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Sample records for 4-5 times greater

  1. 18 CFR 4.5 - Time for filing protest.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Time for filing protest... protest. Thirty days after service thereof will be allowed to such licensee within which to file a protest to such reports. If no protest is filed within the time allowed, the Commission will issue such...

  2. Deuterium-tritium neutron yield measurements with the 4.5 m neutron-time-of-flight detectors at NIF

    SciTech Connect

    Moran, M. J.; Bond, E. J.; Clancy, T. J.; Eckart, M. J.; Khater, H. Y.; Glebov, V. Yu.

    2012-10-15

    The first several campaigns of laser fusion experiments at the National Ignition Facility (NIF) included a family of high-sensitivity scintillator/photodetector neutron-time-of-flight (nTOF) detectors for measuring deuterium-deuterium (DD) and DT neutron yields. The detectors provided consistent neutron yield (Y{sub n}) measurements from below 10{sup 9} (DD) to nearly 10{sup 15} (DT). The detectors initially demonstrated detector-to-detector Y{sub n} precisions better than 5%, but lacked in situ absolute calibrations. Recent experiments at NIF now have provided in situ DT yield calibration data that establish the absolute sensitivity of the 4.5 m differential tissue harmonic imaging (DTHI) detector with an accuracy of {+-}10% and precision of {+-}1%. The 4.5 m nTOF calibration measurements also have helped to establish improved detector impulse response functions and data analysis methods, which have contributed to improving the accuracy of the Y{sub n} measurements. These advances have also helped to extend the usefulness of nTOF measurements of ion temperature and downscattered neutron ratio (neutron yield 10-12 MeV divided by yield 13-15 MeV) with other nTOF detectors.

  3. Storm-time fingerprints of Pc 4-5 waves on energetic electron flux at geosynchronous orbit

    NASA Astrophysics Data System (ADS)

    Georgiou, Marina; Daglis, Ioannis A.; Zesta, Eftyhia; Balasis, George; Mann, Ian R.; Tsinganos, Kanaris

    2014-05-01

    Geospace magnetic storms, associated with either coronal mass ejections (CMEs) or high speed solar streams, involve global variations of the geomagnetic field as well as acceleration of charged particles in the magnetosphere. Ultra low frequency (ULF) waves with frequencies in the range of a few mHz (Pc 4-5 waves) can be generated externally by compressive variations in the solar wind or shear flow along the magnetopause unstable to the Kelvin-Helmholtz effect. Furthermore, low frequency instabilities of ring current ions are also considered as a possible internal driver of ULF wave growth. We examine power enhancements of ULF waves during four successive magnetic storms, which occurred in July 2004 and were characterized by a decreasing minimum of the Dst index, from -76 nT down to -197 nT. During the course of the magnetic storms, ULF wave power variations have been observed nearly simultaneously at different magnetic latitudes and longitudes by the ground-based CARISMA, IMAGE, 210 MM and SAMBA magnetometer networks. Nonetheless, stronger magnetic storms were accompanied by greater ULF wave power enhancements tending to be more pronounced at magnetic stations located at lower L shells. Furthermore, the generation and penetration of ULF wave power deep into the inner magnetosphere seems to be contributing to the energization and transport of relativistic electrons. Except for the magnetic storm on 25 July 2000, the three magnetic storms on 17, 23 and 27 July 2004 were characterized by a significant increase in the flux of electrons with energies higher than 1 MeV, as measured by GOES-10 and -12 during the recovery phase of each storm. On the other hand, when looking at the magnetic storm on 17 August 2001, the initial decrease was followed by an increase six days after the commencement of the storm. The electron flux decrease was more than two orders of magnitude and remained low after the recovery of the Dst index. These observations provided us the basis for

  4. Development and Validation of Quantitative Real-time Polymerase Chain Reaction Assays to Detect Elephant Endotheliotropic Herpesviruses-2, 3, 4, 5, and 6

    PubMed Central

    Stanton, Jeffrey J.; Nofs, Sally; Peng, Rongsheng; Hayward, Gary S.; Ling, Paul D.

    2012-01-01

    Elephant endotheliotropic herpesviruses (EEHV) can cause lethal hemorrhagic disease in both African and Asian elephants. At least seven EEHV types have been described, and sensitive real-time PCR tests have been developed for EEHV1A and 1B, which are associated with the majority of characterized Asian elephant deaths. Despite growing knowledge of the different EEHV types, the prevalence of each type within African and Asian elephants remains to be determined and there is considerable need for diagnostic tests to detect and discriminate between each EEHV species for clinical management of African and Asian elephants that develop illness from one or more of these viruses. To begin to address these issues, we developed real-time PCR assays for EEHV2, 3, 4, 5, and 6. Overall, each assay had robust PCR efficiency, a dynamic linear range over 5 log10 concentrations, a limit of detection of 10 copies/test reaction with 100% sensitivity, and low intra- and inter-assay variability. Each assay proved to be specific for the EEHV targets for which it was designed, with the exception of EEHV3 and EEHV4, which was expected because of greater DNA sequence similarity between these two EEHV species than the others. These new tools will be useful for conducting surveys of EEHV prevalence within captive and range country elephants, for diagnostic testing of elephants with suspected EEHV-associated disease, and for managing the treatment of elephants with EEHV-induced illness. PMID:22842286

  5. The association between greater continuity of care and timely measles-mumps-rubella vaccination.

    PubMed Central

    Christakis, D A; Mell, L; Wright, J A; Davis, R; Connell, F A

    2000-01-01

    OBJECTIVES: This study assessed whether greater continuity of care is associated with timely administration of measles-mumps-rubella (MMR) vaccination. METHODS: We studied 11,233 patients continuously enrolled in Group Health Cooperative (GHC) from birth to 15 months. We used a preestablished index to quantify continuity of care based on the number of primary care providers in relation to the number of clinic visits. MMR vaccination status at 15 months was assessed with automated immunization data systems at GHC. RESULTS: In a logistic regression model, both medium continuity (odds ratio [OR] = 1.20, 95% confidence interval [CI] = 1.08, 1.33) and high continuity (OR = 1.36, 95% CI = 1.22, 1.52) were associated with increased likelihood of being immunized by 15 months compared with patients in the lowest tercile of continuity of care. CONCLUSION: Greater continuity of care is associated with more timely immunization. PMID:10846516

  6. 4.5 Years of Multi-wavelength Observations of MRK 421 During the ARGO-YBJ and FERMI Common Operation Time

    NASA Astrophysics Data System (ADS)

    Bartoli, B.; Bernardini, P.; Bi, X. J.; Cao, Z.; Catalanotti, S.; Chen, S. Z.; Chen, T. L.; Cui, S. W.; Dai, B. Z.; D'Amone, A.; Danzengluobu; De Mitri, I.; D'Ettorre Piazzoli, B.; Di Girolamo, T.; Di Sciascio, G.; Feng, C. F.; Feng, Zhaoyang; Feng, Zhenyong; Gou, Q. B.; Guo, Y. Q.; He, H. H.; Hu, Haibing; Hu, Hongbo; Iacovacci, M.; Iuppa, R.; Jia, H. Y.; Labaciren; Li, H. J.; Liu, C.; Liu, J.; Liu, M. Y.; Lu, H.; Ma, L. L.; Ma, X. H.; Mancarella, G.; Mari, S. M.; Marsella, G.; Mastroianni, S.; Montini, P.; Ning, C. C.; Perrone, L.; Pistilli, P.; Salvini, P.; Santonico, R.; Shen, P. R.; Sheng, X. D.; Shi, F.; Surdo, A.; Tan, Y. H.; Vallania, P.; Vernetto, S.; Vigorito, C.; Wang, H.; Wu, C. Y.; Wu, H. R.; Xue, L.; Yang, Q. Y.; Yang, X. C.; Yao, Z. G.; Yuan, A. F.; Zha, M.; Zhang, H. M.; Zhang, L.; Zhang, X. Y.; Zhang, Y.; Zhao, J.; Zhaxiciren; Zhaxisangzhu; Zhou, X. X.; Zhu, F. R.; Zhu, Q. Q.; ARGO-YBJ Collaboration

    2016-01-01

    We report on the extensive multi-wavelength observations of the blazar Markarian 421 (Mrk 421) covering radio to γ-rays, during the 4.5 year period of ARGO-YBJ and Fermi common operation time, from 2008 August to 2013 February. These long-term observations, extending over an energy range of 18 orders of magnitude, provide a unique chance to study the variable emission of Mrk 421. In particular, due to the ARGO-YBJ and Fermi data, the entire energy range from 100 MeV to 10 TeV is covered without any gap. In the observation period, Mrk 421 showed both low- and high-activity states at all wavebands. The correlations among flux variations in different wavebands were analyzed. The X-ray flux is clearly correlated with the TeV γ-ray flux, while the GeV γ-rays only show a partial correlation with the TeV γ-rays. Radio and UV fluxes seem to be weakly or not correlated with the X-ray and γ-ray fluxes. Seven large flares, including five X-ray flares and two GeV γ-ray flares with variable durations (3-58 days), and one X-ray outburst phase were identified and used to investigate the variation of the spectral energy distribution with respect to a relative quiescent phase. During the outburst phase and the seven flaring episodes, the peak energy in X-rays is observed to increase from sub-keV to a few keV. The TeV γ-ray flux increases up to 0.9-7.2 times the flux of the Crab Nebula. The behavior of GeV γ-rays is found to vary depending on the flare, a feature that leads us to classify flares into three groups according to the GeV flux variation. Finally, the one-zone synchrotron self-Compton model was adopted to describe the emission spectra. Two out of three groups can be satisfactorily described using injected electrons with a power-law spectral index around 2.2, as expected from relativistic diffuse shock acceleration, whereas the remaining group requires a harder injected spectrum. The underlying physical mechanisms responsible for different groups may be related to

  7. Trend analysis of long-term temperature time series in the Greater Toronto Area (GTA)

    NASA Astrophysics Data System (ADS)

    Mohsin, Tanzina; Gough, William A.

    2010-08-01

    As the majority of the world’s population is living in urban environments, there is growing interest in studying local urban climates. In this paper, for the first time, the long-term trends (31-162 years) of temperature change have been analyzed for the Greater Toronto Area (GTA). Annual and seasonal time series for a number of urban, suburban, and rural weather stations are considered. Non-parametric statistical techniques such as Mann-Kendall test and Theil-Sen slope estimation are used primarily for the assessing of the significance and detection of trends, and the sequential Mann test is used to detect any abrupt climate change. Statistically significant trends for annual mean and minimum temperatures are detected for almost all stations in the GTA. Winter is found to be the most coherent season contributing substantially to the increase in annual minimum temperature. The analyses of the abrupt changes in temperature suggest that the beginning of the increasing trend in Toronto started after the 1920s and then continued to increase to the 1960s. For all stations, there is a significant increase of annual and seasonal (particularly winter) temperatures after the 1980s. In terms of the linkage between urbanization and spatiotemporal thermal patterns, significant linear trends in annual mean and minimum temperature are detected for the period of 1878-1978 for the urban station, Toronto, while for the rural counterparts, the trends are not significant. Also, for all stations in the GTA that are situated in all directions except south of Toronto, substantial temperature change is detected for the periods of 1970-2000 and 1989-2000. It is concluded that the urbanization in the GTA has significantly contributed to the increase of the annual mean temperatures during the past three decades. In addition to urbanization, the influence of local climate, topography, and larger scale warming are incorporated in the analysis of the trends.

  8. Decreased reaction time variability is associated with greater cardiovascular responses to acute stress.

    PubMed

    Wawrzyniak, Andrew J; Hamer, Mark; Steptoe, Andrew; Endrighi, Romano

    2016-05-01

    Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75-min recovery. RT measures were generated from an ex-Gaussian distribution that yielded three predictors: mu-RT, sigma-RT, and tau-RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = -.009, SE = .005, p = .09) and diastolic (B = -.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = -.007, SE = .003, p = .03) and impaired vagal tone (B = -.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. PMID:26894967

  9. Decreased reaction time variability is associated with greater cardiovascular responses to acute stress

    PubMed Central

    Hamer, Mark; Steptoe, Andrew; Endrighi, Romano

    2016-01-01

    Abstract Cardiovascular (CV) responses to mental stress are prospectively associated with poor CV outcomes. The association between CV responses to mental stress and reaction times (RTs) in aging individuals may be important but warrants further investigation. The present study assessed RTs to examine associations with CV responses to mental stress in healthy, older individuals using robust regression techniques. Participants were 262 men and women (mean age = 63.3 ± 5.5 years) from the Whitehall II cohort who completed a RT task (Stroop) and underwent acute mental stress (mirror tracing) to elicit CV responses. Blood pressure, heart rate, and heart rate variability were measured at baseline, during acute stress, and through a 75‐min recovery. RT measures were generated from an ex‐Gaussian distribution that yielded three predictors: mu‐RT, sigma‐RT, and tau‐RT, the mean, standard deviation, and mean of the exponential component of the normal distribution, respectively. Decreased intraindividual RT variability was marginally associated with greater systolic (B = −.009, SE = .005, p = .09) and diastolic (B = −.004, SE = .002, p = .08) blood pressure reactivity. Decreased intraindividual RT variability was associated with impaired systolic blood pressure recovery (B = −.007, SE = .003, p = .03) and impaired vagal tone (B = −.0047, SE = .0024, p = .045). Study findings offer tentative support for an association between RTs and CV responses. Despite small effect sizes and associations not consistent across predictors, these data may point to a link between intrinsic neuronal plasticity and CV responses. PMID:26894967

  10. Do ewes born with a male co-twin have greater longevity with lambing over time?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on a recent analysis of historical records, ewes born co-twin to a ram had greater lifetime reproductive performance than ewes born co-twin to a ewe. We are interested in determining what component(s) of lifetime reproductive performance may be associated with a ewe’s co-twin sex. As an initi...

  11. Increasing Time and Enriching Learning for Greater Equity in Schools: Perspective from Two Community Funders

    ERIC Educational Resources Information Center

    Lopez, Janet; Rivera, Peter

    2015-01-01

    Foundations across the country engage in grantmaking to eliminate the opportunity and achievement gaps in K-12 public schools. Many of the strategies and investments that funders have supported in recent years focus not only on "more time" but also on "better use of time" in schools. This better use of time centers on outcomes…

  12. Web-Based Time Entry Systems: Providing Greater Automation and Compliance

    ERIC Educational Resources Information Center

    Williams, Tracy

    2005-01-01

    Time and resources are becoming increasingly scarce in most higher education institutions today. As a result, colleges and universities are looking to streamline and simplify many costly, labor-intensive administrative processes. In this article, Tracy Williams examines how Web-based time-entry systems can help institutions save valuable time and…

  13. Zodiacal Exoplanets in Time (ZEIT). I. A Neptune-sized Planet Orbiting an M4.5 Dwarf in the Hyades Star Cluster

    NASA Astrophysics Data System (ADS)

    Mann, Andrew W.; Gaidos, Eric; Mace, Gregory N.; Johnson, Marshall C.; Bowler, Brendan P.; LaCourse, Daryll; Jacobs, Thomas L.; Vanderburg, Andrew; Kraus, Adam L.; Kaplan, Kyle F.; Jaffe, Daniel T.

    2016-02-01

    Studying the properties of young planetary systems can shed light on how the dynamics and structure of planets evolve during their most formative years. Recent K2 observations of nearby young clusters (10-800 Myr) have facilitated the discovery of such planetary systems. Here we report the discovery of a Neptune-sized planet transiting an M4.5 dwarf (K2-25) in the Hyades cluster (650-800 Myr). The light curve shows a strong periodic signal at 1.88 days, which we attribute to spot coverage and rotation. We confirm that the planet host is a member of the Hyades by measuring the radial velocity of the system with the high-resolution near-infrared spectrograph Immersion Grating Infrared Spectrometer. This enables us to calculate a distance based on K2-25's kinematics and membership to the Hyades, which in turn provides a stellar radius and mass to ≃5%-10%, better than what is currently possible for most Kepler M dwarfs (12%-20%). We use the derived stellar density as a prior on fitting the K2 transit photometry, which provides weak constraints on eccentricity. Utilizing a combination of adaptive optics imaging and high-resolution spectra, we rule out the possibility that the signal is due to a bound or background eclipsing binary, confirming the transits’ planetary origin. K2-25b has a radius ({3.43}-0.31+0.95 R⊕) much larger than older Kepler planets with similar orbital periods (3.485 days) and host-star masses (0.29 M⊙). This suggests that close-in planets lose some of their atmospheres past the first few hundred million years. Additional transiting planets around the Hyades, Pleiades, and Praesepe clusters from K2 will help confirm whether this planet is atypical or representative of other close-in planets of similar age.

  14. Time Use Differences in Activity Participation among Children 4-5 Years Old with and without the Risk of Developing Conduct Problems

    ERIC Educational Resources Information Center

    Yu, Mong-Lin; Ziviani, Jenny; Baxter, Janeen; Haynes, Michele

    2012-01-01

    Conduct problems in childhood are associated with the way in which children engage in daily activities. Research, to date, on conduct problems in relation to time use has primarily focused on school aged children and their participation in discrete activities such as watching TV and sport. The purpose of the present study is to determine if…

  15. A time-series analysis of mortality and air temperature in Greater Beirut.

    PubMed

    El-Zein, Abbas; Tewtel-Salem, Mylene; Nehme, Gebran

    2004-09-01

    The literature on the association between health and weather in the temperate to semi-arid cities of the Eastern Mediterranean is scarce. The quantification of the relationship between temperature and daily mortality can be useful for developing policy interventions such as heat-warning systems. A time-series analysis of total daily mortality and weather data for the city of Beirut was carried out. The study covered the period between 1997 and 1999. Poisson auto-regressive models were constructed, with mean daily temperature and mean daily humidity as explanatory variables. Delayed effects, up to 2 weeks, were accounted for. The regression models were used next to assess the effect of an average increase in temperature on yearly mortality. The association between temperature and mortality was found to be significant. A relatively high minimum-mortality temperature (TMM) of 27.5 degrees C was calculated. A 1 degrees C rise in temperature yielded a 12.3% increase (95% confidence interval: 5.7-19.4%) and 2.9% decrease (95% confidence interval: 2-3.7%) in mortality, above and below TMM, respectively. Lag temperature variables were found to be significant below TMM but not above it. Where the temperature change was less than 0.5 degrees C, annual above-TMM losses were offset by below-TMM gains, within a 95% confidence interval. TMM for Beirut fell within the range usually associated with warm climates. However, the mild below-TMM and steep above-TMM slopes were more typical of cities with temperate to cold climates. Our findings suggest that heat-related mortality at moderately high temperatures can be a significant public health issue in countries with warm climates. Moreover, at the projected climate change over the next 50 years, heat-related losses are unlikely to be offset by cold-related gains. PMID:15325159

  16. 2,4,5-Trichlorophenol

    Integrated Risk Information System (IRIS)

    2,4,5 - Trichlorophenol ; CASRN 95 - 95 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcino

  17. Greater India

    NASA Astrophysics Data System (ADS)

    Ali, Jason R.; Aitchison, Jonathan C.

    2005-10-01

    "Greater India" is an 80-yr-old concept that has been used by geoscientists in plate tectonic models of the India-Asia collision system. Numerous authors working on the orogen and/or plate models of the broader region have added various sized chunks of continental lithosphere to the now northern edge of their reconstructed Indian plate. Prior to plate tectonic theory, Emile Argand (1924) [Argand, E., 1924. La tectonique de l' Asie. Proc. 13th Int. Geol. Cong. 7 (1924), 171-372.] and Arthur Holmes (1965) [Holmes, A., 1965. Principles of Physical Geology, Second Edition. The Ronald Press Company, New York, 1128.] thought that the Himalayan Mountains and Tibetan Plateau had been raised due to the northern edge of the Indian craton under-thrusting the entire region. Since the advent of plate tectonic theory, Greater India proposals have been based principally on three lines of logic. One group of workers has added various amounts of continental lithosphere to India as part of their Mesozoic Gondwana models. A second form of reconstruction is based on Himalayan crustal-shortening estimates. A third body of researchers has used India continent extensions as means of allowing initial contact between the block and the Eurasian backstop plate in southern Tibet to take place at various times between the Late Cretaceous and late Eocene in what we call "fill-the-gap" solutions. The Indian craton and the southern edge of Eurasia were almost invariably some distance from one another when the collision was supposed to have started; extensions to the sub-continent were used to circumvent the problem. Occasionally, Greater India extensions have been based on a combination of fill-the-gap and shortening estimate arguments. In this paper, we exhume and re-examine the key Greater India proposals. From our analysis, it is clear that many proponents have ignored key information regarding the sub-continent's pre break-up position within Gondwana and the bathymetry of the Indian Ocean

  18. Oman-India pipeline sets survey challenges. Crossing involves most rugged terrain, water depths four times greater than previous attempts

    SciTech Connect

    Flynn, J.

    1995-02-01

    Decisions concerning the route for the world`s deepest pipeline call for some of the most challenging commercial oceanographic and engineering surveys ever undertaken. Oman Oil Co.`s 1, 170-kilometer pipeline will carry 2 billion cubic feet of gas daily across the Arabian Sea from Oman to the northern coast of India at the Gulf of Kutch. Not only will the project be in water depths four times greater than any previous pipeline, but it will cross some of the world`s most rugged seabed terrain, traversing ridges and plunging into deep canyons. Project costs are likely to approach $5 billion.

  19. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  20. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 19 Customs Duties 1 2013-04-01 2013-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  1. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  2. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  3. 19 CFR 4.5 - Government vessels.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Government vessels. 4.5 Section 4.5 Customs Duties... VESSELS IN FOREIGN AND DOMESTIC TRADES Arrival and Entry of Vessels § 4.5 Government vessels. (a) No... that is the property of, the U.S. Department of Defense (DoD) will be treated as a Government...

  4. Greater-than-Class C low-level radioactive waste characterization. Appendix A-2: Timing of greater-than-Class C low-level radioactive waste from nuclear power plants

    SciTech Connect

    Steinke, W.F.

    1994-09-01

    Planning for the storage or disposal of greater-than-Class C low-level radioactive waste (GTCC LLW) requires characterization of that waste. Timing, or the date the waste will require storage or disposal, is an integral aspect of that planning. The majority of GTCC LLW is generated by nuclear power plants, and the length of time a reactor remains operational directly affects the amount of GTCC waste expected from that reactor. This report uses data from existing literature to develop high, base, and low case estimates for the number of plants expected to experience (a) early shutdown, (b) 40-year operation, or (c) life extension to 60-year operation. The discussion includes possible effects of advanced light water reactor technology on future GTCC LLW generation. However, the main focus of this study is timing for shutdown of current technology reactors that are under construction or operating.

  5. Testing Age-Paced Parenting Newsletters up to Age 3: Greater Impact on First-Time Parents

    ERIC Educational Resources Information Center

    Ostergren, Carol S.; Riley, David A.

    2012-01-01

    An age-paced newsletter for parents of toddlers was evaluated. Mothers reported the newsletters were as useful as information from doctors or nurses and more useful than other sources of information. We hypothesized and found that first-time mothers reported the newsletters more useful than experienced mothers--reading more of the newsletters and…

  6. Real-time earthquake alert system for the greater San Francisco Bay Area: a prototype design to address operational issues

    SciTech Connect

    Harben, P.E.; Jarpe, S.; Hunter, S.

    1996-12-10

    The purpose of the earthquake alert system (EAS) is to outrun the seismic energy released in a large earthquake using a geographically distributed network of strong motion sensors that telemeter data to a rapid CPU-processing station, which then issues an area-wide warning to a region before strong motion will occur. The warning times involved are short, from 0 to 30 seconds or so; consequently, most responses must be automated. The San Francisco Bay Area is particularly well suited for an EAS because (1) large earthquakes have relatively shallow hypocenters (10- to 20-kilometer depth), giving favorable ray-path geometries for larger warning times than deeper from earthquakes, and (2) the active faults are few in number and well characterized, which means far fewer geographically distributed strong motion sensors are (about 50 in this region). An EAS prototype is being implemented in the San Francisco Bay Area. The system consists of four distinct subsystems: (1) a distributed strong motion seismic network, (2) a central processing station, (3) a warning communications system and (4) user receiver and response systems. We have designed a simple, reliable, and inexpensive strong motion monitoring station that consists of a three-component Analog Devices ADXLO5 accelerometer sensing unit, a vertical component weak motion sensor for system testing, a 16-bit digitizer with multiplexing, and communication output ports for RS232 modem or radio telemetry. The unit is battery-powered and will be sited in fire stations. The prototype central computer analysis system consists of a PC dam-acquisition platform that pipes the incoming strong motion data via Ethernet to Unix-based workstations for dam processing. Simple real-time algorithms, particularly for magnitude estimation, are implemented to give estimates of the time since the earthquake`s onset its hypocenter location, its magnitude, and the reliability of the estimate. These parameters are calculated and transmitted

  7. A Commercial Real-Time PCR Kit Provides Greater Sensitivity than Direct Sequencing to Detect KRAS Mutations

    PubMed Central

    Angulo, Bárbara; García-García, Elena; Martínez, Rebeca; Suárez-Gauthier, Ana; Conde, Esther; Hidalgo, Manuel; López-Ríos, Fernando

    2010-01-01

    KRAS mutation testing has become a standard procedure in the management of patients with carcinomas. The most frequently used method for KRAS testing is direct sequencing of PCR products. The development of commercial real-time quantitative PCR kits offers a useful alternative since they are in theory much more sensitive than direct sequencing and they avoid post- PCR handling. We present our experience as a reference center for the study of KRAS mutations, comparing direct sequencing and the use of a commercial real-time quantitative PCR kit, as well as determining the sensitivity of both procedures in clinical practice. The TheraScreen K-RAS Mutation Kit identified mutations in 75 (44%) of the 170 tumors. Three cases were tested positive using TheraScreen K-RAS Mutation Kit and negative by direct sequencing. We then compared the sensitivity of the kit and that of direct sequencing using 74 mutant tumors. The kit was able to detect the presence of a mutation in a 1% dilution of the total DNA in 13.5% of the tumors and, in 84%, KRAS mutation was identified at a dilution of 5%. Sequencing was able to detect KRAS mutations when the mutant DNA represented 10% of the total DNA in 20/74 (27%) of the tumors. When the mutant DNA represented 30% of the total DNA, sequencing could detect mutations in 56/74 (76%). PMID:20203003

  8. Role-Playing and Real-Time Strategy Games Associated with Greater Probability of Internet Gaming Disorder.

    PubMed

    Eichenbaum, Adam; Kattner, Florian; Bradford, Daniel; Gentile, Douglas A; Green, C Shawn

    2015-08-01

    Research indicates that a small subset of those who routinely play video games show signs of pathological habits, with side effects ranging from mild (e.g., being late) to quite severe (e.g., losing a job). However, it is still not clear whether individual types, or genres, of games are most strongly associated with Internet gaming disorder (IGD). A sample of 4,744 University of Wisconsin-Madison undergraduates (Mage=18.9 years; SD=1.9 years; 60.5% female) completed questionnaires on general video game playing habits and on symptoms of IGD. Consistent with previous reports: 5.9-10.8% (depending on classification criteria) of individuals who played video games show signs of pathological play. Furthermore, real-time strategy and role-playing video games were more strongly associated with pathological play, compared with action and other games (e.g., phone games). The current investigation adds support to the idea that not all video games are equal. Instead, certain genres of video games, specifically real-time strategy and role-playing/fantasy games, are disproportionately associated with IGD symptoms. PMID:26252934

  9. Constraining the Sahara freshwater discharge during sapropel S5 time by a stable isotope record from the Greater Sirte

    NASA Astrophysics Data System (ADS)

    Zirks, Eleen; Kucera, Michal; Bachem, Paul; Schulz, Hartmut

    2016-04-01

    The Nile River and the Black Sea were long considered as the only significant eastern Mediterranean freshwater sources and therefore inferred as the primary agents promoting surface stratification associated with sapropel formation. Sapropel S5, deposited during the last interglacial, marks a time of possible movement of Homo sapiens out of Africa. Satellite images revealed the existence of ancient rivers that once ran through the Sahara desert and drained into the Gulf of Sirte. Anomalous Nd isotope records from sapropel S5 deposits indicate that these rivers may have been active during MIS 5e, implying another freshwater source into the eastern Mediterranean Sea during that period. To constrain the extent of freshwater discharge into the Mediterranean from the Kufrah River during MIS 5e, a new δ18O record of five planktonic foraminifera species was generated from sediment core GeoTü SL 96, located proximal to the assumed outflow of the Kufrah River. The record from core GeoTü SL 96 compared with seven other records from the eastern Mediterranean Sea reveal a pattern of oxygen isotope anomalies which implies that the Kufrah River delivered detectable amount of freshwater during the second part of sapropel S5. These results reinforce the hypothesis that Sahara river systems were active during MIS 5e, which has ramifications for the understanding of sapropel events, reconstruction of coastal landscape, and the better understanding of migration routes of early humans.

  10. 1,2,4,5-Tetrachlorobenzene

    Integrated Risk Information System (IRIS)

    1,2,4,5 - Tetrachlorobenzene ; CASRN 95 - 94 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Nonca

  11. 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T)

    Integrated Risk Information System (IRIS)

    2,4,5 - Trichlorophenoxyacetic acid ( 2,4,5 - T ) ; CASRN 93 - 76 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard

  12. 2(2,4,5-Trichlorophenoxy) propionic acid (2,4,5-TP)

    Integrated Risk Information System (IRIS)

    2 ( 2,4,5 - Trichlorophenoxy ) propionic acid ( 2,4,5 - TP ) ; CASRN 93 - 72 - 1 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Hea

  13. Effects of lindane, paraquat, toxaphene, and 2,4,5-trichlorophenoxyacetic acid on mallard embryo development

    USGS Publications Warehouse

    Hoffman, D.J.; Eastin, W.C., Jr.

    1982-01-01

    The effects were determined of externally treating mallard (Anas platyrhynchos) eggs with two insecticides (lindane and toxaphene) and two herbicides (paraquat and 2,4,5-T) with formulations and concentrations similar to field applications. Paraquat was the most embryotoxic of the four compounds regardless of the type of vehicle. The LC50 for paraquat was 1.5 lb of active ingredient/ acre in aqueous emulsion and 0.1 lb/acre in the oil vehicle. The other compounds had LC50's that were several orders of magnitude higher. Both paraquat and toxaphene caused some mortality at 1/2 of the field level of application. Paraquat impaired growth and was slightly teratogenic at 1/2 of the field level of application, but required higher concentrations (1.5 to 3 times the field level) to produce brain and visceral defects. Lindane was teratogenic, resulting in multiple defects but only at doses that were greater than five times the field level of application. Toxaphene resulted in defects of the joints at doses close to or exceeding the LC50. The herbicide 2,4,5-T resulted in few toxic effects and relatively few abnormal survivors with gross defects. The overall embryotoxicity with either vehicle was paraquat > lindane > toxaphene > 2,4,5-T on a lb per acre basis. However the potential hazard at exposures of up to five times the field level of application was paraquat > toxaphene; neither lindane nor 2,4,5-T constituted much of a hazard. Both paraquat and lindane were more toxic on a lb-peracre basis when administered in oil vehicle but only paraquat represented a potential hazard at five times the field level of application.

  14. Professional Rugby Union players have a 60% greater risk of time loss injury after concussion: a 2-season prospective study of clinical outcomes

    PubMed Central

    Cross, Matthew; Kemp, Simon; Smith, Andrew; Trewartha, Grant; Stokes, Keith

    2016-01-01

    Aim To investigate incidence of concussion, clinical outcomes and subsequent injury risk following concussion. Methods In a two-season (2012/2013, 2013/2014) prospective cohort study, incidence of diagnosed match concussions (injuries/1000 h), median time interval to subsequent injury of any type (survival time) and time spent at each stage of the graduated return to play pathway were determined in 810 professional Rugby Union players (1176 player seasons). Results Match concussion incidence was 8.9/1000 h with over 50% occurring in the tackle. Subsequent incidence of any injury for players who returned to play in the same season following a diagnosed concussion (122/1000 h, 95% CI 106 to 141) was 60% higher (IRR 1.6, 95% CI 1.4 to 1.8) than for those who did not sustain a concussion (76/1000 h, 95% CI 72 to 80). Median time to next injury following return to play was shorter following concussion (53 days, 95% CI 41 to 64) than following non-concussive injuries (114 days, 95% CI 85 to 143). 38% of players reported recurrence of symptoms or failed to match their baseline neurocognitive test during the graduated return to play protocol. Summary and conclusions Players who returned to play in the same season after a diagnosed concussion had a 60% greater risk of time-loss injury than players without concussion. A substantial proportion of players reported recurrence of symptoms or failed to match baseline neurocognitive test scores during graduated return to play. These data pave the way for trials of more conservative and comprehensive graduated return to play protocols, with a greater focus on active rehabilitation. PMID:26626266

  15. Population cycles are highly correlated over long time series and large spatial scales in two unrelated species: Greater sage-grouse and cottontail rabbits

    USGS Publications Warehouse

    Fedy, B.C.; Doherty, K.E.

    2011-01-01

    Animal species across multiple taxa demonstrate multi-annual population cycles, which have long been of interest to ecologists. Correlated population cycles between species that do not share a predator-prey relationship are particularly intriguing and challenging to explain. We investigated annual population trends of greater sage-grouse (Centrocercus urophasianus) and cottontail rabbits (Sylvilagus sp.) across Wyoming to explore the possibility of correlations between unrelated species, over multiple cycles, very large spatial areas, and relatively southern latitudes in terms of cycling species. We analyzed sage-grouse lek counts and annual hunter harvest indices from 1982 to 2007. We show that greater sage-grouse, currently listed as warranted but precluded under the US Endangered Species Act, and cottontails have highly correlated cycles (r = 0. 77). We explore possible mechanistic hypotheses to explain the synchronous population cycles. Our research highlights the importance of control populations in both adaptive management and impact studies. Furthermore, we demonstrate the functional value of these indices (lek counts and hunter harvest) for tracking broad-scale fluctuations in the species. This level of highly correlated long-term cycling has not previously been documented between two non-related species, over a long time-series, very large spatial scale, and within more southern latitudes. ?? 2010 US Government.

  16. Microstructural examination of irradiated V-(4-5%)Cr-(4-5%)Ti.

    SciTech Connect

    Gelles, D. S.

    1998-05-04

    Microstructural examination results are reported for two heats of V-(4-5%) Cr-(4-5%)Ti irradiated in the EBR-II X530 experiment to 4.5 dpa at {approximately}400 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment at 950-1125 C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations. Analytical investigations successfully demonstrated that the precipitates were enriched in titanium, depleted in vanadium and contained no nitrogen. These results are discussed in terms of future alloy development options.

  17. Thermophysical and mechanical properties of V-(4-5)%Cr-(4-5)%Ti alloys

    SciTech Connect

    Zinkle, S.J.

    1998-03-01

    Solid solution V-Cr-Ti alloys exhibit a good combination of high thermal conductivity, adequate tensile strength, and low thermal expansion. The key thermophysical and mechanical properties for V-(4-5)%Cr-(4-5)%Ti alloys are summarized in this report. Some of these data are available in the ITER Materials Properties Handbook (IMPH), whereas other data have been collected from recent studies. The IMPH is updated regularly, and should be used as the reference point for design calculations whenever possible.

  18. Microstructural examination of V-(4-5%) Cr-(4-5%)Ti irradiated in X530

    SciTech Connect

    Gelles, D.S.; Chung, H.M.

    1997-08-01

    Microstructural examination results are reported for two heats of V-(4-5%)Cr-(4-5%)Ti irradiated in the X530 experiment to {approximately}400{degrees}C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment at 950-1125{degrees}C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations.

  19. Tensile properties of V-(4-5)Cr-(4-5)Ti alloys

    SciTech Connect

    Chung, H.M.; Nowicki, L.; Busch, D.; Smith, D.L.

    1996-04-01

    The current focus of the U.S program of research on V-base alloys is on V-(4-5)Cr(4-5)Ti that contains 500-1000 wppm Si. in this paper, we present experimental results on baseline tensile properties of two laboratory-scale heats of this alloy and of a 500-kg production heat of V-4Cr-4Ti (heat 832665) that were measured at 23-700 C. Both the production- and laboratory scale heats of the reference alloy V-4Cr-4Ti exhibited excellent tensile properties at temperatures up to {approx}650{degrees}C.

  20. The NIF 4.5-m nTOF Detectors

    SciTech Connect

    Moran, M J; Bond, E J; Clancy, T J; Eckart, M J; Khater, H Y; Glebov, V Y

    2012-05-07

    The first several campaigns of laser fusion experiments at the National Ignition Facility (NIF) included a family of high-sensitivity scintillator/photodetector neutron-time-of-flight (nTOF) detectors for measuring DD and DT neutron yields. The detectors provided consistent neutron yield benchmarks from below 1E9 (DD) to nearly 1E15 (DT). The detectors demonstrated DT yield measurement precisions better than 5%, but the absolute accuracy relies on cross calibration with independent measurements of absolute neutron yield. The 4.5-m nTOF data have provided a useful testbed for testing improvements in nTOF data processing, especially with respect to improving the accuracies of the detector impulse response functions. The resulting improvements in data analysis methods have produced more accurate results. In summary, results from the NIF 4.5-m nTOF detectors have provided consistent measurements of DD and DT neutron yields from laser-fusion implosions.

  1. Bagging, boosting, and C4.5

    SciTech Connect

    Quinlan, J.R.

    1996-12-31

    Breiman`s bagging and Freund and Schapire`s boosting are recent methods for improving the predictive power of classifier learning systems. Both form a set of classifiers that are combined by voting, bagging by generating replicated bootstrap samples of the data, and boosting by adjusting the weights of training instances. This paper reports results of applying both techniques to a system that learns decision trees and testing on a representative collection of datasets. While both approaches substantially improve predictive accuracy, boosting shows the greater benefit. On the other hand, boosting also produces severe degradation on some datasets. A small change to the way that boosting combines the votes of learned classifiers reduces this downside and also leads to slightly better results on most of the datasets considered.

  2. Microstructural examination of irradiated V-(4-5%)Cr-(4-5%)Ti

    SciTech Connect

    Gelles, D.S.; Rice, P.M.; Zinkle, S.J.; Chung, H.M.

    1998-03-01

    Microstructural examination results are reported for two heats of V-(4-5%)Cr-(4-5%)Ti irradiated in the EBR-II X530 experiment to {approximately}4 dpa at {approximately}400 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to b affected by preirradiation heat treatment at 950--1125 C. There was no evidence for a significant density of large (diameter >10 nm) dislocation loops or network dislocations. Analytical investigators successfully demonstrated that the precipitates were enriched in titanium, depleted in vanadium and contained no nitrogen.

  3. Influence of lipolysis on the mobilization of 2,4,5,2'4',5'-hexachlorobiphenyl from adipocytes in vitro

    SciTech Connect

    Gallenberg, L.A.; Ring, B.J.; Vodicnik, M.J.

    1987-01-01

    Epididymal adipocytes, isolated from rats pretreated with (/sup 14/C)-2,4,5,2',4',5'-hexachlorobiphenyl (6-CB), were utilized to examine the relationship between the mobilization of lipid and 6-CB and to determine whether 6-CB was differentially associated with subcellular organelles over time as has been demonstrated for newly synthesized lipid. Lipolysis, depleted approximately 1% of total cellular triacylglycerols (TG) regardless of time from treatment with 6-CB. The percentage of cellular 6-CB released from adipocytes to incubation buffer infranatants was not correlated with the magnitude of lipolysis produced over the 50-min incubation period; nor was the percentage of 6-CB released to the buffers correlated with the length of the incubation period, regardless of the presence of ISO. Although adipocytes responded similarly to lipolytic stimuli independent of time (days) since 6-CB treatment, significant decreases were found in the percentage of 6-CB released from adipocytes over time. The in vitro labeling of this newly synthesized TG in fat cells with (U-/sup 14/C)glucose or (1-/sup 14/C)palmitate demonstrated that TG was differentially distributed among adipocyte organelles. Newly synthesized TG was also the first to be mobilized under lipolytic stimulus. 6-CB was not released in a similar fashion, since radioactivity associated with the chemical levels of (/sup 14/C)-6-CB and glucose-derived /sup 14/C in buffers were not correlated over time.

  4. Degradation of 4,5-dichloroguaiacol by soil microorganisms.

    PubMed

    González, B; Brezny, R; Herrera, M; Joyce, T W

    1995-09-01

    No microorganisms could be isolated from chemostats or from a soil column fed with 4,5-dichloroguaiacol as the only carbon source. If guaiacol was added to chemostats with 4,5-dichloroguaiacol, either soil microbial consortia or guaiacol-degrading bacteria could dechlorinate the 4,5-dichloroguaiacol provided it was <0.2MM. A microbial consortium from farm soil removed 4,5-dichloroguaiacol under aerobic or anoxic conditions, with or without chlorolignin. Dichlorocatechol was the only 4,5-dichloroguaiacol-derived metabolite detected. In aerobic incubations, 4,5-dichlorocatechol was further degraded whereas under anoxic conditions it accumulated. PMID:24414909

  5. Holocene peatland initiation in the Greater Everglades

    NASA Astrophysics Data System (ADS)

    Dekker, Stefan; de Boer, Hugo; Dermody, Brian; Wagner-Cremer, Friederike; Wassen, Martin; Eppinga, Maarten

    2015-04-01

    The mechanisms involved in the initiation and development of the Greater Everglades peatland ecosystems in South Florida (USA) remain a topic of discussion. In this study, we present an overview of basal ages of peat deposits in South Florida, which shows two major episodes of peatland initiation between 7.0-4.5 kyr and 3.5-2.0 kyr. Our analysis of regional climate proxy datasets led to three alternative hypotheses that may explain the timing and duration of these two peatland initiation episodes: (1) decreased drainage due to relative sea level (RSL) rise during the Holocene (2) gradual increase in precipitation throughout the Holocene, and (3) a combination of increasing precipitation, rising RSL and oscillations in the climate system. We test whether these three hypotheses can explain the pattern of initiation and development of the Greater Everglades peatlands using models that simulate the non-linear processes involved in peat production and decomposition in combination with the local drainage conditions of Southern Florida. The model results suggest that RSL-rise alone cannot predict the onset of peat initiation in the Greater Everglades using our model setup. The model also implies that the climate was wet enough for peat development also during the early Holocene. The first two hypothesized mechanisms in combination with climate oscillations may explain the onset of peat accumulation at 8.2 kyr BP. The two-phased character of peat land initiation may be explained by the spatial distribution of local drainage conditions. As peatland development is highly non-linear, our model uncovers a mechanistic way how peats can suddenly shift from a dry high equilibrium to a wet low equilibrium resulting in lake formation as observed in paleo-ecological studies in the Greater Everglades.

  6. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  7. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Notice by publication. 4.5 Section 4.5 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the...

  8. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  9. 45 CFR 4.5 - Effect of regulations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Effect of regulations. 4.5 Section 4.5 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION SERVICE OF PROCESS § 4.5 Effect of regulations. The regulations in this part are intended solely to identify Department officials who...

  10. Role of calcium in membrane interactions by PI(4,5)P₂-binding proteins.

    PubMed

    Monteiro, Marina E; Sarmento, Maria J; Fernandes, Fábio

    2014-10-01

    Ca²⁺ and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P₂] are key agents in membrane-associated signalling events. Their temporal and spatial regulation is crucial for activation or recruitment of proteins in the plasma membrane. In fact, the interaction of several signalling proteins with PI(4,5)P₂ has been shown to be tightly regulated and dependent on the presence of Ca²⁺, with co-operative binding in some cases. In these proteins, PI(4,5)P₂ and Ca²⁺ binding typically occurs at different binding sites. In addition, several PI(4,5)P₂-binding proteins are known targets of calmodulin (CaM), which, depending on the presence of calcium, can compete with PI(4,5)P₂ for protein interaction, translating Ca²⁺ transient microdomains into variations of PI(4,5)P₂ lateral organization in time and space. The present review highlights different examples of calcium-dependent PI(4,5)P₂-binding proteins and discusses the possible impact of this dual regulation on fine-tuning of protein activity by triggering target membrane binding in the presence of subtle changes in the levels of calcium or PI(4,5)P₂. PMID:25233429

  11. Holocene peatland initiation in the Greater Everglades

    NASA Astrophysics Data System (ADS)

    Dekker, Stefan C.; Boer, Hugo J.; Dermody, Brian J.; Wagner-Cremer, Friederike; Wassen, Martin J.; Eppinga, Maarten B.

    2015-02-01

    The mechanisms involved in the initiation and development of the Greater Everglades peatland ecosystems remain a topic of discussion. In this study, we first present an overview of basal ages of peat deposits in South Florida, which shows two major episodes of peatland initiation between 7.0-4.5 kyr and 3.5-2.0 kyr. Our analysis of regional climate proxy data sets led to three alternative hypotheses that may explain the timing and duration of these two peatland initiation episodes: (1) decreased drainage due to relative sea level (RSL) rise during the Holocene, (2) gradual increase in precipitation throughout the Holocene, and (3) a combination of increasing precipitation, rising RSL, and oscillations in the climate system. We test whether these three hypotheses can explain the pattern of initiation and development of the Greater Everglades peatlands using models that simulate the nonlinear processes involved in peat production and decomposition. The model results suggest that RSL rise could explain the onset of peatland initiation and imply that the climate was wet enough for peat development also during the early Holocene. The first two hypothesized mechanisms in combination with climate oscillations may explain the onset of peat accumulation at 8.2 kyr B.P. The two-phased character of peatland initiation maybe explained by the spatial distribution of local drainage conditions. As peatland development is highly nonlinear, our model uncovers a mechanistic way how peats can suddenly shift from a dry high equilibrium to a wet low equilibrium resulting in lake formation as observed in paleoecological studies in the Greater Everglades.

  12. Greater arch injuries.

    PubMed

    Shivanna, Deepak; Manjunath, Dayanand; Amaravathi, Rajkumar

    2014-12-01

    Dislocations and fracture dislocations of carpal bones are uncommon injuries which invariably poses challenges in the management. Perilunate fracture dislocations are the combination of ligamentous and osseous injury that involve the "greater arc" of the perilunate associated instability. Despite their severity, these injuries often go unrecognized in the emergency department leading to delayed diagnosis and treatment. A Prospective study was done from June 2008 to December 2013 in 15 cases of complex wrist injuries which included of greater arch injuries, perilunate fracture dislocation and one dorsal dislocation of Scaphoid. 10 cases of perilunate fracture dislocation underwent open reduction and internal fixation with Herbert screw and k-wire, 4 cases of greater arch injury underwent closed reduction and kwire fixation and one case of neglected dorsal dislocation underwent proximal row carpectomy. One patient had Sudecks osteodystrophy 1 had Scaphoid nonunion and 6 had median nerve compression. Overall outcome according to Mayo wrist score was 53 % excellent, 33 % good and 14 % fair. Greater arch injuries are difficult to treat because injuries to many ligaments are involved and failure to recognize early leads to persistent pain, disability and early onset of arthritis. Prompt recognition requires CT scan and MRI. Management requires reduction and multiple K-Wiring according to merits of the case. PMID:25414554

  13. Random variation in rectal position during radiotherapy for prostate cancer is two to three times greater than that predicted from prostate motion

    PubMed Central

    Harrison, K; Romanchikova, M; Parker, A; Sutcliffe, M; Bond, S; Thomas, S; Freeman, S; Jena, R; Bates, A; Burnet, N

    2014-01-01

    Objective: Radiotherapy for prostate cancer does not explicitly take into account daily variation in the position of the rectum. It is important to accurately assess accumulated dose (DA) to the rectum in order to understand the relationship between dose and toxicity. The primary objective of this work was to quantify systematic (Σ) and random (σ) variation in the position of the rectum during a course of prostate radiotherapy. Methods: The rectum was manually outlined on the kilo-voltage planning scan and 37 daily mega-voltage image guidance scans for 10 participants recruited to the VoxTox study. The femoral heads were used to produce a fixed point to which all rectal contours were referenced. Results: Σ [standard deviation (SD) of means] between planning and treatment was 4.2 mm in the anteroposterior (AP) direction and 1.3 mm left–right (LR). σ (root mean square of SDs) was 5.2 mm AP and 2.7 mm LR. Superior–inferior variation was less than one slice above and below the planning position. Conclusion: Our results for Σ are in line with published data for prostate motion. σ, however, was approximately twice as great as that seen for prostate motion. This suggests that DA may differ from planned dose in some patients treated with radiotherapy for prostate cancer. Advances in knowledge: This work is the first to use daily imaging to quantify Σ and σ of the rectum in prostate cancer. σ was found to be greater than published data, providing strong rationale for further investigation of individual DA. PMID:25138155

  14. Elimination of 2,4,5,2',4',5'-hexachlorobiphenyl by the purple sea urchin, Strongylocentrotus purpuratus, following single exposure

    SciTech Connect

    Tjeerdema, R.S.; Jacobs, R.S.

    1987-06-01

    Understanding the fate of a single PCB isomer in a resident species may aid in assessing the risk to the marine community. Therefore, the elimination of 2,4,5,2',4',5'-hexachlorobiphenyl (HCBP) by the purple sea urchin, Strongylocentrotus purpuratus, following a single exposure, was investigated. The purple sea urchin was chosen because of its economic importance and ability to proliferate in certain polluted conditions. Single exposure may best mimic the effects of intermittent oceanic incineration or disposal, and 2,4,5,2',4',5'-HCBP was chosen due to its presence in common PCB mixtures and high chlorine content, thus strong lipophilicity.

  15. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Formulation of alternatives. 1610.4-5 Section 1610.4-5 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR GENERAL MANAGEMENT (1000) PLANNING, PROGRAMMING, BUDGETING...

  16. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  17. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  18. 43 CFR 1610.4-5 - Formulation of alternatives.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Formulation of alternatives. 1610.4-5... Management Planning § 1610.4-5 Formulation of alternatives. At the direction of the Field Manager, in collaboration with any cooperating agencies, BLM will consider all reasonable resource management...

  19. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  20. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  1. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  2. 43 CFR 2650.4-5 - National forest lands.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false National forest lands. 2650.4-5 Section... Selections: Generally § 2650.4-5 National forest lands. Every conveyance which includes lands within the boundaries of a national forest shall, as to such lands, contain reservations that: (a) Until December...

  3. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  4. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  5. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7... Federal Elections FEDERAL ELECTION COMMISSION PUBLIC RECORDS AND THE FREEDOM OF INFORMATION ACT § 4.5..., provided that such statute (A) requires that the matters be withheld from the public in such a manner as...

  6. 41 CFR 51-4.5 - Violations by nonprofit agencies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Violations by nonprofit agencies. 51-4.5 Section 51-4.5 Public Contracts and Property Management Other Provisions Relating to Public Contracts COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED...

  7. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Notice by publication. 4.5... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the... where the USPTO's Web site is unavailable for publication will the USPTO publish the Notice of...

  8. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 37 Patents, Trademarks, and Copyrights 1 2011-07-01 2011-07-01 false Notice by publication. 4.5... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the... where the USPTO's Web site is unavailable for publication will the USPTO publish the Notice of...

  9. The 2-Year Checkup on 10 SNe IIn Discovered by Spitzer to Exhibit Late-Time (is greater than 100 Day) IR Emission

    NASA Technical Reports Server (NTRS)

    Fox, Ori Dosovitz; Chevalier, R. A.; Skrutskie, A. V.; Filippenko, A. V.; Silverman, J. M.; Ganeshalingam, M.

    2012-01-01

    Two years ago, a warm Spitzer survey of sixty-eight SNe IIn identified between the years 1998-2008 discovered 10 events with unreported late-time infrared (IR) excesses, in some cases more than 5 years post-explosion. These data nearly double the database of existing mid-IR observations of SNe IIn and offer important clues regarding the SN circumstellar.

  10. Formation and metabolism of inositol 1,4,5-trisphosphate in human platelets.

    PubMed Central

    Daniel, J L; Dangelmaier, C A; Smith, J B

    1987-01-01

    1. myo-[3H]Inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], when added to lysed platelets, was rapidly converted into [3H]inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4], which was in turn converted into [3H]inositol 1,3,4-trisphosphate [Ins(1,3,4)P3]. This result demonstrates that platelets have the same metabolic pathways for interconversion of inositol polyphosphates that are found in other cells. 2. Labelling of platelets with [32P]Pi, followed by h.p.l.c., was used to measure thrombin-induced changes in the three inositol polyphosphates. Interfering compounds were removed by a combination of enzymic and non-enzymic techniques. 3. Ins(1,4,5)P3 was formed rapidly, and reached a maximum at about 4 s. It was also rapidly degraded, and was no longer detectable after 30-60 s. 4. Formation of Ins(1,3,4,5)P4 was almost as rapid as that of Ins(1,4,5)P3, and it remained detectable for a longer time. 5. Ins(1,3,4)P3 was formed after an initial lag, and this isomer reached its maximum, which was 10-fold higher than that of Ins(1,4,5)P3, at 30 s. 6. Comparison of the intracellular Ca2+ concentration as measured with fura-2 indicates that agents other than Ins(1,4,5)P3 are responsible for the sustained maintenance of a high concentration of intracellular Ca2+. It is proposed that either Ins(1,3,4)P3 or Ins(1,3,4,5)P4 may also be Ca2+-mobilizing agents. PMID:3499898

  11. Greater Trochanteric Pain Syndrome.

    PubMed

    Redmond, John M; Chen, Austin W; Domb, Benjamin G

    2016-04-01

    Patients who have lateral hip pain historically have been diagnosed with trochanteric bursitis and treated with nonsteroidal anti-inflammatory medications, corticosteroid injections, and physical therapy. Although this strategy is effective for most patients, a substantial number of patients continue to have pain and functional limitations. Over the past decade, our understanding of disorders occurring in the peritrochanteric space has increased dramatically. Greater trochanteric pain syndrome encompasses trochanteric bursitis, external coxa saltans (ie, snapping hip), and abductor tendinopathy. A thorough understanding of the anatomy, examination findings, and imaging characteristics aids the clinician in treating these patients. Open and endoscopic treatment options are available for use when nonsurgical treatment is unsuccessful. PMID:26990713

  12. Hemolymphangioma of Greater Omentum

    PubMed Central

    Pandey, Sagar; Fan, Miao; Chang, Dandan; Zhu, Junfeng; Zhu, Ying; Li, Ziping

    2016-01-01

    Abstract Hemolymphangioma is a rare vascular developmental error. It comprises malformed venous and lymphatic component in various proportion. To the best of our knowledge, only a few cases have been reported in the literature so far. Here, we report a case of huge intraperitoneal cystic mass in a 3-year-old boy that was presented to hospital with intractable abdominal pain. On examination, he had fever along with associated symptoms like cough and sputum. Abdomen was distended with no tenderness or rebound tenderness. On computed tomography scan, huge cystic mass was seen and was diagnosed as intraperitoneal benign cystic lesion. Excisional surgery of the lesion was planned. On surgery, lesion was found to be originated from greater omentum and no adhesion was seen in surrounding tissue. Complete excision of the lesion was done. Histopathological specimen after surgery suggested it to be hemolymphangioma. Follow-up for 6 months showed no recurrence. Hemolymphangioma of the greater omentum is benign tumor and accurate diagnosis before surgery is still a challenge. Presentation of disease may vary from simple well-defined cystic lesion to aggressive ill-defined lesion mimicking malignancy. Therefore, further research is needed to help doctor with preoperative radiological diagnosis and avoid unnecessary radical surgery. PMID:27124058

  13. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7..., or foreign agency or authority or any private institution which furnished information on...

  14. 11 CFR 4.5 - Categories of exemptions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... individual. (b) Whenever a request is made which involves access to records described in 11 CFR 4.5(a)(7..., or foreign agency or authority or any private institution which furnished information on...

  15. 4,5-Diphenyl-1-methylimidazole: An Undergraduate Laboratory Experiment.

    ERIC Educational Resources Information Center

    Anastas, Paul T.; And Others

    1985-01-01

    Background information and procedures used are provided for the synthesis of 4,5-diphenyl-methylimidazole. This experiment on the chemistry of heterocycles is ideally suited for beginning undergraduate organic chemistry students. (JN)

  16. ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 ...

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

    ANCHOR SETTING PLAN FOR PIERS 1, 2, 3, 4, 5 AND 6, APALACHICOLA RIVER BRIDGE, SHEET 5505 TO 8-M1 - Apalachicola River Bridge, State Route 20 spanning the Apalachicola River, Blountstown, Calhoun County, FL

  17. More features, greater connectivity.

    PubMed

    Hunt, Sarah

    2015-09-01

    Changes in our political infrastructure, the continuing frailties of our economy, and a stark growth in population, have greatly impacted upon the perceived stability of the NHS. Healthcare teams have had to adapt to these changes, and so too have the technologies upon which they rely to deliver first-class patient care. Here Sarah Hunt, marketing co-ordinator at Aid Call, assesses how the changing healthcare environment has affected one of its fundamental technologies - the nurse call system, argues the case for wireless such systems in terms of what the company claims is greater adaptability to changing needs, and considers the ever-wider range of features and functions available from today's nurse call equipment, particularly via connectivity with both mobile devices, and ancillaries ranging from enuresis sensors to staff attack alert 'badges'. PMID:26548128

  18. 3,4,5-Trinitropyrazole-based energetic salts.

    PubMed

    Zhang, Yanqiang; Guo, Yong; Joo, Young-Hyuk; Parrish, Damon A; Shreeve, Jean'ne M

    2010-09-17

    High-density energetic salts that are comprised of nitrogen-rich cations and the 3,4,5-trinitropyrazolate anion were synthesized in high yield by neutralization or metathesis reactions. The resulting salts were fully characterized by (1)H, (13)C NMR, and IR spectroscopy; differential scanning calorimetry; and elemental analysis. Additionally, the structures of the 3,5-diaminotriazolium and triaminoguanidinium 3,4,5-trinitropyrazolates were confirmed by single-crystal X-ray diffraction. Based on the measured densities and calculated heats of formation, the detonation performances (pressure: 23.74-31.89 GPa; velocity: 7586-8543 ms(-1); Cheetah 5.0) of the 3,4,5-trinitropyrazolate salts are comparable with 1,3,5-triamino-2,4,6-trinitrobenzene (TATB; 31.15 GPa and 8114 ms(-1)). Impact sensitivities were determined to be no less than 35 J by hammer tests, which places these salts in the insensitive class. PMID:20661962

  19. 2,2\\',4,4\\',5-Pentabromodiphenyl ether (BDE-99)

    Integrated Risk Information System (IRIS)

    EPA / 635 / R - 07 / 006F www.epa.gov / iris TOXICOLOGICAL REVIEW OF 2,2 ' , 4,4 ' , 5 - PENTABROMODIPHENYL ETHER ( BDE - 99 ) ( CAS No . 60348 - 60 - 9 ) In Support of Summary Information on the Integrated Risk Information System ( IRIS ) June 2008 U.S . Environmental Protection Agency Washington ,

  20. CURRICULUM GUIDE FOR SCIENCE, GRADES 4-5-6.

    ERIC Educational Resources Information Center

    GRAHAM, KATHRYN A.; AND OTHERS

    COURSE CONTENT, ACTIVITIES, AND REFERENCE INFORMATION FOR TEACHING SCIENCE IN GRADES 4, 5, AND 6 ARE INCLUDED IN THIS VOLUME. INTRODUCTORY REMARKS RELATE TO AN APPROACH TO TEACHING SCIENCE AND THE GENERAL OBJECTIVES OF THE SCIENCE PROGRAM. THE FIVE UNITS INCLUDED FOR GRADE 4 ARE (1) INSECTS AND SPIDERS, (2) LIVING THINGS OF SIMILAR AREAS, (3) THE…

  1. Multicultural Education Guide for Grades 4, 5, and 8.

    ERIC Educational Resources Information Center

    Millbrae School District, CA.

    This resource guide, prepared by teachers, is designed to incorporate minority group studies into the district's social studies curriculum at levels 4, 5, and 8 as a start toward goals specified in the state law. Introductory material discusses the California Education Code requirements, local district policy, and the work of the curriculum…

  2. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the invention promoter is returned undelivered, then the USPTO will primarily... in the Official Gazette and/or the Federal Register. The invention promoter will be given 30...

  3. 37 CFR 4.5 - Notice by publication.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... COMMERCE GENERAL COMPLAINTS REGARDING INVENTION PROMOTERS § 4.5 Notice by publication. If the copy of the complaint that is mailed to the invention promoter is returned undelivered, then the USPTO will primarily... in the Official Gazette and/or the Federal Register. The invention promoter will be given 30...

  4. 13. PRATT STREET BULKHEAD: SECTIONS 2, 3, 4, 5, AND ...

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

    13. PRATT STREET BULKHEAD: SECTIONS 2, 3, 4, 5, AND 6, DRAWER 10, PLAN NO. 1, 1 IN. = 15 FT. AND 1/2 IN. = 1 FT., APRIL 25, 1906, DRAWING SHOWS DESIGN FOR PRATT STREET BULKHEAD BETWEEN PIERS - Baltimore Inner Harbor, Pier 5, South of Pratt Street between Market Place & Concord Street, Baltimore, Independent City, MD

  5. 4.5 Doses to Patients in Diagnostics

    NASA Astrophysics Data System (ADS)

    Noßke, D.; Mattsson, S.; Johansson, L.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Section '4.5 Doses to Patients in Diagnostics' of the Chapter '4 Dosimetry in Nuclear Medicine Diagnosis and Therapy' with the contents:

  6. Changes in time-use and drug use by young adults in poor neighbourhoods of Greater Buenos Aires, Argentina, after the political transitions of 2001-2002: Results of a survey

    PubMed Central

    2011-01-01

    Background In some countries, "Big Events" like crises and transitions have been followed by large increases in drug use, drug injection and HIV/AIDS. Argentina experienced an economic crisis and political transition in 2001/2002 that affected how people use their time. This paper studies how time use changes between years 2001 and 2004, subsequent to these events, were associated with drug consumption in poor neighbourhoods of Greater Buenos Aires. Methods In 2003-2004, 68 current injecting drug users (IDUs) and 235 young non-IDUs, aged 21-35, who lived in impoverished drug-impacted neighbourhoods in Greater Buenos Aires, were asked about time use then and in 2001. Data on weekly hours spent working or looking for work, doing housework/childcare, consuming drugs, being with friends, and hanging out in the neighbourhood, were studied in relation to time spent using drugs. Field observations and focus groups were also conducted. Results After 2001, among both IDUs and non-IDUs, mean weekly time spent working declined significantly (especially among IDUs); time spent looking for work increased, and time spent with friends and hanging out in the neighbourhood decreased. We found no increase in injecting or non-injecting drug consumption after 2001. Subjects most affected by the way the crises led to decreased work time and/or to increased time looking for work--and by the associated increase in time spent in one's neighbourhood--were most likely to increase their time using drugs. Conclusions Time use methods are useful to study changes in drug use and their relationships to every day life activities. In these previously-drug-impacted neighbourhoods, the Argentinean crisis did not lead to an increase in drug use, which somewhat contradicts our initial expectations. Nevertheless, those for whom the crises led to decreased work time, increased time looking for work, and increased time spent in indoor or outdoor neighbourhood environments, were likely to spend more time

  7. Heat treatment effects on tensile properties of V-(4-5) wt.% Cr-(4-5) wt.% Ti alloys

    SciTech Connect

    Natesan, K.; Soppet, W.K.

    1997-08-01

    Effects of thermomechanical treatments on microstructures and mechanical properties are of interest for long term application of V-Cr-Ti alloys in fusion reactor systems. Influence of thermal annealing at 1050{degrees}C on stress/strain behavior, maximum engineering strength, and uniform and total elongation were evaluated. The results show that multiple annealing has minimal effect on the tensile properties of V-(4-5)Cr-(4-5)Ti alloys tested at room temperature and at 500{degrees}C.

  8. VLF study of low magnitude Earthquakes (4.5

    NASA Astrophysics Data System (ADS)

    Wolbang, Daniel; Biernat, Helfried; Schwingenschuh, Konrad; Eichelberger, Hans; Prattes, Gustav; Besser, Bruno; Boudjada, Mohammed; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier Francesco; Friedrich, Martin

    2014-05-01

    In the course of the European VLF/LF radio receiver network (International Network for Frontier Research on Earthquake Precursors, INFREP), radio signals in the frequency range from 10-50 kilohertz are received, continuously recorded (temporal resolution 20 seconds) and analyzed in the Graz/Austria knot. The radio signals are generated by dedicated distributed transmitters and detected by INFREP receivers in Europe. In case the signal is crossing an earthquake preparation zone, we are in principle able to detect seismic activity if the signal to noise ratio is high enough. The requirements to detect a seismic event with the radio link methods are given by the magnitude M of the Earthquake (EQ), the EQ preparation zone and the Fresnel zone. As pointed out by Rozhnoi et al. (2009), the VLF methods are suitable for earthquakes M>5.0. Furthermore, the VLF/LF radio link gets only disturbed if it is crossing the EQ preparation zone which is described by Molchanov et al. (2008). In the frame of this project I analyze low seismicity EQs (M≤5.6) in south/eastern Europe in the time period 2011-2013. My emphasis is on two seismic events with magnitudes 5.6 and 4.8 which we are not able to adequately characterize using our single parameter VLF method. I perform a fine structure analysis of the residua of various radio links crossing the area around the particular 2 EQs. Depending on the individual paths not all radio links are crossing the EQ preparation zone directly, so a comparative study is possible. As a comparison I analyze with the same method the already good described EQ of L'Aquila/Italy in 2009 with M=6.3 and radio links which are crossing directly the EQ preparation zone. In the course of this project we try to understand in more detail why it is so difficult to detect EQs with 4.5

  9. 4.5 Meter high level waste canister study

    SciTech Connect

    Calmus, R. B.

    1997-10-01

    The Tank Waste Remediation System (TWRS) Storage and Disposal Project has established the Immobilized High-Level Waste (IBLW) Storage Sub-Project to provide the capability to store Phase I and II BLW products generated by private vendors. A design/construction project, Project W-464, was established under the Sub-Project to provide the Phase I capability. Project W-464 will retrofit the Hanford Site Canister Storage Building (CSB) to accommodate the Phase I I-ILW products. Project W-464 conceptual design is currently being performed to interim store 3.0 m-long BLW stainless steel canisters with a 0.61 in diameter, DOE is considering using a 4.5 in canister of the same diameter to reduce permanent disposal costs. This study was performed to assess the impact of replacing the 3.0 in canister with the 4.5 in canister. The summary cost and schedule impacts are described.

  10. New 4,5-dichlorophthalhydrazidate-bridged chained coordination polymers

    NASA Astrophysics Data System (ADS)

    Jin, Juan; Wu, Di; Jia, Ming-Jun; Peng, Yu; Yu, Jie-Hui; Wang, Yu-Chang; Xu, Ji-Qing

    2011-03-01

    The hydrothermal self-assemblies of Pb 2+/Cd 2+ salt, 4,5-dichlorophthalic acid (dcpha), N 2H 4·H 2O together with 1,10-phenanthroline·H 2O (phen) or 2,2'-bipyridine (bpy) generated two new monoacylhydrazidate-bridged 1-D chained coordination polymers [Pb 2(DCPTH) 4(phen) 2] 1 and [Cd 3(DCPTH) 2(dcph) 2(bpy) 2] 2 (DCPTH=4,5-dichlorophthalhydrazidate, dcph=4,5-dichlorophthalate). The monoacylhydrazidate ligand DCPTH originated from the hydrothermal in situ acylation reaction between dcpha and N 2H 4·H 2O. In compound 1, two types of coordination modes for DCPTH are found, which link alternately the Pb(II) centers into a 1-D chain structure of compound 1 with ancillary phen molecules. In compound 2, DCPTH and dcph as the mixed bridges extend the Cd(II) centers into a 1-D chain structure of compound 2 with auxiliary bpy molecules. DCPTH in compound 2 shows a different coordination mode from those observed in compound 1.

  11. PTEN interaction with tethered bilayer lipid membranes containing PI(4,5)P2

    NASA Astrophysics Data System (ADS)

    Moldovan, R.; Shenoy, S.; Shekhar, P.; Kalinowski, A.; Gericke, A.; Heinrich, F.; Loesche, M.

    2009-03-01

    Synthetic lipid membrane models are frequently used for the study of biophysical processes at cell membranes. We use a robust membrane model, the tethered bilayer lipid membrane (tBLM), based on a (C14)2-(PEO)6-thiol anchor, WC14 [1]. Such membranes can be prepared to contain single phospholipids or complex lipid mixtures [2], including functional lipids involved in cell signaling, such as the highly charged phosphatidylinositol phosphates (PIPs). To study the interaction between the tumor suppressor PTEN (phosphatase and tensin homologue deleted on chromosome 10) and model membranes we have incorporated phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) in tBLMs and use fluorescence correlation spectroscopy (FCS), neutron reflectometry (NR) and surface plasmon resonance (SPR) for their characterization. NR shows that tBLMs formed with PI(4,5)P2 are complete. FCS of labeled PI(4,5)P2 shows that diffusion occurs at the time scale characteristic of membrane-incorporated lipid. Finally, SPR shows specific binding of PTEN to the model membrane thus confirming the incorporation of PI(4,5)P2 into the tBLM. [1] McGillivray et al, Biointerphases 2, 21-33 (2007) [2] Heinrich et al, Langmuir, submitted

  12. The 18 May 2012 (Ms 4.5) Chapala Lake, Jalisco, Mexico Earthquake

    NASA Astrophysics Data System (ADS)

    Yamamoto, J.; Espindola, J. M.

