was specifically sensitive to the ubiquitin-proteasome proteolytic pathway. We also screened more over 26,000 skeletal muscle genes in rats exposed to real weightlessness and found that the expression of Ubiquitin Ligase, Muscle specific Ring Finger-1 (MuRF-1) upregulated under microgravity. In the present study, we examined the role of MuRF-1 in microgravity-induced muscle atrophy. The amounts of MuRF-1 transcripts significantly increased in skeletal muscle after denervation, an in vivo model of microgravity-induced unloading. MuRF-1 deficient (MuRF-1-/-) mice significantly inhibited reduction of muscle weight for muscle atrophy, compared with wild type mice. Interestingly, MuRF-1-/- mice significantly inhibited upregulation of myosin heavy chain (MyHC) type IIa transcrips, while wild type mice significantly increased expression of MyHC type IIa transcripts in denervated skeletal muscle. Our present results suggest that MuRF-1 may play an important role in regulation of MyHC type IIa during muscle atrophy under microgravity conditions.

  18. Platelets release mitochondria serving as substrate for bactericidal group IIA-secreted phospholipase A2 to promote inflammation

    Science.gov (United States)

    Boudreau, Luc H.; Duchez, Anne-Claire; Cloutier, Nathalie; Soulet, Denis; Martin, Nicolas; Bollinger, James; Paré, Alexandre; Rousseau, Matthieu; Naika, Gajendra S.; Lévesque, Tania; Laflamme, Cynthia; Marcoux, Geneviève; Lambeau, Gérard; Farndale, Richard W.; Pouliot, Marc; Hamzeh-Cognasse, Hind; Cognasse, Fabrice; Garraud, Olivier; Nigrovic, Peter A.; Guderley, Helga; Lacroix, Steve; Thibault, Louis; Semple, John W.; Gelb, Michael H.

    2014-01-01

    Mitochondrial DNA (mtDNA) is a highly potent inflammatory trigger and is reportedly found outside the cells in blood in various pathologies. Platelets are abundant in blood where they promote hemostasis. Although lacking a nucleus, platelets contain functional mitochondria. On activation, platelets produce extracellular vesicles known as microparticles. We hypothesized that activated platelets could also release their mitochondria. We show that activated platelets release respiratory-competent mitochondria, both within membrane-encapsulated microparticles and as free organelles. Extracellular mitochondria are found in platelet concentrates used for transfusion and are present at higher levels in those that induced acute reactions (febrile nonhemolytic reactions, skin manifestations, and cardiovascular events) in transfused patients. We establish that the mitochondrion is an endogenous substrate of secreted phospholipase A2 IIA (sPLA2-IIA), a phospholipase otherwise specific for bacteria, likely reflecting the ancestral proteobacteria origin of mitochondria. The hydrolysis of the mitochondrial membrane by sPLA2-IIA yields inflammatory mediators (ie, lysophospholipids, fatty acids, and mtDNA) that promote leukocyte activation. Two-photon microscopy in live transfused animals revealed that extracellular mitochondria interact with neutrophils in vivo, triggering neutrophil adhesion to the endothelial wall. Our findings identify extracellular mitochondria, produced by platelets, at the midpoint of a potent mechanism leading to inflammatory responses. PMID:25082876

  19. Type IIA Monteggia Fracture Dislocation with Ipsilateral Distal Radius Fracture in Adult – A Rare Association

    Science.gov (United States)

    James, Boblee

    2016-01-01

    Monteggia fracture constitutes about 5-10% of the forearm fractures. Monteggia fracture by definition is proximal ulnar fracture with disruption of proximal radioulnar joint. Bado classified Monteggia fracture dislocation into four types and Jupiter subclassified type II Bado’s fractures into four types. The associated injury in the form of distal radial fractures and distal humerus fractures are rare though many cases of distal radial physeal injuries have been reported in paediatric population. Hereby we report a rare association of type IIA Monteggia fracture dislocation with ipsilateral distal radius fracture in an adult patient. This case report also highlights on proper examination and full length radiographs of forearm to avoid missing injury at wrist in cases of elbow injuries. Management of such complex injuries included open reduction and internal fixation of olecronon fracture, distal radius fracture and radial head resection. Functional outcome at six months was good at wrist whereas at elbow, stiffness was a major concern with elbow range of movement from 40°-110°. PMID:27656518

  20. Supersymmetry of IIA warped flux AdS and flat backgrounds

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2015-09-01

    We identify the fractions of supersymmetry preserved by the most general warped flux AdS and flat backgrounds in both massive and standard IIA supergravities. We find that AdS n × w M 10 - n preserve {2}^{[n/2]}k for n ≤ 4 and {2}^{[n/2]+1}k for 4 0. In addition we show that, for suitably restricted fields and M 10 - n , the killing spinors of AdS backgrounds are given in terms of the zero modes of Dirac like operators on M 10 - n . This generalizes the Lichnerowicz theorem for connections whose holonomy is included in a general linear group. We also adapt our results to ℝ 1, n - 1 × w M 10 - n backgrounds which underpin flux compactifications to ℝ 1, n - 1 and show that these preserve {2}^{[n/2]}k for 2

  1. Tracy-Widom distribution as instanton sum of 2D IIA superstrings

    CERN Document Server

    Nishigaki, Shinsuke M

    2014-01-01

    We present an analytic expression of the nonperturbative free energy of a double-well supersymmetric matrix model in its double scaling limit, which corresponds to two-dimensional type IIA superstring theory on a nontrivial Ramond-Ramond background. To this end we draw upon the wisdom of random matrix theory developed by Tracy and Widom,that expresses the largest eigenvalue distribution of unitary ensembles in terms of a Painleve II transcendent. Regularity of the result at any value of the string coupling constant shows that the third-order phase transition between a supersymmetry-preserving phase and a supersymmetry-broken phase, previously found at the planar level, becomes a smooth crossover in the double scaling limit. Accordingly, the supersymmetry is always broken spontaneously as its order parameter stays nonzero for the whole region of the coupling constant. Coincidence of the result with the unitary one-matrix model suggests that two-dimensional U(N) gauge theory corresponds to a sector of the type ...

  2. ART CCIM Phase II-A Off-Gas System Evaluation Test Plan

    Energy Technology Data Exchange (ETDEWEB)

    Nick Soelberg; Jay Roach

    2009-01-01

    This test plan defines testing to be performed using the Idaho National Laboratory (INL) engineering-scale cold crucible induction melter (CCIM) test system for Phase II-A of the Advanced Remediation Technologies (ART) CCIM Project. The multi-phase ART-CCIM Project is developing a conceptual design for replacing the joule-heated melter (JHM) used to treat high level waste (HLW) in the Defense Waste Processing Facility (DWPF) at the Savannah River Site (SRS) with a cold crucible induction melter. The INL CCIM test system includes all feed, melter off-gas control, and process control subsystems needed for fully integrated operation and testing. Testing will include operation of the melter system while feeding a non-radioactive slurry mixture prepared to simulate the same type of waste feed presently being processed in the DWPF. Process monitoring and sample collection and analysis will be used to characterize the off-gas composition and properties, and to show the fate of feed constituents, to provide data that shows how the CCIM retrofit conceptual design can operate with the existing DWPF off-gas control system.

  3. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.

    Science.gov (United States)

    Morin, Nicole A; Oakes, Patrick W; Hyun, Young-Min; Lee, Dooyoung; Chin, Y Eugene; Chin, Eugene Y; King, Michael R; Springer, Timothy A; Shimaoka, Motomu; Tang, Jay X; Reichner, Jonathan S; Kim, Minsoo

    2008-01-21

    Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.

  4. Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a phase I/IIa clinical study.

    Science.gov (United States)

    Périé, Sophie; Trollet, Capucine; Mouly, Vincent; Vanneaux, Valérie; Mamchaoui, Kamel; Bouazza, Belaïd; Marolleau, Jean Pierre; Laforêt, Pascal; Chapon, Françoise; Eymard, Bruno; Butler-Browne, Gillian; Larghero, Jérome; St Guily, Jean Lacau

    2014-01-01

    Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant genetic disease mainly characterized by ptosis and dysphagia. We conducted a phase I/IIa clinical study (ClinicalTrials.gov NCT00773227) using autologous myoblast transplantation following myotomy in adult OPMD patients. This study included 12 patients with clinical diagnosis of OPMD, indication for cricopharyngeal myotomy, and confirmed genetic diagnosis. The feasibility and safety end points of both autologous myoblast transplantation and the surgical procedure were assessed by videoendoscopy in addition to physical examinations. Potential therapeutic benefit was also assessed through videoendoscopy and videofluoroscopy of swallowing, quality of life score, dysphagia grade, and a drink test. Patients were injected with a median of 178 million myoblasts following myotomy. Short and long-term (2 years) safety and tolerability were observed in all the patients, with no adverse effects. There was an improvement in the quality of life score for all 12 patients, and no functional degradation in swallowing was observed for 10 patients. A cell dose-dependant improvement in swallowing was even observed in this study. This trial supports the hypothesis that a local injection of autologous myoblasts in the pharyngeal muscles is a safe and efficient procedure for OPMD patients.

  5. Evidence for the holographic dual of N =3 solution in massive type IIA supergravity

    Science.gov (United States)

    Pang, Yi; Rong, Junchen

    2016-03-01

    We calculate the Kaluza-Klein spectrum of spin-2 fluctuations around the N =3 warped AdS4×M6 solution in massive IIA supergravity. This solution was conjectured to be dual to the D =3 N =3 superconformal SU (N ) Chern-Simons matter theory with level k and 2 adjoint chiral multiplets. The SO (3 )R×SO (3 )D isometry of the N =3 solution is identified with the SU (2 )F×SU (2 )R global symmetry of the dual N =3 supersymmetric conformal field theory (SCFT). We show that the SO (3 )R×SO (3 )D quantum numbers and the AdS energies carried by the BPS spin-2 modes match precisely with those of the spin-2 gauge invariant operators in the short multiplets of operators in the N =3 SCFT. We also compute the Euclidean action of the N =3 solution and the free energy of the N =3 SCFT on S3, in the limit N ≫k . Remarkably, the results show a complete agreement.

  6. Detection of Listeria monocytogenes with short peptide fragments from class IIa bacteriocins as recognition elements.

    Science.gov (United States)

    Azmi, Sarfuddin; Jiang, Keren; Stiles, Michael; Thundat, Thomas; Kaur, Kamaljit

    2015-03-09

    We employed a direct peptide-bacteria binding assay to screen peptide fragments for high and specific binding to Listeria monocytogenes. Peptides were screened from a peptide array library synthesized on cellulose membrane. Twenty four peptide fragments (each a 14-mer) were derived from three potent anti-listerial peptides, Leucocin A, Pediocin PA1, and Curvacin A, that belong to class IIa bacteriocins. Fragment Leu10 (GEAFSAGVHRLANG), derived from the C-terminal region of Leucocin A, displayed the highest binding among all of the library fragments toward several pathogenic Gram-positive bacteria, including L. monocytogenes, Enterococcus faecalis, and Staphylococcus aureus. The specific binding of Leu10 to L. monocytogenes was further validated using microcantilever (MCL) experiments. Microcantilevers coated with gold were functionalized with peptides by chemical conjugation using a cysteamine linker to yield a peptide density of ∼4.8×10(-3) μmol/cm2 for different peptide fragments. Leu10 (14-mer) functionalized MCL was able to detect Listeria with same sensitivity as that of Leucocin A (37-mer) functionalized MCL, validating the use of short peptide fragments in bacterial detection platforms. Fragment Leu10 folded into a helical conformation in solution, like that of native Leucocin A, suggesting that both Leu10 and Leucocin A may employ a similar mechanism for binding target bacteria. The results show that peptide-conjugated microcantilevers can function as highly sensitive platforms for Listeria detection and hold potential to be developed as biosensors for pathogenic bacteria.

  7. Nisin and class IIa bacteriocin resistance among Listeria and other foodborne pathogens and spoilage bacteria.

    Science.gov (United States)

    Kaur, Gurpreet; Malik, Ravinder Kumar; Mishra, Santosh Kumar; Singh, Tejinder Pal; Bhardwaj, Arun; Singroha, Garima; Vij, Shilpa; Kumar, Naresh

    2011-06-01

    Food safety has been an important issue globally due to increasing foodborne diseases and change in food habits. To inactivate foodborne pathogens, various novel technologies such as biopreservation systems have been studied. Bacteriocins are ribosomally synthesized peptides or proteins with antimicrobial activity produced by different groups of bacteria, but the bacteriocins produced by many lactic acid bacteria offer potential applications in food preservation. The use of bacteriocins in the food industry can help reduce the addition of chemical preservatives as well as the intensity of heat treatments, resulting in foods that are more naturally preserved. However, the development of highly tolerant and/or resistant strains may decrease the efficiency of bacteriocins as biopreservatives. Several mechanisms of bacteriocin resistance development have been proposed among various foodborne pathogens. The acquiring of resistance to bacteriocins can significantly affect physiological activity profile of bacteria, alter cell-envelope lipid composition, and also modify the antibiotic susceptibility/resistance profile of bacteria. This article presents a brief review on the scientific research about the various possible mechanisms involved in the development of resistance to nisin and Class IIa bacteriocins among the foodborne pathogens.

  8. Reduction of atrial fibrillation by Tanshinone IIA in chronic heart failure.

    Science.gov (United States)

    He, Zhifeng; Sun, Changzheng; Xu, Yi; Cheng, Dezhi

    2016-12-01

    The aim of the present study was to confirm the effect of Tanshinone IIA (TAN) on the prevention of AF in chronic heart failure (CHF), and to elucidate the underlying electrophysiological mechanisms for the antiarrhythmic effects of TAN at the level of the atrium in an experimental model of CHF. In 10 female rabbits, CHF was induced by rapid ventricular pacing, leading to a significant decrease in ejection fraction in the presence of a dilated left ventricle and atrial enlargement. Twelve rabbits were sham-operated and served as controls. Isolated hearts were perfused using the Langendorff method. Burst pacing was used to induce AF. Monophasic action potential recordings showed an increase of atrial action potential duration (aAPD) and effective refractory period (aERP) in CHF hearts compared with sham hearts. Infusion of acetylcholine (1μm) and isoproterenol (1μm) led to AF in all failing hearts and in 11 sham hearts. Simultaneous infusion of TAN (10μm) remarkably reduced inducibility of AF in 50% of sham and 50% of failing hearts. TAN had no effect on aAPD but significantly increased aERP, leading to a marked increase in atrial post-repolarization refractoriness. Moreover, TAN application moderately increased interatrial conduction time. TAN has been shown to be effective in reducing the inducibility of AF in an experimental model of AF. The antiarrhythmic effect is mainly due to prolongations of atrial post-repolarization refractoriness and a moderate increase in interatrial conduction time.

  9. Preparation, characterization, and in vivo evaluation of tanshinone IIA solid dispersions with silica nanoparticles

    Science.gov (United States)

    Jiang, Yan-rong; Zhang, Zhen-hai; Liu, Qi-yuan; Hu, Shao-ying; Chen, Xiao-yun; Jia, Xiao-bin

    2013-01-01

    We prepared solid dispersions (SDs) of tanshinone IIA (TSIIA) with silica nanoparticles, which function as dispersing carriers, using a spray-drying method and evaluated their in vitro dissolution and in vivo performance. The extent of TSIIA dissolution in the silica nanoparticles/TSIIA system (weight ratio, 5:1) was approximately 92% higher than that of the pure drug after 60 minutes. However, increasing the content of silica nanoparticles from 5:1 to 7:1 in this system did not significantly increase the rate or extent of TSIIA dissolution. The physicochemical properties of SDs were investigated using scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, and Fourier transforms infrared spectroscopy. Studying the stability of the SDs of TSIIA revealed that the drug content of the formulation and dissolution behavior was unchanged under the applied storage conditions. In vivo tests showed that SDs of the silica nanoparticles/TSIIA had a significantly larger area under the concentration-time curve, which was 1.27 times more than that of TSIIA (P plasma concentration and the time to reach maximum plasma concentration of the SDs were higher than those of TSIIA and the physical mixing system. Based on these results, we conclude that the silica nanoparticle based SDs achieved complete dissolution, increased absorption rate, maintained drug stability, and showed improved oral bioavailability compared to TSIIA alone. PMID:23836971

  10. SLIT2/ROBO2 signaling pathway inhibits nonmuscle myosin IIA activity and destabilizes kidney podocyte adhesion

    Science.gov (United States)

    Fan, Xueping; Yang, Hongying; Kumar, Sudhir; Tumelty, Kathleen E.; Pisarek-Horowitz, Anna; Sharma, Richa; Chan, Stefanie; Tyminski, Edyta; Shamashkin, Michael; Belghasem, Mostafa; Henderson, Joel M.; Coyle, Anthony J.; Berasi, Stephen P.

    2016-01-01

    The repulsive guidance cue SLIT2 and its receptor ROBO2 are required for kidney development and podocyte foot process structure, but the SLIT2/ROBO2 signaling mechanism regulating podocyte function is not known. Here we report that a potentially novel signaling pathway consisting of SLIT/ROBO Rho GTPase activating protein 1 (SRGAP1) and nonmuscle myosin IIA (NMIIA) regulates podocyte adhesion downstream of ROBO2. We found that the myosin II regulatory light chain (MRLC), a subunit of NMIIA, interacts directly with SRGAP1 and forms a complex with ROBO2/SRGAP1/NMIIA in the presence of SLIT2. Immunostaining demonstrated that SRGAP1 is a podocyte protein and is colocalized with ROBO2 on the basal surface of podocytes. In addition, SLIT2 stimulation inhibits NMIIA activity, decreases focal adhesion formation, and reduces podocyte attachment to collagen. In vivo studies further showed that podocyte-specific knockout of Robo2 protects mice from hypertension-induced podocyte detachment and albuminuria and also partially rescues the podocyte-loss phenotype in Myh9 knockout mice. Thus, we have identified SLIT2/ROBO2/SRGAP1/NMIIA as a potentially novel signaling pathway in kidney podocytes, which may play a role in regulating podocyte adhesion and attachment. Our findings also suggest that SLIT2/ROBO2 signaling might be a therapeutic target for kidney diseases associated with podocyte detachment and loss. PMID:27882344

  11. Agujeros negros cu\\'anticos en la teor\\'ia de cuerdas tipo-IIA

    CERN Document Server

    Bueno, Pablo

    2013-01-01

    In the context of Type-IIA String Theory compactified to four dimensions on a Calabi-Yau manifold (CY), we study the effect of considering perturbative and non-perturbative corrections (in alpha prime) to the prepotential of the resulting effective Supergravity theory on the space of black hole solutions. Considering the large volume limit of the CY, in which the non-perturbative corrections are exponentially suppressed, we define a new class of solutions which turn out to be genuinely quantum, in the sense that not only their classical limit is not well defined, but also the truncation under consideration becomes inconsistent in such a limit. Next, we construct the first non-extremal black hole solution with non-constant scalars in the presence of perturbative corrections. Right after, restricting ourselves to the case of self-mirror CY, we study the case in which the sub-dominant contribution has a non-perturbative origin, obtaining the first family of explicit supersymmetric solutions of this kind. Surpris...

  12. Myosin IIA participates in docking of Glut4 storage vesicles with the plasma membrane in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Le Thi Kim, E-mail: ngocanh@nutr.med.tokushima-u.ac.jp [Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503 (Japan); Hosaka, Toshio [Department of Public Health and Applied Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima (Japan); Harada, Nagakatsu; Jambaldorj, Bayasgalan; Fukunaga, Keiko; Nishiwaki, Yuka [Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503 (Japan); Teshigawara, Kiyoshi [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan); Sakai, Tohru [Department of Public Health and Applied Nutrition, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima (Japan); Nakaya, Yutaka [Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503 (Japan); Funaki, Makoto, E-mail: m-funaki@clin.med.tokushima-u.ac.jp [Clinical Research Center for Diabetes, Tokushima University Hospital, 2-50-1 Kuramoto-cho, Tokushima 770-8503 (Japan)

    2010-01-01

    In adipocytes and myocytes, insulin stimulation translocates glucose transporter 4 (Glut4) storage vesicles (GSVs) from their intracellular storage sites to the plasma membrane (PM) where they dock with the PM. Then, Glut4 is inserted into the PM and initiates glucose uptake into these cells. Previous studies using chemical inhibitors demonstrated that myosin II participates in fusion of GSVs and the PM and increase in the intrinsic activity of Glut4. In this study, the effect of myosin IIA on GSV trafficking was examined by knocking down myosin IIA expression. Myosin IIA knockdown decreased both glucose uptake and exposures of myc-tagged Glut4 to the cell surface in insulin-stimulated cells, but did not affect insulin signal transduction. Interestingly, myosin IIA knockdown failed to decrease insulin-dependent trafficking of Glut4 to the PM. Moreover, in myosin IIA knockdown cells, insulin-stimulated binding of GSV SNARE protein, vesicle-associated membrane protein 2 (VAMP2) to PM SNARE protein, syntaxin 4 was inhibited. These data suggest that myosin IIA plays a role in insulin-stimulated docking of GSVs to the PM in 3T3-L1 adipocytes through SNARE complex formation.

  13. Mixed waste management facility groundwater monitoring report. Fourth quarter 1995 and 1995 summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-03-01

    During fourth quarter 1995, seven constituents exceeded final Primary Drinking Water Standards (PDWS) in groundwater samples from downgradient monitoring wells at the Mixed Waste Management Facility. No constituents exceeded final PDWS in samples from the upgradient monitoring wells. As in previous quarters, tritium and trichloroethylene were the most widespread elevated constituents. Chloroethene, gross alpha, lead, mercury, and tetrachloroethylene also exceeded final PDWS in one or more wells. Elevated constituents were found in numerous Aquifer Zone IIB{sub 2} (Water Table) and Aquifer Zone IIB{sub 1} (Barnwell/McBean) wells and in three Aquifer Unit IIA (Congaree) wells. The groundwater flow directions and rates in the three hydrostratigraphic units were similar to those of previous quarters.

  14. Mixed Waste Management Facility (MWMF) groundwater monitoring report. First quarter 1993

    Energy Technology Data Exchange (ETDEWEB)

    1993-06-01

    During first quarter 1993, eight constituents exceeded final Primary Drinking Water Standards in groundwater samples from downgradient monitoring wells at the Mixed Waste anagement Facility, the Old Burial Ground, the E-Area Vaults, and the proposed Hazardous Waste/Mixed Waste Disposal Vaults (HWMWDV). As in previous quarters, tritium and trichloroethylene were the most widespread constituents. Tetrachloroethylene, chloroethene, 1,1-dichloroethylene, gross alpha, lead, or nonvolatile beta levels also exceeded standards in one or more wells. The elevated constituents were found primarily in Aquifer Zone IIB{sub 2} (Water Table) and Aquifer Zone IIB{sub 1}, (Barnwell/McBean) wells. However, several Aquifer Unit IIA (Congaree) wells also contained elevated constituent levels. The groundwater flow directions and rates in the three hydrostratigraphic units were similar to previous quarters.

  15. Mixed Waste Management Facility groundwater monitoring report, First quarter 1994

    Energy Technology Data Exchange (ETDEWEB)

    1994-06-01

    During first quarter 1994, nine constituents exceeded final Primary Drinking Water Standards in groundwater samples from downgradient monitoring wells at the Mixed Waste Management Facility, the Old Burial Ground, the E-Area Vaults, the proposed Hazardous Waste/Mixed Waste Disposal Vaults, and the F-Area Sewage Sludge Application Site. As in previous quarters, tritium and trichloroethylene were the most widespread elevated constituents. Chloroethene (vinyl chloride), copper, 1,1-dichloroethylene, lead, mercury, nonvolatile beta, or tetrachloroethylene also exceeded standards in one or more wells. Elevated constituents were found in numerous Aquifer Zone IIB{sub 2} (Water Table) and Aquifer Zone IIB{sub 1}, (Barnwell/McBean) wells and in one Aquifer Unit IIA (Congaree) well. The groundwater flow directions and rates in the three hydrostratigraphic units were similar to those of previous quarters.

  16. Secreted phospholipase A2-IIA-induced a phenotype of activated microglia in BV-2 cells requires epidermal growth factor receptor transactivation and proHB-EGF shedding

    Directory of Open Access Journals (Sweden)

    Martín Rubén

    2012-07-01

    Full Text Available Abstract Background Activation of microglia, the primary component of the innate immune response in the brain, is a hallmark of neuroinflammation in neurodegenerative disorders, including Alzheimer’s disease (AD and other pathological conditions such as stroke or CNS infection. In response to a variety of insults, microglial cells produce high levels of inflammatory cytokines that are often involved in neuronal injury, and play an important role in the recognition, engulfment, and clearance of apoptotic cells and/or invading microbes. Secreted phospholipase A2-IIA (sPLA2-IIA, an enzyme that interacts with cells involved in the systemic immune/inflammatory response, has been found up-regulated in the cerebrospinal fluid and brain of AD patients. However, despite several approaches, its functions in mediating CNS inflammation remain unknown. In the present study, the role of sPLA2-IIA was examined by investigating its direct effects on microglial cells. Methods Primary and immortalized microglial cells were stimulated by sPLA2-IIA in order to characterize the cytokine-like actions of the phospholipase. The hallmarks of activated microglia analyzed include: mitogenic response, phagocytic capabilities and induction of inflammatory mediators. In addition, we studied several of the potential molecular mechanisms involved in those events. Results The direct exposure of microglial cells to sPLA2-IIA stimulated, in a time- and dose-dependent manner, their phagocytic and proliferative capabilities. sPLA2-IIA also triggered the synthesis of the inflammatory proteins COX-2 and TNFα. In addition, EGFR phosphorylation and shedding of the membrane-anchored heparin-binding EGF-like growth factor (pro-HB-EGF ectodomain, as well as a rapid activation/phosphorylation of the classical survival proteins ERK, P70S6K and rS6 were induced upon sPLA2-IIA treatment. We further demonstrated that the presence of an EGFR inhibitor (AG1478, a matrix metalloproteinase

  17. Adjuvant radiotherapy following radical hysterectomy for patients with stage IB and IIA cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Soisson, A.P.; Soper, J.T.; Clarke-Pearson, D.L.; Berchuck, A.; Montana, G.; Creasman, W.T. (Duke Univ. Medical Center, Durham, NC (USA))

    1990-06-01

    From 1971 through 1984, 320 women underwent radical hysterectomy as primary therapy of stage IB and IIA cervical cancer. Two hundred forty-eight patients (78%) were treated with surgery alone and 72 patients (22%) received adjuvant postoperative external-beam radiotherapy. Presence of lymph node metastasis, large lesion (greater than 4 cm in diameter), histologic grade, race (noncaucasian), and age (greater than 40 years) were significant poor prognostic factors for the entire group of patients. Patients treated with surgery alone had a better disease-free survival than those who received combination therapy (P less than 0.001). However, patients receiving adjuvant radiation therapy had a higher incidence of lymphatic metastases, tumor involvement of the surgical margin, and large cervical lesions. Adjuvant pelvic radiation therapy did not improve the survival of patients with unilateral nodal metastases or those who had a large cervical lesion with free surgical margins and the absence of nodal involvement. Radiation therapy appears to reduce the incidence of pelvic recurrences. Unfortunately, 84% of patients who developed recurrent tumor after combination therapy had a component of distant failure. The incidence of severe gastrointestinal or genitourinary tract complications was not different in the two treatment groups. However, the incidence of lymphedema was increased in patients who received adjuvant radiation therapy. Although adjuvant radiation therapy appears to be tolerated without a significant increase in serious complications, the extent to which it may improve local control rates and survival in high-risk patients appears to be limited. In view of the high incidence of distant metastases in high-risk patients, consideration should be given to adjuvant systemic chemotherapy in addition to radiation therapy.

  18. Effects of escins Ia, Ib, IIa, and IIb from horse chestnuts on gastric emptying in mice.

    Science.gov (United States)

    Matsuda, H; Li, Y; Murakami, T; Yamahara, J; Yoshikawa, M

    1999-03-05

    Inhibitory effects of the saponin fraction and its principal constituents, escins Ia, Ib, IIa, and IIb, from horse chestnuts on gastric emptying were investigated in mice loaded with a non-nutrient or nutrient meal. The saponin fraction and escins Ia-IIb inhibited gastric emptying of a 1.5% carboxymethyl cellulose sodium salt (CMC-Na) meal by 11.1-54.2% (12.5-200 mg/kg). Escins Ia-IIb (50 mg/kg) also inhibited gastric emptying of a 40% glucose meal by 21.1-23.5% except for escin Ia, a milk meal by 18.4-33.1%, and a 30% ethanol meal by 13.5-15.9%. The effects of escins Ia-IIb on gastric emptying of the CMC-Na meal were attenuated by pretreatment with streptozotocin (100 mg/kg, i.v.), capsaicin (75 mg/kg in total, s.c.), or insulin (1 U/kg, s.c.). The effect of insulin was reduced by glucose (2 g/kg, i.v.) which can directly nourish the brain, but not by fructose (2 g/kg, i.v.) which cannot be utilized by the brain. The effects of escins Ia-IIb (50 mg/kg) were overridden in 60% ethanol-loaded mice, in which the central nervous system was suppressed by ethanol. These results suggest that capsaicin-sensitive sensory nerves and central nervous system partly participate in the effects of escins Ia-IIb.

  19. The Development of IIA Method and the Application on the 1661 Luermen event

    Science.gov (United States)

    Wu, T. R.; Wu, H.; Hu, S. K.; Tsai, Y. L.

    2016-12-01

    In 1661, Chinese navy led by General Koxinga at the end of Ming Dynasty had a naval battle against the Netherlands. This battle was not only the first official sea warfare that China confronted the Western world, but also the only naval battle won by Chinese Navy so far. This case was significant because it altered the fate of Taiwan until today. Ace of the critical points that General Zheng won the battle was entering Lakjemuyse bay unexpected. Luermen bay was and is an extremely shallow bay with a 2.1m maximum water depth during the high tide, which was not possible for a fleet of 20,000 marines to cross. Hence, no defense was deployed from the Netherlands side. However, plenty of historical literatures mentioned a strange phenomenon that helped Chinese warships entered the Luermen bay, the rise of water level. In this study, we will discuss the possible causes that might rise the water level, e.g. Tsunami, storm surge, and high tide. We analyzed it based on the knowledge of hydrodynamics. We performed the newly developed Impact Intensify Analysis (IIA) for finding the potential tsunami sources, and the COMCOT tsunami model was adopted for the nonlinear scenario simulations, associated with the high resolution bathymetry data. Both earthquake and mudslide tsunamis were inspected. Other than that, we also collected the information of tide and weather for identifying the effects from high tide and storm surge. After the thorough study, a scenario that satisfies most of the descriptions in the historical literatures will be presented. The results will explain the cause of mysterious event that changed the destiny of Taiwan.

  20. Tanshinone IIA inhibits TNF-α-mediated induction of VCAM-1 but not ICAM-1 through the regulation of GATA-6 and IRF-1.

    Science.gov (United States)

    Nizamutdinova, Irina Tsoy; Kim, Young Min; Jin, Hana; Son, Kun Ho; Lee, Jae Heun; Chang, Ki Churl; Kim, Hye Jung

    2012-12-01

    The goal of this study was to investigate the differential effect of tanshinone IIA on the induction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by TNF-α and the possible molecular mechanisms by which it regulates ICAM-1 and VCAM-1 expression differentially. Stimulation of human umbilical vein endothelial cells (HUVEC) with TNF-α increased ICAM-1 and VCAM-1 expressions, and the pretreatment with tanshinone IIA concentration dependently inhibited VCAM-1 expression but not ICAM-1 expression. In previous study, PI3K/Akt, PKC and Jak/STAT-3 pathways were involved in the TNF-α-mediated induction of VCAM-1 but not ICAM-1. Thus, we examined the effect of tanshinone IIA on TNF-α-mediated activations of PI3K/Akt, PKC and Jak/STAT-3 pathways. Tanshinone IIA efficiently inhibited the phosphorylations of Akt, PKC and STAT-3 by TNF-α. Moreover, we determined the effect of tanshinone IIA on IRF-1 or GATAs induction and binding activity to VCAM-1 promoter since the upstream promoter region of VCAM-1 but not ICAM-1 contains IRF-1 and GATA binding motifs. Western blot analysis and ChIP assay showed that tanshinone IIA efficiently inhibited TNF-α-increased nuclear level of IRF-1 and GATA-6 and their binding affinity to VCAM-1 promoter region. Taken together, tanshinone IIA selectively inhibits TNF-α-mediated expression of VCAM-1 but not ICAM-1 through modulation of PI3/Akt, PKC and Jak/STAT-3 pathway as well as IRF-1 and GATA-6 binding activity.

  1. High ω-3:ω-6 fatty acids ratio increases fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in human ectopic endometrial cells

    Science.gov (United States)

    Khanaki, Korosh; Sadeghi, Mohammad Reza; Akhondi, Mohammad Mehdi; Darabi, Masoud; Mehdizadeh, Amir; Shabani, Mahdi; Rahimipour, Ali; Nouri, Mohammad

    2014-01-01

    Background: Endometriosis, a common chronic inflammatory disorder, is defined by the atypical growth of endometrium- like tissue outside of the uterus. Secretory phospholipase A2 group IIa (sPLA2-IIa) and fatty acid binding protein4 (FABP4) play several important roles in the inflammatory diseases. Objective: Due to reported potential anti-inflammatory effects of ω-3 and ω-6 fatty acids, the purpose of the present study was to investigate the effects of ω-3 and ω-6 polyunsaturated fatty acids (PUFAs) on fatty acid binding protein 4 and extracellular secretory phospholipase A2IIa in cultured endometrial cells. Materials and Methods: Ectopic and eutopic endometrial tissues obtained from 15 women were snap frozen. After thawing and tissue digestion, primary mixed stromal and endometrial epithelial cell culture was performed for 8 days in culture mediums supplemented with normal and high ratios of ω-3 and ω-6 PUFA. sPLA2-IIa in the culture medium and FABP4 level was determined using enzyme immuno assay (EIA) technique. Results: Within ectopic endometrial cells group, the level of cellular FABP4 and extracellular sPLA2-IIa were remarkably increased under high ω-3 PUFA exposure compared with control condition (p=0.014 and p=0.04 respectively). Conclusion: ω-3 PUFAs may increase the level of cellular FABP4 and extracellular sPLA2-IIa in ectopic endometrial cells, since sPLAIIa and FABP4 may affect endometriosis via several mechanisms, more relevant studies are encouraged to know the potential effect of increased cellular FABP4 and extracellular sPLA2-IIa on endometriosis. PMID:25709631

  2. Identification of structural determinants for inhibition strength and specificity of wheat xylanase inhibitors TAXI-IA and TAXI-IIA.

    Science.gov (United States)

    Pollet, Annick; Sansen, Stefaan; Raedschelders, Gert; Gebruers, Kurt; Rabijns, Anja; Delcour, Jan A; Courtin, Christophe M

    2009-07-01

    Triticum aestivum xylanase inhibitor (TAXI)-type inhibitors are active against microbial xylanases from glycoside hydrolase family 11, but the inhibition strength and the specificity towards different xylanases differ between TAXI isoforms. Mutational and biochemical analyses of TAXI-I, TAXI-IIA and Bacillus subtilis xylanase A showed that inhibition strength and specificity depend on the identity of only a few key residues of inhibitor and xylanase [Fierens K et al. (2005) FEBS J 272, 5872-5882; Raedschelders G et al. (2005) Biochem Biophys Res Commun335, 512-522; Sorensen JF & Sibbesen O (2006) Protein Eng Des Sel 19, 205-210; Bourgois TM et al. (2007) J Biotechnol 130, 95-105]. Crystallographic analysis of the structures of TAXI-IA and TAXI-IIA in complex with glycoside hydrolase family 11 B. subtilis xylanase A now provides a substantial explanation for these observations and a detailed insight into the structural determinants for inhibition strength and specificity. Structures of the xylanaseinhibitor complexes show that inhibition is established by loop interactions with active-site residues and substrate-mimicking contacts in the binding subsites. The interaction of residues Leu292 of TAXI-IA and Pro294 of TAXI-IIA with the -2 glycon subsite of the xylanase is shown to be critical for both inhibition strength and specificity. Also, detailed analysis of the interaction interfaces of the complexes illustrates that the inhibition strength of TAXI is related to the presence of an aspartate or asparagine residue adjacent to the acid/base catalyst of the xylanase, and therefore to the pH optimum of the xylanase. The lower the pH optimum of the xylanase, the stronger will be the interaction between enzyme and inhibitor, and the stronger the resulting inhibition.

  3. Magnetic Resonance Imaging as a Valuable Tool for Predicting Parametrial Invasion in Stage IB1 to IIA2 Cervical Cancer.

    Science.gov (United States)

    Kim, Miseon; Suh, Dong Hoon; Kim, Kidong; Lee, Hak Jong; Kim, Yong Beom; No, Jae Hong

    2017-02-01

    The aims of study were to determine the predictive value of preoperative magnetic resonance imaging (MRI) for parametrial invasion (PMI) and to develop a predictive model for PMI in patients with stage IB1 to IIA2 cervical cancer. We retrospectively analyzed patients with stage IB1 to IIA2 cervical cancer (n = 215) who underwent radical hysterectomy between 2003 and 2014. The presence of PMI from postoperative pathological reports and its association with preoperative MRI findings were evaluated. We developed a predictive model for PMI using independent predictive factors identified by logistic regression and estimated its predictive performance. Thirty patients (14.0%) had PMI from postoperative pathological reports. Among the preoperative MRI findings, a greater tumor diameter (4.2 vs 2.0 cm; P PMI (53.3% vs 8.6%; P PMI. Multivariate analysis identified tumor volume (odds ratio, 7.0; 95% confidence interval, 2.63-18.53; P PMI (odds ratio, 6.1; 95% confidence interval, 2.31-15.97; P PMI. Our predictive model demonstrates that the presence of PMI or a tumor volume of greater than 18.0 cm has a higher sensitivity (86.7% vs 53.3%) and lower specificity (74.6% vs 91.4%) than the presence of PMI alone. Specifically, the model's negative predictive value was superior to that of PMI only (97.2% vs 92.3%). In the low-risk group, defined as preoperative MRI findings suggesting no PMI and a tumor volume of 18.0 cm or less, the proportion of false negative cases was just 2.8%. When tumor volume with findings suggesting that PMI is considered, preoperative MRI is useful in excluding PMI. A predictive model based on preoperative MRI findings seems to be valuable in identifying potential candidates for less radical surgery in stage IB1 to IIA2 cervical cancer.

  4. The elusive third subunit IIa of the bacterial B-type oxidases: the enzyme from the hyperthermophile Aquifex aeolicus.

    Directory of Open Access Journals (Sweden)

    Laurence Prunetti

    Full Text Available The reduction of molecular oxygen to water is catalyzed by complicated membrane-bound metallo-enzymes containing variable numbers of subunits, called cytochrome c oxidases or quinol oxidases. We previously described the cytochrome c oxidase II from the hyperthermophilic bacterium Aquifex aeolicus as a ba(3-type two-subunit (subunits I and II enzyme and showed that it is included in a supercomplex involved in the sulfide-oxygen respiration pathway. It belongs to the B-family of the heme-copper oxidases, enzymes that are far less studied than the ones from family A. Here, we describe the presence in this enzyme of an additional transmembrane helix "subunit IIa", which is composed of 41 amino acid residues with a measured molecular mass of 5105 Da. Moreover, we show that subunit II, as expected, is in fact longer than the originally annotated protein (from the genome and contains a transmembrane domain. Using Aquifex aeolicus genomic sequence analyses, N-terminal sequencing, peptide mass fingerprinting and mass spectrometry analysis on entire subunits, we conclude that the B-type enzyme from this bacterium is a three-subunit complex. It is composed of subunit I (encoded by coxA(2 of 59000 Da, subunit II (encoded by coxB(2 of 16700 Da and subunit IIa which contain 12, 1 and 1 transmembrane helices respectively. A structural model indicates that the structural organization of the complex strongly resembles that of the ba(3 cytochrome c oxidase from the bacterium Thermus thermophilus, the IIa helical subunit being structurally the lacking N-terminal transmembrane helix of subunit II present in the A-type oxidases. Analysis of the genomic context of genes encoding oxidases indicates that this third subunit is present in many of the bacterial oxidases from B-family, enzymes that have been described as two-subunit complexes.

  5. Mixed Waste Management Facility (MWMF) groundwater monitoring report

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, C.Y.

    1992-06-01

    During first quarter 1992, tritium, trichloroethylene, tetrachloroethylene, lead, antimony, I,I-dichloroethylene, 1,2-dichloroethane, gross alpha, mercury, nickel, nitrate, nonvolatile beta, and total alpha-emitting radium (radium-224 and radium-226) exceeded the US Environmental Protection Agency Primary Drinking Water Standards (PDWS) in groundwater samples from monitoring wells at the Mixed Waste Management Facility (MWMF) and adjacent facilities. Tritium and trichloroethylene were the most widespread constituents; 57 (49%) of the 116 monitored wells contained elevated tritium activities, and 21 (18%) wells exhibited elevated trichloroethylene concentrations Sixty-one downgradient wells screened in Aquifer Zone IIB2 (Water Table), Aquifer Zone IIB[sub 2] (Barnwell/McBean), and Aquifer Unit IIA (Congaree) contained constituents that exceeded the PDWS during first quarter 1992. Upgradient wells BGO 1D and HSB 85A, BC, and 85C did not contain any constituents that exceeded the PDWS. Upgradient well BGO 2D contained elevated tritium.

  6. Mixed Waste Management Facility (MWMF) groundwater monitoring report. First quarter 1992

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, C.Y.

    1992-06-01

    During first quarter 1992, tritium, trichloroethylene, tetrachloroethylene, lead, antimony, I,I-dichloroethylene, 1,2-dichloroethane, gross alpha, mercury, nickel, nitrate, nonvolatile beta, and total alpha-emitting radium (radium-224 and radium-226) exceeded the US Environmental Protection Agency Primary Drinking Water Standards (PDWS) in groundwater samples from monitoring wells at the Mixed Waste Management Facility (MWMF) and adjacent facilities. Tritium and trichloroethylene were the most widespread constituents; 57 (49%) of the 116 monitored wells contained elevated tritium activities, and 21 (18%) wells exhibited elevated trichloroethylene concentrations Sixty-one downgradient wells screened in Aquifer Zone IIB2 (Water Table), Aquifer Zone IIB{sub 2} (Barnwell/McBean), and Aquifer Unit IIA (Congaree) contained constituents that exceeded the PDWS during first quarter 1992. Upgradient wells BGO 1D and HSB 85A, BC, and 85C did not contain any constituents that exceeded the PDWS. Upgradient well BGO 2D contained elevated tritium.

  7. Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

    Science.gov (United States)

    Andruchov, Oleg; Galler, Stefan

    2008-03-01

    This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

  8. A Precision Measurement of the W Boson Mass with 1 Inverse Femtobarn of DZero Run IIa Data

    Energy Technology Data Exchange (ETDEWEB)

    Osta, Jyotsna [Univ. of Notre Dame, IN (United States)

    2009-12-01

    This thesis is a detailed presentation of a precision measurement of the mass of the W boson. It has been obtained by analyzing W → ev decays. The data used for this analysis was collected from 2002 to 2006 with the D0 detector, during Run IIa of the Fermilab Tevatron collider. It corresponds to a total integrated luminosity of 1 fb-1. With a sample of 499,830 W → ev candidate events, we obtain a mass measurement of MW = 80.401 ± 0.043 GeV. This is the most precise measurement from a single experiment to date.

  9. Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

    OpenAIRE

    Khan, Saeed R.; Glenton, Patricia A.

    2008-01-01

    The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric an...

  10. C1-C3 lateral mass fusion for type IIa and type III Hangman′s fracture

    Directory of Open Access Journals (Sweden)

    Natarajan Muthukumar

    2012-01-01

    Full Text Available Hangman′s fractures, also known as traumatic spondylolisthesis of axis, can be managed either conservatively with immobilization or by surgery. Surgery is usually indicated in cases with instability or failure of conservative treatment. Different surgical approaches, both anterior and posterior, have been described for treating Hangman′s fracture. We report two patients, one with type IIa and another with type III Hangman′s fracture treated with C1-C3 lateral mass fusion and discuss the advantages and limitations of this technique when compared to other techniques for fusion in patients with Hangman′s fracture.

  11. Advanced Start of Combustion Sensor Phases I and II-A: Feasibility Demonstration, Design and Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Chad Smutzer

    2010-01-31

    Homogeneous Compressed Charge Ignition (HCCI) has elevated the need for Start of Combustion (SOC) sensors. HCCI engines have been the exciting focus of engine research recently, primarily because HCCI offers higher thermal efficiency than the conventional Spark Ignition (SI) engines and significantly lower NOx and soot emissions than conventional Compression Ignition (CI) engines, and could be fuel neutral. HCCI has the potential to unify all the internal combustion engine technology to achieve the high-efficiency, low-emission goal. However, these advantages do not come easy. It is well known that the problems encountered with HCCI combustion center on the difficulty of controlling the Start of Combustion. TIAX has an SOC sensor under development which has shown promise. In previous work, including a DOE-sponsored SBIR project, TIAX has developed an accelerometer-based method which was able to determine SOC within a few degrees crank angle for a range of operating conditions. A signal processing protocol allows reconstruction of the combustion pressure event signal imbedded in the background engine vibration recorded by the accelerometer. From this reconstructed pressure trace, an algorithm locates the SOC. This SOC sensor approach is nonintrusive, rugged, and is particularly robust when the pressure event is strong relative to background engine vibration (at medium to high engine load). Phase I of this project refined the previously developed technology with an engine-generic and robust algorithm. The objective of the Phase I research was to answer two fundamental questions: Can the accelerometer-based SOC sensor provide adequate SOC event capture to control an HCCI engine in a feedback loop? And, will the sensor system meet cost, durability, and software efficiency (speed) targets? Based upon the results, the answer to both questions was 'YES'. The objective of Phase II-A was to complete the parameter optimization of the SOC sensor prototype in order

  12. Glucose-specific enzyme IIA has unique binding partners in the vibrio cholerae biofilm.

    Science.gov (United States)

    Pickering, Bradley S; Smith, Daniel R; Watnick, Paula I

    2012-11-06

    Glucose-specific enzyme IIA (EIIA(Glc)) is a central regulator of bacterial metabolism and an intermediate in the phosphoenolpyruvate phosphotransferase system (PTS), a conserved phosphotransfer cascade that controls carbohydrate transport. We previously reported that EIIA(Glc) activates transcription of the genes required for Vibrio cholerae biofilm formation. While EIIA(Glc) modulates the function of many proteins through a direct interaction, none of the known regulatory binding partners of EIIA(Glc) activates biofilm formation. Therefore, we used tandem affinity purification (TAP) to compare binding partners of EIIA(Glc) in both planktonic and biofilm cells. A surprising number of novel EIIA(Glc) binding partners were identified predominantly under one condition or the other. Studies of planktonic cells revealed established partners of EIIA(Glc), such as adenylate cyclase and glycerol kinase. In biofilms, MshH, a homolog of Escherichia coli CsrD, was found to be a dominant binding partner of EIIA(Glc). Further studies revealed that MshH inhibits biofilm formation. This function was independent of the Carbon storage regulator (Csr) pathway and dependent on EIIA(Glc). To explore the existence of multiprotein complexes centered on EIIA(Glc), we also affinity purified the binding partners of adenylate cyclase from biofilm cells. In addition to EIIA(Glc), this analysis yielded many of the same proteins that copurified with EIIA(Glc). We hypothesize that EIIA(Glc) serves as a hub for multiprotein complexes and furthermore that these complexes may provide a mechanism for competitive and cooperative interactions between binding partners. EIIA(Glc) is a global regulator of microbial physiology that acts through direct interactions with other proteins. This work represents the first demonstration that the protein partners of EIIA(Glc) are distinct in the microbial biofilm. Furthermore, it provides the first evidence that EIIA(Glc) may exist in multiprotein complexes with

  13. Advanced Start of Combustion Sensor Phases I and II-A: Feasibility Demonstration, Design and Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Chad Smutzer

    2010-01-31

    Homogeneous Compressed Charge Ignition (HCCI) has elevated the need for Start of Combustion (SOC) sensors. HCCI engines have been the exciting focus of engine research recently, primarily because HCCI offers higher thermal efficiency than the conventional Spark Ignition (SI) engines and significantly lower NOx and soot emissions than conventional Compression Ignition (CI) engines, and could be fuel neutral. HCCI has the potential to unify all the internal combustion engine technology to achieve the high-efficiency, low-emission goal. However, these advantages do not come easy. It is well known that the problems encountered with HCCI combustion center on the difficulty of controlling the Start of Combustion. TIAX has an SOC sensor under development which has shown promise. In previous work, including a DOE-sponsored SBIR project, TIAX has developed an accelerometer-based method which was able to determine SOC within a few degrees crank angle for a range of operating conditions. A signal processing protocol allows reconstruction of the combustion pressure event signal imbedded in the background engine vibration recorded by the accelerometer. From this reconstructed pressure trace, an algorithm locates the SOC. This SOC sensor approach is nonintrusive, rugged, and is particularly robust when the pressure event is strong relative to background engine vibration (at medium to high engine load). Phase I of this project refined the previously developed technology with an engine-generic and robust algorithm. The objective of the Phase I research was to answer two fundamental questions: Can the accelerometer-based SOC sensor provide adequate SOC event capture to control an HCCI engine in a feedback loop? And, will the sensor system meet cost, durability, and software efficiency (speed) targets? Based upon the results, the answer to both questions was 'YES'. The objective of Phase II-A was to complete the parameter optimization of the SOC sensor prototype in order

  14. Behavior of crystal defects in synthetic type-IIa single-crystalline diamond at high temperatures under normal pressure

    Science.gov (United States)

    Tatsumi, Natsuo; Tamasaku, Kenji; Ito, Toshimichi; Sumiya, Hitoshi

    2017-01-01

    The behavior of dislocation lines (DLs) and stacking faults (SFs) in synthetic type-IIa single-crystalline diamond at high temperatures under normal pressure has been investigated. After annealing the diamond at 1500 °C for 60 min in pure N2 atmosphere, straight DLs were bent to converge to fewer curved dislocation bundles, so that some of the stacking faults were extinct while new DLs appeared at the edges of the removed SFs. These results indicate that SFs in the diamond examined belong to the Shockley type, and that the Shockley partials changed to a perfect dislocation. From this result, the following generation mechanism has been proposed for SFs in diamond. On one hand, because [112] dislocations in the (111) growth sector are contained in the slip plane labelled as (1 ̅ 1 ̅ 1), one perfect dislocation tends to be split into two Shockley partials and a SF when an appropriate stress is applied. On the other hand, the angle between the {111} slip plane and the direction of bundled dislocations in the (001) growth sector is as high as 54.7°, so that a perfect dislocation can hardly slip into partial dislocations. Thus, SFs exist only in the (111) growth sector of type IIa diamond.

  15. Circadian pattern and the effect of standardized physical exercise on procollagen IIA N-peptide (PIIANP) in rheumatoid arthritis at different stages and in healthy individuals

    DEFF Research Database (Denmark)

    Christensen, Anne Friesgaard; Lottenburger, T; Lindegaard, Hanne Merete;

    2010-01-01

    Background: Variant collagen IIA is re-expressed in diseased cartilage. Low procollagen IIA N-peptide (PIIANP) levels in serum have recently been reported in rheumatoid arthritis (RA). We investigated circadian rhythmicity and effect of physical activity on PIIANP in early and longstanding RA...... and in healthy subjects. Methods: Patients with early and longstanding RA and controls were included. Fasting and serial blood samples were collected during 24 h. PIIANP response to physical activity was studied before and serially after standardized exercise. Results and conclusion: In RA at different stages...

  16. Preoperatively Assessable Clinical and Pathological Risk Factors for Parametrial Involvement in Surgically Treated FIGO Stage IB-IIA Cervical Cancer.

    Science.gov (United States)

    Canaz, Emel; Ozyurek, Eser Sefik; Erdem, Baki; Aldikactioglu Talmac, Merve; Yildiz Ozaydin, Ipek; Akbayir, Ozgur; Numanoglu, Ceyhun; Ulker, Volkan

    2017-06-14

    Determining the risk factors associated with parametrial involvement (PMI) is of paramount importance to decrease the multimodality treatment in early-stage cervical cancer. We investigated the preoperatively assessable clinical and pathological risk factors associated with PMI in surgically treated stage IB1-IIA2 cervical cancer. A retrospective cohort study of women underwent Querleu-Morrow type C hysterectomy for cervical cancer stage IB1-IIA2 from 2001 to 2015. All patients underwent clinical staging examination under anesthesia by the same gynecological oncologists during the study period. Evaluated variables were age, menopausal status, body mass index, smoking status, FIGO (International Federation of Obstetrics and Gynecology) stage, clinically measured maximal tumor diameter, clinical presentation (exophytic or endophytic tumor), histological type, tumor grade, lymphovascular space invasion, clinical and pathological vaginal invasion, and uterine body involvement. Endophytic clinical presentation was defined for ulcerative tumors and barrel-shaped morphology. Two-dimensional transvaginal ultrasonography was used to measure tumor dimensions. Of 127 eligible women, 37 (29.1%) had PMI. On univariate analysis, endophytic clinical presentation (P = 0.01), larger tumor size (P PMI. In multivariate analysis endophytic clinical presentation (odds ratio, 11.34; 95% confidence interval, 1.34-95.85; P = 0.02) and larger tumor size (odds ratio, 32.31; 95% confidence interval, 2.46-423.83; P = 0.008) were the independent risk factors for PMI. Threshold of 31 mm in tumor size predicted PMI with 71% sensitivity and 75% specificity. We identified 18 patients with tumor size of more than 30 mm and endophytic presentation; 14 (77.7%) of these had PMI. Endophytic clinical presentation and larger clinical tumor size (>3 cm) are independent risk factors for PMI in stage IB-IIA cervical cancer. Approximately 78% of the patients with a tumor size of more than 3 cm and endophytic

  17. 不同治疗方案治疗IB2、IIA2期宫颈癌预后分析%Comparison of different treatment regimens for IB2 and IIA2 cervical cancer

    Institute of Scientific and Technical Information of China (English)

    Dongxia Liang; Yanna Zhang; Xueming Sun; Jinrui Sun; Liqun Xu

    2012-01-01

    Objective: The aim of this study was to explore the difference of long-term prognosis of different treatment regimens in patients with stage IB2, IIA2 cervical cancer. Methods: From August 1995 to September 2005, radical hysterectomy was chosen as primary treatment regimen for 122 patients (group A), 85 patients underwent radical hysterectomy after effective neoadjuvant therapy (group B), and 98 patients received surgery after ineffective preoperative therapy (group C). All patients received postoperative therapy. Results: A total of 305 patients were analyzed. The maximum diameter of tumor was largest in group B, while the pathological risk factors (cervical infiltration, positive surgical margins) were in the lowest proportion. The 5-year mortality rate and relapse rate of group B were the highest, and the overall survival (OS) and progression-free survival (PFS) were the shortest (P < 0.05). No significant difference of long-term survival was found in group C and group A. No difference was found in the surgical of three groups. Large tumor more than 5.5 cm had higher effective ratio of treatment than those 5.5 cm or less. Patients received effective preoperative radiotherapy had better long-term prognosis than those received chemotherapy or radiochemotherapy. Conclusion: neoadjuvant treatment using for patients with IB2, IIA2 cervical cancer is effective in reducing risk factors of pathological, but it could not improve the long-term survival. The indications of adjuvant therapy after surgery should be reconsidered. Those tumors of diameter 5.5 cm or less response poor to neoadjuvant treatment, and no improvement of survival was found, so direct surgical treatment is suggested for these patients. Radiotherapy is a better choice of preoperative treatment.

  18. Genetic and antigenic characteristics of ApxIIA and ApxIIIA from Actinobacillus pleuropneumoniae serovars 2, 3, 4, 6, 8 and 15.

    Science.gov (United States)

    To, Ho; Nagai, Shinya; Iwata, Akira; Koyama, Tomohiro; Oshima, Atsushi; Tsutsumi, Nobuyuki

    2016-07-01

    Apx toxins produced by Actinobacillus pleuropneumoniae are essential components of new generation vaccines. In this study, apxIIA and apxIIIA genes of serovars 2, 3, 4, 6, 8 and 15 were cloned and sequenced. Amino acid sequences of ApxIIA proteins of serovars 2, 3, 4, 6, 8 and 15 were almost identical to those of serovars 1, 5, 7, 9 and 11-13. Immunoblot analysis showed that rApxIIA from serovars 2 and 15 reacts strongly with sera from animals infected with various serovars. Sequence analysis revealed that ApxIIIA proteins has two variants, one in strains of serovar 2 and the other in strains of serovars 3, 4, 6, 8 and 15. A mouse cross-protection study showed that mice actively immunized with rApxIIIA/2 or rApxIIIA/15 are protected against challenge with A. pleuropneumoniae strains of serovars 3, 4, 6, 8, 15, and 2 expressing ApxIII/15 and ApxIII/2, respectively. Similarly, mice passively immunized with rabbit anti-rApxIIIA/2 or anti-rApxIIIA/15 sera were found to be protected against challenge with strains of serovars 2 and 15. Our study revealed antigenic and sequence similarities within ApxIIA and ApxIIIA proteins, which may help in the development of effective vaccines against disease caused by A. pleuropneumoniae. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

  19. Evaluation of heat-labile enterotoxins type IIa and type IIb in the pathogenicity of enterotoxigenic Escherichia coli for neonatal pigs

    Science.gov (United States)

    Type II heat-labile enterotoxins (LT-II) have been reported in Escherichia coli isolates from humans, animals, food and water samples. The roles of the antigenically distinguishable LT-IIa and LT-IIb subtypes in pathogenesis and virulence of enterotoxigenic E. coli (ETEC) have not been previously re...

  20. ATP6V0A2 mutations present in two Mexican Mestizo children with an autosomal recessive cutis laxa syndrome type IIA

    Directory of Open Access Journals (Sweden)

    D. Bahena-Bahena

    2014-01-01

    Full Text Available Patients with ARCL-IIA harbor mutations in ATP6V0A2 that codes for an organelle proton pump. The ARCL-IIA syndrome characteristically presents a combined glycosylation defect affecting N-linked and O-linked glycosylations, differentiating it from other cutis laxa syndromes and classifying it as a Congenital Disorder of Glycosylation (ATP6V0A2-CDG. We studied two Mexican Mestizo patients with a clinical phenotype corresponding to an ARCL-IIA syndrome. Both patients presented abnormal transferrin (N-linked glycosylation but Patient 1 had a normal ApoCIII (O-linked glycosylation profile. Mutational screening of ATP6V0A2 using cDNA and genomic DNA revealed in Patient 1 a previously reported homozygous nonsense mutation c.187C>T (p.R63X associated with a novel clinical finding of a VSD. In Patient 2 we found a homozygous c.2293C>T (p.Q765X mutation that had been previously reported but found that it also altered RNA processing generating a novel transcript not previously identified (r.2176_2293del; p.F726Sfs*10. This is the first report to describe Mestizo patients with molecular diagnosis of ARCL-IIA/ATP6V0A2-CDG and to establish that their mutations are the first to be found in patients from different regions of the world and with different genetic backgrounds.

  1. Induction of protective immune responses against the challenge of Actinobacillus pleuropneumoniae by the oral administration of transgenic tobacco plant expressing ApxIIA toxin from the bacteria.

    Science.gov (United States)

    Lee, Kyung-Yeol; Kim, Dong-Heon; Kang, Tae-Jin; Kim, Ju; Chung, Gook-Hyun; Yoo, Han-Sang; Arntzen, Charles J; Yang, Moon-Sik; Jang, Yong-Suk

    2006-12-01

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia. Among the virulence factors, ApxIIA, a bacterial exotoxin, is reportedly expressed in many serotypes and is considered as a candidate for the development of a vaccine against the bacterial infection. Previously, we isolated a field strain of A. pleuropneumoniae serotype 2 in Korea and characterized its exotoxins to develop an oral vaccine. In this study, we initially confirmed the immunogenicity of ApxIIA expressed in Escherichia coli. We then developed transgenic tobacco expressing ApxIIA and tested its efficacy to induce a protective immune response against A. pleuropneumoniae infection after oral administration of the plant powder. We observed that protective immune responses were induced in mice after oral administration of the plant powder once a week for 4 weeks. Immunoassays revealed that the levels of antigen-specific immunoglobulin G against ApxIIA increased in mice that were fed a powder made from the transgenic plant, but not in mice fed a powder made from wild-type tobacco. Additionally, mice fed the transgenic plant powder were protected from an injection of a lethal dose of A. pleuropneumoniae. These results support that the transgenic plant may be a suitable candidate for an oral vaccine that could be used effectively against A. pleuropneumoniae infection.

  2. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    Energy Technology Data Exchange (ETDEWEB)

    Kuroki, Tsunehide, E-mail: kuroki@dg.kagawa-nct.ac.jp [General Eduction, National Institute of Technology, Kagawa College, 551 Kohda, Takuma-cho, Mitoyo, Kagawa 769-1192 (Japan); Sugino, Fumihiko, E-mail: fusugino@gmail.com [Okayama Institute for Quantum Physics, Furugyocho 1-7-36, Naka-ku, Okayama 703-8278 (Japan)

    2017-06-15

    In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond–Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  3. Targeted delivery of tanshinone IIA-conjugated mPEG-PLGA-PLL-cRGD nanoparticles to hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Yan; Song, Daqian; Costanza, Frankie; Ji, Guang; Fan, Zhongze; Cai, Jianfeng; Li, Qi

    2014-11-01

    Tanshinone IIA (TSIIA) is an active constituent of the traditional Chinese medicinal plant Salvia miltiorrhiza that is known to have anti-tumor properties. In order to increase the selectivity of TSIIA's anti-tumor activity, the current study evaluated the tumor-targeting efficacy of TSIIA incorporated into nanoparticles (NPs). TSIIA was loaded into mPEG-PLGA-PLL-cRGD (methoxy polyethylene glycol, polylactic-co-glycolic acid, poly-L-lysine, cyclic arginine-glycine-aspartic acid) nanoparticles (TNPs) and used to treat hepatocellular carcinoma in vitro and in vivo. Our data demonstrate that TNPs were stable and had an even size distribution as well as an extended TSIIA releasing time, and improved tumor-targeting activity. As a novel drug carrier system, TNPs significantly inhibited the development of liver cancer both in vitro and in vivo, proving to be a novel promising targeted treatment for liver cancer.

  4. Heritability assessment of cartilage metabolism. A twin study on circulating procollagen IIA N-terminal propeptide (PIIANP)

    DEFF Research Database (Denmark)

    Munk, H L; Svendsen, A J; Hjelmborg, J V B;

    2014-01-01

    OBJECTIVE: The aim of this investigation was to estimate the heritability of circulating collagen IIA N-terminal propeptide (PIIANP) by studying mono- and dizygotic healthy twin pairs at different age and both genders. DESIGN: 598 monozygotic (MZ) and dizygotic (DZ) twin individuals aged 18......-59 years were recruited from the Danish Twin Registry. PIIANP was measured by competitive ELISA. The similarity of circulating PIIANP among MZ and DZ twins was assessed by intraclass correlations according to traits. The heritability was estimated by variance component analysis accounting for additive...... and dominant genetic factors as well as shared and non-shared environment but ignoring epistasis (genetic inter-locus interaction) and gene-environment interaction. RESULTS: The intraclass correlation of PIIANP in MZ and DZ twins was 0.69 (0.60-0.76) and 0.46 (0.34-0.58) respectively indicating a significant...

  5. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    CERN Document Server

    Kuroki, Tsunehide

    2016-01-01

    In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond-Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supers...

  6. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    Science.gov (United States)

    Kuroki, Tsunehide; Sugino, Fumihiko

    2017-06-01

    In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond-Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  7. Inhibition of Tanshinone IIA, Salvianolic Acid A and Salvianolic Acid B on Areca Nut Extract-Induced Oral Submucous Fibrosis in Vitro

    Directory of Open Access Journals (Sweden)

    Jian-Ping Dai

    2015-04-01

    Full Text Available Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA, salvianolic acid A (Sal-A and salvianolic acid B (Sal-B, the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE-induced oral submucous fibrosis (OSF in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs, inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

  8. Qualitative detection of class IIa bacteriocinogenic lactic acid bacteria from traditional Chinese fermented food using a YGNGV-motif-based assay.

    Science.gov (United States)

    Liu, Wenli; Zhang, Lanwei; Yi, Huaxi; Shi, John; Xue, Chaohui; Li, Hongbo; Jiao, Yuehua; Shigwedha, Nditange; Du, Ming; Han, Xue

    2014-05-01

    In the present study, a YGNGV-motif-based assay was developed and applied. Given that there is an increasing demand for natural preservatives, we set out to obtain lactic acid bacteria (LAB) that produce bacteriocins against Gram-positive and Gram-negative bacteria. We here isolated 123 LAB strains from 5 types of traditional Chinese fermented food and screened them for the production of bacteriocins using the agar well diffusion assay (AWDA). Then, to acquire LAB producing class IIa bacteriocins, we used a YGNGV-motif-based assay that was based on 14 degenerate primers matching all class IIa bacteriocin-encoding genes currently deposited in NCBI. Eight of the LAB strains identified by AWDA could inhibit Gram-positive and Gram-negative bacteria; 5 of these were YGNGV-amplicon positive. Among these 5 isolates, amplicons from 2 strains (Y31 and Y33) matched class IIa bacteriocin genes. Strain Y31 demonstrated the highest inhibitory activity and the best match to a class IIa bacteriocin gene in NCBI, and was identified as Enterococcus faecium. The bacteriocin from Enterococcus avium Y33 was 100% identical to enterocin P. Both of these strains produced bacteriocins with strong antimicrobial activity against Listeria monocytogenes, Escherichia coli, and Bacillus subtilis, hence these bacteriocins hold promise as potential bio-preservatives in the food industry. These findings also indicated that the YGNGV-motif-based assay used in this study could identify novel class IIa bacteriocinogenic LAB, rapidly and specifically, saving time and labour by by-passing multiple separation and purification steps.

  9. Inhibition of Tanshinone IIA, salvianolic acid A and salvianolic acid B on Areca nut extract-induced oral submucous fibrosis in vitro.

    Science.gov (United States)

    Dai, Jian-Ping; Zhu, Dan-Xia; Sheng, Jiang-Tao; Chen, Xiao-Xuan; Li, Wei-Zhong; Wang, Ge-Fei; Li, Kang-Sheng; Su, Yun

    2015-04-15

    Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

  10. Therapeutic options in early stage testicular seminoma. Literature survey on first results of a prospective multi-center study on radiotherapy of seminoma in the clinical stages I, IIA and IIB; Therapieoptionen bei testikulaeren Seminomen in den fruehen Stadien. Literaturuebersicht mit ersten Ergebnissen einer prospektiven multizentrischen Studie zur Radiotherapie bei Seminomen in den klinischen Stadien I, IIA und IIB

    Energy Technology Data Exchange (ETDEWEB)

    Schmidberger, H. [Radiologische Universitaetsklinik Tuebingen (Germany). Abt. fuer Strahlentherapie; Bamberg, M. [Radiologische Universitaetsklinik Tuebingen (Germany). Abt. fuer Strahlentherapie

    1995-03-01

    Testicular seminoma in the early stages is treated with orchiectomy and radiotherapy to the retroperitoneal nodes. Despite the high cure rates of this treatment, there is an ongoing controversy concerning the extent of the radiation fields and the radiation doses to be given in the clinical stages I, IIA and IIB. In the present literature review, these controversial issues are discussed. Four hundred and ninety-one patients in stage I testicular seminoma received adjuvant paraaortic irradiation with a total dose of 26 Gy. Forty-one patients in stage IIA, and 19 patients in stage IIB received 30 Gy or 36 Gy respectively to the paraaortic and ipsilateral iliacal nodes. Paraaortic radiotherapy in stage I disease was associated with low acute side effects and a disease-free survival in 97.1% of the patients after a median observation of 13 months. In stage IIA the disease-free survival was 100%, in stage IIB 94.7%. The literature review and preliminary results of the reported ongoing trial are indicating that paraaortic irradiation in stage I and paraaortic with ipsilateral iliacal irradiation in stages IIA and IIB seem to be a sufficient treatment in early stage testicular seminoma with low treatment associated morbidity. (orig./MG) [Deutsch] Testikulaere Seminome in den fruehen Stadien werden nach der Semikastratio mit einer Radiatio der retroperitonealen Lymphknotenstationen behandelt. Trotz der hohen Heilungsraten dieser Behandlung bestehen kontroverse Ansichten sowohl ueber die adaequate Ausdehnung der Bestrahlungsfelder als auch ueber die Dosierung der Bestrahlung in den klinischen Stadien I, IIA und IIB. In dem vorliegenden Literaturueberblick werden diese kontroversen Standpunkte diskutiert. 491 Patienten mit testikulaeren Seminomen im Stadium I erhielten eine adjuvante Bestrahlung der Paraaortalregion mit einer Gesamtdosis von 26 Gy. 41 Patienten im Stadium IIA und 19 Patienten im Stadium IIB erhielten eine Bestrahlung mit jeweils 30 Gy bzw. 36 Gy auf die

  11. Preoperative radium therapy and radical hysterectomy in the treatment of cervical cancer stage IB, IIA, and initial IIB.; Radiumterapia pre-operatoria e histerectomia radical no tratamento do cancer do colo uterino IB, IIA e IIB inicial

    Energy Technology Data Exchange (ETDEWEB)

    Salum, Resalla; Lopes, Edison R.; Souza, Maria A.H. de [Faculdade de Medicina do Triangulo Mineiro, Uberaba, MG (Brazil). Hospital Escola

    1995-07-01

    Patients with IB, IIa and in initial IIb cervical cancer were randomized for combined therapy, consisting of one or two radium insertion followed by Wertheim Meigs operation performed 40 days later. We look for the early and late complications of the treatment, residual cancer after radiotherapy and survival without recurrence. The project begin in 1965 and ended in 1986. All the operations were done by one of the investigators and 116 patients were analysed. The age ranged from 21 to 75 years with an average of 4.18 years. During the operations 31 (26.72%) patients needed 1.500 cc or greater amount of blood transfusion and we have 3 iliac veins lesions. Managing the ureters, we do our best to leave the posterior fascia as intact as possible. Post operative complications ranged from minor (fever, localised pelvic infections, temporary popliteal nerve paralysis) to evisceration (3 patients) deep venous thrombosis (3 patients) and two early urinary fistulas. Late complications were seen in patients submitted to sequential teletherapy irradiation. One uretrovaginal fistula occurred 10 month after treatment, another one, 7 years later and the third one 24 years later. One patient develop hydronefrosis and enterocolite after 7.000 rads of teletherapy and another one rectovaginal fistula 13 years after initial therapy. The shortening of the vagina making impossible the intercourse was seen in 7 patients. By the histological examination, the cervix was sterilized in 73.3 % of the patients. Residual cancer was found according the original size of the tumour and the stage of the disease. Studying different combinations between the existence of residual cervical cancer with positive or negative limphnodes and making a correlation with survival, we found the critical points is to have positive cervix and positive lymphonodes. The five years survival (life table methodology) for stage 1 lesion was 96%; stage II, 67%. At ten years survival was slighted different. With positive

  12. [Effects of tanshinone IIA on the expressions of p53, pp53 and apoptosis in the rats with Alzheimer's disease].

    Science.gov (United States)

    Li, Jian; Wang, Fang; Zhou, Jun; Li, Wenwen

    2015-11-01

    目的:观察丹参酮IIA(tanshinone IIA,Tan IIA)对β-淀粉样蛋白(Aβ)诱导的阿尔茨海默病(Alzheimer’s disease,AD)模型大鼠脑组织中p53与磷酸化p53(phosphate p53,pp53)表达以及细胞凋亡的影响。方法:将30只雄性SD大鼠随机分为假手术组、AD模型组和Tan IIA治疗组。在大鼠海马内注射Aβ建立AD动物模型,采用免疫组织化学法和Western印迹检测AD大鼠脑组织p53与pp53的表达水平,TUNEL法检测大鼠脑组织中的细胞凋亡。结果:Aβ在假手术组中无表达;而在AD模型组和Tan IIA治疗组均有表达且两组间差异无统计学意义(P>0.05),证明AD模型建造成功。AD模型组p53与pp53的表达水平明显高于假手术组(P<0.05)和Tan IIA治疗组(P<0.05)。AD模型组凋亡细胞数显著多于假手术组(P<0.05)和Tan IIA治疗组(P<0.05)。结论:Aβ引起脑组织p53与pp53的表达明显增高,凋亡细胞增多;Tan IIA可能是通过降低大鼠p53与pp53的表达而抑制细胞的凋亡,从而起到神经保护作用。.

  13. Inhibition of group IIA secretory phospholipase A2and its inflammatory reactions in mice by ethanolic extract of Andrographis paniculata, a well-known medicinal food

    Directory of Open Access Journals (Sweden)

    V Kishore

    2016-01-01

    This study emphasis the anti-inflammatory effect of A. paniculata by inhibiting the inflammatory Group IIA sPLA2 and its associated inflammatory activities such as edema. It was found that there is a strong correlation between lipolytic activity and pro-inflammatory activity inhibition. Therefore, the study suggests that the extract processes potent anti-inflammatory agents, which could be developed as a potential therapeutic agent against inflammatory and related diseases.

  14. The field and Killing spinor equations of M-theory and type IIA/IIB supergravity in coordinate-free notation

    CERN Document Server

    Hamilton, M J D

    2016-01-01

    We review the actions of the supergravity theory in eleven dimensions as well as the type IIA and IIB supergravities in ten dimensions and derive the bosonic equations of motion in a coordinate-free notation. We also consider the existence of supersymmetries and the associated generalized Killing spinor equations. The aim of this note is to serve as a formulary and make the equations of supergravity more easily accessible to mathematicians.

  15. The antitumor effect of tanshinone IIA on anti-proliferation and decreasing VEGF/VEGFR2 expression on the human non-small cell lung cancer A549 cell line

    Directory of Open Access Journals (Sweden)

    Jun Xie

    2015-11-01

    Full Text Available The effects of tanshinone IIA on the proliferation of the human non-small cell lung cancer cell line A549 and its possible mechanism on the VEGF/VEGFR signal pathway were investigated. The exploration of the interaction between tanshinone IIA and its target proteins provides a feasible platform for studying the anticancer mechanism of active components of herbs. The CCK-8 assay was used to evaluate the proliferative activity of A549 cells treated with tanshinone IIA (2.5−80 μmol/L for 24, 48 and 72 h, respectively. Flow cytometry was used for the detection of cell apoptosis and cell cycle perturbation. VEGF and VEGFR2 expression were studied by Western blotting. The binding mode of tanshinone IIA within the crystal structure of the VEGFR2 protein was evaluated with molecular docking analysis by use of the CDOCKER algorithm in Discovery Studio 2.1. The CCK-8 results showed that tanshinone IIA can significantly inhibit A549 cell proliferation in a dose- and time-dependent manner. Flow cytometry results showed that the apoptosis rate of tested group was higher than the vehicle control, and tanshinone IIA-treated cells accumulated at the S phase, which was higher than the vehicle control. Furthermore, the expression of VEGF and VEGFR2 was decreased in Western blot. Finally, molecular docking analysis revealed that tanshinone IIA could be stably docked into the kinase domain of VEGFR2 protein with its unique modes to form H-bonds with Cys917 and π–π stacking interactions with Val848. In conclusion, tanshinone IIA may suppress A549 proliferation, induce apoptosis and cell cycle arrest at the S phase. This drug may suppress angiogenesis by targeting the protein kinase domains of VEGF/VEGFR2.

  16. Frequency of anti-glycoprotein Ia/IIa (anti-HPA-5b,-5a and anti-glycoprotein IIb/IIIa (anti-HPA-1a,-3a,-4a alloantibodies in multiparous women of African descent

    Directory of Open Access Journals (Sweden)

    Zaccheaus A Jeremiah

    2010-05-01

    Full Text Available Zaccheaus A Jeremiah1, Justina E Oburu2, Osaro Erhabor1, Fiekumo I Buseri1, Teddy C Adias31Haematology and Blood Transfusion Science Unit, Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Nigeria; 2Department of Haematology and Blood Transfusion, University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria; 3Rivers State University of Science and Technology, Port Harcourt, NigeriaBackground: Human platelet antibodies are often implicated in some disease conditions, such as neonatal alloimmune thrombocytopenia (NAIT, idiopathic thrombocytopenic purpura (ITP and platelet refractoriness. The frequencies of these alloantibodies have not been reported in Nigeria and West Africa.Methods: Screening for allontibodies to human platelet antigens (HPA was undertaken using the GTI PakPlus® qualitative solid phase ELISA reagent. Platelet count was done using the ICSH approved procedure using 1% ammonium oxalate reagent.Study design: A cross-section of apparently healthy adult Nigerian multiparous non-pregnant women, who were staff of a tertiary health facility in the Niger Delta, Nigeria, were screened for alloantibodies to human platelet antigens.Results: Of the one hundred (100 women screened, the prevalence of anti-glycoprotein IIb/IIIa (anti-HPA-Ia,-3a,-4a was zero percent (0%, anti-glycoprotein Ia/IIa (anti-HPA-5b accounted for 30% of results, while anti-glycoprotein Ia/IIa (anti-HPA-5a was 18%. Parity was found to exert significant influence on the development to HPA antibodies (Fisher’s Exact Test = 11.683, P < 0.05; 13.577, P < 0.01. The platelet count of the women did not appear to exert any influence on the development of the antibodies (P > 0.05.Conclusion: This study has observed a high prevalence of anti-HPA-5b in our sample population. The prevalence of alloantibodies to HPA antigens was found to associate strongly with parity. These results indicate that there is a

  17. Platelet half-life in patients with primary hyperlipoproteinemia type IIa, IIb, and IV according to Fredrickson with and without clinical signs of atherosclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Jaeger, E.; Sinzinger, H.; Widhalm, K.; Kaliman, J.; Hoefer, R. (Vienna Univ. (Austria). 2. Medizinische Klinik; Ludwig Boltzmann-Institut fuer Nuklearmedizin, Vienna (Austria); Vienna Univ. (Austria). Kinderklinik; Vienna Univ. (Austria). Kardiologische Klinik)

    1982-09-01

    It is generally accepted that platelet half-life is shortened in atherosclerotic vascular diseases. Concerning changes due to hyperlipoproteinemia (HLP), however, there exist only few data. Therefore, we examined the platelet-half life in 60 patients with recently discovered HLP type IIa, IIb and IV according to Fredrickson before treatment in comparison to 60 controls. 33 of the HLP-patients had no clinical symptoms of angiopathy. 27 patients suffered from peripheral vascular disease or from coronary heart disease as verified by angiography. The labelling of autologous platelets was performed with 100..mu..Ci of /sup 111/Indium-oxine-sulfate at 37/sup 0/C for 5 minutes. The mean labelling efficiency was 90%, the recovery after 2 hours about 70%. Serum lipoproteins were estimated by means of ultracentrifugation and polyanionprecipitation according to Lipid Research Clinic Methods. In the patients with HLP platelet half-life was significantly shortened in comparison to the control group (p < 0.01). These changes were most pronounced in patients with HLP-type IIa and with atherosclerotic lesions, respectively. In patients with HLP-type IIa a very close correlation could be demonstrated between platelet half-life and LDL-cholesterol (r = -0.72; p < 0.001) as well as total cholesterol (r = -0.73; p < 0.001). These data prove that in HLP in-vivo platelet function as measured by platelet survival is significantly influenced even before the occurrence of clinically relevant symptoms of atherosclerosis.

  18. Pharmacokinetics of Caffeic Acid, Ferulic Acid, Formononetin, Cryptotanshinone, and Tanshinone IIA after Oral Administration of Naoxintong Capsule in Rat by HPLC-MS/MS

    Directory of Open Access Journals (Sweden)

    Jin Li

    2017-01-01

    Full Text Available Naoxintong capsule (NXTC was a famous patent medicine of Traditional Chinese Medicine (TCM to treat cerebrovascular diseases in China. An LC-MS/MS method was developed for simultaneous determination of 11 major ingredients (paeoniflorin, ecdysterone, amygdalin, mulberroside A, caffeic acid, ferulic acid, salvianolic acid B, astragaloside IV, formononetin, cryptotanshinone, and tanshinone IIA in NXTC in rat plasma. All analytes were separated on an Eclipse plus C18 column using a gradient mobile phase system of acetonitrile-0.1% formic acid aqueous solution. The lower limits of quantification of 11 ingredients were between 0.075 and 10 ng mL−1. The precision was less than 15% and the accuracies were between 85% and 115%. The results showed that caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA could be detected after oral administration of NXTC. The validated method was successfully applied to pharmacokinetic study of the caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA in rats after oral administration of NXTC at single and triple dose.