    2015-12-01

    The central part of Jalisco, Mexico has experienced at different times the occurrence of low magnitude earthquakes series. Although the effect of these earthquakes have been limited to relatively small areas have caused general alarm within the population and even in some cases true catastrophes (e.g. San Cristobal 1875). These groups of earthquakes that have lasted for weeks and even months have greater importance because they affect the most populous state area including the capital city of Guadalajara. An extraordinary example of these series of earthquakes occurred on 8 may 1912 that lasted until September. In the first 18 days 64 events were felt by residents of Guadalajara. Since then, there has been a relative seismic activity calm in the region. This paper analyzes the earthquake of May 18, 2012 (03:07 UT) occurred at the West edge of Lake Chapala. While it's an event of low magnitude (4.5 Ms) it has the importance of having occurred just 60 km to the South of Guadalajara and for which instrumental data of first quality is available. The focus of the earthquake was located at 20.30 ° N and 103.49 ° W at a depth of 0 km using arrivals of P and S waves at 16 regional seismic stations. However, by the errors of localization inherent in the method focus could be in a range of 0 to 5 km deep. The mechanism of failure using the polarities of the first arrivals favors a clear faulting of dip slip type along a plane with strike = 227 °, Dip = 80 °, and Rake = 93 °. Waveforms analysis is being used to corroborate these results.

  13. Software for the Canadian Advanced Nanospace eXperiment-4/5 (CanX-4/-5) Mission

    NASA Astrophysics Data System (ADS)

    Leonard, Matthew Leigh

    The CanX-4 and CanX-5 mission currently under development at The University of Toronto Institute for Aerospace Studies Space Flight Laboratory UTIAS/SFL is a challenging formation flying technology demonstration. Its requirements of sub-metre control accuracy have yet to be realized with nanosatellites. Many large technical challenges must be addressed in order to ensure the success of the CanX-4/5 mission. This includes the development of software for an intersatellite communication system, integration and optimization of key formation flying algorithms onto the Payload On-Board Computer as well as the development of a Hardware-In-The-Loop simulator for full on-orbit mission simulations. This thesis will provide background knowledge of the Space Flight Laboratory and its activities, the CanX-4/5 mission, and finally highlight the authors contributions to overcoming each of these technical challenges and ensuring the success of the CanX-4 and CanX-5 mission.

  14. ED case managers save $4.5 million.

    PubMed

    2011-08-01

    Emergency department case managers at Lee Memorial Health System in Fort Myers, FL saved more than $4.5 million by ensuring that patients were in the right status and transferring patients who did not meet admission criteria to a more appropriate level of care. Case managers and social workers cover the emergency department at peak hours, seven days a week. Case managers screen patients for admission criteria and make sure admission orders are complete and correct. Case managers and social workers coordinate community services and placement for patients who don't meet admission criteria. Social workers intervene when there are concerns about abuse and neglect, and they facilitate placement to other acute care facilities. PMID:21789904

  15. Inositol 1,4,5-trisphosphate induced calcium waves

    NASA Astrophysics Data System (ADS)

    Falcke, M.

    Traveling waves of high concentration of Ca2+ are observed in many different cells and have attracted great interest in experimental and theoretical biological research in recent years. They are created by the nonlinear dynamics of the release and uptake of Ca2+ by intracellular Ca2+ stores like the endoplasmatic or sarcoplasmatic reticulum. Their characteristics depend on other cellular organelles and components like mitochondria and Ca2+ buffers too. Here, we present some mathematical models and results of recent research on intracellular Ca2+ waves generated by the inositol 1,4,5-trisphosphate receptor channel including the modeling of Calcium induced Calcium release, buffer dynamics, impact of mitochondria on wave formation and the effect of the spatial discreteness of the channels releasing Ca2+. Modeling of the communication of Ca2+ waves to adjacent cells through gap junctions concludes this report.

  16. Low-molecular-weight (4.5S) ribonucleic acid in higher-plant chloroplast ribosomes.

    PubMed Central

    Whitfeld, P R; Leaver, C J; Bottomley, W; Atchison, B

    1978-01-01

    A species of RNA that migrates on 10% (w/v) polyacrylamide gels between 5S and 4S RNA was detected in spinach chloroplasts. This RNA (referred to as 4.5 S RNA) was present in amounts equimolar to the 5S RNA and its molecular weight was estimated to be approx. 33 000. Fractionation of the chloroplast components showed that the 4.5S RNA was associated with the 50 S ribosomal subunit and that it could be removed by washing the ribosomes with a buffer containing 0.01 M-EDTA and 0.5 M-KCl. It did not appear to be a cleavage product of the labile 23 S RNA of spinach chloroplast ribosomes. When 125I-labelled 4.5 S RNA was hybridized to fragments of spinach chloroplast DNA produced by SmaI restriction endonuclease, a single fragment (mol.wt. 1.15 times 10(6)) became labelled. The same DNA fragment also hybridized to chloroplast 5 S RNA and part of the 23 S RNA. It was concluded that the coding sequence for 4.5 S RNA was part of, or immediately adjacent to, the rRNA-gene region in chloroplast DNA . A comparable RNA species was observed in chloroplasts of tobacco and pea leaves. Images Fig. 8. PMID:743229

  17. Tissue distribution and metabolism of the putative cancer chemopreventive agent 3',4',5'-trimethoxyflavonol (TMFol) in mice.

    PubMed

    Saad, Shaban E A; Jones, Donald J L; Norris, Leonie M; Horner-Glister, Emma; Patel, Ketan R; Britton, Robert G; Steward, William P; Gescher, Andreas J; Brown, Karen; Sale, Stewart

    2012-12-01

    3',4',5'-Trimethoxyflavonol (TMFol) is a synthetic flavonol with preclinical cancer chemopreventive properties. The hypothesis was tested that, in mice, p.o. administration of TMFol results in measureable levels of the parent in target tissues. A single oral dose (240 mg/kg) was administered to mice (n = 4 per time point) with time points ranging from 5 to 1440 min. TMFol and its metabolites were identified and quantitated in all tissues by high-performance liquid chromatography (HPLC). Plasma levels of TMFol were at the limit of quantification or below, although metabolites were identified. Peak levels of TMFol in the gastrointestinal tract and the prostate averaged 1671 ± 265 µg/g (5.3 µmol/g) and 6.0 ± 1.6 µg/g (18.4 nmol/g), and occurred 20 and 360 min post-dose, respectively. The area under the tissue concentration-time curve (AUC) for TMFol was greater than those of the metabolites, indicating that TMFol is relatively metabolically stable. Micromolar TMFol levels are easily achieved in the prostate and gastrointestinal tract, suggesting that TMFol might exert chemopreventive efficacy at these tissue sites. Further investigations are warranted to elucidate the potential chemopreventive potency of TMFol. PMID:22454297

  18. Gliotoxin Suppresses Macrophage Immune Function by Subverting Phosphatidylinositol 3,4,5-Trisphosphate Homeostasis

    PubMed Central

    Schlam, Daniel; Canton, Johnathan; Carreño, Marvin; Kopinski, Hannah; Freeman, Spencer A.; Grinstein, Sergio

    2016-01-01

    ABSTRACT Aspergillus fumigatus, an opportunistic fungal pathogen, spreads in the environment by releasing numerous conidia that are capable of reaching the small alveolar airways of mammalian hosts. In otherwise healthy individuals, macrophages are responsible for rapidly phagocytosing and eliminating these conidia, effectively curbing their germination and consequent invasion of pulmonary tissue. However, under some circumstances, the fungus evades phagocyte-mediated immunity and persists in the respiratory tree. Here, we report that A. fumigatus escapes macrophage recognition by strategically targeting phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] metabolism through gliotoxin, a potent immunosuppressive mycotoxin. Time-lapse microscopy revealed that, in response to the toxin, macrophages cease to ruffle, undergo abrupt membrane retraction, and fail to phagocytose large targets effectively. Gliotoxin was found to prevent integrin activation and interfere with actin dynamics, both of which are instrumental for phagocytosis; similar effects were noted in immortalized and primary phagocytes. Detailed studies of the underlying molecular mechanisms of toxicity revealed that inhibition of phagocytosis is attributable to impaired accumulation of PtdIns(3,4,5)P3 and the associated dysregulation of downstream effectors, including Rac and/or Cdc42. Strikingly, in response to the diacylglycerol mimetic phorbol 12-myristate 13-acetate, gliotoxin-treated macrophages reactivate beta integrins, reestablish actin dynamics, and regain phagocytic capacity, despite the overt absence of plasmalemmal PtdIns(3,4,5)P3. Together, our findings identify phosphoinositide metabolism as a critical upstream target of gliotoxin and also indicate that increased diacylglycerol levels can bypass the requirement for PtdIns(3,4,5)P3 signaling during membrane ruffling and phagocytosis. PMID:27048806

  19. Ca(2+) signals mediated by Ins(1,4,5)P(3)-gated channels in rat ureteric myocytes.

    PubMed Central

    Boittin, F X; Coussin, F; Morel, J L; Halet, G; Macrez, N; Mironneau, J

    2000-01-01

    Localized Ca(2+)-release signals (puffs) and propagated Ca(2+) waves were characterized in rat ureteric myocytes by confocal microscopy. Ca(2+) puffs were evoked by photorelease of low concentrations of Ins(1,4,5)P(3) from a caged precursor and by low concentrations of acetylcholine; they were also observed spontaneously in Ca(2+)-overloaded myocytes. Ca(2+) puffs showed some variability in amplitude, time course and spatial spread, suggesting that Ins(1,4,5)P(3)-gated channels exist in clusters containing variable numbers of channels and that within these clusters a variable number of channels can be recruited. Immunodetection of Ins(1,4,5)P(3) receptors revealed the existence of several spots of fluorescence in the confocal cell sections, supporting the existence of clusters of Ins(1,4,5)P(3) receptors. Strong Ins(1,4,5)P(3) photorelease and high concentrations of acetylcholine induced Ca(2+) waves that originated from an initiation site and propagated in the whole cell by spatial recruitment of neighbouring Ca(2+)-release sites. Both Ca(2+) puffs and Ca(2+) waves were blocked selectively by intracellular applications of heparin and an anti-Ins(1,4,5)P(3)-receptor antibody, but were unaffected by ryanodine and intracellular application of an anti-ryanodine receptor antibody. mRNAs encoding for the three subtypes of Ins(1,4,5)P(3) receptor and subtype 3 of ryanodine receptor were detected in these myocytes, and the maximal binding capacity of [(3)H]Ins(1,4,5)P(3) was 10- to 12-fold higher than that of [(3)H]ryanodine. These results suggest that Ins(1,4,5)P(3)-gated channels mediate a continuum of Ca(2+) signalling in smooth-muscle cells expressing a high level of Ins(1,4,5)P(3) receptors and no subtypes 1 and 2 of ryanodine receptors. PMID:10861244

  20. Specific binding sites for inositol 1,3,4,5-tetrakisphosphate are located predominantly in the plasma membranes of human platelets.

    PubMed Central

    Cullen, P J; Patel, Y; Kakkar, V V; Irvine, R F; Authi, K S

    1994-01-01

    In the present study we describe the characterization and localization of Ins(1,3,4,5)P4-binding sites in human platelet membranes. Specific binding sites for Ins(1,3,4,5)P4 have been identified on mixed, plasma and intracellular membranes from neuraminidase-treated platelets using highly purified carrier-free [32P]Ins(1,3,4,5)P4. The displacement of Ins(1,3,4,5)P4 from these sites by Ins(1,4,5)P3 and InsP6 occurs at greater than two orders of magnitude higher concentrations and with Ins(1,3,4,5,6)P5 at about 40-fold higher concentrations than with Ins(1,3,4,5)P4. The membranes were further separated by free-flow electrophoresis into plasma and intracellular membranes. The Ins(1,3,4,5)P4-binding sites separated with plasma membranes, and showed similar affinities and specificities as mixed membranes, whereas Ins(1,4,5)P3-binding sites were predominantly in the intracellular membranes. These results suggest a predominantly plasma membrane location for putative Ins(1,3,4,5)P4 receptors in human platelets. PMID:8141791

  1. Metal complexes of 4,5-dimethylpyrazole-3-carboxaldehyde phenylthiosemicarbazone

    NASA Astrophysics Data System (ADS)

    El-Dissouky, Ali

    Several new transition metal complexes derived from 4,5-dimethyl-3-carboxaldehyde phenyl- thiosemicarbazone, LH, have been synthesized. The complexes are of stoichiometry, [CoL 2]X, X = Cl -, Br -, ClO -4 or NO -3, [MnL 2] and [CuX nL m], X = Cl -, Br -, NCS - or N -3; n = 1 or 0; m = 1 or 2 and L = the anion of LH. All complexes have been characterized by elemental analysis, spectral (i.r., electronic, NMR, ESR) and magnetic measurements. The ligand acts as tridentate monobasic co-ordinated to the metal ion via azomethine, pyrazole (N 2) nitrogen atoms and the thiolo-sulphur. The ligand field and ESR parameters are used to interpret the nature of bonding of LH with the metal ion, ground state and the ligand field strength of LH and the various co-ordinated simple ions. The coupling constants of various co-ordinated nuclei with copper (II) are estimated from ESR spectra of copper (II) complexes.

  2. Intracellular calcium channels: inositol-1,4,5-trisphosphate receptors

    PubMed Central

    Fedorenko, Olena A.; Popugaeva, Elena; Enomoto, Masahiro; Stathopulos, Peter B.; Ikura, Mitsuhiko; Bezprozvanny, Ilya

    2014-01-01

    The inositol-1,4,5-trisphosphate receptors (InsP3Rs) are the major intracellular Ca2+-release channels in cells. Activity of InsP3Rs is essential for elementary and global Ca2+ events in the cell. There are three InsP3Rs isoforms that are present in mammalian cells. In this review review we will focus primarily on InsP3R type 1. The InsP3R1 is a predominant isoform in neurons and it is most extensively studied isoform. Combination of biophysical and structural methods revealed key mechanisms of InsP3R function and modulation. Cell biological and biochemical studies lead to identification of a large number of InsP3R-binding proteins. InsP3Rs are involved in the regulation of numerous physiological processes, including learning and memory, proliferation, differentiation, development and cell death. Malfunction of InsP3R1 play a role in a number of neurodegenerative disorders and other disease states. InsP3Rs represent a potentially valuable drug target for treatment of these disorders and for modulating activity of neurons and other cells. Future studies will provide better understanding of physiological functions of InsP3Rs in health and disease. PMID:24300389

  3. 4.5-kW Hall Effect Thruster Evaluated

    NASA Technical Reports Server (NTRS)

    Mason, Lee S.

    2000-01-01

    As part of an Interagency Agreement with the Air Force Research Lab (AFRL), a space simulation test of a Russian SPT 140 Hall Effect Thruster was completed in September 1999 at Vacuum Facility 6 at the NASA Glenn Research Center at Lewis Field. The thruster was subjected to a three-part test sequence that included thrust and performance characterization, electromagnetic interference, and plume contamination. SPT 140 is a 4.5-kW thruster developed under a joint agreement between AFRL, Atlantic Research Corp, and Space Systems/Loral, and was manufactured by the Fakal Experimental Design Bureau of Russia. All objectives were satisfied, and the thruster performed exceptionally well during the 120-hr test program, which comprised 33 engine firings. The Glenn testing provided a critical contribution to the thruster development effort, and the large volume and high pumping speed of this vacuum facility was key to the test s success. The low background pressure (1 10 6 torr) provided a more accurate representation of space vacuum than is possible in most vacuum chambers. The facility had been upgraded recently with new cryogenic pumps and sputter shielding to support the active electric propulsion program at Glenn. The Glenn test team was responsible for all test support equipment, including the thrust stand, power supplies, data acquisition, electromagnetic interference measurement equipment, and the contamination measurement system.

  4. Performance of three 4. 5 m dipoles for SSC reference design D

    SciTech Connect

    Dahl, P.; Cottingham, J.; Fernow, R.; Garber, M.; Ghosh, A.; Goodzeit, C.; Greene, A.; Herrera, J.; Kahn, S.; Kelly, E.

    1985-01-01

    Three 4.5 m long dipoles for Reference Design D of the proposed Superconducting Super Collider have been successfully tested. The magnets are cold-iron (and cold bore) 1-in-1 dipoles, wound with current density-graded high homogeneity NbTi cable in a two-layer cos theta coil of 40 mm inner diameter. The coil is prestressed by 15 mm wide stainless steel collars, and mounted in a circular, split iron yoke of 267 mm outer diameter, supported in a cylindrical yoke containment vessel. At 4.5 K the magnets reached a field of about 6.6T with little training, or the short sample limit of the conductor, and in subcooled (2.6 to 2.4 K) liquid, 8T was achieved. The allowed harmonics were close to the predicted values, and the unallowed harmonics small. The sextupole trim coil operated at eight times the required current without training.

  5. Understanding the O4,5 edge structure of actinide metals

    SciTech Connect

    Butterfield, M; Moore, K; der Laan, G v; Wall, M; Haire, D

    2007-12-12

    Using electron energy-loss spectroscopy (EELS) and many-electron atomic spectral calculations, we examine the O{sub 4,5} (5d {yields} 5f) edge structure of the ground-state {alpha} phase of Th, U, Np, Pu, Am, and Cm metal. Results show that the dipole-allowed transitions are contained within the giant resonance and that the small pre-peak in the actinide 5d {yields} 5f transition should not be labeled the O{sub 5} peak, but rather the {Delta}S=1 peak. Lastly, we present for the first time the O{sub 4,5} EELS spectra for Np, Am, and Cm metal.

  6. A novel DNA intercalator, butylamino-pyrimido[4',5':4,5]selenolo(2,3-b)quinoline, induces cell cycle arrest and apoptosis in leukemic cells.

    PubMed

    Shahabuddin, M S; Nambiar, Mridula; Choudhary, Bibha; Advirao, Gopal M; Raghavan, Sathees C

    2010-02-01

    DNA intercalators are one of the most commonly used chemotherapeutic agents. Novel intercalating compounds of pyrimido[4',5':4,5]selenolo(2,3-b)quinoline series having a butylamino or piperazino group at fourth position (BPSQ and PPSQ, respectively) are studied. Our results showed that BPSQ induced cytotoxicity whereas PPSQ was cytostatic. The cytotoxicity induced by BPSQ was concentration- and time-dependent. Cell cycle analysis and tritiated thymidine assay revealed that BPSQ affects the cell cycle progression by arresting at S phase. The absence of p-histone H3 and reduction in the levels of PCNA in the cells treated with BPSQ further confirmed the cell cycle arrest. Further, annexin V staining, DNA fragmentation, nuclear condensation and changes in the expression levels of BCL2/BAD confirmed the activation of apoptosis. Activation of caspase 8 and lack of cleavage of caspase 9, caspase 3 and PARP suggest the possibility of BPSQ triggering extrinsic pathway for induction of apoptosis, which is discussed. Hence, we have identified a novel compound which would have clinical relevance in cancer chemotherapeutics. PMID:19142583

  7. Trading Accountability for Greater Flexibility.

    ERIC Educational Resources Information Center

    Sanders, Ted

    1991-01-01

    Describes the plight of two risk-taking principals who drastically improved their schools' academic performance, only to be defeated by bureaucratic regulations and business-as-usual attitudes. Allowing schools greater flexibility in exchange for increased accountability will free talented teachers and principals to restructure schools and solve…

  8. Paleotectonic and paleogeographic evolution of greater China

    SciTech Connect

    Yilmaz, P.O.; Norton, I.O.

    1996-12-31

    In this study, we utilize plate tectonic history of Central Asia to constrain understanding of sedimentary basin development and to show how regional scale tectonic events affect play elements for major basins of greater China. Tectonic framework and paleogeography are used as a constraint on models for basin formation, climate distribution and accommodation which in turn control distribution of reservoir, source, seal and trap. Greater China is an artifact of Phanerozoic tectonics. It has a protracted history of continental deformation as amalgamation of crustal blocks and island arc/subduction and accretion complexes occurred. Early Paleozoic hydrocarbon systems are dominated by extensive carbonate platform and Permian and younger systems are dominated by continental and lacustrine sedimentation. The basement of greater China consists of continental and accretion crust. The crustal blocks include South and North China, Indochina, Tibet and Tarim, and accretion blocks include the Altaids and Manchurides. The relative positions and interactions of these blocks during Paleozic and Mesozoic time resulted in formation of greater China. Final amalgamation and deformation occurred in Eocene time when India collided with Asia. The discussions consist of presentation of a model for tectonic evolution of these blocks and their paleogeography through Phanerozoic time. This is done with maps at 1:8 million scale covering nine time slices, three in the Paleozoic, three in the Mesozoic and three in the Cenozoic.

  9. Paleotectonic and paleogeographic evolution of greater China

    SciTech Connect

    Yilmaz, P.O.; Norton, I.O. )

    1996-01-01

    In this study, we utilize plate tectonic history of Central Asia to constrain understanding of sedimentary basin development and to show how regional scale tectonic events affect play elements for major basins of greater China. Tectonic framework and paleogeography are used as a constraint on models for basin formation, climate distribution and accommodation which in turn control distribution of reservoir, source, seal and trap. Greater China is an artifact of Phanerozoic tectonics. It has a protracted history of continental deformation as amalgamation of crustal blocks and island arc/subduction and accretion complexes occurred. Early Paleozoic hydrocarbon systems are dominated by extensive carbonate platform and Permian and younger systems are dominated by continental and lacustrine sedimentation. The basement of greater China consists of continental and accretion crust. The crustal blocks include South and North China, Indochina, Tibet and Tarim, and accretion blocks include the Altaids and Manchurides. The relative positions and interactions of these blocks during Paleozic and Mesozoic time resulted in formation of greater China. Final amalgamation and deformation occurred in Eocene time when India collided with Asia. The discussions consist of presentation of a model for tectonic evolution of these blocks and their paleogeography through Phanerozoic time. This is done with maps at 1:8 million scale covering nine time slices, three in the Paleozoic, three in the Mesozoic and three in the Cenozoic.

  10. Molecular Determinants of Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Binding to Transient Receptor Potential V1 (TRPV1) Channels*

    PubMed Central

    Poblete, Horacio; Oyarzún, Ingrid; Olivero, Pablo; Comer, Jeffrey; Zuñiga, Matías; Sepulveda, Romina V.; Báez-Nieto, David; González Leon, Carlos; González-Nilo, Fernando; Latorre, Ramón

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) has been recognized as an important activator of certain transient receptor potential (TRP) channels. More specifically, TRPV1 is a pain receptor activated by a wide range of stimuli. However, whether or not PI(4,5)P2 is a TRPV1 agonist remains open to debate. Utilizing a combined approach of mutagenesis and molecular modeling, we identified a PI(4,5)P2 binding site located between the TRP box and the S4-S5 linker. At this site, PI(4,5)P2 interacts with the amino acid residues Arg-575 and Arg-579 in the S4-S5 linker and with Lys-694 in the TRP box. We confirmed that PI(4,5)P2 behaves as a channel agonist and found that Arg-575, Arg-579, and Lys-694 mutations to alanine reduce PI(4,5)P2 binding affinity. Additionally, in silico mutations R575A, R579A, and K694A showed that the reduction in binding affinity results from the delocalization of PI(4,5)P2 in the binding pocket. Molecular dynamics simulations indicate that PI(4,5)P2 binding induces conformational rearrangements of the structure formed by S6 and the TRP domain, which cause an opening of the lower TRPV1 channel gate. PMID:25425643

  11. Bison in the greater Yellowstone

    USGS Publications Warehouse

    Meagher, Mary

    1994-01-01

    In the Greater Yellowstone Area, free-ranging bison occur in Jackson Hole, Wyoming, and Yellowstone National Park. The Yellowstone population is discussed, with emphasis on changes in numbers from approximately 400 in 1968 to about 3500 now. Major influences for change initially were natural; more recently the winter road system used by snowmobiles appeared to be the dominant factor. The situation is in a state of flux. Interagency planning is in progress to address management alternatives for conflicts outside the park.

  12. GATA4-mediated cardiac hypertrophy induced by D-myo-inositol 1,4,5-tris-phosphate

    SciTech Connect

    Zhu Zhiming . E-mail: zhuzming@mail.dph-fsi.com; Zhu Shanjun; Liu Daoyan; Yu Zengping; Yang Yongjian; Giet, Markus van der; Tepel, Martin . E-mail: Martin.Tepel@charite.de

    2005-12-16

    We evaluated the effects of D-myo-inositol 1,4,5-tris-phosphate on cardiac hypertrophy. D-myo-inositol 1,4,5-tris-phosphate augmented cardiac hypertrophy as evidenced by its effects on DNA synthesis, protein synthesis, and expression of immediate-early genes c-myc and c-fos, {beta}-myosin heavy chain, and {alpha}-actin. The administration of D-myo-inositol 1,4,5-tris-phosphate increased the expression of nuclear factor of activated T-cells and cardiac-restricted zinc finger transcription factor (GATA4). Real-time quantitative RT-PCR showed that D-myo-inositol 1,4,5-tris-phosphate-induced GATA4 mRNA was significantly enhanced even in the presence of the calcineurin inhibitor, cyclosporine A. The effect of D-myo-inositol 1,4,5-tris-phosphate was blocked after inhibition of inositol-trisphosphate receptors but not after inhibition of c-Raf/mitogen-activated protein kinase kinase (MEK)/mitogen-activated protein kinase (ERK) or p38 mitogen-activated protein kinase pathways. The study shows that D-myo-inositol 1,4,5-tris-phosphate-induced cardiac hypertrophy is mediated by GATA4 but independent from the calcineurin pathway.

  13. Ion channel regulation by phosphoinositides analyzed with VSPs—PI(4,5)P2 affinity, phosphoinositide selectivity, and PI(4,5)P2 pool accessibility

    PubMed Central

    Rjasanow, Alexandra; Leitner, Michael G.; Thallmair, Veronika; Halaszovich, Christian R.; Oliver, Dominik

    2015-01-01

    The activity of many proteins depends on the phosphoinositide (PI) content of the membrane. E.g., dynamic changes of the concentration of PI(4,5)P2 are cellular signals that regulate ion channels. The susceptibility of a channel to such dynamics depends on its affinity for PI(4,5)P2. Yet, measuring affinities for endogenous PIs has not been possible directly, but has relied largely on the response to soluble analogs, which may not quantitatively reflect binding to native lipids. Voltage-sensitive phosphatases (VSPs) turn over PI(4,5)P2 to PI(4)P when activated by depolarization. In combination with voltage-clamp electrophysiology VSPs are useful tools for rapid and reversible depletion of PI(4,5)P2. Because cellular PI(4,5)P2 is resynthesized rapidly, steady state PI(4,5)P2 changes with the degree of VSP activation and thus depends on membrane potential. Here we show that titration of endogenous PI(4,5)P2 with Ci-VSP allows for the quantification of relative PI(4,5)P2 affinities of ion channels. The sensitivity of inward rectifier and voltage-gated K+ channels to Ci-VSP allowed for comparison of PI(4,5)P2 affinities within and across channel subfamilies and detected changes of affinity in mutant channels. The results also reveal that VSPs are useful only for PI effectors with high binding specificity among PI isoforms, because PI(4,5)P2 depletion occurs at constant overall PI level. Thus, Kir6.2, a channel activated by PI(4,5)P2 and PI(4)P was insensitive to VSP. Surprisingly, despite comparable PI(4,5)P2 affinity as determined by Ci-VSP, the Kv7 and Kir channel families strongly differed in their sensitivity to receptor-mediated depletion of PI(4,5)P2. While Kv7 members were highly sensitive to activation of PLC by Gq-coupled receptors, Kir channels were insensitive even when PI(4,5)P2 affinity was lowered by mutation. We hypothesize that different channels may be associated with distinct pools of PI(4,5)P2 that differ in their accessibility to PLC and VSPs. PMID

  14. DRINKING WATER CRITERIA DOCUMENT FOR 2(2,4,5-TRICHLOROPHENOXY)PROPIONIC ACID (2,4,5-TP) (FINAL DRAFT)

    EPA Science Inventory

    The Office of Drinking Water (ODW), U.S. Environmental Protection Agency has prepared a Drinking Water Criteria Document on 2,4,5-TP. This Criteria Document is an extensive review of the following topics: Physical and chemical properties of 2,4,5-TP; Toxicokinetics and human expo...

  15. Synthesis of pyrimido[4,5-c]azepine- and pyrimido[4,5-c]oxepine-based γ-secretase modulators.

    PubMed

    Wu, Yong-Jin; Zhang, Yunhui; Toyn, Jeremy H; Macor, John E; Thompson, Lorin A

    2016-03-15

    This Letter describes an efficient ring-closing metathesis approach to 2-chloro-4-amino-pyrimido[4,5-c]azepines and 2-chloro-4-amino-pyrimido[4,5-c]oxepines. These chlorides were applied to the synthesis of several potent γ-secretase modulators (GSMs). PMID:26898338

  16. DISTRIBUTION OF 2,4,5-TRICHLOROPHENOXYACETIC ACID IN THE MOUSE FETUS

    EPA Science Inventory

    The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) readily crosses the placenta in the mouse on gestational day 13. Concentrations of 2,4,5-T in maternal tissues and fetuses were obvious at 30 min., highest at 8 h, diminished by 24 h and almost entirely eliminated by 48 h....

  17. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 39 Postal Service 1 2012-07-01 2012-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  18. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  19. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  20. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  1. 39 CFR 4.5 - Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Assistant Postmasters General, General Counsel, Judicial Officer, Chief Postal Inspector. 4.5 Section 4.5 Postal Service UNITED STATES POSTAL SERVICE THE BOARD OF GOVERNORS OF THE U.S. POSTAL SERVICE OFFICIALS (ARTICLE IV) § 4.5 Assistant Postmasters...

  2. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  3. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  4. 42 CFR 4.5 - Use of materials from the collections.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Use of materials from the collections. 4.5 Section 4.5 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS NATIONAL LIBRARY OF MEDICINE § 4.5 Use of materials from the collections. (a) Unrestricted...

  5. [Autoerotic fatalities in Greater Dusseldorf].

    PubMed

    Hartung, Benno; Hellen, Florence; Borchard, Nora; Huckenbeck, Wolfgang

    2011-01-01

    Autoerotic fatalities in the Greater Dusseldorf area correspond to the relevant medicolegal literature. Our results included exclusively young to middle-aged, usually single men who were found dead in their city apartments. Clothing and devices used showed a great variety. Women's or fetish clothing and complex shackling or hanging devices were disproportionately frequent. In most cases, death occurred due to hanging or ligature strangulation. There was no increased incidence of underlying psychiatric disorders. In most of the deceased no or at least no remarkable alcohol intoxication was found. Occasionally, it may be difficult to reliably differentiate autoerotic accidents, accidents occurring in connection with practices of bondage & discipline, dominance & submission (BDSM) from natural death, suicide or homicide. PMID:22039693

  6. Control of diverse subcellular processes by a single multi-functional lipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2].

    PubMed

    Kolay, Sourav; Basu, Urbashi; Raghu, Padinjat

    2016-06-15

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a multi-functional lipid that regulates several essential subcellular processes in eukaryotic cells. In addition to its well-established function as a substrate for receptor-activated signalling at the plasma membrane (PM), it is now recognized that distinct PI(4,5)P2 pools are present at other organelle membranes. However, a long-standing question that remains unresolved is the mechanism by which a single lipid species, with an invariant functional head group, delivers numerous functions without loss of fidelity. In the present review, we summarize studies that have examined the molecular processes that shape the repertoire of PI(4,5)P2 pools in diverse eukaryotes. Collectively, these studies indicate a conserved role for lipid kinase isoforms in generating functionally distinct pools of PI(4,5)P2 in diverse metazoan species. The sophistication underlying the regulation of multiple functions by PI(4,5)P2 is also shaped by mechanisms that regulate its availability to enzymes involved in its metabolism as well as molecular processes that control its diffusion at nanoscales in the PM. Collectively, these mechanisms ensure the specificity of PI(4,5)P2 mediated signalling at eukaryotic membranes. PMID:27288030

  7. Potential GPS user architecture for the NASA Space Station based on Landsat 4/5 experience

    NASA Technical Reports Server (NTRS)

    Korenstein, David A.

    1987-01-01

    A Landsat 4/5 GPS system is described which uses an inertial reference attitude control system and precision real-time ephemeris generation to achieve precision earth pointing. The system has application to the validation of the use of GPS for the low earth orbit navigation of the Space Station. The present system consists of a receiver/processor assembly (R/PA), an L-band GPS antenna, a precision oscillator, and the Landsat computer. The R/PA is integrated with a GPS receiver which selects, acquires, tracks, times, and decodes navigation signals from GPS satellites in order to derive ephemerides. Ephemeris estimates were found to be accurate to better than 50 meters.

  8. International Space Station Increment-4/5 Microgravity Environment Summary Report

    NASA Technical Reports Server (NTRS)

    Jules, Kenol; Hrovat, Kenneth; Kelly, Eric; McPherson, Kevin; Reckart, Timothy

    2003-01-01

    This summary report presents the results of some of the processed acceleration data measured aboard the International Space Station during the period of December 2001 to December 2002. Unlike the past two ISS Increment reports, which were increment specific, this summary report covers two increments: Increments 4 and 5, hereafter referred to as Increment-4/5. Two accelerometer systems were used to measure the acceleration levels for the activities that took place during Increment-4/5. Due to time constraint and lack of precise timeline information regarding some payload operations and station activities, not a11 of the activities were analyzed for this report. The National Aeronautics and Space Administration sponsors the Microgravity Acceleration Measurement System and the Space Acceleration Microgravity System to support microgravity science experiments which require microgravity acceleration measurements. On April 19, 2001, both the Microgravity Acceleration Measurement System and the Space Acceleration Measurement System units were launched on STS-100 from the Kennedy Space Center for installation on the International Space Station. The Microgravity Acceleration Measurement System supports science experiments requiring quasi-steady acceleration measurements, while the Space Acceleration Measurement System unit supports experiments requiring vibratory acceleration measurement. The International Space Station Increment-4/5 reduced gravity environment analysis presented in this report uses acceleration data collected by both sets of accelerometer systems: The Microgravity Acceleration Measurement System, which consists of two sensors: the low-frequency Orbital Acceleration Research Experiment Sensor Subsystem and the higher frequency High Resolution Accelerometer Package. The low frequency sensor measures up to 1 Hz, but is routinely trimmean filtered to yield much lower frequency acceleration data up to 0.01 Hz. This filtered data can be mapped to arbitrary

  9. INTRAMOLECULAR MOTION AND REORIENTATIONAL BARRIERS IN 9-FLUORENONE, 4-METHYL-9-FLUORENONE AND 4,5-DIMETHYL-9-FLUORENONE

    EPA Science Inventory

    Carbon-13 nuclear magnetic resonance spin-lattice relaxation times and nuclear Overhauser enhancements were measured as functions of temperature for the hydrogen-bearing carbons in 9-fluorenone, 4-methyl-9-fluorenone, and 4,5-dimethyl-9-fluorenone. Reorientational diffusion const...

  10. Adsorption and photodegradation kinetics of herbicide 2,4,5-trichlorophenoxyacetic acid with MgFeTi layered double hydroxides.

    PubMed

    Nguyen, Thi Kim Phuong; Beak, Min-wook; Huy, Bui The; Lee, Yong-Ill

    2016-03-01

    The calcined layered double hydroxides (cLDHs) Ti-doped and undoped MgFe for this study were prepared by co-precipitation method followed by calcination at 500 °C. The as-prepared samples were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Brunauer Emmett Teller (BET) and UV-Vis diffuse reflectance spectrum (DRS) techniques and tested for adsorption and photodegradation (including photocatalytic and photo-Fenton-like) of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in aqueous solutions under visible light irradiation. In the range of studied operating conditions, the as-prepared samples exhibited excellent photo-Fenton-like activity, leading to more than 80-95% degradation of 2,4,5-T at initial concentration of 100 mg L(-1) with 4 g calcined LDHs per liter, was accomplished in 360 min, while 2,4,5-T half-life time was as short as 99-182 min. The kinetics of adsorption and photodegradation of 2,4,5-T were also discussed. These results offered a green, low cost and high efficiency photocatalyst for environmental remediation. PMID:26706931

  11. Analysis of Phosphatidylinositol-4,5-Bisphosphate Signaling in Cerebellar Purkinje Spines

    PubMed Central

    Brown, Sherry-Ann; Morgan, Frank; Watras, James; Loew, Leslie M.

    2008-01-01

    A 3D model was developed and used to explore dynamics of phosphatidylinositol-4,5-bisphosphate (PIP2) signaling in cerebellar Purkinje neurons. Long-term depression in Purkinje neurons depends on coincidence detection of climbing fiber stimulus evoking extracellular calcium flux into the cell and parallel fiber stimulus evoking inositol-1,4,5-trisphosphate (IP3)-meditated calcium release from the endoplasmic reticulum. Experimental evidence shows that large concentrations of IP3 are required for calcium release. This study uses computational analysis to explore how the Purkinje cell provides sufficient PIP2 to produce large amounts of IP3. Results indicate that baseline PIP2 concentration levels in the plasma membrane are inadequate, even if the model allows for PIP2 replenishment by lateral diffusion from neighboring dendrite membrane. Lateral diffusion analysis indicates apparent anomalous diffusion of PIP2 in the spiny dendrite membrane, due to restricted diffusion through spine necks. Stimulated PIP2 synthesis and elevated spine PIP2 mediated by a local sequestering protein were explored as candidate mechanisms to supply sufficient PIP2. Stimulated synthesis can indeed lead to high IP3 amplitude of long duration; local sequestration produces high IP3 amplitude, but of short duration. Simulation results indicate that local sequestration could explain the experimentally observed finely tuned timing between parallel fiber and climbing fiber activation. PMID:18487300

  12. Effects of Solution Heat Treatment on Microstructure and Mechanical Properties of the Mg-4.5Zn-4.5Sn-2Al-0.6Sr Alloy

    NASA Astrophysics Data System (ADS)

    Zhang, Guanghao; Chen, Jihua; Yan, Hongge; Su, Bin

    2014-11-01

    Microstructure and mechanical properties of the Mg-4.5Zn-4.5Sn-2Al-0.6Sr alloy are investigated both in the as-cast condition and after the different three-step solution heat treatments (a solution heat treatment of 310 °C × 4 h + 340 °C × 28 h followed by a high-temperature solution treatment) to explore the optimal solution treatment cycle. The as-cast alloy contains a microstructure consisting of the α-Mg matrix, Mg2Sn, Mg51Zn20, Mg32(Al, Zn)49, and MgSnSr phases. After the solution heat treatment, all the Mg51Zn20, the Mg32(Al, Zn)49 phases, and most of the Mg2Sn phase are dissolved into the matrix, only the MgSnSr phase and a minority of the Mg2Sn phase are remained in the granular form or the fine dot-like. The volume fraction of the residual second phases decreases from 5.61 to 1.84% with the increasing solution time from 0 to 4 h at 420 °C and it decreases from 2.9 to 0.4% with the increasing solution temperature from 420 to 480 °C for 2 h. The alloy that experiences the solution treatment of 310 °C × 4 h + 340 °C × 28 h + 460 °C × 2 h exhibits the highest strength and the best plasticity among all the solution-treated alloys. Therefore, the optimal solution treatment is 310 °C × 4 h + 340 °C × 28 h + 460 °C × 2 h. The residual second phases in the alloy that experiences the optimal solution treatment are confirmed to be the Mg2Sn phase and the MgSnSr phase which are related to their relatively high thermal stability. The ultimate tensile strength and the elongation to rupture of the as-solutionized alloy are 238 MPa and 12%, respectively, about 25 MPa and 2.4% higher than the counterparts of the as-cast alloy.

  13. n-3 polyunsaturated fatty acids suppress CD4(+) T cell proliferation by altering phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P2] organization.

    PubMed

    Hou, Tim Y; Barhoumi, Rola; Fan, Yang-Yi; Rivera, Gonzalo M; Hannoush, Rami N; McMurray, David N; Chapkin, Robert S

    2016-01-01

    The mechanisms by which n-3 polyunsaturated fatty acids (n-3 PUFA), abundant in fish oil, exert their anti-inflammatory effects have not been rigorously defined. We have previously demonstrated that n-3 PUFA decrease the amount of phosphatidylinositol-(4,5)-bisphosphate, [PI(4,5)P2], in CD4(+) T cells, leading to suppressed actin remodeling upon activation. Since discrete pools of PI(4,5)P2 exist in the plasma membrane, we determined whether n-3 PUFA modulate spatial organization of PI(4,5)P2 relative to raft and non-raft domains. We used Förster resonance energy transfer (FRET) to demonstrate that lipid raft mesodomains in the plasma membrane of CD4(+) T cells enriched in n-3 PUFA display increased co-clustering of Lck(N10) and LAT(ΔCP), markers of lipid rafts. CD4(+) T cells enriched in n-3 PUFA also exhibited a depleted plasma membrane non-raft PI(4,5)P2 pool as detected by decreased co-clustering of Src(N15), a non-raft marker, and PH(PLC-δ), a PI(4,5)P2 reporter. Incubation with exogenous PI(4,5)P2 rescued the effects on the non-raft PI(4,5)P2 pool, and reversed the suppression of T cell proliferation in CD4(+) T cells enriched with n-3 PUFA. Furthermore, CD4(+) T cells isolated from mice fed a 4% docosahexaenoic acid (DHA)-enriched diet exhibited a decrease in the non-raft pool of PI(4,5)P2, and exogenous PI(4,5)P2 reversed the suppression of T cell proliferation. Finally, these effects were not due to changes to post-translational lipidation, since n-3 PUFA did not alter the palmitoylation status of signaling proteins. These data demonstrate that n-3 PUFA suppress T cell proliferation by altering plasma membrane topography and the spatial organization of PI(4,5)P2. PMID:26476105

  14. 1H-Imidazol-4(5H)-ones and thiazol-4(5H)-ones as emerging pronucleophiles in asymmetric catalysis

    PubMed Central

    Mielgo, Antonia

    2016-01-01

    Summary Asymmetric catalysis represents a very powerful tool for the synthesis of enantiopure compounds. In this context the main focus has been directed not only to the search for new efficient chiral catalysts, but also to the development of efficient pronucleophiles. This review highlights the utility and first examples of 1H-imidazol-4(5H)-ones and thiazol-4(5H)-ones as pronucleophiles in catalytic asymmetric reactions. PMID:27340482

  15. Activationless charge transport across 4.5 to 22 nm in molecular electronic junctions

    PubMed Central

    Yan, Haijun; Bergren, Adam Johan; McCreery, Richard; Della Rocca, Maria Luisa; Martin, Pascal; Lafarge, Philippe; Lacroix, Jean Christophe

    2013-01-01

    In this work, we bridge the gap between short-range tunneling in molecular junctions and activated hopping in bulk organic films, and greatly extend the distance range of charge transport in molecular electronic devices. Three distinct transport mechanisms were observed for 4.5–22-nm-thick oligo(thiophene) layers between carbon contacts, with tunneling operative when d < 8 nm, activated hopping when d > 16 nm for high temperatures and low bias, and a third mechanism consistent with field-induced ionization of highest occupied molecular orbitals or interface states to generate charge carriers when d = 8–22 nm. Transport in the 8–22-nm range is weakly temperature dependent, with a field-dependent activation barrier that becomes negligible at moderate bias. We thus report here a unique, activationless transport mechanism, operative over 8–22-nm distances without involving hopping, which severely limits carrier mobility and device lifetime in organic semiconductors. Charge transport in molecular electronic junctions can thus be effective for transport distances significantly greater than the 1–5 nm associated with quantum-mechanical tunneling. PMID:23509271

  16. Activationless charge transport across 4.5 to 22 nm in molecular electronic junctions.

    PubMed

    Yan, Haijun; Bergren, Adam Johan; McCreery, Richard; Della Rocca, Maria Luisa; Martin, Pascal; Lafarge, Philippe; Lacroix, Jean Christophe

    2013-04-01

    In this work, we bridge the gap between short-range tunneling in molecular junctions and activated hopping in bulk organic films, and greatly extend the distance range of charge transport in molecular electronic devices. Three distinct transport mechanisms were observed for 4.5-22-nm-thick oligo(thiophene) layers between carbon contacts, with tunneling operative when d < 8 nm, activated hopping when d > 16 nm for high temperatures and low bias, and a third mechanism consistent with field-induced ionization of highest occupied molecular orbitals or interface states to generate charge carriers when d = 8-22 nm. Transport in the 8-22-nm range is weakly temperature dependent, with a field-dependent activation barrier that becomes negligible at moderate bias. We thus report here a unique, activationless transport mechanism, operative over 8-22-nm distances without involving hopping, which severely limits carrier mobility and device lifetime in organic semiconductors. Charge transport in molecular electronic junctions can thus be effective for transport distances significantly greater than the 1-5 nm associated with quantum-mechanical tunneling. PMID:23509271

  17. Hydrogeodeformation field in the Caucasus related to the preparation of Tbilisi earthquakes (M>4.5)

    NASA Astrophysics Data System (ADS)

    Aliev, A.; Bendukidze, G.; Biagi, P. F.; Chelidze, T.; Devidze, M.; Garalov, B.; Melikadze, G.; Vartanian, G.

    2003-04-01

    Here we present the relation between the variations of the underground water level in boreholes and the deformation processes associated with the occurrence of Tbilisi earthquakes with Mge4.5. The hydrogeodeformation field (HGDF) has been pointed out on the basis of the data collected in networks located in Armenia, Azerbaijan, Georgia and Russia. The boreholes are uniformly distributed in the Caucasus and they cover all the main geological blocks of the region; their depth ranges from 250 m to 3.500 m. On the basis of the water variations related to the gravity tides, a preliminary calibration of the boreholes was carried out at the purpose to evaluate the sensitivity and to normalize the hydrodynamic signals. The hydrodynamical and hydrochemical data have been processed by means of spectral analyses to separate the disturbance background field from the valid signals. The processed data cover the period 1999-2002 in which 3 earthquakes (Mge4.5) occurred in Tbilisi at December 14, 2000, January 03, 2001 and April 25, 2002. The formation of an extension zone in the eastern Caucasus and of a compression zone in the western Georgia and northern Caucasus was observed 3 months before the April 2002 earthquake. The boundary between these 2 zones was along a well known sub horizontal fault. The largest deformation gradient was observed in a zone that is the joint of deep faults. This zone is the place where the previous earthquake was generated. After the earthquake occurrence, the zone of the largest gradient migrated towards East and the residual HGDF could be considered as source of the Ujarma earthquake (August 2002). Thus, HGDF seems to indicate a migration of the deformation field along the slope of the Greater Caucasus 3 months prior the earthquake. Another observation is that before the earthquakes, when the deformation reaches its critical value, the natural pattern of tidal variations in each observation point was disturbed. The period of the perturbation (from

  18. Specific receptor for inositol-1,4,5-trisphosphate in permeabilized rabbit neutrophils

    SciTech Connect

    Bradford, P.G.; Spat, A.; Rubin, R.P.

    1986-03-05

    Neutrophil chemotaxis and degranulation are resultant, in part, from the mobilization of intracellular calcium by inositol-1,4,5-trisphosphate ((1,4,5)IP/sub 3/), one of the products of chemoattractant-stimulated phospholipase C activity. High specific activity (ca. 40 Ci/mmol) (/sup 32/P)(1,4,5)IP/sub 3/ was prepared from (..gamma..-/sup 32/P)ATP-labeled human erythrocyte ghosts and was used in binding assays with saponin-permeabilized rabbit peritoneal neutrophils. At 4/sup 0/C and in the presence of inhibitors of the IP/sub 3/ 5-phosphomonoesterase, (/sup 32/P)(1,4,5)IP/sub 3/ rapidly associated with a specific binding component which saturated within 60s. Nonspecific binding, taken as the residual binding in the presence of 10 ..mu..M (1,4,5)IP/sub 3/, was 15% of the total. No specific binding was detected using intact cells. The specific binding to permeable cells was reversible (t/sup 1/2/ approx. 60s) and could be inhibited in a dose-dependent manner by (1,4,5)IP/sub 3/ (EC/sub 50/ = 30 nM) and by other calcium mobilizing inositol phosphates ((2,4,5)IP/sub 3/) but not by inactive analogs ((1,4)IP/sub 2/, (4,5)IP/sub 2/, (1)IP). The dose-responses of (1,4,5)IP/sub 3/ and (2,4,5)IP/sub 3/ in inhibiting (/sup 32/P)(1,4,5)IP/sub 3/ specific binding correlated well with their abilities to release Ca/sup 2 +/ from nonmitochondrial vesicular stores in the same preparation of cells, suggesting that the authors have identified the physiological receptor for (1,4,5)IP/sub 3/.

  19. Implementation and comparison of a suite of heat stress metrics within the Community Land Model version 4.5

    NASA Astrophysics Data System (ADS)

    Buzan, J. R.; Oleson, K.; Huber, M.

    2014-08-01

    We implement and analyze 13 different metrics (4 moist thermodynamic quantities and 9 heat stress metrics) in the Community Land Model (CLM4.5), the land surface component of the Community Earth System Model (CESM). We call these routines the HumanIndexMod. These heat stress metrics embody three philosophical approaches: comfort, physiology, and empirically based algorithms. The metrics are directly connected to CLM4.5 BareGroundFuxesMod, CanopyFluxesMod, SlakeFluxesMod, and UrbanMod modules in order to differentiate between the distinct regimes even within one gridcell. This allows CLM4.5 to calculate the instantaneous heat stress at every model time step, for every land surface type, capturing all aspects of non-linearity in moisture-temperature covariance. Secondary modules for initialization and archiving are modified to generate the metrics as standard output. All of the metrics implemented depend on the covariance of near surface atmospheric variables: temperature, pressure, and humidity. Accurate wet bulb temperatures are critical for quantifying heat stress (used by 5 of the 9 heat stress metrics). Unfortunately, moist thermodynamic calculations for calculating accurate wet bulb temperatures are not in CLM4.5. To remedy this, we incorporated comprehensive water vapor calculations into CLM4.5. The three advantages of adding these metrics to CLM4.5 are (1) improved thermodynamic calculations within climate models, (2) quantifying human heat stress, and (3) that these metrics may be applied to other animals as well as industrial applications. Additionally, an offline version of the HumanIndexMod is available for applications with weather and climate datasets. Examples of such applications are the high temporal resolution CMIP5 archived data, weather and research forecasting models, CLM4.5 flux tower simulations (or other land surface model validation studies), and local weather station data analysis. To demonstrate the capabilities of the HumanIndexMod, we

  20. Zircon SHRIMP U-Pb dating of metamorphic complexes in the conjunction of the Greater and Lesser Xing'an ranges, NE China: Timing of formation and metamorphism and tectonic implications

    NASA Astrophysics Data System (ADS)

    Miao, Laicheng; Zhang, Fuqin; Zhu, Mingshuai; Liu, Dunyi

    2015-12-01

    Metamorphic complexes, including the Luomahu, Xinkailing and Fengshuigouhe groups, are scattered in the conjunction of the Greater and the Lesser Xing'an ranges, NE China, and have long been interpreted to represent the Precambrian basement of the so-called "Xing'an" and "Songnen" blocks although reliable evidence is lacking. Thin-section examination and mineral assemblage indicate that the protoliths of these metamorphic rocks are mainly meta-sedimentary and meta-volcanic rocks and have experienced greenschist- to amphibolite-facies metamorphism and strong deformation. Zircon SHRIMP U-Pb dating results of the metamorphic complexes and associated pre- or syn-kinematic veins constrained the formation and metamorphic ages of the Luomahuo Group at 175 ± 3 Ma and 159 ± 3 Ma, the Xingkailing Group at 200 ± 2 Ma and 158 ± 3 Ma, and the Fengshuigouhe Group at between 230-310 Ma and 170 ± 3 Ma, respectively. Additionally, all these rocks contain some Late Paleozoic detrital or inherited zircons with ages between 290-390 Ma, but no Precambrian, even if Early Paleozoic, age information was detected from these metamorphic rocks. These new data suggest that the metamorphic complexes were formed during Mesozoic-Late Paleozoic period, rather than in Precambrian as previously inferred, and that all of them underwent metamorphism and deformation during Middle Jurassic between 170-160 Ma. Consequently, these metamorphic complexes are not basement rocks of the so-called Precambrian continental blocks. Instead, there are likely metamorphosed Late Paleozoic-Mesozoic accretionary complexes and/or arc terranes. These results, in combination with published data, illustrate an overall young trend from north to south in the tectonic evolution of the northern Xing'an region. Significantly, the Jurassic (170-160 Ma) metamorphism and deformation event firstly identified by this study from the metamorphic complexes likely recorded the coinstantaneous Mongol-Okhotsk collisional and

  1. QSAR studies on 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] Pyridine derivatives as angiotensin II (AT1) receptor antagonist.

    PubMed

    Sharma, Mukesh C

    2015-06-01

    QSAR studies were performed for correlating the chemical composition of 3-(4-biphenylmethyl) 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridines bearing aryl acetic acid esters and acetamides as angiotensin II AT(1) receptor antagonist. Four different quantitative structure-property relationship (QSAR) methods namely two-dimensional (2D-QSAR), group-based QSAR, k-nearest neighbor and Pharmacophore Modeling were employed to obtain statistically significant models. The statistically significant best 2D-QSAR model having correlation coefficient r(2) = 0:8940 and cross-validated squared correlation coefficient q(2) = 0:7648 with external predictive ability of pred_r(2) = 0:8177,pred_r(2)se = 0.4119 and best group-based QSAR model having r(2) = 0:7392 and q(2) = 0:6710with pred_r(2) = 0:7503was developed by SA-principal component regression. The most predictive k-nearest neighbor model derived from the superposition of conformations has good cross-validated q(2) = 0:7637 and satisfied predictive ability r(2)_pred = 0.7143. Continuing with compounds of substituted 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine derivatives chemical feature-based pharmacophore models with lowest RMSD value (0.3292 Å) consists of two Hac (Hydrogen bond acceptor), negative ionizable, and two AroC (Aromatic) features are important for the activity. The study suggested that substitution of group at R, R 1, R 2 and Ar, and position on 4, 5-dihydro-4-oxo-3H-imidazo [4, 5-c] pyridine ring with more electronegative nature and low bulkiness are favorable for the antihypertensive activity. These theoretical results may provide a useful reference for understanding the action mechanism and designing potential angiotensin II (AT1) receptor antagonist. PMID:26215494

  2. Dynamics of receptor-operated Ca2+ currents through TRPC channels controlled via the PI(4,5)P2-PLC signaling pathway

    PubMed Central

    Mori, Masayuki X.; Itsuki, Kyohei; Hase, Hideharu; Sawamura, Seishiro; Kurokawa, Tatsuki; Mori, Yasuo; Inoue, Ryuji

    2015-01-01

    Transient receptor potential canonical (TRPC) channels are Ca2+-permeable, nonselective cation channels that carry receptor-operated Ca2+ currents (ROCs) triggered by receptor-induced, phospholipase C (PLC)-catalyzed hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Within the vasculature, TRPC channel ROCs contribute to smooth muscle cell depolarization, vasoconstriction, and vascular remodeling. However, TRPC channel ROCs exhibit a variable response to receptor-stimulation, and the regulatory mechanisms governing TRPC channel activity remain obscure. The variability of ROCs may be explained by their complex regulation by PI(4,5)P2 and its metabolites, which differentially affect TRPC channel activity. To resolve the complex regulation of ROCs, the use of voltage-sensing phosphoinositide phosphatases and model simulation have helped to reveal the time-dependent contribution of PI(4,5)P2 and the possible role of PI(4,5)P2 in the regulation of ROCs. These approaches may provide unprecedented insight into the dynamics of PI(4,5)P2 regulation of TRPC channels and the fundamental mechanisms underlying transmembrane ion flow. Within that context, we summarize the regulation of TRPC channels and their coupling to receptor-mediated signaling, as well as the application of voltage-sensing phosphoinositide phosphatases to this research. We also discuss the controversial bidirectional effects of PI(4,5)P2 using a model simulation that could explain the complicated effects of PI(4,5)P2 on different ROCs. PMID:25717302

  3. Inositol 1,4,5-trisphosphate receptor subtypes differentially recognize regioisomers of D-myo-inositol 1,4,5-trisphosphate.

    PubMed Central

    Hirata, M; Takeuchi, H; Riley, A M; Mills, S J; Watanabe, Y; Potter, B V

    1997-01-01

    The Ins(1,4,5)P3 regioisomers, Ins(1,4,6)P3 and Ins(1,3,6)P3, which can mimic the 1,4,5-arrangement on the inositol ring of Ins(1,4,5)P3, were examined for Ca2+ release by using four types of saponin-permeabilized cell possessing various abundances of receptor subtypes, with special reference to the relation of potency to receptor subtype. Ins(1,4,6)P3 and Ins(1,3,6)P3 were weak agonists in rat basophilic leukaemic cells (RBL cells), which possess predominantly subtype II receptors, with respective potencies of 1/200 and less than 1/500 that of Ins(1,4,5)P3 [the EC50 values were 0.2, 45 and more than 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively]. Similar rank order potencies were also evaluated for the displacement of [3H]Ins(1,4,5)P3 bound to RBL cell membranes by these regioisomers. However, they caused Ca2+ release from GH3 rat pituitary cells possessing predominantly subtype I receptors more potently; Ins(1,4,6)P3 and Ins(1,3,6)P3 evoked release at respective concentrations of only one-third and one-twentieth that of Ins(1,4,5)P3 (the EC50 values were 0.4, 1.2 and 8 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In COS-1 African green-monkey kidney cells, with the relative abundances of 37% of the subtype II and of 62% of the subtype III receptor, potencies of 1/40 and approx. 1/200 for Ins(1, 4,6)P3 and Ins(1,3,6)P3 respectively were exhibited relative to Ins(1,4,5)P3 (the EC50 values were 0.4, 15 and approx. 80 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). In HL-60 human leukaemic cells, in spite of the dominant presence of subtype I receptors (71%), similar respective potencies to those seen with COS-1 cells were exhibited (the EC50 values were 0.3, 15 and approx. 100 microM for Ins(1,4,5)P3, Ins(1,4,6)P3 and Ins(1,3,6)P3 respectively). These results indicate that these regioisomers are the first ligands that distinguish between receptor subtypes; the present observations are of

  4. 24 CFR 4.5 - Notice and documentation of assistance subject to section 102(a).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Notice and documentation of assistance subject to section 102(a). 4.5 Section 4.5 Housing and Urban Development Office of the Secretary, Department of Housing and Urban Development HUD REFORM ACT Accountability in the Provision of HUD...

  5. 47 CFR 4.5 - Definitions of outage, special offices and facilities, and 911 special facilities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Definitions of outage, special offices and facilities, and 911 special facilities. 4.5 Section 4.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL DISRUPTIONS TO COMMUNICATIONS Reporting Requirements for Disruptions to Communications §...

  6. 47 CFR 4.5 - Definitions of outage, special offices and facilities, and 911 special facilities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Definitions of outage, special offices and facilities, and 911 special facilities. 4.5 Section 4.5 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL DISRUPTIONS TO COMMUNICATIONS Reporting Requirements for Disruptions to Communications §...

  7. Thermodynamics of lanthanide and uranyl complexes with tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THFTCA).

    SciTech Connect

    Morss, L. R.; Nash, K. L.; Tennessee Technological Univ.

    2000-01-01

    We present the results of an investigation of the thermochemistry of the complexation of La{sup 3+} Nd{sup 3+}, Eu{sup 3+}, Dy{sup 3+}, Tm{sup 3+}, and UO{sub 2}{sup 2+} by tetrahydrofuran-2,3,4,5-tetracarboxylic acid (THFTCA). This predisposed structural analog to oxydiacetic acid (ODA) has been previously shown both to exhibit greater sensitivity to lanthanide cation radius than complexes with the unconstrained ODA and to form anomalously weak complexes with UO{sub 2}{sup 2+}. Our purpose is to interpret these observations in terms of the balance between enthalpy and entropy contributions to the overall complexation thermodynamics. Enthalpies have been calculated from titration calorimetry experiments both for the protonation of the free ligand and for the formation of selected 1:1 and 1:2 complexes in pH 2-3 acidic media (I = 0.1 M). The complexation entropies for the lanthanide complexes have been calculated using the previously reported stability constants for the MH{sub 2}L{sup +}, MHL, and M(H{sub 2}L){sup 2-}. The stability constants for the uranyl complexes have been determined by potentiometric titration and these values used to calculate the thermodynamic parameters. Complexation enthalpies for the 1:1 lanthanide-THFTCA complexes (MH{sub 2}L{sup +} species) are nearly identical to those of the lanthanide ODA complexes. Therefore, the size-selectivity observed in the lanthanide-THFTCA complexes arises from the complexation entropy. The comparative weakness of the uranyl complexes with THFTCA also is accounted for thermodynamically in the entropy term. Calculations based on an electrostatic model for complexation entropy and molecular mechanics modeling are used to help interpret the experimental results.

  8. Nonlinear finite element analysis of anular lesions in the L4/5 intervertebral disc.

    PubMed

    Little, J P; Adam, C J; Evans, J H; Pettet, G J; Pearcy, M J

    2007-01-01

    Degenerate intervertebral discs exhibit both material and structural changes. Structural defects (lesions) develop in the anulus fibrosus with age. While degeneration has been simulated in numerous previous studies, the effects of structural lesions on disc mechanics are not well known. In this study, a finite element model (FEM) of the L4/5 intervertebral disc was developed in order to study the effects of anular lesions and loss of hydrostatic pressure in the nucleus pulposus on the disc mechanics. Models were developed to simulate both healthy and degenerate discs. Degeneration was simulated with either rim, radial or circumferential anular lesions and by equating nucleus pressure to zero. The anulus fibrosus ground substance was represented as a nonlinear incompressible material using a second-order polynomial, hyperelastic strain energy equation. Hyperelastic material parameters were derived from experimentation on sheep discs. Endplates were assumed to be rigid, and annulus lamellae were assumed to be vertical in the unloaded state. Loading conditions corresponding to physiological ranges of rotational motion were applied to the models and peak rotation moments compared between models. Loss of nucleus pulposus pressure had a much greater effect on the disc mechanics than the presence of anular lesions. This indicated that the development of anular lesions alone (prior to degeneration of the nucleus) has minimal effect on disc mechanics, but that disc stiffness is significantly reduced by the loss of hydrostatic pressure in the nucleus. With the degeneration of the nucleus, the outer innervated anulus or surrounding osteo-ligamentous anatomy may therefore experience increased strains. PMID:17383659

  9. Phenanthro[4,5-fgh]quinoxaline-Fused Subphthalocyanines: Synthesis, Structure, and Spectroscopic Characterization.

    PubMed

    Pan, Houhe; Liu, Wenbo; Wang, Chiming; Wang, Kang; Jiang, Jianzhuang

    2016-07-01

    A series of four phenanthro[4,5-fgh]quinoxaline-fused subphthalocyanine derivatives 0-3 containing zero, one, two, and three phenanthro[4,5-fgh]quinoxaline moieties, respectively, were isolated from the mixed cyclotrimerization reaction of 2,9-di-tert-butylphenanthro[4,5-fgh]quinoxaline-5,6-dicarbonitrile with 4,5-bis(2,6-diisopropylphenoxy)phthalonitrile and characterized by a series of spectroscopic methods including MALDI-TOF mass, (1) H NMR, electronic absorption, magnetic circular dichroism (MCD), and fluorescence spectroscopy. The molecular structures for the compounds 0 and 2 were clearly revealed on the basis of single-crystal X-ray diffraction analysis. Their electrochemical properties were also studied by cyclic voltammetry. In particular, theoretical calculations in combination with the electronic absorption and electrochemical analyses revealed the significant influence of the fused-phenanthro[4,5-fgh]quinoxaline units on the electronic structures. PMID:27123546

  10. Synthesis and biological activity of substituted-4,5,6,7-tetrahydrothieno pyridines: a review.

    PubMed

    Sangshetti, Jaiprakash N; Zambare, Abhay S; Khan, Firoz A Kalam; Gonjari, Indrajeet; Zaheer, Zahid

    2014-01-01

    4,5,6,7-Tetrahydrothieno pyridine is an important class of heterocyclic nucleus. Various 4,5,6,7-tetrahydrothieno pyridine derivatives have been synthesized and evaluated for various biological activities in different models with desired findings. Some analogs have shown potent biological activities and may be considered as lead molecule for the development of future drugs. Number of drug molecules are available in the market and many molecules are in clinical development containing 4,5,6,7-tetrahydrothieno pyridine nucleus as an important core. This review is an attempt to organize the chemical and biological aspects of 4,5,6,7-tetrahydrothieno pyridine analogs reported in last 20 year to till date. Review mainly focuses on the important role of the core in synthesis of drug or drug intermediates giving emphasis on synthetic schemes and biological activities of the different 4,5,6,7-tetrahydrothieno pyridine analogs. PMID:25373848

  11. Intercalative pyrimido[4',5':4,5]thieno(2,3-b)quinolines induce apoptosis in leukemic cells: a comparative study of methoxy and morpholino substitution.

    PubMed

    Shahabuddin, M S; Nambiar, Mridula; Advirao, Gopal M; Raghavan, Sathees C

    2011-10-01

    DNA intercalating molecules are promising anticancer agents. Polycyclic aromatic molecules such as ellipticine intercalate into double-stranded DNA and affect major physiological functions. In the present study, we have characterized two molecules with the same chemical backbone but different side chains, namely 8-methoxy pyrimido[4',5':4,5]thieno (2,3-b)quinoline-4(3H)-one (MPTQ) and 4-morpholino pyrimido[4',5':4,5]thieno(2,3-b)quinoline (morpho-PTQ) at the 8th and 4th position, respectively. Although both MPTQ and morpho-PTQ show similar biophysical properties with high DNA affinity, here we show that they differ in their biological activities. We find that MPTQ is many fold more potent than morpho-PTQ and is cytotoxic against different leukemic cell lines. IC(50) value of methoxy PTQ was estimated between 2-15 µM among the leukemic cells studied, while it was more than 200 µM when morpho-PTQ was used. Cell cycle analysis shows an increase in sub-G1 phase, without any particular cell cycle arrest. Annexin V staining in conjunction with comet assay and DNA fragmentation suggest that MPTQ induces cytotoxicity by activating apoptosis. Thus the observed low IC(50) value of MPTQ makes it a promising cancer chemotherapeutic agent. PMID:20424886

  12. Natural selection for 2,4,5-trichlorophenoxyacetic acid mineralizing bacteria in agent orange contaminated soil.

    PubMed

    Rice, J F; Menn, F M; Hay, A G; Sanseverino, J; Sayler, G S

    2005-12-01

    Agent Orange contaminated soils were utilized in direct enrichment culture studies to isolate 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,4-dichlorophenoxyacetic acid (2,4-D) mineralizing bacteria. Two bacterial cultures able to grow at the expense of 2,4,5-T and/or 2,4-D were isolated. The 2,4,5-T degrading culture was a mixed culture containing two bacteria, Burkholderia species strain JR7B2 and Burkholderia species strain JR7B3. JR7B3 was able to metabolize 2,4,5-T as the sole source of carbon and energy, and demonstrated the ability to affect metabolism of 2,4-D to a lesser degree. Strain JR7B3 was able to mineralize 2,4,5-T in pure culture and utilized 2,4,5-T in the presence of 0.01% yeast extract. Subsequent characterization of the 2,4-D degrading culture showed that one bacterium, Burkholderia species strain JRB1, was able to utilize 2,4-D as a sole carbon and energy source in pure culture. Polymerase chain reaction (PCR) experiments utilizing known genetic sequences from other 2,4-D and 2,4,5-T degrading bacteria demonstrated that these organisms contain gene sequences similar to tfdA, B, C, E, and R (Strain JRB1) and the tftA, C, and E genes (Strain JR7B3). Expression analysis confirmed that tftA, C, and E and tfdA, B, and C were transcribed during 2,4,5-T and 2,4-D dependent growth, respectively. The results indicate a strong selective pressure for 2,4,5-T utilizing strains under field condition. PMID:15865343

  13. Highly cooperative Ca2+ elevations in response to Ins(1,4,5)P3 microperfusion through a patch-clamp pipette.

    PubMed Central

    Schrenzel, J; Demaurex, N; Foti, M; Van Delden, C; Jacquet, J; Mayr, G; Lew, D P; Krause, K H

    1995-01-01

    To study the initial kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations with a high time resolution and to avoid the problem of cell-to-cell heterogeneity, we have used the combined patch-clamp/microfluorimetry technique. The mathematical description of the microperfusion of Ins(1,4,5)P3 and the subsequent Ca2+ release consists of a monoexponential decay (cytosolic Ins(1,4,5)P3 concentration) and a Hill equation (Ins(1,4,5)P3 dose-response curve). Two additional Hill equations and an integration were necessary to include a putative dependence of Ins(1,4,5)P3-induced Ca2+ release on [Ca2+]i. Best-fitting analysis assuming [Ca2+]i-independent Ca2+ release yielded Hill coefficients between 4 and 12. The high cooperativity was also observed with the poorly metabolizable analog Ins(2,4,5)P3 and was independent of extracellular [Ca2+]. Best-fitting analysis including a positive [Ca2+]i feedback suggested a cooperativity on the level of Ins(1,4,5)P3-induced channel opening (n = 2) and an enhancement of Ins(1,4,5)P3-induced Ca2+ release by [Ca2+]i. In summary, the onset kinetics of Ins(1,4,5)P3-induced [Ca2+]i elevations in single HL-60 granulocytes showed a very high cooperativity, presumably because of a cooperativity on the level of channel opening and a positive Ca2+ feedback, but not because of Ca2+ influx or Ins(1,4,5)P3 metabolism. This high cooperativity, acting in concert with negative feedback mechanisms, might play an important role in the fine-tuning of the cellular Ca2+ signal. Images FIGURE 5 PMID:8599644

  14. Future Climate Data from RCP 4.5 and Occurrence of Malaria in Korea

    PubMed Central

    Kwak, Jaewon; Noh, Huiseong; Kim, Soojun; Singh, Vijay P.; Hong, Seung Jin; Kim, Duckgil; Lee, Keonhaeng; Kang, Narae; Kim, Hung Soo

    2014-01-01

    Since its reappearance at the Military Demarcation Line in 1993, malaria has been occurring annually in Korea. Malaria is regarded as a third grade nationally notifiable disease susceptible to climate change. The objective of this study is to quantify the effect of climatic factors on the occurrence of malaria in Korea and construct a malaria occurrence model for predicting the future trend of malaria under the influence of climate change. Using data from 2001–2011, the effect of time lag between malaria occurrence and mean temperature, relative humidity and total precipitation was investigated using spectral analysis. Also, a principal component regression model was constructed, considering multicollinearity. Future climate data, generated from RCP 4.5 climate change scenario and CNCM3 climate model, was applied to the constructed regression model to simulate future malaria occurrence and analyze the trend of occurrence. Results show an increase in the occurrence of malaria and the shortening of annual time of occurrence in the future. PMID:25321875

  15. Future climate data from RCP 4.5 and occurrence of malaria in Korea.

    PubMed

    Kwak, Jaewon; Noh, Huiseong; Kim, Soojun; Singh, Vijay P; Hong, Seung Jin; Kim, Duckgil; Lee, Keonhaeng; Kang, Narae; Kim, Hung Soo

    2014-01-01

    Since its reappearance at the Military Demarcation Line in 1993, malaria has been occurring annually in Korea. Malaria is regarded as a third grade nationally notifiable disease susceptible to climate change. The objective of this study is to quantify the effect of climatic factors on the occurrence of malaria in Korea and construct a malaria occurrence model for predicting the future trend of malaria under the influence of climate change. Using data from 2001-2011, the effect of time lag between malaria occurrence and mean temperature, relative humidity and total precipitation was investigated using spectral analysis. Also, a principal component regression model was constructed, considering multicollinearity. Future climate data, generated from RCP 4.5 climate change scenario and CNCM3 climate model, was applied to the constructed regression model to simulate future malaria occurrence and analyze the trend of occurrence. Results show an increase in the occurrence of malaria and the shortening of annual time of occurrence in the future. PMID:25321875

  16. RCP4.5: A Pathway for Stabilization of Radiative Forcing by 2100

    SciTech Connect

    Thomson, Allison M.; Calvin, Katherine V.; Smith, Steven J.; Kyle, G. Page; Volke, April C.; Patel, Pralit L.; Delgado Arias, Sabrina; Bond-Lamberty, Benjamin; Wise, Marshall A.; Clarke, Leon E.; Edmonds, James A.