  19. Higgs mechanism from fluxes and two mass hierarchies in the "fat" throat solution of Type IIA supegravity

    CERN Document Server

    Altshuler, Boris L

    2008-01-01

    Spectra of Kaluza-Klein gauge fields are calculated at the background of the magnetic fluxbrane throat-like solution of the Type IIA supergravity equations. Magnetic flux plays the role of Higgs scalar generating the electroweak scale mass of non-abelian KK gauge field. The same "flux-Higgs" mechanism gives the scale of the "second mass hierarchy", 0.001 eV, in the spectrum of KK excitations at the background of the throat deformed in a Reissner-Nordstrom way. Gauge coupling constants in 4 dimensions are calculated; they prove to be of the physically sensible values for the EW scale massive modes of the gauge fields and are extremely small for the long range gauge fields. 5D effective Action with the flux-generated mass terms of the KK gauge fields associated with isometries of compactified subspaces is put down, correspondence of the "classical" KK approach and dual holography approach to the low-dimensional gauge theories is discussed, and idea of Bootstrap Holography is set forth.

  20. Design of group IIA secreted/synovial phospholipase A(2 inhibitors: an oxadiazolone derivative suppresses chondrocyte prostaglandin E(2 secretion.

    Directory of Open Access Journals (Sweden)

    Jean-Edouard Ombetta

    Full Text Available Group IIA secreted/synovial phospholipase A(2 (GIIAPLA(2 is an enzyme involved in the synthesis of eicosanoids such as prostaglandin E(2 (PGE(2, the main eicosanoid contributing to pain and inflammation in rheumatic diseases. We designed, by molecular modeling, 7 novel analogs of 3-{4-[5(indol-1-ylpentoxy]benzyl}-4H-1,2,4-oxadiazol-5-one, denoted C1, an inhibitor of the GIIAPLA(2 enzyme. We report the results of molecular dynamics studies of the complexes between these derivatives and GIIAPLA(2, along with their chemical synthesis and results from PLA(2 inhibition tests. Modeling predicted some derivatives to display greater GIIAPLA(2 affinities than did C1, and such predictions were confirmed by in vitro PLA(2 enzymatic tests. Compound C8, endowed with the most favorable energy balance, was shown experimentally to be the strongest GIIAPLA(2 inhibitor. Moreover, it displayed an anti-inflammatory activity on rabbit articular chondrocytes, as shown by its capacity to inhibit IL-1beta-stimulated PGE(2 secretion in these cells. Interestingly, it did not modify the COX-1 to COX-2 ratio. C8 is therefore a potential candidate for anti-inflammatory therapy in joints.

  1. Dlc1 interaction with non-muscle myosin heavy chain II-A (Myh9 and Rac1 activation

    Directory of Open Access Journals (Sweden)

    Mohammad G. Sabbir

    2016-04-01

    Full Text Available The Deleted in liver cancer 1 (Dlc1 gene codes for a Rho GTPase-activating protein that also acts as a tumour suppressor gene. Several studies have consistently found that overexpression leads to excessive cell elongation, cytoskeleton changes and subsequent cell death. However, none of these studies have been able to satisfactorily explain the Dlc1-induced cell morphological phenotypes and the function of the different Dlc1 isoforms. Therefore, we have studied the interacting proteins associated with the three major Dlc1 transcriptional isoforms using a mass spectrometric approach in Dlc1 overexpressing cells. We have found and validated novel interacting partners in constitutive Dlc1-expressing cells. Our study has shown that Dlc1 interacts with non-muscle myosin heavy chain II-A (Myh9, plectin and spectrin proteins in different multiprotein complexes. Overexpression of Dlc1 led to increased phosphorylation of Myh9 protein and activation of Rac1 GTPase. These data support a role for Dlc1 in induced cell elongation morphology and provide some molecular targets for further analysis of this phenotype.

  2. Molecular characterization of Activin Receptor Type IIA and its expression during gonadal maturation and growth stages in rohu carp.

    Science.gov (United States)

    Patnaik, Siddhi; Mohanty, Mausumee; Bit, Amrita; Sahoo, Lakshman; Das, Sachidananda; Jayasankar, Pallipuram; Das, Paramananda

    2017-01-01

    Activin receptor type IIA (ActRIIA), a transmembrane serine/threonine kinase receptor is an important regulator of physiological traits, viz., reproduction and body growth in vertebrates including teleosts. However, existing knowledge of its role in regulating fish physiology is limited. To address this, we have cloned and characterized the ActRIIA cDNA of Labeo rohita (rohu), an economically important fish species of the Indian subcontinent. Comparative expression profiling of the receptor gene at various reproductive and growth stages supports to its role in promoting oocyte maturation, spermatogenesis and skeletal muscle development via interaction with multiple ligands of transforming growth factor-β (TGF-β) family. The full-length cDNA of rohu ActRIIA was found to be of 1587bp length encoding 528 amino acids. The three-dimensional structure of the intracellular kinase domain of rohu ActRIIA has also been predicted. Phylogenetic relationship studies showed that the gene is evolutionarily conserved across the vertebrate lineage implicating that the functioning of the receptor is more or less similar in vertebrates. Taken together, these findings could be an initial step towards the use of ActRIIA as a potential candidate gene marker for understanding the complex regulatory mechanism of fish reproduction and growth.

  3. The 763C>G Polymorphism of The Secretory PLA2IIa Gene Is Associated with Endometriosis in Iranian Women

    Directory of Open Access Journals (Sweden)

    Mehdi Sahmani

    2015-02-01

    Full Text Available Background: Endometriosis is a chronic gynecological disease resulting from complex interactions between genetic, hormonal, environmental and oxidative stress and intrinsic inflammatory components. The aim of this study was to investigate the potential association of the 763C>G polymorphism in the secretory phospholipase A2 group IIa gene (PLA2G2A with the risk of endometriosis in Iranian women. Materials and Methods: Ninety seven patients with endometriosis along with 107 women who were negative for endometriosis after laparoscopy and laparatomy, and served as the control group, were enrolled for this cross-sectional study. Samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Results: Multivariate analysis was used to examine the association between the risk of endometriosis and the 763C>G polymorphism of PLA2G2A. Genotype distributions of PLA- 2G2A were significantly different between patients and the controls (pG polymorphism of PLA2G2A plays an important role as an independent factor in the risk of endometriosis in Iranian women.

  4. One-point functions of non-SUSY operators at arbitrary genus in a matrix model for type IIA superstrings

    Directory of Open Access Journals (Sweden)

    Tsunehide Kuroki

    2017-06-01

    Full Text Available In the previous paper, the authors pointed out correspondence between a supersymmetric double-well matrix model and two-dimensional type IIA superstring theory on a Ramond–Ramond background from the viewpoint of symmetry and spectrum. This was confirmed by agreement between planar correlation functions in the matrix model and tree-level amplitudes in the superstring theory. In order to investigate the correspondence further, in this paper we compute correlation functions to all order of genus expansion in the double scaling limit of the matrix model. One-point functions of operators protected by supersymmetry terminate at some finite order, whereas those of unprotected operators yield non-Borel summable series. The behavior of the latter is characteristic in string perturbation series, providing further evidence that the matrix model describes a string theory. Moreover, instanton corrections to the planar one-point functions are also computed, and universal logarithmic scaling behavior is found for non-supersymmetric operators.

  5. Radiotherapy or chemotherapy for clinical stage IIA and IIB seminoma: a systematic review and meta-analysis of patient outcomes.

    Science.gov (United States)

    Giannatempo, P; Greco, T; Mariani, L; Nicolai, N; Tana, S; Farè, E; Raggi, D; Piva, L; Catanzaro, M; Biasoni, D; Torelli, T; Stagni, S; Avuzzi, B; Maffezzini, M; Landoni, G; De Braud, F; Gianni, A M; Sonpavde, G; Salvioni, R; Necchi, A

    2015-04-01

    Outcomes of radiotherapy (RT) compared with chemotherapy (CT) remain poorly defined for clinical stage (CS) IIA and IIB seminoma. We aimed to evaluate the current role of the two treatment modalities in this setting of testicular seminoma. A systematic review and meta-analysis (MA) was carried out to identify all evaluable studies. Search was limited to studies published after 1990 and included the Medline, Embase databases, and abstracts from ASCO (GU), ESMO, AUA, and ASTRO meetings up to April 2014. Sensitivity analyses were applied including the following: CSIIA and CSIIB, paraortic + iliac RT only in both stages, RT dose (≥30 versus seminoma, a trend in favor of CT for a lower incidence of side-effects and RR in CSIIB was found. This evidence is limited by the retrospective quality of studies and their small sample size. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  6. Group IIA secretory phospholipase A2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons.

    Science.gov (United States)

    Wei, S; Ong, W Y; Thwin, M M; Fong, C W; Farooqui, A A; Gopalakrishnakone, P; Hong, W

    2003-01-01

    Recent evidence shows that secretory phospholipase A2 (sPLA2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA2 on vesicle exocytosis. External application of group IIA sPLA2 (purified crotoxin subunit B or purified human synovial sPLA2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA2 was dependent on calcium and sPLA2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.

  7. Discriminative Features in Three Autosomal Recessive Cutis Laxa Syndromes: Cutis Laxa IIA, Cutis Laxa IIB, and Geroderma Osteoplastica

    Directory of Open Access Journals (Sweden)

    Ariana Kariminejad

    2017-03-01

    Full Text Available Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A, cutis laxa IIB (ARCL2B, and geroderma osteodysplastica (GO, have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient’s clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.

  8. Role of acetate in production of an autoinducible Class IIa Bacteriocin in Carnobacterium piscicola A9b

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Nielsen, Michael Krogsgaard; Ng, Yin

    2002-01-01

    was to purify the compound and describe factors affecting its production, with particular emphasis on food-relevant factors. Amino acid sequencing showed that the compound is a class IIa bacteriocin with an N-terminal amino acid sequence identical to that of carnobacteriocin B2. The production...... of the bacteriocin was autoinducible, and the threshold level for induction was 9.6 x 10(-10) M. We also report, for the first time, that acetate acts as an induction factor, with a threshold concentration of 0.3 to 12 mM. Acetate could not act as an inducer during the late exponential phase of C. piscicola A9b....... The induction of bacteriocin production showed a dose-dependent relationship at acetate concentrations of up to 10 to 20 mM (depending on the growth medium) and at a concentration of 1.9 x 10(-8) M for the bacteriocin itself; a saturation level of bacteriocin specific activity was reached...

  9. Expression of group IIA phospholipase A2 is an independent predictor of favorable outcome for patients with gastric cancer.

    Science.gov (United States)

    Wang, Xi; Huang, Chun-Jin; Yu, Guan-Zhen; Wang, Jie-Jun; Wang, Rui; Li, Yu-Mei; Wu, Qiong

    2013-10-01

    Growing evidence suggests that phospholipase A2 (PLA2) plays a pivotal role in tumorigenesis in human gastrointestinal cancer. One of the well-studied isoforms of PLA2, group IIA PLA2 (PLA2G2A), appears to exert its protumorigenic or antitumorigenic effects in a tissue-specific manner. The present study was designed to determine the expression profile and prognostic value of PLA2G2A in gastric cancer in a large Chinese cohort. By using real-time polymerase chain reaction, the amount of PLA2G2A messenger RNA in 60 pairs of fresh gastric tumors and adjacent noncancerous mucosa was measured. The immunostaining of PLA2G2A in 866 gastric cancers with paired noncancerous tissues was assayed. No expression of PLA2G2A was found in normal gastric mucosa, and focal expression of PLA2G2A was noticed in intestinal metaplasia, whereas significantly increased expression of PLA2G2A was observed in the cytoplasm of gastric cancer cells. Furthermore, the extent of PLA2G2A expression was associated with tumor size (P gastric cancer. Multivariate analysis showed that PLA2G2A expression was an independent predictor of survival for patients with gastric cancer (P = .024). Expression of PLA2G2A seems to be protective for patients with gastric cancer (hazard ratio, 1.423; 95% confidence interval, 1.047-1.935), and it may be a target for achieving better treatment outcomes.

  10. Antinociceptive effects of systemic tanshinone IIA on visceral and somatic persistent nociception and pain hypersensitivity in rats.

    Science.gov (United States)

    Cao, Fa-Le; Su, Xue-Jia; Wang, Yan; Xu, Min; Shan, Liang

    2014-09-01

    Previous studies showed that tanshinone IIA (TIIA), an important lipophilic component of Danshen, has been well-established to exhibit various neuroprotective actions in the nervous system. Although we previously reported that TIIA had a significant anti-nociceptive effect in complete Freund's adjuvant (CFA)-induced pain, it is surprisingly noted that few pharmacological studies have been carried out to explore the possible analgesic action of TIIA in animals and the appropriate indications for treatment of clinical pain remain unclear. Therefore, in the present study, by using both somatic and visceral pain models, the antinociceptive and antihyperalgesic effects of TIIA were evaluated by intraperitoneal administration in rats. In the bee venom (BV) test, when compared with saline controls, systemic pre- and post-treatment with TIIA resulted in an apparent antinociception against persistent spontaneous nociception (PSN) and primary heat and mechanical hypersensitivity, while for the mirror-image heat hypersensitivity, only pre-treatment was effective. Moreover, in the formalin test, the antinociception of TIIA was significant for both phases 1 and 2 in the pretreatment groups, but only effective for phase 2 in the post-treatment group. In the acetic acid writhing test, the number of writhes was effectively blocked by both pre- and post-treatment of TIIA. Taken together, these results provide a new line of evidence showing that TIIA is also able to produce analgesia against various 'phenotypes' of nociception and hypersensitivity.

  11. On Simon's two-stage design for single-arm phase IIA cancer clinical trials under beta-binomial distribution.

    Science.gov (United States)

    Liu, Junfeng; Lin, Yong; Shih, Weichung Joe

    2010-05-10

    Simon (Control. Clin. Trials 1989; 10:1-10)'s two-stage design has been broadly applied to single-arm phase IIA cancer clinical trials in order to minimize either the expected or the maximum sample size under the null hypothesis of drug inefficacy, i.e. when the pre-specified amount of improvement in response rate (RR) is not expected to be observed. This paper studies a realistic scenario where the standard and experimental treatment RRs follow two continuous distributions (e.g. beta distribution) rather than two single values. The binomial probabilities in Simon's (Control. Clin. Trials 1989; 10:1-10) design are replaced by prior predictive Beta-binomial probabilities that are the ratios of two beta functions and domain-restricted RRs involve incomplete beta functions to induce the null hypothesis acceptance probability. We illustrate that Beta-binomial mixture model based two-stage design retains certain desirable properties for hypothesis testing purpose. However, numerical results show that such designs may not exist under certain hypothesis and error rate (type I and II) setups within maximal sample size approximately 130. Furthermore, we give theoretical conditions for asymptotic two-stage design non-existence (sample size goes to infinity) in order to improve the efficiency of design search and to avoid needless searching.

  12. TanshinoneIIA and Alprostadil treatment acute time brain blocks the clinical curative effect%丹参酮域A 联合前列地尔治疗急性脑梗死的临床研究

    Institute of Scientific and Technical Information of China (English)

    邵志坚; 庄大和; 王俊松

    2014-01-01

    目的探讨丹参酮域A联合前列地尔治疗急性脑梗死的临床疗效。方法 急性脑梗死患者143例,随机分为治疗组(72例)及对照组(71例)。对照组给予丹参酮域A50mg加入到生理盐水250ml静滴,1次/天,连用10天。治疗组在对照组的基础上给前列地尔注射液10滋g加入到生理盐水10ml静脉注射,1次/天,连用10天。观察两组治疗前后临床疗效、神经功能缺损评分(采用美国国立卫生研究院卒中量表NIHSS评定)和日常生活能力评分(BI)的变化并进行对比分析。结果 两组患者治疗后临床疗效、神经功能缺损评分(NIHSS)和日常生活能力评分(BI)的变化差异有显著性(P<0.05),临床疗效治疗组明显优于对照组。结论 丹参酮域A联合前列地尔治疗急性脑梗死临床疗效显著,能有效改善神经功能缺损症状,提高日常生活能力。%Objective Discussing TanshinoneIIA and Alprostadil treatment acute time brain blocks the clinical cura-tive effect. Method 143 cases of acute cerebral infarction patients were randomly divided into treatment group (72 cases) and control group (71 cases). Control group given tanshinoneIIA 50mg join the physiological salt, 250 ml static drops, 1 time/day, stay for 10 days. Treatment group on the basis of the control group of alprostadil injection 10μg,including into physiological salt 10 ml intravenous, 1 time/day, stay for 10 days. Observe two groups before and after treatment clinical curative effect, neural function defect score ( in the United States national institutes of health stroke scale, NIHSS evaluation) and changes in the daily life ability score ( BI) and were analyzed. Result Two groups of patients after treatment clinical curative effect and neural function defect score ( NIHSS) scores and daily life ability score (BI) the change of the difference was statistically significant (P<0. 05), Results of clinical efficacy of the treatment group significantly better than the

  13. Co-Circulation of Canine Coronavirus I and IIa/b with High Prevalence and Genetic Diversity in Heilongjiang Province, Northeast China.

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    Xinyu Wang

    Full Text Available To trace the evolution of canine coronavirus (CCoV, 201 stool samples from diarrheic dogs in northeast China were subjected to reverse transcription-polymerase chain reactions (RT-PCRs targeting the partial M and S genes of CCoV, followed by an epidemiological analysis. M gene RT-PCRs showed that 28.36% (57/201 of the samples were positive for CCoV; of the 57 positive samples, CCoV-I and CCoV-II accounted for 15.79% (9/57 and 84.21% (48/57, respectively. A sequence comparison of the partial M gene revealed nucleotide homologies of 88.4%-100% among the 57 CCoV strains, and 88.7%-96.2% identity between the 57 CCoV strains and the Chinese reference strain HF3. The CCoV-I and CCoV-II strains exhibited genetic diversity when compared with reference strains from China and other countries. The 57 CCoV strains exhibited high co-infection rates with canine kobuvirus (CaKV (33.33% and canine parvovirus-2 (CPV-2 (31.58%. The CCoV prevalence in diarrheic dogs differed significantly with immunization status, regions, seasons, and ages. Moreover, 28 S genes were amplified from the 57 CCoV-positive samples, including 26 CCoV-IIa strains, one CCoV-IIb strain, and one CCoV-I strain. A sequence comparison of the partial S gene revealed 86.3%-100% nucleotide identity among the 26 CCoV-IIa strains, and 89.6%-92.2% identity between the 26 CCoV-IIa strains and the Chinese reference strain V1. The 26 CCoV-IIa strains showed genetic diversity when compared with reference strains from China and other countries. Our data provide evidence that CCoV-I, CCoV-IIa, and CCoV-IIb strains co-circulate in the diarrhoetic dogs in northeast China, high co-infection rates with CaKV and CPV-2 were observed, and the CCoV-II strains exhibited high prevalence and genetic diversity.

  14. Effects of salvianolic acid B and tanshinone IIA on the pharmacokinetics of losartan in rats by regulating the activities and expression of CYP3A4 and CYP2C9.

    Science.gov (United States)

    Wang, Rong; Zhang, Hai; Wang, Yujie; Yu, Xiaoyan; Yuan, Yongfang

    2016-03-02

    Losartan (LST) is a common chemical drug used to treat high blood pressure and reduce the risk of stroke in certain people with heart disease. Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge, has been widely used for prevention and treatment of various cardiovascular and cerebrovascular diseases. There are more than 35 formulations containing Danshen indexed in the 2010 Chinese Pharmacopoeia, which are often combined with LST to treat cardiovascular and cerebrovascular diseases in the clinic. The effects of the two major components of Danshen, salvianolic acid B (SA-B) and tanshinone IIA (Tan IIA), on the pharmacokinetics of losartan and its metabolite, EXP3174, in rats were investigated by liquid chromatography coupled with mass spectrometry (LC-MS). Male Sprague-Dawley rats were randomly assigned to 3 groups: LST, LST+SA-B and LST+Tan IIA, and the main pharmacokinetic parameters were estimated after oral administration of LST, LST+SA-B and LST+Tan IIA. It was found that there are significant differences in the pharmacokinetic parameters among the three groups: Cmax, t1/2, AUC, AUMC in the LST+SA-B group was smaller than those in group LST, while larger in group LST+Tan IIA. Further, the effects of SA-B and Tan IIA on the metabolism of losartan was also investigated using rat liver microsomes in vitro. The results indicated that SA-B can induce the metabolism of LST, while Tan IIA can inhibit the metabolism of LST in rat liver microsomes in vitro by regulating activities of CYP450 enzymes. In addition, the effect of SA-B and Tan IIA on CYP3A4 and CYP2C9 expression was studied in Chang liver cells by western-blotting and Real-time PCR. It was concluded that the two components of Danshen, SA-B and Tan IIA have different influences on the metabolism of LST: SA-B can obviously speed up the metabolism of LST by inducing CYP3A4/CYP2C9 activities and expression, however, Tan IIA can slow down the metabolism of LST by inhibiting CYP3A4/CYP2C

  15. Hyperactivity in 103P/Hartley 2: Chunks from the sub-surface in Type IIa jet regions

    Science.gov (United States)

    Belton, Michael J. S.

    2017-03-01

    We analyze the observed radial distribution of column densities of water-ice particulates embedded in the primary jet region (J1) of 103P's inner coma at altitudes between 439 and 1967 m (Protopapa et al., 2014, Icarus 238, 191-204) and determine the speed and acceleration of particles and their mass-flow within the filaments of the jet. This is done by applying a CO2 driven (Type IIa) jet model proposed by Belton (2010, Icarus 210, 881-897). The model utilizes water-ice particles dislodged in the source regions of the jet filaments and accelerated by CO2 to explain the radial distribution of water-ice particulates. We provide an explanation for the remarkably different radial distribution of refractory dust particles by hypothesizing that the majority of the dust originates directly from the nucleus surface in inter-filament regions of the jet complex and is accelerated by H2O. Our model provides a mass-flow of water from the J1 jet complex that is ∼40 times greater than the constant speed sublimation model discussed by Protopapa et al. but is still too small to explain the hyperactivity of the comet. Speeds in the flow are increased by a factor up to ∼20 over those found by Protopapa et al. To account for the hyperactivity, most of the mass dislodged in the filament source regions must be in weakly accelerated large chunks that achieve only low speeds en route to the region of observation. These chunks soon leave the filamentary jet structure due to the rotation of the nucleus and do not contribute to the column densities observed at higher altitudes in the jet filaments. Employing the results of Kelley et al. (2015. Icarus 262, 187-189)) on total cross-section and mass-flow in the coma we find that large chunks with the same bulk properties as the nucleus can increase the active fraction of the comet by two or three times. With the exception that the chunks do not need to be "nearly pure water ice", these results support the hypothesis that hyperactivity in

  16. Effects of tanshinone IIA on the transforming growth factor β1/Smad signaling pathway in rat cardiac fibroblasts

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    Cheng-Ye Zhan

    2014-01-01

    Full Text Available Objectives: This study explores the mechanism of tanshinone IIA (TSN-mediated inhibition of myocardial fibrosis by investigating the effect of TSN on transforming growth factor β1 (TGFβ1 signal transduction in rat cardiac fibroblasts (CFs. Materials and Methods: CFs were isolated from neonatal Sprague-Dawley rats by trypsin digestion and differential adhesion and stimulated with 5 ng/mL TGFβ1 and TSN (10−6 , 10−5 , or 10−4 mol/L. The expression of fibronectin (FN mRNA in the CFs was determined using reverse transcriptase-polymerase chain reaction and the protein expression of FN and Smads in CFs was detected using Western blot. The intracellular expression and localization of Smads in the CFs were analyzed using immunocytochemistry. Results: TGFβ1 induced the expression of FN and Smads in a time-dependent manner. At the end of the culture treatment, the mRNA expression of FN and the expression of phosphorylated Smad2/3 (p-Smad2/3 increased significantly (P < 0.01. TSN pretreatment (10−5 and 10−4 mol/L reduced the expression of FN and p-Smad2/3 (P < 0.01 following TGFβ1 stimulation and led to a significant decrease in the nuclear staining intensity and a positive rate of p-Smad2/3 (P < 0.05 and P < 0.01, respectively. Conclusion: The inhibitory effect of TSN on myocardial fibrosis may be associated with its inhibition of TGFβ1-induced Smad2/3 phosphorylation and p-Smad2/3 nuclear translocation, which blocks the TGFβ1/Smad signaling pathway in CFs.

  17. TanshinoneIIA and cryptotanshinone protect against hypoxia-induced mitochondrial apoptosis in H9c2 cells.

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    Hyou-Ju Jin

    Full Text Available Mitochondrial apoptosis pathway is an important target of cardioprotective signalling. Tanshinones, a group of major bioactive compounds isolated from Salvia miltiorrhiza, have been reported with actions against inflammation, oxidative stress, and myocardial ischemia reperfusion injury. However, the actions of these compounds on the chronic hypoxia-related mitochondrial apoptosis pathway have not been investigated. In this study, we examined the effects and molecular mechanisms of two major tanshonones, tanshinone IIA (TIIA and cryptotanshinone (CT on hypoxia induced apoptosis in H9c2 cells. Cultured H9c2 cells were treated with TIIA and CT (0.3 and 3 μΜ 2 hr before and during an 8 hr hypoxic period. Chronic hypoxia caused a significant increase in hypoxia inducible factor 1α expression and the cell late apoptosis rate, which was accompanied with an increase in caspase 3 activity, cytochrome c release, mitochondria membrane potential and expression of pro-apoptosis proteins (Bax and Bak. TIIA and CT (0.3 and 3 μΜ, in concentrations without affecting the cell viability, significantly inhibited the late apoptosis and the changes of caspase 3 activity, cytochrome c release, and mitochondria membrane potential induced by chronic hypoxia. These compounds also suppressed the overexpression of Bax and reduced the ratio of Bax/Bcl-2. The results indicate that TIIA and CT protect against chronic hypoxia induced cell apoptosis by regulating the mitochondrial apoptosis signaling pathway, involving inhibitions of mitochondria hyperpolarization, cytochrome c release and caspase 3 activity, and balancing anti- and pro-apoptotic proteins in Bcl-2 family proteins.

  18. Effects of escins Ia, Ib, IIa, and IIb from horse chestnuts on gastrointestinal transit and ileus in mice.

    Science.gov (United States)

    Matsuda, H; Li, Y; Yoshikawa, M

    1999-08-01

    The effects of saponin fraction and its principal constituents escins Ia (1), Ib (2), IIa (3), and IIb (4) from horse chestnuts on gastrointestinal transit (GIT) and ileus were investigated in mice. Ileus was induced by acetic acid peritoneal irritation or by laparotomy with manipulation. One hour after the oral administration, the saponin fraction (12.5-100 mg/kg) and 14 (12.5-50 mg/ kg, except for 3 at 12.5 mg/kg) dose-dependently accelerated GIT. The optimal effects of the saponin fraction (25 mg/kg) occurred 5-240 min (applied intervals between the fraction and the charcoal meal) after the oral administration. The fraction (12.5-100 mg/ kg) and 1-4 (12.5-50 mg/kg, except for 1 and 2 at 12.5 mg/kg) dose-dependently prevented the inhibition of GIT induced by the acetic acid peritoneal irritation. They (12.5-100mg/kg) also dose-dependently prevented the inhibition of GIT induced by the laparotomy with manipulation. Desacylescins I (5) and II (6) (50 mg/kg) showed no such effects. These results demonstrated that the saponin fraction and 1-4 accelerated GIT and prevented the experimental ileus, and indicate that the 21, 22-acyl groups are essential for the accelerative effects of 1-4. The accelerations of GIT by 1-4 were completely abolished by the pretreatment with streptozotocin (100 mg/kg, iv), but not by the pretreatment with capsaicin (75 mg/kg in total, sc) or atropine (10 mg/kg, sc). These results imply that the sympathetic nervous system may be, but neither capsaicin-sensitive sensory nerves nor the cholinergic mechanism, involved in the accelerations of GIT by escins 1-4.

  19. Correlation between tumor size and surveillance of lymph node metastasis for IB and IIA cervical cancer by magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Kim, See Hyung, E-mail: kseehdr@dsmc.or.kr [Keimyung University, Dongsan Hospital, Department of Radiology Keimyung University Dongsan Hospital, 216 Dalsungro, Jung-gu, Daegu 700-712 (Korea, Republic of); Lee, Hee Jung, E-mail: hjlee@dsmc.or.kr [Keimyung University, Dongsan Hospital, Department of Radiology Keimyung University Dongsan Hospital, 216 Dalsungro, Jung-gu, Daegu 700-712 (Korea, Republic of); Kim, Young Whan, E-mail: yhkim68@dsmc.or.kr [Keimyung University, Dongsan Hospital, Department of Radiology Keimyung University Dongsan Hospital, 216 Dalsungro, Jung-gu, Daegu 700-712 (Korea, Republic of)

    2012-08-15

    Purpose: To assess the feasibility of preoperative MRI based measurement of tumor size with regard to lymph node (LN) metastasis in early uterine cervical cancer. Material and Methods: A retrospective review of patients with FIGO stage IB-IIA cervical cancer who underwent lymphadenectomy was performed. Diagnostic accuracy of MRI in detecting LN metastasis and rate of LN recurrence in terms of tumor size ({<=}4 cm versus >4 cm) were analyzed. ROC curve analysis was used to determine LN size for differentiating LN metastasis in terms of tumor size. P < 0.05 was considered statistically significant. Results: Of the 200 patients, 45 (22.3%) had LN metastasis. There was no statistical difference between patients-based and region-specific analysis. The patients with tumor size with >4 cm revealed higher diagnostic accuracy of MRI in detecting LN metastasis (85.4% versus 50.6%, P = 0.023) and rate of LN recurrence (20.0% versus 6.4%, P = 0.031) in than those with size with {<=}4 cm, the differences were statistically significant. Discriminant analysis of LN size for the differentiation of metastasis from non-metastasis resulted in cut-off values (11.8 mm; size with >4 cm versus 8.3 mm; size with {<=}4 cm) and diagnostic accuracy (84.0% of size with >4 cm versus 72.0% of size with {<=}4 cm). Conclusion: MRI has limited sensitivity, but high specificity in predicting surveillance of LN metastasis in the preoperative early cervical cancer, especially useful tool for patients with tumor size with >4 cm.

  20. Interleukin-22-Induced Antimicrobial Phospholipase A2 Group IIA Mediates Protective Innate Immunity of Nonhematopoietic Cells against Listeria monocytogenes.

    Science.gov (United States)

    Okita, Yamato; Shiono, Takeru; Yahagi, Ayano; Hamada, Satoru; Umemura, Masayuki; Matsuzaki, Goro

    2015-12-07

    Listeria monocytogenes is a bacterial pathogen which establishes intracellular parasitism in various cells, including macrophages and nonhematopoietic cells, such as hepatocytes. It has been reported that several proinflammatory cytokines have pivotal roles in innate protection against L. monocytogenes infection. We found that a proinflammatory cytokine, interleukin 22 (IL-22), was expressed by CD3(+) CD4(+) T cells at an early stage of L. monocytogenes infection in mice. To assess the influence of IL-22 on L. monocytogenes infection in hepatocytes, cells of a human hepatocellular carcinoma line, HepG2, were treated with IL-22 before L. monocytogenes infection in vitro. Gene expression analysis of the IL-22-treated HepG2 cells identified phospholipase A2 group IIA (PLA2G2A) as an upregulated antimicrobial molecule. Addition of recombinant PLA2G2A to the HepG2 culture significantly suppressed L. monocytogenes infection. Culture supernatant of the IL-22-treated HepG2 cells contained bactericidal activity against L. monocytogenes, and the activity was abrogated by a specific PLA2G2A inhibitor, demonstrating that HepG2 cells secreted PLA2G2A, which killed extracellular L. monocytogenes. Furthermore, colocalization of PLA2G2A and L. monocytogenes was detected in the IL-22-treated infected HepG2 cells, which suggests involvement of PLA2G2A in the mechanism of intracellular killing of L. monocytogenes by HepG2 cells. These results suggest that IL-22 induced at an early stage of L. monocytogenes infection enhances innate immunity against L. monocytogenes in the liver by stimulating hepatocytes to produce an antimicrobial molecule, PLA2G2A.

  1. Tanshinone IIA attenuates the inflammatory response and apoptosis after traumatic injury of the spinal cord in adult rats.

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    Xin Yin

    Full Text Available BACKGROUND: Spinal cord injury (SCI, including immediate mechanical injury and secondary injury, is associated with the inflammatory response, apoptosis and oxidative stress in response to traumatic injury. Tanshinone IIA (TIIA is one of the major extracts obtained from Salvia miltiorrhiza BUNGE, which has anti-inflammatory and anti-apoptotic effects on many diseases. However, little is known about the effects of TIIA treatment on SCI. Therefore, the aim of the present study is to evaluate the pharmacological action of TIIA on secondary damage and the underlying mechanisms of experimental SCI in rats. METHODOLOGY/PRINCIPAL FINDINGS: SCI was generated using a weight drop device on the dorsal spinal cord via a two-level T9-T11 laminectomy. SCI in rats resulted in severe trauma, characterized by locomotor disturbance, edema, neutrophil infiltration, the production of astrocytes and inflammatory mediators, apoptosis and oxidative stress. TIIA treatment (20 mg/kg, i.p. after SCI induced significant effects: (1 improved motor function (Basso, Beattie and Bresnahan scores, (2 reduced the degree of tissue injury (histological score, neutrophil infiltration (myeloperoxidase activity and the expression of astrocytes, (3 inhibited the activation of SCI-related pathways, such as NF-κB and MAPK signaling pathways, (4 decreased the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6 and iNOS, (5 reduced apoptosis (TUNEL staining, and Bcl-2 and caspase-3 expression and (6 reversed the redox state imbalance. CONCLUSIONS/SIGNIFICANCE: The results clearly show that TIIA has a prominent protective effect against SCI through inhibiting the inflammatory response and apoptosis in the spinal cord tissue after SCI.

  2. Nasal immunization with major epitope-containing ApxIIA toxin fragment induces protective immunity against challenge infection with Actinobacillus pleuropneumoniae in a murine model.

    Science.gov (United States)

    Seo, Ki-Weon; Kim, Sae-Hae; Park, Jisang; Son, Youngok; Yoo, Han Sang; Lee, Kyung-Yeol; Jang, Yong-Suk

    2013-01-15

    Actinobacillus pleuropneumoniae is an infective agent that leads to porcine pleuropneumonia, a disease that causes severe economic losses in the swine industry. Based on the fact that the respiratory tract is the primary site for bacterial infection, it has been suggested that bacterial exclusion in the respiratory tract through mucosal immune induction is the most effective disease prevention strategy. ApxIIA is a vaccine candidate against A. pleuropneumoniae infection, and fragment #5 (aa. 439-801) of ApxIIA contains the major epitopes for effective vaccination. In this study, we used mice to verify the efficacy of intranasal immunization with fragment #5 in the induction of protective immunity against nasal challenge with A. pleuropneumoniae and compared its efficacy with that of subcutaneous immunization. Intranasal immunization of the fragment induced significantly higher systemic and mucosal immune responses measured at the levels of antigen-specific antibodies, cytokine-secreting cells after antigen exposure, and antigen-specific lymphocyte proliferation. Intranasal immunization not only efficiently inhibited the bacterial colonization in respiratory organs, but also prevented alveolar tissue damage in infectious condition similar to that of a contaminated pig. Moreover, intranasal immunization with fragment #5 provided acquired protective immunity against intranasal challenge with A. pleuropneumoniae serotype 2. In addition, it conferred cross-protection against serotype 5, a heterologous pathogen that causes severe disease by ApxI and ApxII secretion. Collectively, intranasal immunization with fragment #5 of ApxIIA can be considered an efficient protective immunization procedure against A. pleuropneumoniae infection. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type IIa (USH2A) gene in 1q41

    Energy Technology Data Exchange (ETDEWEB)

    Sumegi, Janos; Wang, Ji-Yi; Zhen, Dong-Kai [Univ. of Nebraska Medical Center, Omaha, NE (United States)] [and others

    1996-07-01

    The gene for Usher syndrome type II (USH2A), and autosomal recessive syndromic deafness, has been mapped to a region of 1q41 flanked proximally by D1S217 and distally by D1S439. Using sequence-tagged sites (STSs) within the region, a total of 21 yeast artificial chromosome (YAC) clones were isolated and ordered into a single contig that spans approximately 11.0 Mb. The order of microsatellite and STS markers in this region was established as D1S505-D1S425-DXS217-D1S556-D1S237-D1S474-EB1-KB6-AFM144XF2-KB1-KB4-D1S229-D1S490-D1S227-TGF{beta}2-D1S439. Analysis of newly positioned polymorphic markers in recombinant individuals in two Usher syndrome type IIa families has enabled us to identify DXS474 and AFM144XF2 as two flanking markers for the Usher type IIa locus. The physical distance between the two markers is 1.0 Mb. This region is covered by eight YACs from the CEPH library: 945f7, 867g9, 762a6, 919h3, 794b8, 785h4, 848b9, and 841g2. A long range physical map of the Usher type IIa critical region, using MluI, BssHII, NotI, EagI, and SacII, has been developed. 41 refs., 5 figs.

  4. Analysis of the type II-A CRISPR-Cas system of Streptococcus agalactiae reveals distinctive features according to genetic lineages

    Directory of Open Access Journals (Sweden)

    Clément eLier

    2015-06-01

    Full Text Available CRISPR-Cas systems (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins are found in 90% of archaea and about 40% of bacteria. In this original system, CRISPR arrays comprise short, almost unique sequences called spacers that are interspersed with conserved palindromic repeats. These systems play a role in adaptive immunity and participate to fight non-self DNA such as integrative and conjugative elements, plasmids, and phages. In Streptococcus agalactiae, a bacterium implicated in colonisation and infections in humans since the 1960s, two CRISPR-Cas systems have been described. A type II-A system, characterised by proteins Cas9, Cas1, Cas2 and Csn2, is ubiquitous, and a type I-C system, with the Cas8c signature protein, is present in about 20% of the isolates. Unlike type I-C, which appears to be non-functional, type II-A appears fully functional. Here we studied type II-A CRISPR-Cas loci from 126 human isolates of S. agalactiae belonging to different clonal complexes that represent the diversity of the species and that have been implicated in colonisation or infection. The CRISPR-Cas locus was analysed both at spacer and repeat levels. Major distinctive features were identified according to the phylogenetic lineages previously defined by multilocus sequence typing, especially for the Sequence Type (ST 17, which is considered hypervirulent. Among other idiosyncrasies, ST-17 shows a significantly lower number of spacers in comparison with other lineages. This characteristic could reflect the peculiar virulence or colonisation specificities of this lineage.

  5. Treatment outcomes in patients with FIGO stage IB-IIA cervical cancer and a focally disrupted cervical stromal ring on magnetic resonance imaging: A propensity score matching study.