    2011-07-29

    Representative Concentration Pathway (RCP) 4.5 is a scenario that stabilizes radiative forcing at 4.5 W m{sup -2} in the year 2100 without ever exceeding that value. Simulated with the Global Change Assessment Model (GCAM), RCP4.5 includes long-term, global emissions of greenhouse gases, short-lived species, and land-use-land-cover in a global economic framework. RCP4.5 was updated from earlier GCAM scenarios to incorporate historical emissions and land cover information common to the RCP process and follows a cost-minimizing pathway to reach the target radiative forcing. The imperative to limit emissions in order to reach this target drives changes in the energy system, including shifts to electricity, to lower emissions energy technologies and to the deployment of carbon capture and geologic storage technology. In addition, the RCP4.5 emissions price also applies to land use emissions; as a result, forest lands expand from their present day extent. The simulated future emissions and land use were downscaled from the regional simulation to a grid to facilitate transfer to climate models. While there are many alternative pathways to achieve a radiative forcing level of 4.5 W m{sup -2}, the application of the RCP4.5 provides a common platform for climate models to explore the climate system response to stabilizing the anthropogenic components of radiative forcing.

  17. Mouse nucleolin binds to 4.5S RNAH, a small noncoding RNA

    SciTech Connect

    Hirose, Yutaka Harada, Fumio

    2008-01-04

    4.5S RNAH is a rodent-specific small noncoding RNA that exhibits extensive homology to the B1 short interspersed element. Although 4.5S RNAH is known to associate with cellular poly(A)-terminated RNAs and retroviral genomic RNAs, its function remains unclear. In this study, we analyzed 4.5S RNAH-binding proteins in mouse nuclear extracts using gel mobility shift and RNA-protein UV cross-linking assays. We found that at least nine distinct polypeptides (p170, p110, p93, p70, p48, p40, p34, p20, and p16.5) specifically interacted with 4.5S RNAHin vitro. Using anti-La antibody, p48 was identified as mouse La protein. To identify the other 4.5S RNAH-binding proteins, we performed expression cloning from a mouse cDNA library and obtained cDNA clones derived from nucleolin mRNA. We identified p110 as nucleolin using nucleolin-specific antibodies. UV cross-linking analysis using various deletion mutants of nucleolin indicated that the third of four tandem RNA recognition motifs is a major determinant for 4.5S RNAH recognition. Immunoprecipitation of nucleolin from the subcellular fractions of mouse cell extracts revealed that a portion of the endogenous 4.5S RNAH was associated with nucleolin and that this complex was located in both the nucleoplasm and nucleolus.

  18. Mouse nucleolin binds to 4.5S RNAh, a small noncoding RNA.

    PubMed

    Hirose, Yutaka; Harada, Fumio

    2008-01-01

    4.5S RNAh is a rodent-specific small noncoding RNA that exhibits extensive homology to the B1 short interspersed element. Although 4.5S RNAh is known to associate with cellular poly(A)-terminated RNAs and retroviral genomic RNAs, its function remains unclear. In this study, we analyzed 4.5S RNAh-binding proteins in mouse nuclear extracts using gel mobility shift and RNA-protein UV cross-linking assays. We found that at least nine distinct polypeptides (p170, p110, p93, p70, p48, p40, p34, p20, and p16.5) specifically interacted with 4.5S RNAhin vitro. Using anti-La antibody, p48 was identified as mouse La protein. To identify the other 4.5S RNAh-binding proteins, we performed expression cloning from a mouse cDNA library and obtained cDNA clones derived from nucleolin mRNA. We identified p110 as nucleolin using nucleolin-specific antibodies. UV cross-linking analysis using various deletion mutants of nucleolin indicated that the third of four tandem RNA recognition motifs is a major determinant for 4.5S RNAh recognition. Immunoprecipitation of nucleolin from the subcellular fractions of mouse cell extracts revealed that a portion of the endogenous 4.5S RNAh was associated with nucleolin and that this complex was located in both the nucleoplasm and nucleolus. PMID:17971306

  19. LPS-induced clustering of CD14 triggers generation of PI(4,5)P2.

    PubMed

    Płóciennikowska, Agnieszka; Zdioruk, Mykola I; Traczyk, Gabriela; Świątkowska, Anna; Kwiatkowska, Katarzyna

    2015-11-15

    Bacterial lipopolysaccharide (LPS) induces strong pro-inflammatory reactions after sequential binding to CD14 protein and TLR4 receptor. Here, we show that CD14 controls generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] in response to LPS binding. In J774 cells and HEK293 cells expressing CD14 exposed to 10-100 ng/ml LPS, the level of PI(4,5)P2 rose in a biphasic manner with peaks at 5-10 min and 60 min. After 5-10 min of LPS stimulation, CD14 underwent prominent clustering in the plasma membrane, accompanied by accumulation of PI(4,5)P2 and type-I phosphatidylinositol 4-phosphate 5-kinase (PIP5K) isoforms Iα and Iγ (encoded by Pip5k1a and Pip5k1c, respectively) in the CD14 region. Clustering of CD14 with antibodies, without LPS and TLR4 participation, was sufficient to trigger PI(4,5)P2 elevation. The newly generated PI(4,5)P2 accumulated in rafts, which also accommodated CD14 and a large portion of PIP5K Iα and PIP5K Iγ. Silencing of PIP5K Iα and PIP5K Iγ, or application of drugs interfering with PI(4,5)P2 synthesis and availability, abolished the LPS-induced PI(4,5)P2 elevation and inhibited downstream pro-inflammatory reactions. Taken together, these data indicate that LPS induces clustering of CD14, which triggers PI(4,5)P2 generation in rafts that is required for maximal pro-inflammatory signaling of TLR4. PMID:26446256

  20. Is inositol (1,3,4,5)-tetrakisphosphate a new second messenger

    SciTech Connect

    Hansen, C.A.; Williamson, J.R.

    1986-05-01

    Hormone-stimulated hydrolysis of inositol (Ins) lipids results in the rapid formation of Ins(1,4,5)P/sub 3/, the second messenger for intracellular Ca/sup 2 +/ mobilization. Recently, a more polar inositol phosphate, Ins(1,3,4,5)P/sub 4/ as well as its probable hydrolysis product Ins(1,3,4)P/sub 3/ have been reported to accumulate in carbachol-stimulated brain slices. Vasopressin addition to hepatocytes prelabeled with (/sup 3/H)-Ins also showed a rapid increase of Ins(1,3,4,5)P/sub 4/, which was similar to that of Ins(1,4,5)P/sub 3/, while the accumulation of Ins(1,3,4)P/sub 3/ was slower. In order to examine whether Ins(1,3,4,5)P/sub 4/ has any functional effects on Ca/sup 2 +/ homeostasis, it was synthesized enzymatically from (/sup 3/H)-Ins(1,4,5)P/sub 3/ using a partially purified phosphoinositol kinase activity from rat brain cortex. (/sup 3/H)-labeled inositol phosphates were separated by anion exchange chromatography and analyzed by HPLC using ammonium formate/phosphoric acid gradient elution. Preliminary experiments indicate that Ins(1,3,4,5)P/sub 4/ up to 10 ..mu..M does not release Ca/sup 2 +/ from vesicular pools in saponin-permeabilized hepatocytes. It has a slight inhibitory effect on Ins(1,4,5)P/sub 3/-induced Ca/sup 2 +/ release. The effect of Ins(1,3,4,5)P/sub 4/ on plasma membrane Ca/sup 2 +/ fluxes are presently being investigated.

  1. A series of 2, 4, 5-trisubstituted oxazole: Synthesis, characterization and DFT modelling

    NASA Astrophysics Data System (ADS)

    Kadam, Vinay S.; Shaikh, Saminaparwin G.; Patel, Arun L.

    2016-06-01

    A new series of 2,4,5-trisubstituted oxazole were synthesized with good yields using simple methodology. All the compounds were thoroughly characterized by IR, NMR (1H and 13C) and mass spectrometry and structures of 2-(4-butyloxyphenyl)-4,5-dimethyloxazole (5b) and 4,5-dimethyl-2-(4-(octyloxy)phenyl)oxazole(5e) were unambiguously determined by X-ray crystallography. Evidently, the crystal structures of these compounds showed C-H⋯N and C-H⋯O intermolecular interactions. The electronic structures of these compounds were also studied by DFT at B3LYP/6-311G ++ level of theory.

  2. Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

    PubMed

    Kim, Jin Ho; Shyam, Pranab K; Kim, Mi Jeong; Lee, Hwa-Jung; Lee, Jeong Tae; Jang, Hye-Young

    2016-07-01

    In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity. PMID:27177825

  3. Energetic Trinitro- and Fluorodinitroethyl Ethers of 1,2,4,5-Tetrazines.

    PubMed

    Chavez, David E; Parrish, Damon A; Mitchell, Lauren

    2016-07-18

    Several new energetic ethyl ethers of 1,2,4,5-tetrazine have been synthesized. These molecules display good thermal stability, good oxygen balance, and high densities. Included in these studies are a 2,2,2-trinitroethoxy 1,2,4,5-tetrazine and two fluorodinitroethoxy 1,2,4,5-tetrazines. One of these compounds was converted into the di-N-oxide derivative. The sensitivity of these materials towards destructive stimuli was determined, and overall the materials show promising energetic performance properties. PMID:27273564

  4. 2,4,5,2',4',5'-Hexachlorobiphenyl-lipoprotein (LDL, HDL, VLDL) interaction and induced lipidosis in cultured skin fibroblasts

    SciTech Connect

    Kling, D.; Becker, M.M.; Kruth, H.S.; Gamble, W.

    1984-06-01

    2,4,5,2',4',5'-Hexachlorobiphenyl (HCB) induced cytoplasmic inclusions and lipidosis in normal (AG1437) and hypercholesterolemic (GM488) human skin fibroblasts. Quantitative and qualitative microscopic fluorescence analysis showed that the cytoplasmic inclusions are formed as early as 3 hr after treatment with HCB. The inclusions contain lipids but no detectable nonesterified cholesterol or cholesteryl ester. High density lipoproteins (HDL), low density lipoproteins (LDL), and very low density lipoproteins (VLDL) facilitate the apparent uptake of HCB by skin fibroblasts. HDL and LDL appeared to reverse the induction of cytoplasmic inclusions and lipidosis when cells were pretreated with HCB, the HCB was removed from media, and the cells were incubated with LDL or HDL. The results suggest that lipoproteins participate in the uptake and egress of HCB from skin fibroblasts.

  5. Processable, high temperature polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and bis-dienes

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.

    1988-01-01

    1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene reacts with various anthracene end-capped polyimide oligomers to form Diels-Alder cycloaddition copolymers. The polymers are soluble in common organic solvents, and have molecular weights of approximately 21,000 to 32,000. These resins exhibit lower weight loss in air than in nitrogen. This is suggested to be due to dehydration (loss of water ranges from 2 to 5 percent) at temperatures of 390 to 400 C to give thermooxidatively stable pentiptycene units along the polymer backbone. Because of their high softening points and good thermooxidative stability, the polymers have potential as processable, matrix resins for high temperature composite applications.

  6. Addition polymers from 1,4,5,8-tetrahydro-1,4;5,8-diepoxyanthracene and Bis-dienes: Processable resins for high temperature application

    NASA Technical Reports Server (NTRS)

    Meador, Mary Ann B.

    1987-01-01

    1,4,5,8-Tetrahydro-1,4;5,8-diepoxyanthracene reacts with various anthracene endcapped polyimide oligomers to form Diels-Alder cycloaddition copolymers. The polymers are soluble in common organic solvents, and have molecular weights of approximately 21,000 to 32,000. Interestingly, these resins appear to be more stable in air then in nitrogen. This is shown to be due to a unique dehydration (loss of water ranges from 2 to 5 percent) at temperatures of 390 to 400 C to give thermo-oxidatively stable pentiptycene units along the polymer backbone. Because of their high softening points and good thermo-oxidative stability, the polymers have potential as processible, matrix resins for high temperature composite applications.

  7. Direct Alkynylation of 3H-Imidazo[4,5-b]pyridines Using gem-Dibromoalkenes as Alkynes Source.

    PubMed

    Aziz, Jessy; Baladi, Tom; Piguel, Sandrine

    2016-05-20

    C2 direct alkynylation of 3H-imidazo[4,5-b]pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe2 or Cu(OAc)2), a phosphine ligand (DPEphos) and a base (LiOtBu) in 1,4-dioxane at 120 °C. This C-H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and gem-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3H-imidazo[4,5-b]pyridines, a valuable scaffold in drug design. PMID:27111189

  8. Highly Dynamic and Specific Phosphatidylinositol 4,5-Bisphosphate, Septin, and Cell Wall Integrity Pathway Responses Correlate with Caspofungin Activity against Candida albicans.

    PubMed

    Badrane, Hassan; Nguyen, M Hong; Clancy, Cornelius J

    2016-06-01

    Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] activates the yeast cell wall integrity pathway. Candida albicans exposure to caspofungin results in the rapid redistribution of PI(4,5)P2 and septins to plasma membrane foci and subsequent fungicidal effects. We studied C. albicans PI(4,5)P2 and septin dynamics and protein kinase C (PKC)-Mkc1 cell wall integrity pathway activation following exposure to caspofungin and other drugs. PI(4,5)P2 and septins were visualized by live imaging of C. albicans cells coexpressing green fluorescent protein (GFP)-pleckstrin homology (PH) domain and red fluorescent protein-Cdc10p, respectively. PI(4,5)P2 was also visualized in GFP-PH domain-expressing C. albicans mkc1 mutants. Mkc1p phosphorylation was measured as a marker of PKC-Mkc1 pathway activation. Fungicidal activity was assessed using 20-h time-kill assays. Caspofungin immediately induced PI(4,5)P2 and Cdc10p colocalization to aberrant foci, a process that was highly dynamic over 3 h. PI(4,5)P2 levels increased in a dose-response manner at caspofungin concentrations of ≤4× MIC and progressively decreased at concentrations of ≥8× MIC. Caspofungin exposure resulted in broad-based mother-daughter bud necks and arrested septum-like structures, in which PI(4,5)P2 and Cdc10 colocalized. PKC-Mkc1 pathway activation was maximal within 10 min, peaked in response to caspofungin at 4× MIC, and declined at higher concentrations. The caspofungin-induced PI(4,5)P2 redistribution remained apparent in mkc1 mutants. Caspofungin exerted dose-dependent killing and paradoxical effects at ≤4× and ≥8× MIC, respectively. Fluconazole, amphotericin B, calcofluor white, and H2O2 did not impact the PI(4,5)P2 or Cdc10p distribution like caspofungin did. Caspofungin exerts rapid PI(4,5)P2-septin and PKC-Mkc1 responses that correlate with the extent of C. albicans killing, and the responses are not induced by other antifungal agents. PI(4,5)P2-septin regulation is crucial in early

  9. Application of preprocessing filtering on Decision Tree C4.5 and rough set theory

    NASA Astrophysics Data System (ADS)

    Chan, Joseph C. C.; Lin, Tsau Y.

    2001-03-01

    This paper compares two artificial intelligence methods: the Decision Tree C4.5 and Rough Set Theory on the stock market data. The Decision Tree C4.5 is reviewed with the Rough Set Theory. An enhanced window application is developed to facilitate the pre-processing filtering by introducing the feature (attribute) transformations, which allows users to input formulas and create new attributes. Also, the application produces three varieties of data set with delaying, averaging, and summation. The results prove the improvement of pre-processing by applying feature (attribute) transformations on Decision Tree C4.5. Moreover, the comparison between Decision Tree C4.5 and Rough Set Theory is based on the clarity, automation, accuracy, dimensionality, raw data, and speed, which is supported by the rules sets generated by both algorithms on three different sets of data.

  10. Calcium Promotes the Formation of Syntaxin 1 Mesoscale Domains through Phosphatidylinositol 4,5-Bisphosphate*

    PubMed Central

    Platen, Mitja; Junius, Meike; Diederichsen, Ulf; Schaap, Iwan A. T.; Honigmann, Alf; Jahn, Reinhard; van den Bogaart, Geert

    2016-01-01

    Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is a minor component of total plasma membrane lipids, but it has a substantial role in the regulation of many cellular functions, including exo- and endocytosis. Recently, it was shown that PI(4,5)P2 and syntaxin 1, a SNARE protein that catalyzes regulated exocytosis, form domains in the plasma membrane that constitute recognition sites for vesicle docking. Also, calcium was shown to promote syntaxin 1 clustering in the plasma membrane, but the molecular mechanism was unknown. Here, using a combination of superresolution stimulated emission depletion microscopy, FRET, and atomic force microscopy, we show that Ca2+ acts as a charge bridge that specifically and reversibly connects multiple syntaxin 1/PI(4,5)P2 complexes into larger mesoscale domains. This transient reorganization of the plasma membrane by physiological Ca2+ concentrations is likely to be important for Ca2+-regulated secretion. PMID:26884341

  11. 4,5-Dimethylangelicin effects on lymphocytes with and without UV-radiation.

    PubMed

    Gast, W; Rytter, M; Hofmann, C; Haustein, U F; Barth, J; Walther, T

    1987-03-01

    Compared to the linear derivative 8-methoxypsoralen (8-MOP) the angular structured furocoumarin 4,5'-dimethylangelicin (4,5'-DMA) causes smaller photosensitization effects (loss of viability, inhibition of phytohemagglutinin (PHA)-induced transformation rate and E-rosette formation of T-cells, respectively) on cultured human lymphocytes. When 4,5'-DMA or 8-MOP are added to the cultures without additional UV-irradiation, increased or decreased PHA-stimulation rates are observed, respectively. In addition, 4,5'-DMA is able to reduce the binding of sheep erythrocytes to lymphocytes in a higher degree than 8-MOP. These findings suggest different action mechanisms on cytoplasma membranes and intracellular structures of lymphocytes by different furocoumarins. PMID:3653385

  12. A new FPGA with 4/5-input LUT and optimized carry chain

    NASA Astrophysics Data System (ADS)

    Zhidong, Mao; Liguang, Chen; Yuan, Wang; Jinmei, Lai

    2012-07-01

    A new LUT and carry structure embedded in the configurable logic block of an FPGA is proposed. The LUT is designed to support both 4-input and 5-input structures, which can be configured by users according to their needs without increasing interconnect resources. We also develop a new carry chain structure with an optimized critical path. Finally a newly designed configurable scan-chain is inserted. The circuit is fabricated in 0.13 μm 1P8M 1.2/2.5/3.3 V logic CMOS process. The test results show a correct function of 4/5-input LUT and scan-chain, and a speedup in carry performance of nearly 3 times over current architecture in the same technology at the cost of an increase in total area of about 72.5%. Our results also show that the logic utilization of this work is better than that of a Virtex II/Virtex 4/Virtex 5/Virtex 6/Virtex 7 FPGA when implemented using only 4-LUT and better than that of a Virtex II/Virtex 4 FPGA when implemented using only 5-LUT.

  13. Csátalja, the largest H4-5 chondrite from Hungary

    NASA Astrophysics Data System (ADS)

    Kovács, János; Sajó, István; Márton, Zsuzsanna; Jáger, Viktor; Hegedüs, Tibor; Berecz, Tibor; Tóth, Tamás; Gyenizse, Péter; Podobni, András

    2015-01-01

    We report here for the first time the composition and mineralogical studies on a new meteorite, which was found in August 2012 near the village of Csátalja, Hungary (46°0'21''N; 18°59'27'E). The Csátalja meteorite is classified as a H4-5 ordinary chondrite with shock stage S2 and a degree of weathering W1 and the total mass is 15 kg. The Csátalja meteorite is characterized by well-defined chondrules composed either of olivine or pyroxene. X-ray diffractogram shows the primary phases olivine, pyroxene, kamacite, and albite. Metal particles were extracted from the bulk powdered samples exhibit only kamacite and small amounts of the intergrowth taenite/kamacite. Raman spectra of forsterite indicate that Csátalja meteorite suffered from relatively low shock pressure regime. The texture of chondrules varies from nonporphyritic (e.g., barred olivine, radial pyroxene) to porphyritic ones (e.g., granular olivine as well as olivine pyroxene). The meteorite name has not yet approved by the Nomenclature Committee of the Meteoritical Society.

  14. Absolute configuration of 2-sec-butyl-4,5-dihydrothiazole in male mouse urine.

    PubMed

    Cavaggioni, Andrea; Mucignat-Caretta, Carla; Zagotto, Giuseppe

    2003-11-01

    The absolute configuration of 2-sec-butyl-4,5-dihydrothiazole (DHT) in urine of adult male mice was determined through chiral trifluoroacetyl derivative capillary chromatography by comparing the retention time with synthetic standards. (S)-DHT was extracted from fresh urine, while neither (R)-DHT nor the racemization of (S)-DHT were detected. We can conclude that DHT in urine possesses the S configuration, although we cannot exclude a minor component in the R configuration. (S)-DHT was then characterized for binding to the complex of major urinary proteins of male mouse urine (MUP) and for a behavioral response, the competitive scent marking behavior (countermarking). The binding constant of (S)-DHT to MUP (determined by competitive displacement) was 8.2 +/- 0.6 microM (mean +/- SD) and was 10.5 +/- 0.6 microM for R-DHT, thus excluding a relevant difference in binding. (S)-DHT modified countermarking in a peculiar way. Male mice were slow in countermarking urinary spots streaked 2 days earlier and on top of which (S)-DHT was added shortly before the test. This response was not seen when adding (S)-DHT to freshly streaked urinary spots or to clean paper. Unlike (S)-DHT, (R)-DHT prompted countermarking rather than delaying it. We can further conclude that (S)-DHT in male mouse urine is an aversive chemosignal for countermarking. PMID:14654447

  15. Dislocation distributions in an Al-4. 5% Mg alloy during superplastic deformation

    SciTech Connect

    Li, F.; Roberts, W.T.; Bate, P.S. . IRC in Materials for High Performance Applications)

    1993-10-01

    Superplasticity has been studied actively for several decades. Many models of the phenomenon have been proposed, in most of which normal dislocation glide has either not been considered or been considered only as an accommodation process to maintain continuity during grain boundary sliding. Although evidence of dislocation activity during superplastic deformation has been observed several times by TEM studies following deformation, the published results appear to be inconsistent and occasionally contradict themselves, and so are unable to provide systematic and convincing evidence for the development of any theoretical model. A major experimental problem associated with those results is the delay between unloading and quenching the specimens from the high testing temperatures. Dislocations can be lost by relaxation and annealing during the unloading and also during the preparation of TEM thin foils. A facility was developed to preserve the high temperature deformation microstructure for consequent TEM examination by quenching and aging under constant stress. This technique and some preliminary results are given elsewhere. The work presented here is from a more comprehensive TEM study of the dislocation distributions in an Al-4.5%Mg alloy developed during deformation at an elevated temperature and a range of strain rates.

  16. Phosphatidylinositol 4,5-bisphosphate phospholipase C and phosphomonoesterase in Dunaliella salina membranes

    SciTech Connect

    Einspahr, K.J.; Peeler, T.C.; Thompson, G.A. Jr. )

    1989-07-01

    In comparison with other cell organelles, the Dunaliella salina plasma membrane was found to be highly enriched in phospholipase C activity toward exogenous ({sup 3}H)phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}). Based on release of ({sup 3}H)inositol phosphates, the plasma membrane exhibited a PIP{sub 2}-phospholipase C activity nearly tenfold higher than the nonplasmalemmal, nonchloroplast bottom phase (BP) membrane fraction and 47 times higher than the chloroplast membrane fraction. The majority of phospholipase activity was clearly of a phospholipase C nature since over 80% of ({sup 3}H)inositol phosphates released were recovered as ({sup 3}H)inositol trisphosphate (IP{sub 3}). These results suggest a plausible mechanism for the rapid breakdown of PIP{sub 2} and phosphatidylinositol 4-phosphate (PIP) following hypoosmotic shock. The authors have also examined some of the in vitro characteristics of the plasma membrane phospholipase C activity and have found it to be calcium sensitive, reaching maximal activity at 10 micromolar free (Ca{sup 2+}). They also report here that 100 micromolar GTP{gamma}S stimulates phospholipase C activity over a range of free (Ca{sup 2+}). Together, these results provide evidence that the plasma membrane PIP{sub 2}-phospholipase C of D. salina may be subject to Ca{sup 2+} and G-protein regulation.

  17. BIOTRANSFORMATION OF TRANS-4,5-DIHYDROXY-4,5-DIHYDROBENZO[A]PYRENE TO BENZO[A]PYRENE-BIS-DIOLS AND DNA ADDUCTS BY INDUCED RAT LIVER MICROSOMES

    EPA Science Inventory

    The biotransformation of (+)-trans-4,5-dihydroxy-4,5-dihydrobenzo[a]pyrene trans-B[a]P-4,5-diol), the K-region dihydrodiol of B[a]P, by B-naphthoflavone (BNF)-induced rat liver microsomes was studied. Trans-B[a]P-4,5-diol was metabolized to six major products as characterized by...

  18. Signal-dependent Hydrolysis of Phosphatidylinositol 4,5-Bisphosphate without Activation of Phospholipase C

    PubMed Central

    Lev, Shaya; Katz, Ben; Tzarfaty, Vered; Minke, Baruch

    2012-01-01

    In Drosophila, a phospholipase C (PLC)-mediated signaling cascade, couples photo-excitation of rhodopsin to the opening of the transient receptor potential (TRP) and TRP-like (TRPL) channels. A lipid product of PLC, diacylglycerol (DAG), and its metabolites, polyunsaturated fatty acids (PUFAs) may function as second messengers of channel activation. However, how can one separate between the increase in putative second messengers, change in pH, and phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) depletion when exploring the TRPL gating mechanism? To answer this question we co-expressed the TRPL channels together with the muscarinic (M1) receptor, enabling the openings of TRPL channels via G-protein activation of PLC. To dissect PLC activation of TRPL into its molecular components, we used a powerful method that reduced plasma membrane-associated PI(4,5)P2 in HEK cells within seconds without activating PLC. Upon the addition of a dimerizing drug, PI(4,5)P2 was selectively hydrolyzed in the cell membrane without producing DAG, inositol trisphosphate, or calcium signals. We show that PI(4,5)P2 is not an inhibitor of TRPL channel activation. PI(4,5)P2 hydrolysis combined with either acidification or application of DAG analogs failed to activate the channels, whereas PUFA did activate the channels. Moreover, a reduction in PI(4,5)P2 levels or inhibition of DAG lipase during PLC activity suppressed the PLC-activated TRPL current. This suggests that PI(4,5)P2 is a crucial substrate for PLC-mediated activation of the channels, whereas PUFA may function as the channel activator. Together, this study defines a narrow range of possible mechanisms for TRPL gating. PMID:22065576

  19. Localized Biphasic Changes in Phosphatidylinositol-4,5-Bisphosphate at Sites of Phagocytosis

    PubMed Central

    Botelho, Roberto J.; Teruel, Mary; Dierckman, Renee; Anderson, Richard; Wells, Alan; York, John D.; Meyer, Tobias; Grinstein, Sergio

    2000-01-01

    Phagocytosis requires localized and transient remodeling of actin filaments. Phosphoinositide signaling is believed to play an important role in cytoskeletal organization, but it is unclear whether lipids, which can diffuse along the membrane, can mediate the focal actin assembly required for phagocytosis. We used imaging of fluorescent chimeras of pleckstrin homology and C1 domains in live macrophages to monitor the distribution of phosphatidylinositol-4,5-bisphosphate (4,5-PIP2) and diacylglycerol, respectively, during phagocytosis. Our results reveal a sequence of exquisitely localized, coordinated steps in phospholipid metabolism: a focal, rapid accumulation of 4,5-PIP2 accompanied by recruitment of type Iα phosphatidylinositol phosphate kinase to the phagosomal cup, followed by disappearance of the phosphoinositide as the phagosome seals. Loss of 4,5-PIP2 correlated with mobilization of phospholipase Cγ (PLCγ) and with the localized formation of diacylglycerol. The presence of 4,5-PIP2 and active PLCγ at the phagosome was shown to be essential for effective particle ingestion. The temporal sequence of phosphoinositide metabolism suggests that accumulation of 4,5-PIP2 is involved in the initial recruitment of actin to the phagocytic cup, while its degradation contributes to the subsequent cytoskeletal remodeling. PMID:11134066

  20. Analysis and risk assessment of 4(5)-methylimidazole in brown colored foods and beverages.

    PubMed

    Lee, Sumin; Lee, Kwang-Geun

    2016-01-01

    In this study, the 4(5)-methylimidazole (4(5)-MI) levels in various 144 brown coloured foods and beverages were determined. The brown coloured foods and beverages were 62 processed sauces, 40 coffee, 9 caramel syrups, 18 red ginseng juice and 15 Japanese apricot fruit juice. The amount of 4(5)-MI in brewed coffee (1821.3 ng/g) was the highest level among the samples. The 4(5)-MI concentration in processed sauce (47.6 ng/g) was the lowest level among the samples. The levels of 4(5)-MI in various samples were found as follows: 47.6-1748.5 ng/g in processed sauces, 64.1-1821.3 ng/g in commercial coffee, 115.5-491.9 ng/g in caramel syrups, 91.0-854.1 ng/g in red ginseng juice and 137.6-587.4 ng/g in Japanese apricot fruit juice. Based on the 4(5)-MI levels, the estimated daily intake (EDI) and chronic daily intake (CDI) were calculated. EDI and CDI of red ginseng juice was the highest among all samples, and they were 1618.6 and 1256.8 ng/kg bw/day, respectively. PMID:26653824

  1. Milestone Report - Complete New Adsorbent Materials for Marine Testing to Demonstrate 4.5 g-U/kg Adsorbent

    SciTech Connect

    Janke, Christopher James; Das, Sadananda; Oyola, Yatsandra; Mayes, Richard T.; Saito, Tomonori; Brown, Suree; Gill, Gary; Kuo, Li-Jung; Wood, Jordana

    2014-08-01

    This report describes work on the successful completion of Milestone M2FT-14OR03100115 (8/20/2014) entitled, “Complete new adsorbent materials for marine testing to demonstrate 4.5 g-U/kg adsorbent”. This effort is part of the Seawater Uranium Recovery Program, sponsored by the U.S. Department of Energy, Office of Nuclear Energy, and involved the development of new adsorbent materials at the Oak Ridge National Laboratory (ORNL) and marine testing at the Pacific Northwest National Laboratory (PNNL). ORNL has recently developed two new families of fiber adsorbents that have demonstrated uranium adsorption capacities greater than 4.5 g-U/kg adsorbent after marine testing at PNNL. One adsorbent was synthesized by radiation-induced graft polymerization of itaconic acid and acrylonitrile onto high surface area polyethylene fibers followed by amidoximation and base conditioning. This fiber showed a capacity of 4.6 g-U/kg adsorbent in marine testing at PNNL. The second adsorbent was prepared by atom-transfer radical polymerization of t-butyl acrylate and acrylonitrile onto halide-functionalized round fibers followed by amidoximation and base hydrolysis. This fiber demonstrated uranium adsorption capacity of 5.4 g-U/kg adsorbent in marine testing at PNNL.

  2. Regulation of Inositol 1,4,5-Trisphosphate Receptor Function During Mouse Oocyte Maturation

    PubMed Central

    Wakai, Takuya; Vanderheyden, Veerle; Yoon, Sook-Young; Cheon, Banyoon; Zhang, Nan; Parys, Jan B.; Fissore, Rafael A.

    2011-01-01

    At the time of fertilization, an increase in the intracellular Ca2+ concentration ([Ca2+]i) underlies egg activation and initiation of development in all species studied to date. The inositol 1,4,5-trisphosphate receptor (IP3R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca2+ release. The sensitivity of IP3R1, i.e. its Ca2+ releasing capability, is increased during oocyte maturation so that the optimum [Ca2+]i response concurs with fertilization, which in mammals occurs at metaphase of second meiosis. Multiple IP3R1 modifications affect its sensitivity, including phosphorylation, sub-cellular localization and ER Ca2+ concentration ([Ca2+]ER). Here we evaluated using mouse oocytes how each of these factors affected IP3R1 sensitivity. The capacity for IP3-induced Ca2+ release markedly increased at the germinal vesicle breakdown stage, although oocytes only acquire the ability to initiate fertilization-like oscillations at later stages of maturation. The increase in IP3R1 sensitivity was underpinned by an increase in [Ca2+]ER and receptor phosphorylation(s) but not by changes in IP3R1 cellular distribution, as inhibition of the former factors reduced Ca2+ release, whereas inhibition of the latter had no impact. Therefore, the results suggest that the regulation of [Ca2+]ER and IP3R1 phosphorylation during maturation enhance IP3R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP3R1 sensitivity and acquisition of mature oscillatory capacity suggest that other mechanisms that regulate Ca2+ homeostasis also shape the pattern of oscillations in mammalian eggs. PMID:21465476

  3. A WHITE LIGHT MEGAFLARE ON THE dM4.5e STAR YZ CMi

    SciTech Connect

    Kowalski, Adam F.; Hawley, Suzanne L.; Wisniewski, John P.; Hilton, Eric J.; Holtzman, Jon A.

    2010-05-01

    On UT 2009 January 16, we observed a white light megaflare on the dM4.5e star YZ CMi as part of a long-term spectroscopic flare-monitoring campaign to constrain the spectral shape of optical flare continuum emission. Simultaneous U-band photometric and 3350-9260 A spectroscopic observations were obtained during 1.3 hr of the flare decay. The event persisted for more than 7 hr and at flare peak, the U-band flux was almost 6 mag brighter than in the quiescent state. The properties of this flare mark it as one of the most energetic and longest-lasting white light flares ever to be observed on an isolated low-mass star. We present the U-band flare energetics and a flare continuum analysis. For the first time, we show convincingly with spectra that the shape of the blue continuum from 3350 A to 4800 A can be represented as a sum of two components: a Balmer continuum as predicted by the Allred et al. radiative hydrodynamic flare models and a T{approx} 10,000 K blackbody emission component as suggested by many previous studies of the broadband colors and spectral distributions of flares. The areal coverage of the Balmer continuum and blackbody emission regions vary during the flare decay, with the Balmer continuum emitting region always being significantly ({approx}3-16 times) larger. These data will provide critical constraints for understanding the physics underlying the mysterious blue continuum radiation in stellar flares.

  4. Design and Synthesis of Potent in Vitro and in Vivo Anticancer Agents Based on 1-(3',4',5'-Trimethoxyphenyl)-2-Aryl-1H-Imidazole.

    PubMed

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Prencipe, Filippo; Oliva, Paola; Baraldi, Stefania; Tabrizi, Mojgan Aghazadeh; Lopez-Cara, Luisa Carlota; Ferla, Salvatore; Brancale, Andrea; Hamel, Ernest; Ronca, Roberto; Bortolozzi, Roberta; Mariotto, Elena; Basso, Giuseppe; Viola, Giampietro

    2016-01-01

    A novel series of tubulin polymerization inhibitors, based on the 1-(3',4',5'-trimethoxyphenyl)-2-aryl-1H-imidazole scaffold and designed as cis-restricted combretastatin A-4 analogues, was synthesized with the goal of evaluating the effects of various patterns of substitution on the phenyl at the 2-position of the imidazole ring on biological activity. A chloro and ethoxy group at the meta- and para-positions, respectively, produced the most active compound in the series (4o), with IC50 values of 0.4-3.8 nM against a panel of seven cancer cell lines. Except in HL-60 cells, 4o had greater antiproliferative than CA-4, indicating that the 3'-chloro-4'-ethoxyphenyl moiety was a good surrogate for the CA-4 B-ring. Experiments carried out in a mouse syngenic model demonstrated high antitumor activity of 4o, which significantly reduced the tumor mass at a dose thirty times lower than that required for CA-4P, which was used as a reference compound. Altogether, our findings suggest that 4o is a promising anticancer drug candidate that warrants further preclinical evaluation. PMID:27216165

  5. Egg incubation position affects toxicity of air cell administered PCB 126 (3,3?4,4?,5- pentachlorobiphenyl) in chicken (Gallus domesticus) embryos

    USGS Publications Warehouse

    McKernan, M.A.; Rattner, B.A.; Hale, R.C.; Ottinger, M.A.

    2007-01-01

    The avian egg is used extensively for chemical screening and determining the relative sensitivity of species to environmental contaminants (e.g., metals, pesticides, polyhalogenated compounds). The effect of egg incubation position on embryonic survival, pipping, and hatching success was examined following air cell administration of polychlorinated biphenyl (PCB) congener 126 (3,3',4,4',5-pentachlorobiphenyl [PCB 126]; 500?2,000 pg/g egg) on day 4 of development in fertile chicken (Gallus gallus) eggs. Depending on dose, toxicity was found to be up to nine times greater in vertically versus horizontally incubated eggs. This may be due to enhanced embryonic exposure to the injection bolus in vertically incubated eggs compared to more gradual uptake in horizontally incubated eggs. Following air cell administration of PCB 126, horizontal incubation of eggs may more closely approximate uptake and toxicity that has been observed with naturally incorporated contaminants. These data have implications for chemical screening and use of laboratory data for ecological risk assessments.

  6. Strain rate dependence of the tensile properties of V-(4--5%)Cr-(4--5%)Ti irradiated in EBR-II and HFBR

    SciTech Connect

    Zinkle, S.J.; Snead, L.L.; Robertson, J.P.; Rowcliffe, A.F.

    1998-03-01

    Elevated temperature tensile tests performed on V-(405)Cr-(4-5)Ti indicate that the yield stress increases with increasing strain rate for irradiation and test temperatures near 200 C, and decreases with increasing strain rate for irradiation and test temperatures near 400 C. This observation is in qualitative agreement with the temperature-dependent strain rate effects observed on unirradiated specimens, and implies that some interstitial solute remains free to migrate in irradiated specimens. Additional strain rate data at different temperatures are needed.

  7. Temporal profiling of changes in phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate and diacylglycerol allows comprehensive analysis of phospholipase C-initiated signalling in single neurons1

    PubMed Central

    Nelson, Carl P; Nahorski, Stefan R; Challiss, R A John

    2008-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) fulfils vital signalling roles in an array of cellular processes, yet until recently it has not been possible selectively to visualize real-time changes in PIP2 levels within living cells. Green fluorescent protein (GFP)-labelled Tubby protein (GFP-Tubby) enriches to the plasma membrane at rest and translocates to the cytosol following activation of endogenous Gαq/11-coupled muscarinic acetylcholine receptors in both SH-SY5Y human neuroblastoma cells and primary rat hippocampal neurons. GFP-Tubby translocation is independent of changes in cytosolic inositol 1,4,5-trisphosphate and instead reports dynamic changes in levels of plasma membrane PIP2. In contrast, enhanced GFP (eGFP)-tagged pleckstrin homology domain of phospholipase C (PLCδ1) (eGFP-PH) translocation reports increases in cytosolic inositol 1,4,5-trisphosphate. Comparison of GFP-Tubby, eGFP-PH and the eGFP-tagged C12 domain of protein kinase C-γ [eGFP-C1(2); to detect diacylglycerol] allowed a selective and comprehensive analysis of PLC-initiated signalling in living cells. Manipulating intracellular Ca2+ concentrations in the nanomolar range established that GFP-Tubby responses to a muscarinic agonist were sensitive to intracellular Ca2+ up to 100–200 nM in SH-SY5Y cells, demonstrating the exquisite sensitivity of agonist-mediated PLC activity within the range of physiological resting Ca2+ concentrations. We have also exploited GFP-Tubby selectively to visualize, for the first time, real-time changes in PIP2 in hippocampal neurons. PMID:18665913

  8. Phosphatidylinositol-3,4,5-Triphosphate and Cellular Signaling: Implications for Obesity and Diabetes

    PubMed Central

    Manna, Prasenjit; Jain, Sushil K.

    2015-01-01

    Phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) is one of the most important phosphoinositides and is capable of activating a wide range of proteins through its interaction with their specific binding domains. Localization and activation of these effector proteins regulate a number of cellular functions, including cell survival, proliferation, cytoskeletal rearrangement, intracellular vesicle trafficking, and cell metabolism. Phosphoinositides have been investigated as an important agonist-dependent second messenger in the regulation of diverse physiological events depending upon the phosphorylation status of their inositol group. Dysregulation in formation as well as metabolism of phosphoinositides is associated with various pathophysiological disorders such as inflammation, allergy, cardiovascular diseases, cancer, and metabolic diseases. Recent studies have demonstrated that the impaired metabolism of PtdIns(3,4,5)P3 is a prime mediator of insulin resistance associated with various metabolic diseases including obesity and diabetes. This review examines the current status of the role of PtdIns(3,4,5)P3 signaling in the regulation of various cellular functions and the implications of dysregulated PtdIns(3,4,5)P3 signaling in obesity, diabetes, and their associated complications. PMID:25721445

  9. Ab initio and molecular dynamics studies of crystalline TNAD (trans-1,4,5,8-tetranitro-1,4,5,8-tetraazadecalin).

    PubMed

    Qiu, Ling; Xiao, He-Ming; Zhu, Wei-Hua; Xiao, Ji-Jun; Zhu, Wei

    2006-06-01

    The structural and electronic properties of the energetic crystal TNAD (trans-1,4,5,8-tetranitro-1,4,5,8- tetraazadecalin) have been studied using plane-wave ab initio calculations based on the density function theory method with the ultrasoft pseudopotentials. It is found that the predicted crystal structure is in good agreement with experimental data and there are strong inter- and intramolecular interactions in bulk TNAD. Band structure calculations indicate that TNAD is an insulator with the band gap of ca. 3.3 eV. The hydrostatic compression effect on TNAD has been studied in the pressure range of 0-600 GPa. The results show that a pressure less than 10 GPa does not significantly change the geometric parameters, charge distributions, and electronic bands. When the pressure is over 10 GPa, increasing the pressure determines significant changes of the geometrical and electronic structures and large broadening of the electronic bands together with a sharp decrease of the band gap. Isothermal-isobaric molecular dynamics simulations at atmospheric pressure were further performed on the TNAD crystal in the temperature range 5-500 K. Average equilibrium lattice parameters and elastic properties as functions of temperature were determined. The thermal expansion coefficients calculated for the crystal indicate anisotropic behavior with the largest expansion along the b axis. PMID:16771311

  10. Physical chemistry of binary organic eutectic and monotectic alloys; 1,2,4,5-tetrachlorobenzene-β-naphthol and 1,2,4,5-tetramethylbenzene-succinonitrile systems

    NASA Astrophysics Data System (ADS)

    Rai, U. S.; Pandey, Pinky; Rai, R. N.

    2000-12-01

    Phase diagrams of 1,2,4,5-tetrachlorobenzene-β-naphthol and 1,2,4,5-tetramethylbenzene-succinonitrile systems which are organic analogues of a nonmetal-nonmetal and a nonmetal-metal system, respectively, show the formation of a simple eutectic (melting point 103.7°C) with 0.71 mole fraction of β-naphthol in the former case and a monotectic (melting point 76.0°C) with 0.07 mole fraction of succinonitrile and a eutectic (melting point 52.5°C) with 0.97 mole fraction of succinonitrile in the latter case. The growth behaviour of the pure components, the eutectics and the monotectic studied by measuring the rate of movement of the solid-liquid interface in a capillary, suggests that the data obey the Hillig-Turnbull equation, v= u(Δ T) n, where v is the growth velocity, Δ T is the undercooling and u and n are constants depending on the nature of the materials involved. From the values of enthalpy of fusion determined by the DSC method using Mettler DSC-4000 system, entropy of fusion, interfacial energy, enthalpy of mixing and excess thermodynamic functions were calculated. The optical microphotographs of pure components and polyphase materials show their characteristic features.

  11. Room-temperature fracture in V-(4-5)Cr-(4-5)Ti tensile specimens irradiated in Fusion-1 BOR-60 experiment

    SciTech Connect

    Gazda, J.; Meshii, M.; Tsai, H.

    1998-09-01

    Specimens of V-(4-5)Cr-(4-5)Ti alloys were irradiated to {approx}18 dpa at 320 C in the Fusion-1 capsule inserted into the BOR-60 reactor. Tensile tests at 23 C indicated dramatic yield strength increase (>300%), lack of work hardening, and minimal (<1%) total elongations. SEM analysis of fracture and side surfaces were conducted to determine reduction in are and the mode of fracture. The reduction of area was negligible. All but one specimen failed by a combination of ductile shear deformation and cleavage crack growth. Transgranular cleavage cracks were initiated by stress concentrations at the tips of the shear bands. In side-view observations, evidence was found of slip bands typically associated with dislocation channeling. No differences due to pre-irradiation heat treatment and heat-to-heat composition variations were detected. The only deviation from this behavior was found in V-4Cr-4Ti-B alloy, which failed in the grip portion by complete cleavage cracking.

  12. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit

    PubMed Central

    Pronk, Sander; Páll, Szilárd; Schulz, Roland; Larsson, Per; Bjelkmar, Pär; Apostolov, Rossen; Shirts, Michael R.; Smith, Jeremy C.; Kasson, Peter M.; van der Spoel, David; Hess, Berk; Lindahl, Erik

    2013-01-01

    Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from http://www.gromacs.org. Contact: erik.lindahl@scilifelab.se Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23407358

  13. 3,4,5-Trichloroaniline Nephrotoxicity in Vitro: Potential Role of Free Radicals and Renal Biotransformation

    PubMed Central

    Racine, Christopher; Ward, Dakota; Anestis, Dianne K.; Ferguson, Travis; Preston, Deborah; Rankin, Gary O.

    2014-01-01

    Chloroanilines are widely used in the manufacture of drugs, pesticides and industrial intermediates. Among the trichloroanilines, 3,4,5-trichloroaniline (TCA) is the most potent nephrotoxicant in vivo. The purpose of this study was to examine the nephrotoxic potential of TCA in vitro and to determine if renal biotransformation and/or free radicals contributed to TCA cytotoxicity using isolated renal cortical cells (IRCC) from male Fischer 344 rats as the animal model. IRCC (~4 million cells/mL; 3 mL) were incubated with TCA (0, 0.1, 0.25, 0.5 or 1.0 mM) for 60–120 min. In some experiments, IRCC were pretreated with an antioxidant or a cytochrome P450 (CYP), flavin monooxygenase (FMO), cyclooxygenase or peroxidase inhibitor prior to incubation with dimethyl sulfoxide (control) or TCA (0.5 mM) for 120 min. At 60 min, TCA did not induce cytotoxicity, but induced cytotoxicity as early as 90 min with 0.5 mM or higher TCA and at 120 min with 0.1 mM or higher TCA, as evidenced by increased lactate dehydrogenase (LDH) release. Pretreatment with the CYP inhibitor piperonyl butoxide, the cyclooxygenase inhibitor indomethacin or the peroxidase inhibitor mercaptosuccinate attenuated TCA cytotoxicity, while pretreatment with FMO inhibitors or the CYP inhibitor metyrapone had no effect on TCA nephrotoxicity. Pretreatment with an antioxidant (α-tocopherol, glutathione, ascorbate or N-acetyl-l-cysteine) also reduced or completely blocked TCA cytotoxicity. These results indicate that TCA is directly nephrotoxic to IRCC in a time and concentration dependent manner. Bioactivation of TCA to toxic metabolites by CYP, cyclooxygenase and/or peroxidase contributes to the mechanism of TCA nephrotoxicity. Lastly, free radicals play a role in TCA cytotoxicity, although the exact nature of the origin of these radicals remains to be determined. PMID:25402648

  14. Greater trochanteric pain syndrome diagnosis and treatment.

    PubMed

    Mallow, Michael; Nazarian, Levon N

    2014-05-01

    Lateral hip pain, or greater trochanteric pain syndrome, is a commonly seen condition; in this article, the relevant anatomy, epidemiology, and evaluation strategies of greater trochanteric pain syndrome are reviewed. Specific attention is focused on imaging of this syndrome and treatment techniques, including ultrasound-guided interventions. PMID:24787333

  15. Changes to extreme wave climates of islands within the Western Tropical Pacific throughout the 21st century under RCP 4.5 and RCP 8.5, with implications for island vulnerability and sustainability

    USGS Publications Warehouse

    Shope, James B.; Storlazzi, Curt; Erikson, Li; Hegermiller, Christie

    2016-01-01

    Waves are the dominant influence on coastal morphology and ecosystem structure of tropical Pacific islands. Wave heights, periods, and directions for the 21st century were projected using near-surface wind fields from four atmosphere-ocean coupled global climate models (GCM) under representative concentration pathways (RCP) 4.5 and 8.5. GCM-derived wind fields forced the global WAVEWATCH-III wave model to generate hourly time-series of bulk wave parameters around 25 islands in the mid to western tropical Pacific Ocean for historical (1976–2005), mid-, and end-of-century time periods. Extreme significant wave heights decreased (~10.0%) throughout the 21st century under both climate scenarios compared to historical wave conditions and the higher radiative forcing 8.5 scenario displayed a greater and more widespread decrease in extreme significant wave heights compared to the lower forcing 4.5 scenario. An exception was for the end-of-century June–August season. Offshore of islands in the central equatorial Pacific, extreme significant wave heights displayed the largest changes from historical values. The frequency of extreme events during December–February decreased under RCP 8.5, whereas the frequency increased under RCP 4.5. Mean wave directions often rotated more than 30° clockwise at several locations during June–August, which could indicate a weakening of the trade winds’ influence on extreme wave directions and increasing dominance of Southern Ocean swell or eastern shift of storm tracks. The projected changes in extreme wave heights, directions of extreme events, and frequencies at which extreme events occur will likely result in changes to the morphology and sustainability of island nations.

  16. Aromatic fluorine compounds. II. 1,2,4,5-Tetrafluorobenzene and related compounds

    USGS Publications Warehouse

    Finger, G.C.; Reed, F.H.; Burness, D.M.; Fort, D.M.; Blough, R.R.

    1951-01-01

    The synthesis and properties of 1,2,4,5-tetrafluorobenzene and a group of bromofluoro and chlorofluorobenzenes with a predominating 1,2,4,5-structure are described. Flash point and surface tension data for the fluorinated benzenes and the influence of chlorine substitution upon these values were studied. Under nitration conditions, 1,2,4,5-tetrafluorobenzene will not form a nitro derivative, but will undergo a preferential 1,4-fluorine displacement-oxidation mechanism to give 2,5-difluoro-1,4-benzoquinone. Diazotization reactions on 2-nitro-3,4,6-trifluoroaniline reveal that the nitro group or a fluorine atom in the 4- or 6-position may become labilized, under certain conditions, and undergo replacement.

  17. Molecular control of PtdIns(3,4,5)P3 signaling in neutrophils

    PubMed Central

    Luo, Hongbo R; Mondal, Subhanjan

    2015-01-01

    Neutrophils play critical roles in innate immunity and host defense. However, excessive neutrophil accumulation or hyper-responsiveness of neutrophils can be detrimental to the host system. Thus, the response of neutrophils to inflammatory stimuli needs to be tightly controlled. Many cellular processes in neutrophils are mediated by localized formation of an inositol phospholipid, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3), at the plasma membrane. The PtdIns(3,4,5)P3 signaling pathway is negatively regulated by lipid phosphatases and inositol phosphates, which consequently play a critical role in controlling neutrophil function and would be expected to act as ideal therapeutic targets for enhancing or suppressing innate immune responses. Here, we comprehensively review current understanding about the action of lipid phosphatases and inositol phosphates in the control of neutrophil function in infection and inflammation. PMID:25576302

  18. Immunogenicity of Plasmodium yoelii merozoite surface protein 4/5 produced in transgenic plants.

    PubMed

    Wang, Lina; Webster, Diane E; Campbell, Alison E; Dry, Ian B; Wesselingh, Steve L; Coppel, Ross L

    2008-01-01

    Malaria is a major global health problem for which effective control measures are urgently needed. Considerable effort has been focused on the development of effective vaccines against the causative parasite and protective vaccine trials are now being reported. Due to the relative poverty and lack of infrastructure in malaria-endemic areas, a successful immunisation strategy will depend critically on cheap and scaleable methods of vaccine production, distribution and delivery. One promising technology is transgenic plants, both as a bioreactor for the vaccine-manufacturing process as well as a matrix for oral immunisation. In this study, we investigated the feasibility of using transgenic plants to induce protective immunity against malaria infection using Plasmodium yoelii merozoite surface protein 4/5 (PyMSP4/5) in a mouse model of malaria infection. Our data show that the PyMSP4/5 protein can be produced in plants in a configuration that reacts with protective antibodies. Optimisation of codon usage for the PyMSP4/5 gene resulted in significantly increased antigen expression in plants. PyMSP4/5 protein from the codon-optimised construct accumulated to 0.25% of total soluble protein, a sixfold increase over the native gene sequence. Tobacco-made PyMSP4/5 was able to induce antigen-specific antibodies in mice following parenteral delivery, as well as boost the antibody responses induced by DNA vaccination when delivered parenterally or orally. We believe this is the first report to show that plant-made malaria antigens are immunogenic. However, the antibody levels were not high enough to protect the immunised mice against a lethal challenge with P. yoelii. Further strategies are needed to achieve a protective dose, including improvements to antigen expression levels in plants and strategies to enhance the immunogenicity of the expressed antigen. PMID:17681344

  19. Phosphatidylinositol(4,5)bisphosphate and phosphatidylinositol(4)phosphate in plant tissues. [Pisum sativum

    SciTech Connect

    Irvine, R.F.; Letcher, A.J.; Lander, D.J. ); Dawson, A.P. ); Musgrave, A. ); Drobak, B.K. )

    1989-03-01

    Pea (Pisum sativum) leaf discs or swimming suspensions of Chlamydomonas eugametos were radiolabeled with ({sup 3}H)myo-inositol or ({sup 32}P)Pi and the lipids were extracted, deacylated, and their glycerol moieties removed. The resulting inositol trisphosphate and bisphosphate fractions were examined by periodate degradation, reduction and dephosphorylation, or by incubation with human red cell membranes. Their likely structures were identified as D-myo-inositol(1,4,5)trisphosphate and D-myo-inositol(1,4,)-bisphosphate. It is concluded that plants contain phosphatidylinositol(4)phosphate and phosphatidylinositol(4,5)bisphosphate; no other polyphosphoinositides were detected.

  20. Synthesis, characterization, and crystal structure of 2-iodo-3,4,5-trimethoxybenzoic acid

    NASA Astrophysics Data System (ADS)

    Kolev, Iliyan N.; Petrova, Svetlana P.; Nikolova, Rositsa P.; Dimowa, Louiza T.; Shivachev, Boris L.

    2013-02-01

    This work describes the synthesis of 2-iodo-3,4,5-trimethoxybenzoic acid. The combination of iodine and silver trifluoroacetate (AgTFA) reagents was used successfully for the iodination of 3,4,5-trimetoxybenzoic acid. To improve the efficiency of the synthetic process a significant modification on the experimental design was also performed. The main structural features of the obtained aryl iodide were investigated by a single crystal X-ray diffraction analysis, FTIR, 1H and 13C NMR spectroscopy.

  1. Synthesis and Biological Activity of New [1,3]Thiazolo[4,5-d]pyridazin-4(5H)-ones

    PubMed Central

    Demchenko, Anatoly; Bobkova, Ludmila; Yadlovskiy, Oleh; Buchtiarova, Tatiana; Demchenko, Sergey

    2016-01-01

    A series of novel 2-(N-pyrrolidino, N-piperidino or N-morpholino)-7-phenyl(α-furoyl or α-thienyl)-[1,3]thiazolo[4,5-d]pyridazinones 10a–c, 14–16a,b was synthesized in 78–87% yields via the reaction of methyl 5-benzoyl(α-furoyl or α-thienyl)-2-aminosubstituted-thiazol-4-carboxylates 9a–c, 13a–e with hydrazine. These new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. All compounds have been characterized by 1H-NMR, 13C-NMR spectroscopy, and liquid chromatography–mass spectrometry. PMID:27222602

  2. Synthesis and Biological Activity of New [1,3]Thiazolo[4,5-d]pyridazin-4(5H)-ones.

    PubMed

    Demchenko, Anatoly; Bobkova, Ludmila; Yadlovskiy, Oleh; Buchtiarova, Tatiana; Demchenko, Sergey

    2016-01-01

    A series of novel 2-(N-pyrrolidino, N-piperidino or N-morpholino)-7-phenyl(α-furoyl or α-thienyl)-[1,3]thiazolo[4,5-d]pyridazinones 10a-c, 14-16a,b was synthesized in 78-87% yields via the reaction of methyl 5-benzoyl(α-furoyl or α-thienyl)-2-aminosubstituted-thiazol-4-carboxylates 9a-c, 13a-e with hydrazine. These new compounds have been tested for their in vivo analgesic and anti-inflammatory activities. All compounds have been characterized by (1)H-NMR, (13)C-NMR spectroscopy, and liquid chromatography-mass spectrometry. PMID:27222602

  3. Characteristics of 2,4,5,2',4',5'-hexachlorobiphenyl distribution among lipoproteins in vitro. [Rats and human whole blood, plasma, and lipoprotein fractions

    SciTech Connect

    Vomachka, M.S.; Vodicnik, M.J.; Lech, J.J.

    1983-09-01

    The uptake, distribution, and transfer of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) were examined in vitro with human and rat whole blood, plasma, and lipoprotein fractions. 6-CB distribution between plasma and erythrocytes as well as among lipoproteins was determined following sedimentation of erythrocytes and ultracentrifugal fractionation of plasma. In both rat and human whole blood, 70 to 75% of 6-CB partitioned into plasma and 25 to 30% into erythrocytes. The uptake of 6-CB into plasma was extremely rapid and the rate of uptake was found to be dependent upon temperature. The distribution of 6-CB among lipoproteins was relatively homogeneous with 20 to 30% being distributed in very low-density lipoproteins (VLDL, d . 0.95-1.006 g/ml), 15 to 20% in low-density lipoproteins (LDL, d . 1.006-1.063 g/ml), and 15 to 25% in high-density lipoproteins (HDL, d . 1.063-1.21 g/ml). Over 25% of 6-CB was found in the remaining bottom fraction. In addition, each isolated fraction when incubated alone with 6-CB was shown capable of uptake. The relative proportion of 6-CB among the lipoproteins was independent of the level taken up by plasma. 6-CB was also found to transfer among lipoproteins. This exchange of 6-CB proved to be dependent upon the concentrations of both protein and triacylglycerol in the incubations. Two proteins in the bottom fraction (Bf), albumin and a steroid binding globulin, were capable of competing with the lipoproteins for 6-CB uptake.

  4. Analysis of the Rotational Spectra of 2,3,4,5,6-PENTAFLUOROTOLUENE and 1-CHLORO-2,3,4,5,6-PENTAFLUOROBENZENE

    NASA Astrophysics Data System (ADS)

    Osthoff, Ashley A.; Peebles, Rebecca A.; Peebles, Sean A.; Grubbs, Garry S. Grubbs, II; Cooke, Stephen A.; Pate, Brooks H.; Neill, Justin L.; Muckle, Matt T.

    2009-06-01

    The microwave spectra of two substituted pentafluorobenzenes have been obtained. 2,3,4,5,6-Pentafluorotoluene was measured using the FTMW spectrometer at Eastern Illinois University and the chirped-pulse FTMW spectrometer at University of North Texas. The heavy atom structure has been obtained from the assigned ^{13}C transitions and is in reasonable agreement with ab initio calculations at the MP2/6-311++G(2d, 2p) level. The ground state rotational constants are A = 1036.61253(10) MHz, B = 1030.94126(10) MHz, and C = 516.92062(9) MHz, and the single dipole moment component is μ_b = 1.98(17) D. Very small splittings for many of the assigned transitions and multiple, as yet unassigned, lines were presumably due to excited torsional states of the methyl group. In a related study, the microwave spectrum of 1-chloro-2,3,4,5,6-pentafluorobenzene was obtained for both the ^{35}Cl and the ^{37}Cl isotopologues using the chirped-pulse microwave spectrometer at University of Virginia. The preliminary ground state rotational constants for this compound are A = 1028.5403(14) MHz, B = 751.8198(3) MHz and C = 434.3533(4) MHz for ^{35}Cl and A = 1028.5435(7) MHz, B = 734.4786(2) MHz and C = 428.5082(2) MHz for ^{37}Cl. Initial fits of the nuclear quadrupole coupling constants give χ_{aa} = -79.512(15) MHz, χ_{bb} = 43.593(8) MHz, χ_{cc} = 35.92(2) MHz for the ^{35}Cl species and χ_{aa} = -62.68(2) MHz, χ_{bb} = 34.38(4) MHz, χ_{cc} = 28.29(17) MHz for the ^{37}Cl species. These results will be compared with pentafluorotoluene to observe the effects on the structure of the benzene ring when substituting a chlorine atom for a methyl group.

  5. 60. MISSISSIPPI, NOXUBEE CO. MACON MAHORNER' S BRIDGE, 1884, 4.5 ...

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

    60. MISSISSIPPI, NOXUBEE CO. MACON MAHORNER' S BRIDGE, 1884, 4.5 miles S on McLeod-Shuqualak road. Bottom of swing span and top of center pier. Sarcone Photography, Columbus, Ms. Sep 1978. - Bridges of the Upper Tombigbee River Valley, Columbus, Lowndes County, MS

  6. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 5 2011-04-01 2011-04-01 false Plan amendments and plan terminations. 1.401(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This...

  7. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Plan amendments and plan terminations. 1.401(a)(4... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This...

  8. 26 CFR 1.401(a)(4)-5 - Plan amendments and plan terminations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Plan amendments and plan terminations. 1.401(a... (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(a)(4)-5 Plan amendments and plan terminations. (a) Introduction—(1) Overview. This paragraph (a)...

  9. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  10. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  11. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  12. 17 CFR 275.206(4)-5 - Political contributions by certain investment advisers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... investment adviser that has reported on its annual updating amendment to Form ADV (17 CFR 279.1) that it has... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Political contributions by....206(4)-5 Political contributions by certain investment advisers. (a) Prohibitions. As a...

  13. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  14. 40 CFR 721.10584 - Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10584 Cyclopentene, 1,3,3,4,4,5,5-heptafluoro-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  15. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  16. 40 CFR 721.10433 - Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ....80(f) and (j) (dry etching agent and chemical vapor deposition agent for the production of...) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.10433 Cyclopentene, 1,2,3,3,4,4,5,5-octafluoro-. (a) Chemical...

  17. Fragmentation of silicon nuclei at 4. 5 A GeV/c

    SciTech Connect

    Ahmad, T.; Irfan, M. )

    1991-11-30

    1024 interactions caused by 4.5 A GeV/c {sup 28}Si in emulsion are studied. In this paper result on the mean free path is discussed and compared with the corresponding results obtained for the interactions initiated by other projectiles. Multiplicity distributions for Z = 1, 2 and {ge}3 fragments are also investigated.

  18. Spt4/5 stimulates transcription elongation through the RNA polymerase clamp coiled-coil motif

    PubMed Central

    Hirtreiter, Angela; Damsma, Gerke E.; Cheung, Alan C. M.; Klose, Daniel; Grohmann, Dina; Vojnic, Erika; Martin, Andrew C. R.; Cramer, Patrick; Werner, Finn

    2010-01-01

    Spt5 is the only known RNA polymerase-associated factor that is conserved in all three domains of life. We have solved the structure of the Methanococcus jannaschii Spt4/5 complex by X-ray crystallography, and characterized its function and interaction with the archaeal RNAP in a wholly recombinant in vitro transcription system. Archaeal Spt4 and Spt5 form a stable complex that associates with RNAP independently of the DNA–RNA scaffold of the elongation complex. The association of Spt4/5 with RNAP results in a stimulation of transcription processivity, both in the absence and the presence of the non-template strand. A domain deletion analysis reveals the molecular anatomy of Spt4/5—the Spt5 Nus-G N-terminal (NGN) domain is the effector domain of the complex that both mediates the interaction with RNAP and is essential for its elongation activity. Using a mutagenesis approach, we have identified a hydrophobic pocket on the Spt5 NGN domain as binding site for RNAP, and reciprocally the RNAP clamp coiled-coil motif as binding site for Spt4/5. PMID:20197319

  19. Priming 4.5-Month-Old Infants to Use Height Information by Enhancing Retrieval

    ERIC Educational Resources Information Center

    Wang, Su-hua

    2011-01-01

    How do infants select and use information that is relevant to the task at hand? Infants treat events that involve different spatial relations as distinct, and their selection and use of object information depends on the type of event they encounter. For example, 4.5-month-olds consider information about object height in occlusion events, but…

  20. Bifunctional Ag/C3N4.5 composite nanobelts for photocatalysis and antibacterium.

    PubMed

    Lei, Renbo; Jian, Jikang; Zhang, Zhihua; Song, Bo; Wu, Rong

    2016-09-30

    Multiple functions can be achieved in carbon nitride-based composite nanomaterials by tuning their components and structures. Here, we report on a large-scale synthesis of novel bifunctional Ag/C3N4.5 composite nanobelts (CNBs) with efficient photocatalytic and antibacterial activity. The Ag/C3N4.5 CNBs were synthesized in high yield by a two-step route including a homogeneous precipitation process and a subsequent calcination treatment. The structural, morphological, compositional, and spectroscopic characterizations revealed that the Ag/C3N4.5 CNBs are composed of N-deficient melem ultrathin nanobelts and crystalline Ag nanoparticles attached to the surface of the nanobelts with good contact. The band gap of the Ag/C3N4.5 CNBs is determined to be about 3.04 eV. The efficient photocatalytic and antibacterial activities of the composite nanomaterials are verified by testing the degradation of Rhodamine B (RhB) and the inhibition zone to bacterium E. coli. The work provides a facile route to bifunctional carbon nitride-based composites with potential applications in the fields of the environment and biology. PMID:27560165

  1. The Role of PI(3,4,5)P3 Signaling During Axonal Growth Cone Chemotaxis

    NASA Astrophysics Data System (ADS)

    Henle, Steven J.