    Science.gov (United States)

    Kong, Tae-Wook; Lee, Jung-Dong; Son, Joo-Hyuk; Paek, Jiheum; Chun, Mison; Chang, Suk-Joon; Ryu, Hee-Sug

    2016-10-01

    The aim of this study was to compare treatment outcomes of primary concurrent chemoradiation therapy (CCRT) versus radical hysterectomy (RH) followed by adjuvant RT or CCRT in patients with FIGO stage IB-IIA cervical cancer with focal disruption of the cervical stromal ring on magnetic resonance imaging (MRI). We retrospectively analyzed the clinicopathological data of 156 patients with FIGO stage IB-IIA cervical cancer showing a focal disruption of the stromal ring on MRI between March 2000 and March 2015. Treatment outcomes were compared between the RT-based (n=54) group and RH-based group (n=54) after propensity score matching of each of the patients using a logistic regression model, including age, tumor size on MRI, pelvic lymph node enlargement on MRI, and histology. Five-year disease-free survival rate was 83.1% for the RT-based group and 77.4% for the RH-based group (p=0.228). Five-year disease-specific survival rate was 84.3% for the RT-based group and 83.5% for the RH-based group (p=0.434). Incidence rates of late grade 3 genitourinary adverse reactions (14.8% vs. 0.0%, p=0.006) were significantly higher in the RH-based group than those in the RT-based group. Primary CCRT might be the preferred treatment for FIGO stage IB-IIA cervical cancer patients with focal disruption of cervical stromal ring on MRI given that no difference in patient's survival was found, but higher incidence of treatment-related complications was observed in the RH-based group. Also, primary radical surgery should be done more cautiously in these patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Tanshinone IIA attenuates interleukin-17A-induced systemic sclerosis patient-derived dermal vascular smooth muscle cell activation via inhibition of the extracellular signal-regulated kinase signaling pathway

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    Mengguo Liu

    2015-04-01

    Full Text Available OBJECTIVE: Salvia miltiorrhiza has long been used to treat systemic sclerosis. Tanshinone IIA, one of the phytochemicals derived from the roots of Salvia miltiorrhiza, exhibits multiple biological activities. The present study aimed to investigate whether tanshinone IIA has an effect on the interleukin-17A-induced functional activation of systemic sclerosis patient-derived dermal vascular smooth muscle cells. METHODS: Systemic sclerosis patient-derived dermal vascular smooth muscle cells were incubated with various dosages of tanshinone IIA in the presence of interleukin-17A or the serum of systemic sclerosis patients. Cell proliferation was assessed using Cell Counting Kit-8. The expression of collagen 1 and 3 in cells was evaluated by immunofluorescence. Cell migration was measured using a transwell assay. The expression of phospho-extracellular signal-regulated kinase was detected by Western blotting. RESULTS: Our data demonstrate that tanshinone IIA exerts an inhibitory effect on interleukin-17A-induced systemic sclerosis patient-derived dermal vascular smooth muscle cell proliferation, collagen synthesis and migration. CONCLUSION: These findings suggest that tanshinone IIA might serve as a promising therapeutic agent for the treatment of systemic sclerosis.

  7. Fermionic T-duality in massive type IIA supergravity on AdS{sub 10-k} x M{sub k}

    Energy Technology Data Exchange (ETDEWEB)

    Bakhmatov, Ilya [Kazan Federal University, General Relativity Department, Institute of Physics, Kazan (Russian Federation)

    2016-04-15

    Fermionic T-duality transformation is studied for supersymmetric solutions of massive type IIA supergravity with the metric AdS{sub 10-k} x M{sub k} for k = 3 and 5. We derive the Killing spinors of these backgrounds and use them as input for the fermionic T-duality transformation. The resulting dual solutions form a large family of supersymmetric deformations of the original solutions by complex valued RR fluxes. We observe that the Romans mass parameter does not change under fermionic T-duality, and prove its invariance in the k = 3 case. (orig.)

  8. The 2010 ILSO-ISRU Field Test at Mauna Kea, Hawaii: Results from the Miniaturised Mossbauer Spectrometers Mimos II and Mimos IIA

    Science.gov (United States)

    Klingelhoefer, G.; Morris, R. V.; Blumers, M.; Bernhardt, B.; Graff, T.

    2011-01-01

    For the advanced Moessbauer instrument MIMOS IIA, the new detector technologies and electronic components increase sensitivity and performance significantly. In combination with the high energy resolution of the SDD it is possible to perform X-ray fluorescence analysis simultaneously to Moessbauer spectroscopy. In addition to the Fe-mineralogy, information on the sample's elemental composition will be gathered. The ISRU 2010 field campaign demonstrated that in-situ Moessbauer spectroscopy is an effective tool for both science and feedstock exploration and process monitoring. Engineering tests showed that a compact nickel metal hydride battery provided sufficient power for over 12 hr of continuous operation for the MIMOS instruments.

  9. Nasal immunization with M cell-targeting ligand-conjugated ApxIIA toxin fragment induces protective immunity against Actinobacillus pleuropneumoniae infection in a murine model.

    Science.gov (United States)

    Park, Jisang; Seo, Ki-Weon; Kim, Sae-Hae; Lee, Ha-Yan; Kim, Bumseok; Lim, Chae Woong; Kim, Jin-Hee; Yoo, Han Sang; Jang, Yong-Suk

    2015-05-15

    Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia and severe economic loss in the swine industry has been caused by the infection. Therefore, the development of an effective vaccine against the bacteria is necessary. ApxII toxin, among several virulence factors expressed by the bacteria, is considered to be a promising vaccine candidate because ApxII toxin not only accompanies cytotoxic and hemolytic activities, but is also expressed in all 15 serotypes of bacteria except serotypes 10 and 14. In this study, we identified the peptide ligand capable of targeting the ligand-conjugated ApxIIA #5 fragment antigen to nasopharynx-associated lymphoid tissue. It was found that nasal immunization with ligand-conjugated ApxIIA #5 induced efficient mucosal and systemic immune responses measured at the levels of antigen-specific antibodies, cytokine-secreting cells after antigen exposure, and antigen-specific lymphocyte proliferation. More importantly, the nasal immunization induced protective immunity against nasal challenge infection of the bacteria, which was confirmed by histopathological studies and bacterial clearance after challenge infection. Collectively, we confirmed that the ligand capable of targeting the ligand-conjugated antigen to nasopharynx-associated lymphoid tissue can be used as an effective nasal vaccine adjuvant to induce protective immunity against A. pleuropneumoniae infection. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. Tanshinone IIA inhibits endothelin-1 production in TNF-α-induced brain microvascular endothelial cells through suppression of endothelin-converting enzyme-1 synthesis

    Institute of Scientific and Technical Information of China (English)

    Chao TANG; An-hua WU; Hong-li XUE; Yun-jie WANG

    2007-01-01

    Aim: To investigate the effects of tanshinone ⅡA (Tan ⅡA) on the regulation of the production of endothelin (ET)-1 (including large ET-1), mRNA levels of ET-1,endothelin-converting enzyme- 1 (ECE- 1), endothelin-A receptor (ETA) and endothelin-B receptor (ETB) induced by TNF-α in rat brain microvascular endo-thelial cells (BMVEC). Methods: The ET-1 release (including large ET-1) into the culture medium was determined by enzyme immunoassay. The levels of ET-1,ECE- 1, ETA, and ETB mRNA were measured by RT-PCR. Endothelin receptor bind-ing was also tested. Results: The induction of ET- 1 release by TNF-α from cul-tured BMVEC was dose-dependently reduced by Tan IIA, but large ET-1 levels progressively increased in response to Tan IIA; the mRNA expression of ET-1 was unaffected. Tan ⅡA also caused a decrease in ETA receptor mRNA and ECE-1expression in a dose-dependent manner. Endothelin receptor binding was unal-tered in BMVEC stimulated with TNF-α alone or a combination of TNF-α and Tan ⅡA. Conclusion: These findings suggest that Tan ⅡA may inhibit ET-1 produc-tion in TNF-α-induced BMVEC through the suppression of ECE-1 synthesis.

  11. Detection of HTLV-IIa in blood donors in an urban area of the Amazon Region of Brazil (Belém, PA

    Directory of Open Access Journals (Sweden)

    Ishak R.

    1998-01-01

    Full Text Available The human lymphotropic viruses type I (HTLV-I and type II (HTLV-II are members of a group of mammalian retroviruses with similar biological properties, and blood transfusion is an important route of transmission. HTLV-I is endemic in a number of different geographical areas and is associated with several clinical disorders. HTLV-II is endemic in several Indian groups of the Americas and intravenous drug abusers in North and South America, Europe and Southeast Asia. During the year of 1995, all blood donors tested positive to HTLV-I/II in the State Blood Bank (HEMOPA, were directed to a physician and to the Virus Laboratory at the Universidade Federal do Pará for counselling and laboratory diagnosis confirmation. Thirty-five sera were tested by an enzyme immune assay, and a Western blot that discriminates HTLV-I and HTLV-II infection. Two HTLV-II positive samples were submitted to PCR analysis of pX and env genomic region, and confirmed to be of subtype IIa. This is the first detection in Belém of the presence of HTLV-IIa infection among blood donors. This result emphasizes that HTLV-II is also present in urban areas of the Amazon region of Brazil and highlights the need to include screening tests that are capable to detect antibodies for both types of HTLV.

  12. pbp2229-mediated nisin resistance mechanism in Listeria monocytogenes confers cross-protection to class IIa bacteriocins and affects virulence gene expression.

    Science.gov (United States)

    Gravesen, Anne; Kallipolitis, Birgitte; Holmstrøm, Kim; Høiby, Poul Erik; Ramnath, Manilduth; Knøchel, Susanne

    2004-03-01

    It was previously shown that enhanced nisin resistance in some mutants was associated with increased expression of three genes, pbp2229, hpk1021, and lmo2487, encoding a penicillin-binding protein, a histidine kinase, and a protein of unknown function, respectively. In the present work, we determined the direct role of the three genes in nisin resistance. Interruption of pbp2229 and hpk1021 eliminated the nisin resistance phenotype. Interruption of hpk1021 additionally abolished the increase in pbp2229 expression. The results indicate that this nisin resistance mechanism is caused directly by the increase in pbp2229 expression, which in turn is brought about by the increase in hpk1021 expression. We also found a degree of cross-protection between nisin and class IIa bacteriocins and investigated possible mechanisms. The expression of virulence genes in one nisin-resistant mutant and two class IIa bacteriocin-resistant mutants of the same wild-type strain was analyzed, and each mutant consistently showed either an increase or a decrease in the expression of virulence genes (prfA-regulated as well as prfA-independent genes). Although the changes mostly were moderate, the consistency indicates that a mutant-specific change in virulence may occur concomitantly with bacteriocin resistance development.

  13. Developing Anticancer Copper(II) Pro-drugs Based on the Nature of Cancer Cells and the Human Serum Albumin Carrier IIA Subdomain.

    Science.gov (United States)

    Gou, Yi; Qi, Jinxu; Ajayi, Joshua-Paul; Zhang, Yao; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong

    2015-10-01

    To synergistically enhance the selectivity and efficiency of anticancer copper drugs, we proposed and built a model to develop anticancer copper pro-drugs based on the nature of human serum albumin (HSA) IIA subdomain and cancer cells. Three copper(II) compounds of a 2-hydroxy-1-naphthaldehyde benzoyl hydrazone Schiff-base ligand in the presence pyridine, imidazole, or indazole ligands were synthesized (C1-C3). The structures of three HSA complexes revealed that the Cu compounds bind to the hydrophobic cavity in the HSA IIA subdomain. Among them, the pyridine and imidazole ligands of C1 and C2 are replaced by Lys199, and His242 directly coordinates with Cu(II). The indazole and Br ligands of C3 are replaced by Lys199 and His242, respectively. Compared with the Cu(II) compounds alone, the HSA complexes enhance cytotoxicity in MCF-7 cells approximately 3-5-fold, but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent. We find that the HSA complex has a stronger capacity for cell cycle arrest in the G2/M phase of MCF-7 by targeting cyclin-dependent kinase 1 (CDK1) and down-regulating the expression of CDK1 and cyclin B1. Moreover, the HSA complex promotes MCF-7 cell apoptosis possibly through the intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.

  14. Single Photon Emission Computed Tomography (SPECT) Experience with (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[123I]IA) in the Living Human Brain of Smokers and Nonsmokers

    Science.gov (United States)

    BRAŠIĆ, JAMES ROBERT; ZHOU, YUN; MUSACHIO, JOHN L.; HILTON, JOHN; FAN, HONG; CRABB, ANDREW; ENDRES, CHRISTOPHER J.; REINHARDT, MELVIN J.; DOGAN, AHMET S.; ALEXANDER, MOHAB; ROUSSET, OLIVIER; MARIS, MARIKA A.; GALECKI, JEFFREY; NANDI, AYON; WONG, DEAN F.

    2009-01-01

    (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-[123I]IA), a novel potent radioligand for high-affinity α4β2* neuronal nicotinic acetylcholine receptors (nAChRs), provides a means to evaluate the density and the distribution of nAChRs in the living human brain. We sought in healthy adult smokers and nonsmokers to (1) evaluate the safety, tolerability, and efficacy of 5-[123I]IA in an open nonblind trial and (2) to estimate the density and distribution of α4β2* nAChRs in the brain. Single photon emission computed tomography (SPECT) was performed for five hours after the intravenous administration of approximately 0.001 μg/kg (approximately 10 mCi) 5-[123I]IA. Blood pressure, heart rate, and neurobehavioral status were monitored before, during, and after the administration of 5-[123I]IA to twelve healthy adults (8 men and 4 women) (6 smokers and 6 nonsmokers) ranging in age from 19 to 46 years (mean = 28.25, standard deviation = 8.20). High plasma nicotine level was significantly associated with low 5-[123I]IA binding in (1) the caudate head, the cerebellum, the cortex, and the putamen, utilizing both the Sign and Mann-Whitney U tests, (2) the fusiform gyrus, the hippocampus, the parahippocampus, and the pons utilizing the Mann-Whitney U test, and (3)the thalamus utilizing the Sign test. We conclude that 5-[123I]IA is a safe, well-tolerated, and effective pharmacologic agent for human subjects to estimate high-affinity α4/β2 nAChRs in the living human brain. PMID:19140167

  15. Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae.

    Science.gov (United States)

    Yamamoto, Shouji; Ohnishi, Makoto

    2017-09-15

    In Vibrio cholerae, the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326-347, 2014, https://doi.org/10.1111/mmi.12462). TfoS specifically activates the transcription of tfoR, encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned off tfoR::lacZ expression but possessed intact chiS and tfoS genes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIA(glc)) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIA(glc) inactivated natural competence and tfoR transcription. Chitin-induced expression of the chb operon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIA(glc) Furthermore, the regulation of tfoR and chb expression by EIIA(glc) was dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIA(glc) These results define a previously unknown connection between the PTS and chitin signaling pathways in V. cholerae and suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.IMPORTANCE The EIIA

  16. Synthesis and characterization of novel Schiff bases containing pyrimidine unit

    Directory of Open Access Journals (Sweden)

    Jumbad H. Tomma

    2014-01-01

    Full Text Available The work involves synthesis of novel Schiff base derivatives containing a pyrimidine unit starting with chalcones. 4-Aminoacetophenone was reacted with 4-nitrobenzaldehyde or 4-chlorobenzaldehyde in basic medium giving chalcones, [I]a and [I]b, respectively, by Claisen-Schemidt reaction. The chalcones [I]a and [I]b were reacted with urea in HCl medium giving oxopyrimidines, [II]a and [II]b. They were also reacted with thiourea in basic medium to give thioxopyrimidines, [III]a and [III]b. The novel mono and bis Schiff bases, [VIII]na, [VIII]nb, [IX]na, [IX]nb, [X]na, [X]nb, [XI]na, and [XI]nb were synthesized by the reaction of pyrimidine derivatives; oxopyrimdines, [II]a and [II]b and thioxopyrimidines, [III]a and [III]b with 4-(4′-n-alkoxybenzoloxybenzaldehyde [VI] and polymethylene-α,ω-bis-4-oxybenzaldehydes [VII]m, respectively, in dry benzene using drops of glacial acetic acid as a catalyst. The synthesized compounds were characterized by melting points, elemental analysis, FTIR, and 1H NMR spectroscopy.

  17. Immunological study of an attenuated Salmonella Typhimurium expressing ApxIA, ApxIIA, ApxIIIA and OmpA of Actinobacillus pleuropneumoniae in a mouse model.

    Science.gov (United States)

    Hur, Jin; Eo, Seong Kug; Park, Sang-Youel; Choi, Yoonyoung; Lee, John Hwa

    2016-01-01

    Salmonella Typhimurium strain expressing the Actinobacillus pleuropneumoniae antigens, ApxIA, ApxIIA, ApxIIIA and OmpA, was previously constructed as a vaccine candidate for porcine pleuropneumonia. This strain was a live attenuated (∆lon∆cpxR∆asd)Salmonella as a delivery host and contained a vector containing asd. An immunological study of lymphocyte proliferation, T-lymphocyte subsets and cytokines in the splenocytes of a mouse model was carried out after stimulation with the candidate Salmonella Typhimurium by intranasal inoculation. The splenic lymphocyte proliferation and the levels of IL-4, IL-6 and IL-12 of the inoculated mice were significantly increased, and the T- and B-cell populations were also elevated. Collectively, the candidate may efficiently induce the Th1- and Th2-type immune responses.

  18. Phase IIa Clinical Trial of Trans-1-Amino-3-18F-Fluoro- Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Inoue

    2014-10-01

    Full Text Available Objective(s: We performed a phase IIa clinical trial of trans-1-amino-3-18Ffluoro-cyclobutane carboxylic acid (anti-18F-FACBC, a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326.

  19. Phase IIa Clinical Trial of Trans-1-Amino-3-18F-Fluoro-Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer

    Science.gov (United States)

    Inoue, Yusuke; Asano, Yuji; Satoh, Takefumi; Tabata, Ken-ichi; Kikuchi, Kei; Woodhams, Reiko; Baba, Shiro; Hayakawa, Kazushige

    2014-01-01

    Objective(s): We performed a phase IIa clinical trial of trans-1-amino-3-18F-fluoro-cyclobutane carboxylic acid (anti-18F-FACBC), a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326. PMID:27408864

  20. Intensity of cervical inflammatory reaction as a risk factor for recurrence of carcinoma of the uterine cervix in stages IB and IIA

    Directory of Open Access Journals (Sweden)

    José Humberto Tavares Guerreiro Fregnani

    Full Text Available CONTEXT AND OBJECTIVE: Inflammatory reaction intensity has been indicated as a possible recurrence risk factor in carcinoma of the uterine cervix. Some authors observed greater risk with weak inflammatory reaction, while others described the opposite. This study aimed to evaluate risk factors for initial-stage uterine cervix carcinoma recurrence (IB and IIA, considering inflammatory reaction intensity. DESIGN AND SETTING: Retrospective cohort at Hospital do Câncer A. C. Camargo. METHODS: 289 patients with diagnosed uterine cervix carcinoma (stages IB and IIA who underwent radical surgery between 1980 and 1999 were studied. Data were collected from medical records. Histological sections from tumors and lymph nodes could be reviewed in 247 cases. Five-year disease-free survival rates were calculated using the Kaplan-Meier method and curves were compared using the log-rank test. Cox's proportional-hazards model was used for multivariate analysis. Recurrence risk was estimated using hazard ratios (HR. RESULTS: Forty-three recurrences were found. Multivariate analysis identified the following independent recurrence risk factors: number of metastatic pelvic lymph nodes (one lymph node: HR = 3.3 [1.3-8.3]; two or three: HR = 5.3 [1.5-18.6]; four or more: HR = 7.6 [1.7-33.2], tumor invasion depth (deepest third: HR = 2.1 [1.1-4.1] and inflammatory reaction intensity in the uterine cervix (absent or slight: HR = 2.5 [1.1-5.7]. CONCLUSION: This study identified that absent or slight inflammatory reaction was an independent risk factor for recurrence. The other risk factors were the number of metastatic pelvic lymph nodes and invasion of the deepest third of the uterine cervix.

  1. Unique action of sodium tanshinone II-A sulfonate (DS-201) on the Ca(2+) dependent BK(Ca) activation in mouse cerebral arterial smooth muscle cells.

    Science.gov (United States)

    Tan, Xiaoqiu; Yang, Yan; Cheng, Jun; Li, Pengyun; Inoue, Isao; Zeng, Xiaorong

    2011-04-10

    Sodium tanshinone II-A sulfonate (DS-201) is a water-soluble derivative of tanshinone IIA, a main active constituent of Salvia miltiorrhiza which has been used for treatments of cardio- and cerebro-vascular diseases. DS-201 activates large conductance Ca(2+)-sensitive K(+) channels (BK(Ca)) in arterial smooth muscle cells, and reduces the vascular tone. Here we investigated the effect of DS-201 on the BK(Ca) channel kinetics by analyzing single channel currents. Smooth muscle cells were freshly isolated from mouse cerebral arteries. Single channel currents of BK(Ca) were recorded by patch clamp. DS-201 increased the total open probability (NPo) of BK(Ca) in a concentration-dependent manner. But this action required intracellular Ca(2+), and the effect depended on the Ca(2+) concentration ([Ca(2+)](free)). DS-201 activated BK(Ca) with the half maximal effective concentration (EC(50)) of 111.5μM at 0.01μM [Ca(2+)](free), and 68.5μM at 0.1μM [Ca(2+)](free.) The effect of DS-201 on NPo was particularly strong in the range of [Ca(2+)](free) between 0.1 and 1μM. Analysis of the channel kinetics revealed that DS-201 had only the effect on the channel closing without affecting the channel opening, which was a striking contrast to the effect of [Ca(2+)](free), that is characterized by changing the channel opening without changing the channel closing. DS-201 may be bound to the open state of BK(Ca), and have an inhibitory effect on the transition from the open to closed state. By this way DS-201 may enhance the activity of BK(Ca), and exhibit a strong vasodilating effect against vasoconstriction in the range of [Ca(2+)](free) between 0.1 and 1μM. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Tanshinone II-A sodium sulfonate (DS-201) enhances human BKCa channel activity by selectively targeting the pore-forming α subunit.

    Science.gov (United States)

    Tan, Xiao-qiu; Cheng, Xiu-li; Yang, Yan; Yan, Li; Gu, Jing-li; Li, Hui; Zeng, Xiao-rong; Cao, Ji-min

    2014-11-01

    Tanshinone II-A sodium sulfonate (DS-201), a water-soluble derivative of Tanshinone II-A, has been found to induce vascular relaxation and activate BKCa channels. The aim of this study was to explore the mechanisms underlying the action of DS-201 on BKCa channels. Human BKCa channels containing α subunit alone or α plus β1 subunits were expressed in HEK293 cells. BKCa currents were recorded from the cells using patch-clamp technique. The expression and trafficking of BKCa subunits in HEK293 cells or vascular smooth muscle cells (VSMCs) were detected by Western blotting, flow cytometry and confocal microscopy. DS-201 (40-160 μmol/L) concentration-dependently increased the total open probability of BKCa channels in HEK293 cells, associated with enhancements of Ca(2+) and voltage dependence as well as a delay in deactivation. Coexpression of β1 subunit did not affect the action of DS-201: the values of EC50 for BKCa channels containing α subunit alone and α plus β1 subunit were 66.6±1.5 and 62.0±1.1 μmol/L, respectively. In both HEK293 cells and VSMCs, DS-201 (80 μmol/L) markedly increased the expression of α subunit without affecting β1 subunit. In HEK293 cells, DS-201 enriched the membranous level of α subunit, likely by accelerating the trafficking and suppressing the internalization of α subunit. In both HEK293 cells and VSMCs, DS-201 (≥320 μmol/L) induced significant cytotoxicity. DS-201 selectively targets the pore-forming α subunit of human BKCa channels, thus enhancing the channel activities and increasing the subunit expression and trafficking, whereas the β1 subunit does not contribute to the action of DS-201.

  3. Generating Units

    Data.gov (United States)

    Department of Homeland Security — Generating Units are any combination of physically connected generators, reactors, boilers, combustion turbines, and other prime movers operated together to produce...

  4. Congaree National Park Data Landcover Product - NOAA C-CAP Source

    Data.gov (United States)

    National Park Service, Department of the Interior — NPScape CCAP landcover (CCAP_LAC - 1996, 2001 and 2006) and landcover change (CCAP_LCC) products. Landcover change is produced from the 1996-2001 NOAA C-CAP and...

  5. UNIT, TIBET.

    Science.gov (United States)

    Louisiana Arts and Science Center, Baton Rouge.

    THE UNIT OF STUDY DESCRIBED IN THIS BOOKLET DEALS WITH THE GEOGRAPHY AND HISTORY OF TIBET. THE UNIT COVERS SOME OF THE GENERAL FEATURES OF THE COUNTRY AND THEIR EFFECT UPON THE LIVES OF THE TIBETAN PEOPLE. DISCUSSION QUESTIONS ARE INSERTED TO STIMULATE THOUGHT. THE RELIGION OF TIBET IS DISCUSSED IN RELATION TO ITS INFLUENCE ON THE ART AND CULTURE…

  6. Mixed Waste Management Facility (MWMF) Groundwater Monitoring Report: Fourth quarter 1991 and 1991 summary

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, C.Y.

    1992-03-01

    During fourth quarter 1991, tritium, trichloroethylene, tetrachloroethylene, chloroethene (vinyl chloride), total radium, mercury, and lead exceeded the US Environmental Protection Agency primary drinking water standards (PDWS) in groundwater samples from monitoring wells at the Mixed Waste Management Facility (MWMF) and adjacent facilities. Tritium and trichloroethylene were the most widespread contaminants; 55 (49%) wells exhibited elevated tritium activities, and 24 (21%) wells exhibited elevated trichloroethylene concentrations. Tritium and trichloroethylene levels exceeding the PDWS also occurred in several wells in Aquifer Unit IIA (Congaree). Levels of manganese, total organic halogens, nickel, iron, 1,1-dichloroethane, aluminum, nonvolatile beta, and trichlorofluoromethane that exceeded Flag 2 criteria were found in one or more wells beneath the MWMF. Downgradient wells in the three hydrostratigraphic units at the MWMF contained elevated levels of tritium, trichloroethylene, tetrachloroethylene, total radium, chloroethene (vinyl chloride), lead, mercury, manganese, total organic halogens, nickel, iron, 1,1-dichloroethane, aluminum, nonvolatile beta, or trichlorofluoromethane. Groundwater samples from 81 (72%) of the monitoring wells at the MWMF and adjacent facilities contained elevated levels of several contaminants.

  7. 丹参酮IIA对肾癌786-O细胞生长抑制作用及其分子机制%Inhibitive Effect and Molecular Mechanism of Tanshinone IIA on Growth of Renal Carcinoma Cell 786-O

    Institute of Scientific and Technical Information of China (English)

    肖建勇; 谭宇蕙; 张广献

    2012-01-01

    Objective To explore the inhibitive effect and molecular mechanism of Tanshinone IIA (Tan IIA) on the growth of renal carcinoma cell 786-0. Methods MTT assay was used to detect the vitality of 786-0 cells after treatment with Tan IIA. Flow Cytometry was employed to examine the cell cycle distribution in 786-0 cells induced by Tan IIA. Immunoblotting method was utilized to determine the expression level of target proteins related to cell cycle arrest. The translocation of Nucleophosmin (NPM )/B23 after Tan IIA treatment was observed by confocal microscopy. Results Tan IIA remarkably inhibited 786-0 cells vitality in dose-dependent manner(p< 0.05). The results of cell cycle analysis indicated that 786-0 cells were arrested in S phase after Tan IIA treatment. Furthermore, the upregulation of cyclin A, p53 and its downstream gene p21 in 786-0 cells was shown by Immunoblotting. Translocation of NPM from nucleolus to nucleoplasm was found under confocal microscopy. Conclusion Treatment with Tan IIA can induce 786-0 cell cycle S arrest, and the underlying mechanism might relate to the translocation of NPM and to the upregulation of p53 and p21.%目的 研究丹参酮IIA对肾癌细胞生长抑制作用及其分子机制.方法 MTT法检测丹参酮IIA对肾癌细胞活力影响;流式细胞分析检测丹参酮IIA对肾癌细胞周期阻滞;免疫印迹检测细胞周期阻滞相关靶蛋白蛋白表达水平;激光共聚焦观察核仁蛋白Nucleophosmin (NPM)/B23定位的变化.结果 丹参酮能够呈浓度依赖方式显著抑制肾癌细胞生长活力(P<0.05);细胞周期分析表明丹参酮IIA处理的肾癌细胞阻滞在S期;免疫印迹结果证明丹参酮IIA处理肾癌细胞,cyclin A,p53及其下游基因p21显著上调;激光共聚焦结果表明在丹参酮IIA作用下,NPM蛋白定位从核仁移位到核浆.结论 丹参酮IIA作用786-O细胞导致细胞周期S阻滞,其机制可能与NPM移位促使其相互作用靶蛋白p53和p21蛋白水平上调有关.

  8. Hydrolysis of lipoproteins by sPLA2's enhances mitogenesis and eicosanoid release from vascular smooth muscle cells: Diverse activity of sPLA2's IIA, V and X.

    Science.gov (United States)

    Pruzanski, Waldemar; Kopilov, Julia; Kuksis, Arnis

    2016-01-01

    Mitogenesis of Vascular Smooth Muscle Cells (VSMC) plays an important role in atherogenesis. Until recently, the effect of lipid subfractions has not been clarified. Secretory phospholipases A2 (sPLA2's) hydrolyse glycerophospholipids and release pro-inflammatory lyso-lipids, oxidized and non-oxidized fatty acids and isoprostanes. They localize in the vascular wall. We hypothesized that structurally similar sPLA2's may exert different impact on VSMC. The influence of sPLA2's, IIA, V, X, HDL, LDL, and hydrolysis products was tested on mitogenesis of VSMC, i.e., the early effect on the cell membrane phospholipids, and on PGE2 and LTB4 release, i.e., late effect of Cyclooxygenase and 5-lipooxygenase activity in VSMC. Mitogenesis was significantly enhanced by HDL and LDL, and by products of sPLA2 hydrolysis. Hydrolysis of HDL or LDL enhanced mitogenic activity in order V>X>IIA. The release of PGE2 was enhanced by group X sPLA2 and by HDL hydrolyzed by groups V and X. LDL and its hydrolysis products enhanced the release of PGE2 in order X>V>IIA. The release of LTB4 was markedly increased by LDL and HDL, and by hydrolytic products of group V and X, but not group IIA sPLA2. Our study demonstrates a diverse interaction of pro-inflammatory sPLA2's with HDL and LDL affecting both mitogenesis and eicosanoid release from VSMC, therefore potentially enhancing their pro-atherogenic activity.

  9. Turnley Unit

    Data.gov (United States)

    Federal Laboratory Consortium — Facilities at this unit include cattle working pens, hydraulic squeeze chute and electronic scale, a maintenance building, and four hay storage sheds. There is one...

  10. Operable Units

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset consists of operable unit data from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and...

  11. Detector Unit

    CERN Multimedia

    1960-01-01

    Original detector unit of the Instituut voor Kernfysisch Onderzoek (IKO) BOL project. This detector unit shows that silicon detectors for nuclear physics particle detection were already developed and in use in the 1960's in Amsterdam. Also the idea of putting 'strips' onto the silicon for high spatial resolution of a particle's impact on the detector were implemented in the BOL project which used 64 of these detector units. The IKO BOL project with its silicon particle detectors was designed, built and operated from 1965 to roughly 1977. Detector Unit of the BOL project: These detectors, notably the ‘checkerboard detector’, were developed during the years 1964-1968 in Amsterdam, The Netherlands, by the Natuurkundig Laboratorium of the N.V. Philips Gloeilampen Fabrieken. This was done in close collaboration with the Instituut voor Kernfysisch Onderzoek (IKO) where the read-out electronics for their use in the BOL Project was developed and produced.

  12. Detailed scrutiny of the anion receptor pocket in subdomain IIA of serum proteins toward individual response to specific ligands: HSA-pocket resembles flexible biological slide-wrench unlike BSA.

    Science.gov (United States)

    Datta, Shubhashis; Halder, Mintu

    2014-06-12

    Present study reveals that the subdomain IIA cavity of two homologous serum albumins (HSA, BSA) has inherent mutual structural and functional deviations which render noticeable difference in behavior toward specific ligands. The major drug binding site (subdomain IIA) of HSA is found to be largely hydrophobic while that of BSA is partially exposed to water. Larger shift in REE spectra and greater change in solvent reorganization energy of coumarin 343 (C343)-anion in HSA clearly reveals that binding pocket is relatively large and water molecules penetrate deeper into it unlike BSA. The individual response of proteins to perturbation by ligands is found to be way different. Although the subdomain IIA is primarily anion receptive (prefers anionic ligands), the present study suggests that HSA may also like to bind neutral guests due to its remarkable conformational features. Actually, HSA is capable of adopting favorable conformation like mechanical slide-wrench, when required, to accommodate neutral ligands [e.g., coumarin 314 (C314)], as well. But due to less flexible solution structure, BSA behaves like fixed mechanical spanners and hence is not very responsive to C314. Therefore, the generally speaking functional-structural similarities of homologous proteins can be apparent and needs to be analyzed exhaustively.

  13. Determination of Sodium Tanshinone IIA Sulfonate in human plasma by LC-MS/MS and its application to a clinical pharmacokinetic study.

    Science.gov (United States)

    Qin, WeiWei; Wang, Bin; Lu, XiaoPei; Liu, HaiMing; Wang, Li; Qi, WeiLin

    2016-03-20

    An assay based on protein precipitation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed and validated for the quantitative analysis of Sodium Tanshinone IIA Sulfonate (STS) in human plasma. After the addition of dehydroepiandrosterone-D5-3-sulfate sodium salt (DHEAS-D5) as internal standard (IS) and formic acid, plasma samples were prepared by one-step protein precipitation with a mixture of acetonitrile and methanol. Isocratic mobile phase consisted of 0.4 mmol/L ammonium formate buffer (16 ppm formic acid)/acetonitrile (40/60, v/v) on a XSELECT™ HSS T3 column. Detection was performed on a triple-quadrupole mass spectrometer utilizing an electrospray ionization (ESI) interface operating in positive ion and selected reaction monitoring (SRM) mode with the precursor to product ion transitions m/z 373.3→357.1 for STS and m/z 373.0→97.8 for the IS. Calibration curves of STS in human plasma were linear (r=0.9957-0.9998) over the concentration range of 2-1000 ng/mL with acceptable accuracy and precision. The lower limit of quantification in human plasma was 2 ng/mL. The validated LC-MS/MS method has been successfully applied to a pharmacokinetic study of STS in Chinese healthy male volunteers.

  14. Tanshinone IIA inhibits myocardial remodeling induced by pressure overload via suppressing oxidative stress and inflammation: Possible role of silent information regulator 1.

    Science.gov (United States)

    Feng, Jun; Li, Shusheng; Chen, Huawen

    2016-11-15

    Tanshinone IIA (Tan) exerts potential protective effects against cardiovascular diseases. Oxidative stress and inflammation are involved in cardiac hypertrophy. Activation of silent information regulator 1 (SIRT1) signaling has been suggested to attenuate cardiac hypertrophy. This study aims to evaluate the antioxidative and anti-inflammatory effects of Tan treatment in pressure overload-induced myocardial remodeling and elucidated its potential mechanisms. Sprague-Dawley rats were treated with Tan in the absence or presence of the SIRT1 inhibitor sirtinol (Snl) and then subjected to transverse aortic constriction (TAC). Tan conferred cardioprotective effects by improving cardiac function, reducing apoptosis and myocardial remodeling, upregulating SIRT1, Bcl-2 expressions, and downregulating Bax and caspase-3 expressions. Snl attenuated these effects by inhibiting SIRT1 signaling. Tan treatment also reduced myocardium malondialdehyde (MDA) content, and cardiac inflammatory cytokines (TNF-α and IL-6) and increased myocardium superoxide dismutase (SOD) level. However, these effects were also abolished by Snl. In conclusion, these results indicate that Tan significantly attenuates TAC-induced myocardial remodeling possibly due to its strong anti-oxidative and anti-inflammatory activity. Importantly, SIRT1 signaling activation is involved in this process. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection

    Science.gov (United States)

    Furuyama, Wakako; Marzi, Andrea; Maruyama, Junki; Kuroda, Makoto; Miyamoto, Hiroko; Manzoor, Rashid; Yoshida, Reiko; Igarashi, Manabu; Feldmann, Heinz; Takada, Ayato

    2016-01-01

    Antibody-dependent enhancement (ADE) of Ebola virus (EBOV) infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fcγ-receptor IIa (FcγRIIa)-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs) is required for ADE of EBOV infection. We found that deletion of the FcγRIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface FcγRIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection. PMID:28036370

  16. Finite-size corrections in the SU(2) x SU(2) sector of type IIA string theory on AdS_4 x CP^3

    CERN Document Server

    Astolfi, Davide; Grignani, Gianluca; Harmark, Troels; Orselli, Marta

    2008-01-01

    We consider finite-size corrections in the SU(2) x SU(2) sector of type IIA string theory on AdS_4 x CP^3, which is the string dual of the recently constructed N=6 superconformal Chern-Simons theory of Aharony, Bergman, Jafferis and Maldacena (ABJM theory). The string states we consider are in the R x S^2 x S^2 subspace of AdS_4 x CP^3 with an angular momentum J on CP^3 being large. We compute the finite-size corrections using two different methods, one is to consider curvature corrections to the Penrose limit giving an expansion in 1/J, the other by considering a low energy expansion in lambda'=lambda/J^2 of the string theory sigma-model, lambda being the 't Hooft coupling of the dual ABJM theory. For both methods there are interesting issues to deal with. In the near-pp-wave method there is a 1/\\sqrt{J} interaction term for which we use zeta-function regularization in order to compute the 1/J correction to the energy. For the low energy sigma-model expansion we have to take into account a non-trivial coupli...

  17. Comparison of Methylmercury Ecology in Adjacent Coastal Plain Rivers in South Carolina

    Science.gov (United States)

    Bradley, P. M.; Journey, C. A.; Chapelle, F. H.; Lowery, M. A.; Conrads, P. A.

    2010-12-01

    Fish-tissue mercury concentrations (approximately 2 micrograms per gram) in the Edisto River basin of South Carolina are among the highest recorded in the United States. Substantially lower mercury concentrations (approximately 0.2 microgram per gram) are reported in fish from the adjacent Congaree River sub-basin and the Congaree National Park. Concentrations of total mercury were statistically higher in sediments from the Congaree River compared with those in sediments from the Edisto River. No statistically significant differences were observed in concentrations of methylmercury or in the range of net methylation potentials in sediments collected from various Edisto and Congaree hydrologic settings. In both systems, net methylation potentials were an order of magnitude or more lower in stream-channel sediments than in wetland sediments. These results are not consistent with the hypothesis that differences in fish-tissue mercury between the Edisto and Congaree basins reflect fundamental differences in the potential for each system to methylate mercury. The marked differences in net methylation potential observed between the wetland and in-stream settings suggested an alternative hypothesis: differences in the efficiency of methylmercury transport from zones of production (wetlands) to points of entry into the food chain (channels) contribute to the observed differences in fish-tissue mercury concen¬trations between the two river systems. An assessment of the flood hydrodynamics of these two rivers is consistent with the alternative hypothesis.

  18. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Each of the six instructional units deals with one aspect of conservation: forests, water, rangeland, minerals (petroleum), and soil. The area of the elementary school curriculum with which each correlates is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the…

  19. [Conservation Units.

    Science.gov (United States)

    Texas Education Agency, Austin.

    Instructional units deal with each aspect of conservation: forests, wildlife, rangelands, water, minerals, and soil. The area of the secondary school curriculum with which each is correlated is indicated. Lists of general and specific objectives are followed by suggested teaching procedures, including ideas for introducing the topic, questions to…

  20. An NQO1-initiated and p53-independent apoptotic pathway determines the anti-tumor effect of tanshinone IIA against non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Fang Liu

    Full Text Available NQO1 is an emerging and promising therapeutic target in cancer therapy. This study was to determine whether the anti-tumor effect of tanshinone IIA (TSA is NQO1 dependent and to elucidate the underlying apoptotic cell death pathways. NQO1(+ A549 cells and isogenically matched NQO1 transfected and negative H596 cells were used to test the properties and mechanisms of TSA induced cell death. The in vivo anti-tumor efficacy and the tissue distribution properties of TSA were tested in tumor xenografted nude mice. We observed that TSA induced an excessive generation of ROS, DNA damage, and dramatic apoptotic cell death in NQO1(+ A549 cells and H596-NQO1 cells, but not in NQO1(- H596 cells. Inhibition or silence of NQO1 as well as the antioxidant NAC markedly reversed TSA induced apoptotic effects. TSA treatment significantly retarded the tumor growth of A549 tumor xenografts, which was significantly antagonized by dicoumarol co-treatment in spite of the increased and prolonged TSA accumulations in tumor tissues. TSA activated a ROS triggered, p53 independent and caspase dependent mitochondria apoptotic cell death pathway that is characterized with increased ratio of Bax to Bcl-xl, mitochondrial membrane potential disruption, cytochrome c release, and subsequent caspase activation and PARP-1 cleavage. The results of these findings suggest that TSA is a highly specific NQO1 target agent and is promising in developing as an effective drug in the therapy of NQO1 positive NSCLC.

  1. Clinical value of 12 occlusal features for the prediction of disc displacement with reduction (RDC/TMD Axis I group IIa).

    Science.gov (United States)

    Chiappe, G; Fantoni, F; Landi, N; Biondi, K; Bosco, M

    2009-05-01

    The purpose of this study is to quantify the clinical value of 12 occlusal variables for the prediction of disc displacement with reduction diagnosed according to research diagnostic criteria (RDC)/temporomandibular disorder (TMD). Twelve occlusal features were clinically assessed by the same three operators. The sample consisted of 165 TMD patients (65 males, 100 females; mean age: 32.55 +/-11.685 years) with only disc displacement with reduction (RDC/TMD Axis I group IIa) and a control sample of 145 healthy subjects (65 males, 80 females; mean age:31.24+/-12.436 years) diagnosed with RDC/TMD Axis I group 0. A stepwise multiple logistic regression model was used to identify the significant correlation between occlusal features and disease. The odds ratio for disc displacement was 2.84 for absence of canine guidance, 2.14 for mediotrusive interference and 1.75 for retruded contact position (RCP)/maximum intercuspation (MI) slide >or=2 mm. Other occlusal variables did not reveal to be statistically significant. The percentage of the total log likelihood for disc displacement explained by the significant occlusal factors was acceptable with a Nagelkerke's R(2) = 0.124. The final model including the significant occlusal features revealed an optimal discriminant capacity to predict patients with disc displacement with a sensitivity of 63.6% or with a specificity of 64.8% for healthy subjects and an accuracy of 64.2%. Occlusal features showed a low predictive value for detecting disc displacement. Multifactorial complex pathologies such as TMD should be investigated using a multivariate statistical analysis; moreover,the future of aetiopathogenic research in this matter requires a multifactorial approach.

  2. Identification of clinically antibiotic resistant genes Aac(3-IIa and Aac(6’-Ib in wastewater samples by multiplex PCR

    Directory of Open Access Journals (Sweden)

    Naser Samadi

    2015-06-01

    Full Text Available Background: Aminoglycoside antibiotics are widely used in medical centers, particularly to treat infections. The resistance developed against these agents is a huge concern in health care. A number of researchers have reported that hospital and municipal wastewaters are among the most important dissemination sources of these agent into the environment. Some, however, do not agree with this opinion. In the present study, the prevalence of aminoglycoside resistance genes was investigated in raw and effluent wastewater from hospital and municipal wastewater treatment plants. Methods: To conduct this descriptive-analytical study, 30 samples were taken according to sampling principles and cold cycle and transferred to the molecular laboratory. DNA was extracted by the freeze-thaw method using a kit (Promega. The genes aac(3-IIa and aac(6’-Ib which code aminoglycoside resistance were examined in this study. Results: The results indicated that the studied genes are present in 35% of urban and hospital wastewaters, and their frequency percentage is higher in hospital wastewater (52% than urban wastewater (48%. The studied genes were identified in 61% of raw hospital wastewater samples; however, they were not detected in the output wastewater from the studied treatment plants. Conclusion: Although, the studied genes were not detected in the final effluent, there is a high potential for their release into the environment. The current study demonstrated that the coding genes of aminoglycoside antibiotic resistance are present in raw urban and hospital wastewaters. In the case of improper exploitation of wastewater treatment plants, the output water can contaminate other environmental sections, such as soil and water resources, and result in the emission of these contaminants.

  3. Impairment of the class IIa bacteriocin receptor function and membrane structural changes are associated to enterocin CRL35 high resistance in Listeria monocytogenes.

    Science.gov (United States)

    Masias, Emilse; Dupuy, Fernando G; da Silva Sanches, Paulo Ricardo; Farizano, Juan Vicente; Cilli, Eduardo; Bellomio, Augusto; Saavedra, Lucila; Minahk, Carlos

    2017-07-01

    Enterocin CRL35 is a class IIa bacteriocin with anti-Listeria activity. Resistance to these peptides has been associated with either the downregulation of the receptor expression or changes in the membrane and cell walls. The scope of the present work was to characterize enterocin CRL35 resistant Listeria strains with MICs more than 10,000 times higher than the MIC of the WT sensitive strain. Listeria monocytogenes INS7 resistant isolates R2 and R3 were characterized by 16S RNA gene sequencing and rep-PCR. Bacterial growth kinetic was studied in different culture media. Plasma membranes of sensitive and resistant bacteria were characterized by FTIR and Langmuir monolayer techniques. The growth kinetic of the resistant isolates was slower as compared to the parental strain in TSB medium. Moreover, the resistant isolates barely grew in a glucose-based synthetic medium, suggesting that these cells had a major alteration in glucose transport. Resistant bacteria also had alterations in their cell wall and, most importantly, membrane lipids. In fact, even though enterocin CRL35 was able to bind to the membrane-water interface of both resistant and parental sensitive strains, this peptide was only able to get inserted into the latter membranes. These results indicate that bacteriocin receptor is altered in combination with membrane structural modifications in enterocin CRL35-resistant L. monocytogenes strains. Highly enterocin CRL35-resistant isolates derived from Listeria monocytogenes INS7 have not only an impaired glucose transport but also display structural changes in the hydrophobic core of their plasma membranes. Copyright © 2017. Published by Elsevier B.V.

  4. Sodium tanshinone IIA silate inhibits high glucose-induced vascular smooth muscle cell proliferation and migration through activation of AMP-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Wen-yu Wu

    Full Text Available The proliferation of vascular smooth muscle cells may perform a crucial role in the pathogenesis of diabetic vascular disease. AMPK additionally exerts several salutary effects on vascular function and improves vascular abnormalities. The current study sought to determine whether sodium tanshinone IIA silate (STS has an inhibitory effect on vascular smooth muscle cell (VSMC proliferation and migration under high glucose conditions mimicking diabetes without dyslipidemia, and establish the underlying mechanism. In this study, STS promoted the phosphorylation of AMP-activated protein kinase (AMPK at T172 in VSMCs. VSMC proliferation was enhanced under high glucose (25 mM glucose, HG versus normal glucose conditions (5.5 mM glucose, NG, and this increase was inhibited significantly by STS treatment. We utilized western blotting analysis to evaluate the effects of STS on cell-cycle regulatory proteins and found that STS increased the expression of p53 and the Cdk inhibitor, p21, subsequent decreased the expression of cell cycle-associated protein, cyclin D1. We further observed that STS arrested cell cycle progression at the G0/G1 phase. Additionally, expression and enzymatic activity of MMP-2, translocation of NF-κB, as well as VSMC migration were suppressed in the presence of STS. Notably, Compound C (CC, a specific inhibitor of AMPK, as well as AMPK siRNA blocked STS-mediated inhibition of VSMC proliferation and migration. We further evaluated its potential for activating AMPK in aortas in animal models of type 2 diabetes and found that Oral administration of STS for 10 days resulted in activation of AMPK in aortas from ob/ob or db/db mice. In conclusion, STS inhibits high glucose-induced VSMC proliferation and migration, possibly through AMPK activation. The growth suppression effect may be attributable to activation of AMPK-p53-p21 signaling, and the inhibitory effect on migration to the AMPK/NF-κB signaling axis.

  5. Efficacy of mirtazapine for the treatment of fibromyalgia without concomitant depression: a randomized, double-blind, placebo-controlled phase IIa study in Japan.

    Science.gov (United States)

    Miki, Kenji; Murakami, Masato; Oka, Hiroshi; Onozawa, Kaname; Yoshida, Sadahiro; Osada, Kenichi

    2016-09-01

    To evaluate the efficacy and safety of mirtazapine in Japanese patients with fibromyalgia (FM), a parallel-group, randomized, double-blind, placebo-controlled phase IIa study was conducted at 57 sites between November 2012 and February 2014. Patients aged 20 to 64 years who met the American College of Rheumatology 1990 diagnostic FM criteria and had stably high pain scores during a placebo run-in period were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to receive mirtazapine orally (15 mg/d for 1 week and then 30 mg/d) or matching placebo for 12 weeks. The primary endpoint was change in mean numerical rating scale (NRS) pain score from baseline to endpoint (week 12 or early discontinuation). Of the 430 patients randomized (n = 215 each group), 422 (n = 211 each group) were analyzed for the primary endpoint. At the study endpoint, mirtazapine caused a significantly greater reduction in the mean NRS pain score compared with placebo (difference, 0.44; 95% confidence interval, -0.72 to -0.17; P = 0.0018). The reduction by mirtazapine remained significantly greater compared with placebo from week 6 onward. More patients treated with mirtazapine had their NRS pain score reduced by ≥30% from baseline (45.5% vs 30.8%). Mirtazapine also improved pain-related quality of life assessed by the Japanese version of the Fibromyalgia Impact Questionnaire and the Short-Form 36 Questionnaire. Adverse events were more common with mirtazapine than placebo (68.8% vs 56.7%), including somnolence (32.1% vs 7.4%), weight gain (17.7% vs 0.9%), and increased appetite (11.6% vs 3.3%). In conclusion, mirtazapine was an effective and safe treatment for Japanese patients with FM.

  6. Anti-nociceptive effects of Tanshinone IIA (TIIA) in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain.

    Science.gov (United States)

    Sun, Shukai; Yin, Yue; Yin, Xin; Cao, Fale; Luo, Daoshu; Zhang, Ting; Li, Yunqing; Ni, Longxing

    2012-09-01

    Inflammatory pain is an important clinical symptom. The levels of extracellular signal-regulated kinases (ERKs) and the levels of cytokines such as interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) play important roles in inflammatory pain. Tanshinone IIA (TIIA) is an important component of Danshen, a traditional Chinese medicine that has been commonly used to treat cardiovascular disease. In this study, we investigated the potential anti-inflammatory nociceptive effects of TIIA on complete Freund's adjuvant (CFA)-induced inflammation and inflammatory pain in rats. The effects of TIIA on CFA-induced thermal and mechanical hypersensitivity were investigated using behavioral tests. The levels of ERKs, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transient receptor potential vanilloid 1 (TRPV1) in the fifth segment of the lumbar spinal cord (L5) ganglia were detected by Western blot, and the levels of mRNA and protein production of IL1-β, IL-6 and TNF-α were detected by real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immuno sorbent assay (ELISA). In this study, we found that TIIA attenuates the development of CFA-induced mechanical and thermal hypersensitivity. In addition, p-ERK and NF-κB expression levels were inhibited by TIIA, and the levels of the pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were reduced. Finally, we found that the expression level of TRPV1 was significantly decreased after TIIA injection. This study demonstrated that TIIA has significant anti-nociceptive effects in a rat model of CFA-induced inflammatory pain. TIIA can inhibit the activation of ERK signaling pathways and the expression of pro-inflammatory cytokines. These results suggest that TIIA may be a potential anti-inflammatory and anti-nociceptive drug. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. The ISRU Field Tests 2010 and 2012 at Mauna Kea, Hawaii: Results from the Miniaturised Mossbauer Spectrometers Mimos II and Mimos IIA

    Science.gov (United States)

    Klingelhoefer, G.; Morris, R. V.; Blumers, M; Bernhardt, B.; Graff, T.

    2014-01-01

    The 2010 and 2012 In-Situ Resource Utilization Analogue Test (ISRU) [1] on the Mauna Kea volcano in Hawai'i was coordinated by the Northern Centre for Advanced Technology (NORCAT) in collaboration with the Canadian Space Agency (CSA), the German Aerospace Center (DLR), and the National Aeronautics and Space Administration (NASA), through the PISCES program. Several instruments were tested as reference candidates for future analogue testing at the new field test site at the Mauna Kea volcano in Hawai'i. The fine-grained, volcanic nature of the material is a suitable lunar and martian analogue, and can be used to test excavation, site preparation, and resource utilization techniques. The 2010 location Pu'u Hiwahine, a cinder cone located below the summit of Mauna Kea (19deg45'39.29" N, 155deg28'14.56" W) at an elevation of 2800 m, provides a large number of slopes, rock avalanches, etc. to perform mobility tests, site preparation or resource prospecting. Besides hardware testing of technologies and systems related to resource identification, also in situ science measurements played a significant role in integration of ISRU and science instruments. For the advanced Mössbauer instrument MIMOS IIA, the new detector technologies and electronic components increase sensitivity and performance significantly. In combination with the high energy resolution of the SDD it is possible to perform Xray fluorescence analysis simultaneously to Mössbauer spectroscopy. In addition to the Fe-mineralogy, information on the sample's elemental composition will be gathered. The 2010 and 2012 field campaigns demonstrated that in-situ Mössbauer spectroscopy is an effective tool for both science and feedstock exploration and process monitoring. Engineering tests showed that a compact nickel metal hydride battery provided sufficient power for over 12 hr of continuous operation for the MIMOS instruments.

  8. An attempt to stabilize tanshinone IIA solid dispersion by the use of ternary systems with nano-CaCO 3 and poloxamer 188

    Directory of Open Access Journals (Sweden)

    Hong-mei Yan

    2014-01-01

    Full Text Available Background: Tanshinone IIA (TSIIA on solid dispersions (SDs has thermodynamical instability of amorphous drug. Ternary solid dispersions (tSDs can extend the stability of the amorphous form of drug. Poloxamer 188 was used as a SD carrier. Nano-CaCO 3 played an important role in adsorption of biomolecules and is being developed for a host of biotechnological applications. Objective: The aim of the present study was to investigate the dissolution behavior and accelerated stability of TSIIA on solid dispersions (SDs by the use of ternary systems with nano-CaCO 3 and poloxamer 188. Materials and Methods: The TSIIA tSDs were prepared by a spray-drying method. First, the effect of combination of poloxamer 188 and nano-CaCO 3 on TSIIA dissolution was studied. Subsequently, a set of complementary techniques (DSC, XRPD, SEM and FTIR was used to monitor the physical changes of TSIIA in the SDs. Finally, stability test was carried out under the conditions 40°C/75% RH for 6 months. Results: The characterization of tSDs by differential scanning calorimetry analysis (DSC and X-ray powder diffraction (XRPD showed that TSIIA was present in its amorphous form. Fourier transforms infrared spectroscopy (FTIR suggested the presence of interactions between TSIIA and carriers in tSDs. Improvement in the dissolution rate was observed for all SDs. The stability study conducted on SDs with nano-CaCO 3 showed stable drug content and dissolution behavior, over the period of 6 months as compared with freshly prepared SDs. Conclusion: SDs preparation with nano-CaCO 3 and poloxamer 188 may be a promising approach to enhance the dissolution and stability of TSIIA.

  9. FLYING UNITED

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Apart from selling hundreds of airplanes to China, Boeing buys locally made aircraft parts and transfers technology, in the true spirit of partnership Whenever Boeing's senior manager hear of a visit by one of China's state leaders, it's no doubt cause for celebration. Since China and the United States established diplomatic ties in 1978, every official trip by China's top statesmen has included a meeting with Boeing that

  10. More Accurate Definition of Clinical Target Volume Based on the Measurement of Microscopic Extensions of the Primary Tumor Toward the Uterus Body in International Federation of Gynecology and Obstetrics Ib-IIa Squamous Cell Carcinoma of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Wen-Jia [Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Wu, Xiao [Department of Pathology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Xue, Ren-Liang; Lin, Xiang-Ying [Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Kidd, Elizabeth A. [Department of Radiation Oncology, Stanford University, Stanford, California (United States); Yan, Shu-Mei [Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province (China); Zhang, Yao-Hong [Department of Radiation Oncology, Chaozhou Hospital of Chaozhou City, Guangdong Province (China); Zhai, Tian-Tian; Lu, Jia-Yang; Wu, Li-Li; Zhang, Hao [Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Huang, Hai-Hua [Department of Pathology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Chen, Zhi-Jian; Li, De-Rui [Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China); Xie, Liang-Xi, E-mail: xieliangxi1@qq.com [Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong Province (China)

    2015-01-01

    Purpose: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). Patients and Methods: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. Results: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. Conclusion: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

  11. United States

    Directory of Open Access Journals (Sweden)

    Stephen Bernow

    1998-12-01

    Full Text Available This paper presents and discusses an integrated set of policies designed to reduce U.S. carbon emissions over the next four decades. This innovation path also aims to promote environmental quality, particularly by reducing emissions of criteria air pollutants, to reduce U.S. dependence on imported oil, and to induce technological innovation and diffusion in energy production and consumption. The innovation path would reduce economy-wide carbon emissions by 26% below baseline projections for 2010 and by 62% below baseline projections for 2030; this translates into 10% below 1990 levels in 2010 and 45% below 1990 levels in 2030. Emissions of criteria pollutants also would be significantly reduced, as would petroleum imports by the United States. Moreover, the innovation path would yield cumulative net savings for the United States of $218 billion (1993 dollars through 2010, or $19 billion on a leveled annual basis, and would result in 800,000 additional jobs nationwide by 2010. Although the overall findings from the innovation path analysis are robust, the results should be taken as indicative, rather than precisely predictive, owing to uncertainties in future costs, prices, technology performance, and consumer behavior.

  12. Rapid Healing of Cutaneous Leishmaniasis by High-Frequency Electrocauterization and Hydrogel Wound Care with or without DAC N-055: A Randomized Controlled Phase IIa Trial in Kabul

    Science.gov (United States)

    Steiner, Reto; Wentker, Pia; Mahfuz, Farouq; Stahl, Hans-Christian; Amin, Faquir Mohammad; Bogdan, Christian; Stahl, Kurt-Wilhelm

    2014-01-01

    Background Anthroponotic cutaneous leishmaniasis (CL) due to Leishmania (L.) tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL. Methodology/Principal Findings From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC) followed by daily moist-wound-treatment (MWT) with polyacrylate hydrogel with (group I) or without (group II) pharmaceutical sodium chlorite (DAC N-055). Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immuno)histopathological analyses were taken prior to EC (1st), after wound closure (2nd) and after 6 months (3rd). The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d) and II (54 patients, 42 d; p = 0.83). In patients with Leishmania-positive 2nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08). Superinfections occurred in both groups at the same rate (8.8%). Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158) were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes. Conclusions/Significance Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of

  13. Sodium Tanshinone IIA Sulfonate Ameliorates Bladder Fibrosis in a Rat Model of Partial Bladder Outlet Obstruction by Inhibiting the TGF-β/Smad Pathway Activation.

    Directory of Open Access Journals (Sweden)

    Xiaoxiao Jiang

    Full Text Available Transforming growth factor (TGF-β1 is known to play a pivotal role in a diverse range of biological systems including modulation of fibrosis in several organs. The precise role of TGF-β/Smad signaling in the progression of bladder fibrosis secondary to partial bladder outlet obstruction (PBOO is yet to be conclusively. Using a rat PBOO model, we investigated TGF-β1 expression and exaimined whether sodium tanshinone IIA sulfonate (STS could inhibit TGF-β/Smad signaling pathway activation and ameliorate bladder fibrosis. Forty-eight female Sprague-Dawley rats were randomly divided into three groups: sham operation group (n = 16, PBOO operation without STS treatment group (n = 16 and PBOO operation with STS treatment group (n = 16. Thirty-two rats underwent the operative procedure to create PBOO and subsequently received intraperitoneal injections of STS (10 mg/kg/d; n = 16 or vehicle (n = 16 two days after the surgery. Sham surgery was conducted on 16 rats, which received intraperitoneal vehicle injection two days later. In each of the three groups, an equal number of rats were sacrificed at weeks 4 and 8 after the PBOO or sham operation. The TGF-β/Smad signaling pathway was analyzed using western blotting, immunohistochemical staining and reverse transcriptase polymerase chain reaction (RT-PCR. One-way analysis of variance was conducted to draw statistical inferences. At 4 and 8 weeks, the expression of TGF-β1 and phosphorylated Smad2 and Smad3 in STS-treated PBOO rats was significantly lower than in the PBOO rats not treated with STS. Alpha smooth muscle actin (α-SMA, collagen I and collagen III expression at 4 and 8 weeks post PBOO was lower in STS-treated PBOO rats when compared to that in PBOO rats not treated with STS. Our findings indicate that STS ameliorates bladder fibrosis by inhibiting TGF-β/Smad signaling pathway activation, and may prove to be a potential therapeutic measure for preventing bladder fibrosis secondary to PBOO

  14. Rapid healing of cutaneous leishmaniasis by high-frequency electrocauterization and hydrogel wound care with or without DAC N-055: a randomized controlled phase IIa trial in Kabul.

    Directory of Open Access Journals (Sweden)

    Ahmad Fawad Jebran

    2014-02-01

    Full Text Available Anthroponotic cutaneous leishmaniasis (CL due to Leishmania (L. tropica infection is a chronic, frequently disfiguring skin disease with limited therapeutic options. In endemic countries healing of ulcerative lesions is often delayed by bacterial and/or fungal infections. Here, we studied a novel therapeutic concept to prevent superinfections, accelerate wound closure, and improve the cosmetic outcome of ACL.From 2004 to 2008 we performed a two-armed, randomized, double-blinded, phase IIa trial in Kabul, Afghanistan, with patients suffering from L. tropica CL. The skin lesions were treated with bipolar high-frequency electrocauterization (EC followed by daily moist-wound-treatment (MWT with polyacrylate hydrogel with (group I or without (group II pharmaceutical sodium chlorite (DAC N-055. Patients below age 5, with facial lesions, pregnancy, or serious comorbidities were excluded. The primary, photodocumented outcome was the time needed for complete lesion epithelialization. Biopsies for parasitological and (immunohistopathological analyses were taken prior to EC (1(st, after wound closure (2(nd and after 6 months (3(rd. The mean duration for complete wound closure was short and indifferent in group I (59 patients, 43.1 d and II (54 patients, 42 d; p = 0.83. In patients with Leishmania-positive 2(nd biopsies DAC N-055 caused a more rapid wound epithelialization (37.2 d vs. 58.3 d; p = 0.08. Superinfections occurred in both groups at the same rate (8.8%. Except for one patient, reulcerations (10.2% in group I, 18.5% in group II; p = 0.158 were confined to cases with persistent high parasite loads after healing. In vitro, DAC N-055 showed a leishmanicidal effect on pro- and amastigotes.Compared to previous results with intralesional antimony injections, the EC plus MWT protocol led to more rapid wound closure. The tentatively lower rate of relapses and the acceleration of wound closure in a subgroup of patients with parasite persistence warrant

  15. Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach

    Science.gov (United States)

    Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

    2017-01-01

    Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient (r2) value of 0.6774, cross-validated correlation coefficient (q2) of 0.6157 and co-relation coefficient for external test set (pred_r2) of 0.7570. A high F-test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of −10.097 and −9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free

  16. Mechanistic Insights into the Binding of Class IIa HDAC Inhibitors toward Spinocerebellar Ataxia Type-2: A 3D-QSAR and Pharmacophore Modeling Approach.

    Science.gov (United States)

    Sinha, Siddharth; Goyal, Sukriti; Somvanshi, Pallavi; Grover, Abhinav

    2016-01-01

    Spinocerebellar ataxia (SCA-2) type-2 is a rare neurological disorder among the nine polyglutamine disorders, mainly caused by polyQ (CAG) trinucleotide repeats expansion within gene coding ataxin-2 protein. The expanded trinucleotide repeats within the ataxin-2 protein sequesters transcriptional cofactors i.e., CREB-binding protein (CBP), Ataxin-2 binding protein 1 (A2BP1) leading to a state of hypo-acetylation and transcriptional repression. Histone de-acetylases inhibitors (HDACi) have been reported to restore transcriptional balance through inhibition of class IIa HDAC's, that leads to an increased acetylation and transcription as demonstrated through in-vivo studies on mouse models of Huntington's. In this study, 61 di-aryl cyclo-propanehydroxamic acid derivatives were used for developing three dimensional (3D) QSAR and pharmacophore models. These models were then employed for screening and selection of anti-ataxia compounds. The chosen QSAR model was observed to be statistically robust with correlation coefficient (r(2)) value of 0.6774, cross-validated correlation coefficient (q(2)) of 0.6157 and co-relation coefficient for external test set (pred_r(2)) of 0.7570. A high F-test value of 77.7093 signified the robustness of the model. Two potential drug leads ZINC 00608101 (SEI) and ZINC 00329110 (ACI) were selected after a coalesce procedure of pharmacophore based screening using the pharmacophore model ADDRR.20 and structural analysis using molecular docking and dynamics simulations. The pharmacophore and the 3D-QSAR model generated were further validated for their screening and prediction ability using the enrichment factor (EF), goodness of hit (GH), and receiver operating characteristics (ROC) curve analysis. The compounds SEI and ACI exhibited a docking score of -10.097 and -9.182 kcal/mol, respectively. An evaluation of binding conformation of ligand-bound protein complexes was performed with MD simulations for a time period of 30 ns along with free

  17. Stadium IB - IIA cervical cancer patient’s survival rate after receiving definitive radiation and radical operation therapy followed by adjuvant radiation therapy along with analysis of factors affecting the patient’s survival rate

    Science.gov (United States)

    Ruslim, S. K.; Purwoto, G.; Widyahening, I. S.; Ramli, I.

    2017-08-01

    To evaluate the characteristics and overall survival rates of early stage cervical cancer (FIGO IB-IIA) patients who receive definitive radiation therapy and those who are prescribed adjuvant postoperative radiation and to conduct a factors analysis of the variables that affect the overall survival rates in both groups of therapy. The medical records of 85 patients with cervical cancer FIGO stages IB-IIA who were treated at the Department of Radiotherapy of Cipto Mangunkusumo Hospital were reviewed and analyzed to determine their overall survival and the factors that affected it between a definitive radiation group and an adjuvant postoperative radiation group. There were 25 patients in the definitive radiation and 60 patients in the adjuvant radiation group. The overall survival rates in the adjuvant radiation group at years one, two, and three were 96.7%, 95%, and 93.3%, respectively. Negative lymph node metastasis had an average association with overall survival (p 12 g/dl was a factor with an average association with the overall survival (p 12 g/dl tended to affect the overall survival in the definitive radiation group patients.

  18. Exploration of pH-dependent behavior of the anion receptor pocket of subdomain IIA of HSA: determination of effective pocket charge using the Debye-Hückel limiting law.

    Science.gov (United States)

    Bolel, Priyanka; Datta, Shubhashis; Mahapatra, Niharendu; Halder, Mintu

    2014-01-09

    Protein-ligand electrostatic interaction can be looked upon as ion receptor-ligand interaction, and the binding cavity of protein can be either an anion or cation receptor depending on the charge of the guest. Here we focus on the exploration of pH-modulated binding of a number of anionic ligands, specific to the subdomain IIA cavity of HSA, such as carmoisine, tartrazine, cochineal red, and warfarin. The logarithm of the binding constant is found to vary linearly with the square-root of ionic strength, indicating applicability of the Debye-Hückel limiting law to protein-ligand electrostatic binding equilibrium, and concludes that the subdomain IIA cavity is an anion receptor. The present approach is very unique that one can calculate the effective charge of the protein-based anion receptor pocket, and the calculated charge has been found to vary between +1 and +3 depending on the pH and ligand itself. The study also indicates that in such cases of specific ligand binding the pocket charge rather than the overall or surface charge of the macromolecule seems to have a paramount role in determining the strength of interaction. For the first time, it is demonstrated that the Debye-Hückel interionic interaction model can be successfully applied to understand the protein-based receptor-ligand electrostatic interaction in general.

  19. Termination unit

    Energy Technology Data Exchange (ETDEWEB)

    Traeholt, Chresten; Willen, Dag; Roden, Mark; Tolbert, Jerry C.; Lindsay, David; Fisher, Paul W.; Nielsen, Carsten Thidemann

    2016-05-03

    Cable end section comprises end-parts of N electrical phases/neutral, and a thermally-insulation envelope comprising cooling fluid. The end-parts each comprises a conductor and are arranged with phase 1 innermost, N outermost surrounded by the neutral, electrical insulation being between phases and N and neutral. The end-parts comprise contacting surfaces located sequentially along the longitudinal extension of the end-section. A termination unit has an insulating envelope connected to a cryostat, special parts at both ends comprising an adapter piece at the cable interface and a closing end-piece terminating the envelope in the end-section. The special parts houses an inlet and/or outlet for cooling fluid. The space between an inner wall of the envelope and a central opening of the cable is filled with cooling fluid. The special part at the end connecting to the cryostat houses an inlet or outlet, splitting cooling flow into cable annular flow and termination annular flow.

  20. Nucleotide diversity in starch synthase IIa and validation of single nucleotide polymorphisms in relation to starch gelatinization temperature and other physicochemical properties in rice (Oryza sativa L.).

    Science.gov (United States)

    Bao, J S; Corke, H; Sun, M

    2006-11-01

    The characteristics of starch, such as gelatinization temperature (GT), apparent amylose content (AAC), pasting temperature (PT) and other physicochemical properties, determine the quality of various products of rice, e.g., eating, cooking and processing qualities. The GT of rice flour is controlled by the alk locus, which has been co-mapped to the starch synthase IIa (SSIIa) locus. In this study, we sequenced a 2,051 bp DNA fragment spanning part of intron 6, exon 7, intron 7, exon 8 and part of 3' untranslated region of SSIIa for 30 rice varieties with diverse geographical distribution and variation in starch physicochemical properties. A total of 24 single nucleotide polymorphisms (SNPs) and one insertion/deletion (InDel) were identified, which could be classified into nine haplotypes. The mean pairwise nucleotide diversity pi was 0.00292, and Watterson's estimator theta was 0.00296 in this collection of rice germplasm. Tajima's D test for selection showed no significant deviation from the neutral expectation (D = - 0.04612, P > 0.10). However, significant associations were found between seven of the SNPs and peak GT (T (p)) at P < 0.05, of which two contiguous SNPs (GC/TT) showed a very strong association with T (p) (P < 0.0001). With some rare exception, this GC/TT polymorphism alone can differentiate rice varieties with high or intermediate GT (possessing the GC allele) from those with low GT (possessing the TT allele). In contrast, none of these SNPs or InDel was significantly associated with amylose content. A further 509 rice varieties with known physicochemical properties (e.g., AAC and PT) and known alleles of other starch synthesizing genes were genotyped for the SSIIa GC/TT alleles. Association analysis indicated that 82% of the total variation of AAC in these samples could be explained by a (CT)n simple sequence repeat (SSR) and a G/T SNP of Waxy gene (Wx), and 62.4% of the total variation of PT could be explained by the GC/TT polymorphism. An

  1. ANNUAL UPDATE OF THE SOLID WASTE MANAGEMENT UNIT (SWMU) LIST FOR THE OAK RIDGE Y-12 PLANT.

    Energy Technology Data Exchange (ETDEWEB)

    Deakin, J.M.

    1997-01-01

    In accordance with the terms of Paragraph II.A.8 of the Resource Conservation and Recovery Act (RCRA), 1984 Hazardous and Solid Waste Amendments (HSWA) Permit TN 001, and the Tennessee Department of Environment and Conservation (TDEC), RCRA Permit TN1 890 090 003 for Building 7652 at the Oak Ridge National Laboratory, the list of the solid waste management units (SWMUs) for the Oak Ridge Reservation, including the Oak Ridge Y-12 Plant, must be updated and submitted to personnel at the Environmental Protection Agency, Region IV, and TDEC by January 30, 1997. This report includes information satisfying the {section}II.A.8 requirements, to update the SWMU list for the Y-12 Plant. Newly identified SWMUs include discernible units which have accumulated, treated, stored, or disposed of waste; areas contaminated by routine, deliberate, or systematic releases from process components; RCRA 90-day accumulation areas; and TSCA one-year areas.

  2. F-area seepage basins groundwater monitoring report. Volume 1. First and second quarters 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-09-01

    Groundwater at the F-Area Seepage Basins (FASB) is monitored in compliance with Module 111, Section C, of South Carolina Hazardous Waste Permit SCl-890-008-989, effective November 2, 1992. The monitoring well network is composed of 86 FSB wells and well HSB 85A. These wells are screened in the three hydrostratigraphic Units that make up the uppermost aquifer beneath the FASB. A detailed description of the uppermost aquifer is included in the Resource Conservation and Recovery Act Part B post-closure care permit application for the F-Area Hazardous Waste Management Facility submitted to the South Carolina Department of Health and Environmental Control (SCDHEC) in December 1900. Data from 9 FSL wells are included in this report only to provide additional information for this area; the FSL wells are not part of Permit SCl-890-008-989. Monitoring results are compared to the SCDHEC Groundwater Protection Standard (GWPS), which is specified in the approved F-Area Seepage Basins Part B permit (November 1992). Historically and currently, gross alpha, nitrate, nonvolatile beta, and tritium are among the primary constituents to exceed standards. Numerous other radionuclides and hazardous constituents also exceeded the GWPS in the groundwater at the FASB during the first half of 1995, notably aluminum, iodine-129, pH, strontium-90, and zinc. The elevated constituents are found primarily in Aquifer Zone IIB{sub 2} (Water Table) and Aquifer Zone IIB{sub 1}, (Barnwell/McBean) wells. However, several Aquifer Unit IIA (Congaree) wells also contain elevated levels of constituents. Isoconcentration/isoactivity maps included in this report indicate both the concentration/activity and extent of the primary contaminants in each of the three hydrostratigraphic units. Geologic cross sections indicate both the extent and depth of contamination of the primary contaminants in all of the hydrostratigraphic units during the first half of 1995.

  3. Analysis of Genome Sequence of App ApxIIA and Its Prediction of Related B Cell Epitopes%猪胸膜肺炎放线杆菌ApxIIA基因的序列分析及其B细胞表位预测

    Institute of Scientific and Technical Information of China (English)

    李任峰; 田香勤; 何启盖; 王自良; 赵坤; 李学斌; 王三虎

    2009-01-01

    The research was to analyze the identity matrix of ApxIIA genes of App isolates and to predict the B cell epitopes of this ApxIIA protein. The ApxIIA genes of the six different App were selected from GenBank to analyze their identity matrix of nucleotide and amino acid by the bioinformatics analysis software. The B cell epitopes of the AY232288.1 ApxIIA protein were predicted based on the analysis parameters of B cell epitopes and the characteristicof the secondary structure. The results showed the ApxIIA genes of six strains share 65.56 % and 88.42% homology at nucleotide and amino acid level respectively. The B cell epitope of ApxIIA protein of AY232288.1 was probably locate or adjacent to its N-terminal region 745~751和801~807. These results provided references for further research of ApxIIA protein function and design of multiepitope-based vaccine of APP.%为了进一步研究猪胸膜肺炎放线杆菌(Actionobacillus pleuropneumoniae,App)ApxIIA基因的结构和功能,选取GenBank中6株不同App分离株,采用生物信息学方法对其ApxIIA基因及其编码氨基酸序列进行同源性比对,并选择其中AY232288.1菌株(湖北分离株)ApxIIA基因为研究对象,分析该基因所编码蛋白质的理化性质,并对其可能形成的二级结构及B细胞表位进行预测和分析.结果表明,6株不同App分离株ApxIIA基因核苷酸及氨基酸序列同源性分别为65.56﹪和88.42﹪,在AY232288.1菌株ApxIIA蛋白的肽链中,745~751和801~807区段可能是其B细胞表位优势区.本研究首次利用生物信息学方法对ApxIIA基因及其蛋白质结构进行了分析和预测,为ApxIIA基因功能的深入研究及APP多表位疫苗的设计奠定了基础.

  4. Differential association of the N-propeptide of collagen IIA (PIIANP) and collagen II C-telopeptide (CTX-II) with synovitis and erosions in early and longstanding rheumatoid arthritis

    DEFF Research Database (Denmark)

    Christensen, A F; Lottenburger, T; Lindegaard, H

    2009-01-01

    OBJECTIVES: To determine the N-terminal propeptide of collagen IIA (PIIANP) in early and established rheumatoid arthritis (RA) and to study the association with collagen II degradation assessed by its C-telopeptide (CTX-II), x-ray status and disease activity measures. METHODS: Two cohorts of RA......-ray progression (p=0.84). There was no correlation between PIIANP and CTX-II. CONCLUSION: Declining PIIANP with increasing RA duration and persistently increased CTX-II indicate that cartilage anabolic and degradative pathways are unbalanced from clinical RA onset. Furthermore, that collagen II depletion in RA...... is both mediated by anti-anabolic effects unassociated with synovitis (decreased PIIANP) and by excess collagen II degradation linked to synovitis (increased CTX-II)....

  5. Yield of routine provocative cardiac testing among patients in an emergency department-based chest pain unit.

    Science.gov (United States)

    Hermann, Luke K; Newman, David H; Pleasant, W Andrew; Rojanasarntikul, Dhanadol; Lakoff, Daniel; Goldberg, Scott A; Duvall, W Lane; Henzlova, Milena J

    2013-06-24

    The American Heart Association recommends routine provocative cardiac testing in accelerated diagnostic protocols for coronary ischemia. The diagnostic and therapeutic yield of this approach are unknown. To assess the yield of routine provocative cardiac testing in an emergency department-based chest pain unit. We examined a prospectively collected database of patients evaluated for possible acute coronary syndrome between March 4, 2004, and May 15, 2010, in the emergency department-based chest pain unit of an urban academic tertiary care center. Patients with signs or symptoms of possible acute coronary syndrome and without an ischemic electrocardiography result or a positive biomarker were enrolled in the database. All patients were evaluated by exercise stress testing or myocardial perfusion imaging. Demographic and clinical features, results of routine provocative cardiac testing and angiography, and therapeutic interventions were recorded. Diagnostic yield (true-positive rate) was calculated, and the potential therapeutic yield of invasive therapy was assessed through blinded, structured medical record review using American Heart Association designations (class I, IIa, IIb, or lower) for the potential benefit from percutaneous intervention. In total, 4181 patients were enrolled in the study. Chest pain was initially reported in 93.5%, most (73.2%) were at intermediate risk for coronary artery disease, and 37.6% were male. Routine provocative cardiac testing was positive for coronary ischemia in 470 (11.2%), of whom 123 underwent coronary angiography. Obstructive disease was confirmed in 63 of 123 (51.2% true positive), and 28 (0.7% overall) had findings consistent with the potential benefit from revascularization (American Heart Association class I or IIa). In an emergency department-based chest pain unit, routine provocative cardiac testing generated a small therapeutic yield, new diagnoses of coronary artery disease were uncommon, and false-positive results

  6. 丹参酮ⅡA 对压力超负荷大鼠心肌血红素加氧酶-1 mRNA 基因表达的作用%Study of Tanshinone - IIA on the expression of myocardium hemo oxygenase - 1 mRNA in pressure - over-loaded rats

    Institute of Scientific and Technical Information of China (English)

    蔡辉; 朱凯媛; 赵凌杰; 赵智明; 董晓蕾; 张蓓蓓

    2016-01-01

    目的:观察丹参酮ⅡA(TanⅡA)对压力超负荷大鼠心肌血红素加氧酶-1(HO -1)mRNA基因表达的影响,并探讨其对心肌纤维化、心室重构的保护作用。方法40只 SD 大鼠随机抽取8只为假手术组,其余32只大鼠为手术组采用腹主动脉缩窄术制备压力超负荷模型,术后手术组存活的22只大鼠再随机分成3组,分别为模型组(n =7)、TanⅡA 组(n =7)及 TanⅡA + HO -1抑制剂处理组[TanⅡA +锌原卟啉(ZnPP)注射液组,n =8)。造模术后第4周开始给药,假手术组、模型组均以0.9%氯化钠注射液4 mL/(kg· d)腹腔注射;TanIIA 组以丹参酮ⅡA 磺酸钠(STS)注射液20 mg/(kg·d)腹腔注射;TanIIA + ZnPP 组以 STS注射液20 mg/(kg·d)+ ZnPP 注射液1 mg/(kg·d)腹腔注射。各组每日上午给药1次,疗程为4周。检测4组大鼠心肌组织 HO -1mRNA 基因表达,观察大鼠心肌组织结构变化。结果 TanⅡA 组 HO -1 mRNA 基因表达高于其余3组(均 P <0.01),当使用 HO -1抑制剂 ZnPP 注射液后可见 HO -1 mRNA 基因表达较 TanIIA明显下降(P <0.01)。光镜下假手术组大鼠心肌纤维排列整齐、横纹明显,胞核结构清晰,无坏死灶,心肌间质及微血管正常;与假手术组比较,模型组心肌纤维明显增粗且排列紊乱,部分胞核固缩,并有局灶性、片状坏死灶和炎性细胞浸润,血管周围及间质有胶原纤维的沉积;TanIIA 组和 TanIIA + ZnPP 组心肌的组织形态学均有不同程度改善,而 TanIIA 组改善更明显。结论 TanⅡA 可以抑制心肌纤维化,减缓心室重构,此作用可能与 TanIIA 诱导 HO -1过表达有关。%Objective To observe the Tanshinone - IIA(TanIIA)on the expression of myocardium hemo oxygenase - 1(HO - 1)mRNA in pressure - overloaded rats,and to investigate its protection of myocardial fibrosis and ventricular remodeling. Methods 40 SD rats were

  7. Genotypic characterization of canine coronaviruses associated with fatal canine neonatal enteritis in the United States.