    Development of the nervous system is a remarkably complex process that involves the birth of billions of neurons leading to the formation of trillions of synapses. Many biological programs underlie the formation of a functional nervous system. I focused on trying to understand the process by which a newly formed axon navigates a series of signals in the environment that guide it to a synaptic partner. At the tip of the extending neurite is a conical expansion known as the growth cone that primarily is responsible for performing this pathfinding process. In order to do so it senses the environment, and induces a program of intracellular signaling that in turn leads to directed axon extension. My work has focused on understanding this signaling machinery. I have aimed to understand the role the phosphoinositde PI(3,4,5)P3 due to the critical role it plays in amoeboid chemotaxis. I discovered that PI(3,4,5)P3 and its downstream kinase Akt define the leading edge during growth cone chemotaxis and lead to activation of a TRP (Transient Receptor Potential) channel. Furthermore, I found that the PI(3,4,5)P3 phosphatase PTEN appears to be exclusively linked to guiding growth cone migration in response to a gradient of chemorepellent. Taken together my data demonstrate that PI(3,4,5)P3 functions as a key instructive mediator of growth cone chemotaxis.

  2. Effectiveness of Multipurpose Unit Early Classroom Intervention Program for 4-5-Year-Old Children

    ERIC Educational Resources Information Center

    Celebioglu Morkoc, Ozlem; Aktan Acar, Ebru

    2014-01-01

    This research examined the effectiveness of Multipurpose Unit Early Classroom Intervention Program (MUECIP) prepared for 4-5-year-old (48-60 months) children whose development is at risk because of their families' socioeconomic conditions. The research adopted a preliminary test-final test control group trial model. The research participants…

  3. Synthesis and antifungal activity of natural product-based 6-alkyl-2 3 4 5-tetrahydropyridines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural products piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexa...

  4. Ensemble Perception of Size in 4-5-Year-Old Children

    ERIC Educational Resources Information Center

    Sweeny, Timothy D.; Wurnitsch, Nicole; Gopnik, Alison; Whitney, David

    2015-01-01

    Groups of objects are nearly everywhere we look. Adults can perceive and understand the "gist" of multiple objects at once, engaging ensemble-coding mechanisms that summarize a group's overall appearance. Are these group-perception mechanisms in place early in childhood? Here, we provide the first evidence that 4-5-year-old children use…

  5. 4,5-Disubstituted oxazolidinones: High affinity molecular effectors of RNA function.

    PubMed

    Anupam, Rajaneesh; Nayek, Abhijit; Green, Nicholas J; Grundy, Frank J; Henkin, Tina M; Means, John A; Bergmeier, Stephen C; Hines, Jennifer V

    2008-06-15

    The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination function of the T box riboswitch. PMID:18502126

  6. 2,2\\',4,4\\',5,5\\'-Hexabromodiphenyl ether (BDE-153)

    Integrated Risk Information System (IRIS)

    2,2 ' , 4,4 ' , 5,5 ' - Hexabromodiphenyl ether ( BDE - 153 ) ; CASRN 68631 - 49 - 2 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I (

  7. 2,2\\',3,3\\',4,4\\',5,5\\',6,6\\'-Decabromodiphenyl ether (BDE-209)

    Integrated Risk Information System (IRIS)

    2,2 ' , 3,3 ' , 4,4 ' , 5,5 ' , 6,6 ' - Decabromodiphenyl ether ( BDE - 209 ) ; CASRN 1163 - 19 - 5 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process

  8. Strand I: Physical Health. Sensory Perception. Health Curriculum Materials Grades 4, 5, 6.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Elementary Curriculum Development.

    GRADES OR AGES: Grades 4, 5, and 6. SUBJECT MATTER: Sensory perceptions, the organs involved, and eye and hearing care. ORGANIZATION AND PHYSICAL APPEARANCE: The guide is divided into six different sectional steps organized around a gradual, ascending understanding of the sense organs. OBJECTIVES AND ACTIVITIES: The material is divided into…

  9. Physical Education, Junior Division: Grades 4, 5, 6. Curriculum J.5.

    ERIC Educational Resources Information Center

    Ontario Dept. of Education, Toronto.

    This manual was prepared to give teachers assistance in carrying out programs in physical education in grades 4, 5, and 6. Because many schools have space and equipment deficiencies, some emphasis has been placed on improvisation and the fullest possible use of available space and equipment. The manual is divided into two sections: organization…

  10. Synthetic studies towards Zetekitoxin AB: preparation of 4,5-epi-11-hydroxy-saxitoxinol

    PubMed Central

    Pearson, Aaron D.; Williams, Robert M.

    2014-01-01

    A concise synthesis of 4,5-epi-11-hydroxy-saxitoxinol utilizing D-ribose to direct an asymmetric Mannich reaction. This approach allows many modes of reactivity, which can be used to access various analogs of saxitoxin. PMID:25313264

  11. Synthesis of inositol phosphate-based competitive antagonists of inositol 1,4,5-trisphosphate receptors.

    PubMed

    Konieczny, Vera; Stefanakis, John G; Sitsanidis, Efstratios D; Ioannidou, Natalia-Anastasia T; Papadopoulos, Nikolaos V; Fylaktakidou, Konstantina C; Taylor, Colin W; Koumbis, Alexandros E

    2016-02-16

    Inositol 1,4,5-trisphosphate receptors (IP3Rs) are intracellular Ca(2+) channels that are widely expressed in animal cells, where they mediate the release of Ca(2+) from intracellular stores evoked by extracellular stimuli. A diverse array of synthetic agonists of IP3Rs has defined structure-activity relationships, but existing antagonists have severe limitations. We combined analyses of Ca(2+) release with equilibrium competition binding to IP3R to show that (1,3,4,6)IP4 is a full agonist of IP3R1 with lower affinity than (1,4,5)IP3. Systematic manipulation of this meso-compound via a versatile synthetic scheme provided a family of dimeric analogs of 2-O-butyryl-(1,3,4,6)IP4 and (1,3,4,5,6)IP5 that compete with (1,4,5)IP3 for binding to IP3R without evoking Ca(2+) release. These novel analogs are the first inositol phosphate-based competitive antagonists of IP3Rs with affinities comparable to that of the only commonly used competitive antagonist, heparin, the utility of which is limited by off-target effects. PMID:26818818

  12. Preparation of 3,3'-azobis(6-amino-1,2,4,5-tetrazine)

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2002-01-01

    The compound of the structure ##STR1## where a, b, c, d and e are 0 or 1 and a+b+c+d+e is from 0 to 5 is disclosed together with the species 3,3'-azobis(6-amino-1,2,4,5-tetrazine) and a process of preparing such compounds.

  13. IMMUNOHISTOCHEMICAL ANALYSIS OF ZNT1, 4, 5, 6, AND 7 IN THE MOUSE GASTROINTESTINAL TRACT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Expression of five zinc transporters (ZnT1, 4, 5, 6, and 7) of the Slc30 family in the mouse gastrointestinal tract was studied by immunohistochemical analysis. The results demonstrated unique expression patterns, levels, and cellular localization among ZnT proteins in the mouse gastrointestinal tra...

  14. Netscape Communicator 4.5. Volume I: The Basic Functions of the Navigator Component.

    ERIC Educational Resources Information Center

    Gallo, Gail; Wichowski, Chester P.

    This first of two guides on Netscape Communicator 4.5 contains six lessons on the basic functions of the Navigator component. Lesson 1 covers terminology and methods to connect to the World Wide Web, hardware needed, and a Netscape Communicator overview. Lesson 2 introduces the Navigator window, toolbars, and menus, and how to change the default…

  15. Median CBO Salary Rises by 4.5 Percent, Annual Study Finds.

    ERIC Educational Resources Information Center

    Business Officer, 1997

    1997-01-01

    An annual national survey of college and university salaries found chief business officers' salaries rose 4.5 percent in 1996-97, less than the previous year. Salaries of women and minority CBOs continued to gain equity with that of men. Rates of increase varied by institution type. Salary gains for all administrative job types were less than in…

  16. Men Face Greater Risk of Cardiac Arrest

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_159651.html Men Face Greater Risk of Cardiac Arrest: Study Heart ... 30, 2016 THURSDAY, June 30, 2016 (HealthDay News) -- Men are significantly more likely to have their heart ...

  17. Men Face Greater Risk of Cardiac Arrest

    MedlinePlus

    ... fullstory_159651.html Men Face Greater Risk of Cardiac Arrest: Study Heart disease tends to develop earlier than ... About one in nine men will suffer a cardiac arrest before the age of 70, compared to about ...

  18. Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid by metal-oxide-coated Ti electrodes.

    PubMed

    Maharana, Dusmant; Xu, Zesheng; Niu, Junfeng; Rao, Neti Nageswara

    2015-10-01

    Electrochemical oxidation of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) over metal-oxide-coated Ti anodes, i.e., Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb and Ti/RuO2, was examined. The degradation efficiency of over 90% was attained at 20 min at different initial concentrations (0.5-20 mg L(-1)) and initial pH values (3.1-11.2). The degradation efficiencies of 2,4,5-T on Ti/SnO2-Sb/Ce-PbO2, Ti/SnO2-Sb and Ti/RuO2 anodes were higher than 99.9%, 97.2% and 91.5% at 30 min, respectively, and the respective total organic carbon removal ratios were 65.7%, 54.6% and 37.2%. The electrochemical degradation of 2,4,5-T in aqueous solution followed pseudo-first-order kinetics. The compounds, i.e., 2,5-dichlorohydroquinone and 2,5-dihydroxy-p-benzoquinone, have been identified as the main aromatic intermediates by liquid chromatography-mass spectrometry. The results showed that the energy efficiencies of 2,4,5-T (20 mg L(-1)) degradation with Ti/SnO2-Sb/Ce-PbO2 anode at the optimal current densities from 2 to 16 mA cm(-2) ranged from 8.21 to 18.73 kWh m(-3). PMID:25981800

  19. Conformational Changes in Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase upon Substrate Binding

    PubMed Central

    Baños-Sanz, José Ignacio; Sanz-Aparicio, Julia; Whitfield, Hayley; Hamilton, Chris; Brearley, Charles A.; González, Beatriz

    2012-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP5. Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP5 2-K, which shed light on aspects of substrate recognition. However, failure of IP5 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP5 2-K in its different conformations by crystallography. Thus, the IP5 2-K apo-form structure displays an open conformation, whereas the nucleotide-bound form shows a half-closed conformation, in contrast to the inositide-bound form obtained previously in a closed conformation. Both nucleotide and inositide binding produce large conformational changes that can be understood as two rigid domain movements, although local changes were also observed. Changes in intrinsic fluorescence upon nucleotide and inositide binding are in agreement with the crystallographic findings. Our work suggests that the clasp might be involved in enzyme kinetics, with the N-terminal lobe being essential for inositide binding and subsequent conformational changes. We also show how IP5 2-K discriminates between inositol 1,3,4,5-tetrakisphosphate and 3,4,5,6-tetrakisphosphate enantiomers and that substrate preference can be manipulated by Arg130 mutation. Altogether, these results provide a framework for rational design of specific inhibitors with potential applications as biological tools for in vivo studies, which could assist in the identification of novel roles for IP5 2-K in mammals. PMID:22745128

  20. Degradation of 2,4,5-trichlorophenol by the lignin-degrading basidiomycete Phanerochaete chrysosporium.

    PubMed Central

    Joshi, D K; Gold, M H

    1993-01-01

    Under secondary metabolic conditions the white rot basidiomycete Phanerochaete chrysosporium rapidly mineralizes 2,4,5-trichlorophenol. The pathway for degradation of 2,4,5-trichlorophenol was elucidated by the characterization of fungal metabolites and oxidation products generated by purified lignin peroxidase (LiP) and manganese peroxidase (MnP). The multistep pathway involves cycles of peroxidase-catalyzed oxidative dechlorination reactions followed by quinone reduction reactions to yield the key intermediate 1,2,4,5-tetrahydroxybenzene, which is presumably ring cleaved. In the first step of the pathway, 2,4,5-trichlorophenol is oxidized to 2,5-dichloro-1,4-benzoquinone by either MnP or Lip. 2,5-Dichloro-1,4-benzoquinone is then reduced to 2,5-dichloro-1,4-hydroquinone. The 2,5-dichloro-1,4-hydroquinone is oxidized by MnP to generate 5-chloro-4-hydroxy-1,2-benzoquinone. The orthoquinone is in turn reduced to 5-chloro-1,2,4-trihydroxybenzene. Finally, the 5-chlorotrihydroxybenzene undergoes another cycle of oxidative dechlorination and reduction reactions to generate 1,2,4,5-tetrahydroxybenzene. The latter is presumably ring cleaved, with subsequent degradation to CO2. In this pathway, the substrate is oxidatively dechlorinated by LiP or MnP in a reaction which produces a quinone. The quinone intermediate is recycled by a reduction reaction to regenerate an intermediate which is again a substrate for peroxidase-catalyzed oxidative dechlorination. This pathway apparently results in the removal of all three chlorine atoms before ring cleavage occurs. PMID:8328802

  1. Comparison of the virulence of O:9,12 and O:4,5,12 Salmonella typhimurium his+ transductants for mice.

    PubMed Central

    Lyman, M B; Stocker, B A; Roantree, R J

    1977-01-01

    The purpose of these experiments was to determine whether qualitative differences in the O repeat unit of the lipopolysaccharide of pathogenic Salmonella species affected virulence for mice. O:4,5,12 and O:9,12 sister his+ transductants were derived from a virulent Salmonella typhimurium. Fermentation markers were introduced by transduction to differentiate these strains, and the strains were used as mixed challenge to CF1 and C57B1/6J mice. Liver and spleen cultures of the mice of various intervals after challenge indicated that the O:4,5,12 member of the nearly isogenic pair regularly multiplied to a greater extent than the O:9,12 after intraperitoneal challenge for both strains of mice. After oral challenge, there was little difference in the amount of multiplication of the O:4,5,12 and O:9,12 strains in CF1 mice, but the O:4,5,12 was the predominant strain recovered in 8 of 10 instances in the C57B1/6J mice. PMID:321351

  2. Effects of prenatal exposure to 2,4-D/2,4,5-T mixture on postnatal changes in rat brain glutamate, GABA protein, and nucleic acid levels

    SciTech Connect

    Mohammad, F.K.; Omer, V.E.V.

    1988-02-01

    The opportunity of maternal exposure to various chemicals in the work place and the general environments have increased, and the fetus and neonate may be at greater risk than the adult. However, the embryotoxic and teratogenic effects of the chlorinated phenoxy herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), the main chemicals in Agent Orange, are well documented only in laboratory animals. The brain of the developing fetus is vulnerable to the toxic effects of the phenoxy herbicides which readily cross the placental barrier and distribute into fetal tissues, including brain. Although the neurochemical basis for the behavioral teratogenicity of the phenoxy herbicides is not know, it was recently reported that non-teratogenic doses of a 1:1 mixture of 2,4-D and 2,4,5-T delayed the ontogeny of dopamine and serotonin in the brain of the developing rate. This communication provides further descriptive information about the ontogeny of rat brain nucleic acid, protein, glutamate and ..gamma..-aminobutyrate (GABA) following in utero exposure to non-teratogenic levels of a 1:1 mixture of 2,4-D/2,4,5-T.

  3. Cellulosimicrobium cellulans strain E4-5 enzymatic hydrolysis of curdlan for production of (1 → 3)-linked β-D-glucan oligosaccharides.

    PubMed

    Fu, Yunbin; Cheng, Likun; Meng, Yanyu; Li, Shuguang; Zhao, Xiaoming; Du, Yuguang; Yin, Heng

    2015-12-10

    In order to find an efficient enzymatic tool for curdlan degradation to produce (1 → 3)-linked β-D-glucan oligosaccharides, strain E4-5 (registration number JN089883, Genbank) was isolated from seaside soil. The 16S rRNA gene sequencing classified it as Cellulosimicrobium cellulans. It was the first reported microorganism that succeeded in degrading high-set heated curdlan blocks. The ferments of strain E4-5 also showed good degradation effects on laminaran and alkali-neutralized curdlan. Due to the products with less amount of glucose, it was assumed that endo-1,3-β-glucanases of strain E4-5 had a greater hydrolyzing effect than exo-1,3-β-glucanases. This indicated that strain E4-5 was a promising microorganism to hydrolyze (1 → 3)-linked β-D-glucan. Moreover, alkali-neutralization pretreatment was effective for promoting a more diversified degree of polymerization (DP) of (1 → 3)-linked β-D-glucan oligosaccharides under enzymatic hydrolysis and will pave the way for making full use of curdlan for production of glucan oligosaccharides. PMID:26428180

  4. Patterns and variability of projected bioclimatic habitat for Pinus albicaulis in the Greater Yellowstone Area.

    PubMed

    Chang, Tony; Hansen, Andrew J; Piekielek, Nathan

    2014-01-01

    Projected climate change at a regional level is expected to shift vegetation habitat distributions over the next century. For the sub-alpine species whitebark pine (Pinus albicaulis), warming temperatures may indirectly result in loss of suitable bioclimatic habitat, reducing its distribution within its historic range. This research focuses on understanding the patterns of spatiotemporal variability for future projected P.albicaulis suitable habitat in the Greater Yellowstone Area (GYA) through a bioclimatic envelope approach. Since intermodel variability from General Circulation Models (GCMs) lead to differing predictions regarding the magnitude and direction of modeled suitable habitat area, nine bias-corrected statistically down-scaled GCMs were utilized to understand the uncertainty associated with modeled projections. P.albicaulis was modeled using a Random Forests algorithm for the 1980-2010 climate period and showed strong presence/absence separations by summer maximum temperatures and springtime snowpack. Patterns of projected habitat change by the end of the century suggested a constant decrease in suitable climate area from the 2010 baseline for both Representative Concentration Pathways (RCPs) 8.5 and 4.5 climate forcing scenarios. Percent suitable climate area estimates ranged from 2-29% and 0.04-10% by 2099 for RCP 8.5 and 4.5 respectively. Habitat projections between GCMs displayed a decrease of variability over the 2010-2099 time period related to consistent warming above the 1910-2010 temperature normal after 2070 for all GCMs. A decreasing pattern of projected P.albicaulis suitable habitat area change was consistent across GCMs, despite strong differences in magnitude. Future ecological research in species distribution modeling should consider a full suite of GCM projections in the analysis to reduce extreme range contractions/expansions predictions. The results suggest that restoration strageties such as planting of seedlings and controlling

  5. Patterns and Variability of Projected Bioclimatic Habitat for Pinus albicaulis in the Greater Yellowstone Area

    PubMed Central

    Chang, Tony; Hansen, Andrew J.; Piekielek, Nathan

    2014-01-01

    Projected climate change at a regional level is expected to shift vegetation habitat distributions over the next century. For the sub-alpine species whitebark pine (Pinus albicaulis), warming temperatures may indirectly result in loss of suitable bioclimatic habitat, reducing its distribution within its historic range. This research focuses on understanding the patterns of spatiotemporal variability for future projected P.albicaulis suitable habitat in the Greater Yellowstone Area (GYA) through a bioclimatic envelope approach. Since intermodel variability from General Circulation Models (GCMs) lead to differing predictions regarding the magnitude and direction of modeled suitable habitat area, nine bias-corrected statistically down-scaled GCMs were utilized to understand the uncertainty associated with modeled projections. P.albicaulis was modeled using a Random Forests algorithm for the 1980–2010 climate period and showed strong presence/absence separations by summer maximum temperatures and springtime snowpack. Patterns of projected habitat change by the end of the century suggested a constant decrease in suitable climate area from the 2010 baseline for both Representative Concentration Pathways (RCPs) 8.5 and 4.5 climate forcing scenarios. Percent suitable climate area estimates ranged from 2–29% and 0.04–10% by 2099 for RCP 8.5 and 4.5 respectively. Habitat projections between GCMs displayed a decrease of variability over the 2010–2099 time period related to consistent warming above the 1910–2010 temperature normal after 2070 for all GCMs. A decreasing pattern of projected P.albicaulis suitable habitat area change was consistent across GCMs, despite strong differences in magnitude. Future ecological research in species distribution modeling should consider a full suite of GCM projections in the analysis to reduce extreme range contractions/expansions predictions. The results suggest that restoration strageties such as planting of seedlings and

  6. Insights of the Crystallization Process of Molecular Sieve AlPO4-5 Prepared by Solvent-Free Synthesis.

    PubMed

    Sheng, Na; Chu, Yueying; Xin, Shaohui; Wang, Qiang; Yi, Xianfeng; Feng, Zhaochi; Meng, Xiangju; Liu, Xiaolong; Deng, Feng; Xiao, Feng-Shou

    2016-05-18

    Crystallization of AlPO4-5 with AFI structure under solvent-free conditions has been investigated. Attention was mainly focused on the characterization of the intermediate phases formed at the early stages during the crystallization. The development in the long-range ordering of the solid phases as a function of crystallization time was monitored by XRD, SEM, IR, UV-Raman, and MAS NMR techniques. Particularly, the UV-Raman spectroscopy was employed to obtain the information on the formation process of the framework. J-HMQC (27)Al/(31)P double-resonance NMR experiments were used to identify the P-O-Al bonded species in the intermediate phases. For the first time the P-O-Al bonded species in the intermediate phases can be correctly described through using this advanced NMR technique. The crystallization under solvent-free conditions appears to follow the pathway: The initial amorphous raw material is converted to an intermediate phase which has four-/six-membered ring species, then gradually transformed into crystalline AlPO4-5. This observation is not consistent with the common idea that the intermediate phase is the semicrystalline intermediates with a three-dimensional structure. PMID:27116300

  7. An extraordinarily long larval duration of 4.5 years from hatching to metamorphosis for teleplanic veligers of Fusitriton oregonensis.

    PubMed

    Strathmann, Megumi F; Strathmann, Richard R

    2007-10-01

    Veliger larvae of the NE Pacific snail Fusitriton oregonensis were reared in culture for 4.5 to 4.6 years from hatching to metamorphosis and through postlarval growth to reproduction. Larval shells grew in length from 0.20 to 3.9 mm. Late veligers grew slowly, but shell sizes increased even in the 4th and 5th years. Widths of larval shells at late stages equaled or exceeded those of the protoconchs of two juveniles from the field. Cultured larvae did not metamorphose until presented with subtidal rocks and associated biota. There was no indication of larval senescence: the first 2 years of postmetamorphic shell growth were slightly faster, and time from metamorphosis to first reproduction (3.3 years) was slightly less than for an individual that had developed to metamorphic competence in the plankton. A 4.5-year larval phase exceeds previous estimates for teleplanic larval durations and greatly exceeds estimates of the time for transport across oceans. This extraordinarily long larval period may exceed the usual duration in nature but shows that larval periods can be much longer than previously suspected without complete stasis in growth and with little if any loss of viability. PMID:17928522

  8. Hybrid Modified K-Means with C4.5 for Intrusion Detection Systems in Multiagent Systems

    PubMed Central

    Laftah Al-Yaseen, Wathiq; Ali Othman, Zulaiha; Ahmad Nazri, Mohd Zakree

    2015-01-01

    Presently, the processing time and performance of intrusion detection systems are of great importance due to the increased speed of traffic data networks and a growing number of attacks on networks and computers. Several approaches have been proposed to address this issue, including hybridizing with several algorithms. However, this paper aims at proposing a hybrid of modified K-means with C4.5 intrusion detection system in a multiagent system (MAS-IDS). The MAS-IDS consists of three agents, namely, coordinator, analysis, and communication agent. The basic concept underpinning the utilized MAS is dividing the large captured network dataset into a number of subsets and distributing these to a number of agents depending on the data network size and core CPU availability. KDD Cup 1999 dataset is used for evaluation. The proposed hybrid modified K-means with C4.5 classification in MAS is developed in JADE platform. The results show that compared to the current methods, the MAS-IDS reduces the IDS processing time by up to 70%, while improving the detection accuracy. PMID:26161437

  9. Hybrid Modified K-Means with C4.5 for Intrusion Detection Systems in Multiagent Systems.

    PubMed

    Laftah Al-Yaseen, Wathiq; Ali Othman, Zulaiha; Ahmad Nazri, Mohd Zakree

    2015-01-01

    Presently, the processing time and performance of intrusion detection systems are of great importance due to the increased speed of traffic data networks and a growing number of attacks on networks and computers. Several approaches have been proposed to address this issue, including hybridizing with several algorithms. However, this paper aims at proposing a hybrid of modified K-means with C4.5 intrusion detection system in a multiagent system (MAS-IDS). The MAS-IDS consists of three agents, namely, coordinator, analysis, and communication agent. The basic concept underpinning the utilized MAS is dividing the large captured network dataset into a number of subsets and distributing these to a number of agents depending on the data network size and core CPU availability. KDD Cup 1999 dataset is used for evaluation. The proposed hybrid modified K-means with C4.5 classification in MAS is developed in JADE platform. The results show that compared to the current methods, the MAS-IDS reduces the IDS processing time by up to 70%, while improving the detection accuracy. PMID:26161437

  10. The mass function of black holes 14.5: comparison of models with observations

    NASA Astrophysics Data System (ADS)

    Natarajan, Priyamvada; Volonteri, Marta

    2012-05-01

    In this paper, we compare the observationally derived black hole mass function (BHMF) of luminous (>1045-1046 erg s-1) broad-line quasars (BLQSOs) at 1 < z < 4.5 drawn from the Sloan Digital Sky Survey (SDSS) presented by Kelly et al., with models of merger-driven black hole (BH) growth in the context of standard hierarchical structure formation models. In these models, we explore two distinct black hole seeding prescriptions at the highest redshifts: 'light seeds'- remnants of Population III stars and 'massive seeds' that form from the direct collapse of pre-galactic discs. The subsequent merger triggered mass build-up of the black hole population is tracked over cosmic time under the assumption of a fixed accretion rate as well as rates drawn from the distribution derived by Merloni & Heinz. Four model snapshots at z= 1.25, 2, 3.25 and 4.25 are compared with the SDSS-derived BHMFs of BLQSOs. We find that the light seed models fall short of reproducing the observationally derived mass function of BLQSOs at MBH > 109 M⊙ throughout the redshift range; the massive seed models with a fixed accretion rate of 0.3 Edd, or with accretion rates drawn from the Merloni & Heinz distribution provide the best fit to the current observational data at z > 2, although they overestimate the high-mass end of the mass function at lower redshifts. At low redshifts, a drastic drop in the accretion rate is observed and this is explained as arising due to the diminished gas supply available due to consumption by star formation or changes in the geometry of the inner feeding regions. Therefore, the overestimate at the high-mass end of the black hole mass function for the massive seed models can be easily modified, as the accretion rate is likely significantly lower at these epochs than what we assume. For the Merloni & Heinz model, examining the Eddington ratio distributions fEdd, we find that they are almost uniformly sampled from fEdd= 10-2 to 1 at z≃ 1, while at high redshift

  11. Stretch increases inositol 1,4,5-trisphosphate concentration in airway epithelial cells.

    PubMed

    Felix, J A; Woodruff, M L; Dirksen, E R

    1996-03-01

    Mechanical stimulation of airway epithelial cells with a microprobe leads to an increase in cytoplasmic [Ca2+] that appears to be due, in part, to release of Ca2+ from inositol 1,4,5-trisphosphate (IP3)-sensitive stores (Boitano et al., Science 258:292[1992]). To investigate whether intracellular IP3 concentration ([IP3]i) increases in response to mechanical stimulation, we grew confluent monolayers from rabbit tracheal mucosal explants on flexible substrates and measured [IP3]i after stretching the substrate. The effect of stretch on [IP3]i was measured in the presence of Li+, an inhibitor of IP3 degradation. In unstretched cells, IP3 measured approximately 5.1 pmol/10(6) cells, from which we estimated [IP3]i to be 1.8 microM. Addition of Li+ had no effect on resting [IP3]i. When the flexible cell support was stretched to increase its surface area by 13%, mean [IP3]i increased about 3-fold with a half-time of approximately 1 s. The increased [IP3]i was maintained in a plateau phase for approximately 8 s and then decayed to near the unstretched level over the next 10 s, despite the sustained application of stretch. A transient stretch (0.5 s) induced a similar rate of increase and peak [IP3]i; however, [IP3]i subsided without a plateau phase. The magnitude of the [IP3]i increase was proportional to stimulus intensity between 0 and 13% increase in substrate surface area. In addition, dissociated airway epithelial cells were exposed to hypotonic solution to induce cell swelling. [IP3]i increased about 4-fold above control levels after 10 s of exposure to hypotonic solution. Basal [IP3]i of dissociated cells in isotonic solution was estimated to be 0.7 microM. These results are consistent with mechanical stimulation leading to phospholipase C synthesis of IP3, which mediates intracellular and intercellular Ca2+ signaling. PMID:8845181

  12. Inhibition of thalamic excitability by 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol: a selective role for delta-GABA(A) receptors.

    PubMed

    Herd, Murray B; Foister, Nicola; Chandra, Dev; Peden, Dianne R; Homanics, Gregg E; Brown, Verity J; Balfour, David J K; Lambert, Jeremy J; Belelli, Delia

    2009-03-01

    The sedative and hypnotic agent 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP) is a GABA(A) receptor (GABA(A)R) agonist that preferentially activates delta-subunit-containing GABA(A)Rs (delta-GABA(A)Rs). To clarify the role of delta-GABA(A)Rs in mediating the sedative actions of THIP, we utilized mice lacking the alpha(1)- or delta-subunit in a combined electrophysiological and behavioural analysis. Whole-cell patch-clamp recordings were obtained from ventrobasal thalamic nucleus (VB) neurones at a holding potential of -60 mV. Application of bicuculline to wild-type (WT) VB neurones revealed a GABA(A)R-mediated tonic current of 92 +/- 19 pA, which was greatly reduced (13 +/- 5 pA) for VB neurones of delta(0/0) mice. Deletion of the delta- but not the alpha(1)-subunit dramatically reduced the THIP (1 mum)-induced inward current in these neurones (WT, -309 +/- 23 pA; delta(0/0), -18 +/- 3 pA; alpha(1) (0/0), -377 +/- 45 pA). Furthermore, THIP selectively decreased the excitability of WT and alpha(1) (0/0) but not delta(0/0) VB neurones. THIP did not affect the properties of miniature inhibitory post-synaptic currents in any of the genotypes. No differences in rotarod performance and locomotor activity were observed across the three genotypes. In WT mice, performance of these behaviours was impaired by THIP in a dose-dependent manner. The effect of THIP on rotarod performance was blunted for delta(0/0) but not alpha(1) (0/0) mice. We previously reported that deletion of the alpha(1)-subunit abolished synaptic GABA(A) responses of VB neurones. Therefore, collectively, these findings suggest that extrasynaptic delta-GABA(A)Rs vs. synaptic alpha(1)-subunit-containing GABA(A)Rs of thalamocortical neurones represent an important molecular target underpinning the sedative actions of THIP. PMID:19302153

  13. GENOTOXICITY OF 2,4,5-TRICHLOROPHENOXYACETIC ACID BIODEGRADATION PRODUCTS IN THE SALMONELLA REVERSION AND LAMBDA PROPHAGE-INDUCTION BIOASSAYS

    EPA Science Inventory

    The herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), is still an environmental hazard because of its persistent nature even though its use was outlawed in this country in the 1960's. n order to eliminate the contamination created by 2,4,5-T application, storage, and dispos...

  14. 8-Methly-4-(3-diethylaminopropylamino) pyrimido [4',5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivate that causes ROS-mediated apoptosis in leukemia cell lines

    SciTech Connect

    Shenoy, Sudheer; Vasania, Viraf S.; Gopal, M.; Mehta, Ashish . E-mail: ashish_mehta@relbio.com

    2007-07-01

    The present study reports the biological activity of 8-methly-4-(3-diethylamino-propylamino) pyrimido [4';5';4,5] thieno (2,3-b) quinoline (MDPTQ), a quinoline derivative structurally related to ellipticine and suggests a possible mechanism through which the compound induces apoptosis in carcinoma cell lines. Out of the 8 cell lines used in the study as representatives of different types of cancer, MDPTQ was found to be effective only against leukemia cell lines (HL-60 and K-562) whereas it had no effect on normal human bone marrow cells (BMC) which were used as controls. Fall mitochondrial membrane potential and increased reactive oxygen species (ROS) were mainly responsible for inducing apoptosis in the two cell lines. Cell death was demonstrated by increase in caspase 3 activity as well as phosphatidyl serine exposure. Pre-incubation with N-acetylcysteine (NAC) reduced the increased ROS and caspase 3 activity as well as phosphatidyl serine exposure. MDPTQ also caused cell cycle arrest in these cell lines. The above study for the first time reports the mode of action of a quinoline derivative, which could be a possible future candidate for leukemia therapy. However, there are lot of questions that need to be answered in terms of signalling pathways and its effects on animal models.

  15. Performance of six 4. 5 m SSC (Superconducting Super Collider) dipole model magnets

    SciTech Connect

    Willen, E.; Dahl, P.; Cottingham, J.; Garber, M.; Ghosh, A.; Goodzeit, C.; Green, A.; Herrera, J.; Kahn, S.; Kelly, E.

    1986-01-01

    Six 4.5 m long dipole models for the proposed Superconducting Super Collider have been successfully tested. The magnets are cold-iron (and cold bore) 1-in-1 dipoles, wound with current density-graded high homogeneity NbTi cable in a two-layer cos theta coil of 40 mm inner diameter. The coil is prestressed by 15 mm wide stainless steel collars, and mounted in a circular, split iron yoke of 267 mm outer diameter, supported in a cylindrical yoke containment vessel. At 4.5 K the magnets reached a field of about 6.6 T with little training, or the short sample limit of the conductor, and in subcooled (2.6 - 2.4 K) liquid, 8 T was achieved. The allowed harmonics were close to the predicted values, and the unallowed harmonics small. The sextupole trim coil operated well above the required current with little training.

  16. Heterogeneous Hadean hafnium: evidence of continental crust at 4.4 to 4.5 ga.

    PubMed

    Harrison, T M; Blichert-Toft, J; Müller, W; Albarede, F; Holden, P; Mojzsis, S J

    2005-12-23

    The long-favored paradigm for the development of continental crust is one of progressive growth beginning at approximately 4 billion years ago (Ga). To test this hypothesis, we measured initial 176Hf/177Hf values of 4.01- to 4.37-Ga detrital zircons from Jack Hills, Western Australia. epsilonHf (deviations of 176Hf/177Hf from bulk Earth in parts per 10(4)) values show large positive and negative deviations from those of the bulk Earth. Negative values indicate the development of a Lu/Hf reservoir that is consistent with the formation of continental crust (Lu/Hf approximately 0.01), perhaps as early as 4.5 Ga. Positive epsilon(Hf) deviations require early and likely widespread depletion of the upper mantle. These results support the view that continental crust had formed by 4.4 to 4.5 Ga and was rapidly recycled into the mantle. PMID:16293721

  17. Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts.

    PubMed

    Lebensohn, Andres M; Ma, Le; Ho, Hsin-Yi Henry; Kirschner, Marc W

    2006-01-01

    Xenopus egg cytoplasmic extracts have been used to study a variety of complex cellular processes. Given their amenability to biochemical manipulation and physiological balance of regulatory proteins, these extracts are an ideal system to dissect signal transduction pathways leading to actin assembly. We have developed methods to study Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts. In this chapter, we describe detailed procedures to prepare Xenopus egg extracts, Cdc42, and PI(4,5)P2 for use in actin assembly experiments. We also describe a fluorometric pyrene actin assay for quantitative kinetic analysis of actin polymerization and a microscopic rhodamine actin assay for quick measurement of actin rearrangements in extracts. Finally we provide a protocol for immunodepletion of proteins and discuss the use of immunodepletion and rescue experiments for functional analysis of components in the extracts. PMID:16472657

  18. Synthesis and antifungal activity of 2-hydroxy-4,5-methylenedioxyaryl ketones as analogues of kakuol.

    PubMed

    Musso, Loana; Dallavalle, Sabrina; Merlini, Lucio; Farina, Gandolfina

    2010-04-01

    In a study aiming to determine the structural elements essential to the antifungal activity of kakuol, we synthesized a series of 2-hydroxy-4,5-methylenedioxyaryl ketones, and we assayed their in vitro antifungal activity. The most sensitive target organisms to the action of these class of compounds were Phytophthora infestans, Phytium ultimum, Cercospora beticola, Cladosporium cucumerinum, and Rhizoctonia solani. Most of the analogs showed a remarkable in vitro activity, and some of them appeared significantly more effective than the natural product. The biological activity was mainly affected by introducing structural modification on the carbonyl moiety of the natural-product molecule. In particular, compound 5a, bearing a C=C bond conjugated to the C=O group, was found active with a MIC value of 10 microg ml(-1) against Cladosporium cucumerinum. The results suggest that 2-hydroxy-4,5-methylenedioxyaryl ketones can be considered promising candidates in the development of new antifungal compounds. PMID:20397224

  19. Constructions of Optimal (v,{4,5,6},1,Q)-OOCs

    NASA Astrophysics Data System (ADS)

    Li, Xiyang; Fan, Pingzhi; Wu, Dianhua

    Optical code-division multiple-access (OCDMA) is a promising technique for multimedia transmission in fiber-optic local-area networks (LANs). Variable-weight optical orthogonal codes (OOCs) can be used for OCDMA networks supporting multiple quality of services (QoS). Most constructions for optimal variable-weight OOCs have focused on the case where the number of distinct Hamming weights of all codewords is equal to two, and the codewords of weight 3 are normally included. In this letter, four explicit constructions of optimal (v,{4,5,6},1,Q)-OOCs are presented, and more new optimal (v,{4,5,6},1,Q)-OOCs are obtained via recursive constructions. These improve the existing results on optimal variable-weight OOCs with at least three distinct Hamming weights and minimum Hamming weight 4.

  20. Ballooning-mirror instability and internally driven Pc 4--5 wave events

    SciTech Connect

    Cheng, C.Z.; Qian, Q.; Takahashi, K.; Lui, A.T.Y.

    1994-03-01

    A kinetic-MHD field-aligned eigenmode stability analysis of low frequency ballooning-mirror instabilities has been performed for anisotropic pressure plasma sin the magnetosphere. The ballooning mode is mainly a transverse wave driven unstable by pressure gradient in the bad curvature region. The mirror mode with a dominant compressional magnetic field perturbation is excited when the product of plasma beta and pressure anisotropy (P{sub {perpendicular}}/P{sub {parallel}} > 1) is large. From the AMPTE/CCE particle and magnetic field data observed during Pc 4--5 wave events the authors compute the ballooning-mirror instability parameters and perform a correlation study with the theoretical instability threshold. They find that compressional Pc 5 waves approximately satisfy the ballooning-mirror instability condition, and transverse Pc 4--5 waves are probably related to resonant ballooning instabilities with small pressure anisotropy.

  1. Backside optimization for improving avalanche breakdown behavior of 4.5 kV IGBT

    NASA Astrophysics Data System (ADS)

    Xiaoli, Tian; Jiang, Lu; Yuan, Teng; Wenliang, Zhang; Shuojin, Lu; Yangjun, Zhu

    2015-03-01

    The static avalanche breakdown behavior of 4.5 kV high-voltage IGBT is studied by theory analysis and experiment. The avalanche breakdown behaviors of the 4.5 kV IGBTs with different backside structures are investigated and compared by using the curve tracer. The results show that the snap back behavior of the breakdown waveform is related to the bipolar PNP gain, which leads to the deterioration of the breakdown voltage. There are two ways to optimize the backside structure, one is increasing the implant dose of the N+ buffer layer, the other is decreasing the implant dose of the P+ collector layer. It is found that the optimized structure is effective in suppressing the snap back behavior and improving the breakdown characteristic of high voltage IGBT. Project supported by the National Major Science and Technology Special Project of China (No. 2011ZX02503-003).

  2. 4,5-Bis(dimethylamino)quinolines: proton sponge versus azine behavior.

    PubMed

    Dyablo, Olga V; Shmoilova, Elena A; Pozharskii, Alexander F; Ozeryanskii, Valery A; Burov, Oleg N; Starikova, Zoya A

    2012-08-17

    Two first representatives, 5 and 6, of the still unknown 4,5-bis(dimethylamino)quinoline have been synthesized and studied. While the former, being protonated either at the peri-NMe(2) groups or at the ring nitrogen, has been shown to display properties of both a proton sponge and azine, its counterpart 6 behaves exclusively as azine giving only a quinolinium salt. PMID:22860688

  3. Synthesis of oxazolo[4,5-c]quinoline TRPV1 antagonists.

    PubMed

    Voight, Eric A; Daanen, Jerome F; Kort, Michael E

    2010-12-17

    An efficient synthesis of 2-amino-oxazolo[4,5-c]quinoline TRPV1 antagonists is described via a thiourea formation/carbodiimide cyclization sequence. Synthetic route optimization eliminates intermediate isolations and facilitates the rapid preparation of a series of novel pentacyclic TRPV1 antagonists. From this series, compound (S)-4 was identified as a potent and selective ligand for the TRPV1 ion channel. PMID:21090730

  4. Analysis of cellular phosphatidylinositol (3,4,5)-trisphosphate levels and distribution using confocal fluorescent microscopy.

    PubMed

    Palmieri, Michelle; Nowell, Cameron J; Condron, Melanie; Gardiner, James; Holmes, Andrew B; Desai, Jayesh; Burgess, Antony W; Catimel, Bruno

    2010-11-01

    We have developed an immunocytochemistry method for the semiquantitative detection of phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3) at the cell plasma membrane. This protocol combines the use of a glutathione S-transferase-tagged pleckstrin homology (PH) domain of the general phosphoinositides-1 receptor (GST-GRP1PH) with fluorescence confocal microscopy and image segmentation using cell mask software analysis. This methodology allows the analysis of PI(3,4,5)P3 subcellular distribution in resting and epidermal growth factor (EGF)-stimulated HEK293T cells and in LIM1215 (wild-type phosphoinositide 3-kinase (PI3K)) and LIM2550 (H1047R mutation in PI3K catalytic domain) colonic carcinoma cells. Formation of PI(3,4,5)P3 was observed 5min following EGF stimulation and resulted in an increase of the membrane/cytoplasm fluorescence ratio from 1.03 to 1.53 for HEK293T cells and from 2.2 to 3.3 for LIM1215 cells. Resting LIM2550 cells stained with GST-GRP1PH had an elevated membrane/cytoplasm fluorescence ratio of 9.8, suggesting constitutive PI3K activation. The increase in the membrane/cytoplasm fluorescent ratio was inhibited in a concentration-dependent manner by the PI3K inhibitor LY294002. This cellular confocal imaging assay can be used to directly assess the effects of PI3K mutations in cancer cell lines and to determine the potential specificity and effectiveness of PI3K inhibitors in cancer cells. PMID:20599646

  5. Development of a 4.5 K Pulse Tube Cryocooler for Superconducting Electronics

    NASA Astrophysics Data System (ADS)

    Nast, Ted; Olson, Jeff; Champagne, Patrick; Mix, Jack; Evtimov, Bobby; Roth, Eric; Collaco, Andre

    2008-03-01

    Lockheed Martin's (LM) Advanced Technology Center (ATC) has developed a four stage pulse tube cryocooler (stirling-type pulse tube system) to provide cooling at 4.5 K for superconducting digital electronics communications programs. These programs utilize superconducting niobium integrated circuits [1, 2]. A prior ATC 4 stage unit has provided cooling to 3.8 K. [3] The relatively high cooling loads for the present program led us to a new design which improves the 4.5 K power efficiency over prior systems. This design includes a unique pulse tube approach using both He-3 and He-4 working gas in two compression spaces. The compressor utilizes our standard moving magnet linear motor, clearance seal and flexure bearing system. The system is compact, lightweight and reliable and utilizes our aerospace cooler technology to provide unlimited lifetime. The unit is a proof of concept, but the construction is at an engineering model level. Follow on activities for improvements of performance and more compact packaging and future production for ground based communication systems is anticipated. This paper presents the experimental results at various cooling conditions. Primary results are shown for HYPRES cooling requirements and data is also included at lower cooling loads that may be required for future space missions. The system provides a maximum of 42 mW @ 4.5 K and a no load temperature of 3 K. The majority of this work was subcontracted by HYPRES and funded by the Army and Navy. A small part of this effort to obtain data at lower cooling loads (1-10 mW @ 4.5 K) was funded by LM internal funds.

  6. Investigation of 4,5-epoxymorphinan degradation during analysis by HPLC.

    PubMed

    Quarry, Mary Ann; Sebastian, Dolores S; Diana, Frank

    2002-08-22

    Compounds of the 4,5-epoxymorphinan series have been shown to degrade in solution to the corresponding 2,2'-dimers when stored in amber glass HPLC vials. A colorant in the glass has been shown to catalyze the degradation. Although amber glass is routinely used to protect solutions from light degradation, it should not be used without evaluating its effect on sample stability. PMID:12151069

  7. Deterministic methods in radiation transport. A compilation of papers presented February 4--5, 1992

    SciTech Connect

    Rice, A.F.; Roussin, R.W.

    1992-06-01

    The Seminar on Deterministic Methods in Radiation Transport was held February 4--5, 1992, in Oak Ridge, Tennessee. Eleven presentations were made and the full papers are published in this report, along with three that were submitted but not given orally. These papers represent a good overview of the state of the art in the deterministic solution of radiation transport problems for a variety of applications of current interest to the Radiation Shielding Information Center user community.

  8. Long-life vibration-free 4.5 K sorption cooler for space applications.

    PubMed

    Burger, J F; ter Brake, H J M; Holland, H J; Meijer, R J; Veenstra, T T; Venhorst, G C F; Lozano-Castelló, D; Coesel, M; Sirbi, A

    2007-06-01

    A breadboard 4.5 K helium sorption cooler for use in vibration-sensitive space missions was developed and successfully tested. This type of cooler has no moving parts and is, therefore, essentially vibration-free. The absence of moving parts also simplifies scaling down of the cooler to small sizes, and it contributes to achieving a very long lifetime. In addition, the cooler operates with limited dc's so that hardly any electromagnetic interference is generated. This cooler is a favorite option for future missions such as ESA's Darwin mission, a space interferometer in which the sensitive optics and detectors can hardly accept any vibration. The system design consists of a hydrogen stage cooling from 80 to 14.5 K and a helium stage establishing 5 mW at 4.5 K. Both stages use microporous activated carbon as the adsorption material. The two cooler stages need about 3.5 W of total input power and are heat sunk at two passive radiators at temperatures of about 50 and 80 K-radiators which are constructed at the cold side of the spacecraft. We developed, built, and tested a demonstrator of the helium cooler. This demonstrator has four sorption compressor cells in two compressor stages. Test experiments on this cooler showed that it performs within all specifications imposed by ESA. The cooler delivered 4.5 mW at 4.5 K with a long-term temperature stability of 1 mK and an input power of 1.96 W. So far, the cooler has operated continuously for a period of 2.5 months and has not shown any sign of performance degradation. PMID:17614633

  9. Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels.

    PubMed

    Trebak, Mohamed; Lemonnier, Loic; DeHaven, Wayne I; Wedel, Barbara J; Bird, Gary S; Putney, James W

    2009-02-01

    The canonical transient receptor potential (TRPC) proteins have been recognized as key players in calcium entry pathways activated through phospholipase-C-coupled receptors. While it is clearly demonstrated that members of the TRPC3/6/7 subfamily are activated by diacylglycerol, the mechanism by which phospholipase C activates members of the TRPC1/4/5 subfamily remains a mystery. In this paper, we provide evidence for both negative and positive modulatory roles for membrane polyphosphoinositides in the regulation of TRPC5 channels. Depletion of polyphosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate (PIP2) through inhibition of phosphatidylinositol 4-kinase activates calcium entry and membrane currents in TRPC5-expressing but not in TRPC3- or TRPC7-expressing cells. Inclusion of polyphosphatidylinositol 4-phosphate or PIP2, but not phosphatidylinositol 3,4,5-trisphosphate, in the patch pipette inhibited TRPC5 currents. Paradoxically, depletion of PIP2 with a directed 5-phosphatase strategy inhibited TRPC5. Furthermore, when the activity of single TRPC5 channels was examined in excised patches, the channels were robustly activated by PIP2. These findings indicate complex functions for regulation of TRPC5 by PIP2, and we propose that membrane polyphosphoinositides may have at least two distinct functions in regulating TRPC5 channel activity. PMID:18665391

  10. The co-chaperones Fkbp4/5 control Argonaute2 expression and facilitate RISC assembly

    PubMed Central

    Martinez, Natalia J.; Chang, Hao-Ming; Borrajo, Jacob de Riba; Gregory, Richard I.

    2013-01-01

    Argonaute2 (Ago2) protein and associated microRNAs (miRNAs) or small interfering RNAs (siRNAs) form the RNA-induced silencing complex (RISC) for target messenger RNA cleavage and post-transcriptional gene silencing. Although Ago2 is essential for RISC activity, the mechanism of RISC assembly is not well understood, and factors controlling Ago2 protein expression are largely unknown. A role for the Hsc70/Hsp90 chaperone complex in loading small RNA duplexes into the RISC has been demonstrated in cell extracts, and unloaded Ago2 is unstable and degraded by the lysosome in mammalian cells. Here we identify the co-chaperones Fkbp4 and Fkbp5 as Ago2-associated proteins in mouse embryonic stem cells. Pharmacological inhibition of this interaction using FK506 or siRNA-mediated Fkbp4/5 depletion leads to decreased Ago2 protein levels. We find FK506 treatment inhibits, whereas Fkbp4/5 overexpression promotes, miRNA-mediated stabilization of Ago2 expression. Simultaneous treatment with a lysosome inhibitor revealed the accumulation of unloaded Ago2 complexes in FK506-treated cells. We find that, consistent with unloaded miRNAs being unstable, FK506 treatment also affects miRNA abundance, particularly nascent miRNAs. Our results support a role for Fkbp4/5 in RISC assembly. PMID:24049110

  11. On the nature of bright compact radio sources at z>4.5

    NASA Astrophysics Data System (ADS)

    Coppejans, Rocco; Frey, Sándor; Cseh, Dávid; Müller, Cornelia; Paragi, Zsolt; Falcke, Heino; Gabányi, Krisztina É.; Gurvits, Leonid I.; An, Tao; Titov, Oleg

    2016-09-01

    High-redshift radio-loud quasars are used to, among other things, test the predictions of cosmological models, set constraints on black hole growth in the early universe and understand galaxy evolution. Prior to this paper, 20 extragalactic radio sources at redshifts above 4.5 have been imaged with very long baseline interferometry (VLBI). Here we report on observations of an additional ten z > 4.5 sources at 1.7 and 5 GHz with the European VLBI Network (EVN), thereby increasing the number of imaged sources by 50 per cent. Combining our newly observed sources with those from the literature, we create a substantial sample of 30 z > 4.5 VLBI sources, allowing us to study the nature of these objects. Using spectral indices, variability and brightness temperatures, we conclude that of the 27 sources with sufficient information to classify, the radio emission from one source is from star formation, 13 are flat-spectrum radio quasars and 13 are steep-spectrum sources. We also argue that the steep-spectrum sources are off-axis (unbeamed) radio sources with rest-frame self-absorption peaks at or below GHz frequencies and that these sources can be classified as gigahertz peaked-spectrum (GPS) and megahertz peaked-spectrum (MPS) sources.

  12. Computational research on memory effects in AlPO4-5 nanoporous material

    NASA Astrophysics Data System (ADS)

    Gulín-González, J.; Demontis, P.; Navas Conyedo, E.; Suffritti, G. B.

    2012-06-01

    Reversible amorphization and memory effects of both dense and open frameworks have received a great attention due to their prospective industrial applications. In this paper, the results of a computational study related to phase transition and memory effects in AlPO4-5 nanoporous material at high external pressure is presented. The behavior of the AlPO4-5 unit cell at high external pressures was studied by energy minimization techniques using classical potentials. A combination of interatomic potentials was used to describe the crystalline structure of the aluminophosphate. According to simulation's result a decrease of crystalline order is observed at a pressure about 3.5 GPa. The behavior of the simulated infrared spectra of compressed structures is an unambiguous evidence of structural disorder. Also, an abrupt change in the slope of the unit cell volume vs. pressure curve was obtained. At P≤3.5 GPa the process was found reversible. Contrary to what has been reported in other aluminosilicate systems the final crystalline state of AlPO4-5 at the highest simulated pressure was not amorphous. According to our knowledge this is the first evidence of a reversible first-order crystal-crystal phase transition in AlPO- family materials. This result could be important in future industrial and catalytic applications of these materials.

  13. Sonochemical synthesis of 1,2,4,5-tetrasubstituted imidazoles using nanocrystalline MgAl2O4 as an effective catalyst.

    PubMed

    Safari, Javad; Gandomi-Ravandi, Soheila; Akbari, Zahra

    2013-11-01

    An efficient four-component synthesis of 1,2,4,5-tetrasubstituted imidazoles is described by one-step condensation of an aldehyde, benzil, ammonium acetate and primary aromatic amine with nanocrystalline magnesium aluminate in ethanol under ultrasonic irradiation. High yields, short reaction times, mild conditions, simplicity of operation and easy work-up are some advantages of this protocol. PMID:25685459

  14. Sonochemical synthesis of 1,2,4,5-tetrasubstituted imidazoles using nanocrystalline MgAl2O4 as an effective catalyst☆

    PubMed Central

    Safari, Javad; Gandomi-Ravandi, Soheila; Akbari, Zahra

    2012-01-01

    An efficient four-component synthesis of 1,2,4,5-tetrasubstituted imidazoles is described by one-step condensation of an aldehyde, benzil, ammonium acetate and primary aromatic amine with nanocrystalline magnesium aluminate in ethanol under ultrasonic irradiation. High yields, short reaction times, mild conditions, simplicity of operation and easy work-up are some advantages of this protocol. PMID:25685459

  15. Changes in Preference for Infant-Directed Speech in Low and Moderate Noise by 4.5- to 13-Month-Olds

    ERIC Educational Resources Information Center

    Newman, Rochelle S.; Hussain, Isma

    2006-01-01

    Although a large literature discusses infants' preference for infant-directed speech (IDS), few studies have examined how this preference might change over time or across listening situations. The work reported here compares infants' preference for IDS while listening in a quiet versus a noisy environment, and across 3 points in development: 4.5

  16. Changes to extreme wave climates of islands within the Western Tropical Pacific throughout the 21st century under RCP 4.5 and RCP 8.5, with implications for island vulnerability and sustainability

    NASA Astrophysics Data System (ADS)

    Shope, James B.; Storlazzi, Curt D.; Erikson, Li H.; Hegermiller, Christie A.

    2016-06-01

    Waves are the dominant influence on coastal morphology and ecosystem structure of tropical Pacific islands. Wave heights, periods, and directions for the 21st century were projected using near-surface wind fields from four atmosphere-ocean coupled global climate models (GCM) under representative concentration pathways (RCP) 4.5 and 8.5. GCM-derived wind fields forced the global WAVEWATCH-III wave model to generate hourly time series of bulk wave parameters around 25 islands in the mid to western tropical Pacific Ocean for historical (1976-2005), mid-century, and end-century time periods for the December-February and June-August seasons. The December-February regional wave climate is dominated by strong winds and large swell from extratropical cyclones in the north Pacific while the June-August season brings smaller waves generated by the trade winds and swell from Southern Hemisphere extratropical storms. Extreme significant wave heights decreased (~ 10.0%) throughout the 21st century under both climate scenarios compared to historical wave conditions and the higher radiative forcing RCP 8.5 scenario displayed a greater and more widespread decrease in extreme significant wave heights compared to the lower forcing RCP 4.5 scenario. An exception was for the end-century June-August season. Offshore of islands in the central equatorial Pacific, extreme significant wave heights displayed the largest changes from historical values. The frequency of extreme events during December-February decreased under RCP 8.5, whereas the frequency increased under RCP 4.5. Mean wave directions rotated more than 30° clockwise at several locations during June-August, which could indicate a weakening of the trade winds' influence on extreme wave directions and increasing dominance of Southern Ocean swell. The results of this study underscore that December-February large wave events will become smaller and less frequent in most regions, reducing the likelihood and magnitude of wave

  17. Research and Development Toward a 4.5-1.5 {Angstrom} Linac Coherent Light Source (LCLS) at SLAC

    SciTech Connect

    Tatchyn, R.; Arthur, J.; Baltay, M.

    1995-08-01

    In recent years significant studies have been initiated on the feasibility of utilizing a portion of the 3km S-band accelerator at SLAC to drive a short wavelength (4.5-1.5 A) Linac Coherent Light Source (LCLS), a Free Electron Laser (FEL) operating in the Self- Amplified Spontaneous Emission (SASE) regime. Electron beam requirements for single-pass saturation in a minimal time include: (1) a peak current in the 7 kA range, (2) a relative energy spread of {lt}0.05%, and (3) a transverse emittance, {epsilon}[r-m], approximating the diffraction limit condition {epsilon} = {lambda} / 4{pi}, where lambda(m) is the output wavelength. Requirements on the insertion device include field error levels of 0.02% for keeping the electron bunch centered on and in phase with the amplified photons, and a focusing beta of 8 m/rad for inhibiting the dilution of its transverse density. Although much progress has been made in developing individual components and beam processing techniques necessary for LCLS operation down to approx. 20 A, a substantial amount of research and development is still required in a number of theoretical and experimental areas leading to the construction and operation of a 4.5-1.5 A LCLS. In this paper we report on a research and development program underway and in planning at SLAC for addressing critical questions in these areas.

  18. The ALMA Patchy Deep Survey: a blind search for [C II] emitters at z ˜ 4.5

    NASA Astrophysics Data System (ADS)

    Matsuda, Y.; Nagao, T.; Iono, D.; Hatsukade, B.; Kohno, K.; Tamura, Y.; Yamaguchi, Y.; Shimizu, I.

    2015-07-01

    We present a result of a blind search for [C II] 158 μm emitters at z ˜ 4.5 using Atacama Large Millimeter Array (ALMA) Cycle 0 archival data. We collected extragalactic data covering at 330-360 GHz (band 7) from 8 Cycle 0 projects from which initial results have been already published. The total number of fields is 243 and the total on-source exposure time is 19.2 h. We searched for line emitters in continuum-subtracted data cubes with spectral resolutions of ˜50, 100, 300 and 500 km s-1. We could not detect any new line emitters above a 6σ significance level. This result provides upper limits to the [C II] luminosity function at z ˜ 4.5 over L_[C II] ˜ 10^8-10^{10} L_{⊙} or star formation rate, SFR ˜ 10-1000 M_^{⊙}yr-1. These limits are at least two orders of magnitude larger than the [C II] luminosity functions expected from the z ˜ 4 UV luminosity function or from numerical simulation. However, this study demonstrates that we would be able to better constrain the [C II] luminosity function and to investigate possible contributions from dusty galaxies to the cosmic star formation rate density by collecting Cycle 1+2 archival data as the ALMA Patchy Deep Survey.

  19. 2-(Alkylamino)-3-aryl-6,7-dihydrobenzofuran-4(5H)-ones: Improved Synthesis and their Photophysical Properties

    PubMed Central

    Kumar, Manoj; Kumawat, Lokesh Kumar; Gupta, Vinod Kumar; Sharma, Anuj

    2015-01-01

    Furans are an important class of compounds and exhibit a diverse range of activities and properties. As such, improved synthetic access to furans is an important research goal. In the present report, a solvent- and catalyst-free reaction between 5,5-dimethyl-1,3-cyclohexanedione (dimedone), an aryl aldehyde and an isocyanide under microwave irradiation is presented. This method is significantly improved from previously described protocols in terms of applicability of wide ranging aryl aldehydes, better yields, shorter reaction times, facile work up and essentially no need of column chromatography. The photophysical properties of this series of compounds were studied for their possible applicability in the field of metal ion sensors. In solution, two compounds, 2-(cyclohexylamino)-3-(1H-indol-3-yl)-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-one (1 i) and 2-(tert-butylamino)-3-(1H-indol-3-yl)-6,6-dimethyl-6,7-dihydrobenzofuran-4(5H)-one (1 j), underwent an observable color change from yellow to colorless in the presence of aluminum(III) ions. Further studies to investigate the UV absorption and luminescence behavior of these compounds revealed their utility as “naked-eye sensors” for aluminum detection. PMID:26491643

  20. Identification of a new membrane-permeable inhibitor against inositol-1,4,5-trisphosphate-3-kinase A.

    PubMed

    Schröder, Dominik; Rehbach, Christoph; Seyffarth, Carola; Neuenschwander, Martin; Kries, Jens V; Windhorst, Sabine

    2013-09-20

    Ectopic expression of the neuron-specific inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) in lung cancer cells increases their metastatic potential because the protein exhibits two actin regulating activities; it bundles actin filaments and regulates inositol-1,4,5-trisphosphate (InsP3)-mediated calcium signals by phosphorylating InsP3. Thus, in order to inhibit the metastasis-promoting activity of ITPKA, both its actin bundling and its InsP3kinase activity has to be blocked. In this study, we performed a high throughput screen in order to identify specific and membrane-permeable substances against the InsP3kinase activity. Among 341,44 small molecules, 237 compounds (0.7%) were identified as potential InsP3kinase inhibitors. After determination of IC50-values, the three compounds with highest specificity and highest hydrophobicity (EPPC-3, BAMB-4, MEPTT-3) were further characterized. Only BAMB-4 was nearly completely taken up by H1299 cells and remained stable after cellular uptake, thus exhibiting a robust stability and a high membrane permeability. Determination of the inhibitor type revealed that BAMB-4 belongs to the group of mixed type inhibitors. Taken together, for the first time we identified a highly membrane-permeable inhibitor against the InsP3kinase activity of ITPKA providing the possibility to partly inhibit the metastasis-promoting effect of ITPKA in lung tumor cells. PMID:23981806

  1. Photophysics of 2-(4'-amino-2'-hydroxyphenyl)-1H-imidazo-[4,5-c]pyridine and its analogues: intramolecular proton transfer versus intramolecular charge transfer.

    PubMed

    Behera, Santosh Kumar; Karak, Ananda; Krishnamoorthy, G

    2015-02-12

    Photophysical characteristics of 2-(4'-amino-2'-hydroxyphenyl)-1H-imidazo-[4,5-c]pyridine (AHPIP-c) have been studied in various aprotic and protic solvents using UV-visible, steady state fluorescence and time-resolved fluorescence spectroscopic techniques. To comprehend the competition between the intramolecular charge transfer (ICT) and the excited state intramolecular proton transfer (ESIPT) processes, the photophysical properties of 2-(4'-amino-2'-methoxyphenyl)-1H-imidazo-[4,5-c]pyridine (AMPIP-c) and 2-(4'-aminophenyl)-1H-imidazo-[4,5-c]pyridine (APIP-c) were also investigated. Though APIP-c displays twisted ICT (TICT) emission in protic solvents, AHPIP-c exhibits normal and tautomer emissions in aprotic as well as in protic solvents due to ESIPT. However, the methoxy derivative, AMPIP-c, emits weak TICT fluorescence in methanol. PMID:25337987

  2. 4.1N binding regions of inositol 1,4,5-trisphosphate receptor type 1.

    PubMed

    Fukatsu, Kazumi; Bannai, Hiroko; Inoue, Takafumi; Mikoshiba, Katsuhiko

    2006-04-01

    Zhang et al. and Maximov et al. [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056; A. Maximov, T. S. Tang, and I. Bezprozvanny, Association of the type 1 inositol (1,4,5)-trisphosphate receptor with 4.1N protein in neurons, Mol. Cell. Neurosci. 22 (2003) 271-283.] reported that 4.1N is a binding partner of inositol 1,4,5-trisphosphate receptor type 1 (IP(3)R1), however the binding site of IP(3)R1 differed: the former determined the C-terminal 14 amino acids of the cytoplasmic tail (CTT14aa) as the binding site, while the latter assigned another segment, cytoplasmic tail middle 1 (CTM1). To solve this discrepancy, we performed immunoprecipitation and found that both the segments had binding activity to 4.1N. Both segments also interfered the 4.1N-regulated IP(3)R1 diffusion in neuronal dendrites. However, IP(3)R1 lacking the CTT14aa (IP(3)R1-DeltaCTT14aa) does not bind to 4.1N [S. Zhang, A. Mizutani, C. Hisatsune, T. Higo, H. Bannai, T. Nakayama, M. Hattori, and K. Mikoshiba, Protein 4.1N is required for translocation of inositol 1,4,5-trisphosphate receptor type 1 to the basolateral membrane domain in polarized Madin-Darby canine kidney cells, J. Biol. Chem. 278 (2003) 4048-4056.] and its diffusion constant is larger than that of IP(3)R1 full-length in neuronal dendrites [K. Fukatsu, H. Bannai, S. Zhang, H. Nakamura, T. Inoue, and K. Mikoshiba, Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 is regulated by actin filaments and 4.1N in neuronal dendrites, J. Biol. Chem. 279 (2004) 48976-48982.]. We conclude that both the CTT14aa and CTM1 sequences can bind to 4.1N in peptide fragment forms. However, we propose that the responsible binding site for 4.1N binding in full-length tetramer form of IP

  3. Greater Capital Region Career Pathways Initiative

    ERIC Educational Resources Information Center

    Workforce Strategy Center, 2005

    2005-01-01

    This case study documents the activities of the Greater Capital Region Career Pathways Initiative (CPI), a partnership to develop regional, demand driven career pathways for the biotechnology sector in and around Albany, NY. This document is written for three primary audiences. First, it provides a report to the New York State Department of Labor…

  4. Spread of English across Greater China

    ERIC Educational Resources Information Center

    Feng, Anwei

    2012-01-01

    Greater China is used in this article to refer to mainland China, Hong Kong, Singapore, Taiwan and Macao. While a holistic approach is adopted to present and compare the rapid spread of English and development in English language education in these geographically close, and sociopolitically, culturally and economically interrelated but hugely…

  5. Waste Management in Greater Dhaka City.

    ERIC Educational Resources Information Center

    Rahman, M. H.

    1993-01-01

    This study focuses on the environmental degradation of Greater Dhaka City (GDC) resulting from pollution created by the indiscriminate disposal of industrial wastes, open dumping of solid wastes, inadequate treatment and disposal of domestic sewage, and unplanned disposal of leachate from agricultural land. Measures to protect the GDC environment…

  6. Signal phase switches offer greater dynamic range

    NASA Technical Reports Server (NTRS)

    Crow, R. B.

    1970-01-01

    Circuit, placed in the signal path of a closed-loop receiver to modulate telemetered data in the 10-MHz spectrum, improves signal-to-noise ratio by 3 db in a communication receiver. The switch enables bandwidth reduction which reduces noise overload on the following stages, giving the system greater dynamic range.

  7. 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors.

    PubMed

    Liu, Genyan; Ozoe, Fumiyo; Furuta, Kenjiro; Ozoe, Yoshihisa

    2015-07-22

    The insect GABA receptor (GABAR), which is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol analogues, were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas synthesized analogues did not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in compounds that exhibited significantly enhanced antagonism with IC50 values in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 μM analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed competitive antagonism, with IC50 values of 30, 34, 107, and 96 μM in the ac, bc, ad, and bd variants, respectively, and exhibited moderate insecticidal activity against houseflies, with an LD50 value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs. PMID:26120732

  8. Discriminating "top-heavy" versus "bottom-heavy" geometric patterns in 2- to 4.5-month-old infants.

    PubMed

    Chien, Sarina Hui-Lin; Hsu, Hsin-Yueh; Su, Bai-Horng

    2010-09-24

    Simion, Valenza, Macchi Cassia, Turati, and Umiltà (2002) suggested that newborns preferred "top-heavy" stimuli and such bias may account for neonatal face preference. However, convergent evidence for the discriminability between the top-heavy versus bottom-heavy patterns has not been demonstrated. We used a modified familiarization/novelty procedure (Chien, Palmer, & Teller, 2003) to assess basic discriminability between "top-heavy" and "bottom-heavy" geometric patterns in 2- to 4.5-month-old infants. Each infant was tested with three types of top-heavy and bottom-heavy geometric figures and received both familiarized-to-top-heavy and familiarized-to-bottom-heavy conditions. If infants of this age can discriminate the two configurations and there is no intrinsic bias toward either pattern, we expected to see significant and about equal novelty effects in both familiarization conditions. If there is a strong intrinsic bias for the top-heavy configuration, we expect to see a greater preference for the top-heavy patterns in the familiarization-to-bottom-heavy condition. Our results (N=24) showed significant and equal novelty preferences in both familiarization conditions across age and figure types, suggesting a reliable discriminability between top-heavy and bottom-heavy configurations and there is no intrinsic bias towards either configuration at this age. PMID:20603142

  9. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD[sub 30/50] values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  10. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD{sub 30/50} values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  11. Synthesis, structures, and properties of 1,2,4,5-benzenetetrathiolate linked group 10 metal complexes.