    Science.gov (United States)

    Licitra, Beth N; Whittaker, Gary R; Dubovi, Edward J; Duhamel, Gerald E

    2014-12-01

    Emerging canine coronavirus (CCoV) variants that are associated with systemic infections have been reported in the European Union; however, CCoV-associated disease in the United States is incompletely characterized. The purpose of this study was to correlate the clinicopathological findings and viral antigen distribution with the genotypic characteristics of CCoV in 11 puppies from nine premises in five states that were submitted for diagnostic investigation at Cornell University between 2008 and 2013. CCoV antigen was found in epithelial cells of small intestinal villi in all puppies and the colon in 2 of the 10 puppies where colon specimens were available. No evidence of systemic CCoV infection was found. Comparative sequence analyses of viral RNA extracted from intestinal tissues revealed CCoV-II genotype in 9 out of 11 puppies. Of the nine CCoV-IIs, five were subtyped as group IIa and one as IIb, while three CCoVs could not be subtyped. One of the CCoV-IIa variants was isolated in cell culture. Infection with CCoV alone was found in five puppies, of which two also had small intestinal intussusception. Concurrent infections with either parvovirus (n = 1), attaching-effacing Escherichia coli (n = 4), or protozoan parasites (n = 3) were found in the other six puppies. CCoV is an important differential diagnosis in outbreaks of severe enterocolitis among puppies between 4 days and 21 weeks of age that are housed at high population density. These findings will assist with the rapid laboratory diagnosis of enteritis in puppies and highlight the need for continued surveillance for CCoV variants and intestinal viral diseases of global significance.

  8. Using SI Units in Astronomy

    Science.gov (United States)

    Dodd, Richard

    2011-12-01

    1. Introduction; 2. An introduction to SI units; 3. Dimensional analysis; 4. Unit of angular measure (radian); 5. Unit of time (second); 6. Unit of length (metre); 7. Unit of mass (kilogram); 8. Unit of luminous intensity (candela); 9. Unit of thermodynamic temperature (kelvin); 10. Unit of electric current (ampere); 11. Unit of amount of substance (mole); 12. Astronomical taxonomy; Index.

  9. Sodium Tanshinone IIA Sulfonate Injection and Inflammatory Factors of Coronary Heart Diseases%丹参酮ⅡA 磺酸钠注射液与冠心病炎症因子的研究进展

    Institute of Scientific and Technical Information of China (English)

    焦阳; 李思铭; 高铸烨; 徐浩

    2013-01-01

    大量的基础和临床研究均证实炎症反应在动脉粥样硬化的发生发展过程中起着重要作用。炎症反应促使冠状动脉内不稳定斑块的形成和破裂,在此基础上导致的血栓形成,是大多数急性冠脉综合征( ACS)发生的主要原因。丹参酮IIA磺酸钠( sodium tanshinone IIA sulfonate ,STS)具有改善血液循环、抑制炎症反应等作用,主要用于冠心病的治疗。本文对STS与冠心病相关炎症因子C反应蛋白、同型半胱氨酸、肿瘤坏死因子-α、人白细胞分化抗原40、纤维蛋白原、白细胞介素-6、基质金属蛋白酶、核因子-кB的相关性进行综述,以期为探索STS对冠心病炎症因子的具体作用环节提供参考。%A large number of basic and clinical studies have demonstrated that inflammation plays a vital role in atherosclerosis forma -tion and evolution .Inflammation factors stimulate the formation and rupture of unstable coronary atherosclerotic plaque .Then the throm-bosis formed is the main reason of most acute coronary syndromes (ACS).Sodium tanshinone IIA sulfonate(STS) is applied for Coro-nary Heart Disease ( CHD) which can improve blood circulation and inhibit inflammation .This paper reviewed on the relevance between STS and CHD related inflammatory factors including C-reactive protein (CRP),homocysteine(Hcy),Tumor necrosis factor-α(TNF -α),Human leukocyte differentiation antigen 40 (CD40),fibrinogen(Fib),interleukin-6(IL-6),matrix metal loprotoinases (MMPs),nu-clear factor-кB( NF-кB) ,so as to explore specific links of STS ’ s affection in inflammatory factors with CHD to provide curing reference in the future .

  10. The calibration of photographic and spectroscopic films. Part 1: Film batch variations of reciprocity failure in IIaO film. Part 2: Thermal and aging effects in relationship to reciprocity failure. P art 3: Shifting of reciprocity failure points as a function of thermal and aging effects

    Science.gov (United States)

    Peters, Kevin A.; Atkinson, Pamela F.; Hammond, Ernest C., Jr

    1987-01-01

    Reciprocity failure was examined for IIaO spectroscopic film. Three separate experiments were performed in order to study film batch variations, thermal and aging effects in relationship to reciprocity failure, and shifting of reciprocity failure points as a function of thermal and aging effects. The failure was examined over ranges of time between 5 and 60 seconds. The variation to illuminance was obtained by using thirty neutral density filters. A standard sensitometer device imprinted the wedge pattern on the film as exposure time was subjected to variation. Results indicate that film batch differences, temperature, and aging play an important role in reciprocity failure of IIaO spectroscopic film. A shifting of the failure points was also observed in various batches of film.

  11. Malaria Treatment (United States)

    Science.gov (United States)

    ... a CDC Malaria Branch clinician. malaria@cdc.gov Malaria Treatment (United States) Recommend on Facebook Tweet Share Compartir Treatment of Malaria: Guidelines For Clinicians (United States) Download PDF version ...

  12. United Cerebral Palsy

    Science.gov (United States)

    ... be sure to follow us on Twitter . United Cerebral Palsy UCP educates, advocates and provides support services to ... Partners Merz Logo Sprint Relay Copyright © 2015 United Cerebral Palsy 1825 K Street NW Suite 600 Washington, DC ...

  13. Unit Cost Compendium Calculations

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Unit Cost Compendium (UCC) Calculations raw data set was designed to provide for greater accuracy and consistency in the use of unit costs across the USEPA...

  14. Selective Inhibition of Human Group IIA-secreted Phospholipase A2 (hGIIA) Signaling Reveals Arachidonic Acid Metabolism Is Associated with Colocalization of hGIIA to Vimentin in Rheumatoid Synoviocytes*

    Science.gov (United States)

    Lee, Lawrence K.; Bryant, Katherine J.; Bouveret, Romaric; Lei, Pei-Wen; Duff, Anthony P.; Harrop, Stephen J.; Huang, Edwin P.; Harvey, Richard P.; Gelb, Michael H.; Gray, Peter P.; Curmi, Paul M.; Cunningham, Anne M.; Church, W. Bret; Scott, Kieran F.

    2013-01-01

    Human group IIA secreted phospholipase A2 (hGIIA) promotes tumor growth and inflammation and can act independently of its well described catalytic lipase activity via an alternative poorly understood signaling pathway. With six chemically diverse inhibitors we show that it is possible to selectively inhibit hGIIA signaling over catalysis, and x-ray crystal structures illustrate that signaling involves a pharmacologically distinct surface to the catalytic site. We demonstrate in rheumatoid fibroblast-like synoviocytes that non-catalytic signaling is associated with rapid internalization of the enzyme and colocalization with vimentin. Trafficking of exogenous hGIIA was monitored with immunofluorescence studies, which revealed that vimentin localization is disrupted by inhibitors of signaling that belong to a rare class of small molecule inhibitors that modulate protein-protein interactions. This study provides structural and pharmacological evidence for an association between vimentin, hGIIA, and arachidonic acid metabolism in synovial inflammation, avenues for selective interrogation of hGIIA signaling, and new strategies for therapeutic hGIIA inhibitor design. PMID:23482564

  15. Effect of encapsulation in the anion receptor pocket of sub-domain IIA of human serum albumin on the modulation of pKa of warfarin and structurally similar acidic guests: a possible implication on biological activity.

    Science.gov (United States)

    Datta, Shubhashis; Halder, Mintu

    2014-01-05

    Supramolecular and bio-supramolecular host assisted pKa shift of biologically relevant acidic guests, warfarin and coumarin 343, has been monitored using both steady-state and time resolved fluorescence spectroscopy. The anion receptors present in sub-domain IIA of human serum albumin (HSA) stabilize the anionic form of the guest and thereby shift pKa towards acidic range. On the other hand, the preferential binding of the neutral form of guests in the non-polar hydrophobic cavity of β-cyclodextrin results in up-shifted pKa. This shifting of pKa of drugs like warfarin, etc., whose therapeutic activity depends on the position of the acid-base equilibrium in human system, is of great importance in pharmacokinetics. The release of the active form of such drugs from macrocyclic carrier and subsequent distribution through the carrier protein should depend on the modulation of the overall pKa window brought about by the encapsulation in these hosts. Present work also suggests that properly optimized encapsulation in appropriate receptor pocket can enhance the bioavailability of drugs. This work also opens up the possibility to use HSA as encapsulator, instead of traditional cyclodextrins or other polymeric hosts, since such system may overcome toxicity as well as biocompatibility issues.

  16. Type IIA string theory on T{sup 6}/(Z{sub 2} x Z{sub 6} x ΩR). Model building and string phenomenology with intersecting D6-branes

    Energy Technology Data Exchange (ETDEWEB)

    Ecker, Jill

    2016-07-27

    In this doctoral thesis, various aspects of string model building and phenomenology are investigated within the framework of Type IIA string theory on the T{sup 6}/(Z{sub 2} x Z{sub 6} x ΩR) orbifold with discrete torsion. The aim is the reproduction of supersymmetric versions of well-known particle physics models using intersecting rigid D6-branes wrapped on fractional three-cycles. The models analyzed include the minimal supersymmetric Standard Model as well as supersymmetric Pati-Salam models, left-right symmetric models and SU(5) models. Systematic computer scans test numerous combinations of intersecting D6-branes in order to detect those that give rise to the correct chiral particle content of the considered models. For each type of the afore mentioned models, concrete examples will be found which satisfy the constraints on the particle spectrum and fulfill all consistency conditions. Finally, the thesis focuses on phenomenological aspects of the particle physics models found, including the detection of massless U(1) combinations, discrete Z{sub n}-symmetries and cubic couplings such as the Yukawa couplings.

  17. Safety and Efficacy of Tien-Hsien Liquid Practical in Patients with Refractory Metastatic Breast Cancer: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Phase IIa Trial

    Directory of Open Access Journals (Sweden)

    Wen-Hung Kuo

    2012-01-01

    Full Text Available To evaluate the safety and efficacy of Tien-Hsien Liquid Practical (THL-P, a Chinese herbal mixture, in patients with refractory metastatic breast cancer, we performed a randomized, double-blind, placebo-controlled, parallel-group, phase IIa pilot trial. Patients were randomly assigned to either receive THL-P or matching placebo and followed up every 4 weeks for 24 weeks. The primary endpoint was changes in the global health status/quality of life (GHS/QOL scale. The secondary endpoints were changes in functional and symptom scales, immunomodulating effects, and adverse events. Sixty-three patients were enrolled between June 2009 and June 2011. The intent-to-treat population included 28 patients in the THL-P group and 11 patients in the placebo group. Compared to the placebo group, the THL-P group had significant improvement from baseline to last visit in GHS/QOL (41.7 versus −33.3; P<0.05, CD3, CD4/CD8, CD19, CD16+56 positive cells (P<0.05, and higher levels of physical, role, emotional, and cognitive functioning, as well as decreased fatigue and systemic side effects. Treatment-related adverse events were mild constipation and localized itching, and no serious adverse events were reported. THL-P appears to be a safe alternative adjuvant treatment for patients with refractory metastatic breast cancer, as it effectively improves QOL and palliates cancer-related symptoms.

  18. Role of plasma bactericidal/permeability-increasing protein, group IIA phospholipase A(2), C-reactive protein, and white blood cell count in the early detection of severe sepsis in the emergency department.

    Science.gov (United States)

    Uusitalo-Seppälä, Raija; Peuravuori, Heikki; Koskinen, Pertti; Vahlberg, Tero; Rintala, Esa M

    2012-09-01

    To study the diagnostic values of bactericidal/permeability-increasing protein (BPI), group IIA phospholipase A(2) (PLA(2)GIIA), white blood cell count (WBC), and C-reactive protein (CRP) in identifying severe sepsis upon admission in an emergency room. This was a single-centre prospective cohort study involving 525 adult patients admitted to the emergency room with suspected infection. Plasma samples were taken concurrently with the blood cultures. Forty-nine patients with severe sepsis and 476 other patients (58 with no systemic inflammatory response syndrome (SIRS) and no bacterial infection, 63 with bacterial infection but no SIRS, 53 with SIRS but no bacterial infection, and 302 with sepsis but no organ dysfunction) were evaluated. BPI and PLA(2)GIIA were measured by time-resolved fluoroimmunoassay, and CRP with an immunoturbidimetric assay. WBC was measured using an automatic cell counter. There was a positive correlation between the plasma levels of PLA(2)GIIA and CRP (Pearson's correlation coefficient 0.60, p sepsis from others (OR 1.37, 95% Cl 1.05-1.78, p = 0.019). After adjusting for confounders PLA(2)GIIA remained a significant independent predictor of severe sepsis. PLA(2)GIIA seemed to be superior to CRP, BPI, and WBC in differentiating patients with severe sepsis. BPI gave no additional information in this respect.

  19. Antithrombin Cambridge II(A384S) mutation frequency and antithrombin activity levels in 120 of deep venous thrombosis and 150 of cerebral infarction patients in a single center in Southern China.

    Science.gov (United States)

    Zhang, Guang-sen; Tang, Yang-ming; Tang, Mei-qing; Qing, Zi-Ju; Shu, Chang; Tang, Xiang-qi; Deng, Ming-yang; Tan, Li-ming

    2010-09-01

    Antithrombin Cambridge II(A384S) mutation shows a relatively high frequency in western population. Some studies suggest that the mutation is an independent genetic risk factor both for deep vein thrombosis (DVT) and for arterial thrombosis, but whether the mutation has racial difference or has a general significance for thrombophilia remains unclear. In this study we performed an analysis of the prevalence of the mutation in Chinese southern population; Also, the antithrombin activity levels were evaluated in each investigated individual. The studies included 120 patients with DVT, 150 patients with cerebral infarction, and 110 controls. The mutation was detected using polymerase chain reaction/PvuII restrictive fragment length polymorphism procedures. Antithrombin activity assay was done using chromogenic substrate method. The results showed that no antithrombin Cambridge II mutation was detected in all three groups (DVT, cerebral infarction and controls), the incidence was 0/380. Plasma antithrombin activity was 91.37% +/- 16.15% in the DVT patients and 102.68% +/- 13.10% in the controls; the antithrombin activity was significantly reduced in the DVT group (P Cambridge II mutation has a racial difference, and may not be a valuable risk factor of thrombophilia in Asian population, and antithrombin deficiency remains a major genetic risk factor for DVT patients in China.

  20. Establishing the Intermediate Unit.

    Science.gov (United States)

    Pennsylvania State Dept. of Education, Harrisburg.

    The State of Pennsylvania Act 102 establishes a system of 29 intermediate units, creates intermediate unit boards of directors, spells out their duties and functions, and provides a system of financing their operations. This handbook has been prepared by the Pennsylvania Department of Education to provide intermediate unit boards of directors,…

  1. Unitals in Projective Planes

    CERN Document Server

    Barwick, Susan

    2008-01-01

    Unitals are key structures in projective planes, and have connections with other structures in algebra. This book presents a monograph on unitals embedded in finite projective planes. It offers a survey of the research literature on embedded unitals. It is suitable for graduate students and researchers who want to learn about this topic

  2. Stage I-IIA Non-Bulky Hodgkin's Lymphoma. Is Further Distinction Based on Prognostic Factors Useful? The Stanford Experience

    Energy Technology Data Exchange (ETDEWEB)

    Advani, Ranjana H., E-mail: radvani@stanford.edu [Department of Medicine, Division of Medical Oncology, Stanford University Medical Center, Stanford, California (United States); Hoppe, Richard T. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Maeda, Lauren S. [Department of Medicine, Division of Medical Oncology, Stanford University Medical Center, Stanford, California (United States); Baer, David M. [Northern California Kaiser Permanente, Oakland, California (United States); Mason, Joseph [Northern California Kaiser Permanente, San Jose, California (United States); Rosenberg, Saul A.; Horning, Sandra J. [Department of Medicine, Division of Medical Oncology, Stanford University Medical Center, Stanford, California (United States)

    2011-12-01

    Purpose: In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center. Methods and Materials: This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n = 84 patients) or 20-Gy (n = 17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors. Results: At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n = 55%; European Organization for Research and Treatment of Cancer, n = 33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n = 61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p = 0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged. Conclusions: The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

  3. Freestanding midwifery units versus obstetric units

    DEFF Research Database (Denmark)

    Overgaard, Charlotte; Fenger-Grøn, Morten; Sandall, Jane

    2012-01-01

    women intending to give birth in two freestanding midwifery units (FMU) versus two obstetric units in Denmark differed by level of social disadvantage Methods The study was designed as a cohort study with a matched control group. It included 839 lowrisk women intending to give birth in an FMU, who were...... prospectively and individually matched on nine selected obstetric/socio-economic factors to 839 low-risk women intending OU birth. Educational level was chosen as a proxy for social position. Analysis was by intention-to-treat. Results Women intending to give birth in an FMU had a significantly higher...

  4. ENERGY STAR Unit Reports

    Data.gov (United States)

    Department of Housing and Urban Development — These quarterly Federal Fiscal Year performance reports track the ENERGY STAR qualified HOME units that Participating Jurisdictions record in HUD's Integrated...

  5. 31 CFR 535.321 - United States; continental United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States; continental United... General Definitions § 535.321 United States; continental United States. The term United States means the United States and all areas under the jurisdiction or authority thereof including the Trust Territory...

  6. 31 CFR 515.321 - United States; continental United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States; continental United... General Definitions § 515.321 United States; continental United States. The term United States means the United States and all areas under the jurisdiction or authority thereof, including the Trust Territory...

  7. 31 CFR 500.321 - United States; continental United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States; continental United... General Definitions § 500.321 United States; continental United States. The term United States means the United States and all areas under the jurisdiction or authority thereof, including U.S. trust...

  8. Clinical efficacy of FDG-PET scan as preoperative diagnostic tool in cervical cancer stage Ib and IIa: comparison between the results of FDG-PET scan and operative findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Hoon

    1999-12-01

    This study was done to evaluate the clinical feasibility of FDG-PET scan for routine preoperative diagnostic methods in cervical carcinoma. PET-scans were performed from March, 1999 to November, 1999. There were 6 stage Ib and 7 IIa patients and all patients were performed radical hysterectomy and bilateral pelvic lymph node dissections and were evaluated by FDG-PET scan before operation. The mean age of the patients were 50.3 years old. Six cases had lymph node metastases by pelvis MRI, and three cases by FDG-PET scan. We could not find any lymph node metastases at surgery in 3 patients (50.0%) among 6 patients who were diagnosed by nodal metastases by pelvis MRI. And we found 1 patients with nodal metastases who had negative findings by pelvis MRI. By FDG-PET scan, we could find metastases in all positive patients. But we also found 2 additional metastatic cases in the patients with negative findings. In this study, the comparison was very difficult due to the individual differences in the comparison would be made by site-specific not person. The sensitivity of MRI and FDG-PET scan were 50.0% and 30.0%. The specificity were 94.1 % and 95.6%. The positive predictive value were 55.6 % and 50.0 %. In conclusion, we could find any superiority of FDG-PET scan in the diagnosis of lymph node metastases the pelvis MRI. So there are limitations to use the FDG-PET scan in the routine preoperative diagnostic tools in cervical cancer. But if we have more experiences to use the FDG-PET scan such as precise cut-off value of SUV and combination of other imaging technique, the FDG-PET scan are still promising diagnostic tools in cervical cancer.

  9. TGF-β1 Causes EMT by regulating N-Acetyl Glucosaminyl Transferases via Downregulation of Non Muscle Myosin II-A through JNK/P38/PI3K pathway in lung cancer.

    Science.gov (United States)

    Khan, Ghulam Jilany; Gao, Yingsheng; Gu, Ming; Wang, Lai; Khan, Sara; Naeem, Farah; Yousef, Bashir Alsiddig; Roy, Debmalya; Semukunzi, Herve; Yuan, Shengtao; Sun, Li

    2017-08-07

    Epithelial to mesenchymal transition (EMT) is a major determinant of cancer metastasis and is closely linked with TGF-β1. Intracellular proteins, including E. Cadherin, N. Cadherin and Vimentin are directly related to EMT that affect cell migration and adhesion; on the other hand, non muscle myosin (NM) has a central role in cytokinesis, migration and adhesion. We aimed to explore the association of EMT and metastasis with TGF-β1 through regulation of non-muscle myosin II-A (NMII-A) and its interaction with Hexosamine Biosynthesis Pathway (HBP). Protein expression changes were assessed by western blotting and immunofluorescent staining while transcription level changes were assessed by qRT-PCR. EMT was assessed by phenotypic analysis, wound healing, proliferation and transwell migration assay in vitro while in vivo studies were conducted in BALB/c nude mice for lung orthotopic and tail vein metastasis models. We demonstrated that regulation of JNK/ P38/PI3K by TGF-β1 led to down expression of NMII-A which promoted EMT and lung cancer metastasis. This down expression of NMII-A conversely upregulated the expression of Core 2 N-acetyl Glucosaminyl Transferase mucin type (C2GnT-M) and further facilitated up and down regulation of N-acetylglucosaminyltransferase (GnT) -V and -III respectively; moreover, NMII-A K.D cells showed 3 times more tendency to migrate towards brain in vivo. The study reports a novel pathway through which NMII-A negatively regulates EMT and metastasis via up regulation of C2GnT-M, GnT-V and down expression of GnT-III. These findings of lung cancer may further be required to study in other cancer types. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Reduction and fixation by high anterior cervical approach for treatment of type II and type IIA Hangman's fractures%高位颈前入路复位固定治疗Ⅱ型及ⅡA型Hangman骨折

    Institute of Scientific and Technical Information of China (English)

    谢学义; 彭新生

    2014-01-01

    目的:评价高位颈前入路复位固定治疗Ⅱ型及ⅡA型Hangman骨折的临床疗效。方法对2005年1月至2013年5月中山大学第一附属医院收治的21例Ⅱ型及ⅡA型Hangman骨折患者行高位颈前入路C2~C3椎间盘切除、复位及融合固定手术。记录手术时间、术中出血量,测量术后1周及末次随访时C2~C3前凸角;观察复位及并发症发生情况。结果手术时间50~90 min(平均75 min);术中出血量20~100 mL(平均55 mL)。术中无神经血管损伤并发症,所有患者成功获得固定。19例C2前脱位患者中,16例获得完全复位;3例基本复位。术后1周C2~C3平均前凸角为(3.1±0.8)°,优于术前的(-9±2.5)°(P<0.05);19例患者获得平均3年3个月(6个月至7年)的有效随访,末次随访时C2~C3平均前凸角为(2.6±0.5)°,未有明显丢失。所有患者获得椎间融合,未出现内固定松动、脱出、断裂等并发症。结论高位颈前入路C2~C3椎间盘切除、复位及融合固定治疗Ⅱ型及ⅡA型Hangman骨折,复位理想,内固定牢靠,能有效纠正和维持患者的颈椎前凸,融合率高,疗效满意。%Objective To evaluate the clinical effects of reduction and fixation by high anterior cervical approach for treatment of type II and type IIA Hangman's fractures. Methods From January 2005 to May 2013, 21 patients with type II and type IIA hangman's fractures underwent C2-C3 discectomy, reduction and intervertebral fusion with internal fixation by high anterior cervical approach. The operative time and intraoperative estimate blood loss were recorded, C2-C3 lordosis angles at one week postoperatively and the final follow-up were determined respectively, and the reduction and complications were observed. Results The average operative time was 75 min (50-90 min), the intraoperative estimate blood loss was 20-100 mL, with the average of 55 mL. No intraoperative

  11. REACH. Air Conditioning Units.

    Science.gov (United States)

    Garrison, Joe; And Others

    As a part of the REACH (Refrigeration, Electro-Mechanical, Air-Conditioning, Heating) electromechanical cluster, this student manual contains individualized instructional units in the area of air conditioning. The instructional units focus on air conditioning fundamentals, window air conditioning, system and installation, troubleshooting and…

  12. REACH. Air Conditioning Units.

    Science.gov (United States)

    Garrison, Joe; And Others

    As a part of the REACH (Refrigeration, Electro-Mechanical, Air-Conditioning, Heating) electromechanical cluster, this student manual contains individualized instructional units in the area of air conditioning. The instructional units focus on air conditioning fundamentals, window air conditioning, system and installation, troubleshooting and…

  13. Conflict Resolution Unit.

    Science.gov (United States)

    Busselle, Tish

    This 7-day unit, intended for use with secondary students, contains a statement of rationale and objectives, lesson plans, class assignments, teacher and student bibliographies, and suggestions for instructional materials on conflict resolution between individuals, groups, and nations. Among the six objectives listed for the unit are: 1) explain…

  14. REACH. Refrigeration Units.

    Science.gov (United States)

    Snow, Rufus; And Others

    As a part of the REACH (Refrigeration, Electro-Mechanical, Air-Conditioning, Heating) electromechanical cluster, this student manual contains individualized instructional units in the area of refrigeration. The instructional units focus on refrigeration fundamentals, tubing and pipe, refrigerants, troubleshooting, window air conditioning, and…

  15. Unit on Existentialism.

    Science.gov (United States)

    Rowell, Bobby

    1971-01-01

    A unit on existentialism is suggested to counteract the indifferent attitude that students have toward much of the literature with which they are presented. The key to a successful literature unit is immediate and total student involvement. Topics, authors, and works which may be used to arouse student interest are presented. (CK)

  16. United nations Orchestra

    CERN Multimedia

    MusiClub

    MusiClub United nations Orchestra www.ungenevaorchestra.ch An organizing committee has taken the initiative to create an Orchestra of the united nations at Geneva. In the context of this initiative, musicians in the following categories are invited to become members of the Orchestra and the Association: Active or retired staff of International organizations in Geneva; Active or retired employees of Permanent Missions to the United Nations at Geneva; as well as children and spouses of the above persons. For enrolment or for additional information, please contact: un.orchestra@yahoo.com

  17. Does size matter? Animal units and animal unit months

    Science.gov (United States)

    Lamar Smith; Joe Hicks; Scott Lusk; Mike Hemmovich; Shane Green; Sarah McCord; Mike Pellant; John Mitchell; Judith Dyess; Jim Sprinkle; Amanda Gearhart; Sherm Karl; Mike Hannemann; Ken Spaeth; Jason Karl; Matt Reeves; Dave Pyke; Jordan Spaak; Andrew Brischke; Del Despain; Matt Phillippi; Dave Weixelmann; Alan Bass; Jessie Page; Lori Metz; David Toledo; Emily Kachergis

    2017-01-01

    The concepts of animal units, animal unit months, and animal unit equivalents have long been used as standards for range management planning, estimating stocking rates, reporting actual use, assessing grazing fees, ranch appraisal, and other purposes. Increasing size of cattle on rangelands has led some to suggest that the definition of animal units and animal unit...

  18. Tax Unit Boundaries

    Data.gov (United States)

    Kansas Data Access and Support Center — The Statewide GIS Tax Unit boundary file was created through a collaborative partnership between the State of Kansas Department of Revenue Property Valuation...

  19. United Mitochondrial Disease Foundation

    Science.gov (United States)

    ... Other Ways to Give Matching Gifts Donate Your Car Online Options United Way Close About UMDF Our ... Rights Reserved | UMDF Donor Privacy Policy Facebook Twitter Google+ Youtube Vimeo Instagram Email STAY UPDATED! Join the ...

  20. Voltage verification unit

    Science.gov (United States)

    Martin, Edward J.

    2008-01-15

    A voltage verification unit and method for determining the absence of potentially dangerous potentials within a power supply enclosure without Mode 2 work is disclosed. With this device and method, a qualified worker, following a relatively simple protocol that involves a function test (hot, cold, hot) of the voltage verification unit before Lock Out/Tag Out and, and once the Lock Out/Tag Out is completed, testing or "trying" by simply reading a display on the voltage verification unit can be accomplished without exposure of the operator to the interior of the voltage supply enclosure. According to a preferred embodiment, the voltage verification unit includes test leads to allow diagnostics with other meters, without the necessity of accessing potentially dangerous bus bars or the like.

  1. Cereal Crops Research Unit

    Data.gov (United States)

    Federal Laboratory Consortium — The mission of the Cereal Crops Research Unit is to 1) conduct basic research to identify and understand the biological processes affecting the growth, development...

  2. Cereal Crops Research Unit

    Data.gov (United States)

    Federal Laboratory Consortium — The mission of the Cereal Crops Research Unit is to 1) conduct basic research to identify and understand the biological processes affecting the growth, development...

  3. Operable Unit Boundaries

    Data.gov (United States)

    U.S. Environmental Protection Agency — This dataset consists of operable unit data from multiple Superfund sites in U.S. EPA Region 8. These data were acquired from multiple sources at different times and...

  4. Insects: An Interdisciplinary Unit

    Science.gov (United States)

    Leger, Heather

    2007-01-01

    The author talks about an interdisciplinary unit on insects, and presents activities that can help students practice communication skills (interpersonal, interpretive, and presentational) and learn about insects with hands-on activities.

  5. Dimensionless Units in the SI

    CERN Document Server

    Mohr, Peter J

    2014-01-01

    The International System of Units (SI) is supposed to be coherent. That is, when a combination of units is replaced by an equivalent unit, there is no additional numerical factor. Here we consider dimensionless units as defined in the SI, {\\it e.g.} angular units like radians or steradians and counting units like radioactive decays or molecules. We show that an incoherence may arise when different units of this type are replaced by a single dimensionless unit, the unit "one", and suggest how to properly include such units into the SI in order to remove the incoherence. In particular, we argue that the radian is the appropriate coherent unit for angles and that hertz is not a coherent unit in the SI. We also discuss how including angular and counting units affects the fundamental constants.

  6. Priming with a simplified intradermal HIV-1 DNA vaccine regimen followed by boosting with recombinant HIV-1 MVA vaccine is safe and immunogenic: a phase IIa randomized clinical trial.

    Directory of Open Access Journals (Sweden)

    Patricia J Munseri

    Full Text Available Intradermal priming with HIV-1 DNA plasmids followed by HIV-1MVA boosting induces strong and broad cellular and humoral immune responses. In our previous HIVIS-03 trial, we used 5 injections with 2 pools of HIV-DNA at separate sites for each priming immunization. The present study explores whether HIV-DNA priming can be simplified by reducing the number of DNA injections and administration of combined versus separated plasmid pools.In this phase IIa, randomized trial, priming was performed using 5 injections of HIV-DNA, 1000 μg total dose, (3 Env and 2 Gag encoding plasmids compared to two "simplified" regimens of 2 injections of HIV-DNA, 600 μg total dose, of Env- and Gag-encoding plasmid pools with each pool either administered separately or combined. HIV-DNA immunizations were given intradermally at weeks 0, 4, and 12. Boosting was performed intramuscularly with 108 pfu HIV-MVA at weeks 30 and 46.129 healthy Tanzanian participants were enrolled. There were no differences in adverse events between the groups. The proportion of IFN-γ ELISpot responders to Gag and/or Env peptides after the second HIV-MVA boost did not differ significantly between the groups primed with 2 injections of combined HIV-DNA pools, 2 injections with separated pools, and 5 injections with separated pools (90%, 97% and 97%. There were no significant differences in the magnitude of Gag and/or Env IFN-γ ELISpot responses, in CD4+ and CD8+ T cell responses measured as IFN-γ/IL-2 production by intracellular cytokine staining (ICS or in response rates and median titers for binding antibodies to Env gp160 between study groups.A simplified intradermal vaccination regimen with 2 injections of a total of 600 μg with combined HIV-DNA plasmids primed cellular responses as efficiently as the standard regimen of 5 injections of a total of 1000 μg with separated plasmid pools after boosting twice with HIV-MVA.World Health Organization International Clinical Trials Registry

  7. Microdrilled cartilage defects treated with thrombin-solidified chitosan/blood implant regenerate a more hyaline, stable, and structurally integrated osteochondral unit compared to drilled controls.

    Science.gov (United States)

    Marchand, Catherine; Chen, Gaoping; Tran-Khanh, Nicolas; Sun, Jun; Chen, Hongmei; Buschmann, Michael D; Hoemann, Caroline D

    2012-03-01

    This study analyzed the long-term cartilage and subchondral bone repair of microdrilled defects treated with chitosan glycerol-phosphate/blood implant, using thrombin (Factor IIa) to accelerate in situ solidification. We also evaluated the cartilage repair response to six smaller microdrill holes compared with two larger holes. Bilateral knee trochlear cartilage defects were created in n=8 skeletally mature rabbits, drilled with six proximal 0.5 mm and two distal 0.9 mm holes, then covered with in situ-solidified IIa-implants (treated) or with IIa-alone (control). After 6.5 months of repair, cartilage repair tissues were analyzed by histological scoring and histomorphometry for hyaline matrix characteristics and osseous integration. Subchondral repair bone was analyzed by 3D microcomputed tomography and compared to acute defects (n=6) and intact trochlea (n=8). Implant-treated cartilage repair tissues had higher structural integrity through the entire defect (p=0.02), twofold higher percent staining for glycosaminoglycan (p=0.0004), and ~24% more collagen type II staining over the smaller drill holes (p=0.008) compared with controls. Otherwise, hole diameter had no specific effect on cartilage repair. The subchondral bone plate was partially restored in treated and control defects but less dense than intact trochlea, with evidence of incomplete regeneration of the calcified cartilage layer. More residual drill holes (p=0.054) were detected in control versus treated defects, and control defects with more than 40% residual holes presented abnormally thicker trabeculae compared with treated defects. Low osteoclast numbers after 6.5 months repair suggested that bone was no longer remodeling. The subchondral bone plate surrounding the defects exhibited a significant thickening compared with age-matched intact trochlea. These data suggest that debridement and drilling can lead to long-term subchondral bone changes outside the cartilage defect. Compared with drilled

  8. PARKA II-A Bottom Loss Measurements

    Science.gov (United States)

    1970-06-29

    obvious %ngle dependance between 15 to 85 degraes and, appear to be only slightly dependent of frequency; showing an approximate 2 db difference in mean... dependance . between 15 to 85 degrees and indicates a slight frequency dependance of 2 db over the frequency rang3e. The major reflected energy is from the...the low CONFIDENTIAL 10 NUSL Tech Memo 2211-023-70 CONFIDENTIAL sound v Locity sediment, resulting in significant angular dependance of bottom Loss at

  9. Lifshitz black holes in IIA supergravity

    NARCIS (Netherlands)

    Barclay, Luke; Gregory, Ruth; Parameswaran, Susha; Tasinato, Gianmassimo; Zavala, Ivonne

    2012-01-01

    We compute string theoretic black hole solutions having Lifshitz asymptotics with a general dynamical exponent z > 1. We start by constructing solutions in a flux compactification of six dimensional supergravity, then uplift them to massive type HA supergravity. Alongside the Lifshitz black holes we

  10. Lifshitz black holes in IIA supergravity

    NARCIS (Netherlands)

    Barclay, Luke; Gregory, Ruth; Parameswaran, Susha; Tasinato, Gianmassimo; Zavala, Ivonne

    2012-01-01

    We compute string theoretic black hole solutions having Lifshitz asymptotics with a general dynamical exponent z > 1. We start by constructing solutions in a flux compactification of six dimensional supergravity, then uplift them to massive type HA supergravity. Alongside the Lifshitz black holes we

  11. Circuit II--A Conversational Graphical Interface.

    Science.gov (United States)

    Singer, Ronald A.

    1993-01-01

    Provides an overview of Circuit II, an interactive system that provides users with a graphical representation of an electronic circuit within which questions may be posed and manipulated, and discusses how mouse selections have analogous roles to certain natural language features, such as anaphora, deixis, and ellipsis. (13 references) (EA)

  12. Battery thermal management unit

    Science.gov (United States)

    Sanders, Nicholas A.

    1989-03-01

    A battery warming device has been designed which uses waste heat from an operating internal combustion engine to warm a battery. A portion of the waste heat is stored in the sensible and latent heat of a phase change type material for use in maintaining the battery temperature after the engine is shut off. The basic design of the device consists of a Phase Change Material (PCM) reservoir and a simple heat exchanger connected to the engineer's cooling system. Two types of units were built, tested and field trialed. A strap-on type which was strapped to the side of an automotive battery and was intended for the automotive after-market and a tray type on which a battery or batteries sat. This unit was intended for the heavy duty truck market. It was determined that both types of units increased the average cranking power of the batteries they were applied to. Although there were several design problems with the units such as the need for an automatic thermostatically controlled bypass valve, the overall feeling is that there is a market opportunity for both the strap-on and tray type battery warming units.

  13. Coherence for weak units

    CERN Document Server

    Joyal, André

    2009-01-01

    We define weak units in a semi-monoidal 2-category $\\CC$ as cancellable pseudo-idempotents: they are pairs $(I,\\alpha)$ where $I$ is an object such that tensoring with $I$ from either side constitutes a biequivalence of $\\CC$, and $\\alpha: I \\tensor I \\to I$ is an equivalence in $\\CC$. We show that this notion of weak unit has coherence built in: Theorem A: $\\alpha$ has a canonical associator 2-cell, which automatically satisfies the pentagon equation. Theorem B: every morphism of weak units is automatically compatible with those associators. Theorem C: the 2-category of weak units is contractible if non-empty. Finally we show (Theorem E) that the notion of weak unit is equivalent to the notion obtained from the definition of tricategory: $\\alpha$ alone induces the whole family of left and right maps (indexed by the objects), as well as the whole family of Kelly 2-cells (one for each pair of objects), satisfying the relevant coherence axioms.

  14. Dispersion in unit disks

    CERN Document Server

    Dumitrescu, Adrian

    2009-01-01

    We present two new approximation algorithms with (improved) constant ratios for selecting $n$ points in $n$ unit disks such that the minimum pairwise distance among the points is maximized. (I) A very simple $O(n \\log{n})$-time algorithm with ratio 0.5110 for disjoint unit disks. In combination with an algorithm of Cabello \\cite{Ca07}, it yields a $O(n^2)$-time algorithm with ratio of 0.4487 for dispersion in $n$ not necessarily disjoint unit disks. (II) A more sophisticated LP-based algorithm with ratio 0.6495 for disjoint unit disks that uses a linear number of variables and constraints, and runs in polynomial time. The algorithm introduces a novel technique which combines linear programming and projections for approximating distances. The previous best approximation ratio for disjoint unit disks was 1/2. Our results give a partial answer to an open question raised by Cabello \\cite{Ca07}, who asked whether 1/2 could be improved.

  15. Signal processing unit

    Energy Technology Data Exchange (ETDEWEB)

    Boswell, J.

    1983-01-01

    The architecture of the signal processing unit (SPU) comprises an ROM connected to a program bus, and an input-output bus connected to a data bus and register through a pipeline multiplier accumulator (pmac) and a pipeline arithmetic logic unit (palu), each associated with a random access memory (ram1,2). The system pulse frequency is from 20 mhz. The pmac is further detailed, and has a capability of 20 mega operations per second. There is also a block diagram for the palu, showing interconnections between the register block (rbl), separator for bus (bs), register (reg), shifter (sh) and combination unit. The first and second rams have formats 64*16 and 32*32 bits, respectively. Further data are a 5-v power supply and 2.5 micron n-channel silicon gate mos technology with about 50000 transistors.

  16. Allocating multiple units

    DEFF Research Database (Denmark)

    Tranæs, Torben; Krishna, Kala

    2002-01-01

    This paper studies the allocation and rent distribution in multi-unit, combinatorial-bid auctions under complete information. We focus on the natural multi-unit analogue of the first-price auction, where buyers bid total payments, pay their bids, and where the seller allocates goods to maximize his...... revenue. While there are many equilibria in this auction, only efficient equilibria remain when the truthful equilibrium restriction of the menu-auction literature is used. Focusing on these equilibria we first show that the first-price auction just described is revenue and outcome equivalent to a Vickrey...