    PubMed

    Arumugam, Kuppuswamy; Shaw, Mohamed C; Chandrasekaran, P; Villagrán, Dino; Gray, Thomas G; Mague, Joel T; Donahue, James P

    2009-11-16

    Dimetallic compounds [(P-P)M(S(2)C(6)H(2)S(2))M(P-P)] (M = Ni, Pd; P-P = chelating bis(phosphine), 3a-3f) are prepared from O=CS(2)C(6)H(2)S(2)C=O or (n)Bu(2)SnS(2)C(6)H(2)S(2)Sn(n)Bu(2), which are protected forms of 1,2,4,5-benzenetetrathiolate. Selective monodeprotections of O=CS(2)C(6)H(2)S(2)C=O or (n)Bu(2)SnS(2)C(6)H(2)S(2)Sn(n)Bu(2) lead to [(P-P)Ni(S(2)C(6)H(2)S(2)C=O)] or [(P-P)Ni(S(2)C(6)H(2)S(2)Sn(n)Bu(2))]; the former is used to prepare trimetallic compounds [(dcpe)Ni(S(2)C(6)H(2)S(2))M(S(2)C(6)H(2)S(2))Ni(dcpe)] (M = Ni (6a) or Pt (6b); dcpe = 1,2-bis(dicyclohexylphosphino)ethane). Compounds 3a-3f are redox active and display two oxidation processes, of which the first is generally reversible. Dinickel compound [(dcpe)Ni(S(2)C(6)H(2)S(2))Ni(dcpe)] (3d) reveals two reversible oxidation waves with DeltaE(1/2) = 0.66 V, corresponding to K(c) of 1.6 x 10(11) for the mixed valence species. Electrochemical behavior is unstable to repeated scanning in the presence of [Bu(4)N][PF(6)] electrolyte but indefinitely stable with Na[BArF(24)] (BArF(24) = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate), suggesting that the radical cation generated by oxidation is vulnerable to reaction with PF(6)(-). Chemical oxidation of 3d with [Cp(2)Fe][BArF(24)] leads to formation of [3d][BArF(24)]. Structural identification of [3d][BArF(24)] reveals appreciable shortening and lengthening of C-S and C-C bond distances, respectively, within the tetrathioarene fragment compared to charge-neutral 3d, indicating this to be the redox active moiety. Attempted oxidation of [(dppb)Ni(S(2)C(6)H(2)S(2))Ni(dppb)] (3c) (dppb = 1,2-bis(diphenylphosphino)benzene) with AgBArF(24) produces [[(dppb)Ni(S(2)C(6)H(2)S(2))Ni(dppb)](2)(mu-Ag(2))][BArF(24)](2), [4c][BArF(24)](2), in which no redox chemistry has occurred. Crystal structures of bis(disulfide)-linked compounds [(P-P)Ni(S(2)C(6)H(2)(mu-S(2))(2)C(6)H(2)S(2))Ni(P-P)] are reported. Near IR spectroscopy upon cationic [3d](+) and neutral 6a

  12. Greater sadness reactivity in late life

    PubMed Central

    Seider, Benjamin H.; Shiota, Michelle N.; Whalen, Patrick

    2011-01-01

    Although previous research suggests that overall emotional reactivity does not change with normal aging, it is possible that different emotions follow different developmental courses. We examined emotional reactivity to films selected to elicit sadness, disgust, and a neutral state in young, middle-aged and older adults (total N = 222). Physiology and expressive behavior were measured continuously and reports of subjective emotional experience were obtained following each film. Results indicated that older adults reported greater sadness in response to all films and greater physiological responses to the sadness film than did the younger age groups. There were no age differences found in self-reported disgust or in behavioral expressions of sadness or disgust in response to any film. The age differences that were found were maintained even after controlling for pre-film self-reported sadness and for personal experiences of loss. These findings support the notion that sadness reactivity is heightened with age. PMID:20650943

  13. Metabolic evidence for PtdIns(4,5)P2-directed phospholipase C in permeabilized plant protoplasts.

    PubMed Central

    Brearley, C A; Parmar, P N; Hanke, D E

    1997-01-01

    Comparison of the sequences of the genes encoding phospholipase C (PLC) which have been cloned to date in plants with their mammalian counterparts suggests that plant PLC is similar to PLCdelta of mammalian cells. The physiological role and mechanism of activation of PLCdelta is unclear. It has recently been shown that Ins(1,4,5)P3 may not solely be the product of PtdIns(4,5)P2-directed PLC activity. Enzyme activities capable of producing Ins(1,4,5)P3 from endogenous inositol phosphates are present in Dictyostelium and also in rat liver. Significantly it has not been directly determined whether Ins(1,4,5)P3 present in higher plants is the product of a PtdIns(4, 5)P2-directed PLC activity. Therefore we have developed an experimental strategy for the identification of d-Ins(1,4,5)P3 in higher plants. By the use of a short-term non-equilibrium labelling strategy in permeabilized plant protoplasts, coupled to the use of a 'metabolic trap' to prevent degradation of [32P]Ins(1,4,5)P3, we were able to determine the distribution of 32P in individual phosphate esters of Ins(1,4,5)P3. The [32]Ins(1,4,5)P3 identified showed the same distribution of label in individual phosphate esters as that of [32P]PtdIns(4,5)P2 isolated from the same tissue. We thus provide in vivo evidence for the action of a PtdIns(4,5)P2-directed PLC activity in plant cells which is responsible for the production of Ins(1,4,5)P3 observed here. This observation does not, however, exclude the possibility that in other cells or under different conditions Ins(1,4,5)P3 can be generated by alternative routes. PMID:9164848

  14. Cytochrome P450-Mediated Metabolism and DNA Binding of 2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline and its Carcinogenic Isomer 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Mice

    PubMed Central

    Turesky, Robert J.; Bessette, Erin E.; Dunbar, Deborah; Liberman, Rosa G.; Skipper, Paul L.

    2012-01-01

    2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline (MeIgQx) is a recently discovered heterocyclic aromatic amine (HAA) that is formed during the cooking of meats. MeIgQx is an isomer of 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), a rodent carcinogen and possible human carcinogen that also occurs in cooked meats. MeIgQx is a bacterial mutagen but knowledge about its metabolism and carcinogenic potential is lacking. Metabolism studies on MeIgQx and MeIQx were conducted with human and mouse liver microsomes, and recombinant human P450s. DNA binding studies were also investigated in mice to ascertain the genotoxic potential of MeIgQx in comparison to MeIQx. Both HAAs underwent comparable rates of N-oxidation to form genotoxic N-hydroxylated metabolites with mouse liver microsomes (0.2 - 0.3 nmol/min/mg protein). The rate of N-oxidation of MeIQx was 4-fold greater than the rate of N-oxidation of MeIgQx with human liver microsomes (1.7 vs 0.4 nmol/min/mg protein). The rate of N-oxidation, by recombinant human P450 1A2, was comparable for both substrates (6 pmol/min/pmol P450 1A2). MeIgQx also underwent N-oxidation by human P450s 1A1 and 1B1 at appreciable rates, whereas MeIQx was poorly metabolized by these P450s. The potential of MeIgQx and MeIQx to form DNA adducts was assessed in female C57BL/6 mice given [14C]-MeIgQx (10 μCi, 9.68 mg/kg body wt) or [14C]-MeIQx (10 μCi, 2.13 mg/kg body wt). DNA adduct formation in liver, pancreas and colorectum was measured by accelerator mass spectrometry at 4, 24 or 48 h post-treatment. Variable levels of adducts were detected in all organs. The adduct levels were similar for both HAAs, when adjusted for dose, and ranged from 1 to 600 adducts per 107 nucleotides per mg/kg dose. Thus, MeIgQx undergoes metabolic activation and binds to DNA at levels that are comparable to MeIQx. Given the high amounts of MeIgQx formed in cooked meats, further investigations are warranted to assess the carcinogenic potential of this HAA. PMID

  15. Genomic landscape of the Greater Middle East.

    PubMed

    Özçelik, Tayfun; Onat, Onur Emre

    2016-08-30

    Study of the Greater Middle East (GME), home to approximately 10% of the world's population, has made invaluable contributions to the characterization of rare genetic disease, especially recessive conditions arising from the tradition of consanguinity and large families with multiple children. A new study now reports 1,111 unrelated exomes from the GME and provides a comprehensive view of genetic variation for enhanced discovery of disease-associated genes. PMID:27573686

  16. Increasing Phosphatidylinositol (4,5)-Bisphosphate Biosynthesis Affects Basal Signaling and Chloroplast Metabolism in Arabidopsis thaliana

    PubMed Central

    Im, Yang Ju; Smith, Caroline M.; Phillippy, Brian Q.; Strand, Deserah; Kramer, David M.; Grunden, Amy M.; Boss, Wendy F.

    2014-01-01

    One challenge in studying the second messenger inositol(1,4,5)-trisphosphate (InsP3) is that it is present in very low amounts and increases only transiently in response to stimuli. To identify events downstream of InsP3, we generated transgenic plants constitutively expressing the high specific activity, human phosphatidylinositol 4-phosphate 5-kinase Iα (HsPIPKIα). PIP5K is the enzyme that synthesizes phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2); this reaction is flux limiting in InsP3 biosynthesis in plants. Plasma membranes from transgenic Arabidopsis expressing HsPIPKIα had 2–3 fold higher PIP5K specific activity, and basal InsP3 levels in seedlings and leaves were >2-fold higher than wild type. Although there was no significant difference in photosynthetic electron transport, HsPIPKIα plants had significantly higher starch (2–4 fold) and 20% higher anthocyanin compared to controls. Starch content was higher both during the day and at the end of dark period. In addition, transcripts of genes involved in starch metabolism such as SEX1 (glucan water dikinase) and SEX4 (phosphoglucan phosphatase), DBE (debranching enzyme), MEX1 (maltose transporter), APL3 (ADP-glucose pyrophosphorylase) and glucose-6-phosphate transporter (Glc6PT) were up-regulated in the HsPIPKIα plants. Our results reveal that increasing the phosphoinositide (PI) pathway affects chloroplast carbon metabolism and suggest that InsP3 is one component of an inter-organelle signaling network regulating chloroplast metabolism. PMID:27135490

  17. Crystal structures of three 3,4,5-tri-meth-oxy-benzamide-based derivatives.

    PubMed

    Gomes, Ligia R; Low, John Nicolson; Oliveira, Catarina; Cagide, Fernando; Borges, Fernanda

    2016-05-01

    The crystal structures of three benzamide derivatives, viz. N-(6-hy-droxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C16H25NO5, (1), N-(6-anilinohex-yl)-3,4,5-tri-meth-oxy-benzamide, C22H30N2O4, (2), and N-(6,6-di-eth-oxy-hex-yl)-3,4,5-tri-meth-oxy-benzamide, C20H33NO6, (3), are described. These compounds differ only in the substituent at the end of the hexyl chain and the nature of these substituents determines the differences in hydrogen bonding between the mol-ecules. In each mol-ecule, the m-meth-oxy substituents are virtually coplanar with the benzyl ring, while the p-meth-oxy substituent is almost perpendicular. The carbonyl O atom of the amide rotamer is trans related with the amidic H atom. In each structure, the benzamide N-H donor group and O acceptor atoms link the mol-ecules into C(4) chains. In 1, a terminal -OH group links the mol-ecules into a C(3) chain and the combined effect of the C(4) and C(3) chains is a ribbon made up of screw related R 2 (2)(17) rings in which the ⋯O-H⋯ chain lies in the centre of the ribbon and the tri-meth-oxy-benzyl groups forms the edges. In 2, the combination of the benzamide C(4) chain and the hydrogen bond formed by the terminal N-H group to an O atom of the 4-meth-oxy group link the mol-ecules into a chain of R 2 (2)(17) rings. In 3, the mol-ecules are linked only by C(4) chains. PMID:27308017

  18. Cost-Effectiveness of Thrombolysis within 4.5 Hours of Acute Ischemic Stroke in China

    PubMed Central

    Zhao, Xingquan; Liao, Xiaoling; Wang, Chunjuan; Du, Wanliang; Liu, Gaifen; Liu, Liping; Wang, Chunxue; Wang, Yilong; Wang, Yongjun

    2014-01-01

    Background Previous economic studies conducted in developed countries showed intravenous tissue-type plasminogen activator (tPA) is cost-effective for acute ischemic stroke. The present study aimed to determine the cost-effectiveness of tPA treatment in China, the largest developing country. Methods A combination of decision tree and Markov model was developed to determine the cost-effectiveness of tPA treatment versus non-tPA treatment within 4.5 hours after stroke onset. Outcomes and costs data were derived from the database of Thrombolysis Implementation and Monitor of acute ischemic Stroke in China (TIMS-China) study. Efficacy data were derived from a pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials. Costs and quality-adjusted life-years (QALYs) were compared in both short term (2 years) and long term (30 years). One-way and probabilistic sensitivity analyses were performed to test the robustness of the results. Results Comparing to non-tPA treatment, tPA treatment within 4.5 hours led to a short-term gain of 0.101 QALYs at an additional cost of CNY 9,520 (US$ 1,460), yielding an incremental cost-effectiveness ratio (ICER) of CNY 94,300 (US$ 14,500) per QALY gained in 2 years; and to a long-term gain of 0.422 QALYs at an additional cost of CNY 6,530 (US$ 1,000), yielding an ICER of CNY 15,500 (US$ 2,380) per QALY gained in 30 years. Probabilistic sensitivity analysis showed that tPA treatment is cost-effective in 98.7% of the simulations at a willingness-to-pay threshold of CNY 105,000 (US$ 16,200) per QALY. Conclusions Intravenous tPA treatment within 4.5 hours is highly cost-effective for acute ischemic strokes in China. PMID:25329637

  19. Myopes experience greater contrast adaptation during reading.

    PubMed

    McGonigle, Colm; van der Linde, Ian; Pardhan, Shahina; Engel, Stephen A; Mallen, Edward A H; Allen, Peter M

    2016-04-01

    In this study, we investigated whether reading influences contrast adaptation differently in young adult emmetropic and myopic participants at the spatial frequencies created by text rows and character strokes. Pre-adaptation contrast sensitivity was measured for test gratings with spatial frequencies of 1cdeg(-1) and 4cdeg(-1), presented horizontally and vertically. Participants then adapted to reading text corresponding to the horizontal "row frequency" of text (1cdeg(-1)), and vertical "stroke frequency" of the characters (4cdeg(-1)) for 180s. Following this, post-adaptation contrast sensitivity was measured. Twenty young adults (10 myopes, 10 emmetropes) optimally corrected for the viewing distance participated. There was a significant reduction in logCS post-text adaptation (relative to pre-adaptation logCS) at the row frequency (1cdeg(-1) horizontal) but not at the stroke frequency (4cdeg(-1) vertical). logCS changes due to adaptation at 1cdeg(-1) horizontal were significant in both emmetropes and myopes. Comparing the two refractive groups, myopic participants showed significantly greater adaptation compared to emmetropic participants. Reading text on a screen induces contrast adaptation in young adult observers. Myopic participants were found to exhibit greater contrast adaptation than emmetropes at the spatial frequency corresponding to the text row frequency. No contrast adaptation was observed at the text stroke frequency in either participant group. The greater contrast adaptation experienced by myopes after reading warrants further investigation to better understand the relationship between near work and myopia development. PMID:26804636

  20. Greater trochanter apophysitis in the adolescent athlete.

    PubMed

    Young, Simon W; Safran, Marc R

    2015-05-01

    Lower limb traction apophysitis is common in young athletes, occurring at sites such as the tibial tubercle (Osgood-Schlatter disease) and distal patella (Sinding-Larsen-Johansson disease). Around the hip, iliac apophysitis is well recognized, but no cases of greater trochanter apophysitis have previously been reported. We describe the case of a 15-year-old male basketball player with a 2-month history of the right hip pain and significant functional limitation. X-rays revealed widening of the greater trochanter apophysis with subchondral sclerosis, consistent with a diagnosis of traction apophysitis. The patient was treated with a period of relative rest and anti-inflammatory medication. He gradually returned to full athletic activity, including basketball, without recurrence of pain or limitation. We describe the first reported case of traction apophysitis of the greater trochanter. The unique muscular anatomy of this apophysis with balanced forces explains the rarity of this condition. If encountered, rest and activity modification is the recommended treatment. PMID:24942622

  1. Room temperature photoluminescence at 4.5 {mu}m from InAsN

    SciTech Connect

    Zhuang, Q.; Godenir, A. M. R.; Krier, A.; Lai, K. T.; Haywood, S. K.

    2008-03-15

    Nitrogen incorporation in InAsN epilayers grown by radio-frequency plasma-assisted molecular beam epitaxy was investigated as a function of growth conditions. Reduced growth rate, growth temperature, and arsenic flux significantly enhance the nitrogen incorporation. Optimal growth conditions allowed us to obtain high quality InAsN with nitrogen composition of up to 2.5%. The epilayers exhibit intense 4 K photoluminescence (PL) with double-peak features, which were attributed to free carrier recombination and localized carrier recombination. Strong room temperature PL emission up to a wavelength of 4.5 {mu}m is obtained.

  2. SeizAlert could give patients 4.5 hour warning of seizure

    ScienceCinema

    Dr. Lee Hively and Kara Kruse

    2010-01-08

    One percent of Americans, 3 million people, suffer from epilepsy. And their lives are about to be dramatically changed by scientists at Oak Ridge National Laboratory. For 15 years, Dr. Lee Hively has been working on "SeizAlert", a seizure-detecting device that resembles a common PDA. "It allows us to analyze scalp brain waves and give us up to 4.5 hours' forewarning of that event," he said. With the help of partner Kara Kruse, he's now able to help patients predict the previously unpredictable.

  3. SeizAlert could give patients 4.5 hour warning of seizure

    SciTech Connect

    Dr. Lee Hively and Kara Kruse

    2009-01-16

    One percent of Americans, 3 million people, suffer from epilepsy. And their lives are about to be dramatically changed by scientists at Oak Ridge National Laboratory. For 15 years, Dr. Lee Hively has been working on "SeizAlert", a seizure-detecting device that resembles a common PDA. "It allows us to analyze scalp brain waves and give us up to 4.5 hours' forewarning of that event," he said. With the help of partner Kara Kruse, he's now able to help patients predict the previously unpredictable.

  4. Photophysics of poly(2,3,4,5,6-pentafluorostyrene) film

    SciTech Connect

    O'Connor, D.B.; Scott, G.W. ); Coulter, D.R.; Miskowski, V.M.; Yavrouian, A. )

    1990-08-09

    The temperature-dependent steady-state emission, emission polarization anisotropy, and fluorescence kinetics of poly(2,3,4,5,6-pentafluorostyrene) film are reported. Two interconverting excited-state conformations of the chromophore have been identified. The fluorescence of the higher energy conformation results from excitation on the red edge of the polymer absorption band at temperatures below 180 K. The energy barrier for conversion of the higher energy conformer to the lower energy conformer is estimated to be E/hc = 27 {plus minus} 7 cm{sup {minus}1}. Electronic energy migration is not evident in this polymer.

  5. Accurate labeling of the light-actinide O4,5 ionization edges

    SciTech Connect

    Moore, K; der Laan, G v

    2006-08-23

    In this short article the accurate labeling of the O4,5 edges of the light actinides is addressed. The O4 and O5 edges are both contained in what is termed the ''giant resonance'' and the smaller ''pre-peak'' that is observed is a consequence of first-order perturbation by the 5d spin-orbit interaction. Thus, the small prepeak in the actinide 5d {yields} 5f transition should not be labeled the O5 peak, but rather the {Delta}S=1 peak.

  6. Size evolution of star-forming galaxies with 2 4.5 in the VIMOS Ultra-Deep Survey

    NASA Astrophysics Data System (ADS)

    Ribeiro, B.; Le Fèvre, O.; Tasca, L. A. M.; Lemaux, B. C.; Cassata, P.; Garilli, B.; Maccagni, D.; Zamorani, G.; Zucca, E.; Amorín, R.; Bardelli, S.; Fontana, A.; Giavalisco, M.; Hathi, N. P.; Koekemoer, A.; Pforr, J.; Tresse, L.; Dunlop, J.

    2016-08-01

    Context. The size of a galaxy encapsulates the signature of the different physical processes driving its evolution. The distribution of galaxy sizes in the Universe as a function of cosmic time is therefore a key to understand galaxy evolution. Aims: We aim to measure the average sizes and size distributions of galaxies as they are assembling before the peak in the comoving star formation rate density of the Universe to better understand the evolution of galaxies across cosmic time. Methods: We used a sample of ~1200 galaxies in the COSMOS and ECDFS fields with confirmed spectroscopic redshifts 2 ≤ zspec ≤ 4.5 in the VIMOS Ultra Deep Survey (VUDS), representative of star-forming galaxies with iAB ≤ 25. We first derived galaxy sizes by applying a classical parametric profile-fitting method using GALFIT. We then measured the total pixel area covered by a galaxy above a given surface brightness threshold, which overcomes the difficulty of measuring sizes of galaxies with irregular shapes. We then compared the results obtained for the equivalent circularized radius enclosing 100% of the measured galaxy light r100T ~2.2 to those obtained with the effective radius re,circ measured with GALFIT. Results: We find that the sizes of galaxies computed with our non-parametric approach span a wide range but remain roughly constant on average with a median value r100T ~2.2 kpc for galaxies with 2 4.5. This is in stark contrast with the strong downward evolution of re with increasing redshift, down to sizes of <1 kpc at z ~ 4.5. We analyze the difference and find that parametric fitting of complex, asymmetric, multicomponent galaxies is severely underestimating their sizes. By comparing r100T with physical parameters obtained through fitting the spectral energy distribution we find that the star-forming galaxies that are the largest at any redshift are, on average, more massive and form more stars. We discover that galaxies present more concentrated light profiles with

  7. Satellite observations of the spatial extent and structure of Pc 3, 4, 5 pulsations near the magnetospheric equator

    NASA Technical Reports Server (NTRS)

    Singer, H. J.; Russell, C. T.; Kivelson, M. G.; Fritz, T. A.; Lennartsson, W.

    1979-01-01

    Simultaneous observations of Pc 3, 4, 5 pulsations by five satellites in the pre-noon local time sector at and near synchronous orbit are examined. The periods of these simultaneous pulsations are not the same at the different observation points. This difference is attributed to site dependent resonant conditions. The spatial properties of the temporal phenomenon are demonstrated with observations by ISEE-1 and -2 as they pass through oscillations in a spatially limited region. Fundamental and second harmonic standing Alfven waves are observed simultaneously on the same field line. The periods are consistent with model predictions when the measured plasma composition, which by mass consists mainly of singly ionized oxygen, is taken into account.

  8. Neutron scattering differential cross sections for 23Na from 1.5 to 4.5 MeV

    NASA Astrophysics Data System (ADS)

    Vanhoy, J. R.; Hicks, S. F.; Chakraborty, A.; Champine, B. R.; Combs, B. M.; Crider, B. P.; Kersting, L. J.; Kumar, A.; Lueck, C. J.; Liu, S. H.; McDonough, P. J.; McEllistrem, M. T.; Peters, E. E.; Prados-Estévez, F. M.; Sidwell, L. C.; Sigillito, A. J.; Watts, D. W.; Yates, S. W.

    2015-07-01

    Measurements of neutron elastic and inelastic scattering cross sections from 23Na have been performed for sixteen incident neutron energies between 1.5 and 4.5 MeV. These measurements were complemented by γ-ray excitation functions using the (n ,n‧ γ) reaction to include excited levels not resolved in the neutron detection measurements. The time-of-flight (TOF) technique was employed for background reduction in both neutron and γ-ray measurements and for energy determination in neutron detection measurements. Previous reaction model evaluations relied primarily on neutron total cross sections and four (n, n0) and (n, n1) angular distributions in the 5 to 9 MeV range. The inclusion of more inelastic channels and measurements at lower incident neutron energies provide additional information on direct couplings between elastic and inelastic scattering as a function of angular momentum transfer. Reaction model calculations examining collective direct-coupling and compound absorption components were performed.

  9. Total Synthesis of 4,5-Didehydroguadiscine: A Potent Melanogenesis Inhibitor from the Brazilian Medicinal Herb, Hornschuchia obliqua.

    PubMed

    Tanabe, Genzoh; Sugano, Youta; Shirato, Miki; Sonoda, Naoki; Tsutsui, Nozomi; Morikawa, Toshio; Ninomiya, Kiyofumi; Yoshikawa, Masayuki; Muraoka, Osamu

    2015-07-24

    The first total synthesis of the 7,7-dimethylaporphinoid, 4,5-didehydroguadiscine (6), originally isolated from the stems and roots of Hornschuchia oblique (Annonaceae), was achieved by the condensation of homopiperonylamine (7) with an α,α-dimethylphenylacetic acid derivative (8) and subsequent Pschorr reaction of the resulting benzylisoquinoline intermediate (22). The reported (13)C NMR data were partially revised on the basis of the analysis of HMBC spectra measured under different conditions. The melanogenesis inhibitory activity (IC50 = 4.7 μM) of 6 was 40 times stronger than that of arbutin (174 μM), which was used as reference standard. Furthermore, 6 was the most potent natural melanogenesis inhibitor within this class of compounds. PMID:26135746

  10. The metabolism of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene and gamma-hexachlorocyclohexane in rats.

    PubMed

    Grover, P L; Sims, P

    1965-08-01

    1. After intraperitoneal administration, gamma-hexachlorocyclohexane (Gammexane) and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene were converted by rats into 2,3,5- and 2,4,5-trichlorophenol, which were excreted as free phenols and as sulphuric acid and glucuronic acid conjugates. 2. Derivatives of 2,4,5-trichlorophenol and 2,4,5-trichlorophenyl glucosiduronic acid and 2,4-dichlorophenylmercapturic acid were isolated from the urine as metabolites of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene. 3. The phenolic metabolites of gamma-hexachlorocyclohexane and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene isolated from urine were similar to those of 1,2,4-trichlorobenzene, which indicates that the two latter compounds are intermediates in gamma-hexachlorocyclohexane metabolism in rats. PMID:4158352

  11. The yeast transcription elongation factor Spt4/5 is a sequence-specific RNA binding protein.

    PubMed

    Blythe, Amanda J; Yazar-Klosinski, Berra; Webster, Michael W; Chen, Eefei; Vandevenne, Marylène; Bendak, Katerina; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

    2016-09-01

    The heterodimeric transcription elongation factor Spt4/Spt5 (Spt4/5) tightly associates with RNAPII to regulate both transcriptional elongation and co-transcriptional pre-mRNA processing; however, the mechanisms by which Spt4/5 acts are poorly understood. Recent studies of the human and Drosophila Spt4/5 complexes indicate that they can bind nucleic acids in vitro. We demonstrate here that yeast Spt4/5 can bind in a sequence-specific manner to single stranded RNA containing AAN repeats. Furthermore, we show that the major protein determinants for RNA-binding are Spt4 together with the NGN domain of Spt5 and that the KOW domains are not required for RNA recognition. These findings attribute a new function to a domain of Spt4/5 that associates directly with RNAPII, making significant steps towards elucidating the mechanism behind transcriptional control by Spt4/5. PMID:27376968

  12. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species.

    PubMed

    Amann, Barbara; Kleinwort, Kristina J H; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M; Deeg, Cornelia A

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  13. 4.5-K Cold Box for SNS - A Successful Cooperation

    SciTech Connect

    Fleck, U.; Kurtcuoglu, K.; Urbin, J.; Howe, D.

    2004-06-23

    The US Department of Energy is constructing the next generation, accelerator-based, neutron source, the Spallation Neutron Source at the Oak Ridge National Laboratory. The superconducting LINAC requires a large custom cryogenic helium system that was specified and ordered by the Thomas Jefferson National Accelerator Laboratory. Two groups of Linde AG's engineering division teamed to design, fabricate, and deliver the 4.5-K cold box for the SNS Central He liquefier. Linde Kryotechnik AG (LK), Switzerland provided design, engineering support and the gas bearing turbine systems. Process design for 4.5 K cooling as well as 38-K shield cooling will be explained. Control logic, including turbine related logic, was specified by LK and implemented successfully by ORNL in their control system in cooperation with LK. Linde BOC Process Plants LLC, Tulsa, Oklahoma fabricated, tested and delivered the cold box. Skills and techniques specific to helium cold box fabrication will be discussed. Finally, an overview of the commissioning will be provided according to the project status.

  14. 4.5-K Cold Box for SNS — A Successful Cooperation

    NASA Astrophysics Data System (ADS)

    Fleck, U.; Urbin, J.; Kurtcuoglu, K.; Howe, D.

    2004-06-01

    The US Department of Energy is constructing the next generation, accelerator-based, neutron source, the Spallation Neutron Source at the Oak Ridge National Laboratory. The superconducting LINAC requires a large custom cryogenic helium system that was specified and ordered by the Thomas Jefferson National Accelerator Laboratory. Two groups of Linde AG's engineering division teamed to design, fabricate, and deliver the 4.5-K cold box for the SNS Central He liquefier. Linde Kryotechnik AG (LK), Switzerland provided design, engineering support and the gas bearing turbine systems. Process design for 4.5 K cooling as well as 38-K shield cooling will be explained. Control logic, including turbine related logic, was specified by LK and implemented successfully by ORNL in their control system in cooperation with LK. Linde BOC Process Plants LLC, Tulsa, Oklahoma fabricated, tested and delivered the cold box. Skills and techniques specific to helium cold box fabrication will be discussed. Finally, an overview of the commissioning will be provided according to the project status.

  15. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species

    PubMed Central

    Amann, Barbara; Kleinwort, Kristina J. H.; Hirmer, Sieglinde; Sekundo, Walter; Kremmer, Elisabeth; Hauck, Stefanie M.; Deeg, Cornelia A.

    2016-01-01

    Aquaporins (AQPs) are small integral membrane proteins with 13 members in mammals and are essential for water transport across membranes. They are found in many different tissues and cells. Currently, there are conflicting results regarding retinal aquaporin expression and subcellular localization between genome and protein analyses and among various species. AQP4, 7, 9 and 11 were described in the retina of men; whereas AQP6, 8 and 10 were earlier identified in rat retinas and AQP4, 5 and 11 in horses. Since there is a lack of knowledge regarding AQP expression on protein level in retinas of different animal models, we decided to analyze retinal cellular expression of AQP4, 5 and 11 in situ with immunohistochemistry. AQP4 was detected in all 15 explored species, AQP5 and AQP11 in 14 out of 15. Interestingly, AQP4 was unambiguously expressed in Muller glial cells, whereas AQP5 was differentially allocated among the species analyzed. AQP11 expression was Muller glial cell-specific in 50% of the animals, whereas in the others, AQP11 was detected in ganglion cell layer and at photoreceptor outer segments. Our data indicate a disparity in aquaporin distribution in retinas of various animals, especially for AQP5 and 11. PMID:27438827

  16. Genotoxicity of chryseno[4,5-bcd]thiophene and its sulfone derivative

    SciTech Connect

    Sinsheimer, J.E.; Hooberman, B.H.; Das, S.K.; Savla, P.M.; Ashe, A.J. III )

    1992-01-01

    The authors' recent syntheses of cryseno[4,5-bcd]thiophene together with its potential sulfone metabolite, chryseno[4,5-bcd]thiophene-4,4-dioxide, have made these compounds available for genotoxicity testing. Such toxicity testing is of interest as this thiophene is an isoster of the established carcinogen benzo[a]pyrene and is one of the thiaarenes which are potential environmental contaminants found in fossil fuels. Although the thiophene was less mutagenic than benzo[a]pyrene in Salmonella strains TA98 and TA100 after S9 activation, it exhibited in vivo chromosomal aberration activity equal to that of benzo[a]pyrene in the bone-marrow cells of mice. A reduced activity with Salmonella as well as in the bone-marrow cell assay for the sulfone does not support its role as the key active metabolic intermediate for the genotoxicity of the thiophene. Molecular orbital calculations would be consistent with the concept of activation through a diol-epoxide mechanism and offers an explanation for the reduced genotoxicity of the sulfone via this mechanism. These genotoxicity studies support the concern that sulfur isosters of established carcinogenic polycyclic aromatic hydrocarbons could themselves be toxic. 21 refs., 2 figs., 3 tabs.

  17. PtdIns(4,5)P(2) and phospholipase C-independent Ins(1,4,5)P(3) signals induced by a nitrogen source in nitrogen-starved yeast cells.

    PubMed Central

    Bergsma, J C; Kasri, N N; Donaton, M C; De Wever, V; Tisi, R; de Winde, J H; Martegani, E; Thevelein, J M; Wera, S

    2001-01-01

    Addition of ammonium sulphate to nitrogen-depleted yeast cells resulted in a transient increase in Ins(1,4,5)P(3), with a maximum concentration reached after 7-8 min, as determined by radioligand assay and confirmed by chromatography. Surprisingly, the transient increase in Ins(1,4,5)P(3) did not trigger an increase in the concentration of intracellular calcium, as determined in vivo using the aequorin method. Similar Ins(1,4,5)P(3) signals were also observed in wild-type cells treated with the phospholipase C inhibitor 3-nitrocoumarin and in cells deleted for the only phospholipase C-encoding gene in yeast, PLC1. This showed clearly that Ins(1,4,5)P(3) was not generated by phospholipase C-dependent cleavage of PtdIns(4,5)P(2). Apart from a transient increase in Ins(1,4,5)P(3), we observed a transient increase in PtdIns(4,5)P(2) after the addition of a nitrogen source to nitrogen-starved glucose-repressed cells. Inhibition by wortmannin of the phosphatidylinositol 4-kinase, Stt4, which is involved in PtdIns(4,5)P(2) formation, did not affect the Ins(1,4,5)P(3) signal, but significantly delayed the PtdIns(4,5)P(2) signal. Moreover, wortmannin addition inhibited the nitrogen-induced activation of trehalase and the subsequent mobilization of trehalose, suggesting a role for PtdIns(4,5)P(2) in nitrogen activation of the fermentable-growth-medium-induced signalling pathway. PMID:11672425

  18. Greater Sage-Grouse National Research Strategy

    USGS Publications Warehouse

    Hanser, Steven E.; Manier, Daniel J.

    2013-01-01

    The condition of the sagebrush ecosystem has been declining in the Western United States, and greater sage-grouse (Centrocercus urophasianus), a sagebrush-obligate species, has experienced concurrent decreases in distribution and population numbers. This has prompted substantial research and management over the past two decades to improve the understanding of sage-grouse and its habitats and to address the observed decreases in distribution and population numbers. The amount of research and management has increased as the year 2015 approaches, which is when the U.S. Fish and Wildlife Service (FWS) is expected to make a final decision about whether or not to protect the species under the Endangered Species Act. In 2012, the Sage-Grouse Executive Oversight Committee (EOC) of the Western Association of Fish and Wildlife Agencies (WAFWA) requested that the U.S. Geological Survey (USGS) lead the development of a Greater Sage-Grouse National Research Strategy (hereafter Research Strategy). This request was motivated by a practical need to systematically connect existing research and conservation plans with persisting or emerging information needs. Managers and researchers also wanted to reduce redundancy and help focus limited funds on the highest priority research and management issues. The USGS undertook the development of this Research Strategy, which addresses information and science relating to the greater sage-grouse and its habitat across portions of 11 Western States. This Research Strategy provides an outline of important research topics to ensure that science information gaps are identified and documented in a comprehensive manner. Further, by identifying priority topics and critical information needed for planning, research, and resource management, it provides a structure to help coordinate members of an expansive research and management community in their efforts to conduct priority research.

  19. Carcinogenic 4(5)-methylimidazole found in beverages, sauces, and caramel colors: chemical properties, analysis, and biological activities.

    PubMed

    Hengel, Matt; Shibamoto, Takayuki

    2013-01-30

    Since the National Toxicology Program (NTP) identified 4(5)-methylimidazole [4(5)-MI] as a cancer causing chemical in 2007 and the State of California added it to the Proposition 65 list of compounds as a carcinogen on January 7, 2011, many researchers and regulatory agencies have become focused on the presence of 4(5)-MI in foods and beverages. 4(5)-MI has been known to form in the Maillard reaction system consisting of a sugar and ammonia-a typical caramel-color preparation method for beverages. 4(5)-MI is identified in various beverages and sauces, which are colored with caramel, as well as in caramel color itself. Analysis of 4(5)-MI is extremely difficult due to its high water solubility, but the analytical method for 4(5)-MI has progressed from conventional paper chromatography, gas chromatography, and gas chromatography-mass spectrometry to the most advanced high-performance liquid chromatography-mass spectrometry. Various studies indicate that caramel colors and carbonated beverages contain 4(5)-MI in levels ranging from 0 to around 1000 ppm and from 0 to about 500 ppm, respectively. Reports of the toxicity of 4(5)-MI at relatively high levels suggest that it may cause some adverse effects on human consumers. PMID:23294412

  20. Greater auricular nerve masquerading as lymph node.

    PubMed

    Saxena, Shilpi; Deb, Prabal; Nijhawan, Vijay Shrawan; Kharayat, Veena; Verma, Rajesh

    2015-01-01

    Hansen's disease is on the verge of being eliminated from India and often missed by clinicians due to low index of suspicion. We present an unusual case in which greater auricular nerve thickening masqueraded as enlarged lymph node in the neck. The patient was referred for fine needle aspiration cytology, which revealed epithelioid cell granulomas suggestive of Hansen's disease. Further clinical examination and investigations including the skin biopsy confirmed the disease, highlighting the role of pathologist in the management of such unusual presentation of a common disease. PMID:26229249

  1. Greater auricular nerve masquerading as lymph node

    PubMed Central

    Saxena, Shilpi; Deb, Prabal; Nijhawan, Vijay Shrawan; Kharayat, Veena; Verma, Rajesh

    2015-01-01

    Hansen's disease is on the verge of being eliminated from India and often missed by clinicians due to low index of suspicion. We present an unusual case in which greater auricular nerve thickening masqueraded as enlarged lymph node in the neck. The patient was referred for fine needle aspiration cytology, which revealed epithelioid cell granulomas suggestive of Hansen's disease. Further clinical examination and investigations including the skin biopsy confirmed the disease, highlighting the role of pathologist in the management of such unusual presentation of a common disease. PMID:26229249

  2. Interspecific hybridization between greater kudu and nyala.

    PubMed

    Dalton, Desiré L; Tordiffe, Adrian; Luther, Ilse; Duran, Assumpta; van Wyk, Anna M; Brettschneider, Helene; Oosthuizen, Almero; Modiba, Catherine; Kotzé, Antoinette

    2014-06-01

    Hybridization of wildlife species, even in the absence of introgression, is of concern due to wasted reproductive effort and a reduction in productivity. In this study we detail an accidental mating between a female nyala (Tragelaphus angasii) and a male greater kudu (T. strepsiceros). The hybrid was phenotypically nyala and was identified as such based on mitochondrial DNA. Further genetic analysis based on nine microsatellite markers, chromosome number and chromosome morphology however, confirmed its status as an F1 hybrid. Results obtained from a reproductive potential assessment indicated that this animal does not have the potential to breed successfully and can be considered as sterile. PMID:24906427

  3. New approaches seek greater safety, appeal.

    PubMed

    Blaney, C L

    1995-06-01

    Researchers are developing new progestin-only contraceptives that are more appealing and may improve safety for certain users than such existing progestin methods as injectables (e.g., DMPA), the contraceptive implant Norplant, and progestin-only contraceptive pills (POPs). Progestin-only vaginal methods (rings and suppositories) allow users control over when to start and to discontinue their use. After removal of vaginal rings, the progestin level decreases within 24 hours and fertility returns quickly. Potential concerns about rings include expulsion, interference with intercourse, cervical changes, vaginal irritation, infection, and that they are more expensive to produce than other methods. A vaginal suppository being developed by the Contraceptive Research and Development Program is inserted daily, regardless of intercourse, and releases the natural female hormone progesterone. New implant systems should ease insertion and removal (e.g., a 2- or 1- rod vs. the existing 6-rod system) or avoid the need for removal (e.g., 4-5 biodegradable rice-grain-sized capsules of norethindrone and cholesterol). New injectable contraceptives have a lower amount of hormone than do other injectables without compromising the high contraceptive effectiveness. There is a need for more research on long-term effects of progestins (e.g., cardiovascular effects) as well as on whether progestins affect HIV transmission and whether DMPA has any effect on bone density. Another issue is how to reduce menstrual irregularities among users of progestin-only methods. The US National Institute of Child Health and Development has commissioned five new studies to address menstrual irregularities. The new progestin Nestorone (ST-1435), may be more beneficial for lactating mothers because it is not readily absorbed into an infant's system. It is being used for vaginal rings, implants, and a transdermal contraceptive cream. The IUD that releases levonorgestrel may prevent pregnancy for up to five

  4. Six lessons learned for greater success.

    PubMed

    Leander, W J

    1993-01-01

    These six lessons learned for greater success with your Patient Focused communications can help keep your cultural change process in sync with your operational change process. Of course, there are other key elements of the former, including: formal Patient Focused educational programs; restructured Human Resources "systems" (e.g., job descriptions and compensation programs); and migration toward greater organizational empowerment and more self-directed work teams. Still, your Patient Focused communications campaign will spearhead the cultural change process. As such, it will have the opportunity to make the very first impact. Basically, your communications can make or break your Patient Focused Care program from Day One. It's up to you--learn the lessons learned by others and your organization may follow the words of Marx rather than those of Brand: "Workers of the world, unite (on behalf of your Patient Focused Care program)!" Karl Marx.p6 "Workers of the world, fan out (in formation against your Patient Focused Care program)!" Stewart Brand. PMID:10133393

  5. Molecular Cytotoxic Mechanisms of 1-(3,4,5-Trihydroxyphenyl)-dodecylbenzoate in Human Leukemia Cell Lines

    PubMed Central

    Maioral, M. F.; Bubniak, L.D.S.; Marzarotto, M.A.L.; De Moraes, A.C.R.; Leal, P.; Nunes, R.; Yunes, R. A.; Santos-Silva, M. C.

    2016-01-01

    Recent studies have shown that gallic acid and its alkylesters induce apoptosis in different cell lines. Since new compounds with biological activity and less cytotoxicity to normal cells are necessary for cancer therapy, the aim of this study was to evaluate the cytotoxic effect of 1-(3,4,5-trihydroxyphenyl)-dodecylbenzoate on human acute myeloid leukemia K562 cells and on human acute lymphoblastic leukemia Jurkat cells. The cell viability was determined by MTT method. The apoptosis induction was assessed by bromide and acridine orange staining and by Annexin V-FITC Apoptosis Detection kit. The cell cycle analysis was carried out by flow cytometry using propidium iodide. Cytometric analysis was also performed to evaluate the expression of the following proteins: AIF, p53, Bcl-2 and Bax. The mitochondrial potential was also assessed by flow cytometry using MitoView633 kit. The results showed that the compound significantly reduced the cell viability of K562 and Jurkat cells in a concentration and time dependent manner (IC50 of 30 μM). The compound induced cell cycle arrest in G0/G1phase and significantly increased the proportion of cells in the sub-G0/G1phase. Apoptosis was confirmed by the sight of morphological characteristics of apoptosis and by phosphatidylserine externalization (73.47±5.71% of cells expressing annexin). The results also showed that the compound promotes a modification in Bax:Bcl-2 ratio and increases p53 expression. Thus, it is possible to conclude that 1-(3,4,5-trihydroxyphenyl)-dodecylbenzoate induces apoptosis by inhibiting the antiapoptotic protein Bcl-2 and by increasing the release of AIF, Bax and p53. In addition, it blocks the cell cycle at G0/G1, stopping cell proliferation. So far, the results suggest that this compound may have a potential therapeutic effect against leukemia cells. PMID:27168690

  6. Transient and sustained increases in inositol 1,4,5-trisphosphate precede the differential growth response in gravistimulated maize pulvini

    NASA Technical Reports Server (NTRS)

    Perera, I. Y.; Heilmann, I.; Boss, W. F.; Davies, E. (Principal Investigator)

    1999-01-01

    The internodal maize pulvinus responds to gravistimulation with differential cell elongation on the lower side. As the site of both graviperception and response, the pulvinus is an ideal system to study how organisms sense changes in orientation. We observed a transient 5-fold increase in inositol 1,4,5-trisphosphate (IP3) within 10 s of gravistimulation in the lower half of the pulvinus, indicating that the positional change was sensed immediately. Over the first 30 min, rapid IP3 fluctuations were observed between the upper and lower halves. Maize plants require a presentation time of between 2 and 4 h before the cells on the lower side of the pulvinus are committed to elongation. After 2 h of gravistimulation, the lower half consistently had higher IP3, and IP3 levels on the lower side continued to increase up to approximately 5-fold over basal levels before visible growth. As bending became visible after 8-10 h, IP3 levels returned to basal values. Additionally, phosphatidylinositol 4-phosphate 5-kinase activity in the lower pulvinus half increased transiently within 10 min of gravistimulation, suggesting that the increased IP3 production was accompanied by an up-regulation of phosphatidylinositol 4, 5-bisphosphate biosynthesis. Neither IP3 levels nor phosphatidylinositol 4-phosphate 5-kinase activity changed in pulvini halves from vertical control plants. Our data indicate the involvement of IP3 and inositol phospholipids in both short- and long-term responses to gravistimulation. As a diffusible second messenger, IP3 provides a mechanism to transmit and amplify the signal from the perceiving to the responding cells in the pulvinus, coordinating a synchronized growth response.

  7. Cooperative Binding of Annexin A2 to Cholesterol- and Phosphatidylinositol-4,5-Bisphosphate-Containing Bilayers

    PubMed Central

    Drücker, Patrick; Pejic, Milena; Grill, David; Galla, Hans-Joachim; Gerke, Volker

    2014-01-01

    Biological membranes are organized into dynamic microdomains that serve as sites for signal transduction and membrane trafficking. The formation and expansion of these microdomains are driven by intrinsic properties of membrane lipids and integral as well as membrane-associated proteins. Annexin A2 (AnxA2) is a peripherally associated membrane protein that can support microdomain formation in a Ca2+-dependent manner and has been implicated in membrane transport processes. Here, we performed a quantitative analysis of the binding of AnxA2 to solid supported membranes containing the annexin binding lipids phosphatidylinositol-4,5-bisphosphate and phosphatidylserine in different compositions. We show that the binding is of high specificity and affinity with dissociation constants ranging between 22.1 and 32.2 nM. We also analyzed binding parameters of a heterotetrameric complex of AnxA2 with its S100A10 protein ligand and show that this complex has a higher affinity for the same membranes with Kd values of 12 to 16.4 nM. Interestingly, binding of the monomeric AnxA2 and the AnxA2-S100A10 complex are characterized by positive cooperativity. This cooperative binding is mediated by the conserved C-terminal annexin core domain of the protein and requires the presence of cholesterol. Together our results reveal for the first time, to our knowledge, that AnxA2 and its derivatives bind cooperatively to membranes containing cholesterol, phosphatidylserine, and/or phosphatidylinositol-4,5-bisphosphate, thus providing a mechanistic model for the lipid clustering activity of AnxA2. PMID:25418092

  8. Time?

    NASA Astrophysics Data System (ADS)

    Amoroso, Richard L.

    2013-09-01

    The concept of time in the `clockwork' Newtonian world was irrelevant; and has generally been ignored until recently by several generations of physicists since the implementation of quantum mechanics. We will set aside the utility of time as a property relating to physical calculations of events relating to a metrics line element or as an aspect of the transformation of a particles motion/interaction in a coordinate system or in relation to thermodynamics etc., i.e. we will discard all the usual uses of time as a concept used to circularly define physical parameters in terms of other physical parameters; concentrating instead on time as an aspect of the fundamental cosmic topology of our virtual reality especially as it inseparably relates to the nature and role of the observer in natural science.

  9. Influence of Solar and Thermal Radiation on Future Heat Stress Using CMIP5 Archive Driving the Community Land Model Version 4.5

    NASA Astrophysics Data System (ADS)

    Buzan, J. R.; Huber, M.

    2015-12-01

    The summer of 2015 has experienced major heat waves on 4 continents, and heat stress left ~4000 people dead in India and Pakistan. Heat stress is caused by a combination of meteorological factors: temperature, humidity, and radiation. The International Organization for Standardization (ISO) uses Wet Bulb Globe Temperature (WBGT)—an empirical metric this is calibrated with temperature, humidity, and radiation—for determining labor capacity during heat stress. Unfortunately, most literature studying global heat stress focuses on extreme temperature events, and a limited number of studies use the combination of temperature and humidity. Recent global assessments use WBGT, yet omit the radiation component without recalibrating the metric.Here we explicitly calculate future WBGT within a land surface model, including radiative fluxes as produced by a modeled globe thermometer. We use the Community Land Model version 4.5 (CLM4.5), which is a component model of the Community Earth System Model (CESM), and is maintained by the National Center for Atmospheric Research (NCAR). To drive our CLM4.5 simulations, we use greenhouse gasses Representative Concentration Pathway 8.5 (business as usual), and atmospheric output from the CMIP5 Archive. Humans work in a variety of environments, and we place the modeled globe thermometer in a variety of environments. We modify CLM4.5 code to calculate solar and thermal radiation fluxes below and above canopy vegetation, and in bare ground. To calculate wet bulb temperature, we implemented the HumanIndexMod into CLM4.5. The temperature, wet bulb temperature, and radiation fields are calculated at every model time step and are outputted 4x Daily. We use these fields to calculate WBGT and labor capacity for two time slices: 2026-2045 and 2081-2100.

  10. Parallel synthesis of an oligomeric imidazole-4,5-dicarboxamide library.

    PubMed

    Xu, Zhigang; DiCesare, John C; Baures, Paul W

    2010-03-01

    A library of oligomeric compounds was synthesized based on the imidazole-4,5-dicarboxylic acid scaffold along with amino acid esters and chiral diamines derived from amino acids. The final compounds incorporate nonpolar amino acids (Leu, Phe, Trp), polar amino acids (Ser, Asp, Arg), and neutral amino acids (Gly, Ala), and were designed to be useful in screening for inhibitors of protein-protein interactions. Many of the protected and deprotected oligomers show evidence of conformational isomers persistent at room temperature in aqueous solution. A total of 317 final oligomers, out of 441 targeted compounds, were obtained in high analytical purity and of sufficient quantity to submit them for high-throughput screening as part of the NIH Roadmap. PMID:20170086

  11. Human health effects of 2,4,5-T and its toxic contaminants.

    PubMed

    Suskind, R R; Hertzberg, V S

    1984-05-11

    A clinical epidemiologic study was conducted to determine the long-term health effects of workplace exposure to the process of manufacturing the herbicide (2,4,5-trichlorophenoxy)acetic acid including contaminants such as 2,3,7,8-tetrachlorodibenzo-rho-dioxin. The population consisted of two cohorts: 204 clearly exposed and 163 not exposed. Among the exposed, clinical evidence of chloracne persisted in 55.7%. None of the not exposed experienced chloracne development. An association was found between the persistence of chloracne and the presence and severity of actinic elastosis of the skin. There is an association between exposure and the history of gastrointestinal tract ulcer. Pulmonary function values among those who were exposed and who currently smoked were lower than those who were not exposed and who currently smoked. The data assembled in the study indicate no evidence of increased risk for cardiovascular disease, hepatic disease, renal damage, or central or peripheral nervous system problems. PMID:6231388

  12. Outbreaks of monophasic Salmonella enterica serovar 4,[5],12:i:- in Luxembourg, 2006.

    PubMed

    Mossong, J; Marques, P; Ragimbeau, C; Huberty-Krau, P; Losch, S; Meyer, G; Moris, G; Strottner, C; Rabsch, W; Schneider, F

    2007-06-01

    A monophasic Salmonella enterica serovar 4,[5],12:i:- phage type DT193 emerged as the dominant serovar in Luxembourg in 2006, when it caused two major outbreaks involving 133 laboratory-confirmed human cases, 24 hospitalisations, and one death. The outbreak strain had an uncommon pulsed-field gel electrophoresis pattern STYMXB.0031 and antibiotic resistance profile ASSuT. A high proportion of cases were clustered in institutions for the elderly and in day-care centers. Strains identical to the outbreak strain were recovered from two control meals, a nappy changing table, retail sausages and caecal porcine samples at an abattoir. Locally produced pork meat is strongly suspected to have been the vehicle for the outbreaks, although the precise mechanisms remain unclear. PMID:17991400

  13. Inositol 1,4,5-trisphosphate-induced calcium release from platelet plasma membrane vesicles

    SciTech Connect

    Rengasamy, A.; Feinberg, H.

    1988-02-15

    A platelet membrane preparation, enriched in plasma membrane markers, took up /sup 45/Ca/sup 2 +/ in exchange for intravesicular Na+ and released it after the addition of inositol 1,4,5-trisphosphate (IP3). The possibility that contaminating dense tubular membrane (DTS) vesicles contributed the Ca/sup 2 +/ released by IP3 was eliminated by the addition of vanadate to inhibit Ca/sup +/-ATPase-mediated DTS Ca/sup 2 +/ sequestration and by the finding that only plasma membrane vesicles exhibit Na/sup +/-dependent Ca/sup 2 +/ uptake. Ca/sup 2 +/ released by IP3 was dependent on low extravesicular Ca/sup 2 +/ concentrations. IP3-induced Ca/sup 2 +/ release was additive to that released by Na/sup +/ addition while GTP or polyethylene glycol (PEG) had no effect. These results strongly suggest that IP3 facilitates extracellular Ca/sup 2 +/ influx in addition to release from DTS membranes.

  14. Fifth dimension of life and the 4/5 allometric scaling law for human brain.

    PubMed

    He, Ji-Huan; Zhang, Juan

    2004-01-01

    Brain cells are not spherical. The basal metabolic rate (B) of a spherical cell scales as B approximately r2, where r is the radius of the cell; that of a brain cell scales as B approximately r(d), where r is the characteristic radius of the cell and d is the fractal dimensionality of its contour. The fractal geometry of the cell leads to a 4/5 allometric scaling law for human brain, uniquely endowing humans with a 5th dimension and successfully explains why the scaling exponent varies during rest and exercise. A striking analogy between Kleiber's 3/4 law and Newton's second law is heuristically illustrated. A physical explanation is given for the 4th dimension of life for three-dimensional organisms and the 5th dimension for human brain. PMID:15563403

  15. Studying isoform-specific inositol 1,4,5-trisphosphate receptor function and regulation

    PubMed Central

    Betzenhauser, Matthew J.; Wagner, Larry E.; Won, Jong-Hak; Yule, David I.

    2011-01-01

    Inositol 1,4,5-trisphosphate receptors (InsP3R) are a family of ubiquitously expressed intracellular Ca2+ channels. Isoform-specific properties of the three family members may play a prominent role in defining the rich diversity of the spatial and temporal characteristics of intracellular Ca2+ signals. Studying the properties of the particular family members is complicated because individual receptor isoforms are typically never expressed in isolation. In this article, we discuss strategies for studying Ca2+ release through individual InsP3R family members with particular reference to methods applicable following expression of recombinant InsP3R and mutant constructs in the DT40-3KO cell line, an unambiguously null InsP3R expression system. PMID:18929664

  16. 4.5S ribonucleic acid, a novel ribosome component in the chloroplasts of flowering plants.

    PubMed Central

    Bowman, C M; Dyer, T A

    1979-01-01

    A species of low-molecular-weight ribosomal RNA, referred to as '4.5S rRNA', was found in addition to 5S rRNA in the large subunit of chloroplast ribosomes of a wide range of flowering plants. It was shown by sequence analysis that several variants of this RNA may occur in a plant. Furthermore, although in most flowering plants the predominant variant contains about 100 nucleotides, in the broad bean it has less than 80. It seems, therefore, to be much more diverse in size and sequence than the other ribosomal RNA species. Like 5S rRNA , it does not contain modified nucleotides and it is also unusual in having an unphosphorylated 5'-end. It is apparently neither a homologue of cytosol 5.8S rRNA nor a fragment of 23S rRNA. Images Fig. 1. Fig. 3. Fig. 4. PMID:540035

  17. Dendrite growth morphologies in rapidly solidified Al-4.5wt.%Cu droplets

    NASA Astrophysics Data System (ADS)

    Bedel, M.; Reinhart, G.; Bogno, A.-A.; Nguyen-Thi, H.; Boller, E.; Gandin, Ch-A.; Henein, H.

    2016-03-01

    The impulse atomization process developed at the University of Alberta (Canada) enables metallic powders to be solidified with controlled process parameters and improved properties. In order to investigate the microstructure morphologies in droplets of Al- 4.5wt.%Cu alloys, three-dimensional reconstructions of several droplets are obtained by using synchrotron X-ray micro-tomography, allowing a visualization of the inner microstructure in three dimensions. The analysis of the reconstructed volumes reveals that a wide range of morphology, from highly branched to “finger-bundle”, can be obtained for different droplets of similar diameter and produced in the same batch. Unexpectedly for this alloy, microstructural features also indicate that the development of the dendrite arms (primary and of higher orders) occurs in most droplets along <111> crystallographic axes, instead of the usual <100> directions observed in conventional casting technologies.

  18. Crystal structure of phenyl 2,4,5-tri­chloro­benzene­sulfonate

    PubMed Central

    Riley, Sean; Staples, Richard J.; Biros, Shannon M.; Ngassa, Felix N.

    2016-01-01

    The title compound, C12H7Cl3O3S, was synthesized via a nucleophilic substitution reaction between phenol and 2,4,5-tri­chloro­benzene­sulfonyl chloride. The two aryl rings are oriented gauche to one another around the sulfonate S—O bond, with a C—S—O—C torsion angle of −70.68 (16)°, and the two rings are inclined to one another by 72.40 (7)°. In the crystal, mol­ecules are linked via various C—Cl⋯π inter­actions, forming ribbons propagating along [100]. Neighboring ribbons are linked by a weak C—Cl⋯π inter­action, forming layers parallel to (010). PMID:27308043

  19. Synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr)

    NASA Astrophysics Data System (ADS)

    Froes, F. H.; Highberger, W. T.

    1980-05-01

    The synthesis of CORONA 5 (Ti-4.5Al-5Mo-1.5Cr) is described from the viewpoints of alloy chemistry and microstructure. Lenticular alpha is shown to maximize fracture resistance parameters, while a globular alpha optimizes hightemperature flow characteristics. The processing and application of CORONA 5 as forging, plate, sheet and powder metallurgy products are presented. The weldability of the alloy is described and potential use of the alloy for engine applications discussed. The improved mechanical property behavior over the "workhorse" Ti-6Al-4V alloy combined with cost-effective production should result in use of CORONA 5 in many applications. Future developments for CORONA 5 are suggested both in terms of further mechanical property optimization and in light of the economics of producing the alloy.

  20. Complex self-assembly of pyrimido[4,5-d]pyrimidine nucleoside supramolecular structures

    NASA Astrophysics Data System (ADS)

    Zhao, Hang; Guo, Xiurong; He, Shiliang; Zeng, Xin; Zhou, Xinglong; Zhang, Chaoliang; Hu, Jing; Wu, Xiaohua; Xing, Zhihua; Chu, Liangyin; He, Yang; Chen, Qianming

    2014-01-01

    Supramolecular self-assembly is not only one of the chemical roots of biological structure but is also drawing attention in different industrial fields. Here we study the mechanism of the formation of a complex flower-shaped supramolecular structure of pyrimido[4,5-d]pyrimidine nucleosides by dynamic light scattering, scanning electron microscopy, differential scanning calorimetry, nuclear magnetic resonance and X-ray analysis. Upon removing the hydroxyl group of sugars, different flower-shaped superstructures can be produced. These works demonstrate that complex self-assembly can indeed be attained through hierarchical non-covalent interactions of single molecules. Furthermore, chimerical structures built from molecular recognition by these monomers indicate their potential in other fields if combined with other chemical entities.

  1. Inositol 1,4,5‐trisphosphate receptors and their protein partners as signalling hubs

    PubMed Central

    Taylor, Colin W.

    2016-01-01

    Abstract Inositol 1,4,5‐trisphosphate receptors (IP3Rs) are expressed in nearly all animal cells, where they mediate the release of Ca2+ from intracellular stores. The complex spatial and temporal organization of the ensuing intracellular Ca2+ signals allows selective regulation of diverse physiological responses. Interactions of IP3Rs with other proteins contribute to the specificity and speed of Ca2+ signalling pathways, and to their capacity to integrate information from other signalling pathways. In this review, we provide a comprehensive survey of the proteins proposed to interact with IP3Rs and the functional effects that these interactions produce. Interacting proteins can determine the activity of IP3Rs, facilitate their regulation by multiple signalling pathways and direct the Ca2+ that they release to specific targets. We suggest that IP3Rs function as signalling hubs through which diverse inputs are processed and then emerge as cytosolic Ca2+ signals. PMID:26830355

  2. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD {sub 30/50} value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  3. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD [sub 30/50] value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  4. Human cardiac phospholipase D activity is tightly controlled by phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Kurz, Thomas; Kemken, Dorit; Mier, Kenneth; Weber, Isabel; Richardt, Gert

    2004-02-01

    Phospholipase D (PLD) plays a central role in receptor-mediated breakdown of choline phospholipids and formation of phosphatidic acid (PA), an important regulator of cardiac function. However, specific mechanisms that regulate myocardial PLD activity remain largely unknown, particularly in the human heart. We hypothesized that phosphatidylinositol 4,5-bisphosphate (PIP2), best known as substrate for phospholipase C (PLC) isozymes, plays a critical role in regulating myocardial PLD activity. We examined the effect of PIP2 on human myocardial PLD activity in vitro by utilizing a fluorescence HPLC assay. PIP2 increased 10-fold the maximal activity of a partially solubilized PLD from human atrial myocardium. PIP2-stimulated PLD activity was accompanied by a consecutive increase in diacylglycerol, indicating dephosphorylation of PA by PA phosphohydrolase. Likewise, phosphatidylinositol 3,4,5-trisphosphate, which is produced from PIP2 by phosphatidylinositol 3-kinase, increased PLD activity with about the same potency but with somewhat lower efficacy. In contrast, other phospholipids were ineffective, indicating that the action of PIP2 on PLD is highly specific. Neomycin, a high-affinity ligand of PIP2, inhibited PLD activity in human atrial myocardium, but had no effect on the activity of partially solubilized enzyme. The addition of PIP2 restored the sensitivity of solubilized PLD to neomycin inhibition, indicating that neomycin inhibits PLD activity by binding to endogenous PIP2. Our results demonstrate a critical role for PIP2 in human cardiac PLD activity and suggest that PIP2 synthesis (by phosphatidylinositol 4-phosphate 5-kinase) and hydrolysis (by PIP2-specific PLC) could be important determinants in regulating PLD signal transduction in the human heart. PMID:14871550

  5. Synthetic polyspermine imidazole-4, 5-amide as an efficient and cytotoxicity-free gene delivery system

    PubMed Central

    Duan, Shi-Yue; Ge, Xue-Mei; Lu, Nan; Wu, Fei; Yuan, Weien; Jin, Tuo

    2012-01-01

    A chemically dynamic spermine-based polymer: polyspermine imidazole-4, 5-amide (PSIA, Mw > 7 kDa) was designed, synthesized, and evaluated in terms of its ability to deliver nucleic acids. This polymer was made from an endogenous monomer professionally condensing genes in sperms, spermine, and a known safety drug metabolite, imidazole-4, 5-dicarboxylic acid, through a bis-amide bond conjugated with the imidazole ring. This polymer can condense pDNA at a W/W ratio above 10 to form polyplexes (100–200 nm in diameter), which is consistent with the observation by transmission electron microscopy (TEM), and the zeta potential was in the range of 10–20 mV. The pDNA packaged polymer was stable in phosphate buffer solution (PBS) at pH 7.4 (simulated body fluid) while the polyplexes were releasing pDNA into the solution at pH 5.8 (simulated endo-lysosomes) due to the degradation of the bis-amide linkages in response to changes in pH values. PSIA-polyplexes were able to achieve efficient cellular uptake and luciferase gene silencing by co-transfection of pDNA and siRNA in COS-7 cells and HepG2 cells with negligible cytotoxicity. Biodistribution of Rhodamine B-labeled PSIA-polyplexes after being systemically injected in BALB/c nude-mice showed that the polyplexes circulated throughout the body, accumulated mainly in the kidney at 4 hours of sample administration, and moved to the liver and spleen after 24 hours. All the results suggested that PSIA offered a promising example to balance the transfection efficiency and toxicity of a synthetic carrier system for the delivery of therapeutic nucleic acids. PMID:22888236

  6. THE NATURE OF EXTREMELY RED H - [4.5] > 4 GALAXIES REVEALED WITH SEDS AND CANDELS

    SciTech Connect

    Caputi, K. I.; Dunlop, J. S.; McLure, R. J.; Cirasuolo, M.; Huang, J.-S.; Fazio, G. G.; Ashby, M. L. N.; Castellano, M.; Fontana, A.; Almaini, O.; Bell, E. F.; Dickinson, M.; Donley, J. L.; Ferguson, H. C.; Grogin, N. A.; Koekemoer, A. M.; Faber, S. M.; Kocevski, D. D.; Koo, D. C.; and others

    2012-05-01

    We have analyzed a sample of 25 extremely red H - [4.5] > 4 galaxies, selected using 4.5 {mu}m data from the Spitzer SEDS survey and deep H-band data from the Hubble Space Telescope CANDELS survey, over {approx}180 arcmin{sup 2} of the UKIDSS Ultra-Deep Survey field. Our aim is to investigate the nature of this rare population of mid-infrared (mid-IR) sources that display such extreme near-to-mid-IR colors. Using up to 17-band photometry (U through 8.0 {mu}m), we have studied in detail their spectral energy distributions, including possible degeneracies in the photometric redshift/internal extinction (z{sub phot}-A{sub V} ) plane. Our sample appears to include sources of very different nature. Between 45% and 75% of them are dust-obscured, massive galaxies at 3 < z{sub phot} < 5. All of the 24 {mu}m detected sources in our sample are in this category. Two of these have S(24 {mu}m)>300 {mu}Jy, which at 3 < z{sub phot} < 5 suggests that they probably host a dust-obscured active galactic nucleus. Our sample also contains four highly obscured (A{sub V} > 5) sources at z{sub phot} < 1. Finally, we analyze in detail two z{sub phot} {approx} 6 galaxy candidates, and discuss their plausibility and implications. Overall, our red galaxy sample contains the tip of the iceberg of a larger population of z > 3 galaxies to be discovered with the future James Webb Space Telescope.

  7. Pulsations in magnetic field and ion flux observed at L = 4. 5 on August 5, 1972

    SciTech Connect

    Engebretson, M.J.; Cahill, L.J. Jr.; Williams, D.J.

    1983-01-01

    After the unusually strong compression of the earth's magnetosphere associated with the August 1972 geomagnetic storm, large amplitude ULF pulsations were observed for several hours in space by Explorer 45 magnetic field and particle instruments near L = 4.5 and at magnetic observatories on the ground over a large range of latitudes. Spectral analysis of Explorer 45 magnetometer data suggests that a compressional mode oscillation coupled to a transverse mode oscillation. Enhancements in amplitude of a 300-s period wave near 0040 UT August 5 coincide with an intensification of 100- to 1000-Hz magnetic and electric field oscillations and with the appearance of enhancements of fluxes of energetic ions. During this period the ion pitch angle distribution in each available energy channel (24--300 keV) followed a periodic sequence, apparently synchronized with the magnetic pulsations, from normal trappping (highest fluxes near 90/sup 0/ and lowest near 0/sup 0/ and 180/sup 0/) to a nearly isotropic particle distribution. During the transitions the particle flux near 90/sup 0/ pitch angle was alternately larger earthward of the satellite (before isotropy) and larger radially outward from the satellite (after isotropy). Intense field-aligned fluxes of lower energy ions (E< or =5 keV) were observed periodically throughout the interval. Possible configurations of the magnetosphere consistent with the wave and particle observations are discussed, the most likely candidate being the presence of a wavelike boundary near the satellite. It is possible that the satellite sensed the low-latitude boundary layer at L = 4.5 during this period of extreme magnetospheric compression.

  8. Stereopsis Results at 4.5 Years of Age in the Infant Aphakia Treatment Study

    PubMed Central

    Hartmann, E. Eugenie; Stout, Ann U.; Lynn, Michael J.; Yen, Kimberly G.; Kruger, Stacey J.; Lambert, Scott R.

    2014-01-01

    Purpose To determine whether stereopsis of infants treated for monocular cataracts varies with the type of optical correction used. Design Randomized prospective clinical trial Methods The Infant Aphakia Treatment Study randomized 114 patients with unilateral cataracts at age 1 to 7 months to either primary intraocular lens (IOL) or contact lens correction. At 4.5 years of age a masked examiner assessed stereopsis on these patients using three different tests: 1) Frisby; 2) Randot Preschool; and 3) Titmus fly. Results Twenty-eight patients (25%) had a positive response to at least one of the stereopsis tests. There was no statistically significant difference in stereopsis between the two treatment groups. Frisby (contact lens, 6 (11%); IOL, 7 (13%); p=0.99), Randot (contact lens, 3 (6%); IOL, 1 (2%); p=0.62) or Titmus: (contact lens, 8 (15%); IOL, 13 (23%); p=0.34). The median age at surgery for patients with stereopsis was younger than for those without stereopsis (1.2 versus 2.4 months; p=0.002). The median visual acuity for patients with stereopsis was better than for those without stereopsis (20/40 vs. 20/252; p=0.0003). Conclusion The type of optical correction did not influence stereopsis outcomes. However, two other factors did: age at surgery and visual acuity in the treated eye at age 4.5 years. Early surgery for unilateral congenital cataract and the presence of visual acuity better than or equal to 20/40 appear to be more important than the type of initial optical correction used for the development of stereopsis. PMID:25261241

  9. Coordination polymer template synthesis of hierarchical MnCo2O4.5 and MnNi6O8 nanoparticles for electrochemical capacitors electrode

    NASA Astrophysics Data System (ADS)

    Wang, Kuaibing; Xu, Jiangyan; Lu, Aimin; Shi, Ying; Lin, Zixia

    2016-08-01

    Two types of ternary metal oxides, MnCo2O4.5 and MnNi6O8 nanoparticles have been separately synthesized through chemical transformation from the corresponding bimetallic coordination polymer particles precursor under high-heating conditions. Series of electrochemical measurements are performed to examine the MnCo2O4.5 and MnNi6O8 electrodes, and the result shows that MnCo2O4.5 structure, especially for Mn/Co-600, has much higher capacitance than that of MnNi6O8 nanoparticles, indicating MnCo2O4.5 electrode is more suitable for applying in neutral electrolyte system. The Mn/Co-600 electrode exhibits a specific capacitance of 158 F g-1 at 5 mV s-1, good rate capability of 53.8% with a 20 times current density increase, good cycle performance (92.9% capacitance retention after 1000 cycles) and high power density (a specific power of 5760 W kg-1 at 4.0 A g-1) with low charge transfer resistance value of 1.8 Ω.