  17. United States Attorney Prosecutions

    Science.gov (United States)

    1993-10-01

    Berceda, 572 F.2d 630 (9th Cir. 1978).. A mere request, such as that made by the defendant, is not sufficient; United States v. Trejo- Zambrano , 582 F.2d...a mere request and more than mere speculation that disclosure will be helpful. United States v. Trejo- Zambrano , 582 F.2d 460 (9th Cir. 1978), eect. dt...both known and unknown to the Grand Jury, including Lane Boudreau, Scott Willard Holland, James Allen Halperin, Maria Ximena Erlandsen, Derek Adrian

  18. A multi-locus study of cryptosporidium parasites isolated from patients living in iran, Malawi, Nigeria, the United kingdom, and Vietnam.

    Directory of Open Access Journals (Sweden)

    Salman Ghaffari

    2014-03-01

    Full Text Available Cryptosporidium species are important cause of diarrheal diseases in both developing and developed countries. This study aimed to compare the performance of several molecular methods for identification of Cryptosporidium species, and to detect genetic variation among each of these species isolated from Iran, Malawi, Nigeria, Vietnam and the United Kingdom.The oocysts DNA samples were derived from 106 Cryptosporidium positive feces. Polymerase chain reaction, PCR- restriction fragment length polymorphism and DNA sequence analysis of the 18S rRNA and the Cryptosporidium oocysts wall protein genes; PCR and DNA sequence analysis of a fragment of 70 kDa heat shock protein and 60 kDa glycoprotein genes were carried out.Based on these analysis, three species of Cryptosporidium including C. hominis, C. parvum and C. meleagridis, and both C. hominis and C. parvum were found in Iranian and the UK samples, respectively. Also, three C. hominis (Ib, Ib3& Id and three C. parvum (IIa, IIc & IId subtypes were identified by sequence analysis of the GP60 gene. Of these, C. hominis Ib was predominant and interestingly, one subgenotype (C. hominis Ib A10G2 accounted for the majority of the samples.The current study demonstrates the complex subtypes of Cryptosporidium isolates in both developing and developed countries. This is the first report of C. parvum IId subgenotype and three new subtypes of C. parvum IIa in the UK, a new subtype of C. hominis Id from Malawi; and the first multi-locus study of three species of Cryptosporidium in human from Iran.

  19. Women's Rights Unit.

    Science.gov (United States)

    Weiss, Helen; Weigel, Margaret

    Designed for use in the intermediate grades, this interdisciplinary unit helps students examine traditional and modern roles of women. Fourteen lessons focus on women's activities in colonial America, reasons for women's discontent, the women's rights movement of the 1800's, changes in the roles of women, enfranchisement of women, women's role…

  20. Consumer Mathematics. Teaching Units.

    Science.gov (United States)

    North Carolina State Dept. of Public Instruction, Raleigh.

    GRADES OR AGES: Secondary school. SUBJECT MATTER: Consumer mathematics including--money management, transportation, probability, swindles and gyps, insurance, housing, taxes, consumer credit, banks, savings, and investments. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into ten parallel units, one for each of the above areas, which…

  1. United in change

    NARCIS (Netherlands)

    Hanneke Posthumus; Josje den Ridder; Joep de Hart

    2014-01-01

    Original title: Verenigd in verandering The importance of citizens who unite in civil society organisations is broadly recognised. Organisations bind people to each other, to the community and to the political system. How are civil-society organisations in the Netherlands faring? Is there

  2. Outdoorsman, Unit III.

    Science.gov (United States)

    Alberta Dept. of Agriculture, Edmonton.

    The third and final unit of the 4-H Outdoorsman Program covers the most advanced and challenging campcraft skills for 4-H members in British Columbia, Alberta, Saskatchewan and Manitoba. Survival camping (including building shelters and finding food), in-depth map-reading and orienteering, game management, hiking themes and recordkeeping are all…

  3. Sickle Cell Unit.

    Science.gov (United States)

    Canipe, Stephen L.

    Included in this high school biology unit on sickle cell anemia are the following materials: a synopsis of the history of the discovery and the genetic qualities of the disease; electrophoresis diagrams comparing normal, homozygous and heterozygous conditions of the disease; and biochemical characteristics and population genetics of the disease. A…

  4. Whale Teaching Unit.

    Science.gov (United States)

    Peninsula Humane Society, San Mateo, CA.

    Materials in this teaching unit are designed to foster an interest in whale preservation among intermediate grade and junior high school students. Several readings provide background information on various types of whales and the economic value of whales. Student activities include a true and false game, a crossword, and a mobile. A resource list…

  5. Whale Teaching Unit.

    Science.gov (United States)

    Peninsula Humane Society, San Mateo, CA.

    Materials in this teaching unit are designed to foster an interest in whale preservation among intermediate grade and junior high school students. Several readings provide background information on various types of whales and the economic value of whales. Student activities include a true and false game, a crossword, and a mobile. A resource list…

  6. Transfer of manufacturing units

    DEFF Research Database (Denmark)

    Madsen, Erik Skov; Riis, Jens Ove; Sørensen, Brian Vejrum

    2008-01-01

    The ongoing and unfolding relocation of activities is one of the major trends, that calls for attention in the domain of operations management. In particular, prescriptive models outlining: stages of the process, where to locate, and how to establish the new facilities have been studied, while...... and dilemmas to be addressed when transferring manufacturing units....

  7. Laser color recording unit

    Science.gov (United States)

    Jung, E.

    1984-05-01

    A color recording unit was designed for output and control of digitized picture data within computer controlled reproduction and picture processing systems. In order to get a color proof picture of high quality similar to a color print, together with reduced time and material consumption, a photographic color film material was exposed pixelwise by modulated laser beams of three wavelengths for red, green and blue light. Components of different manufacturers for lasers, acousto-optic modulators and polygon mirrors were tested, also different recording methods as (continuous tone mode or screened mode and with a drum or flatbed recording principle). Besides the application for the graphic arts - the proof recorder CPR 403 with continuous tone color recording with a drum scanner - such a color hardcopy peripheral unit with large picture formats and high resolution can be used in medicine, communication, and satellite picture processing.

  8. LIDAR COMBINED SCANNING UNIT

    Directory of Open Access Journals (Sweden)

    V. V. Elizarov

    2016-11-01

    Full Text Available Subject of Research. The results of lidar combined scanning unit development for locating leaks of hydrocarbons are presented The unit enables to perform high-speed scanning of the investigated space in wide and narrow angle fields. Method. Scanning in a wide angular field is produced by one-line scanning path by means of the movable aluminum mirror with a frequency of 20Hz and amplitude of 20 degrees of swing. Narrowband scanning is performed along a spiral path by the deflector. The deflection of the beam is done by rotation of the optical wedges forming part of the deflector at an angle of ±50. The control function of the scanning node is performed by a specialized software product written in C# programming language. Main Results. This scanning unit allows scanning the investigated area at a distance of 50-100 m with spatial resolution at the level of 3 cm. The positioning accuracy of the laser beam in space is 15'. The developed scanning unit gives the possibility to browse the entire investigated area for the time not more than 1 ms at a rotation frequency of each wedge from 50 to 200 Hz. The problem of unambiguous definition of the beam geographical coordinates in space is solved at the software level according to the rotation angles of the mirrors and optical wedges. Lidar system coordinates are determined by means of GPS. Practical Relevance. Development results open the possibility for increasing the spatial resolution of scanning systems of a wide range of lidars and can provide high positioning accuracy of the laser beam in space.

  9. Unit 5. Thermodynamics (Summary)

    OpenAIRE

    Beléndez Vázquez, Augusto

    2012-01-01

    Summary of the "Unit 5. Thermodynamics" of course "Physical Foundations of Engineering I". Degree in Sound and Image Engineering, in Telecommunications. Polytechnic School of the University of Alicante Resumen del "Tema 5. Termodinámica" de la asignatura "Fundamentos Físicos de la Ingeniería I". Grado en Ingeniería en Sonido e Imagen en Telecomunicaciones. Escuela Politécnica Superior. Universidad de Alicante.

  10. 丹参酮ⅡA磺酸钠治疗牙周病伴冠心病患者效果观察%Ef ect of tanshinone IIA sulfonate injection on periodontal disease patients with coronary heart disease (CHD)with periodontal condition

    Institute of Scientific and Technical Information of China (English)

    张丽萍; 李雪琴; 张春光; 门秀丽

    2014-01-01

    Objective To observe tanshinone IIA sulfonate injection ef ect on periodontal disease patients with coronary heart disease (CHD)with periodontal condition.Broaden the tan-shinone A sulfonate injection treatment range.Methods Selected 116 patients with coronary heart disease (CHD)with periodontal disease were divided into two groups,observation group of rou-tine coronary heart disease treatment and periodontal disease treatment of combined use of tanshinone IIA sulfonate injection,the control group routine treatment and periodontal disease conven-tional coronary heart disease.Results Patients with the results of application of tanshinoneⅡA,gingival index and gingival sulcus bleeding index change obviously.Conclusion Combined tanshi-none IIA sulfonate injection treatment of periodontal disease with coronary heart disease have certain curative ef ect,tanshinone can ef ectively restrain periodontal disease associated with inflam-mation in patients with coronary heart disease.%目的:观察丹参酮ⅡA磺酸钠治疗牙周病伴冠心病患者牙周状况效果,拓宽丹参酮ⅡA磺酸钠的治疗范围。方法选取牙周病伴冠心病患者116例随机分为两组,观察组58例,常规治疗冠心病同时常规治疗联合应用丹参酮ⅡA磺酸钠治疗牙周病。对照组58例,常规治疗冠心病同时常规治疗牙周病。结果观察组和对照组牙龈指数、龈沟出血指数、简化口腔卫生指数和牙周病指数治疗后与治疗前差值比较,两组4种牙周病指数差值均有统计学意义。结论联合丹参酮ⅡA磺酸钠治疗牙周病伴冠心病具有一定疗效,可以有效抑制牙周病伴冠心病患者炎症反应。

  11. UNIT COMMITMENT: A NEW TRUNCATED METHOD OF UNIT ...

    African Journals Online (AJOL)

    NIJOTECH

    limits, minimum up/down times. Other ... incremental heat rate in ₦/hour for unit i ... approaches to treating thermal unit during its ... (d) Load Balance: During each interval of time, k, the .... The unit information and initial conditions are shown in.

  12. Dynamic Torque Calibration Unit

    Science.gov (United States)

    Agronin, Michael L.; Marchetto, Carl A.

    1989-01-01

    Proposed dynamic torque calibration unit (DTCU) measures torque in rotary actuator components such as motors, bearings, gear trains, and flex couplings. Unique because designed specifically for testing components under low rates. Measures torque in device under test during controlled steady rotation or oscillation. Rotor oriented vertically, supported by upper angular-contact bearing and lower radial-contact bearing that floats axially to prevent thermal expansion from loading bearings. High-load capacity air bearing available to replace ball bearings when higher load capacity or reduction in rate noise required.

  13. Small Unit Operations

    Science.gov (United States)

    2007-11-02

    best demonstrated value for small (< AA size) lithium - thionyl - chloride batteries (Halpert 1993). Equation (2-3) shows that the solar power...However, this energy den- sity this is only ~ 3 times larger than the demonstrated performance of the best lithium batteries , and the fuel cells are...Units 13 2.2.2 ASIC Capability 15 2.2.3 Power and Size 17 2.2.4 Cost 19 2.3 Power Sources 20 2.3.1 Batteries 21 2.3.2 Solar Augmentation

  14. Order Units in a *-Algebra

    Indian Academy of Sciences (India)

    Anil K Karn

    2003-02-01

    Order unit property of a positive element in a *-algebra is defined. It is proved that precisely projections satisfy this order theoretic property. This way, unital hereditary *-subalgebras of a *-algebra are characterized.

  15. DS796 California Groundwater Units

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The California Groundwater Units dataset classifies and delineates the State into one of three groundwater based polygon units: (1) those areas defined as alluvial...

  16. Trend of hydraulic units

    Energy Technology Data Exchange (ETDEWEB)

    Deshimaru, Jun' ichi

    1988-11-01

    The gear, vane and piston pumps occupy a more then 90% share in the hydraulic pumps. Comparatively large pumps are mainly variable delivery piston pumps. The piston pumps are comparatively high in output density (output per unit weight), indicating the hydraulic pump in performance, and tend to become higher and higher in it. Though they are mainly 210 to 350kgf/cm/sup 2/ in rated pressure, some of them come to surpass 400kgf/cm/sup 3/ in it. While the progress in computation also requires the high speed operation, high accuracy and other severe conditions for the hydraulic units, which accordingly and increasingly intensify the requirement for hydraulic oil in abrasion resistibility, oxidation stability and response characteristics. While cavitation comes to easily occur, which considerably and disadvantageously influences hydraulic oil in life through degradation, noise level and respondingness. From now on, the development of high performance oil and study of mechanical structure are important. 19 references, 9 figures, 2 tables.

  17. An ISOLDE target unit

    CERN Multimedia

    Maximilien Brice

    2002-01-01

    A good dozen different targets are available for ISOLDE, made of different materials and equipped with different kinds of ion-sources, according to the needs of the experiments. Each separator (GPS: general purpose; HRS: high resolution) has its own target. Because of the high radiation levels, robots effect the target changes, about 80 times per year. In the standard unit shown in picture _01, the target is the cylindrical object in the front. It contains uranium-carbide kept at a temperature of 2200 deg C, necessary for the isotopes to be able to escape. At either end, one sees the heater current leads, carrying 700 A. The Booster beam, some 3E13 protons per pulse, enters the target from left. The evaporated isotope atoms enter a hot-plasma ion source (the black object behind the target). The whole unit sits at 60 kV potential (pulsed in synchronism with the arrival of the Booster beam) which accelerates the ions (away from the viewer) towards one of the 2 separators.

  18. Snakes: An Integrated Unit Plan.

    Science.gov (United States)

    Lawrence, Lisa

    This document presents an integrated unit plan on snakes targeting second grade students. Objectives of the unit include developing concepts of living things, understanding the contribution and importance of snakes to the environment, and making connections between different disciplines. The unit integrates the topic of snakes into the areas of…

  19. Design of hydraulic recuperation unit

    Directory of Open Access Journals (Sweden)

    Jandourek Pavel

    2016-01-01

    Full Text Available This article deals with design and measurement of hydraulic recuperation unit. Recuperation unit consist of radial turbine and axial pump, which are coupled on the same shaft. Speed of shaft with impellers are 6000 1/min. For economic reasons, is design of recuperation unit performed using commercially manufactured propellers.

  20. United Arab Emirates.

    Science.gov (United States)

    1985-02-01

    This discussion of the United Arab Emirates focuses on the following: the people; geography; history; government; political conditions; defense; the economy; foreign relations; and relations between the US and the United Arab Emirates. In 1983 the population was estimated at 1,194,000. In 1984 the annual growth rate was negative. Life expectancy is about 60 years. Fewer than 20% of the population are UAE citizens. Indigenous Emiris are Arab; the rest of the population includes significant numbers of other Arabs -- Palestinians, Egyptians, Jordanians, Yemenis, Omanis, as well as many Iranians, Pakistanis, Indians, and West Europeans, especially in Dubai. The UAE is in the eastern Arabian Peninsula, bounded on the north by the Persian Gulf. European and Arab pirates roamed the Trucial Coast area from the 17th century into the 19th century. Early British expeditions against the pirates led to further campaigns against their headquarters. Piracy continued intermittently until 1835, when the shaikhs agreed not to engage in hostilities at sea. Primarily in reaction to the ambitions of other European countries, the UK and the Trucial States established closer bonds in an 1892 treaty. In 1968 the British government announced its decision, reaffirmed in March 1971, to end the treaty relationship with the gulf shaikhdoms. When the British protective treaty with the Trucial Shaikhdoms ended on December 1, they became fully independent. On December 2, 1971, 6 of them entered into a union called the United Arab Emirates. The 7th, Ras al-Khaimah, joined in early 1972. Administratively, the UAE is a loose federation of 7 emirates, each with its own ruler. The pace at which local government in each emirate is evolving, from traditional to modern, is set primarily by the ruler. Under the provisional constitution of 1971, each emirate reserves considerable powers, including control over mineral rights, taxation, and police powers. In this milieu, the growth of federal powers has

  1. Learning unit: Thin lenses

    Science.gov (United States)

    Nita, L.-S.

    2012-04-01

    Learning unit: Thin lenses "Why objects seen through lenses are sometimes upright and sometimes reversed" Nita Laura Simona National College of Arts and Crafts "Constantin Brancusi", Craiova, Romania 1. GEOMETRIC OPTICS. 13 hours Introduction (models, axioms, principles, conventions) 1. Thin lenses (Types of lenses. Defining elements. Path of light rays through lenses. Image formation. Required physical quantities. Lens formulas). 2. Lens systems (Non-collated lenses. Focalless systems). 3. Human eye (Functioning as an optical system. Sight defects and their corrections). 4. Optical instruments (Characteristics exemplified by a magnifying glass. Paths of light rays through a simplified photo camera. Path of light rays through a classical microscope) (Physics curriculum for the IXth grade/ 2011). This scenario exposes a learning unit based on experimental sequences (defining specific competencies), as a succession of lessons started by noticing a problem whose solution assumes the setup of an experiment under laboratory conditions. Progressive learning of theme objectives are realised with sequential experimental steps. The central cognitive process is the induction or the generalization (development of new knowledge based on observation of examples or counterexamples of the concept to be learnt). Pupil interest in theme objectives is triggered by problem-situations, for example: "In order to better see small objects I need a magnifying glass. But when using a magnifier, small object images are sometimes seen upright and sometimes seen reversed!" Along the way, pupils' reasoning will converge to the idea: "The image of an object through a lens depends on the relative distances among object, lens, and observer". Associated learning model: EXPERIMENT Specific competencies: derived from the experiment model, in agreement with the following learning unit steps I. Evoking - Anticipation: Size of the problem, formulation of hypotheses and planning of experiment. II

  2. Tanshinone type IIA inhibits osteoprotegerin and osteoclast differentiation factor expression at relapse stage after orthodontic tooth movement%丹参酮ⅡA局部注射正畸牙移动后复发阶段破骨细胞分化因子的表达

    Institute of Scientific and Technical Information of China (English)

    张世英; 刘继光; 赵刚

    2014-01-01

    BACKGROUND:In recent years, many drugs emerge to control tooth movement, and scholars in China begin to investigate Chinese herbs with moderate nature and smal adverse reaction. OBJECTIVE:To observe the relapse after orthodontic tooth movement, osteoprotegerin and osteoclast differentiation factor expression in periodontal tissue after rats were treated with local tanshinone type IIA at different doses. METHODS:A total of 48 male Wistar rats were randomly divided into four groups:control, low dose (tanshinone type IIA 0.36 mg/d), medium dose (tanshinone type IIA 0.72 mg/d), and high dose (tanshinone type IIA 1.44 mg/d) groups. Taking anterior teeth as the anchorage, the maxil ary first molar of rats was tracted to mesial movement. In experimental groups, gingival mucosa of the first molar was local injected with tanshinone type IIA 1 day before the force device was removed, while control group was injected with physiological saline, once a day, for 4 weeks. Immediately, 1 week, and 4 weeks after the force device was removed, the distance between the maxil ary first molar and second molar was measured and body mass was weighted. The animals were kil ed after 4 weeks, osteoprotegerin and osteoclast differentiation factor expression in maxil ary first molar and periodontal tissue were determined using immunohistochemical staining. RESULTS AND CONCLUSION:There was no obvious change in the body weight of rats in each group (P>0.05). In low, medium and high dose groups, recurrent distance of the teeth was shorter than that in control group (P smal er the degree of recurrence was. Osteoprotegerin expression in the periodontal tissue was significantly higher in the experimental groups than the control group (P  目的:观察局部给予不同剂量丹参酮ⅡA 后,大鼠正畸牙齿移动后的复发过程中复发程度、牙周组织中的骨保护素及破骨细胞分化因子的表达。  方法:选用48只雄性Wistar大鼠,随机分成4组,对照

  3. Last call for units

    Science.gov (United States)

    Randall, Stuart; Rosen, Ronald; Jones, Clifford; Bean, Leonard W.; Lane, Frank

    2009-09-01

    I am writing with regard to Kevin McGuigan's definition of the darwin unit, Dw, as "the mathematical probability of one undergraduate (or faculty) fatality per practical if the person in question is left to their own devices" (July p60). Although it is clear how the loss of genitals in a laboratory accident would result in a student's removal from the gene pool, McGuigan does not explain how the loss of finger (a 1 mDw event, he suggests) might impede procreation in the slightest. Perhaps McGuigan is confusing Darwin's evolution by natural selection with Lamarck's discredited theory of evolution by the inheritance of acquired characteristics. If so, the gulf between physicists and biologists seems as wide as ever.

  4. Forward Deployed Robotic Unit

    Science.gov (United States)

    Brendle, Bruce E., Jr.; Bornstein, Jonathan A.

    2000-07-01

    Forward Deployed Robotic Unit (FDRU) is a core science and technology objective of the US Army, which will demonstrate the impact of autonomous systems on all phases of future land warfare. It will develop, integrate and demonstrate technology required to achieve robotic and fire control capabilities for future land combat vehicles, e.g., Future Combat Systems, using a system of systems approach that culminates in a field demonstration in 2005. It will also provide the required unmanned assets and conduct the demonstration. Battle Lab Warfighting Experiments and data analysis required to understand the effects of unmanned assets on combat operations. The US Army Tank- Automotive & Armaments Command and the US Army Research Laboratory are teaming in an effort to leverage prior technology achievements in the areas of autonomous mobility, architecture, sensor and robotics system integration; advance the state-of-the-art in these areas; and to provide field demonstration/application of the technologies.

  5. [United theory of aging].

    Science.gov (United States)

    Trubitsyn, A G

    2012-01-01

    In attempts to develop a means of life prolongation the humankind has created more than three hundred theories of the aging; each of them offers the original cause of aging. However, none of them has given practical result by now. The majority of the theories have now only historical interest. There are several different theories that are mainly under consideration currently. They are based on reliable, proven evidence: the free radical theory, the protein error theory, the replicative senescence theory, the theory of reparation weakening, the immunological theory, several versions of neuroendocrinal theories, and programmed aging theory. The theory presented here is based on conception that the life as the phenomenon represents many of the interconnected physical and chemical processes propelled by energy of the mitochondrial bioenergetical machine. Gradual degradation of all vital processes is caused by the programmed decrease in level of bioenergetics. This theory unites all existing theories of aging constructed on authentic facts: it is shown, that such fundamental phenomena accompanying aging process as the increase in level of reactive oxygen species (ROS), the decrease in the general level of protein synthesis, the limitation of cellular dividing (Haiflick limit), decrease in efficiency of reparation mechanisms are caused by bioenergetics attenuation. Each of these phenomena in turn generates a number of harmful secondary processes. Any of the theories bases on one of these destructive phenomena or their combination. Hence, each of them describes one of sides of process of the aging initially caused by programmed decrease of level of bioenergetics. This united theory gives the chance to understand the nature of aging clock and explains a phenomenon of increase in longevity at the condition of food restriction. Failures of attempts to develop means from aging are explained by that the manipulations with the separate secondary phenomena of attenuation of

  6. Friendly units for coldness

    CERN Document Server

    Fraundorf, P

    2006-01-01

    Measures of temperature that center around human experience get lots of use. Of course thermal physics insights of the last century have shown that reciprocal temperature (1/kT) has applications that temperature addresses less well. In addition to taking on negative absolute values under population inversion (e.g. of magnetic spins), bits and bytes turn 1/kT into an informatic measure of the thermal ambient for developing correlations within any complex system. We show here that, in the human-friendly units of bytes and food Calories, water freezes when 1/kT ~200 ZB/Cal or kT ~5 Cal/YB. Casting familiar benchmarks into these terms shows that habitable human space requires coldness values (part of the time, at least) between 0 and 40 ZB/Cal with respect body temperature ~100 degrees F, a range in kT of ~1 Cal/YB. Insight into these physical quantities underlying thermal equilibration may prove useful for budding scientists, as well as the general public, in years ahead.

  7. Mobile contingency unit

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Sergio O. da; Magalhaes, Milton P. de [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil); Junqueira, Rodrigo A.; Torres, Carlos A.R. [PETROBRAS Transporte S/A (TRANSPETRO), Rio de Janeiro, RJ (Brazil)

    2009-07-01

    This paper is aimed at presenting what is already a reality in TRANSPETRO in the area covered by OSBRA, a pipeline that carries by-products to the Mid-West region of Brazil. In order to meet the needs of covering occasional accidents, TRANSPETRO counts on a standardized system of emergency management. It is a great challenge to secure an efficient communication along the 964 km of extension, considering that there are shadow zones where it is not possible to use conventional means of communication such as mobile telephony and internet. It was in this context that the Mobile Contingency Unit Via Satellite - MCU was developed, to extend the communication facilities existing in fixed installations to remote places, mainly the pipeline right of ways. In case of emergency, simulation and work in the pipeline right of way, MCU is fully able to provide the same data, voice, closed-circuit TV and satellite video conference facilities that are available in any internal area of the PETROBRAS system. (author)

  8. Portable Virtual Training Units

    Science.gov (United States)

    Malone, Reagan; Johnston, Alan

    2015-01-01

    The Mission Operations Lab initiated a project to design, develop, deliver, test, and validate a unique training system for astronaut and ground support personnel. In an effort to keep training costs low, virtual training units (VTUs) have been designed based on images of actual hardware and manipulated by a touch screen style interface for ground support personnel training. This project helped modernized the training system and materials by integrating them with mobile devices for training when operators or crew are unavailable to physically train in the facility. This project also tested the concept of a handheld remote device to control integrated trainers using International Space Station (ISS) training simulators as a platform. The portable VTU can interface with the full-sized VTU, allowing a trainer co-located with a trainee to remotely manipulate a VTU and evaluate a trainee's response. This project helped determine if it is useful, cost effective, and beneficial for the instructor to have a portable handheld device to control the behavior of the models during training. This project has advanced NASA Marshall Space Flight Center's (MSFC's) VTU capabilities with modern and relevant technology to support space flight training needs of today and tomorrow.

  9. Cohesion in Multinational Military Units

    Science.gov (United States)

    2010-12-10

    He openly admitted his homosexual orientation at a staff meeting; by doing that he clearly stated his guidelines toward gays . He had developed a...of units and consequentially unit effectiveness (Dupuy 1993, 2948). Some nations permit openly gay and lesbian personnel and others may not. Social...may cause less tension. However, for some nations involvement of gays and lesbians in multinational units may be offensive, while other nations are

  10. Inlet Geomorphology Evolution Work Unit

    Science.gov (United States)

    2015-10-30

    the expected behavior and benefits of nearshore placement. Nearshore placement studies have been documented in two journal papers, one technical...Coastal Inlets Research Program Inlet Geomorphology Evolution Work Unit The Inlet Geomorphology Evolution work unit of the CIRP develops methods...sensing measurements, and USACE projects to create valuable guidance that address geomorphic questions. The present focus of the work unit is a common

  11. From stroke unit care to stroke care unit

    NARCIS (Netherlands)

    De Keyser, J; Sulter, G.

    1999-01-01

    In some stroke units continuous monitoring of blood pressure, electrocardiogram, body temperature, and oxygen saturation has become an integral part of the management of acute stroke. In addition, regular measurements of blood glucose are performed. Stroke units equipped with such monitoring facilit

  12. From stroke unit care to stroke care unit

    NARCIS (Netherlands)

    De Keyser, J; Sulter, G.

    1999-01-01

    In some stroke units continuous monitoring of blood pressure, electrocardiogram, body temperature, and oxygen saturation has become an integral part of the management of acute stroke. In addition, regular measurements of blood glucose are performed. Stroke units equipped with such monitoring

  13. GPS Metric Tracking Unit

    Science.gov (United States)

    2008-01-01

    As Global Positioning Satellite (GPS) applications become more prevalent for land- and air-based vehicles, GPS applications for space vehicles will also increase. The Applied Technology Directorate of Kennedy Space Center (KSC) has developed a lightweight, low-cost GPS Metric Tracking Unit (GMTU), the first of two steps in developing a lightweight, low-cost Space-Based Tracking and Command Subsystem (STACS) designed to meet Range Safety's link margin and latency requirements for vehicle command and telemetry data. The goals of STACS are to improve Range Safety operations and expand tracking capabilities for space vehicles. STACS will track the vehicle, receive commands, and send telemetry data through the space-based asset, which will dramatically reduce dependence on ground-based assets. The other step was the Low-Cost Tracking and Data Relay Satellite System (TDRSS) Transceiver (LCT2), developed by the Wallops Flight Facility (WFF), which allows the vehicle to communicate with a geosynchronous relay satellite. Although the GMTU and LCT2 were independently implemented and tested, the design collaboration of KSC and WFF engineers allowed GMTU and LCT2 to be integrated into one enclosure, leading to the final STACS. In operation, GMTU needs only a radio frequency (RF) input from a GPS antenna and outputs position and velocity data to the vehicle through a serial or pulse code modulation (PCM) interface. GMTU includes one commercial GPS receiver board and a custom board, the Command and Telemetry Processor (CTP) developed by KSC. The CTP design is based on a field-programmable gate array (FPGA) with embedded processors to support GPS functions.

  14. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...

  15. Fatigue of Concrete Armour Units

    DEFF Research Database (Denmark)

    Sørensen, N. B.; Burcharth, H. F.; Liu, Z.

    1995-01-01

    In the present article fatigue as a possible reason for failure of Dolosse armour units made of plain concrete is discussed.......In the present article fatigue as a possible reason for failure of Dolosse armour units made of plain concrete is discussed....

  16. Multicultural Mini-Units. Elementary.

    Science.gov (United States)

    Flora, Sherrill B.

    The teaching mini-units in this teacher's guide are designed for use with elementary level students. Thematic study units are given for each of the following countries or continents: Africa, Australia, Brazil, Canada, China, England, France, Germany, Greece, India, Israel, Italy, Japan, Mexico, Netherlands, Russia, Spain, Sweden, Thailand, and the…

  17. Studying in the United Kingdom

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The United Kingdom is among the world leaders in recruiting international students.Joanna Burke,Cultural Counselor in the Cultural and Education Section of the British Embassy in China,recently spoke about international students,especially Chinese students in the United Kingdom,with Beijing Review reporter Wang Hairong.

  18. Fatigue of Concrete Armour Units

    DEFF Research Database (Denmark)

    Sørensen, N. B.; Burcharth, H. F.; Liu, Z.

    1995-01-01

    In the present article fatigue as a possible reason for failure of Dolosse armour units made of plain concrete is discussed.......In the present article fatigue as a possible reason for failure of Dolosse armour units made of plain concrete is discussed....

  19. Unit 03 - Introduction to Computers

    OpenAIRE

    Unit 74, CC in GIS; National Center for Geographic Information and Analysis

    1990-01-01

    This unit provides a brief introduction to computer hardware and software. It discusses binary notation, the ASCII coding system and hardware components including the central processing unit (CPU), memory, peripherals and storage media. Software including operating systems, word processors database packages, spreadsheets and statistical packages are briefly described.

  20. Multicultural Mini-Units. Elementary.

    Science.gov (United States)

    Flora, Sherrill B.

    The teaching mini-units in this teacher's guide are designed for use with elementary level students. Thematic study units are given for each of the following countries or continents: Africa, Australia, Brazil, Canada, China, England, France, Germany, Greece, India, Israel, Italy, Japan, Mexico, Netherlands, Russia, Spain, Sweden, Thailand, and the…

  1. Edison Home Community Study Unit.

    Science.gov (United States)

    Lee County School District, Ft. Myers, FL. Dept. of Environmental Education and Instructional Development Services.

    History is not merely events that occurred in the past. The past has influenced the present, as the present will influence the future. The purpose of this community study unit is to provide fourth grade students with an opportunity to investigate some of the history of Lee County, Florida. The unit's focus is on Thomas Edison, who built a home in…

  2. Views of Appalachia: Resource Unit.

    Science.gov (United States)

    Chafin, Shirley R.

    Designed to teach twelfth grade English honors students in Kentucky to think critically, to write creatively, to develop a better self-concept, and to stimulate appreciation and pride for Appalachian literature and culture, this 9-week resource unit features mini-units on (1) Man and His Values; (2) Death; (3) Prejudice; (4) Strip Mining; and (5)…

  3. 7 CFR 1160.104 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true United States. 1160.104 Section 1160.104 Agriculture... Definitions § 1160.104 United States. United States means the 48 contiguous states in the continental United States and the District of Columbia, except that United States means the 50 states of the United......

  4. 丹参酮ⅡA 磺酸钠联合氯吡格雷对冠心病心绞痛疗效及血管内皮功能的影响%Effect of TanshinoneIIA Sulfonic Sodium combined with Clopidogrel on coronary heart disease and angina pectoris and vascular endothelium function

    Institute of Scientific and Technical Information of China (English)

    周芸羽; 吴敏; 叶张章; 陈明华

    2016-01-01

    Objective It is to explore the effect of TanshinoneIIA Sulfonic Sodium combined with Clopidogrel on coronaryheart disease and angina pectoris and vascular endothelium function .Methods 60 patients with coronary heart disease and anginapectoris were randomly divided into experimental group and control group , both the groups were given normal therapy , onthis basis the control group was treated with Clopidogrel , the experimental group was treated with TanshinoneIIA Sulfonic Sodi -um combined with Clopidogrel.The attack times and lasting time of angina pectoris and dosage needed of nitroglycerin beforeand after treatment were observed in both groups , and the levels of NO, ET and TXB2 were determined.Results The attacktimes and lasting time of angina pectoris and dosage needed of nitroglycerin, the levels of ET and TXB2 all decreased aftertreatment while that of NO increased in both groups compared with that before treatment , and the decrease or increase in experimentalgroup was more significant (P <0.05).The total effective rate in experimental group was obviously higher thanthat in control group (P <0.05).Conclusion TanshinoneIIA Sulfonic Sodium combined with Clopidogrel can promote coro -nary artery dilatation, improve vascular endothelium function in the treatment with coronary heart disease and angina pectoris ,the curative effect is good and it is worthy of popularization and application .%目的:探讨丹参酮ⅡA磺酸钠联合氯吡格雷对冠心病心绞痛疗效及血管内皮功能的影响。方法将冠心病心绞痛患者60例随机分为实验组和对照组,均给予常规治疗,对照组在此基础上联合氯吡格雷进行治疗,实验组在对照组治疗基础上加用丹参酮ⅡA磺酸钠进行治疗,观察2组治疗前后心绞痛发作次数、持续时间以及缓解所需硝酸甘油剂量,同时检测2组治疗前后血液内一氢化氮( NO)、内皮素( ET)及血栓素A2( TXB2)水平。结果2组治疗后

  5. Design of Dolos Armour Units

    DEFF Research Database (Denmark)

    Burcharth, H. F.; Liu, Zhou

    1993-01-01

    The slender, complex types of armour units, such as Tetrapods and Dolosse are widely used. Many of the recent failures are such rubble mound breakwaters revealed that there is an imbalance between strength (structural integrity) of the units and the hydraulic stability (resistance to displacements......) of the armour layers. The paper deals only with dolos armour and presents the first design diagrammes and formulae where stresses from static, quasistatic and impact loads are implemented as well as the hydraulic stability. The dolos is treated as a multi shape unit where the thickness can be adjusted...

  6. Geysers Unit 18

    Energy Technology Data Exchange (ETDEWEB)

    Finney, John P.

    1980-12-01

    likely. For all of its risk aversion, SDG&E still remains one of the best potential markets for any energy producer. A recent article in FORBES MAGAZINE found that SDG&E had the third highest price per kilowatt of any utility in the country--5.9{cents} per kilowatt hour for commercial customers. That was in March, 1980. Energy cost adjustment clause increases resulted in an average commercial price per kilowatt hour of 7.2{cents} in May. In July it is expected to climb to 9.2{cents}. SDG&E's rate territory continues to expand at the rate of 5% annually and it is located just over 100 miles from a major source of geothermal heat in the Imperial Valley. But today, SDG&E has no commercial geothermal heat or power purchase contracts with domestic producers. You may ask, ''Why not?'' With no incentive to spend its own money and with a high growth rate, what is SDG&E doing to obtain capacity for its existing and future customers? At the present time, most of SDG&E's capital expenditure for generation is going to the construction of San Onofre Units 2 and 3 , a nuclear project which has been under way for ten years and which is expected to start generating commercial power in 1982 and 1983. San Onofre 2 and 3 will add 440 MW of capacity from a reliable, proven generating technology to SDG&E's system.

  7. Tax_Units_2011_Final

    Data.gov (United States)

    Kansas Data Access and Support Center — The Statewide GIS Tax Unit boundary file was created through a collaborative partnership between the State of Kansas Department of Revenue Property Valuation...

  8. Fundamental units: physics and metrology

    CERN Document Server

    Okun, Lev Borisovich

    2003-01-01

    The problem of fundamental units is discussed in the context of achievements of both theoretical physics and modern metrology. On one hand, due to fascinating accuracy of atomic clocks, the traditional macroscopic standards of metrology (second, metre, kilogram) are giving way to standards based on fundamental units of nature: velocity of light $c$ and quantum of action $h$. On the other hand, the poor precision of gravitational constant $G$, which is widely believed to define the ``cube of theories'' and the units of the future ``theory of everything'', does not allow to use $G$ as a fundamental dimensional constant in metrology. The electromagnetic units in SI are actually based on concepts of prerelativistic classical electrodynamics such as ether, electric permitivity and magnetic permeability of vacuum. Concluding remarks are devoted to terminological confusion which accompanies the progress in basic physics and metrology.

  9. Studying in the United Kingdom

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Beijing Review:The United Kingdom has many top universities in the world. Could you please tell us how many inter-national students are enrolled in UK institutes of higher learning and how many are from China?

  10. Environmental Control Unit Harness Project

    Science.gov (United States)

    Oliva-Buisson, Yvette J.

    2014-01-01

    Testing four new Environmental Control Unit Harnesses for improved user comfort during SCAPE operations. Phase I, testing in a lab environment, Phase II will continue testing the best candidates in a field environment.

  11. Electronegativity Equalization with Pauling Units.

    Science.gov (United States)

    Bratsch, Steven G.

    1984-01-01

    Discusses electronegativity equalization using Pauling units. Although Pauling has qualitatively defined electronegativity as the power of an atom in a molecule to attract electrons to itself, Pauling electronegativities are treated in this paper as prebonded, isolated-atom quantities. (JN)

  12. Decommissioning of an irradiation unit

    Energy Technology Data Exchange (ETDEWEB)

    Richards, A.G. [Radiation Protection and Safety Services, Univ. of Leeds, Leeds (United Kingdom)

    2000-05-01

    Distributed throughout hospital, research establishments in the United Kingdom and many other countries are Irradiation Units and Teletherapy machines used for either research purposes or treatment of patients for radiotherapy. These Irradiation Units and Teletherapy machines are loaded with radioactive sources of either Cobalt 60 or Caesium 137. The activity of these sources can range from 1 Terabecquerel up to 100 Terabecquerels or more. Where it is possible to load the radioactive sources without removal from the shielded container into a transport package which is suitable for transport decommissioning of a Teletherapy machine is not a major exercise. When the radioactive sources need to be unloaded from the Irradiation Unit or Teletherapy machine the potential exists for very high levels of radiation. The operation outlined in the paper involved the transfer from an Irradiation Unit to a transport package of two 3.25 Terabecquerel sources of Cobalt 60. The operation of the removal and transfer comes within the scope of the United Kingdom Ionising Radiation Regulations 1985 which were made following the Recommendations of the International Commission on Radiological Protection. This paper illustrates a safe method for this operation and how doses received can be kept within ALARA. (author)

  13. United Kingdom: Health System Review.

    Science.gov (United States)

    Cylus, Jonathan; Richardson, Erica; Findley, Lisa; Longley, Marcus; O'Neill, Ciaran; Steel, David

    2015-01-01

    This analysis of the United Kingdom health system reviews recent developments in organization and governance, health financing, health care provision, health reforms and health system performance. It provides an overview of how the national health services operate in the four nations that make up the United Kingdom, as responsibility for organizing health financing and services was devolved from 1997. With devolution, the health systems in the United Kingdom have diverged in the details of how services are organized and paid for, but all have maintained national health services which provide universal access to a comprehensive package of services that are mostly free at the point of use. These health services are predominantly financed from general taxation and 83.5% of total health expenditure in the United Kingdom came from public sources in 2013. Life expectancy has increased steadily across the United Kingdom, but health inequalities have proved stubbornly resistant to improvement, and the gap between the most deprived and the most privileged continues to widen, rather than close. The United Kingdom faces challenges going forward, including how to cope with the needs of an ageing population, how to manage populations with poor health behaviours and associated chronic conditions, how to meet patient expectations of access to the latest available medicines and technologies, and how to adapt a system that has limited resources to expand its workforce and infrastructural capacity so it can rise to these challenges.

  14. 75 FR 5373 - United States Mint

    Science.gov (United States)

    2010-02-02

    ... United States Mint ACTION: Notification of Pricing for 2010 United States Mint Presidential $1 Coin Proof Set. \\TM\\ SUMMARY: The United States Mint is announcing the price of the 2010 United States Mint Presidential $1 Coin Proof Set. The 2010 United States Mint Presidential $1 Coin Proof Set, featuring $1...

  15. 31 CFR 800.225 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 800.225 Section 800... TAKEOVERS BY FOREIGN PERSONS Definitions § 800.225 United States. The term United States or U.S. means the United States of America, the States of the United States, the District of Columbia, and any...

  16. A BASIC CAMERA UNIT FOR MEDICAL PHOTOGRAPHY.

    Science.gov (United States)

    SMIALOWSKI, A; CURRIE, D J

    1964-08-22

    A camera unit suitable for most medical photographic purposes is described. The unit comprises a single-lens reflex camera, an electronic flash unit and supplementary lenses. Simple instructions for use of th's basic unit are presented. The unit is entirely suitable for taking fine-quality photographs of most medical subjects by persons who have had little photographic training.

  17. Some Relationships among Unit Subsystem Characteristics, Unit Task Characteristics, and Unit Effectiveness

    Science.gov (United States)

    1988-10-01

    C.J. (1980) The behavoiral antd affective consequences of performance- relevant situational variables. Organizational Behavior and Human Performance...cies, practices, and procedures facilitate and/or inhibit organizational work unit effectiveness. This dissertation introduces an additional variable...people in an organizational work unit perform rather than a person. Roberts, lulin, and Rousseau (1978) provided an adaptation of Lewin’s work that

  18. Global Units modulo Circular Units : descent without Iwasawa's Main Conjecture

    CERN Document Server

    Belliard, Jean-Robert

    2009-01-01

    Iwasawa's classical asymptotical formula relates the orders of the $p$-parts $X_n$ of the ideal class groups along a $\\ZM_p$-extension $F_\\infty/F$ of a number field $F$, to Iwasawa structural invariants $\\la$ and $\\mu$ attached to the inverse limit $X_\\infty=\\limpro X_n$. It relies on "good" descent properties satisfied by $X_n$. If $F$ is abelian and $F_\\infty$ is cyclotomic it is known that the $p$-parts of the orders of the global units modulo circular units $U_n/C_n$ are asymptotically equivalent to the $p$-parts of the ideal class numbers. This suggests that these quotients $U_n/C_n$, so to speak unit class groups, satisfy also good descent properties. We show this directly, i.e. without using Iwasawa's Main Conjecture.

  19. Unsupervised segmentation with dynamical units.

    Science.gov (United States)

    Rao, A Ravishankar; Cecchi, Guillermo A; Peck, Charles C; Kozloski, James R

    2008-01-01

    In this paper, we present a novel network to separate mixtures of inputs that have been previously learned. A significant capability of the network is that it segments the components of each input object that most contribute to its classification. The network consists of amplitude-phase units that can synchronize their dynamics, so that separation is determined by the amplitude of units in an output layer, and segmentation by phase similarity between input and output layer units. Learning is unsupervised and based on a Hebbian update, and the architecture is very simple. Moreover, efficient segmentation can be achieved even when there is considerable superposition of the inputs. The network dynamics are derived from an objective function that rewards sparse coding in the generalized amplitude-phase variables. We argue that this objective function can provide a possible formal interpretation of the binding problem and that the implementation of the network architecture and dynamics is biologically plausible.

  20. THOR Particle Processing Unit PPU

    Science.gov (United States)

    Federica Marcucci, Maria; Bruno, Roberto; Consolini, Giuseppe; D'Amicis, Raffaella; De Lauretis, Marcello; De Marco, Rossana; De Michelis, Paola; Francia, Patrizia; Laurenza, Monica; Materassi, Massimo; Vellante, Massimo; Valentini, Francesco

    2016-04-01

    Turbulence Heating ObserveR (THOR) is the first mission ever flown in space dedicated to plasma turbulence. On board THOR, data collected by the Turbulent Electron Analyser, the Ion Mass Spectrum analyser and the Cold Solar Wind ion analyser instruments will be processed by a common digital processor unit, the Particle Processing Unit (PPU). PPU architecture will be based on the state of the art space flight processors and will be fully redundant, in order to efficiently and safely handle the data from the numerous sensors of the instruments suite. The approach of a common processing unit for particle instruments is very important for the enabling of an efficient management for correlative plasma measurements, also facilitating interoperation with other instruments on the spacecraft. Moreover, it permits technical and programmatic synergies giving the possibility to optimize and save spacecraft resources.

  1. Ad valorem versus unit taxes

    DEFF Research Database (Denmark)

    Schröder, Philipp J.H.; Sørensen, Allan

    2010-01-01

    Real-world industries are composed from heterogeneous firms and substantial intra-industry reallocations take place, i.e. high productivity firms squeeze out low productivity firms. Previous tax-tool comparisons have not included these central forces of industry structure. This paper examines...... a general equilibrium monopolistic competition model with heterogeneous firms and intra-industry reallocations. We show that the welfare superiority of ad valorem over unit taxes under imperfect competition is not only preserved but amplified. The additional difference between the tools arises because unit...... taxes distort relative prices, which in turn reduces average industry productivity through reallocations (the survival and increased market share of lower productivity firms). Importantly, numerical solutions of the model reveal that the relative welfare loss from using the unit tax increases...

  2. Unit for cleaning drilling muds

    Energy Technology Data Exchange (ETDEWEB)

    Dorosh, M.M.; Dera, Ya.I.; Fesenko, M.M.; Makedonov, N.I.; Surkov, V.T.

    1983-01-01

    A design is proposed for a unit for cleaning drilling muds which includes a settling tank with input sleeve and a sleeve of the purified mud and hydrocyclones. In order to improve the effectiveness of the degree of purification, the unit is equipped with an ejector and sludge filter arranged under the settling tank in the form of a grid installed in the upper part of the settling tank and connected to the sleeve of purified mud, while the inlet sleeve is arranged tangentially. The proposed unit can operate during drilling with the use of muds on water and carbon bases. As a result of its use, the degree of purification of the drilling mud reaches 30-35%; there is an increase in mechanical drilling rate, the service life of the sand-separator and the silt separators and decrease in wear of the pump equipment.

  3. Unit Reconstitutions: Combat Stress as an Indicator of Unit Effectiveness

    Science.gov (United States)

    2014-06-13

    professional military education or writing for trade journals supplemented the brief “reconstitution renaissance ” with scholarly excursus. This literature...United Sates Army, neuropsychiatry in World War II, Vol. II, overseas theatres . Washington, DC: Government Printing Office. 60 Nash, William P. 2007

  4. Auto Body Repair. Supplementary Units. Instructor Key and Student Units.

    Science.gov (United States)

    Daniel, Linda; Muench, James F., Ed.

    These supplementary units are designed to help students with special needs learn and apply auto body repair skills. The material specifically supplements the Auto Body Repair Curriculum Guide (University of Missouri-Columbia 1988), and is intended for instructors serving the occupational needs of various categories of disadvantaged and handicapped…

  5. The Work Unit Information System

    Science.gov (United States)

    1990-03-01

    detl- il 𔃻’ 1hiLS. dIxam.rnt. no.y be- used in conjuctien with tlie video, or !sep1aTate’ly. 114. SUBJECT TERMS 1%. NUMLItH Of 01 AuLAS 12, yi N~I) I T...6145, (202) 274-6817, (AV) 284-6817. 1I 10. WINS AND INPUT WRAP-UP The Army Material Command has implemented its own PC-based work unit input system...extrusion and composite materials . An example of a contract search would be: Find all work units that relate to contract F33615-84-K-2458. An example

  6. AC410 Unit 9 Assignment

    OpenAIRE

    Laynebaril1

    2017-01-01

     AC410 Unit 9 Assignment Click Link Below To Buy: http://hwcampus.com/shop/ac410-unit-9-assignment/   18–29. The CPA firm of Carson & Boggs LLP is performing an internal control audit in accordance with PCAOB Standard No. 5. The partner in charge of the engagement has asked you to explain the process of determining which controls to test. Describe the process, presenting each of the links in this process and a short summary of how the auditors approach each of them. v ...

  7. Comparison Of Digital Radiographic Units

    Science.gov (United States)

    Wang, Yen

    1986-06-01

    A total PACS will be inevitable for radiology practice within several years. To achieve a total PACS for radiology, a satisfactory digital radiographic unit is required, because approximately 65% of digital data for PACS comes from digital radiographs. There are several possibilities for producing digital radiographs, and 3 - 4 companies have been marketing digital radiographic devices. Some data regarding the digital radiographic units on the market are compared. It will aid in assessing the current status and availability of this aspect of development, as well as providing a summary of further development of digital radiographic technology.

  8. On the Unit of Translation

    Institute of Scientific and Technical Information of China (English)

    张曼

    2013-01-01

      The unit of translation has been the focus of debate through the history of translation. Barkhudarov suggests six levels of UT, each level could serve as unit of different levels of translation. Many Chinese translators also expressed their opinions on this issue, but there is no settled answer yet. This paper tends to make a distinction between different texts:ordinary and special. Ordinary ones can adopt the UT of paragraph, while special ones should adopt special UTs according to their own characteristics.

  9. Photovoltaic mounting/demounting unit

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to a photovoltaic arrangement comprising a photovoltaic assembly comprising a support structure defining a mounting surface onto which a photovoltaic module is detachably mounted; and a mounting/demounting unit comprising at least one mounting/demounting apparatus...... which when the mounting/demounting unit is moved along the mounting surface, causes the photovoltaic module to be mounted or demounted to the support structure; wherein the photovoltaic module comprises a carrier foil and wherein a total thickness of the photo voltaic module is below 500 muiotaeta....... The present invention further relates to an associated method for mounting/demounting photovoltaic modules....

  10. "Mexico in Transition." Curriculum Units.

    Science.gov (United States)

    Oregon Univ., Eugene. Foreign Language Resource Center.

    These curriculum units were developed in a National Endowment for the Humanities 1994 summer seminar "Mexico in Transition." The 23 lessons are written in Spanish. Lessons are entitled: (1) "La Migracion Mexicana Vista a Traves del Cuento 'Paso del Norte' de Juan Rulfo" (Jose Jorge Armendariz); (2) "Los Grupos Indigenas de…

  11. Dimensionality and the sample unit

    Science.gov (United States)

    Francis A. Roesch

    2009-01-01

    The sample unit and its implications for the Forest Service, U.S. Department of Agriculture's Forest Inventory and Analysis program are discussed in light of a generalized three-dimensional concept of continuous forest inventories. The concept views the sampled population as a spatial-temporal cube and the sample as a finite partitioning of the cube. The sample...

  12. Semasiological measurements of phraseological units

    Directory of Open Access Journals (Sweden)

    Khavpacheva Oksana Khautievna

    2015-06-01

    Full Text Available The article deals with semantic relations in phraseology in modern English. In particular, the authors attempt to analyze different perspectives on the problem of correlation of concepts such as phraseological variance and synonyms existing in Russian linguistics. In addition, the article reviews and analyzes the nature and mechanism of phraseological variance. Particular attention is paid to the criteria of a particular phraseological unit to variants or synonyms. It substantiates the idea that the most suitable for the modern English language seems the point of view that considers the variance of phraseological unit as a fixed rate of transformation of the language of this unit does not violate its semantic identity. The main content of the study is an analysis of the main types of options phraseological units of modern English language: the structural and grammatical (morphological, syntactic, lexical, lexical and stylistic and of quantitative. The article also examines the characteristics of phraseological synonyms that unlike phraseological variants are built on different images, different logical-conceptual and shades of meaning, scope and use of stylistic coloring.

  13. Compiler validates units and dimensions

    Science.gov (United States)

    Levine, F. E.

    1980-01-01

    Software added to compiler for automated test system for Space Shuttle decreases computer run errors by providing offline validation of engineering units used system command programs. Validation procedures are general, though originally written for GOAL, a free-form language that accepts "English-like" statements, and may be adapted to other programming languages.

  14. Education in the United States

    Institute of Scientific and Technical Information of China (English)

    钱富奎

    2009-01-01

    As might be expected,educational institutions in the United States reflect the nation's basic values,especially the ideal of equality of opportunity.From elementary school through college,Americans believe that everyone deserves an equal opportunity to get a good education.

  15. Unit 23 - History of GIS

    OpenAIRE

    Unit 55, CC in GIS; National Center for Geographic Information and Analysis

    1990-01-01

    This unit provides a very brief review of some important milestones in the development of GIS. It provides early examples of spatial analysis performed with multiple theme maps, then introduces people, applications and systems that were significant in the early days of computerized cartography and spatial analysis.

  16. Professional Cosmetology Practices. Instructional Units.

    Science.gov (United States)

    Hopcus, Sharron; Armstrong, Ivan J.

    This publication is designed to assist the instructor and students in understanding the latest concepts and techniques of the instructional phase of cosmetology programs. The instructional units are in five areas: (1) orientation, (2) professional practices: hair, (3) professional practices: skin and nails, (4) cosmetology science, and (5)…

  17. Tractor Safety. Unit A-9.

    Science.gov (United States)

    Luft, Vernon D.; Backlund, Paul

    This document is a teacher's guide for a unit in tractor and machinery safety for college freshmen. It is intended to be used for 10 hours of instruction for freshmen who are intending to work on or around machinery. Safety hazards directly and indirectly related to many types of machinery are covered in addition to tractors. The objectives of the…

  18. Solar Renewable Energy. Teaching Unit.

    Science.gov (United States)

    Buchanan, Marion; And Others

    This unit develops the concept of solar energy as a renewable resource. It includes: (1) an introductory section (developing understandings of photosynthesis and impact of solar energy); (2) information on solar energy use (including applications and geographic limitations of solar energy use); and (3) future considerations of solar energy…

  19. Trip Report United Arab Emirates

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, K; Rodgers, A

    2004-10-06

    Keith Nakanishi and Arthur Rodgers traveled to the United Arab Emirates in February, 2004 to continue an on-going technical collaboration with UAE University and to service the two temporary LLNL seismic stations. Nakanishi and Rodgers then participated in the Gulf Seismic Forum, which was organized by LLNL and sponsored by the University of Sharjah.

  20. "Mexico in Transition." Curriculum Units.

    Science.gov (United States)

    Oregon Univ., Eugene. Foreign Language Resource Center.

    These curriculum units were developed in a National Endowment for the Humanities 1994 summer seminar "Mexico in Transition." The 23 lessons are written in Spanish. Lessons are entitled: (1) "La Migracion Mexicana Vista a Traves del Cuento 'Paso del Norte' de Juan Rulfo" (Jose Jorge Armendariz); (2) "Los Grupos Indigenas de Mexico: Condiciones…

  1. United States Navy DL Perspective

    Science.gov (United States)

    2010-08-10

    United States Navy DL Perspective CAPT Hank Reeves Navy eLearning Project Director 10 August 2010 Report Documentation Page Form ApprovedOMB No...Marine Corps (USMC) Navy eLearning Ongoing Shared with USMC, Coast Guard 9 NeL Help Site https://ile-help.nko.navy.mil/ile/ https://s-ile

  2. "Mexico in Transition." Curriculum Units.

    Science.gov (United States)

    Oregon Univ., Eugene. Foreign Language Resource Center.

    These curriculum units were developed in a National Endowment for the Humanities 1994 summer seminar "Mexico in Transition." The 23 lessons are written in Spanish. Lessons are entitled: (1) "La Migracion Mexicana Vista a Traves del Cuento 'Paso del Norte' de Juan Rulfo" (Jose Jorge Armendariz); (2) "Los Grupos Indigenas de…

  3. Norovirus in the United States

    Centers for Disease Control (CDC) Podcasts

    2013-09-09

    Dr. Aron Hall, a CDC epidemiologist specializing in norovirus, discusses the impact of norovirus in the United States.  Created: 9/9/2013 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 9/17/2013.

  4. Cholera in the United States

    Centers for Disease Control (CDC) Podcasts

    2011-11-08

    Anna Newton, Surveillance Epidemiologist at CDC, discusses cholera that was brought to the United States during an outbreak in Haiti and the Dominican Republic (Hispaniola).  Created: 11/8/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 11/8/2011.

  5. A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204.

    Directory of Open Access Journals (Sweden)

    Gavin J Churchyard

    Full Text Available BACKGROUND: The safety and immunogenicity of a vaccine regimen consisting of a 6-plasmid HIV-1 DNA prime (envA, envB, envC, gagB, polB, nefB boosted by a recombinant adenovirus serotype-5 (rAd5 HIV-1 with matching inserts was evaluated in HIV-seronegative participants from South Africa, United States, Latin America and the Caribbean. METHODS: 480 participants were evenly randomized to receive either: DNA (4 mg i.m. by Biojector at 0, 1 and 2 months, followed by rAd5 (10(10 PU i.m. by needle/syringe at 6 months; or placebo. Participants were monitored for reactogenicity and adverse events throughout the 12-month study. Peak and duration of HIV-specific humoral and cellular immune responses were evaluated after the prime and boost. RESULTS: The vaccine was well tolerated and safe. T-cell responses, detected by interferon-γ (IFN-γ ELISpot to global potential T-cell epitopes (PTEs were observed in 70.8% (136/192 of vaccine recipients overall, most frequently to Gag (54.7% and to Env (54.2%. In U.S. vaccine recipients T-cell responses were less frequent in Ad5 sero-positive versus sero-negative vaccine recipients (62.5% versus 85.7% respectively, p = 0.035. The frequency of HIV-specific CD4+ and CD8+ T-cell responses detected by intracellular cytokine staining were similar (41.8% and 47.2% respectively and most secreted ≥2 cytokines. The vaccine induced a high frequency (83.7%-94.6% of binding antibody responses to consensus Group M, and Clades A, B and C gp140 Env oligomers. Antibody responses to Gag were elicited in 46% of vaccine recipients. CONCLUSION: The vaccine regimen was well-tolerated and induced polyfunctional CD4+ and CD8+ T-cells and multi-clade anti-Env binding antibodies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00125970.

  6. 75 FR 25925 - United States Mint

    Science.gov (United States)

    2010-05-10

    ... United States Mint ACTION: Notification of Citizens Coinage Advisory Committee May 25, 2010 Public Meeting. SUMMARY: Pursuant to United States Code, Title 31, section 5135(b)(8)(C), the United States Mint...: May 25, 2010. Time: 9 a.m. to 12 p.m. Location: 8th Floor Board Room, United States Mint, 801...

  7. 31 CFR 560.307 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 560.307 Section 560.307 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 560.307 United States. The term United States means the United States, including its territories...

  8. 31 CFR 547.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 547.310 Section 547.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... General Definitions § 547.310 United States. The term United States means the United States,...

  9. 7 CFR 1250.308 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1250.308 Section 1250.308 Agriculture... Research and Promotion Order Definitions § 1250.308 United States. United States means the 48 contiguous States of the United States of America and the District of Columbia....

  10. 31 CFR 548.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 548.310 Section 548.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....310 United States. The term United States means the United States, its territories and...

  11. 31 CFR 586.318 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 586.318 Section 586...) KOSOVO SANCTIONS REGULATIONS General Definitions § 586.318 United States. The term United States means the United States, its territories and possessions, and all areas under the jurisdiction or...

  12. 7 CFR 1212.31 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1212.31 Section 1212.31 Agriculture..., Consumer Education, and Industry Information Order Definitions § 1212.31 United States. “United States... territories and possessions of the United States....

  13. 31 CFR 543.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 543.310 Section 543.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 543.310 United States. The term United States means the United States, its territories...

  14. 31 CFR 592.311 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 592.311 Section 592... § 592.311 United States. The term United States, when used in the geographic sense, means the several States, the District of Columbia, and any commonwealth, territory, or possession of the United States....

  15. 31 CFR 546.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 546.310 Section 546.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....310 United States. The term United States means the United States, its territories and...

  16. 31 CFR 538.314 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 538.314 Section 538.314 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 538.314 United States. The term United States means the United States, its territories and...

  17. 7 CFR 1205.23 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1205.23 Section 1205.23 Agriculture... Procedures for Conduct of Sign-up Period Definitions § 1205.23 United States. The term United States means the 50 states of the United States of America. Procedures...

  18. 31 CFR 594.313 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 594.313 Section 594.313 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 594.313 United States. The term United States means the United States, its territories...

  19. 31 CFR 588.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 588.310 Section 588.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 588.310 United States. The term United States means the United States, its territories...

  20. 7 CFR 1205.313 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1205.313 Section 1205.313 Agriculture... Research and Promotion Order Definitions § 1205.313 United States. United States means the 50 States of the United States of America....

  1. 31 CFR 593.311 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 593.311 Section 593.311 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... REGULATIONS General Definitions § 593.311 United States. The term United States means the United States,...

  2. 22 CFR 120.13 - United States.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false United States. 120.13 Section 120.13 Foreign... United States. United States, when used in the geographical sense, includes the several states, the Commonwealth of Puerto Rico, the insular possessions of the United States, the District of Columbia,...

  3. 31 CFR 537.318 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 537.318 Section 537.318 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....318 United States. The term United States means the United States, its territories and...

  4. 31 CFR 575.319 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 575.319 Section 575.319 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....319 United States. The term United States means the United States, its territories and...

  5. 31 CFR 595.314 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 595.314 Section 595.314 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 595.314 United States. The term United States means the United States, its territories and...

  6. 31 CFR 596.312 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 596.312 Section 596.312 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... General Definitions § 596.312 United States. The term United States means the United States, including...

  7. 31 CFR 587.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 587.310 Section 587...) MILOSEVIC SANCTIONS REGULATIONS General Definitions § 587.310 United States. The term United States means the United States, its territories and possessions, and all areas under the jurisdiction or...

  8. 31 CFR 542.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 542.310 Section 542.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....310 United States. The term United States means the United States, its territories and...

  9. 31 CFR 540.313 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 540.313 Section 540.313 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... REGULATIONS General Definitions § 540.313 United States. The term United States means the United States,...

  10. 7 CFR 1219.26 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1219.26 Section 1219.26 Agriculture..., AND INFORMATION Hass Avocado Promotion, Research, and Information Order Definitions § 1219.26 United States. United States means collectively the several 50 States of the United States, the District...

  11. 31 CFR 597.318 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 597.318 Section 597.318 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... General Definitions § 597.318 United States. The term United States means the United States,...

  12. 31 CFR 544.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 544.310 Section 544.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... REGULATIONS General Definitions § 544.310 United States. The term United States means the United States,...

  13. 31 CFR 545.313 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 545.313 Section 545.313 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 545.313 United States. The term United States means the United States, its territories...

  14. 31 CFR 585.316 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 585.316 Section 585.316 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... General Definitions § 585.316 United States. The term United States means the United States,...

  15. 7 CFR 65.255 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 3 2010-01-01 2010-01-01 false United States. 65.255 Section 65.255 Agriculture..., PEANUTS, AND GINSENG General Provisions Definitions § 65.255 United States. United States means the 50... United States....

  16. 31 CFR 536.315 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 536.315 Section 536.315 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 536.315 United States. The term United States means the United States, its territories...

  17. 7 CFR 1150.106 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 9 2010-01-01 2009-01-01 true United States. 1150.106 Section 1150.106 Agriculture... Order Definitions § 1150.106 United States. United States means the 48 contiguous States in the continental United States....

  18. 7 CFR 1206.23 - United States.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false United States. 1206.23 Section 1206.23 Agriculture... INFORMATION Mango Promotion, Research, and Information Order Definitions § 1206.23 United States. United... Rico, and the territories and possessions of the United States....

  19. 31 CFR 541.310 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 541.310 Section 541.310 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... § 541.310 United States. The term United States means the United States, its territories and...

  20. 31 CFR 598.317 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 598.317 Section 598.317 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... Definitions § 598.317 United States. The term United States means the United States, its territories...

  1. 31 CFR 551.309 - United States.

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false United States. 551.309 Section 551.309 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF....309 United States. The term United States means the United States, its territories and...

  2. Detailed Analysis of Motor Unit Activity

    DEFF Research Database (Denmark)

    Nikolic, Mile; Sørensen, John Aasted; Dahl, Kristian

    1997-01-01

    System for decomposition of EMG signals intotheir constituent motor unit potentials and their firing patterns.The aim of the system is detailed analysis ofmotor unit variability.......System for decomposition of EMG signals intotheir constituent motor unit potentials and their firing patterns.The aim of the system is detailed analysis ofmotor unit variability....

  3. Bi-Cell Unit for Fuel Cell.

    Science.gov (United States)

    The patent concerns a bi-cell unit for a fuel cell . The bi-cell unit is comprised of two electrode packs. Each of the electrode packs includes an...invention relates in general to a bi-cell unit for a fuel cell and in particular, to a bi-cell unit for a hydrazine-air fuel cell .

  4. 78 FR 64385 - United Nations Day, 2013

    Science.gov (United States)

    2013-10-28

    ... October 28, 2013 Part V The President Proclamation 9045--United Nations Day, 2013 #0; #0; #0; Presidential... Documents#0;#0; #0; #0;Title 3-- #0;The President ] Proclamation 9045 of October 23, 2013 United Nations Day..., 68 years after the adoption of the United Nations Charter, we mark United Nations Day by...

  5. Detailed Analysis of Motor Unit Activity

    DEFF Research Database (Denmark)

    Nikolic, Mile; Sørensen, John Aasted; Dahl, Kristian

    1997-01-01

    System for decomposition of EMG signals intotheir constituent motor unit potentials and their firing patterns.The aim of the system is detailed analysis ofmotor unit variability.......System for decomposition of EMG signals intotheir constituent motor unit potentials and their firing patterns.The aim of the system is detailed analysis ofmotor unit variability....

  6. Polyetheretherketone cage for treating type II and type IIa Hangman’s fractures:6-month follow-up%应用多聚醚酮椎间融合器修复Ⅱ型及Ⅱa型Hangman骨折:6个月随访评价

    Institute of Scientific and Technical Information of China (English)

    黄阳亮; 钟祎; 刘少喻

    2015-01-01

    背景:Hangman骨折即创伤性枢椎滑脱,不稳定Hangman骨折的Ⅱ型、Ⅱa型及ⅡI 型骨折需要手术治疗。咽后入路是上颈椎前路手术显露的常用手段。然而,重要结构周围的牵拉与分离使得手术程序复杂,增加了神经损伤的发生率。  目的:评价创新性应用多聚醚酮椎间融合器治疗Hangman骨折的临床疗效及安全性。  方法:收集Ⅱ型及Ⅱa型Hangman骨折患者8例,均进行C2/3椎间融合。术后随访进行X射线检查,评价融合时间及内植物位置。比较术前与术后6个月骨折处成角及移位数据和复位情况,以颈椎创伤后评分评价功能恢复,以目测类比评分评价颈部疼痛。  结果与结论:所有8例患者均得以成功随访,平均随访13个月(6-26个月)。与术前相比,术后6个月患者颈椎创伤后评分增高,目测类比评分及成角畸形和移位均降低(P OBJECTIVE:To evaluate the clinical curative effect and safety of an innovative operative technique in which a polyetheretherketone cage was used to perform cervical spinal fusion for the treatment of Hangman’s fracture. METHODS: Eight patients with type II or IIa Hangman’s fracture were enroled in this study and received cervical fusions at C2/3 levels. During folow-up postoperatively, they received X-ray examination. Fusion time and implant position were evaluated. The angle of deformity (α) and the displacement distance (β) were compared pre-operatively and 6-month post-operatively to measure reduction. The functional outcomes were also compared using the Post-Traumatic Neck Score (Mayo) pre-operatively and 6-month post-operatively, while neck pain was further investigated by Visual Analogue Scale score. RESULTS AND CONCLUSION:Al eight patients were folowed-up successfuly, with an average folow-up of 13 months (range 6-26 months). Compared with pre-operatively, Clinical Post-Traumatic Neck Score (Mayo) was increased

  7. ISS EPS Orbital Replacement Unit Block Diagrams

    Science.gov (United States)

    Schmitz, Gregory V.

    2001-01-01

    The attached documents are being provided to Switching Power Magazine for information purposes. This magazine is writing a feature article on the International Space Station Electrical Power System, focusing on the switching power processors. These units include the DC-DC Converter Unit (DDCU), the Bi-directional Charge/Discharge Unit (BCDU), and the Sequential Shunt Unit (SSU). These diagrams are high-level schematics/block diagrams depicting the overall functionality of each unit.

  8. Masturbation in the United States.

    Science.gov (United States)

    Das, Aniruddha

    2007-01-01

    Using data from the nationally representative National Health and Social Life Survey, this study queried the correlates of masturbation in the United States in 1992. Among those aged 18-60, 38% (CI, 35-41) of women and 61% (CI, 57-65) of men reported any masturbation over the preceding year. The system of factors underlying masturbation was similar for both genders, consistent with a convergence in gender patterns of sexual expression in the United States. Among both women and men, masturbation responded to a stable sexualized personality pattern, catalyzed by early-life factors and manifested in current sexual traits. Strikingly, the masturbation-partnered sex linkage, often conceptualized either as compensating for unsatisfying sex or complementing a satisfactory sex life, appeared to be bimodal for both genders. For some, masturbation complemented an active and pleasurable sex life, while among others, it compensated for a lack of partnered sex or satisfaction in sex.

  9. Portable Presentation And Instruction Unit

    Science.gov (United States)

    Christman, L.; Hoang, N.

    1994-01-01

    Proposed electronic display unit reminiscent of kiosk serves as portable, interactive, multimedia information terminal. Used as traveling science exhibit, aid for teaching science in schools, or training and skill-refresher device for space flight crews. Provides interactive video and audio displays, including three-dimensional-appearing video simulations. Speeds learning and improves retention by applying principles of scientific visualization. Also helps previously trained but recently unpracticed personnel relearn special skills and procedures quickly.

  10. Drought in Southwestern United States

    Science.gov (United States)

    2007-01-01

    The southwestern United States pined for water in late March and early April 2007. This image is based on data collected by the Moderate Resolution Imaging Spectroradiometer (MODIS) on NASA's Terra satellite from March 22 through April 6, 2007, and it shows the Normalized Difference Vegetation Index, or NDVI, for the period. In this NDVI color scale, green indicates areas of healthier-than-usual vegetation, and only small patches of green appear in this image, near the California-Nevada border and in Utah. Larger areas of below-normal vegetation are more common, especially throughout California. Pale yellow indicates areas with generally average vegetation. Gray areas appear where no data were available, likely due to persistent clouds or snow cover. According to the April 10, 2007, update from the U.S. Drought Monitor, most of the southwestern United Sates, including Utah, Nevada, California, and Arizona, experienced moderate to extreme drought. The hardest hit areas were southeastern California and southwestern Arizona. Writing for the Drought Monitor, David Miskus of the Joint Agricultural Weather Facility reported that March 2007 had been unusually dry for the southwestern United States. While California's and Utah's reservoir storage was only slightly below normal, reservoir storage was well below normal for New Mexico and Arizona. In early April, an international research team published an online paper in Science noting that droughts could become more common for the southwestern United States and northern Mexico, as these areas were already showing signs of drying. Relying on the same computer models used in the Intergovernmental Panel on Climate Change (IPCC) report released in early 2007, the researchers who published in Science concluded that global warming could make droughts more common, not just in the American Southwest, but also in semiarid regions of southern Europe, Mediterranean northern Africa, and the Middle East.

  11. 77 FR 48542 - United States

    Science.gov (United States)

    2012-08-14

    ... outside of the `reaches of the public interest'''); see generally United States v. SBC Commc'ns, Inc., 489... judicial power.'' SBC ] Commc'ns, 489 F. Supp. 2d at 14-15 (citing Microsoft, 56 F.3d at 1462). With... effect of proposed remedies. See, e.g., KeySpan, 763 F. Supp. 2d at 642; SBC Commc'ns, 489 F. Supp. 2d...

  12. President of the United States

    Institute of Scientific and Technical Information of China (English)

    蔡东丽

    2005-01-01

    President of the United States is the chief executive officer of the federal government, the leader of the executive branch1, and the corn man der-in-chief of the armed forces2. The president has the power to make treaties with other nations, with the advice and consent of two-thirds of the Senate3. The president also appoints4, with Senate's consent, diplomatic representatives ,Supreme Court judges5, and many other officials.

  13. Environmental performance reviews: United States

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-01-15

    This book presents OECD assessments and recommendations regarding the United States' effort to manage its environment including air, water nature, and biodiversity to do this in a sustainable manner; and to do this in co-operation with its global neighbours. In particular, it assesses progress made since 1996, when OECD's previous review on the US was done. 40 figs., 21 tabs.

  14. Unit Performance Assessment System Development

    Science.gov (United States)

    1994-08-01

    Overview of the enhanced UPAS ...... . 57 xiv UNIT PERFORMANCE ASSESSMENT SYSTEM DEVELOPMENT Introduccion The networking of combat vehicle simulators...converting SIMNET terrain data from the UNIX format to a DOS format as part of their work on the development of Intelligent Semi-Automated Forces. The...and Social Sciences. (AD A226 956). LB&M Associates (1992). Phase I Small Business Innovative Research (SBIR) Program for Simulation Networkinc Training

  15. Agricultural Water Pricing: United States

    OpenAIRE

    2010-01-01

    In summary, irrigation costs and prices are rising in most regions of the United States, due to a combination of increasing scarcity, changes in public preferences regarding water allocation among competing uses, increasing budget scrutiny in the national and state legislatures, rising energy prices, and increasing awareness of climate change and the potential implications for rainfall and the availability of surface water resources. These issues likely will continue encouraging public offici...

  16. Strategic renewal for business units.

    Science.gov (United States)

    Whitney, J O

    1996-01-01

    Over the past decade, business units have increasingly taken the role of strategy formulation away from corporate headquarters. The change makes sense: business units are closer to customers, competitors, and costs. Nevertheless, business units can fail, just as headquarters once did, by losing their focus on the organization's priorities and capabilities. John Whitney--turnaround expert and professor of management at Columbia University--offers a method for refocusing companies that he calls the strategic-renewal process. The principles behind the process are straightforward, but its execution demands extensive data, rigorous analysis, and the judgment of key decision makers. However, when applied with diligence, it can produce a strategy that yields both growth and profit. To carry out the process, managers must analyze, one by one or in logical groupings, the company's customers, the products it sells, and the services it offers in light of three criteria: strategic importance, significance, and profitability. Does a given customer, product, or service mesh with the organization's goals? Is it significant in terms of current and future revenues? And is it truly profitable when all costs are care fully considered? Customers, products, and services that do not measure up, says the author, must be weeded out relentlessly. Although the process is a painstaking one, the article offers clear thinking on why-and how-to go about it. A series of exhibits takes managers through the questions they need to raise, and two matrices offer Whitney's concentrated wisdom on when to cultivate--and when to prune.

  17. Low cost balancing unit design

    Science.gov (United States)

    Golembiovsky, Matej; Dedek, Jan; Slanina, Zdenek

    2017-06-01

    This article deals with the design of a low-cost balancing system which consist of battery balancing units, accumulator pack units and coordinator unit with interface for higher level of battery management system. This solution allows decentralized mode of operation and the aim of this work is implementation of controlling and diagnostic mechanism into an electric scooter project realized at Technical university of Ostrava. In todays world which now fully enjoys the prime of electromobility, off-grid battery systems and other, it is important to seek the optimal balance between functionality and the economy side of BMS that being electronics which deals with secondary cells of batery packs. There were numerous sophisticated, but not too practical BMS models in the past, such as centralized system or standalone balance modules of individual cells. This article aims at development of standalone balance modules which are able to communicate with the coordinator, adjust their parameters and ensure their cells safety in case of a communication failure. With the current worldwide cutting cost trend in mind, the emphasis was put on the lowest price possible for individual component. The article is divided into two major categories, the first one being desing of power electronics with emphasis on quality, safety (cooling) and also cost. The second part describes development of a communication interface with reliability and cost in mind. The article contains numerous graphs from practical measurements. The outcome of the work and its possible future is defined in the conclusion.

  18. Graphemes are perceptual reading units.

    Science.gov (United States)

    Rey, A; Ziegler, J C; Jacobs, A M

    2000-04-14

    Graphemes are commonly defined as the written representation of phonemes. For example, the word 'BREAD' is composed of the four phonemes /b/, /r/, /e/ and /d/, and consequently, of the four graphemes 'B', 'R', 'EA', and 'D'. Graphemes can thus be considered the minimal 'functional bridges' in the mapping between orthography and phonology. In the present study, we investigated the hypothesis that graphemes are processed as perceptual units by the reading system. If the reading system processes graphemes as units, then detecting a letter in a word should be harder when this letter is embedded in a multi-letter grapheme than when it corresponds to a single-letter grapheme. In Experiment 1A, done in English, participants were slower to detect a target letter in a word when the target letter was embedded in multi-letter grapheme (i.e. 'A' in 'BEACH') than when it corresponded to a single-letter grapheme (i.e. 'A' in 'PLACE'). In Experiment 1B, this effect was replicated in French. In Experiment 2, done in English, this grapheme effect remained when phonemic similarity between the target letter alone and the target letter inside the word was controlled. Together, the results are consistent with the assumption that graphemes are processed as perceptual reading units in alphabetic writing systems such as English or French.

  19. Dixie Valley Bottoming Binary Unit

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, Dale [Terra-Gen Sierra Holdings, LLC, Reno, NV (United States)

    2014-12-21

    This binary plant is the first air cooled, high-output refrigeration based waste heat recovery cycle in the industry. Its working fluid is environmentally friendly and as such, the permits that would be required with a hydrocarbon based cycle are not necessary. The unit is largely modularized, meaning that the unit’s individual skids were assembled in another location and were shipped via truck to the plant site. The Air Cooled Condensers (ACC), equipment piping, and Balance of Plant (BOP) piping were constructed at site. This project further demonstrates the technical feasibility of using low temperature brine for geothermal power utilization. The development of the unit led to the realization of low temperature, high output, and environmentally friendly heat recovery systems through domestic research and engineering. The project generates additional renewable energy, resulting in cleaner air and reduced carbon dioxide emissions. Royalty and tax payments to governmental agencies will increase, resulting in reduced financial pressure on local entities. The major components of the unit were sourced from American companies, resulting in increased economic activity throughout the country.

  20. The First Drinking Simulator Unit

    Directory of Open Access Journals (Sweden)

    Saied Mostafa Moazzami

    2014-03-01

    Full Text Available Introduction: Current Thermal cycling units fail to simulate the drinking behaviors, and oral balancing temperature. They cannot also simulate other oral conditions such as drink coloring, and chemicals like tea, coffee, carbonated and noncarbonated, citrus juices as well as alcoholic and nonalcoholic drinks and also saliva and milk itself. The main objective of this study is to introduce the designing and manufacturing the first Drinking Simulator Unit (DSU that reproduces the thermal, color and chemicalcycling as well as the drinking behavior and oral temperature in lab conditions uniquely. Methods: The invented system generally has two parts: the hardware and the software parts. The hardware consists of the mechanical and electronic parts. The software part is responsible for controlling the heating and cooling systems, electric valves, the pumps, and automatic filling systems of tanks as well as the sensors of the machine. Results: DSU is the first unit can reproduce the thermal, color and chemical cycling as well as the drinking behavior and oral temperature in lab conditions. Different kinds of colored and acidic drinks and also other chemical materials such as bleaching substances as well as detergents and antiseptics used for dentistry, industrial and medical purposes can be tested by DSU. DSU has also to be considered as an appliance performing in-vitro researches on dental structures. Conclusion: The invented system can greatly improve and validate the results of such researches.