  10. Planning for greater-confinement disposal

    SciTech Connect

    Gilbert, T.L.; Luner, C.; Meshkov, N.K.; Trevorrow, L.E.; Yu, C.

    1984-01-01

    This contribution is a progress report for preparation of a document that will summarize procedures and technical information needed to plan for and implement greater-confinement disposal (GCD) of low-level radioactive waste. Selection of a site and a facility design (Phase I), and construction, operation, and extended care (Phase II) will be covered in the document. This progress report is limited to Phase I. Phase I includes determination of the need for GCD, design alternatives, and selection of a site and facility design. Alternative designs considered are augered shafts, deep trenches, engineered structures, high-integrity containers, hydrofracture, and improved waste form. Design considerations and specifications, performance elements, cost elements, and comparative advantages and disadvantages of the different designs are covered. Procedures are discussed for establishing overall performance objectives and waste-acceptance criteria, and for comparative assessment of the performance and cost of the different alternatives. 16 references.

  11. Greater confinement disposal of radioactive wastes

    SciTech Connect

    Trevorrow, L.E.; Gilbert, T.L.; Luner, C.; Merry-Libby, P.A.; Meshkov, N.K.; Yu, C.

    1985-01-01

    Low-level radioactive waste (LLW) includes a broad spectrum of different radionuclide concentrations, half-lives, and hazards. Standard shallow-land burial practice can provide adequate protection of public health and safety for most LLW. A small volume fraction (approx. 1%) containing most of the activity inventory (approx. 90%) requires specific measures known as greater-confinement disposal (GCD). Different site characteristics and different waste characteristics - such as high radionuclide concentrations, long radionuclide half-lives, high radionuclide mobility, and physical or chemical characteristics that present exceptional hazards - lead to different GCD facility design requirements. Facility design alternatives considered for GCD include the augered shaft, deep trench, engineered structure, hydrofracture, improved waste form, and high-integrity container. Selection of an appropriate design must also consider the interplay between basic risk limits for protection of public health and safety, performance characteristics and objectives, costs, waste-acceptance criteria, waste characteristics, and site characteristics.

  12. Planning for greater-confinement disposal

    NASA Astrophysics Data System (ADS)

    Gilbert, T. L.; Luner, C.; Meshkov, N. K.; Trevorrow, L. E.; Yu, C.

    The preparation of a document that will summarize procedures and technical information needed to plan for and implement greater-confinement disposal (CGD) of low-level radioactive waste is presented. Selection of a site and a facility design (Phase I), and construction, operation, and extended care (Phase II) will be covered in the document. Phase I includes determination of the need for GCD, design alternatives, and selection of a site and facility design. Alternative designs considered are augered shafts, deep trenches, engineered structures, high-integrity containers, hydrofracture, and improved waste form. Design considerations and specifications, performance elements, cost elements, and comparative advantages and disadvantages of the different designs are covered. Procedures are discussed for establishing overall performance objectives and waste-acceptance criteria, and for comparative assessment of the performance and cost of the different alternatives.

  13. Health and Greater Manchester in Historical Perspective

    PubMed Central

    Snow, Stephanie J.

    2015-01-01

    This article maps the history of health organisation across Greater Manchester (GM), primarily since the Second World War, to show how against a continuing backdrop of health inequalities, services have been driven (and constrained) by the needs and the politics of each period. Defining ‘success’ as benefits for patients the article identifies examples such as Salford’s mental health services (1950s and 1960s), public health in North Manchester (1970s and 1980s), the creation of centres for diabetes, sickle-cell and thalassaemia (1980s) and the formation of the Joint Health Unit in 2002. What this history shows is that over the period the common factors influencing the ‘success’ of health organisation across GM have been the championing of particular issues by multi-disciplinary groups working across health and social care and stability in structures and personnel. PMID:27499557

  14. CLONING AND CHARACTERIZATION OF A CHROMOSOMAL DNA REGION REQUIRED FOR GROWTH ON 2,4,5-T BY PSEUDOMONAS CEPACIA AC1100

    EPA Science Inventory

    A series of spontaneous 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) nonmetabolizing mutants of Pseudomonas cepacia AC1100 were characterized to be defective in either 2,4,5-T uptake or conversion of this compound to 2,4,5-trichlorophenol (2,4,5-TCP). Two of these mutants, RHC22 a...

  15. CLONING AND CHARACTERIZATION OF A CHROMOSOMAL DNA REGION REQUIRED FOR GROWTH ON 2,4,5-T BY PSEUDOMONAS CEPACIA AC1100

    EPA Science Inventory

    A series of spontaneous 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) nonmetaolizing mutants of Pseudomonas cepacia AC1100 were characterized to be defective in either 2,4,5-T uptake or conversion of this compound to 2,4,5-trichlorophenol (2,4,5TCP). wo of these mutants, RHC22 and ...

  16. Integrin adhesion and force coupling are independently regulated by localized PtdIns(4,5)2 synthesis

    PubMed Central

    Legate, Kyle R; Takahashi, Seiichiro; Bonakdar, Navid; Fabry, Ben; Boettiger, David; Zent, Roy; Fässler, Reinhard

    2011-01-01

    The 90-kDa isoform of the lipid kinase PIP kinase Type I γ (PIPKIγ) localizes to focal adhesions (FAs), where it provides a local source of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Although PtdIns(4,5)P2 regulates the function of several FA-associated molecules, the role of the FA-specific pool of PtdIns(4,5)P2 is not known. We report that the genetic ablation of PIPKIγ specifically from FAs results in defective integrin-mediated adhesion and force coupling. Adhesion defects in cells deficient in FA-PtdIns(4,5)P2 synthesis are corrected within minutes while integrin–actin force coupling remains defective over a longer period. Talin and vinculin, but not kindlin, are less efficiently recruited to new adhesions in these cells. These data demonstrate that the specific depletion of PtdIns(4,5)P2 from FAs temporally separates integrin–ligand binding from integrin–actin force coupling by regulating talin and vinculin recruitment. Furthermore, it suggests that force coupling relies heavily on locally generated PtdIns(4,5)P2 rather than bulk membrane PtdIns(4,5)P2. PMID:21926969

  17. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  18. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  19. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  20. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  1. 40 CFR 721.4468 - 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 1H-Imidazole, 2-ethyl-4,5-dihydro-4... Specific Chemical Substances § 721.4468 1H-Imidazole, 2-ethyl-4,5-dihydro-4-methyl-. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  2. HERPUD1 protects against oxidative stress-induced apoptosis through downregulation of the inositol 1,4,5-trisphosphate receptor.

    PubMed

    Paredes, Felipe; Parra, Valentina; Torrealba, Natalia; Navarro-Marquez, Mario; Gatica, Damian; Bravo-Sagua, Roberto; Troncoso, Rodrigo; Pennanen, Christian; Quiroga, Clara; Chiong, Mario; Caesar, Christa; Taylor, W Robert; Molgó, Jordi; San Martin, Alejandra; Jaimovich, Enrique; Lavandero, Sergio

    2016-01-01

    Homocysteine-inducible, endoplasmic reticulum (ER) stress-inducible, ubiquitin-like domain member 1 (HERPUD1), an ER resident protein, is upregulated in response to ER stress and Ca(2+) homeostasis deregulation. HERPUD1 exerts cytoprotective effects in various models, but its role during oxidative insult remains unknown. The aim of this study was to investigate whether HERPUD1 contributes to cytoprotection in response to redox stress and participates in mediating stress-dependent signaling pathways. Our data showed that HERPUD1 protein levels increased in HeLa cells treated for 30 min with H2O2 or angiotensin II and in aortic tissue isolated from mice treated with angiotensin II for 3 weeks. Cell death was higher in HERPUD1 knockdown (sh-HERPUD1) HeLa cells treated with H2O2 in comparison with control (sh-Luc) HeLa cells. This effect was abolished by the intracellular Ca(2+) chelating agent BAPTA-AM or the inositol 1,4,5-trisphosphate receptor (ITPR) antagonist xestospongin B, suggesting that the response to H2O2 was dependent on intracellular Ca(2+) stores and the ITPR. Ca(2+) kinetics showed that sh-HERPUD1 HeLa cells exhibited greater and more sustained cytosolic and mitochondrial Ca(2+) increases than sh-Luc HeLa cells. This higher sensitivity of sh-HERPUD1 HeLa cells to H2O2 was prevented with the mitochondrial permeability transition pore inhibitor cyclosporine A. We concluded that the HERPUD1-mediated cytoprotective effect against oxidative stress depends on the ITPR and Ca(2+) transfer from the ER to mitochondria. PMID:26616647

  3. Effect of inositol 1,4,5-trisphosphate receptor stimulation on mitochondrial [Ca2+] and secretion in chromaffin cells.

    PubMed Central

    Montero, Mayte; Alonso, Maria Teresa; Albillos, Almudena; Cuchillo-Ibáñez, Inmaculada; Olivares, Román; Villalobos, Carlos; Alvarez, Javier

    2002-01-01

    Ca(2+) uptake by mitochondria is a potentially important buffering system able to control cytosolic [Ca(2+)]. In chromaffin cells, we have shown previously that stimulation of either Ca(2+) entry or Ca(2+) release via ryanodine receptors triggers large increases in mitochondrial [Ca(2+)] ([Ca(2+)](M)) approaching the millimolar range, whose blockade dramatically enhances catecholamine secretion [Montero, Alonso, Carnicero, Cuchillo-Ibañez, Albillos, Garcia, Carcia-Sancho and Alvarez (2000) Nat. Cell Biol. 2, 57-61]. In the present study, we have studied the effect of stimulation of inositol 1,4,5-trisphosphate (InsP(3)) receptors using histamine. We find that histamine produces a heterogeneous increase in [Ca(2+)](M), reaching peak levels at approx. 1 microM in 70% of the mitochondrial space to several hundred micromolar in 2-3% of mitochondria. Intermediate levels were found in the rest of the mitochondrial space. Single-cell imaging experiments with aequorin showed that the heterogeneity had both an intercellular and a subcellular origin. Those mitochondria responding to histamine with increases in [Ca(2+)](M) much greater than 1 microM (30%) were the same as those that also responded with large increases in [Ca(2+)](M) following stimulation with either high-K(+) medium or caffeine. Blocking mitochondrial Ca(2+) uptake with protonophores or mitochondrial inhibitors also enhanced catecholamine secretion induced by histamine. These results suggest that some InsP(3) receptors tightly co-localize with ryanodine receptors and voltage-dependent Ca(2+) channels in defined subplasmalemmal functional units designed to control secretion induced by different stimuli. PMID:11931633

  4. Synthesis of 5-chloro-4,5-diaryl-. delta. /sup 3/-1,3-oxazolin-2-ones

    SciTech Connect

    Bal'on, Ya.G.; Smirnov, V.A.

    1987-09-20

    During an attempt at the synthesis of the oxazoles by the reactions of the oxazolines (I) with phosphorus pentachloride the authors obtained the 5-chloro-4,5-diaryl-..delta../sup 3/-1,3-oxazolin-2-ones instead of the expected 4,5-diaryl-2-chlorooxazoles. As electrophiles, these compounds are active in nucleophilic addition and substitution reactions. Thus, in their reaction with methanol the 4,5-dimethoxy-4,5-diaryl-1,3-oxazolidin-2-ones are formed with quantitative yields. When heated they are easily converted into 5-methoxy-4,5-diaryl-..delta..-1,3-oxazolin-2-ones. The compositions and structures were proved by IR and PMR spectroscopy and elemental analysis.

  5. A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate.

    PubMed

    Iwasaki, Hirohide; Murata, Yoshimichi; Kim, Youngjun; Hossain, Md Israil; Worby, Carolyn A; Dixon, Jack E; McCormack, Thomas; Sasaki, Takehiko; Okamura, Yasushi

    2008-06-10

    Phosphatidylinositol lipids play diverse physiological roles, and their concentrations are tightly regulated by various kinases and phosphatases. The enzymatic activity of Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP), recently identified as a member of the PTEN (phosphatase and tensin homolog deleted on chromosome 10) family of phosphatidylinositol phosphatases, is regulated by its own voltage-sensor domain in a voltage-dependent manner. However, a detailed mechanism of Ci-VSP regulation and its substrate specificity remain unknown. Here we determined the in vitro substrate specificity of Ci-VSP by measuring the phosphoinositide phosphatase activity of the Ci-VSP cytoplasmic phosphatase domain. Despite the high degree of identity shared between the active sites of PTEN and Ci-VSP, Ci-VSP dephosphorylates not only the PTEN substrate, phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3], but also, unlike PTEN, phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Enzymatic action on PI(4,5)P2 removes the phosphate at position 5 of the inositol ring, resulting in the production of phosphatidylinositol 4-phosphate [PI(4)P]. The active site Cys-X(5)-Arg (CX(5)R) sequence of Ci-VSP differs with that of PTEN only at amino acid 365 where a glycine residue in Ci-VSP is replaced by an alanine in PTEN. Ci-VSP with a G365A mutation no longer dephosphorylates PI(4,5)P2 and is not capable of inducing depolarization-dependent rundown of a PI(4,5)P2-dependent potassium channel. These results indicate that Ci-VSP is a PI(3,4,5)P3/PI(4,5)P2 phosphatase that uniquely functions in the voltage-dependent regulation of ion channels through regulation of PI(4,5)P2 levels. PMID:18524949

  6. Spectral approach to finite Reynolds number effects on Kolmogorov's 4/5 law in isotropic turbulence

    NASA Astrophysics Data System (ADS)

    Tchoufag, J.; Sagaut, P.; Cambon, C.

    2012-01-01

    The Kolmogorov's 4/5 law is often considered as the sole exact relationship of inertial range statistics. Its asymptotic character, however, has been evidenced, investigating the finite Reynolds number (FRN) effect for the third-order structure function S3(r) (e.g., for longitudinal velocity increments with r separation length) using variants of the Kármán-Howarth equation in physical space. Similar semi-empirical fits were proposed for the maximum of the normalized structure function, C3 = -maxrS3(r)/(ɛr), expressing C3 - 4/5 as a power law of the Taylor-based Reynolds number. One of the most complete studies in this domain is by Antonia and Burratini [J. Fluid Mech. 550, 175 (2006)]. Considering that these studies are based on a model for the unsteady second-order structure function S2(r,t), with no explicit model for the third-order structure function itself, we propose to revisit the FRN effect by a spectral approach, in the line of Qian [Phys. Rev. E 55, 337 (1997), Phys. Rev. E 60, 3409 (1999)]. The spectral transfer term T(k,t), from which S3(r,t) is derived by an exact quadrature, is directly calculated by solving the Lin equation for the energy spectrum E(k,t), closed by a standard triadic (or three-point) theory, here Eddy Damped Quasi Normal Markovian. We show that the best spectral approach to the FRN effect is found by separately investigating the negative (largest scales) and positive (smaller scales) bumps of the transfer term, and not only by looking at the maximum of the spectral flux or maxk ∫k∞T(p ,t)dp→ɛ. In the forced case, previous results are well reproduced, with Reynolds numbers as high as Reλ = 5 000 to nearly recover the 4/5 value. In the free decay case, the general trend is recovered as well, with an even higher value of Reλ = 50 000, but the EDQNM plots are systematically below those in Antonia and Burattini [J. Fluid Mech. 550, 175 (2006)]. This is explained by the sensitivity to initial data for E(k) in solving the Lin

  7. Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation and NLO, HOMO-LUMO, NBO analysis of organic 2,4,5-trichloroaniline

    NASA Astrophysics Data System (ADS)

    Govindarajan, M.; Karabacak, M.; Periandy, S.; Tanuja, D.

    2012-11-01

    In this work, the experimental and theoretical study on the molecular structure and vibrational spectra of 2,4,5-trichloroaniline (C6H4NCl3, abbreviated as 2,4,5-TClA) were studied. The FT-IR and FT-Raman spectra were recorded. The molecular geometry and vibrational frequencies in the ground state were calculated by using the Hartree-Fock (HF) and density functional theory (DFT) methods (B3LYP) with 6-311++G(d,p) basis set. Comparison of the observed fundamental vibrational frequencies of 2,4,5-TClA with calculated results by HF and DFT indicates that B3LYP is superior to HF method for molecular vibrational problems. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The theoretically predicted FT-IR and FT-Raman spectra of the title molecule have been constructed. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. Besides, molecular electrostatic potential (MEP) and thermodynamic properties were performed. The electric dipole moment (μ) and the first hyperpolarizability (β) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the 2,4,5-TClA molecule may have microscopic nonlinear optical (NLO) behavior with non-zero values. Mulliken atomic charges of 2,4,5-TClA was calculated and compared with aniline and chlorobenzene molecules. The 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results.

  8. Spectroscopic (FT-IR, FT-Raman, UV and NMR) investigation and NLO, HOMO-LUMO, NBO analysis of organic 2,4,5-trichloroaniline.

    PubMed

    Govindarajan, M; Karabacak, M; Periandy, S; Tanuja, D

    2012-11-01

    In this work, the experimental and theoretical study on the molecular structure and vibrational spectra of 2,4,5-trichloroaniline (C(6)H(4)NCl(3), abbreviated as 2,4,5-TClA) were studied. The FT-IR and FT-Raman spectra were recorded. The molecular geometry and vibrational frequencies in the ground state were calculated by using the Hartree-Fock (HF) and density functional theory (DFT) methods (B3LYP) with 6-311++G(d,p) basis set. Comparison of the observed fundamental vibrational frequencies of 2,4,5-TClA with calculated results by HF and DFT indicates that B3LYP is superior to HF method for molecular vibrational problems. The difference between the observed and scaled wavenumber values of most of the fundamentals is very small. The theoretically predicted FT-IR and FT-Raman spectra of the title molecule have been constructed. A study on the electronic properties, such as HOMO and LUMO energies, were performed by time-dependent DFT (TD-DFT) approach. Besides, molecular electrostatic potential (MEP) and thermodynamic properties were performed. The electric dipole moment (μ) and the first hyperpolarizability (β) values of the investigated molecule were computed using ab initio quantum mechanical calculations. The calculated results also show that the 2,4,5-TClA molecule may have microscopic nonlinear optical (NLO) behavior with non-zero values. Mulliken atomic charges of 2,4,5-TClA was calculated and compared with aniline and chlorobenzene molecules. The (13)C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the gauge independent atomic orbital (GIAO) method and compared with experimental results. PMID:22765942

  9. Aldolase A Ins(1,4,5)P3-binding domains as determined by site-directed mutagenesis.

    PubMed Central

    Baron, C B; Tolan, D R; Choi, K H; Coburn, R F

    1999-01-01

    We substituted neutral amino acids for some positively charged residues (R42, K107, K146, R148 and K229) that line the active site of aldolase A in an effort to determine binding sites for inositol 1, 4,5-trisphosphate. In addition, D33 (involved in carbon-carbon bond cleavage) was mutated. K229A and D33S aldolases showed almost no catalytic activity, but Ins(1,4,5)P(3) binding was similar to that determined with the use of wild-type aldolase A. R42A, K107A, K146R and R148A had markedly decreased affinities for Ins(1,4,5)P(3) binding, increased EC(50) values for Fru(1,6)P(2)-evoked release of bound Ins(1,4,5)P(3) and increased K(i) values for Ins(1,4, 5)P(3)-evoked inhibition of aldolase activity. K146Q (positive charge removal) had essentially no catalytic activity and could not bind Ins(1,4,5)P(3). Computer-simulated docking of Ins(1,4,5)P(3) in the aldolase A structure was consistent with electrostatic binding of Ins(1,4,5)P(3) to K107, K146, R148, R42, R303 and backbone nitrogens, as has been reported for Fru(1,6)P(2) binding. Results indicate that Ins(1,4,5)P(3) binding occurs at the active site and is not dependent on having a catalytically active enzyme; they also suggest that there is competition between Ins(1,4,5)P(3) and Fru(1, 6)P(2) for binding. Although Ins(1,4,5)P(3) binding to aldolase involved electrostatic interactions, the aldolase A Ins(1,4, 5)P(3)-binding domain did not show other similarities to pleckstrin homology domains or phosphotyrosine-binding domains known to bind Ins(1,4,5)P(3) in other proteins. PMID:10417347

  10. Photocatalysis of 2,2',3,4,4',5'-hexachlorobiphenyl and its intermediates using various catalytical preparing methods.

    PubMed

    Lin, Y J; Chen, Y L; Huang, C Y; Wu, M F

    2006-08-25

    Four etching solutions used on support materials and two coating methods of TiO(2) were conducted to investigate the effects of catalytical preparing methods on the photocatalysis of 2,2',3,4,4',5'-hexachlorobiphenyl (PCB congener 138). The results of XRD analyses confirmed that various etching solutions used on support substrates did not influence the characteristics of titanium(IV) oxide. The XRD patterns of crystallization for the catalysts before and after purification remained unchanged. Hydrofluoric acid used as an etching solution for the support substrates provided the best adhesion stability for the catalysts that demonstrated the highest photocatalytic efficiency for congener 138. Xenon and ultraviolet lamps were used to compare the irradiation effect on photocatalysis. The shortest half-lives of congener 138 were 7.4 and 12.2 h using xenon and UV reactors, respectively. Lower chlorinated biphenyls (lower congener numbers) were identified through the continuous dechlorination of congener 138. PCB congeners 99, 87, 66, 49, 28, 17, 9, and 7 were detected as a result of dechlorination from higher chlorinated congeners to lower chlorinated congeners along with the extension of exposure times. The concentrations of chloride ion were increased with increasing exposure time through dechlorination, while the concentrations of organic chlorine of congener 138 were decreased. Meta-dechlorination was the most commonly found mechanism for the photocatalysis of PCB 138. The activation energy of the photocatalysis of congener 138 was 70.8 kJ mol(-1). PMID:16494999

  11. Biosensors to measure inositol 1,4,5-trisphosphate concentration in living cells with spatiotemporal resolution.

    PubMed

    Remus, Timothy P; Zima, Aleksey V; Bossuyt, Julie; Bare, Dan J; Martin, Jody L; Blatter, Lothar A; Bers, Donald M; Mignery, Gregory A

    2006-01-01

    Phosphoinositides participate in many signaling cascades via phospholipase C stimulation, which hydrolyzes phosphatidylinositol 4,5-bisphosphate, producing second messengers diacylglycerol and inositol 1,4,5-trisphosphate (InsP3). Destructive chemical approaches required to measure [InsP3] limit spatiotemporal understanding of subcellular InsP3 signaling. We constructed novel fluorescence resonance energy transfer-based InsP3 biosensors called FIRE (fluorescent InsP3-responsive element) by fusing plasmids encoding the InsP3-binding domain of InsP3 receptors (types 1-3) between cyan fluorescent protein and yellow fluorescent protein sequences. FIRE was expressed and characterized in COS-1 cells, cultured neonatal cardiac myocytes, and incorporated into an adenoviral vector for expression in adult cardiac ventricular myocytes. FIRE-1 exhibits an approximately 11% increase in the fluorescence ratio (F530/F480) at saturating [InsP3] (apparent K(d) = 31.3 +/- 6.7 nm InsP3). In COS-1 cells, neonatal rat cardiac myocytes and adult cat ventricular myocytes FIRE-1 exhibited comparable dynamic range and a 10% increase in donor (cyan fluorescent protein) fluorescence upon bleach of yellow fluorescent protein, indicative of fluorescence resonance energy transfer. In FIRE-1 expressing ventricular myocytes endothelin-1, phenylephrine, and angiotensin II all produced rapid and spatially resolved increases in [InsP3] using confocal microscopy (with free [InsP3] rising to approximately 30 nm). Local entry of intracellular InsP3 via membrane rupture by a patch pipette (containing InsP3)in myocytes expressing FIRE-1 allowed detailed spatiotemporal monitoring of intracellular InsP3 diffusion. Both endothelin-1-induced and direct InsP3 application (via pipette rupture) revealed that InsP3 diffusion into the nucleus occurs with a delay and blunted rise of [InsP3] versus cytosolic [InsP3]. These new biosensors allow studying InsP3 dynamics at high temporal and spatial resolution that

  12. Malaria situation in the Greater Mekong Subregion.

    PubMed

    Hewitt, Sean; Delacollette, Charles; Chavez, Irwin

    2013-01-01

    The epidemiology of malaria in the Greater Mekong Subregion is complex and rapidly evolving. Malaria control and elimination efforts face a daunting array of challenges including multidrug-resistant parasites. This review presents secondary data collected by the national malaria control programs in the six countries between 1998 and 2010 and examines trends over the last decade. This data has a number of limitations: it is derived exclusively from public sector health facilities; falciparum-specific and then pan-specific rapid diagnostic tests were introduced during the period under review; and, recently there has been a massive increase in case detection capability as a result of increased funding. It therefore requires cautious interpretation. A series of maps are presented showing trends in incidence, mortality and proportion of cases caused by Plasmodium falciparum over the last decade. A brief overview of institutional and implementation arrangements, historical background, demographics and key issues affecting malaria epidemiology is provided for each country. National malaria statistics for 2010 are presented and their robustness discussed in terms of the public sector's share of cases and other influencing factors such as inter-country variations in risk stratification, changes in diagnostic approach and immigration. Targets are presented for malaria control and where appropriate for elimination. Each country's artemisinin resistance status is described. The epidemiological trends presented reflect the improvement in the malaria situation, however the true malaria burden is as yet unknown. There is a need for continuing strengthening and updating of surveillance and response systems. PMID:24159830

  13. Early tectonic history of the Greater Antilles

    SciTech Connect

    Lewis, J.F.; Draper, G.; Mattson, P.

    1985-01-01

    The islands of the Greater Antilles exhibit differing pre-Oligocene tectonic styles and histories, but all display the results of convergent plate activity from the Early Cretaceous to the Middle Eocene. Western and central Cuba consist of autochthonous, Jurassic and older continental crust, which was overthrust by Cretaceous ophiolites in the Early to Middle Eocene. In contrast, eastern Cuba seems to be similar to Northern Hispaniola, and both areas consist of complexes of upper Cretaceous to Eocene magmatic-arc rocks, and trench generated ophiolites and blueschists produced by SW directed subduction. The oldest rocks in central Hispaniola are exposed in NW trending linear fault-bounded belts. Unusual high-Mg greenschists and amphibolites, quartz-feldspathic greenschists, together with N-type MORB basalts and keratophyric volcanics, are juxtaposed against a medial serpentinite belt. Central and eastern Puerto Rico consist of Lower to Upper Cretaceous volcanic rocks intruded by upper Cretaceous to Eocene plutons. Similar Cretaceous volcanics occur in SW Puerto Rico, but they are overthrust by Upper Jurassic cherts, spilites and amphibolites. Jamaica lies along the Nicaraguan Rise to the SW of the other islands and consists of Barremian to Maastrichtian volcanics and volcanogenic sediments intruded by upper Cretaceous calc-alkalic plutons. Blueschists and related rocks in eastern Jamaica, and geochemical zonation in the igneous rocks suggest that the subduction was to the NW. Change in tectonic movements from convergence to left lateral shear took place during the Late Eocene/Early Oligocene.

  14. Greater Green River Basin Production Improvement Project

    SciTech Connect

    DeJarnett, B.B.; Lim, F.H.; Calogero, D.

    1997-10-01

    The Greater Green River Basin (GGRB) of Wyoming has produced abundant oil and gas out of multiple reservoirs for over 60 years, and large quantities of gas remain untapped in tight gas sandstone reservoirs. Even though GGRB production has been established in formations from the Paleozoic to the Tertiary, recent activity has focused on several Cretaceous reservoirs. Two of these formations, the Ahnond and the Frontier Formations, have been classified as tight sands and are prolific producers in the GGRB. The formations typically naturally fractured and have been exploited using conventional well technology. In most cases, hydraulic fracture treatments must be performed when completing these wells to to increase gas production rates to economic levels. The objectives of the GGRB production improvement project were to apply the concept of horizontal and directional drilling to the Second Frontier Formation on the western flank of the Rock Springs Uplift and to compare production improvements by drilling, completing, and testing vertical, horizontal and directionally-drilled wellbores at a common site.

  15. Effect on fast neutron irradiation to 4 dpa at 400{degrees}C on the properties of V-(4-5)Cr-(4-5)Ti alloys

    SciTech Connect

    Zinkle, S.J.; Alexander, D.J.; Robertson, J.P.

    1997-04-01

    Tensile, Charpy impact and electrical resistivity measurements have been performed at ORNL on V-4Cr-4Ti and V-5Cr-5Ti specimens that were prepared at ANL and irradiated in the lithium-bonded X530 experiment in the EBR-II fast reactor. All of the specimens were irradiated to a damage level of about 4 dpa at a temperature of {approximately}400{degrees}C. A significant amount of radiation hardening was evident in both the tensile and Charpy impact tests. The irradiated V-4Cr-4Ti yield strength measured at {approximately}390{degrees}C was >800 MPa, which is more than three times as high as the unirradiated value. The uniform elongations of the irradiated tensile specimens were typically {approximately}1%, with corresponding total elongations of 4-6%. The ductile to brittle transition temperature of the irradiated specimens was less than the unirradiated resistivity, which suggests that hardening associated with interstitial solute pickup was minimal.

  16. Dietary breadth of grizzly bears in the Greater Yellowstone Ecosystem

    USGS Publications Warehouse

    Gunther, Kerry A.; Shoemaker, Rebecca; Frey, Kevin L.; Haroldson, Mark A.; Cain, Steven L; van Manen, Frank T.; Fortin, Jennifer K.

    2014-01-01

    Grizzly bears (Ursus arctos) in the Greater Yellowstone Ecosystem (GYE) are opportunistic omnivores that eat a great diversity of plant and animal species. Changes in climate may affect regional vegetation, hydrology, insects, and fire regimes, likely influencing the abundance, range, and elevational distribution of the plants and animals consumed by GYE grizzly bears. Determining the dietary breadth of grizzly bears is important to document future changes in food resources and how those changes may affect the nutritional ecology of grizzlies. However, no synthesis exists of all foods consumed by grizzly bears in the GYE. We conducted a review of available literature and compiled a list of species consumed by grizzly bears in the GYE. We documented >266 species within 200 genera from 4 kingdoms, including 175 plant, 37 invertebrate, 34 mammal, 7 fungi, 7 bird, 4 fish, 1 amphibian, and 1 algae species as well as 1 soil type consumed by grizzly bears. The average energy values of the ungulates (6.8 kcal/g), trout (Oncorhynchus spp., 6.1 kcal/g), and small mammals (4.5 kcal/g) eaten by grizzlies were higher than those of the plants (3.0 kcal/g) and invertebrates (2.7 kcal/g) they consumed. The most frequently detected diet items were graminoids, ants (Formicidae), whitebark pine seeds (Pinus albicaulis), clover (Trifolium spp.), and dandelion (Taraxacum spp.). The most consistently used foods on a temporal basis were graminoids, ants, whitebark pine seeds, clover, elk (Cervus elaphus), thistle (Cirsium spp.), and horsetail (Equisetum spp.). Historically, garbage was a significant diet item for grizzlies until refuse dumps were closed. Use of forbs increased after garbage was no longer readily available. The list of foods we compiled will help managers of grizzly bears and their habitat document future changes in grizzly bear food habits and how bears respond to changing food resources.

  17. Regulation of Ins(3,4,5,6)P(4) signaling by a reversible kinase/phosphatase.

    PubMed

    Ho, Melisa W Y; Yang, Xiaonian; Carew, Mark A; Zhang, Tong; Hua, Len; Kwon, Yong-Uk; Chung, Sung-Kee; Adelt, Stephan; Vogel, Günter; Riley, Andrew M; Potter, Barry V L; Shears, Stephen B

    2002-03-19

    Regulation of Cl(-) channel conductance by Ins(3,4,5,6)P(4) provides receptor-dependent control over salt and fluid secretion, cell volume homeostasis, and electrical excitability of neurones and smooth muscle. Ignorance of how Ins(3,4,5,6)P(4) is synthesized has long hindered our understanding of this signaling pathway. We now show Ins(3,4,5,6)P(4) synthesis by Ins(1,3,4,5,6)P(5) 1-phosphatase activity by an enzyme previously characterized as an Ins(3,4,5,6)P(4) 1-kinase. Rationalization of these phenomena with a ligand binding model unveils Ins(1,3,4)P(3) as not simply an alternative kinase substrate, but also an activator of Ins(1,3,4,5,6)P(5) 1-phosphatase. Stable overexpression of the enzyme in epithelial monolayers verifies its physiological role in elevating Ins(3,4,5,6)P(4) levels and inhibiting secretion. It is exceptional for a single enzyme to catalyze two opposing signaling reactions (1-kinase/1-phosphatase) under physiological conditions. Reciprocal coordination of these opposing reactions offers an alternative to general doctrine that intracellular signals are regulated by integrating multiple, distinct phosphatases and kinases. PMID:11909533

  18. Removal of 2,4,5-trichlorophenol by bacterial isolates from the secondary sludge of pulp and paper mill.

    PubMed

    Karn, Santosh Kr; Reddy, M Sudhakara

    2013-09-01

    2,4,5-trichlorophenol (2,4,5-TCP) mineralizing bacteria were isolated from the secondary sludge of pulp and paper industry. These isolates used 2,4,5-TCP as a source of carbon and energy and were capable of degrading this compound, as indicated by stoichimetric release of chloride and biomass formation. Based on 16S rRNA sequence analysis, these bacteria were identified as Kocuria sp. (CL2), Bacillus pumillus (CL5), Pseudomonas stutzeri (CL7). HPLC analysis revealed that these isolates were able to degrade 2,4,5-TCP at higher concentrations (600 mg/l or 3.0 mM). A consortia of these isolates completely removed 2,4,5-TCP from the sludge obtained from pulp and paper mill within 2 weeks when supplemented at a rate of 100 mg l(-1) . Bacterial consortium also significantly reduced absorbable organic halogen (AOX) and extractable organic halogen (EOX) by 61% and 63%, respectively from the sludge. These isolates have high potential to remove 2,4,5-TCP and may be used for remediation of pulp paper mill waste containing 2,4,5-TCP. PMID:22961799

  19. Iraq challenges sanctions, offers 4.5 million b/d developable capacity

    SciTech Connect

    Stauffer, T.R.

    1995-04-10

    The prospective oil deals of the century were unveiled last month in Baghdad at the unlikely venue of the first international oil conference in Iraq in decades. In a dramatic twist Iraq detailed 33 oil fields that are now open for joint development with foreign partners. The productive capacity of the listed fields totals some 4.5 million b/d, and the underlying proved reserves exceed 50 billion bbl--equal to more than US and Canadian reserves combined. Reversing its prior compulsive secretiveness concerning oil affairs, the government cleared at the highest level the proposal to publicize the available resources and to offer corroborative detail. ``Four and a half million b/d is an awful lot of oil,`` noted one foreign oilman who was loath to be quoted because his company feared possible reprisals in the US. The economic bait was both clear and enticing. Iraq chose the public forum to signal to the world the gains that could accrue to the first countries that break with the US over continuing the sanctions. The paper discusses the political impacts, the substantial offerings, exploitation costs, and bypassing sanctions.

  20. Geological Mapping Uses Landsat 4-5TM Satellite Data in Manlai Soum of Omnogovi Aimag

    NASA Astrophysics Data System (ADS)

    Norovsuren, B.

    2014-12-01

    Author: Bayanmonkh N1, Undram.G1, Tsolmon.R2, Ariunzul.Ya1, Bayartungalag B31 Environmental Research Information and Study Center 2NUM-ITC-UNESCO Space Science and Remote Sensing International Laboratory, National University of Mongolia 3Geology and Hydrology School, Korea University KEY WORDS: geology, mineral resources, fracture, structure, lithologyABSTRACTGeologic map is the most important map for mining when it does exploration job. In Mongolia geological map completed by Russian geologists which is done by earlier technology. Those maps doesn't satisfy for present requirements. Thus we want to study improve geological map which includes fracture, structural map and lithology use Landsat TM4-5 satellite data. If we can produce a geological map from satellite data with more specification then geologist can explain or read mineralogy very easily. We searched all methodology and researches of every single element of geological mapping. Then we used 3 different remote sensing methodologies to produce structural and lithology and fracture map based on geographic information system's softwares. There can be found a visible lithology border improvement and understandable structural map and we found fracture of the Russian geological map has a lot of distortion. The result of research geologist can read mineralogy elements very easy and discovered 3 unfound important elements from satellite image.

  1. Formation of carcinogenic 4(5)-methylimidazole in caramel model systems: a role of sulphite.

    PubMed

    Lee, Kwang-Geun; Jang, Haewon; Shibamoto, Takayuki

    2013-02-15

    Aqueous caramel model systems consisted the D-glucose/NH(3)/sulphite were heated at 100°C for 2 h and amounts of carcinogenic 4(5)-methylimidazole (4-MI) formed were determined. The amount formed ranged from 7.0 to 155.0 ppm. A system with 0.1 M sulphite yielded the greatest amount of 4-MI, which was 54% more than that yielded from a system without sulphite. When the amount of sulphite increased over 0.1 M, the amount of 4-MI reduced. The greatest reduction was achieved with 0.2 M sulphite by 68% compared to 0 M sulphite, suggesting that sulphite plays an important role in the formation of carcinogenic 4-MI in caramel colour. Also, a system with 0.1 M sulphite yielded the most intense caramel colour but the other levels of sulphite did not change the colour intensity significantly. Sulphite contributed slightly to the level of flavour chemicals evaluated using pyrazine formation. The results suggest that sulphite addition at appropriate amount reduces 4-MI formation in caramel colour without sacrificing flavour and colour formation. PMID:23194510

  2. A map of dust reddening to 4.5 kpc from Pan-STARRS1

    SciTech Connect

    Schlafly, E. F.; Rix, H.-W.; Martin, N. F.; Green, G.; Finkbeiner, D. P.; Jurić, M.; Burgett, W. S.; Chambers, K. C.; Hodapp, K. W.; Kaiser, N.; Kudritzki, R.-P.; Magnier, E. A.; Morgan, J. S.; Tonry, J. L.; Wainscoat, R. J.; Waters, C.; Draper, P. W.; Metcalfe, N.; Price, P. A.; Stubbs, C. W.

    2014-07-01

    We present a map of the dust reddening to 4.5 kpc derived from Pan-STARRS1 stellar photometry. The map covers almost the entire sky north of declination –30° at a resolution of 7'-14', and is based on the estimated distances and reddenings to more than 500 million stars. The technique is designed to map dust in the Galactic plane, where many other techniques are stymied by the presence of multiple dust clouds at different distances along each line of sight. This reddening-based dust map agrees closely with the Schlegel et al. (SFD) far-infrared emission-based dust map away from the Galactic plane, and the most prominent differences between the two maps stem from known limitations of SFD in the plane. We also compare the map with Planck, finding likewise good agreement in general at high latitudes. The use of optical data from Pan-STARRS1 yields reddening uncertainty as low as 25 mmag E(B – V).

  3. Acoustic Receptivity of Mach 4.5 Boundary Layer with Leading- Edge Bluntness

    NASA Technical Reports Server (NTRS)

    Malik, Mujeeb R.; Balakumar, Ponnampalam

    2007-01-01

    Boundary layer receptivity to two-dimensional slow and fast acoustic waves is investigated by solving Navier-Stokes equations for Mach 4.5 flow over a flat plate with a finite-thickness leading edge. Higher order spatial and temporal schemes are employed to obtain the solution whereby the flat-plate leading edge region is resolved by providing a sufficiently refined grid. The results show that the instability waves are generated in the leading edge region and that the boundary-layer is much more receptive to slow acoustic waves (by almost a factor of 20) as compared to the fast waves. Hence, this leading-edge receptivity mechanism is expected to be more relevant in the transition process for high Mach number flows where second mode instability is dominant. Computations are performed to investigate the effect of leading-edge thickness and it is found that bluntness tends to stabilize the boundary layer. Furthermore, the relative significance of fast acoustic waves is enhanced in the presence of bluntness. The effect of acoustic wave incidence angle is also studied and it is found that the receptivity of the boundary layer on the windward side (with respect to the acoustic forcing) decreases by more than a factor of 4 when the incidence angle is increased from 0 to 45 deg. However, the receptivity coefficient for the leeward side is found to vary relatively weakly with the incidence angle.

  4. Phosphatidylinositol-4,5-Bisphosphate Enhances Anionic Lipid Demixing by the C2 Domain of PKCα

    PubMed Central

    Egea-Jiménez, Antonio L.; Fernández-Martínez, Ana M.; Pérez-Lara, Ángel; de Godos, Ana; Corbalán-García, Senena; Gómez-Fernández, Juan C.

    2014-01-01

    The C2 domain of PKCα (C2α) induces fluorescence self-quenching of NBD-PS in the presence of Ca2+, which is interpreted as the demixing of phosphatidylserine from a mixture of this phospholipid with phosphatidylcholine. Self-quenching of NBD-PS was considerably increased when phosphatidylinositol-4,5-bisphosphate (PIP2) was present in the membrane. When PIP2 was the labeled phospholipid, in the form of TopFluor-PIP2, fluorescence self-quenching induced by the C2 domain was also observed, but this was dependent on the presence of phosphatidylserine. An independent indication of the phospholipid demixing effect given by the C2α domain was obtained by using 2H-NMR, since a shift of the transition temperature of deuterated phosphatidylcholine was observed as a consequence of the addition of the C2α domain, but only in the presence of PIP2. The demixing induced by the C2α domain may have a physiological significance since it means that the binding of PKCα to membranes is accompanied by the formation of domains enriched in activating lipids, like phosphatidylserine and PIP2. The formation of these domains may enhance the activation of the enzyme when it binds to membranes containing phosphatidylserine and PIP2. PMID:24763383

  5. Novel Phosphotidylinositol 4,5-Bisphosphate Binding Sites on Focal Adhesion Kinase.

    PubMed

    Feng, Jun; Mertz, Blake

    2015-01-01

    Focal adhesion kinase (FAK) is a protein tyrosine kinase that is ubiquitously expressed, recruited to focal adhesions, and engages in a variety of cellular signaling pathways. Diverse cellular responses, such as cell migration, proliferation, and survival, are regulated by FAK. Prior to activation, FAK adopts an autoinhibited conformation in which the FERM domain binds the kinase domain, blocking access to the activation loop and substrate binding site. Activation of FAK occurs through conformational change, and acidic phospholipids such as phosphatidylinositol 4,5-bisphosphate (PIP2) are known to facilitate this process. PIP2 binding alters the autoinhibited conformation of the FERM and kinase domains and subsequently exposes the activation loop to phosphorylation. However, the detailed molecular mechanism of PIP2 binding and its role in FAK activation remain unclear. In this study, we conducted coarse-grained molecular dynamics simulations to investigate the binding of FAK to PIP2. Our simulations identified novel areas of basic residues in the kinase domain of FAK that potentially undergo transient binding to PIP2 through electrostatic attractions. Our investigation provides a molecular picture of PIP2-initiated FAK activation and introduces promising new pathways for future studies of FAK regulation. PMID:26186725

  6. The Ca2+-activated cation channel TRPM4 is regulated by phosphatidylinositol 4,5-biphosphate

    PubMed Central

    Nilius, Bernd; Mahieu, Frank; Prenen, Jean; Janssens, Annelies; Owsianik, Grzegorz; Vennekens, Rudi; Voets, Thomas

    2006-01-01

    Transient receptor potential (TRP) channel, melastatin subfamily (TRPM)4 is a Ca2+-activated monovalent cation channel that depolarizes the plasma membrane and thereby modulates Ca2+ influx through Ca2+-permeable pathways. A typical feature of TRPM4 is its rapid desensitization to intracellular Ca2+ ([Ca2+]i). Here we show that phosphatidylinositol 4,5-biphosphate (PIP2) counteracts desensitization to [Ca2+]i in inside-out patches and rundown of TRPM4 currents in whole-cell patch-clamp experiments. PIP2 shifted the voltage dependence of TRPM4 activation towards negative potentials and increased the channel's Ca2+ sensitivity 100-fold. Conversely, activation of the phospholipase C (PLC)-coupled M1 muscarinic receptor or pharmacological depletion of cellular PIP2 potently inhibited currents through TRPM4. Neutralization of basic residues in a C-terminal pleckstrin homology (PH) domain accelerated TRPM4 current desensitization and strongly attenuated the effect of PIP2, whereas mutations to the C-terminal TRP box and TRP domain had no effect on the PIP2 sensitivity. Our data demonstrate that PIP2 is a strong positive modulator of TRPM4, and implicate the C-terminal PH domain in PIP2 action. PLC-mediated PIP2 breakdown may constitute a physiologically important brake on TRPM4 activity. PMID:16424899

  7. All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

    NASA Astrophysics Data System (ADS)

    Keddie, Neil S.; Slawin, Alexandra M. Z.; Lebl, Tomas; Philp, Douglas; O'Hagan, David

    2015-06-01

    The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C-F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (˜2.77 Å) are longer than the vicinal Fax···Feq­ distances (˜2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.

  8. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels

    PubMed Central

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-01-01

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1–KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4–S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  9. Molecular structure, spectroscopic and DFT computational studies on 4,5-bis(tert-butylsulfanyl)phthalonitrile

    NASA Astrophysics Data System (ADS)

    Tanak, H.

    2015-06-01

    The molecular geometry, vibrational frequencies and gauge including atomic orbital (GIAO) 1H and 13C NMR chemical shift values of 4,5-bis(tert-butylsulfanyl)phthalonitrile in the ground state were calculated using the density functional method (B3LYP) with 6-311++G(d,p) basis set. The calculated results show that the optimized geometry can well reproduce the crystal structure, and the theoretical vibrational frequencies and chemical shift values show good agreement with experimental values. To investigate the NLO properties of the title compound, the electric dipole moment (μ), the polarizability (α) and the first hyperpolarizability (β) were calculated using the density functional B3LYP method with the 6-311++G(d,p) basis set. For the results, the title compound shows nonzero (β) value revealing second order NLO behavior. The molecular electrostatic potential (MEP) at the B3LYP/6-311++G(d,p) basis optimized geometry has also been calculated to predict reactive sites for electrophilic or nucleophilic attack for the title compound.

  10. Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.

    PubMed

    Fan, Maomin; Duesler, Eileen N; Nöth, Heinrich; Paine, Robert T

    2010-03-15

    The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6-pentamethyl-2-aminoborazine have been examined. An amine alane adduct (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH] (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6) have been isolated. Compounds 1, 2, 4-6 have been spectroscopically characterized, and single crystal X-ray diffraction structure determinations have been completed for 1-4 and 6. The molecular chemistry provides insight into the reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon pyrolysis, produces AlN/BN composite ceramic materials. PMID:20158196

  11. 2-Aminoethoxydiphenyl borate, a inositol 1,4,5-triphosphate receptor inhibitor, prevents atrial fibrillation.

    PubMed

    Xiao, Junjie; Liang, Dandan; Zhao, Hong; Liu, Ying; Zhang, Hong; Lu, Xiaowei; Liu, Yi; Li, Jun; Peng, Luying; Chen, Yi-Han

    2010-07-01

    The expression of the inositol 1,4,5-triphosphate receptor (IP3R) is upregulated and the function of IP3R also increases during atrial fibrillation (AF). 2-Aminoethoxydiphenyl borate (2-APB) is a membrane-permeable inhibitor of IP3R. However, the effect of 2-APB on AF is unknown. The aim of the present study is to explore the effects of 2-APB on AF. In vitro rabbit heart models of ischemia-, stretch- and cholinergic agitation-induced AF were developed. Fura-2-acetoxymethyl (Fura-2-AM) and Mg2+-Fura-2-AM were used to monitor alterations of intracellular Ca2+ and ATP, respectively, in HL-1 cells, an atrial muscle cell line, under chemical ischemia or cholinergic agitation. The results showed that inhibition of IP3R significantly reduced the incidence and its probability of being sustained in all three types of AF. IP3R inhibition ameliorated the cytoplasmic Ca2+ overload and energy compromise resulting from chemical ischemia or cholinergic agitation. Thus, IP3R inhibition may be a novel target for AF treatment, and IP3R may be an important molecule in the context of different kinds of AF. PMID:20472714

  12. Structural and Theoretical Investigation of Anhydrous 3,4,5-Triacetoxybenzoic Acid

    PubMed Central

    Carvalho, Paulo S.; Almeida, Leonardo R.; Araújo Neto, João H.; Medina, Ana Carolina Q. D.; Menezes, Antonio C. S.; Sousa, José E. F.; Oliveira, Solemar S.; Camargo, Ademir J.; Napolitano, Hamilton B.

    2016-01-01

    A comprehensive investigation of anhydrous form of 3,4,5-Triacetoxybenzoic acid (TABA) is reported. Single crystal X-ray diffraction, Thermal analysis, Fourier Transform Infrared spectroscopy (FTIR) and DFT calculations were applied for TABA characterization. This anhydrous phase crystallizes in the triclinic P1¯ space group (Z' = 1) and its packing shows a supramolecular motif in a classical R22(4) ring formed by acid-acid groups association. The phase stability is accounted in terms of supramolecular architecture and its thermal behaviour. Conformation search at B3LYP/6-311++G(2d,p) level of theory shows the existence of three stable conformers and the most stable conformation was found experimentally. The reactivity of TABA was investigated using the molecular orbital theory and molecular electrostatic potential. The calculation results were used to simulate the infrared spectrum. There is a good agreement between calculated and experimental IR spectrum, which allowed the assignment of the normal vibrational modes PMID:27355378

  13. Preparations, structures and properties of heterobimetallic complexes based on tetrahydrofuran-2,3,4,5-tetracarboxylate

    NASA Astrophysics Data System (ADS)

    Jia, Tian-Jing; Li, Shu-Mu; Cao, Wei; Li, Li-Cun; Zheng, Xiang-Jun; Yuan, Da-Qiang

    2013-05-01

    Transition heterobimetallic metal-organic frameworks based on tetrahydrofuran-2,3,4,5-tetracarboxylicate (FTA), namely [M(H2O)6][Cu2M(FTA)2(H2O)2]·4H2O [M=Mn (1), Co (2)], and [CuZn(FTA)(H2O)5]·H2O (3) have been synthesized and characterized. Single-crystal X-ray diffraction indicates that complexes 1 and 2 are isomorphic. In 1 and 2, FTA ligand links the metal ions to a 2-D wave-like negative-charged layer with a topology of {4;62}2{4;63;82}2{6}. They possess 1-D channels with [M(H2O)6]2+ and lattice water molecules enclathrated. While in the complex 3, Cu2+ and Zn2+ ions are bridged by FTA to a 2-D neutral layer structure with a {8}2{84;122} topology. Magnetic properties of 1-3 were analyzed in connection with their structures, which show that there exist weak antiferromagnetic interactions between metal ions.

  14. Molecular Mapping of Wheat: Major Genes and Rearrangements in Homoeologous Groups 4, 5, and 7

    PubMed Central

    Nelson, J. C.; Sorrells, M. E.; Van-Deynze, A. E.; Lu, Y. H.; Atkinson, M.; Bernard, M.; Leroy, P.; Faris, J. D.; Anderson, J. A.

    1995-01-01

    A molecular-marker linkage map of hexaploid wheat (Triticum aestivum L. em. Thell) provides a framework for integration with the classical genetic map and a record of the chromosomal rearrangements involved in the evolution of this crop species. We have constructed restriction fragment length polymorphism (RFLP) maps of the A-, B-, and D-genome chromosomes of homoeologous groups 4, 5, and 7 of wheat using 114 F(7) lines from a synthetic X cultivated wheat cross and clones from 10 DNA libraries. Chromosomal breakpoints for known ancestral reciprocal translocations involving these chromosomes and for a known pericentric inversion on chromosome 4A were localized by linkage and aneuploid analysis. Known genes mapped include the major vernalization genes Vrn1 and Vrn3 on chromosome arms 5AL and 5DL, the red-coleoptile gene Rc1 on 7AS, and presumptively the leaf-rust (Puccinia recondita f.sp. tritici) resistance gene Lr34 on 7DS and the kernel-hardness gene Ha on 5DS. RFLP markers previously obtained for powdery-mildew (Blumeria graminis f.sp. tritici) resistance genes Pm2 and Pm1 were localized on chromosome arms 5DS and 7AL. PMID:8647405

  15. Investigations of shot reproducibility for the SMP diode at 4.5 MV.

    SciTech Connect

    Bennett, Nichelle; Crain, Marlon D.; Droemer, Darryl W.; Gignac, Raymond Edward; Lare, Gregory A.; Molina, Isidro; Obregon, Rafael; Smith, Chase C.; Wilkins, Frank Lee; Welch, Dale Robert; Cordova, Steve Ray; Gallegos, M.; Johnston, Mark D.; Kiefer, Mark Linden; Leckbee, Joshua J.; Nielsen, Daniel Scott; Oliver, Bryan Velten; Renk, Timothy Jerome; Romero, Tobias; Webb, Timothy Jay; Ziska, Derek Raymond

    2013-11-01

    In experiments conducted on the RITS-6 accelerator, the SMP diode exhibits sig- ni cant shot-to-shot variability. Speci cally, for identical hardware operated at the same voltage, some shots exhibit a catastrophic drop in diode impedance. A study is underway to identify sources of shot-to-shot variations which correlate with diode impedance collapse. To remove knob emission as a source, only data from a shot series conducted with a 4.5-MV peak voltage are considered. The scope of this report is limited to sources of variability which occur away from the diode, such as power ow emission and trajectory changes, variations in pulsed power, dustbin and transmission line alignment, and di erent knob shapes. We nd no changes in the transmission line hardware, alignment, or hardware preparation methods which correlate with impedance collapse. However, in classifying good versus poor shots, we nd that there is not a continuous spectrum of diode impedance behavior but that the good and poor shots can be grouped into two distinct impedance pro les. This result forms the basis of a follow-on study focusing on the variability resulting from diode physics. 3

  16. Design and Operating Features of the ITER 4.5 K Cryoplant

    SciTech Connect

    Kalinine, V.; Haange, R.; Shatil, N.; Millet, F.; Jager, B.; Briend, P.; Crispel, S.; Dauguet, P.

    2004-06-23

    The main cryogenic users of ITER are the superconducting magnet system and the cryogenic vacuum pumps. The magnet system consists of 18 toroidal field and six poloidal field coils and the central solenoid coils. The cryogenic vacuum pumps contain eight pumps for the vacuum vessel, up to four pumps for the neutral beam injectors and two for the tokamak cryostat.The paper presents the current design status of the ITER cryoplant and its operating features that allow stable and flexible operation for different plasma pulsing scenarios and transient operating modes including cool-down and coil quench. The LHe plant operates in a combined liquefaction / refrigeration mode. Liquefied helium is used for the coil current leads and for cool-down of the cryopumps after their regeneration at 80 K. The operating temperature of the LHe plant can vary in the range of 4.3 K to 4.5 K to satisfy different cooling demands of various plasma scenarios. The LHe plant is designed for a large variation ratio of refrigeration to liquefaction in order to facilitate filling of the coils with a large amount of supercritical helium after a standard cool-down or specific cool-down mode following a fast energy discharge.

  17. Inositol 1,4,5-Trisphosphate Signaling Regulates Mating Behavior in Caenorhabditis elegans MalesD⃞

    PubMed Central

    Gower, Nicholas J. D.; Walker, Denise S.; Baylis, Howard A.

    2005-01-01

    Complex behavior requires the coordinated action of the nervous system and nonneuronal targets. Male mating in Caenorhabditis elegans consists of a series of defined behavioral steps that lead to the physiological outcomes required for successful impregnation. We demonstrate that signaling mediated by inositol 1,4,5-trisphosphate (IP3) is required at several points during mating. Disruption of IP3 receptor (itr-1) function results in dramatic loss of male fertility, due to defects in turning behavior (during vulva location), spicule insertion and sperm transfer. To elucidate the signaling pathways responsible, we knocked down the six C. elegans genes encoding phospholipase C (PLC) family members. egl-8, which encodes PLC-β, functions in spicule insertion and sperm transfer. itr-1 and egl-8 are widely expressed in the male reproductive system. An itr-1 gain-of-function mutation rescues infertility caused by egl-8 RNA interference, indicating that egl-8 and itr-1 function together as central components of the signaling events controlling sperm transfer. PMID:15958491

  18. Synthesis of New Thiazolo[4,5-d]pyrimidines as Corticotropin Releasing Factor Modulators

    PubMed Central

    Kuppast, Bhimanna; Spyridaki, Katerina; Lynch, Christophina; Hu, Yueshan; Liapakis, George; Davies, Gareth E.; Fahmy, Hesham

    2015-01-01

    Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role in integrating the body’s overall response to stress. It appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF is released in response to various triggers such as chronic stress. The role of CRF and its involvement in these neurological disorders suggest that new drugs that can target the CRF function or bind to its receptors may represent a new development of neuropsychiatric medicines to treat various stress-related disorders including depression, anxiety and addictive disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor (CRF) receptor modulators and the prepared compounds carry groups shown to produce optimum binding affinity to CRF receptors. Twenty two compounds were evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors. Selected compounds (5c and 5f) were also evaluated for their effect on expression of genes associated with depression and anxiety disorders such as CRF1, CREB, MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA has been observed with compound 5c. PMID:25059547

  19. Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors.

    PubMed

    Brvar, Matjaž; Perdih, Andrej; Renko, Miha; Anderluh, Gregor; Turk, Dušan; Solmajer, Tom

    2012-07-26

    Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials. Starting from the available structural information about the binding of the natural product inhibitor, clorobiocin, we identified a novel series of 4'-methyl-N(2)-phenyl-[4,5'-bithiazole]-2,2'-diamine inhibitors of gyrase B with a low micromolar inhibitory activity by implementing a two-step structure-based design procedure. This novel class of DNA gyrase inhibitors was extensively investigated by various techniques (differential scanning fluorimetry, surface plasmon resonance, and microscale thermophoresis). The binding mode of the potent inhibitor 18 was revealed by X-ray crystallography, confirming our initial in silico binding model. Furthermore, the high resolution of the complex structure allowed for the placement of the Gly97-Ser108 flexible loop, thus revealing its role in binding of this class of compounds. The crystal structure of the complex protein G24 and inhibitor 18 provides valuable information for further optimization of this novel class of DNA gyrase B inhibitors. PMID:22731783

  20. Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase

    PubMed Central

    Brehm, Maria A.; Schenk, Tobias M. H.; Zhou, Xuefei; Fanick, Werner; Lin, Hongying; Windhorst, Sabine; Nalaskowski, Marcus M.; Kobras, Mario; Shears, Stephen B.; Mayr, Georg W.

    2007-01-01

    InsP6 is an intracellular signal with several proposed functions that is synthesized by IP5K [Ins(1,3,4,5,6)P5 2-kinase]. In the present study, we overexpressed EGFP (enhanced green fluorescent protein)–IP5K fusion proteins in NRK (normal rat kidney), COS7 and H1299 cells. The results indicate that there is spatial microheterogeneity in the intracellular localization of IP5K that could also be confirmed for the endogenous enzyme. This may facilitate changes in InsP6 levels at its sites of action. For example, overexpressed IP5K showed a structured organization within the nucleus. The kinase was preferentially localized in euchromatin and nucleoli, and co-localized with mRNA. In the cytoplasm, the overexpressed IP5K showed locally high concentrations in discrete foci. The latter were attributed to stress granules by using mRNA, PABP [poly(A)-binding protein] and TIAR (TIA-1-related protein) as markers. The incidence of stress granules, in which IP5K remained highly concentrated, was further increased by puromycin treatment. Using FRAP (fluorescence recovery after photobleaching) we established that IP5K was actively transported into the nucleus. By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K. PMID:17705785

  1. Design of a 4.5 MJ/1 MW sectored toroidal superconducting energy storage magnet

    NASA Astrophysics Data System (ADS)

    Bhunia, Uttam; Akhter, Javed; Nandi, Chinmay; Pal, Gautam; Saha, Subimal

    2014-09-01

    A 4.5 MJ/1 MW superconducting magnetic energy storage (SMES) system is being developed at VECC centre, Kolkata. The magnet system consists of the cryostat and coil assembly comprising eight superconducting solenoid coils made of custom-made NbTi based Rutherford-type cable and arranged in toroidal fashion with finite inter-sector gap. Since the strong electromagnetic force distributed to the coil is asymmetric and non-uniform in nature, a precise 3-D finite element analysis (FEA) has been carried out to design a mechanically stable coil and support structure under various operational scenarios. The results reveal that maximum stress developed on coil and its support structure is below allowable stress limit. Extensive transient analysis has also been carried out to evaluate transient loss and assess the feasibility of using helium re-condensation technology with commercially available cryo-refrigerators. Finally, quench protection scenario has also been discussed suitable for this toroidal-type SMES system. The article investigates the design concept of the cryostat and coil assembly.

  2. Performance appraisal of VAS radiometry for GOES-4, -5 and -6

    NASA Technical Reports Server (NTRS)

    Chesters, D.; Robinson, W. D.

    1983-01-01

    The first three VISSR Atmospheric Sounders (VAS) were launched on GOES-4, -5, and -6 in 1980, 1981 and 1983. Postlaunch radiometric performance is assessed for noise, biases, registration and reliability, with special attention to calibration and problems in the data processing chain. The postlaunch performance of the VAS radiometer meets its prelaunch design specifications, particularly those related to image formation and noise reduction. The best instrument is carried on GOES-5, currently operational as GOES-EAST. Single sample noise is lower than expected, especially for the small longwave and large shortwave detectors. Detector to detector offsets are correctable to within the resolution limits of the instrument. Truncation, zero point and droop errors are insignificant. Absolute calibration errors, estimated from HIRS and from radiation transfer calculations, indicate moderate, but stable biases. Relative calibration errors from scanline to scanline are noticeable, but meet sounding requirements for temporarily and spatially averaged sounding fields of view. The VAS instrument is a potentially useful radiometer for mesoscale sounding operations. Image quality is very good. Soundings derived from quality controlled data meet prelaunch requirements when calculated with noise and bias resistant algorithms.

  3. Phosphatidylinositol 4,5-bisphosphate (PIP2) controls magnesium gatekeeper TRPM6 activity

    PubMed Central

    Xie, Jia; Sun, Baonan; Du, Jianyang; Yang, Wenzhong; Chen, Hsiang-Chin; Overton, Jeffrey D.; Runnels, Loren W.; Yue, Lixia

    2011-01-01

    TRPM6 is crucial for human Mg2+ homeostasis as patients carrying TRPM6 mutations develop hypomagnesemia and secondary hypocalcemia (HSH). However, the activation mechanism of TRPM6 has remained unknown. Here we demonstrate that phosphatidylinositol-4,5-bisphophate (PIP2) controls TRPM6 activation and Mg2+ influx. Stimulation of PLC-coupled M1-receptors to deplete PIP2 potently inactivates TRPM6. Translocation of over-expressed 5-phosphatase to cell membrane to specifically hydrolyze PIP2 also completely inhibits TRPM6. Moreover, depolarization-induced-activation of the voltage-sensitive-phosphatase (Ci-VSP) simultaneously depletes PIP2 and inhibits TRPM6. PLC-activation induced PIP2-depletion not only inhibits TRPM6, but also abolishes TRPM6-mediated Mg2+ influx. Furthermore, neutralization of basic residues in the TRP domain leads to nonfunctional or dysfunctional mutants with reduced activity by PIP2, suggesting that they are likely to participate in interactions with PIP2. Our data indicate that PIP2 is required for TRPM6 channel function; hydrolysis of PIP2 by PLC-coupled hormones/agonists may constitute an important pathway for TRPM6 gating, and perhaps Mg2+ homeostasis. PMID:22180838

  4. Reactivity and synthetic applications of 4,5-dicyanopyridazine: an overview.

    PubMed

    Alfini, Renzo; Cecchi, Marco; Giomi, Donatella

    2010-03-01

    Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives. PMID:20336010

  5. Phosphatidylinositol 4,5-bisphosphate alters pharmacological selectivity for epilepsy-causing KCNQ potassium channels.

    PubMed

    Zhou, Pingzheng; Yu, Haibo; Gu, Min; Nan, Fa-jun; Gao, Zhaobing; Li, Min

    2013-05-21

    Pharmacological augmentation of neuronal KCNQ muscarinic (M) currents by drugs such as retigabine (RTG) represents a first-in-class therapeutic to treat certain hyperexcitatory diseases by dampening neuronal firing. Whereas all five potassium channel subtypes (KCNQ1-KCNQ5) are found in the nervous system, KCNQ2 and KCNQ3 are the primary players that mediate M currents. We investigated the plasticity of subtype selectivity by two M current effective drugs, retigabine and zinc pyrithione (ZnPy). Retigabine is more effective on KCNQ3 than KCNQ2, whereas ZnPy is more effective on KCNQ2 with no detectable effect on KCNQ3. In neurons, activation of muscarinic receptor signaling desensitizes effects by retigabine but not ZnPy. Importantly, reduction of phosphatidylinositol 4,5-bisphosphate (PIP2) causes KCNQ3 to become sensitive to ZnPy but lose sensitivity to retigabine. The dynamic shift of pharmacological selectivity caused by PIP2 may be induced orthogonally by voltage-sensitive phosphatase, or conversely, abolished by mutating a PIP2 site within the S4-S5 linker of KCNQ3. Therefore, whereas drug-channel binding is a prerequisite, the drug selectivity on M current is dynamic and may be regulated by receptor signaling pathways via PIP2. PMID:23650395

  6. Phosphatidylinositol 4,5-bisphosphate Directs Spermatid Cell Polarity and Exocyst Localization in Drosophila

    PubMed Central

    Fabian, Lacramioara; Wei, Ho-Chun; Rollins, Janet; Noguchi, Tatsuhiko; Blankenship, J. Todd; Bellamkonda, Kishan; Polevoy, Gordon; Gervais, Louis; Guichet, Antoine; Fuller, Margaret T.

    2010-01-01

    During spermiogenesis, Drosophila melanogaster spermatids coordinate their elongation in interconnected cysts that become highly polarized, with nuclei localizing to one end and sperm tail growth occurring at the other. Remarkably little is known about the signals that drive spermatid polarity and elongation. Here we identify phosphoinositides as critical regulators of these processes. Reduction of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2) by low-level expression of the PIP2 phosphatase SigD or mutation of the PIP2 biosynthetic enzyme Skittles (Sktl) results in dramatic defects in spermatid cysts, which become bipolar and fail to fully elongate. Defects in polarity are evident from the earliest stages of elongation, indicating that phosphoinositides are required for establishment of polarity. Sktl and PIP2 localize to the growing end of the cysts together with the exocyst complex. Strikingly, the exocyst becomes completely delocalized when PIP2 levels are reduced, and overexpression of Sktl restores exocyst localization and spermatid cyst polarity. Moreover, the exocyst is required for polarity, as partial loss of function of the exocyst subunit Sec8 results in bipolar cysts. Our data are consistent with a mechanism in which localized synthesis of PIP2 recruits the exocyst to promote targeted membrane delivery and polarization of the elongating cysts. PMID:20237161

  7. Superplasticity and the development of dislocation structures in an Al-4.5% Mg alloy

    SciTech Connect

    Li, F.; Roberts, W.T.; Bate, P.S.

    1996-01-01

    The mechanical behavior and development of microstructure in tension of an Al-4.5% Mg alloy at temperatures from 450 to 570C and strain rates from 10{sup {minus}6} to 10{sup {minus}2} s{sup {minus}1} has been investigated. High strain rate sensitivities, up to m = 0.7, but relatively small elongations, between 120 and 280%, were observed. A single activation energy for deformation, close to reported values for self diffusion in aluminium, was obtained over the temperature and strain rate range used, and the strain rate and stress could be related using a hyperbolic sine function at constant strain. Tensile specimens were quenched and aged under stress to preserve the dislocation structures for examination by transmission electron microscopy. The dislocation structures observed showed a gradual and systematic change between regimes of power law creep at higher strain rates and diffusional creep at lower strain rates, and in the superplastic regime there was a tendency for small grains to be free of dislocations. Many of the dislocations had Burgers vectors inclined at about 45{degree} to the stress axis, which suggests that they were active directly in response to the applied stress rather than as the result of a relaxation process accommodating grain boundary sliding.

  8. Fe L-shell lines from n (n=4, 5, 6) to 2 transitions

    NASA Astrophysics Data System (ADS)

    Chen, H.; Beiersdorfer, P.; Brown, G.; Behar, E.

    2003-03-01

    Fe L-shell emission lines at wavelengths less than 10 angstroms come from n (n great than 3) to 2 transitions. These lines embed information such as electron density and temperature that is of fundamental importance to understanding the physics of astrophysical objects. Unresolved by previous x-ray observatories, these low wavelength Fe lines are clearly observable by Chandra and XMM x-ray satellites. To meet the needs of using these lines as diagnostics, we have studied the n to 2 transitions (n = 4, 5, 6) Fe L-shell lines using the atomic codes HULLAC and FAC. Using the LLNL electron beam ion trap, we also made laboratory measurements for this wavelength region, following the success of our Fe L-shell emission lines for the 3-2 transitions (Brown et al, APJ supp. 2002). Our measurements and their comparison with code simulations will be reported, together with a discussion of the possible use of these low wavelength lines as diagnostics for astrophysics. This work was performed under the auspices of the U.S. DOE by LLNL under contract No. W-7405-Eng-48 and supported by NASA SARA grants to LLNL, GSFC, and Columbia University.

  9. Performance appraisal of VAS radiometry for GOES-4, -5 and -6

    NASA Astrophysics Data System (ADS)

    Chesters, D.; Robinson, W. D.

    1983-12-01

    The first three VISSR Atmospheric Sounders (VAS) were launched on GOES-4, -5, and -6 in 1980, 1981 and 1983. Postlaunch radiometric performance is assessed for noise, biases, registration and reliability, with special attention to calibration and problems in the data processing chain. The postlaunch performance of the VAS radiometer meets its prelaunch design specifications, particularly those related to image formation and noise reduction. The best instrument is carried on GOES-5, currently operational as GOES-EAST. Single sample noise is lower than expected, especially for the small longwave and large shortwave detectors. Detector to detector offsets are correctable to within the resolution limits of the instrument. Truncation, zero point and droop errors are insignificant. Absolute calibration errors, estimated from HIRS and from radiation transfer calculations, indicate moderate, but stable biases. Relative calibration errors from scanline to scanline are noticeable, but meet sounding requirements for temporarily and spatially averaged sounding fields of view. The VAS instrument is a potentially useful radiometer for mesoscale sounding operations. Image quality is very good. Soundings derived from quality controlled data meet prelaunch requirements when calculated with noise and bias resistant algorithms.

  10. Dual Effect of Phosphatidyl (4,5)-Bisphosphate PIP2 on Shaker K+ Channels*

    PubMed Central

    Abderemane-Ali, Fayal; Es-Salah-Lamoureux, Zeineb; Delemotte, Lucie; Kasimova, Marina A.; Labro, Alain J.; Snyders, Dirk J.; Fedida, David; Tarek, Mounir; Baró, Isabelle; Loussouarn, Gildas

    2012-01-01

    Phosphatidylinositol (4,5)-bisphosphate (PIP2) is a phospholipid of the plasma membrane that has been shown to be a key regulator of several ion channels. Functional studies and more recently structural studies of Kir channels have revealed the major impact of PIP2 on the open state stabilization. A similar effect of PIP2 on the delayed rectifiers Kv7.1 and Kv11.1, two voltage-gated K+ channels, has been suggested, but the molecular mechanism remains elusive and nothing is known on PIP2 effect on other Kv such as those of the Shaker family. By combining giant-patch ionic and gating current recordings in COS-7 cells, and voltage-clamp fluorimetry in Xenopus oocytes, both heterologously expressing the voltage-dependent Shaker channel, we show that PIP2 exerts 1) a gain-of-function effect on the maximal current amplitude, consistent with a stabilization of the open state and 2) a loss-of-function effect by positive-shifting the activation voltage dependence, most likely through a direct effect on the voltage sensor movement, as illustrated by molecular dynamics simulations. PMID:22932893

  11. Synthesis of new thiazolo[4,5-d]pyrimidines as Corticotropin releasing factor modulators.

    PubMed

    Kuppast, Bhimanna; Spyridaki, Katerina; Lynch, Christophina; Hu, Yueshan; Liapakis, George; Davies, Gareth E; Fahmy, Hesham

    2014-01-01

    Corticotropin-releasing factor (CRF) is a neurohormone that plays a crucial role in integrating the body's overall response to stress. It appears necessary and sufficient for the organism to mount functional, physiological and endocrine responses to stressors. CRF is released in response to various triggers such as chronic stress. The role of CRF and its involvement in these neurological disorders suggest that new drugs that can target the CRF function or bind to its receptors may represent a new development of neuropsychiatric medicines to treat various stress-related disorders including depression, anxiety and addictive disorders. Based on pharmacophore of the CRF1 receptor antagonists, a new series of thiazolo[4,5-d] pyrimidines were synthesized as Corticotropin-releasing factor (CRF) receptor modulators and the prepared compounds carry groups shown to produce optimum binding affinity to CRF receptors. Twenty two compounds were evaluated for their CRF1 receptor binding affinity in HEK 293 cell lines and two compounds 5o and 5s showed approximately 25% binding affinity to CRF1 receptors. Selected compounds (5c and 5f) were also evaluated for their effect on expression of genes associated with depression and anxiety disorders such as CRF1, CREB1, MAO-A, SERT, NPY, DatSLC6a3, and DBH and significant upregulation of CRF1 mRNA has been observed with compound 5c. PMID:25059547

  12. Cloning and expression of a cDNA encoding human inositol 1,4,5-trisphosphate 3-kinase C.

    PubMed Central

    Dewaste, V; Pouillon, V; Moreau, C; Shears, S; Takazawa, K; Erneux, C

    2000-01-01

    Inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] 3-kinase catalyses the phosphorylation of Ins(1,4,5)P(3) to Ins(1,3,4,5)P(4). cDNAs encoding two isoenzymes of Ins(1,4,5)P(3) 3-kinase (3-kinases A and B) have been described previously. In the present study, we report the cloning of a full-length 2052 bp cDNA encoding a third human isoenzyme of the Ins(1,4,5)P(3) 3-kinase family, referred to as isoform C. This novel enzyme has a calculated molecular mass of 75. 207 kDa and a K(m) for Ins(1,4,5)P(3) of 6 microM. Northern-blot analysis showed the presence of a transcript of approx. 3.9 kb in various human tissues. Inositol trisphosphate 3-kinase C demonstrates enzymic activity when expressed in DH5alphaF' bacteria or COS-7 cells. Calcium alone decreases the Ins(1,4,5)P(3) 3-kinase activity of the 3-kinase C isoenzyme in transfected COS-7 cells. This inhibitory effect is reversed in the presence of calmodulin. The recombinant bacterial 3-kinase C can be adsorbed on calmodulin-Sepharose in the presence of calcium. The present data show that Ins(1,4,5)P(3) 3-kinase C: (i) shares a conserved catalytic domain of about 275 amino acids with the two other mammalian isoforms, (ii) could be purified on a calmodulin-Sepharose column and (iii) could be distinguished from the A and B isoenzymes by the effects of calcium and of calmodulin. PMID:11085927

  13. Inter- and intrachannel exchange interference in photoinduced Auger decay: The Kr M4,5-N1N23 and Xe N4,5-O1O23 cases

    NASA Astrophysics Data System (ADS)

    Žitnik, M.; Bučar, K.; Mihelič, A.; Lablanquie, P.; Penent, F.; Paladoux, J.; Andrić, L.; Bolognesi, P.; Avaldi, L.

    2013-01-01

    We study interference effects that appear in the cross section due to detection of two indistinguishable electrons in a photoelectron-Auger-electron pair (intrachannel exchange interference), or due to detection of two indistinguishable photoelectron-Auger electron pairs that share the final state but are emitted via two different intermediate states (interchannel exchange interference). For photoinduced Kr M4,5-N1N23 (Xe N4,5-O1O23) Auger decay, the intrachannel exchange interference is “switched on” at 131.3 eV (87.0 eV) and 133.8 eV (91.0 eV) photon impact energy for the M5 (N5) and M4 (N4) holes, respectively. The interchannel exchange interference is expected to appear at 132.6 eV (89.0 eV) when the photoelectron ejected from the M4 (N4) subshell is emitted with the same energy as the Auger electron emitted in the decay of the M5 (N5) hole, and vice versa, the energy of the photoelectron ejected from the M5 (N5) subshell equals the energy of the Auger electron emitted in the decay of the M4 (N5) hole. We use the approach of Vegh and Macek [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.50.4031 50, 4031 (1994)], and Vegh [Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.50.4036 50, 4036 (1994)] to model these phenomena in a unified manner and examine their effects in an angle-resolved and angle-integrated coincidence spectra considering also the postcollision interaction (PCI). The previous and the present angle-resolved experimental results, together with the data obtained by a magnetic bottle time-of-flight spectrometer, indicate that in this particular case the exchange interference effects in the angle-integrated cross sections are considerably weaker than in the angle-resolved (γ,2e) cross sections.

  14. Characteristics of Salmonella enterica Serovar 4,[5],12:i:- as a Monophasic Variant of Serovar Typhimurium

    PubMed Central

    Ido, Noriko; Lee, Ken-ichi; Iwabuchi, Kaori; Izumiya, Hidemasa; Uchida, Ikuo; Kusumoto, Masahiro; Iwata, Taketoshi; Ohnishi, Makoto; Akiba, Masato

    2014-01-01

    Salmonella enterica subspecies enterica serovar 4,[5],12:i:- (S. 4,[5]12:i:-) is believed to be a monophasic variant of S. enterica serovar Typhimurium (S. Typhimurium). This study was conducted to corroborate this hypothesis and to identify the molecular and phenotypic characteristics of the S. 4,[5]12:i:- isolates in Japan. A total of 51 S. 4,[5]12:i:- isolates derived from humans, cattle, swine, chickens, birds, meat (pork), and river water in 15 prefectures in Japan between 2000 and 2010 were analyzed. All the S. 4,[5],12:i:- isolates were identified as S. Typhimurium by two different polymerase chain reactions (PCR) for identification of S. Typhimurium. Of the 51 S. 4,[5],12:i:- isolates, 39 (76.5%) harbored a 94-kb virulence plasmid, which is known to be specific for S. Typhimurium. These data suggest that the S. 4,[5],12:i:- isolates are monophasic variants of S. Typhimurium. The flagellar phase variation is induced by three adjacent genes (fljA, fljB, and hin) in the chromosome. The results of PCR mapping of this region and comparative genomic hybridization analysis suggested that the deletion of the fljAB operon and its flanking region was the major genetic basis of the monophasic phenotype of S. 4,[5],12:i:-. The fljAB operon and hin gene were detectable in eight of the S. 4,[5],12:i:- isolates with common amino acid substitutions of A46T in FljA and R140L in Hin. The introduction of these mutations into S. Typhimurium isolates led to the loss of selectability of isolates expressing the phase 2 H antigen. These data suggested that a point mutation was the genetic basis, at least in part, of the S. 4,[5],12:i:- isolates. The results of phenotypic analysis suggested that the S. 4,[5],12:i:- isolates in Japan consist of multiple distinct clones. This is the first detailed characterization of the S. 4,[5],12:i:- isolates derived from various sources across Japan. PMID:25093666

  15. Changing Water Environment in the Greater Jakarta Basins

    NASA Astrophysics Data System (ADS)

    Pawitan, H.; Delinom, R.; Lubis, R. F.

    2014-12-01

    Recent rapid economic development in the greater Jakarta areas has caused not only increased water resources demands but also affects the water environment due to population increase and land use changes, that further causes land degradation, and changes in hydrologic regimes and environmental qualities. In the present study, the water environmental capacities as indicated by the changing landscapes in the greater Jakarta basins were investigated to understand the role of land use management and its impact on water resources, ecosystem and environmental services. The Ciliwung river basin where rapid population increases and progresses of the land use/cover changes occurring was selected as a representative basin, and 41 water samplings were taken at different time of Jan. 08, Apr. 08, Jul. 08, and Oct. 08 during 2009 to understand the effect of rainfall variation on water quality, and clarify the characteristics of hydrological cycle. Landuse changes of the upper basins as can be seen for the upper basin indicated the expansion of settlements during 1990 to 2004 from 4.1% to 17.6% or in acreage increased almost five times, not only converting forested area, but mostly taking place from paddy fields that contributed about 50% of the additional land for new settlements. Urbanization expanding around the greater Jakarta basins, is closely related to the increased fluctuations of river discharges in recent years, with recurrence floods quickly after heavy rainfall events. Furthermore, the study results indicated that water quality of Ciliwung river, especially the loading concentrations of nitric acid closely reflects the population densities of the watershed. These results suggest that the land use/cover changes of the greater Jakarta basins affect largely the change of water environment of the areas and resulting a deteriorated factor for water resources, ecosystems and environmental services in both of quantity and quality

  16. 3,3,6,6,9,9-Hexaethyl-1,2,4,5,7,8-hexaoxacyclononane at 296 K.

    PubMed

    Cerna, Jorge; Bernès, Sylvain; Cañizo, Adriana; Eyler, Nora

    2009-11-01

    The title molecule (diethyl ketone triperoxide, DEKTP), C(15)H(30)O(6), is a cyclic triperoxide closely related to triacetone triperoxide (TATP), one of the most unstable explosives known. However, the stability of DEKTP is ca 20-50 times greater than that of TATP. DEKTP crystallizes with two molecules in the asymmetric unit, with virtually identical geometry. The cyclononane core is stabilized in a twisted boat-chair conformation (approximate D(3) symmetry), very close to that previously described for TATP. The explanation for the safe thermal behaviour of DEKTP compared with TATP should thus not be sought in the molecular dimensions, but rather in the thermal decomposition kinetics. PMID:19893236

  17. Interconversion of inositol (1,4,5)-trisphosphate to inositol (1,3,4,5)-tetrakisphosphate and (1,3,4)-trisphosphate in permeabilized adrenal glomerulosa cells is calcium-sensitive and ATP-dependent

    SciTech Connect

    Rossier, M.F.; Dentand, I.A.; Lew, P.D.; Capponi, A.M.; Vallotton, M.B.

    1986-08-29

    The metabolism of (/sub 3/H)inositol (1,4,5)-trisphosphate was followed in permeabilized bovine adrenal glomerulosa cells. At low Ca++ concentration (pCa = 7.2), more than 90% of (/sub 3/H)inositol (1,4,5)-trisphosphate had disappeared within 2 min, while two other metabolites, (/sub 3/H)inositol (1,3,4)-trisphosphate and (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate appeared progressively. At higher Ca++ concentrations (pCa = 5.7 and 4.8), the formation of these two metabolites was markedly increased, but completely abolished if the medium was ATP-depleted. The peak levels for the generation of (/sub 3/H)inositol (1,3,4,5)-tetrakisphosphate (1 min) preceded those of (3H)inositol (1,3,4)-trisphosphate and were closely correlated. These results suggest that, in adrenal glomerulosa cells, the isomer inositol (1,3,4)-trisphosphate is generated from inositol (1,4,5)-trisphosphate via a calcium-sensitive and ATP-dependent phosphorylation/dephosphorylation pathway involving the formation of inositol (1,3,4,5)-tetrakisphosphate.

  18. Role of Phosphatidylinositol 4,5-Bisphosphate in Regulating EHD2 Plasma Membrane Localization

    PubMed Central

    Simone, Laura C.; Caplan, Steve; Naslavsky, Naava

    2013-01-01

    The four mammalian C-terminal Eps15 homology domain-containing proteins (EHD1-EHD4) play pivotal roles in endocytic membrane trafficking. While EHD1, EHD3 and EHD4 associate with intracellular tubular/vesicular membranes, EHD2 localizes to the inner leaflet of the plasma membrane. Currently, little is known about the regulation of EHD2. Thus, we sought to define the factors responsible for EHD2’s association with the plasma membrane. The subcellular localization of endogenous EHD2 was examined in HeLa cells using confocal microscopy. Although EHD partner proteins typically mediate EHD membrane recruitment, EHD2 was targeted to the plasma membrane independent of two well-characterized binding proteins, syndapin2 and EHBP1. Additionally, the EH domain of EHD2, which facilitates canonical EHD protein interactions, was not required to direct overexpressed EHD2 to the cell surface. On the other hand, several lines of evidence indicate that the plasma membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) plays a crucial role in regulating EHD2 subcellular localization. Pharmacologic perturbation of PIP2 metabolism altered PIP2 plasma membrane distribution (as assessed by confocal microscopy), and caused EHD2 to redistribute away from the plasma membrane. Furthermore, overexpressed EHD2 localized to PIP2-enriched vacuoles generated by active Arf6. Finally, we show that although cytochalasin D caused actin microfilaments to collapse, EHD2 was nevertheless maintained at the plasma membrane. Intriguingly, cytochalasin D induced relocalization of both PIP2 and EHD2 to actin aggregates, supporting a role of PIP2 in controlling EHD2 subcellular localization. Altogether, these studies emphasize the significance of membrane lipid composition for EHD2 subcellular distribution and offer new insights into the regulation of this important endocytic protein. PMID:24040268

  19. Genetic polymorphisms in metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine.

    PubMed

    Kim, Dojung; Lee, Young-Joo; Ryu, Heui-Young; Lee, Jin-Hee; Kim, Hyun-Kyung; Kim, Eunhee; Moon, Jae-Dong; Chang, Dong Deuk; Yoon, Hae-Seong

    2013-01-01

    Heterocyclic amines (HCAs) are naturally produced during common cooking processes for meats and fish. HCAs are metabolized by various enzymes, including cytochromes P450, N-acetyl transferases, and sulfotransferases, and their bioactivated metabolites are considered to bind to DNA or protein to show carcinogenic effects. More than 20 HCAs have been identified, of which 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is classified as 'reasonably anticipated to be a human carcinogen' to develop cancers in breast, colon and prostate. The purpose of this study was to evaluate human exposure levels of PhIP and to understand the role of genetic polymorphisms of enzymes on PhIP metabolism. Urine samples were collected from subjects (n = 100) before 3-day meat-restricted diets. Subjects consumed grilled chicken, and their blood and urine were collected before and after the administration of the chickens to investigate genetic polymorphisms and PhIP levels. The mean PhIP levels were 4.22 ± 0.12, 0.61 ± 0.19 and 22.64 ± 1.00 pg ml(-1) in urine under normal conditions and before and after chicken administration, respectively. Among 21 Single-nucleotide polymorphisms (SNP) of CYP1A1, CYP1A2, NATs and UGTs investigated in this study, genotypic groups of CYP1A1/T6235C (MSP I) and CYP1A2/-2467delT showed significant differences in PhIP excretion (P < 0.05). These results suggest that genetic polymorphisms might affect PhIP metabolism, which could improve understanding of populations subject to PhIP-derived health risk. PMID:22131055

  20. Inositol 1,4,5-tripshosphate receptor, calcium signaling and polyglutamine expansion disorders

    PubMed Central

    Bezprozvanny, Ilya

    2016-01-01

    Huntington’s disease (HD), spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) are autosomal-dominant neurodegenerative disorders. HD is caused by polyglutamine (polyQ) expansion (exp) in the amino-terminal region of a protein huntingtin (Htt) and primarily affects medium spiny striatal neurons (MSN). SCA2 is caused by a polyQ expansion in the amino-terminal region of a cytosolic protein ataxin-2 (Atxn2) and primarily affects cerebellar Purkinje neurons. SCA3 is caused by a polyQ expansion in the carboxy-terminal portion of a cytosolic protein ataxin-3 (Atxn3) and primarily affects dentate and pontine nuclei and substantia nigra. The reasons for neuronal dysfunction and death in HD, SCA2 and SCA3 remain poorly understood and no cure is available for the patients. My laboratory discovered that mutant Huntingtin, ataxin-2 and ataxin-3 proteins specifically binds to the carboxy-terminal region of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), an intracellular Ca2+ release channel. Moreover, we found that association with IP3R1 causes sensitization of IP3R1 to activation by IP3 in planar lipid bilayers and in neuronal cells. These results suggested that deranged neuronal Ca2+ signaling might play an important role in pathogenesis of HD, SCA2 and SCA3. In support of this idea, we demonstrated a connection between abnormal Ca2+ signaling and neuronal cell death in experimnts with HD, SCA2 and SCA3 transgenic mouse models. Based on these results I propose that IP3R and other Ca2+ signaling proteins should be considered as potential therapeutic targets for treatment of HD, SCA2 and SCA3. PMID:22353486

  1. Proteolytic fragmentation of inositol 1,4,5-trisphosphate receptors: a novel mechanism regulating channel activity?

    PubMed

    Wang, Liwei; Alzayady, Kamil J; Yule, David I

    2016-06-01

    Inositol 1,4,5-trisphosphate receptors (IP3 Rs) are a family of ubiquitously expressed intracellular Ca(2+) release channels. Regulation of channel activity by Ca(2+) , nucleotides, phosphorylation, protein binding partners and other cellular factors is thought to play a major role in defining the specific spatiotemporal characteristics of intracellular Ca(2+) signals. These properties are, in turn, believed pivotal for the selective and specific physiological activation of Ca(2+) -dependent effectors. IP3 Rs are also substrates for the intracellular cysteine proteases, calpain and caspase. Cleavage of the IP3 R has been proposed to play a role in apoptotic cell death by uncoupling regions important for IP3 binding from the channel domain, leaving an unregulated leaky Ca(2+) pore. Contrary to this hypothesis, we demonstrate following proteolysis that N- and C-termini of IP3 R1 remain associated, presumably through non-covalent interactions. Further, we show that complementary fragments of IP3 R1 assemble into tetrameric structures and retain their ability to be regulated robustly by IP3 . While peptide continuity is clearly not necessary for IP3 -gating of the channel, we propose that cleavage of the IP3 R peptide chain may alter other important regulatory events to modulate channel activity. In this scenario, stimulation of the cleaved IP3 R may support distinct spatiotemporal Ca(2+) signals and activation of specific effectors. Notably, in many adaptive physiological events, the non-apoptotic activities of caspase and calpain are demonstrated to be important, but the substrates of the proteases are poorly defined. We speculate that proteolytic fragmentation may represent a novel form of IP3 R regulation, which plays a role in varied adaptive physiological processes. PMID:26486785

  2. Preparations, structures and properties of heterobimetallic complexes based on tetrahydrofuran-2,3,4,5-tetracarboxylate

    SciTech Connect

    Jia, Tian-Jing; Li, Shu-Mu; Cao, Wei; Li, Li-Cun; Zheng, Xiang-Jun; Yuan, Da-Qiang

    2013-05-01

    Transition heterobimetallic metal-organic frameworks based on tetrahydrofuran-2,3,4,5-tetracarboxylicate (FTA), namely [M(H₂O)₆][Cu₂M(FTA)₂(H₂O)₂]·4H₂O [M=Mn (1), Co (2)], and [CuZn(FTA)(H₂O)₅]·H₂O (3) have been synthesized and characterized. Single-crystal X-ray diffraction indicates that complexes 1 and 2 are isomorphic. In 1 and 2, FTA ligand links the metal ions to a 2-D wave-like negative-charged layer with a topology of (4;6²)₂(4;6³;8²)₂(6). They possess 1-D channels with [M(H₂O)₆]²⁺ and lattice water molecules enclathrated. While in the complex 3, Cu²⁺ and Zn²⁺ ions are bridged by FTA to a 2-D neutral layer structure with a (8)₂(8⁴;12²) topology. Magnetic properties of 1–3 were analyzed in connection with their structures, which show that there exist weak antiferromagnetic interactions between metal ions. - Graphical abstract: Three heterobimetallic MOFs were constructed through the size-selectivity of TFA coordination sites for different transition metal ions based on the concept of “Hard and Soft Acids and Bases”. Highlights: • Complexes 1 and 3 contain 2-D wave-like negative-charged layers. • Complex 2 is a 2-D neutral layer structure with a (8)₂(8⁴;12²) topology. • Complexes 1–3 are the first example of heterobimetallic MOFs based on FTA. • The coordination sites of FTA show size-selectivity to metal ions.

  3. Mechanism of protein kinase C activation by phosphatidylinositol 4,5-bisphosphate

    SciTech Connect

    Lee, Myungho; Bell, R.M. )

    1991-01-29

    The mechanism of protein kinase C (PKC) activation by phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}), phosphatidylinositol 4-monophosphate (PIP), and phosphatidylinositol (PI) was investigated by using Triton X-100 mixed micellar methods. The activation of PKC by PIP{sub 2}, for which maximal activity was 60% of that elicited by sn-1,2-diacylglycerol (DAG), was similar to activation by DAG in several respects: (1) activation by PIP{sub 2} and DAG required phosphatidylserine (PS) as a phospholipid cofactor, (2) PIP{sub 2} and DAG reduced the concentration of Ca{sup 2+} and PS required for activation, (3) the concentration dependences of activation by PIP{sub 2} and DAG depended on the concentration of PS, and (4) PIP{sub 2} and DAG complemented one another to achieve maximal activation. On the other hand, PIP{sub 2} activation of the PKC differed from activation by DAG in several respects. With increasing concentrations of PIP{sub 2}, (1) the optimal concentration of PS required was constant at 12 mol%, (2) the maximal activity at 12 mol% PS increased, and (3) the cooperativity for PS decreased. PIP{sub 2} did not inhibit ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) binding of PKC at saturating levels of PS; however, at subsaturating levels of PS, PIP{sub 2} enhanced ({sup 3}H)PDBu binding by acting as a phospholipid cofactor. PIP did not function as an activator but served as a phospholipid cofactor in the presence of PS. These data establish that PIP{sub 2}, PIP, and PI can function to spare, in part, the PS phospholipid cofactor requirement of PKC, and they demonstrate that PIP{sub 2} but not PIP and PI can function as a lipid activator of PKC by mechanisms distinct from those of DAG and phorbol esters.

  4. Phosphatidylinositol 4,5-bisphosphate competitively inhibits phorbol ester binding to protein kinase C

    SciTech Connect

    Chauhan, A.; Cauhan, V.P.S.; Deshmukh, D.S.; Brokerhoff, H. )

    1989-06-13

    Calcium phospholipid dependent protein kinase C (PKC) is activated by diacylglycerol (DG) and by phorbol esters and is recognized to be the phorbol ester receptor of cells; DG displaces phorbol ester competitively from PKC. A phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP{sub 2}), can also activate PKC in the presence of phosphatidylserine (PS) and Ca{sup 2+} with a K{sub PIP{sub 2}} of 0.04 mol %. Preliminary experiments have suggested a common binding site for PIP{sub 2} and DG on PKC. Here, the authors investigate the effect of PIP{sub 2} on phorbol ester binding to PKC in a mixed micellar assay. In the presence of 20 mol % PS, PIP{sub 2} inhibited specific binding of ({sup 3}H)phorbol 12,13-dibutyrate (PDBu) in a dose-dependent fashion up to 85% at 1 mol %. Inhibition of binding was more pronounced with PIP{sub 2} than with DG. Scatchard analysis indicated that the decrease in binding of PDBu in the presence of PIP{sub 2} is the result of an altered affinity for the phorbol ester rather than of a change in maximal binding. The plot of apparent dissociation constants (K{sub d{prime}}) against PIP{sub 2} concentration was linear over a range of 0.01-1 mol % with a K{sub i} of 0.043 mol % and confirmed the competitive nature of inhibition between PDBu and PIP{sub 2}. Competition between PIP{sub 2} and phorbol ester could be determined in a liposomal assay system also. These results indicate that PIP{sub 2}, DG, and phorbol ester all compete for the same activator-receiving region on the regulatory moiety of protein kinase C, and they lend support to the suggestion that PIP{sub 2} is a primary activator of the enzyme.

  5. Morphological evaluation of eccentric sets guide-plates of dcp-l 4.5 mm

    PubMed Central

    Borges, José Humberto de Souza; da Silva Filho, Antonio Lisboa; Pereira Neto, Francisco; Daher, Walter Rodrigo; de Mesquita, Alessandro Queiroz; Freitas, Anderson

    2012-01-01

    Objective To carry out isolated and comparative evaluations of the measurements of the set eccentric guide plates used in 4.5mm surgical implants, and to determine the effect of these measurements on compression strength. Methods Four eccentric guides, four large dynamic compression plates (L-DCP) from four local manufacturers, and a Vonder® 200 mm caliper brand were used. Five standard parameter measurements were created for the set eccentric guide-plate, which were identified as A to E. Four sets were made, using materials of the same factory, and identified as groups I to IV. The analyses were performed by measuring all the parameters from a ventral view of the plate, with the eccentric guide placed in the plate hole. Results Groups I and II showed the same values for all the parameters. All the groups showed the same measurements for E = 8.15 e B = 3.60. Group III: A = 8.10mm, C = 3.25mm, D = 1.25mm. Group IV: A = 7.00mm, C = 3.10mm, D = 0.30mm. Maximum compression force was (F Max.): Group I 80.58 N, Group. II: F Max. 81.63 N, Group. III: F Max. 36.32N, Group. IV: F Max. 37.52N Conclusion The measurements evaluated show a lack of standardization in the manufacture of orthopedic instruments and its effects on the values for compression strength. Level of Evidence: Level III, analytical study. PMID:24453573

  6. Chronic alteration in phosphatidylinositol 4,5-bisphosphate levels regulates capsaicin and mustard oil responses

    PubMed Central

    Patil, Mayur J.; Belugin, Sergei; Akopian, Armen N.

    2011-01-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP2) modulate TRPV1 and TRPA1 activities. Since inflammation results in PIP2 depletion, persisting for long periods (hours-to-days) in pain models and in clinic, we examined whether chronic depletion and accumulation of PIP2 affects capsaicin and mustard oil responses. In addition we also wanted to evaluate whether the effects of PIP2 depend on TRPV1 and TRPA1 co-expression, and whether the PIP2 actions vary in expression cells versus sensory neurons. Chronic PIP2 production was stimulated by over-expression of phosphatidylinositol-4-phosphate-5-kinase, while PIP2-specific phospholipid 5′-phosphatase was selected to reduce plasma membrane levels of PIP2. Our results demonstrate that capsaicin (100 nM; CAP) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP2 levels in wild-type (WT) or TRPA1 null-mutant sensory neurons, as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP2 depletion in cells containing TRPV1 alone, but not TRPV1 together with TRPA1. Mustard oil (25 μM; MO) responses were also not affected by PIP2 in WT sensory neurons and cells co-expressing TRPA1 and TRPV1. In contrast, PIP2 reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP2 on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP2 levels regulate magnitude of CAP and MO responses, as well as MO-tachyphylaxis. This regulation depends on co-expression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

  7. Structural Studies of Inositol 1,4,5-Trisphosphate Receptor COUPLING LIGAND BINDING TO CHANNEL GATING

    SciTech Connect

    Chan, Jenny; Yamazaki, Haruka; Ishiyama, Noboru; Seo, Min-Duk; Mal, Tapas K.; Michikawa, Takayuki; Mikoshiba, Katsuhiko; Ikura, Mitsuhiko

    2010-11-22

    The three isoforms of the inositol 1,4,5-trisphosphate receptor (IP{sub 3}R) exhibit distinct IP{sub 3} sensitivities and cooperativities in calcium (Ca{sup 2+}) channel function. The determinants underlying this isoform-specific channel gating mechanism have been localized to the N-terminal suppressor region of IP3R. We determined the 1.9 {angstrom} crystal structure of the suppressor domain from type 3 IP{sub 3}R (IP{sub 3}R3{sub SUP}, amino acids 1-224) and revealed structural features contributing to isoform-specific functionality of IP{sub 3}R by comparing it with our previously determined structure of the type 1 suppressor domain (IP{sub 3}R1{sub SUP}). The molecular surface known to associate with the ligand binding domain (amino acids 224-604) showed marked differences between IP{sub 3}R3{sub SUP} and IP{sub 3}R1{sub SUP}. Our NMR and biochemical studies showed that three spatially clustered residues (Glu-20, Tyr-167, and Ser-217 in IP{sub 3}R1 and Glu-19, Trp-168, and Ser-218 in IP{sub 3}R3) within the N-terminal suppressor domains of IP{sub 3}R1{sub SUP} and IP{sub 3}R3{sub SUP} interact directly with their respective C-terminal fragments. Together with the accompanying paper (Yamazaki, H., Chan, J., Ikura, M., Michikawa, T., and Mikoshiba, K. (2010) J. Biol. Chem. 285, 36081-36091), we demonstrate that the single aromatic residue in this region (Tyr-167 in IP{sub 3}R1 and Trp-168 in IP{sub 3}R3) plays a critical role in the coupling between ligand binding and channel gating.

  8. Protein kinase Cζ exhibits constitutive phosphorylation and phosphatidylinositol-3,4,5-triphosphate-independent regulation

    PubMed Central

    Tobias, Irene S.; Kaulich, Manuel; Kim, Peter K.; Simon, Nitya; Jacinto, Estela; Dowdy, Steven F.; King, Charles C.; Newton, Alexandra C.

    2016-01-01

    Atypical protein kinase C (aPKC) isoenzymes are key modulators of insulin signalling, and their dysfunction correlates with insulin-resistant states in both mice and humans. Despite the engaged interest in the importance of aPKCs to type 2 diabetes, much less is known about the molecular mechanisms that govern their cellular functions than for the conventional and novel PKC isoenzymes and the functionally-related protein kinase B (Akt) family of kinases. Here we show that aPKC is constitutively phosphorylated and, using a genetically-encoded reporter for PKC activity, basally active in cells. Specifically, we show that phosphorylation at two key regulatory sites, the activation loop and turn motif, of the aPKC PKCζ in multiple cultured cell types is constitutive and independently regulated by separate kinases: ribosome-associated mammalian target of rapamycin complex 2 (mTORC2) mediates co-translational phosphorylation of the turn motif, followed by phosphorylation at the activation loop by phosphoinositide-dependent kinase-1 (PDK1). Live cell imaging reveals that global aPKC activity is constitutive and insulin unresponsive, in marked contrast to the insulin-dependent activation of Akt monitored by an Akt-specific reporter. Nor does forced recruitment to phosphoinositides by fusing the pleckstrin homology (PH) domain of Akt to the kinase domain of PKCζ alter either the phosphorylation or activity of PKCζ. Thus, insulin stimulation does not activate PKCζ through the canonical phosphatidylinositol-3,4,5-triphosphate-mediated pathway that activates Akt, contrasting with previous literature on PKCζ activation. These studies support a model wherein an alternative mechanism regulates PKCζ-mediated insulin signalling that does not utilize conventional activation via agonist-evoked phosphorylation at the activation loop. Rather, we propose that scaffolding near substrates drives the function of PKCζ. PMID:26635352

  9. Chronic alteration in phosphatidylinositol 4,5-biphosphate levels regulates capsaicin and mustard oil responses.

    PubMed

    Patil, Mayur J; Belugin, Sergei; Akopian, Armen N

    2011-06-01

    There is an agreement that acute (in minutes) hydrolysis and accumulation of phosphatidylinositol 4,5-bisphosphate (PIP(2) ) modulate TRPV1 and TRPA1 activities. Because inflammation results in PIP(2) depletion, persisting for long periods (hours to days) in pain models and in the clinic, we examined whether chronic depletion and accumulation of PIP(2) affect capsaicin (CAP) and mustard oil (MO) responses. In addition, we wanted to evaluate whether the effects of PIP(2) depend on TRPV1 and TRPA1 coexpression and whether the PIP(2) actions vary in expression cells vs. sensory neurons. Chronic PIP(2) production was stimulated by overexpression of phosphatidylinositol-4-phosphate-5-kinase, and PIP(2) -specific phospholipid 5'-phosphatase was selected to reduce plasma membrane levels of PIP(2) . Our results demonstrate that CAP (100 nM) responses and receptor tachyphylaxis are not significantly influenced by chronic changes in PIP(2) levels in wild-type (WT) or TRPA1 null-mutant sensory neurons as well as CHO cells expressing TRPV1 alone or with TRPA1. However, low concentrations of CAP (20 nM) produced a higher response after PIP(2) depletion in cells containing TRPV1 alone but not TRPV1 together with TRPA1. MO (25 μM) responses were also not affected by PIP(2) in WT sensory neurons and cells coexpressing TRPA1 and TRPV1. In contrast, PIP(2) reduction leads to pronounced tachyphylaxis to MO in cells with both channels. Chronic effect of PIP(2) on TRPA1 activity depends on presence of the TRPV1 channel and cell type (CHO vs. sensory neurons). In summary, chronic alterations in PIP(2) levels regulate magnitude of CAP and MO responses as well as MO tachyphylaxis. This regulation depends on coexpression profile of TRPA1 and TRPV1 and cell type. PMID:21337373

  10. Searching for Organics Preserved in 4.5 Billion Year Old Salt

    NASA Technical Reports Server (NTRS)

    Zolensky, Michael E.; Fries, M.; Steele, A.; Bodnar, R.

    2012-01-01

    Our understanding of early solar system fluids took a dramatic turn a decade ago with the discovery of fluid inclusion-bearing halite (NaCl) crystals in the matrix of two freshly fallen brecciated H chondrite falls, Monahans and Zag. Both meteorites are regolith breccias, and contain xenolithic halite (and minor admixed sylvite -- KCl, crystals in their regolith lithologies. The halites are purple to dark blue, due to the presence of color centers (electrons in anion vacancies) which slowly accumulated as 40K (in sylvite) decayed over billions of years. The halites were dated by K-Ar, Rb-Sr and I-Xe systematics to be 4.5 billion years old. The "blue" halites were a fantastic discovery for the following reasons: (1) Halite+sylvite can be dated (K is in sylvite and will substitute for Na in halite, Rb substitutes in halite for Na, and I substitutes for Cl). (2) The blue color is lost if the halite dissolves on Earth and reprecipitates (because the newly-formed halite has no color centers), so the color serves as a "freshness" or pristinity indicator. (3) Halite frequently contains aqueous fluid inclusions. (4) Halite contains no structural oxygen, carbon or hydrogen, making them ideal materials to measure these isotopic systems in any fluid inclusions. (5) It is possible to directly measure fluid inclusion formation temperatures, and thus directly measure the temperature of the mineralizing aqueous fluid. In addition to these two ordinary chondrites halite grains have been reliably reported in several ureilites, an additional ordinary chondrite (Jilin), and in the carbonaceous chondrite (Murchison), although these reports were unfortunately not taken seriously. We have lately found additional fluid inclusions in carbonates in several additional carbonaceous chondrites. Meteoritic aqueous fluid inclusions are apparently relatively widespread in meteorites, though very small and thus difficult to analyze.

  11. Detection and quantification of 4(5)-methylimidazole in cooked meat.

    PubMed

    Karim, Faris; Smith, J Scott

    2015-02-01

    4(5)-Methylimidazole (4-MeI) is a nitrogen-containing heterocyclic compound found in class III and IV ammoniated caramel colors, a group of additives widely used in the food industry. A suspected carcinogen and neurotoxin and efforts are underway to limit its presence in foods. Several methods have been developed to detect and quantitate 4-MeI in different food matrices, including roasted coffee, beer, soft drinks, and soy sauce; however, no methods are available to measure 4-MeI in cooked meat and meat products containing lipids and high levels of interfering nitrogen compounds, such as amino acids and peptides. A rapid method using 0.1 M sodium acetate buffer (pH 5) as an extraction solvent followed by derivatization with isobutylchloroformate and gas chromatograph mass-spectrometry was developed to quantify 4-MeI in cooked meat products with added caramel colors containing 4-MeI. Selected ion monitoring mode was used to monitor 4-MeI ions fragments. In the 8 commercial meat products tested, 4-MeI levels ranged from 0.041 to 1.015 mg/kg, with recovery of 94.76% to 103.94%. In addition, a matrix-matched calibration performed by analyzing a spiked cooked meat sample indicated no significant difference (P > 0.05), which means the meat matrix had no effect on the developed method. This method proved useful in analyzing 4-MeI in meat products with added caramel color containing 4-MeI. PMID:25603986

  12. Results from heater-induced quenches of A 4. 5 m Reference Design D dipole for the SSC

    SciTech Connect

    Ganetis, G.; Prodell, A.

    1986-01-01

    Quench studies were performed using a 4.5 m long Reference Design D, SSC dipole to determine the temperature rise of the magnet conductor during a quench by measuring the resistance of the conductor cable in the immediate vicinity of the quench. The single bore magnet was wound with improved NbTi conductor in a 2-layer cosine theta coil configuration of 4.0 cm inner diameter. Eight pairs of voltage taps were installed at various locations on the right side of the inner coil of the magnet. ''Spot'' heaters were centrally located between the voltage taps of 4 of these pairs on the midplane turn of the inner coil to initiate magnet quenches. A redundant array of voltage taps and heaters was also installed on the left side of the inner coil. The resistance of the conductor was obtained from observations of the current and voltage during a magnet quench. The temperature of the conductor was then determined by comparing its resistance to an R vs T curve appropriate for the conductor. The quantity ..integral.. I/sup 2/dt and the temperature, T, are presented as a function of current, and the maximum conductor temperature is shown as a function of ..integral.. I/sup 2/dt. Measured longitudinal and azimuthal quench propagation velocities are also presented as a function of magnet current, and the temperatures at several locations on the inner magnet coil are plotted as a function of the time after a quench was initiated.

  13. The role of inositol 1,4,5-trisphosphate 3-kinase A in regulating emotional behavior and amygdala function

    PubMed Central

    Chung, Sooyoung; Kim, Il Hwan; Lee, Dongmin; Park, Kyungjoon; Kim, Joo Yeon; Lee, Yeon Kyung; Kim, Eun Joo; Lee, Hyun Woo; Choi, June-seek; Son, Gi Hoon; Sun, Woong; Shin, Ki Soon; Kim, Hyun

    2016-01-01

    Inositol 1,4,5-trisphosphate 3-kinase A (IP3K-A) is a molecule enriched in the brain and neurons that regulates intracellular calcium levels via signaling through the inositol trisphosphate receptor. In the present study, we found that IP3K-A expression is highly enriched in the central nucleus of the amygdala (CeA), which plays a pivotal role in the processing and expression of emotional phenotypes in mammals. Genetic abrogation of IP3K-A altered amygdala gene expression, particularly in genes involved in key intracellular signaling pathways and genes mediating fear- and anxiety-related behaviors. In agreement with the changes in amygdala gene expression profiles, IP3K-A knockout (KO) mice displayed more robust responses to aversive stimuli and spent less time in the open arms of the elevated plus maze, indicating high levels of innate fear and anxiety. In addition to behavioral phenotypes, decreased excitatory and inhibitory postsynaptic current and reduced c-Fos immunoreactivity in the CeA of IP3K-A KO mice suggest that IP3K-A has a profound influence on the basal activities of fear- and anxiety-mediating amygdala circuitry. In conclusion, our findings collectively demonstrate that IP3K-A plays an important role in regulating affective states by modulating metabotropic receptor signaling pathways and neural activity in the amygdala. PMID:27053114

  14. DISCOVERY OF A PROBABLE 4-5 JUPITER-MASS EXOPLANET TO HD 95086 BY DIRECT IMAGING

    SciTech Connect

    Rameau, J.; Chauvin, G.; Lagrange, A.-M.; Delorme, P.; Quanz, S. P.; Bonnefoy, M.; Klahr, H.; Mordasini, C.; Girard, J. H.; Dumas, C.; Desidera, S.; Bonavita, M.

    2013-08-01

    Direct imaging has only begun to inventory the population of gas giant planets on wide orbits around young stars in the solar neighborhood. Following this approach, we carried out a deep imaging survey in the near-infrared using VLT/NaCo to search for substellar companions. Here we report the discovery of a probable companion orbiting the young (10-17 Myr), dusty, early-type (A8) star HD 95086 at 56 AU in L' (3.8 {mu}m) images. This discovery is based on observations with more than a year time lapse. Our first epoch clearly revealed the source at {approx_equal} 10{sigma}, while our second epoch lacks good observing conditions, yielding a {approx_equal} 3{sigma} detection. Various tests were thus made to rule out possible artifacts. This recovery is consistent with the signal at the first epoch but requires cleaner confirmation. Nevertheless, our astrometric precision suggests that the companion is comoving with the star with a 3{sigma} confidence level. The planetary nature of the source is reinforced by a non-detection in the Ks-band (2.18 {mu}m) images according to its possible extremely red Ks-L' color. Conversely, background contamination is rejected with good confidence level. The luminosity yields a predicted mass of about 4-5 M{sub Jup} (at 10-17 Myr) using ''hot-start'' evolutionary models, making HD 95086 b the exoplanet with the lowest mass ever imaged around a star.

  15. Biotransformation of 2,4,6-trinitrotoluene with Phanaerochaete chrysosporium in agitated cultures at pH 4. 5

    SciTech Connect

    Hawari, J.; Halasz, A.; Beaudet, S.; Paquet, L. . Biotechnology Research Inst.); Ampleman, G.; Thiboutot, S. . Defence Research Establishment Valcartier)

    1999-07-01

    The biotransformation of 2,4,6-trinitrotoluene (TNT) by Phanerochaete chrysosporium with molasses and citric acid at pH 4.5 was studied. In less than 2 weeks, TNT disappeared completely, but mineralization did not exceed 1%. A time study revealed the presence of several intermediates, marked by the initial formation of two monohydroxylaminodinitrotoluenes (2- and 4-HADNT) followed by their successive transformation to several other products, including monoaminodinitrotoluenes (ADNT). A group of nine acylated intermediates were also detected. They included 2-N-acetylamido-4,6-dinitrotoluene and its p isomer, 2-formylamido-4,6-dinitrotoluene and its p isomer (as acylated ADNT), 4-N-acetylamino-2-amino-6-nitrotoluene and 4-N-formylamido-2-amino-6-nitrotoluene (as acetylated DANT), 4-N-acetylhydroxy-2,6-dinitrotoluene and 4-N-acetoxy-2,6-dinitrotoluene (as acetylated HADNT), and finally 4-N-acetylamido-2-hydroxylamino-6-nitrotoluene. Furthermore, a fraction of HADNTs were found to rearrange to their corresponding phenolamines, while another group dimerized to azoxytoluenes which in turn transformed to azo compounds and eventually to the corresponding hydrazo derivatives. After 30 days, all of these metabolites, except traces of 4-ADNT and the hydrazo derivatives, disappeared, but mineralization did not exceed 10% even after the incubation period was increased to 120 days.

  16. Homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system at ER-PM junctions.

    PubMed

    Chang, Chi-Lun; Liou, Jen

    2016-08-01

    The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2)-Ca(2+) signaling system is important for cell activation in response to various extracellular stimuli. This signaling system is initiated by receptor-induced hydrolysis of PI(4,5)P2 in the plasma membrane (PM) to generate the soluble second messenger inositol 1,4,5-trisphosphate (IP3). IP3 subsequently triggers the release of Ca(2+) from the endoplasmic reticulum (ER) store to the cytosol to activate Ca(2+)-mediated responses, such as secretion and proliferation. The consumed PM PI(4,5)P2 and ER Ca(2+) must be quickly restored to sustain signaling responses, and to maintain the homeostasis of PI(4,5)P2 and Ca(2+). Since phosphatidylinositol (PI), the precursor lipid for PM PI(4,5)P2, is synthesized in the ER membrane, and a Ca(2+) influx across the PM is required to refill the ER Ca(2+) store, efficient communications between the ER and the PM are critical for the homeostatic regulation of the PI(4,5)P2-Ca(2+) signaling system. This review describes the major findings that established the framework of the PI(4,5)P2-Ca(2+) signaling system, and recent discoveries on feedback control mechanisms at ER-PM junctions that sustain the PI(4,5)P2-Ca(2+) signaling system. Particular emphasis is placed on the characterization of ER-PM junctions where efficient communications between the ER and the PM occur, and the activation mechanisms of proteins that dynamically localize to ER-PM junctions to provide the feedback control during PI(4,5)P2-Ca(2+) signaling, including the ER Ca(2+) sensor STIM1, the extended synaptotagmin E-Syt1, and the PI transfer protein Nir2. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID:26924250

  17. Translocation between membranes and cytosol of p42IP4, a specific inositol 1,3,4,5-tetrakisphosphate/phosphatidylinositol 3,4, 5-trisphosphate-receptor protein from brain, is induced by inositol 1,3,4,5-tetrakisphosphate and regulated by a membrane-associated 5-phosphatase.

    PubMed

    Stricker, R; Adelt, S; Vogel, G; Reiser, G

    1999-10-01

    The highly conserved 42-kDa protein, p42IP4 was identified recently from porcine brain. It has also been identified similarly in bovine, rat and human brain as a protein with two pleckstrin homology domains that binds Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3 with high affinity and selectivity. The brain-specific p42IP4 occurs both as membrane-associated and cytosolic protein. Here, we investigate whether p42IP4 can be translocated from membranes by ligand interaction. p42IP4 is released from cerebellar membranes by incubation with Ins(1,3,4,5)P4. This dissociation is concentration-dependent (> 100 nM), occurs within a few minutes and and is ligand-specific. p42IP4 specifically associates with PtdIns(3, 4,5)P3-containing lipid vesicles and can dissociate from these vesicles by addition of Ins(1,3,4,5)P4. p42IP4 is only transiently translocated from the membranes as Ins(1,3,4,5)P4 can be degraded by a membrane-associated 5-phosphatase to Ins(1,3,4)P3. Then, p42IP4 re-binds to the membranes from which it can be re-released by re-addition of Ins(1,3,4,5)P4. Thus, Ins(1,3,4,5)P4 specifically induces the dissociation from membranes of a PtdIns(3,4,5)P3 binding protein that can reversibly re-associate with the membranes. Quantitative analysis of the inositol phosphates in rat brain tissue revealed a concentration of Ins(1,3,4,5)P4 comparable to that required for p42IP4 translocation. Thus, in vivo p42IP4 might interact with membranes in a ligand-controlled manner and be involved in physiological processes induced by the two second messengers Ins(1,3,4,5)P4 and PtdIns(3,4,5)P3. PMID:10504414

  18. Optimization of the catalytic asymmetric addition of nitroalkanes to cyclic enones with trans-4,5-methano-L-proline.

    PubMed

    Hanessian, Stephen; Shao, Zhihui; Warrier, Jayakumar S

    2006-10-12

    [reaction: see text] The conjugate addition of symmetrical 2-nitroalkanes to 2-cycloalkenones catalyzed by trans-4,5-methano-l-proline proceeds with >99% ee and excellent chemical yields. 1-Nitroalkanes afford diastereomeric syn/anti products that can be separated with good individual enantioselectivities. Proline hydroxamic acid and its trans-4,5-methano -l-proline hydroxamic acid are also effective organocatalysts in the addition of 2-nitropropane to 2-cyclohexenone (75% and 81% ee, respectively). PMID:17020303

  19. Conformation of 4.5S RNA in the signal recognition particle and on the 30S ribosomal subunit

    PubMed Central

    GU, SHAN-QING; JÖCKEL, JOHANNES; BEINKER, PHILIPP; WARNECKE, JENS; SEMENKOV, YURI P.; RODNINA, MARINA V.; WINTERMEYER, WOLFGANG

    2005-01-01

    The signal recognition particle (SRP) from Escherichia coli consists of 4.5S RNA and protein Ffh. It is essential for targeting ribosomes that are translating integral membrane proteins to the translocation pore in the plasma membrane. Independently of Ffh, 4.5S RNA also interacts with elongation factor G (EF-G) and the 30S ribosomal subunit. Here we use a cross-linking approach to probe the conformation of 4.5S RNA in SRP and in the complex with the 30S ribosomal subunit and to map the binding site. The UV-activatable cross-linker p-azidophenacyl bromide (AzP) was attached to positions 1, 21, and 54 of wild-type or modified 4.5S RNA. In SRP, cross-links to Ffh were formed from AzP in all three positions in 4.5S RNA, indicating a strongly bent conformation in which the 5′ end (position 1) and the tetraloop region (including position 54) of the molecule are close to one another and to Ffh. In ribosomal complexes of 4.5S RNA, AzP in both positions 1 and 54 formed cross-links to the 30S ribosomal subunit, independently of the presence of Ffh. The major cross-linking target on the ribosome was protein S7; minor cross-links were formed to S2, S18, and S21. There were no cross-links from 4.5S RNA to the 50S subunit, where the primary binding site of SRP is located close to the peptide exit. The functional role of 4.5S RNA binding to the 30S subunit is unclear, as the RNA had no effect on translation or tRNA translocation on the ribosome. PMID:16043501

  20. Synthesis and biological activities of some new 4,5-dihydro-1H-1,2,4-triazol-5-ones.

    PubMed

    Demirbas, A; Johansson, C B; Duman, N; Ikizler, A A

    1996-01-01

    The reactions of 3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-triazol-5-ones with appropriate alkyl halides via sodio derivatives were studied and the corresponding 1-alkyl-3-alkyl(aryl)-4-phenylamino-4,5-dihydro-1H-1,2,4-traizol-5 -ones were synthesized. Next, the new compounds were tested for their in vitro antimicrobial activities. PMID:8960286

  1. Selectively fluorinated cyclohexane building blocks: Derivatives of carbonylated all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane

    PubMed Central

    Ayoup, Mohammed Salah; Cordes, David B; Slawin, Alexandra M Z

    2015-01-01

    Summary Palladium catalysed carbonylation reactions using the meta- and para-iodo derivatives of all-cis-3-phenyl-1,2,4,5-tetrafluorocyclohexane (4) are illustrated as the start point for a variety of functional group interconversions. The resultant benzaldehyde and benzoic acids offer novel building blocks for further derivatisation and facilitate the incorporation of the facially polarised all-cis-1,2,4,5-tetrafluorocyclohexane motif into more advanced molecular scaffolds. PMID:26877788

  2. Inositol-1,4,5-trisphosphate 3-kinase A regulates dendritic morphology and shapes synaptic Ca2+ transients.

    PubMed

    Windhorst, Sabine; Minge, Daniel; Bähring, Robert; Hüser, Svenja; Schob, Claudia; Blechner, Christine; Lin, Hong-Ying; Mayr, Georg W; Kindler, Stefan

    2012-03-01

    Inositol-1,4,5-trisphosphate 3-kinase-A (itpka) accumulates in dendritic spines and seems to be critically involved in synaptic plasticity. The protein possesses two functional activities: it phosphorylates inositol-1,4,5-trisphosphate (Ins(1,4,5)P(3)) and regulates actin dynamics by its F-actin bundling activity. To assess the relevance of these activities for neuronal physiology, we examined the effects of altered itpka levels on cell morphology, Ins(1,4,5)P(3) metabolism and dendritic Ca(2+) signaling in hippocampal neurons. Overexpression of itpka increased the number of dendritic protrusions by 71% in immature primary neurons. In mature neurons, however, the effect of itpka overexpression on formation of dendritic spines was weaker and depletion of itpka did not alter spine density and synaptic contacts. In synaptosomes of mature neurons itpka loss resulted in decreased duration of Ins(1,4,5)P(3) signals and shorter Ins(1,4,5)P(3)-dependent Ca(2+) transients. At synapses of itpka deficient neurons the levels of Ins(1,4,5)P(3)-5-phosphatase (inpp5a) and sarcoplasmic/endoplasmic reticulum calcium ATPase pump-2b (serca2b) were increased, indicating that decreased duration of Ins(1,4,5)P(3) and Ca(2+) signals results from compensatory up-regulation of these proteins. Taken together, our data suggest a dual role for itpka. In developing neurons itpka has a morphogenic effect on dendrites, while the kinase appears to play a key role in shaping Ca(2+) transients at mature synapses. PMID:22120525

  3. Stereospecific microbial reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl-1H-1)-benzazepin+ ++-2-o ne.

    PubMed

    Patel, R N; Robison, R S; Szarka, L J; Kloss, J; Thottathil, J K; Mueller, R H

    1991-11-01

    A key intermediate, (3R-cis)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluorome thyl)- 2H-1-benzazepin-2-one (compound II or SQ32191), with high optical purity was made by the stereoselective microbial reduction of the parent ketone 1. Several strains of bacterial and yeast cultures were screened for the ability to catalyse the stereoselective reduction of 4,5-dihydro-4-(4-methoxyphenyl)-6-(trifluoromethyl)-1H-1-benzazepin++ +-2,3-dione [compound I or SQ32425]. Microorganisms from the genera Nocardia, Rhodococcus, Alkaligenes, Corynebacterium, Arthrobacter, Hansenula, and Candida reduced compound I to compound II with 60-70% conversion yield. In contrast, microorganisms from the genera Pseudomonas and Acinetobacter reduced compound I stereospecifically to (trans)-1,3,4,5-tetrahydro-3-hydroxy-4-(4-methoxyphenyl)-6-(trifluoromet hyl-2H- 1-benzazepin-2-one (compound III or SQ32408). Among various cultures evaluated, N. salmonicolor SC6310 effectively catalysed the transformation of compound I to compound II with 96% conversion yield at 1.5-2.0 gl-1 concentration. Compound II was isolated and identified by NMR analysis, mass spectrometry, and comparison to an authentic sample. Preparative scale fermentation process and transformation process were developed using cell suspensions of N. salmonicolor SC6310 to catalyse the transformation of compound I to compound II. The isolated compound II had a melting point of 222 degrees C (reference 221-223 degrees C), optical rotation of +130.4 (reference +128 degrees C), and optical purity of greater than 99.9% as analyzed by NMR and chiral HPLC. PMID:1368001

  4. Rock Art of the Greater Southwest

    NASA Astrophysics Data System (ADS)

    Krupp, Edwin C.

    Archaeoastronomical studies in the American Southwest began in 1955 with recognition of what seemed to be pictorial eyewitness records of the Crab supernova of 1054 AD In time, reports of seasonally significant light-and-shadow effects on rock art and associations of rock art with astronomical alignments also emerged. Most astronomical rock art studies remained problematic, however, because criteria for proof of ancient intent were elusive. Disciplined methods for assessing cultural function were difficult to develop, but review of ethnographically documented astronomical traditions of California Indians and of Indians in the American Southwest subsequently increased confidence in the value of some astronomical rock art initiatives.

  5. Does Unemployment Lead to Greater Alcohol Consumption?

    PubMed Central

    Popovici, Ioana; French, Michael T.

    2013-01-01

    Using panel data from Waves 1 and 2 of the NESARC, we estimate gender-specific effects of changes in employment status on overall alcohol consumption, binge drinking episodes, and a diagnosis of alcohol abuse and/or dependence. We employ various fixed-effects models to address potential bias from unobserved and time-invariant individual heterogeneity. All results show a positive and significant effect of unemployment on drinking behaviors and the findings are robust to numerous sensitivity tests. Perhaps macroeconomic policy decisions intended to stimulate the economy during economic downturns should also consider the avoided personal costs and externalities associated with alcohol misuse. PMID:23543880

  6. Promoting greater Federal energy productivity [Final report

    SciTech Connect

    Hopkins, Mark; Dudich, Luther

    2003-03-05

    This document is a close-out report describing the work done under this DOE grant to improve Federal Energy Productivity. Over the four years covered in this document, the Alliance To Save Energy conducted liaison with the private sector through our Federal Energy Productivity Task Force. In this time, the Alliance held several successful workshops on the uses of metering in Federal facilities and other meetings. We also conducted significant research on energy efficiency, financing, facilitated studies of potential energy savings in energy intensive agencies, and undertook other tasks outlined in this report.

  7. The RSPO-LGR4/5-ZNRF3/RNF43 module controls liver zonation and size.

    PubMed

    Planas-Paz, Lara; Orsini, Vanessa; Boulter, Luke; Calabrese, Diego; Pikiolek, Monika; Nigsch, Florian; Xie, Yang; Roma, Guglielmo; Donovan, Adriana; Marti, Patricia; Beckmann, Nicolau; Dill, Michael T; Carbone, Walter; Bergling, Sebastian; Isken, Andrea; Mueller, Matthias; Kinzel, Bernd; Yang, Yi; Mao, Xiaohong; Nicholson, Thomas B; Zamponi, Raffaella; Capodieci, Paola; Valdez, Reginald; Rivera, Daniel; Loew, Andreas; Ukomadu, Chinweike; Terracciano, Luigi M; Bouwmeester, Tewis; Cong, Feng; Heim, Markus H; Forbes, Stuart J; Ruffner, Heinz; Tchorz, Jan S

    2016-05-01

    LGR4/5 receptors and their cognate RSPO ligands potentiate Wnt/β-catenin signalling and promote proliferation and tissue homeostasis in epithelial stem cell compartments. In the liver, metabolic zonation requires a Wnt/β-catenin signalling gradient, but the instructive mechanism controlling its spatiotemporal regulation is not known. We have now identified the RSPO-LGR4/5-ZNRF3/RNF43 module as a master regulator of Wnt/β-catenin-mediated metabolic liver zonation. Liver-specific LGR4/5 loss of function (LOF) or RSPO blockade disrupted hepatic Wnt/β-catenin signalling and zonation. Conversely, pathway activation in ZNRF3/RNF43 LOF mice or with recombinant RSPO1 protein expanded the hepatic Wnt/β-catenin signalling gradient in a reversible and LGR4/5-dependent manner. Recombinant RSPO1 protein increased liver size and improved liver regeneration, whereas LGR4/5 LOF caused the opposite effects, resulting in hypoplastic livers. Furthermore, we show that LGR4(+) hepatocytes throughout the lobule contribute to liver homeostasis without zonal dominance. Taken together, our results indicate that the RSPO-LGR4/5-ZNRF3/RNF43 module controls metabolic liver zonation and is a hepatic growth/size rheostat during development, homeostasis and regeneration. PMID:27088858

  8. Synthesis, biological evaluation and molecular docking studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives as novel anticancer agents.

    PubMed

    Patel, Vijay K; Rajak, Harish

    2016-05-01

    A series of novel 2-amino-3,4,5 trimethoxyaroylindole derivatives was synthesized and evaluated against selected human cancer cell lines of breast (MCF-7) and colon (HT-29). Introduction of an amino group at the C-2 position on ring A of 3,4,5-trimethoxyaroylindole derivatives resulted in novel compounds, i.e., 2-amino-3,4,5-trimethoxyaroylindole derivatives exhibiting excellent cytotoxic activity against human cancer cell lines. Substitution with methoxy group at R(6) in 2-amino-3,4,5-trimethoxyaroylindole 5d exhibited excellent cytotoxic activity against MCF-7 (0.013μM) and colon HT-29 (0.143μM) indicating slightly higher potency than Combretastatin A-4. Molecular modeling studies of 2-amino-3,4,5-trimethoxyaroylindole derivatives have similar structural alignment as colchicine in protein (PDB code: 1SA0) and exhibited hydrogen bond interaction between para position of 3,4,5-trimethoxyphenyl ring with CYS 241 and N-H molecule of indole ring with Val 315 of receptor molecule. PMID:27040661

  9. Characterization of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid-degrading fungi in Vietnamese soils.

    PubMed

    Itoh, Kazuhito; Kinoshita, Masahiro; Morishita, Shigeyuki; Chida, Masateru; Suyama, Kousuke

    2013-04-01

    Sixty-nine fungal strains were isolated countrywide from 10 Vietnamese soils, in areas both with and without a history of exposure to Agent Orange, and their degrading activities on the phenoxy acid herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), as well as related compounds, were examined. Among taxonomically various fungi, 45, 12 and 4% of the isolates degraded phenoxyacetic acid (PA), 2,4-D and 2,4,5-T, respectively. While the PA-degrading fungi were distributed to all sites and among many genera, the 2,4-D-degraders were found only in order Eurotiales in class Eurotiomycetes. All of the 2,4,5-T-degrading fungal strains were phylogenetically close to Eupenicillium spp. and were isolated from southern Vietnam. As a degradation intermediate, the corresponding phenol compounds were detected in some strains. The degradation substrate spectrum for 26 compounds of Eupenicillium spp. strains including 2,4,5-T-degraders and -non-degraders seemed to be related to phylogenetic similarity and soil sampling location of the isolates. These results suggest that the heavily contaminated environments enhanced the adaptation of the phylogenetic group of Eupenicillium spp. toward to obtain the ability to degrade 2,4,5-T. PMID:23167922

  10. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes.

    PubMed

    Goñi, Guillermina M; Epifano, Carolina; Boskovic, Jasminka; Camacho-Artacho, Marta; Zhou, Jing; Bronowska, Agnieszka; Martín, M Teresa; Eck, Michael J; Kremer, Leonor; Gräter, Frauke; Gervasio, Francesco Luigi; Perez-Moreno, Mirna; Lietha, Daniel

    2014-08-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation. PMID:25049397

  11. Phosphatidylinositol 4,5-bisphosphate triggers activation of focal adhesion kinase by inducing clustering and conformational changes

    PubMed Central

    Goñi, Guillermina M.; Epifano, Carolina; Boskovic, Jasminka; Camacho-Artacho, Marta; Zhou, Jing; Bronowska, Agnieszka; Martín, M. Teresa; Eck, Michael J.; Kremer, Leonor; Gräter, Frauke; Gervasio, Francesco Luigi; Perez-Moreno, Mirna; Lietha, Daniel

    2014-01-01

    Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase (NRTK) with key roles in integrating growth and cell matrix adhesion signals, and FAK is a major driver of invasion and metastasis in cancer. Cell adhesion via integrin receptors is well known to trigger FAK signaling, and many of the players involved are known; however, mechanistically, FAK activation is not understood. Here, using a multidisciplinary approach, including biochemical, biophysical, structural, computational, and cell biology approaches, we provide a detailed view of a multistep activation mechanism of FAK initiated by phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. Interestingly, the mechanism differs from canonical NRTK activation and is tailored to the dual catalytic and scaffolding function of FAK. We find PI(4,5)P2 induces clustering of FAK on the lipid bilayer by binding a basic region in the regulatory 4.1, ezrin, radixin, moesin homology (FERM) domain. In these clusters, PI(4,5)P2 induces a partially open FAK conformation where the autophosphorylation site is exposed, facilitating efficient autophosphorylation and subsequent Src recruitment. However, PI(4,5)P2 does not release autoinhibitory interactions; rather, Src phosphorylation of the activation loop in FAK results in release of the FERM/kinase tether and full catalytic activation. We propose that PI(4,5)P2 and its generation in focal adhesions by the enzyme phosphatidylinositol 4-phosphate 5-kinase type Iγ are important in linking integrin signaling to FAK activation. PMID:25049397

  12. Phospholipid-binding sites of phosphatase and tensin homolog (PTEN): exploring the mechanism of phosphatidylinositol 4,5-bisphosphate activation.

    PubMed

    Wei, Yang; Stec, Boguslaw; Redfield, Alfred G; Weerapana, Eranthie; Roberts, Mary F

    2015-01-16

    The lipid phosphatase activity of the tumor suppressor phosphatase and tensin homolog (PTEN) is enhanced by the presence of its biological product, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). This enhancement is suggested to occur via the product binding to the N-terminal region of the protein. PTEN effects on short-chain phosphoinositide (31)P linewidths and on the full field dependence of the spin-lattice relaxation rate (measured by high resolution field cycling (31)P NMR using spin-labeled protein) are combined with enzyme kinetics with the same short-chain phospholipids to characterize where PI(4,5)P2 binds on the protein. The results are used to model a discrete site for a PI(4,5)P2 molecule close to, but distinct from, the active site of PTEN. This PI(4,5)P2 site uses Arg-47 and Lys-13 as phosphate ligands, explaining why PTEN R47G and K13E can no longer be activated by that phosphoinositide. Placing a PI(4,5)P2 near the substrate site allows for proper orientation of the enzyme on interfaces and should facilitate processive catalysis. PMID:25429968

  13. Effect of Various Food Additives on the Levels of 4(5)-Methylimidazole in a Soy Sauce Model System.

    PubMed

    Lee, Sumin; Lee, Jung-Bin; Hwang, Junho; Lee, Kwang-Geun

    2016-01-01

    In this study, the effect of food additives such as iron sulfate, magnesium sulfate, zinc sulfate, citric acid, gallic acid, and ascorbic acid on the reduction of 4(5)-methylimidazole (4(5)-MI) was investigated using a soy sauce model system. The concentration of 4(5)-MI in the soy sauce model system with 5% (v/v) caramel colorant III was 1404.13 μg/L. The reduction rate of 4(5)-MI level with the addition of 0.1M additives followed in order: iron sulfate (81%) > zinc sulfate (61%) > citric acid (40%) > gallic acid (38%) > ascorbic acid (24%) > magnesium sulfate (13%). Correlations between 4(5)-MI levels and the physicochemical properties of soy sauce, including the amount of caramel colorant, pH value, and color differences, were determined. The highest correlations were found between 4(5)-MI levels and the amount of caramel colorant and pH values (r(2) = 0.9712, r(2) = 0.9378). The concentration of caramel colorants in 8 commercial soy sauces were estimated, and ranged from 0.01 to 1.34% (v/v). PMID:26661512

  14. Distribution of Permo-Carboniferous clastics of Greater Arabian basin

    SciTech Connect

    Al-Laboun, A.A.

    1987-05-01

    Strikingly correlative sequences of sediments composed of sandstones, siltstones, shales, and thin argillaceous carbonate beds are present, practically everywhere, underlying the Late Permian carbonates in the Greater Arabian basin. The Greater Arabian basin as defined here occupies the broad Arabian Shelf that borders the Arabian shield. This basin is composed of several smaller basins. These clastics are exposed as thin bands and scattered small exposures in several localities around the margins of the basin. The Permo-Carboniferous clastics are represented by the Unayzah Formation of Arabia, the Doubayat Group of Syria, the Hazro Formation of southeast Turkey, the Ga'arah Formation of Iraq, the Faraghan Formation of southwest Iran, and the Haushi Group of Oman. A Late Carboniferous-Early Permian age is assigned to these clastics because they contain fossil plants and palynomorphs. These sediments represent time-transgressive fluctuating sea deposits following a phase of regional emergence, erosion, and structural disturbance which preceded the Permian transgression. The basal contact of these clastics is marked by a well-pronounced angular unconformity with various older units, ranging in age from early Carboniferous to late Precambrian. This regional unconformity is probably related to the Hercynian movements. The upper contact is conformable with the Permian carbonates. The porous sandstones of the Permo-Carboniferous sediments are important hydrocarbon exploration targets. These reservoir rocks sometimes overlie mature source rocks and are capped by shales, marls, and tight carbonates. Significant quantities of hydrocarbons are contained in these reservoirs in different parts of the Greater Arabian basin.

  15. Integrating parasitology and marine ecology: Seven challenges towards greater synergy

    NASA Astrophysics Data System (ADS)

    Poulin, Robert; Blasco-Costa, Isabel; Randhawa, Haseeb S.

    2016-07-01

    Despite their very different historical origins as scientific disciplines, parasitology and marine ecology have already combined successfully to make important contributions to our understanding of the functioning of natural ecosystems. For example, robust assessments of the contribution of parasites to ecosystem biomass and energetics, and of their impact on community-wide biodiversity and food web structure, have all been made for the first time in marine systems. Nevertheless, for the marriage between parasitology and marine ecology to remain fruitful, several challenges must first be overcome. We discuss seven such challenges on the road to a greater synergy between these disciplines: (1) Raising awareness of parasitism as an ecological force by increasing the proportion of articles about parasites and diseases in marine ecology journals; (2) Making greater use of theory and conceptual frameworks from marine ecology to guide parasitological research; (3) Speeding up or at least maintaining the current rate at which marine parasites are found and described; (4) Elucidating a greater proportion of life cycles in all major groups of marine parasites; (5) Increasing the number of host-parasite model systems on which our knowledge is based; (6) Extending parasitological research offshore and into ocean depths; and (7) Developing, as needed, new epidemiological theory and transmission models for the marine environment. None of these challenges is insurmountable, and addressing just a few of them should guarantee that parasitology and marine ecology will continue to join forces and make further substantial contributions.

  16. Formation of inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate from inositol 1,3,4,5-tetrakisphosphate and their pathways of degradation in RBL-2H3 cells

    SciTech Connect

    Cunha-Melo, J.R.; Dean, N.M.; Ali, H.; Beaven, M.A.

    1988-10-05

    Previous studies with antigen-stimulated rat basophilic leukemia (RBL-2H3) cells indicated the formation of multiple isomers of each of the various categories of inositol phosphates. The identities of the different isomers have been elucidated by selective labeling of (3H)inositol 1,3,4,5-tetrakisphosphate with (32P)phosphate in the 3'-or 4',5'-positions and by following the metabolism of different radiolabeled inositol phosphates in extracts of RBL-2H3 cells. We report here that inositol 1,3,4,5-tetrakisphosphate, when incubated with the membrane fraction of extracts of RBL-2H3 cells, was converted to inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate. Further dephosphorylation of the inositol polyphosphates proceeded rapidly in whole extracts of cells, although the process was significantly retarded when ATP (2 mM) levels were maintained by an ATP-regenerating system. The degradation of inositol 1,4,5-trisphosphate proceeded with the sequential formation of inositol 1,4-bisphosphate, the inositol 4-monophosphate (with smaller amounts of the 1-monophosphate), and finally inositol. Inositol 1,3,4-trisphosphate, on the other hand, was converted to inositol 1,3-bisphosphate and inositol 3,4-bisphosphate and subsequently to inositol 4-monophosphate and inositol 1-monophosphate (stereoisomeric forms were undetermined). The possible implications of the apparent interconversion between inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate in regulating histamine secretion in the RBL-2H3 cells are discussed.

  17. Near-IR electrochromism in electropolymerized films of a biscyclometalated ruthenium complex bridged by 1,2,4,5-tetra(2-pyridyl)benzene.

    PubMed

    Yao, Chang-Jiang; Zhong, Yu-Wu; Nie, Hai-Jing; Abruña, Héctor D; Yao, Jiannian

    2011-12-28

    Reductive electropolymerization of the biscyclometalated ruthenium complex [(vtpy)Ru(tpb)Ru(vtpy)](2+) [vtpy = 4'-vinyl-2,2':6',2″-terpyridine; tpb = 1,2,4,5-tetra(2-pyridyl)benzene] proceeded smoothly on electrode surfaces. Thanks to the strong electron coupling between the ruthenium centers of the individual monomeric units and strong intervalence charge-transfer absorption in the mixed valence state, the produced adherent metallopolymeric films exhibited near-IR electrochromism with tricolor switching, good contrast ratio (40% at 1165 nm), short response time, low-switching voltage, and long memory time. PMID:22133035

  18. Paleo- and Environmental Magnetic Record of U1396: a 4.5Myr Record from the Caribbean Sea

    NASA Astrophysics Data System (ADS)

    Hatfield, R. G.; Stoner, J. S.

    2014-12-01

    Long continuous paleomagnetic records provide unique insights into the evolution of the geomagnetic field. Sediments recovered from IODP Site U1396 (16.51°N, 62.45°W) contain a 140 m sequence of hemiplegic sediment and intercalated tephra related to the evolution of the Lesser Antilles volcanic arc. Shipboard measurements of the NRM demagnetized at 20mT documented 17 polarity reversals dating back ~4.5Myrs with magnetic susceptibility (MS) efficient at identifying the visible tephra. These initial results suggested Site U1396 presents a rare, low-latitude, sedimentary magnetic record stretching back into the Gilbert chron. After developing a composite depth scale for the site, we sampled the continuous splice with u-channels to improve the 2.5cm shipboard resolution. Centimeter scale u-channel measurements of MS, NRM AF demagnetized in 12 steps between 20-80mT, and ARM were accompanied by hysteresis measurements of discrete samples to assess lithologic variability, establish the magnetic carriers and quality of the geomagnetic signal, refine the shipboard magneto-stratigraphic reversal record, and derive an estimate for relative paleointensity (RPI). Magnetic mineralogy is dominated by PSD-MD size ferrimagnetic minerals and MS efficiently discriminates sub-cm scale tephra that can drive lithologic variances in the NRM from the carbonate dominated hemipelagic sediment. Maximum angular deviation (MAD) values range from < 1° to > 40° in volcanogenic deposits, though 5-10° are more representative of hemipelagic intervals whose average values are lower in the Pliocene than the Pleistocene. Inclination varies around GAD predictions for both polarities which alongside azimuthally orientated declination establishes the refined reversal based age model. Pliocene sedimentation rates (~4 cm ky-1) are twice that of the Pleistocene and MS reveals a greater Pliocene eruption frequency potentially identifying a behavioral change in the volcanic history of the arc. The NRM

  19. ULF waves and radiation belts: earthward penetration of Pc 4-5 waves and energetic electron flux enhancements during geospace magnetic storms

    NASA Astrophysics Data System (ADS)

    Georgiou, Marina; Daglis, Ioannis; Zesta, Eftyhia; Balasis, George; Tsinganos, Kanaris

    2013-04-01

    Energetic particle fluxes in the outer radiation belt can vary over orders of magnitude on time scales ranging from minutes, to days and years. Geospace magnetic storms when sufficiently strong to exceed key thresholds of the Dst index may either increase or decrease the fluxes of energetic electrons. We examine the responses of energetic electrons to nine moderate, intense and weak magnetic storms, which occurred at different phases of the solar cycle, and compare these with concurrent variations of ULF wave power. Pc 4-5 waves with frequencies in the range of a few mHz may be generated internally in the magnetosphere by low frequency instabilities of ring current ions and externally by shear instabilities at the magnetopause flanks, or compressive variations in the solar wind. Here, we present multipoint observations from ground-based magnetometer arrays collocated with electron drift orbits, which are complemented and measurements by conjugate multi-point satellites, such as CHAMP, Cluster, GOES and THEMIS. We discuss the excitation, growth and decay characteristics of Pc 4-5 waves during the different phases of the magnetic storms with particular emphasis on the distribution of Pc 4-5 wave power over a variety of L shells. We investigate whether Pc 4-5 wave power penetrates to lower L shell values during periods of relatively intense geomagnetic activity as compared to weak magnetic storms. Structural changes of the magnetosphere during intense geomagnetic storms can play an important role in the generation and penetration of Pc 4-5 waves deep into the inner magnetosphere, which in turn is of significance for the wave-particle interactions contributing to the acceleration, transport and loss of electrons in the outer radiation belt. We present preliminary statistics of Pc 4-5 waves observed during magnetic storms of varying intensity, which occurred over the course of the previous solar cycle. This work is supported by the European Community's Seventh Framework

  20. The environmental impact of 4(5)-methylbenzotriazole from aircraft deicing operations

    NASA Astrophysics Data System (ADS)

    Cornell, Jeffrey Scott

    2002-01-01

    Hundreds of millions of gallons of aircraft deicer fluid (ADF) are applied to aircraft and runway surfaces annually. Recently public and regulatory attention has forced the air transport industry and military aviation community to examine the environmental impacts of aircraft deicing operations (ADOs), and to seek a balance between flight safety and environmental impact. Little data exists which is useful to evaluate the impact of ADF additives. 4(5)-methylbenzotriazole (MeBT) is used in a variety of industrial and commercial fluids to inhibit metal corrosion; it is a standard additive to most common ADF (approx. 0.5%). This MeBT component is actually a mixture of two isomers: 4-methylbenzotriazole (4-MeBT) and 5-methylbenzotriazole (5-MeBT). A significant amount of MeBT enters the natural environment through aircraft deicing operations. Research was conducted to address important data gaps impacting the ability to assess the environmental impact of MeBT and ADOs. Matrixed toxicity studies were conducted to determine the effect of different additives on ADF ecotoxicity. Aerobic liquid batch-fed microcosms were employed to investigate how MeBT affects the toxicity of wastewater containing ADF, describe how MeBT affects the aerobic biodegradation of propylene glycol (PG), and determine the biodegradability of MeBT. Field samples from contaminated areas were collected and analyzed for comparison. Cell energy production and electron transport assays were conducted to determine if MeBT was capable of disrupting oxidative phosphorylation via uncoupling, as its chemical structure would suggest. MicrotoxRTM studies indicated MeBT was toxic to test bacteria below 10 mg/L. C. dubia and P. promelas , however, were less sensitive to MeBT than bacteria but more sensitive to other ADF additives. The effect of MeBT on PG biodegradation was complex and concentration-dependent. Cell yield and PG biodegradation rates generally decreased with increasing reactor MeBT concentration

  1. Bimodal regulation of an Elk subfamily K+ channel by phosphatidylinositol 4,5-bisphosphate

    PubMed Central

    Li, Xiaofan; Anishkin, Andriy; Liu, Hansi; van Rossum, Damian B.; Chintapalli, Sree V.; Sassic, Jessica K.; Gallegos, David; Pivaroff-Ward, Kendra

    2015-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) regulates Shaker K+ channels and voltage-gated Ca2+ channels in a bimodal fashion by inhibiting voltage activation while stabilizing open channels. Bimodal regulation is conserved in hyperpolarization-activated cyclic nucleotide–gated (HCN) channels, but voltage activation is enhanced while the open channel state is destabilized. The proposed sites of PIP2 regulation in these channels include the voltage-sensor domain (VSD) and conserved regions of the proximal cytoplasmic C terminus. Relatively little is known about PIP2 regulation of Ether-á-go-go (EAG) channels, a metazoan-specific family of K+ channels that includes three gene subfamilies, Eag (Kv10), Erg (Kv11), and Elk (Kv12). We examined PIP2 regulation of the Elk subfamily potassium channel human Elk1 to determine whether bimodal regulation is conserved within the EAG K+ channel family. Open-state stabilization by PIP2 has been observed in human Erg1, but the proposed site of regulation in the distal C terminus is not conserved among EAG family channels. We show that PIP2 strongly inhibits voltage activation of Elk1 but also stabilizes the open state. This stabilization produces slow deactivation and a mode shift in voltage gating after activation. However, removal of PIP2 has the net effect of enhancing Elk1 activation. R347 in the linker between the VSD and pore (S4–S5 linker) and R479 near the S6 activation gate are required for PIP2 to inhibit voltage activation. The ability of PIP2 to stabilize the open state also requires these residues, suggesting an overlap in sites central to the opposing effects of PIP2 on channel gating. Open-state stabilization in Elk1 requires the N-terminal eag domain (PAS domain + Cap), and PIP2-dependent stabilization is enhanced by a conserved basic residue (K5) in the Cap. Our data shows that PIP2 can bimodally regulate voltage gating in EAG family channels, as has been proposed for Shaker and HCN channels. PIP2 regulation

  2. Gas Phase Chromatography of some Group 4, 5, and 6 Halides

    SciTech Connect

    Sylwester, Eric Robert

    1998-10-01

    Gas phase chromatography using The Heavy Element Volatility Instrument (HEVI) and the On Line Gas Apparatus (OLGA III) was used to determine volatilities of ZrBr{sub 4}, HfBr{sub 4}, RfBr{sub 4}, NbBr{sub 5}, TaOBr{sub 3}, HaCl{sub 5}, WBr{sub 6}, FrBr, and BiBr{sub 3}. Short-lived isotopes of Zr, Hf, Rf, Nb, Ta, Ha, W, and Bi were produced via compound nucleus reactions at the 88-Inch Cyclotron at Lawrence Berkeley National Laboratory and transported to the experimental apparatus using a He gas transport system. The isotopes were halogenated, separated from the other reaction products, and their volatilities determined by isothermal gas phase chromatography. Adsorption Enthalpy ({Delta}H{sub a}) values for these compounds were calculated using a Monte Carlo simulation program modeling the gas phase chromatography column. All bromides showed lower volatility than molecules of similar molecular structures formed as chlorides, but followed similar trends by central element. Tantalum was observed to form the oxybromide, analogous to the formation of the oxychloride under the same conditions. For the group 4 elements, the following order in volatility and {Delta}H{sub a} was observed: RfBr{sub 4} > ZrBr{sub 4} > HfBr{sub 4}. The {Delta}H{sub a} values determined for the group 4, 5, and 6 halides are in general agreement with other experimental data and theoretical predictions. Preliminary experiments were performed on Me-bromides. A new measurement of the half-life of {sup 261}Rf was performed. {sup 261}Rf was produced via the {sup 248}Cm({sup 18}O, 5n) reaction and observed with a half-life of 74{sub -6}{sup +7} seconds, in excellent agreement with the previous measurement of 78{sub -6}{sup +11} seconds. We recommend a new half-life of 75{+-}7 seconds for {sup 261}Rf based on these two measurements. Preliminary studies in transforming HEVI from an isothermal (constant temperature) gas phase chromatography instrument to a thermochromatographic (variable temperature

  3. Probing the regulation of TASK potassium channels by PI(4,5)P2 with switchable phosphoinositide phosphatases

    PubMed Central

    Lindner, Moritz; Leitner, Michael G; Halaszovich, Christian R; Hammond, Gerald R V; Oliver, Dominik

    2011-01-01

    Abstract TASK channels are background K+ channels that contribute to the resting conductance in many neurons. A key feature of TASK channels is the reversible inhibition by Gq-coupled receptors, thereby mediating the dynamic regulation of neuronal activity by modulatory transmitters. The mechanism that mediates channel inhibition is not fully understood. While it is clear that activation of Gαq is required, the immediate signal for channel closure remains controversial. Experimental evidence pointed to either phospholipase C (PLC)-mediated depletion of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) as the cause for channel closure or to a direct inhibitory interaction of active Gαq with the channel. Here, we address the role of PI(4,5)P2 for G-protein-coupled receptor (GPCR)-mediated TASK inhibition by using recently developed genetically encoded tools to alter phosphoinositide (PI) concentrations in the living cell. When expressed in CHO cells, TASK-1- and TASK-3-mediated currents were not affected by depletion of plasma membrane PI(4,5)P2 either via the voltage-activated phosphatase Ci-VSP or via chemically triggered recruitment of a PI(4,5)P2-5′-phosphatase. Depletion of both PI(4,5)P2 and PI(4)P via membrane recruitment of a novel engineered dual-specificity phosphatase also did not inhibit TASK currents. In contrast, each of these methods produced robust inhibition of the bona fide PI(4,5)P2-dependent channel KCNQ4. Efficient depletion of PI(4,5)P2 and PI(4)P was further confirmed with a fluorescent phosphoinositide sensor. Moreover, TASK channels recovered normally from inhibition by co-expressed muscarinic M1 receptors when resynthesis of PI(4,5)P2 was prevented by depletion of cellular ATP. These results demonstrate that TASK channel activity is independent of phosphoinositide concentrations within the physiological range. Consequently, Gq-mediated inhibition of TASK channels is not mediated by depletion of PI(4,5)P2. PMID:21540350

  4. Learning curves of percutaneous endoscopic lumbar discectomy in transforaminal approach at the L4/5 and L5/S1 levels: a comparative study

    PubMed Central

    Wu, Xin-bo; Fan, Guo-xin; Gu, Xin; Shen, Tu-gang; Guan, Xiao-fei; Hu, An-nan; Zhang, Hai-long; He, Shi-sheng

    2016-01-01

    Objectives: This study aimed to compare the learning curves of percutaneous endoscopic lumbar discectomy (PELD) in a transforaminal approach at the L4/5 and L5/S1 levels. Methods: We retrospectively reviewed the first 60 cases at the L4/5 level (Group I) and the first 60 cases at the L5/S1 level (Group II) of PELD performed by one spine surgeon. The patients were divided into subgroups A, B, and C (Group I: A cases 1–20, B cases 21–40, C cases 41–60; Group II: A cases 1–20, B cases 21–40, C cases 41–60). Operation time was thoroughly analyzed. Results: Compared with the L4/5 level, the learning curve of transforaminal PELD at the L5/S1 level was flatter. The mean operation times of Groups IA, IB, and IC were (88.75±17.02), (67.75±6.16), and (64.85±7.82) min, respectively. There was a significant difference between Groups A and B (P<0.05), but no significant difference between Groups B and C (P=0.20). The mean operation times of Groups IIA, IIB, and IIC were (117.25±13.62), (109.50±11.20), and (92.15±11.94) min, respectively. There was no significant difference between Groups A and B (P=0.06), but there was a significant difference between Groups B and C (P<0.05). There were 6 cases of postoperative dysesthesia (POD) in Group I and 2 cases in Group IIA (P=0.27). There were 2 cases of residual disc in Group I, and 4 cases in Group II (P=0.67). There were 3 cases of recurrence in Group I, and 2 cases in Group II (P>0.05). Conclusions: Compared with the L5/S1 level, the learning curve of PELD in a transforaminal approach at the L4/5 level was steeper, suggesting that the L4/5 level might be easier to master after short-term professional training. PMID:27381732

  5. 3.6 AND 4.5 {mu}m PHASE CURVES AND EVIDENCE FOR NON-EQUILIBRIUM CHEMISTRY IN THE ATMOSPHERE OF EXTRASOLAR PLANET HD 189733b

    SciTech Connect

    Knutson, Heather A.; Lewis, Nikole; Showman, Adam P.; Fortney, Jonathan J.; Laughlin, Gregory; Burrows, Adam; Cowan, Nicolas B.; Agol, Eric; Aigrain, Suzanne; Charbonneau, David; Desert, Jean-Michel; Deming, Drake; Henry, Gregory W.; Langton, Jonathan

    2012-07-20

    We present new, full-orbit observations of the infrared phase variations of the canonical hot Jupiter HD 189733b obtained in the 3.6 and 4.5 {mu}m bands using the Spitzer Space Telescope. When combined with previous phase curve observations at 8.0 and 24 {mu}m, these data allow us to characterize the exoplanet's emission spectrum as a function of planetary longitude and to search for local variations in its vertical thermal profile and atmospheric composition. We utilize an improved method for removing the effects of intrapixel sensitivity variations and robustly extracting phase curve signals from these data, and we calculate our best-fit parameters and uncertainties using a wavelet-based Markov Chain Monte Carlo analysis that accounts for the presence of time-correlated noise in our data. We measure a phase curve amplitude of 0.1242% {+-} 0.0061% in the 3.6 {mu}m band and 0.0982% {+-} 0.0089% in the 4.5 {mu}m band, corresponding to brightness temperature contrasts of 503 {+-} 21 K and 264 {+-} 24 K, respectively. We find that the times of minimum and maximum flux occur several hours earlier than predicted for an atmosphere in radiative equilibrium, consistent with the eastward advection of gas by an equatorial super-rotating jet. The locations of the flux minima in our new data differ from our previous observations at 8 {mu}m, and we present new evidence indicating that the flux minimum observed in the 8 {mu}m is likely caused by an overshooting effect in the 8 {mu}m array. We obtain improved estimates for HD 189733b's dayside planet-star flux ratio of 0.1466% {+-} 0.0040% in the 3.6 {mu}m band and 0.1787% {+-} 0.0038% in the 4.5 {mu}m band, corresponding to brightness temperatures of 1328 {+-} 11 K and 1192 {+-} 9 K, respectively; these are the most accurate secondary eclipse depths obtained to date for an extrasolar planet. We compare our new dayside and nightside spectra for HD 189733b to the predictions of one-dimensional radiative transfer models from

  6. The Carnegie Hubble Program: The Leavitt Law at 3.6 microns and 4.5 microns in the Large Magellanic Cloud

    NASA Technical Reports Server (NTRS)

    Scowcroft, Victoria; Freedman, Wendy L.; Madore, Barry F.; Monson, Andrew J.; Persson, S. E.; Seibert, Mark; Rigby, Jane R.; Sturch, Laura

    2011-01-01

    The Carnegie Hubble Program (CHP) is designed to improve the extragalactic distance scale using data from the post-cryogenic era of Spitzer. The ultimate goal is a determination of the Hubble constant to an accuracy of 2%. This paper is the first in a series on the Cepheid population of the Large Magellanic Cloud, and focuses on the period-luminosity relations (Leavitt laws) that will be used, in conjunction with observations of Milky Way Cepheids, to set the slope and zero-point of the Cepheid distance scale in the mid-infrared. To this end, we have obtained uniformly-sampled light curves for 85 LMC Cepheids, having periods between 6 and 140 days. Period- luminosity and period-color relations are presented in the 3.6 micron and 4.5 micron bands. We demonstrate that the 3.6 micron band is a superb distance indicator. The cyclical variation of the [3.6]-[4.5] color has been measured for the first time. We attribute the amplitude and phase of the color curves to the dissociation and recombination of CO molecules in the Cepheid s atmosphere. The CO affects only the 4.5 micron flux making it a potential metallicity indicator.

  7. THE CARNEGIE HUBBLE PROGRAM: THE LEAVITT LAW AT 3.6 {mu}m AND 4.5 {mu}m IN THE LARGE MAGELLANIC CLOUD

    SciTech Connect

    Scowcroft, Victoria; Freedman, Wendy L.; Madore, Barry F.; Monson, Andrew J.; Persson, S. E.; Seibert, Mark; Rigby, Jane R.; Sturch, Laura E-mail: wendy@obs.carnegiescience.edu E-mail: amonson@obs.carnegiescience.edu E-mail: mseibert@obs.carnegiescience.edu E-mail: lsturch@bu.edu

    2011-12-10

    The Carnegie Hubble Program is designed to improve the extragalactic distance scale using data from the post-cryogenic era of Spitzer. The ultimate goal is a determination of the Hubble constant to an accuracy of 2%. This paper is the first in a series on the Cepheid population of the Large Magellanic Cloud, and focusses on the period-luminosity (PL) relations (Leavitt laws) that will be used, in conjunction with observations of Milky Way Cepheids, to set the slope and zero point of the Cepheid distance scale in the mid-infrared. To this end, we have obtained uniformly sampled light curves for 85 LMC Cepheids, having periods between 6 and 140 days. PL and period-color relations are presented in the 3.6 {mu}m and 4.5 {mu}m bands. We demonstrate that the 3.6 {mu}m band is a superb distance indicator. The cyclical variation of the [3.6]-[4.5] color has been measured for the first time. We attribute the amplitude and phase of the color curves to the dissociation and recombination of CO molecules in the Cepheid's atmosphere. The CO affects only the 4.5 {mu}m flux making it a potential metallicity indicator.

  8. Regulation of autophagy in cardiomyocytes by Ins(1,4,5)P(3) and IP(3)-receptors.

    PubMed

    Wong, Albert; Grubb, David R; Cooley, Nicola; Luo, Jieting; Woodcock, Elizabeth A

    2013-01-01

    Autophagy is a process that removes damaged proteins and organelles and is of particular importance in terminally differentiated cells such as cardiomyocytes, where it has primarily a protective role. We investigated the involvement of inositol(1,4,5)trisphosphate (Ins(1,4,5)P(3)) and its receptors in autophagic responses in neonatal rat ventricular myocytes (NRVM). Treatment with the IP(3)-receptor (IP(3)-R) antagonist 2-aminoethoxydiphenyl borate (2-APB) at 5 or 20 μmol/L resulted in an increase in autophagosome content, defined as puncta labeled by antibody to microtubule associated light chain 3 (LC3). 2-APB also increased autophagic flux, indicated by heightened LC3II accumulation, which was further enhanced by bafilomycin (10nmol/L). Expression of Ins(1,4,5)P(3) 5-phosphatase (IP(3)-5-Pase) to deplete Ins(1,4,5)P(3) also increased LC3-labeled puncta and LC3II content, suggesting that Ins(1,4,5)P(3) inhibits autophagy. The IP(3)-R can act as an inhibitory scaffold sequestering the autophagic effector, beclin-1 to its ligand binding domain (LBD). Expression of GFP-IP(3)-R-LBD inhibited autophagic signaling and furthermore, beclin-1 co-immunoprecipitated with the IP(3)-R-LBD. A mutant GFP-IP(3)-R-LBD with reduced ability to bind Ins(1,4,5)P(3) bound beclin-1 and inhibited autophagy similarly to the wild type sequence. These data provide evidence that Ins(1,4,5)P(3) and IP(3)-R act as inhibitors of autophagic responses in cardiomyocytes. By suppressing autophagy, IP(3)-R may contribute to cardiac pathology. PMID:23137780

  9. Synthesis, spectral characterization, single crystal X-ray diffraction and DFT studies of 4-((2,4,5-triphenyl-1H-imidazol-1-yl)methyl)pyridine derivatives

    NASA Astrophysics Data System (ADS)

    Rajkumar, R.; Kamaraj, A.; Bharanidharan, S.; Saleem, H.; Krishnasamy, K.

    2015-03-01

    We have synthesized a series of novel 4-((2,4,5-triphenyl-1H-imidazol-1-yl)methyl)pyridine derivatives. The structures of these compounds were confirmed by IR, HR-MS, 1H and 13C NMR spectra. The compound 5g was also confirmed by single crystal XRD. The geometry of the synthesized compounds 5a-5g were examined by density functional theory (DFT) method at B3LYP/6-31G(d,p) level. The optimized geometrical parameters obtained by DFT calculation are in good agreement with single crystal XRD data. The HOMO-LUMO energies describes charge transfer takes place within the molecule. Furthermore, Mulliken and NBO charges were also calculated. The stability and charge delocalization of the molecule were also studied by natural bond orbital (NBO) analysis. Compound 5g exhibited good non linear optical activity and was 20 times greater than that of urea. In addition, molecular electrostatic potential map (MEP) was studied for predicting the reactive sites.

  10. Greater Burgan of Kuwait: world's second largest oil field

    SciTech Connect

    Youash, Y.Y.

    1989-03-01

    Greater Burgan (Main burgan, Magwa, and Ahmadi) field is located in the Arabian Platform geologic province and the stable shelf tectonic environment of the Mesopotamian geosyncline, a sedimentary basin extending from the Arabian shield on the west to the complexly folded and faulted Zagros Mountains on the east. The structural development in Cretaceous time represents a major anticlinorium bounded by a basin to the west and a synclinorium to the east. Greater Burgan is located within this anticlinorium. The field consists of three dome structures 25 km wide and 65 km long with gentle dips of only few degrees. Faults have little throw and did not contribute to the trapping mechanism. The structural deformation may have been caused by halokinetic movements and most likely by basement block faulting that may have started in the Paleozoic. Greater Burgan was discovered in 1938. All production during the last 40 years has been by its natural pressure. Although natural gas injection has been carried out for some time, no waterflooding has been initiated yet. Recoverable reserves of the field are 87 billion bbl of oil. During the last 5 years giant reserves have been added in this field from the deeper strata of Jurassic age. Several deep wells have been drilled to the Permian for the purpose of discovering gas. So far, no Permian gas has been found in Kuwait. The Permian is 25,000 ft deep, and it is unlikely gas will be found there in the future. However, the potential of the Jurassic reservoirs will be a major target in the future. Also, there is a great possibility of discovering oil in stratigraphic traps, as several producing strata in the nearby fields pinch out on the flanks of this giant structure. Enhanced oil recovery should add significant reserves in the future.

  11. Synthesis, structure and antimicrobial evaluation of new 3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl-thiazol-4(5H)-ones

    NASA Astrophysics Data System (ADS)

    Gautam, Deepika; Chaudhary, R. P.

    2015-01-01

    The reaction of semicarbazide or thiosemicarbazide with 2-arylidene-1-tetralones under alkaline condition affords 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbo(thio)amides as a mixture of cis and trans diastereoisomers of 3-H and 3a-H. The synthesis of new indazolyl-thiazol-4(5H)-ones from the condensation of cis isomer and α-halo acids is reported. A DFT study along with X-ray single crystal data of a representative compound is presented. All the eight newly synthesised indazolyl-thiazol-4(5H)-ones were screened for their antibacterial and antifungal activities and some compounds have shown promising activities.

  12. Synthesis, structure and antimicrobial evaluation of new 3,3a,4,5-tetrahydro-2H-benzo[g]indazol-2-yl-thiazol-4(5H)-ones.

    PubMed

    Gautam, Deepika; Chaudhary, R P

    2015-01-25

    The reaction of semicarbazide or thiosemicarbazide with 2-arylidene-1-tetralones under alkaline condition affords 3,3a,4,5-tetrahydro-2H-benzo[g]indazole-2-carbo(thio)amides as a mixture of cis and trans diastereoisomers of 3-H and 3a-H. The synthesis of new indazolyl-thiazol-4(5H)-ones from the condensation of cis isomer and α-halo acids is reported. A DFT study along with X-ray single crystal data of a representative compound is presented. All the eight newly synthesised indazolyl-thiazol-4(5H)-ones were screened for their antibacterial and antifungal activities and some compounds have shown promising activities. PMID:25064506

  13. Prevalence and Characterization of Monophasic Salmonella Serovar 1,4,[5],12:i:- of Food Origin in China

    PubMed Central

    Yang, Xiaojuan; Wu, Qingping; Zhang, Jumei; Huang, Jiahui; Guo, Weipeng; Cai, Shuzhen

    2015-01-01

    Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:- is a monophasic variant of Salmonella Typhimurium, which has recently been recognized as an emerging cause of infection worldwide. This bacterium has also ranked among the four most frequent serovars causing human salmonellosis in China. However, there are no reports on its contamination in Chinese food. Serotyping, polymerase chain reaction, antibiotic resistance, virulotyping, and multilocus sequence typing (MLST) assays were used to investigate the prevalence of this serological variant in food products in China, and to determine phenotypic and genotypic difference of monophasic isolates and Salmonella Typhimurium isolated over the same period. Salmonella 1,4,[5],12:i:- was prevalent in various food sources, including beef, pork, chicken, and pigeon. The study also confirmed the high prevalence (53.8%) of resistance to ampicillin, streptomycin, sulfonamides, and tetracycline in Salmonella 1,4,[5],12:i:-, which was higher than that in Salmonella Typhimurium. Moreover, Salmonella 1,4,[5],12:i:- isolates in our study were different from Salmonella Typhimurium isolates by the absence of three plasmid-borne genes (spvC, pefA, and rck) and the presence of gipA in all isolates. All Salmonella 1,4,[5],12:i:- isolates demonstrated MLST pattern ST34. Genomic deletions within the fljBA operon and surrounding genes were only found in Salmonella 1,4,[5],12:i:- isolates, with all isolates containing a deletion of fljB. However, hin and iroB were identified in all Salmonella 1,4,[5],12:i:- isolates. Three different deletion profiles were observed and two of them were different from the reported Salmonella 1,4,[5],12:i:- clones from Spain, America, and Italy, which provided some new evidence on the independent evolution of the multiple successful monophasic clones from Salmonella Typhimurium ancestors. This study is the first report of Salmonella 1,4,[5],12:i:- in food products from China. The data are more

  14. Prevalence and Characterization of Monophasic Salmonella Serovar 1,4,[5],12:i:- of Food Origin in China.

    PubMed

    Yang, Xiaojuan; Wu, Qingping; Zhang, Jumei; Huang, Jiahui; Guo, Weipeng; Cai, Shuzhen

    2015-01-01

    Salmonella enterica subsp. enterica serovar 1,4,[5],12:i:- is a monophasic variant of Salmonella Typhimurium, which has recently been recognized as an emerging cause of infection worldwide. This bacterium has also ranked among the four most frequent serovars causing human salmonellosis in China. However, there are no reports on its contamination in Chinese food. Serotyping, polymerase chain reaction, antibiotic resistance, virulotyping, and multilocus sequence typing (MLST) assays were used to investigate the prevalence of this serological variant in food products in China, and to determine phenotypic and genotypic difference of monophasic isolates and Salmonella Typhimurium isolated over the same period. Salmonella 1,4,[5],12:i:- was prevalent in various food sources, including beef, pork, chicken, and pigeon. The study also confirmed the high prevalence (53.8%) of resistance to ampicillin, streptomycin, sulfonamides, and tetracycline in Salmonella 1,4,[5],12:i:-, which was higher than that in Salmonella Typhimurium. Moreover, Salmonella 1,4,[5],12:i:- isolates in our study were different from Salmonella Typhimurium isolates by the absence of three plasmid-borne genes (spvC, pefA, and rck) and the presence of gipA in all isolates. All Salmonella 1,4,[5],12:i:- isolates demonstrated MLST pattern ST34. Genomic deletions within the fljBA operon and surrounding genes were only found in Salmonella 1,4,[5],12:i:- isolates, with all isolates containing a deletion of fljB. However, hin and iroB were identified in all Salmonella 1,4,[5],12:i:- isolates. Three different deletion profiles were observed and two of them were different from the reported Salmonella 1,4,[5],12:i:- clones from Spain, America, and Italy, which provided some new evidence on the independent evolution of the multiple successful monophasic clones from Salmonella Typhimurium ancestors. This study is the first report of Salmonella 1,4,[5],12:i:- in food products from China. The data are more

  15. Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phosphatidylinositol 4,5-bisphosphate

    PubMed Central

    Gerber, Pehuén Pereyra; Cabrini, Mercedes; Jancic, Carolina; Paoletti, Luciana; Banchio, Claudia; von Bilderling, Catalina; Sigaut, Lorena; Pietrasanta, Lía I.; Duette, Gabriel; Freed, Eric O.; de Saint Basile, Genevieve; Moita, Catarina Ferreira; Moita, Luis Ferreira; Amigorena, Sebastian; Benaroch, Philippe; Geffner, Jorge

    2015-01-01

    During the late stages of the HIV-1 replication cycle, the viral polyprotein Pr55Gag is recruited to the plasma membrane (PM), where it binds phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and directs HIV-1 assembly. We show that Rab27a controls the trafficking of late endosomes carrying phosphatidylinositol 4-kinase type 2 α (PI4KIIα) toward the PM of CD4+ T cells. Hence, Rab27a promotes high levels of PM phosphatidylinositol 4-phosphate and the localized production of PI(4,5)P2, therefore controlling Pr55Gag membrane association. Rab27a also controls PI(4,5)P2 levels at the virus-containing compartments of macrophages. By screening Rab27a effectors, we identified that Slp2a, Slp3, and Slac2b are required for the association of Pr55Gag with the PM and that Slp2a cooperates with Rab27a in the recruitment of PI4KIIα to the PM. We conclude that by directing the trafficking of PI4KIIα-positive endosomes toward the PM, Rab27a controls PI(4,5)P2 production and, consequently, HIV-1 replication. PMID:25940347

  16. Role of Phosphatidylinositol(4,5)bisphosphate Organization in Membrane Transport by the Unc104 Kinesin Motor

    PubMed Central

    Klopfenstein, Dieter R.; Tomishige, Michio; Stuurman, Nico; Vale, Ronald D.

    2010-01-01

    Summary Unc104 (KIF1A) kinesin transports membrane vesicles along microtubules in lower and higher eukaryotes. Using an in vitro motility assay, we show that Unc104 uses a lipid binding pleckstrin homology (PH) domain to dock onto membrane cargo. Through its PH domain, Unc104 can transport phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P2)-containing liposomes with similar properties to native vesicles. Interestingly, liposome movement by monomeric Unc104 motors shows a very steep dependence on PtdIns(4,5)P2 concentration (Hill coefficient of ~20), even though liposome binding is noncooperative. This switch-like transition for movement can be shifted to lower PtdIns(4,5)P2 concentrations by the addition of cholesterol/sphingomyelin or GM1 ganglioside/cholera toxin, conditions that produce raft-like behavior of Unc104 bound to lipid bilayers. These studies suggest that clustering of Unc104 in PtdIns(4,5)P2-containing rafts provides a trigger for membrane transport. PMID:12015984

  17. Formation of persistent organic pollutants from 2,4,5-trichlorothiophenol combustion: a density functional theory investigation.

    PubMed

    Dar, Tajwar; Shah, Kalpit; Moghtaderi, Behdad; Page, Alister J

    2016-06-01

    Polychlorinated dibenzothiophene (PCDT) and polychlorinated thianthrene (PCTA) are sulfur analogues of dioxins, such as polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/F). In this work, we present a detailed mechanistic and kinetic analysis of PCDT and PCTA formation from the combustion of 2,4,5-trichlorothiophenol. It is shown that the formation of these persistent organic pollutants is more favourable, both kinetically and thermodynamically, than their analogous dioxin counterparts. This is rationalised in terms of the different influences of the S-H and O-H moieties in the 2,4,5-trichlorothiophenol and 2,4,5-trichlorophenol precursors. Kinetic parameters also indicate that the yield of PCDT should exceed that of PCDD. Finally, we demonstrate here that the degree and pattern of chlorination on the 2,4,5-trichlorothiophenol precursor leads to subtle thermodynamic and kinetic changes to the PCDT/PCTA formation mechanisms. Graphical abstract Formation mechanisms of persistant organic pollutants, PCDT and PCTA, from 2,4,5-trichlorothiophenol combustion, has been investigated using density functional theory. PMID:27179803

  18. Reduced phosphatidylinositol 4,5-bisphosphate synthesis impairs inner ear Ca2+ signaling and high-frequency hearing acquisition

    PubMed Central

    Rodriguez, Laura; Simeonato, Elena; Scimemi, Pietro; Anselmi, Fabio; Calì, Bianca; Crispino, Giulia; Ciubotaru, Catalin D.; Bortolozzi, Mario; Ramirez, Fabian Galindo; Majumder, Paromita; Arslan, Edoardo; De Camilli, Pietro; Pozzan, Tullio; Mammano, Fabio

    2012-01-01

    Phosphatidylinositol phosphate kinase type 1γ (PIPKIγ) is a key enzyme in the generation of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and is expressed at high levels in the nervous system. Homozygous knockout mice lacking this enzyme die postnatally within 24 h, whereas PIPKIγ+/− siblings breed normally and have no reported phenotype. Here we show that adult PIPKIγ+/− mice have dramatically elevated hearing thresholds for high-frequency sounds. During the first postnatal week we observed a reduction of ATP-dependent Ca2+ signaling activity in cochlear nonsensory cells. Because Ca2+ signaling under these conditions depends on inositol-1,4,5-trisphosphate generation from phospholipase C (PLC)-dependent hydrolysis of PI(4,5)P2, we conclude that (i) PIPKIγ is primarily responsible for the synthesis of the receptor-regulated PLC-sensitive PI(4,5)P2 pool in the cell syncytia that supports auditory hair cells; (ii) spatially graded impairment of this signaling pathway in cochlear nonsensory cells causes a selective alteration in the acquisition of hearing in PIPKIγ+/− mice. This mouse model also suggests that PIPKIγ may determine the level of gap junction contribution to cochlear development. PMID:22891314

  19. Syndecan-1 interaction with the LG4/5 domain in laminin-332 is essential for keratinocyte migration.

    PubMed

    Bachy, Sophie; Letourneur, François; Rousselle, Patricia

    2008-01-01

    Laminin 5/laminin 332 (LN332) is an adhesion substrate for epithelial cells. After secretion of LN332, a regulated cleavage occurs at the carboxy-terminus of its alpha3 subunit, which releases a tandem of two globular modules named LG4/5. We show that the presence of the LG4/5 domain in precursor LN332 decreases its integrin-mediated cell adhesion properties in comparison with mature LN332. Whereas cell adhesion to the recombinant LG4/5 fragment relies solely on the heparan sulfate proteoglycan (HSPG) receptor syndecan-1, we reveal that both syndecan-1 and the alpha3beta1 integrin bind to precursor LN332. We further demonstrate that syndecan-1 mediated cell adhesion to the LG4/5 fragment and pre-LN332 allows the formation of fascin-containing protrusions, depending on the GTPases Rac and Cdc42 activation. Reducing syndecan-1 expression in normal keratinocytes prevents cell protrusions on pre-LN332 with subsequent failure of the peripheral localization of the alpha3beta1 integrin. We finally show that cell migration on pre-LN332 requires syndecan-1. Therefore, the LG4/5 domain in precursor LN332 appears to trigger intracellular signaling events, which participate in keratinocyte motility. PMID:17579341

  20. Depletion of plasma membrane PtdIns(4,5)P2 reveals essential roles for phosphoinositides in flagellar biogenesis

    PubMed Central

    Wei, Ho-Chun; Rollins, Janet; Fabian, Lacramioara; Hayes, Madeline; Polevoy, Gordon; Bazinet, Christopher; Brill, Julie A.

    2011-01-01

    Summary Axonemes are microtubule-based organelles of crucial importance in the structure and function of eukaryotic cilia and flagella. Despite great progress in understanding how axonemes are assembled, the signals that initiate axoneme outgrowth remain unknown. Here, we identified phosphatidylinositol phosphates (phosphoinositides) as key regulators of early stages of axoneme outgrowth in Drosophila melanogaster spermatogenesis. In a study of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] function in developing Drosophila male germ cells, we depleted PtdIns(4,5)P2 by expression of a potent phosphoinositide phosphatase. Phosphatase expression dramatically inhibited sperm tail formation and perturbed microtubule organization in a manner reversible by co-expression of a PtdIns 4-phosphate 5-kinase. Depletion of PtdIns(4,5)P2 caused increased levels of basal body γ-tubulin and altered the distribution of proteins known to be required for axoneme assembly. Examination of PtdIns(4,5)P2-depleted spermatids by transmission electron microscopy revealed defects in basal body docking to the nuclear envelope, and in axoneme architecture and integrity of the developing flagellar axoneme and axial sheath. Our results provide the first evidence that phosphoinositides act at several steps during flagellar biogenesis, coordinately regulating microtubule and membrane organization. They further suggest that phosphoinositides play evolutionarily conserved roles in flagella and cilia, across phyla and in structurally diverse cell types. PMID:18334551

  1. Role of inositol-1,4,5-trisphosphate receptor in the regulation of calcium transients in neonatal rat ventricular myocytes.

    PubMed

    Zeng, Zheng; Zhang, Heping; Lin, Na; Kang, Man; Zheng, Yuanyuan; Li, Chen; Xu, Pingxiang; Wu, Yongquan; Luo, Dali

    2014-01-01

    This study determined the regulatory effect of inositol 1,4,5-trisphosphate receptors (IP3Rs) on the basal Ca(2+) transients in cardiomyocytes. In cultured neonatal rat ventricular myocytes (NRVMs) at different densities, we used confocal microscopy to assess the effect of IP3Rs on the endogenous spontaneous Ca(2+) oscillations through specific activation of IP3Rs with myo-IP3 hexakis (butyryloxymethyl) ester (IP3BM), a membrane permeable IP3, and interference of IP3R expression with shRNA. We found that NRVMs at the monolayer state displayed coordinated Ca(2+) transients with less rate, shorter duration, and higher amplitude compared to single NRVMs. In addition, monolayer NRVMs exhibited 4 or 10 times more increased Ca(2+) transients in response to phenylephrine, an α-adrenergic receptor agonist, or IP3BM than single NRVMs did, while the transient pattern remained unaltered, suggesting that the sensitivity of intracellular Ca(2+) response to IP3R activation is different between single and monolayer NRVMs. However, interference of IP3R expression with shRNA reduced the frequency and amplitude of the spontaneous Ca(2+) fluctuates similarly in both densities of NRVMs, resembling the effects of ryanodine receptor inhibition by ryanodine or tetracaine. Our findings suggest that IP3Rs are involved, in part, in the regulation of native Ca(2+) transients, in profiles of their initiation and Ca(2+) release extent, in developing cardiomyocytes. In addition, caution should be paid in evaluating the behavior of Ca(2+) signaling in primary cultured cardiomyocytes at different densities. PMID:25242084

  2. Kinetics and threshold level of 2,3,4,5-tetrachlorobiphenyl dechlorination by an organohalide respiring bacterium.

    PubMed

    Lombard, Nathalie J; Ghosh, Upal; Kjellerup, Birthe V; Sowers, Kevin R

    2014-04-15

    The time required for a PCB-contaminated site to recover cannot yet be predicted due in part to lack of quantitative information on rates of PCB dechlorination in the porewater phase. We developed a method to measure rate of dechlorination in the aqueous phase at very low PCB concentrations. This approach utilizes a polymer functioning concurrently as a passive dosing system for maintaining a steady-state PCB substrate concentration in the water phase and as a passive equilibrium sampler to monitor the dechlorination product. Rates of dechlorination of 2,3,4,5-tetrachlorobiphenyl (PCB 61) to 2,3,5-trichlorobiphenyl (PCB 23) by an organohalide respiring bacterium, Dehalobium chlorocoercia DF-1, were measured over an environmentally relevant range of 1 to 500 ng L(-1) in sediment-free medium using a high concentration of cells (>10(6) cells mL(-1)). The results indicate that rate of dechlorination is a linear function of PCB substrate concentration below the maximum aqueous solubility of PCB 61 and occurs at concentrations as low as 1 ng L(-1). Demonstration of PCB 61 dechlorination at environmentally relevant concentrations suggests that low numbers of organohalide respiring bacteria rather than bioavailability accounts for low rates of dechlorination typically observed in sediments. Using passive samplers to measure the concentration of dissolved PCBs in the porewater combined with knowledge of congener-specific rates for organohalide respirer(s), it will be possible to project the in situ rate and final concentration of PCBs for a specific site after treatment by bioaugmentation. PMID:24625226

  3. Kinetics and Threshold Level of 2,3,4,5-Tetrachlorobiphenyl Dechlorination by an Organohalide Respiring Bacterium

    PubMed Central

    2015-01-01

    The time required for a PCB-contaminated site to recover cannot yet be predicted due in part to lack of quantitative information on rates of PCB dechlorination in the porewater phase. We developed a method to measure rate of dechlorination in the aqueous phase at very low PCB concentrations. This approach utilizes a polymer functioning concurrently as a passive dosing system for maintaining a steady-state PCB substrate concentration in the water phase and as a passive equilibrium sampler to monitor the dechlorination product. Rates of dechlorination of 2,3,4,5-tetrachlorobiphenyl (PCB 61) to 2,3,5-trichlorobiphenyl (PCB 23) by an organohalide respiring bacterium, Dehalobium chlorocoercia DF-1, were measured over an environmentally relevant range of 1 to 500 ng L–1 in sediment-free medium using a high concentration of cells (>106 cells mL–1). The results indicate that rate of dechlorination is a linear function of PCB substrate concentration below the maximum aqueous solubility of PCB 61 and occurs at concentrations as low as 1 ng L–1. Demonstration of PCB 61 dechlorination at environmentally relevant concentrations suggests that low numbers of organohalide respiring bacteria rather than bioavailability accounts for low rates of dechlorination typically observed in sediments. Using passive samplers to measure the concentration of dissolved PCBs in the porewater combined with knowledge of congener-specific rates for organohalide respirer(s), it will be possible to project the in situ rate and final concentration of PCBs for a specific site after treatment by bioaugmentation. PMID:24625226

  4. Cellular analysis of residual hemopoietic deficiencies in mice after 4 repeated doses of 4. 5 Gray x rays

    SciTech Connect

    Hendry, J.H.; Xu, C.X.; Testa, N.G.

    1983-11-01

    A sub-optimal plateau in numbers of femoral stem-cells (CFU-S) in mice after 4 doses of 4.5 Gray x rays (each separated by 21 days), was shown to persist at 20 to 30% of control up to 1 year after the last dose, when about 50% of the mice had survived. The concentration of white cells in the blood was maintained persistently at about 70% of control, whereas the concentration of red cells was normal up to 4 months and then it declined to about 75% of control at 10 months after irradiation. Concentrations of some committed progenitor cells in the marrow (GM-CFC and ERC), which are capable of amplification cell divisions, were intermediate between the concentrations of marrow stem cells and mature blood cells in both the granuloid and the erythroid cell lineages, respectively. Hence increased amplification was a mechanism operating for a prolonged period in the production of numbers of mature cells. The numbers were subnormal, however, and this corresponded to only 1 extra amplification division on average. There was a slow decline after 6 months in the numbers of CFU-S, BFU-E and GM-CFC, and in the hematocrit, with reference to age-matched controls. The decline was due partly to a prevention of the natural increase in cell numbers in the marrow with the age of the mice, which was also seen with the femoral content of a stromal progenitor cell (CFU-F). A defect in the repeatedly-irradiated CFU-S population was detected as a persistent inability to produce colonies containing the same number of daughter CFU-S as contained in colonies derived from unirradiated marrow and assayed at the same time.

  5. Nicotinic acetylcholine receptors regulate type 1 inositol 1,4,5-trisphosphate receptor expression via calmodulin kinase IV activation.

    PubMed

    Mizuno, Koji; Kurokawa, Kazuhiro; Ohkuma, Seitaro

    2015-04-01

    Type 1 inositol 1,4,5-trisphosphate receptors (IP3 R-1) are among the important calcium channels regulating intracellular Ca(2+) concentration in the central nervous system. In a previous study, we showed that drugs of abuse, such as cocaine, methamphetamine, and ethanol, induced IP3 R-1 upregulation via the calcium signal transduction pathway in psychological dependence. Although nicotine, a major component in tobacco smoke, participates in psychological and/or physical dependence, it has not yet been clarified how nicotine alters IP3 R-1 expression. The present study, therefore, seeks to clarify the mechanism bgy which nicotine modifies IP3 R-1 expression by using mouse cerebral cortical neurons in primary culture. Nicotine induced dose- and time-dependent upregulation of IP3 R-1 protein following its mRNA increase, and the latter was significantly suppressed by a nonselective nicotinic acetylcholine receptors (nAChR) antagonist, mecamylamine. Both cFos and phosphorylated-cJun (p-cJun) were immediately increased in the nucleus, together with an increase of calmodulin kinase (CaMK) IV but not CaMKII expression after nicotine exposure. A nonselective inhibitor of CaMKs, KN-93, and a calcium chelating regent, BAPTA-AM, completely suppressed the expression of cFos and p-cJun in the nucleus as well as the nicotine-induced IP3 R-1 upregulation. These results indicate that nAChR activation by nicotine upregulates IP3 R-1 via increase of activator protein-1, which is a cFos and cJun dimmer, in the nucleus, with activation of Ca(2+) signaling transduction processes. PMID:25430056

  6. A mechanistic study of the photodegradation of herbicide 2,4,5-trichlorophenoxyacetic acid in aqueous solution.

    PubMed

    Yurkova, Maria P; Pozdnyakov, Ivan P; Plyusnin, Victor F; Grivin, Vycheslav P; Bazhin, Nikolay M; Kruppa, Alexandr I; Maksimova, Tatiana A

    2013-04-01

    Photodegradation of herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) in aqueous solution was investigated by stationary (254 nm) and nanosecond laser (266 nm) flash photolysis techniques. It was shown that in the primary photochemical step both photoionization (which generates a hydrated electron-radical cation pair) and heterolytic cleavage of a C-Cl bond takes place. The major products of substitution of one of the chlorine atoms in the 2-, 4- or 5-position by a hydroxyl group as well as the products of hydroxylation of the benzene ring in 3- and 6-positions were identified by HPLC and LC-MS methods. The complexation of 2,4,5-T with β- and γ-cyclodextrins (β(γ)CD) was investigated. The influence of such complexation on the quantum yield of herbicide photolysis and on the ratio of photodegradation products was determined. PMID:23085749

  7. Modification of molecular sieves MCM-41 and SBA-15 with covalently grafted pyromellitimide and 1,4,5,8-naphthalenediimide.

    PubMed

    Trindade, Fabiane Jesus; Rey, José Fernando Queiruga; Brochsztain, Sergio

    2012-02-15

    This article describes the covalent grafting of pyromellitimide and 1,4,5,8-naphthalenediimide, which are organic semiconductors with very interesting electro-optical properties, onto the walls of mesoporous molecular sieves. The mesoporous materials MCM-41 and SBA-15 were first treated with 3-aminopropyltriethoxysilane, generating materials with a surface coverage of primary amino groups. These materials were further reacted with either pyromellitic dianhydride or 1,4,5,8-naphthalenetetracarboxylic dianhydride, generating surface-bound pyromellitimide or 1,4,5,8-naphthalenediimide, respectively. The success of the modification reactions was confirmed by elemental and thermogravimetric analyses, X-ray diffraction patterns and infrared, reflectance and fluorescence spectroscopies. The results indicated that the mesoporous structure of the new materials was preserved after the modification reactions and that the chromophores were included inside the mesoporous channels with stacked aromatic rings. PMID:22153336

  8. Synthesis and Antifungal Activity of Natural Product-Based 6-Alkyl-2,3,4,5-tetrahydropyridines

    PubMed Central

    Dai, Liyan; Jacob, Melissa R.; Khan, Shabana I.; Khan, Ikhlas A.; Clark, Alice M.; Li, Xing-Cong

    2011-01-01

    Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5-tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the most active. Compound 5e exhibited minimum fungicidal concentrations (MFCs) of 3.8, 15.0, 7.5, and 7.5 μg/mL against Cryptococcus neoformans, Candida albicans, Candida glabrata, and Candida krusei, respectively. The antifungal activities of these compounds appear to be associated with the C-6 side chain length. This study represents the first effort to evaluate antifungal activities of synthetic analogs of the newly identified fire ant venom alkaloids. PMID:21905650

  9. Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY

    PubMed Central

    BUSKIEWICZ, IWONA; KUBARENKO, ANDRIY; PESKE, FRANK; RODNINA, MARINA V.; WINTERMEYER, WOLFGANG

    2005-01-01

    The signal recognition particle (SRP) mediates membrane targeting of translating ribosomes displaying a signal-anchor sequence. In Escherichia coli, SRP consists of 4.5S RNA and a protein, Ffh, that recognizes the signal peptide emerging from the ribosome and the SRP receptor at the membrane, FtsY. In the present work, we studied the interactions between the NG and M domains in Ffh and their rearrangements upon complex formation with 4.5S RNA and/or FtsY. In free Ffh, the NG and M domains are facing one another in an orientation that allows cross-linking between positions 231 in the G domain and 377 in the M domain. There are binding interactions between the two domains, as the isolated domains form a strong complex. The interdomain contacts are disrupted upon binding of Ffh to 4.5S RNA, consuming a part of the total binding energy of 4.5S RNA-Ffh association that is roughly equivalent to the free energy of domain binding to each other. In the SRP particle, the NG domain binds to 4.5S RNA in a region adjacent to the binding site of the M domain. Ffh binding to FtsY also requires a reorientation of NG and M domains. These results suggest that in free Ffh, the binding sites for 4.5S RNA and FtsY are occluded by strong domain–domain interactions which must be disrupted for the formation of SRP or the Ffh-FtsY complex. PMID:15923378

  10. Domain rearrangement of SRP protein Ffh upon binding 4.5S RNA and the SRP receptor FtsY.

    PubMed

    Buskiewicz, Iwona; Kubarenko, Andriy; Peske, Frank; Rodnina, Marina V; Wintermeyer, Wolfgang

    2005-06-01

    The signal recognition particle (SRP) mediates membrane targeting of translating ribosomes displaying a signal-anchor sequence. In Escherichia coli, SRP consists of 4.5S RNA and a protein, Ffh, that recognizes the signal peptide emerging from the ribosome and the SRP receptor at the membrane, FtsY. In the present work, we studied the interactions between the NG and M domains in Ffh and their rearrangements upon complex formation with 4.5S RNA and/or FtsY. In free Ffh, the NG and M domains are facing one another in an orientation that allows cross-linking between positions 231 in the G domain and 377 in the M domain. There are binding interactions between the two domains, as the isolated domains form a strong complex. The interdomain contacts are disrupted upon binding of Ffh to 4.5S RNA, consuming a part of the total binding energy of 4.5S RNA-Ffh association that is roughly equivalent to the free energy of domain binding to each other. In the SRP particle, the NG domain binds to 4.5S RNA in a region adjacent to the binding site of the M domain. Ffh binding to FtsY also requires a reorientation of NG and M domains. These results suggest that in free Ffh, the binding sites for 4.5S RNA and FtsY are occluded by strong domain-domain interactions which must be disrupted for the formation of SRP or the Ffh-FtsY complex. PMID:15923378

  11. Lipotoxic disruption of NHE1 interaction with PI(4,5)P2 expedites proximal tubule apoptosis

    PubMed Central

    Khan, Shenaz; Abu Jawdeh, Bassam G.; Goel, Monu; Schilling, William P.; Parker, Mark D.; Puchowicz, Michelle A.; Yadav, Satya P.; Harris, Raymond C.; El-Meanawy, Ashraf; Hoshi, Malcolm; Shinlapawittayatorn, Krekwit; Deschênes, Isabelle; Ficker, Eckhard; Schelling, Jeffrey R.

    2014-01-01

    Chronic kidney disease progression can be predicted based on the degree of tubular atrophy, which is the result of proximal tubule apoptosis. The Na+/H+ exchanger NHE1 regulates proximal tubule cell survival through interaction with phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but pathophysiologic triggers for NHE1 inactivation are unknown. Because glomerular injury permits proximal tubule luminal exposure and reabsorption of fatty acid/albumin complexes, we hypothesized that accumulation of amphipathic, long-chain acyl-CoA (LC-CoA) metabolites stimulates lipoapoptosis by competing with the structurally similar PI(4,5)P2 for NHE1 binding. Kidneys from mouse models of progressive, albuminuric kidney disease exhibited increased fatty acids, LC-CoAs, and caspase-2–dependent proximal tubule lipoapoptosis. LC-CoAs and the cytosolic domain of NHE1 directly interacted, with an affinity comparable to that of the PI(4,5)P2-NHE1 interaction, and competing LC-CoAs disrupted binding of the NHE1 cytosolic tail to PI(4,5)P2. Inhibition of LC-CoA catabolism reduced NHE1 activity and enhanced apoptosis, whereas inhibition of proximal tubule LC-CoA generation preserved NHE1 activity and protected against apoptosis. Our data indicate that albuminuria/lipiduria enhances lipotoxin delivery to the proximal tubule and accumulation of LC-CoAs contributes to tubular atrophy by severing the NHE1-PI(4,5)P2 interaction, thereby lowering the apoptotic threshold. Furthermore, these data suggest that NHE1 functions as a metabolic sensor for lipotoxicity. PMID:24531551

  12. Phosphatidylinositol (3,4,5)-Trisphosphate Activity Probes for the Labeling and Proteomic Characterization of Protein Binding Partners

    PubMed Central

    Rowland, Meng M.; Bostic, Heidi E.; Gong, Denghuang; Speers, Anna E.; Lucas, Nathan; Cho, Wonhwa; Cravatt, Benjamin F.; Best, Michael D.

    2013-01-01

    Phosphatidylinositol polyphosphate lipids, such as phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P3), regulate critical biological processes, many of which are aberrant in disease. These lipids often act as site-specific ligands in interactions that enforce membrane-association of protein binding partners. Herein, we describe the development of bifunctional activity probes corresponding to the headgroup of PI(3,4,5)P3 that are effective for identifying and characterizing protein binding partners from complex samples, namely cancer cell extracts. These probes contain both a photoaffinity tag for covalent labeling of target proteins as well as a secondary handle for subsequent detection or manipulation of labeled proteins. Probes bearing different secondary tags were exploited, either by direct attachment of a fluorescent dye for optical detection or by using an alkyne that can be derivatized after protein labeling via click chemistry. First, we describe the design and modular synthetic strategy used to generate multiple probes with different reporter tags of use for characterizing probe-labeled proteins. Next, we report initial labeling studies using purified protein, the PH domain of Akt, in which probes were found to label this target, as judged by on-gel detection. Furthermore, protein labeling was abrogated by controls including competition with an unlabeled PI(3,4,5)P3 headgroup analog as well as through protein denaturation, indicating specific labeling. In addition, probes featuring different linker lengths between the PI(3,4,5)P3 headgroup and photoaffinity tag led to variations in protein labeling, indicating that a shorter linker was more effective in this case. Finally, proteomic labeling studies were performed using cell extracts, labeled proteins were observed by in-gel detection and characterized using post-labeling with biotin, affinity chromatography and identification via tandem mass spectrometry. These studies yielded a total of 265 proteins

  13. A Turn-on and Reversible Fluorescence Sensor for Zinc Ion Based on 4,5-Diazafluorene Schiff Base.

    PubMed

    Li, Hui; Zhang, ShuJiang; Gong, ChenLiang; Wang, JianZhi; Wang, Feng

    2016-09-01

    A new 4,5-diazafluorene-based fluorescent chemosensor has been synthesized by Schiff base condensation of 9,9-bis(3,5-dimethyl-4-aminophenyl)-4,5-diazafluorene with salicylaldehyde. The interaction of Schiff base with different metal ions has been studied over photofluorescent spectra. The results showed that Schiff base exhibited 194-fold enhancements in fluorescence at 465 nm after Zn(2+) ions. Such fluorescent responses could be detected by naked eye under UV-lamp. The complex solution (L-Zn(2+)) exhibited reversibility with EDTA. PMID:27430628

  14. Composite lead for conducting an electrical current between 75-80K and 4.5K temperatures

    DOEpatents

    Negm, Yehia; Zimmerman, George O.; Powers, Jr., Robert E.; McConeghy, Randy J.; Kaplan, Alvaro

    1994-12-27

    A composite lead is provided which electrically links and conducts a current between about 75-80K. and liquid helium temperature of about 4.5K. The composite lead may be employed singly or in multiples concurrently to provide conduction of electrical current from normal conductors and semi-conductors at room temperature to superconductors operating at 4.5K. In addition, a variety of organizationl arrangements and assemblies are provided by which the mechanical strength and electrical reliability of the composite lead is maintained.

  15. Composite lead for conducting an electrical current between 75--80K and 4. 5K temperatures

    DOEpatents

    Negm, Y.; Zimmerman, G.O.; Powers, R.E. Jr.; McConeghy, R.J.; Kaplan, A.

    1994-12-27

    A composite lead is provided which electrically links and conducts a current between about 75-80K and liquid helium temperature of about 4.5K. The composite lead may be employed singly or in multiples concurrently to provide conduction of electrical current from normal conductors and semi-conductors at room temperature to superconductors operating at 4.5K. In addition, a variety of organizational arrangements and assemblies are provided by which the mechanical strength and electrical reliability of the composite lead is maintained. 12 figures.

  16. Process for manufacturing bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene

    SciTech Connect

    Rasmussen, Paul George; Lawton, Richard Graham

    2014-06-03

    A process to manufacture substituted tetracyano-hexaazatricyclics with the substitutions occurring at the 9 and 10 hydrogens. The process begins with 2,3-dichloro-5,6-dicyanopyrazine, which is reacted to form the desired tetracyano-hexaazatricyclic. Different process embodiments enable different reaction paths to the desired tetracyano-hexaazatricyclic. Different tetracyano-hexaazatricyclic embodiments include bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene and bis(2-methoxyethoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracen- e.

  17. Tetrazolo(1,5-a)pyridines and furazano(4,5-b)pyridine 1-oxides

    SciTech Connect

    Lowe-Ma, C.K.; Nissan, R.A.; Wilson, W.S. )

    1990-06-08

    Tetrazolo(1,5-a)pyridines may be prepared by the reaction of azide ion with 2-chloropyridines. These tetrazolo(1,5-a)pyridines are shown to be in equilibrium with the corresponding 2-azidopyridines. Furazano(4,5-b)pyridine 1-oxides may be prepared by thermolysis of the appropriate 4-nitrotetrazolo(1,2-a)pyridines, presumably via the corresponding 2-azido-3-nitropyridines. The furazano(4,5-b)pyridine 1-oxides are found to be in equilibrium with the 3-oxides. {sup 1}H and {sup 13}C NMR are used to examine this equilibrium.

  18. Molecular design of new nitramine explosives: 1,3,5,7-tetranitro-8-(nitromethyl)-4-imidazolino[4,5-b]4-imidazolino-[4,5-e] pyridine and its N-oxide.

    PubMed

    Liu, Hui; Du, Hongchen; Wang, Guixiang; Liu, Yan; Gong, Xuedong

    2012-04-01

    Two new nitramine compounds containing pyridine, 1,3,5,7-tetranitro-8-(nitromethyl) -4-imidazolino[4,5-b]4-imidazolino-[4,5-e]pyridine and its N-oxide 1,3,5,7-tetranitro-8- (nitromethyl)-4-imidazolino[4,5-b]4-imidazolino-[4,5-e]pyridine-4-ol were proposed. Density functional theory (DFT) has been employed to study the molecular geometries, electronic structures, infrared spectra, and thermodynamic properties at the B3LYP/6-31G* level. Their detonation performances evaluated using the Kamlet-Jacobs equations with the calculated densities and heats of formation are superior to those of HMX. The predicted densities of them were ca. 2 g cm(-3), detonation velocities were over 9 km s(-1), and detonation pressures were about 40 GPa, showing that they may be potential candidates of high energy density materials (HEDMs). The natural bond orbital analysis indicated that N-NO(2) bond is the trigger bond during thermolysis process. The stability of the title compounds is slightly lower than that of 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12- hexaazaisowurtzitane (CL-20). The results of this study may provide basic information for the molecular design of new HEDMs. PMID:21748326

  19. The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma membrane and viral egress

    PubMed Central

    Johnson, Kristen A.; Taghon, Geoffrey J. F.; Scott, Jordan L.; Stahelin, Robert V.

    2016-01-01

    VP40 is one of eight proteins encoded by the Ebola Virus (EBOV) and serves as the primary matrix protein, forming virus like particles (VLPs) from mammalian cells without the need for other EBOV proteins. While VP40 is required for viral assembly and budding from host cells during infection, the mechanisms that target VP40 to the plasma membrane are not well understood. Phosphatidylserine is required for VP40 plasma membrane binding, VP40 hexamer formation, and VLP egress, However, PS also becomes exposed on the outer membrane leaflet at sites of VP40 budding, raising the question of how VP40 maintains an interaction with the plasma membrane inner leaflet when PS is flipped to the opposite side. To address this question, cellular and in vitro assays were employed to determine if phosphoinositides are important for efficient VP40 localization to the plasma membrane. Cellular studies demonstrated that PI(4,5)P2 was an important component of VP40 assembly at the plasma membrane and subsequent virus like particle formation. Additionally, PI(4,5)P2 was required for formation of extensive oligomers of VP40, suggesting PS and PI(4,5)P2 have different roles in VP40 assembly where PS regulates formation of hexamers from VP40 dimers and PI(4,5)P2 stabilizes and/or induces extensive VP40 oligomerization at the plasma membrane. PMID:26753796

  20. Sexual predators, energy development, and conservation in greater Yellowstone.

    PubMed

    Berger, Joel; Beckmann, Jon P

    2010-06-01

    In the United States, as elsewhere, a growing debate pits national energy policy and homeland security against biological conservation. In rural communities the extraction of fossil fuels is often encouraged because of the employment opportunities it offers, although the concomitant itinerant workforce is often associated with increased wildlife poaching. We explored possible positive and negative factors associated with energy extraction in the Greater Yellowstone Ecosystem (GYE), an area known for its national parks, intact biological diversity, and some of the New World's longest terrestrial migrations. Specifically, we asked whether counties with different economies-recreation (ski), agrarian (ranching or farming), and energy extractive (petroleum)-differed in healthcare (gauged by the abundance of hospital beds) and in the frequency of sexual predators. The absolute and relative frequency of registered sex offenders grew approximately two to three times faster in areas reliant on energy extraction. Healthcare among counties did not differ. The strong conflation of community dishevel, as reflected by in-migrant sexual predators, and ecological decay in Greater Yellowstone is consistent with patterns seen in similar systems from Ecuador to northern Canada, where social and environmental disarray exist around energy boomtowns. In our case, that groups (albeit with different aims) mobilized campaigns to help maintain the quality of rural livelihoods by protecting open space is a positive sign that conservation can matter, especially in the face of rampant and poorly executed energy extraction projects. Our findings further suggest that the public and industry need stronger regulatory action to instill greater vigilance when and where social factors and land conversion impact biological systems. PMID:20184654